Effects of sulfatide on peripheral nerves in metachromatic leukodystrophy.

OBJECTIVE: To evaluate the longitudinal correlations between sulfatide/lysosulfatide levels and central and peripheral nervous system function in children with metachromatic leukodystrophy (MLD) and to explore the impact of intravenous recombinant human arylsulfatase A (rhASA) treatment on myelin turnover. METHODS: A Phase 1/2 study of intravenous rhASA investigated cerebrospinal fluid (CSF) and sural nerve sulfatide levels, 88-item Gross Motor Function Measure (GMFM-88) total score, sensory and motor nerve conduction, brain N-acetylaspartate (NAA) levels, and sural nerve histology in 13 children with MLD. Myelinated and unmyelinated nerves from an untreated MLD mouse model were also analyzed. RESULTS: CSF sulfatide levels correlated with neither Z-scores for GMFM-88 nor brain NAA levels; however, CSF sulfatide levels correlated negatively with Z-scores of nerve conduction parameters, number of large (≥7 µm) myelinated fibers, and myelin/fiber diameter slope, and positively with nerve g-ratios and cortical latencies of somatosensory-evoked potentials. Quantity of endoneural litter positively correlated with sural nerve sulfatide/lysosulfatide levels. CSF sulfatide levels decreased with continuous high-dose treatment; this change correlated with improved nerve conduction. At 26 weeks after treatment, nerve g-ratio decreased by 2%, and inclusion bodies per Schwann cell unit increased by 55%. In mice, abnormal sulfatide storage was observed in non-myelinating Schwann cells in Remak bundles of sciatic nerves but not in unmyelinated urethral nerves. INTERPRETATION: Lower sulfatide levels in the CSF and peripheral nerves correlate with better peripheral nerve function in children with MLD; intravenous rhASA treatment may reduce CSF sulfatide levels and enhance sulfatide/lysosulfatide processing and remyelination in peripheral nerves.

Epididymal Adenomatoid Tumour: A Case Report.

Adenomatoid tumours are rare benign neoplasm involving the para testicular region, mostly the tail of the epididymis. They are typically small, firm and asymptomatic masses in the scrotal region and often discovered incidentally during physical examination or imaging studies. It is very challenging to differentiate them clinically and radiologically from malignant intratesticular solid tumours, which may lead to unnecessary orchidectomies. This case report presents the clinical management of a 57-year-old male patient with adenomatoid tumour of the epididymis, highlighting the diagnostic workup, surgical approach and postoperative outcomes. In addition, a comprehensive literature review was conducted to discuss the morphological and immunohistochemical features to improve understanding of these rare lesions and assist in accurate diagnosis and appropriate management.

Bilateral Ureteral Nephrogenic Adenoma: An Unusual Mimicker of Malignancy.

Nephrogenic adenoma (NA) is a rare, benign lesion of the urinary tract that is induced by chronic irritation or injury to the urinary tract. Ureteral nephrogenic adenoma arising from both ureters is an exceptionally rare condition. We report an unusual case of a 73-year-old male who presented with a several-month history of recurrent UTI-like symptoms. Subsequent imaging showed bilateral hydronephrosis and ureteral wall thickening. A retrograde ureteroscopy revealed several papillary masses filling the lumens of both ureters. Ureteroscopic biopsies revealed NA in both ureters.

Evaluation of an established colorectal robotic programme at an NHS district general hospital: audit of outcomes and systematic review of published data.

