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Summary: Precise localization of peripheral nerve injuries and evaluation of their prognosis based on clinical and electrodiagnostic examinations are particularly challenging in the acute phase. High-resolution ultrasound (HRUS) may offer a viable and cost-effective imaging option for assessing the morphology of nerve injuries. Consequently, a systematic review and meta-analysis of studies on the use of ultrasound for diagnosing traumatic nerve injuries were conducted. A total of 15 studies were included, reporting the most recent findings on using HRUS in the diagnosis of traumatic nerve injury. These studies assessed the diagnostic test accuracy of ultrasound for the detection of traumatic nerve injury in 272 participants, with the cross-sectional area at the site of traumatic nerve injury also reported in 1,249 participants. The pooled sensitivity and specificity of the included studies were 92% confidence interval (CI) (0.89-0.95) and 86% CI (0.82-0.89), respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 13.76 CI (1.41-134.34), 0.08 CI (0.03-0.18), and 286.23 CI (21.22-3,860.40), respectively. In the summary of the receiver operating characteristic curve, the area under the curve was 0.986, and the Q* index was 0.949. Based on the current literature, HRUS has shown promising results in addition to its availability and feasibility. HRUS can serve as a valuable complement to clinical and electrodiagnostic examinations for diagnosing traumatic peripheral nerve injuries. Further research is recommended to better understand the ultrasound characteristics of these injuries., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Background: Concurrent neoadjuvant chemo-radiation (nCRT) with total mesorectal excision (TME) alone sometimes fails to cure lateral lymph node metastasis (LLNM). Therefore, additional lateral lymph node dissection (LLND) can help in the treatment of these patients. This is what we refer to as extended total mesorectal excision (eTME). Such operations (TME alone or eTME) can be performed using conventional laparoscopic techniques and robotic-assisted techniques as well. Our meta-analysis aims to compare the results of robot-assisted (R-eTME) versus laparoscopic-assisted extended mesorectal excision (L-eTME) in terms of short- and long-term outcomes., Methodology: Databases searched using title and abstract included Medline (via PubMed), Web of Science, Scopus, and Embase, up to February 20, 2024. All studies that documented robotic versus laparoscopic procedures for extended total mesorectal excision (R-eTME versus L-eTME) and reported more than two relevant outcomes, were included in the study., Results: Our meta-analysis demonstrates four significant outcomes (operative time, urinary complications, overall recurrence, and admission days) between the laparoscopic and robotic groups. The robotic approach shows advantages over the laparoscopic approach in these outcomes except for the operative time (minute), which was longer in the robotic group compared to the laparoscopic group. The laparoscopic group is associated with a higher overall recurrence than the robotic group with an Odds Ratio of 2(95% CI, 1-4, p = 0.05)., Conclusion: This meta-analysis study showed that the R-eTME group had a lower recurrence rate compared to the L-eTME group. Additionally, hospital admission days increased significantly in the laparoscopic group. Other long-term outcomes did not differ significantly between the two groups. Short-term outcomes were similar, except for more urinary complications in the laparoscopic group. In conclusion, the study suggests that robotic surgery may offer advantages over laparoscopic surgery for eTME. Further research and analysis could provide further insight into the potential benefits of robotic surgery in this procedure, particularly when surgeon experience, center volume, and learning curve are taken into consideration., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/ Aim: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons, causing progressive atrophy of muscles, hypertonia, and paralysis. This study aimed to evaluate the current evidence and effectiveness of ultrasound in investigating nerve cross-sectional area (CSA) of peripheral nerves, vagus and cervical roots in those with ALS compared with healthy controls and to pool the CSA measurements., Methods: A systematic search was conducted on Cochrane, Clarivate Web of Science, PubMed, Scopus, and Embase for the mesh terms nerve, ultrasonography, and amyotrophic lateral sclerosis. A quality assessment was performed using the New-Ottawa scale. In addition, a double-arm meta-analysis using Review Manager 5 software version 5.4 was performed., Results: From the seventeen studies included in this review, the overall mean difference showed that individuals with ALS had a significantly smaller CSA in comparison to healthy controls for median, ulnar, C6 root, and phrenic nerves. However, no significant difference in the CSA was found in radial, vagal, sural, and tibial nerves., Discussion: This study confirmed results of some of the included studies regards the anatomic sites, where nerve atrophy in ALS could be detected to potentially support the diagnosis of ALS. However, we recommend further large, prospective studies to assess the diagnostic value of these anatomical sites for the diagnosis of ALS., Conclusions: Our findings confirmed specific anatomic sites to differentiate ALS patients from healthy controls through ultrasound. However, these findings cannot be used to confirm the ALS diagnosis, but rather assist in differentiating it from other diagnoses., Trial Registration: Retrospectively registered on July 30th 2024 in PROSPERO (PROSPERO (york.ac.uk)) with ID574702., (© 2024. The Author(s).)

Introduction: Recently, the positive effects of photobiomodulation (PBM) and nano-bone on bone regeneration have garnered significant attention. The purpose of the research was to assess the impact of PBM and nano-bone on the process of mandibular bone repair in mice. Methods: A 4-mm diameter bone defect was created in the left mandibular angle of 24 mice separated into 4 equal groups: group I: control; group II: PBM by irradiation at 100 mW of a 980 nm diode laser for one minute (three sessions per week; day on and day off); group III: nano-bone; group IV: PBM with nano-bone. Every group was sectioned into 3 equal subgroups corresponding to the evaluation method period: (A) one week, (B) two weeks, and (C) four weeks. Histological examination was done with hematoxylin, eosin, and Masson's Trichrome after one, two and four weeks for inflammation, bone defect coverage, vascularization within the newly formed bone, and new bone formation. Statistical analysis of the data was done and presented as percentage values using chi-square. The significance level was set at P value≤0.05 within all tests. Results: In general, by histological examination of the mandibular bone defect of the rats, the intensity of inflammation was the least in group IV when compared with groups II and III and the control group at all evaluation periods ( P <0.001). Also, group IV showed a high significant rise in the percentage of new bone formation following four weeks when compared with the control ( P ≤ 0.001) and groups II and III ( P <0.001). Conclusion: The present research results confirmed that the combination of PBM and nano-bone can aid in the repair of mandibular bone abnormalities. This animal study suggests that the use of PBM and nano-bone should be investigated further in clinical studies., Competing Interests: None declared., (Copyright © 2024 J Lasers Med Sci.)

