HLA-DRB1 genes and the expression dynamics of HLA CIITA determine the susceptibility to T2DM.

Type 2 diabetes mellitus (T2DM) is a disease with polygenic inheritance. The expression of major histocompatibility complex class II genes are regulated by several trans-activators. We have studied the expression of HLA-DRB1, RFX, CIITA-P1, PIV transactivators, immunophenotyping of cells, SNPs in CIITA-168 (A/G) and IFN-γ + 874 (T/A) in T2DM patients and controls (n = 201 each). We observed increased frequencies of DRB1*03, DRB1*04 and DRB1*07 and decreased frequencies of DRB1*10, DRB1*14, and DRB1*15 alleles among patients. Significant up-regulations of HLA-DRB1 genes were observed in patients (p < 0.0001). Down-regulated expressions were documented in DRB1*03-homo (p < 0.002) and DRB1*04-homo (p < 0.009) patients. No significant differences were observed for CIITA-P1 expression except DRB1*04-pooled (p < 0.0113). The CIITA-PIV was up-regulated in overall (p < 0.0001), DRB1*03-pooled (p < 0.0006), DRB1*03-hetero (p < 0.0006) and DRB1*03-homo (p < 0.001) T2DM patients. However, significant down-regulations were documented for DRB1*04-pooled (p < 0.040), DRB1*04-hetero (p < 0.060), and DRB1*04-homo (p < 0.027) combinations. Further, significant down-regulations of RFX5 were observed in overall (p < 0.0006), DRB1*04-pooled (p < 0.0022), and DRB1*04-hetero (p < 0.0004) combinations. Immunophenotyping studies revealed significant increase of CD45+ CD14-, CD19+, CD14- and CD8 cells and elevated level of expression of IFN-γ (p < 0.0001) in patients. A significant increase of TT (p < 3.35 × 10-6) and decrease of TA (p < 4.57 × 10-4) genotypes of IFN-γ + 874 (T/A) and an increase of GG (p < 0.001) and decrease of AG (p < 8.24 × 10-5) genotypes of CIITA-168 A/G SNPs were observed. The combinatorial analysis revealed susceptible associations for DRB1*03 + AA, *03 + AG, *03 + GG and *04 + GG and protective associations for DRB1*10 + AG, *10 + GG, *15 + AG, and *14 + GG combinations. Thus, the present study corroborated the effect of differential expressions of promoters of risk alleles in the pathogenesis of T2DM.

The little things are big: evaluation of a compassionate community approach for promoting the health of vulnerable persons.

BACKGROUND: Vulnerable persons are individuals whose life situations create or exacerbate vulnerabilities, such as low income, housing insecurity and social isolation. Vulnerable people often receive a patchwork of health and social care services that does not appropriately address their needs. The cost of health and social care services escalate when these individuals live without appropriate supports. Compassionate Communities apply a population health theory of practice wherein citizens are mobilized along with health and social care supports to holistically address the needs of persons experiencing vulnerabilities. AIM: The purpose of this study was to evaluate the implementation of a compassionate community intervention for vulnerable persons in Windsor Ontario, Canada. METHODS: This applied qualitative study was informed by the Consolidated Framework for Implementation Research. We collected and analyzed focus group and interview data from 16 program stakeholders: eight program clients, three program coordinators, two case managers from the regional health authority, one administrator from a partnering community program, and two nursing student volunteers in March through June 2018. An iterative analytic process was applied to understand what aspects of the program work where and why. RESULTS: The findings suggest that the program acts as a safety net that supports people who are falling through the cracks of the formal care system. The 'little things' often had the biggest impact on client well-being and care delivery. The big and little things were achieved through three key processes: taking time, advocating for services and resources, and empowering clients to set personal health goals and make authentic community connections. CONCLUSION: Compassionate Communities can address the holistic, personalized, and client-centred needs of people experiencing homelessness and/or low income and social isolation. Volunteers are often untapped health and social care capital that can be mobilized to promote the health of vulnerable persons. Student volunteers may benefit from experiencing and responding to the needs of a community's most vulnerable members.

