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Yasser Rehman1, Jonathan E Rosenberg21Division of Hospital Medicine, UMass Memorial Healthcare, Worcester, MA, USA; 2Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USAAbstract: Prostate cancer is the second leading cause of cancer death in men in the US and Europe. The treatment of advanced-stage prostate cancer has been androgen deprivation. Medical castration leads to decreased production of testosterone and dihydrotestosterone by the testes, but adrenal glands and even prostate cancer tissue continue to produce androgens, which eventually leads to continued prostate cancer growth despite castrate level of androgens. This stage is known as castrate-resistant prostate cancer (CRPC), which continues to be a challenge to treat. Addition of androgen antagonists to hormonal deprivation has been successful in lowering the prostate-specific antigen levels further, but has not actually translated into life-prolonging options. The results of several contemporary studies have continued to demonstrate activation of the androgen receptor as being the key factor in the continued growth of prostate cancer. Blockade of androgen production by nongonadal sources has led to clinical benefit in this setting. One such agent is abiraterone acetate, which significantly reduces androgen production by blocking the enzyme, cytochrome P450 17 alpha-hydroxylase (CYP17). This has provided physicians with another treatment option for patients with CRPC. The landscape for prostate cancer treatment has changed with the approval of cabazitaxel, sipuleucel-T and abiraterone. Here we provide an overview of abiraterone acetate, its mechanism of action, and its potential place for therapy in CRPC.Keywords: CRPC, abiraterone, CYP17, inhibitors, androgens, castration resistant prostate cancer

Abstract: Aims: The aim of this study was to analyse arsenic (As) transformation and biosorption by indigenous As‐resistant bacteria both in planktonic and biofilm modes of growth. Methods and Results: As‐resistant bacteria were isolated from industrial waste water and strain PT2, and identified as Exiguobacterium profundum through 16S rRNA gene sequencing was selected for further study. As transformation and biosorption by E. profundumPT2 was determined by HPLC‐ICP‐MS analysis. Planktonic cultures reduced 3·73 mmol l−1 As5+ into As3+ from artificial waste water effluent after 48‐h incubation. In case of biosorption, planktonic cultures and biofilms exhibited 25·2 and 29·4 mg g−1 biomass biosorption, respectively. As biosorption kinetics followed Freundlich isotherm and pseudo second‐order model. Biofilm formation peaked after 3 days of incubation, and in the presence of As stress, biofilm formation was significantly affected in contrast to control (P < 0·05). Homogeneous nature of mature biofilms with an increased demand of nutrients was revealed by minimum roughness and maximum surface to biovolume ratio measured through CLSM analysis. Conclusion: Indigenous As‐resistant E. profundumPT2 was found capable of As transformation and biosorption both in the form of planktonic cultures and biofilms. Significance and Impact of the Study: Indigenous biofilm forming E. profundum PT2 revealing As biosorption and biotransformation potential is presented an eco‐friendly and cost‐effective source for As remediation that can be implemented for waste water treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT Amylases are starch hydrolyzing enzymes and have commercial applications in different industries, such as food, fermentation, detergent and pharmaceuticals. In the current study amylases were extracted from bacteria found in kitchen wastes and rice fields. Isolates with maximum starch hydrolysis determined by the clear zones formation against blue background were selected and examined for further extracellular amylase activity. 16S rRNA gene sequencing confirmed these isolates as Bacillus subtilis, Bacillus sp. and Lysinibacillus sp. Highest dextrizing activity (83%) and starch hydrolysis ratio (2.8) were shown by Bacillus subtilis G3. Furthermore optimum amylase activity was also checked at different temperatures, pH, media composition and substrate concentration. Optimum reaction temperature and pH for crude amylase activity from Bacillus subtilis G3 was 60°C-75°C and 9pH in minimal media supplemented with 0.1% soluble starch. Thin layer chromatography and high performance liquid chromatography were carried out to investigate the starch hydrolyzed products (glucose, maltose and maltosaccharides) produced by amylolytic action of amylase. In addition to it molecular weight of amylase was found to be about 68kDa as revealed by SDS PAGE analysis after acetone precipitation. These bacteria could be genetically manipulated for large scale enzyme production which can be ultimately used for commercial purposes. [ABSTRACT FROM AUTHOR]

Diaphragmatic injuries are quite uncommon and often result from either blunt or penetrating trauma. Diaphragmatic ruptures are usually associated with abdominal trauma; however, it can occur in isolation. Acute traumatic rupture of the diaphragm may go unnoticed and there is often a delay between the injury and the diagnosis. Patients present with non-specific symptoms and may complain of chest pain, abdominal pain, dyspnoea, tachypnoea and cough, heartburn and symptoms of gastro-oesophageal reflux. Respiratory distress and faeco-pneumothorax have been reported. We present an interesting case of traumatic diaphragmatic hernia presenting 5 years after a road traffic accident as acute abdomen and massive haematemesis due to strangulated gangrenous gastric hernia. [ABSTRACT FROM AUTHOR]

