Electrokinetics in antimicrobial resistance analysis: A review.

Infections caused by antimicrobial resistance are a serious problem in the world. Currently, commercial devices for antimicrobial susceptibility testing and resistant bacteria identification are time-consuming. There is an urgent need to develop fast and accurate methods, especially in the process of sample pretreatment. Electrokinetic (EK) is a family of electric-field-based kinetic phenomena of fluid or embedded objects, and EK applications have been found in various fields. In this paper, EK bacteria manipulation, including enrichment and separation, is reviewed. Focus is given to the rapid electric-based minimum inhibitory concentration measurement. The future directions and major challenges in this field are also outlined.

Community-based follow-up of participants of a mother-friendly clinical trial: A patient-centric methodology for pregnant women.

Repeated visits to clinical trial sites inflict hardships on study participants, especially pregnant women. A newer trend is community-based follow-up for measurements, dosage, or monitoring, through technology or physical visits. We conducted a methodological experiment of performing "community-based physical follow-up" of participants of a trial, receiving facility-based diagnosis and pathogen-specific antibiotics for asymptomatic bacteriuria, guided by an optical-sensor-based rapid point-of-care test. We were able to retain 95.8% participants in the study. Here we describe challenges faced and socio-economic and gender issues encountered in this approach in a low-resource Indian scenario, to guide researchers world-wide for designing mother-friendly clinical trials.

Study of APOE Gene and D2S439 Marker in Patients of Rheumatoid Arthritis and their Correlation with Severity of Disease: A Case Control Study.

AIM: To delineate the genetic differences in polymorphism of the APOE and D2S439 marker genes for patients with and without rheumatoid arthritis and to study the distribution frequency of the prevalent alleles of these genes in clinically defined sub groups of patients/controls of Indian origin, specifically and their correlation with severity of disease using DAS score. MATERIAL AND METHODS: This is a case control study where peripheral blood samples 160 cases and 150 controls were collected. RESULTS: We evaluated the association of the tetra nucleotide repeat microsatellite marker D2S439 lying at 231.27cM position on the q arm of chromosome-2. The alleles of this marker ranged in size from 163bp-203bp in PCR product length corresponding to 5-15 (CTAT)n tetra repeats. The allele frequencies for this marker in the North Indian population are different from the CEPH populations. The longer alleles, >199bp (=14 or 15 CTAT repeats) were not observed. The genotypes after bimodal distribution differ significantly among cases and controls (p=0.003). Statistically significant difference was seen between cases and controls for ≥(CTAT) 10 longer allele which was more prevalent in the adult RA cases than in controls. Severity of RA was defined by a DAS28 score of >6 on a scale of ten. No significant association was seen with the APOE polymorphism and disease severity. CONCLUSION: The long allele of D2S439 marker representing an expansion of the CTAT, tetranucleotide repeat doubles an individual's the risk for developing RA.

Role of µ-Opioid Receptor Polymorphism in Patients of Rheumatoid Arthritis and their Correlation with Severity of Disease.

INTRODUCTION: With 1 billion tobacco users worldwide, nicotine dependence has a major impact on global health. Advances in medication development for nicotine dependence require an improved understanding of the neurobiology of this complex, relapsing brain disorder. AIMS: To study association of µ Opioid Receptor polymorphism in patients of rheumatoid arthritis and its correlation with severity of disease and prevalent alleles of the OPRM1 genes. MATERIAL AND METHODS: This is a case control study wherein all available patients and volunteers were recruited. 142 controls subjects with no known history of disease and 85 study group cases were included. RESULTS: Comparison of genotype frequencies showed a statistically significant difference between the studied groups (p<0.004). A statistically significant difference was found when the allelic frequencies between the two groups were compared (p<0.0001), with the 17T allele having a-1.7518 fold higher risk of having RA (risk ratio (RR)=1.7518, 95%CI of RR=1.2988-2.3627, OR =3.2914; 95%CI =1.9608-5.5251). Significant difference was also found when the allelic frequencies between the two groups were compared (p<0.0001), with the 118G allele having a 1.5-fold higher risk of developing RA (RR)=1.5801, 95%CI =1.3091-1.9071, OR=3.1357; 95%CI 2.1083-4.6638). CONCLUSION: The study definitely needs to be extended to larger cohort of patients and control samples and to a larger set of candidate µ opioid receptors. Extending the studies to a larger cohort will also allow genetic analyses of clinically defined endophenotypes observed in the patients of this chronic metabolic disease with attributes of autoimmune disorder and multiple symptoms in patients.