INTRODUCTION: Robotic-assisted surgery (RAS) offers potential advantages over traditional surgical approaches. This study aimed to assess outcomes from a district general hospital (DGH) robotic colorectal programme against published data. MATERIALS AND METHODS: The robotic programme was established following simulator, dry/wet lab training, and proctoring. We performed a case series analysing technical, patient, and oncological outcomes extracted from a prospective database of colorectal RAS cases (2015-2022). A registered systematic review (PROSPERO CRD42022300773; PubMed, Web of Science, EMBASE) of single-centre colorectal series from established robotic centres (n>200 cases) was completed and compared to local data using descriptive summary statistics. Risk of bias assessment was performed using an adapted version of the Cochrane ROBINS-I tool. RESULTS: Two hundred thirty-two RAS cases were performed including 122 anterior resections, 56 APERs, 19 rectopexies, and 15 Hartmann's procedures. The median duration was 325 (IQR 265-400) min. Blood loss was < 100 ml in 97% of cases with 2 (0.9%) cases converted to open. Complications (Clavien-Dindo 3-5) occurred in 19 (8%) patients, with 3 (1.3%) deaths in < 30 days. Length of stay was 7 (IQR 5-11) days. In 169 rectal cancer cases, there were 9 (5.3%) cases with a positive circumferential or distal margin and lymph node yield of 17 (IQR 13-24). A systematic review of 1648 abstracts identified 13 studies from established robotic centres, totaling 4930 cases, with technical, patient, and oncological outcomes comparable to our own case series. CONCLUSIONS: Outcomes from our robotic colorectal programme at a UK DGH are comparable with the largest published case series from world-renowned centres. Training and proctoring together with rolling audit must accompany the expansion of robotic surgery to safeguard outcomes.

Primary Carcinoma In Situ of the Ureter Without Concurrent Renal Pelvis or Bladder Carcinoma: A Case Report and Literature Review.

Primary carcinoma in situ (CIS) solely affecting the ureter without concurrent involvement of the kidney or bladder is an exceptionally rare condition. This case report presents the clinical management of a 67-year-old male patient with primary ureteral CIS, highlighting the diagnostic workup, surgical approach, and postoperative outcomes. The diagnosis was established through the use of CT and ureteroscopy, leading to the decision for radical laparoscopic nephroureterectomy. Additionally, a comprehensive literature review was conducted to discuss the diagnostic challenges and management options for primary ureteral CIS.

Enhanced axonal regeneration of ALS patient iPSC-derived motor neurons harboring SOD1A4V mutation.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by degeneration of upper and lower motor neurons that leads to muscle weakness, paralysis, and death, but the effects of disease-causing mutations on axonal outgrowth of neurons derived from human induced pluripotent stem cells (iPSC)-derived motor neurons (hiPSC-MN) are poorly understood. The use of hiPSC-MN is a promising tool to develop more relevant models for target identification and drug development in ALS research, but questions remain concerning the effects of distinct disease-causing mutations on axon regeneration. Mutations in superoxide dismutase 1 (SOD1) were the first to be discovered in ALS patients. Here, we investigated the effect of the SOD1A4V mutation on axonal regeneration of hiPSC-MNs, utilizing compartmentalized microfluidic devices, which are powerful tools for studying hiPSC-MN distal axons. Surprisingly, SOD1+/A4V hiPSC-MNs regenerated axons more quickly following axotomy than those expressing the native form of SOD1. Though initial axon regrowth was not significantly different following axotomy, enhanced regeneration was apparent at later time points, indicating an increased rate of outgrowth. This regeneration model could be used to identify factors that enhance the rate of human axon regeneration.

Vesical Haemangioma in Klippel-Trenaunay-Weber Syndrome: A Clinical Case Report.

Klippel-Trenaunay-Weber (KTW) syndrome, a rare vascular disorder, often presents with cutaneous capillary malformations and soft tissue hypertrophy. However, urinary tract involvement in the form of vesical haemangiomas is a seldom-encountered clinical condition. We present a case of a 37-year-old male with KTW syndrome who exhibited recurrent gross haematuria, prompting clinical evaluation. Initial diagnostic assessments revealed erythematous changes in the bladder, consistent with haemangiomas. Despite an initial biopsy and diathermy, the patient's symptoms recurred, leading to a subsequent management strategy involving laser fulguration. This case underscores the significance of recognizing cutaneous haemangiomas as potential indicators of urinary tract involvement in KTW syndrome and highlights the challenges in managing vesical haemangiomas, where a multidisciplinary approach is essential for optimal care.

Maternal Risk Factors Associated with Preterm Births among Pregnant Women in Mogadishu, Somalia.