Development of a production chain from vegetable biowaste to platform chemicals.

BACKGROUND: A future bioeconomy relies on the development of technologies to convert waste into valuable compounds. We present here an attempt to design a biotechnological cascade for the conversion of vegetable waste into acetoin and electrical energy. RESULTS: A vegetable waste dark fermentation effluent containing mainly acetate, butyrate and propionate was oxidized in a bioelectrochemical system. The achieved average current at a constant anode potential of 0 mV against standard hydrogen electrode was 177.5 ± 52.5 µA/cm2. During this step, acetate and butyrate were removed from the effluent while propionate was the major remaining component of the total organic carbon content comprising on average 75.6%. The key players with regard to carbon oxidation and electrode reduction were revealed using amplicon sequencing and metatranscriptomic analysis. Using nanofiltration, it was possible to concentrate the propionate in the effluent. The effluent was revealed to be a suitable medium for biotechnological production strains. As a proof of principle, the propionate in the effluent of the bioelectrochemical system was converted into the platform chemical acetoin with a carbon recovery of 86%. CONCLUSIONS: To the best of our knowledge this is the first report on a full biotechnological production chain leading from vegetable waste to the production of a single valuable platform chemical that integrates carbon elimination steps leading to the production of the valuable side product electrical energy.

Association of HLA-DR/DQ alleles and haplotypes with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is a debilitating renal problem in children resulting from an interaction between environmental and genetic factors including human leukocyte antigen genes (HLA). The aim of this work was to study the probable link between HLA alleles/haplotypes and NS in south India. METHODS: HLA DRB1*/DQB1* alleles were genotyped in 183 NS (76 steroid sensitive-SSNS; 107 steroid resistant-SRNS) and paediatric healthy controls (PHCs; n = 91) using polymerase chain reaction-sequence specific primers (PCR-SSP). HLA-A/-B genotyping was performed for patients (n = 70) positive for DRB1*07-DQB1*02 haplotype to identify four locus extended haplotype. RESULTS: The following alleles and haplotypes were strongly associated with NS (P < 0.05 as significant): DRB1*07 (SSNS, P < 7.98 × 10(-6) ; SRNS, P < 0.008), DQB1*02 (SSNS, P < 3.99 × 10(-6) ; SRNS, P < 0.002), DRB1*07-DQB1*02 (SSNS, P < 1.32 × 10(-4) ; SRNS, P < 0.010), DRB1*07-DQB1*0301,0304 (DQ7) (SSNS, P < 0.001) and DRB1*03-DQB1*02 (SRNS, P < 0.048). Protective associations were observed for alleles DRB1*10 (SRNS, P < 0.013), DQB1*05 (SSNS, P < 4.34 × 10(-6) ; SRNS, P < 0.01), DQB1*06 (SSNS, P < 0.003), and haplotypes DRB1*10-DQB1*06 (SSNS, P < 0.046; SRNS, P < 0.032) and DRB1*15-DQB1*05 (SSNS, P < 0.018). HLA-A/-B typing of 70 NS cases with two locus haplotype DRB1*07-DQB1*02 (70/183; 38.25%) revealed the presence of an extended haplotype 'A*03-B*07-DRB1*07-DQB1*02' (n = 35; 50%). CONCLUSION: Our study revealed strong susceptible association of DRB1*07 with SRNS and DQB1*02 with SSNS. A gender predominant protective association was observed for DRB1*10 with SRNS females; DQB1*05 with SSNS and SRNS males. Further, the study documented the presence of an extended haplotype and pleiotropic action of DRB1*/DQB1* alleles in immune-mediated aetiology of NS in south India.

Benefits of Reporting and Analyzing Nursing Students' Near-Miss Medication Incidents.

