Disseminated malignant phyllodes: Presentation after a decade.

Phyllodes tumors are rare biphasic fibroepithelial lesions of the breast and account for 0.3%-0.5% of primary breast tumors. Malignant phyllodes tumor has a 10%-26% risk of distant metastasis. The most common site of metastasis is lungs followed by bone and soft tissue. This is a rare case of a 42-year-old female with a previous history of malignant phyllodes tumor breast. She presented after 10 years with metastases to multiple sites including lung, abdominal wall, retroperitoneum, bone, and brain. These tumors have a poor overall survival. Accurate diagnosis and aggressive management of malignant phyllodes tumors can help in effective treatment at diagnosis and for close follow-up of the patients.

Autoantibody Positivity Has No Impact on Histological Parameters in Nonalcoholic Fatty Liver Diseases.

Objectives: Previous reports on association of autoantibodies with histological severity in nonalcoholic fatty liver disease (NAFLD) have revealed inconsistent results. Therefore, this study was undertaken to find the impact of autoantibodies on histological severity of NAFLD. Methods: All cases with histological diagnosis of NAFLD during January 2016 to January 2021 were included in the study. Laboratory parameters were recorded, and histological assessment was done. The positivity of autoimmune markers was defined as presence of either antinuclear antibody (ANA; titer >1:80), anti-smooth muscle antibodies (ASMA), or anti-liver-kidney-microsomal antibodies (LKM-1; titer >1:40). Serum levels of CK18 - M30 and PIIINP were evaluated to assess the subtle changes in necroinflammatory activity and fibrosis in the liver. Results: Autoantibodies were present in 281/683 (41.1%, 95% CI 37.4-44.9) patients. ANA, ASMA, ANA + ASMA was seen in 20.9% (95% CI 17.9-24.2); 14.5% (95% CI 11.9-17.4); and 5.7% (95% CI 4.1-7.7) cases, respectively. No significant difference was noted between the two groups in terms of age and metabolic tests. No significant difference was noted in the histological parameters between groups with autoantibodies positivity and no-positivity. Mean value of CK18-M30 between cases with negative autoantibody; ANA positivity; ASMA positivity; and combined positivity of autoantibody were 178.2 ± 81.8, 161.6 ± 63.7, 153.2 ± 70.3 and 169.8 ± 42.9, respectively (P = 0.57). However, CK18-M30 and PIIINP showed a rising trend with NAFL, NASH, NASH + AIH (P < 0.001). Conclusions: Autoantibodies noted in 41% NAFLD cases. No significant necroinflammatory activity or fibrosis associated with presence of antibodies in NAFLD cases. However, CK-18-M30 showed a rising trend from NAFL to NASH to NASH + AIH.

Biphasic squamoid alveolar renal cell carcinoma: A rare entity with an even rarer presentation as cutaneous metastases - A case report.

Biphasic squamoid alveolar renal cell carcinoma (BSARCC) is a newly emerging distinct and rare morphologic variant of renal cell carcinoma (RCC). Morphological, immunohistochemical, and molecular data have shown that BSARCC is closely related to papillary RCC type 1. We report a case of Biphasic squamoid alveolar renal cell carcinoma with a rare presentation as cutaneous metastases. This variant tends to show an aggressive behavior. Hence, accurate histopathological diagnosis can help in effective treatment and for close follow-up of the patients.

Plasmodium falciparum Malaria Susceptibility and Severity: Influence of MyD88-Adaptor-Like Gene (rs8177374) Polymorphism.

