Efficacy of Cerebellar Transcranial Magnetic Stimulation in Treating Essential Tremor: A Randomized, Sham-Controlled Trial.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) of the cerebellar hemisphere represents a new option in treating essential tremor (ET) patients. We aimed to determine the efficacy of cerebellar rTMS in treating ET using different protocols regarding the number of sessions, exposure duration, and follow-up duration. METHODS: A randomized sham-controlled trial was conducted, in which 45 recruit patients were randomly allocated to 2 groups. The first (active group) comprised 23 patients who were exposed to 12 sessions of active rTMS with 900 pulses of 1-Hz rTMS at 90% of the resting motor threshold daily on each side of the cerebellar hemispheres over 4 weeks. The second group (sham group) comprised 22 patients who were exposed to 12 sessions of sham rTMS. Both groups were reassessed at baseline and after 1 day, 1 month, 2 months, and 3 months using the Fahn-Tolosa-Marin tremor-rating scale (FTM). RESULTS: Demographic characteristics did no differ between the two groups. There were significant reductions both in FTM subscores A and B and in the FTM total score in the active-rTMS group during the period of assessment and after 3 months (p=0.031 and 0.011, respectively). However, subscore C did not change significantly from baseline when assessed at 2 and 3 months (p=0.073 and 0.236, respectively). Furthermore, the global assessment score was significantly higher in the active-rTMS group (p>0.001). CONCLUSIONS: Low-frequency rTMS over the cerebellar cortex for 1 month showed relative safety and long-lasting efficacy in patients with ET. Further large-sample clinical trials are needed that include different sites of stimulation and longer follow-ups.

Validation of the arabic version of the EuroQol-5-dimension 5-level (EQ-5D-5 L) in patients with spinal degenerative diseases.

OBJECTIVE: This study aims to test the reliability and validity of the translated Arabic version of EQ-5D-5 L. METHODS: The study was conducted on 100 patients operated upon for degenerative spine diseases coming for follow up in the outpatient clinic of a Tertiary care hospital. Test-retest reliability was assessed by completing the self-administered tool in two follow up visits, one week apart, by 50 patients. Internal consistency was evaluated by Cronbach's alpha. Intra-class correlation coefficients and kappa statistics were performed to test for the agreement between the two ratings. Criterion validity was assessed by comparing the responses of 100 patients to the EQ-5D-5 L with scores of two validated questionnaires; the Arabic version of the Oswestry disability index and the Arabic version of short-form health survey-36. The construct validity was assessed using known-groups comparison to test for hypothesized differences concerning demographic and clinical variables. RESULTS: The Arabic version of EQ-5D-5 L questionnaire had a high reliability with high observed internal consistency (Cronbach's alpha = 0.816, CI: 0.719-0.886). It showed strong temporal stability, with ICCs of the EQ-5D-5 L score, index and EQ-visual analog scale (EQ-VAS) of 0.852, 0.801, and 0.839 respectively. Agreement by kappa was moderate; above 0.4, for all domains, except for the "Usual activities" domain. EQ-5D-5 L domains, VAS and index had moderate to strong significant correlations with SF-36 and ODI subscales and total scores in the correct direction indicating a good criterion validity of the instrument. CONCLUSION: The Arabic version of EQ-5D-5 L is reliable and valid for assessment of HRQoL of Arabic speaking patients.

