Effectiveness of elephantorhiza elephantina as traditional plant used as the alternative for controlling coccidia infections in goats.

Elephantorrhiza elephantina Bruch Skeels is used by farmers in the Eastern Cape Province of South Africa to control Gastro-intestinal parasites in goats. The objective of the study was to determine the effects of E. elephantina on coccidia oocysts and determine the effectiveness of the dose levels on goats. Thirty six goats (18 males and 18 females) between ages of 8-12 months were used; randomly assigned to six treatments (A-F).  Treatments A and B received Prodose orange® at 2ml/10kg and distilled water at 0.5 ml/kg per goat respectively, whereas treatments C (12.5mg/ml), D (25mg/ml), E (50mg/ml) and F (75mg/ml) received aqueous extract of E. elephantina at different concentrations dosed at 2ml/10kg.  Faecal samples were collected on first month, second month and third month for faecal egg counts (FEC) and body-weights recorded to assess weight changes. Animals receiving the extract had weight increases of between 3 to 4 kg by end of experiment, but those drenched with Prodose orange ® gained by less than 2 kg. Findings are indicative that E. elephantina possess some anti-coccidian properties against coccidia oocysts in goats. Keywords: Elephantorrhiza elephantina; faecal egg counts; coccidia oocysts, Ethno-veterinary medicine

The CDEX-1 1 kg Point-Contact Germanium Detector for Low Mass Dark Matter Searches

The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.Comment: 6 pages, 8 figure

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis:Erase

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.</p

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis:Erase

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.</p

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation

Paternal Origins and Migratory Episodes of Domestic Sheep

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy

Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure

Steroids in the Treatment of IgA Nephropathy to the Improvement of Renal Survival: A Systematic Review and Meta-Analysis

Studies have shown that steroids can improve kidney survival and decrease the risk of proteinuria in patients with Immunoglobulin A nephropathy, but the overall benefit of steroids in the treatment of Immunoglobulin A nephropathy remains controversial. The aim of this study was to evaluate the benefits and risks of steroids for renal survival in adults with Immunoglobulin A nephropathy.We searched the Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE and EMBASE databases. All eligible studies were measuring at least one of the following outcomes: end-stage renal failure, doubling of serum creatinine and urinary protein excretion. Fifteen relevant trials (n = 1542) that met our inclusion criteria were identified. In a pooled analysis, steroid therapy was associated with statistically significant reduction of the risk in end-stage renal failure (RR: 0.46, 95% CI: 0.27 to 0.79), doubling of serum creatinine (RR = 0.34, 95%CI = 0.15 to 0.77) and reduced urinary protein excretion (MD = −0.47g/day, 95%CI = −0.64 to −0.31).We identified that steroid therapy was associated with a decrease of proteinuria and with a statistically significant reduction of the risk in end-stage renal failure. Moreover, subgroup analysis also suggested that long-term steroid therapy had a higher efficiency than standard and short term therapy