Thursday, 26 May 2022

Lupine Publishers | Genetic Counseling and Testing for Colorectal Cancer in Young Adults: Mini-Review

 Lupine Publishers | Journal of Forensic & Genetic Sciences


Abstract

Colorectal cancer (CRC) has one of the largest proportions of familial cases. Two to 5% of all colon cancers arise in the setting of inherited syndromes, including Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), familial adenomatous polyposis (FAP), attenuated FAP, MUTYH-associated polyposis (MAP), and certain hamartomatous polyposis conditions like Peutz-Jeghers syndrome (PJS) and juvenile polyposis syndrome (JPS). All of these conditions are inherited, autosomal dominant disorders, except MAP, which is autosomal recessive [l]. Although clinical similarities do exist, each has different cancer risks, characteristic clinical features, and separate genetical etiologies. In addition to these syndromes, up to 30 % of colon cancers exhibit increased familial risk, likely related to inheritance. A number of less penetrant, but possibly more frequent susceptibility genes have been identified for this level of inheritance. Determination of predisposing genes allows for accurate risk assessment and more precise screening approaches. Examples include common polymorphisms in genes that regulate metabolism or genes that are regulated by environmental or other genetic factors.

Abbreviations: CRC: Colorectal cancer; HNPCC: Nonpolyposis Colorectal Cancer; FAP: Familial Adenomatous Polyposis; MAP: MUTYH- Associated Polyposis; JPS: Juvenile Polyposis Syndrome.

Introduction

Lynch syndrome is the result of a germline mutation in a class of hMSH2, hMLHl, hMSH6, and hPMS2. The MMR system is and insertion-deletion loops that form during DNA replication. Germline mutations in genes involved in DNA MMR (necessary for maintaining genomic stability by correcting single-base mismatches), including hMSH2 and hMLHl account for the up to 90% of Lynch syndrome cases; mutations in hMSH6 account for approximately l0% and mutations in hPMS2 are detected on rare occasions [2]. FAP (development of hundreds to thousands of colonic adenomas, beginning in early adolescence, and inevitable CRC in untreated individuals by 39 years), attenuated FAP (70% lifetime risk of CRC, an average of approximately 30 colonic adenomatous polyps), and Gardner syndrome (FAP with osteomas, epidermoid cysts, dental disorders, and/or desmoid tumors) all result from mutations in gene APC, which encodes a tumor suppressor that is part of the WNT signaling pathway.MAP is caused by biallelic mutations in MUTYH (MYH;part of the base-excision repair pathway, which is involved in defending against oxidative DNA damage) and is characterized by the presence of adenomatous polyposis of colo-rectum, and an increased risk of especially proximal colonic neoplasms, like attenuated FAP [3]. PJS and JPS are hamartomatous polyposis diseases hat are both associated with an increased risk for CRC and other malignancies. Gastrointestinal symptoms first occur in the early teenage years and include small bowel obstruction and intussusception. Mutations in STKll (LKBl) are the only known cause of PJS, whereas JPS is caused by mutations in either SMAD4 or BMPRlA [4]. Another known very rare hamartomatous condition, Cowden syndrome, arises from mutations of PTEN [5].

Identification of the genes that cause these colon cancer syndromes has led to the development of specific management guidelinesand genetic teststhat can diagnose these familial disorders. These guidelines are important, not only for the affected patient, but also for their family members. If a patient has FAP, close family members should be tested early on, usually as teenagers. This is because CRC in patients with FAP tends to arise at a very young age. If a patient has Lynch syndrome, family members can wait until they are about 20 to 25 years old to undergo genetic testing. At-risk patients can be offered genetic counseling and testing to determine whether they carry a detectable mutation for such a syndrome. If so, this information provides the clinician with valuable data about the patient's risk for other cancers, and alerts surgeon about the correct time for surgery.

Conclusion

In conclusion, genetic testing is available for most hereditary CRC syndromes and can be used to confirm suspected diagnosis, to clarify risks of extra-colonic cancers in affected individuals, and to identify relatives who are also at risk. Therefore, genetics analyses of CRC risk need to be included in mainstream clinical practice.

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Wednesday, 25 May 2022

Lupine Publishers | The Development Fortified Pan Bread by Increasing Its Protein Content with High Levels of Live Yeast cells Saccharomyces Cerevisiae

 Lupine Publishers | Journal of Dairy & Veterinary Sciences


Abstract

The main objective of the research is to develop pan bread nutritional value through fortification with high concentration of live yeast cells (Saccharomyces Cerevisiae). Fortified pan bread boosts the nutritional status of poor people and reduces the incidence of infertility diseases. The bread was reformulated by adding various concentrations of S. Cerevisiae at 5, 10, 15, 20 and 30g/ kg wheat flour. The bread was baked using the straight dough method. Protein, carbohydrate, moisture, fat, vitamin B complex, minerals, energy value, amino acids profile and Sensory evaluation were conducted on the fortified pan bread were evaluated. Results revealed that the carbohydrate, moisture, vitamin B complex, minerals, protein content and amino acids pattern increased with the increase in concentration of S. Cerevisiae. The sensory test showed that pan bread fortified with S. Cerevisiae concentration at 5, 10, 15 &20g/kg wheat flour were accepted by panelists, while pan bread at 30g/kg concentration was unacceptable. This study shows the potential of using high concentration of S. Cerevisiaein improving protein quality and nutritional value of pan bread consumed by economically disadvantaged communities.

Keywords: Bread; Fortification; Nutrition; Protein Amino Acids; Yeast; Saccharomyces Cerevisae; Carbohydrate; Vitamin Supplements; Nutritional Yeast; Biomass Production; Sensorial Quality

Introduction

Bread is the main product of wheat which is manufactured commercially. Eating grain foods, like bread consumed a lot by economically disadvantaged communities. it is plays an important role in the diet by providing many nutrients, such as carbohydrate, Protein, dietary fiber, vitamins and minerals, which are vital for the health and maintenance of the body Pareyt [1]. But wheat flour which is the basic ingredient in bread is lack crucial nutrients such as essential amino acid lysine and B complex vitamins Wardlaw [2]. One way of improving the nutritional quality of pan bread is fortification with bakery yeast Saccharomyces Cerevisiaeto enhancing bread protein content Friedman & Finot [3]. Saccharomyces Cerevisiae has high nutritional value is rich in content of the proteins, vitamin B complexes and minerals such as calcium, phosphorus, manganese, magnesium, zinc and copper and has high biological value of essential and nonessential amino acids so it has several health benefits Shrinandan [4]. Saccharomyces Cerevisiae as a single cell protein is a rich source of proteins which are necessary for replacing worn out tissues or recovery after infections and contains 18 amino acids and is considered to be 55% high quality protein. It is a rich source of B vitamins which aid in lowering stress, help in metabolism, prevent cancer and ensure a healthy skin and it is low in fat and hence low in cholesterol content it maintains optimum cholesterol levels, improves blood production and also improves liver health and function Bekatorou Saccharomyces Cerevisiae also contains gluthanione, an antioxidant and beta glucan which stimulates the immune system Hong [5]. Of the 15 minerals that it contains, Saccharomyces Cerevisiae consists of chromium a trace mineral which is known as glucose tolerance factor which is essential in the prevention of diabetes, lowers blood pressure and fluctuating blood sugar Zetic [6]. Production of proteins from Saccharomyces Cerevisiae (Biomass) is advantageous, because of high protein content and short growth times, leading to rapid biomass production be propagated using cheap raw materials and easily harvested due to their bigger cell sizes and flocculation abilities so it is utilized by biscuits manufacturing companies, as vitamin supplements. It is also used in pharmaceuticals and animal feeds as a source of proteins and vitamin supplements Yamada & Sgarbieri [7]. This work aims at using increased concentration of Saccharomyces Cerevisiae biomass as live cells to be added to bread dough for the formation of high protein content of bread for promoting good health. This was performed by determining the proximate chemical composition, vitamins, minerals, amino acids profile and sensory evaluation tests of bread.