Human glycans are capped with sialic acids and these nine-carbon sugars mediate many of the biological functions and interactions of glycans. Structurally diverse sialic acid caps mark human cells as self and they form the ligands for the Siglec immune receptors and other glycan-binding proteins. Sialic acids enable host interactions with the human microbiome and many human pathogens utilize sialic acids to infect host cells. Alterations in sialic acid-carrying glycans, sialoglycans, can be found in every major human disease including inflammatory conditions and cancer. Twenty sialyltransferase family members in the Golgi apparatus of human cells transfer sialic acids to distinct glycans and glycoconjugates. Sialyltransferases catalyze specific reactions to form unique sialoglycans or they have shared functions where multiple family members generate the same sialoglycan product. Moreover, some sialyltransferases compete for the same glycan substrate, but create different sialic acid caps. The redundant and competing functions make it difficult to understand the individual roles of the human sialyltransferases in biology and to reveal the specific contributions to pathobiological processes. Recent insights hint towards the existence of biosynthetic rules formed by the individual functions of sialyltransferases, their interactions, and cues from the local Golgi environment that coordinate sialoglycan biosynthesis. In this review, we discuss the current structural and functional understanding of the human sialyltransferase family and we review recent technological advances that enable the dissection of individual sialyltransferase activities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christian Bull reports a relationship with GlycoTherapeutics BV that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A few studies regarding the epidemiology and risk factors of Non-muscle Invasive Bladder Cancer (NMIBC) are reported from Sub-Saharan African countries (SSA), including Somalia, and the African literature is scant on the management of NMIBC. The present study aims to evaluate the clinical-histopathological characteristics and factors associated with the survival rate of patients with NMIBC., Method: This six-year cohort study included 196 patients with NMIBC. It reviewed the clinical and histopathological characteristics and factors predicting cancer-specific survival for these patients., Results: The mean patient age was 59.01 ± 11.50 years, with a male-to-female ratio of 2.8:1. Urothelial carcinoma (UC) constituted the most common pathological type, accounting for 90.8%; Ta LG and T1HG were the most common histopathological tumour stage and grade (n = 90, 45.9%, vs. n = 56, 28.6%), respectively. The mean tumour size was 4.72 ± 2.81 cm. The cancer-specific mortality(CSM) was 13.3%. Age [2.252(2.310-2.943], p < 0.001], Gender [1.031(0.981-1.1.242),p < 0.001], tumour stage and grade [4.902(3.607-5.614),p < 0.001], tumour location [1.135(0.806-1.172),p < 0.001], number [0.510(0.410-0.920),p = 0.03], tumour size [1.523(0.936-1.541),p < 0.001], use of intravesical chemotherapy or BCG [2.810(1.972-4.381),p < 0.001], preoperative hydronephrosis grade [1.517(1.172-2.154),p < 0.001], and follow-up compliance [3.376(2.633-5.018),p < 0.001] were all associated with CSM. The 5-year overall survival was 57.1%, and cardiovascular diseases were the leading cause of mortality (n = 34), followed by diabetes (n = 28)., Conclusion: Our study findings revealed that UC constituted the most common pathological subtype, though less than forty per cent of our patients receive intravesical adjuvant therapies, which are crucial to minimizing disease morbidity and mortality. Initiatives improving uro-oncological care, including subspecialty training in oncology and essential cancer therapies, better access to urology services, and cancer screening programs, are much needed for optimal management plans and care in the country., (© 2024. The Author(s).)

Primary rhabdomyosarcoma of the testis is an exceptionally rare and highly malignant sarcoma. To date, there are only 23 reported cases in the literature. We report a 17-year-old male patient presented with massive scrotal swelling that had been progressively enlarging over seven-months. Scrotal ultrasound and contrast-enhanced CT revealed a 10 × 10cm left testicular heterogeneously enhancing mass that extends into the spermatic cord. A left inguinal orchiectomy was performed, and histopathological examinations showed findings consistent with Rhabdomyosarcoma, Embryonic-type. Primary embryonal testicular rhabdomyosarcoma has poor prognosis, particularly for adolescents, and tumour size greater than 10cm. Early diagnosis and radical orchiectomy improve the prognosis., (© 2024 The Author(s).)

Competing Interests: The authors have no conflicts to report.

Objective: Understanding the lateralization factors, including the anatomic and hemodynamic mechanisms, is essential for diagnosing cardio-embolic stroke. This study aims to investigate the elements, for the first time together, that could affect the laterality of stroke., Methods: We performed a monocentric retrospective case-control study based on prospective registries of acute ischemic stroke patients in the comprehensive stroke center of the RWTH University hospital of Aachen for three years (June 2018-June 2021). We enrolled 222 patients with cardioembolic stroke (136 left stroke and 86 right stroke) admitted for first-ever acute ischemic stroke with unilateral large vessel occlusion of the anterior circulation. The peak systolic velocity (PSV) asymmetry of middle cerebral artery (MCA) was assessed by doppler as well as internal carotid artery (ICA) angle, aortic arch (AA) branching pattern and anatomy were assessed by CT-Angiography., Results: We found that the increasing left ICA angle (p = 0.047), presence of bovine type AA anatomy (p = 0.041) as well as slow PSV of the right MCA with a value of >15% than left (p = 0.005) were the predictors for left stroke lateralization, while the latter was an independent predictor for the left stroke (OR=3.341 [1.415-7.887]). Inter-Rater Reliability ranged from moderate to perfect agreement., Conclusion: The predictors for left stroke lateralization include the higher values of left ICA angle, presence of the bovine type AA and the slow right MCA PSV., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has had a major effect on HIV-related healthcare services. Zanzibar has experienced several interruptions of HIV services in the areas of testing and counselling, prevention of mother-to-child transmission of HIV, key population, care and treatment services as well due to the hospital operating at a reduced capacity and the strict visit restrictions with health care allocations to COVID 19 pandemic. The community HIV initiatives, such as index testing and ARVs medicine refills, were used to mitigate the consequences of the epidemic and can be applied in future emergencies. This report tries to reveal COVID-19's unnoticed consequences on HIV services in Zanzibar., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background/aim: As the clinical differentiation between epileptic seizures, psychogenic non-epileptic seizures (PNES), and syncope depends mainly on a detailed report of the event, which may not be available, an objective assessment of a potential biochemical analysis is needed. We aimed to investigate whether serum creatine kinase (CK) could be used to differentiate epileptic seizure from PNES and syncope and to assess the strength of evidence present., Methods: We directed a retrospective cohort study coupled with a systematic review and meta-analysis of studies that measured CK in patients with epilepsy, PNES, syncope, and healthy controls., Results: The cohort study, which traced 202 patients, showed that the CK level was significantly higher 48 h after the event in the epilepsy group versus patients with syncope (p < 0.01) Along with 1086 patients obtained through a database search for meta-analysis, CK level compared to different types of seizures from PNES was higher in epileptic seizure patients with a mean difference of 568.966 mIU/ml (95% CI 166.864, 971.067). The subgroup analysis of CK showed that it was higher in GTCS compared to syncope with a mean difference of 125.39 mIU/ml (95% CI 45.25, 205.52)., Discussion: Increased serum levels of CK have been associated mainly with epileptic seizures in relation to non-epileptic events. However, further studies would try to explore the variation in measurements and any other potential diagnostic marker., Conclusion: The cohort study shows that the CK level in epilepsy seizures is higher after 48 h from the event compared to syncope. Moreover, the meta-analysis results show the present diagnostic utility of CK and its importance to be used in accordance with a detailed report of the event., (© 2023. Deutsche Gesellschaft für Neurologie e.V.)

The assembly of α-synuclein into cross-β structured amyloid fibers results in Lewy body deposits and neuronal degeneration in Parkinson's disease patients. As the cell environment is highly crowded, interactions between the formed amyloid fibers and a range of biomolecules can occur in cells. Although amyloid fibers are considered chemically inert species, recent in vitro work using model substrates has shown α-synuclein amyloids, but not monomers, to catalyze the hydrolysis of ester and phosphoester bonds. To search for putative catalytic activity of α-synuclein amyloids on biologically relevant metabolites, we here incubated α-synuclein amyloids with neuronal SH-SY5Y cell lysates devoid of proteins. LC-MS-based metabolomic (principal component and univariate) analysis unraveled distinct changes in several metabolite levels upon amyloid (but not monomer) incubation. Of 63 metabolites identified, the amounts of four increased (3-hydroxycapric acid, 2-pyrocatechuic acid, adenosine, and NAD), and the amounts of seventeen decreased (including aromatic and apolar amino acids, metabolites in the TCA cycle, keto acids) in the presence of α-synuclein amyloids. Many of these metabolite changes match what has been reported previously in Parkinson's disease patients and animal-model metabolomics studies. Chemical reactivity of α-synuclein amyloids may be a new gain-of-function that alters the metabolite composition in cells and, thereby, modulates disease progression.

