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Aims and Background: Dentin hypersensitivity (DH) is characterized by sharp shooting pain due to exposed dentin, and the most common method for treating this pain is the occlusion of the dentinal tubules with the help of desensitizing agents. E-silver diamine fluoride (e-SDF) (Kids-e-Dental, Mumbai, India) is a commercially available 38% SDF solution in the Indian market. Despite the fact that its application for caries prevention has been proven, the fluoride (Fl) and silver (Ag) ion concentrations of e-SDF for use in treating DH have yet to be standardized. The aim of this study is to determine and compare the Fl and Ag ion concentrations released from two commercially available 38% silver diamine fluoride (SDF) solutions., Materials and Methods: The two most common commercially available 38% SDF solution brands, namely Advantage Arrest and e-SDF were used. Two drops of each of these solutions were taken in three beakers and diluted with distilled water. The Fl ion concentration was evaluated using a calibrated ion-specific electrode. The free Ag ion concentration was assessed using an atomic absorption spectrometry (AAS)., Results: Release of Ag ions shows that on days 1, 2, 5, 6, and 7, concentration (mg/L) was higher in the Advantage Arrest group but is statistically nonsignificant. On days 3 and 4, it is higher in an e-SDF group with a t -value of 1.085 and 0.243 and is statistically nonsignificant. Release of Fl ion showed that in comparison to the baseline, it was more with Advantage Arrest on days 2, 4, and 7 with a t -value of -3.766, -0.999, and 0.347 and on day 2 was statistically significant. On days 3, 5, and 6 Fl ion release from baseline was more with e-SDF in comparison with Advantage Arrest but statistically insignificant., Conclusion: The AAS analysis as well as the ion chromatography showed that the Ag and Fl ion release respectively on days 1-7 from e-SDF was similar to the one seen in the case of Advantage Arrest., Clinical Significance: This helps dentists choose among different brands of the same commercially available 38% SDF solutions depending on the cost and availability of the product., How to Cite This Article: Kamath P, Kamath P, P AN, et al. Evaluation of Fluoride and Silver Ion Concentrations in e-Silver Diamine Fluoride and Advantage Arrest: An Ion Chromatography and Atomic Absorption Spectrometer Study. Int J Clin Pediatr Dent 2024;17(10):1141-1145., Competing Interests: Source of support: Nil Conflict of interest: Dr Ashwin Rao is associated as the National Editorial Board member of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of this editorial board member and his research group.Conflict of interest: Dr Ashwin Rao is associated as the National Editorial Board member of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of this editorial board member and his research group., (Copyright © 2024; The Author(s).)

This paper aims to emphasize the occurrence of various emerging contaminant (EC) mixtures in natural ecosystems and highlights the primary concern arising from the unregulated release into soil and water, along with their impacts on human health. Emerging contaminant mixtures, including pharmaceuticals, personal care products, dioxins, polychlorinated biphenyls, pesticides, antibiotics, biocides, surfactants, phthalates, enteric viruses, and microplastics (MPs), are considered toxic contaminants with grave implications. MPs play a crucial role in transporting pollutants to aquatic and terrestrial ecosystems as they interact with the various components of the soil and water environments. This review summarizes that major emerging contaminants (ECs), like trimethoprim, diclofenac, sulfamethoxazole, and 17α-Ethinylestradiol, pose serious threats to public health and contribute to antimicrobial resistance. In addressing human health concerns and remediation techniques, this review critically evaluates conventional methods for removing ECs from complex matrices. The diverse physiochemical properties of surrounding environments facilitate the partitioning of ECs into sediments and other organic phases, resulting in carcinogenic, teratogenic, and estrogenic effects through active catalytic interactions and mechanisms mediated by aryl hydrocarbon receptors. The proactive toxicity of ECs mixture complexation and, in part, the yet-to-be-identified environmental mixtures of ECs represent a blind spot in current literature, necessitating conceptual frameworks for assessing the toxicity and risks with individual components and mixtures. Lastly, this review concludes with an in-depth exploration of future scopes, knowledge gaps, and challenges, emphasizing the need for a concerted effort in managing ECs and other organic pollutants., 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 B.V. All rights reserved.)

Background and Objectives: Omigapil is a small molecule which inhibits the GAPDH-Siah1-mediated apoptosis pathway. Apoptosis is a pathomechanism underlying the congenital muscular dystrophy subtypes LAMA2-related dystrophy (LAMA2-RD) and COL6-related dystrophy (COL6-RD). Studies of omigapil in the (dy w /dy w ) LAMA2-RD mouse model demonstrated improved survival, and studies in the (dy 2J /dy 2J ) LAMA2-RD mouse model and the (Col6a1 -/- ) COL6-RD mouse model demonstrated decreased apoptosis., Methods: A phase 1 open-label, sequential group, ascending oral dose, cohort study of omigapil in patients with LAMA2-RD or COL6-RD ages 5-16 years was performed (1) to establish the pharmacokinetic (PK) profile of omigapil at a range of doses, (2) to evaluate the safety and tolerability of omigapil at a range of doses, and (3) to establish the feasibility of conducting disease-relevant clinical assessments. Patients were enrolled in cohorts of size 4, with each patient receiving 4 weeks of vehicle run-in and 12 weeks of study drug (at daily doses ranging from 0.02 to 0.08 mg/kg). PK data from each cohort were analyzed before each subsequent dosing cohort was enrolled. A novel, adaptive dose-finding method (stochastic approximation with virtual observation recursion) was used to allow for dose escalation/reduction between cohorts based on PK data., Results: Twenty patients were enrolled at the NIH (LAMA2-RD: N = 10; COL6-RD: N = 10). Slightly greater than dose-proportional increases in systemic exposure to omigapil were seen at doses 0.02-0.08 mg/kg/d. The dose which achieved patient exposure within the pre-established target area under the plasma concentration-vs-time curve (AUC 0-24h ) range was 0.06 mg/kg/d. In general, omigapil was safe and well tolerated. No consistent changes were seen in the disease-relevant clinical assessments during the duration of the study., Discussion: This study represents the thus far only clinical trial of a therapeutic small molecule for LAMA2-RD and COL6-RD, completed with an adaptive trial design to arrive at dose adjustments. The trial met its primary end point and established that the PK profile of omigapil is suitable for further development in pediatric patients with LAMA2-RD or COL6-RD, the most common forms of congenital muscular dystrophy. While within the short duration of the study disease-relevant clinical assessments did not demonstrate significant changes, this study establishes the feasibility of performing interventional clinical trials in these rare disease patient populations., Classification of Evidence: This study provides Class IV evidence of omigapil in a dose-finding phase 1 study., Trial Registration Information: Clinical Trials NCT01805024., Competing Interests: A.R. Foley, P. Yun, M.E. Leach, S. Neuhaus, G. Averion, Y. Hu, L.H. Hayes, S. Donkervoort, M. Jain, M. Waite, R. Parks, D.X. Bharucha-Goebel, O.H. Mayer, Y. Zou, M. Fink, J. DeCoster, C. Mendoza, C. Arévalo, and K. Cheung report no disclosures relevant to the manuscript; R. Hausmann was an employee and a shareholder of Santhera Pharmaceuticals at the time of this study; D. Petraki was an employee of Santhera Pharmaceuticals at the time of this study; C.G. Bönnemann was the site principal investigator for this study sponsored by Santhera Pharmaceuticals. Go to Neurology.org/NG for full disclosures., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Aim: To compare the sealing ability of three different materials when used as postendodontic restoration barriers to coronal microleakage in root-filled teeth., Materials and Methods: In the present study, 60 single-rooted mandibular premolars with single canals were selected. After endodontic treatment was done with protaper files, they were divided into three groups of 20 teeth each, which were restored with Zirconomer (Group I), Hi-Dense (Group II), and Surefil composite (Group III), respectively. After storing in artificial saliva for 10 days, all teeth were then immersed in Rhodamine 6G fluorescent dye. Teeth were then sectioned buccolingually in a longitudinal direction. The coronal microleakage was measured in both halves under a fluorescence microscope and images were taken with a digital camera. Data obtained from the study in the form of scoring as per specific criteria was subjected to statistical analysis., Result: Results of the study showed that the minimum amount of coronal microleakage was seen in Group II restored with Hi-Dense followed by Group III restored with Surefil Composite and the maximum amount of coronal microleakage was seen in Group I restored with Zirconomer., Conclusion: On the basis of the results of the present study, it may be concluded that Hi-Dense showed better coronal sealing ability in access cavities. Surefil composite exhibited coronal microleakage less than Zirconomer but more than Hi-Dense., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Background: RYR1 -related myopathies ( RYR1 -RM) are caused by pathogenic variants in the RYR1 gene which encodes the type 1 ryanodine receptor (RyR1). RyR1 is the sarcoplasmic reticulum (SR) calcium release channel that mediates excitation-contraction coupling in skeletal muscle. RyR1 sub-conductance, SR calcium leak, reduced RyR1 expression, and oxidative stress often contribute to RYR1 -RM pathogenesis. Loss of RyR1-calstabin1 association, SR calcium leak, and increased RyR1 open probability were observed in 17 RYR1 -RM patient skeletal muscle biopsies and improved following ex vivo treatment with Rycal compounds. Thus, we initiated a first-in-patient trial of Rycal S48168 (ARM210) in ambulatory adults with genetically confirmed RYR1 -RM., Methods: Participants received 120 mg (n = 3) or 200 mg (n = 4) S48168 (ARM210) daily for 29 days. The primary endpoint was safety and tolerability. Exploratory endpoints included S48168 (ARM210) pharmacokinetics (PK), target engagement, motor function measure (MFM)-32, hand grip and pinch strength, timed functional tests, PROMIS fatigue scale, semi-quantitative physical exam strength measurements, and oxidative stress biomarkers. The trial was registered with clinicaltrials.gov (NCT04141670) and was conducted at the National Institutes of Health Clinical Center between October 28, 2019 and December 12, 2021., Findings: S48168 (ARM210) was well-tolerated, did not cause any serious adverse events, and exhibited a dose-dependent PK profile. Three of four participants who received the 200 mg/day dose reported improvements in PROMIS-fatigue at 28 days post-dosing, and also demonstrated improved proximal muscle strength on physical examination., Interpretation: S48168 (ARM210) demonstrated favorable safety, tolerability, and PK, in RYR1 -RM affected individuals. Most participants who received 200 mg/day S48168 (ARM210) reported decreased fatigue, a key symptom of RYR1 -RM. These results set the foundation for a randomized, double-blind, placebo-controlled proof of concept trial to determine efficacy of S48168 (ARM210) in RYR1 -RM., Funding: NINDS and NINR Intramural Research Programs, NIH Clinical Center Bench to Bedside Award (2017-551673), ARMGO Pharma Inc., and its development partner Les Laboratoires Servier., Competing Interests: E.E.M is an employee of ARMGO Pharma, Inc., during the conduct of the study; an employee of ARMGO Pharma, Inc., outside the submitted work; In addition, E.E.M has a patent US2023/0372358 pending. Y.W is an employee of ARMGO Pharma, Inc. In addition, Y.W has a patent US8853198 issued. A.R.M. is a co-founder of ARMGO Pharma Inc, chairs the Scientific Advisory Board of ARMGO Pharma Inc., and holds stock in the company. All other authors declare no conflict of interest with the research in this manuscript., (© 2024 The Author(s).)