Background: MyD88-adapter-like (MAL), as an essential adapter protein for a variety of TLRs (Toll-like receptors), modulates the inflammatory response. Many infectious illnesses are influenced by single nucleotide polymorphisms (SNPs) that modify MAL function. We aimed to examine the influence of the MAL rs8177374 polymorphism on Plasmodium falciparum malaria susceptibility and severity. Patients and Methods: Samples from 141 Plasmodium falciparum malaria patients and 147 healthy controls were used in the study. Patients were subdivided into mild and severe groups based on their clinical results, as defined by the World Health Organization (WHO). Genotypes for MAL rs8177374 were identified by allele-specific PCR technique, and TNF-alpha and IL-12 levels were measured using ELISA. Results: The MAL rs8177374 (CT) genotype is associated with an increased risk of malaria (OR: 2.52; 95% CI: 1.44-4.41). Furthermore, the CT and TT genotypes gave considerable protection against severe malaria (OR: 0.07; 95% CI: 0.03-0.19 and OR: 0.03; 95% CI: 0.007-0.1 respectively). And the T allele was linked to a higher risk of malaria (OR: 1.7; 95% CI: 1.18-2.5), while protecting patients from severe malaria (OR: 0.135; 95% CI: 0.07-0.3). Mutants (CT and TT) have greater TNF-alpha and IL-12 levels compared to wild-type (CC). Conclusion: Malaria risk is linked to single nucleotide polymorphism in the MyD88-adaptor-like gene. People with the MAL rs8177374 mutant variant may be less likely to get severe malaria.

The Psychological and Economic Impacts of Caregiving on Family Carers for People with Probable Dementia in Rural South India.

Informal carers play a vital role in the care and well-being of older people with dementia. This article examines the psychological and economic impacts caregiving has on carers of people with suspected dementia and the mechanisms by which they cope with challenges. A mixed-method design was adopted. A baseline survey of 123 older people was undertaken in a resource-poor setting in Kerala, India, using Addenbrooke's Cognitive Examination - Malayalam Version (ACE-m) to identify those with probable dementia. This was followed by in-depth interviews with ten carers of those identified as having cognitive impairment. The data were later transcribed and thematically analysed using N-Vivo to identify main concepts and themes. Analysis of the in-depth interviews with carers revealed that dementia was often interpreted as a 'second childhood', but that this conceptualisation aided carers to cope better. Anger and irritation were the commonly expressed psychological reactions which got accentuated by lack of reciprocation of emotion on the part of care recipient. Government support through social security measures and medical care, along with traditional social practises, helped carers to tide over care expenses. These support systems lessened the psychological and economic impacts of caring. Misconstruction of the disease nature, for example by considering it a normal part of ageing, also seem inadvertently to have helped in coping with care requirements, although this comes at a cost of lower than optimal healthcare access for older people with cognitive impairment.

Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial).

IMPORTANCE: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. OBJECTIVE: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. DESIGN, SETTING AND PARTICIPANTS: A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. INTERVENTION: One group received COPLA with SMT (n=200), and another group received SMT only (n=200). MAIN OUTCOME MEASURES: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. RESULTS: The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. CONCLUSION AND RELEVANCE: Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. TRIAL REGISTRATION NUMBER: NCT04425915.

Nigella sativa as a promising intervention for metabolic and inflammatory disorders in obese prediabetic subjects: A comparative study of Nigella sativa versus both lifestyle modification and metformin.

AIM: This study aimed at evaluating the effect of Nigella sativa (NS) on anthropometric, metabolic and inflammatory parameters and examining its related molecular mechanisms in obese prediabetic individuals as compared to both lifestyle modification (LM) and Metformin (Met). METHODS: This study included 117 obese prediabetic subjects who were randomized into LM group which followed controlled diet and exercise regimen, metformin group received metformin 500 mg tablets twice daily and NS group received NS oil soft gelatin capsules 450 mg twice daily. Anthropometric (weight, BMI), glycemic, lipid, inflammatory parameters and genetic expressions of Sirtuin-1 (SIRT1) and p53 genes were assessed before and six months after interventions. RESULTS: Post-intervention pairwise comparison revealed that, NS was statistically similar to metformin in improving anthropometric, glycemic parameters and SIRT1 gene expression. There was non-significant difference between LM and NS regarding their effects on anthropometric and most of glycemic parameters. Lifestyle modification group showed significantly higher HOMA-B and SIRT1 expression than NS and metformin. Nigella sativa improved lipid panel and significantly reduced TNF-α level and Castelli risk index-I as compared to other interventions. CONCLUSION: Nigella sativa uniquely improved lipid panel and significantly suppressed inflammation. Therefore, Nigella sativa may represent a promising intervention for obese prediabetic subjects. Clinicaltrial.gov ID: NCT03925714.

