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A 7-week-old infant presented to the emergency department with fussiness, abstract decreased oral intake, loose stool, and respiratory distress for 2 days. The patient was born full-term with an uncomplicated birth history but had a history of slow weight gain. He was alert, but toxic-appearing at presentation, hypothermic with signs of dehydration, and with respiratory failure. He was found to have severe anion gap metabolic acidosis, hypokalemia, elevated lactate, and hyperammonemia. He responded well to initial resuscitation and was admitted to the ICU for intravenous electrolyte replacement, bowel rest, and respiratory support. A workup was pursued for failure to thrive with severe malnutrition, hyperammonemia, hyperlactatemia, anemia, vitamin D deficiency, and electrolyte abnormalities. After stabilization, he was restarted on enteral feeds and had a recurrence of loose stool and severe electrolyte abnormalities, which were refractory to enteral supplementations and required readmission to the ICU. His hospital course extended several weeks, included several subspecialty consultations, and ended with a surprising diagnosis of exclusion based on his clinical response to therapy. [ABSTRACT FROM AUTHOR]

Redox status plays a multifaceted role in the intricate physiology and pathology of pancreatic β-cells, the pivotal regulators of glucose homeostasis through insulin secretion. They are highly responsive to changes in metabolic cues where reactive oxygen species are part of it, all arising from nutritional intake. These molecules not only serve as crucial signaling intermediates for insulin secretion but also participate in the nuanced heterogeneity observed within the β-cell population. A central aspect of β-cell redox biology revolves around the localized production of hydrogen peroxide and the activity of NADPH oxidases which are tightly regulated and serve diverse physiological functions. Pancreatic β-cells possess a remarkable array of antioxidant defense mechanisms although considered relatively modest compared to other cell types, are efficient in preserving redox balance within the cellular milieu. This intrinsic antioxidant machinery operates in concert with redox-sensitive signaling pathways, forming an elaborate redox relay system essential for β-cell function and adaptation to changing metabolic demands. Perturbations in redox homeostasis can lead to oxidative stress exacerbating insulin secretion defect being a hallmark of type 2 diabetes. Understanding the interplay between redox signaling, oxidative stress, and β-cell dysfunction is paramount for developing effective therapeutic strategies aimed at preserving β-cell health and function in individuals with type 2 diabetes. Thus, unraveling the intricate complexities of β-cell redox biology presents exciting avenues for advancing our understanding and treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: Women with cardiometabolic pregnancy complications are at increased risk of future diabetes and heart disease which can be reduced through lifestyle management postpartum. Objectives: This study aimed to explore preferred intervention characteristics and behaviour change needs of women with or without prior cardiometabolic pregnancy complications for engaging in postpartum lifestyle interventions. Design: Quantitative cross-sectional study. Methods: Online survey. Results: Overall, 473 women were included, 207 (gestational diabetes (n = 105), gestational hypertension (n = 39), preeclampsia (n = 35), preterm birth (n = 65) and small for gestational age (n = 23)) with and 266 without prior cardiometabolic pregnancy complications. Women with and without complications had similar intervention preferences, with delivery ideally by a healthcare professional with expertise in women's health, occurring during maternal child health nurse visits or online, commencing 7 weeks to 3 months post birth, with 15- to 30-min monthly sessions, lasting 1 year and including monitoring of progress and social support. Women with prior complications preferred intervention content on women's health, mental health, exercise, mother's diet and their children's health and needed to know more about how to change behaviour, have more time to do it and feel they want to do it enough to participate. There were significant differences between groups, with more women with prior cardiometabolic pregnancy complications wanting content on women's health (87.9% vs 80.8%, p = 0.037), mother's diet (72.5% vs 60.5%, p = 0.007), preventing diabetes or heart disease (43.5% vs 27.4%, p < 0.001) and exercise after birth (78.3% vs 68.0%, p = 0.014), having someone to monitor their progress (69.6% vs 58.6%, p = 0.014), needing the necessary materials (47.3% vs 37.6%, p = 0.033), triggers to prompt them (44.0% vs 31.6%, p = 0.006) and feeling they want to do it enough (73.4%, 63.2%, p = 0.018). Conclusion: These unique preferences should be considered in future postpartum lifestyle interventions to enhance engagement, improve health and reduce risk of future cardiometabolic disease in these high-risk women. [ABSTRACT FROM AUTHOR]

Background: Natural compounds can positively impact health, and various studies suggest that they regulate glucose‒lipid metabolism by influencing short-chain fatty acids (SCFAs). This metabolism is key to maintaining energy balance and normal physiological functions in the body. This review explores how SCFAs regulate glucose and lipid metabolism and the natural compounds that can modulate these processes through SCFAs. This provides a healthier approach to treating glucose and lipid metabolism disorders in the future. Methods: This article reviews relevant literature on SCFAs and glycolipid metabolism from PubMed and the Web of Science Core Collection (WoSCC). It also highlights a range of natural compounds, including polysaccharides, anthocyanins, quercetins, resveratrols, carotenoids, and betaines, that can regulate glycolipid metabolism through modulation of the SCFA pathway. Results: Natural compounds enrich SCFA-producing bacteria, inhibit harmful bacteria, and regulate operational taxonomic unit (OTU) abundance and the intestinal transport rate in the gut microbiota to affect SCFA content in the intestine. However, most studies have been conducted in animals, lack clinical trials, and involve fewer natural compounds that target SCFAs. More research is needed to support the conclusions and to develop healthier interventions. Conclusions: SCFAs are crucial for human health and are produced mainly by the gut microbiota via dietary fiber fermentation. Eating foods rich in natural compounds, including fruits, vegetables, tea, and coarse fiber foods, can hinder harmful intestinal bacterial growth and promote beneficial bacterial proliferation, thus increasing SCFA levels and regulating glucose and lipid metabolism. By investigating how these compounds impact glycolipid metabolism via the SCFA pathway, novel insights and directions for treating glucolipid metabolism disorders can be provided. [ABSTRACT FROM AUTHOR]

The article focuses on the screening and management practices of specialists treating prostate cancer patients undergoing androgen deprivation therapy (ADT) regarding cardiac, bone, and metabolic health issues. The study reveals that specialized physicians generally feel unlikely to screen and manage metabolic and cardiac health but are more comfortable addressing bone health, suggesting a need for comprehensive management strategies to enhance patient care.