BACKGROUND: Developing competencies in reporting medication errors and near-miss incidents is a critical component of nursing student education. The benefits of reporting near-miss incidents by nursing students are unknown. PURPOSE: The aim was to analyze nursing students' near-miss incident reports for types of incidents and their contributing factors, assess the effectiveness of current procedures in catching these errors, and offer guidance on curricular improvements for medication administration content. METHOD: This quality improvement project analyzed 3 years of near-miss incidents (N = 236) submitted through the school's incident reporting system. RESULTS: Five incident types accounted for 81.4% of incidents. Factors contributing to most incidents were communication (47.9%), competency and education (44.1%), environmental/human limitations (35.2%), and policies/procedures (29.2%). CONCLUSION: Safety experts emphasize that near-miss reports offer free lessons to prevent future errors. Nursing students' near-miss reporting is beneficial for both students and nursing programs.

Nurse-pharmacist collaborations for promoting medication safety among community-dwelling adults: A scoping review.

Background: Despite good evidence that supports improved clinical health outcomes and the cost effectiveness of nurse-pharmacist collaboration for promoting medication safety among adults in acute care settings, there is limited research in community settings. Objective: This scoping review examines, maps, and identifies gaps in the existing literature on nurse-pharmacist collaboration to augment medication safety among community-dwelling adults. Design: Setting(s): Community setting. Participants: This review consists of 3,464 participants across 23 studies. Methods: We used the enhanced Arksey and O'Malley framework by Levac and colleagues. Studies from MEDLINE, CINAHL, ProQuest, Scopus, and PubMed databases implementing medication safety through nurse-pharmacist collaboration for community-dwelling adults were included. We extracted data according to country of origin, intervention, and relevance to the current review. Results: Twenty-three studies were included in this review. Nurse-pharmacist collaborations in community settings are still evolving and are in a nascent form. Five sub-themes emerged from literature review of collaboration between nurses and pharmacists in community settings for medication safety. They are creating new opportunities to address gaps in community medication safety, enabling complementary interprofessional roles in medication safety, facilitating of efficient and cost-effective measures for medication safety, diverse nature of assessments done by nurses and pharmacists, and incohesive teams due to poor collaborative practices. Conclusions: Nurse-pharmacist collaborations in community settings improved disease management, prevented adverse drug events, and reduced hospitalizations. They resulted in early identification and correction of medication safety related issues, reduced wait periods to see general practitioners, and enhanced chronic disease self-management skills among community-dwelling adults. There is a need to improve existing systems and policies through research for sustaining such collaborations especially in community settings.

HLA-DRB1* and DQB1* allele and haplotype diversity in eight tribal populations: Global affinities and genetic basis of diseases in South India.

The distribution of HLA class-II DRB1* and DQB1* alleles/ haplotypes were studied in 438 individuals of 8 Dravidian tribal groups inhabiting the Western Ghats, south India. The HLA typing was performed by PCR-SSP method. In order to identify the 5-locus Ancestral Extended Haplotypes (AEH), the alleles of HLA-A, -B and -C loci were typed for DNAs with predominant 2-locus haplotypes. The analyses have revealed allele HLA-DRB1*15 as the most predominant allele (Lowest / Highest range: Urali, 14.81 / Malasar, 48.94), followed by the alleles DRB1*10 (Katunayakan, 1.85 / Paliyan, 48.21), DRB1*14 (Paliyan 4.46 / Katunayakan, 40.74), DRB1*12 (Mannan, 1.64 / Katunayakan, 20.37) and DRB1*03 (Mannan, 1.64 / Urali, 29.63). The most frequent DQB1* alleles were DQB1*02 (Paliyan 3.57 / Urali, 23.15), DQB1*05 (Katunayakan, 27.77 / Paliyan 84.82) and DQB1*06 (Malasar, 8.51 / Kuruman, 33.51). The most predominant two-locus haplotypes observed were DRB1*15-DQB1*05, DRB1*10-DQB1*05, DRB1*15-DQB1*06 and DRB1*04-DQB1*05. The present study of HLA immunogenetics of south Indian tribes have revealed the presence of globally shared two and 5-locus haplotypes. Many of these haplotypes were implicated in a number of diseases in south India. We observed the presence of ancestral extended haplotypes (AEHs), hitherto not reported in Indian populations such as, A*68-B*35-C*02-DRB1*15:01-DQB1*05:01, A*24-B*57-C*06-DRB1*04:01-DQB1*05:01 and A*24-B*35-C*02-DRB1*15:01-DQB1*05:02. The dendrogram based phylogenetic analyses have revealed the Caucasian affinity of Urali, palaeo-Mediterranean and Indo-European affinity of Malasar tribes. The presence of globally shared susceptible and protective haplotypes reiterated the mosaic immunogenetic fabric of south Indian tribes.

