British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults.

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.

Cladistics of Rhipicephalus microplus and laboratory assessment of acaricidal efficacy of different Cassia fistula extracts against R. microplus larvae.

The present study aimed to analyze the cladistics and population structure analysis of Rhipicephalus microplus ticks infesting buffaloes in Haryana, India, as well as the assessment of the anti-tick efficacy of the ethanolic extracts of Cassia fistula (bark, pod pulp, and flowers) against R. microplus larvae. The molecular characterization and population structure analysis were performed by targeting the amplification of the partial mitochondrial cytochrome C oxidase subunit 1 (cox1) gene, whereas anti-tick efficacy was evaluated using a larval packet test. The sequences generated herein revealed a homology of 98.26-100% to the GenBank-archived R. microplus sequences. In population structure analysis, high haplotype (0.500 ± 0.265) and low nucleotide (0.002 ± 0.001) diversities were recorded for the sequences generated in this study. Significantly negative neutrality indices were recorded for the overall dataset. The extracts were found to significantly affect mortality rates in a dose-dependent manner, and the ethanolic extracts of the bark, pod pulp, and flowers of C. fistula exhibited median lethal concentration (LC50) values of 27.989, 40.457, and 49.43 mg/mL, respectively. The LC50 value recorded for the combination of the ethanolic extracts of the bark, flower, and pod pulp of C. fistula was 19.724 mg/mL, whereas the synthetic acaricide ivermectin had an LC50 value of 351.56 mg/mL. In conclusion, R. microplus populations infesting cattle and buffalo hosts in India exhibited negligible genetic differentiation and high gene flow between them. Additionally, the combination of all C. fistula extracts could serve as a potential substitute for the synthetic acaricide.

Molecular dynamics simulation-based trinucleotide and tetranucleotide level structural and energy characterization of the functional units of genomic DNA.

Genomes of most organisms on earth are written in a universal language of life, made up of four units - adenine (A), thymine (T), guanine (G), and cytosine (C), and understanding the way they are put together has been a great challenge to date. Multiple efforts have been made to annotate this wonderfully engineered string of DNA using different methods but they lack a universal character. In this article, we have investigated the structural and energetic profiles of both prokaryotes and eukaryotes by considering two essential genomic sites, viz., the transcription start sites (TSS) and exon-intron boundaries. We have characterized these sites by mapping the structural and energy features of DNA obtained from molecular dynamics simulations, which considers all possible trinucleotide and tetranucleotide steps. For DNA, these physicochemical properties show distinct signatures at the TSS and intron-exon boundaries. Our results firmly convey the idea that DNA uses the same dialect for prokaryotes and eukaryotes and that it is worth going beyond sequence-level analyses to physicochemical space to determine the functional destiny of DNA sequences.

Development of duplex real-time PCR for quick detection of cryptosporidiosis in goats.

Cryptosporidium spp. is the most important foodborne and waterborne pathogens and a leading cause of mortality from foodborne and waterborne gastrointestinal diseases. In neonates of domestic animals, it is associated with consistent diarrhea and dehydration. Cryptosporidium infection begins with the ingestion of sporulated oocytes disseminated by carrier animals that consistently contaminate the environment. Many diagnostic tests are available including microscopy and antigen trap-ELISA, but none of the diagnostic tests available currently cannot differentiate between active and passive infection in the host. In the current study, to address this challenge an mRNA-based duplex TaqMan® probe PCR was developed to target the Cryptosporidium oocyst wall protein gene and 18SSU rRNA gene in a single tube that can detect metabolically active cryptosporidial oocysts. The mRNA transcripts are the direct indicator of any actively replicating cell and they will help decipher the active stages of its lifecycle in a host. This diagnostic assay was standardized by computing transcript copy number-based limit of detection (LOD). For COWP and 18SSU rRNA genes, the LOD was 7.08 × 1004 and 5.95 × 1005 , respectively. During active infections, the oocyst wall protein will be active and so its COWP gene transcripts will act as a marker for active infection. While transcripts for 18SSU rRNA are constitutively expressed in cryptosporidial life cycle. This current diagnostic assay will be a quantitative marker that will help assess the active stages of Cryptosporidium infection in neonates. The disease dynamics will help better understand to formulate the control strategies and contain infection among healthy animals.