Material and Method

Starter cultures

A commercial mesophilic Saccharomyces Cerevisiae starter culture obtained from (Pakmaya instant yeast, made in Turkey by Pak Gida) was used in bread manufacture as a negative control. One selected strain MY Saccharomyces Cerevisiae from my identified yeasts isolation (my previous work in protein research department- GEBRI/ SRTA- City) was used in four treatments and positive control to improve, increasing protein and amino acids content, fortification and enhances the flavor and texture of bread. MY Saccharomyces Cerevisiae was grown in YPD medium (10g/L yeast extract; 20g/L peptone; 20g/L glucose) broth at 30-35oC for 24-48h. then centrifuged on sterilized cups at 3000rpm in 25oC for 10 min to remove broth medium, then inoculated overnight in sterilized skim milk at 30 - 35oC, then re-centrifuged to get mediumfreelive cells. The viable count of Saccharomyces Cerevisiae after incubation was 6-8×104 CFU/g by Homothito meter method.

Bread Preparation by Straight-Dough Method

The straight dough method is the easiest of the dough-making methods where all the ingredients are mixed at the same time in the mixer as described by Ayele [8] with some modification. The bread was reformulated by adding a commercial Saccharomyces Cerevisiae starter culture at 5g/kg wheat flour as a negative control, and selected strain MY Saccharomyces Cerevisiae at 5g/ kg wheat flour as positive control. Several of MY Saccharomyces Cerevisiae at concentrations of 10g/kg, 15g/kg, 20g/ kg and 30g/ kg wheat flour were prepared. Wheat flour was mixed with salt (10g/kg), sugar (30g/kg), live cell of starter culture Saccharomyces Cerevisiae (divided for negative control, positive control and other treatments) and water to make dough. Proofing of the dough was done at a standard time of 50 - 60 minutes at 30-35oC as first fermentation, then divided to five parts for positive control and treatments. More addition of Saccharomyces Cerevisiae live cells at 5, 10, 15, 25g /kg dough were added then putt in stainless pans and left for another 30 minutes as a final proofing step (second fermentation).Treatment and control baked in the electric oven at 250°C for 20min., then cooled for 2h., baked breads were packed in low-density polyethylene plastic bags and stored for three days at room temperature (24 ± 2°C).These dough mixtures and bread samples were evaluated for nutritional value and sensory evaluation.

Quality attributes evaluation

Proximate chemical composition

a) Moisture content

The sample (5g) was transferred into a Petri-dish of known weight. The weighed sample was put into an oven at 105 oC until constant weight was obtained AOAC [9]. The difference between the initial and final weight of the sample was recorded as the moisture content.

b) Determination of total carbohydrate

Determination of total carbohydrate was done using the phenol-sulfuric acid method as described by DuBois [10]. The total concentration of Carbohydrate obtained from bread samples was: Total carbohydrate (%) = (carbohydrate content from calibration curve/weight of sample) x 100.

c) Determination of crude protein

Nitrogen content was determined after digestion of about 0.5g sample by micro-Kjeldahl method and the ammonia was received in 4% boric acid according to the method of AOAC [9]. The crude protein (%) was determined by multiplying the total nitrogen by factor of 6.25.

d) Determination of fat content

Crude fat content was determined after extraction of 3.5 g sample with 50 mL diethyl ether by Soxhlet extraction method. The solvent was evaporated. The residue was recorded as crude fat content according to AOAC [9].

e) Determination of Energy value: Energy value (kcal per 100 g) was estimated using the Atwater conversion factor (Osborne & Voogt [11].

Energy (kcal per 100 g) = [9 × Lipids% + 4 × Proteins% + 4 × Carbohydrates%].

f) Determination of Vitamin B complex: The vitamin B group was extracted according to a previously described method (AOAC1990) the prepared sample was injected into the HPLC system. Quantification of vitamin B content was accomplished by comparison to vitamin B standards. Standard stock solutions for Thiamine,Riboflavin, Niacin, Pyridoxine, and Cobalamin were prepared as reported previously Aslam [12] and Ringling [13] .Chromatographic separation was achieved on a reversed phase- (RP-) HPLC column(Agilent ZORBAX Eclipse Plus C18; 250 × 4.6mm i.d., 5𝜇m) through the isocratic delivery mobile phase (A/B 33/67; A: MeOH, B: 0.023M H3PO4, pH = 3.54) at a flow rate of 0.5mL/ min. Ultraviolet (UV) absorbance was recorded at 270nm at room temperature Marzougui [14] and Rokayya [15].

g) Determination and analysis of Minerals: The mineral contents were assessed by flame atomic absorption spectrophotometer (FAAS - Analytik Jena, Germany) according to AOAC Official Method 985.35 [16] then expressed in fresh weight (mg/100g).

h) Determination of Amino Acids: Amino acids have been extracted from the wheat bread according to Knežević [17]. Each of the defatted samples was weighed (200mg) in to a glass ampoule, 5ml of 6N HCl/L was added to the ampoule, and the contents were hydrolyzed in an electric oven preset at 105°C for 22h. Oxygen was expelled in the ampoule by passing nitrogen gas in to it. Amino acid analysis was done by (SYKAM S433 Amino Acids Analyzer). The analysis was carried out with a gas flow rate of 0.5ml/min at 60°C, and the reproducibility was 3%. The amino acid composition was calculated from the areas of standards obtained from the integrator and expressed as percentages of the total protein according to Trajković [18].

i) Sensory Quality Attributes: Sensorial quality was evaluated by a10-panalists, from dept. of food science to score quality attributes of bread. Samples were scored for overall visual quality by using an interval hedonic scale, where the extremes and center of the interval were represented as follows: zero (dislike extremely, no characteristic of the product), 5 (neither like nor dislike, limit of acceptance from the consumer’s point of view), and 10 (like extremely, very characteristic of the product). The tested attributes such as texture, taste, odor, color and appearance and overall acceptance were evaluated, according to Eddy [19]. The end of shelf-life was reached when the average value of the samples was judged as unacceptable for consumption by the sensory panel.

j) Statistical analysis: All results were presented as means ± standard deviation (SD). (n =3) Values were statistically analyzed by one-way analysis of variance (ANOVA test) according to Steel [20] using SPSS 22 software package. Differences were considered significant at (P values) less than 0.05 using Duncan Multiple Range test.

Results and Discussion

Nutrient Analysis

Table 1 shows the nutrient composition of bread. An increase in nutritional yeast concentration resulted in increase in the protein content of bread. Similar results were reported by Shogran [21] Udofia [22] Noorfarahzilah [23] and Masamba [24].The nutritional yeast used to fortify bread contains high quality protein which was reflected in the fortified bread. Proposed that nutritional yeast is a rich source of protein. Therefore the consumption of nutritional yeast fortified bread means exposure to higher quantity and quality protein Goesaert [25] and Gary [26]). The nutritional yeast fortified bread had a slightly higher content of carbohydrate, moisture and B complex vitamins (Thiamine B1, Riboflavine B2, Niacin B3, Pyridoxamine B6, folic acid B9 and Cyanocobalamin B12) compared to the non-fortified bread sample. These results are in agreement with Ndife [27] and Pareyt [1]. Table 1 revealed also that the fortified bread had higher content of minerals such as (Potassium, Phosphorus, Magnesium, Calcium, Iron and Zinc) compared to the non-fortified bread sample. These results are in agreement with Nwanekezi [28]. It was also noted that lipids and Sodium content were lower in fortified bread because of the addition volume of nutritional yeast. These results are in agreement with (Mashayekh [29] Sanful [30] [Table 1].

Table 1: Means of nutritional value of fortificated bread as influenced by adding three different concentrations of active Saccharomyces Cerevisiae.

Lupinepublishers-openaccess-Dairy-Veterinary-Sciences

Sensory Evaluation

Color and Appearance of Bread: Data in Table 2 shows people responses to the appearances of bread samples. All the bread samples were baked using white flour and the change in color was a result of incorporation of different nutritional yeast concentrations. The darker color noticed in bread samples with higher concentrations of nutritional yeast was a result of enhanced Maillard reactions [42] between reducing sugars and proteins. Vaclavik and Christian [43] described appearance of food as the size, color, structure, transparency of turbidity and degree of wholeness or damage of the product. Structure and color are important in baked goods for example bread should have white and brown color and should have many holes uniformly spread throughout otherwise a slight drift from normal will be judged as a quality defect. Most people referred the appearance of bread sample T1 since it resembled the color of brown bread available on commercial market. This shows that many consumers prefer brown bread to white bread when considering color only. Sample T3was regarded as unacceptable by the respondents due to its dark brown color which they perceived as unattractive.