Objectives: To describe the multidisciplinary investigation and management of a rapidly increasing number of cases of Legionnaires' disease in the North Shropshire area, UK during August 2006. Study design: Epidemiological and environmental investigation of a cluster of cases of Legionnaires' disease. Methods: Outbreak investigation included: agreeing case definitions; case finding; epidemiological survey; identification and environmental investigation of potential sources; microbiological analysis of clinical and environmental samples; mapping the location of potential sources; and the movement and residence of cases. Results: Three cases of Legionnaires' disease were admitted to a local hospital between 30 and 31 August 2006. Two of these cases were Shropshire residents, with the third living in Wales. A fourth case was also identified which, it was thought, may have been linked to this cluster as the patient had a history of travel to the same area as the two Shropshire residents. Over the next few weeks, three more cases were identified, two of whom were admitted to hospital. Subsequent detailed environmental, epidemiological and microbiological investigation did not support the hypothesis that any of these cases could be linked to a common source. Conclusions: The results of this investigation strongly suggest that a single source was not responsible for the cluster, and it was concluded that this incident was a pseudo-outbreak. This investigation serves as a reminder that clusters can and do occur, and that an apparent outbreak may be a collection of sporadic cases distinguishable only by rigorous epidemiological, environmental and microbiological investigation. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of mesenchymal stem cells (MSCs) for chronic knee pain secondary to osteoarthritis (OA)., Methods: We searched MEDLINE, EMBASE, CINAHL, and Cochrane Central to September 2023 for trials that (1) enrolled patients with chronic pain associated with knee OA, and (2) randomized them to MSC therapy vs. placebo or usual care. We performed random-effects meta-analysis and used Grading of Recommendations, Assessment, Development, and Evaluation to assess the certainty of evidence., Results: We included 16 trials (807 participants). At 3-6 months, MSC therapy probably results in little to no difference in pain relief (weighted mean difference [WMD] -0.74 cm on a 10 cm visual analog scale [VAS], 95% confidence interval [95%CI] -1.16 to -0.33; minimally important difference [MID] 1.5 cm) or physical functioning (WMD 2.23 points on 100-point 36-item Short Form Survey (SF-36) physical functioning subscale, 95%CI -0.97 to 5.43; MID 10-points; both moderate certainty). At 12 months, injection of MSCs probably results in little to no difference in pain (WMD -0.73 cm on a 10 cm VAS, 95%CI -1.69 to 0.24; moderate certainty) and may improve physical functioning (WMD 19.36 points on 100-point SF-36 PF subscale, 95%CI -0.19 to 38.9; low certainty). MSC therapy may increase risk of any adverse events (risk ratio [RR] 2.67, 95%CI 1.19 to 5.99; low certainty) and pain and swelling of the knee joint (RR 1.58, 95%CI 1.04 to 2.38; low certainty)., Conclusions: Intra-articular injection of MSCs for chronic knee pain associated with OA probably provides little to no improvement in pain or physical function., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Alzheimer's disease (AD) presents a complex pathology involving amyloidogenic proteolysis, neuroinflammation, mitochondrial dysfunction, and cholinergic deficits. Oxidative stress exacerbates AD progression through pathways like macromolecular peroxidation, mitochondrial dysfunction, and metal ion redox potential alteration linked to amyloid-beta (Aβ). Despite limited approved medications, heterocyclic compounds have emerged as promising candidates in AD drug discovery. This review highlights recent advancements in synthetic heterocyclic compounds targeting oxidative stress, mitochondrial dysfunction, and neuroinflammation in AD. Additionally, it explores the potential of nanomaterial-based drug delivery systems to overcome challenges in AD treatment. Nanoparticles with heterocyclic scaffolds, like polysorbate 80-coated PLGA and Resveratrol-loaded nano-selenium, show improved brain transport and efficacy. Micellar CAPE and Melatonin-loaded nano-capsules exhibit enhanced antioxidant properties, while a tetra hydroacridine derivative (CHDA) combined with nano-radiogold particles demonstrates promising acetylcholinesterase inhibition without toxicity. This comprehensive review underscores the potential of nanotechnology-driven drug delivery for optimizing the therapeutic outcomes of novel synthetic heterocyclic compounds in AD management. Furthermore, the inclusion of various promising heterocyclic compounds with detailed ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) data provides valuable insights for planning the development of novel drug delivery treatments for AD., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phyto-pathogenic fungal species is a leading biotic stress factor to agri-food production and ecosystem of globe. Chemical (Systemic fungicides) and biological treatment (micro-organism) are globally accepted methods that are being used against biotic stress (disease) management. Plant Growth-Promoting Microbes are being used as an alternative to ease chemical dependency as their overdoses have generated injurious effects on plants and environment. Therefore, present study performs to evaluate the photochemical and physiological profiling of plants exposed to chemical and biological treatment in biotic stress (disease) environment. Two concentrations of each chemical treatment i.e. Topsin-M 70 (Dimethyl 4,4'-o-phenylene bis 3-thioallaphanate, MF1 = 3 g kg -1 and MF2 = 6 g kg -1 seeds) and biological treatment i.e. Trichoderma harzianum strain Th-6 (MT1 = 10 6 spores mL -1 and MT2 = 10 7 spores mL -1 ) were used in this experiment. Macrophomina phaseolina (MP) were used as biotic stress factor causing root rot disease in soybean plants. Morpho-physiological assessments and light harvesting efficiency of photosystem II were conducted after 52 days of treatment. Maximum quantum yield (F v /F m ), number and size of active reaction center (F v /F o ), photochemical quenching (qP), efficiency of photosystem II (Φ PSII ), electron transport rate (ETR), chlorophyll content index (CCI), relative water content (RWC) and stomatal conductance (SC) were increased in MT2 and MF1 treatments as compared to stress plants (MP). Biological (MT2) and chemical (MF1) treatment lessen the production of stress markers showing -48.0 to -54.3% decline in malondialdehyde (MDA) and -42.0 to -53.7% in hydrogen peroxide (H 2 O 2 ) as compared to stress plant (MP). Biological treatment in both concentration (MF1 & MF2) while chemical treatment at low dose effectively mitigates biotic stress and eases the magnitude of disease. Increasing doses of chemical treatment persuaded deleterious effects on the physiology and light harvesting efficiency of stressed plant suggesting the role of biological treatment (T. harzianum) against biotic stress management in future of crop protection., 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 © 2024 Elsevier Masson SAS. All rights reserved.)