Molecular characterization of Hyalomma dromedarii and evaluation of acaricidal potential of herbal methanolic extracts against H. dromedarii larvae in comparison to synthetic acaricides.

The present study had two aims: molecular characterization of Hyalomma dromedarii infesting one-humped camels of Haryana (North India), and assessment of the acaricidal potential of herbal methanolic extracts against H. dromedarii larvae in comparison to synthetic acaricides. Phylogenetics and population neutrality indices were assessed by targeting partial amplification of mitochondrial 16S rDNA sequences. Larval packet test (LPT) was performed to evaluate the acaricidal efficacy of herbal extracts (Ferula asafoetida and Trachyspermum ammi) and synthetic acaricides (deltamethrin and fipronil). Phylogenetic studies established the collected ticks to be H. dromedarii, exhibiting a homology of 99.8-100%. However, the present study isolates formed a different sub-clade compared to H. dromedarii sequences from Egypt, Senegal, Tunisia and Saudi Arabia. Nucleotide and haplotype diversity values were indicative of demographic expansion and low gene flow. Negative values of Tajima's D (-0.612) and Fu and Li's Fst (-0.479) highlighted deviations from neutrality and emphasized recent population expansion. The median lethal concentration (LC50) values recorded for T. ammi, F. asafoetida and their combination were 3.68, 2.87 and 2.59 mg/mL, respectively, whereas the 90% lethal concentration (LC90) values were 4.09, 3.58 and 3.35 mg/mL, respectively. It was also observed that the H. dromedarii population under study was completely susceptible to both the formulated synthetic acaricides. In conclusion, combination of methanolic extracts of F. asafoetida and T. ammi could provide a potential substitute to toxic synthetic chemical acaricides and might prove a valuable component of integrated tick management strategies.

Are the Patterns of Cytomegalovirus Viral Load Seen After Solid Organ Transplantation Affected by Circadian Rhythm?

BACKGROUND: Cytomegalovirus (CMV) is an important opportunistic pathogen after transplantation. Some virological variation in transplant recipients is explained by donor and recipient CMV serostatus, but not all. Circadian variability of herpesviruses has been described, so we investigated the effect of time of day of transplantation on posttransplant CMV viremia. METHODS: We performed a retrospective analysis of 1517 patients receiving liver or kidney allografts at a single center from 2002 to 2018. All patients were given preemptive therapy with CMV viremia monitoring after transplantation. Circulatory arrest and reperfusion time of donor organ were categorized into 4 periods. Patients were divided into serostatus groups based on previous CMV infection in donor and recipient. CMV viremia parameters were compared between time categories for each group. Factor analysis of mixed data was used to interrogate this complex data set. RESULTS: Live-donor transplant recipients were less likely to develop viremia than recipients of deceased-donor organs (48% vs 61%; P < .001). After controlling for this, there was no evidence of time of day of transplantation affecting CMV parameters in any serostatus group, by logistic regression or factor analysis of mixed data. DISCUSSION: We found no evidence for a circadian effect of transplantation on CMV viremia, but these novel results warrant confirmation by other centers.

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies.

PURPOSE: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies. MATERIALS AND METHODS: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7-21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging. RESULTS: Eight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441-404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%-100%). There were no significant changes in perfusion imaging parameters after TACE. CONCLUSIONS: BTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.

Prevalence and phylogeography of Taenia hydatigena metacestodes from goats of India.

The study determined the prevalence and genetic population structure relationships of Cysticercus tenuicollis (Taenia hydatigena metacestode) retrieved from the goats slaughtered in north India. An overall prevalence of 9.62% (59/613) was recorded. Genetic population structure relationships were assessed by targeting partial cytochrome c oxidase subunit 1 mitochondrial gene sequence. Phylogenetic tree analysis revealed that all the present study representative isolates (n = 7) formed a major clade and grouped with T. hydatigena isolates retrieved from sheep, goats, pigs and dogs, originating from China, Iran, Nigeria, Ghana and Poland. However, a single isolate from Himachal Pradesh (isolate 3) formed a subgroup within the clade. The neutrality and diversity indices revealed high values of haplotype diversity [Hd = 0.99695 (0.95238­1.0000)] and low nucleotide diversity (π = 0.49276), which was indicative of demographic expansion and low gene flow, suggesting that Indian T. hydatigena isolates were not genetically differentiated. Tajima's D (−1.26988) and Fu and Li's D statistics values (−0.74556) were negative, demonstrating deviations from neutrality and both propounded recent population expansion or purifying selection. Results highlighted a low genetic diversity of T. hydatigena metacestodes across the geographical range of north India.

