Innovative Management of a Difficult Case of Hepatic Hydrothorax.

Hepatic hydrothorax affects 5%-15% of decompensated cirrhosis patients, with up to 26% being refractory to standard treatments. For those ineligible for transjugular intrahepatic systemic shunts or liver transplants, alternatives to repeated thoracentesis are limited but can include the insertion of an indwelling pleural catheter. We present the first case of the use of an automatic low-flow ascites pump (alfapump) to manage nonmalignant pleural effusion in an elderly patient with cirrhosis.

Biosynthesis of carotenoids in Azospirillum brasilense Cd is mediated via squalene (C30) route.

Azospirillum brasilense is a non-photosynthetic α-Proteobacteria, belongs to the family of Rhodospirillaceae and produces carotenoids to protect itself from photooxidative stress. In this study, we have used Resonance Raman Spectra to show similarity of bacterioruberins of Halobacterium salinarum to that of A. brasilense Cd. To navigate the role of genes involved in carotenoid biosynthesis, we used mutational analysis to inactivate putative genes predicted to be involved in carotenoid biosynthesis in A. brasilense Cd. We have shown that HpnCED enzymes are involved in the biosynthesis of squalene (C30), which is required for the synthesis of carotenoids in A. brasilense Cd. We also found that CrtI and CrtP desaturases were involved in the transformation of colorless squalene into the pink-pigmented carotenoids. This study elucidates role of some genes which constitute very pivotal role in biosynthetic pathway of carotenoid in A. brasilense Cd.

Polyglycerol-Functionalized ß-Cyclodextrins as Crosslinkers in Thermoresponsive Nanogels for the Enhanced Dermal Penetration of Hydrophobic Drugs.

Thermoresponsive nanogels (tNGs) are promising candidates for dermal drug delivery. However, poor incorporation of hydrophobic drugs into hydrophilic tNGs limits the therapeutic efficiency. To address this challenge, ß-cyclodextrins (ß-CD) are functionalized by hyperbranched polyglycerol serving as crosslinkers (hPG-ßCD) to fabricate ßCD-tNGs. This novel construct exhibits augmented encapsulation of hydrophobic drugs, shows the appropriate thermal response to dermal administration, and enhances the dermal penetration of payloads. The structural influences on the encapsulation capacity of ßCD-tNGs for hydrophobic drugs are analyzed, while concurrently retaining their efficacy as skin penetration enhancers. Various synthetic parameters are considered, encompassing the acrylation degree and molecular weight of hPG-ßCD, as well as the monomer composition of ßCD-tNGs. The outcome reveals that ßCD-tNGs substantially enhance the aqueous solubility of Nile Red elevating to 120 µg mL-1 and augmenting its dermal penetration up to 3.33 µg cm-2. Notably, the acrylation degree of hPG-ßCD plays a significant role in dermal drug penetration, primarily attributed to the impact on the rigidity and hydrophilicity of ßCD-tNGs. Taken together, the introduction of the functionalized ß-CD as the crosslinker in tNGs presents a novel avenue to enhance the efficacy of hydrophobic drugs in dermatological applications, thereby offering promising opportunities for boosted therapeutic outcomes.

Improving palliative and supportive care in advanced cirrhosis: the HepatoCare model of integrated collaborative care.

BACKGROUND: Patients with advanced cirrhosis experience an unpredictable disease trajectory but are infrequently referred to palliative care (PC) services and rarely undertake advance care planning (ACP). AIM: We assessed whether a novel model of care increased provision of meaningful PC in advanced cirrhosis compared with standard of care (SOC). METHODS: Thirty consecutive hepatology clinic outpatients with advanced cirrhosis, meeting one or more cirrhosis-related PC referral criteria, consented to treatment in the HepatoCare clinic (PC physician, specialist liver nurse, pharmacist) in parallel with usual specialist hepatology care. A control cohort of 30 consecutive outpatients with advanced cirrhosis undergoing SOC treatment was retrospectively identified for comparison. The primary outcome was provision of meaningful PC using HepatoCare versus SOC. Additional clinical outcomes were assessed over 12 months or until death and significant differences were identified. RESULTS: The intervention and control cohorts had similarly advanced cirrhosis (mean Child-Pugh scores 8.7 vs 8.2, P = 0.46; mean model for end-stage liver disease scores 14.4 vs 14.6, P = 0.88) but a lower 12-month mortality rate (33% HepatoCare vs 67% SOC; P = 0.02). The intervention cohort experienced higher uptake of formal ACP (100% vs 25% for the control cohort) and outpatient PC referral (100% vs 40%), and were more likely to die at home or in a PC bed/hospice (80% vs 30%). The majority of the HepatoCare cohort (81%) had medications safely deprescribed and experienced fewer unplanned admission days (470 vs 794). CONCLUSIONS: HepatoCare is a novel multidisciplinary model of care that integrates effective PC and specialist hepatology management to improve outcomes in advanced cirrhosis.

