High-fat diet during pregnancy promotes fetal skeletal muscle fatty acid oxidation and insulin resistance in an ovine model.

Maternal diet during pregnancy is associated with offspring metabolic risk trajectory in humans and animal models, but the prenatal origins of these effects are less clear. We examined the effects of a high-fat diet (HFD) during pregnancy on fetal skeletal muscle metabolism and metabolic risk parameters using an ovine model. White-faced ewes were fed a standardized diet containing 5% fat wt/wt (CON), or the same diet supplemented with 6% rumen-protected fats (11% total fat wt/wt; HFD) beginning 2 wk before mating until midgestation (GD75). Maternal HFD increased maternal weight gain, fetal body weight, and low-density lipoprotein levels in the uterine and umbilical circulation but had no significant effects on circulating glucose, triglycerides, or placental fatty acid transporters. Fatty acid (palmitoylcarnitine) oxidation capacity of permeabilized hindlimb muscle fibers was >50% higher in fetuses from HFD pregnancies, whereas pyruvate and maximal (mixed substrate) oxidation capacities were similar to CON. This corresponded to greater triacylglycerol content and protein expression of fatty acid transport and oxidation enzymes in fetal muscle but no significant effect on respiratory chain complexes or pyruvate dehydrogenase expression. However, serine-308 phosphorylation of insulin receptor substrate-1 was greater in fetal muscle from HFD pregnancies along with c-jun-NH2 terminal kinase activation, consistent with prenatal inhibition of skeletal muscle insulin signaling. These results indicate that maternal high-fat feeding shifts fetal skeletal muscle metabolism toward a greater capacity for fatty acid over glucose utilization and favors prenatal development of insulin resistance, which may predispose offspring to metabolic syndrome later in life.NEW & NOTEWORTHY Maternal diet during pregnancy is associated with offspring metabolic risk trajectory in humans and animal models, but the prenatal origins of these effects are less clear. This study examined the effects of a high-fat diet during pregnancy on metabolic risk parameters using a new sheep model. Results align with findings previously reported in nonhuman primates, demonstrating changes in fetal skeletal muscle metabolism that may predispose offspring to metabolic syndrome later in life.

Long-chain fatty acid oxidation and respiratory complex I deficiencies distinguish Barth Syndrome from idiopathic pediatric cardiomyopathy.

Barth syndrome (BTHS) is an X-linked disorder that results from mutations in the TAFAZZIN gene, which encodes a phospholipid transacylase responsible for generating the mature form of cardiolipin in inner mitochondrial membranes. BTHS patients develop early onset cardiomyopathy and a derangement of intermediary metabolism consistent with mitochondrial disease, but the precise alterations in cardiac metabolism that distinguish BTHS from idiopathic forms of cardiomyopathy are unknown. We performed the first metabolic analysis of myocardial tissue from BTHS cardiomyopathy patients compared to age- and sex-matched patients with idiopathic dilated cardiomyopathy (DCM) and nonfailing controls. Results corroborate previous evidence for deficiencies in cardiolipin content and its linoleoyl enrichment as defining features of BTHS cardiomyopathy, and reveal a dramatic accumulation of hydrolyzed (monolyso-) cardiolipin molecular species. Respiratory chain protein deficiencies were observed in both BTHS and DCM, but a selective depletion of complex I was seen only in BTHS after controlling for an apparent loss of mitochondrial density in cardiomyopathic hearts. Distinct shifts in the expression of long-chain fatty acid oxidation enzymes and the tissue acyl-CoA profile of BTHS hearts suggest a specific block in mitochondrial fatty acid oxidation upstream of the conventional matrix beta-oxidation cycle, which may be compensated for by a greater reliance upon peroxisomal fatty acid oxidation and the catabolism of ketones, amino acids, and pyruvate to meet cardiac energy demands. These results provide a comprehensive foundation for exploring novel therapeutic strategies that target the adaptive and maladaptive metabolic features of BTHS cardiomyopathy.

Quality of life of Malaysian children with CHD.