Association of HLA-DRB1, DQA1 and DQB1 alleles and haplotype in Parkinson's disease from South India.

Parkinson's disease (PD) is a chronic, neurodegenerative motor disease exhibiting familial and sporadic forms. The present study was aimed to elucidate the association of HLA-DRB1*, DQA1* and DQB1* alleles with PD. A total of 105 PD patients and 100 healthy controls were typed by PCR-SSP method. We further carried out high-resolution genotyping for DQB1 and DQA1. Results revealed the increased frequencies of alleles DRB1*04 (OR = 2.36), DRB1* 13 (OR = 4.04), DQA1* 01:04:01 (OR = 4.51), DQB1*02:01 (OR = 2.66) and DQB1*06:03 (OR = 2.65) in PD patients suggesting susceptible associations. Further, decreased frequencies observed for alleles DRB1*10 (OR = 0.34), DRB1*15 (OR = 0.44), DQA1*04:01 (OR = 0.28), DQA1*06:01 (OR = 0.11) and HLA-DQB1*05:01 (OR = 0.37) among patients have suggested protective associations. Significant disease associations were observed for two-locus haplotype such as DRB1*13-DQB1*06:03 (OR = 11.52), DQA1*01:041-DQB1*06:03 (OR = 16.50), DQA1*01:041-DQB1*05:02 (OR = 5.38) and DQA1*04:01-DQB1*06:03 (OR = 3.027). Protective associations were observed for haplotypes DRB1*10-DQB1*05:01 (OR = 0.21), DRB1*15-DQB1*06 (OR = 0.006), DQA1*04:01-DQB1*05:01 (OR = 0.400) and DQA1*04:01-DQB1*05:03 (OR = 0.196). The critical amino acid residue analyses have revealed strong susceptible association for the residues of DQB1 alleles such as: L26, S28, K71, T71 and A74, Y9, S30, D37, I37, A38, A57 and S57; and for the residues of DQA1 alleles such as: C11, F61, I74, and M76. Similarly, amino acid residues such as A13, G26, Y26, A71, S74, L9 and V38 of HLA-DQB1 alleles and residues such as Y11, G61, S74 and L76 of DQA1 alleles showed protective associations. Thus, our study documented the susceptible and protective associations of DRB1*, DQB1 and DQA1 alleles and haplotypes in developing the disease and their influence on longevity of PD patients in south India.

Association of slow acetylator genotype of N-acetyltransferase 2 with Parkinson's disease in south Indian population.

AIM: Parkinson's Disease (PD) is a neurodegenerative disorder with predisposing genetic and environmental factors. The present study was undertaken to elucidate the possible association of NAT2 gene polymorphism in PD patients from south India. METHODS: Using previously validated PCR-RFLP assays, we genotyped 105 PD subjects and 101 healthy controls for N-acetyl transferase (NAT2) gene polymorphism. RESULTS: We observed a significantly elevated frequencies of NAT2 *5/6 (OR = 4.21; p < 0.029) and *5/7 (OR = 2.73; p < 0.025) genotypes and NAT2*5 (OR = 1.83; p < 0.039) allele among PD cases showing susceptible associations. The age at onset analysis revealed a significant association of NAT2 *4/6 (OR = 4.62; p < 0.05) genotype with early onset PD (EOPD). A positive association with early onset disease was observed for *5/7 (OR = 3.88; p < 0.075) genotype, however without statistical significance. Whereas, in late onset PD (LOPD) cases, significant susceptible association was observed for NAT2 *5/7 (OR = 5.27; p < 0.029) genotype. We observed a highly significant protective association of NAT2 *4/6 (OR = 0.27; p < 0.012) genotype and NAT2 *4 (OR = 0.52; p < 0.027) allele with LOPD. The acetylator status phenotype analysis have revealed a higher risk for, 'NAT2 slow acetylator' in both overall PD (OR = 2.39; p < 0.002) and LOPD (OR = 2.88; p < 0.007). However, 'NAT2 intermediate acetylator' with a lower risk in both overall PD (OR = 0.47; p < 0.011) and LOPD (OR = 0.36; p < 0.007) cases revealed protective associations. CONCLUSIONS: Thus, our results revealed the possible susceptible association of NAT2 slow acetylator in PD pathogenesis in south Indian population.