Taste of Bread:b Taste was the main attribute in rating of the samples since addition of the nutritional yeast had an effect of changing the taste of the bread. Tepper and Ulrich [44] defined taste as a combination of five major tastes: salty; sweet; sour; bitter and umami. Taste is detected by taste buds at the tips, sides and back of the tongue and the sensitivity to a particular taste depends on the concentration of the substance responsible for the taste. The responses to the taste of different bread samples are shown in Table 2 the respondents liked the taste of sample T1 most largely because it had the taste of what they already perceive as normal and fresh bread taste. Samples T2 and T3 had low scores due to the cheese like taste of the nutritional yeast which was appealing to most respondents who originally prefer cheese. Bread sampleT4 was regarded as unacceptable for human consumption as a result of a bitter aftertaste experienced by the consumers.

Table 2: Means of sensory score values of bread as influenced by adding four different concentrations of active yeast.

Lupinepublishers-openaccess-Dairy-Veterinary-Sciences

Values are means of three determinations ± standard deviation (n = 3). Values in the same row are not statistically different (p<0.05).
(Negative Control) = Reformulated by adding a commercial Saccharomyces Cerevisiae starter culture in the range 5g / kg wheat flour
(Positive Control) = Reformulated by adding selected isolated strain MY Saccharomyces Cerevisiae in the range 5g / kg wheat flour
(Treatment 1) = Reformulated by adding selected isolated strain MY Saccharomyces Cerevisiae in the range 10g / kg wheat flour
(Treatment 2) = Reformulated by adding selected isolated strain MY Saccharomyces Cerevisiae in the range 15g /kg wheat flour
(Treatment 3) = Reformulated by adding selected isolated strain MY Saccharomyces Cerevisiae in the range 20g /kg wheat flour
(Treatment 4) = Reformulated by adding selected isolated strain MY Saccharomyces Cerevisiae in the range 30g /kg wheat flour

Flavor of Bread: Flavor is one of the major sensory properties which are decisive in acceptance and selection. Vaclavik and Christian [43] defined flavor as a combination of smell and taste which is largely subjective. Table 2 shows consumer responses to bread flavor of different nutritional yeast concentration. As the level of nutritional yeast increased, the typical flavor associated with bread decreased. The respondents accepted flavor of bread samples T1, T2 and T3 but rejected bread samples T4 as a result of strong yeast smell. Consumers are more likely to accept products that they are familiar with. Any deviation in flavor is deemed as quality defect.

Bread Texture: Texture refers to those qualities of food that can be felt with fingers, tongue, palate or teeth Murano [34]. The texture of bread samples is shown in Table 2. The respondents found the texture of samples T1, T2 and T3 as highly acceptable. Sample T4was regarded as unacceptable in terms of texture due to the high amounts of moisture in the bread samples which resulted in a lumpy crumb structure instead of an open texture.

Amino acids Analysis: The results of Table 3 the qualitative analysis showed the variability in the amino acid composition in the examined wheat genotype. For all analyzed cultivars have been identified 18 different amino acids. These results suggest that wheat flour and non-fortified bread protein is deficient in certain essential amino acids, such as lysine, tryptophan, threonine, methionine and histidine. Wheat protein is rich in glutamic acid and proline, which are the dominating non- essential amino acids. Paterson [35] also reported the deficiency of lysine, tryptophan and methionine in wheat protein; likewise Khan [36] reported that lysine is the limiting essential amino acid in wheat grain protein. In contrast fortified bread treatments showed highly increase in certain essential and non- essential amino acids. At the same time it should be noted that the lysine has been higher increase value in fortified bread treatments which is in agreement with the experience of Yalçın [37] who used a similar technique with fortified bread. According to the results of the analysis the most present amino acids in the examined wheat flour were glutamic acid, glycine, sarcosine, valine, norvaline and tryptophan. It is well known, that glutamic acid and glycine are principal amino acids in all cereal protein fractions. Likewise Sejian [38] and Knezevic [39] found that increase in the protein content of wheat grain showed differences among wheat genotypes. Considering that amino acid composition of wheat flour proteins is genetically determined, it mean that changes of amino-acid composition is possible realize through changes of backing proceed. Similar results were reported by Paterson [35] there was a significant loss of lysine when dough is baked into bread. Ahmad & Hussain [40] and Jensen [41] also reported negative relation between the protein and lysine content of wheat (Table 3).

Table 3: Means of Amino acids concentration value of wheat flour and fortificated wheat bread as influenced by adding three different concentrations of active Saccharomyces Cerevisiae as (mg/gm).

Lupinepublishers-openaccess-Dairy-Veterinary-Sciences

Values are means of three determinations ± standard deviation (n = 3). Values in the same row are not statistically different (p<0.05).
(Negative Control)= Reformulated by adding a commercial Saccharomyces Cerevisiae starter culture in the range 5g / kg wheat flour
(Postive Control)= Reformulated by adding selected isoleted strain MY Saccharomyces Cerevisiae in the range 5g / kg wheat flour
(Treatment 1)= Reformulated by adding selected isoleted strain MY Saccharomyces Cerevisiae in the range 10g / kg wheat flour
(Treatment 2)= Reformulated by adding selected isoleted strain MY Saccharomyces Cerevisiae in the range 15g / kg wheat flour
(Treatment 3)= Reformulated by adding selected isoleted strain MY Saccharomyces Cerevisiae in the range 20g / kg wheat flour

Conclusion

The protein content spatially essential amino acids content of the homemade bread was improved through nutritional yeast fortification. The carbohydrate, B complex vitamins and minerals content of the fortified bread were improved. The flavor and taste greatly influenced consumer acceptance of the product. Addition of artificial flavorings to mask the strong flavor of the nutritional yeast could help improve the taste and consumer acceptability of the fortified bread. For increasing of amino acid content as well composition of free essential amino acids in grain of wheat we need to increase our knowledge about mechanisms of the control grain protein accumulation at the molecular, biochemical and physiological levels. Also, for improving nutritional value are necessary to select wheat genotypes in terms of essential amino acids content and higher protein content.

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Tuesday, 24 May 2022

Lupine Publishers | Features of Rheumatic Disease Management while Pregnancy

 Lupine Publishers | Journal of Gynaecology and Women's Healthcare


Abstract

Rheumatism is a systemic inflammatory disease of connective tissue and joints with a predominantly affected heart. Children and young people are ill mostly: women are 3 times more likely than men. Therefore, the problem of rheumatism in pregnant women is quite common.

Keywords: Rheumatism; Pregnancy; Orthopedist

Etiology & Pathogenesis

The main etiological factor in acute forms of the disease is betahemolytic streptococcus of group A [1]. In patients with prolonged and continuously recurrent forms of rheumatic heart disease, the association of the disease with streptococcus often fails to be established. In such cases, the defeat of the heart, which fully meets all the main criteria for rheumatism, apparently has a different nature - allergic (not related to streptococcus or, in general, infectious antigens), infectious-toxic, viral. Speaking of rheumatism, it is implied that the process involves the musculoskeletal system and the cardiovascular system [2]. Given this fact, it becomes extremely clear that pregnancy with such extra genital pathology should proceed under the compulsory supervision of not only the obstetrician-gynecologist, but also the rheumatologist. According to statistical data, pregnancy itself rarely leads to the development of an unpleasant phenomenon of the future mother, such as rheumatism.

Usually, women already suffer from this ailment, only during pregnancy the disease worsens in 20% of women and causes many pregnant women to seek medical help [3]. The development of rheumatism is observed in the first months of pregnancy, when there is a weakening of immunity and the body as a whole. This indicates that the body is not able to withstand various diseases, which are mostly infectious. Births also play a significant role in the development of extra genital pathology. After all, it is well known that after giving birth, the body is significantly weakened and loses ability to fight against many diseases, including rheumatism. It takes sufficient time for the body to recover and the woman to return to her former strength. The most unpleasant thing is that if rheumatism worsens at the initial stage of pregnancy, it can lead to an interruption of the process, because any acute inflammation occurring in the body requires mandatory medical intervention and the admission of certain groups of drugs [4]. How rheumatism is manifested and how can it happen in pregnant women? Most often it is caused by beta-hemolytic streptococcus group A.

The development of the rheumatic pathological process consists of several stages:

a) a disease with sore throat, pharyngitis, scarlet fever, or other ENT infection of streptococcal nature;

b) In response to the penetration of β-hemolytic streptococcus, the immune system produces specific antibodies - the so-called “antibodies”. C-reactive proteins;

c) In the presence of a genetic predisposition to rheumatism, C-reactive proteins begin to attack their connective tissue cells (similar antigens exist on their surface, as in hemolytic streptococcus);

d) An autoimmune inflammatory process develops in the affected area - most often in the joints, myocardium, endocardium, vessels, etc. [5,6].

