Oleanolic acid exerts bone anabolic effects via activation of osteoblastic 25-hydroxyvitamin D 1-alpha hydroxylase.

Oleanolic acid (OA) is previously shown to exert bone protective effects in aged animals. However, its role in regulating osteoblastic vitamin D bioactivation, which is one of major causes of age-related bone loss, remains unclear. Our results revealed that treatment of OA significantly increased skeletal CYP27B1 expression and circulating 1,25(OH)2D3 in ovariectomized mice (p <0.01). Moreover, OA upregulated CYP27B1 protein expression and activity, as well as the vitamin D-responsive bone markers alkaline phosphatase (ALP) activity and osteopontin (OPN) protein expression, in human osteoblast-like MG-63 cells (p<0.05). CYP27B1 expression increased along with the osteoblastic differentiation of human bone marrow derived mesenchymal stem cells (hMSCs). CYP27B1 expression and cellular 1,25(OH)2D3 production were further potentiated by OA in cells at mature osteogenic stages. Notably, our study suggested that the osteogenic actions of OA were CYP27B1 dependent. In summary, the bone protective effects of OA were associated with the induction of CYP27B1 activity and expression in bone tissues and osteoblastic lineages. Hence, OA might be a potential approach for management of age-related bone loss.

PAX7, a Key for Myogenesis Modulation in Muscular Dystrophies through Multiple Signaling Pathways: A Systematic Review.

Muscular dystrophy is a heterogenous group of hereditary muscle disorders caused by mutations in the genes responsible for muscle development, and is generally defined by a disastrous progression of muscle wasting and massive loss in muscle regeneration. Pax7 is closely associated with myogenesis, which is governed by various signaling pathways throughout a lifetime and is frequently used as an indicator in muscle research. In this review, an extensive literature search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed to identify research that examined signaling pathways in living models, while quantifying Pax7 expression in myogenesis. A total of 247 articles were retrieved from the Web of Science (WoS), PubMed and Scopus databases and were thoroughly examined and evaluated, resulting in 19 articles which met the inclusion criteria. Admittedly, we were only able to discuss the quantification of Pax7 carried out in research affecting various type of genes and signaling pathways, rather than the expression of Pax7 itself, due to the massive differences in approach, factor molecules and signaling pathways analyzed across the research. However, we highlighted the thorough evidence for the alteration of the muscle stem cell precursor Pax7 in multiple signaling pathways described in different living models, with an emphasis on the novel approach that could be taken in manipulating Pax7 expression itself in dystrophic muscle, towards the discovery of an effective treatment for muscular dystrophy. Therefore, we believe that this could be applied to the potential gap in muscle research that could be filled by tuning the well-established marker expression to improve dystrophic muscle.

Comprehensive review of SGLT2 inhibitors' efficacy through their diuretic mode of action in diabetic patients.

SGLT2 inhibitors (SGLT2i) are now the mainstay therapy for both diabetes and heart failure. Post-hoc publications, meta-analysis, and conference presentations of the eight SGLT2i Cardiovascular Outcomes trials (CVOTS) done in diabetic patients constantly echo that this class of drug decreases mortality, reduces cardiovascular events, and prevents heart failure and kidney disease. This review of medical agencies' SGLT2i analysis (FDA and EMA) helps to understand the reality of SGLT2i results in those trials, avoiding to consider observational and statistically undemonstrated endpoints as validated. They also confirmed the unique diuretic mode of action of SGLT2i, promoting osmotic diuresis, and its potential adverse events secondary to hypovolemia and hematocrit increase. They also support the understanding that the beliefs in SGLT2i morbi-mortality benefits are largely overstated mostly based on undemonstrated endpoints. Finally, it is clear that SGLT2i's antidiabetic action, secondary to its renal mode of action, plateaued after a few months and decreased strongly over time, questioning its long-term goal of maintaining diabetic patients' HbA1c below 7%. Also, this effect in patients with renal impairment is quasi null. We think that this review would be very helpful to every physician treating diabetic patients to better balance belief and reality of SGLT2i prescription effects.

Identification of the Microbial Transformation Products of Secoisolariciresinol Using an Untargeted Metabolomics Approach and Evaluation of the Osteogenic Activities of the Metabolites.