Evaluating the effect of diallyl sulfide on regulation of inflammatory mRNA expression in 3T3L1 adipocytes and RAW 264.7 macrophages during ethanol treatment.

Diallyl sulfide (DAS) has been studied extensively for its alleged role as an anticancer and protective agent. Alcohol influences and effects on human health have been extensively studied. However, investigations toward developing and testing therapeutic agents that can reduce the tissue injury caused by ethanol are scarce. In this backdrop, this study was designed to explore the potential effect of DAS in reducing alcohol induced damage of 3T3L1 adipocytes and RAW 264.7 macrophages. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was performed to determine the DAS effect on cell viability. Reactive oxygen species (ROS) production was assessed by flow cytometer. Expression of inflammatory genes was studied by the qRT-PCR method. Our study results showed that DAS at concentrations less than 200 µM was not toxic to the cells and the viability of ethanol-exposed 3T3L1 adipocyte cells was found to be significantly increased when ethanol-exposed cells were treated with DAS. Further, treatment of ethanol-exposed 3T3L1 cells with 100 µM DAS for 24 h was found to reduce ethanol induced ROS production, expression of pro-inflammatory cytokines, and enhance anti-inflammatory cytokine production in the cells. Also, 100 µM DAS was found to increase the expression of M2 phenotype-specific genes in ethanol-exposed RAW 264.7 macrophage cells. Further, 100 µM DAS also improved the levels of lipid accumulation in 3T3L1 adipocytes that was down-regulated by ethanol exposure. Taken together, our study results imply that DAS may be effective in reducing ethanol induced injury of cells thereby suggesting its potential to be used in drug formulations.

SNP in KCNQ1 Gene is Associated with Susceptibility to Diabetic Nephropathy in Subjects with Type 2 Diabetes in India.

OBJECTIVE: Diabetic nephropathy (DN) remains the most common cause of end stage renal disease (ESRD) as the burden of diabetes increases worldwide. Only 25 to 40% of patients with type 2 diabetes mellitus (T2DM) develop diabetic nephropathy irrespective of glycemic control so there should be a specific genetic basis for the development of diabetic nephropathy. METHODS: We have collected venous blood samples from 50 cases (Diabetic nephropathy) and 20 controls (T2DM without nephropathy) diagnosed by spot urine albumin creatinine ratio (ACR). DNA was isolated from processed samples. PCR study and sequencing was done to detect polymorphism of rs2237897 in KCNQ1 gene. RESULTS: Statistically significant difference was found when the allelic frequencies between the two groups were compared (p=0.03), with the C allele having a 2.4 fold higher risk of having diabetic nephropathy (risk ratio, RR )= 1.16, 95%CI of RR = 1.01 to 1.3, Odds Ratio (OR) =2.4; 95% CI of OR =1.06 to 4.6). Chi-square analysis showed a significant difference in genotype frequency of rs2237897 (χ2 = 4.63, p=0.03) in Diabetic nephropathy subjects, compared with that of controls. CONCLUSIONS: This study suggested that, KCNQ1 being an established type 2 diabetes gene, genetic variation in this gene may contribute to susceptibility to diabetic nephropathy and the C allele is the risk allele for diabetic nephropathy, which is different from Japanese population where the T allele was the risk allele.

A Study of Genetic Markers in Patients of Rheumatoid Arthritis and their Co-Relation with Severity of the Disease.