Cognitive effects of the GSK-3 inhibitor "lithium" in LPS/chronic mild stress rat model of depression: Hippocampal and cortical neuroinflammation and tauopathy.

Low-dose repeated lipopolysaccharide pre-challenge followed by chronic mild stress (LPS/CMS) protocol has been introduced as a rodent model of depression combining the roles of immune activation and chronic psychological stress. However, the impact of this paradigm on cognitive functioning has not been investigated hitherto. METHODS: This study evaluated LPS/CMS-induced cognitive effects and the role of glycogen synthase kinase-3ß (GSK-3ß) activation with subsequent neuroinflammation and pathological tau deposition in the pathogenesis of these effects using lithium (Li) as a tool for GSK-3 inhibition. RESULTS: LPS pre-challenge reduced CMS-induced neuroinflammation, depressive-like behavior and cognitive inflexibility. It also improved spatial learning but increased GSK-3ß expression and exaggerated hyperphosphorylated tau accumulation in hippocampus and prefrontal cortex. Li ameliorated CMS and LPS/CMS-induced depressive and cognitive deficits, reduced GSK-3ß over-expression and tau hyperphosphorylation, impeded neuroinflammation and enhanced neuronal survival. CONCLUSION: This study draws attention to LPS/CMS-triggered cognitive changes and highlights how prior low-dose immune challenge could develop an adaptive capacity to buffer inflammatory damage and maintain the cognitive abilities necessary to withstand threats. This work also underscores the favorable effect of Li (as a GSK-3ß inhibitor) in impeding exaggerated tauopathy and neuroinflammation, rescuing neuronal survival and preserving cognitive functions. Yet, further in-depth studies utilizing different low-dose LPS challenge schedules are needed to elucidate the complex interactions between immune activation and chronic stress exposure.

Effect of Tricalcium Phosphate and Calcium Sucrose Phosphate on the Inhibition of Streptococcus mutans: An In Vivo Study.

AIM: To determine the efficacy of tricalcium phosphate (TCP) and calcium sucrose phosphate (CSP) on the inhibition of Streptococcus mutans (SM). MATERIALS AND METHODS: Thirty healthy children between 13 and 18 years of age were divided into two groups of 15 each; Group I receiving TCP-containing cream and Group II receiving calcium sucrose phosphate-containing cream. On the first day of the study, 30 minutes after breakfast, baseline plaque samples were taken from the buccal surface of first mandibular permanent molar using a sterile wedge which was immediately transferred to sterile container containing 1 mL of saline, and were subjected to microbiological examination. On the following days, both the creams were applied to the respective groups. On the 16th day, plaque samples were collected from the same site, and colony forming units were recorded using agar plate as a culture medium. RESULTS: The mean of S. mutans count before application of TCP-containing paste was 16.27 cfu per mL and before calcium sucrose phosphate-containing paste was 15.33 cfu per mL. The mean after application of TCP-containing paste and calcium sucrose phosphate-containing paste was 3.53 and 9.87 cfu per mL, respectively. And, there was a statistically significant difference found within the groups. CONCLUSION: Both TCP and CSP have an inhibitory effect on S. mutans. CLINICAL SIGNIFICANCE: This can be an effective preventive tool for children with high caries risk and even for special child. Both TCP and CSP deposit the mineral reservoir in plaque and saliva; it may help resist the future cariogenic challenges.