Secoisolariciresinol (SECO) is one of the major lignans occurring in various grains, seeds, fruits, and vegetables. The gut microbiota plays an important role in the biotransformation of dietary lignans into enterolignans, which might exhibit more potent bioactivities than the precursor lignans. This study aimed to identify, synthesize, and evaluate the microbial metabolites of SECO and to develop efficient lead compounds from the metabolites for the treatment of osteoporosis. SECO was fermented with human gut microbiota in anaerobic or micro-aerobic environments at different time points. Samples derived from microbial transformation were analyzed using an untargeted metabolomics approach for metabolite identification. Nine metabolites were identified and synthesized. Their effects on cell viability, osteoblastic differentiation, and gene expression were examined. The results showed that five of the microbial metabolites exerted potential osteogenic effects similar to those of SECO or better. The results suggested that the enterolignans might account for the osteoporotic effects of SECO in vivo. Thus, the presence of the gut microbiota could offer a good way to form diverse enterolignans with bone-protective effects. The current study improves our understanding of the microbial transformation products of SECO and provides new approaches for new candidate identification in the treatment of osteoporosis.

Correlation Between Hemoglobin Glycation Index Measured by Continuous Glucose Monitoring With Complications in Type 1 Diabetes.

OBJECTIVE: HbA1C is the "gold standard" parameter to evaluate glycemic control in diabetes; however, its correlation with mean glucose is not always perfect. The objective of this study was to correlate continuous glucose monitoring (CGM)-derived hemoglobin glycation index (HGI) with microvascular complications. METHODS: We conducted a cross-sectional study including permanent users of CGM with type 1 diabetes mellitus or latent autoimmune diabetes of the adult. HGI was estimated, and presence of microvascular complications was compared in subgroups with high or low HGI. A logistic regression analysis to assess the contribution of high HGI to chronic kidney disease (CKD) was performed. RESULTS: In total, 52 participants who were aged 39.7 ± 14.7 years, with 73.1% women and 15.5 years (IQR, 7.5-29 years) since diagnosis, were included; 32.7% recorded diabetic retinopathy, 25% CKD, and 19.2% neuropathy. The median HbA1C was 7.6% (60 mmol/mol) and glucose management indicator (GMI) 7.0% (53 mmol/mol). The average HGI was 0.55% ± 0.66%. The measured HbA1C was higher in the group with high HGI (8.1% [65 mmol/mol] vs 6.9% [52 mmol/mol]; P < .001), whereas GMI (7.0% [53 mmol/mol] vs 7.0% [53 mmol/mol]; P = .495) and mean glucose were similar in both groups (153 mg/dL vs 153 mg/dL; P = .564). In the high HGI group, higher occurrence of CKD (P = .016) and neuropathy were observed (P = .025). High HGI was associated with increased risk of CKD (odds ratio [OR]: 5.05; 95% CI: 1.02-24.8; P = .04) after adjusting for time since diagnosis (OR: 1.09; 95% CI: 1.02-1.16; P = .008). CONCLUSION: High HGI measured by CGM may be a useful marker for increased risk of microvascular diabetic complications.

The promising role of risk scoring system for Cushing syndrome: Time to reconsider current screening recommendations.

Despite the current screening approach for Cushing syndrome (CS), delayed diagnosis is common due to broad spectrum of presentation, poor discriminant symptoms featured in diabetes and obesity, and low clinical index of suspicion. Even if initial tests are recommended to screen CS, divergent results are not infrequent. As global prevalence of type 2 diabetes and obesity increases, CS may not be frequent enough to back routine screening to avoid false-positive results. This represents a greater challenge in countries with limited health resources. The development of indexes incorporates clinical features and biochemical data that are largely used to provide a tool to predict the presence of disease. In clinical endocrinology, indexes have been used in Graves' ophthalmology, hirsutism, and hypothyroidism. The use of clinical risk scoring system may assist clinicians in discriminating CS in the context of at-risk populations and, thus, may provide a potential intervention to decrease time to diagnosis. Development and validation of clinical model to estimate pre-test probability of CS in different geographic source population may help to establish regional prediction model for CS. Here, we review on the latest progress in clinical risk scoring system for CS and attempt to raise awareness for the use, validation, and/or development of clinical risk scores in CS.

Linking maternal involvement in child online learning to child adjustment during the COVID-19 pandemic: The moderating role of maternal mindfulness.

