Domestic violence and its relationship with depression, anxiety and quality of life: A hidden dilemma of Pakistani women.

OBJECTIVES: To find out the relationship of domestic violence with depression, anxiety and quality of life in married women in hospitals of Rawalpindi and Islamabad. METHODS: This co-relational study was conducted in Rawalpindi Institute of Health Sciences from January 2019 to December 2019. All the females' patients who were the victim of domestic violence were the population of the study. Consecutive non-probability sampling technique was used for selection of sampling from the target population. The inclusion criterion for this study was diagnosed case of domestic violence. DASS 21 (The Depression, Anxiety and Stress Scale) and Quality of life (WHO) scales were administered to 116 patients. RESULTS: The study's key results were that domestic abuse has positive relationship with depression, anxiety, and stress. It was also found that domestic abuse has a negative relationship with quality of life of those who have been subjected to domestic violence of this sort. CONCLUSION: It was concluded that domestic violence whether verbal, physical, emotional or sexual has strongly effects the mental health and quality of life of abused women.

Effects of different metabolic states and surgical models on glucose metabolism and secretion of ileal L-cell peptides: results from the HIPER-1 study.

AIM: To compare the impact of four surgical procedures (mini-gastric bypass, sleeve gastrectomy, ileal transposition and transit bipartition) vs medical management on gut peptide secretion, ß-cell function and resolution of hyperglycaemia in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A mixed-meal tolerance test was administered 6-24 months after each surgical procedure (mini-gastric bypass, sleeve gastrectomy, ileal transposition and transit bipartition; n=30 in each group) and the results were compared with those obtained in matched lean (n=30) and obese (n=30) people with type 2 diabetes undergoing medical management. RESULTS: Participants in the mini-gastric bypass and ileal transposition groups had a greater increase in plasma glucose concentration after the mixed-meal tolerance test than those in the sleeve gastrectomy and transit bipartition groups. Participants in the mini-gastric bypass group exhibited the greatest increase in the incremental area under the curve of plasma glucose concentration above baseline (P<0.0001). Insulin sensitivity was similar across surgical groups, and statistically greater in participants in the surgical groups than in obese participants in the non-surgical group (P<0.0001). ß-cell responsiveness to glucose was greater in participants in the sleeve gastrectomy and transit bipartition groups than in the mini-gastric bypass and ileal transposition groups (P<0.001) despite a smaller incremental increase above baseline in the area under the plasma glucagon-like peptide-1 concentration curve relative to ileal transposition. Postoperative ß-cell function was the strongest predictor of hyperglycaemia resolution. CONCLUSIONS: The present study showed that the level of ß-cell function after bariatric surgery is the strongest predictor of hyperglycaemia resolution. The study also demonstrates a disconnect between postprandial GLP-1 levels and ß-cell function among the studied surgical procedures.

Astaxanthin improves the developmental competence of in vitro-grown oocytes and modifies the steroidogenesis of granulosa cells derived from bovine early antral follicles.

In this study we investigated the effect of astaxanthin (Ax), which exhibits strong antioxidant activity, during invitro growth (IVG) on the developmental competence of oocytes and steroidogenesis of granulosa cells derived from early antral follicles. Bovine oocyte-cumulus-granulosa complexes collected from early antral follicles were cultured for 12 days in the presence or absence (control) of 500µM Ax. The viability of oocytes and antrum formation in the granulosa cell layer during IVG culture were greater in the presence than absence of Ax (P<0.05). Regardless of Ax treatment, 17ß-oestradiol production increased during IVG culture; however, progesterone production was significantly lower in the presence than absence of Ax (P<0.05). Reactive oxygen species levels were lower in Ax-treated oocytes than in controls after IVG (P<0.05). Although nuclear maturation and cleavage rates did not differ between the Ax-treated and control groups, Ax treatment led to weaker cathepsin B activity in oocytes and better blastocyst rates than in controls (P<0.05). Accordingly, Ax treatment during IVG increased the total number of cells in blastocysts (P<0.05). These results indicate that Ax supplementation of IVG medium improves the quality of bovine oocytes due to its antioxidative effects on growing oocytes and its suppression of the luteinisation of granulosa cells.

