Background: and Purpose Randomized trials proved the benefits of mechanical thrombectomy (MT) for select patients with large vessel occlusion (LVO) within 24 hours of last-known-well (LKW). Recent data suggest that LVO patients may benefit from MT beyond 24 hours. This study reports the safety and outcomes of MT beyond 24 hours of LKW compared to standard medical therapy (SMT). Methods: This is a retrospective analysis of LVO patients presented to 11 comprehensive stroke centers in the United States beyond 24 hours from LKW between January 2015 and December 2021. We assessed 90-day outcomes using the modified Rankin Scale (mRS). Results: Of 334 patients presented with LVO beyond 24 hours, 64% received MT and 36% received SMT only. Patients who received MT were older (67±15 vs. 64±15 years, P=0.047) and had a higher baseline National Institutes of Health Stroke Scale (NIHSS; 16±7 vs.10±9, P<0.001). Successful recanalization (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 83%, and 5.6% had symptomatic intracranial hemorrhage compared to 2.5% in the SMT group (P=0.19). MT was associated with mRS 0–2 at 90 days (adjusted odds ratio [aOR] 5.73, P=0.026), less mortality (34% vs. 63%, P<0.001), and better discharge NIHSS (P<0.001) compared to SMT in patients with baseline NIHSS ≥6. This treatment benefit remained after matching both groups. Age (aOR 0.94, P<0.001), baseline NIHSS (aOR 0.91, P=0.017), Alberta Stroke Program Early Computed Tomography (ASPECTS) score ≥8 (aOR 3.06, P=0.041), and collaterals scores (aOR 1.41, P=0.027) were associated with 90-day functional independence. Conclusion In patients with salvageable brain tissue, MT for LVO beyond 24 hours appears to improve outcomes compared to SMT, especially in patients with severe strokes. Patients’ age, ASPECTS, collaterals, and baseline NIHSS score should be considered before discounting MT merely based on LKW.

Background: and Purpose Effect of endovascular therapy (EVT) in acute large vessel occlusion (LVO) patients with tandem lesions (TLs) within 6–24 hours after last known well (LKW) remains unclear. We evaluated the clinical and safety outcomes among TL-LVO patients treated within 6–24 hours. Methods: This multicenter cohort was divided into two groups, based on LKW to puncture time: early window (<6 hours), and late window (6–24 hours). Primary clinical and safety outcomes were 90-day functional independence measured by the modified Rankin Scale (mRS: 0–2) and symptomatic intracranial hemorrhage (sICH). Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), first-pass effect, early neurological improvement, ordinal mRS, and in-hospital and 90-day mortality. Results: Of 579 patients (median age 68, 32.1% females), 268 (46.3%) were treated in the late window and 311 (53.7%) in the early window. Late window group had lower median National Institutes of Health Stroke Scale score at admission, Alberta Stroke Program Early Computed Tomography Score, rates of intravenous thrombolysis, and higher rates for perfusion imaging. After adjusting for confounders, the odds of 90-day mRS 0–2 (47.7% vs. 45.0%, adjusted odds ratio [aOR] 0.71, 95% confidence interval [CI] 0.49–1.02), favorable shift in mRS (aOR 0.88, 95% CI 0.44–1.76), and sICH (3.7% vs. 5.2%, aOR 0.56, 95% CI 0.20–1.56) were similar in both groups. There was no difference in secondary outcomes. Increased time from LKW to puncture did not predicted the probability of 90-day mRS 0–2 (aOR 0.99, 95% CI 0.96–1.01, for each hour delay) among patients presenting <24 hours. Conclusion EVT for acute TL-LVO treated within 6–24 hours after LKW was associated with similar rates of clinical and safety outcomes, compared to patients treated within 6 hours.