Efficacy of selenium on patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

INTRODUCTION: Postoperative complications pose significant challenges in cardiac surgery and with the evolution of selenium as a potential anti-inflammatory agent, some studies reported its inefficiency. Thus, we conducted our meta-analysis to evaluate the impact of selenium supplementation on cardiac surgery patients. METHODS: Different databases such as PubMed, Embase, and Cochrane Library from inception till January 2024 were searched identifying a total of seven randomized-controlled trials involving selenium supplementation after cardiac surgery. Risk ratio (RR) and Mean difference (MD) were calculated with a 95% confidence interval (CI). RESULTS: The selenium intervention significantly raised the incidence of Acute Kidney injury (RR 0.76; 95% CI: 0.59, 0.98; P = 0.04) while significantly reducing the duration of hospital stay (MD -1.33; 95% CI: -2.51, -0.16; P = 0.03) and postoperative CRP levels (SMD -0.18; 95% CI: -0.34, -0.02; P = 0.03). The effect of selenium intervention on days spent in ICU (MD -0.01; 95% CI: -0.28, 0.25; P = 0.92), mortality (RR 1.07; 95% CI: 0.84, 1.37; P = 0.57) and incidence of hospital acquired infections (RR 0.98; 95% CI: 0.76, 1.26; P = 0.88) is insignificant. CONCLUSION: Selenium supplementation did not significantly reduce major postoperative complications in cardiac surgery patients. However, its ability to modulate inflammation, as reflected in decreased C-reactive protein levels, highlights its potential role in managing the inflammatory response. Future investigations should focus on optimized selenium supplementation strategies in conjunction with other antioxidants to enhance its benefits.

Discovery of Potent Indolyl-Hydrazones as Kinase Inhibitors for Breast Cancer: Synthesis, X-ray Single-Crystal Analysis, and In Vitro and In Vivo Anti-Cancer Activity Evaluation.

According to data provided by the World Health Organization (WHO), a total of 2.3 million women across the globe received a diagnosis of breast cancer in the year 2020, and among these cases, 685,000 resulted in fatalities. As the incidence of breast cancer statistics continues to rise, it is imperative to explore new avenues in the ongoing battle against this disease. Therefore, a number of new indolyl-hydrazones were synthesized by reacting the ethyl 3-formyl-1H-indole-2-carboxylate 1 with thiosemicarbazide, semicarbazide.HCl, 4-nitrophenyl hydrazine, 2,4-dinitrophenyl hydrazine, and 4-amino-5-(1H-indol-2-yl)-1,2,4-triazole-3-thione to afford the new hit compounds, which were assigned chemical structures as thiosemicarbazone 3, bis(hydrazine derivative) 5, semicarbzone 6, Schiff base 8, and the corresponding hydrazones 10 and 12 by NMR, elemental analysis, and X-ray single-crystal analysis. The MTT assay was employed to investigate the compounds' cytotoxicity against breast cancer cells (MCF-7). Cytotoxicity results disclosed potent IC50 values against MCF-7, especially compounds 5, 8, and 12, with IC50 values of 2.73 ± 0.14, 4.38 ± 0.23, and 7.03 ± 0.37 µM, respectively, compared to staurosproine (IC50 = 8.32 ± 0.43 µM). Consequently, the activities of compounds 5, 8, and 12 in relation to cell migration were investigated using the wound-healing test. The findings revealed notable wound-healing efficacy, with respective percentages of wound closure measured at 48.8%, 60.7%, and 51.8%. The impact of the hit compounds on cell proliferation was assessed by examining their apoptosis-inducing properties. Intriguingly, compound 5 exhibited a significant enhancement in cell death within MCF-7 cells, registering a notable increase of 39.26% in comparison to the untreated control group, which demonstrated only 1.27% cell death. Furthermore, the mechanism of action of compound 5 was scrutinized through testing against kinase receptors. The results revealed significant kinase inhibition, particularly against PI3K-α, PI3K-ß, PI3K-δ, CDK2, AKT-1, and EGFR, showcasing promising activity, compared to standard drugs targeting these receptors. In the conclusive phase, through in vivo assay, compound 5 demonstrated a substantial reduction in tumor volume, decreasing from 106 mm³ in the untreated control to 56.4 mm³. Moreover, it significantly attenuated tumor proliferation by 46.9%. In view of these findings, the identified leads exhibit promises for potential development into future medications for the treatment of breast cancer, as they effectively hinder both cell migration and proliferation.

Do corporate anti-bribery and corruption commitments enhance environmental management performance? The moderating role of corporate social responsibility accountability and executive compensation governance.

