An Anti-C1s Monoclonal, TNT003, Inhibits Complement Activation Induced by Antibodies Against HLA.

Antibody-mediated rejection (AMR) of solid organ transplants (SOT) is characterized by damage triggered by donor-specific antibodies (DSA) binding donor Class I and II HLA (HLA-I and HLA-II) expressed on endothelial cells. While F(ab')2 portions of DSA cause cellular activation and proliferation, Fc regions activate the classical complement cascade, resulting in complement deposition and leukocyte recruitment, both hallmark features of AMR. We characterized the ability of an anti-C1s monoclonal antibody, TNT003, to inhibit HLA antibody (HLA-Ab)-induced complement activation. Complement deposition induced by HLA-Ab was evaluated using novel cell- and bead-based assays. Human aortic endothelial cells (HAEC) were cultured with HLA-Ab and human complement; production of activated complement proteins was measured by flow cytometry. Additionally, C3d deposition was measured on single antigen beads (SAB) mixed with HLA-Ab and human complement. TNT003 inhibited HLA-Ab mediated complement deposition on HAEC in a concentration-dependent manner; C3a, C4a and C5a anaphylatoxin production was also diminished by TNT003. Finally, TNT003 blocked C3d deposition induced by Class I (HLAI-Ab)- and Class II (HLAII-Ab)-specific antibodies on SAB. These data suggest TNT003 may be useful for modulating the effects of DSA, as TNT003 inhibits complement deposition and split product formation generated by HLA-I/II-Ab in vitro

Microbiological Load of Selected Oral Liquid Pharmaceuticals

The microbiological quality of 24 samples of oral pharmaceuticals comprising antacids, cough and paracetamolsyrups purchased randomly from different drug stores operating in Abakaliki metropolis were assessed. They wereanalyzed by pour plate method. Their microbial load was determined using the viable cell count method. The resulting contaminating microorganisms were isolated and characterized by standard methods. The results revealed fungal and bacterial contaminations in 16 and 19 samples respectively. Contaminant bacteria include Bacillus spp.,Staphylococcus spp., E.coli, Proteus spp, Klebsiella spp. and Pseudomonas spp. with Staphylococcus spp. being the most predominant bacterial contaminant, while fungi contaminants were basically Mucor and Aspergillus species. The pH values of the analyzed drugs ranged from 5 to 9. The variations in the stated pH of sampled products were however, not justified in this work; thus queries the stated drug pH and why certain isolated organisms could grow on such pH outside their normal habitats’ pH. This study has shown therefore, that some oral pharmaceuticals sold in drug stores maybe heavily contaminated by varying microbial agents.Keywords: Oral, Pharmaceuticals, Bacteria, Fungi, Contamination

Estimating δ15N fractionation and adjusting the lipid correction equation using Southern African freshwater fishes

Stable isotope analysis is an important tool for characterising food web structure; however, interpretation of isotope data can often be flawed. For instance, lipid normalisation and trophic fractionation values are often assumed to be constant, but can vary considerably between ecosystems, species and tissues. Here, previously determined lipid normalisation equations and trophic fractionation values were re-evaluated using freshwater fish species from three rivers in the Upper Zambezian floodplain ecoregion in southern Africa. The parameters commonly used in lipid normalisation equations were not correct for the 18 model species (new D and I parameters were estimated as D = 4.46‰ [95% CI: 2.62, 4.85] and constant I = 0 [95% CI: 0, 0.17]). We suggest that future isotopic analyses on freshwater fishes use our new values if the species under consideration do not have a high lipid content in their white muscle tissue. Nitrogen fractionation values varied between species and river basin; however, the average value closely matched that calculated in previous studies on other species (δ15N fractionation factor of 3.37 ± 1.30 ‰). Here we have highlighted the need to treat stable isotope data correctly in food web studies to avoid misinterpretation of the data

Observational study of the association of first insulin type in uncontrolled type 2 diabetes with macrovascular and microvascular disease