Blunt renal injuries in pregnancy are seldom isolated, with resultant renal vascular injury following this type of injury being extremely rare. We present a rare case of complete blockage of the left renal artery about 1 cm from the aortic opening in a second-trimester pregnant woman after she sustained a motor-vehicle-accident. She was managed successfully with NOM. Traumatic renal artery blockage is a rare condition with devastating consequences if missed on imaging. Although blunt renal trauma during pregnancy is a rare condition, NOM has become increasingly popular to reduce morbidity associated with nephrectomy resulting in higher rates of renal salvage., (© 2023 The Authors.)

Introduction: This study compares five augmented reality (AR) vasculature visualization techniques in a mixed-reality laparoscopy simulator with 50 medical professionals and analyzes their impact on the surgeon. Material and methods : ​​The different visualization techniques' abilities to convey depth were measured using the participant's accuracy in an objective depth sorting task. Demographic data and subjective measures, such as the preference of each AR visualization technique and potential application areas, were collected with questionnaires. Results : Despite measuring differences in objective measurements across the visualization techniques, they were not statistically significant. In the subjective measures, however, 55% of the participants rated visualization technique II, 'Opaque with single-color Fresnel highlights', as their favorite. Participants felt that AR could be useful for various surgeries, especially complex surgeries (100%). Almost all participants agreed that AR could potentially improve surgical parameters, such as patient safety (88%), complication rate (84%), and identifying risk structures (96%). Conclusions : More studies are needed on the effect of different visualizations on task performance, as well as more sophisticated and effective visualization techniques for the operating room. With the findings of this study, we encourage the development of new study setups to advance surgical AR.

Purpose: Only a few studies have evaluated Augmented Reality (AR) in in vivo simulations compared to traditional laparoscopy; further research is especially needed regarding the most effective AR visualization technique. This pilot study aims to determine, under controlled conditions on a 3D-printed phantom, whether an AR laparoscope improves surgical outcomes over conventional laparoscopy without augmentation., Methods: We selected six surgical residents at a similar level of training and had them perform a laparoscopic task. The participants repeated the experiment three times, using different 3D phantoms and visualizations: Floating AR, Occlusion AR, and without any AR visualization (Control). Surgical performance was determined using objective measurements. Subjective measures, such as task load and potential application areas, were collected with questionnaires., Results: Differences in operative time, total touching time, and SurgTLX scores showed no statistical significance ([Formula: see text]). However, when assessing the invasiveness of the simulated intervention, the comparison revealed a statistically significant difference ([Formula: see text]). Participants felt AR could be useful for various surgeries, especially for liver, sigmoid, and pancreatic resections (100%). Almost all participants agreed that AR could potentially lead to improved surgical parameters, such as operative time (83%), complication rate (83%), and identifying risk structures (83%)., Conclusion: According to our results, AR may have great potential in visceral surgery and based on the objective measures of the study, may improve surgeons' performance in terms of an atraumatic approach. In this pilot study, participants consistently took more time to complete the task, had more contact with the vascular tree, were significantly more invasive, and scored higher on the SurgTLX survey than with AR., (© 2022. The Author(s).)

Importance: Patients with decompensated cirrhosis are hospitalized for acute management with temporizing and lifesaving procedures. Published data to inform intervention development in this area are more than a decade old, and it is not clear whether there have been improvements in disparities in the receipt of these procedures over time., Objective: To evaluate the associations of race and ethnicity with receipt of procedures to treat decompensated cirrhosis over time in the US., Design, Setting, and Participants: This retrospective cross-sectional study analyzed National Inpatient Sample data on cirrhosis admissions among patients with portal hypertension-related complications from 2009 to 2018. All hospital discharges for individuals aged 18 years and older from 2009 to 2018 were assessed for inclusion. Admissions were included if they contained at least 1 cirrhosis-related International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code and at least 1 cirrhosis-related complication ICD-9-CM or ICD-10-CM code (ie, ascites, hepatic encephalopathy, variceal hemorrhage [VH], and hepatorenal syndrome [HRS]). Data were analyzed from January to June 2022., Exposure: Hospitalization for decompensated cirrhosis., Main Outcomes and Measures: The outcomes of interest were trends in the odds ratios (ORs) for receiving procedures (upper endoscopy, transjugular portosystemic shunt [TIPS], hemodialysis, and liver transplantation [LT]) for decompensated cirrhosis and mortality by race and ethnicity, modeled over time. Multivariable logistic regression was used to assess these outcomes., Results: Among 717 580 admissions (median [IQR] age, 58 [52-67] years), 345 644 patients (9.8%) were Black, 623 991 patients (17.6%) were Hispanic, and 2 340 031 patients (47.4%) were White. Based on the modeled trends, by 2018, there were no significant differences by race or ethnicity in the odds of receiving upper endoscopy for VH. However, Black patients remained less likely than White patients to undergo TIPS for VH (OR, 0.54; 95% CI, 0.47-0.62) and ascites (OR, 0.34; 95% CI, 0.31-0.38). The disparity in receipt of LT improved for Black and Hispanic patients over the study period; however, by 2018, both groups remained less likely to undergo LT than their White counterparts (Black: OR, 0.66; 95% CI, 0.61-0.70; Hispanic: OR, 0.74; 95% CI, 0.70-0.78). The odds of death in Black and Hispanic patients declined over the study period but remained higher in Black patients than White patients in 2018 (OR, 1.08; 95% CI, 1.05-1.11)., Conclusions and Relevance: In this cross-sectional study of individuals hospitalized with decompensated cirrhosis, there were racial and ethnic disparities in receipt of complex lifesaving procedures and in mortality that persisted over time.