This study aims to examine the potential impact (substantive or symbolic) of firms' anti-bribery and corruption commitments (ABCC) on environmental management performance (ENVS). We also seek to explore whether this link is contingent on corporate social responsibility (CSR) accountability and executive compensation governance. To achieve these aims, we use a sample of 2151 firm-year observations representing 214 FTSE 350 non-financial companies from 2002 to 2016. Our findings support a positive association between firms' ABCC and ENVS. In addition, our evidence shows that CSR accountability and executive compensation governance are significant substitutes for ABCC to engender enhanced ENVS. Our study highlights practical implications for organisations, regulators and policymakers, and suggests several avenues for future environmental management research. Overall, our findings are unsensitive to alternative measures of ENVS, different types of multivariate regression methods, namely ordinary least squares (OLS) and two-step generalized method of moments (GMM) regressions, and controlling for industry environmental risk and the implementation of the UK Bribery Act 2010.

Stroke services in the Middle East and adjacent region: A survey of 34 hospital-based stroke services.

Background: Acute stroke care is complex and requires multidisciplinary networking. There are insufficient data on stroke care in the Middle East and adjacent regions in Asia and Africa. Objective: Evaluate the state of readiness of stroke programs in the Middle East North Africa and surrounding regions (MENA+) to treat acute stroke. Method: Online questionnaire survey on the evaluation of stroke care across hospitals of MENA+ region between April 2021 and January 2022. Results: The survey was completed by 34/50 (68%) hospitals. The median population serviced by participating hospitals was 2 million. The median admission of patients with stroke/year was 600 (250-1,100). The median length of stay at the stroke units was 5 days. 34/34 (100%) of these hospitals have 24/7 CT head available. 17/34 (50%) have emergency guidelines for prehospital acute stroke care. Mechanical thrombectomy with/without IVT was available in 24/34 (70.6%). 51% was the median (IQR; 15-75%) of patients treated with IVT within 60 min from arrival. Thirty-five minutes were the median time to reverse warfarin-associated ICH. Conclusion: This is the first large study on the availability of resources for the management of acute stroke in the MENA+ region. We noted the disparity in stroke care between high-income and low-income countries. Concerted efforts are required to improve stroke care in low-income countries. Accreditation of stroke programs in the region will be helpful.

In-vitro viability of laser cladded Fe-based metallic glass as a promising bioactive material for improved osseointegration of orthopedic implants.

The commonly used metallic biomaterials fail to prove durability for orthopedics due to their lack of biocompatibility and poor bioactivity which weakens the bonding to bones. Metallic glasses (MGs) have attracted attention as an alternative biomaterial for orthopedics owing to their superior mechanical properties and acceptable biocompatibility. Nevertheless, their uses are limited due to geometrical constraints and brittleness. In this research, the in-vitro bioactivity of laser cladded FeCrMoCB MG on nickel-free stainless-steel was investigated. The proposed MG coating exhibited a remarkable in-vitro bioactivity behavior without prior treatment after immersion in simulated body fluid which is a key factor for better osseointegration. The surface morphology showed that apatite nucleated from the first day and completely covered the surface after 21 days. The energy dispersive spectroscopy spectra showed an increase in the Ca/P ratio from 0.51 at 3 days to 1.61 at 21 days, thus approaching the stoichiometric ratio of bone apatite. The infra-red examination revealed the existence of Ca+2, PO4-2 and OH- indicating the nucleation of brushite and B-type apatite. Additionally, the X-ray diffraction examination revealed the existence of amorphous and nanocrystalline calcium phosphates. These results show the potential of FeCrMoCB MGs as a promising bioactive coating for excellent osseointegration of metallic implants with bone tissue.

Effective combinatorial immunotherapy for penile squamous cell carcinoma.

Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular mechanisms and therapies of PSCC are understudied, owing to scarcity of laboratory models. Herein, we describe a genetically engineered mouse model of PSCC, by co-deletion of Smad4 and Apc in the androgen-responsive epithelium of the penis. Mouse PSCC fosters an immunosuppressive microenvironment with myeloid-derived suppressor cells (MDSCs) as a dominant population. Preclinical trials in the model demonstrate synergistic efficacy of immune checkpoint blockade with the MDSC-diminishing drugs cabozantinib or celecoxib. A critical clinical problem of PSCC is chemoresistance to cisplatin, which is induced by Pten deficiency on the backdrop of Smad4/Apc co-deletion. Drug screen studies informed by targeted proteomics identify a few potential therapeutic strategies for PSCC. Our studies have established what we believe to be essential resources for studying PSCC biology and developing therapeutic strategies.