With a shift towards plant-based diets for human and planetary health, monitoring the mineral content of staple crops is important to ensure population nutrient requirements can be met. This review aimed to explore changes in the iron content of unprocessed wheat and rice in Australia over time. A comprehensive systematic search of four electronic databases and the gray literature was conducted. A total of 25 papers published between 1930 and 2023 that measured the iron content of unprocessed wheat and rice were included. Triticum aestivum was the most common wheat type studied, including 26 cultivars; iron content ranged from 40 to 50 µg/g in the 1930s and 1970s and was more variable after this time due to the introduction of modern cultivars, with most values between 25 and 45 µg/g. The iron content of rice ( Oryza sativa ) was more consistent at 10-15 µg/g between the 1980s and 2020s. Variations over the years may be attributed to environmental, biological, and methodological factors but these were not well documented across all studies, limiting the interpretation of findings. As the number of individuals following plant-based diets continues to rise, the ongoing monitoring of the mineral content in commonly consumed plant-based foods is warranted.

Aims: This study compared patient-reported outcomes of three total knee arthroplasty (TKA) designs from one manufacturer: one cruciate-retaining (CR) design, and two cruciate-sacrificing designs, anterior-stabilized (AS) and posterior-stabilized (PS)., Methods: Patients scheduled for primary TKA were included in a single-centre, prospective, three-armed, blinded randomized trial (n = 216; 72 per group). After intraoperative confirmation of posterior cruciate ligament (PCL) integrity, patients were randomly allocated to receive a CR, AS, or PS design from the same TKA system. Insertion of an AS or PS design required PCL resection. The primary outcome was the mean score of all five subscales of the Knee injury and Osteoarthritis Outcome Score (KOOS) at two-year follow-up. Secondary outcomes included all KOOS subscales, Oxford Knee Score, EuroQol five-dimension health questionnaire, EuroQol visual analogue scale, range of motion (ROM), and willingness to undergo the operation again. Patient satisfaction was also assessed., Results: Patients reported similar levels of pain, function, satisfaction, and general health regardless of the prosthetic design they received. Mean maximal flexion (129° (95% confidence interval (CI) 127° to 131°) was greater in the PS group than in the CR (120° (95% CI 121° to 124°)) and AS groups (122° (95% CI 120° to 124°))., Conclusion: Despite differences in design and constraint, CR, AS, and PS designs from a single TKA system resulted in no differences in patient-reported outcomes at two-year follow-up. PS patients had statistically better ROM, but the clinical significance of this finding is unclear., Competing Interests: A. Aamodt reports research grants from South-Eastern Norway Regional Health Authority and Norwegian Research Council, unrelated to this study., (© 2023 Rehman et al.)