Cold stimulation has been shown to regulate glucose, lipid, and amino acid metabolism, while also increasing heat production and energy expenditure in the body. Disordered energy metabolism is a key factor in the onset and progression of chronic metabolic conditiones such as diabetes, obesity, and cardiovascular disease. Recent research has unveiled the myriad pathways through which cold stimulation affects human energy metabolism. This article provides an overview of how cold stimulation affects energy metabolism across the three major metabolic pathways. Furthermore, it explores the implications and potential therapeutic applications of cold stimulation in the prevention and treatment of various metabolic diseases. [ABSTRACT FROM AUTHOR]

Background: People living with HIV (PLWH) are at increased risk of cardiometabolic disorders (CMD). Adequate access to care for both HIV and CMD is crucial to improving health outcomes; however, there is limited research that have examined couples' experiences accessing such care in resource-constrained settings. We aimed to identify barriers to accessing CMD care among PLWH in Malawi and the role of partners in mitigating these barriers. Methods: We conducted a qualitative investigation of barriers to CMD care among 25 couples in Malawi. Couples were eligible if at least one partner was living with HIV and had hypertension or diabetes (i.e., the index patient). Index patients were recruited from HIV care clinics in the Zomba district, and their partners were enrolled thereafter. Interviews were conducted separately with both partners to determine barriers to CMD care access and how partners were involved in care. Results: Participants framed their experiences with CMD care by making comparisons to HIV treatment, which was free and consistently available. The main barriers to accessing CMD care included shortage of medications, cost of tests and treatments, high cost of transportation to health facilities, lengthy wait times at health facilities, faulty or unavailable medical equipment and supplies, inadequate monitoring of patients' health conditions, some cultural beliefs about causes of illness, use of herbal therapies as an alternative to prescribed medicine, and inadequate knowledge about CMD treatments. Partners provided support through decision-making on accessing medical care, assisting partners in navigating the healthcare system, and providing financial assistance with transportation and treatment expenses. Partners also helped manage care for CMD, including communicating health information to their partners, providing appointment reminders, supporting medication adherence, and supporting recommended lifestyle behaviors. Conclusions: Couples identified many barriers to CMD care access, which were perceived as greater challenges than HIV care. Partners provided critical forms of support in navigating these barriers. With the rise of CMD among PLWH, improving access to CMD care should be prioritized, using lessons learned from HIV and integrated care approaches. Partner involvement in CMD care may help mitigate most barriers to CMD care. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) affects millions of people globally since it is linked to multiple risk factors, including obesity, dyslipidemia, high blood pressure, and type 2 diabetes mellitus (T2DM). Several molecular factors are contributing to MetS developments, including insulin-like growth factor-1 receptor (IGF-1R), peroxisome proliferator-activated receptor α (PPAR-α), and Toll-like receptor-4 (TLR4). Green tea (GT) and green coffee (GC) have unique flavors due to their bioactive compounds, which act as antioxidants, anti-inflammatories, and antihypertension. This work aimed to examine the pathways implicated in the development of MetS and discover bioactive chemicals contained in GT and GC that have promising as inhibitors of IGF-1R, PPAR-α, and TLR4. The protein-protein interaction was explored using STRING, and the roles of bioactive compounds were evaluated in STITCH. The interaction between (-)-epigallocatechin (EC), catechin gallate (CG), epicatechin (EC), epigallocatechin gallate (EGCG), theobromine, trigonelline, chlorogenic acid, and caffeic acid against IGF-1R, PPAR-α, and TLR4 was measured by molecular docking. The present result demonstrated that eight protein interactions are involved in Mets development. The molecular docking result demonstrated that EGCG from GT has the best binding affinity (kcal/mol) to IGF-1R (-9.1), PPAR-α (-9.5), and TLR4 (-6.5). In conclusion, bioactive compounds from GT were superior to GT through computational study. Both might be promising as anti-inflammatories and regulate the metabolism under MetS conditions. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction–associated fatty liver disease (MAFLD) is a multisystem disorder characterized by the presence of fatty liver degeneration associated with excess adiposity or prediabetes/type 2 diabetes or metabolic dysregulation. An intricate relationship between the liver and thyroid has been reported in both health and disease. Simultaneously, there is a strong correlation between obesity and both MAFLD and thyroid dysfunction. In this narrative review, we highlighted the relationship between MAFLD and thyroid function in children and adolescents with obesity in order to explore how thyroid hormones (THs) act as predisposing factors in the onset, progression, and sustainability of MAFLD. THs are integral to the intricate balance of metabolic activities, ensuring energy homeostasis, and are indispensable for growth and development. Regarding liver homeostasis, THs have been suggested to interact with liver lipid homeostasis through a series of processes, including stimulating the entry of free fatty acids into the liver for esterification into triglycerides and increasing mitochondrial β-oxidation of fatty acids to impact hepatic lipid accumulation. The literature supports a correlation between MAFLD and obesity, THs and obesity, and MAFLD and THs; however, results in the pediatric population are very limited. Even though the underlying pathogenic mechanism involved in the relationship between MAFLD and thyroid function remains not fully elucidated, the role of THs as predisposing factors of MAFLD could be postulated. A potential vicious circle among these three conditions cannot be excluded. Identifying novel elements that may contribute to MAFLD could offer a practical approach to assessing children at risk of developing the condition. [ABSTRACT FROM AUTHOR]

Background: Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized that metabolic acidosis would be highly prevalent and associated with worse allograft function in pediatric KTRs. Methods: Pediatric KTRs at Montefiore Medical Center from 2010 to 2018 were included. Metabolic acidosis was defined as serum bicarbonate < 22 mEq/L or receiving alkali therapy. Regression models were adjusted for demographic factors and donor/recipient characteristics. Results: Sixty-three patients were identified with a median age at transplant of 10.5 (interquartile range (IQR) 4.4–15.2) years and post-transplant follow-up of 3 (IQR 1–5) years. Baseline serum bicarbonate was 21.7 ± 2.4 mEq/L, serum bicarbonate < 22 mEq/L was present in 28 (44%), and 44% of all patients were receiving alkali therapy. The prevalence of acidosis ranged from 58 to 70% during the first year of follow-up. At baseline, each 1-year higher age at transplant and every 10 ml/min/1.73 m2 higher eGFR were associated with 0.16 mEq/L (95% CI: 0.03–0.3) and 0.24 mEq/L (95% CI: 0.01–0.5) higher serum bicarbonate, respectively. Older age at transplant was associated with lower odds of acidosis (OR: 0.84; 95% CI: 0.72–0.97). During follow-up, metabolic acidosis was independently associated with 8.2 ml/min/1.73 m2 (95% CI 4.4–12) lower eGFR compared to not having acidosis; furthermore, eGFR was significantly lower among KTRs with unresolved acidosis compared with resolved acidosis. Conclusions: Among pediatric KTRs, metabolic acidosis was highly prevalent in the first year post-transplantation and was associated with lower eGFR during follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: Erythropoietic protoporphyria is a rare, inherited disorder presenting in early childhood with severe, painful phototoxicity. EPP has significant impacts on health-related quality of life, though there is variable disease severity. Accurately capturing how much time individuals with EPP can spend outdoors before they develop symptoms is critical to understanding HRQoL and measuring therapeutic response. Therefore, the goal of this study was to develop a comprehensive and content valid sun exposure diary to assess the efficacy of new therapies in individuals with EPP. Methods: Qualitative interviews were conducted with adult and adolescent EPP participants, as well as five clinical experts, to obtain their input on the content of an existing sun exposure diary. Revisions to the diary were made based on evidence generated in cognitive debriefing interviews analyzed in eight consecutive groups of EPP participant. Results: Interviews were conducted with 17 adults and 6 adolescents with EPP. The average age of adults was 40 years and of adolescents was 14 years. Clinical experts thought the original diary needed clarification on the description of symptoms, how time outdoors was captured, and the distinction between direct vs. indirect sunlight. Participants with EPP also noted these items needed revision, and that the distinction between prodromal symptoms and full reaction symptoms should be clarified. In the final diary version, participants with EPP found most items to be clear and easy to complete/think about. Seventy-six percent of participants (13/17) asked thought the diary was easy to complete. The remainder thought the majority of the diary was easy to complete with the exception of select questions. Conclusions: Evaluating a new treatment for EPP requires accurately capturing time in sunlight and symptoms in this unique disorder. The newly developed sun exposure diary is content valid and can be used to assess important aspects of symptoms and daily life and therefore evaluate clinically meaningful therapeutic response. [ABSTRACT FROM AUTHOR]