Impact of good and poor mobilizers on hematopoietic progenitor cell collection efficiency and product quality.

BACKGROUND: Mobilization regimen choice is a significant contributing factor for successful hematopoietic progenitor cell (HPC) collection by leukocytapheresis and reaching the target CD34+ cell dose. How mobilization regimen affects collection efficiency and the quality of products collected using the Spectra Optia apheresis instrument is not fully known. METHODS: We evaluated the impact of granulocyte-colony stimulating factor (GCSF) and GCSF/plerixafor mobilization regimens on CE and product composition. We studied 373 leukocytapheresis HPC collections for 147 autologous transplants from January 1, 2010 to December 31, 2014. Patients were categorized in two groups; good mobilizers, mobilized with GCSF only (GM) and poor mobilizers, mobilized with GCSF and Plerixafor (PM). RESULTS: Overall, compared with PM group, total nucleated cell (TNC) yield was significantly lower in GM group (P = <.001). In contrast, median percent mononuclear cell (MNC) collected from GM (86.5%) was significantly higher than products collected from PM group (79.5%; P < .001). Compared with GM group, CD34+ cell CE was about 10% lower in PM group (P < .008). In addition, daily CD34+ cell/Kg yield was significantly higher in GM (2.08 × 10/Kg) compared with PM group (1.64 x 10/Kg, P = .019). Overall, the median number of collections per patient was two for GM and three for PM (P = .004). CONCLUSION: Products collected from PM group contained higher TNC content relative to GM group but had lower MNC enrichment, CD34+ cell CE and daily CD34+ cell yield per Kg.

γ-Aminobutyric Acid (GABA) Induced in Vitro Differentiation of Rat Pancreatic Ductal Stem Cells into Insulin-Secreting Islet-Like Cell Clusters.

In vitro produced ß-like cells can provide promising cell therapy for curing the epidemic of diabetes. In this context, we aimed to investigate the effects of different concentrations of γ-aminobutyric acid (GABA) on the differentiation of rat pancreatic ductal epithelial-like stem cells (PDESCs) into ß-like cells. The PDESC line cells were cultured in the basal media (DMEM/F12 + 10% FBS + 1% penicillinstreptomycin) supplemented with 0 µM, 5 µM, 50 µM, 500 µM, and 5 mM of GABA for 28 days to induce their differentiation. The differentiated cells were detected by cell morphology, dithizone (DTZ) staining, immunofluorescence staining, real-time polymerase chain reaction (qPCR), and glucose-stimulated insulin secretion (GSIS) assay to validate their identity. At the end of 28 days, compared with the control group, enrichment of induced cells was high among the 5 µM, 50 µM, 500 µM, and 5 mM GABA induction groups. The formation of islet-like cell clusters (ICCs) began at 14 days, and the cell clusters showed a growth trend with the culture time. The induced ICCs were positive for DTZ staining, while the control group showed negative results for DTZ staining and the differentiated cells were also positive for ß-cell-specific markers (Ins1 and Pdx1). GSIS assay of 50 µM induction group cells at 28 days showed significantly higher levels of C-peptide and insulin secretion than the control, 5 µM, 500 µM, and 5 mM GABA-treated groups (P < 0.01). At the same time, the 50 µM induction group cells also showed significantly higher levels of Ins1, Pdx1 and Nkx6.1 mRNA as compared to the 5 µM, 500 µM and 5 mM GABA groups (P < 0.01). Thus, the addition of GABA to the basal medium effectively induced differentiation of adult rat PDESCs into insulin-secreting ß-like cells, and 50 µM was the most effective concentration for the induction.

Validity of screening tools for dementia and mild cognitive impairment among the elderly in primary health care: a systematic review.