INTRODUCTION: Dyslipidemia has been reported to attribute to early death due to increased atherosclerosis leading to CVDs in patients with RA. Recent reports have suggested a role of adipocytokines in mediating joint damage rheumatoid arthritis (RA). RA has long been associated with increased cardiovascular risk as atherosclerosis is more prevalent in patients of RA than in the general population. Specific alleles of APOE gene have been reported to be associated with risk for atherosclerosis and LEP gene alleles have been associated with increased BMI. We evaluated the association of polymorphisms in the APOE and the LEP gene, with risk for developing RA and severity of joint damage in patients with RA. MATERIAL & METHODS: Peripheral blood samples from age and ethnicity matched healthy controls and RA patients, recruited for the study, were collected and used for DNA isolation and allele typing for D7S1875 (LEP gene) and APOE using PCR-LP/RFLP based method reported in literature4,5 followed by data analysis using Medcalc. RESULTS AND CONCLUSIONS: Based on the findings of this study no correlation was seen between RA and LEP gene (D7S1875) allele/genotypes. It was seen that the APOE*4 allele was more prevalent in controls than in cases indicating that this allele is probably playing a significant protective role (p=0.0002, OR=0.3336, CI:0.1856-0.5997) as opposed to the other two Apo E alleles. The Apo E*3 allele was the most prevalent allele in both cases and controls which is similar to earlier reports from several different groups. No significant association was observed between the APOE genotype and the DAS28 score. Finally, it can be concluded that while the short allele of the D7S1875 (LEP gene) marker increases the risk for developing RA (OR=1.72, p=0.038) the APOE*4 allele seems to play a protective role in RA (OR=0.3336, p=0.0002).

Triphala and its constituents ameliorate visceral adiposity from a high-fat diet in mice with diet-induced obesity.

CONTEXT: In India, vaidyas (Ayurvedic physicians) traditionally administer triphala and its constituents as therapeutic agents for promoting digestion and satiety. OBJECTIVE: The research team performed the present study to investigate the effects of triphala and its constituents (T bellirica [bibhitaki], T chebula [haritaki], and E officinalis [amalaki]) on the dietary induction of obesity (diet-induced obesity [DIO]), and other symptoms of visceral obesity syndrome, in mice fed a high-fat diet (HFD). DESIGN: The research team obtained 42 fertile, male, Swiss albino mice, weighing 20 g each, and housed them individually in an approved small-animal facility, in a pathogen-free environment. The team generated DIO mice by feeding them a HFD. SETTING: The study took place at the Birla Institute of Technology and Science (BITS) in Pilani, India. INTERVENTION: The research team fed all mice, except those in a control group (ND), a HFD for 10 weeks beginning at 7 weeks of age, supplementing the HFDs with herbal treatments for 4 of the groups. The team divided the mice into six weight-matched groups of seven mice each: (1) normal diet (ND), (2) high-fat diet (HFD), (3) triphala (HFD+T), (4) amalaki (HFD+A), (5) haritaki (HFD+H), and (6) bibhitaki (HFD+B). OUTCOME MEASURES: The research team evaluated daily energy intake, fasting plasma glucose, serum lipid profile, and liver cytology. The team measured food and energy intake daily for 10 weeks and measured the body weight of each mouse every third day during the course of the experiment. The team drew blood samples at 2, 4, 8, and 10 weeks posttreatment and determined fasting plasma-glucose concentrations and fasting plasma concentrations of cholesterol, triglycerides (TG), LDL, HDL, and plasma alanine transaminase (ALT) using commercial kits. At the completion of the study, a pathologist examined the livers and diagnosed a fatty liver based on the presence of macrovesicular or microvesicular fat in the hepatocytes. RESULTS: The research team's results showed that mice fed a HFD for a 10-week period, supplemented with herbal preparation(s) of triphala or its constituents, resulted in significant reductions in body weight (P < .0001), energy intake, and percentage of body fat (P < .001), as compared with mice in the HFD group. Herbal treatment significantly improved the lipid profiles of the mice by lowering serum total cholesterol (Total-C), TG, and low-density lipoprotein cholesterol (LDL-C) and increasing levels of high-density lipoprotein cholesterol (HDL-C) as compared to the mice in the HFD group. The research team also found that herbal treatment attenuated glucose levels, oral glucose tolerance as measured by the oral glucose tolerance test (OGTT), and levels of ALT. In addition to treatment with its three individual components, treatment with a popular Ayurvedic formulation of triphala also reversed the pathological changes in liver tissue and decreased the relative weight of visceral adipose fat pads. CONCLUSIONS: The present findings suggest that triphala and its constituents can counter the effects of an environment (ie, high dietary intake of fats) and have the potential for use as antiobesity agents with desirable lipid-profile modulating properties.

Alterations in intestinal permeability and endotoxemia in severe acute pancreatitis.