OBJECTIVES: The objectives of this study were to compare the quality-of-life scores of Malaysian children with CHD and their healthy siblings, to determine the level of agreement between proxy-reports and child self-reports, and to examine variables that have an impact on quality of life in those with CHD. METHODS: Parental-proxy scores of the Pediatric Quality of Life Inventory 4.0 core scales were obtained for 179 children with CHD and 172 siblings. Intra-class coefficients were derived to determine the levels of proxy-child agreement in 66 children aged 8-18 years. Multiple regression analysis was used to determine factors that impacted Pediatric Quality of Life Inventory scores. RESULTS: Proxy scores were lower in children with CHD than siblings for all scales except physical health. Maximum differences were noted in children aged 5-7 years, whereas there were no significant differences in the 2-4 and 13-18 years age groups. Good levels of proxy-child agreement were found in children aged 8-12 years for total, psychosocial health, social, and school functioning scales (correlation coefficients 0.7-0.8). In children aged 13-18 years, the level of agreement was poor to fair for emotional and social functioning. The need for future surgery and severity of symptoms were associated with lower scores. CONCLUSION: Differences in proxy perception of quality of life appear to be age related. The level of proxy-child agreement was higher compared with other reported studies, with lower levels of agreement in teenagers. Facilitating access to surgery and optimising control of symptoms may improve quality of life in this group of children.

Exploring vaccine hesitancy and acceptance in the general population of Pakistan: Insights into COVID-19-related distress, risk perception, and stigma.

The coronavirus disease 2019 (COVID-19) caused several impacts. Focusing on 360 participants (178 males, 182 females), this study explored the association between COVID-19 related distress, risk perception, stigma, and vaccine hesitancy and acceptance in the general population. Measures used included the Hospital Anxiety and Depression Scale (HADS) and COVID Stress Scale (CSS) to evaluate anxiety, depression, and COVID-19 related distress, the COVID-19 Risk Perception Scale and COVID-19 Stigma Discrimination Scale to assess risk perception and stigma, and the Oxford COVID-19 Vaccine Hesitancy Scale and Vaccine Acceptance Instrument to measure vaccine hesitancy and acceptance. The findings revealed that 66.9% of participants exhibited vaccine hesitancy, and stress and risk perception were significant predictors of both vaccine hesitancy and acceptance, even after controlling for demographic factors. This study highlights the importance of understanding the factors mentioned above that will contribute to vaccine hesitancy and acceptance, which will contribute to promoting vaccine acceptance.

Pulmonary arterial pressure in fattened Angus steers at moderate altitude influences early postmortem mitochondria functionality and meat color during retail display.

Pulmonary hypertension is a noninfectious disease of cattle at altitudes > 1524 m (5,000 ft). Mean pulmonary arterial pressures (PAP) are used as an indicator for pulmonary hypertension in cattle. High PAP cattle (≥50 mmHg) entering the feedlot at moderate elevations have lower feed efficiency as compared to low PAP cattle (< 50 mmHg). The impact of pulmonary arterial pressure on mitochondrial function, oxidative phosphorylation (OXPHOS) protein abundance, and meat color was examined using longissimus lumborum (LL) from high (98 ± 13 mmHg; n = 5) and low (41 ± 3 mmHg; n = 6) PAP fattened Angus steers (live weight of 588 ± 38 kg) during early postmortem period (2 and 48 h) and retail display (days 1 to 9), respectively. High PAP muscle had greater (P = 0.013) OXPHOS-linked respiration and proton leak-associated respiration than low PAP muscles at 2 h postmortem but rapidly declined to be similar (P = 0.145) to low PAP muscle by 48 h postmortem. OXPHOS protein expression was higher (P = 0.045) in low PAP than high PAP muscle. During retail display, redness, chroma, hue, ratio of reflectance at 630 and 580 nm, and metmyoglobin reducing activity decreased faster (P < 0.05) in high PAP steaks than low PAP. Lipid oxidation significantly increased (P < 0.05) in high PAP steaks but not (P > 0.05) in low PAP. The results indicated that high PAP caused a lower OXPHOS efficiency and greater fuel oxidation rates under conditions of low ATP demand in premortem beef LL muscle; this could explain the lower feed efficiency in high PAP feedlot cattle compared to low PAP counterparts. Mitochondrial integral function (membrane integrity or/and protein function) declined faster in high PAP than low PAP muscle at early postmortem. LL steaks from high PAP animals had lower color stability than those from the low PAP animals during simulated retail display, which could be partially attributed to the loss of muscle mitochondrial function at early postmortem by ROS damage in high PAP muscle.

The impact of pulmonary arterial pressure (PAP) on mitochondrial function, oxidative phosphorylation protein abundance, and meat color was examined using longissimus lumborum (LL) from high (98 ± 13 mmHg) and low (41 ± 3 mmHg) PAP fattened Angus steers (live weight of 588 ± 38 kg) during early postmortem period (2 and 48 h) and retail display (days 1 to 9), respectively. The results indicated that high PAP caused a lower oxidative phosphorylation efficiency and greater fuel oxidation rates under conditions of positive energy balance in beef LL muscle. This could explain the lower feed efficiency in high PAP feedlot cattle compared to low PAP counterparts. Mitochondrial integral function declined faster in high PAP than low PAP muscle at early postmortem. LL steaks from high PAP animals had lower color stability than those from the low PAP animals during simulated retail display, which could be partially attributed to the loss of muscle mitochondrial function at early postmortem in high PAP muscle.