In the face of COVID-19, many schools have to educate their students using online activities. During this time, whether and how parents are involved may be of particular importance for young children-who are less able to learn independently via the Internet due to their developmental immaturity. Therefore, this study examined the cross-sectional association of maternal involvement in child online learning with child adjustment during the COVID-19 pandemic and tested maternal mindfulness as a moderator. Data were collected from 236 mothers of kindergarten-aged children (mean age = 55.91 months; 75% of them were girls) during the fourth wave of COVID-19 outbreak in Hong Kong, China. Using paper-and-pencil questionnaires, mothers rated their involvement and mindfulness and their children's pre-academic ability and internalizing and externalizing behaviors and provide demographic information. Regression models revealed that maternal involvement was associated positively with child pre-academic ability and negatively with child internalizing behaviors, but such associations were only significant for children with more mindful mothers. Maternal mindfulness did not moderate the negative association between maternal involvement and child externalizing behaviors. Findings highlighted the role of maternal mindfulness in child development, suggesting that it may be crucial to promote maternal involvement and mindfulness during the pandemic and perhaps beyond.

Does Mindfulness Moderate the Link of Worry About COVID-19 With Adjustment? An Actor-Partner Interdependence Model Approach.

Objectives: COVID-19 constitutes an unprecedented mental health challenge to the world. At this critical time, it is important to identify factors that may boost individuals' well-being or render individuals more resistant to the negative impact of COVID-19-related stressors. The goals of this study were to examine whether individuals' and their partners' worry about COVID-19 were linked to individuals' psychological, social, and cognitive adjustment and test individuals' and their partners' mindfulness as possible moderators. Methods: Cross-sectional, dyadic data were collected from 211 Chinese couples with kindergarten-aged children living in Hong Kong, China, during its fourth major outbreak of COVID-19 (between December 2020 and January 2021). Using paper-and-pencil questionnaires, fathers and mothers independently reported their worry about COVID-19, mindfulness, depressive symptoms, social difficulties, and cognitive problems. Results: Actor-Partner-Interdependence Models revealed that, controlling for individuals' gender and education levels, individuals' worry about COVID-19 and mindfulness were positively and negatively associated with their own depressive symptoms, social difficulties, and cognitive problems, respectively. The worry of individuals' partners was also positively associated with individuals' depressive symptoms and social difficulties. These associations, however, were only significant when the partners had low but not high levels of mindfulness. Conclusions: Our study highlighted the importance of studying the potential benefits of mindfulness at not only the individual but also the dyadic level.

Biochemical and Hematological Relationship with the Evaluation of Autonomic Dysfunction by Heart Rate Recovery in Patients with Asthma and Type 2 Diabetes.

There are several methods to assess the function of the autonomic nervous system. Among them, heart rate recovery (HRR) is an accepted, easy, low-cost technique. Different pathological conditions have been related to the development of autonomic dysfunction. Our study aimed to evaluate the relationship between HRR and HRR-derived parameters in ambulatory patients with asthma or type 2 diabetes followed at the National Institutes of Health in Mexico City. A total of 78 participants, 50 women and, 28 men were enrolled; anthropometric, respiratory evaluations, and fasting blood samples were taken before participants performed a 6-min walking test (6MWT). Abnormal HRR was defined as a drop of ≤8 and ≤11 beats/min at 1 or 2 min and correlated negatively with basal oxygen saturation at 1 min. Heart rate at 1 min, correlated negatively with final oxygen saturation (p < 0.01). Statistically significant negative correlations were also observed between red cell count and white blood cell count and HOMA-IR with a p < 0.01. Since discrete hematological but significant changes correlated with HRR and HRR-derived parameters, we consider that these measures are helpful in clinical settings to identify subclinical autonomic dysfunction that permits us to prevent or anticipate chronic and fatal clinical outcomes.

Association of estimated glucose disposal rate and chronic diabetic complications in patients with type 1 diabetes.