BACKGROUND: Premature birth impacts millions of newborns annually. Sixty percent of the world's preterm births occur in Sub-Saharan Africa and South Asia. Somalia's premature birth rates and maternal risk factors are poorly studied; hence, this study aims to identify maternal risk factors related to premature births in Mogadishu, Somalia. METHODS: This unmatched case-control study was conducted at four maternity hospitals in Mogadishu, Somalia. The cases were newborns with gestational ages of less than 37 weeks; controls were newborns with gestational ages of 37 to 42 weeks. All were live singletons. Cross-tabulation and binary logistic regression were used to analyze the data; a p-value of 0.05 was deemed statistically significant. RESULT: Of the total of 499 newborns, 70 were cases, and 429 were controls. Adequate prenatal care, maternal urine analysis, tetanus toxoid (TT) vaccination, hemoglobin (Hb) measurement, ultrasound monitoring, intake of iron + folic acid (IFA) supplement, blood pressure (BP) measurement during the current pregnancy, as well as partograph usage during labor all significantly decreased risk of having premature births. A prior history of preterm delivery and preeclampsia, obstetric complications, and female genital mutilation (FGM) significantly increased the risk of preterm births. CONCLUSION: The utilization of antenatal care services, use of a partograph, obstetric complications, and prior history of premature birth and preeclampsia had a substantial effect on preterm birth rates. This study identifies female genital mutilation (FGM) as a previously unidentified risk factor for preterm birth that needs additional investigation.

Predictors of type-2 diabetes remission following bariatric surgery after a two-year follow-up.

PURPOSE: Bariatric surgery is evolving as a successful tool for managing morbid obesity and T2DM. This study aimed to identify predictors of diabetes remission after two types of bariatric procedures. METHODS: This prospective study enrolled 172 patients with morbid obesity associated with T2DM scheduled for bariatric surgery. Two laparoscopic bariatric procedures were done; single anastomosis gastric bypass (SAGB, n = 83) and sleeve gastrectomy (LSG, n = 68). Lipid accumulation product index (LAP) and quantitative insulin sensitivity check index (QUICKI) were used to evaluate lipid profile and insulin sensitivity. Two years after surgery condition of DM was evaluated as complete remission (CR), partial remission (PR), or improvement. The primary outcome measure was predictors of diabetes remission. RESULTS: Two years after surgery, 151 patients were available for evaluation, where 75 patients (49.7%) achieved CR, while PR was found in 36 (23.8%). CR was significantly associated with younger age, shorter duration of DM (p < 0.001, for both), higher C-peptide and GLP-1 levels (p < 0.001 and p = 0.002, respectively), and bypass surgery (p = 0.027). On multivariate analysis, shorter duration of DM, lower BMI, and higher C-peptide levels were the independent factors predicting CR. CONCLUSION: Complete remission of T2DM can be achieved in nearly half of the patients two years after SG or SAGB. The duration of diabetes and preoperative BMI and C-peptide levels are the independent factors predicting complete remissions.

Nutritional Complications After Laparoscopic Roux-en-Y Gastric Bypass and One-Anastomosis Gastric Bypass: A Comparative Systematic Review and Meta-Analysis.

A systematic review and meta-analysis were carried out involving studies that compared the nutritional complications of Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB); these included the incidence of malnutrition as well as deficiencies of other nutritional elements, such as total protein, albumin, calcium and iron. A comprehensive search strategy was implemented in PubMed, Embase, and the Cochrane Library. Effect sizes included the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as mean differences (MDs) and 95% CIs of the percentage total weight loss (%TWL) and excess weight loss percentage (%EWL). Thirteen studies were included (12,964 patients, 66.27% females, 53.82% underwent OAGB). At the longest follow-up period (≥3 years), OAGB was associated with significantly higher %TWL (MD=5.41%, 95%CI, 1.52 to 9.29) and %EWL (MD=13.81%, 95%CI, 9.60 to 18.02) compared to RYGB. However, OAGB procedures were associated with malnutrition (OR=3.00, 95%CI, 1.68 to 5.36, p<0.0001), hypoalbuminemia (OR=2.38, 95%CI, 1.65 to 3.43, p<0.0001), hypoproteinemia (OR=1.85, 95%CI, 1.09 to 3.14, p=0.022), anemia (OR=1.38, 95%CI, 1.08 to 1.77, p=0.011), and hypocalcemia (OR=1.78, 95%CI, 1.01 to 3.12, p=0.046). On subgroup analyses, the proportions of anemia and hypoalbuminemia remained significantly higher at longer follow-up periods and in studies published in Asia. Despite the favorable weight loss profile, the unfavorable nutritional consequences of OAGB merits further investigations to explore the malabsorptive element, ethnic variation, and the role of biliopancreatic limb length.

