Isolation and characterization of native Bacillus thuringiensis strains from Saudi Arabia with enhanced larvicidal toxicity against the mosquito vector Anopheles gambiae (s.l.).

BACKGROUND: Worldwide, mosquito vectors are transmitting several etiological agents of important human diseases, including malaria, causing millions of deaths every year. In Saudi Arabia, as elsewhere, vector-control is based mostly on chemical insecticides which may be toxic and cause environmental deprivation. Here, to support the development of bio-pesticide alternatives, a study was conducted to identify native Bacillus thuringiensis (Bt) isolates with improved toxicity against the malaria vector, Anopheles gambiae (s.l.). METHODS: Sixty-eight Bt isolates were obtained from 300 soil and other samples collected from 16 sites across Saudi Arabia. Bt identification was based on morphological characteristics of colonies, shape of parasporal crystals and biochemical profiles. After characterization of their mosquitocidal activity, larvicidal strains were described through 16S ribosomal DNA gene sequencing, cry, cyt and chi genes PCR-amplification profiles, and SDS-PAGE protein analyses. RESULTS: Spherical Bt crystals were predominant amongst the 68 isolates (34%), while irregular, bi-pyramidal and spore-attached crystals were found in 32, 13 and 21% of strains, respectively. LC50 and LC90 bioassays showed that 23/68 isolates were larvicidal, with distinct biochemical activity profiles compared to non-larvicidal Bt strains. Eight larvicidal strains showed larvicidal activity up to 3.4-fold higher (LC50 range: 3.90-7.40 μg/ml) than the reference Bti-H14 strain (LC50 = 13.33 μg/ml). Of these, 6 strains had cry and cyt gene profiles similar to Bti-H14 (cry4Aa, cry4Ba, cry10, cry11, cyt1Aa, cyt1Ab, cyt2Aa). The seventh strain (Bt63) displaying the highest larvicidal activity (LC50 = 3.90 μg/ml) missed the cry4Aa and cyt1Ab genes and had SDS-PAGE protein profiles and spore/crystal sizes distinct from Bti-H14. The eight strain (Bt55) with LC50 of 4.11μg/ml had cry and cyt gene profiles similar to Bti-H14 but gave a chi gene PCR product size of 2027bp. No strains harbouring cry2, cry17 + 27, cry24 + 40, cry25, cry29, cry30, or cyt2Ba were detected. CONCLUSION: This study represents the first report of several Saudi indigenous Bt strains with significantly higher larvicidal efficacy against An. gambiae than the reference Bti-H14 strain. The very high toxicity of the Bt63 strain, combined with distinct cry and cyt genes and SDS-PAGE-protein profiles makes it a promising candidate for future applications in mosquito bio-control

Predictors of the Late Renal Outcome after Posterior Urethral Valves Ablation in a Developing Country: Long Term Study

Introduction: Posterior urethral valves are the commonest form of obstructive uropathy in pediatrics and a common cause of chronic kidney disease (CKD) during childhood with estimated renal failure rate of 25-40%. This study aims at evaluating long term changes in kidney and bladder functions of children with posterior urethral valves after ablation, and at assessing predictors of late renal outcome, considering challenges in Egypt as a developing country.   Materials and Methods: A retrospective study of 30 surgically managed  PUVs patients who attended at Alexandria University Children’s Hospital for follow up. Patients underwent surgery between 2005 and 2016. Mean postoperative follow up period was 6.7±3.8 years (range 3.1 to 14.6 years). Data collected included age at presentation, clinical presentation, serum creatinine (initial, nadir, and last follow up), eGFR at last follow up, renal ultrasound (initial, and last follow up), voiding cystourethrogram (initial, and last follow up), and urodynamic studies at last follow up.   Results: Thirty patients underwent PUVs ablation at a median age of 9 months. Ten (33.3%) patients were diagnosed antenatally. At the last follow up visit, 14 (46.7%) patients had moderate-severe CKD. Twenty-five (83.3%) patients had abnormalities in their urodynamic studies. Univariate analysis showed the need for re-ablation, use of anti-cholinergics, high initial serum creatinine, high nadir creatinine, presence of VUR, history of febrile UTIs and presence of proteinuria were significantly associated with low eGFR. Multivariate analysis showed that high nadir creatinine and presence of VUR were independent factors associated with lower e-GFR at last follow-up. Antenatal diagnosis was significantly associated with better e-GFR. Conculsion: Nadir creatinine and vesicoureteral reflux have high prognostic value for late renal functions, and antenatal diagnosis is associated with better renal functions in patients with posterior urethral valves. Increasing family awareness, antenatal care facilities,and referal to tertiary care centers are priorities for promoting the antenatal diagnosis and management in developing countries.Facilities and training for prenatal intervention should be encouraged

Pulmonary Aspergillosis: A Review on Diagnosis and Management

Aspergillosis is acquired by inhalation of spores of Aspergillus, a ubiquitous species in the environment. In normal hosts, spore inhalation rarely causes lung disease. Pulmonary aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive aspergillosis to Aspergillus bronchitis and colonization. Invasive aspergillosis occurs in severely immunocompromised patients, typically with neutropenia. Chronic pulmonary aspergillosis affects patients with chronic structural lung disease such as chronic obstructive pulmonary disease, mycobacterial lung disease, but without significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such as bronchiectasis. Allergic bronchopulmonary aspergillosis affects patients with bronchial asthma or cystic fibrosis, and is due to an allergic response to Aspergillus. In this review of literature, we discuss the pulmonary manifestations of Aspergillus infection, its diagnosis and treatments

