HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes

HOXA10 is necessary for embryonic patterning of skeletal elements, but its function in bone formation beyond this early developmental stage is unknown. Here we show that HOXA10 contributes to osteogenic lineage determination through activation of Runx2 and directly regulates osteoblastic phenotypic genes. In response to bone morphogenic protein BMP2, Hoxa10 is rapidly induced and functions to activate the Runx2 transcription factor essential for bone formation. A functional element with the Hox core motif was characterized for the bone-related Runx2 P1 promoter. HOXA10 also activates other osteogenic genes, including the alkaline phosphatase, osteocalcin, and bone sialoprotein genes, and temporally associates with these target gene promoters during stages of osteoblast differentiation prior to the recruitment of RUNX2. Exogenous expression and small interfering RNA knockdown studies establish that HOXA10 mediates chromatin hyperacetylation and trimethyl histone K4 (H3K4) methylation of these genes, correlating to active transcription. HOXA10 therefore contributes to early expression of osteogenic genes through chromatin remodeling. Importantly, HOXA10 can induce osteoblast genes in Runx2 null cells, providing evidence for a direct role in mediating osteoblast differentiation independent of RUNX2. We propose that HOXA10 activates RUNX2 in mesenchymal cells, contributing to the onset of osteogenesis, and that HOXA10 subsequently supports bone formation by direct regulation of osteoblast phenotypic genes. <br/

Resting-state Networks in Tinnitus: A Scoping Review

Chronic subjective tinnitus is the constant perception of a sound that has no physical source. Brain imaging studies show alterations in tinnitus patients’ resting-state networks (RSNs). This scoping review aims to provide an overview of resting-state fMRI studies in tinnitus, and to evaluate the evidence for changes in different RSNs. A total of 29 studies were included, 26 of which found alterations in networks such as the auditory network, default mode network, attention networks, and visual network; however, there is a lack of reproducibility in the field which can be attributed to the use of different regions of interest and analytical methods per study, and tinnitus heterogeneity. Future studies should focus on replication by using the same regions of interest in their analysis of resting-state data, and by controlling adequately for potential confounds. These efforts could potentially lead to the identification of a biomarker for tinnitus in the future

Transplantation for renal failure secondary to enteric hyperoxaluria: a case report

Enteric hyperoxaluria can lead to renal failure. There have only been a few reports of renal transplantation as treatment of endstage renal disease secondary to enteric hyperoxaluria and results have been mixed. This report describes a patient with Crohn's disease who developed chronic renal failure from enteric hyperoxaluria. He subsequently had a successful renal transplant without any post-operative oxalate related complications and has satisfactory renal function almost three years later. Aggressive pre-transplant hemodialysis was not done. The literature associated with renal transplantation for enteric hyperoxaluria is reviewed

Smallholder farmers' adaptation to climate change and determinants of their adaptation decisions in the Central Rift Valley of Ethiopia

Background: The agricultural sector remains the main source of livelihoods for rural communities in Ethiopia, but faces the challenge of changing climate. This study investigated how smallholder farmers perceive climate change, what adaptation strategies they practice, and factors that influence their adaptation decisions. Both primary and secondary data were used for the study, and a multinomial logit model was employed to identify the factors that shape smallholder farmers’ adaptation strategies. Results: The results show that 90% of farmers have already perceived climate variability, and 85% made attempts to adapt using practices like crop diversification, planting date adjustment, soil and water conservation and management, increasing the intensity of input use, integrating crop with livestock, and tree planting. The econometric model indicated that education, family size, gender, age, livestock ownership, farming experience, frequency of contact with extension agents, farm size, access to market, access to climate information and income were the key factors determining farmers’ choice of adaptation practice. Conclusion: In the Central Rift Valley of Ethiopia, climate change is a pressing problem, which is beyond the capacity of smallholders to respond to autonomously. Farmers’ capacity to choose effective adaptation options is influenced by household demography, as well as positively by farm size, income, access to markets, access to climate information and extension, and livestock production. This implies the need to support the indigenous adaptation strategies of the smallholder farmers with a wide range of institutional, policy, and technology support; some of it targeted on smaller, poorer or female-headed households. Moreover, creating opportunities for non-farm income sources is important as this helps farmers to engage in those activities that are less sensitive to climate change. Furthermore, providing climate change information, extension services, and creating access to markets are crucial

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

<p>Abstract</p> <p>Background</p> <p>Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.</p> <p>Methods/Design</p> <p>This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part^®Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10) days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10) days and 3 months (±14 days) after surgery.</p> <p>Discussion</p> <p>This trial aims to assess, whether the intra-peritoneal application of A-Part^®Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls.</p> <p>Trial registration</p> <p>NCT00646412</p

Ammonia-Nitrogen Recovery from Synthetic Solution using Agricultural Waste Fibers

In this study, modification of Empty Fruit Bunch (EFB) fibers as a means to recover ammonianitrogen from a synthetic solution was investigated. Methods: The EFB fiber was modified using sodium hydroxide.Adsorption-desorption studies of ammonia nitrogen into the modified EFB fiber were investigated Findings: Theincrease in adsorption capacity was found to be proportional with the increase of pH up to 7, temperature and ammoniaconcentration. The maximum adsorption capacity is 0.53-10.89 mg/g. The attachment of ammonia nitrogen involves ionexchange-chemisorption. The maximum desorption capacity of 0.0999 mg/g. Applications: This study can be used as abaseline for designing a low cost adsorbent system for ammonia nitrogen recovery drainage and industrial wastewater aswell as EFBs-palm oil mill effluent composting

Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (RAPID - Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) in adults with pleural infection. METHODS: Prospective observational cohort study recruiting patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment, and lung function at 3 months. RESULTS: Mortality data were available in 542 of 546 (99.3%) patients recruited. Overall mortality was 10% (54/542) at 3 months and 19% (102/542) at 12 months. The RAPID risk category predicted mortality at 3 months; low-risk (RAPID score 0-2) mortality 5/222 (2.3%, 95%CI 0.9 to 5.7), medium-risk (RAPID score 3-4) mortality 21/228 (9.2%, 95%CI 6.0 to 13.7), and high-risk (RAPID score 5-7) mortality 27/92 (29.3%, 95%CI 21.0 to 39.2). C-statistics for the score at 3 and 12 months were 0.78 (95%CI 0.71 to 0.83) and 0.77 (95%CI 0.72 to 0.82) respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population