Clinical characteristics and prognostic marker for hospitalization in children with influenza infection in an emergency setting.

BACKGROUND: Influenza is a main cause of illnesses during seasonal outbreaks. Identifying children with influenza who may need hospitalization may lead to better influenza outcomes. OBJECTIVE: To identify factors associated with the severity of influenza infection, specifically among children who were admitted to the hospital after being diagnosed with influenza at the emergency department. METHODS: A retrospective cohort study was conducted among pediatric patients (age < 18 years) with a positive influenza rapid test who visited the emergency department at Srinagarind hospital between January2015-December2019. The dependent variable was hospital admission, while the independent variables included clinical parameters, laboratory results, and emergency severity index(ESI). The association between these variables and hospital admission was analyzed. RESULTS: There were 542 cases of influenza included in the study. The mean age was 7.50 ± 4.52 years. Males accounted for 52.4% of the cases. A total of 190(35.05%) patients, needed hospitalization. Patients with pneumonia, those who required hospitalization or were admitted to the critical care unit, consistently exhibited an elevated absolute monocyte count and a reduced lymphocyte-to-monocyte ratio (LMR). Various factors contribute to an increased risk for hospitalization, including ESI level 1-2, co-morbidity in patients, age < 1 year old, and an LMR below 2. CONCLUSIONS: ESI level 1-2 and co-morbidity in patients represent significant risk factors that contribute to higher hospitalization admissions. A LMR below 2 can be used as a prognostic marker for hospitalization in children with influenza infection.

Survey of Thai Physicians' Practice in Pediatric Septic Shock.

(1) Background: Sepsis management in children is crucial, especially in emergency services. This study aims to evaluate Thai physicians' knowledge gaps in the emergency management of sepsis in children and to evaluate their adherence to the current sepsis clinical practice guidelines. (2) Methods: This is a cross-sectional survey of Thai physicians' management of septic shock in children. The survey was conducted through online questionnaires from March 2019-April 2019. (3) Results: Of the 366 responders, 362 (98.9%) were completed. Most of the responders were general practitioners (89.2%) and pediatricians (10.8%). The time from positive sepsis screening to being evaluated by physicians within 15 min was reported by 83.9%. The most common choice of fluid resuscitation was normal saline solution (77.3%). The practice of a fluid loading dose (20 mL/kg) consistent with the guidelines was 56.3%. The selection of the first vasoactive agent in warm shock (norepinephrine) and cold shock (epinephrine) according to recommendations in the guidelines was 74.3% and 36.2%, respectively. There was a significant difference between general practitioners and pediatricians in terms of knowledge about initial fluid resuscitation and the optimal vasoactive agent in cold shock (p-value < 0.001). In the multivariate model, factors associated with the guideline-based decision-making of vasoactive agent choice for cold shock were specialist training (pediatrician) and the completion of sepsis management training certification, with adjusted odds ratios (AORs) of 7.81 and 2.96, but working experience greater than ten years was inconsistent with the guideline-based decision-making (AOR 0.14). (4) Conclusions: Thai clinicians were unfamiliar with pediatric sepsis therapy standards, specifically the quantity of early fluid resuscitation and the appropriate vasoactive medications for cold shock. To encourage adherence to the guidelines, we propose a regularly required training course on pediatric sepsis management.

Meta-Analysis of Prophylactic Renal Replacement Therapy after Cardiac Catheterization in Patients with Chronic Kidney Disease.