ESR1 gene polymorphism (rs827421) as a potential genetic marker for constitutional delay of growth and puberty in Egyptian adolescents.

Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress. It is the most common form of delayed puberty in both genders. The genetic director of CDGP is ill-understood despite the positive family history result noted in those patients. The current study aimed at assessing the role of estrogen receptor 1 (ESR1) gene variant (rs827421) in Egyptian adolescents with CDGP. A cross-sectional study with follow-up part was carried out on 6760 children aged 4 to15 years. The study focused generally on children aged 13-15 years in order to evaluate the prevalence of delayed puberty in relation to all ages in general and to their peers in specific. Assessment of serum TSH, FSH, and LH was conducted on all participants, along with the measurement of serum-free testosterone for males and estradiol for females. Genotyping of ESR1 (rs827421) was done to all subjects through the use of TaqMan discrimination assay by real-time PCR. ESR1 (rs827421) GG genotype and G allele were significantly dominant among CDGP adolescents in comparison with controls (OR = 25.67 and 6.90). As regards follow-up of testicular size, AA genotype was significantly associated with increased size in the right and left testis compared to other genotypes (P = 0.021 and 0.006, respectively). Moreover, AA genotype showed significantly higher Tanner stage in both males and females in comparison with other genotypes. Serum estradiol level was significantly higher in AA genotype group than other genotypes groups. ESR1 gene polymorphism can be considered a potential genetic marker for CDGP in both sexes in a sample of Egyptian adolescents.

Granular cell ameloblastoma - A rare entity with recurrence after 48 years.

A 64-year-old female with complaints of swelling right preauricular region was referred to our tertiary cancer center with fine-needle aspiration cytology (FNAC) report of mucoepidermoid carcinoma and radiological differential of malignant salivary gland neoplasm and sarcoma. On examination, there was a mass over her right parotid region Clinical diagnosis was malignant salivary gland neoplasm. Slide review of FNAC was inconclusive. Biopsy was done. Histopathology showed neoplasm comprising of nests of cells with abundant granular eosinophilic cytoplasm with focal area showing peripherally arranged columnar cells with palisading. On enquiry, the patient gave a history of surgery of right mandible 48 years back. Correlating histopathology and clinical history, a diagnosis of granular cell ameloblastoma was rendered. Radiological evaluation showed a solid-cystic lesion in the right masticator space. Right mandible showed only part of head of mandible consistent with previous surgery. Radical surgery was done. Final report confirmed the biopsy diagnosis.

Risk factors for severe acute malnutrition among children aged 6-59 months: A community-based case-control study from Vellore, Southern India.

BACKGROUND: Malnutrition plays an important role in the economic burden of society as well as the country. This study aimed to identify the various risk factors and determinants of severe acute malnutrition (SAM) as defined by WHO growth reference standards in children aged 6 months to 59 months living in Vellore. METHODS: A community-based case-control study matched for age (±2months), gender and location was done among the children of the age group 6- 59 months residing in both rural and urban Vellore. Children of age group 6-59 months with SAM according to WHO definition, i.e., weight for height of less than -3SD with or without nutritional oedema were classified as cases. Children with weight-for-height z-score more than -1 SD and MUAC ≥13.5cms were classified as controls. With 2 controls per case, the required sample size was 54 cases and 108 controls. A questionnaire used to identify the risk factors including dietary intake. Uni-variate and multivariate analysis was done to generate an odds ratio and 95% confidence interval for the risk factors. RESULTS: Majority of the cases 64.8% and 50% of the controls belonged to low SES. After adjusting all confounders, Severe Acute Malnutrition was significantly associated with birth weight <2.499kg [AOR- 8.95 (95% CI: 2.98-26.85)], not exclusively breastfed for 6 months [AOR 4.67 (95% CI: 1.72-12.65)], inadequate calorie intake [AOR 8.09 (95% CI: 3.15-20.82)] and mother being underweight [AOR 6.87 (95% CI: 1.92-24.55)]. CONCLUSION: Programs should be implemented to reduce the poor nutritional status of young girls and women in the reproductive age group. The importance of exclusive breastfeeding for the first six months, the time of weaning and appropriate feeding practice for the child should be emphasized to postnatal mothers during their hospital visits.