INTRODUCTION: The role of insulin resistance in diabetic chronic complications among individuals with type 1 diabetes (T1D) has not been clearly defined. The aim of this study was to examine the performance of insulin resistance, evaluated using the estimated glucose disposal rate (eGDR) for the identification of metabolic syndrome (MS) and diabetic chronic complications. METHODS: Cross-sectional study in a tertiary care centre. We included patients of 18 years and older, with at least 6 months of T1D duration. Anthropometric, clinical and biochemical data were collected. RESULTS: Seventy patients, 41 (58.6%) women, with a median age of 36.6 years (range 18-65). Mean age of onset and duration of diabetes was 13.5 ± 6.5 and 23.6 ± 12.2 years, respectively. Twenty-one (30%) patients met the metabolic syndrome (MS) criteria. Patients with MS had lower eGDR compared to patients without (5.17 [3.10-8.65] vs. 8.86 [6.82-9.85] mg/kg/min, respectively, p = .003). Median eGDR in patients with nephropathy, retinopathy and neuropathy compared with those without was 6.75 (4.60-8.20) versus 9.53 (8.57-10.3); p < .001, 6.45 (4.60-7.09) versus 9.50 (8.60-10.14); p < .001, 5.56 (4.51-6.81) versus 9.49 [8.19-10.26] mg/kg/min; p < .001, respectively. The eGDR showed an area under the curve of 0.909, 0.879, 0.897 and 0.836 for the discrimination of MS, retinopathy, neuropathy and nephropathy, respectively. CONCLUSIONS: Patients with T1D diabetic complications have higher insulin resistance. The eGDR discriminates patients with chronic diabetic complications and MS. While more ethnic-specific studies are required, this study suggests the possibility to incorporate eGDR into routine diabetes care.

Occurrence of Klinefelter Syndrome Mosaic 45,X/46,XY/47,XXY/48,XXYY/48,XXXY and Primary Hyperparathyroidism.

OBJECTIVE: The presence of primary hyperparathyroidism (PHPT) and Klinefelter syndrome (KS) is rare, and its association with KS mosaicism is even rarer. We report an unusual combination of these entities with a mild phenotype of KS. METHODS: The patient was a 44-year-old male with a history of PHPT who had recurrent urolithiasis despite being treated with a successful parathyroidectomy. On examination, he had axillary hair growth, bilateral gynecomastia, a large port-wine stain at the right hemithorax and upper right limb, and genitalia and pubic hair corresponding to Tanner IV classification with small, normal consistency testicles. RESULTS: Laboratory findings were unremarkable except for a slightly elevated luteinizing hormone, which was normal on repeat testing. Because of the picture of unexplained gynecomastia, laboratory findings, and low-volume testis, a diagnosis of KS was considered. Chromosomal analysis revealed a rare 45,X/46,XY/47,XXY/48,XXYY/48,XXXY KS mosaic. CONCLUSIONS: KS phenotypes are largely variable, and their association with PHPT remains to be elucidated.

Patients with Gilbert syndrome and type 2 diabetes have lower prevalence of microvascular complications.

OBJECTIVE: Accumulating clinical evidence indicates an inverse relationship between oxidative stress and unconjugated hyperbilirubinemia. This study aimed to compare the prevalence of diabetes microvascular complications in patients with Gilbert syndrome and type 2 diabetes mellitus (T2D). METHODS: A total of 1200 electronic records with T2D were reviewed. From them, 50 patients with Gilbert syndrome (cases [indirect bilirubin ≥1.2 mg/dl without evidence of hemolysis or liver disease]) and 50 controls (T2D without hyperbilirubinemia) were included. Linear and logistic regression models were performed to evaluate the independent association between indirect hyperbilirubinemia with microvascular complications related with T2D. RESULTS: Both case and control group had the same proportion of gender (female = 20 [40 %]) and diabetes duration (14.0 ± 6.5 years) and similar mean of age (60 ± 9.6 and 60 ± 9.2 years, respectively, p = 0.91). The median of unconjugated bilirubin of case and control group was 1.4 (1.2-1.6) vs. 0.4 (0.2-0.6) mg/dl (p < 0.001), respectively. Patients with elevated unconjugated bilirubin had less urine albumin-creatinine ratio compared with control group (8.5 [4.3-23] vs. 80 [8-408] mg/g, p < 0.001), and lower rate of diabetes microvascular complications and metabolic syndrome. After adjustment for BMI, age, HbA1c, blood pressure, triglycerides, and the metabolic syndrome, the lineal regression analysis showed that unconjugated bilirubin protects against microalbuminuria in T2D patients (ß = -414.11, 95 % CI [-747.9, -80.3], p = 0.006. Also, unconjugated hyperbilirubinemia was independently associated with a better glomerular filtration rate (GFR) (ß = 9.87, 95 % CI [1.5, 18.3], P = 0.02). CONCLUSIONS: Patients with Gilbert syndrome and T2D had a lower prevalence of diabetes microvascular complications.