Host-Viral Interactions at the Maternal-Fetal Interface. What We Know and What We Need to Know.

In humans, the hemochorial placenta is a unique temporary organ that forms during pregnancy to support fetal development, gaseous exchange, delivery of nutrition, removal of waste products, and provides immune protection, while maintaining tolerance to the HLA-haploidentical fetus. In this review, we characterize decidual and placental immunity during maternal viral (co)-infection with HIV-1, human cytomegalovirus (HCMV), and Zika virus. We discuss placental immunology, clinical presentation, and epidemiology, before characterizing host susceptibility and cellular tropism, and how the three viruses gain access into specific placental target cells. We describe current knowledge on host-viral interactions with decidual and stromal human placental macrophages or Hofbauer cells, trophoblasts including extra villous trophoblasts, T cells, and decidual natural killer (dNK) cells. These clinically significant viral infections elicit both innate and adaptive immune responses to control replication. However, the three viruses either during mono- or co-infection (HIV-1 and HCMV) escape detection to initiate placental inflammation associated with viral transmission to the developing fetus. Aside from congenital or perinatal infection, other adverse pregnancy outcomes include preterm labor and spontaneous abortion. In addition, maternal HIV-1 and HCMV co-infection are associated with impaired fetal and infant immunity in postnatal life and poor clinical outcomes during childhood in exposed infants, even in the absence of vertical transmission of HIV-1. Given the rapidly expanding numbers of HIV-1-exposed uninfected infants and children globally, further research is urgently needed on neonatal immune programming during maternal mono-and co-infection. This review therefore includes sections on current knowledge gaps that may prompt future research directions. These gaps reflect an emerging but poorly characterized field. Their significance and potential investigation is underscored by the fact that although viral infections result in adverse consequences in both mother and developing fetus/newborn, antiviral and immunomodulatory therapies can improve clinical outcomes in the dyad.

The Impact of Drain and Reinforcement on the Outcomes of Bariatric Surgery: A Prospective Study.

Purpose We aimed to investigate the impact of reinforcement and abdominal drains on the outcome of laparoscopic sleeve gastrectomy (LSG). Methods The present study was a prospective study that included obese patients scheduled to undergo LSG. Patients were assigned to receive drain, reinforcement, or both according to the surgeon's preference and followed up for one month after surgery. The present study's primary outcome was the identification of the association between intraoperative drain/reinforcement and the incidence of postoperative complications. Results A total of 125 (20.3%) patients received intraoperative drains. The proportion of postoperative morbidity was comparable between the drain and non-drain groups (3.2% versus 1.6%; p = 0.25). Patients in the drain group had similar incidence of blood transfusion (2.4% versus 1.7% in non-drain group; p = 0.43) and postoperative leakage (0.8% versus 0.2% in non-drain group; p = 0.36). The incidences of blood transfusion (p = 0.56) and reoperation (p = 0.98) were comparable between the drain and non-drain groups. There were no statistically significant differences between the drain and non-drain groups regarding postoperative mortality and wound infection (p > 0.05). On the other hand, 440 (71.3%) patients received reinforcement. The proportion of postoperative morbidity was comparable between the reinforcement and non-reinforcement groups (1.6% versus 2.8%, p = 0.07). Patients in the reinforcement group were less likely to develop postoperative bleeding (0.7% versus 4% in the non-reinforcement group; p = 0.004), while no significant difference was detected in terms of postoperative leakage (p = 0.33) and in-hospital mortality. Conclusion In conclusion, abdominal drainage did not reduce the complications of LSG patients. Reinforcement has some role in controlling the bleeding but not leaks. Both techniques did not significantly impact the mortality rate. In the future, additional, large randomized trials are needed to examine the gastrointestinal-related quality of life.