Fat deposition and lipid metabolism are closely related to the morphology, structure and function of mitochondria. The morphology of mitochondria between fusion and fission processes is mainly regulated by protein posttranslational modification. Intermittent fasting (IF) promotes high expression of Sirtuin 3 (Sirt3) and induces mitochondrial fusion in high-fat diet (HFD)-fed mice. However, the mechanism by which Sirt3 participates in mitochondrial protein acetylation during IF to regulate mitochondrial fusion and fission dynamics remains unclear. This article demonstrates that IF promotes mitochondrial fusion and improves mitochondrial function in HFD mouse inguinal white adipose tissue. Proteomic sequencing revealed that IF increased protein deacetylation levels in HFD mice and significantly increased Sirt3 mRNA and protein expression. After transfecting with Sirt3 overexpression or interference vectors into adipocytes, we found that Sirt3 promoted adipocyte mitochondrial fusion and improved mitochondrial function. Furthermore, Sirt3 regulates the JNK-FIS1 pathway by deacetylating malate dehydrogenase 2 (MDH2) to promote mitochondrial fusion. In summary, our study indicates that IF promotes mitochondrial fusion and improves mitochondrial function by upregulating the high expression of Sirt3 in HFD mice, promoting deacetylation of MDH2 and inhibiting the JNK-FIS1 pathway. This research provides theoretical support for studies related to energy limitation and animal lipid metabolism. [ABSTRACT FROM AUTHOR]

Metabolic diseases, such as obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and liver disease, have become increasingly prevalent around the world. As an alternative to bariatric surgery, glucagon-like peptide 1 (GLP-1) receptor agonists have been at the forefront of weight loss medication to combat these metabolic complications. Recently, there has been an exciting rapid emergence of new weight loss medications that combine GLP-1 receptor (GLP-1R) agonists with other gut- and pancreatic-derived hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) receptor agonists. Dual-agonist (GLP-1/GIP and GLP-1/GCG) and tri-agonist (GLP-1/GIP/GCG) administration generally result in greater weight loss, reduction of blood sugar and lipid levels, restoration of tissue function, and improvement in whole-body substrate metabolism compared to when GLP-1R agonists are used alone. The aim of this review is to summarize the recent literature of both preclinical and clinical studies on how these emerging gut-peptide therapies further improve weight loss and metabolic health outcomes for various metabolic diseases. [ABSTRACT FROM AUTHOR]

Objective: Liver transplantation is an accepted treatment modality in the pediatric patient group due to metabolic diseases. Patients are a more special population due to the presence of concomitant metabolic problems and the pediatric age group. There is no consensus on the long-term prognosis of pediatric patients with various rare liver diseases and inherited metabolic diseases. For this reason, we retrospectively evaluated our pediatric patients who underwent liver transplantation for pediatric metabolic liver diseases between 2012 and 2021. Methods: Seventeen patients were included in the study. The mean Pediatric End-Stage Liver Disease (PELD) score was 21.47 (±8.47). Eight (47,1%) children received cadaveric, and 9 (52,9%) children received living liver transplantation. The mean age was 8.03 years (±6.37) (13 months-18 years). Left lateral graft was used in 11 patients (64%), right lobe graft in 3 patients (18%) and left lobe graft in 3 patients (18%). Six patients had biliary strictures out of which, 5 (29.4%) had percutaneous transhepatic biliary dilatation, and ERCP was performed in 1 (5.8%) patient. Results: Our early survival rate was 100% and 2 patients (11,7%) were exitus in the late period for reasons unrelated to liver transplantation. Our mean follow-up period after transplantation was 70,6 months (±20.75) and no additional metabolic crisis was detected during the follow-up of the patients, including patients whose donors were relatives. Conclusion: Metabolic liver diseases have severe systemic effects, and it is important to be evaluated by a multidisciplinary team in their diagnosis and treatment and to perform planned liver transplants rapidly without delay. Liver transplantation performed at the right time can prevent permanent additional organ damage. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Pediatric Emergency & Intensive Care Medicine / Çocuk Acil ve Voğun Bakım Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Vagus nerve stimulation (VNS) is a technology that provides electrical stimulation to the cervical vagus nerve and can be applied in the treatment of a wide variety of neuropsychiatric and systemic diseases. VNS exerts its effect by stimulating vagal afferent and efferent fibers, which project upward to the brainstem nuclei and the relayed circuits and downward to the internal organs to influence the autonomic, neuroendocrine, and neuroimmunology systems. The neuroimmunomodulation effect of VNS is mediated through the cholinergic anti-inflammatory pathway that regulates immune cells and decreases pro-inflammatory cytokines. Traditional and non-invasive VNS have Food and Drug Administration (FDA)-approved indications for patients with drug-refractory epilepsy, treatment-refractory major depressive disorders, and headaches. The number of clinical trials and translational studies that explore the therapeutic potentials and mechanisms of VNS is increasing. In this review, we first introduced the anatomical and physiological bases of the vagus nerve and the immunomodulating functions of VNS. We covered studies that investigated the mechanisms of VNS and its therapeutic implications for a spectrumof brain disorders and systemic diseases in the context of neuroimmunomodulation. [ABSTRACT FROM AUTHOR]

Copyright of Forum Zaburzen Metabolicznych is the property of VM Medica-VM Group (Via Medica) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This review compared the effects of eccentric versus concentric exercise training in healthy people and people with metabolic disease. A systematic search on Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, SPORTDiscus, Web of Science, SCOPUS and PubMed was conducted in February 2022. Randomised controlled trials conducted on sedentary healthy adults or those with an existing metabolic disease that compared eccentric versus concentric exercise training interventions of four weeks or longer that involved multiple joints and large muscle groups (e.g., walking, whole-body resistance training) were included in the review. The primary outcome was glucose handling, measured as HbA1c, HOMA, fasting glucose or insulin. Measures of cardiovascular health, muscle strength, and functional physical fitness were secondary outcomes. Nineteen trials involving 618 people were included. Results of meta-analyses showed that eccentric exercise had no benefit to glucose handling (HbA1c level; SMD - 0.99; 95% CI, -2.96 to 0.98; n = 74; P = 0.32) but resulted in significant increases in overall muscle strength (SMD 0.70; 95% CI 0.25 to 1.15; n = 224; P = 0.003) and decreases in blood pressure (Systolic Blood Pressure; MD - 6.84; 95% CI, -9.84 to -3.84; n = 47, P = 0.00001, and Diastolic Blood Pressure; MD -6.39; 95% CI -9.62 to -3.15; n = 47, P = 0.0001). Eccentric exercise is effective for improving strength and some markers of cardiovascular health compared to traditional exercise modalities. Additional high-quality studies are necessary to validate these results. (PROSPERO registration: CRD42021232167). [ABSTRACT FROM AUTHOR]