BACKGROUND: The benefits of prophylactic renal replacement therapy after cardiac catheterization in patients with chronic kidney disease remain unclear. The aim of this study is to confirm the benefit of prophylactic renal replacement therapy after cardiac catheterization. METHODS: We systematically searched for studies published from inception to December 2022 examining the benefits of prophylactic renal replacement therapy after cardiac catheterization in MEDLINE and EMBASE. Data analysis was performed according to the PRISMA statement using the Mantel-Haenszel method. RESULTS: Five studies met the inclusion criteria, which comprised of 532 chronic kidney disease patients who underwent coronary angiography (268 had prophylactic renal replacement therapy and 264 did not have prophylactic renal replacement therapy). The pooled analysis revealed a non-significant decreased risk of 1-year mortality in chronic kidney disease patients who underwent coronary angiography and prophylactic renal replacement therapy compared to those who did not have prophylactic renal replacement therapy (RR = 0.59; P =.18; CI: 0.28-1.2795, I2 = 60.4%). The risk of hemodialysis during hospitalization and renal replacement therapy requirement in 1 year in chronic kidney disease patients who underwent coronary angiography and prophylactic renal replacement therapy were lower than in those who did not have prophylactic renal replacement therapy (RR = 0.13; P =.001; CI: 0.04-0.43, I2 = 9.1% and RR = 0.29; P =.015; CI: 0.11-0.78, I2 = 49.9%, respectively). The sensitivity analysis demonstrated that the overall findings remained consistent and did not significantly alter. CONCLUSIONS: Prophylactic renal replacement therapy did not seem to lower 1-year mortality among chronic kidney disease patients who underwent coronary angiography. However, prophylactic renal replacement therapy appeared to reduce the risk of hemodialysis during hospitalization and renal replacement therapy requirement in 1 year.

Effectiveness of a Mobile App (KhunLook) Versus the Maternal and Child Health Handbook on Thai Parents' Health Literacy, Accuracy of Health Assessments, and Convenience of Use: Randomized Controlled Trial.

BACKGROUND: Children of parents who have higher health literacy (HL) benefit more from preventive child health care. Digital interventions have been used to improve parents' HL with high satisfaction. KhunLook is a Thai mobile app conceived using strategies to improve HL. It was developed to assist parents in assessing and keeping track of their child's health in complement to the standard Maternal and Child Health Handbook (MCHH). OBJECTIVE: This trial focuses on the effectiveness of using the KhunLook app with the MCHH and standard care (intervention) compared with the conventional MCHH and standard care (control) on parents' HL. Data on accuracy of parents' assessment of their child's health and growth as well as convenience of use of the tool (app or MCHH) in the well-child clinic were collected at 2 visits (immediate=visit 1, and intermediate=visit 2). METHODS: Parents of children under 3 years of age who (1) had a smartphone or tablet and the MCHH and (2) could participate in 2 visits, 2-6 months apart at Srinagarind Hospital, Khon Kaen, Thailand, were enrolled in this 2-arm parallel randomized controlled trial between April 2020 and May 2021. Parents were randomized 1:1 to 2 groups. At visit 1, data on demographics and baseline HL (Thailand Health Literacy Scales) were collected. Parents in the app group used the KhunLook app and the control group used their child's handbook to assess their child's growth, development, nutrition and feeding, immunization status and rated the convenience of the tool they used. At visit 2, they repeated the assessments and completed the HL questionnaire. RESULTS: A total of 358 parents completed the study (358/408, 87.7%). After the intervention, the number of parents with high total HL significantly increased from 94/182 (51.6%) to 109/182 (59.9%; 15/182; Δ 8.2%; P=.04), specifically in the health management (30/182; Δ 16.4%; P<.001) and child health management (18/182; Δ 9.9%; P=.01) domains in the app group, but not in the control group. Parents in the app group could correctly assess their child's head circumference (172/182, 94.5% vs 124/176, 70.5%; P<.001) and development (173/182, 95.1% vs 139/176, 79.0%; P<.001) better than those in the control group at both visits. A higher proportion of parents in the app group rated their tool as very easy or easy to use (174-181/182, 95.6%-99.5% vs 141-166/176, 80.1%-94.3%; P<.001) on every item since the first visit. CONCLUSIONS: Our results suggest the potential of a smartphone app (KhunLook) to improve parents' HL as well as to promote superior accuracy of parents' assessment of their child's head circumference and development, with a similar effect on weight, height, nutrition and feeding, and immunization as in traditional interventions. Using the KhunLook app is useful and more convenient for parents in promoting a healthy child preventive care during early childhood. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20200312003; https://www.thaiclinicaltrials.org/show/TCTR20200312003.