Background: Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as risk factors for opioid overdose; however, the magnitude of these associations and their credibility are unclear. We sought to identify predictors of fatal and nonfatal overdose from prescription opioids., Methods: We systematically searched MEDLINE, Embase, CINAHL, PsycINFO and Web of Science up to Oct. 30, 2022, for observational studies that explored predictors of opioid overdose after their prescription for chronic pain. We performed random-effects meta-analyses for all predictors reported by 2 or more studies using odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Twenty-eight studies (23 963 716 patients) reported the association of 103 predictors with fatal or nonfatal opioid overdose. Moderate- to high-certainty evidence supported large relative associations with history of overdose (OR 5.85, 95% CI 3.78-9.04), higher opioid dose (OR 2.57, 95% CI 2.08-3.18 per 90-mg increment), 3 or more prescribers (OR 4.68, 95% CI 3.57-6.12), 4 or more dispensing pharmacies (OR 4.92, 95% CI 4.35-5.57), prescription of fentanyl (OR 2.80, 95% CI 2.30-3.41), current substance use disorder (OR 2.62, 95% CI 2.09-3.27), any mental health diagnosis (OR 2.12, 95% CI 1.73-2.61), depression (OR 2.22, 95% CI 1.57-3.14), bipolar disorder (OR 2.07, 95% CI 1.77-2.41) or pancreatitis (OR 2.00, 95% CI 1.52-2.64), with absolute risks among patients with the predictor ranging from 2-6 per 1000 for fatal overdose and 4-12 per 1000 for nonfatal overdose., Interpretation: We identified 10 predictors that were strongly associated with opioid overdose. Awareness of these predictors may facilitate shared decision-making regarding prescribing opioids for chronic pain and inform harm-reduction strategies SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (https://osf.io/vznxj/)., Competing Interests: Competing interests: Corey Hayes reports support from the National Institute on Drug Abuse Clinical Trials Network (5UG1DA013732-23S3). David Juurlink is an unpaid member of Physicians for Responsible Opioid Prescribing. David Juurlink is also a member of the American College of Medical Toxicology. David Juurlink has received payment for lectures from Texas Tech University Health Sciences Centre and payment for expert testimony regarding analgesics, including opioids. He has received travel support for presentations and scientific meetings from the Canadian Institutes of Health Research, Stanford University and Texas Tech University Health Sciences Centre. Jason Busse is the Principal Investigator for the update of the 2017 Canadian Opioid Guideline, which is funded by Health Canada. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Due to the rise in bacterial resistance towards various therapeutic agents, interest is now developing towards fatty acid based antimicrobials because of their non-specific mode of action. A strain SORS 24 isolated from Sonchus oleraceus (Sow thistle) showed significant activity against Escherichia coli ATCC 25922 (25 mm), Chlorella vulgaris (20 mm), Bacillus subtilis DSM 10 (ATCC 6051) and Pseudomonas sp. (15 mm). It displayed an LC50 value of 10 µg/ml against Artemia salina (Brine shrimp) nauplii and an EC50 value of 0.8 µg/ml in the (DPPH) diphenylpicrylhydrazyl antioxidant assay. The strain also displayed genotoxicity against a PolA deficient strain, E. coli K-12 AB 3027 (15 mm). Mass spectrometry (HPLC-MS) showed that the strain produced oleamide (9-Octadecenamide) and erucamide (13-Docosenamide). Both of the purified fatty acid amides showed prominent activity against B. subtilis DSM 10 (ATCC 6051) (20 mm) and E. coli ATCC 25922 (15 mm). Significant genotoxicity was observed against E. coli K-12 AB 3027 (15 mm). The 16S gene sequencing revealed that the strain belonged to species, Streptomyces tanashiensis. As far as our understanding, this is the first report of this species producing these fatty acid based antimicrobials., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Arsenic is a ubiquitous toxic metalloid, the concentration of which is beyond WHO safe drinking water standards in many areas of the world, owing to many natural and anthropogenic activities. Long-term exposure to arsenic proves lethal for plants, humans, animals, and even microbial communities in the environment. Various sustainable strategies have been developed to mitigate the harmful effects of arsenic which include several chemical and physical methods, however, bioremediation has proved to be an eco-friendly and inexpensive technique with promising results. Many microbes and plant species are known for arsenic biotransformation and detoxification. Arsenic bioremediation involves different pathways such as uptake, accumulation, reduction, oxidation, methylation, and demethylation. Each of these pathways has a certain set of genes and proteins to carry out the mechanism of arsenic biotransformation. Based on these mechanisms, various studies have been conducted for arsenic detoxification and removal. Genes specific for these pathways have also been cloned in several microorganisms to enhance arsenic bioremediation. This review discusses different biochemical pathways and the associated genes which play important roles in arsenic redox reactions, resistance, methylation/demethylation, and accumulation. Based on these mechanisms, new methods can be developed for effective arsenic bioremediation., (© 2023. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Chronic post-surgical pain is reported by up to 40% of patients after lumbar microdiscectomy for sciatica, a complaint associated with disability and loss of productivity. We conducted a systematic review of observational studies to explore factors associated with persistent leg pain and impairments after microdiscectomy for sciatica. We searched eligible studies in MEDLINE, Embase, and CINAHL that explored, in an adjusted model, predictors of persistent leg pain, physical impairment, or failure to return to work after microdiscectomy for sciatica. When possible, we pooled estimates of association using random-effects models using the Grading of Recommendations Assessment, Development, and Evaluation approach. Moderate-certainty evidence showed that the female sex probably has a small association with persistent post-surgical leg pain (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 0.63 to 2.08; absolute risk increase (ARI) = 1.8%, 95% CI = -4.7% to 11.3%), large association with failure to return to work (OR = 2.79, 95% CI = 1.27 to 6.17; ARI = 10.6%, 95% CI = 1.8% to 25.2%), and older age is probably associated with greater postoperative disability (β = 1.47 points on the 100-point Oswestry Disability Index for every 10-year increase from age (>/=18 years), 95% CI = -4.14 to 7.28). Among factors that were not possible to pool, two factors showed promise for future study, namely, legal representation and preoperative opioid use, which showed large associations with worse outcomes after surgery. The moderate-certainty evidence showed female sex is probably associated with persistent leg pain and failure to return to work and that older age is probably associated with greater post-surgical impairment after a microdiscectomy. Future research should explore the association between legal representation and preoperative opioid use with persistent pain and impairment after microdiscectomy for sciatica., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Rehman et al.)