Purpose: Resistance exercise is a well-established intervention to counteract musculoskeletal and metabolic toxicities from prostate cancer treatment. In this study, we reported resistance exercise attendance and compliance, and examined if these variables can influence changes in outcomes of interest in men with localized or locally advanced prostate cancer. Methods: A total of 83 prostate cancer patients (age, 68.2 ± 7.0 yr; body mass index, 27.7 ± 3.8 kg·m−2) who had undergone 6 months of resistance-based exercise and had data available on exercise training from logbook records were examined. Attendance outcomes such as missed sessions, interruptions and permanent discontinuation, and metrics such as dosage completed (sessions × number of exercises × sets × repetitions × external load), compliance, tolerance, reductions, and escalations were assessed. Outcomes assessed were body composition, physical function, and muscle strength. Results: Median resistance exercise attendance was 80.6%, with a median resistance exercise compliance of 88.5% (interquartile range [IQR], 61.1%–107.1%) per participant. A median of 11 (IQR, 1–26) and 0 (IQR, 0–2) sessions were escalated or reduced, respectively. Significant improvements were observed in whole-body lean mass, 400-m walk, repeated chair rise, leg press, and chest press strength after 6 months of intervention (P < 0.05) regardless of resistance exercise compliance (P trend = 0.199–0.950). Participants with higher levels of resistance exercise compliance presented greater improvements in trunk fat mass (P trend = 0.026) and appendicular lean mass (P trend = 0.047). Conclusions: A higher resistance exercise compliance led to greater improvements in regional fat and lean mass, whereas physical function and muscle strength improvements were achieved with lower compliance. In addition, patients experienced a high number of dose escalations during the intervention. These findings are important to improve the reproducibility/precision of exercise medicine prescription. [ABSTRACT FROM AUTHOR]

Urea cycle disorders (UCDs) are one of the more common groups of inherited metabolic disorders (IMDs). The urea cycle carried out by cells of the liver, detoxifies ammonia into urea which the body then excretes in the urine. UCDs are genetically inherited deficiencies in the enzymes of the urea cycle. UCDs cause hyperammonaemia, a metabolic emergency which requires prompt and meticulous management to prevent significant neurological harm and death. Timely investigation and treatment alongside liaison with the specialist metabolic centre are essential for improved patient outcomes and diagnosis. This review highlights the importance of early recognition of UCDs and the initiation of clinical management. Three case presentations of UCDs are discussed including argininosuccinate lyase (ASL) deficiency, ornithine transcarbamylase (OTC) deficiency and carbamoylaspartate synthetase 1 (CPS1) deficiency. [ABSTRACT FROM AUTHOR]

Fecal microbiota transplantation (FMT) restores a balanced intestinal flora, which helps to cure recurrent Clostridium difficile infections (RCDI). FMT has also been used to treat other gastrointestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation, as well as a variety of non-GI disorders. The purpose of this review is to discuss gut microbiota and FMT treatment of GI and non-GI diseases. An imbalanced gut microbiota is known to predispose one to Clostridium difficile infections (CDI), IBD, and IBS. However, the complex role of the gut microbiota in maintaining health is a newer concept that is being increasingly studied. The microbiome plays a major role in cellular immunity and metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity, and even some neuropsychiatric disorders. Many recent studies have reported that viral gastroenteritis can affect intestinal epithelial cells, and SARS-CoV-2 virus has been identified in the stool of infected patients. FMT is a highly effective cure for RCDI, but a better understanding of the gut microbiota in maintaining health and controlled studies of FMT in a variety of conditions are needed before FMT can be accepted and used clinically. [ABSTRACT FROM AUTHOR]

After orthotopic lung transplantation, hyperammonemia can be a rare complication secondary to infection by organisms that produce urease or inhibit the urea cycle. This can cause neurotoxicity, cerebral edema, and seizures. Ammonia is unique in that it has a large volume of distribution. However, it is also readily dialyzable given its small molecular weight. As such, removal of ammonia requires renal replacement modalities that can both rapidly remove ammonia from the plasma space and allow for continuous removal to prevent rebound accumulation from intracellular stores. Prevention of iatrogenic osmotic lowering in this setting is required to prevent worsening of cerebral edema. Herein, we describe use of sequential in-line renal replacement therapy using both intermittent hemodialysis and continuous venovenous hemofiltration within an extracorporeal membrane oxygenation circuit in conjunction with higher sodium dialysate and 7.5% hypertonic saline to achieve these treatment goals. [ABSTRACT FROM AUTHOR]

Copyright of ESPOCH Congresses: The Ecuadorian Journal of S.T.E.A.M. is the property of Knowledge E DMCC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

There is mounting evidence that microbiome composition is intimately and dynamically connected with host energy balance and metabolism. The gut microbiome is emerging as a novel target for counteracting the chronically positive energy balance in obesity, a disease of pandemic scale which contributes to >70 % of premature deaths. This scoping review explores the potential for therapeutic modulation of gut microbiota as a means of prevention and/or treatment of obesity and obesity-associated metabolic disorders. The evidence base for interventional approaches which have been shown to affect the composition and function of the intestinal microbiome is summarised, including dietary strategies, oral probiotic treatment, faecal microbiota transplantation and bariatric surgery. Evidence in this field is still largely derived from preclinical rodent models, but interventional studies in obese populations have demonstrated metabolic improvements effected by microbiome-modulating treatments such as faecal microbiota transplantation, as well as drawing attention to the unappreciated role of microbiome modulation in well-established anti-obesity interventions, such as dietary change or bariatric surgery. The complex relationship between microbiome composition and host metabolism will take time to unravel, but microbiome modulation is likely to provide a novel strategy in the limited armamentarium of effective treatments for obesity. [ABSTRACT FROM AUTHOR]