OBJECTIVES: This systematic review aims to provide updated and comprehensive evidence on the validity and feasibility of screening tools for mild cognitive impairment (MCI) and dementia among the elderly at primary healthcare level. STUDY DESIGN: A review of articles was performed. METHODS: A search strategy was used by using electronic bibliographic databases including PubMed, Embase and CENTRAL for published studies and reference list of published studies. The articles were exported to a bibliographic database for further screening process. Two reviewers worked independently to screen results and extract data from the included studies. Any discrepancies were resolved and confirmed by the consensus of all authors. RESULTS: There were three screening approaches for detecting MCI and dementia - screening by a healthcare provider, screening by a self-administered questionnaire and caretaker informant screening. Montreal Cognitive Assessment (MoCA) was the most common and preferable tool for MCI screening (sensitivity [Sn]: 81-97%; specificity [Sp]: 60-86%), whereas Addenbrooke's Cognitive Examination (ACE) was the preferable tool for dementia screening (Sn: 79-100%; Sp: 86%). CONCLUSION: This systematic review found that there are three screening approaches for detecting early dementia and MCI at primary health care. ACE and MoCA are recommended tools for screening of dementia and MCI, respectively.

Changing trends in anti-psychotic prescription pattern in Pakistan.

BACKGROUND AND OBJECTIVE: This study was designed to identify the changing trends in Anti-psychotic prescription pattern in Pakistan. It was part of the research project Research on East Asian Psychotropic Prescription Pattern (REAP) carried out to identify the prescription patterns of schizophrenic patients in different countries located in Asia.Our objective was to assess the trend and change of psychotropic drug prescriptions for patients with schizophrenia. METHODS: The design of the study was quantitative and of descriptive epidemiology. This study was carried out from 30th March 2017. Data was collected on a unified protocol by the Psychiatrists from Pakistan. Three (3) centers i.e., Lahore, Karachi and Islamabad provided the data. Indoor and outdoor cases with Schizophrenia were recruited. A web based recording system for collection of data done at Taipei Taiwan, and statistical analysis was performed and transferred to all participating centers including Pakistan. RESULTS: The main findings of the study were that majority of the patients were prescribed antipsychotic poly pharmacy drug. It was also found that Anxiolytics, anti-depressants and Anti-parkinsonian drugs were also co-prescribed. CONCLUSION: It was concluded that antipsychotic poly pharmacy along with Anxiolytics, anti-depressants and Anti-parkinsonian drugs were prescribed to patients with schizophrenia in Pakistan.

Effect of pH on rheotaxis of bull sperm using microfluidics.

The aim of the present research is to study the effect of pH values on the sperm rheotaxis properties. Semen collected from bulls was diluted with SOF medium (1:10). pH of the medium was adjusted using a digital pH meter to the following pH values: 6.0, 6.2, 6.4, 6.4, 6.8, 7.0. All kinetic parameters of sperm (n = 3,385) were determined through a computer-assisted sperm analysis (CASA) system using microfluidic devices with controlled flow velocity. The following parameters were determined: total motility (TM%), positive rheotaxis (PR%), straightline velocity (VSL, µm/s), average path velocity (VAP, µm/s), linearity (LIN, as VSL/VCL, %), beat cross-frequency (BCF, Hz) and curvilinear velocity (VCL, µm/s). Nitric oxide, calcium and potassium were estimated in semen at different pH values. To confirm the effect of nitric oxide and K+ , we used sodium nitroprusside (an NO donor) and KCL as (a K+ donor) to see their effect on sperm PR%. The results showed no difference in TM% at pH (6-7). The PR% was the lowest at pH 6 and 7. The best parameters for the PR% were at pH 6.4-6.6. The concentration of Ca+2 did not change at different pH values. The mean NO values decreased with the increase of pH; however, the mean values of K+ increased with the increase of pH. Addition of high concentration of NO and K+ to the semen media at fixed pH level had a negative effect on TM% and PR%. In conclusion, the bull sperm had the best rheotaxis properties at pH 6.4-6.6 and sensitive to the change of seminal NO and K+ .

Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor.

The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM.

Effect of growth differentiation factor-9 (GDF-9) on the progression of buffalo follicles in vitrified-warmed ovarian tissues.