Effects of lithium on cytokine neuro-inflammatory mediators, Wnt/ß-catenin signaling and microglial activation in the hippocampus of chronic mild stress-exposed rats.

Microglial in vivo production of pro-inflammatory cytokines is central to the pathogenesis of multiple neurological disorders including depression, with a rising role of Wnt/ß-catenin signaling as potential regulator of microglia-mediated neuro-inflammation. This study aimed at investigating the hippocampal expression of the Wnt/ß-catenin pathway in chronic mild stress (CMS)-exposed rats and the effects of Lithium (Li) on the expression of this pathway as a method to identify a plausible link between exposure to chronic stress, microglial activation, and neuroinflammation. METHODS: The effect of chronic administration of Li was investigated on behavioral changes, hippocampal expression of Wnt-DVL-GSK3ß-ß-catenin signaling pathway, and microglial activation in CMS-exposed male Wistar rats RESULTS: CMS induced a depressive-like behavior associated with increased pro-inflammatory microglial activation and reduced hippocampal expression of the Wnt/ß-catenin signaling pathway. Chronic Li treatment ameliorated stress induced-behavioral changes, reduced microglial activation and enhanced the hippocampal expression of Wnt/ß-catenin signaling pathway. CONCLUSION: This work highlights that Li-induced inhibition of GSK-3ß with subsequent accumulation of ß-catenin could impede pro-inflammatory microglia activation which is a key pathological hallmark associated with depression. Wnt/ß-catenin signaling represents a promising therapeutic target, not only for alleviation of depression, but also for a wide array of neurological disorders.

Strategies for home nutritional support in dementia care and its relevance in low-middle-income countries.

Older people suffering from dementia are prone to develop malnutrition. Ensuring adequate nutrition among such patients has always been a challenge for the carers due to the pathological and chronic nature of the disease. In this article, the author tries to analyze the use of five different strategies in providing adequate nutrition for such patients in their own homes by the carers using a narrative literature review method. The strategies include nutrition screening and assessment, training and education program for the caregiver, mealtime environment and routine modification, provision of nutritional supplements, and role of artificial nutrition and hydration (ANH). An attempt was made to critically engage the readers while exploring the feasibility and challenges involved in implementing such strategies in resource-poor settings like low-middle-income countries. The article concludes that the first four strategies should be used in tandem to prevent the risk of malnutrition. It does not recommend ANH and concludes that it does not bring in any added benefit and may worsen the quality of life.

Carvedilol Combined With Ivabradine Improves Left Ventricular Diastolic Dysfunction, Clinical Progression, and Survival in Cirrhosis.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis. PATIENTS AND METHODS: THR was defined as heart rate reduction to 55 to 65 beats per minute. Of 260 patients with cirrhosis, 189 (72%) with LVDD were randomized to THR [group (Gr.)A; n=94; carvedilol±ivabradine)] or standard care (Gr.B; n=95; no ß-blockers) and followed for 12 months. RESULTS: In Gr.A, THR was achieved at 4 weeks in 88 (93%) patients (responders, R): 48 (61.5%) with carvedilol alone and 40 (86.9%) of 46 patients with additional ivabradine. In Gr.A, LVDD reversed in 16 (20.5%) and improved from grade 2 to 1 in 34 (35.4%)], whereas in Gr.B, it progressed from grade 1 to 2 in 10 (10.5%) patients. At 12 months, 21 (11.1%) patients died, 6 (14%) in Gr.A and 15 (18%) in Gr.B (P=0.240), but no mortality was seen in those who had persistent THR at 1 year (n=78; P=0.000). In multivariate analysis, model for end-stage liver disease [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.22-2.75; P=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28; 95% CI, 1.23-2.42; P=0.048) predicted 1-year mortality. Nonresponders had an increased mortality risk (HR, 1.3; 95% CI, 1.2-1.8; P=0.046) independent of age, gender, and baseline model for end-stage liver disease. Levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone were reduced (P<0.01) in responders. More patients in Gr.B developed acute kidney injury (odds ratio, 4.2; 95% CI, 2.8-10.5; P=0.027) and encephalopathy (odds ratio, 6.6; 95% CI, 1.9-9.7; P=0.040). CONCLUSIONS: Ivabradine combined with carvedilol improves LVDD, achieves THR more often and reduces risk of encephalopathy, acute kidney injury with improved survival in patients with cirrhosis.

