Frequency and determinants of intracranial atherosclerotic stroke in urban Pakistan.

BACKGROUND: Intracranial atherosclerosis (ICAD) is a frequent underlying mechanism of ischemic stroke. There is little direct evidence on its frequency and determinants from regions of high prevalence. This study explores the conventional and socioeconomic risk factors of ICAD in a South Asian population. METHODS: The Karachi Intracranial Stenosis Study is a case-control study of 313 cases of ischemic stroke secondary to ICAD and 331 controls enrolled from 4 major hospitals in Karachi, Pakistan. Stroke subtype was verified by a vascular neurologist using the Trial of Org 10172 in Acute Stroke Treatment classification. Relationships of conventional and socioeconomic risk factors with ICAD-related strokes are reported by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: ICAD was the cause of stroke in 81.1% cases with large-artery atherosclerosis and 19.5% of all stroke events. Along with risk factors like history of hypertension (OR, 3.33; CI, 2.31-4.78), history of diabetes (OR, 2.29; CI, 1.56-3.35), use of tobacco (OR, 1.49; CI, 1.03-2.16), waist-to-hip ratio (OR, 1.58; CI, 1.04-2.41), and family history of stroke (OR, 1.89; CI, 1.21-2.95), other significant social determinants of ICAD strokes were monthly income (OR, 1.59; CI, 1.01-2.51), unemployment (OR, 2.15; CI, 1.21-3.83), and chronic stress (OR, 3.67; CI, 2.13-6.34). These social determinants were independent predictors of the risk of ICAD, in addition to those described in other world populations. CONCLUSIONS: ICAD accounted for one fifth of all strokes making it the most common ischemic stroke mechanism. In addition to aggressive risk factor control, data also indicated broader holistic efforts on ameliorating inequity, unemployment, and stress reduction to reduce stroke because of ICAD.

Total Intravenous Anesthesia Versus Inhalation Anesthesia on Postoperative Analgesia and Nausea and Vomiting After Bariatric Surgery: A Systematic Review and Meta-Analysis.

Anesthesia for patients with morbid obesity can be challenging because of increased risk of opioid-related adverse events, postoperative nausea and vomiting (PONV), and poor pain control. We conducted a systematic review and meta-analysis to compare the safety and efficacy of total intravenous anesthesia (TIVA) with inhalation anesthesia in patients undergoing bariatric surgery. We searched MEDLINE, EMBASE, CENTRAL, and the Clinical Trials Registry database from inception to July 22, 2020. Primary outcomes were postoperative pain and PONV scores. Secondary outcomes included opioid requirements, intraoperative time, complications, and time to recovery. Grading of Recommendations Assessment, Development, and Evaluation framework was used to rate the certainty of evidence. Among 722 studies identified in our search, 7 randomized studies involving a total of 682 patients met the inclusion criteria. Bariatric surgery with TIVA resulted in a lower incidence of nausea (relative risk [RR], 0.54; 95% CI, 0.31-0.94; P = 0.03; moderate certainty) and vomiting (RR, 0.31; 95% CI, 0.13-0.74; P = 0.008; moderate certainty). There was no difference in postoperative pain at 30 minutes, 1 hour, or 24 hours, or in postoperative opioid requirements. Patients undergoing bariatric surgery with TIVA had significantly lower incidence of PONV but no difference in postoperative pain when TIVA was compared to inhalation anesthesia techniques. These benefits should be considered in order to improve the quality of care and enhance recovery for the bariatric population, who are at an increased baseline risk of perioperative complications. Future adequately powered randomized controlled trials are needed to compare the efficacy of the anesthesia regimens in patients undergoing bariatric surgery.

Management of Frailty: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To analyze and determine the comparative effectiveness of interventions targeting frailty prevention or treatment on frailty as a primary outcome and quality of life, cognition, depression, and adverse events as secondary outcomes. DESIGN: Systematic review and network meta-analysis (NMA). METHODS: Data sources-Relevant randomized controlled trials (RCTs) were identified by a systematic search of several electronic databases including MEDLINE, EMBASE, CINAHL, and AMED. Duplicate title and abstract and full-text screening, data extraction, and risk of bias assessment were performed. Data extraction-All RCTs examining frailty interventions aimed to decrease frailty were included. Comparators were standard care, placebo, or another intervention. Data synthesis-We performed both standard pairwise meta-analysis and Bayesian NMA. Dichotomous outcome data were pooled using the odds ratio effect size, whereas continuous outcome data were pooled using the standardized mean difference (SMD) effect size. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome. The quality of evidence was evaluated using the GRADE approach. RESULTS: A total of 66 RCTs were included after screening of 7090 citations and 749 full-text articles. NMA of frailty outcome (including 21 RCTs, 5262 participants, and 8 interventions) suggested that the physical activity intervention, when compared to placebo and standard care, was associated with reductions in frailty (SMD -0.92, 95% confidence interval -1.55, -0.29). According to SUCRA, physical activity intervention and physical activity plus nutritional supplementation were probably the most effective intervention (100% and 71% likelihood, respectively) to reduce frailty. Physical activity was probably the most effective or the second most effective interventions for all included outcomes. CONCLUSION AND IMPLICATIONS: Physical activity is one of the most effective frailty interventions. The quality of evidence of the current review is low and very low. More robust RCTs are needed to increase the confidence of our NMA results and the quality of evidence.

Identification and Characterization of Segregation Distortion Loci on Cotton Chromosome 18.