Managing diabetic complications with alternative therapeutic strategies.

Diabetes is a chronic metabolic disease affecting millions worldwide. It is characterized by a lack of insulin production or impaired insulin function, leading to elevated blood glucose levels. Conventional treatment methods for diabetes management typically include lifestyle changes and medications. However, alternative therapies have gained attention in recent years, including traditional medicine containing bioactive compounds, supplements like vitamin D and Omega-3 fatty acids, aromatherapy, and homeopathy. Diabetic complications are common in patients with uncontrolled diabetes and can lead to serious health problems, including diabetic retinopathy, impaired wound healing, kidney disease, nerve damage, and cardiovascular disease. Alternative remedies, such as traditional medicine containing bioactive compounds, supplements, and aromatherapy, have been studied for their potential benefits in managing these complications. Traditional medicines like bitter melon, cinnamon, and fenugreek have been shown to have anti-diabetic effects due to their bioactive compounds. Similarly, supplements like vitamin D and Omega-3 fatty acids have been found to improve glycemic control in patients with diabetes. Aromatherapy, which involves the use of essential oils, has also been explored for its potential benefits in diabetes management. Homeopathy, which uses highly diluted substances to stimulate the body's natural healing abilities, has been used to treat diabetes-related symptoms like neuropathy and wounds. Personalized care is essential in natural diabetes management because each person's body and health needs are unique. A holistic approach that addresses the individual's physical, emotional, and spiritual well-being is essential. As research in this field continues to expand, a more comprehensive understanding of diabetes management will lead to improved outcomes for those living with this condition.

Dyshomeostasis of Iron and Its Transporter Proteins in Cypermethrin-Induced Parkinson's Disease.

The etiology of Parkinson's disease (PD) is highly complex and is still indefinable. However, a number of studies have indicated the involvement of pesticides and transition metals. Copper, magnesium, iron, and zinc have emerged as important metal contributors. Exposure to pesticides causes an accumulation of transition metals in the substantia nigra (SN) region of the brain. The cypermethrin model of PD is characterized by mitochondrial dysfunction, autophagy impairment, oxidative stress, etc. However, the effect of cypermethrin on metal homeostasis is not yet explored. The study was designed to delineate the role of metals and their transporter proteins in cypermethrin-induced animal and cellular models of PD. The level of copper, magnesium, iron, and zinc was checked in the nigrostriatal tissue and serum by atomic absorption spectroscopy. Since cypermethrin consistently increased iron content in the nigrostriatal tissue and serum after 12 weeks of exposure, the level of iron transporter proteins, such as divalent metal transporter-1 (DMT-1), ceruloplasmin, transferrin, ferroportin, and hepcidin, and their in silico interaction with cypermethrin were checked. 3,3'-Diaminobenzidine-enhanced Perl's staining showed an elevated number of iron-positive cells in the SN of cypermethrin-treated rats. Molecular docking studies revealed a strong binding affinity between cypermethrin and iron transporter protein receptors of humans and rats. Furthermore, cypermethrin increased the expression of DMT-1 and hepcidin while reducing the expression of transferrin, ceruloplasmin, and ferroportin in the nigrostriatal tissue and human neuroblastoma cells. These observations suggest that cypermethrin alters the expression of iron transporter proteins leading to iron dyshomeostasis, which could contribute to dopaminergic neurotoxicity.

Organ dysfunction and failure in liver disease.

Acute-on-chronic liver failure (ACLF) is a complex syndrome defined by the existence of different organ failures (OFs) in patients with chronic liver disease, mainly cirrhosis. Several definitions have been proposed to define the syndrome, varying in the grade of the subjacent liver disease, the type of precipitants and the organs considered in the definition. Liver, coagulation, brain, kidney, circulatory and pulmonary are the six types of OFs proposed in the different classifications, with different prevalence worldwide. Irrespective of the definition used, patients who develop ACLF present a hyperactive immune system, profound haemodynamic disturbances and several metabolic alterations that finally lead to organ dysfunction. These disturbances are triggered by different factors such as bacterial infections, alcoholic hepatitis, gastrointestinal bleeding or hepatitis B virus flare, among others. Because patients with ACLF present high short-term mortality, a prompt recognition is needed to start treatment of the trigger event and specific organ support. Liver transplantation is also feasible in carefully selected patients and should be evaluated.