Phyto-Facilitated Bimetallic ZnFe2O4 Nanoparticles via Boswellia carteri: Synthesis, Characterization, and Anti-Cancer Activity.

BACKGROUND: The growing dissatisfaction with the available traditional chemotherapeutic agents has enhanced the need to develop new methods for obtaining materials with more effective and safe anti-cancer properties. Over the past few years, the usage of metallic nanoparticles has been a target for researchers of different scientific and commercial fields due to their tiny sizes, environment-friendly properties, and a wide range of applications. To overcome the obstacles of traditional physical and chemical methods for the synthesis of such nanoparticles, a new, less expensive, and eco-friendly method has been adopted using natural existing organisms as a reducing agent to mediate the synthesis of the desired metallic nanoparticles from their precursors, a process called green biosynthesis of nanoparticles. OBJECTIVE: In the present study, zinc-iron bimetallic nanoparticles (ZnFe2O4) were synthesized via an aqueous extract of Boswellia carteri resin mixed with zinc acetate and iron chloride precursors, and they were tested for their anticancer activity. METHODS: Various analytic methods were applied for the characterization of the phyto synthesized ZnFe2O4, and they were tested for their anticancer activity against MDA-MB-231, K562, MCF-7 cancer cell lines, and normal fibroblasts. RESULTS: Our results demonstrate the synthesis of cubic structured bimetallic nanoparticles ZnFe2O4 with an average diameter of 10.54 nm. MTT cytotoxicity assay demonstrates that our phyto-synthesized ZnFe2O4 nanoparticles exhibited a selective and potent anticancer activity against K562 and MDA-MB-231 cell lines with IC50 values 4.53 µM and 4.19 µM, respectively. CONCLUSION: In conclusion, our biosynthesized ZnFe2O4 nanoparticles show a promising, environmentally friendly, and low coast chemotherapeutic approach against selective cancers with a predicted low adverse side effect toward normal cells. Further, in vivo, advanced animal research should be done to execute their applicability in living organisms.

Drug administration errors in paediatric wards: a direct observation approach.

Paediatric patients are more vulnerable to drug administration errors due to a lack of appropriate drug dosages and strengths for use in this group of patients. Therefore, the aim of the present study was to determine the extent and types of drug administration errors in two paediatric wards and to identify measures to reduce such errors. A researcher was stationed in two paediatric wards of a teaching hospital to observe all drugs administered to paediatric inpatients in each of the ward, for 1 day in a week over ten consecutive weeks. All data were recorded in a data collection form and then compared with the actual drugs and dosages prescribed for the patients. Of the 857 drug administrations observed, 100 doses had errors, and this gave an error rate of 11.7% [95% confidence interval (CI) 9.5-13.9%]. If wrong time administration errors were excluded, the error rate reduced to 7.8% (95% CI 6.0-9.6%). The most common types of drug administration errors were incorrect time of administration (28.8%), followed by incorrect drug preparation (26%), omission errors (16.3%) and incorrect dose (11.5%). None of the errors observed were considered as potentially life threatening, although 40.4% could possibly cause patient harm. Drug administration errors are as common in paediatric wards in Malaysia as in other countries. Double-checking should be conducted, as this could reduce drug administration errors by about 20%, but collaborative efforts between all healthcare professionals are essential.

Effects of sharing information on drug administration errors in pediatric wards: a pre-post intervention study.

BACKGROUND AND PURPOSE: Drug administration errors are more likely to reach the patient than other medication errors. The main aim of this study was to determine whether the sharing of information on drug administration errors among health care providers would reduce such problems. PATIENTS AND METHODS: This study involved direct, undisguised observations of drug administrations in two pediatric wards of a major teaching hospital in Kuala Lumpur, Malaysia. This study consisted of two phases: Phase 1 (pre-intervention) and Phase 2 (post-intervention). Data were collected by two observers over a 40-day period in both Phase 1 and Phase 2 of the study. Both observers were pharmacy graduates: Observer 1 just completed her undergraduate pharmacy degree, whereas Observer 2 was doing her one-year internship as a provisionally registered pharmacist in the hospital under study. A drug administration error was defined as a discrepancy between the drug regimen received by the patient and that intended by the prescriber and also drug administration procedures that did not follow standard hospital policies and procedures. Results from Phase 1 of the study were analyzed, presented and discussed with the ward staff before commencement of data collection in Phase 2. RESULTS: A total of 1,284 and 1,401 doses of drugs were administered in Phase 1 and Phase 2, respectively. The rate of drug administration errors reduced significantly from Phase 1 to Phase 2 (44.3% versus 28.6%, respectively; P<0.001). Logistic regression analysis showed that the adjusted odds of drug administration errors in Phase 1 of the study were almost three times that in Phase 2 (P<0.001). The most common types of errors were incorrect administration technique and incorrect drug preparation. Nasogastric and intravenous routes of drug administration contributed significantly to the rate of drug administration errors. CONCLUSION: This study showed that sharing of the types of errors that had occurred was significantly associated with a reduction in drug administration errors.