A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value –8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Introduction: Insertion of Peripheral intravenous catheter (PIVC) is a common invasive procedure performed on patients that may contribute to several complications. Nurses are required to have adequate knowledge and practice to ensure the successful of the procedure. The objective of this study was to determine the knowledge and practice of nurses towards PIVC insertion procedures. Methods: A descriptive cross-sectional study design was conducted at Universiti Kebangsaan Malaysia Medical Centre. A total of seventy- seven nurses working in the emergency department, obstetrics & gynecology patient admission centre, daycare oncology were participated in this study. The data was gathered using a modified questionnaire and standard PIVC insertion guidelines. Results: 21 (27.3%) nurses had high knowledge and 56 (72.7%) had low knowledge of PIVC insertion (M=7.77, SD=1.87). All 77 (100%) nurses performed insertion of PIVC according to the standard of practice (M=23.16, SD=1.51). A positive correlation between age and knowledge (rho=0.123) but a negative correlation towards practice (rho=-0.413). A positive correlation between working experience and knowledge (rho=0.094) but a negative correlation towards practice (rho=-0.047). There was a positive correlation between nurses’ knowledge and practice (rho=0.038). Conclusion: Nurses with good knowledge of PIVC insertion performed better as they were aware of the negative consequences of the procedure if conducted incorrectly. Knowledgeable and competent nurses are essential to ensure the quality of nursing care and safe practice towards patients. Future studies with larger samples of nurses involved in more hospitals in Malaysia are recommended.

Methods: We assessed 23 patients with a mean age of 57.3±15 years. According to the Japanese Orthopedic Association (JOA) scale; eight patients had grade 0, nine had grade I, and six had grade II. All patients underwent plain radiography and magnetic resonance imaging of the cervical spine. The foramen magnum was involved in 10 patients, C1–2 in seven, C2–3 in four, and C3–4 in two. All patients were operated via the far-lateral approach. Results: Gross total resection was achieved in 21 patients. Sixteen lesions were psammomatous, five were fibroblastic, and two were meningothelial meningiomas. The mean operative duration was 135±40 minutes, while the mean operative blood loss was 450±210 mL, and the mean hospital stay was 4.3±2.2 days. At the final follow-up that was conducted at 27.6±21 months and as per the JOA score; 16 patients were classified into grade 0 and 7 into grade II. The condition of none of our patients deteriorated postoperatively. There was no significant correlation of the clinical outcome with tumor level, pathological subtype of the tumor, symptom duration, age, and sex. There was no significant correlation of tumor resection completeness with tumor level, tumor pathological subtype, or tumor topography (ventral or ventrolateral). Conclusions The far-lateral approach is a safe and effective access for ventral and ventrolateral cervical meningiomas. It allows direct access to tumor with no spinal cord or nerve roots traction, and thus may yield a fairly better outcome than the standard posterior approach.

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases. A natural fragment of serum albumin, named EPI-X4, has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated diseases. To generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/CXCR4. Subsequent rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4. The EPI-X4 derivative JM#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. EPI-X4 JM#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model. Moreover, topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Thus, rationally designed EPI-X4 JM#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted.

We aimed to explore the population dynamics of snail in 3 sites of the White Nile in Sudan. More specifically, we aimed to investigate the annual patterns of snail populations that act as intermediate hosts of schistosomes and monthly snail infection rates and ecological characteristics presumably related to snail populations. We collected snails for 1 year monthly at 3 different shore sites in the vicinity of El Shajara along the White Nile river in Khartoum State, Sudan. In addition, we measured air and water temperatures, water turbidities, vegetation coverages, and water depths and current speeds. Most of the collected snails were Biomphalaria pfeifferi and Bulinus truncatus. The population densities of snails and their infection rates varied across survey sites. The collected snails liberated S. mansoni and S. haematobium cercariae as well as Amphistome and Echinostome cercariae. Infected snails were found during March-June. The ecological characteristics found to be associated with the absence of snails population were: high turbidity, deep water, low vegetation coverage (near absence of vegetation), high water temperature, and high current speed. To our knowledge, this is the first longitudinal study of the snail population and ecological characteristics in the main basin of the White Nile river.