BACKGROUND: Intestinal permeability increases early in the course of acute pancreatitis and is associated with sepsis and organ failure. AIM: To evaluate the intestinal permeability (IP) and anti-endotoxin antibodies immunoglobulin G and A (AEA IgG and A) in severe acute pancreatitis (SAP) as compared to healthy controls and determine their significance in relation to various complications of SAP. METHODS: IP was measured by urinary lactulose/mannitol (LM) excretion ratio and anti-endotoxin antibodies by Endocab ELISA kit at days one and seven of admission (D1 and D7). RESULTS: Thirty one patients of SAP [mean age (42.0 +/- 15.8) years, APACHE II scores (8.8 +/- 5.4) and CT severity index (6.4 +/- 2.0)] were included in this study. Infected pancreatic necrosis was detected in 13 (42%) patients of whom three died. Six died of persistent organ failure. Median values of LM ratio at D1 and D7 were similar to those in healthy controls. Patients experiencing complications [organ failure (4/9, 44%), infected pancreatic necrosis (5/10, 50%) and death (1/2, 50%)] manifested a substantial increase in their intestinal permeability at D7. Anti-endotoxin antibodies IgG were lower (p = 0.003) in patients than the controls at admission. AEA IgG were lower (p = 0.03) in non-survivors as compared to survivors at D7. CONCLUSION: Patients experiencing complications of severe acute pancreatitis showed an increase in intestinal permeability. Higher endotoxemia predicted poor outcome in severe acute pancreatitis.

Type-2 diabetes mellitus-associated cancer risk: In pursuit of understanding the possible link.

BACKGROUND AND AIM: The insulin resistance-mediated abnormal gluconeogenesis when exceeds a given threshold culminates in type 2 diabetes mellitus (T2DM). This induces severe cellular oxidative stress that may eventually facilitate typical neoplastic transformations. This narrative review aims to portray some of the plausible key mechanistic links bridging T2DM and specific cancers. METHODS: A thorough literature search was conducted in the PubMedCentral database to retrieve information from various reputed biomedical reports/articles published from the year 2000. The information regarding the key biochemical signaling pathways mediating the carcinogenic transformation, especially in T2DM patients, was extensively excavated to systematically compile and present a narrative review. RESULTS: T2DM-associated insulin resistance is known to negatively influence certain crucial genetic and metabolic components (such as insulin/IGFs, PI-3K/Akt, AMPK, and AGEs/RAGE) that may eventually lead to neoplastic transformation. In particular, the risk of developing cancers like pancreatic, colorectal, breast, liver, endometrial, and bladder seems to be more significant in T2DM patients. CONCLUSION: Despite the fact that several studies have suggested a possible correlation between T2DM and cancer mortality, a more detailed research at both pre-clinical and clinical levels is still required so as to fully understand the intricate relationship and make a precise conclusion.

Role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis: a double-blind randomized controlled trial.

GOALS: To study the role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis (AP). BACKGROUND: Bacterial translocation has been implicated in infective complications in AP, which has been shown to be prevented by probiotics. STUDY: A double-blind, randomized placebo-controlled trial was conducted. Consecutive patients with AP presenting within 72 hours after the onset of abdominal pain or who had been nil orally at the time of presentation for up to 5 days were included in the study. The probiotic group received 4 sachets of Probiotics (2.5 billion bacteria per sachet) whereas the placebo group received 4 sachets of placebo for 7 days. Primary outcome measures were effect on gut permeability [assessed by lactulose/mannitol (L/M) excretion in urine] and endotoxemia assessed by endotoxin-core antibody types IgG and IgM (EndoCab IgG and IgM). Secondary outcome measures were mortality, total hospital/intensive care unit stay, abdominal discomfort, organ failure, C-reactive protein, and prealbumin levels. The study was prematurely stopped after the publication of probiotic prophylaxis in patients with predicted severe acute pancreatitis trial. RESULTS: From March 2007 to May 2008, 50 patients with AP were included in the study (26 in placebo group and 24 in probiotic group). There was no difference after intervention in gut permeability, whereas values of C-reactive protein and immunoglobulins decreased significantly [IgG: 140 (20-920) to 90 (20-600) GGU/mL and IgM: 65 (13-230) to 51 (9-240) GMU/mL] in the probiotic group. No difference was observed in prealbumin values, duration of hospital/intensive care unit stay, and mortality in both the groups. CONCLUSIONS: No significant trend was identified for an effect of probiotics on gut permeability or endotoxemia in AP. However, the study was underpowered owing to premature study termination.