The construction industry substantially impacts a country's economic growth and ecological progress. Due to the competitive nature of the construction business and intense rivalry between construction companies, the industry's focus is progressively becoming customer-centric. Efforts are being taken to ensure high-quality buildings are built at reasonable rates and on time. Companies are trying to ensure on-time building projects are completed within allocated budgets. This can be accomplished by ensuring minimal waste generation from various activities during the construction process. Implementing lean tools and techniques can improve work efficiency and reduce waste in the building process. This research study offers a basic understanding of lean tools and emphasizes their contribution in terms of time, effort, and sustainability. The primary purpose of this study is to present the effectiveness of the lean process for construction waste management. Through a case study, this research shows the deployment of lean tools and principles for efficient construction waste management and optimal use of building resources. The improvement in reduced waste generation and enhanced organizational resource productivity is closely monitored. The study results indicated that the lean framework could reduce waste by 25 to 50%. It is demonstrated that lean construction significantly improves construction sustainability and productivity. If it is implemented along with automation tools and circular economy concepts, more than 50% of waste reduction can be achieved. These viable initiatives are necessary to improve the performance of the Indian construction industry to achieve circularity in waste management which indirectly helps in the sustainability goals of the construction sector., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background : The angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated blood ACE is a marker for granulomatous diseases and elevated ACE expression in tissues is associated with increased risk of cardiovascular diseases. Objective and Methodology: We applied a novel approach -ACE phenotyping-to find a reason for conformationally impaired ACE in the blood of one particular donor. Similar conformationally altered ACEs were detected previously in 2-4% of the healthy population and in up to 20% of patients with uremia, and were characterized by significant increase in the rate of angiotensin I hydrolysis. Principal findings: This donor has (1) significantly increased level of endogenous ACE inhibitor in plasma with MW less than 1000; (2) increased activity toward angiotensin I; (3) M71V mutation in ABCG2 (membrane transporter for more than 200 compounds, including bilirubin). We hypothesize that this patient may also have the decreased level of free bilirubin in plasma, which normally binds to the N domain of ACE. Analysis of the local conformation of ACE in plasma of patients with Gilbert and Crigler-Najjar syndromes allowed us to speculate that binding of mAbs 1G12 and 6A12 to plasma ACE could be a natural sensor for estimation of free bilirubin level in plasma. Totally, 235 human plasma/sera samples were screened for conformational changes in soluble ACE. Conclusions/Significance: ACE phenotyping of plasma samples allows us to identify individuals with conformationally altered ACE. This type of screening has clinical significance because this conformationally altered ACE could not only result in the enhancement of the level of angiotensin II but could also serve as an indicator of free bilirubin levels.

Single cell data integration methods aim to integrate cells across data batches and modalities, and data integration tasks can be categorized into horizontal, vertical, diagonal, and mosaic integration, where mosaic integration is the most general and challenging case with few methods developed. We propose scMoMaT, a method that is able to integrate single cell multi-omics data under the mosaic integration scenario using matrix tri-factorization. During integration, scMoMaT is also able to uncover the cluster specific bio-markers across modalities. These multi-modal bio-markers are used to interpret and annotate the clusters to cell types. Moreover, scMoMaT can integrate cell batches with unequal cell type compositions. Applying scMoMaT to multiple real and simulated datasets demonstrated these features of scMoMaT and showed that scMoMaT has superior performance compared to existing methods. Specifically, we show that integrated cell embedding combined with learned bio-markers lead to cell type annotations of higher quality or resolution compared to their original annotations., (© 2023. The Author(s).)