Malaria infection still remains as one of the most prominent parasitic diseases afflicting mankind in tropical and subtropical regions. The severity of malaria infection has often been associated to exuberant host immune inflammatory responses that could possibly lead to severe immunopathological conditions and subsequent death of host tissues. Activin A is a protein belonging to the transforming growth factor-beta (TGF-β) family that regulates multiple physiological processes and pathological-associated diseases. The biological roles of activin A have been associated with manipulation of inflammation-related processes and modulation of host immune responses. This implies that activin A protein could play a role in malaria pathogenesis since malaria infection has been closely linked to severe immune responses leading to death, However, the actual in vivo role of activin A in malaria infection remains elusive. Hence, this study was undertaken to investigate the involvement of activin A in malaria infection as well as to assess the modulating effects of activin A on the cytokine releases (TNF-α, IFN-γ and IL-10) and histopathological changes in major affected organs (kidney, liver, lung, brain and spleen) in malarial mice infected with Plasmodium berghei ANKA. Our results showed that the concentrations of plasma activin A were significantly increased in malarial mice throughout the study periods. Also. the systemic activin A level was positively correlated with malaria parasitemia. This indicates that activin A could play a role in malaria pathogenesis and malaria parasitemia development. Plasma TNF-α, IFN-γ and IL-10 cytokine levels were significantly increased in malarial mice at day-5 post infection, suggesting that these cytokines attributed to severe malaria pathogenesis. Histopathological features such as sequestration of parasitized red blood cells (pRBCs) and hemozoin formation were amongst the most common pathological conditions observed in tissues of major affected organs (kidney, liver, lung, brain and spleen) in malarial mice. Neutralization of activin A production via recombinant mouse activin RIIA Fc chimera (rmActivin RIIA Fc chimera) had significantly reduced the parasitemia levels in malarial mice. The release of TNF-α cytokine was significantly reduced as well as the sequestration of parasitized pRBCs and hemozoin formation in major affected organs in malarial mice were also alleviated following inhibition of activin A production. Overall, this preliminary study suggests that activin A could play an immune modulation role in malaria pathogenesis through modulation of TNF-α release that benefits host from severe pathological destructions provoked by intensified inflammatory responses. Further studies are warranted to elucidate the precise mechanism of immune modulation mediated by activin A and its associated immune-modulation mediators in regulating the inflammatory responses elicited during the course of malaria infection.

Purpose: Campylobacter species are currently the most common cause of bacterial gastroenteritis. In Lebanon, Campylobacter infection occurrence is underdiagnosed owing to the lack of specific culture and rapid test kits, particularly among children. This study aimed to evaluate the prevalence, laboratory findings, and clinical characteristics of Campylobacter infection in hospitalized children with acute gastroenteritis in South Lebanon. Methods: We conducted a 6-month retrospective cohort study between January and June 2018, including 291 children aged between 1 month and 12 years, who were admitted to a tertiary healthcare center in South Lebanon. The medical files of the patients were reviewed to retrieve the required clinical information, including clinical and laboratory data. Results: The prevalence of campylobacteriosis agents in pediatric patients with acute gastroenteritis is 12.02%. Patients infected with Campylobacter had more severe acute gastroenteritis than Campylobacter-negative patients and often presented with high-grade fever, diarrhea episodes more than six times per day, diarrhea lasting for more than five days, and dehydration. Indeed, children with high-grade fever (≥38.5°C) were five times more likely to test positive for Campylobacter than those with low-grade fever. In addition, the results showed a higher Vesikari score for the majority of Campylobacter-positive patients with severe acute gastroenteritis compared to a moderate profile for Campylobacter-negative patients. Conclusion The present study findings highlight that Campylobacter infection is frequent among children with acute gastroenteritis. Therefore, the detection of Campylobacter should be carried out for the diagnosis of human gastroenteritis in Lebanon, along with the detection of routine enteropathogens.

We aimed to explore the population dynamics of snail in 3 sites of the White Nile in Sudan. More specifically, we aimed to investigate the annual patterns of snail populations that act as intermediate hosts of schistosomes and monthly snail infection rates and ecological characteristics presumably related to snail populations. We collected snails for 1 year monthly at 3 different shore sites in the vicinity of El Shajara along the White Nile river in Khartoum State, Sudan. In addition, we measured air and water temperatures, water turbidities, vegetation coverages, and water depths and current speeds. Most of the collected snails were Biomphalaria pfeifferi and Bulinus truncatus. The population densities of snails and their infection rates varied across survey sites. The collected snails liberated S. mansoni and S. haematobium cercariae as well as Amphistome and Echinostome cercariae. Infected snails were found during March-June. The ecological characteristics found to be associated with the absence of snails population were: high turbidity, deep water, low vegetation coverage (near absence of vegetation), high water temperature, and high current speed. To our knowledge, this is the first longitudinal study of the snail population and ecological characteristics in the main basin of the White Nile river.