Correlation of Female Genital Tuberculosis and Infertility: A Comprehensive Systematic Review, Meta-analysis, and Female Genital Tuberculosis Infertility Pathway Analysis.

Female genital tuberculosis (FGTB) is a significant health concern that can lead to infertility in women. FGTB is a common form of tuberculosis that affects the female reproductive organs. In India, around 27.5 million individuals are facing infertility issues due to female factors, and FGTB might be one of the leading causes. A systematic review and proportion meta-analysis of six studies was conducted using MedCalc 20.116 to examine the association between FGTB and infertility. The studies were identified through an electronic search of PubMed, MEDLINE, Elsevier, and the Cochrane Library from 2010 to 2023. The results showed that FGTB is significantly associated with infertility, with a prevalence of approximately 34.86%. These findings underscore the need for effective interventions to improve reproductive health in women with FGTB. Based on pathway analysis, we conclude that more clinical trials should be conducted to explore the potential utilization of interferon gamma and nuclear receptors as therapeutic drug targets and biomarkers for the prevention of FGTB. The findings of this review will contribute to raising awareness, facilitating accurate diagnosis, and improving the management of FGTB-related infertility.

Fabrication and Characterization of Cu Nanoparticles Dispersed on ZnAl-Layered Double Hydroxide Nanocatalysts for the Oxidation of Cyclohexane.

In the chemical industry, designing high-performance catalysts for the oxidation of cyclohexane into value-added products such as cyclohexanol and cyclohexanone (the combination is known as KA oil) is critical. The catalytic activity of copper nanoparticles supported on layered double hydroxide (LDH) for the liquid phase oxidation of cyclohexane was examined in this study. In this work, we have developed Cu nanoparticles supported on layered double hydroxide nanocatalysts, abbreviated as CuNPs@LDH, by the chemical reduction approach. Various physical methods were used to characterize the resulting material, including ICP-AES, XRD, FTIR, SEM, EDX, HRTEM, and BET surface area. The catalytic activity of copper nanoparticles supported on LDH was examined for the liquid phase oxidation of cyclohexane with tert-butyl hydroperoxide. CuNPs@LDH nanocatalysts with an excellent 52.3% conversion of cyclohexane with 97.2% selectivity of KA oil was obtained after 6 h at 353 K. The hot filtration test further indicated that CuNPs@LDH was a heterogeneous catalyst that could be recycled at least six times without suffering a substantial reduction in its catalytic activity.

A comprehensive analysis of Trehalose-6-phosphate synthase (TPS) gene for salinity tolerance in chickpea (Cicer arietinum L.).

Soil salinity affects various crop cultivation but legumes are the most sensitive to salinity. Osmotic stress is the first stage of salinity stress caused by excess salts in the soil on plants which adversely affects the growth instantly. The Trehalose-6-phosphate synthase (TPS) genes play a key role in the regulation of abiotic stresses resistance from the high expression of different isoform. Selected genotypes were evaluated to estimate for salt tolerance as well as genetic variability at morphological and molecular level. Allelic variations were identified in some of the selected genotypes for the TPS gene. A comprehensive analysis of the TPS gene from selected genotypes was conducted. Presence of significant genetic variability among the genotypes was found for salinity tolerance. This is the first report of allelic variation of TPS gene from chickpea and results indicates that the SNPs present in these conserved regions may contribute largely to functional distinction. The nucleotide sequence analysis suggests that the TPS gene sequences were found to be conserved among the genotypes. Some selected genotypes were evaluated to estimate for salt tolerance as well as for comparative analysis of physiological, molecular and allelic variability for salt responsive gene Trehalose-6-Phosphate Synthase through sequence similarity. Allelic variations were identified in some selected genotypes for the TPS gene. It is found that Pusa362, Pusa1103, and IG5856 are the most salt-tolerant lines and the results indicates that the identified genotypes can be used as a reliable donor for the chickpea improvement programs for salinity tolerance.

Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

Comparison of Outcomes in Unilateral and Bilateral Pediatric Cochlear Implants: Our Experience.