Background: Parkinson's disease (PD) is a major cause of disability. We aimed to assess the benefit of ultrasonography of the vagus nerve (VN) to compare between PD and healthy controls as well as to deliver reference values of nerve cross sectional area (CSA)., Materials and Methods: We performed a systematic search on Medline (PubMed), Scopus, Embase, and Web of Science, up till July 25, 2022. After article selection and screening, we performed a quality assessment using the Newcastle-Ottawa Scale. Furthermore, a statistical analysis and subgroup analysis was performed., Results: Eleven studies were included with a total of 809 participants (409 PD patients and 400 controls). A statistically significant difference in the CSA of the right and left VN between PD patients and healthy controls was observed, indicating the atrophy of VN in PD patients (p < 0.00001). The subgroup meta-analysis for average measurements of VN CSA showed insignificant heterogeneity for age (I 2  = 48.67%, p = 0.058), level of measurements (I 2  = 57.91%, p = 0.05), and disease duration (I 2  = 27.1%, p = 0.241)., Conclusion: Our meta-analysis showed a sonographically detectable degree of neuronal damage in PD, which correlates with VN atrophy with high confidence. Therefore, we believe this is a potential marker for vagus neuronal lesions. Future studies are required to assess the potential clinical correlation., Competing Interests: Declaration of competing interest We declare that all the authors have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Nonmalignant meningioma (NM) is the most common brain tumor in the United States (U.S.), accounting for 54% of nonmalignant brain tumors. This study aims to investigate the causes of death in NM patients and their possible associations with demographic factors., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed 116,430 NM patients diagnosed between the years 2004 and 2018., Results: A total of 31,640 deaths were observed. Non-tumor diseases accounted for 63.9% of all deaths. Out of these non-tumor deaths, we found that the most common causes were heart disease (18.7% of deaths), cerebrovascular disease (7.4% of deaths), and Alzheimer disease (4.5% of deaths). On the other hand, cancer was responsible for 27.4% of deaths, while in situ and benign tumor deaths accounted for only 8.7%., Conclusions: This is the first U.S. population-based study to investigate the causes of death in NM patients. We found that non-tumor diseases accounted for the majority of deaths. The risks of mortality caused by heart disease, cerebrovascular disease, diabetes, and Alzheimer disease were significantly elevated. These data can help improve survival outcomes for NM patients, particularly if adjusted by demographic risk factors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Patients with isolated posterior cerebral artery occlusion (iPCAO) represent up to 6% of all acute ischemic stroke patients. Acute revascularization therapies for these patients were not tested in randomized controlled trials. The aim of this study was to evaluate outcomes of iPCAO patients who undergo endovascular treatment (EVT)., Methods: A systematic search of MEDLINE, Web of Science, CENTRAL, Scopus (inception-03/2022) was conducted for studies reporting 3‑month outcome, symptomatic intracranial hemorrhage (sICH) and/or successful recanalization in iPCAO patients who underwent EVT. Random effect meta-analyses for pooled proportions were calculated. Double-arm meta-analyses for comparison of outcomes of iPCAO patients treated with EVT with age-, sex- and NIHSS-matched iPCAO patients treated with best medical treatment only were performed., Results: Fifteen studies reporting a total of 461 iPCAO patients who underwent EVT were included. Excellent and favorable 3‑month outcome proportions were 36% (95% confidence interval, CI 20-51%) and 57% (95% CI 40-73%), respectively. The 3‑month mortality was 9% (95% CI 5-13), sICH occurred in 1% (95% CI 0-2%), successful recanalization was achieved in 79% (95% CI 71-86%). No significant differences in favorable and excellent 3‑month outcomes, 3‑month mortality and symptomatic intracerebral hemorrhage were found between the groups of patients who underwent EVT and the group of patients who received best medical treatment only., Conclusion: These results support the feasibility and safety of EVT in iPCAO, but do not show an outcome benefit with EVT compared to best medical treatment. Randomized trials are needed to evaluate treatment benefit of EVT in these patients., (© 2022. The Author(s).)

Introduction/aims: Nerve ultrasound is useful in the diagnosis and follow-up of peripheral nerve disorders in children. The aim of this study was to explore and analyze the current literature on nerve cross-sectional area (CSA) in healthy children, with the goal of presenting reference values and discussing their implications., Methods: We performed a systematic review and meta-analysis of studies that reported ultrasound measurements of the upper or lower limb nerves in healthy children through a search of Web of Science, PubMed, Embase, and Scopus., Results: Sixteen studies with measurements of 10 nerves covering a total of 5149 nerves measured in 823 healthy children (445 boys and 378 girls) were included. Mean nerve CSA increased with age in the median nerve at the middle and lower third of the upper arm, mid-forearm, and distal wrist crease, the ulnar nerve at the middle third of the upper arm and elbow, the radial nerve at the spiral groove, and the tibial nerve at the popliteal fossa. Growth charts for nerve CSA for different age groups were developed., Discussion: This meta-analysis provides robust reference values for nerve CSA at different sites in children, and this can inform clinical practice and assist in identifying nerve enlargement. Moreover, it identifies the strength and quality of the current published data. We recommend future studies divide their samples into smaller age subgroups and standardize the anatomic site of measurement., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Very recently, we have developed a new generation of ligands targeting the cannabinoid receptor type 2 (CB2R), namely JR compounds, which combine the pharmacophoric portion of the CB2R positive allosteric modulator (PAM), EC21a , with that of the CB2R selective orthosteric agonist LV62 , both synthesized in our laboratories. The functional examination enabled us to identify JR14a , JR22a , and JR64a as the most promising compounds of the series. In the current study, we focused on the assessment of the bitopic (dualsteric) nature of these three compounds. Experiments in cAMP assays highlighted that only JR22a behaves as a CB2R bitopic (dualsteric) ligand. In parallel, computational studies helped us to clarify the binding mode of these three compounds at CB2R, confirming the bitopic (dualsteric) nature of JR22a . Finally, the potential of JR22a to prevent neuroinflammation was investigated on a human microglial cell inflammatory model.

Purpose: Osteoarthritis (OA) patients demonstrated higher Osteopontin (OPN) plasma, serum, and synovial fluid concentrations than healthy individuals. In the present study, we aimed to investigate whether OPN could be used as a diagnostic or prognostic marker for OA symptom/disease severity., Methods: Using Web of Science, PubMed, Scopus, and Embase, we conducted a systematic review and meta-analysis of studies that measured OPN levels in OA patients' plasma, serum, or synovial fluid. After setting the eligibility criteria, data extraction, and quality assessment of the identified studies, we performed statistical analysis using Revman 5.4 and Open Meta analyst., Results: OPN has been found to be associated with advanced knee joint damage in OA patients. In addition, higher expression of OPN is thought to be associated with disease progression. Nevertheless, further studies should examine the role of other markers of chronic bone damage, such as leptin and sclerostin. This systematic review and meta-analysis included 14 studies with a total of 776 cases and 530 controls. OPN was significantly elevated in osteoarthritis patients' plasma, serum, and synovial fluid samples, with significant heterogeneity between studies., Conclusion: We recommend that OPN plasma and synovial fluid levels be measured as a diagnostic and prognostic marker to determine the severity of OA symptoms., Competing Interests: Declaration of Competing Interest None of the authors has any potential financial conflict of interest related to this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its development. Previous studies have reported elevated plasminogen activator inhibitor-1 (PAI-1) levels in patients with depression, suggesting that PAI-1 levels might be linked to the etiology of MDD., Methods: We systematically searched the following online databases: MEDLINE, Scopus, and Web of Science up to September 10, 2020, to identify studies in which PAI-1 levels were reported in subjects with MDD. Subsequently we used RevMan 5.3 to perform a meta-analysis of data extracted from the included studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO criteria for the search and analysis., Results: Six studies that reported mean ± standard deviation (SD) were included in the analysis, with a total of 507 MDD patients and 3,453 controls. The overall standardized mean difference (SMD) was 0.27 (95% confidence interval [95% CI] 0.01-0.53). PAI-1 serum levels were 0.27 SDs higher in MDD patients than in controls. The test for overall effect was significant (z = 2.04, p = 0.04). Substantial heterogeneity was detected among the studies, demonstrated by the inconsistency test (I² = 72%) and the chi-square test (χ² = 18.32; p = 0.003)., Conclusions: This systematic review and meta-analysis showed that MDD might be related to elevated PAI-1 levels. We propose larger prospective clinical studies to further investigate this clinical correlation and validate the clinical significance of these observations., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Biofilms of sporeformers found in the dairy industry are the major contaminants during processing, as they withstand heat and chemical treatment that are used to control microbes. The present work is aimed to remove these resistant forms of bacterial community (biofilm) present in dairy production lines using ecofriendly agents based on proteinase K (Prot-K) coupled with Zinc oxide nanoparticles (ZnO-NPs). Some metal/metal oxide (Ag, CuO and ZnO) NPs were prepared microbially, and ZnO-NPs were characterized as the most effective ones among them. The produced ZnO-NPs were 15-25 nm in size with spherical shape, and FTIR analysis confirmed the presence of proteins and alkanes surrounding particles as capping agents. Application of Prot-K for eradication (removal) of a model biofilm of mixed sporeformers on food-grade stainless steel resulted in an 83% reduction in the absorbance of crystal violet-stained biofilm. When Prot-K was mixed with the biosynthesized NPs ZnO&#95;G240, the reduction increased to 99.19%. This finding could contribute to an efficient cleaning approach combined with CIP to remove the recalcitrant biofilms in dairy production lines., Competing Interests: Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. AAR: methodology, data curation, formal analysis, writing original draft; OMD: methodology, data curation, formal analysis, writing original draft; MTE: methodology; KAM: data curation, formal analysis, supervision; HMA: supervision, data curation, formal analysis. All authors revised and accept the final form of the manuscript., (© 2022 the Author(s), licensee AIMS Press.)