Objective: Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management., Methods: We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus, and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥3 months) after total knee replacement. We pooled estimates of association for all independent variables reported by >1 study., Results: Thirty studies (26,517 patients) reported the association of 151 independent variables with persistent pain after knee replacement. High certainty evidence demonstrated an increased risk of persistent pain with pain catastrophizing (absolute risk increase [ARI] 23%, 95% confidence interval [CI] 12 to 35), younger age (ARI for every 10-year decrement from age 80, 4%, 95% CI 2 to 6), and moderate-to-severe acute post-operative pain (ARI 30%, 95% CI 20 to 39). Moderate certainty evidence suggested an association with female sex (ARI 7%, 95% CI 3 to 11) and higher pre-operative pain (ARI 35%, 95% CI 7 to 58). Studies did not adjust for both peri-operative pain severity and pain catastrophizing, which are unlikely to be independent. High to moderate certainty evidence demonstrated no association with pre-operative range of motion, body mass index, bilateral or unilateral knee replacement, and American Society of Anesthesiologists score., Conclusions: Rigorously conducted observational studies are required to establish the relative importance of higher levels of peri-operative pain and pain catastrophizing with persistent pain after knee replacement surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To identify the frequency of congenital heart disease (CHD) in various Khyber Pakhtunkhwa (KPK) divisions., Materials and Methods: To perform this research, we reviewed the medical records of pediatric cardiology patients hospitalized between January 2022 and July 2022. Data was taken from the cardiology department's computerized data system between January 1 and July 31, 2022. To prevent any errors in diagnosis and address them during input by the ward clerk, patients' addresses, diagnoses, and gender were verified with the computerized medical record. Data were analyzed, and frequency and percentages were calculated. Per the digital mapping of KPK districts, we stratified and examined the data among various KPK divisions., Results: Out Of the 371 patients with CHD who were admitted, 36.98% (137) were from the Peshawar division, 28.84% (107) from the Malakand division, 16.71% (62) from the Mardan division, 6.1% (23) from the Kohat division, 4.3% (16) from the Bannu division, 3.5% (13) from the Dera Ismail Khan division, and 3.5% (13) from the Hazara division. A total of 371 had CHD, of which 234 (63.07%) were cyanotic and 137 (36.92%) were cyanotic. The most prevalent acynotic congenital heart defect was patent ductus arteriosus (PDA) at 36.32% (85), followed by a ventricular septal defect (VSD) at 35.04 (82). The most frequent acyanotic congenital cardiac abnormality was tetralogy of Fallot (TOF) at 49.63% (68), which was followed by transposition of the great arteries (TGA) at 33.57% (46)., Conclusion: In KPK, congenital heart disease is most prevalent in the divisions of Peshawar and Malakand, while it is least prevalent in Hazara., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ali et al.)