To improve the reproductive performance of water buffalo to level can satisfy our needs, the mechanisms controlling ovarian follicular growth and development should be thoroughly investigated. Therefore, in this study, the expressions of growth differentiation factor-9 (GDF-9) in buffalo ovaries were examined by immunohistochemistry, and the effects of GDF-9 treatment on follicle progression were investigated using a buffalo ovary organ culture system. Frozen-thawed buffalo ovarian follicles within slices of ovarian cortical tissue were cultured for 14 days in the presence or absence of GDF-9. After culture, ovarian slices were fixed, sectioned and stained. The follicles were morphologically analysed and counted. Expression pattern of GDF-9 was detected in oocytes from primordial follicles onwards, besides, also presented in granulosa cells. Moreover, GDF-9 was detected in mural granulosa cells and theca cells of pre-antral follicles. In antral follicles, cumulus cells and theca cells displayed positive expression of GDF-9. In corpora lutea, GDF-9 was expressed in both granulosa and theca lutein cells. After in vitro culture, there was no difference in the number of primordial follicles between cultured plus GDF-9 and cultured control that indicated the GDF-9 treatment has no effect on the primordial to primary follicle transition. GDF-9 treatment caused a significant decrease in the number of primary and secondary follicles compared with controls accompanied with a significant increase in pre-antral and antral follicles. These results suggest that a larger number of primary and secondary follicles were stimulated to progress to later developmental stages when treated with GDF-9. Vitrification/warming of buffalo ovarian tissue had a little remarkable effect, in contrast to culturing for 14 days, on the expression of GDF-9. In conclusion, treatment with GDF-9 was found to promote progression of primary follicle that could provide an alternative approach to stimulate early follicle development and to improve therapies for the most common infertility problem in buffaloes (ovarian inactivity).

Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial.

AIM: To test our hypothesis that initiating therapy with a combination of agents known to improve insulin secretion and insulin sensitivity in subjects with new-onset diabetes would produce greater, more durable reduction in glycated haemoglobin (HbA1c) levels, while avoiding hypoglycaemia and weight gain, compared with sequential addition of agents that lower plasma glucose but do not correct established pathophysiological abnormalities. METHODS: Drug-naïve, recently diagnosed subjects with type 2 diabetes mellitus (T2DM) were randomized in an open-fashion design in a single-centre study to metformin/pioglitazone/exenatide (triple therapy; n = 106) or an escalating dose of metformin followed by sequential addition of sulfonylurea and glargine insulin (conventional therapy; n = 115) to maintain HbA1c levels at <6.5% for 2 years. RESULTS: Participants receiving triple therapy experienced a significantly greater reduction in HbA1c level than those receiving conventional therapy (5.95 vs. 6.50%; p < 0.001). Despite lower HbA1c values, participants receiving triple therapy experienced a 7.5-fold lower rate of hypoglycaemia compared with participants receiving conventional therapy. Participants receiving triple therapy experienced a mean weight loss of 1.2 kg versus a mean weight gain of 4.1 kg (p < 0.01) in those receiving conventional therapy. CONCLUSION: The results of this exploratory study show that combination therapy with metformin/pioglitazone/exenatide in patients with newly diagnosed T2DM is more effective and results in fewer hypoglycaemic events than sequential add-on therapy with metformin, sulfonylurea and then basal insulin.

Lowering plasma glucose concentration by inhibiting renal sodium-glucose cotransport.

Maintaining normoglycaemia not only reduces the risk of diabetic microvascular complications but also corrects the metabolic abnormalities that contribute to the development and progression of hyperglycaemia, that is insulin resistance and beta-cell dysfunction. Progressive beta-cell failure, in addition to side effects associated with many current antidiabetic agents, for example hypoglycaemia and weight gain, presents major obstacles to the achievement of the recommended goal of glycaemic control in patients with type 2 diabetes mellitus (T2DM). Thus, novel effective therapies are needed for optimal glucose control in subjects with T2DM. Most recently, specific inhibitors of the renal sodium-glucose cotransporter 2 (SGLT2) have been developed to produce glucosuria and lower the plasma glucose concentration. Because of the iR unique mechanism of action, which is independent of insulin secretion and insulin action, these agents are effective in lowering the plasma glucose concentration in all stages of the disease and can be combined with all other antidiabetic agents. In this review, we will summarize the available data concerning the mechanism of action, efficacy and safety of this novel class of antidiabetic agents.