It is well known that G protein-coupled receptors (GPCRs) assume multiple active states. Orthosteric ligands and/or allosteric modulators can preferentially stabilize specific conformations, giving rise to pathway-biased signaling. One of the most promising strategies to expand the repertoire of signaling-selective GPCR activators consists of dualsteric agents, which are hybrid compounds consisting of orthosteric and allosteric pharmacophoric units. This approach proved to be very promising showing several advantages over monovalent targeting strategies, including an increased affinity or selectivity, a bias in signaling pathway activation, reduced off-target activity and therapeutic resistance. Our study focused on the cannabinoid receptor type 2 (CB 2 R), considered a clinically promising target for the control of brain damage in neurodegenerative disorders. Indeed, CB 2 R was found highly expressed in microglial cells, astrocytes, and even in some neuron subpopulations. Here, we describe the design, synthesis, and biological evaluation of two new classes of potential dualsteric (bitopic) CB 2 R ligands. The new compounds were obtained by connecting, through different linkers, the pharmacophoric portion of the CB 2 R positive allosteric modulator (PAM), EC21a , with that of the CB 2 R selective orthosteric agonist LV62 , both developed in our laboratories. A preliminary screening enabled us to identify compound JR64a as the most promising of the series. Indeed, functional examination highlighted a signaling 'bias' in favor of G protein activation over βarrestin2 recruitment, combined with high affinity for CB 2 R and the ability to efficiently prevent inflammation in human microglial cells (HMC3) exposed to LPS/TNFα stimulation, thus demonstrating great promise for the treatment of neurodegenerative diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferrisi, Gado, Polini, Ricardi, Mohamed, Stevenson, Ortore, Rapposelli, Saccomanni, Pertwee, Laprairie, Manera and Chiellini.)

Liver transplantation (LT) is the final step in a complex care cascade. Little is known about how race, gender, rural versus urban residence, or neighborhood socioeconomic indicators impact a patient's likelihood of LT waitlisting or risk of death during LT evaluation. We performed a retrospective cohort study of adults referred for LT to the Indiana University Academic Medical Center from 2011 to 2018. Neighborhood socioeconomic status indicators were obtained by linking patients' addresses to their census tract defined in the 2017 American Community Survey. Descriptive statistics were used to describe completion of steps in the LT evaluation cascade. Multivariable analyses were performed to assess the factors associated with waitlisting and death during LT evaluation. There were 3454 patients referred for LT during the study period; 25.3% of those referred were waitlisted for LT. There was no difference seen in the proportion of patients from vulnerable populations who progressed to the steps of financial approval or evaluation start. There were differences in waitlisting by insurance type (22.6% of Medicaid vs. 34.3% of those who were privately insured; p < 0.01) and neighborhood poverty (quartile 1 29.6% vs. quartile 4 20.4%; p < 0.01). On multivariable analysis, neighborhood poverty was independently associated with waitlisting (odds ratio 0.56, 95% confidence interval [CI] 0.38-0.82) and death during LT evaluation (hazard ratio 1.49, 95% CI 1.09-2.09). Patients from high-poverty neighborhoods are at risk of failing to be waitlisted and death during LT evaluation., (© 2022 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Introduction/aims: Ultrasonography of the cranial nerves has recently gained attention for assessment of inflammatory, compressive, or degenerative neuropathies. However, sonographic reference values of cranial nerves have received less attention than those of peripheral nerves. In this systematic review and meta-analysis we aimed to provide current evidence of sonographic reference values for cranial nerve size., Methods: By searching Medline (via PubMed), Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, we conducted a systematic review and meta-analysis of studies that reported ultrasound measurements of the facial, spinal accessory, and hypoglossal nerves in healthy adults. We included studies that reported either the sonographic cross-sectional area (CSA) or the nerve diameter; the included nerves were subgrouped according to the site of nerve measurement., Results: Fourteen studies with a total of 661 participants and 1437 ultrasound nerve measurements met the inclusion criteria. The anatomical sites for each nerve were combined to provide single-nerve mean measurements. We found an overall mean nerve diameter of 0.80 mm for the facial nerve, 0.63 mm for the spinal accessory nerve, and 1.82 mm 2 for hypoglossal nerve CSA., Discussion: This meta-analysis provides reference values for the diameter and cross-sectional area of the facial, spinal accessory, and hypoglossal nerves at different sites, which can be used as guidance in clinical practice to detect pathological changes in cranial nerve size in cranial neuropathies. We recommend further validation in large-scale studies as well as standardization of the scanning protocols., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Because of the insidious character and variations in presenting symptoms, Charcot-Marie-Tooth (CMT) disease is challenging to diagnose in children. Diagnosis is based on clinical and nerve conduction studies, as well as genetic examination. Therefore, competent nerve imaging techniques and non-invasive alternatives to nerve conduction studies are a necessity, especially in children. We performed a systematic review and meta-analysis to evaluate the current evidence and effectiveness of ultrasound in investigating nerve cross-sectional area (CSA) in those with CMT compared with healthy controls and to pool the CSA measurements. We included studies published in international peer-reviewed journals that measured nerve CSA by ultrasound in patients with CMT. We implemented double-arm meta-analyses to compare the mean CSA of nerves between patients with CMT and healthy controls by calculating the pooled mean difference in CSA. Moreover, we performed subgroup analyses by stratifying the studies according to the site of CSA measurement and examined the difference in nerve CSA between CMT1A and other CMT types. The included studies provide measurements of 12 nerve roots and nerves (vagus, C3, C4, C5, C6, greater auricular, phrenic, median, ulnar, fibular, tibial and sural nerves) in 628 patients with CMT and 586 healthy controls with a total of 6061 measured nerves. Meta-analyses of sonographic nerve CSA are provided to express nerve ultrasonography in the diagnosis of CMT patient., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The design of dualsteric/bitopic agents as single chemical entities able to simultaneously interact with both the orthosteric and an allosteric binding site represents a novel approach in medicinal chemistry. Biased dualsteric/bitopic agents could enhance certain signaling pathways while diminishing the others that cause unwanted side effects. We have designed, synthesized, and functionally characterized the first CB2R heterobivalent bitopic ligands. In contrast to the parent orthosteric compound, our bitopic ligands selectively target CB2R versus CB1R and show a functional selectivity for the cAMP signaling pathway versus βarrestin2 recruitment. Moreover, the most promising bitopic ligand FD-22a displayed anti-inflammatory activity in a human microglial cell inflammatory model and antinociceptive activity in vivo in an experimental mouse model of neuropathic pain. Finally, computational studies clarified the binding mode of these compounds inside the CB2R, further confirming their bitopic nature.