This study intended to evaluate the efficacy of Ḥammām-i-yabis (dry bath) in metabolic syndrome as primary objective and perceived improvement and changes in quality of life as secondary objective. The study was designed as single arm, open-labelled, pre and post without control clinical trial comprising 30 diagnosed cases of metabolic syndrome belonging to 20–50 years of age of either sex. The enrolled patients were exposed to the dry heat of Ḥammām-i-yābis for 15 min at a temperature of 60 degree centigrade on every third day for a duration of 30 days (a total of 10 sittings). Objective parameters comprising systolic and diastolic blood pressure and waist circumference were assessed on every follow up, while other objective parameters (FBS, HDL and Serum Triglycerides) were assessed before and after the study. Significant statistical difference was observed in objective parameters. Two tailed paired Student's t-test, (for pre and post) and repeated measure ANOVA (for 0, 15th and 30th day) were used to find the significance of mean change in study parameters. No significant adverse change appeared in safety parameters. Ḥammām-i-yābis was found effective, safer, more feasible and less expensive regimenal modality for the patients of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Inborn errors of metabolism (IEM), including organic acidemias and urea cycle defects, are characterized by systemic accumulation of toxic metabolites with deleterious effect on the developing brain. While hemodialysis (HD) is most efficient in clearing IEM-induced metabolic toxins, data regarding its use during the neonatal period is scarce. Methods: We retrospectively summarize our experience with HD in 20 neonates with IEM-induced metabolic intoxication (seven with maple syrup urine disease, 13 with primary hyperammonia), over a 16-year period, between 2004 and 2020. All patients presented with IEM-induced neurologic deterioration at 48 h to 14 days post-delivery, and were managed with HD in a pediatric intensive care setting. HD was performed through an internal jugular acute double-lumen catheter (6.5–7.0 French), using an AK-200S (Gambro, Sweden) dialysis machine and tubing, with F3 or FXpaed (Fresenius, Germany) dialyzers. Results: Median (interquartile range) age and weight at presentation were 5 (3–8) days and 2830 (2725–3115) g, respectively. Two consecutive HD sessions decreased the mean leucine levels from 2281 ± 631 to 179 ± 91 μmol/L (92.1% reduction) in MSUD patients, and the mean ammonia levels from 955 ± 444 to 129 ± 55 μmol/L (86.5% reduction), in patients with hyperammonemia. HD was uneventful in all patients, and led to marked clinical improvement in 17 patients (85%). Three patients (15%) died during the neonatal period, and four died during long-term follow-up. Conclusions: Taken together, our results indicate that HD is safe, effective, and life-saving for most neonates with severe IEM-induced metabolic intoxication, when promptly performed by an experienced and multidisciplinary team. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

• A classification and genetic basis for hypolipidemia disorders is provided. • We suggest guidance for the diagnosis and treatment of these disorders. • We discuss challenges encountered by patients with hypolipidemia disorders. • Topics for future research are highlighted. The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol and triglyceride, along with malabsorption of fat and fat-soluble vitamins are characteristic features of these diseases. We summarize the genetic basis of these disorders, provide guidance in their diagnosis and suggest treatment regimens including high dose fat-soluble vitamins as therapeutics. A section on preconception counseling and other special considerations pertaining to pregnancy is included. This information may be useful for patients, caregivers, physicians and insurance agencies involved in the management and support of affected individuals. [ABSTRACT FROM AUTHOR]

Epidemiologically, metabolic disorders have garnered much attention, perhaps due to the predominance of obesity. The early postnatal life represents a critical period for programming multifactorial metabolic disorders of adult life. Though altricial rodents are prime subjects for investigating neonatal programming, there is still no sufficiently generalised literature on their usage and methodology. This review focuses on establishing five approach-based models of neonatal rodents adopted for studying metabolic phenotypes. Here, some modelled interventions that currently exist to avoid or prevent metabolic disorders are also highlighted. We also bring forth recommendations, guidelines and considerations to aid research on neonatal programming. It is hoped that this provides a background to researchers focused on the aetiology, mechanisms, prevention and treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor-suppressor genes are involved in DNA break repair through the homologous recombination system and are widely known for their role in hereditary cancer. Beyond breast and ovarian cancer, prostate and pancreatic cancer also have targetable homologous recombination deficiency (HRD) beyond the well-known BRCA1 and BRCA2 with relevance that exceeds diagnostic purposes. In this review, we aim to summarize the roles of HRD across tumor types and the treatment landscape to guide the targeting of damaged DNA repair based on the cancer's genetic features. BRCA1 and BRCA2 are the most recognized tumor-suppressor genes involved in double-strand DNA break repair through the homologous recombination (HR) system. Widely known for its role in hereditary cancer, HR deficiency (HRD) has turned out to be critical beyond breast and ovarian cancer: for prostate and pancreatic cancer also. The relevance for the identification of these patients exceeds diagnostic purposes, since results published from clinical trials with poly-ADP ribose polymerase (PARP) inhibitors (PARPi) have shown how this type of targeted therapy can modify the long-term evolution of patients with HRD. Somatic aberrations in other HRD pathway genes, but also indirect genomic instability as a sign of this DNA repair impairment (known as HRD scar), have been reported to be relevant events that lead to more frequently than expected HR loss of function in several tumor types, and should therefore be included in the current diagnostic and therapeutic algorithm. However, the optimal strategy to identify HRD and potential PARPi responders in cancer remains undefined. In this review, we summarize the role and prevalence of HRD across tumor types and the current treatment landscape to guide the agnostic targeting of damaged DNA repair. We also discuss the challenge of testing patients and provide a special insight for new strategies to select patients who benefit from PARPi due to HRD scarring. [ABSTRACT FROM AUTHOR]

Xanthomas are papulonodular skin lesions present in lipoprotein metabolism disorders, which result in cholesterol deposits in subcutaneous tissue, tendons, ligaments, periosteum, etc. A 28-year-old male presented with multiple soft-tissue swellings, prominently over joints. Fine-needle aspiration (FNA) from multiple sites had similar appearance with foamy histocytes and giant cells. We describe an unusual case of tendinous and tuberous xanthoma diagnosed by cytology. Acquaintance with FNA cytology findings in xanthomas can help to avoid the need of surgical biopsy, as xanthomas can regress on medical therapy alone. [ABSTRACT FROM AUTHOR]

Nutraceuticals are products that are also used as medicine other than nutrition. A nutraceutical product may be defined as a substance, which have physiological benefits nor gives protection against chronic diseases. Nutraceuticals may also be used to improve health, delay the aging process, prevent chronic disease, increase life expectancy, or support the structure or function of the body. Nowadays, nutraceuticals has gained considerable interest due to potential nutritional safety and therapeutic effects. Recent studies have shown promising results for those compounds in various complications. Emphasis has been made to present herbal nutraceuticals effective on hard curative disorders related to oxidative stress including allergy, Alzheimer, cardiovascular, cancer, diabetes, and Parkinson's diseases as well as obesity. [ABSTRACT FROM AUTHOR]

Background: Hyperammonemia is a medical condition described as increased or elevated serum ammonia levels. High serum levels of ammonia can cause neurotoxicity. Sudden onset severe hyperammonemia may cause severe encephalopathy with brain damage. It can result in cerebral edema, emesis, seizures, hypotonia, and death. We report a young postpartum woman who had a sudden rise in serum ammonia levels after vaginal delivery.Case Presentation: A 24-year-old, married, postpartum Pakistani woman was admitted to the intensive care unit through the emergency department, with complaints of fever, severe abdominal pain with distension, and altered levels of consciousness. The patient had a medical history of spontaneous vaginal delivery 2 weeks before this hospital admission, after which she gradually developed the above symptoms. However, the patient's past medical history was unremarkable with no hepatic disease, but her investigations revealed a progressive rise in serum ammonia levels. In the intensive care unit, she developed generalized tonic-clonic seizures. This was followed by a coma, tonsillar herniation, and death.Conclusion: Postpartum hyperammonemia is a rare entity. It is a critical illness and must be evaluated for underlying metabolic disorders. Early diagnosis and treatment may result in better outcomes and reduced mortality among postpartum women with hyperammonemia. [ABSTRACT FROM AUTHOR]