The provoking factors of exacerbation of rheumatism during pregnancy are [7]:

a) Hypothermia;

b) Physiological Reduction of Immunity in early Pregnancy;

c) Bacterial and Viral Infections;

d) Stress;

e) Malnutrition;

f) Exacerbation of Existing Chronic Diseases;

g) Excessive Exposure to the sun.

Speaking about the symptoms of the disease, it should be borne in mind that they are in some ways similar to those with streptococcal angina and are characterized by [8,9]:

a) general weakness;

b) the appearance of pain in the heart;

c) often minor physical exertion can provoke shortness of breath, rapid heart rate;

d) loss of appetite;

e) Joint pain, especially on days when the weather is changing noticeably; increase in temperature.

Due to the fact that during pregnancy many corticosteroid hormones are produced that have anti-inflammatory effect, the signs of exacerbation of rheumatism are blurred and not pronounced. With a heart form of rheumatism, pain in the heart is more pronounced. As a rule, the joint form is combined with the heart. It all starts with pain in the large joints. In this case, the pain passes from one group of joints to another. The cutaneous form is manifested in the appearance of characteristic pink rings on the skin, which eventually pass Rheumatism of pregnant women can lead to a condition like late toxicosis. With the exacerbation of rheumatism, there is often an acute shortage of oxygen, which can lead to placental vasculitis, changes in the placenta, intrauterine hypoxia and hypotrophy. Given the possible complications, those pregnant women who are at risk are kept under close supervision throughout the process, right up to the birth itself. If a woman has suffered several exacerbations of rheumatism, she should definitely mention this at the first visit to the doctor of a woman’s consultation. As a preventive measure, you must take care of acute infectious diseases, and if they arise, immediately go to a doctor who will prescribe an effective treatment. In addition, antirheumatic therapy is performed in pregnant women who have undergone angina or catarrh of the upper respiratory tract.

Diagnosis of rheumatism in pregnancy

Recognize and determine rheumatism in a pregnant woman can only a doctor after the examination and analysis. Diagnosing rheumatism is important in the first trimester. Because of the dangers that rheumatism causes (especially if there is heart failure and heart defects), it may be asked about the need for abortion. The diagnosis of rheumatic carditis is based on ECG (electrocardiogram), ultrasound of the heart [10]. It is necessary to consider those cases when a number of pregnant women do not suspect about the presence of rheumatism. To identify extra genital pathology, laboratory (diagnostic) studies are mandatory. Speaking about the complex of diagnostic examination, we mean the delivery of a blood test, as well as ultrasound, an echocardiogram of the heart. These indicators can give accurate information about whether a pregnant woman suffers from rheumatism or not.

Particular attention is paid to increasing the heart rate. In pregnant women suffering from a disease such as rheumatism, the heart rate has a more pronounced picture than the usual (healthy). Nevertheless, it should not be forgotten that in most cases this picture may indicate more about the development of insufficiency in pregnant blood circulation, rather than the development of rheumatism. Therefore, several methods are used to obtain more accurate and reliable information about the work of the heart. In this case, an important role in the diagnosis is played by ECG (electrocardiogram) indicators, such as: increase / flattening / broadening of the P-Q interval; serration of the tooth P; QRS complex changes; slight or, conversely, a significant decrease in the ST segment and T wave. In addition to the results of ECG and ultrasound of the heart, blood tests are used to diagnose rheumatism. Practice shows that rheumatism, especially if there is a tendency to exacerbate it, leads to an increase in ESR (sedimentation rate erythrocytes) to 35-50 mm / h. When conducting a biochemical blood test in pregnancy, the main indicators are [11]:

a) C-reactive protein;

b) Hexose;

c) Ceruloplasmin;

d) Seromucoid;

e) Hydroxyproline;

f) A2-globulin.

As for the indicator, such as fibrinogen, which is determined by the blood test, it is not given special attention, since it is always elevated in pregnant women and does not indicate an increase in rheumatism. Another issue is the identification of those pregnancy periods in which one can expect activation of the rheumatic process. Almost all authors agree that the most frequent exacerbation of rheumatism occurs in the first trimester of pregnancy. The second vulnerable period is postpartum; sometimes an exacerbation occurs at a gestational age of 28-32 weeks, so it is reasonable to conduct an anti-relapse treatment in these periods and especially in the first 3 months of pregnancy and immediately after delivery. It should be noted that the risk of exacerbation is not limited only to the postpartum period. These people may come several months after the birth, demanding special monitoring of this contingent of women for a longer time (at least, up to 6-12 months).

Many pregnant women are wondering: why should the survey be conducted at an early stage, that is, in the first months and even weeks of pregnancy? The fact is that pregnant women with rheumatism require serious treatment, especially if it is a question of exacerbating it. If the treatment is serious enough, that is, the expectant mother should take strong drugs, then the process should be suspended. That is, in this case, it will be about the termination of pregnancy. There is nothing comforting in this, of course, not, as most of the pregnant women fall into depression and understand that they do not promise birth in the near future. However, such an approach to solving the problem is most appropriate, since rheumatism has the ability to negatively affect the development and formation of the baby’s future. To avoid any consequences, doctors are advised to terminate the pregnancy, undergo a full course of treatment and only then think about re-conception of the child. Exacerbation of the rheumatic process during pregnancy, and even more so if a woman becomes pregnant with an active rheumatic process, is fraught with the possibility of a number of complications of pregnancy. Thus, according to the materials of the authors [12], with an active rheumatic process, deviations from the normal course of pregnancy are observed one and a half times more often than with the inactive and pathological births - more than twofold.

Our observations confirm these data: premature termination of pregnancy, late toxicosis, threatening fetal asphyxia, premature discharge of amniotic fluid was more frequent. Of particular note is the late toxicosis, which in patients with rheumatism often occurs atypically, at a “normal” level of arterial pressure against the background of impaired blood circulation, caused by activation of the rheumatic process. If you recognize the allergic nature of late toxicosis, you can understand why it often occurs with rheumatism. In the case if rheumatism in pregnant women is mild, that is, there is no exacerbation, and the issue of termination of pregnancy is closed. However, the future mother in any case is under the supervision of her attending physician before the birth begins. This is necessary to ensure the safety of both the pregnant woman herself and her future baby. She is recommended to undergo at least two procedures in the hospital mode for the entire period of pregnancy.

Complications

What is the risk of rheumatism in pregnancy?

In the early stages of aggravation of rheumatism can cause miscarriage or defects in the formation of the fetus. In the second and third trimester, exacerbation of rheumatism can lead to the following complications and consequences [13]: damage to the blood vessels of the placenta causes hypoxia, hypotrophy and intrauterine fetal death;.

a) Edema and pulmonary infarction; Thrombophlebitis;

b) Rheumatic carditis of the future mother becomes the cause of fetal hypoxia, which entails various violations of its intrauterine development

c) Severe fetal malformations;

d) Premature separation of amniotic fluid;

e) Threat of premature termination of pregnancy; late toxicosis (gestosis);

f) Threat of fetal asphyxia;

g) Decomposition, threatening the life of a pregnant woman.

Due to active rheumatic endocarditic, in some cases sudden death may occur during childbirth or soon after (Table 1).

Table 1: Possible complications of rheumatism during pregnancy.

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Treatment

What to do in case of an exacerbation of rheumatism and how to cure it during pregnancy?

A. Treatment of pregnant women will depend on the following factors:

a) The degree of the disease;

b) Clinical form of rheumatism;

c) Individual characteristics;

d) Condition of the heart muscle, valvular heart apparatus

e) Results of the survey;

f) Presence of other diseases;

g) The course of the pregnancy process.

To treat rheumatism during pregnancy is necessary, as dangerous complications threatening the life of the future mother and her child can develop.

B. There are several important rules in treatment [14]

a) At detection of foci of infection or expressed activity of pathological processes (2nd or 3rd degree of rheumatism) antibacterial therapy is shown, including the use of drugs from the penicillin group and its synthetic derivatives.

b) In the first 10 weeks of gestation, the use of aspirin is contraindicated because of teratogenic effects. Do not take it before birth, because it has hypo coagulant properties and increases the risk of bleeding.

c) In severe toxicosis, analgin cannot be used because it can cause difficulties in removing the fluid from the body. NSAIDs are also contraindicated, and corticosteroids are resolved only after the end of the first trimester, when antirheumatic therapy does not help.