Prevalence and risk factors for pediatric acute and chronic malnutrition: A multi-site tertiary medical center study in Thailand.

BACKGROUND AND OBJECTIVES: Malnutrition is a major public health concern that increases morbidity and mortality in hospitalized patients, particularly those in developing countries. This study aimed to investigate its prevalence, risk factors, and impact on clinical outcomes in hospitalized children and adolescents. METHODS AND STUDY DESIGN: We conducted a prospective cohort study in patients aged 1 month to 18 years who were admitted to four tertiary care hospitals between December 2018 and May 2019. We collected demographic data, clinical information, and nutritional assessment within 48 hours of admission. RESULTS: A total of 816 patients with 883 admissions were included. Their median age was 5.3 years (interquartile range 9.3). Most patients (88.9%) were admitted with mild medical conditions (e.g., minor infection) or noninvasive procedures. The prevalence of overall malnutrition was 44.5%, while that of acute and chronic malnutrition was 14.3% and 23.6%, respectively. Malnutrition was significantly associated with age ≤2 years, preexisting diseases (cerebral palsy, chronic cardiac diseases, and bronchopulmonary dysplasia), and muscle wasting. Addi-tional risk factors for chronic malnutrition included biliary atresia, intestinal malabsorption, chronic kidney disease, as well as inability to eat and decreased food intake for >7 days. Malnourished patients had a significantly longer hospitalization duration, higher hospital cost, and nosocomial infection rates than did well-nourished patients. CONCLUSIONS: Patients with chronic medical conditions on admission are at risk for malnutrition. Therefore, determination of admission nutritional status must be assessed, and its management are requisites for improved inpatient outcomes.

Reactogenicity and immunogenicity of the intradermal administration of BNT162b2 mRNA vaccine in healthy adults who were primed with an inactivated SARS-CoV-2 vaccine.

Because of the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), safe and effective vaccines are urgently required. The shortage of effective vaccines is a major challenge in many developing countries. We studied intradermal (ID) fractional dose BNT162b2 mRNA (Comirnaty®, Pfizer-BioNTech) as a booster dose in healthy adults who were previously immunized with an inactivated SARS-CoV-2 vaccine. This is a retrospective cohort study that included healthy adults who were immunized with two doses of inactivated SARS-CoV-2 vaccine and received a booster dose with ID fractional dose or intramuscular (IM) full-dose BNT162b2 mRNA between August 1 to August 15, 2021. The primary endpoint was safety that included local and systemic adverse reactions. The secondary endpoints were levels of SARS-CoV-2 spike protein receptor-binding domain IgG antibody (anti-S-RBD IgG) and neutralizing antibody activity against the Delta variant (B.1.617.2) using surrogate viral neutralization test (sVNT) 3 weeks after the booster dose. A total of 43 healthy adults (median age of 31 years) were included in the study; among them, 23 participants received ID fractional dose (6 µg) BNT162b2 mRNA, and 20 participants received IM full-dose (30 µg) BNT162b2 mRNA. No serious adverse reactions were observed. Local adverse reactions occurred more frequently in the ID group. No differences were observed in the baseline level of anti-S-RBD IgG (289 vs 286 AU/mL, p > 0.9, in the ID and IM groups, respectively). After booster, anti-S-RBD IgG titer increased to 13294 (9255-19573) AU/mL in the ID group and 23456 (16943-38539) AU/mL in the IM group. All participants in the IM group and 95.6 % of participants in the ID group had seroconversion evaluated by sVNT (≥68 % inhibition to the Delta variant). ID administration of BNT162b2 mRNA was safe and well-tolerated and generated a robust immune response. Therefore, ID delivery of the BNT162b2 mRNA vaccine has the potential for a dose-sparing strategy.

Epidemiological data on nutritional disorders and outcomes in hospitalized Thai children: an analysis of data from the National Health Database 2015-2019.