Diabetes is one of the most prevalent metabolic disorders worldwide. The incidence of diabetes is increasing in the last decades, and It has become a significant global challenge. The efficacy of current therapeutic methods in the management and treatment of diabetes is not perfect. Hence, finding newer treatment methods or complementary therapies is valuable in patients with diabetes. Kaempferol, as a flavonol found in the variable range of plants such as vegetables and fruits, has been proven to have numerous therapeutic effects on the management of various diseases such as cancer and other metabolic disorders. The efficacy of kaempferol and its derivatives in the management of diabetes complications and glycemic indices has not been discussed so far. Hence, in this paper, we performed a comprehensive review of the protective and pharmaceutical properties of kaempferol in diabetic control. [ABSTRACT FROM AUTHOR]

Transient receptor potential canonical (TRPC) proteins assemble to form homo- or heterotetrameric, nonselective cation channels permeable to K+, Na+, and Ca2+. TRPC channels are thought to act as complex integrators of physical and chemical environmental stimuli. Although the understanding of essential physiological roles of TRPC channels is incomplete, their implication in various pathological mechanisms and conditions of the nervous system, kidneys, and cardiovascular system in combination with the lack of major adverse effects of TRPC knockout or TRPC channel inhibition is driving the search of TRPC channel modulators as potential therapeutics. Here, we review the most promising small-molecule TRPC channel modulators, the understanding of their mode of action, and their potential in the study and treatment of cardiovascular and metabolic disease. [ABSTRACT FROM AUTHOR]

Gene therapy has traditionally involved the delivery of exogenous genetic material to a cell—most commonly to replace defective genes causing monogenic disorders. This allows cells to produce proteins that are otherwise absent in sufficient quantities, ideally for a therapeutic purpose. Since its inception over 40 years ago, the field of gene therapy has significantly expanded and now includes targeted gene editing strategies, including, but not limited to, clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), transcription activator–like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs). [ABSTRACT FROM AUTHOR]

Background: Systemic oxalosis is a severe complication seen in primary hyperoxaluria type I patients with kidney failure. Deposition of insoluble calcium oxalate crystals in multiple organs leads to significant morbidity and mortality. Methods: We describe a retrospective cohort of 11 patients with systemic oxalosis treated at our dialysis unit from 1982 to 1998 (group 1) and 2007–2019 (group 2). Clinical and demographic data were collected from medical records. Imaging studies were only available for patients in group 2 (n = 5). Results: Median age at dialysis initiation was 6.1 months (IQR 4–21.6), 64% were male. Dialysis modality was mostly peritoneal dialysis in group 1 and daily hemodialysis in group 2. Bone disease was the first manifestation of systemic oxalosis, starting with the appearance of sclerotic bands (mean 166 days, range 1–235), followed by pathological fractures in long bones (mean 200.4 days, range 173–235 days). Advanced disease was characterized by vertebral fractures with resulting kyphosis, worsening splenomegaly, and adynamic bone disease. Two patients developed pulmonary hypertension, 4 and 8 months prior to their death. Four of 11 patients developed hypothyroidism 0–60 months after dialysis initiation. Only one patient survived after a successful liver–kidney transplantation. Four patients died after liver or liver–kidney transplantation. Conclusions: This is the first comprehensive description of the natural history of pediatric systemic oxalosis. We hope that our findings will provide basis for a quantitative severity score in future, larger studies. [ABSTRACT FROM AUTHOR]

Clinical Scenario: Managing edema after trauma or injury is a primary concern for health care professionals, as it is theorized that delaying the removal of edema will increase secondary injury and result in a longer recovery period. The inflammatory process generates a series of events, starting with bleeding and ultimately leading to fluid accumulation in intercellular spaces and the formation of edema. Once edema is formed, the lymphatic system plays a tremendous role in removing excess interstitial fluid and returning the fluid to the circulatory system. Therefore, rehabilitation specialists ought to use therapies that enhance the uptake of edema via the lymphatic system to manage edema; however, the modalities commonly used are ice, compression, and elevation. Modalities such as these may be effective at preventing swelling but present limited evidence to suggest that the function of the lymphatic system is enhanced. Manual lymphatic drainage (MLD) is a manual therapy technique that assists the lymphatic system function by promoting variations in interstitial pressures by applying light pressure using different hand movements. Focused Clinical Question: Does MLD improve patient- and disease-oriented outcomes for patients with orthopedic injuries? [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the most common oncological diseases, therefore, the study of this problem is an important issue in clinical practice. This problem becomes especially urgent in case of the formation of anemic syndrome in patients, which causes the emergence of a mutual burden syndrome and increases the risks for a patient. The progressive nature of anemia in colorectal cancer is accompanied by secondary metabolic disorders. The material for the study was the blood plasma of 445 patients (228 men and 217 women). Among them, 53 patients (31 women and 22 men) with iron deficiency anemia were examined and included in the first observation group (І) and 392 patients (206 men (52,55 %) and 186 women (47.45 %)) with colorectal cancer whose course of the underlying disease was burdened with anemia in neoplastic disease were included in the second observation group (II). Among the patients in the second (II) observation group, there were 222 individuals (119 men and 103 women) with malignant neoplasms of the colon (ICD-10 code: С.18), 29 individuals (16 men and 13 women) with malignant neoplasms of the rectosigmoid junction (ICD-10 code: C.19), 138 individuals (82 men and 56 women) with malignant neoplasms of the rectum (code ICD-10 C.20) and 3 patients (2 men and 1 woman) with malignant neoplasms of the anus (ICD-10 code: C.21). The age of the examined patients was from 22 to 79 years. It was found that prior to the initiation of treatment in patients with anemia in neoplastic disease, regardless of the course of colorectal cancer, there was a significant increase in the plasma level of free fractions of heparin, histamine and serotonin (p < 0,001); the ratio of histamine: serotonin was also changed in comparison with the values in the control group (p < 0,05), which indicated both an increased release of heparin, histamine and serotonin from the depot, and an impaired inactivation processes of these biologically active substances. It was correctly concluded that in addition to the baseline therapy the administration of arginine glutamate which causes both antihypoxic and membrane-stabilizing action, reliably contributes to the normalization of secondary metabolic disorders of histamine, serotonin and heparin metabolism in anemia in neoplastic disease in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the effects of a 5-yr exercise intervention on metabolic syndrome (MetS) and health-related variables and medication use for MetS management. Methods: Participants were randomly assigned to an exercise intervention (n = 25, 54 ± 2 yr, 20% women) or control group (n = 26, 54 ± 2 yr, 38% women). The intervention lasted 4 months per year and consisted of high-intensity interval training on a cycloergometer thrice a week. Outcomes were MetS z-score and medication use score, MetS-related variables (including blood pressure, blood glucose homeostasis, and lipid profile), and cardiorespiratory fitness (CRF, as determined by maximal oxygen uptake). Results: MetS z-score was similarly reduced over time in both groups (P = 0.244 for group--time interaction). A quasi-significant and significant group--time interaction was found for MetS number of factors (P = 0.004) and CRF (P < 0.001), respectively. Thus, MetS factors tended to decrease over time only in the exercise group with no change in the control group, whereas CRF increased from baseline to 5-yr assessment in the exercise group (by 1.1MET, P < 0.001) but decreased in the control group (-0.5MET, P = 0.025).Medicine use score increased twofold frombaseline to 5-yr follow-up in the control group (P < 0.001) but did not significantly change (10%, P = 0.52) in the exercise group (P < 0.001 for group--time interaction). The proportion of medicated patients who had to increase antihypertensive (P < 0.001), glucose-lowering (P = 0.036), or total medication (P < 0.0001) over the 5-yr period was lower in the exercise than that in the control group. Conclusions: Exercise training can attenuate the increase in medication that would be otherwise required to manage MetS over a 5-yr period. [ABSTRACT FROM AUTHOR]