Integration of membrane filtration in two-stage anaerobic digestion system: Specific methane yield potentials of hydrolysate and permeate.

Two-stage biogas systems consisting of a CSTR-acidification reactor (AR) and an anaerobic filter (AF) were frequently described for microbial conversion of food and agricultural wastes to biogas. The aim of this study is to investigate the integration of a membrane filtration step in two-stage systems to remove inert particles from hydrolysate produced in AR in order to increase the efficiency of the subsequent AF. Hydrolysates from vegetable waste (VW) and grass/maize silage (G/M) were treated in cross-flow ceramic membrane filtration system (pore size 0.2 µm). Organic acids were extracted efficiently through filtration of hydrolysate. For both the substrates, membrane permeability was stable and high (46.6-49.3 L m-2 h-1 bar-1). Filtration process effectively improved the specific methane yield of permeate by 40% (VW) and 24.5% (G/M) compared to hydrolysate. It could be shown that, the filtration-step increased hydrolysate's degradability, which lead to higher conversion efficiency in the following AF.

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome.

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%-15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS). Angiotensin converting enzyme (ACE) (I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE (I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome (162 boys and 98 girls) and 218 (140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE (I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases (minimal change disease, n=51; focal segmental glomerulosclerosis, n=27; diffuse mesangial proliferation, n=8). We segregated them into the minimal change disease / focal segmental glomerulosclerosis groups and observed that the ACE'D' allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the 'I' allele was assessed as having very weak association in cases of minimal change disease. 'II' genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of 'ID' genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE (I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.

Association of HLA class II alleles/haplotypes and amino acid variations in the peptide binding pockets with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune, inflammatory disease, caused by environmental and genetic factors. AIM: To elucidate the association of human leukocyte antigen (HLA)-DRB1*/DQB1* alleles/haplotypes and the variations of polymorphic amino acid changes in peptide binding pockets in RA patients from south India. METHODS: HLA typing was performed in 176 RA patients and 176 healthy controls by polymerase chain reaction-sequence-specific primers method. RESULTS: Strong susceptible association for alleles such as DRB1*04:01(odds ratio [OR] = 3.66), 04:06 (OR = 3.81), 03:01 (OR = 2.93), 06:01 (OR = 2.53) and protective association for alleles such as DRB1*13:01 (OR = 0.17), 14:01 (OR = 0.15), 05:02 (OR = 0.17), and 05:03 (OR = 0.338) were observed in RA patients. The 2-locus haplotypes such as 04-02:01 (OR = 3.844), 04-06:01 (OR = 6.57), 07-03:01 (OR = 6.16), 07-06:01 (OR = 3.42), 12-06:01 (OR = 5.24), 15-03:01 (OR = 4.69) with susceptible and DRB1*14-DQB1*05:03 (OR = 0.078) with protective associations were observed in RA patients. The acid-base analysis revealed that the basic group BB allele was positively associated (OR = 2.372) and the acidic group AA allele was negatively associated (OR = 0.086). The analysis on shared epitopes has revealed that the combination QKRAA+, (Q)RRAA+ or (Q)RRAA- was positively associated with RA (OR = 2.78). The amino acid variation at HLA-DQß molecule revealed susceptible associations for residues E86 and L87 (P1); E74 (P3); A13 , Y26 , I/S28 , T28 , I71 and E74 (P4); L9 , T30 , D37 and D57 (P9), whereas, the amino acids A86 and T87 (P1); S74 (P3); G13/26 , A71 and S74 (P4); H30 and T37 , S57 (P9), showed protective associations. CONCLUSIONS: Alleles DRB1*04:06 and*04:01 showed strong susceptible and DRB1*13:01 and *14:01 showed protective associations in RA patients. The amino acid variations in DQß molecules revealed significant molecular markers for susceptibility to and protection from RA in south India.