<p>Aims: To compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.</p> <p>Methods: People included in THIN United Kingdom primary care record database who began insulin (2000–2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A1c (HbA1c) and weight change.</p> <p>Results: Mean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA1c had reduced less in basal versus pre-mix or NPH at 6–8 and at 9–11 months, and versus pre-mix at 12–14 months.</p> <p>Conclusion: We found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA1c compared to other insulins.</p&gt

Prevalence of Acid-Alcohol-Fast Bacilli among Patients with Suspected Cases of Pulmonary Tuberculosis in Jos, Nigeria

Mycobacterium tuberculosis is a major public health problem in globally due to its high tendency of person-person transmission, morbidity, and  mortality. This study aimed at determining the prevalence of AAFB within the study area. Sputum samples were collected from three hundred and three (303) patients with suspected cases of pulmonary tuberculosis attending Plateau State Specialist Hospital and Faith Alive Foundation. The samples were examined using Ziehl Neelsen method. Structured  questionnaires were administered to obtain some demographic data from patients that consented. Results were tested statistically for significance at p < 0.05 using Chi-square test. Out of the samples examined,29(9.57.0%) were positive for AAFB .The study showed that the prevalence of smear-positive increased with age between 15 and 45 and then decreased from age groups 46 and above. The study also revealed that males had a higher prevalence with 19(12.34%)than females who had 10(6.71%  ).Marital status showed that divorced individuals had the highest  prevalence of 2(12.50%) followed by married ,singles and the widowed with 18(11.76%),8(6.34%),and 1(5.90%) respectively. Statistically the study reveals that age groups, sex, hospital (location) does not have any effects on the prevalence (p > 0.05) while marital status showed a significant  effect on the prevalence (p < 0.05).There is need for a more collaborative efforts and political will by the government and non-governmental agencies in order to fast track prevention and control measures aimed at eliminating the infection in the nearest future.Key words: AFB, Tuberculosis, Jos, Nigeria

Meniere's disease and the use of proton pump inhibitors.

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Prognosis, characteristics, and provision of care for patients with the unspecified heart failure electronic health record phenotype: a population-based linked cohort study of 95262 individuals

Background: Whether the accuracy of the phenotype ascribed to patients in electronic health records (EHRs) is associated with variation in prognosis and care provision is unknown. We investigated this for heart failure (HF, characterised as HF with preserved ejection fraction [HFpEF], HF with reduced ejection fraction [HFrEF] and unspecified HF). / Methods: We included individuals aged 16 years and older with a new diagnosis of HF between January 2, 1998 and February 28, 2022 from linked primary and secondary care records in the Clinical Practice Research Datalink in England. We investigated the provision of guideline-recommended diagnostic investigations and pharmacological treatments. The primary outcome was a composite of HF hospitalisation or all-cause death, and secondary outcomes were time to HF hospitalisation, all-cause death and death from cardiovascular causes. We used Kaplan–Meier curves and log rank tests to compare survival across HF phenotypes and adjusted for potential confounders in Cox proportional hazards regression analyses. / Findings: Of a cohort of 95,262 individuals, 1271 (1.3%) were recorded as having HFpEF, 10,793 (11.3%) as HFrEF and 83,198 (87.3%) as unspecified HF. Individuals recorded as unspecified HF were older with a higher prevalence of dementia. Unspecified HF, compared to patients with a recorded HF phenotype, were less likely to receive specialist assessment, echocardiography or natriuretic peptide testing in the peri-diagnostic period, or receive angiotensin-converting enzyme inhibitors, beta blockers or mineralocorticoid receptor antagonists up to 12 months after diagnosis (risk ratios compared to HFrEF, 0.64, 95% CI 0.63–0.64; 0.59, 0.58–0.60; 0.57, 0.55–0.59; respectively) and had significantly worse outcomes (adjusted hazard ratios compared to HFrEF, HF hospitalisation and death 1.66, 95% CI 1.59–1.74; all-cause mortality 2.00, 1.90–2.10; cardiovascular death 1.77, 1.65–1.90). / Interpretation: Our findings suggested that absence of specification of HF phenotype in routine EHRs is inversely associated with clinical investigations, treatments and survival, representing an actionable target to mitigate prognostic and health resource burden. / Funding: Japan Research Foundation for Healthy Aging andBritish Heart Foundation