Expression pattern of vascular endothelial growth factor in canine folliculogenesis and its effect on the growth and development of follicles after ovarian organ culture.

In this study, the expressions of VEGF in dog follicles were detected by immunohistochemistry and the effects of VEGF treatment on the primordial to primary follicle transition and on subsequent follicle progression were examined using a dog ovary organ culture system. The frozen-thawed canine ovarian follicles within slices of ovarian cortical tissue were cultured for 7 and 14 days in presence or absence of VEGF. After culture, the ovaries were fixed, sectioned, stained and counted for morphologic analysis. The results showed that VEGF was expressed in the theca cells of antral follicles and in the granulosa cells nearest the oocyte in preantral follicle but not in granulosa cells of primordial and primary follicles; however, the VEGF protein was expressed in CL. After in vitro culture, VEGF caused a decrease in the number of primordial follicles and concomitant increase in the number of primary follicles that showed growth initiation and reached the secondary and preantral stages of development after 7 and 14 days. Follicular viability was also improved in the presence of VEGF after 7 and 14 days in culture. In conclusion, treatment with VEGF was found to promote the activation of primordial follicle development that could provide an alternative approach to stimulate early follicle development in dogs.

Primary hyperparathyroidism: a case report.

Primary hyperparathyroidism results from the excessive secretion of PTH and typically produces frank hypercalcaemia. With the advent of multiphasic screening of serum chemistries, it has been recognized that primary hyperparathyroidism is not an uncommon disorder. Here, a 32 years old lady with burning to colicky recurrent upper abdominal pain, polyuria, polydipsia associated with anorexia, dyspepsia, generalized body ache, joint pain, constipation and weight loss has been described. An initial abdominal ultrasound was performed at hospital and revealed features of cholelithiasis and bilateral nephrocalcinosis. Serum biochemistries revealed that her serum calcium was 12.60mg/dl, serum PTH was 222.80ng/dl, serum creatinine was 0.90mg/dl, 99 Tc-sestamibi scanning for parathyroid evaluation revealed features suggestive of parathyroid adenoma adjoining the lower pole of right lobe of thyroid gland. Bone densitometry of femur and spine by DEXA showed osteoporosis with T score value <-3.5 SD. Right hemithyroidectomy with parathyroid adenoma excision was performed. Patient was closely monitored. Serum calcium and parathyroid hormone levels were markedly reduced near to the normal range within two weeks of surgery. Following five months after surgery, serum PTH was 29.59ng/dl, six months after surgery serum calcium was 9.2mg/dl. Patient is now in good physical condition and under regular follow up.

Relationship between patient satisfactions with diabetes care and treatment.