Comparison of seven heterophile antibody assays for laboratory diagnosis of infectious mononucleosis in pediatric patients.

Heterophile antibody assays have been used to aid the diagnosis of infectious mononucleosis caused by the Epstein-Barr virus. Seven commercially available assays currently widely utilized in clinical laboratories were compared in this study. Variable performance characteristics and assay times are observed, and these pieces of data may assist clinical laboratories in assay selection and result interpretation.

Best practices and opportunities for integrating nutrition specific into nutrition sensitive interventions in fragile contexts: a systematic review.

BACKGROUND: Annually, undernutrition contributes globally to 45% (3.1 million) of preventable deaths in children under 5. Effect following undernutrition i.e. physical growth & cognitive development etc. can be prevented during the first 1000 days also called window of opportunity. There is substantial evidence of positive nutrition outcomes resulting from integrating nutrition-specific interventions into nutrition specific program. However, there is paucity of knowledge on establishing and sustaining effective integration of nutrition intervention in fragile context. The objective of this review is to map and review the integration of nutrition-specific intervention to nutrition sensitive program and its impacts on nutrition outcomes. METHODS: In the study, we systematically searched the literature on integrated nutrition intervention into multi-sectoral programme in PUBMED, Google's Scholar, the Cochrane Library, World Health Organisation (WHO), United Nations Children's Fund (UNICEF), World Bank and trial registers from their inception until Oct 30, 2020 for up-to-date published and grey resources. We screened records, extracted data, and assessed risk of bias in duplicates. This study is registered with PROSPERO (CRD42020209730). RESULT: Forty-four studies were included in this review, outlining the integration of nutrition-specific interventions among children 0-59 months with various existing programme. Most common integration platform in the study included integrated community case management and Integrated Management of Childhood Illness, Child Health Days, immunization, early child development, and cash transfers. Limited quantitative data were suggestive of some positive impact on nutrition and non-nutrition outcomes with a number of model of integration which varies according to the context and demands of the particular setting in which integration occurs. CONCLUSION: Overall, existing evidence for nutrition sensitive and specific interventions is not robust and remains limited. It's worthwhile to note, for future studies/interventions should be based on the context key criteria like relevance, political support, effectiveness, feasibility, expected contribution to health system strengthening, local capacities, ease of integration and targeting for sustainability, cost effectiveness and financial availability.

The influence of BACE1 on macrophage recruitment and activity in the injured peripheral nerve.

Following peripheral nerve injury, multiple cell types, including axons, Schwann cells, and macrophages, coordinate to promote nerve regeneration. However, this capacity for repair is limited, particularly in older populations, and current treatments are insufficient. A critical component of the regeneration response is the network of cell-to-cell signaling in the injured nerve microenvironment. Sheddases are expressed in the peripheral nerve and play a role in the regulation if this cell-to-cell signaling through cleavage of transmembrane proteins, enabling the regulation of multiple pathways through cis- and trans-cellular regulatory mechanisms. Enhanced axonal regeneration has been observed in mice with deletion of the sheddase beta-secretase (BACE1), a transmembrane aspartyl protease that has been studied in the context of Alzheimer's disease. BACE1 knockout (KO) mice display enhanced macrophage recruitment and activity following nerve injury, although it is unclear whether this plays a role in driving the enhanced axonal regeneration. Further, it is unknown by what mechanism(s) BACE1 increases macrophage recruitment and activity. BACE1 has many substrates, several of which are known to have immunomodulatory activity. This review will discuss current knowledge of the role of BACE1 and other sheddases in peripheral nerve regeneration and outline known immunomodulatory BACE1 substrates and what potential roles they could play in peripheral nerve regeneration. Currently, the literature suggests that BACE1 and substrates that are expressed by neurons and Schwann cells are likely to be more important for this process than those expressed by macrophages. More broadly, BACE1 may play a role as an effector of immunomodulation beyond the peripheral nerve.