OBJECTIVES: Malnutrition in hospitalized patients is a frequently overlooked health issue. We aimed to assess the prevalence and pattern of nutritional disorders in hospitalized Thai children from the National Health Database. METHODS: Hospitalized children aged 1 month to 18 years diagnosed with nutritional disorders between 2015 and 2019 were retrospectively reviewed using the National Health Security Office data. Based on the International Classification of Diseases, 10th revision, Clinical Modification, nutritional disorders were classified into 3 major forms of malnutrition: undernutrition (E40-E46), overweight and obesity (E66), and micronutrient deficiencies (D50-D53, E50-E56, E58, E60-E61, and E63). RESULTS: Out of 5,188,033 hospitalized children, malnutrition was identified in 115,254 (2.2%). Protein-energy malnutrition (PEM), overweight and obesity, and micronutrient deficiencies were prevalent in 0.21%, 0.27%, and 1.81%, respectively. Among those with micronutrient deficiencies, 95.0% had iron deficiency anemia, 2.2% had vitamin D deficiency, and 0.7% had zinc deficiency. Children aged under 5 years mostly had PEM, followed by iron deficiency anemia. Teenagers commonly had obesity and vitamin D deficiency. Patients with PEM who were admitted with common diseases had significantly longer hospital stays and higher hospital costs and mortality rates than those without PEM. CONCLUSIONS: Hospitalized children had various nutritional disorders, particularly PEM, which was associated with higher morbidity and mortality. Nutritional screening tools should be utilized for the early detection and treatment of malnutrition. Specific International Classification of Diseases codes for nutritional care services and intervention should be available. Additionally, nutritional interventions should be reimbursed, along with nutritional education and empowerment of healthcare providers, to improve hospital care service and improve patient outcomes.

Monitoring of Metabolic Syndrome and Cardiovascular Disease in Childhood Cancer Survivors.

Advances in cancer treatment have significantly improved childhood cancer survival, although metabolic syndrome and cardiovascular disease are common long-term complications that may occur years after treatment. Childhood cancer survivors may not receive appropriate follow-up due to lack of communication between oncologists and primary care physicians, or, from lack of awareness of possible long-term metabolic and cardiovascular complications after cancer treatment. We, therefore, reviewed current evidence on long-term effects of cancer therapy, and appropriate monitoring for long-term treatment effects in childhood cancer survivors that could lead to early detection and prompt treatment to prevent future cardiovascular events.

Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice.

Mitochondrial remodeling is dysregulated in metabolic diseases but the underlying mechanism is not fully understood. We report here that BDNF (brain derived neurotrophic factor) provokes mitochondrial fission and clearance in skeletal muscle via the PRKAA/AMPK-PINK1-PRKN/Parkin and PRKAA-DNM1L/DRP1-MFF pathways. Depleting Bdnf expression in myotubes reduced fatty acid-induced mitofission and mitophagy, which was associated with mitochondrial elongation and impaired lipid handling. Muscle-specific bdnf knockout (MBKO) mice displayed defective mitofission and mitophagy, and accumulation of dysfunctional mitochondria in the muscle when they were fed with a high-fat diet (HFD). These animals also have exacerbated body weight gain, increased intramyocellular lipid deposition, reduced energy expenditure, poor metabolic flexibility, and more insulin resistance. In contrast, consuming a BDNF mimetic (7,8-dihydroxyflavone) increased mitochondrial content, and enhanced mitofission and mitophagy in the skeletal muscles. Hence, BDNF is an essential myokine to maintain mitochondrial quality and function, and its repression in obesity might contribute to impaired metabolism.Abbreviation: 7,8-DHF: 7,8-dihydroxyflavone; ACACA/ACC: acetyl Coenzyme A carboxylase alpha; ACAD: acyl-Coenzyme A dehydrogenase family; ACADVL: acyl-Coenzyme A dehydrogenase, very long chain; ACOT: acyl-CoA thioesterase; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; BDNF: brain derived neurotrophic factor; BNIP3: BCL2/adenovirus E1B interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CCL2/MCP-1: chemokine (C-C motif) ligand 2; CCL5: chemokine (C-C motif) ligand 5; CNS: central nervous system; CPT1B: carnitine palmitoyltransferase 1b, muscle; Cpt2: carnitine palmitoyltransferase 2; CREB: cAMP responsive element binding protein; DNM1L/DRP1: dynamin 1-like; E2: estrogen; EHHADH: enoyl-CoenzymeA hydratase/3-hydroxyacyl CoenzymeA dehydrogenase; ESR1/ER-alpha: estrogen receptor 1 (alpha); FA: fatty acid; FAO: fatty acid oxidation; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; FFA: free fatty acids; FGF21: fibroblast growth factor 21; FUNDC1: FUN14 domain containing 1; HADHA: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; HFD: high-fat diet; iWAT: inguinal white adipose tissues; MAP1LC3A/LC3A: microtubule-associated protein 1 light chain 3 alpha; MBKO; muscle-specific bdnf knockout; IL6/IL-6: interleukin 6; MCEE: methylmalonyl CoA epimerase; MFF: mitochondrial fission factor; NTRK2/TRKB: neurotrophic tyrosine kinase, receptor, type 2; OPTN: optineurin; PA: palmitic acid; PARL: presenilin associated, rhomboid-like; PDH: pyruvate dehydrogenase; PINK1: PTEN induced putative kinase 1; PPARGC1A/PGC-1α: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PRKAA/AMPK: protein kinase, AMP-activated, alpha 2 catalytic subunit; ROS: reactive oxygen species; TBK1: TANK-binding kinase 1; TG: triacylglycerides; TNF/TNFα: tumor necrosis factor; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1.