Beyond Critical Congenital Heart Disease: Newborn Screening Using Pulse Oximetry for Neonatal Sepsis and Respiratory Diseases in a Middle-Income Country.

BACKGROUND: Studies on pulse oximetry screening for neonatal sepsis and respiratory disease in a middle-income country are lacking. Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is an effective and life-saving strategy in developed countries. While most studies have reported false-positive results during CCHD screening, they have not elaborated on the detected disease types. We studied the effectiveness and outcomes of pulse oximetry newborn screening for non-cardiac hypoxemic diseases such as neonatal sepsis, respiratory diseases, and CCHD in a middle-income country. METHODS AND FINDINGS: In a pilot study performed at the University Malaya Medical Centre (UMMC), Malaysia, all apparently healthy term newborns, delivered at UMMC were screened pre-discharge using pulse oximetry. Echocardiography was performed for newborns that had positive screening results on two separate occasions, 1-h apart. Newborns with normal echocardiograms were evaluated and treated for other non-cardiac diseases. Fifteen of 5247 term newborns had positive screening results. The median age at screening was 20 h. Thirteen newborns (0.24%) had significant non-cardiac diseases: sepsis (n = 2) and respiratory diseases (n = 11) that required hospitalization and treatment. The remaining two newborns with normal antenatal ultrasonograms had positive screening test and confirmed to have CCHD. Another 18 newborns with negative screening test were later admitted for treatment of sepsis (n = 16) and penumonia (n = 2). All newborns were treated and alive at the end of the study. The sensitivity and specificity of pulse oximetry screening for non-cardiac diseases were 42% and 99.9% respectively, and 100% and 99.7% for CCHD, respectively. CONCLUSIONS: Routine pulse oximetry screening test was effective in identifying newborns with CCHD and other hypoxemia illnesses, which may led to potential life-threatening condition. This study showed that the expanded use of pulse oximetry has immediate implications for low- and middle-income countries contemplating strategies to reduce neonatal mortality and morbidity. ABBREVIATIONS: ASD, atrial septal defect; CCHD, critical congenital heart disease; CRP, C-reactive protein; CXR, chest radiographs; NDI, neurodevelopment impairment; PPHN, persistent pulmonary hypertension of the newborn; PDA, patent ductus arteriosus; PFO, patent foramen ovale; TGA, transposition of great artery; TTN, transient tachypnoea of the newborn; VSD, ventricular septal defect.

Combined low-dose oral propranolol and oral prednisolone as first-line treatment in periocular infantile hemangiomas.

PURPOSE: The purpose of this report was to describe 2 cases of periocular infantile hemangiomas (IHs) that were successfully treated with low-dose oral propranolol alone and in combination with oral prednisolone. METHODS: Two infants aged 3 months and 6 weeks, respectively, were referred for management of vision-threatening periocular IHs causing ocular displacement and obscuration of the visual axis. The first infant had a superficial left upper eyelid capillary hemangioma with extraconal extension and the second infant had a deep preseptal capillary hemangioma in the right lower eyelid with intraconal extension. Both cases were started on oral propranolol 0.5 mg/kg/day in divided doses and titrated up to 1.5 mg/kg/day as first-line therapy. The first infant was also given oral prednisolone 2 mg/kg/day during the initial first month of treatment. RESULTS: Rapid regression in sizes of the hemangiomas was seen within the first 3 days of treatment. By 2 months of therapy, both infants had achieved normal ocular alignment. The second infant experienced a transient period of hypotension after the first dose of propranolol was started but recovered spontaneously. Both infants did not experience any adverse effects of propranolol throughout the treatment period. CONCLUSIONS: Low-dose oral propranolol is an effective first-line therapy for the management of vision-threatening IH. Dose escalation in combination with oral prednisolone after pediatric assessment might be useful in avoiding adverse effects of propranolol in young infants.