The aim of our study is to compare the outcomes in unilateral and bilateral cochlear implants in pediatric age and also between simultaneous and sequential cochlear implant surgery. This retrospective study was carried out with 83 children aged between 12 months to 2.5 years which included 41 children with bilateral Cochlear implants and 42 with unilateral implants. Out of these 41 children, 21 were simultaneous and 20 were sequential cochlear implant. All the children were operated at civil hospital Gandhinagar, Gujarat, India. CAP, SIR, localization, traffic noise and speech in noise scores were assessed at regular intervals over the period of 4 years. Also the drug administration time, surgical time, operating room time were assessed for simultaneous and sequential cochlear implant surgery. Children with bilateral simultaneous implants fared significantly better with CAP, SIR, localization, speech noise and traffic noise scores than sequential bilateral implants and unilateral implants with a significant difference of means t tests between the two groups. Simultaneous cochlear implant surgery is associated with reduced surgical time, operating room time, it shortens the total in patient stay. There is less of drug administration and bilateral ones are stimulated simultaneously. Bilateral cochlear implants perform better with respect to auditory perception skills and spontaneous speech when compared with unilateral implants, but simultaneous surgery is better and safe option for pediatric cochlear implantation.

A complex epigenome-splicing crosstalk governs epithelial-to-mesenchymal transition in metastasis and brain development.

Epithelial-to-mesenchymal transition (EMT) renders epithelial cells migratory properties. While epigenetic and splicing changes have been implicated in EMT, the mechanisms governing their crosstalk remain poorly understood. Here we discovered that a C2H2 zinc finger protein, ZNF827, is strongly induced during various contexts of EMT, including in brain development and breast cancer metastasis, and is required for the molecular and phenotypic changes underlying EMT in these processes. Mechanistically, ZNF827 mediated these responses by orchestrating a large-scale remodelling of the splicing landscape by recruiting HDAC1 for epigenetic modulation of distinct genomic loci, thereby slowing RNA polymerase II progression and altering the splicing of genes encoding key EMT regulators in cis. Our findings reveal an unprecedented complexity of crosstalk between epigenetic landscape and splicing programme in governing EMT and identify ZNF827 as a master regulator coupling these processes during EMT in brain development and breast cancer metastasis.

Geography vs. past climate: the drivers of population genetic structure of the Himalayan langur.

BACKGROUND: Contemporary species distribution, genetic diversity and evolutionary history in many taxa are shaped by both historical and current climate as well as topography. The Himalayas show a huge variation in topography and climatic conditions across its entire range, and have experienced major climatic fluctuations in the past. However, very little is known regarding how this heterogenous landscape has moulded the distribution of Himalayan fauna. A recent study examined the effect of these historical events on the genetic diversity of the Himalayan langurs in Nepal Himalaya. However, this study did not include the samples from the Indian Himalayan region (IHR). Therefore, here we revisit the questions addressed in the previous study with a near complete sampling from the IHR, along with the samples from the Nepal Himalaya. We used the mitochondrial Cytochrome-b (Cyt-b, 746 bp) region combined with multiple phylogeographic analyses and palaeodistribution modelling. RESULTS: Our dataset contained 144 sequences from the IHR as well as the Nepal Himalaya. Phylogenetic analysis showed a low divergent western clade nested within high divergent group of eastern lineages and in the network analysis we identified 22 haplotypes over the entire distribution range of the Himalayan langurs. Samples from the Nepal Himalaya showed geographically structured haplotypes corresponding to different river barriers, whereas samples from IHR showed star-like topology with no structure. Our statistical phylogeography analysis using diyABC supported the model of east to west colonisation of these langurs with founder event during colonisation. Analysis of demographic history showed that the effective population size of the Himalayan langurs decreased at the onset of last glacial maximum (LGM) and started increasing post LGM. The palaeodistribution modelling showed that the extent of suitable habitat shifted from low elevation central Nepal, and adjoining parts of north India, during LGM to the western Himalaya at present. CONCLUSION: The current genetic diversity and distribution of Himalayan langurs in the Nepal Himalaya has been shaped by river barriers, whereas the rivers in the IHR had relatively less time to act as a strong genetic barrier after the recent colonisation event. Further, the post LGM expansion could have had confounding effect on Himalayan langur population structure in both Nepal Himalaya and IHR.

Effect of Delayed Umbilical Cord Clamping on Hemodynamic Instability in Preterm Neonates below 35 Weeks.