Differentiating Among Type 1, Type 2 Diabetes, and MODY: Raising Awareness About the Clinical Implementation of Genetic Testing in Latin America.

OBJECTIVE: To describe a case of maturity-onset diabetes of the young (MODY) to highlight the importance of a correct diabetes diagnosis. METHODS: We describe a Mexican family misdiagnosed with T1D and T2D. RESULTS: A 36-year-old woman with diabetes and adverse outcomes during 2 pregnancies had been diagnosed with T2D 10 years ago. Genetic testing was performed due to clinical and family history, which showed a pathogenic heterozygous variant c.544G>T (p.Val182Leu) in the GCK gene. This mutation was also confirmed in most of the family members who had been diagnosed with diabetes. CONCLUSION: This case highlights the need for a correct diabetes classification. Reassessment of diabetes etiology is justified, especially in individuals with unclear clinical presentation or when family history is suggestive.

A Novel, Likely Pathogenic MAX Germline Variant in a Patient With Unilateral Pheochromocytoma.

CONTEXT: Inherited MYC-associated factor X (MAX) gene pathogenic variants (PVs) increase risk for pheochromocytomas (PCCs) and/or paragangliomas (PGLs) in adults and children. There is little clinical experience with such mutations. OBJECTIVE: This report highlights an important approach. METHODS: Clinical assessment, including blood chemistry, imaging studies, and genetic testing were performed. RESULTS: A 38-year-old Hispanic woman was diagnosed with PCC in 2015, treated with adrenalectomy, and referred to endocrinology clinic. Notably, she presented to her primary care physician 3 years earlier complaining of left flank pain, intermittent diaphoresis, and holocranial severe headache. We confirmed severe hypertension (180/100 mm Hg) over multiple antihypertensive regimens. Biochemical and radiological studies workup revealed high plasma metanephrine of 255 pg/mL (normal range, < 65 pg/mL) and plasma normetanephrine of 240 pg/mL (normal range, < 196 pg/mL). A noncontrast computed tomography scan of the abdomen revealed a 4.2 × 4.3 × 4.9-cm, round-shaped and heterogenous contrast enhancement of the left adrenal gland, and a 2-mm nonobstructive left kidney stone. A presumptive diagnosis of secondary hypertension was made. After pharmacological therapy, laparoscopic left adrenalectomy was performed and confirmed the diagnosis of pheochromocytoma. Based on her age, family history, and a high suspicion for genetic etiology, genetic testing was performed that revealed the presence of a novel likely pathogenic variant involving a splice consensus sequence in the MAX gene, designated c0.64-2A > G. CONCLUSION: The phenotype of MAX PV-related disease and paraganglioma are highlighted. The novel c0.64-2A > G mutation is reported here and should be considered in the diagnostic workup of similar cases.

The effect of oral omega-3 polyunsaturated fatty acid supplementation on muscle maintenance and quality of life in patients with cancer: A systematic review and meta-analysis.

BACKGROUND & AIMS: Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as a potential therapy for cancer-related malnutrition, which affects up to 70% of patients with cancer. The aim of this systematic review and meta-analysis was to examine the effects of oral omega-3 PUFA supplementation on muscle maintenance, quality of life, body weight and treatment-related toxicities in patients with cancer. METHODS: Randomised controlled trials in patients with cancer aged ≥18 years were retrieved from 5 electronic databases: MEDLINE (via PubMed), EMBASE, CENTRAL, CINAHL (via EBSCOhost), and Web of Science, from database inception until 31st of December 2019. The quality of included studies was assessed using the Cochrane risk of bias tool. Trials supplementing ≥600 mg/d omega-3 PUFA (oral capsules, pure fish oil or oral nutritional supplements) compared with a control intervention for ≥3 weeks were included. Meta-analyses were performed in RevMan to determine the mean differences (MD) in muscle mass, quality of life and body weight, and odds ratio (OR) for the incidence of treatment-related toxicities between omega-3 PUFA and control groups with 95% confidence intervals (CI) and I2 for heterogeneity. RESULTS: We included 31 publications in patients with various types of cancers and degrees of malnutrition. The Cochrane risk of bias tool graded most trials as 'unclear' or 'high' risk of bias. Meta-analyses showed no significant difference between omega-3 PUFA supplements and control intervention on muscle mass, quality of life and body weight. Oral omega-3 PUFA supplements reduced the likelihood of developing chemotherapy-induced peripheral neuropathy (OR: 0.20; 95% CI: 0.10-0.40; p < 0.001; I2 = 0%). CONCLUSION: This systematic review and meta-analysis indicates that oral omega-3 PUFA supplementation does not improve muscle maintenance, quality of life or body weight in patients with cancer, but may reduce the incidence of chemotherapy-induced peripheral neuropathy. Well-designed large-scale randomised controlled trials in homogenous patient cohorts are required to confirm these findings.