Timely begun therapy in most cases saves the life of the mother and the future baby. In the therapy of any disease, the spirit mood is important. Often, pregnant women become depressed after learning about rheumatism and its consequences. This is extremely untrue. It is necessary to assess together with the doctor all possible outcomes of the pathology and make the right choice. When there is a real threat to the baby and his mother, it makes sense to interrupt the pregnancy in order to undergo a full course of treatment and start planning a re-conception. In the absence of a significant threat, you should follow all the doctor’s recommendations and adjust to the best. This will help the body to regain strength and coupled with competent therapy to stop the progression of the disease.

C. What can the patient do?: The occurrence of the above symptoms should be alerted, you should immediately contact a therapist or rheumatologist. It is better to carry out the treatment even before the onset of pregnancy, since medications negatively affect the intrauterine development of the baby. In case of rheumatism it is advisable to be treated at least twice during the pregnancy period in a hospital. It is necessary to comply with bed rest during the exacerbation stage, to fully eat and fulfill all the prescriptions of the doctor.

D. What does the doctor do?: After examination, the doctor prescribes antibiotics, drugs with hyposensitizing and antiinflammatory action, sedatives, vitamin remedies, etc. It is also important to monitor the condition of the baby. If future mothers are late, you should visit your gynecologist regularly and listen to the fetal heartbeat.

Prevention

A. Is it possible to prevent the onset of rheumatism or its aggravation during pregnancy?

a) the risk can be minimized if one adheres to the following principles: beware of acute infectious catarrhal diseases - avoid public places during epidemics;

b) timely treatment of tonsillitis, pharyngitis, otitis, sinusitis - foci of streptococcal infection;

c) conduct hygiene of the oral cavity - treat tooth decay, periodontal disease, gingivitis, candidiasis of the oral mucosa;

d) do not overcool and do not undergo excessive sun exposure; maintain immunity;

e) Ensure that the diet contains all the necessary vitamins and microelements, the need for which is increased during pregnancy.

B. The likelihood of developing rheumatism or exacerbations during childbearing can be minimized by performing the following preventive measures [15]

a) it is necessary to beware of catarrhal diseases: avoid crowded public places during epidemics, take a complex of vitamins and minerals for pregnant women;

b) timely treatment of foci of streptococcal infection - pharyngitis, tonsillitis, sinusitis and otitis;

c) maintain oral hygiene: brush your teeth daily and treat dental diseases - dental caries, periodontal disease, candidiasis and gingivitis;

d) Do not overcool and avoid long exposure to direct sunlight.

It is necessary to eat fully, walk more, avoid overstrain of muscles, agitation and stress. It is useful to do morning exercises and go swimming. Rheumatism in most pregnant women often occurs before the onset of conception. The period of bearing of the baby aggravates its course, causing a vivid clinic of the disease. This refers to the first months when the body adapts to a new status, and the immune system weakens [16]. As a result, control of the disease is lost, and its symptoms are aggravated, which is a significant threat to the baby and his mother. To reduce the likelihood of all risks to a minimum, it is strongly recommended that you plan your pregnancy and take timely therapy for rheumatism. In this case, you can successfully take a future child and become a mother.

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Monday, 23 May 2022

Lupine Publishers | Why Should We Learn to Swim?

 Lupine Publishers | Journal of Psychology and Behavioral Sciences


Opinion

There is an anecdote in which an intellectual was being transported in a small boat by a person of scarce academic resources, when when trying to mock this poor man he asks “young… do you know? Of mathematics? And the poor boatman answers NO, and the unfriendly scholar tells him “because he thinks you’ve lost 30% of your life, later he asks him if he knew about philosophy and when he answered with a second refusal, the scholar in question tells him that he had he lost another 30% of his life, and he maintained it until suddenly the boatman, smiling, asked him, “Sir, do you? Can you swim? The intellectual in question responds, “naturally not” and the boatman ends up telling him “well, pretend that you lost 100% of your life because the ship sinks”. Every time I see a patient with tension headaches or spinal problems or even insomnia, an important point of recommendation is intense exercise, which is often not walking or doing the job, it is an appropriate athletic behavior with plan and an added diet, which if done to the letter would greatly reduce the problems of spine, metabolism, overweight and many more; I always put swimming ahead of other sports that add to the rehabilitation due to a series of advantages that other sports activities do not have, such as:

a) Exercise in deadlifts and do not injure yourself more by contact and spinal column or knees and even hips.

b) Improve your breathing, not least in patients with sleep problems or anxiety disorders.

c) It improves the paravertebral muscles, which are the main supporting muscles of the spine, balances them and allows the spine to regenerate; Here It Is Important to Point Out That They Do Not Serve The Chiropractic, It Is An Aberration And They Are Not Doctors.

d) It allows you to better socialize and acquire better sports goals.

e) It is excellent for the heart, lungs and digestive disorders.

f) We can mention many advantages of swimming and it would be a very long list, but it goes without saying that the people who really start learning to swim and do it not only improve their health, but also manage to overcome a challenge that was saved in the chest of the defeats.

g) One more point: the only ones I’ve heard who do not recommend swimming are often physiotherapists, and sometimes I think it’s because if people swim they would be out of work.

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Saturday, 21 May 2022

Lupine Publishers | 3D Printing of Pharmaceutical Drug Delivery Systems

 Lupine Publishers | Journal of Organic and Inorganic Chemical Sciences


Abstract

Three-dimensional printing (3DP) enables the development of diverse geometries through computer aided design using different techniques and materials for desired applications such as pharmaceutical drug delivery medicine. The FDA approval (2015) of printed-medicine opens up an unprecedented opportunity for the discovery of new compounds and technologies for the pharmaceutical industry development. This report shows some advantages, limitations, challenges and perspectives in concerning to 3DP of pharmaceutical grade formulations and polymers used for drug delivery systems.

Introduction

Drug delivery refers to approaches, systems, technologies and formulations for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect. The concept of drug delivery has greatly evolved over the years from immediate-release oral dosage forms to targeted-release drug delivery systems. Indeed, the necessity of controlling the drug release profile to modulate the absorption, the distribution, the metabolization and the elimination of the drug rapidly appeared as a key factor for improving product efficacy and safety as well as to increase the compliance of the patients [1]. In the drug delivery area, versatile therapeutic systems intended to yield customized combinations of drugs, drug doses and release kinetics have drawn increasing attention, especially because of the advantages that personalized pharmaceutical treatments would offer [2].

Three dimensional printing (3DP) technology is a novel technique for rapid prototyping, which constructs solid objects by deposition of several layers in sequence. The introduction and application of 3D printing have promoted enormous innovations in many diverse fields, including aerospace industry, architecture, tissue engineer, biomedical research and pharmacy. It seems that 3D printing technology will lead a new epoch of the next industrial revolution based on its versatility and diversity. Along with development and progress in science and technology, the 3D printing technology gets mature enough so that anyone can apply it with open-source software at a relative lower material cost [3]. The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and it's potential yet to be fully explored [4].

3DP is gaining increasing attention in pharmaceutical formulation development as an effective strategy to overcome some challenges of conventional pharmaceutical unit operations. For instance, the conventional manufacturing unit operation involving milling, mixing, granulation and compression can result in disparate qualities of the final products with respect to drug loading, drug release, drug stability and pharmaceutical dosage form stability [5,6]. 3D printing technology has enabled unprecedented flexibility in the design and manufacturing of complex objects, which can be utilized in personalized and programmable medicine [7]. In this report are shown some advantages, limitations, challenges and perspectives of 3D printing in the elaboration of drug delivery systems.

Advantages and Limitations

Various techniques for 3D printing, such as fused deposition modeling (FDM), binder deposition, inkjet printing, material jetting, powder bed fusion, photopolymerization, pen-based 3D printing and molding, have been reported in the literature [8,9]. Fused Deposition Modeling (FDM) 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds [10]. Such a technique holds huge potential for the manufacturing of pharmaceutical products and is currently under extensive investigation. Challenges in this field are mainly related to the paucity of adequate filaments composed of pharmaceutical grade materials, which are needed for feeding the FDM equipment [11] (Figure 1).