Axonal regeneration and sprouting as a potential therapeutic target for nervous system disorders.

Nervous system disorders are prevalent health issues that will only continue to increase in frequency as the population ages. Dying-back axonopathy is a hallmark of many neurologic diseases and leads to axonal disconnection from their targets, which in turn leads to functional impairment. During the course of many of neurologic diseases, axons can regenerate or sprout in an attempt to reconnect with the target and restore synapse function. In amyotrophic lateral sclerosis (ALS), distal motor axons retract from neuromuscular junctions early in the disease-course before significant motor neuron death. There is evidence of compensatory motor axon sprouting and reinnervation of neuromuscular junctions in ALS that is usually quickly overtaken by the disease course. Potential drugs that enhance compensatory sprouting and encourage reinnervation may slow symptom progression and retain muscle function for a longer period of time in ALS and in other diseases that exhibit dying-back axonopathy. There remain many outstanding questions as to the impact of distinct disease-causing mutations on axonal outgrowth and regeneration, especially in regards to motor neurons derived from patient induced pluripotent stem cells. Compartmentalized microfluidic chambers are powerful tools for studying the distal axons of human induced pluripotent stem cells-derived motor neurons, and have recently been used to demonstrate striking regeneration defects in human motor neurons harboring ALS disease-causing mutations. Modeling the human neuromuscular circuit with human induced pluripotent stem cells-derived motor neurons will be critical for developing drugs that enhance axonal regeneration, sprouting, and reinnervation of neuromuscular junctions. In this review we will discuss compensatory axonal sprouting as a potential therapeutic target for ALS, and the use of compartmentalized microfluidic devices to find drugs that enhance regeneration and axonal sprouting of motor axons.

MCT1 Deletion in Oligodendrocyte Lineage Cells Causes Late-Onset Hypomyelination and Axonal Degeneration.

Oligodendrocytes (OLs) are important for myelination and shuttling energy metabolites lactate and pyruvate toward axons through their expression of monocarboxylate transporter 1 (MCT1). Recent studies suggest that loss of OL MCT1 causes axonal degeneration. However, it is unknown how widespread and chronic loss of MCT1 in OLs specifically affects neuronal energy homeostasis with aging. To answer this, MCT1 conditional null mice were generated that allow for OL-specific MCT1 ablation. We observe that MCT1 loss from OL lineage cells is dispensable for normal myelination and axonal energy homeostasis early in life. By contrast, loss of OL lineage MCT1 expression with aging leads to significant axonal degeneration with concomitant hypomyelination. These data support the hypothesis that MCT1 is important for neuronal energy homeostasis in the aging central nervous system (CNS). The reduction in OL MCT1 that occurs with aging may enhance the risk for axonal degeneration and atrophy in neurodegenerative diseases.

Intravenous arylsulfatase A in metachromatic leukodystrophy: a phase 1/2 study.

OBJECTIVE: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A (ASA), resulting in severe motor and cognitive dysfunction. This phase 1/2 study evaluated the safety and efficacy of intravenous (IV) recombinant human ASA (rhASA; HGT-1111, previously known as Metazym) in children with MLD. METHODS: Thirteen children with MLD (symptom onset < 4 years of age) were enrolled in an open-label, nonrandomized, dose-escalation trial and received IV rhASA at 50, 100, or 200 U/kg body weight every 14 (± 4) days for 52 weeks (NCT00418561; NCT00633139). Eleven children continued to receive rhASA at 100 or 200 U/kg during a 24-month extension period (NCT00681811). Outcome measures included safety observations, changes in motor and cognitive function, and changes in nerve conduction and morphometry. RESULTS: There were no serious adverse events considered related to IV rhASA. Motor function and developmental testing scores declined during the study in all dose groups; no significant differences were observed between groups. Nerve conduction studies and morphometric analysis indicated that peripheral nerve pathology did not worsen during the study in any dose group. INTERPRETATION: IV rhASA was generally well tolerated. There was no evidence of efficacy in preventing motor and cognitive deterioration, suggesting that IV rhASA may not cross the blood-brain barrier in therapeutic quantities. The relative stability of peripheral nerve function during the study indicates that rhASA may be beneficial if delivered to the appropriate target site and supports the development of rhASA for intrathecal administration in MLD.