Background: High-flow fistulas related to plexiform nidi are found in 40% of large brain arteriovenous malformations (AVMs). Endovascular occlusion of intranidal fistulas before plexiform components is empirically considered safe, but potential ensuing dangerous re-routing of flow through plexiform vessels may in theory raise their rupture risk. It remains unclear whether it is safer to embolize plexiform or fistulous vessels initially. We used a novel biomathematical AVM model to compare theoretical hemodynamic changes and rupture risks on sequential embolizations of both types of nidus vessels., Methods: We computationally modeled a theoretical AVM as an electrical circuit containing a nidus consisting of a massive stochastic network ensemble comprising 1000 vessels. We sampled and individually simulated 10 000 different nidus morphologies with a fistula angioarchitecturally isolated from its adjacent plexiform nidus. We used network analysis to calculate mean intravascular pressure (P mean ) and flow rate within each nidus vessel; and Monte Carlo analysis to assess overall risks of nidus rupture when simulating sequential occlusions of vessel types in all 10 000 nidi., Results: We consistently observed lower nidus rupture risks with initial fistula occlusion in different network morphologies. Intranidal fistula occlusion simultaneously reduced P mean and flow rate within draining veins., Conclusions: Initial occlusion of AVM fistulas theoretically reduces downstream draining vessel hypertension and lowers the risk of rupture of an adjoining plexiform nidus component. This mitigates the theoretical concern that fistula occlusion may cause dangerous redistribution of hemodynamic forces into plexiform nidus vessels, and supports a clinical strategy favoring AVM fistula occlusion before plexiform nidus embolization., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: cardiac valvular diseases (CVDs) are the major cause of cardiovascular morbidity and mortality globally, with predominance of rheumatic heart disease (RHD) in developing countries. Congenital heart defects (CHD) diagnoses are delayed due to socioeconomic factors. This study aims to evaluate the post-operative surgical outcomes of CHD and valvular RHD., Methods: this study is conducted with 50 patients from Chad, operated on between 2003 and 2012. Post-operative outcomes are evaluated from 2010 to 2012., Results: with the follow-up of 19 RHD patients who underwent plasty, 8 (42.1%) had no complications, 4 (21%) presented with mild regurgitation, 7 (36.8%) required re-operation due to 6 mitral stenosis (MS) cases (mitral surface range from 0.7 to 1.2 cm 2 ) and 1 severe mitral regurgitation (MR) case. While those patients with valve replacement, 2 (50%) had no complications, 1 (25%) had mild regurgitation and 1 (25%) patient died. Two patients with aortic regurgitation (AR) that underwent annuloplasty presented with severe regurgitation. Regarding AR with valve replacement, 3 (60%) had no complications, and 2 (40%) had mild regurgitation. Among the tricuspid regurgitation (TR) patients who had plasty, 6 (85.7%) had no complications, and 1 (14.3%) had severe regurgitation. The surgical repair was curative in all CHD patients. The loss to follow-up rate was 13/50 (26%)., Conclusion: the annuloplasty on rheumatic valve disease (MR and AR) has proven to be disappointing. Plasty is debated without justified indication for AR. The outcomes of CHD, mitral and aortic valve replacement are successful., Competing Interests: The authors declare no competing interests., (Copyright: Neguemadji Ngardig Ngaba et al.)

Meniscus tears are a common orthopedic pathology and planning a single, effective treatment is challenging. The diagnosis of meniscal tears requires detailed history-taking, physical examinations, special diagnostic tests, and most likely magnetic resonance imaging (MRI) to confirm the lesion. A good understanding of the meniscal structure including vascularity, zones, function, and affected movements with associated symptoms plays a crucial role in establishing an optimal management plan. A careful assessment of the patient's characteristics, comorbidities, post-repair rehabilitation, and patient's overall function and satisfaction are also important for ideal management. While conservative management is commonly implemented and the only option for certain patients, partial meniscectomy remains to be the most performed treatment procedure. However, partial meniscectomy is no longer the first-line therapy due to the limitation of certain patient characteristics and side effects in the long run. Instead, meniscal repair has been shown to have better long-term outcomes and is therefore recommended for all tears, especially for young patients with acute traumatic lesions. Tissue engineering has been of high interest in the current research with promising therapeutic results. This review critically evaluates and compares the management of meniscal tears with surgical versus comprehensive management using the current literature., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Luvsannyam et al.)

Mixed connective tissue disease (MCTD) is a rare autoimmune condition that shows an overlap of at least two connective tissue diseases (CTD) including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, Sjögren's syndrome, polymyositis, or dermatomyositis. From a laboratory standpoint, MCTD is associated with high titers of anti-U1-RNP antibodies, which makes it difficult to determine whether it is a variant of each of the respective CTDs or a different entity altogether. Our objective is to report the case of a patient with MCTD presenting with status epilepticus who was ultimately diagnosed with lupus cerebritis. The case also highlights the development of complications unrelated to MCTD that made the management even more challenging. Overall, the authors emphasize the rareness of lupus cerebritis as a presentation, the diagnostic challenges faced due to the lack of classical manifestations of SLE, and how the complicated clinical course makes a downhill prognosis more likely., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Leitao et al.)

Aortic dissection (AD) is a serious condition, which typically affects men more than women. Strongly established risk factors include uncontrolled hypertension, connective tissue disorders, advanced age, cocaine use, and aortic injury. We believe it's important to report this case due to the occurrence of Stanford type A AD in a healthy 40-year-old male devoid of genetic, medical, family, and environmental risk factors. This patient presented with a tearing anterior chest pain radiating to the back and was promptly diagnosed and managed with surgical replacement and grafting of the diseased aorta and its involved branches. Therefore, it is imperative to include AD as a differential in atypical case scenarios and case presentations, as missed and delayed diagnosis and management would worsen the clinical outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jain et al.)

Spatial transcriptomic technologies promise to resolve cellular wiring diagrams of tissues in health and disease, but comprehensive mapping of cell types in situ remains a challenge. Here we present сell2location, a Bayesian model that can resolve fine-grained cell types in spatial transcriptomic data and create comprehensive cellular maps of diverse tissues. Cell2location accounts for technical sources of variation and borrows statistical strength across locations, thereby enabling the integration of single-cell and spatial transcriptomics with higher sensitivity and resolution than existing tools. We assessed cell2location in three different tissues and show improved mapping of fine-grained cell types. In the mouse brain, we discovered fine regional astrocyte subtypes across the thalamus and hypothalamus. In the human lymph node, we spatially mapped a rare pre-germinal center B cell population. In the human gut, we resolved fine immune cell populations in lymphoid follicles. Collectively, our results present сell2location as a versatile analysis tool for mapping tissue architectures in a comprehensive manner., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Schizophrenia is a debilitating disease that presents with both positive and negative symptoms affecting cognition and emotions. Extensive studies have analyzed the different factors that contribute to the disorder. There is evidence of significant genetic etiology involving multiple genes such as dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1). There is no clear link between neurotransmitter changes and the pathophysiology of schizophrenia; however, studies have shown that subcortical dopamine dysfunction is the key mechanism. Specific regions of gray and white matter changes are observed in patients with schizophrenia; gray matter changes being more significant after the onset of psychosis. These pathological changes may be implicated in the impairment of executive functioning, attention, and working memory. The disease can be managed with pharmacological treatments based on individual patient profile, patient compliance, and disease severity. The challenge of disease management sometimes persists due to the side effects. A better understanding of the pathological processes in schizophrenia may lead to more specific and effective therapies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Luvsannyam et al.)

Bile cast nephropathy (BCN) or cholemic nephropathy (CN) is an acute renal dysfunction, including acute kidney injury (AKI) in the setting of liver injury. It is a common phenomenon in patients with liver disease and is associated with significant morbidity and mortality. CN is characterized by hemodynamic changes in the liver, kidney, systemic circulation, intratubular cast formation, and tubular epithelial cell injury. CN has been overlooked as a differential diagnosis in chronic liver disease patients due to more importance to hepatic injury. However, frequent and considerable reporting of case reports recently has further investigated this topic in the last two decades. This review determines the evidence behind the potential role of bile acids and bilirubin in acute renal dysfunction in liver injury, summarizing the implied pathophysiology risk factors, and incorporating the therapeutic mechanisms and outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Somagutta et al.)

Frailty is a complex age-related clinical condition with increased vulnerability to negative health outcomes that manifest as a multidimensional syndrome and hence, a challenge to identify at-risk populations. We aim to summarize the implementation of strategies to diagnose fragility in family practice using current evidence. We searched the PubMed and Google Scholar databases for relevant articles, using the Medical Subject Headings (MeSH) terms "Frailty," "Frailty Scales," and "Primary Health Care." All original research articles on the elderly population (65 years of age or older) published in English and the last five years were included. Frailty diagnosis has resulted in positive outcomes in the overall literature. Recent hospital admission may indicate a health problem that can end up in a negative outcome and has been often described as associated with frailty. It was also shown to affect the intensive care units' mortality, in-hospital mortality, and long-term mortality. However, multiple screening instruments have been developed and validated to improve feasibility in clinical practice. The frequent lack of agreement between frailty instruments has slowed the broad implementation of these tools. The impacts of frailty warrant an upstream, proactive, holistic, interprofessional primary care approach to its identification, assessment, and management. It is a preventable disorder; identifying elderly patients at risk in primary care can help shape appropriate care processes tailored to their needs. This literature review aims to demonstrate the importance and strategies in identifying frailty in primary care settings and assess its impact on several outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Somagutta et al.)

Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Multimodal data is rapidly growing in many fields of science and engineering, including single-cell biology. We introduce MultiMAP, a novel algorithm for dimensionality reduction and integration. MultiMAP can integrate any number of datasets, leverages features not present in all datasets, is not restricted to a linear mapping, allows the user to specify the influence of each dataset, and is extremely scalable to large datasets. We apply MultiMAP to single-cell transcriptomics, chromatin accessibility, methylation, and spatial data and show that it outperforms current approaches. On a new thymus dataset, we use MultiMAP to integrate cells along a temporal trajectory. This enables quantitative comparison of transcription factor expression and binding site accessibility over the course of T cell differentiation, revealing patterns of expression versus binding site opening kinetics., (© 2021. The Author(s).)

Duodenal adenocarcinoma (DA), gastrointestinal stromal tumor (GIST), and pancreatic neuroendocrine tumor (PNET) are a set of rare gastrointestinal (GI) cancers characterized by nonspecific symptoms such as anemia, weight loss, and abdominal pain. We report an interesting case of DA, GIST, and PNET in a 79-year-old African American male who presented to the emergency department with syncope. The patient was tachycardic and found to have severe anemia. Further computed tomography (CT) of the abdomen and pelvis with contrast revealed a mass within the duodenal bulb along with a pancreatic cystic lesion. The patient underwent gastroduodenectomy and distal pancreatectomy with incidental findings of GIST in the posterior gastric wall. The patient after surgical removal of all tumors no longer experienced abdominal pain and had hematocrit and hemoglobin (H&H) level of 9.1/31.7 postoperation day (POD) 14. The case unfolds a rare presentation of three neoplasms that were moderate to well-differentiated with no metastases. It highlights the importance of assessment of rare GI neoplasms concurrently with colorectal cancer when geriatric patients present with nonspecific GI symptoms., Competing Interests: The abstract of this case study has been published as a poster presentation at the following link: https://www.cureus.com/posters/1822-a-case-showcasing-three-rare-gastrointestinal-cancers-in-an-anemic-patient., (Copyright 2021, Hanan et al.)

Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception 1,2 , yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21)., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Human immunodeficiency virus (HIV) associated opportunistic infections are complications of patients with advanced HIV infection who are unaware of their disease or non-compliant with antiretroviral therapy. HIV patients with low CD4 count, generally less than 200 cells/μL, are at risk of developing opportunistic infections. We report a case of a 53-year-old male diagnosed with opportunistic infections, Toxoplasma gondii and cytomegalovirus (CMV). His initial presentation was central nervous system Toxoplasmosis and he later developed CMV colitis. Both are consequences of his undiagnosed advanced HIV status. The patient was promptly treated with appropriate medications for both conditions. The patient's HIV status is well controlled with highly active antiretroviral therapy (HAART) and his CD4 count is improving. It further exhibits the significance of adequate screening protocols and the importance of early treatment for HIV patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Emuze et al.)

Background: Angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated ACE expression in tissues (which is generally reflected by ACE in blood) is associated with increased risk of cardiovascular diseases. Elevated ACE in blood is also a marker for granulomatous diseases., Methods: We applied our novel approach-ACE phenotyping-to characterize serum ACE in 300 unrelated patients and to establish normal values for ACE levels. ACE phenotyping includes (a) determination of ACE activity with 2 substrates (Z-Phe-His-Leu [ZPHL] and Hip-His-Leu [HHL]), (b) calculation of a ratio for hydrolysis of ZPHL and HHL, and (c) quantification of ACE immunoreactive protein levels and ACE conformation with a set of monoclonal antibodies (mAbs) to ACE., Results: Only a combination of ACE activity determination with 2 substrates and quantification of the amount of ACE immunoreactive protein with mAbs 1G12 and 9B9 allows for the unequivocal detection of the presence of ACE inhibitors in the blood. After excluding such subjects, we were able to establish normal values of ACE in healthy populations: 50%-150% from control pooled serum. This ACE phenotyping approach in screening format with special attention to outliers can also identify patients with various mutations in ACE and may help to identify the as yet unknown ACE secretase or other mechanistic details of precise regulation of ACE expression., Conclusions: ACE phenotyping is a promising new approach with potential clinical significance to advance precision medicine screening techniques by establishing different risk groups based on ACE phenotype., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nickel, a silvery-hard metallic element used in corrosion-resistant alloys, is widely used in the medical field. Nickel has aided in medical advancements; however, it has been known to cause hypersensitivity reactions. Retained foreign bodies due to surgical procedures may cause postoperative complications such as allergic reactions. This case involves a 30-year-old female presenting with non-specific symptoms involving multiple organ systems, notably with abdominal pain. Due to chronic symptoms, the patient was tested for metal allergies and diagnosed with hypersensitivity reactions to nickel surgical clips that were previously inserted during cholecystectomy. Subsequently, the patient had surgical removal of the foreign bodies, which led to significant improvement of her symptoms immediately. This case demonstrates a delayed hypersensitivity reaction to a foreign body involving multiple body systems and vague symptoms making the diagnosis challenging. It is important to carefully evaluate the patient's past medical history including history of any allergies. It also brings attention to the necessity of performing metal skin patch tests preoperatively for individuals with a history of any type of allergies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Luvsannyam et al.)

Previous studies have suggested favorable outcomes of hydrocortisone, ascorbic acid (vitamin C), and thiamine (HAT) therapy in patients with sepsis. However, similar results have not been duplicated in sequential studies. This meta-analysis aimed to reevaluate the value of HAT treatment in patients with sepsis. Electronic databases were searched up until October 2020 for any studies that compared the effect of HAT versus non-HAT use in patients with sepsis. Data from 15 studies (eight randomized controlled trials [RCTs] and seven cohort studies) involving 67,349 patients were included. The results from the RCTs show no significant benefit of triple therapy on hospital mortality (risk ratio [RR], 0.99; P=0.92; I2=0%); intensive care unit (ICU) mortality (RR, 0.77; P=0.20; I2=58%); ICU length of stay (weighted mean difference [WMD], 0.11; P=0.86; I2 =37%) or hospital length of stay (WMD: 0.57; P=0.49; I2=17%), and renal replacement therapy (RR, 0.64; P=0.44; I2=39%). The delta Sequential Organ Failure Assessment (SOFA) score favored treatment after a sensitivity analysis (WMD, -0.72; P=0.01; I2=32%). However, a significant effect was noted for the duration of vasopressor use (WMD, -25.49; P<0.001; I2=46%). The results from cohort studies have also shown no significant benefit of HAT therapy on hospital mortality, ICU mortality, ICU length of stay, length of hospital stay, the delta SOFA score, the use of renal replacement therapy, or vasopressor duration. HAT therapy significantly reduced the duration of vasopressor use and improved the SOFA score but appeared not to have significant benefits in other outcomes for patients with sepsis. Further RCTs can help understand its benefit exclusively.