Indian Herb-Derived Phytoconstituent-Based Antiviral, Antimicrobial and Antifungal Formulation: An Oral Rinse Candidate for Oral Hygiene and the Potential Prevention of COVID-19 Outbreaks.

Outbreaks of emerging infectious diseases continue to challenge human health. Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has triggered a global coronavirus pandemic, known as COVID-19. Multiple variants of SARS-CoV-2 virus are circulating, thus raising questions with respect to the effectiveness of different lines of treatment, such as vaccines and antiviral drugs. To find the appropriate prevention/treatment, 21 plant-based ingredients (Glycyrrhizin, Withanone, Aloe-emodin, Rhein, Emodin, Chrysophanol, Physcion, Kaempferol, Progallin A, Gallic acid, Naringin, Quercetin, Luteolin, and Apigenin) having antiviral, antibacterial and antifungal properties were identified. We pseudo-typed SARS-CoV-2 on a lentiviral vector plasmid and tested the impact of five different herbal formulations in mammalian HEK293T cells. Viral inactivation assay showed that the natural extracts in a herb-derived phytoconstituent-based formulation, BITS-003, comprising Bacopa monnieri, Glycyerrhiza glabra, Asparagus racemosus-wild, and Nigella sativa had strong virucidal properties, inactivating enveloped viruses from 2log10 (or 99%) to >4log10 (or 99.99%). Moreover, bacterial and yeast cells treated with BITS-003 displayed reduced growth. Topical use of the formulation as a mouthwash/gargle could be effective in reducing symptoms of respiratory viral infections, with the potential to decrease the viral load in the buccal/oral cavity. This may inhibit the coronavirus spreading to the lungs of infected persons and at the same time may reduce the risk of viral transmission to other susceptible persons through micro-droplets originating from the oral cavity of the infected person.

Effectiveness of antenatal screening of asymptomatic bacteriuria in reduction of prematurity and low birth weight: Evaluating a point-of-care rapid test in a pragmatic randomized controlled study.

BACKGROUND: Premature babies suffer higher mortality and life-long disabilities. Asymptomatic bacteriuria (ASB) is postulated to induce preterm labor. Routine antenatal screening for ASB using urine culture is not feasible in most developing countries due to long turn-around time, user-unfriendliness, and lack of resources. The current parallel-group superiority pragmatic randomized controlled trial evaluated the effect of screening and evidence-based treatment of ASB using an optical-sensor-based point-of-care rapid-test on the incidence of preterm birth and low birthweight (LBW). METHODS: 240 consenting asymptomatic pregnant women visiting an Indian tertiary public hospital for first antenatal check-up, irrespective of trimester/gravida, who had not consumed antibiotics in the preceding week, were enrolled from February-May 2017. Computer-generated concealed simple randomization allocation sequence was used to assign participants to intervention (120) and control arm (120). Usual hospital-care was provided in the control arm. In the intervention arm, urine samples were additionally screened for ASB using the rapid-test and the positive women were prescribed susceptible antibiotics. Blinded outcome assessors followed up with women post-delivery. The study was registered with the Clinical Trials Registry-India (CTRI/2016/09/007240). FINDINGS: 213 participants were analyzed (intervention: 103, control: 110). 21 women were found positive for ASB and prescribed pathogen-specific antibiotics. The incidence of preterm birth/LBW in intervention arm (n = 27) was lower than control arm (n = 45) by 14·7% (95% CI: 2·2-27·2); RR: 0.64, (95% CI: 0·43-0·95); p = 0·023, X2=5·13. INTERPRETATION: Rapid-test-guided treatment for ASB reduced the incidence of preterm birth/LBW in a pragmatic setting without any adverse event. FUNDING: Department of Biotechnology, Government of India.

Association of ADH1B and ALDH2 gene polymorphisms with alcohol dependence: a pilot study from India.

Functional polymorphism in the genes encoding alcohol dehydrogenase (ADH) 1B and aldehyde dehydrogenase (ALDH) 2 are considered most important among several genetic determinants of alcohol dependence, a complex disorder. There is no report on the widely studied Arg47His and Glu487Lys polymorphisms from Indian alcohol-dependent populations. In this paper, we report, for the first time, allelic and genotypic frequencies of Arg47His and Glu487Lys single nucleotide polymorphisms (SNPs) in North Indian alcohol-dependent subjects. A total of 174 alcohol-dependent males, recruited using DSM IV criteria (American Psychiatric Association, 1994), were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. The results obtained from genetic analysis were correlated with clinical parameters using Student's t-test or Mann Whitney's U test. The highlight of the study findings was the uniquely high frequency of the ALDH2*2/*2 genotype (among alcohol-dependent subjects) being a risk-conferring factor for alcohol dependence.