Potentially inappropriate medications prescribed for older persons: A study from two teaching hospitals in Southern India.

BACKGROUND: Potentially inappropriate medications (PIMs) are a major concern in geriatric care. The primary objective of our study was to assess the prevalence of PIMs prescribed for older persons attending outpatient setting of two teaching hospitals in Kerala state in South India, where the population is aging. MATERIALS AND METHODS: A cross-sectional study was carried out in two teaching hospitals in Kerala. Four hundred consecutive outpatient medical records of patients aged 65 years and above were selected. The current medications of the patients were analyzed to identify PIMs by the Beers criteria 2015. Polypharmacy and hyperpolypharmacy were defined as 5-9 medications and ≥10 medications, respectively. Chi-square test was done to identify demographic variables and the pattern of health-care facility use associated with PIM prescription. Binary logistic regression was performed to adjust for confounding associations. RESULTS: The prevalence of PIMs prescription was 34.0% (95% confidence interval: 29.4%-38.6%) and that of polypharmacy and hyperpolypharmacy was 45.8% and 13.5%, respectively. The common PIMs were proton-pump inhibitors, benzodiazepines, peripheral α-1 blockers, and first-generation antihistamines. Inpatient admission, visits to the emergency department, multiple diagnoses, polypharmacy, and hyperpolypharmacy were associated with PIM prescription (P < 0.05). Age, gender, number of outpatient visits, and specialist consultation were not associated with PIM prescription. Polypharmacy (adjusted odds ratio [aOR] =2.11) and hyperpolypharmacy (aOR = 5.55) had independent association with PIM prescription (P < 0.05). CONCLUSION: PIM prescription appears to be common in teaching hospitals in Kerala. Polypharmacy and hyperpolypharmacy in older people should trigger a review of medication to reduce the use of PIM.

Left Ventricular Diastolic Dysfunction is Associated with Renal Dysfunction, Poor Survival and Low Health Related Quality of Life in Cirrhosis.

BACKGROUND: The presence of left ventricular diastolic dysfunction (LVDD) in patients with cirrhosis leads to a restriction of activities and a poor health related quality of life (HRQoL), which should be taken into consideration when treating them for liver and cardiac complications. AIMS: The prevalence, complications, predictors of HRQoL and survival in cirrhotic patients with LVDD were studied. METHODS: We report a prospective cohort study of 145 consecutive cirrhotic patients with LVDD who were evaluated for cardiac functional status at enrollment and followed up for hepatic complications, cardiac events, outcome and HRQoL using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) over a period of 2 years. RESULTS: In total, 145 (mean age 61 years, 59% male) patients were included. Seventeen patients died with 10.5%, 22.5% and 40% mortality rates in patients with Grades 1, 2 and 3 LVDD respectively over 24 months. The parameters that were significant for predicting mortality on bivariate analysis were MELD, MELDNa, hepatic venous pressure gradient, MLHFQ, and left ventricular (LV) diastolic function (e' and E/e' ratio), but only MELD, MELDNa and E/e' remained significant on multivariate analysis. The E/e' ratio (8.7 ± 3.3 in survivors vs. 9.1 ± 2.3 in non-survivors) predicted outcome. On univariate analysis, the predictors of poor HRQoL were the Child-Pugh score ≥9.8 (OR 2.6; 95% confidence intervals (CI) 2.3-9.1, P = 0.041), MELD score ≥ 15.7 (OR 2.48; 95% CI 1.4-3.9, P = 0.029), refractory ascites (OR 1.9; 95% CI 1.1-6.1, P = 0.050), and E/e' ratio ≥7.6 (OR 1.9; 95% CI 1.8-7.1, P = 0.036) The presence of Class II/III (P = 0.046) symptoms of heart failure and MLHFQ≥ 45 (P = 0.042) were predictors of mortality at 24 months. CONCLUSION: The grade of LVDD correlates with liver function, clinical events, risk of renal dysfunction and HRQoL. Evaluation of novel therapies which target symptomatic improvement in LVDD, should be done with suitable outcome measures, including HRQoL assessment.