Acute limb ischemia (ALI) is the sudden decrease in limb perfusion caused by embolism secondary to many blood stasis conditions. Treatment commences with intravenous (IV) unfractionated heparin infusion. Individuals can have an immune-mediated reaction to heparin products which results in heparin-induced thrombocytopenia (HIT). Coronavirus disease 2019 (COVID-19) has added to the difficulty of treating patients with ALI due to increasing the likelihood of HIT via the virus's ability to manipulate the coagulation parameters. We present a case of ALI complicated by HIT in a 49-year-old male with a confirmed asymptomatic COVID-19. The patient initially presented with progressive pain, coldness, and tingling in the right foot. He was treated with a tissue plasminogen activator (TPA) and a heparin drip. The occlusion persisted despite medical intervention leading to right below-knee amputation. The patient returned to the emergency department (ED) 13 days later with massive intracranial hemorrhage and subsequently expired. This case study demonstrates the significance of COVID-19 diagnostic testing due to the possibility of developing blood clots and potential complications, including HIT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Siddiqui et al.)

Bariatric surgery is one of the most successful treatment options for morbid obesity and related comorbidities that is reserved for patients when lifestyle modifications and medical treatments fail. Bariatric surgeries are proven to result in weight reduction and improve obesity-related complications; however, there still are some reported failures. We report the case of a 35-year-old woman with morbid obesity and diabetes mellitus who had failed laparoscopic adjustable gastric band (LAGB) and laparoscopic sleeve gastrectomy (LSG) when done individually. The patient finally had a successful weight loss after undergoing revision LAGB over LSG. Although the present literature reports LAGB being an unsuccessful weight loss procedure, this case highlights the significance of LAGB as an effective bariatric surgery compared to other procedures. Our patient not only lost her weight successfully but also resolved her comorbid conditions and mental illness following the LAGB., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Luvsannyam et al.)

An elevated blood angiotensin I-converting enzyme (ACE) supports diagnosis of sarcoidosis and Gaucher disease. However, some ACE mutations increase ACE shedding, and patients with these mutations are therefore at risk of being incorrectly diagnosed with sarcoidosis because of elevated serum ACE levels. We applied a novel approach called "ACE phenotyping" to identify possible ACE mutations in 3 pulmonary clinic patients that had suspected sarcoidosis based on elevated blood ACE levels. Conformational fingerprinting of ACE indicated that these mutations may be localized in the stalk region of the protein and these were confirmed by whole exome sequencing. Index patient 1 (IP1) had a mutation (P1199L) that had been previously identified, while the other 2 patients had novel ACE mutations. IP2 had 2 mutations, T887M and N1196K (eliminating a putative glycosylation site), while IP3 had a stop codon mutation Q1124X (eliminating the transmembrane anchor). We also performed a comprehensive analysis of the existing database of all ACE mutations to estimate the proportion of mutations increasing ACE shedding. The frequency of ACE mutations resulting in increased blood ACE levels may be much higher than previously estimated. ACE phenotyping, together with whole exome sequencing, is a diagnostic approach that could prevent unnecessary invasive and/or costly diagnostic procedures, or potentially harmful treatment for patients misdiagnosed on the basis of elevated blood ACE levels., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Nemaline myopathy (NM) is a rare neuromuscular condition with clinical and genetic heterogeneity. To establish disease natural history, we performed a cross-sectional study of NM, complemented by longitudinal assessment and exploration of pilot outcome measures., Methods: Fifty-seven individuals with NM were recruited at 2 family workshops, including 16 examined at both time points. Participants were evaluated by clinical history and physical examination. Functional outcome measures included the Motor Function Measure (MFM), pulmonary function tests (PFTs), myometry, goniometry, and bulbar assessments., Results: The most common clinical classification was typical congenital (54%), whereas 42% had more severe presentations. Fifty-eight percent of individuals needed mechanical support, with 26% requiring wheelchair, tracheostomy, and feeding tube. The MFM scale was performed in 44 of 57 participants and showed reduced scores in most with little floor/ceiling effect. Of the 27 individuals completing PFTs, abnormal values were observed in 65%. Last, bulbar function was abnormal in all patients examined, as determined with a novel outcome measure. Genotypes included mutations in ACTA1 (18), NEB (20), and TPM2 (2). Seventeen individuals were genetically unresolved. Patients with pathogenic ACTA1 and NEB variants were largely similar in clinical phenotype. Patients without genetic resolution had more severe disease., Conclusion: We present a comprehensive cross-sectional study of NM. Our data identify significant disabilities and support a relatively stable disease course. We identify a need for further diagnostic investigation for the genetically unresolved group. MFM, PFTs, and the slurp test were identified as promising outcome measures for future clinical trials., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Diabetic ketoacidosis (DKA) is an acute and significant life-threatening complication of diabetes. The association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) with euglycemic diabetic ketoacidosis (EDKA) has been well reported. This literature review was conducted to understand the mechanism of EDKA and identify the potential risk factors and precipitants for patients taking SGLT2i. After reviewing the published literature between 2010 and 2020, 32 articles are included in the final review. The underlying mechanism is mainly enhanced lipolysis and ketone body reabsorption. SGLT2i also stimulates pancreatic alpha cells and inhibits beta cells, causing an imbalance in glucagon/insulin levels, further contributing to lipolysis and ketogenesis. Most patients were diagnosed with blood glucose less than 200 mg/dL, blood pH <7.3, increased anion gap, increased blood, or urine ketones. Perioperative fasting, pancreatic etiology, low carbohydrate or ketogenic diet, obesity, and malignancy are identified precipitants in this review. As normoglycemia can conceal the underlying acidosis, physicians should be cognizant of the EDKA diagnosis and initiate prompt treatment. Patient education on risk factors and triggers is recommended to avoid future events., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Somagutta et al.)

Titanium is a known metal used widely in the medical field and can cause allergic reactions with complications. Our case is about a 28-year-old female presenting with a spectrum of abdominal symptoms with a complicated medical history. The abdominal pain is associated with titanium allergy reaction from previously inserted titanium-based surgical clips. This patient is concurrently found to have a retained pigtail catheter in the cecum discovered incidentally through radiology. We discuss the presentation, investigations, and treatment of this unusual case. The case also unfolds rare differential diagnoses to keep in mind when encountering a patient with abdominal pain and associated nonspecific symptoms., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Molly S. Jain et al.)

Background: Ryanodine receptor 1-related myopathy (RYR1-RM) can present with a selective pattern and gradient of intramuscular fatty infiltration (IMFI) on magnetic resonance imaging (MRI)., Objective: To demonstrate an automated protocol for quantification of IMFI in the lower extremity muscles of individuals with RYR1-RM using T1-weighted MRI and to examine the relationships of IMFI with motor function and clinical severity., Methods: Axial images of the lower extremity muscles were acquired by T1-weighted fast spin-echo and short tau inversion recovery (STIR) sequences. A modified ImageJ-based program was used for quantification. IMFI data was analyzed by mode of inheritance, motor function, and clinical severity., Results: Upper and lower leg IMFI from 36 genetically confirmed and ambulatory RYR1-RM affected individuals (26 dominant and 10 recessive) were analyzed using Grey-scale quantification. There was no statistically significant difference in IMFI between dominant and recessive cases in upper or lower legs. IMFI in both upper and lower legs was inversely correlated with participant performance on the motor function measure (MFM-32) total score (upper leg: p < 0.001; lower leg: p = 0.003) and the six-minute walk test (6MWT) distance (upper leg: p < 0.001; lower leg: p = 0.010). There was no significant difference in mean IMFI between participants with mild versus severe clinical phenotypes (p = 0.257)., Conclusion: A modified ImageJ-based algorithm was able to select and quantify fatty infiltration in a cohort of heterogeneously affected individuals with RYR1-RM. IMFI was not predictive of mode of inheritance but showed strong correlation with motor function and capacity tests including MFM-32 and 6MWT, respectively.

Leiomyomas, also known as uterine fibroids, are the most common benign uterine tumors in women. The most frequently reported symptoms are uterine bleeding and abdominal and/or pelvic pressure; however, most cases are asymptomatic and may be found incidentally. Endometriosis is a condition where the endometrium proliferates outside of the uterine cavity. Extrauterine endometrial implants are usually found in the ovaries, pelvis, and peritoneum, but can extend anywhere throughout the body. Women with endometriosis may exhibit dysmenorrhea, dyspareunia, dyschezia, and infertility. Inflammation caused by endometriosis may lead to fibrosis, scarring, and adhesions. We report a case of an asymptomatic 36-year-old African-American woman with increasing abdominal girth, consistent with a 28-week gestation, presenting to her obstetrician/gynecologist for her annual exam, who on further investigation is found to have multiple large fibroids, bilateral ovarian cysts, and widespread endometriosis with several adhesions ultimately leading to a frozen pelvis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Wazir et al.)

Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin-2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings were consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in three patients showed clinical improvement with increased strength and function. This series further establishes SYT2 as a CMS-disease gene and expands its clinical and genetic spectrum to include recessive loss-of-function variants, manifesting as a severe congenital onset presynaptic CMS with potential treatment implications., (© 2020 Wiley Periodicals LLC.)

Mucinous cystadenomas are among the most common benign ovarian neoplasms. They are known for their massive size causing compressive effects ranging from pressure, pain, bloating, and urinary symptoms. Over time, these adnexal masses can lead to fatal complications, such as ovarian torsion or hemorrhage. Incidental findings of these tumors are common as many of these patients are asymptomatic. Pelvic examinations and imaging studies can be used to further diagnose symptomatic patients and aid physicians in developing an appropriate course of treatment. We report a rare case of a large mucinous cystadenoma, with a size of 25 × 25 cm and concurrent management of postmenopausal bleeding. We present the data from the admission of the patient to her discharge, including history and physical examination, diagnostic reports, transabdominal ultrasound, CT scan, surgical evaluation, and surgical-pathology reports. Abdominal pain can present in a variety of different scenarios, and ovarian masses only represent a small portion of the differentials. Mucinous cystadenomas constitute an even smaller percentage of these ovarian growths. As discussed in this case report, a large ovarian mucinous cystadenoma was compressing the surrounding structures resulting in a wide array of symptoms. The case describes the importance of extensive diagnostic evaluation and prompt surgical management of these ovarian tumors. It also brings attention to the significance of diagnosing a medical condition such as postmenopausal bleeding promptly to avoid potential negative outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Somagutta et al.)

Background: When tested in a controlled clinic environment, individuals with neuromuscular-related symptoms may complete motor tasks within normal predicted ranges. However, measuring activity at home may better reflect typical motor performance. The accuracy of accelerometry measurements in individuals with congenital muscular dystrophy (CMD) is unknown. We aimed to compare accelerometry and manual step counts and assess free-living physical activity intensity in individuals with CMD using accelerometry., Methods: Ambulatory pediatric CMD participants (n = 9) performed the 6-minute walk test in clinic while wearing ActiGraph GT3X accelerometer devices. During the test, manual step counting was conducted to assess concurrent validity of the ActiGraph step count in this population using Bland-Altman analysis. In addition, activity intensity of 6 pediatric CMD participants was monitored at home with accelerometer devices for an average of 7 days. Cut-point values previously validated for neuromuscular disorders were used for data analysis., Results: Bland-Altman and intraclass correlation analyses showed no concurrent validity between manual and ActiGraph-recorded step counts. Fewer steps were recorded by ActiGraph step counts compared with manual step counts (411 ± 74 vs 699 ± 43, respectively; P = .004). Although improved, results were in the same direction with the application of low-frequency extension filters (587 ± 40 vs 699 ± 43, P = .03). ActiGraph step-count data did not correlate with manual step count (Spearman ρ = 0.32, P = .41; with low-frequency extension: Spearman ρ = 0.45, P = .22). Seven-day physical activity monitoring showed that participants spent more than 80% of their time in the sedentary activity level., Conclusions: In a controlled clinic setting, step count was significantly lower by ActiGraph GT3X than by manual step counting, possibly because of the abnormal gait in this population. Additional studies using triaxial assessment are needed to validate accelerometry measurement of activity intensity in individuals with CMD. Accelerometry outcomes may provide valuable measures and complement the 6-minute walk test in the assessment of treatment efficacy in CMD.

Vermicomposting is a traditional technology that produces the best quality of compost, but factors such as maturity, presence of heavy metals, etc. need to be tackled prior to agrarian application. The present study investigates the influence of varying biochar dose (2.5, 5, and 10% on a weight basis) on the maturity of compost and heavy metals during vermicomposting of vegetable waste using epigeic earthworm. Biochar amendment notably enhanced the electrical conductivity (up to 2.7 mS/cm), nitrogen content (up to 3.1%), NO 3 -N (up to 630 mg/kg) and nutritional value. The heavy metals, oxygen uptake rate (below 0.96 mg/g VS/day) and CO 2 evolution rate (below 1 mg/g VS/day) were attenuated along with degradation of complex organic crystals as observed in powder X-Ray Diffraction (PXRD) spectra. Furthermore, biochar aid in reducing pathogens (below 1.1 × 10 3 MPN/g dry weight) as inferred from the Most Probable Number (MPN) results as well as degrading the complex organics into simpler compounds as revealed from the Fourier-transform infrared spectroscopy (FTIR) spectra. The present study inferred that the vegetable waste was biologically stabilized through biochar amendment during vermicomposting process with improved nutritional and physico-chemical properties., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To investigate the efficacy of N -acetylcysteine (NAC) for decreasing elevated oxidative stress and increasing physical endurance in individuals with ryanodine receptor 1-related myopathies ( RYR1 -RM)., Methods: In this 6-month natural history assessment (n = 37) followed by a randomized, double-blinded, placebo-controlled trial, 33 eligible participants were block-randomized (1:1) to receive NAC (n = 16) or placebo (n = 17), orally for 6 months (adult dose 2,700 mg/d; pediatric dose 30 mg/kg/d). The primary endpoint was urine 15-F2t isoprostane concentration and the clinically meaningful co-primary endpoint was 6-minute walk test (6MWT) distance., Results: When compared to the general population, participants had elevated baseline 15-F2t isoprostane concentrations and most had a decreased 6MWT distance (mean ± SD 3.2 ± 1.5 vs 1.1 ± 1.7 ng/mg creatinine and 468 ± 134 vs 600 ± 58 m, respectively, both p < 0.001). 15-F2t isoprostane concentration and 6MWT distance did not change over the 6-month natural history assessment ( p = 0.98 and p = 0.61, respectively). NAC treatment did not improve 15-F2t isoprostane concentration (least squares means difference 0.1 [95% confidence interval [CI] -1.4 to 1.6] ng/mg creatinine, p = 0.88) or 6MWT distance (least squares means difference 24 [95% CI -5.5 to 53.4] m, p = 0.11). NAC was safe and well-tolerated at the doses administered in this study., Conclusion: In ambulatory RYR1 -RM-affected individuals, we observed stable disease course, and corroborated preclinical reports of elevated oxidative stress and decreased physical endurance. NAC treatment did not decrease elevated oxidative stress, as measured by 15-F2t isoprostane., Classification of Evidence: This study provides Class I evidence that, for people with RYR1 -RM, treatment with oral NAC does not decrease oxidative stress as measured by 15-F2t isoprostane., Clinicaltrialsgov Identifier: NCT02362425., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Few neuroimaging anatomic studies to date have investigated in detail the point of entry of cortical bridging veins (CBVs) into the superior sagittal sinus (SSS). Although we know that most CBVs join the SSS at an acute angle opposite to the direction of SSS blood flow, the three-dimensional (3-D) spatial configuration of these venous confluences has not been studied previously. This anatomical information would be pertinent to several clinically applicable scenarios, such as in planning intracranial surgical approaches that preserve bridging veins; studying anatomical factors in the pathophysiology of SSS thrombosis; and when planning endovascular microcatheterization of pial veins to retrogradely embolize brain arteriovenous malformations (AVMs). We used the concept of Euclidean planes in 3-D space to calculate the arccosine of these CBV-SSS angles of confluence. To test the hypothesis that pial AVM draining veins may not be any more acutely angled or difficult to microcatheterize at the SSS than for normal CBVs, we measured 70 angles of confluence on magnetic resonance venography images of 11 normal, and nine AVM patients. There was no statistical difference between normal and AVM patients in the CBV-SSS angles projected in 3-D space (56.2° [SD = 22.4°], and 46.2° [SD = 22.3°], respectively; P > 0.05). Hence, participation of CBVs in drainage of pial AVMs should not confer any added difficulty to their microcatheterization across the SSS, when compared to the acute angles found in normal individuals. This has useful implications for potential choices of strategies requiring endovascular transvenous retrograde approaches to treat AVMs. Clin. Anat. 33:293-299, 2020. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Introduction: Individuals affected with ryanodine receptor isoform-1-related myopathies ( RYR1- RM) commonly experience fatigability in the quadriceps, which may limit physical function and potentially diminish quality of life. Fatigability, in RYR1 -RM, results from skeletal muscle injury secondary to dysfunction of the major skeletal muscle Ca ++ channel. However, during fatigability testing, affected individuals did not always reach the point of local muscle fatigue as defined by a fatigue index (FATI) at 50% of peak torque. Surakka et al. compared three versions of FATI equations, which vary by the area under the force curve (AUC). By performing this comparison, they were able to determine the optimal equation in individuals with Multiple Sclerosis. Purpose: Using a similar comparison, we sought to identify the optimal FATI equation in the RYR1 -RM population. Secondly, because local muscle fatigability might have an impact on independent living, this study also assessed change in local muscle fatigability over a 6-month time frame. Methods: Thirty participants were analyzed from the RYR1 -RM natural history study and double-blind, placebo-controlled N-acetylcysteine (NAC) trial, NCT02362425. Twenty-seven had fatigability data, from isometric knee extension and flexion fatigability tests, available for the purpose of establishing a method for predicting FATI at 50% peak torque. For the natural history study, 30 participants were used to assess disease progression of local muscle fatigability achieved during the knee extension fatigability test, and 29 participants for the knee flexion fatigability test. Results: Surakka's equation 1, using the prediction approach, led to the smallest median error, the smallest square-root of uncorrected sum of squares, and the smallest average of the absolute value of the differences. No difference was observed in FATI at 50% peak torque between month 0 and month 6 for extension ( p = 0.606) and flexion ( p = 0.740). Conclusion: Surakka's equation 1, with the prediction approach, was found to be the most accurate for imputing values when fatigue was not reached during a sustained knee isometric fatigability test in RYR1 -RM. Furthermore, when used to assess fatigability-based disease stability, local muscle fatigability, in this RYR1-RM population remained stable., (Copyright © 2019 Witherspoon, Rekant, Wakim, Vasavada, Waite, Chrismer, Shelton, Jain and Meilleur.)