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

Ageing is the primary risk factor for Parkinson's disease. Progressive motor and coordination decline that occurs with ageing has been linked to nigrostriatal dysfunction. Few studies have investigated the efficacy of mesenchymal stem cells in ameliorating the structural and functional alterations in the ageing nigrostriatal system. This study is the first to evaluate the effects of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose-induced rat model of nigrostriatal ageing. BMMSCs were intravenously injected once every 2 weeks for 8 weeks. The transplanted cells survived, migrated to the brain, and differentiated into dopaminergic neurones and astrocytes. BMMSC transplantation improved locomotor activity, restored dopaminergic system function, preserved atrophic dopaminergic neurones in the substantia nigra, exerted antioxidative effects, and restored neurotrophic factors. Our findings demonstrate the efficacy of BMMSC injection in a nigrostriatal ageing rat model, and suggest that these cells may provide an effective therapeutic approach for the ageing nigrostriatal system

GPCRs and Fibroblast Heterogeneity in Fibroblast-Associated Diseases

G protein-coupled receptors (GPCRs) are the largest and most diverse class of signaling receptors. GPCRs regulate many functions in the human body and have earned the title of most targeted receptors . About one-third of the commercially available drugs for various diseases target the GPCRs. Fibroblasts lay the architectural skeleton of the body, and play a key role in supporting the growth, maintenance, and repair of almost all tissues by responding to the cellular cues via diverse and intricate GPCR signaling pathways. This review discusses the dynamic architecture of the GPCRs and their intertwined signaling in pathological conditions such as idiopathic pulmonary fibrosis, cardiac fibrosis, pancreatic fibrosis, hepatic fibrosis, and cancer as opposed to the GPCR signaling of fibroblasts in physiological conditions. Understanding the dynamics of GPCR signaling in fibroblasts with disease progression can help in the recognition of the complex interplay of different GPCR subtypes in fibroblast-mediated diseases. This review highlights the importance of designing and adaptation of next-generation strategies such as GPCR-omics, focused target identification, polypharmacology, and effective personalized medicine approaches to achieve better therapeutic outcomes for fibrosis and fibrosis associated malignancies

Social Determinants of Health in Pulmonary Arterial Hypertension Patients in the United States: Clinician Perspective and Health Policy Implications

Social determinants of health (SDoH) can impact the vulnerable pulmonary arterial hypertension (PAH) population, especially during the COVID-19 pandemic. Providers\u27 understanding of SDoH at the point of care and their impact is unknown. We conducted semi-structured virtual interviews with US clinicians at 17 pulmonary hypertension (PH) centers and one patient advocate from the Pulmonary Hypertension Association. We sought participants\u27 perspective on SDoH in PAH and their impact. Transcripts were developed and analyzed for key themes to assess potential policy implications. Participants served a large PAH population and demonstrated high awareness of SDoH and its impact on treatment and outcomes. They reported that patients\u27 SDoH, including socioeconomic status, health insurance, access to health care, education levels, health literacy, employment status, and insecurities associated with housing, food, transportation, and family support, impacted health and well-being. COVID-19-related social isolation, mental health, and substance abuse contributed to significant inequities in care provision and outcomes. While telemedicine helped clinicians manage patients remotely during the pandemic, there was a concern for patients with limited access to this medium. Participants reported no formal screening for SDoH at the point of care. With the recognition and the desire to act upon health inequities associated with SDoH, participants felt that it was vital for their centers to have a dedicated PH social worker and support staff to optimize care and outcomes. An approach that integrates SDoH in PAH care management, streamlined through institutional policy, could address health disparities leading to improved healthcare access, outcomes, and quality of care

Developing national obesity policy in middle-income countries: a case study from North Africa

Background The prevalence of overweight and obesity is a rapidly growing threat to public health in both Morocco and Tunisia, where it is reaching similar proportions to high-income countries. Despite this, a national strategy for obesity does not exist in either country. The aim of this study was to explore the views of key stakeholders towards a range of policies to prevent obesity, and thus guide policy makers in their decision making on a national level. Methods Using Multicriteria Mapping, data were gathered from 82 stakeholders (from 33 categories in Morocco and 36 in Tunisia) who appraised 12 obesity policy options by reference to criteria of their own choosing. Results The feasibility of policies in practical or political terms and their cost were perceived as more important than how effective they would be in reducing obesity. There was most consensus and preference for options targeting individuals through health education, compared with options that aimed at changing the environment, i.e. modifying food supply and demand (providing healthier menus/changing food composition/food sold in schools); controlling information (advertising controls/mandatory labelling) or improving access to physical activity. In Tunisia, there was almost universal consensus that at least some environmental-level options are required, but in Morocco, participants highlighted the need to raise awareness within the population and policy makers that obesity is a public health problem, accompanied by improving literacy before such measures would be accepted. Conclusion Whilst there is broad interest in a range of policy options, those measures targeting behaviour change through education were most valued. The different socioeconomic, political and cultural contexts of countries need to be accounted for when prioritizing obesity policy. Obesity was not recognized as a major public health priority; therefore, convincing policy makers about the need to prioritize action to prevent obesity, particularly in Morocco, will be a crucial first step