Effect of Litsea lancifolia Leaf Extract on Glucose Transporter 4 Translocation and Glucose Uptake in 3T3L1 Cell Line.

BACKGROUND: Numerous synthetic drugs have been recommended as a remedy for diabetes, but their role in hypoglycemic effects are diverse. The side effects associated with these drugs due to their extended use led scientists to find unconventional medicines with no or little side effects. AIM: This study was aimed at assessment of in vitro antidiabetic activities of methanolic extract of Litsea lancifolia leaves by using 3T3L1 cell line. MATERIALS AND METHODS: The cytotoxic effect of the leaf extract was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The glucose uptake-inducing capabilities and its correlation with glucose transporter 4 (GLUT4) translocation were measured by flow cytometry in 3T3L1 cells. In addition, the inhibitory effect of L. lancifolia leaf extract on α-amylase activity and α-glucosidase activity was determined by colorimetric methods. RESULTS: Different concentrations of L. lancifolia leaf extract did not show any toxicity on 3T3L1 cells, after the treatment for 24h. On stimulation with leaf extract, 60.22% and 86.26% of 3T3L1 cells showed glucose uptake and GLUT4 expression, respectively. The colorimetric assays showed that the methanolic leaf extract of L. lancifolia has a significant inhibitory effect on the activity of α-amylase enzyme and α-glucosidase enzyme with inhibitory concentration (IC50) value of 248.65 µg/mL and 229.61 µg/mL, respectively. CONCLUSION: On the basis of the results of this study, it is evident that L. lancifolia leaf extract showed promising anti-diabetic effect when compared to the standard drugs metformin and acarbose and was nontoxic to 3T3L1 cells. Thus, it can be further investigated to recommend as a possible alternative treatment in antidiabetic applications.

In vitro wound healing potency of methanolic leaf extract of Aristolochia saccata is possibly mediated by its stimulatory effect on collagen-1 expression.

BACKGROUND: Identification and assessment of therapeutic potential of natural products derived from medicinal plants have led to the discovery of innovative and economical drugs to treat several diseases, including chronic wounds. In vitro cell based scratch assay is an appropriate and inexpensive method for initial understanding of wound healing potential of medicinal plant extracts. The current study was aimed at investigating the wound healing capacity of Aristolochia saccata leaf extract by using scratch assay as a primary model, where proliferative and migratory capabilities of test compounds could be monitored through microscopy studies. A. saccata is an evergreen climbing shrub belongs to the family Aristolochiaceae. METHODS: Methanolic extraction of the plant material was done using Soxhlet apparatus and the cytotoxicity of the extract on L929 cells was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. L929 is a human fibroblast cell line. In vitro scratch assay was performed to evaluate the wound healing properties of A. saccata leaf extract and possible mechanism of action was analyzed by flow cytometric expression studies of an extracellular matrix (ECM) factor, collagen type-1. RESULTS: MTT assay revealed that A. saccata leaf extract had no cytotoxic effect on the cells and at higher concentrations, the extract showed mild toxicity resulting in the death of just 2.88% cells. Scratch assay showed 34.05%, 70.00%, 93.52% wound closure at 12hrs, 24hrs and 48hrs of incubation respectively. These results were similar compared to positive control which showed 37.60, 56.41 and 99.05% of wound closure. Further, flow cytometry-based studies revealed that the A. saccata leaf extract induced the expression of ECM remodelling factor collagen-1. CONCLUSION: Our study revealed the wound healing capabilities of A. saccata In vitro. Hence, A. saccata could be recommended as a potential source of wound healing agents.