Biochar, a recalcitrant carbon, is known to enhance organic matter degradation and improve physical properties. The objective of the study is to examine the probable effect of biochar addition during composting of a fibrous aquatic waste, i.e., water hyacinth though degradation kinetics and spectroscopic (FTIR and PXRD) analysis. Four dosages of biochar (0, 2.5, 5, and 10% w/w) were mixed to a mixture of water hyacinth, cow-dung and saw-dust comprising a total weight of 150 kg and composted using rotary drum composter for 20 days in batch mode. The study outcomes indicated that the amendment of biochar prolonged the duration of the thermophilic temperatures, reduced salinity, and promoted nutritional quality of compost. Moreover, biochar amendment enhanced the organic matter degradation with a rate constant of 0.029 day -1 and increased the total Kjeldahl nitrogen content up to 1.75% from an initial value of 1.10% in the reactor with 2.5% biochar amendment. Concurrently, biochar amendment aided in reducing Cu and Cr in the final product inferring 2.5% biochar is best suited for composting of water hyacinth. However, future studies are encouraged to decipher the microbial shifts and bioavailability of metals due to biochar dosage during composting for mitigating and managing the menace of such fibrous waste like water hyacinth by converting it to a soil conditioner., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To identify the rate of change of clinical outcome measures in children with 2 types of congenital muscular dystrophy (CMD), COL6-related dystrophies (COL6-RDs) and LAMA2-related dystrophies (LAMA2-RDs)., Methods: Over the course of 4 years, 47 individuals (23 with COL6-RD and 24 with LAMA2-RD) 4 to 22 years of age were evaluated. Assessments included the Motor Function Measure 32 (MFM32), myometry (knee flexors and extensors, elbow flexors and extensors), goniometry (knee and elbow extension), pulmonary function tests, and quality-of-life measures. Separate linear mixed-effects models were fitted for each outcome measurement, with subject-specific random intercepts., Results: Total MFM32 scores for COL6-RDs and LAMA2-RDs decreased at a rate of 4.01 and 2.60 points, respectively, each year ( p < 0.01). All muscle groups except elbow flexors for individuals with COL6-RDs decreased in strength between 1.70% ( p < 0.05) and 2.55% ( p < 0.01). Range-of-motion measurements decreased by 3.21° ( p < 0.05) at the left elbow each year in individuals with LAMA2-RDs and 2.35° ( p < 0.01) in right knee extension each year in individuals with COL6-RDs. Pulmonary function demonstrated a yearly decline in sitting forced vital capacity percent predicted of 3.03% ( p < 0.01) in individuals with COL6-RDs. There was no significant change in quality-of-life measures analyzed., Conclusion: Results of this study describe the rate of change of motor function as measured by the MFM32, muscle strength, range of motion, and pulmonary function in individuals with COL6-RDs and LAMA2-RDs., (© 2019 American Academy of Neurology.)

Background: Theoretical modeling allows investigations of cerebral arteriovenous malformation (AVM) hemodynamics, but current models are too simple and not clinically representative. We developed a more realistic AVM model based on graphics processing unit (GPU) computing, to replicate highly variable and complex nidus angioarchitectures with vessel counts in the thousands-orders of magnitude greater than current models., Methods: We constructed a theoretical electrical circuit AVM model with a nidus described by a stochastic block model (SBM) of 57 nodes and an average of 1000 plexiform and fistulous vessels. We sampled and individually simulated 10,000 distinct nidus morphologies from this SBM, constituting an ensemble simulation. We assigned appropriate biophysical values to all model vessels, and known values of mean intravascular pressure (P mean ) to extranidal vessels. We then used network analysis to calculate P mean and volumetric flow rate within each nidus vessel, and mapped these values onto a graphic representation of the nidus network. We derived an expression for nidus rupture risk and conducted a model parameter sensitivity analysis., Results: Simulations revealed a total intranidal volumetric blood flow ranging from 268 mL/min to 535 mL/min, with an average of 463 mL/min. The maximum percentage rupture risk among all vessels in the nidus ranged from 0% to 60%, with an average of 29%., Conclusion: This easy to implement biomathematical AVM model, allowed by parallel data processing using advanced GPU computing, will serve as a useful tool for theoretical investigations of AVM therapies and their hemodynamic sequelae., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Sewage sludge produced is either applied to land or used as fertilizer for crops or disposed of in landfills, causing several environmental problems. Recent studies revealed that composting is a proven technology in reducing organic content, heavy metals, and harmful pathogens, improving the nutritional value of sewage sludge, which is useful for crops. But studies on variation in physical properties are rare. Composting physics or physical properties during composting plays a vital role from handling, management, and utilization of end product, i.e., compost. This study mainly deals with the detailed information on physics involved during the degradation process, which is crucial for land and geotechnical applications. In the present study, sewage sludge was used as a composting substrate in 550 L in-vessel rotary drum composter. Emphasis was given in deciphering the changes in physical parameters such as bulk density, porosity, and air-filled porosity and few chemical parameters during the composting process. Besides, a relationship between different physical properties during rotary drum composting was investigated statistically. Bulk density was observed to have increased from 643 to 707 kg m -3 as a result of volume reduction of compost matrix. Moreover, the gravimetric moisture content was found to be less than 45% in the end product, which is recommended for compost., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