Background: There is no consensus on the importance of the kinematics of the prosthetic joint for the clinical outcome after total knee arthroplasty. A 3-armed randomized controlled trial was done to determine and compare the in vivo kinematics of a posterior cruciate-retaining and two posterior cruciate-sacrificing (Anterior-Stabilized and Posterior-Stabilized) prosthetic designs from the same total knee arthroplasty system. Since the anterior-stabilized and posterior-stabilized designs are posterior cruciate ligament-sacrificing designs, we hypothesized they would have similar contact-point kinematics. Further, we hypothesized that the cruciate-retaining design would have contact-point kinematics different from the anterior-stabilized and the posterior-stabilized designs, but comparable to a native knee., Methods: Thirty-nine patients with a well-functioning total knee arthroplasty one year postoperatively underwent kinematic analysis of a weight-bearing step-up movement under fluoroscopic recording. Model-based radiostereometric analysis was used to determine anteroposterior contact-point translations and rotations through the movement path to assess knee kinematics., Findings: The cruciate-retaining and anterior-stabilized groups' medial and lateral contact-points displayed similar paradoxical posterior translations during step-up in the magnitude of 7 and 2 mm, respectively. In contrast, the posterior-stabilized group's contact-points translated anteriorly by 4 and 10 mm throughout the movement and were significantly more posterior than the cruciate-retaining and the anterior-stabilized groups from >100° to 40° of flexion. The femur rotated internally with all designs., Interpretation: The cruciate-retaining and anterior-stabilized designs displayed similar contact-point translation patterns during a step-up movement. Only the posterior-stabilized design showed a pattern comparable to native knees. Conversion from a cruciate-retaining to an anterior-stabilized design because of posterior cruciate ligament insufficiency will not change knee kinematics., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context: Osteopathic manipulative treatment (OMT) has been utilized by osteopathic clinicians as primary or adjunctive management for dizziness caused by neuro-otologic disorders. To our knowledge, no current systematic reviews provide pooled estimates that evaluate the impact of OMT on dizziness., Objectives: We aimed to systematically evaluate the effectiveness and safety of OMT and analogous techniques in the treatment of dizziness., Methods: We performed a literature search in CINAHL, Embase, MEDLINE, Allied and Complementary Medicine Database (AMED), EMCare, Physiotherapy Evidence Database (PEDro), PubMed, PsycINFO, Osteopathic Medicine Digital Library (OSTMED.DR), and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to March 2021 for randomized controlled trials (RCTs) and prospective or retrospective observational studies of adult patients experiencing dizziness from neuro-otological disorders. Eligible studies compared the effectiveness of OMT or OMT analogous techniques with a comparator intervention, such as a sham manipulation, a different manual technique, standard of care, or a nonpharmacological intervention like exercise or behavioral therapy. Assessed outcomes included disability associated with dizziness, dizziness severity, dizziness frequency, risk of fall, improvement in quality of life (QOL), and return to work (RTW). Assessed harm outcomes included all-cause dropout (ACD) rates, dropouts due to inefficacy, and adverse events. The meta-analysis was based on the similarities between the OMT or OMT analogous technique and the comparator interventions. The risk of bias (ROB) was assessed utilizing a modified version of the Cochrane Risk of Bias Tool for RCTs and the Cochrane Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) for observational studies. The quality of evidence was determined utilizing the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach., Results: There were 3,375 studies identified and screened, and the full text of 47 of them were reviewed. Among those, 12 (11 RCTs, 1 observational study, n=367 participants) met the inclusion criteria for data extraction. Moderate-quality evidence showed that articular OMT techniques were associated with decreases (all p<0.01) in disability associated with dizziness (n=141, mean difference [MD]=-11, 95% confidence interval [CI]=-16.2 to -5.9), dizziness severity (n=158, MD=-1.6, 95% CI=-2.4 to -0.7), and dizziness frequency (n=136, MD=-0.6, 95% CI=-1.1 to -0.2). Low-quality evidence showed that articular OMT was not associated with ACD rates (odds ratio [OR]=2.2, 95% CI=0.5 to 10.2, p=0.31). When data were pooled for any type of OMT technique, findings were similar; however, disability associated with dizziness and ACD rates had high heterogeneity (I 2 =59 and 46%). No studies met all of the criteria for ROB., Conclusions: The current review found moderate-quality evidence that treatment with articular OMT techniques was significantly associated with decreased disability associated with dizziness, dizziness severity, and dizziness frequency. However, our findings should be interpreted cautiously because of the high ROB and small sample sizes in the eligible studies., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Objective The objective is to determine the frequency of different congenital heart diseases and their association in children with Down syndrome (DS). Methodology This cross-sectional observational study was conducted in the pediatric department of Peshawar Institute of Cardiology, Peshawar, Pakistan from August 2021 to July 2022. A total of 123 children with DS and congenital heart disease (CHD) were included in this cross-sectional study. Detailed history and examination were performed, and findings were documented on performed pro forma. Diagnosis of CHD was confirmed through two-dimensional (2D) and Doppler echocardiography performed by a pediatric cardiologist. Patients were managed according to standard protocols and guidelines. The data including age, gender, mother's age at the time of birth, type of CHD and growth failure were documented and analyzed. Percentages were used to express frequencies. Results The mean age was 2.2 years ± 3.4 years (interquartile range (IQR): 10 days to 14 years). There were 65 (52.8%) male and 58 (47.1%) female patients. Out of 123 patients, 101 (82.1%) had acyanotic CHD and 22 (17.8%) had cyanotic CHD. Among acyanotic CHD, isolated ventricular septal defect (VSD) was the most common observation in 23 (22.3%) and among cyanotic CHD, tetralogy of Fallot (TOF) in seven (31.8%) patients. The most common associations of CHD were VSD+ patent ductus arteriosus (PDA) in 11 (9%) patients and atrial septal defect (ASD)+PDA in nine (7.3%) patients. The median age of the mother at delivery was 31 years (interquartile range (IQR): 20 years to 45 years). Growth failure was seen in 70 (56.9%) patients. Conclusion Based on our data, VSD is the most common CHD followed by a complete atrio-VSD (CAVSD) in children with DS. The most common association of CHD in DS is VSD with PDA. Growth failure is seen in most of the patients with DS having a CHD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Rehman et al.)

The development of smart, efficient and multifunctional material systems for diseases treatment are imperative to meet current and future health challenges. Nanomaterials with theranostic properties have offered a cost effective and efficient solution for disease treatment, particularly, metal/oxide based nanotheranostic systems already offering therapeutic and imaging capabilities for cancer treatment. Nanoparticles can selectively generate/scavenge ROS through intrinsic or external stimuli to augment/diminish oxidative stress. An efficient treatment requires higher oxidative stress/toxicity in malignant disease, with a minimal level in surrounding normal cells. The size, shape and surface properties of nanoparticles are critical parameters for achieving a theranostic function in the microenvironment. In the last decade, different strategies for the synthesis of biocompatible theranostic nanostructures have been introduced. The exhibition of therapeutics properties such as selective reactive oxygen species (ROS) scavenging, hyperthermia, antibacterial, antiviral, and imaging capabilities such as MRI, CT and fluorescence activity have been reported in a variety of developed nanosystems to combat cancer, neurodegenerative and emerging infectious diseases. In this review article, theranostic in vitro behaviour in relation to the size, shape and synthesis methods of widely researched and developed nanosystems (Au, Ag, MnO x , iron oxide, maghemite quantum flakes, La 2 O 3- x , TaO x , cerium nanodots, ITO, MgO 1- x ) are presented. In particular, ROS-based properties of the nanostructures in the microenvironment for cancer therapy are discussed. The provided overview of the biological behaviour of reported metal-based nanostructures will help to conceptualise novel designs and synthesis strategies for the development of advanced nanotheranostic systems.