Potential protective effects of Dapagliflozin in gentamicin induced nephrotoxicity rat model via modulation of apoptosis associated miRNAs.

BACKGROUND: Drug-induced kidney injury (DIKI) can be manifested with progressive chronic kidney diseases or end-stage renal diseases. Understanding the molecular disarrangements caused by DIKI is an attractive point of interest. A class of non-coding RNA called microRNAs (miRNAs) is known to play a major role in regulation of gene expression and signaling pathways making miRNAs excellent targets for new therapeutic agents. AIM OF THE STUDY: We aimed to investigate the role of miRNA 21 and 181a in gentamicin (GNT) induced nephrotoxicity rat model and the protective effect of Dapagliflozin (DAPA) in modulating their expression through studying its effect on renal function as well as renal histopathological changes. MATERIALS AND METHODS: Wistar rats were used and divided into: naïve, DAPA, GNT and DAPA + GNT groups. In all studied groups, kidney function, oxidative stress, apoptosis markers and miRNAs' expression in serum and renal biopsies were investigated in addition to the histopathological studies to identify its early renoprotective effect. RESULTS: DAPA was found to improve kidney function, oxidative stress markers, decrease apoptosis of renal tubular cells and increase miR-21 but decrease the expression of miR-181a with restoration of the renal architecture after 14 days of treatment in GNT induced nephrotoxicity rat model. CONCLUSIONS: DAPA produced significant decrease in renal expression of miR-181a on the other hand it increased the expression of renal miR-21, this may introduce a novel early protective effect of DAPA against GNT-induced nephrotoxicity.

Allicin functionalized locust bean gum nanoparticles for improved therapeutic efficacy: An in silico, in vitro and in vivo approach.

The field of nanotechnology has overgrown over the past few years and has even ventured into the field of medicine. The aim of the present study is to develop a novel allicin functionalized locust bean gum nanoparticle using the nanoprecipitation technique. The synthesized nanoparticles were characterized by dynamic light scattering, scanning electron microscopy and transmission electron microscopy. The characterization study revealed the nanoscale structure (∼100nm) of the prepared particles. In silico toxicology analysis were carried out to assess the drug-like properties and virtual toxicity of allicin. Toxicity of the prepared nanoparticles were carried out in RAW 264.7 cell lines in vitro and in vivo studies were carried out in Sprague-Dawley rats. In in vitro study, LBGAN showed a maximum toxicity of 10.51% in MTT assay, no reactive oxygen species generation on DCFDA staining and LBGAN was effective to protect the cells from apoptosis. In in vivo toxicity studies LBGAN showed no significant change in the activities of the marker enzymes like LDH, CK-MB, ALP, ACP, AST and ALT. Thus, the functionalization of nanoparticles with allicin has the benefit of providing protection and stability to the allicin, in addition to increasing its pharmacological activity.