Topical creams of piperine loaded lipid nanocarriers for management of atopic dermatitis: development, characterization, and in vivo investigation using BALB/c mice model.

The aim of the research work was to investigate the efficacy of cream loaded with lipid nanocarriers (ethosomes) of piperine for the management of atopic dermatitis (AD) in comparison to conventional cream. Ethosomes of piperine were formulated with varying concentration of phosphatidylcholine and ethanol; and evaluated for entrapment efficiency (EE), sedimentation behaviour, vesicle size, zeta potential, in vitro drug release, and shape. Creams loaded with optimized ethosomal dispersion of piperine were formulated and evaluated for physicochemical parameters, ex vivo permeation and drug retention in skin layers. Similarly, conventional creams of piperine in the same concentrations were formulated and evaluated. The optimized ethosomal a conventional cream was evaluated for cytotoxicity using HaCat cell lines and in vivo on BALB/c mice model. The EE (%) and vesicle size was 74.30 ± 3.88% and 318.1 nm, respectively, for optimized ethosomal dispersion. The zeta potential was -32.6 mV and vesicles were spherical in shape. The ethosomal cream showed higher deposition in the epidermis and dermis. The creams were non-cytotoxic to HaCat cell lines. In comparison to the negative control, the ethosomal (0.1%) and conventional (0.125%) cream, both significantly decreased the ear and skin thickness, skin severity; and WBC, granulocytes, and IgE antibodies level in the BALB/c mice model. The efficacy of ethosomal cream was significantly higher than conventional cream as compared to tacrolimus (0.1%). Ethosomal cream of piperine showed good potential for the management of AD in comparison to conventional cream.

Epidemiology, virology and clinical aspects of hantavirus infections: an overview.

At the end of 2019 and 2020s, a wave of coronavirus disease 19 (COVID-19) epidemics worldwide has catalyzed a new era of 'communicable infectious diseases'. However, the world is not currently prepared to deal with the growing burden of COVID-19, with the unexpected arrival of Hantavirus infection heading to the next several healthcare emergencies in public. Hantavirus is a significant class of zoonotic pathogens of negative-sense single-stranded ribonucleic acid (RNA). Hemorrhagic renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are the two major clinical manifestations. Till date, there is no effective treatments or vaccines available, public awareness and precautionary measures can help to reduce the spread of hantavirus disease. In this study, we outline the epidemiology, virology, clinical aspects, and existing HFRS and HCPS management approaches. This review will give an understanding of virus-host interactions and will help for the early preparation and effective handling of further outbreaks in an ever-changing environment.

Oleuropein as a Potent Compound against Neurological Complications Linked with COVID-19: A Computational Biology Approach.

The association of COVID-19 with neurological complications is a well-known fact, and researchers are endeavoring to investigate the mechanistic perspectives behind it. SARS-CoV-2 can bind to Toll-like receptor 4 (TLR-4) that would eventually lead to α-synuclein aggregation in neurons and stimulation of neurodegeneration pathways. Olive leaves have been reported as a promising phytotherapy or co-therapy against COVID-19, and oleuropein is one of the major active components of olive leaves. In the current study, oleuropein was investigated against SARS-CoV-2 target (main protease 3CLpro), TLR-4 and Prolyl Oligopeptidases (POP), to explore oleuropein potency against the neurological complications associated with COVID-19. Docking experiments, docking validation, interaction analysis, and molecular dynamic simulation analysis were performed to provide insight into the binding pattern of oleuropein with the three target proteins. Interaction analysis revealed strong bonding between oleuropein and the active site amino acid residues of the target proteins. Results were further compared with positive control lopinavir (3CLpro), resatorvid (TLR-4), and berberine (POP). Moreover, molecular dynamic simulation was performed using YASARA structure tool, and AMBER14 force field was applied to examine an 100 ns trajectory run. For each target protein-oleuropein complex, RMSD, RoG, and total potential energy were estimated, and 400 snapshots were obtained after each 250 ps. Docking analyses showed binding energy as -7.8, -8.3, and -8.5 kcal/mol for oleuropein-3CLpro, oleuropein-TLR4, and oleuropein-POP interactions, respectively. Importantly, target protein-oleuropein complexes were stable during the 100 ns simulation run. However, an experimental in vitro study of the binding of oleuropein to the purified targets would be necessary to confirm the present study outcomes.