BACKGROUND: Measurement of treatment satisfaction in diabetes is important as it has been shown to be associated with positive outcomes, reduced disease cost and better health. AIM: The aim of this study was to assess the relationship between treatment satisfaction of diabetes patients and socioeconomic, clinical, medication adherence and health-related factors in Qatar. DESIGN: This is a cross-sectional study. SETTING: The survey was carried out in primary health care centers and hospitals from April 2010 to May 2011. SUBJECTS: Of a total of 3000 diabetic patients, 2582 patients gave their consent to take part in the study, with a response rate of 86.1%. MATERIALS AND METHODS: The Diabetes Treatment Satisfaction Questionnaire was used to measure the patient satisfaction. The modified Morisky Medication Adherence was used to measure medication taking behavior. A multivariate stepwise linear regression model was performed to identify factors independently associated with patients' satisfaction instrument. RESULTS: Of the studied patients, majority of the diabetes patients were Qataris (61.2%), married (86.1%), above secondary education (46.9%) and unemployed (28.6%). Diabetes patients who had professional jobs (3.97 ± 0.65; P = 0.009) and those who were staying alone had a significantly higher treatment satisfaction score (4.01 ± 0.64; P = 0.001) compared with the other patients. Patients who were taking tablets were significantly more satisfied with treatment (4.08 ± 0.60; P < 0.001). Diabetes patients of primary health care centers (3.96 vs. 3.80; P < 0.001) were more satisfied with treatment than patients visiting hospitals. Multivariate regression analysis revealed that age of the patient (P < 0.001), expatriates (P = 0.023), patients visiting hospitals (P < 0.001), treatment with insulin (P < 0.001) and any diabetes complications (P < 0.001) were significantly less satisfied with the treatment. CONCLUSION: The study findings revealed that patient satisfaction was positively associated with sociodemographic variables like high income, employment, married individuals and those with higher levels of education. We found a lower treatment satisfaction in patients with diabetes-related complications and insulin treatment.

Insulin vs GLP-1 analogues in poorly controlled Type 2 diabetic subjects on oral therapy: a meta-analysis.

AIM: To compare insulin and GLP-1 analogues therapy on glycemic control in poorly controlled Type 2 diabetes (T2DM) subjects failing on oral therapy. METHODS: The electronic database PubMed was systematically searched for randomized controlled trial (RCT) with duration >16 weeks comparing the addition of insulin therapy vs glucagon-like peptide (GLP-1) analogues in poorly controlled T2DM subjects on oral therapy. RESULTS: We identified 7 RCT with 2199 patients of whom 1119 were assigned to insulin therapy and 1080 received a GLP-1 analogue. Both insulin and GLP-1 analogues were effective in lowering glycated hemoglobin (HbA(1c)) with no statistically significant difference between the mean decreases in HbA(1c). However, insulin was more effective than GLP-1 analogues in lowering the fasting plasma glucose concentration, while GLP-1 agonists were more effective in lowering the postprandial glucose concentration. Insulin therapy was associated with weight gain while GLP-1 analogues consistently caused weight loss and the difference between the mean change in body weight between the two therapies was highly statistically significant. Despite a similar decrease in HbA(1c), the risk of hypoglycemia was 35% lower (p=0.001) with GLP-1 therapy compared to insulin. Compared to insulin, GLP-1 analogues caused a significant decrease in systolic blood pressure and were associated with greater rate of gastrointestinal adverse events. CONCLUSION/INTERPRETATION: In poorly controlled T2DM subjects on oral therapy, GLP-1 analogues and insulin are equally effective in lowering the HbA(1c). However, GLP-1 analogues have additional non-glycemic benefits and lower risk of hypoglycemia. Thus, GLP-1 analogues should be considered as a treatment option in this group of diabetic individuals.

Early metabolic defects in Arab subjects with strong family history of Type 2 diabetes.

AIMS AND OBJECTIVE: It is widely accepted that the genetic make-up of the subject plays a pivotal role in the development of insulin resistance and ß cell failure. The objective of this study was to examine whether the same or distinct genetic backgrounds contribute to the development of insulin resistance and ß cell failure. METHODS: We examined insulin sensitivity and ß cell function in lean normal glucose tolerance subjects from 3 multigeneration Arab families. Families 1 and 2 had strong history of Type 2 diabetes (T2DM), while no member of family 3 had T2DM. RESULTS: Subjects in family 1 manifested increased basal plasma free fatty acid (FFA) concentration and impaired suppression of plasma FFA during the OGTT compared to subjects in family 3. Subjects in family 2 had comparable fasting plasma FFA and suppression of plasma FFA during the OGTT to family 3. Both the absolute plasma glucose concentrations, and incremental area under the plasma glucose curve (ΔG0-120) during the OGTT were comparable in subjects of families 1 and 2, and were decreased in subjects of family 3. Whole body and muscle insulin sensitivity were comparable in subjects from families 2 and 3, and both were significantly decreased in subjects of family 1. Beta cell function was comparable in subjects of families 1 and 3 and was significantly decreased in subjects of family 2. CONCLUSION: These results demonstrate that distinct genetic background contributes to the development of insulin resistance and ß cell dysfunction in Arab individuals.