The gut microbiota is part of a complex network that interacts with the host metabolism and plays a key role in the immune system and regulation of hormone secretion. Any change in the gut microbiota (dysbiosis) is associated with various diseases such as metabolic syndromes. Dysbiosis can play a determining role in the pathogenesis of obesity-related metabolic disorders such as insulin resistance, diabetes, and cardiovascular disease. Microbiota is effective in the progression of type 1 diabetes (T1D) by affecting the permeability and status of the intestinal immune system. In healthy conditions, the intestinal epithelium prevents the induction of immune system responses, but in T1D it is stimulated by microbial or dietary antigens following an increase in the permeability of the intestinal immune system. The key link between dysbiosis and type 2 diabetes (T2D) is intestinal epithelial cell dysfunction. By increasing epithelial permeability and causing mild inflammation, it leads to dysfunction of the immune system and changes in glucose and lipid metabolism by affecting signaling pathways. Faecalibacterium (F) prausnitzii is the most abundant bacterium in the human gut microbiota that is actively involved in host metabolism. F. prausnitzii can inhibit the activity of NF-kB, IL-8, and can modulate the intestinal immune system, oxidative stress, and colon cell metabolism by producing butyrate. F. prausnitzii has anti-inflammatory properties by producing MAM protein and salicylic acid, which is effective in reducing colitis. Decreased levels of bacteria in the gut are also linked to inflammatory bowel disease, celiac disease, obesity, and diabetes. [ABSTRACT FROM AUTHOR]

Context Polycystic ovary syndrome (PCOS) is common and associated with metabolic syndrome. In the general population, metabolic disease varies by race and ethnicity. Objective This work aimed to examine in depth the interaction of race and ethnicity with PCOS-related metabolic disease in adolescent youth. Methods A secondary analysis was conducted of data from girls (age 12-21 years) with overweight or obesity (> 90 body mass index [BMI] percentile) and PCOS. Measurements included fasting hormone and metabolic measures, a 2-hour oral glucose tolerance test (OGTT), and magnetic resonance imaging for hepatic fat. Groups were categorized by race or ethnicity. Results Participants included 39 non-Hispanic White (NHW, age 15.7 ± 0.2 years; BMI 97.7 ± 0.2 percentile), 50 Hispanic (HW, 15.2 ± 0.3 years; 97.9 ± 0.3 percentile), and 12 non-Hispanic Black (NHB, 16.0 ± 0.6 years; 98.6 ± 0.4 percentile) adolescents. Hepatic markers of insulin resistance were worse in NHW, including lower sex hormone–binding globulin and higher triglycerides over high-density lipoprotein cholesterol (TGs/HDL-C) ratio (P  = .002 overall, HW vs NHB [ P  = .009] vs NHW [ P  = 0.020]), although homeostasis model assessment of estimated insulin resistance was worst in NHB (P  = .010 overall, NHW vs NHB P  = .014). Fasting and 2-hour OGTT glucose were not different between groups, although glycated hemoglobin A1c (HbA1c) was lowest in NHW (overall P  < .001, NHW 5.2 ± 0.3 vs HW 5.5 ± 0.3 P  < .001 vs 5.7 ± 0.4%, P  < .001). The frequency of hepatic steatosis (HW 62%, NHW 42%, NHB 25%, P  = .032); low HDL-C < 40 mg/dL (HW 82%, NHW 61%, NHB 50%, P  < .001) and prediabetes HbA1c 5.7% to 6.4% (NHB 50%, HW 36%, NHW 5%, P  < .001) were different between the groups. Conclusion Adolescents with PCOS appear to show similar racial and ethnic variation to the general population in terms of metabolic disease components. [ABSTRACT FROM AUTHOR]

Introduction: Central pontine myelinolysis (CPM) is a rare neurological disease characterized by noninflammatory demyelination in the pons. The most frequent cause of CPM is a significant shift in serum osmolality during metabolic corrections, mainly hyponatremia. Case Report: We present the case of a 30-year-old female with no prior medical history, no alcohol consumption, who presented with diplopia, followed after one week by a decrease in muscular strength, gait ataxia, progressive dysarthria, and swallowing difficulties. Neurological examination revealed no meningeal signs, bilateral ataxic gait possible for less than 20m, bilateral divergent strabismus, horizontal diplopia, left peripheral facial palsy, diminished gag reflexes, dysphagia, spastic quadriparesis, brisk deep tendon reflexes, bilateral Babinski sign, bilateral dysmetria, dysarthria, GCS 15 points. Brain MRI with contrast revealed bilateral ponto-mesencephalic and bilateral cerebellar demyelinating lesions with restricted diffusion on DWI, showing a "bat-wing" appearance at the level of the pons, with no contrast enhancement, suggestive of central pontine and extrapontine myelinolysis. There were no recent metabolic abnormalities in the patient's history. Paraclinical investigations, including autoimmune, metabolic, and hormonal panels, were unremarkable except for positive anti-CMV IgM antibodies. The lumbar puncture was within normal parameters, and anti-CMV IgM and IgG antibodies from the cerebrospinal fluid were negative. Treatment with corticosteroids, B vitamins, and kinesiotherapy resulted in favorable evolution. She was discharged with immunosuppressive therapy, azathioprine, which resulted in consistent improvement. At the 6-month reevaluation, the patient was able to walk unassisted, with persistent mild bilateral strabismus, mild left peripheral palsy, quadriparesis grade 4+, and mild bilateral dysmetria. The brain MRI findings remained unchanged. Discussions : The radiological characteristics were suggestive of the diagnosis of CPM, but the patient's clinical history revealed no significant causes for electrolyte and osmotic disturbances. Conclusions: We interpret the case as idiopathic CPM in the absence of any precipitating risk factors. Immunosuppressive therapy with azathioprine and corticosteroids proved to be effective. [ABSTRACT FROM AUTHOR]