Lithium metal batteries have recently gained tremendous attention owing to their high energy capacity compared to other rechargeable batteries. Nevertheless, lithium (Li) dendritic growth causes low Coulombic efficiency, thermal runaway, and safety issues, all of which hinder the practical application of Li metal as an anodic material. In this review, the failure mechanisms of Li metal anode are described according to its infinite volume changes, unstable solid electrolyte interphase, and Li dendritic growth. The fundamental models that describe the Li deposition and dendritic growth, such as the thermodynamic, electrodeposition kinetics, and internal stress models are summarized. From these considerations, porous carbon-based frameworks have emerged as a promising strategy to resolve these issues. Thus, the main principles of utilizing these materials as a Li metal host are discussed. Finally, we also focus on the recent progress on utilizing one-, two-, and three-dimensional carbon-based frameworks and their composites to highlight the future outlook of these materials., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 Crown Copyright. Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

Objective To evaluate children with sinus venosus atrial septal defect (SV-ASD) for associated vascular anomalies. Methodology A total of 72 children with sinus venosus atrial septal defect with partial anomalous pulmonary venous return who presented to pediatric cardiology unit, Lady Reading Hospital Peshawar, from January 2019 till June 2021 were included in this cross-sectional study. Diagnosis of sinus venosus atrial septal defect was confirmed through two-dimensional (2D) and Doppler echocardiography performed by a pediatric cardiologist. Cardiac CT angiography was performed and assessed by a pediatric cardiac interventionist and radiologist. Patients were managed according to standard protocols and guidelines. The data were entered and analyzed with Statistical Package for the Social Sciences (SPSS) version 20. Percentages were used to express frequencies. Results Mean age was 8.3 ± 2.7 years (interquartile range (IQR): two months to 18 years). There were 37 (51.4%) male and 35 (48.6%) female patients. Out of 72 patients, 64 (88.8%) patients had superior sinus venosus atrial septal defect, while inferior sinus venosus atrial septal defect was found in eight (11.1%) patients. In six (8.3%) patients, associated secundum atrial septal defect was identified. Bilateral superior vena cava was found in seven (9.7%) patients. Left aortic arch was seen in 70 (97.2%) patients, whereas two (2.7%) patients had right aortic arch. Conclusion Sinus venosus ASD is a rare type of atrial septal defect which is also associated with both pulmonary and systemic vascular anomalies. Diagnosing these vascular anomalies is of paramount importance before any corrective intervention can be done. Recognizing the pattern of these anomalies should be known to every interventional cardiologist, radiologist, and cardiac surgeon. Echocardiography alone is not a good tool to assess these extracardiac structures. Imaging modalities like CT angiography and MRI have refined our preoperative workup which is essential for the ultimate outcome of the corrective intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Akbar et al.)

Objective The objective is to share our experience of trans-catheter device closure of patent ductus arteriosus (PDA) and review its efficacy and immediate complications. Methodology This cross-sectional observational study was done in the Department of Pediatric cardiology, Lady Reading Hospital, Peshawar from January 2020 to December 2020. A total of 51 patients with isolated PDA, who underwent PDA device closure, were enlisted in this study through consecutive sampling methods, irrespective of their age and gender. Data of the patients were collected on preformed pro forma. Data was entered in SPSS 20 (SPSS Inc., Chicago, IL, USA). Descriptive statistics like mean ± SD for numerical data (age, weight, and hospital stay), while frequency and percentage for categorical variables (Device type, complication, hospital stay, and type of anesthesia given) were calculated. Results Among total 51 patients (33 [64.7%] females and 18 [35.3%] males) with mean age 8.19 ± 6.96 years underwent attempted trans-catheter PDA device closure. In all cases PDA was successfully occluded with appropriate size devices. General anesthesia was given in 38 (74.5%) patients. Complications occurred in only four (7.8%) patients in the form of hemolysis followed by acute kidney injury in one patient, another had device embolization to descending aorta, which was retrieved in cath lab, one had device embolization to the right pulmonary artery, which was retrieved in cath lab and one had mild left ventricular systolic dysfunction. The mean duration of hospital stay was 22.0 ± 10.2 h. Conclusion Trans-catheter PDA device closure is a safe procedure with a high success rate and little morbidity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Khan et al.)