A growing body of evidence underlines the crucial role of GPR55 in physiological and pathological conditions. In fact, GPR55 has recently emerged as a therapeutic target for several diseases, including cancer and neurodegenerative and metabolic disorders. Several lines of evidence highlight GPR55's involvement in the regulation of microglia-mediated neuroinflammation, although the exact molecular mechanism has not been yet elucidated. Nevertheless, there are only a limited number of selective GPR55 ligands reported in the literature. In this work, we designed and synthesized a series of novel GPR55 ligands based on the 3-benzylquinolin-2(1 H )-one scaffold, some of which showed excellent binding properties (with K i values in the low nanomolar range) and almost complete selectivity over cannabinoid receptors. The full agonist profile of all the new derivatives was assessed using the p-ERK activation assay and a computational study was conducted to predict the key interactions with the binding site of the receptor. Our data outline a preliminary structure-activity relationship (SAR) for this class of molecules at GPR55. Some of our compounds are among the most potent GPR55 agonists developed to date and could be useful as tools to validate this receptor as a therapeutic target.

1,8-naphthyridine-3-carboxamide structures were previously identified as a promising scaffold from which to obtain CB2R agonists with anticancer and anti-inflammatory activity. This work describes the synthesis and functional characterization of new 1,8-naphthyridin-2(1 H )-one-3-carboxamides with high affinity and selectivity for CB2R. The new compounds were able to pharmacologically modulate the cAMP response without modulating CB2R-dependent β-arrestin2 recruitment. These structures were also evaluated for their anti-cancer activity against SH-SY5Y and SK-N-BE cells. They were able to reduce the cell viability of both neuroblastoma cancer cell lines with micromolar potency (IC 50 of FG158a = 11.8 μM and FG160a = 13.2 μM in SH-SY5Y cells) by a CB2R-mediated mechanism. Finally, in SH-SY5Y cells one of the newly synthesized compounds, FG158a , was able to modulate ERK1/2 expression by a CB2R-mediated effect, thus suggesting that this signaling pathway might be involved in its potential anti-cancer effect.

Ureteral stents are safe, and because of their widespread usage, complications associated with stenting increased. The knotting of the ureteral stent is an uncommon complication. Until today, only three cases of knotting at the mid-portion and distal ends of the ureteral stents were reported. Herein, we report a rare case of a downward migrated ureteral stent with a knot in its middle portion at the level of the distal ureter in a 25-year-old female patient. Her knotted stent was successfully removed by guidewire insertion and ureteroscopy under fluoroscopic guidance., (© 2022 The Authors. Published by Elsevier Inc.)

Inclusion body myositis (IBM) is a slowly progressive muscle weakness of distal and proximal muscles, which is diagnosed by clinical and histopathological criteria. Imaging biomarkers are inconsistently used and do not follow international standardized criteria. We conducted a systematic review and meta-analysis to investigate the diagnostic value of muscle ultrasound (US) in IBM compared to healthy controls. A systematic search of PubMed/MEDLINE, Scopus and Web of Science was performed. Articles reporting the use of muscle ultrasound in IBM, and published in peer-reviewed journals until 11 September 2021, were included in our study. Seven studies were included, with a total of 108 IBM and 171 healthy controls. Echogenicity between IBM and healthy controls, which was assessed by three studies, demonstrated a significant mean difference in the flexor digitorum profundus (FDP) muscle, which had a grey scale value (GSV) of 36.55 (95% CI, 28.65-44.45, p < 0.001), and in the gastrocnemius (GC), which had a GSV of 27.90 (95% CI 16.32-39.48, p < 0.001). Muscle thickness in the FDP showed no significant difference between the groups. The pooled sensitivity and specificity of US in the differentiation between IBM and the controls were 82% and 98%, respectively, and the area under the curve was 0.612. IBM is a rare disease, which is reflected in the low numbers of patients included in each of the studies and thus there was high heterogeneity in the results. Nevertheless, the selected studies conclusively demonstrated significant differences in echogenicity of the FDP and GC in IBM, compared to controls. Further high-quality studies, using standardized operating procedures, are needed to implement muscle ultrasound in the diagnostic criteria.

Purpose: To establish the first comprehensive and standardized set of vagus nerve (VN) sonographic reference values across all the published studies that can be used to standardize and guide clinical practice and research., Methods: This systematic review includes all possible available data from a total of 27 studies and 21 of them were included in the meta-analysis having a total of 864 participants., Results: The overall mean cross-sectional area ranged from 2.29 to 2.76 mm2 for the right VN and from 1.83 to 2.23 mm2 for the left VN with 95% confidence interval. Sonographic reference values of VN at common carotid artery bifurcation, thyroid gland, and cartilage as well as other anatomic landmarks were provided., Conclusions: The mean cross-sectional area of the right VN of 2.53 mm2 and the left one of 2.03 mm2 can be considered as sonographic reference values in healthy adults. This review provides these reference values to be considered in the further sonographic evaluation of VNs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Objectives: Studies have shown that acute kidney injury (AKI) occurrence post SARS-CoV-2 infection is complex and has a poor prognosis. Therefore, more studies are needed to understand the rate and the predications of AKI involvement among hospitalized COVID-19 patients and AKI's impact on prognosis while under different types of medications., Patients and Methods: This study is a retrospective observational cohort study conducted at Bahrain Defence Force (BDF) Royal Medical Services. Medical records of COVID-19 patients admitted to BDF hospital, treated, and followed up from April 2020 to October 2020 were retrieved. Data were analyzed using univariate and multivariate logistic regression with covariate adjustment, and the odds ratio (OR) and 95% confidence (95% CI) interval were reported., Results: Among 353 patients admitted with COVID-19, 47.6% developed AKI. Overall, 51.8% of patients with AKI died compared to 2.2% of patients who did not develop AKI (p< 0.001 with OR 48.6 and 95% CI 17.2-136.9). Besides, deaths in patients classified with AKI staging were positively correlated and multivariate regression analysis revealed that moderate to severe hypoalbuminemia (<32 g/L) was independently correlated to death in AKI patients with an OR of 10.99 (CI 95% 4.1-29.3, p<0.001). In addition, 78.2% of the dead patients were on mechanical ventilation. Besides age as a predictor of AKI development, diabetes and hypertension were the major risk factors of AKI development (OR 2.04, p<0.01, and 0.05 for diabetes and hypertension, respectively). Also, two or more comorbidities substantially increased the risk of AKI development in COVID-19 patients. Furthermore, high levels upon hospital admission of D-Dimer, Troponin I, and ProBNP and low serum albumin were associated with AKI development. Lastly, patients taking ACEI/ARBs had less chance to develop AKI stage II/III with OR of 0.19-0.27 (p<0.05-0.01)., Conclusions: The incidence of AKI in hospitalized COVID-19 patients and the mortality rate among AKI patients were high and correlated with AKI staging. Furthermore, laboratory testing for serum albumin, hypercoagulability and cardiac injury markers maybe indicative for AKI development. Therefore, clinicians should be mandated to perform such tests on admission and follow-up in hospitalized patients., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Vagus nerve (VN) has been suggested as one of the major routes of Parkinson's disease (PD) progression from enteric nervous system to brain. Therefore, the recent studies have investigated the VN structurally, with a focus on the changes in its size in PD patients using high-frequency ultrasonography. This systematic review and meta-analysis aims to evaluate VN size via ultrasound in PD compared to controls., Methods: Totally, five studies were included with a total of 238 participants (128 PD patients and 111 controls)., Results: The estimate mean difference in four studies showed that the VN CSA was smaller in PD patients with 0.29 mm 2 (95% CI, -0.52 to -0.06) and 0.23 mm 2 (95% CI, -0.42 to -0.05) for right and left VNs respectively. The test for overall effect was significant for both measurements (p = 0.01)., Conclusions: This review reveals that there is a degree of vagus nerve atrophy in PD which could be detected sonographically with high confidence, thus can be used as a marker for vagus neuronal lesion or neuropathy. Further studies are needed to examine its clinical correlation thoroughly., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We previously reported the 2-oxopyridine-3-carboxamide derivative EC21a as the first small synthetic CB2R positive allosteric modulator which displayed antinociceptive activity in vivo in an experimental mouse model of neuropathic pain. Herein, we extended the structure-activity relationships of EC21a through structural modifications regarding the p-fluoro benzyl moiety at position 1 and the amide group in position 3 of the central core. The characterization in vitro was assessed through radioligand binding experiments and functional assays (GTPγS, cAMP, βarrestin2). Among the new compounds, the derivatives A1 (SV-10a) and A5 (SB-13a) characterized respectively by fluorine atom or by chlorine atom in ortho position of the benzylic group at position 1 and by a cycloheptane-carboxamide at position 3 of the central core, showed positive allosteric behavior on CB2R. They enhanced the efficacy of CP55,940 in [ 35 S]GTPγS assay, and modulated CP55,940-dependent βarrestin2 recruitment and cAMP inhibition. The obtained results extend our knowledge of the structural requirements for interaction with the allosteric site of CB2R., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆ 9 -tetrahydrocannabinol (∆ 9 -THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆ 9 -THC is known to bring about the 'high' associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆ 9 -THC, ∆ 9 -tetrahydrocannabinolic acid (∆ 9 -THCa), ∆ 9 -tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.