Expeditious Green Synthesis of Novel 4-Methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one Analogue from Ninhydrin: N/S-Alkylation and Aza-Michael Addition.

A straightforward green synthesis of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 6 is reported from ninhydrin 1 via condensation with ethyl acetoacetate, followed by cyclization with hydrazine hydrate in water as a benign solvent. Tetraazafluoranthen-3-thione 7 was obtained using Lawesson's reagent. N-alkylated tetraazafluoranthen-3-one 8-12 and S-alkylated analogues 13-15 were synthesized via alkylation. The investigation of the unique reactivity of 4-methyl-1,2,5,6-tetraazafluoranthen-3(2H)-one/thione toward the alkylation and aza-Michael additions was explored.

Synthesis of a New Series of Nitrogen/Sulfur Heterocycles by Linking Four Rings: Indole; 1,2,4-Triazole; Pyridazine; and Quinoxaline.

A new series of nitrogen and sulfur heterocyclic systems were efficiently synthesized by linking the following four rings: indole; 1,2,4-triazole; pyridazine; and quinoxaline hybrids. The strength of the acid that catalyzes the condensation of 4-amino-5-(1H-indol-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 1 with aromatic aldehydes controlled the final product. Reflux in glacial acetic acid yielded Schiff bases 2-6, whereas concentrated HCl in ethanol resulted in a cyclization product at C-3 of the indole ring to create indolo-triazolo-pyridazinethiones 7-16. This fascinating cyclization approach was applicable with a wide range of aromatic aldehydes to create the target cyclized compounds in excellent yield. Additionally, the coupling of the new indolo-triazolo-pyridazinethiones 7-13 with 2,3-bis(bromomethyl)quinoxaline, as a linker in acetone and K2CO3, yielded 2,3-bis((5,6-dihydro-14H-indolo[2,3-d]-6-aryl-[1,2,4-triazolo][4,3-b]pyridazin-3 ylsulfanyl)methyl)quinoxalines 19-25 in a high yield. The formation of this new class of heterocyclic compounds in high yields warrants their use for further research. The new compounds were characterized using nuclear magnetic resonance (NMR) and mass spectral analysis. Compound 6 was further confirmed by the single crystal X-ray diffraction technique.

Discovery of hydrazide-based pyridazino[4,5-b]indole scaffold as a new phosphoinositide 3-kinase (PI3K) inhibitor for breast cancer therapy.

Herein, the mono and dialkylation of pyridazino[4,5-b]indole were achieved with a set of alkylating agents, including amyl bromide, allyl bromide, benzyl bromide and ethyl chloroacetate in the presence of K2CO3/acetone or KOH/DMSO. The hydrazinolysis of mono and di-esters 10 and 11 gave the target hydrazides 12 and 13, which displayed promising, potent, and significant cytotoxic activity against the MCF-7 cell line with IC50 values of 4.25 and 5.35 µm compared to that of the standard drug 5-FU (IC50 6.98 µm), respectively. RT-PCR analysis of the most active compound 12 was performed to determine its mode of action through the up-regulation of pro-apoptotic genes and inhibition of anti-apoptotic and PI3K/AKT/mTOR genes. The findings were consistent with the proposed mechanism illustrated in the in silico study. Further, the in vivo analysis exhibited its potent anti-cancer activity through the prolongation of survival parameters, and inhibition of ascetic fluid parameters in EAC-bearing mice.

Vein of Galen malformation treated with the Micro Vascular Plug system: case report.

This case report describes the use of the Micro Vascular Plug (MVP) system in a mural-type vein of Galen aneurysmal malformation, resulting in successful occlusion of the cerebrovascular fistula. This result was confirmed with immediate cessation in blood flow and 6-month follow-up angiography. The unique characteristics of the MVP provide potential advantages over current embolic techniques for occlusion of high-flow, fistulous, intracranial vessels such as those seen in the vein of Galen aneurysmal malformation, and may represent a valuable addition to the currently available options.