How to spot COVID-19 patients: Speech & sound audio analysis for preliminary diagnosis of SARS-COV-2 corona patients.

BACKGROUND: The global cases of COVID-19 increasing day by day. On 25 November 2020, a total of 59 850 910 cases reported globally with a 1 411 216 global death. In India, total cases in the country now stand at 91 77 841 including 86 04 955 recoveries and 4 38 667 active cases as on 24 November 2020, as per the data issued by ICMR. A new generation of voice/audio analysis application can tell whether the person is suffering from COVID-19 or not. AIMS: To describe how to established a new generation of voice/audio analysis application to identify the suspected COVID-19 hidden cases in hotspot areas with the help of an audio sample of the general public. MATERIALS & METHODS: The different patents and data available as literature on the internet are evaluated to make a new generation of voice/audio analysis application with the help of an audio sample of the general public. RESULTS: The collection of the audio sample will be done from the already suffered COVID-19 patients in (.Wave files) personally or through phone calls. The audio samples such as the sound of the cough, the pattern of breathing, respiration rate and way of speech will be recorded. The parameters will be evaluated for loudness, articulation, tempo, rhythm, melody and timbre. The analysis and interpretation of the parameters can be made through machine learning and artificial intelligence to detect corona cases with an audio sample. DISCUSSION: The voice/audio application current project can be merged with a mobile App called 'AarogyaSetu' by the Government of India. The project can be implemented in the high-risk area of COVID-19 in the country. CONCLUSION: This new method of detecting cases will decrease the workload in the COVID-19 laboratory.

Impact of physical activity and cooking oil amongst diabetes with coexisting hypertension patients on economic cost and length of stay: A 1914 patient's observational study.

AIM OF THE STUDY: The study aimed to investigate the impact of the patients' physical activity status and the type of cooking oil consumed by patients in their daily routine on glycaemic profile, lipid profile, the hypertensive profile of the patients, the length of stay and overall cost of the treatment. METHODS: This is a prospective observational study. All the patients referred to the medicine department of the three different hospitals located in Moga, City Punjab, and those hospitalised due to diabetes mellitus (types I and II) with coexisting hypertension were asked to participate in the study. RESULTS: The patients' mean age was found to be M = 53.85, SD = 11.54 years. Out of 1914 patients, 914 were male (47.8%); it was observed that the majority of the patients 525 (27.43%) in North India using butter or ghee-clarified butter as edible oil, followed by mustard oil 517 (27.01%) patients. About 345 (18.03%) of the patients consume soybean oil, whereas 226 (11.81%) of the patients like sunflower oil. CONCLUSION: This study explored that cooking oil and physical activity are associated with length of stay in days and overall cost of the treatment, respectively. Our study results revealed that the type of oil compared with the treatment's overall cost was significant for olive oil, soybean oil and groundnut oil. The study revealed that moderate and low physical activity increases the length of stay compared to high physical activity. The consumption of olive oil as a regular food habit in daily routine decreases patients' length of stay with diabetes with coexisting hypertension when doing high physical activity but increases the overall cost of treatment.

Economic costs of hospitalisation and length of stay in diabetes with coexisting hypertension with correlation to laboratory investigations: Where does India stand? A 5-year ground report.