Figure 1: Schematic view of the different 3DP techniques used to fabricate drug delivery systems.

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Source [12] From the many types of 3DP available, stereolithographic (SLA) printing offers the unique advantage of being able to fabricate objects by cross-linking resins to form networked polymer matrices. Because water can be entrapped in these matrices, it is possible in principle to fabricate pre-wetted, drug-loaded hydrogels and devices [13].

Table 1: Current 3DP technologies and pharmaceutical formulations for drug delivery.

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More information in concerning to these technologies and pharmacology is present in the studies of Jassim-Jaboori & Oyewumi (14), Konta et al. [15], and Mauvi et al. [16].

Challenges and Perspectives

The technological advancements in the pharmaceutical field are constantly improving and provide various possibilities for meeting the needs of personalized drug therapy. The three-dimensional (3D) printing technology has endless potential in the fabrication of patient-specific drug delivery devices (DDD) and dosage forms as the technological development is progressing. Moreover, the rapidly evolving research on 3D printed DDD has enabled.com to determine several challenges related to the manufacturing and marketing of personalized drug delivery systems. The 3D printing has enabled the fabrication of prototypes of DDD with varying complexity and shows that customization of drug products is possible. There is potential to improve patient-specific drug therapies of the future using printing technologies. The technological advancements, new scientific concepts, interdisciplinary work and defined regulatory guidelines will continue to support and strengthen the prospects of 3D printing as an option in the manufacture of medical products [17]. Three-dimensional printing (3DP) is a unique prototyping technology that has advanced over the past 35 years and has the great potential to revolutionize the field of drug delivery with its inherent advantages of customizability and the ability to fabricate complex solid dosage forms with high accuracy and precision. 3DP can fabricate solid dosage forms with variable densities and diffusivities, complex internal geometries, multiple drugs and excipients. 3DP can successfully address the issues relating to the drug delivery of poorly water-soluble drugs, peptides, potent drugs and the release of multi-drugs, etc. However, there are some problems that restrict the applications of 3DP in commercial market, such as the selections of suitable binders, excipients and the pharmaco-technical properties of final products. Further advancement in process performance is required to overcome these issues where 3DP technology can be successfully combined with novel drug delivery system (NDDS) [18].

3D printing encompasses a range of differing techniques, each involving advantages and open issues. Particularly, solidification of powder, extrusion, and stereo lithography have been applied to the manufacturing of drug products. The main challenge to their exploitation for personalized pharmacologic therapy is likely to be related to the regulatory issues involved and to implementation of production models that may allow to efficiently turn the therapeutic needs of individual patients into small batches of appropriate drug products meeting preset quality requirements [19].

Three-dimensional printing has become a useful and potential tool for the pharmaceutical sector, leading to personalized medicine focused on the patients' needs. It offers numerous advantages, such as increasing the cost efficiency and the manufacturing speed, since a rapid prototyping (RP) can be done in a matter of minutes. However, there is still a significant barrier to ensure that 3D printed medicines have the same efficacy, safety, and stability as the pharmaceuticals conventionally manufactured by the Pharmaceutical Industry. Regarding the establishment of guidelines, laws, quality systems and safety of use and consumption of 3D printed medicines, it is a great challenge for the regulatory authorities entailing great obstacles, given the traditional requirements by the pharmaceutical sector [13].

The use of various types of printing technologies offer potential solutions for personalized medicine and tailored dosage forms to meet the needs of individual treatments of the future. Many types of scenario for printed dosage form exist and the concepts include, on the simplest level, accurately deposited doses of drug substances. In addition, computer design allows endless opportunities to create suitable geometries with tailored functionality and different levels of complexity to control the release properties of one or multiple drug substances. It will take some time to convert these technological developments in printing to better treatments for patients, because challenges exist. However, printing technologies are developing fast and have the potential to allow the use of versatile materials to manufacture sophisticated drug-delivery systems and bio functional constructs for personalized treatments [20].

3D printing technology can handle complex internal structure such as internal walls, hollow channels, porosity, multiple material regions and multiple drug distributions. This is a feature traditional pharmaceutical manufacturing processes do not share, which ensures feasibility of realizing rapid release, sustained release, controlled release, multiple drug delivery system and personalized medicine based on structure design [21]. Indeed, drug delivery from 3-dimensional (3D) structures is a rapidly growing area of research. It is essential to achieve structures wherein drug stability is ensured, the drug loading capacity is appropriate and the desired controlled release profile can be attained. Attention must also be paid to the development of appropriate fabrication machinery that allows 3D drug delivery systems (DDS) to be produced in a simple, reliable and reproducible manner [22].

Findings

It is evidenced that through its versatility, speed of production and precision, the use of three-dimensional printing for the elaboration and distribution of controlled drugs plays a key role in the current pharmaceutical industry, considering that drugs can be designed according to the patient's need. The fused deposition modeling (FDM) technique and hot melt extrusion (HME) of filaments for 3DP still excels in relation to the other printing techniques, such as binder deposition, inkjet printing, material jetting, powder bed fusion, photopolymerization, pen-based 3D, printing and molding have been gaining more and more space. The use of3DP in pharmaceutical formulation development is an effective strategy to overcome challenges of conventional pharmaceutical unit operations, since the conventional manufacturing operation can result in disparate qualities of the final products with respect to drug loading, drug release, drug stability and pharmaceutical dosage form stability. 3DP offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture.

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Friday, 20 May 2022

Lupine Publishers | Circadian Disruption, Sleep Loss, and Low-Grade Inflammation

 Lupine Publishers | Journal of Research and Reviews on Health Care


Abbreviations: SCN: suprachiasmatic nucleus; CRP: C-reactive protein; SASP: senescence-associated secretory phenotype; DDR : DNA damage response; AD: Alzheimer's disease

Editorial

Circadian rhythmicity is a fundamental property of the majority of organisms, including bacteria, unicellular eukaryotes, fungi, plants and animals. It is generated by cellular oscillators and may have evolved to cope with adverse phases in the cycle of a day that bear the risk of damage by radiation and reactive metabolites, such as free radicals. In a complex organism like the human, the circadian system is composed of numerous, internally communicating, oscillators including a coordinating master clock, the suprachiasmatic nucleus (SCN) [1]. It provides a program for structuring countless physiological functions in a sophisticated temporal pattern that optimizes the alignment of processes and also the anticipation of regularly expectable changes, such as an approaching time of arousal and locomotor activity, of food intake and even social interactions.

Sleep is one of the functions that are controlled by the circadian system, in addition to the homeostatic drive to sleep and immunological influences. The benefits of sleep concern recovery, but additionally other processes such as memory consolidation take place in specific sleep phases [2]. Shift work and on-call duties during night are necessities in our modern world. Many scientists also know what it means to conduct an experiment that lasts for, e.g., 35 hours, without any chance to sleep in between. The consequence to the body is, however, not just subsequent fatigue, but also a disturbance of the finely tuned physiological rhythms. The resilience of individuals to such disturbances is highly variable. Not rarely, subjects also wake throughout the night for private reasons.

Although this shall not be generally criticized, one should know how many changes are induced by sleep loss, with the potential of pathophysiological alterations that should not accumulate to avoid disorders and diseases. Sleep deprivation is frequently associated with disruptions or inappropriate phase shifts of the circadian system, also known under the term of chronodisruption. In humans, one typical reason of the dual changes results from light exposure at night. This can induce phase shifts of circadian rhythms, but also involves another complication, as light at night causes rapid decreases in the levels of the pineal hormone, melatonin, known as the so-called photic shutoff, in addition to the circadian changes [3]. These reductions in melatonin are in multiple ways undesired. First, melatonin is a highly pleiotropic regulator molecule that orchestrates countless functions in all organs of the body [4].

Second, melatonin participates in the entrainment of the master clock and various peripheral oscillators [5]. Third, melatonin is a neuro protective, antiapoptotic and antioxidant agent, with additional functions in immune modulation [4,6]. Low-grade inflammation is of particular relevance in immunosenescence, in aging acceleration and in neurodegenerative disorders, but contributes to many other pathologies. Immunosenescence can lead, in addition to other traits, to the development of a proinflammatory phenotype characterized by elevated proinflammatory cytokines and C-reactive protein (CRP), especially in subjects that have acquired an immune risk profile [7]. Moreover, the age-dependent increase in DNA-damaged cells represents a further source of proinflammatory factors via the senescence-associated secretory phenotype (SASP).