Renovascular Hypertension Induces Myocardial Mitochondrial Damage, Contributing to Cardiac Injury and Dysfunction in Pigs With Metabolic Syndrome.

BACKGROUND: Renovascular hypertension (RVH) often manifest with metabolic syndrome (MetS) as well. Coexisting MetS and hypertension increases cardiovascular morbidity and mortality, but the mechanisms underlying cardiac injury remain unknown. We hypothesized that superimposition of MetS induces myocardial mitochondrial damage, leading to cardiac injury and dysfunction in swine RVH. METHODS: Pigs were studied after 16 weeks of diet-induced MetS with or without RVH (unilateral renal artery stenosis), and Lean controls (n = 6 each). Systolic and diastolic cardiac function were assessed by multidetector CT, and cardiac mitochondrial morphology (electron microscopy) and myocardial function in tissue and isolated mitochondria. RESULTS: Body weight was similarly higher in MetS groups vs. Lean. RVH groups achieved significant stenosis and developed hypertension. Mitochondrial matrix density and adenosine triphosphate production were lower and H2O2 production higher in RVH groups vs. Lean and MetS. Lean + RVH (but not MetS + RVH) activated mitophagy, which was associated with decreased myocardial expression of mitophagy-related microRNAs. MetS groups exhibited higher numbers of intermitochondrial junctions, which could have prevented membrane depolarization/activation of mitophagy in MetS + RVH. Cardiac fibrosis, hypertrophy (increased left ventricular muscle mass), and diastolic function (decreased E/A ratio) were greater in MetS + RVH vs. Lean + RVH. CONCLUSIONS: MetS+RVH induces myocardial mitochondrial damage and dysfunction. MetS + RVH failed to activate mitophagy, resulting in greater cardiac remodeling, fibrosis, and diastolic dysfunction. Mitochondrial injury and impaired mitophagy may constitute important mechanisms and therapeutic targets to ameliorate cardiac damage and dysfunction in patients with coexisting MetS and RVH.

A Review of Cyber-Ranges and Test-Beds: Current and Future Trends.

Cyber situational awareness has been proven to be of value in forming a comprehensive understanding of threats and vulnerabilities within organisations, as the degree of exposure is governed by the prevailing levels of cyber-hygiene and established processes. A more accurate assessment of the security provision informs on the most vulnerable environments that necessitate more diligent management. The rapid proliferation in the automation of cyber-attacks is reducing the gap between information and operational technologies and the need to review the current levels of robustness against new sophisticated cyber-attacks, trends, technologies and mitigation countermeasures has become pressing. A deeper characterisation is also the basis with which to predict future vulnerabilities in turn guiding the most appropriate deployment technologies. Thus, refreshing established practices and the scope of the training to support the decision making of users and operators. The foundation of the training provision is the use of Cyber-Ranges (CRs) and Test-Beds (TBs), platforms/tools that help inculcate a deeper understanding of the evolution of an attack and the methodology to deploy the most impactful countermeasures to arrest breaches. In this paper, an evaluation of documented CR and TB platforms is evaluated. CRs and TBs are segmented by type, technology, threat scenarios, applications and the scope of attainable training. To enrich the analysis of documented CR and TB research and cap the study, a taxonomy is developed to provide a broader comprehension of the future of CRs and TBs. The taxonomy elaborates on the CRs/TBs dimensions, as well as, highlighting a diminishing differentiation between application areas.