Detection of Enterobacteriaceae in cerebrospinal fluid fluid of neonates with meningitis from tertiary care hospitals.

OBJECTIVE: This study aimed to determine the bacteriological profile of childhood acute bacterial meningitis in Pakistan. PATIENTS AND METHODS: The study included a total of 100 children aged between 1 month and 5 years, who were admitted with a diagnosis of meningitis based on clinical findings and positive cerebrospinal fluid (CSF) tests. Out of the 100 CSF samples collected, 21 isolates were confirmed to contain Enterobacteriaceae. The most prevalent Enterobacteriaceae species were Pseudomonas (n=8, 38.09%), Klebsiella (n=4, 19.04%), E. coli (n=4, 19.04%), and Acinetobacter (n=4, 19.04%), while Citrobacter (n=1, 4.76%) was less common. Antibiotic susceptibility patterns were analyzed for these isolates. RESULTS: Pseudomonas (n=8) exhibited 25% resistance to cefepime and 38% resistance to imipenem. Klebsiella (n=4) showed 75% resistance to imipenem. Acinetobacter (n=4) demonstrated 50% resistance to imipenem, along with varying resistance to cefepime, amikacin, ciprofloxacin, and gentamicin. E. coli (n=4) showed 0% resistance to imipenem and amikacin. However, Citrobacter (n=1) showed 0% resistance to ciprofloxacin, aztreonam, gentamicin, amikacin, levofloxacin, and cefepime. Acute bacterial meningitis primarily affects children under 1 year of age. CONCLUSIONS: CSF culture revealed that Gram-negative bacteria, specifically Pseudomonas spp., were the predominant pathogens in this family based on Pakistani data.

Synthesis, characterization, anti-mycobacterial activity and in silico study of new 2,5-disubstituted-1,3,4-oxadiazole derivatives.

A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value -8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Chromatin occupancy of transcription factor 7-like 2 (TCF7L2) and its role in hepatic glucose metabolism.

AIMS/HYPOTHESIS: The mechanisms by which transcription factor 7-like 2 (TCF7L2) regulates the pathways that are important in the pathogenesis of type 2 diabetes are unknown. We therefore examined the role of TCF7L2 in hepatic glucose production (HGP) in vitro and characterised the whole-genome chromatin occupancy of TCF7L2 in hepatocytes. METHODS: We investigated the effect of TCF7L2 silencing and overexpression on HGP from gluconeogenic precursors and used chromatin-immunoprecipitation (ChIP) combined with massively parallel DNA sequencing (ChIP-Seq) to investigate the DNA binding patterns of TCF7L2 across the whole genome. RESULTS: Silencing of TCF7L2 induced a marked increase in basal HGP, which was accompanied by significant increases in the expression of the gluconeogenic genes Fbp1, Pck1 and G6pc. Overexpression of Tcf7l2 reversed this phenotype and significantly reduced HGP. TCF7L2 silencing did not affect the half-maximal inhibitory concentration of insulin or metformin, but HGP remained elevated in TCF7L2-silenced cells due to the increased baseline HGP. Using ChIP-Seq, we detected 2,119 binding events across the genome. Pathway analysis demonstrated that diabetes genes were significantly over-represented in the dataset. Our results indicate that TCF7L2 binds directly to multiple genes that are important in regulation of glucose metabolism in the liver, including Pck1, Fbp1, Irs1, Irs2, Akt2, Adipor1, Pdk4 and Cpt1a. CONCLUSIONS/INTERPRETATION: TCF7L2 is an important regulator of HGP in vitro and binds directly to genes that are important in pathways of glucose metabolism in the liver. These data highlight the possibility that TCF7L2 may affect fasting and postprandial hyperglycaemia in carriers of at-risk TCF7L2 genetic polymorphisms.