Effects of target pH-value on organic acids and methane production in two-stage anaerobic digestion of vegetable waste.

Vegetable waste is one of the major organic residues available for sustainable bioenergy production. The aim of this work is to study the influence of pH-value on process stability, hydrolysis, degradation degree and methane production in two-stage anaerobic system. A mixture of vegetable wastes with carrot mousse, carrots, celery, cabbage and potatoes was treated in two-stage system at target pH-values 5.5 and 6 in acidification reactor (AR). At pH 6, high concentrations of organic acids were recorded whereas high amount of hydrolysate was produced at pH 5.5. The chemical oxygen demand (COD) concentration in the hydrolysate produced in AR was 21.85% higher at pH 6 compared to pH 5.5, whereas the overall specific methane yield was slightly higher at pH 5.5 (354.35±31.95 and 326.79±41.42Lkg-1 oDMadded, respectively). It could be shown, that the described two-stage system is well suited for manure-free digestion of vegetable waste.

Association of HLA-A, B, DRB1* and DQB1* alleles and haplotypes in south Indian T2DM patients.

The genes of Human Leukocyte Antigen (HLA) system are implicated in the susceptibility of several diseases including Type 2 diabetes (T2DM). Therefore, we aimed to investigate the association of HLA alleles with T2DM in south India. A total of 344 patients (195 males; 149 females) and 309 controls (186 males; 123 females) were genotyped for HLA-DR/-DQ alleles. Based on predominant DR/DQ haplotypes, 222 patients and 222 age/sex matched controls were HLA-A/-B genotyped. HLA alleles were typed by PCR-SSP methods. Susceptible association was observed for the alleles A*33 (OR=13.8), A*01 (OR=3.69), A*02 (OR=2.91), B*07 (OR=4.12), DRB1*11 (OR=2.23), DRB1*04 (OR=1.51), DRB1*03 (OR=1.90) and DQB1*02 (OR=1.49). Protective association was observed for the alleles A*11 (OR=0.59), A*68 (OR=0.68), B*40 (OR=0.50), B*54 (OR=0.42), B*57 (OR=0.31), B*51 (OR=0.29) and DRB1*10 (OR=0.45). Gender stratified analysis too confirmed many of these associations. Predominant susceptible haplotypes were A*33-B*40 (OR=10.27), A*01-B*07 (OR=4.97), A*02-B*07 (OR=6.50), DRB1*03-DQB1*05 (OR=1.88), DRB1*03-DQB1*06 (OR=3.01), DRB1*04-DQB1*05 (2.63), A*01-B*07-DRB1*10 (OR=8.26) and A*11-B*35-DRB1*07 (OR=9.338). Haplotypes A*03-B*07 (OR=0.57; p<0.034) and DRB1*10-DQB1*05 (OR=0.57; p<0.033) were protectively associated. Further, a very strong susceptible association was documented for four-locus haplotypes such as A*11-B*40-DRB1*15-DQB1*06 (n=15; OR=16.01; p<0.001); A*01-B*07-DRB1*10-DQB1*05 (n=8; OR=8.26; p<0.043) and A*11-B*07-DRB1*07-DQB1*05 (n=8; OR=8.26; p<0.043). Thus, a number of HLA alleles and haplotypes showed susceptible and protective association(s) in T2DM patients from south India.

Polymorphic Alu Insertion/Deletion in Different Caste and Tribal Populations from South India.