Gunshot injury to the kidney in pregnant women is extremely rare describing a significant cause of maternal and fetal morbidity and mortality. This case report demonstrates the management of renal trauma by presenting 24years old third-trimester pregnant women who sustained gunshot wounds to the abdomen. Renal trauma management has evolved in the last decades from immediate surgical exploration to non-operative management (NOM). Based on our patient's outcome, we review the role of conservative management to a high grade of penetrating renal trauma which is potentially life-threatening describing the safety of this approach., Competing Interests: None., (© 2019 The Authors.)

In addition to its known actions as a non-selective cyclooxygenase (COX) 1 and 2 inhibitor, we hypothesized that indomethacin can act as an allosteric modulator of the type 1 cannabinoid receptor (CB1R) because of its shared structural features with the known allosteric modulators of CB1R. Indomethacin enhanced the binding of [ 3 H]CP55940 to hCB1R and enhanced AEA-dependent [ 35 S]GTPγS binding to hCB1R in Chinese hamster ovary (CHO) cell membranes. Indomethacin (1 μM) also enhanced CP55940-dependent βarrestin1 recruitment, cAMP inhibition, ERK1/2 and PLCβ3 phosphorylation in HEK293A cells expressing hCB1R, but not in cells expressing hCB2R. Finally, indomethacin enhanced the magnitude and duration of CP55940-induced hypolocomotion, immobility, hypothermia, and anti-nociception in C57BL/6J mice. Together, these data support the hypothesis that indomethacin acted as a positive allosteric modulator of hCB1R. The identification of structural and functional features shared amongst allosteric modulators of CB1R may lead to the development of novel compounds designed for greater CB1R or COX selectivity and compounds designed to modulate both the prostaglandin and endocannabinoid systems., (Copyright © 2019 Laprairie, Mohamed, Zagzoog, Kelly, Stevenson, Pertwee, Denovan-Wright and Thakur.)

Objective: To determine the frequency of suicidal thoughts and suicidal probability among poly-substance abusers in Saudi population, and to examine the relation between dual diagnosis and suicidal thoughts., Study Design: Case control study., Place and Duration of Study: Al-Baha Psychiatric Hospital, Saudi Arabia, from May 2011 to June 2012., Methodology: Participants were 239 subjects, aged 18 - 45 years. We reviewed 122 individuals who fulfilled the DSM-IV-TR criteria of substance abuse for two or more substances, and their data were compared with that collected from 117 control persons., Results: Suicidal cases were highly present among poly-substance abusers 64.75%. Amphetamine and cannabis were the most abused substances, (87.7% and 70.49%, respectively). Astatistically significant association with suicidality was found with longer duration of substance abuse (p < 0.001), using alcohol (p=0.001), amphetamine (p=0.007), volatile substances (p=0.034), presence of comorbid psychiatric disorders (dual diagnosis) as substance induced mood disorder (p=0.001), schizo-affective disorder (p=0.017), major depressive disorders (p=0.001), antisocial (p=0.016) and borderline (p=0.005) personality disorder. Suicidal cases showed significant higher scores (p < 0.001) of suicide probability scale and higher scores in Beck depressive inventory (p < 0.001)., Conclusion: Abusing certain substances for long duration, in addition to comorbid psychiatric disorders especially with disturbed-mood element, may trigger suicidal thoughts in poly-substance abusers. Depression and suicide probability is common consequences of substance abuse.

A series of pyridothieno[3,2-d]pyrimidin-4-amines was designed and synthesized as congeners to the classical 4-anilinoquinazolines as ATP-competitive epidermal growth factor receptor (EGFR) inhibitors. Compound 5a exhibited the most potent and selective inhibitory activity against EGFR with an IC50 value of 36.7 nM. Moreover, compounds 4b and 5a showed remarkable cell growth inhibition against leukemia, central nervous system cancer, and non-small cell lung cancer cell lines that overexpress EGFR, with growth inhibition of 50% (GI50) values of around 10 nM in the full U.S. National Cancer Institute 60 cell panel assay. Cell cycle studies indicated that compounds 4b and 5a induced significant cell cycle arrest in the S-phase and G0/G1, respectively, in addition to boosting P27(kip) expression. Compound 5a did not alter the viability of placental trophoblasts, which reflects its safety for normal cells. The standard COMPARE analyses demonstrated considerable correlation levels between compounds 4b and 5a and erlotinib, with pyridinium chlorochromate (PCC) values of 0.707 and 0.727, respectively.

An extremely rare pellagra-like condition has been described, which was partially responsive to niacin and associated with a multisystem involvement. The condition was proposed to represent a novel autosomal recessive entity but the underlying mutation remained unknown for almost three decades. The objective of this study was to identify the causal mutation in the pellagra-like condition and investigate the mechanism by which niacin confers clinical benefit. Autozygosity mapping and exome sequencing were used to identify the causal mutation, and comet assay on patient fibroblasts before and after niacin treatment to assess its effect on DNA damage. We identified a single disease locus that harbors a novel mutation in ERCC5, thus confirming that the condition is in fact xeroderma pigmentosum/Cockayne syndrome (XP/CS) complex. Importantly, we also show that the previously described dermatological response to niacin is consistent with a dramatic protective effect against ultraviolet-induced DNA damage in patient fibroblasts conferred by niacin treatment. Our findings show the power of exome sequencing in reassigning previously described novel clinical entities, and suggest a mechanism for the dermatological response to niacin in patients with XP/CS complex. This raises interesting possibilities about the potential therapeutic use of niacin in XP., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The burnout syndrome is characterized by emotional exhaustion, depersonalization, and low personal accomplishment. It is associated with impaired job performance., Methods: This descriptive study examined 171 physicians for the presence of burnout and its related risk factors. The evaluation of burnout was through Maslach Burnout Inventory (MBI). The participant was considered to meet the study criteria for burnout if he or she got a "high" score on at least 2 of the three dimensions of MBI., Results: In the current study, the prevalence of burnout in hospital physicians (53.9%) was significantly higher than family physicians (41.94%) with (p=0.001). Participants who work in the internal medicine department scored the highest prevalence (69.64%) followed by Surgeons (56.50%) and Emergency doctors (39.39%). On the other hand, Pediatricians got the lowest prevalence (18.75%). Working in the teaching hospital and being married are strong predictors for occurrence of burnout., Conclusion: There is a significant difference of burnout between hospital physicians and family physicians among the study subjects. Working in the teaching hospital and being married are strong predictors for occurrence of burnout.