Segregation distortion is commonly detected via genetic mapping and this phenomenon has been reported in many species. However, the genetic causes of the segregation distortion regions in a majority of species are still unclear. To genetically dissect the SD on chromosome 18 in cotton, eight reciprocal backcross populations and two F2 populations were developed. Eleven segregation distortion loci (SDL) were detected in these ten populations. Comparative analyses among populations revealed that SDL18.1 and SDL18.9 were consistent with male gametic competition; whereas SDL18.4 and SDL18.11 reflected female gametic selection. Similarly, other SDL could reflect zygotic selection. The surprising finding was that SDL18.8 was detected in all populations, and the direction was skewed towards heterozygotes. Consequently, zygotic selection or heterosis could represent the underlying genetic mechanism for SDL18.8. Among developed introgression lines, SDL18.8 was introgressed as a heterozygote, further substantiating that a heterozygote state was preferred under competition. Six out of 11 SDL on chromosome 18 were dependent on the cytoplasmic environment. These results indicated that different SDL showed varying responses to the cytoplasmic environment. Overall, the results provided a novel strategy to analyze the molecular mechanisms, which could be further exploited in cotton interspecific breeding programs.

Manifestations of bodily isomerism.

We report the findings present in 49 postmortem specimens from patients with so-called heterotaxy, concentrating on those found in the extracardiac systems of organs. Also known as bodily isomerism, we suggest that it is important to segregate the syndromes into their isomeric subtypes to be able to make inferences regarding likely extracardiac and intracardiac findings to allow for proper surveillance. We demonstrate that this is best done on the basis of the atrial appendages, which were isomeric in all the hearts obtained from the specimens available for our inspection. The abdominal organs do not demonstrate isomerism, and they show variable features when compared to the isomeric atrial appendages.

P2RX7 sensitizes Mac-1/ICAM-1-dependent leukocyte-endothelial adhesion and promotes neurovascular injury during septic encephalopathy.

Septic encephalopathy (SE) is a critical factor determining sepsis mortality. Vascular inflammation is known to be involved in SE, but the molecular events that lead to the development of encephalopathy remain unclear. Using time-lapse in vivo two-photon laser scanning microscopy, we provide the first direct evidence that cecal ligation and puncture in septic mice induces microglial trafficking to sites adjacent to leukocyte adhesion on inflamed cerebral microvessels. Our data further demonstrate that septic injury increased the chemokine CXCL1 level in brain endothelial cells by activating endothelial P2RX7 and eventually enhanced the binding of Mac-1 (CD11b/CD18)-expressing leukocytes to endothelial ICAM-1. In turn, leukocyte adhesion upregulated endothelial CX3CL1, thereby triggering microglia trafficking to the injured site. The sepsis-induced increase in endothelial CX3CL1 was abolished in CD18 hypomorphic mutant mice. Inhibition of the P2RX7 pathway not only decreased endothelial ICAM-1 expression and leukocyte adhesion but also prevented microglia overactivation, reduced brain injury, and consequently doubled the early survival of septic mice. These results demonstrate the role of the P2RX7 pathway in linking neurovascular inflammation to brain damage in vivo and provide a rationale for targeting endothelial P2RX7 for neurovascular protection during SE.

Natal and neonatal teeth.

Natal teeth (teeth present at birth) and neonatal teeth (teeth observed in the first 30 days of life) are uncommon. They may cause feeding problems and ulcerations on the ventral surface of the tongue. They can also be alarming to parents and cause discomfort with breastfeeding. A review of literature was conducted to review their etiology, significance, and clinical features with special emphasis on the complications and management. The opportunity of establishing a dental home through the early dental visits was highlighted. Furthermore, this case report details the examination and management of a 24-hour old neonate with 2 neonatal teeth. Natal teeth, although uncommon, are best referred to pediatric dentists for investigation and management.

Targeted therapy of brain ischaemia using Fas ligand antibody conjugated PEG-lipid nanoparticles.

The translation of experimental stroke research from the laboratory to successful clinical practice remains a formidable challenge. We previously reported that PEGylated-lipid nanoparticles (PLNs) effectively transport across the blood-brain barrier along with less inflammatory responses. In the present study, PLNs conjugated to Fas ligand antibody that selectively present on brain ischaemic region were used for therapeutic targeting. Fluorescent analysis of the mice brain show that encapsulated 3-n-Butylphthalide (dl-NBP) in PLNs conjugated with Fas ligand antibody effectively delivered to ipsilateral region of ischaemic brain. Furthermore, the confocal immunohistochemical study demonstrated that brain-targeted nanocontainers specifically accumulated on OX42 positive microglia cells in ischaemic region of mice model. Finally, dl-NBP encapsulated nano-drug delivery system is resulted in significant improvements in brain injury and in neurological deficit after ischaemia, with the significantly reduced dosages versus regular dl-NBP. Overall, these data suggests that PLNs conjugated to an antibody specific to the Fas ligand constituted an ideal brain targeting drug delivery system for brain ischaemia.

The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.

BACKGROUND: Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes. AIMS: To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type 1 and type 2 diabetic rats. METHODS: Early experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting and immunohistochemistry. RESULTS: Our data showed a pronounced decrease in the phosphorylation of Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) in the hippocampi of both type 1 and type 2 diabetic rats compared with age-matched control rats. Unexpectedly, we found a significant increase in the phosphorylation of synapsin I (Ser 603) and GluR1 (Ser 831) in the same experiment. In addition, aberrant changes in hippocampal protein kinase C (PKC) and protein kinase A (PKA) signaling in type 1 and type 2 diabetic rats were also found. Moreover, PP1α and PP2A protein levels were decreased in the hippocampus of type 1 diabetic rats, but significantly up-regulated in type 2 diabetic rats. CONCLUSIONS: The disturbance of CaMKII/PKA/PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes-related cognitive dysfunction.