Sex ratio and age of onset in AQP4 antibody-associated NMOSD: a review and meta-analysis

Background: Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data. Methods: A systematic search of databases was conducted according to the PRISMA guidelines. Articles reporting sex distribution and age of onset for AQP4 antibody-associated NMSOD were reviewed. An initially inclusive approach involving exploration with regression meta-analysis was followed by an analysis of just AQP4 antibody positive cases. Results: A total of 528 articles were screened to yield 89 articles covering 19,415 individuals from 88 population samples. The female:male sex ratio was significantly influenced by the proportion of AQP4 antibody positive cases in the samples studied (p < 0.001). For AQP4 antibody-positive cases the overall estimate of the sex ratio was 8.89 (95% CI 7.78–10.15). For paediatric populations the estimate was 5.68 (95% CI 4.01–8.03) and for late-onset cases, it was 5.48 (95% CI 4.10–7.33). The mean age of onset was significantly associated with the mean life expectancy of the population sampled (p < 0.001). The mean age of onset for AQP4 antibody-positive cases in long-lived populations was 41.7 years versus 33.3 years in the remainder. Conclusions: The female:male sex ratio and the mean age of onset of AQP4 antibody-associated NMOSD are significantly higher than MS. The sex ratio increases with the proportion of cases that are positive for AQP4 antibodies and the mean age of onset increases with population life expectancy

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Phenytoin toxicity presenting with acute visual loss and acute delirium, a case report

Phenytoin is a widely prescribed antiepileptic agent for both focal and generalized seizure. We report a case of a 20-year-old man with focal epilepsy presented with acute bilateral visual loss, and delirium. His random phenytoin serum concentration on admission was 43.6 mg/L, well above the recommended therapeutic range of 10-20 mg/L. Extensive investigations have ruled out other vascular or demyelinating causes. His visual symptoms completely resolved after discontinuing phenytoin for 84 hours. This case shows that acute phenytoin toxicity can result in reversible visual failure

Impact of Crops on the Microclimate and PV System Performance

Faced by land constraints, Singapore needs to look for viable options to bolster renewable energy consumption whilst trying to prop up local food production. Agrivoltaics is seen as a feasible method where hydroponic farming is integrated underneath solar photovoltaics (PV) systems on a common land. This study aims to investigate the impact crops have on the microclimate and whether it contributes to enhanced PV performance. Situated in the SIT@Dover campus in Singapore, the agrivoltaics setup consists of two identical plots, Plot A and Plot B. Each plot consists of twenty solar panels, erected at a height of 2.5m. Beneath the panels contain two hydroponics growth tables, each capable of housing 180 pots of crops. A HOBO External Temperature/RH Sensor Data Loggers were installed 30 cm above each of the growth tables to record data at 5 min logging intervals. A HOBO U30 USB Weather Station Data Logger records meteorological data at intervals of 5 min. Plot A (control) was intentionally left without crops while Plot B was sowed with 90 Brassica oleracea var. sabellica pots (50% capacity). The Brassica oleracea var. sabellica was left to grow in the hydroponics system and harvested on the 32nd day of the crop cycle. Microclimate and energy yield data from the 31st day of the crop cycle were analysed. The 12-h mean temperature from 0700hrs to 1900hrs revealed that the Brassica oleracea var. sabellica on Plot B reduced the temperature above it by 0.97°C as compared to Plot A. The 12-h mean relative humidity tabulated for Plot A and B was 67.45% and 72.30% respectively. During overhead conditions from 1100 hrs to 1300 hrs, Plot B saw the microclimate temperature lowered by 1.33°C as compared to Plot A while the relative humidity elevated by 6.81% as compared to Plot A. The increase in relative humidity is attributed to the transpiration experienced by the Brassica oleracea var. sabellica during photosynthesis which shows that plants have the potential to induce cooler microclimatic conditions. The solar PV on Plot B generated 4.36% lesser energy yield as compared to Plot A. The difference is attributed to uneven irradiance captured by the plots due to building shading caused by the morning sun. Cooler microclimate temperature on Plot B does not contribute to improved PV performance primarily due to the large gap between the growth tables and the underside of the solar panels which encourages sufficient convection to take place.</p

Isolation and identification of plant probiotics for leafy greens.

Plant probiotic bacteria are plant-associated microorganisms that, when applied in a specific amount, improve the growth and yield of the host plants while also suppressing diseases. These plant probiotics have been shown to improve the production of phytohormones, antibiotics, and lytic enzymes; fix atmospheric nitrogen; and even help in the solubilization of soil mineral nutrients (Rahman et al., 2018). Major general of probiotic bacteria that promote plant growth include Bacillus, Pseudomonas, Acinetobacter, Arthrobacter and Serratia (Rahman et al., 2018).This study determined the reproducibility of using three plant probiotics strains (Isolate 4 (Acinetobacter pittii), Isolate 9 (Bacillus altitudinis), and Isolate 8 (Bacillus licheniformis)) on the plant growth of curly kale, Jericho lettuce and Thai basil seeds.Plant probiotic bacteria are plant-associated microorganisms that, when applied in a specific amount, improve the growth and yield of the host plants while also suppressing diseases. These plant probiotics have been shown to improve the production of phytohormones, antibiotics, and lytic enzymes; fix atmospheric nitrogen; and even help in the solubilization of soil mineral nutrients (Rahman et al., 2018). Major general of probiotic bacteria that promote plant growth include Bacillus, Pseudomonas, Acinetobacter, Arthrobacter and Serratia (Rahman et al., 2018).In addition, some PGPR strains are effective in suppressing pest, pathogen and effective as biocontrol agents. Study reported that various Bacillus strains are important in controlling pathogens and improving plant growth due to antagonistic relationships (Rahman et al., 2018). A previous study also showed that PGPR is involved in the production of plant hormones such as indole acetic acid (IAA). The bacteria species most studied and likely to produce this compound are Bradyrhizobium japonicum SB-1 and Bradyrhizobium thuringiensis (Asghari et al., 2020). This study determined the reproducibility of using three plant probiotics strains (Isolate 4 (Acinetobacter pittii), Isolate 9 (Bacillus altitudinis), and Isolate 8 (Bacillus licheniformis)) on the plant growth of curly kale, Jericho lettuce and Thai basil seeds.</p

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale &amp; Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting &amp; Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (&lt;60, 60-69, and &gt;_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 &amp; PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages &lt;60, 60-69, and &gt;_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (&lt;45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791