INTRODUCTION: The coexistence of diabetes mellitus (DM) and hypertension (HTN) worsens clinical outcomes and contributes to increased morbidity and mortality. OBJECTIVE: This study aims to analyse the length of stay and healthcare costs by calculating the direct and indirect costs of diabetes with coexisting hypertension in North India. METHODS: A prospective observational study was conducted at the medicine department of the three different hospitals. RESULTS: The patients' mean age was (M = 53.8, SD = 11.5) years. Out of 1914 patients, 53.65% were female. Our study revealed that the median cost of medical supplies and equipment was 21.2 $. The median cost of dialysis was 47.5 $; the median cost of hospitalisation was 142.6 $. The treatment's median direct cost was 188.5 $, followed by the overall median cost of 295.6 $. The maximum overall cost of treatment was observed at 603.9 $. It was observed that maximum LOS was 14 days for patients having BPS between 140 and 159 mmHg and BPD between 110 and 119 mmHg, and minimum LOS was found 3.5 days. CONCLUSION: The present study highlighted that diabetes coexisting hypertension poses a high-economic burden on patients. This study explored that highly significant result for BPS, BPD, FBS and HbA1 c, whereas the significant results were obtained when RBS is compared with LOS and treatment costs. Our study concluded that mean difference of 9.24 $ in patients having FBS was 261-290 mg/dL and >290 mg/dL. The LOS is increased by 6.57 days for patients with BPS between 140 and 159 mmHg compared with BPS between 180 and 209 and above mmHg, which lowers treatment costs by -21.31$.

Effects of in-person and telephone-based cognitive behavioral therapies on health services use and expenditures among African-American dementia caregivers with depressive symptoms.

Objectives: To compare the effects of telephone-based and in-person cognitive behavioral therapy (CBT) on health services use and expenditures among African-American dementia caregivers (CGs) with depressive symptoms.Methods: We analyzed data collected from 109 caregivers in a randomized controlled trial comparing the effects of telephone-based and in-person CBT on health services use and costs. Study participants were assigned randomly to either telephone or in-person CBT. Data were collected one week before and one week after the 12-week intervention. The Health Service Composite (HSC) was used to collect information on health services (physical and mental health, emergency room, hospital) utilization and associated expenditures. Intervention cost data were collected using micro-costing analysis. We used generalized linear models to examine whether the two groups differed in total health care expenditures over the six-month study period.Results: CG characteristics and health services use were similar at pre-intervention. CGs' monthly health expenditures averaged $924 and $844 in the in-person and telephone-based groups, respectively. However, intervention costs were lower for telephone-based than in-person CBT. Adjusting for CG characteristics and pre-intervention health status, there were no statistically significant differences in average monthly expenditures between the two intervention groups across time.Discussion: Findings suggest that while telephone-based CBT offers more participation flexibility, it has a similar cost profile as compared to the in-person CBT. Despite the lack of cost saving, telephone-based CBT may be an important option for providing skills building and support to older African-American family CGs with barriers to access resources for respite care and transportation.

The impact of mechanical oesophageal deviation on posterior wall pulmonary vein reconnection.

AIMS: During atrial fibrillation ablation, oesophageal heating typically prompts reduction or termination of radiofrequency energy delivery. We previously demonstrated oesophageal temperature rises are associated with posterior left atrial pulmonary vein reconnection (PVR) during redo procedures. In this study, we assessed whether mechanical oesophageal deviation (MED) during an index procedure minimizes posterior wall PVRs during redo procedures. METHODS AND RESULTS: Patients in whom we performed a first-ever procedure followed by a clinically driven redo procedure were divided based on both the use of MED for oesophageal protection and the ablation catheter employed (force or non-force sensing) in the first procedure. The PVR sites were compared between MED using a force-sensing catheter (MEDForce), or no MED with a non-force (ControlNoForce) or force (ControlForce) sensing catheter. Despite similar clinical characteristics, the MEDForce redo procedure rate (9.2%, 26/282 patients) was significantly less than the ControlNoForce (17.2%, 126/734 patients; P = 0.002) and ControlForce (17.5%, 20/114 patients; P = 0.024) groups. During the redo procedure, the posterior PVR rate with MEDForce (2%, 1/50 PV pairs) was significantly less than with either ControlNoForce (17.7%, 44/249 PV pairs; P = 0.004) or ControlForce (22.5%, 9/40 PV pairs; P = 0.003), or aggregate Controls (18.3%, 53/289 PV pairs; P = 0.006). However, the anterior PVR rate with MEDForce (8%, 4/50 PV pairs) was not significantly different than Controls (aggregate Controls-3.5%, 10/289 PV pairs, P = 0.136; ControlNoForce-2.4%, 6/249 PV pairs, P = 0.067; ControlForce-10%, 4/40 PV pairs, P = 1.0). CONCLUSION: Oesophageal deviation improves the durability of the posterior wall ablation lesion set during AF ablation.