Recent Understanding and Future Directions of Recurrent Corticotroph Tumors.

Corticotroph tumors (CTs) are pituitary neoplasms arising from the Tpit lineage, which may or not express adrenocorticotrophic hormone (ACTH). Functioning CTs cause Cushing's disease (CD), which has high morbidity and mortality due to hypercortisolemia. "Non-functioning" or silent CTs (SCT) and the Crooke's cell subtypes do not cause CD and may be asymptomatic until manifested by compressive symptoms and are more frequently found as macroadenoma. Both tend toward more aggressive behavior, recurrence, and a higher rate of malignant transformation to pituitary carcinoma. Tumorigenesis involves genetic, epigenetic, and post-transcriptional disruption of cell-cycle regulators, which increase cell proliferation, POMC overexpression, ACTH transcription, and/or hypersecretion. Furthermore, functioning CTs develop resistance to glucocorticoid-mediated negative feedback on ACTH secretion, through increased expression of testicular orphan nuclear receptor 4 (TR4), heat-shock protein 90 (HSP90), and loss-of-function mutation of CDK5 and ABL enzyme substrate 1 (CABLES1) gene. Overt autonomous hypercortisolemia is difficult to control, and multiple diagnostic studies and therapeutic modalities are commonly required. Cell-cycle regulation depends mainly on p27, cyclin E, cyclin-dependent kinases (CDKs), and the retinoblastoma protein (Rb)/E2F1 transcription factor complex. Gain-of-function mutations of ubiquitin-specific protease (USP) 8, USP48, and BRAF genes may subsequently cause overexpression of epithelial growth factor receptor (EGFR), and enhance POMC transcription, cell proliferation, and tumor growth. Epigenetic changes through micro RNAs and decreased DNA deacetylation by histone deacetylase type 2 (HDAC2), may also affect tumor growth. All the former mechanisms may become interesting therapeutic targets for CTs, aside from temozolomide, currently used for aggressive tumors. Potential therapeutic agents are EGFR inhibitors such as gefitinib and lapatinib, the purine analog R-roscovitine by dissociation of CDK2/Cyclin E complex, the HSP90 inhibitor silibinin (novobiocin), to reduce resistance to glucocorticoid-mediated negative feedback, and BRAF inhibitors vemurafenib and dabrafenib in BRAF V600E positive tumors. This review summarizes the molecular mechanisms related to CTs tumorigenesis, their diagnostic approach, and provides an update of the potential novel therapies, from the lab bench to the clinical translation.

Comparison of Clinical Tests for Peripheral Diabetic Neuropathy in a Type 1 Diabetes Cohort.

OBJECTIVE: To examine the performance and agreement of 5 modalities for testing sensory neuropathy against a neurothesiometer among Hispanic patients with type 1 diabetes (T1D) in an outpatient setting. METHODS: A cross-sectional study was conducted at a tertiary reference center in Mexico City. Sensitivity, specificity, predictive values, and likelihood ratios were calculated using a VibraTip device, 128 Hz tuning fork, and the Semmes-Weinstein 5.07/10 g monofilament test, Ipswich touch test (IpTT), and pinprick test (PPT). The VPT obtained using a neurothesiometer was used as the standard. Agreement between tests was calculated using kappa coefficients. RESULTS: Our study included 78 patients (156 examinations), of whom 56.4% were females. The mean age was 38.2 ± 13.0 years, and the mean body mass index was 24.6 ± 4.8 kg/m2. The best sensitivity was found for IpTT and VibraTip (89.7% and 79.3%, respectively), while the PPT and IpTT had the highest positive predictive values (94.4% and 92.9%, respectively). The highest kappa coefficients were obtained for the IpTT vs neurothesiometer (kappa coefficient [κ] = 0.893, P < .001), followed by VibraTip vs neurothesiometer (κ = 0.782, P < .001). The VibraTip vs IpTT also had a substantial agreement (κ= 0.713, P < .001). CONCLUSION: Our findings demonstrated that the IpTT had the best diagnostic performance and agreement compared with the standard in this cohort of Hispanic patients with T1D. The IpTT is a useful, simple test for diabetic neuropathy screening. These findings support its inclusion in future guidelines for diabetic foot examination.