Modulation of Gut Microbiota through Dietary Phytochemicals as a Novel Anti-infective Strategy.

Quorum Sensing (QS) is a phenomenon in which bacterial cells communicate with each other with the help of several low molecular weight compounds. QS is largely dependent on population density, and it triggers when the concentration of quorum sensing molecules accumulate in the environment and crosses a particular threshold. Once a certain population density is achieved and the concentration of molecules crosses a threshold, the bacterial cells show a collective behavior in response to various chemical stimuli referred to as "auto-inducers". The QS signaling is crucial for several phenotypic characteristics responsible for bacterial survival such as motility, virulence, and biofilm formation. Biofilm formation is also responsible for making bacterial cells resistant to antibiotics. The human gut is home to trillions of bacterial cells collectively called "gut microbiota" or "gut microbes". Gut microbes are a consortium of more than 15,000 bacterial species and play a very crucial role in several body functions such as metabolism, development and maturation of the immune system, and the synthesis of several essential vitamins. Due to its critical role in shaping human survival and its modulating impact on body metabolisms, the gut microbial community has been referred to as "the forgotten organ" by O`Hara et al. (2006) [1]. Several studies have demonstrated that chemical interaction between the members of bacterial cells in the gut is responsible for shaping the overall microbial community. Recent advances in phytochemical research have generated a lot of interest in finding new, effective, and safer alternatives to modern chemical-based medicines. In the context of antimicrobial research various plant extracts have been identified with Quorum Sensing Inhibitory (QSI) activities among bacterial cells. This review focuses on the mechanism of quorum sensing and quorum sensing inhibitors isolated from natural sources.

Reversal of Increase in Intestinal Permeability by Mangifera indica Seed Kernel Extract in High-Fat Diet-Induced Obese Mice.

Obesity and hyper-intestinal permeability are interconnected. This study is designed to evaluate the ability of Mangifera indica seed kernel extract (MESK) in restoring the intestinal barrier and preventing obesity and associated metabolic complications in a high-fat diet-induced obese mouse model. Four groups of Swiss albino mice: (1) normal diet (ND), (2) high-fat diet (HFD), (3) HFD + Orlistat (100 µg/kg), and (4) HFD + MESK (75 µg/kg), were used to monitor various biochemical parameters associated with metabolic syndrome (glucose, total cholesterol, triglycerides) and body weight in an eight-week-long study. In vivo intestinal permeability was determined by the FITC-dextran method. Interestingly, MESK significantly reduced HFD-induced body weight gain, hepatic lipid accumulation, hepatic fibrosis, hyperglycemia, and dyslipidemia. Additionally, MESK treatment restored the expression of tight junction protein Zonula Occludens-1 (ZO-1) and Claudin-1 and hence prevented increased intestinal permeability induced by a high-fat diet. Moreover, it also increased the expression of potent satiety molecule Nesfatin-1 in the mouse jejunum. Our results, for the first time, establish MESK as a nutraceutical which prevents disruption of the intestinal barrier and thereby intercepts the adverse consequences of compromised intestinal permeability such as obesity, hyperglycemia, dyslipidemia, and systemic inflammation.

Genetic variation in D7S1875 repeat polymorphism of leptin gene is associated with increased risk for depression: a case-control study from India.