SASP, being part of the DNA damage response (DDR), allows non-immune cells to release proinflammatory cytokines and chemokines which spread inflammatory responses [8,9]. In the central nervous system, astrocytes with SASP can become neurotoxic [10]. Another brain-related aspect concerns neuronal overexcitation, which results via NO release in microglia activation and astrogliosis, followed in vicious cycles by mutual stimulations between the three cell types [7,11]. Moreover, the balance between formation and clearance of amyloid-β (Aβ) peptides and oligomers, which are both prooxidant and proinflammatory can be disturbed. This is not exclusively a matter of Alzheimer's disease (AD), but rather plays - at lower level - a role in normal aging, too. Finally, insulin resistance in the brain has been identified as an early sign and, presumably, stimulus of neuro inflammation in AD [7,12-14], a potentially important link to the inflammatory aspect of type 2 diabetes and metabolic syndrome.

Sleep deprivation, often in conjunction with circadian disruption, can favor in multiple ways processes that are known to be related to low-grade inflammation. Apart from various reports that demonstrated oxidative stress as a result of primary insomnia or experimental sleep deprivation, which shall not be discussed here in detail, direct evidence for increased inflammation has been obtained in clinical and preclinical studies. In humans, sleep deprivation or disturbance elevated TNF-α [15,16] and IL-6 in monocytes [16,17], CRP [17,18], TNF-α [18,19] and IL-6 [20,21] in the plasma. In whole blood preparations, mRNA levels of TNF-α and of its soluble receptor sTNFR1 were reported to be enhanced [22]. Moreover, sleep deprivation was shown to induce DDR and SASP in elderly subjects [23]. Of course, studies in humans have limitations concerning the availability of tissue material. Moreover, blood analyses revealed a certain degree of divergence with regard to the increases in specific inflammatory markers [24]. However, the basis for judgments is considerably broader in laboratory rodents.

In the murine brain, sleep deprivation enhanced the proinflammatory cytokine TNF-α, and the NO metabolite nitrite, in addition to indicators of oxidative stress [25]. Up regulation of TNF-α, IL- 1β and IL-6 was observed in numerous rat organs, such as adipose tissue, colonic mucosa, liver and spleen, sometimes also rises in IL-17 and IFNϒ (details not cited). More importantly, respective changes were observed in brain regions. Increases of IL-6 and IL-8 were demonstrated in the hippocampus [26-28], and of IL-6 in the cortex [28,29]. Moreover, anti-inflammatory cytokines, IL-4, and IL- 10, were found to be decreased in the hippocampus [26,27]. While data on the important proinflammatory cytokine IL-1β were rather divergent in humans, the situation is rather unambiguous in rats and mice. It was enhanced in the hippocampus [26-31], cortex [2932], basal forebrain [30], and hypothalamus [31]

Finally, findings of utmost interest were detected upon sleep deprivation [33] or slow wave sleep disruption [34] in the CSF of healthy humans, in which the levels of Aβ1-42 or Aβ1-40, respectively, were increased, perhaps a sign of reduced Aβ clearance. With regard to the proinflammatory properties of β peptides and oligomers, these results provide another hint for the role of sleep disturbances in inflammation and, in older subjects, in brain inflammaging. Collectively, results summarized in this editorial emphasize the importance of inflammatory responses to sleep deprivation and disturbances. These may not be generally avoidable during professional life, but they should not be enhanced by lifestyle and can be prevented later in life, when these effects become more relevant and increasingly contribute to inflammaging.

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Thursday, 19 May 2022

Lupine Publishers | An Unusual Case of Pre-Auricular Myiasis

 Lupine Publishers | Journal of Surgery


Abstract

Background: Myiasis-the feeding of fly larvae on living mammals has various clinical presentations depending on involved tissues or organs. The most recognised causative organism Dermatobia hominis. It involves various sites, rarity in this case report is the site of involvement and in turn occurrence of an underlying malignancy.

Case report: 68 year old lady, presented with an ulcer over the right side of the pre-auricular region for 1 year. On examination, it was infested with maggots larvae, which later on had a underlying squamous cell carcinoma with basal cell carcinoma. Patient underwent treatment for the same. Details of the case and the management is been presented.

Conclusion: Myiasis transmitted by Human Botfly, infests all cavities mainly ENT sites, in debilitated individuals. But its occurrence in a open space of the body, and its association is a rarity and has been reported in this case. Author concludes, that all myiasis should be managed meticulously.

Keywords: Myiasis; Pre-auricular; Pit; Squamous Cell Carcinoma

Introduction

Myiasis the feeding of fly larvae on living mammals has various clinical presentations depending on involved tissues or organs [1]. Myiasis is a common travel associated skin disorder as a consequence of short visits to developing countries [2,3]. The commonest clinical manifestations of myiasis infestation include inflammatory and allergic reactions. Ear, eye and respiratory tract infestations are also frequently encountered [2-4], and the human botfly. The most recognised causative organism Dermatobia hominis [5]. In Tropical countries like India, patient debilitation is the main causative etiology for the infection. We present an unusual case of pre-auricular myaisis of a debilitated lady who had no inciting lesion to result in a nidus to cause infection by myiasis larvae.

Case Report

68 year old lady, presented to the ER with complaints of fatiguability, prostration for a period of 1 month and a wound over the left side of the face for 1 year, wound appeared spontaneously, it progressed to an ulcer and was increasing to the current size. There was no h/o trauma, fever. No significant family, past history or travel history. On examination, patient was conscious oriented,vitals were stable. Local examination revealed on the right temporal and cheek region, an ulcer of 7x3cm over the preauricular region, solitary, margin was spreading which was inflamed and edematous with beaded edges, sero-sanguinous discharge, with active maggotfly infestation surrounding area is inflamed. On palpation, the ulcer was nontender, indurated edges, ulcer was resting on the zygomatico-temporal bone and depth been around 1cm, maggots larvae was present, ulcer was bleeding on touch (Figures 1 & 2).

Figure 1: lateral view showing the ulcer with maggot infestation and beaded edges, closely observe the surrounding skin is edematous and inflamed.

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Figure 2: Procedure of removing the maggots.

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After the removal of all the maggots (Figures 3 & 4) with the help of ether, edge wedge biopsy was taken to rule out malignancy and local sterile dressing was done. Patient was started on antibiotics and subjected to CT Paranasal sinus, to rule out infiltration. Biopsy report revealed to be Squamous cell carcinoma with components of Basal cell carcinoma and CT showed no infiltration in the underlying structures. Patient underwent wide local excision and frozen section revealed clear margins. Post-operative recovery was good. Patient was discharged on POD#7 and followed up regularly, 6 month follow-up revealed no signs of recurrence.

Figure 3: lateral view of the patient showing the ulcer - Post procedural.

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Figure 4: Maggot larvae removed from the ulcer site.

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Discussion

Myiasis is defined as the invasion of mammalian tissues, organs, and cavities by the larvae of dipterous insects (two winged flies) [1]. Cutaneous myiasis is divided further into four clinically recognized manifestations, including open wound myiasis with soft-bodied maggots, subcutaneous tunnels or “creeping eruption,” subcutaneous myiasis with migratory swellings, and furuncular myiasis. Myiasis may be obligatory where the host is essential for completion of the botfly cycle, or facultative, where the larval form of the botfly persists after transfer from a more conventional habitat [2,3]. D. hominis is the most common cause of furuncular myiasis in Central and South America. This disease should be considered for any patient who presents with a classical cutaneous lesion and a history of recent travel to the endemic regions of the Western hemisphere, especially those areas between central Mexico and Argentina [1,4,5]. D. hominis, which is found only in Central and South America, is also known as the human botfly, the tropical botfly, the warble fly, the macaw worm, and torsa10. It belongs to the family Oestridae and is found most commonly in hot and humid forests [2,3,6]. Although this fly has a rather unique life cycle and can come into contact with humans during 157 several of its stages, it is the larval form that commonly parasitizes both birds and mammals [5,7]. Mammalian hosts include not only humans, but also many wild and domestic animals. The patient in this case report stated that many of the dogs seen at his work sites and in the local villages demonstrated an abundance of subcutaneous nodules and localized swellings. Cutaneous myiasis typically presents with a characteristic clinical picture. Prominent diagnostic features include the following [8]:

History of recent travel in Central or South America.