Mass Screening Is Associated with Low Rates of Acute Kidney Injury among COVID-19 Patients in Hong Kong.

INTRODUCTION: Renal involvement in COVID-19 is less well characterized in settings with vigilant public health surveillance, including mass screening and early hospitalization. We assessed kidney complications among COVID-19 patients in Hong Kong, including the association with risk factors, length of hospitalization, critical presentation, and mortality. METHODS: Linked electronic records of all patients with confirmed COVID-19 from 5 major designated hospitals were extracted. Duplicated records due to interhospital transferal were removed. Primary outcome was the incidence of in-hospital acute kidney injury (AKI). Secondary outcomes were AKI-associated mortality, incident renal replacement therapy (RRT), intensive care admission, prolonged hospitalization and disease course (defined as >90th percentile of hospitalization duration [35 days] and duration from symptom onset to discharge [43 days], respectively), and change of estimated glomerular filtration rate (GFR). Patients were further stratified into being symptomatic or asymptomatic. RESULTS: Patients were characterized by young age (median: 38.4, IQR: 28.4-55.8 years) and short time (median: 5, IQR: 2-9 days) from symptom onset to admission. Among the 591 patients, 22 (3.72%) developed AKI and 4 (0.68%) required RRT. The median time from symptom onset to in-hospital AKI was 15 days. AKI increased the odds of prolonged hospitalization and disease course by 2.0- and 3.5-folds, respectively. Estimated GFR 24 weeks post-discharge reduced by 7.51 and 1.06 mL/min/1.73 m2 versus baseline (upon admission) in the AKI and non-AKI groups, respectively. The incidence of AKI was comparable between asymptomatic (4.8%, n = 3/62) and symptomatic (3.7%, n = 19/519) patients. CONCLUSION: The overall rate of AKI among COVID-19 patients in Hong Kong is low, which could be attributable to a vigilant screening program and early hospitalization. Among patients who developed in-hospital AKI, the duration of hospitalization is prolonged and kidney function impairment can persist for up to 6 months post-discharge. Mass surveillance for COVID-19 is warranted in identifying asymptomatic subjects for earlier AKI management.

Sibling relationship qualities and peer and academic adjustment: A multi-informant longitudinal study of Chinese families.

Very little is known about sibling influences on child adjustment in non-Western communities. Therefore, this multi-informant study examined the longitudinal associations of sibling warmth and conflict with peer and academic adjustment and tested birth order and gender as moderators among Chinese families from Hong Kong, China. On two occasions separated by about 12 months, data were collected from two siblings in each of 189 families. Data were also collected from the mothers and class teachers of these siblings. At Time 1, older and younger siblings' ages averaged 10.06 years (SD = 1.07) and 7.82 years (SD = 0.95), respectively. Among older siblings, 31% were boys, and among younger siblings, 48% were boys. At Time 1, siblings rated their warmth and conflict with each other. At Times 1 and 2, class teachers rated siblings on their peer exclusion, prosocial/communication skills, and academic performance. At Time 1, mothers rated their warmth and conflict with each sibling and provided family demographic information. Multilevel models revealed that, controlling for mother warmth and conflict and demographic factors, sibling warmth predicted increases in prosocial/communication skills and increases in academic performance, and sibling conflict predicted decreases in academic performance. Moreover, for younger boys, sibling conflict predicted increases in peer exclusion. Theoretically, findings highlighted the unique roles of sibling warmth and conflict, as related but distinct factors, in understanding the peer and academic adjustment of Chinese children. Practically, findings pointed to the utility of improving sibling relationships to promote positive child development. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Familial hypertriglyceridemia: an entity with distinguishable features from other causes of hypertriglyceridemia.

BACKGROUND: Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. METHODS: This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. RESULTS: Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901-0.970, 98.5% sensitivity, 92.2% specificity, P < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG. CONCLUSIONS: The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.