The Role of Catheter Angiography in the Diagnosis of Central Nervous System Vasculitis.

BACKGROUND: Central nervous system vasculitis (CNSV) is a rare disorder, the pathophysiology of which is not fully understood. It involves a combination of inflammation and thrombosis. CNSV is most commonly associated with headache, gradual changes in mental status, and focal neurological symptoms. Diagnosis requires the effective use of history, laboratory testing, imaging, and biopsy. Catheter angiography can be a powerful tool in the diagnosis when common and low-frequency angiographic manifestations of CNSV are considered. We review these manifestations and their place in the diagnostic algorithm of CNSV. SUMMARY: We reviewed the PubMed database for case series of CNSV that included 5 or more patients. Demographic and angiographic findings were collected. Angiographic findings were dichotomized between common and low-frequency findings. A system for incorporating these findings into clinical decision-making is proposed. KEY MESSAGE: CNSV is a diagnostic challenge due to the absence of a true gold standard test. In the absence of such a test, catheter angiography remains a central piece of the diagnostic puzzle when appropriately employed and interpreted.

Protective effect of adipose-derived mesenchymal stem cells against acute kidney injury induced by ischemia-reperfusion in Sprague-Dawley rats.

Acute kidney injury (AKI) is a complex clinical condition associated with significant morbidity and mortality and lacking effective management. Ischemia-reperfusion injury (IRI) remains one of the leading causes of AKI in native and transplanted kidneys. The aim of this study was to evaluate the efficacy of adipose-derived mesenchymal stem cells (ADSCs) in the prevention of renal IRI in rats. The study was conducted on male Sprague-Dawley rats (n=72) weighing 250-300 g. Rats were randomly assigned to three main groups: i) Sham-operated control group (n=24); ii) positive control group, in which rats were subjected to IRI and were administered culture media following 4 h of IRI (n=24); and iii) ADSC group (n=24), in which rats were administered 1×106 ADSCs via the tail vein following 4 h of IRI. Each main group was further divided according to the timing after IRI into four equal-sized subgroups. Renal function was tested via the measurement of serum creatinine levels and creatinine clearance. In addition, malondialdehyde (MDA) levels were determined in serum and renal tissue homogenate as an indicator of oxidative stress. Histopathological changes were analyzed in different regions of the kidney, namely the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla. In each region, the scoring system considered active injury changes, regenerative changes and chronic changes. The ADSCs were assessed and their differentiation capability was verified. IRI resulted in a significant increase in serum creatinine, serum and tissue MDA levels and a significant reduction in creatinine clearance compared with those in sham-operated rats,. These changes were attenuated by the use of ADSCs. The prominent histopathological changes in the cortex, ISOM and OSOM were reflected in the injury score, which was significantly evident in the positive control group. The use of ADSCs was associated with significantly lowered injury scores at days 1 and 3; however, no significant effect was observed on day 7. These results indicate that the use of ADSCs ameliorates renal injury and dysfunction associated with IRI in rats.

Fabrication and deformation behaviour of multilayer Al2O3/Ti/TiO2 nanotube arrays.

In this study, titanium thin films were deposited on alumina substrates by radio frequency (RF) magnetron sputtering. The mechanical properties of the Ti coatings were evaluated in terms of adhesion strength at various RF powers, temperatures, and substrate bias voltages. The coating conditions of 400W of RF power, 250°C, and a 75V substrate bias voltage produced the strongest coating adhesion, as obtained by the Taguchi optimisation method. TiO2 nanotube arrays were grown as a second layer on the Ti substrates using electrochemical anodisation at a constant potential of 20V and anodisation times of 15min, 45min, and 75min in a NH4F electrolyte solution (75 ethylene glycol: 25 water). The anodised titanium was annealed at 450°C and 650°C in a N2 gas furnace to obtain different phases of titania, anatase and rutile, respectively. The mechanical properties of the anodised layer were investigated by nanoindentation. The results indicate that Young's modulus and hardness increased with annealing temperature to 650°C.