BACKGROUND: Epidemiologic data suggest an association between obesity and depression, however findings vary considerably across different studies. Both depression and obesity are disabling disorders associated with loss over appetite control, influenced by genetic and environmental factors and are risk factors for diseases like hypertension, cardiovascular disorders, etc. This study attempts to establish a link between the symptoms of depression, metabolic disorders, and obesity, to unravel the underlying association/s. METHODS: This exploratory case-control study comprises 133 clinically diagnosed depressed individuals and 136 age matched controls. DNA from all 269 subjects was genotyped for D7S1875 repeat polymorphism in the promoter region of Leptin (LEP) gene using polymerase chain reaction. RESULTS: Frequency of the shorter allele of D7S1875 (<208 bp) was 0.73 in the depressive group versus 0.67 in the control group (P=.01). Cases homozygous for D7S1875> or =208 bp alleles had significantly higher value of systolic (130 versus 122; P<.009) and diastolic (85.4 versus 81; P=.01) blood pressure (SBP and DBP) than the individuals homozygous for<208 bp allele. A similar trend was observed for SBP (127.8 versus 123.6; P=.03) among controls homozygous for the longer or the shorter allele. Thus, the LEP gene appears to be an important genetic determinant for susceptibility to depression in the Indian population (OR=1.4913, 95% CI=1.0334-2.1522; P=.04). CONCLUSIONS: Our findings suggest that LEP gene variants could be related to depression and associated co-morbidities such as hypertension.

Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control population of western Indian origin.

AIM: Polymorphisms in gamma-crystallins ( CRYG ) can serve as markers for lens differentiation and eye disorders leading to cataract. Several investigators have reported the presence of sequence variations within crystallin genes, with or without apparent effects on the function of the proteins both in mice and humans. Delineation of these polymorphic sites may explain the differences observed in the susceptibility to cataract observed among various ethnic groups. An easier Restriction Fragment Length Polymorphism (RFLP)-based method has been used to detect the frequency of four single nucleotide polymorphisms (SNPs) in CRYGA / CRYGB genes in control subjects of western Indian origin. MATERIALS AND METHODS: A total of 137 healthy volunteers from western India were studied. Examination was performed to exclude volunteers with any ocular defects. Polymerase chain reaction (PCR)-RFLP based method was developed for genotyping of G198A (Intron A), T196C (Exon 3) of CRYGA and T47C (Promoter), G449T (Exon 2) of CRYGB genes. RESULTS: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied significantly ( P = 0.02) among different age groups. An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor (PR) which may impact the expression of CRYGB gene. CONCLUSIONS: This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract.

Clinical Validation of Innovative Optical-Sensor-Based, Low-Cost, Rapid Diagnostic Test to Reduce Antimicrobial Resistance.

The antibiotic susceptibility test determines the most effective antibiotic treatment for bacterial infection. Antimicrobial stewardship is advocated for the rational use of antibiotics to preserve their efficacy in the long term and provide empirical therapy for disease management. Therefore, rapid diagnostic tests can play a pivotal role in efficient and timely treatment. Here, we developed a novel, rapid, affordable, and portable platform for detecting uropathogens and reporting antibiogram to clinicians in just 4 h. This technology replicates the basic tenets of clinical microbiology including bacterial growth in indigenously formulated medium, and measurement of inhibition of bacterial growth in presence of antibiotic/s. Detection is based on chromogenic endpoints using optical sensors and is analyzed by a lab-developed algorithm, which reports antibiotic sensitivity to the antibiotics panel tested. To assess its diagnostic accuracy, a prospective clinical validation study was conducted in two tertiary-care Indian hospitals. Urine samples from 1986 participants were processed by both novel/index test and conventional Kirby Bauer Disc Diffusion method. The sensitivity and specificity of this assay was 92.5% and 82%, respectively (p < 0.0005). This novel technology will promote evidence-based prescription of antibiotics and reduce the burden of increasing resistance by providing rapid and precise diagnosis in shortest possible time.

Unmet Need of Antenatal Screening for Asymptomatic Bacteriuria: A Risk Factor for Adverse Outcomes of Pregnancy.

Recommended urine culture is unsuitable for screening pregnant women for asymptomatic bacteriuria due to long turn-around time, unaffordability, and user-unfriendliness. The objective of this review was to evaluate the suitability of various tests for this purpose. A PubMed-based systematic review of published articles irrespective of year and language was done. Search terms included asymptomatic bacteriuria, screening test, urinary tract infection, and diagnostic test. Diagnostic accuracy studies conducted on human populations comparing tests with urine culture were included. One author extracted predefined data fields, including quality indicators, another validated it. Of 78 records, 25 studies describing 15 tests were included. All tests were rapid, seven were valid and two of them were affordable and easy-to-use. No test provided comprehensive identification with antibiotic susceptibility. Despite publication bias, no test was found suitable for screening asymptomatic bacteriuria antenatally and providing evidence-based prescription. Further research is needed to develop tests which suit this purpose.