Objective: To establish the benefits of immature reticulocyte fraction (IRF) measurement using an automated hematology cells analyzer over absolute neutrophil count (ANC) in predicting bone marrow recovery post induction chemotherapy., Methods: A prospective observational study was carried out in the Departments of Pathology, Medicine, and Pediatrics, Universiti Kebangsaan Malaysia, Medical Center (UKMMC), Kuala Lumpur, Malaysia during a period of 19 months from April 2009 to December 2010 to assess the bone marrow recovery in patients with acute leukemia. A total of 22 patients in remission induction phases were enrolled in this study. The blood specimens were collected from day zero after chemotherapy, and every 3 days until patients recovered hematologically. All blood samples were measured for ANC and IRF using an automated hematology analyzer (Beckman-Coulter LH750)., Results: The percentage of patients showing IRF recovery earlier than ANC recovery was 63.6% (14 out of 22 patients). There was a significant difference in the mean number of days for IRF recovery as compared with ANC recovery (14.05 and 17.18 days), p=0.005., Conclusion: This study proved that IRF was more useful in predicting bone marrow recovery in a patient with acute leukemia post induction chemotherapy compared with ANC. The IRF is not affected by infection, is easily measured, and inexpensive; thus, it is a reliable parameter to evaluate bone marrow reconstitution.

In this study, four series of 4-anilinoquinazoline derivatives were designed and synthesized as potential anti-proliferative agents. Mechanism of anticancer activity was explained through molecular docking of the target compounds into epidermal growth factor receptor tyrosine kinase (EGFR-TK) active site which displayed comparable binding mode of certain compounds to that of lapatinib. Moreover, the newly synthesized compounds were tested for their anti-proliferative activity on breast carcinoma cell line (MCF-7). 6-(4-Benzylpiperazin-1-ylsulfonyl)-4-(4-bromoanilino)quinazoline (14g) exhibited the most potent inhibitory activity (IC50=5.52 µM).

Background: Most people exposed to M. tuberculosis show no evidence of clinical disease. Five to 10% of individuals with latent infection progress to develop overt disease during their life time. Identification of people with latent TB infection will increase case detection rates and may dictate new treatment policies to control tuberculosis. This study aimed to determine LTBI point prevalence in a population from Sudan using two different diagnostic methods: the tuberculin skin test (TST) and the IFN-γ release assay (IGRA)., Methods: This was a prospective, community-based and case-controlled study. Following informed consent, household contacts (HHCs; n = 98) of smear-positive index cases and Community controls (CCs; 186), were enrolled. Tuberculin skin test (TST), whole blood stimulation with ESAT-6/CFP-10 ± TB7.7 antigens or purified protein derivative (PPD) and IFN-γ levels determination with ELISA were performed. The levels of IFN-γ and TST induration between the CCs and the HHCs were compared using student t-test, Chi-square and Kappa coefficient. Pearson correlation test was used to compare TST and IFN-γ. P levels of <0.05 were considered significant., Results: TST induration of ≥ 10 mm gave an LTBI point prevalence of 327 cases/1000 individuals among HHCs compared to 126 cases/1000 individuals among CCs (p = 0.000). PPD-induced IFN-γ release assay gave an LTBI point prevalence of 418 cases/1000 individuals among HHCs compared to 301 cases/1000 individuals among CCs (p =0.06). On the other hand ESAT-6/CFP-10 ± TB7.7-induced IFN-γ gave an LTBI point prevalence of 429 cases/1000 individuals among HHCs compared to 268 cases/1000 individuals among CCs (p = 0.01). IFN-γ productions levels induced by ESAT-6/CPF-10 ± TB7.7 antigens in HHCS and CCs were not significantly different from those induced by PPD (p = 0.7)., Conclusion: IFN-γ release assay (IGRA) gave higher LTBI point prevalence compared to TST in HHCs and CCs. PPD gave comparable results to ESAT-6/CFP-10 ± TB7.7 antigens in whole blood IFN-γ release, making it a cheap alternative to the recombinant antigens.

Dengue is the most important mosquito-borne viral disease. No specific treatment or vaccine is currently available; traditional vector control methods can rarely achieve adequate control. Recently, the RIDL (Release of Insect carrying Dominant Lethality) approach has been developed, based on the sterile insect technique, in which genetically engineered 'sterile' homozygous RIDL male insects are released to mate wild females; the offspring inherit a copy of the RIDL construct and die. A RIDL strain of the dengue mosquito, Aedes aegypti, OX513A, expresses a fluorescent marker gene for identification (DsRed2) and a protein (tTAV) that causes the offspring to die. We examined whether these proteins could adversely affect predators that may feed on the insect. Aedes aegypti is a peri-domestic mosquito that typically breeds in small, rain-water-filled containers and has no specific predators. Toxorhynchites larvae feed on small aquatic organisms and are easily reared in the laboratory where they can be fed exclusively on mosquito larvae. To evaluate the effect of a predator feeding on a diet of RIDL insects, OX513A Ae. aegypti larvae were fed to two different species of Toxorhynchites (Tx. splendens and Tx. amboinensis) and effects on life table parameters of all life stages were compared to being fed on wild type larvae. No significant negative effect was observed on any life table parameter studied; this outcome and the benign nature of the expressed proteins (tTAV and DsRed2) indicate that Ae. aegypti OX513A RIDL strain is unlikely to have any adverse effects on predators in the environment.

A series of nicotinic acid derivatives structurally related to niflumic acid and certain pyridazine-containing compounds have been synthesized and characterized by analytical and spectral data. All compounds were screened for their potential analgesic and anti-inflammatory activities. The compounds which displayed analgesic and anti-inflammatory activities were tested for ulcerogenicity and screened for in vivo inhibition of certain inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Compounds 1c, 2a, 2b, and 5a have shown potent analgesic and anti-inflammatory activities.

In this work, four nonionic surfactants based on sorbitan monolaurate (Span 20) were synthesized by introducing ethylene oxide gas (n = 20, 40, 60, 80 ethylene oxide units) into Span 20 to give four new surfactants with different hydrophilic-lipophilic balance (HLB), namely, E(20), E(40), E(60), and E(80). The structures of the prepared nonionic surfactants were elucidated using Fourier-transform infrared (FT-IR) and (1)H-nuclear magnetic resonance (NMR) spectroscopy. The surface-tension measurements were recorded. The effects of the prepared nonionic surfactants on the simultaneous saccharification and fermentation (SSF) of microwave/alkali-pretreated rice straw to produce ethanol were investigated. From the obtained data, it was found that the addition of the nonionic surfactants at 2.5 g/L had a positive effect on SSF. The maximum ethanol yield (76 and 55%) was obtained after 72 hr for rice straw using Kluyveromyces marxianus and Saccharomyces cerevisiae, respectively. Also, it was found that the ethanol yield increases with increasing HLB of the prepared nonionic surfactants by increasing ethylene oxide units. The adsorption of nonionic surfactants on lignocelluloses is proposed to be due to hydrophobic and hydrogen bonding interactions between nonionic surfactants and the lignin part in the lignocelulose. It can be concluded that additions of surface-active compounds, such as nonionic surfactants, increase enzymatic conversion of rice straw for bioethanol purposes.