Many chronic disease patients experience a concurrent loss of lean muscle mass. Skeletal muscle is a dynamic tissue maintained by continuous protein turnover and progenitor cell activity. Muscle stem cells, or satellite cells, differentiate (by a process called myogenesis) and fuse to repair and regenerate muscle. During myogenesis, satellite cells undergo extensive metabolic alterations; therefore, pathologies characterized by metabolic derangements have the potential to impair myogenesis, and consequently exacerbate skeletal muscle wasting. How disease-associated metabolic disruptions in satellite cells might be contributing to wasting is an important question that is largely neglected. With this review we highlight the impact of various metabolic disruptions in disease on myogenesis and skeletal muscle regeneration. We also discuss metabolic therapies with the potential to improve myogenesis, skeletal muscle regeneration, and ultimately muscle mass. [ABSTRACT FROM AUTHOR]

Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy. Pajed et al. investigate the role of adipocyte hormone-sensitive lipase (HSL) in whole body energy homeostasis. They show that adipocyte-specific HSL Knockout (AHKO) mice fed high fat diet develop fatty liver. Interestingly, this phenotype reverses in aged AHKO mice, possibly due to blunted lipolytic activity in adipose tissue with pronounced lipodystrophy. [ABSTRACT FROM AUTHOR]

Objective: To establish the intensity, duration and frequency of exercise needed to achieve change in metabolic profiles of pre-diabetes at Moi Teaching and Referral Hospital, Eldoret, Kenya. Design: A randomized controlled experimental study Setting: Moi Teaching and Referral Hospital, Eldoret, Kenya Subjects: Two comparison groups Experimental Group (EG) and Control Group (CG) with both groups having the same size of subjects, 17 patients each Results: The results showed that training reduces FBG by 5% and 13%, in 6 and 12 weeks, respectively. HDL were significantly higher in the experimental than in the control group during post-training (z= -3.20.17, p=0.001). On the other hand the level of LDL decreased in the experimental group during both mid-training and post-training period relative to pre-training (z= -2.908.18, p=0.001). There was a significant reduction of Hemoglobin A1c (HbA1c) (of 3%) after six weeks and an even more marked drop (8%) after 12 weeks in EG compared to CG in which there was no drop in HbA1c levels. High correlation was found between FBG and HbA1c (r=0.95) Conclusion: The knowledge of how much exercise is required to impact change in disease progression would inform the prescription of exercise by physiotherapists to their clients. [ABSTRACT FROM AUTHOR]

Complementary and alternative medicine (CAM) is used often by patients with different diseases. While some authors subsume religiousness and spirituality to CAM, others do not. The objective of the present study was to assess the prevalence and types of CAM usage as well as the participants' spirituality/religiousness in an outpatient department for endocrinology and metabolic diseases. All individuals visiting the outpatient department at a German university hospital from April to June 2009 were offered a standardized questionnaire on the use of dietary supplements and alternative therapies as well as their religiousness/spirituality. Demographic and clinical data of 428 respondents were taken from the electronic health record. Of the respondents, 16.4% (n = 66) classified themselves to be religious/spiritual and 67.9% (n = 273) as not religious/spiritual. Women were more religious/spiritual than men (p = 0.02). 41.4% of the respondents used supplements and 27.4% additional therapies. The use of supplements and additional therapies was more frequent in people with higher religiousness/spirituality (p = 0.005 and p = 0.01,resp.) but there were no associations between religiousness/spirituality and the number of consultations, costs for drugs, appraisal of the physicians treatment methods, the perceived effectiveness of prescribed drugs, fear of late complications or of side effects. A higher religiousness/spirituality is associated with a more frequent use of supplements or additional therapies in individuals with endocrinopathies or metabolic diseases. As CAM has been shown to be associated with worse outcome, addressing religiousness/spirituality which stresses the responsibility of the person for his life might offer an additional resource and should be further studied. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor (FGF) 21 is a class of hepatokines that plays a protective role against obesity, insulin resistance, and liver damage. Despite this, protective effects of FGF21 in human appear to be minimal, possibly due to its proteolytic cleavage by the fibroblast activation protein (FAP). Here, we presented a novel FAP inhibitor, BR103354, and described its pharmacological activities as a potential therapeutic agent for the treatment of metabolic disorders. BR103354 inhibited FAP with an IC50 value of 14 nM, showing high selectivity against dipeptidyl peptidase (DPP)-related enzymes and prolyl oligopeptidase (PREP). In differentiated 3T3/L1 adipocytes, the addition of FAP diminished hFGF21-induced Glut1 and phosphorylated levels of ERK, which were restored by BR103354. BR103354 exhibited good pharmacokinetic properties as evidenced by oral bioavailability of 48.4% and minimal hERG inhibition. Single co-administration of BR103354 with hFGF21 reduced nonfasting blood glucose concentrations, in association with increased intact form of hFGF21 in ob/ob mice. Additionally, chronic treatment of BR103354 for 4 weeks reduced nonfasting blood glucose concentrations with improved glucose tolerance and with reduced triglyceride (TG) content in liver of ob/ob mice. Consistently, BR103354 improved hepatic steatosis and fibrosis in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced non-alcoholic steatohepatitis (NASH) mouse model. FAP inhibitory effects of BR103354 were confirmed in normal cynomolgus monkeys. Together, BR103354 acts as an effective FAP inhibitor in vitro and in vivo, thereby demonstrating its potential application as an anti-diabetic and anti-NASH agent. [ABSTRACT FROM AUTHOR]

Background: Little is known on the trends of aeromedical retrieval (AR) during social isolation. Aim: To compare the pre, lockdown, and post‐lockdown AR patient characteristics during a period of Coronavirus 2019 (COVID‐19) social isolation. Methods: An observational study with retrospective data collection, consisting of AR between 26 January and 23 June 2020. Results: There were 16 981 AR consisting of 1983 (11.7%) primary evacuations and 14 998 (88.3%) inter‐hospital transfers, with a population median age of 52 years (interquartile range 29.0–69.0), with 49.0% (n = 8283) of the cohort being male and 38.0% (n = 6399) being female. There were six confirmed and 230 suspected cases of COVID‐19, with the majority of cases (n = 134; 58.3%) in the social isolation period. As compared to pre‐restriction, the odds of retrieval for the restriction and post‐restriction period differed across time between the major diagnostic groups. This included, an increase in cardiovascular retrieval for both restriction and post‐restriction periods (odds ratio (OR) 1.12, 95% confidence interval (CI) 1.02–1.24 and OR 1.18 95%, CI 1.08–1.30 respectively), increases in neoplasm in the post restriction period (OR 1.31, 95% CI 1.04–1.64) and increases for congenital conditions in the restriction period (OR 2.56, 95% CI 1.39–4.71). Cardiovascular and congenital conditions had increased rates of priority 1 patients in the restriction and post restriction periods. There was a decrease in endocrine and metabolic disease retrievals in the restriction period (OR 0.72, 95% CI 0.53–0.98). There were lower odds during the post‐restriction period for retrievals of the respiratory system (OR 0.78, 95% CI 0.67–0.93), and disease of the skin (OR 0.78, 95% CI 0.6–1.0). Distribution between the 2019 and 2020 time periods differed (P < 0.05), with the lockdown period resulting in a significant reduction in activity. Conclusion: The lockdown period resulted in increased AR rates of circulatory and congenital conditions. [ABSTRACT FROM AUTHOR]