Maternal exposure to high-fat diet during pregnancy and lactation predisposes normal weight offspring mice to develop hepatic inflammation and insulin resistance.

Increasing evidence shows a potential link between the perinatal nutrient environment and metabolic outcome in offspring. Here, we investigated the effects of maternal feeding of a high-fat diet (HFD) during the perinatal period on hepatic metabolism and inflammation in male offspring mice at weaning and in early adulthood. Female C57BL/6 J mice were fed HFD or normal chow (NC) for 4 weeks before mating and during pregnancy and lactation. The male offspring mice were weaned onto an NC diet, and metabolic and molecular experiments were performed in early adulthood. At postnatal day 21, male offspring mice from HFD-fed dams (Off-HFD) showed significant increases in whole body fat mass and fasting levels of glucose, insulin, and cholesterol compared to male offspring mice from NC-fed dams (Off-NC). The RT-qPCR analysis showed two- to fivefold increases in hepatic inflammatory markers (MCP-1, IL-1ß, and F4/80) in Off-HFD mice. Hepatic expression of G6Pase and PEPCK was elevated by fivefold in the Off-HFD mice compared to the Off-NC mice. Hepatic expression of GLUT4, IRS-1, and PDK4, as well as lipid metabolic genes, CD36, SREBP1c, and SCD1 were increased in the Off-HFD mice compared to the Off-NC mice. In contrast, CPT1a mRNA levels were reduced by 60% in the Off-HFD mice. At postnatal day 70, despite comparable body weights to the Off-NC mice, Off-HFD mice developed hepatic inflammation with increased expression of MCP-1, CD68, F4/80, and CD36 compared to the Off-NC mice. Despite normal body weight, Off-HFD mice developed insulin resistance with defects in hepatic insulin action and insulin-stimulated glucose uptake in skeletal muscle and brown fat, and these metabolic effects were associated with hepatic inflammation in Off-HFD mice. Our findings indicate hidden, lasting effects of maternal exposure to HFD during pregnancy and lactation on metabolic homeostasis of normal weight offspring mice.

Hospital-acquired malnutrition in paediatric patients: a multicentre trial focusing on prevalence, risk factors, and impact on clinical outcomes.