Background: Pulmonary valve stenosis (PS) is common congenital heart disease in children and patient can present with cyanosis, chest pain, dyspnea and failure with severe form. The objective of this study was to enlighten the short outcome of balloon pulmonary valvuloplasty in children with severe pulmonary stenosis., Methods: This cross sectional observational study was done in paediatric cardiology department of Lady Reading Hosptial, Peshawer form June 2019 to December 2020 over 1.5 years. Children aged 6 months to 16 years of either sex diagnosed as case of severe stenosis with doming pulmonary valve and having symptoms of chest pain and dysnea on exeration and pregradient pressure of 64 mm Hg or more on echocardiography were included. Patients were interviened with ballon-valvuloplasty. Outcome was taken as discharge from hospital with complications after procedure if any. Patients were followed up for 3 months. Data including age, sex, pre cath echocardiography, cath pulmonary valve annulus, post ballooning pulmonary valve (PV) gradient, PV gradient on echocardiography after intervention and follow up gradient on echocardiography at three months was documented. Data was analyzed by SPSS 20. Chi square test and paired T - Test was applied where required. Results were taken as significant with p value <0.05., Results: There were 51 patients, 35 (68.6%) male and 16 (31.4%) female. Mean age was 8.35±4.93 years. Mean pre cath gradient across the pulmonary valve on echocardiography was 109.14±31.44 mm Hg. Post intervention mean pressure gradient across PV was 32.41±11.49 mm Hg. Pulmonary valve annulus on echocardiography before intervention ranged from 7 to 25 mm with mean of 14.67±3.79 mm. There was no complication in majority (82.4%) of patients. Mild PR was in 5 (9.8%) patients. There was significant relationship between pre and post intervention pressure gradient across PV valve with p value of <0.001., Conclusions: Balloon pulmonary valvuloplasty in one of the safest intervention for PS in children with few complications.

Objective This study aimed to assess the outcome and see the spectrum of presenting symptoms of children with cyanotic congenital heart diseases (CHDs) admitted through the emergency department in Lady Reading Hospital (LRH) in Peshawar, Pakistan. Materials and methods This cross-sectional study included 104 children with cyanotic CHD admitted through the emergency department in the pediatric cardiology unit of LRH from February 2019 to January 2020. Diagnosis of cyanotic CHD was confirmed through two-dimensional echocardiography. Patients were treated according to standard protocols for their presenting symptoms. The data were analyzed using Statistical Package for the Social Sciences (SPSS), version 20.0 (IBM Corp., Armonk, NY) and frequencies were expressed as percentages. Results The study included 65 male cases (62.5%) and 39 female cases (37.5%), and participant ages ranged from 10 days to 15 years (mean, 2.7 ± 3.4 years). Of 104 patients, 70 presented with cyanotic spells (84.5%), 53 with fever (10.7%), 28 with respiratory distress (26.5%), 11 with loose stools (10.5%), 10 with hemiplegia (9.6%), and eight with seizures (7.6%). Pneumonia was a precipitating factor in 13 patients (12.5%), infective endocarditis in 12 patients (11%), gastroenteritis in 11 (11%), brain abscess and cerebrovascular accidents in seven patients each (6% each), meningitis in six patients (6%), and tuberculous pericardial effusion in one patient (<1%). The primary CHD was tetralogy of Fallot (TOF) in 52 patients, tricuspid atresia in 14 patients, pulmonary atresia in 13 patients, double outlet right ventricle in 10 patients, transposition of great arteries (TGA) in seven patients, and total anomalous pulmonary venous return (TAPVR), truncus arteriosus, congenitally corrected TGA, and critical pulmonary stenosis in two patients each. Twenty-six patients received treatment of the acute problem and instructions for follow-up monitoring. Twelve patients died during their hospital stay, and three left against medical advice. Fifteen patients received patent ductus arteriosus stenting, and six received right ventricular outflow tract stenting. One patient received a Blalock-Taussig (BT) shunt stent, and one received a left pulmonary artery stent. Two patients received a balloon pulmonary valvotomy, and one received pericardial effusion drainage. Eleven patients received surgical correction of TOF, 11 received surgical correction for BT shunt, four received surgical correction for brain abscess drainage, and two received TAPVR repair. Conclusion TOF was the most common cyanotic heart disease in our study. Cyanotic spells or increased cyanosis was the most common presenting concern. Cyanotic CHDs present with variable extracardiac signs and symptoms in emergencies. Appropriate assessment, immediate management of the acute problem, and timely intervention or surgical management result in good outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ilyas et al.)

Objective: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain., Design: Systematic review and meta-analysis., Data Sources: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021., Study Selection: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up., Data Extraction and Synthesis: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence., Results: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect)., Conclusions: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form www.icmje.org/disclosure-of-interest/ and declare: no financial support from any industry for the submitted work; IP and SU have received research funds from Northern Green Canada; IP has been a paid consultant for Northern Green Science, Northern Green Canada, Monk-E psychedelics, and Evergreen Pacific Insurance Corporation; SU and IP received honoraria from Spectrum Therapeutics and Tilray Inc. for educational presentations; MAW is the chief medical officer for Canopy Growth Corporation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain., Design: Systematic review., Data Sources: CENTRAL, EMBASE and MEDLINE., Main Outcomes and Measures: Opioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events., Study Selection Criteria and Methods: We included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome., Results: Eligible studies included five randomised trials (all enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) -3.4 milligram morphine equivalent (MME); 95% CI (CI) -12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD -0.18 cm; 95% CI -0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD -0.22 cm; 95% CI -0.4 to -0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD -1%; 95% CI -4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD -22.5 MME; 95% CI -43.06 to -1.97)., Conclusion: Opioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence. PROSPERO registration number CRD42018091098., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)