One or more persistent, dome-shaped furuncles (typically located on exposed skin surfaces) which contain a central sinus or pore that drains serosanguinous or seropurulent fluid;

Localized symptoms including pruritis, fleeting sharp pains, and uncomfortable movement sensations within the lesion;

A small, white, retractile structure that appears in the aperture of the furuncle after irritation or occlusion;

A lack of generalized symptoms, signs, or abnormal laboratory findings.

The most common method to deal with suspected cutaneous myiasis is to occlude the central punctum thereby asphyxiating the larvae [9].

Spontaneous expulsion of the larvae has also been reported to occur with a number of traditional methods including the application of bacon fat, wax, glue, chewing gum, and nail polish to the affected tissue [7]. Once a larvae has been asphyxiated by occlusion of the punctum if not spontaneously expelled, it must be surgically removed. Patients in endemic areas resort to traditional methods as it is cheap and readily carried out by a lay man. In our case significant manual pressure was required for extrusion of the myiasis larvae [10].

Acknowledgement

Authors would like to thank Dr Manan shah, resident of the department of Pathology, Sri Devaraj Urs Medical College.

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Wednesday, 18 May 2022

Lupine Publishers| Heart Failure: Prevalence, Symptoms, Treatments

 Lupine Publishers| Journal of Biomedical Engineering and Biosciences


Mini Review

Heart Failure Prevalence and Cost

Heart failure (HF) is a growing epidemic that affects about six million people in the United States and more than 23 million worldwide [1,2] .The prevalence of HF is greatest among people aged 65 years or older and has been increasing with the growth of this demographic population [3-6]. Around 50% and 90% of patients with HF die within 5 and 10 years of diagnosis, respectively [1]. Total medical costs attributable to diagnosis, treatment, and prevention of HF in the developed countries are approximately 1% - 2% of the total health care expenditure [7-9]. In the United States, total costs for HF care are more than $39 billion annually [2].

Heart Failure Symptoms and Etiology

HF patients suffer from structural or functional heart disease that impairs the ability of the ventricle to fill with or eject blood [10,11]. The symptoms of HF are shortness of breath/orthopnea/ dyspnea, fatigue, weakness, pulmonary congestion, edema, nocturnal cough, and evidence of a decrease in myocardial performance at rest [12,13]. Some of the etiologies that may lead to HF, are myocardial ischemia, hypertension, cardiomyopathies, valvular heart disease, obesity, pulmonary hypertension, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, excessive neuro-humoral stimulation, accelerated apoptosis and genetic mutations congenital heart disease [8,11,14].

Heart Failure Types

Classification of HF can be based on the left ventricular Ejection Fraction (EF): HF with Reduced EF (HFrEF) and HF with Preserved EF (HFpEF). In HFrEF patients, the heart is not able to pump enough blood into the circulation due to ventricular systolic dysfunction. The EF in these patients is less than or equal to 40% [15]. HFpEF is primarily caused by LV diastolic dysfunction (impaired relaxation during LV filling) due to the stiffening of the LV wall with EF>50% [8,16,17]. In addition to this classification schemes, HF can be classified based on ACCF/AHA stages of HF (Figure 1) [10].

Figure 1: ACCF/AHA Stages of HF.

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Heart Failure Treatments

The goal of HF treatment is to reduce the morbidity and mortality in these patients. For stage A and B, changing lifestyle (e.g. regular exercise and restriction of sodium intake), and using antihypertensive agent are recommended [8,10,15]. For stage B, C, and D, pharmacological therapy including diuretic- based antihypertensive therapy, spironolactone, ACE inhibitors, angiotensin receptor blockers, Beta blockers, aldosterone antagonists, hydralazine and isosorbide dinitrates, digoxin, and anticoagulation are recommended. Advanced HF stage might need surgical treatment methods including coronary revascularization, mitral valve repair, ventricular reconstruction, and heart transplantation [8,18].

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Tuesday, 17 May 2022

Lupine Publishers| A Comprehensive Study on EMG Feature Extraction and Classifiers

 Lupine Publishers| Journal of Biomedical Engineering and Biosciences


Abstract

In the past few years the utilization of biological signals as a method of interface with a robotic device has become increasingly more prominent. With the many of these systems being based on EEG and EMG.EMG based control has five main parts data acquisition, signal conditioning, feature extraction, classification, and control. This paper seeks to briefly cover the aspects of data acquisition and signal conditioning. After which, various methods of feature extraction, and classification are discussed.

Introduction

The use of EMG in Brain-Computer Interaction (BCI) as part of a Human-Computer Interface (HCI) is a method of control that allows for a more natural use of one's own existing muscles. Electromyography (EMG) is measured from the muscles as they receive the signal of activation from the brain. This paper presents an analysis of various methods of feature extraction and classification of the EMG signals. As EMG rapidly fluctuates with time and can contain some corruption in the data, due to noise. This means it is critical to choose the methods of feature extraction and classification to improve accuracy and to decrease the computational demand.

The methodology of EMG based control is mainly concerned with data acquisition, signal conditioning, feature extraction, classification, and then control (Figure 1) [1]. This paper presents in the next section a brief description of the method of data acquisition. Then following this will also be a brief description of signal conditioning. Next, the methods of feature extraction are presented. Each method is described with an equation and is then experimental results are presented for easy comparison. All the simulations were done in MATLAB with scripts all using the same sample size, and segment length. The following section then goes on to present different methods of classification in their formal nature. This paper then concludes with a discussion of the pros and cons of the different methods of feature extraction techniques and some specific application of those techniques. As well as a discussion of the different classifiers and some possible specific application of those classifiers.

Figure 1: Block diagram of the process of EMG processing for control.

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Data Acquisition

EMG data can be gathered in two different ways: invasive, and noninvasive [2]. The invasive method is performed by inserting a needle type electrode through the skin into the muscle desired. This technique is mostly used for diagnostic purposes. The invasive method provides high-resolution data, and accurate localized descriptions of muscle activity. This method, however, does cause some discomfort to the patient, and is not suited for repeated daily use. The noninvasive method uses surface mounted electrodes commonly positioned over specific muscles. This decreases the patient s discomfort and allows for the ability to be a fully portable device. The accuracy and resolution of the device depends on the sampling rate and the segment length [3]. This method has commonly used adhesives and conductive gels for the mounting of the electrodes. However, in recent years the improvement of surface mounted EMG sensors has made it possible to mount sensors without adhesive or gel.

Signal Conditioning

Data segmentation is done using two main methods: overlapping segmentation, and disjoint segmentation [4]. Disjoint segmentation uses separate segments with predefined length for feature extraction (Figure 2). While in overlapped segmentation, the new segment slides over the current segment, where the interval of time between two consecutive segments is less than the segment length and more than the processing time (Figure 3). This shows that disjoint segmentation of data is associated with segment length. While overlapped segmentation of data is associated with segment length and increment [5]. In experiments done by Oskoei, and Hu [4], disjoint and overlapped segmentation was compared to display their classification performance. The length of 50ms was used in disjoint segments whereas overlapped systems used segments having a length of 200ms with an increment of 50ms. The results showed that the defined disjoint segmentation 200ms provided high performance in EMG classification and an adequate response time allowing for real-time use. With the defined overlapped segmentation shortening the response time without noticeably degrading the accuracy of data. This indicates that to maintain an efficient use of computational resources while not compromising the accuracy of data, it is imperative to implement an appropriately timed method of overlapped segmentation.

Figure 2: Graphical representation of disjoint segmentation [4].

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Figure 3: Graphical representation of overlapping segmentation [4].

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Feature Extraction

Feature extraction is the transformation of the raw signal data into a relevant data structure by removing noise, and highlighting the important data. There are three main categories of features important for the operation of an EMG based control system. Those being the time domain, frequency domain, and the time-frequency domain [1,5]. However, due to the intense computation needs of transformations required by the features in the time-frequency domain, this method is not used for therapeutic devices.

Time Domain

Features in the time domain are more commonly used for EMG pattern recognition. This is because they are easy, and quick to calculate as they do not require any transformation. Time domain features are computed based upon the input signals amplitude. The resultant values give a measure of the waveform amplitude, frequency, and duration with some limitations [6]. The methods of integrated EMG, mean absolute value, mean absolute value slope, Simple Square integral, variance of EMG, root mean square, and waveform length will be discussed in more detail in the following sub-sections. Each consecutive section will reuse the same notation for better understanding. For each method, a simple test was done with MATLAB scripts for sake of comparison.

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