Alteration of nutrient metabolism during hospital stay may cause a deterioration in patients' nutritional status. The aim of this study was to determine the prevalence and possible risk factors for nutritional deterioration in hospitalized children. A multicentre prospective study was conducted among the patients aged 1 month to 18 years in tertiary-care hospitals, between December 2018 and May 2019. Demographic data, illness, and nutritional assessment on the first and the last day of admission were collected. There were 623 patients enrolled in this study with the median age of 4.3 years. Two thirds of the patients had at least one underlying disease. Eighty-eight percent of the patients were admitted with mild medical conditions including a scheduled cycle of chemotherapy or immunosuppressive drugs, minor infection, and non-invasive procedures. The prevalence of nutritional deterioration (reduction in body mass index ≥ 0.25 Z-score) was 24% and was associated with a significantly higher rate of nosocomial infection (24% vs. 11%, p < 0.001) compared to patients without hospital-acquired malnutrition. Risk factors included moderate to severe medical conditions (AOR 1.90, 95% CI 1.09-3.31, p = 0.024), pneumonia (AOR 1.85, 95% CI 1.05-3.28, p = 0.034), seizure (AOR 2.82, 95% CI 1.28-6.19, p = 0.01), and surgery (AOR 2.98, 95% CI 1.60-5.56, p = 0.001). Nutritional management showed a significant reduction in the incidence of hospital-acquired malnutrition and a trend towards a 60% decrease in infectious complications in patients with moderate to severe medical conditions.Conclusions: Approximately one fourth of paediatric patients developed malnutrition during hospitalization. Nutritional screening, assessment, and treatment should be implemented to improve the outcomes of hospitalized paediatric patients. What is Known: • Malnutrition at admission has a negative impact on outcomes of patients, including prolonged hospitalization, increased costs of care, and a higher rate of nosocomial infection. What is New: • Hospital-acquired malnutrition can occur regardless of prior nutritional status and is predominantly related to illness severity. • Malnourished patients with nutritional intervention experience an improvement in their nutritional status as well as a lower risk of developing hospital morbidity during hospitalization.

The Effects of the Face Mask on the Skin Underneath: A Prospective Survey During the COVID-19 Pandemic.

PURPOSE: The study aimed to explore the prevalence and possible risk factors to prevent the face mask related adverse skin reactions during the ongoing COVID-19 after a recommendation of face mask wearing for public use in Thailand. RESULTS: The prevalence of face mask related adverse skin reactions was 454 cases (54.5%), of which acne was the most frequent (399; 39.9%), followed by rashes on the face (154; 18.4%), and itch symptoms (130; 15.6%). Wearing a surgical mask showed a higher risk of adverse skin reaction compared to a cloth mask, OR (95% CI) = 1.54 (1.16-2.06). A duration of face mask wearing of more than 4 hours/day and the reuse of face masks increased the risk of adverse skin reactions compared to changing the mask every day, adjusted OR(95% CI) = 1.96 (1.29-2.98), and 1.5 (1.11-2.02). CONCLUSION: Suggestions were made for wearing a cloth mask in non-health care workers (HCW) to decrease the risk of face mask related adverse skin reactions. This suggestion could potentially help in decreasing the demand of surgical masks which should be reserved for the HCW population during the ongoing COVID-19 pandemic.

Arrestin domain-containing 3 (Arrdc3) modulates insulin action and glucose metabolism in liver.

Insulin action in the liver is critical for glucose homeostasis through regulation of glycogen synthesis and glucose output. Arrestin domain-containing 3 (Arrdc3) is a member of the α-arrestin family previously linked to human obesity. Here, we show that Arrdc3 is differentially regulated by insulin in vivo in mice undergoing euglycemic-hyperinsulinemic clamps, being highly up-regulated in liver and down-regulated in muscle and fat. Mice with liver-specific knockout (KO) of the insulin receptor (IR) have a 50% reduction in Arrdc3 messenger RNA, while, conversely, mice with liver-specific KO of Arrdc3 (L-Arrdc3 KO) have increased IR protein in plasma membrane. This leads to increased hepatic insulin sensitivity with increased phosphorylation of FOXO1, reduced expression of PEPCK, and increased glucokinase expression resulting in reduced hepatic glucose production and increased hepatic glycogen accumulation. These effects are due to interaction of ARRDC3 with IR resulting in phosphorylation of ARRDC3 on a conserved tyrosine (Y382) in the carboxyl-terminal domain. Thus, Arrdc3 is an insulin target gene, and ARRDC3 protein directly interacts with IR to serve as a feedback regulator of insulin action in control of liver metabolism.

Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility.

The ability of skeletal muscle to switch between lipid and glucose oxidation for ATP production during metabolic stress is pivotal for maintaining systemic energy homeostasis, and dysregulation of this metabolic flexibility is a dominant cause of several metabolic disorders. However, the molecular mechanism that governs fuel selection in muscle is not well understood. Here, we report that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that controls metabolic reprograming through the AMPK/CREB/PGC-1α pathway in female mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were unable to switch the predominant fuel source from carbohydrates to fatty acids during fasting, which reduced ATP production in muscle. Fasting-induced muscle atrophy was also compromised in female MBKO mice, likely a result of autophagy inhibition. These mutant mice displayed myofiber necrosis, weaker muscle strength, reduced locomotion, and muscle-specific insulin resistance. Together, our results show that muscle-derived BDNF facilitates metabolic adaption during nutrient scarcity in a gender-specific manner and that insufficient BDNF production in skeletal muscle promotes the development of metabolic myopathies and insulin resistance.

Adiposity-Independent Effects of Aging on Insulin Sensitivity and Clearance in Mice and Humans.

OBJECTIVE: Aging is associated with impaired insulin sensitivity and increased prevalence of type 2 diabetes. However, it remains unclear whether aging-associated insulin resistance is due to increased adiposity or other age-related factors. To address this question, the impact of aging on insulin sensitivity was investigated independently of changes in body composition. METHODS: Cohorts of mice aged 4 to 8 months ("young") and 18 to 27 months ("aged") exhibiting similar body composition were characterized for glucose metabolism on chow and high-fat diets. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analyses. The relationship between aging and insulin resistance in humans was investigated in 1,250 nondiabetic Mexican Americans who underwent hyperinsulinemic-euglycemic clamps. RESULTS: In mice with similar body composition, age had no detrimental effect on plasma glucose and insulin levels. While aging did not diminish glucose tolerance, hyperinsulinemic-euglycemic clamps demonstrated impaired insulin sensitivity and reduced insulin clearance in aged mice on chow and high-fat diets. Consistent with results in the mouse, age remained an independent determinant of insulin resistance after adjustment for body composition in Mexican American males. CONCLUSIONS: This study demonstrates that in addition to altered body composition, adiposity-independent mechanisms also contribute to aging-associated insulin resistance in mice and humans.

Outcome of neonates exposed to active pulmonary tuberculosis.

OBJECTIVE: To determine the incidence of tuberculosis infection and disease in neonates exposed to an active pulmonary tuberculosis patient in a nursery and maternity ward. MATERIAL AND METHOD: Descriptive cohort study was carried out in Srinagarind Hospital, Khon Kaen University, North-East Thailand. A smear positive pulmonary tuberculosis mother with productive cough was diagnosed on the fifth day of admission. The authors urged parents of all exposed neonates to accept isoniazid (INH) prophylaxis for their infants for six months. All neonates underwent chest x ray (AP, lateral view) and tuberculin skin test on the 24 months follow-up. RESULTS: The 48 neonates were identified as exposed. The age of follow-up ranged from 30 to 32 months. Only three were lost to follow-up. Of the remaining 45 neonates, six refused to take INH prophylaxis. Complete six months of LNH prophylaxis were observed in 27 (60%) of 39 contacts. Tuberculin skin tests (TST) were performed in all of 45 contacts. No cases were positive for TST. Abnormal chest radiographies were found in nine of INH group, three patients had hilar lymphadenopathy and six had pneumonia. The repeat chest x ray, two weeks later was normal in all cases. After 30 to 32 months follow-up, none of the 39 neonates who received INH prophylaxis or the six neonates progressed to have active tuberculosis. CONCLUSION: In exposed neonate identified as the high-risk group, appropriate INH prophylaxis, and long-term follow-up, especially in the first-2 years, seemed to be effective in preventing the development of active tuberculosis.