INTRODUCTION: Delaying umbilical cord clamping facilitates postnatal transition in neonates but evidence on its effect in reducing hemodynamic instability in preterm neonates is inconclusive. AIMS: To evaluate delayed cord clamping (DCC) in reducing the incidence of hemodynamic instability in preterm neonates below 35 weeks gestational age admitted to the neonatal intensive care unit. METHODS: Neonates between 25 weeks and 34 weeks and 6 days gestation were enrolled. Hemodynamic and respiratory parameters were monitored over 48 h. Hemodynamic instability was defined as persistent tachycardia and/or hypotension necessitating therapy. RESULTS: The DCC cohort included 62 neonates with an equal number in the non-DCC group. The birth weight [mean ± standard deviation (SD)] was 1332.90 ± 390.05 g and the gestational age (mean ± SD) was 31.64 ± 2.52 weeks. Hemodynamic instability was noted in 18/62 (29%) neonates in the DCC cohort and 29/62 (46.7%) in the non-DCC group; relative risk (RR) 0.62 [95% confidence interval (CI) 0.38-0.99] (p = 0.023). The duration of inotrope requirement in the DCC cohort (mean ± SD) was 38.38 ± 16.99 h compared to 49.13 ± 22.90 h in the non-DCC cohort (p = 0.090). Significantly higher systolic, diastolic and mean arterial pressures were noted from 6 h to 48 h in the DCC cohort (p < 0.001). The severity of respiratory distress and FiO2 requirement was also less in the first 24 h. There was no difference in the incidence of patent ductus arteriosus, late-onset sepsis or mortality. CONCLUSION: Delaying umbilical cord clamping at birth by 60 s resulted in significantly lower hemodynamic instability in the first 48 h and higher blood pressure parameters.

Insights into microbial diversity on plastisphere by multi-omics.

Plastic pollution is a major concern in marine environment as it takes many years to degrade and is one of the greatest threats to marine life. Plastic surface, referred to as plastisphere, provides habitat for growth and proliferation of various microorganisms. The discovery of these microbes is necessary to identify significant genes, enzymes and bioactive compounds that could help in bioremediation and other commercial applications. Conventional culture techniques have been successful in identifying few microbes from these habitats, leaving majority of them yet to be explored. As such, to recognize the vivid genetic diversity of microbes residing in plastisphere, their structure and corresponding ecological roles within the ecosystem, an emerging technique, called metagenomics has been explored. The technique is expected to provide hitherto unknown information on microbes from the plastisphere. Metagenomics along with next generation sequencing provides comprehensive knowledge on microbes residing in plastisphere that identifies novel microbes for plastic bioremediation, bioactive compounds and other potential benefits. The following review summarizes the efficiency of metagenomics and next generation sequencing technology over conventionally used methods for culturing microbes. It attempts to illustrate the workflow mechanism of metagenomics to elucidate diverse microbial profiles. Further, importance of integrated multi-omics techniques has been highlighted in discovering microbial ecology residing on plastisphere for wider applications.

Nanocarriers for Skin Applications: Where Do We Stand?

Skin penetration of active molecules for treatment of diverse diseases is a major field of research owing to the advantages associated with the skin like easy accessibility, reduced systemic-derived side effects, and increased therapeutic efficacy. Despite these advantages, dermal drug delivery is generally challenging due to the low skin permeability of therapeutics. Although various methods have been developed to improve skin penetration and permeation of therapeutics, they are usually aggressive and could lead to irreversible damage to the stratum corneum. Nanosized carrier systems represent an alternative approach for current technologies, with minimal damage to the natural barrier function of skin. In this Review, the use of nanoparticles to deliver drug molecules, genetic material, and vaccines into the skin is discussed. In addition, nanotoxicology studies and the recent clinical development of nanoparticles are highlighted to shed light on their potential to undergo market translation.

Evaluation of disease resistant and high yielding faba bean germplasm in India.

Faba bean (Vicia faba L.) is one of the earliest domesticated food legumes after chickpea and pea in the world. It is been produced in many countries including China, Ethiopia, Egypt, northern Europe, the Mediterranean region, central Asia, East Asia, Latin America and as a minor crop in India. The crop is affected by many diseases and alternaria leaf blight (Alternaria spp.) is one of the serious threat to faba bean production. Twenty-five lines of faba bean were selected from three international nurseries and were evaluated at ICARDA-FLRP-Amlaha during 2016-2017 and 2017-2018, to identify resistant lines against alternaria blight disease. A wide range of variation to disease reaction was observed among faba bean genotypes. One faba bean line (S2011-134) found tolerant, six genotypes (S2011-116, FLIP15-139, FLIP15-156, FLIP15-159, FLIP15-164-S2 and FLIP15-169) were found moderately tolerant and 16 genotypes were found susceptible to alternaria blight. The faba bean genotypes showed resistance to the disease scoring (0-9) with high yield as compared to the checks, Giza and Gwalior local. The identified sources of resistance can be utilized in faba bean breeding programmes for the development of disease tolerant cultivars with high yield.