There are currently no in vivo techniques to accurately study dynamic equilibrium of blood flow within separate regions (compartments) of a large brain arteriovenous malformation (AVM) nidus. A greater understanding of this AVM compartmentalization, even if theoretical, would be useful for optimal planning of endovascular and multimodal AVM therapies. We aimed to develop a biomathematical AVM model for theoretical investigations of intranidal regions of increased mean intravascular pressure (P mean ) and flow representing hemodynamic compartments, upon simulated AVM superselective angiography (SSA). We constructed an AVM model as a theoretical electrical circuit containing four arterial feeders (AF1-AF4) and a three-dimensional nidus of 97 interconnected plexiform and fistulous components. We simulated SSA by increases in P mean in each AF (with and without occlusion of all other AFs), and then used network analysis to establish resulting increases in P mean and flow within each nidus vessel. We analyzed shifts in hemodynamic compartments consequent to increasing AF injection pressures. SSA simulated by increases of 10 mm Hg in AF1, AF2, AF3, or AF4 resulted in dissipation of P mean over 38, 66, 76, or 20% of the nidus, respectively, rising slightly with simultaneous occlusion of other AFs. We qualitatively analyzed shifting intranidal compartments consequent to varying injection pressures by mapping the hemodynamic changes onto the nidus network. Differences in extent of nidus filling upon SSA injections provide theoretical evidence that hemodynamic and angioarchitectural features help establish AVM nidus compartmentalization. This model based on a theoretical AVM will serve as a useful computational tool for further investigations of AVM embolotherapy strategies., (Copyright © 2019 Jain, Do and Massoud.)

Introduction: The objective of this study was to obtain a 6-month natural history of motor function performance in individuals with RYR1- related myopathy (RYR1-RM) by using the Motor Function Measure-32 (MFM-32) and graded functional tests (GFT) while facilitating preparation for interventional trials., Methods: In total, 34 participants completed the MFM-32 and GFTs at baseline and 6-month visits., Results: Motor deficits according to MFM-32 were primarily observed in the standing and transfers domain (D1; mean 71%). Among the GFTs, participants required the most time to ascend/descend stairs (>7.5 s). Functional movement, determined by GFT grades, was strongly correlated with MFM-32 (D1; r ≥ 0.770, P < 0.001). Motor Function Measure-32 and GFT scores did not reflect any change in performance between baseline and 6-month visits., Discussion: The MFM-32 and GFTs detected motor impairment in RYR1-RM, which remained stable over 6 months. Thus, these measures may be suitable for assessing change in motor function in response to therapeutic intervention. Muscle Nerve 60: 80-87, 2019., (© 2019 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.)

Objective: The aim of this study was to measure musculoskeletal disorders and occupational risk factors among railroad maintenance-of-way (MOW) workers., Methods: Four thousand eight hundred sixteen active, retired, and disabled members of the Brotherhood of Maintenance of Way Employes Division (BMWED) completed a survey., Results: Compared with U.S. employed men, adjusting for age, race, and region, active male MOW workers were more likely to report "repeated lifting, pushing, pulling, or bending" at work (74.6% vs 46.9%), not enough staff (88.1% vs 65.2%), and a diagnosis of carpal tunnel syndrome (7.9% vs 3.6%). They were less likely to report management priority on workplace health and safety (59.37% vs 94.8%), ability to make job decisions on their own (68.4% vs 87.7%), and supervisor support (60.3% vs 90.8%) (all comparisons, P < 0.001)., Conclusion: Prevention programs should address risk of musculoskeletal disorders and occupational hazards faced by MOW workers.

A high lumbar puncture (LP) at L2-L3 or above is often necessary to consider on technical grounds, but complications of conus medullaris (CM) damage during high LP are potentially concerning. We hypothesized that a high LP might be safer than previously thought by accounting for movements of the CM upon patient positional changes. We retrospectively reviewed standard normal supine lumbar spine magnetic resonance imaging of 58 patients and used electronic calipers on axial images at the T12-L1, L1-L2, and L2-L3 disc levels to measure the transverse diameter of the CM relative to the size of the dorsal thecal sac space (DTSS) through which a spinal needle could be inserted. On 142 axial images, the means for CM diameters were 8.2, 6.0, and 2.9 mm at the three levels, respectively. We then used known literature mean CM displacement values in the legs flexed and unflexed lateral decubitus position (LDP) to factor in CM shifts to the dependent side. We found that at all three levels, the likely positional shift of the CM would be too small and insufficient to displace the entire CM out of the DTSS. However, if needle placement could be confined to the midsagittal plane, an LP in the unflexed LDP would theoretically be entirely safe at both L1-L2 and L2-L3, and almost so at L2-L3 in the legs flexed LDP. Thus, high LPs at L1-L2 and L2-L3 are in theory likely safer than considered previously, more so in the legs unflexed than in the flexed LDP. Clin. Anat. 32:618-629, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Composting of the Hydrilla verticillata, an invasive aquatic weed, signifies aquatic waste management as a safe and hygienic method that produces a nutrient-rich end product, i.e., compost. However, its higher moisture content, higher N-losses, and lower degradation rate have shown negative impacts on the composting process. Therefore the primary objective of this study was to assess the composting physics and the degradation kinetics after addition of three different carbon-rich agents with Hydrilla verticillata. To pursue this objective, three carbon-rich agents (viz. dry leaves in Run A, grass clippings in Run B and wood chips in Run C) each were mixed (10% w/w) to the optimized control mixture of Hydrilla verticillata, cow dung and sawdust (8:1:1) as reported in the earlier study. The composting experiments were performed in 550L rotary drum composter for 20 days to evaluate variation in physical, chemical, nutritional properties as well as degradation kinetics. The Run A and Run B were the only two mixtures that attained the temperature (55-70 °C) that indicates standard sterilization capacity in both with maximum moisture reduction (17%) and total Kjeldahl N increment (48%) in the latter. Organic matter losses throughout the process followed a first-order kinetic equation in all the Run (A-C) and control with the higher loss in Run B whereas least in control. Nevertheless, the addition of all carbon-rich agents is found to be beneficial to improve composting physics. Amongst all Runs (A-C), Run B achieved maximum reduction in the initial value of bulk density (64%) and increment in the initial value of free air space (20%). The study also concluded that all the carbon-rich agents have produced compost with the nutritional concentration suitable for agricultural proposes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: RYR1-related disorders (RYR1-RD), are a spectrum of genetic neuromuscular disorders. Affected individuals frequently experience fatigue yet appropriate tools to assess RYR1-RD-associated fatigue remain underdeveloped., Objective: This study assessed the reliability and validity of two self-report questionnaires, the multidimensional fatigue inventory (MFI-20) and adult/pediatric functional assessment of chronic illness-fatigue (FACIT-F/Peds-FACIT-F) as potential fatigue measures in RYR1-RD affected individuals., Methods: Participants (n = 37) were enrolled in an RYR1-RD combined natural history study and clinical trial. At baseline, participants completed fatigue questionnaires, six-minute walk test (6MWT), cardiopulmonary exercise test (CPET) and saliva collection for fatigue biomarker index (FBI) quantification., Results: All questionnaires exhibited good test-retest reliability (n = 18, ICC > 0.80). MFI-20 (n = 37), and FACIT-F (n = 28) also showed good internal consistency (Cronbach's α> 0.80). All MFI-20 subscales, except mental fatigue, and FACIT-F demonstrated evidence of criterion validity when correlated against percent predicted 6MWT distance (MFI-20 n = 37; r = -0.34 to -0.47, all p < 0.05, mental fatigue, r = -0.16, p = 0.35; FACIT-F n = 28, r = 0.41, p = 0.03). This was not the case for percent predicted VO2 peak (all p > 0.05). FBI correlated with MFI-20 general fatigue dimension only (r = -0.35, p = 0.03). Comparison of standardized questionnaire scores revealed that RYR1-RD affected individuals experience significantly greater fatigue than the general population., Conclusions: MFI-20 and FACIT-F are valid and reliable tools for assessing RYR1-RD-associated fatigue, a symptom centrally implicated in this rare disorder.