Seven human-specific Alu markers were studied in 574 unrelated individuals from 10 endogamous groups and 2 hill tribes of Tamil Nadu and Kerala states. DNA was isolated, amplified by PCR-SSP, and subjected to agarose gel electrophoresis, and genotypes were assigned for various Alu loci. Average heterozygosity among caste populations was in the range of 0.292-0.468. Among tribes, the average heterozygosity was higher for Paliyan (0.3759) than for Kani (0.2915). Frequency differences were prominent in all loci studied except Alu CD4. For Alu CD4, the frequency was 0.0363 in Yadavas, a traditional pastoral and herd maintaining population, and 0.2439 in Narikuravars, a nomadic gypsy population. The overall genetic difference (Gst) of 12 populations (castes and tribes) studied was 3.6%, which corresponds to the Gst values of 3.6% recorded earlier for Western Asian populations. Thus, our study confirms the genetic similarities between West Asian populations and South Indian castes and tribes and supported the large scale coastal migrations from Africa into India through West Asia. However, the average genetic difference (Gst) of Kani and Paliyan tribes with other South Indian tribes studied earlier was 8.3%. The average Gst of combined South and North Indian Tribes (CSNIT) was 9.5%. Neighbor joining tree constructed showed close proximity of Kani and Paliyan tribal groups to the other two South Indian tribes, Toda and Irula of Nilgiri hills studied earlier. Further, the analysis revealed the affinities among populations and confirmed the presence of North and South India specific lineages. Our findings have documented the highly diverse (micro differentiated) nature of South Indian tribes, predominantly due to isolation, than the endogamous population groups of South India. Thus, our study firmly established the genetic relationship of South Indian castes and tribes and supported the proposed large scale ancestral migrations from Africa, particularly into South India through West Asian corridor.

MTHFR (C677T) CT genotype and CT-apoE3/3 genotypic combination predisposes the risk of ischemic stroke.

The predisposition to ischemic stroke (IS) might involve interactions of several genes and environmental factors. The present study was aimed to evaluate the influence of polymorphisms in methylenetetrahydrofolate reductase (MTHFR-C677T) and apolipoprotein-E (apo-E) as risk factors for IS patients in south Indian population. 200 IS patients and 193 age and sex matched controls were genotyped for MTHFR-C677T and apoE by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistically significant association was observed for MTHFR CT genotype (IS-Pooled: OR=4.29; p=5.01×10(-5); IS-Males: OR=4.13; p=0.001; IS-Females: OR=8.62; p=0.027; IS-Large Vessel Disease (LVD)- Pooled: OR=4.14; p=0.0002) and T allele (IS-Pooled: OR=4.82; p=1.49×10(-5); IS-Males: OR=4.33; p=0.0002; IS-Females: OR=7.99; p=0.031; IS-LVD-Pooled: OR=4.13; p=0.0001). Further, reduced frequencies of CC genotype (IS-Pooled: OR=0.20; p=9.80×10(-6); IS-Males: OR=0.25; p=0.001; IS-Females: OR=0.12; p=0.027; IS-LVD-Pooled: OR=0.23; p=0.0001) and C allele (IS-Pooled: OR=0.21; p=1.49×10(-5); IS-Males: OR=0.23; p=0.0002; IS-Females: OR=0.13; p=0.031; IS-LVD-Pooled: OR=0.24; p=0.0001) were observed in IS patients than the controls. No association was observed for apoE genotypes/alleles in IS/LVD cases. Our study demonstrated the presence of risk for MTHFR CT genotype/T allele and 'CT-3/3' (n=33 vs. 5; OR=7.42; p=0.001) genotypic combination in the development of IS in south India. Further, follow-up study of these stroke cases i.e., in later stages of the disease whether they are developing the neurological disorders such as Alzheimer's Disease (AD) and vascular dementia (VaD) is needed to draw a fruitful conclusion in connection between neurological disorders and with these two polymorphisms, before translating it into clinical practice.

Correction: Polymorphic Alu Insertion/Deletion in Different Caste and Tribal Populations from South India.

[This corrects the article DOI: 10.1371/journal.pone.0157468.].

Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India.

BACKGROUND: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. OBJECTIVES: To study the predispositions of HLA alleles/haplotypes with cervical cancer. MATERIALS AND METHODS: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. RESULTS: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions ß9 and ß37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. CONCLUSIONS: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.