The Upper Extremity Lymphatic System Is Not Symmetrical in Individuals: An Anatomic Study Utilizing ICG Lymphography and SPECT/CT Lymphoscintigraphy.

OBJECTIVE: We evaluated whether superficial lymphatic anatomy and functional lymph node drainage are symmetric between the right and left upper extremities of healthy female volunteers, and if handedness is associated with symmetry of superficial lymphatic anatomy. BACKGROUND: Symmetry of lymphatic anatomy has been assumed historically. This assumption of individual anatomic symmetry is being utilized clinically and in research without validation. METHODS: 36 normal female volunteers underwent bilateral indocyanine green (ICG) lymphography and lymphoscintigraphy of the upper extremities. Eight collecting vessel pathways of each upper extremity were mapped on ICG lymphography. 13 lymph node groups were visualized on lymphoscintigraphy. Symmetry of lymphatic anatomy and functional drainage were established by comparing the right and left extremities of each participant. Hand dominance was assessed by hand grip strength on a hand dynamometer. RESULTS: Among the 36 participants, 10 (28%) showed symmetry of all eight upper extremity lymphatic pathways with ICG. However, only 1 (3%) participant demonstrated complete symmetry amongst the 13 lymph node groups. Total symmetry of lymphatic channels was observed on ICG in seven (39%) participants with hand dominance and three (17%) participants without hand dominance (X2 = 2.215, P = 0.137). CONCLUSION: Lymphatic anatomy and functional drainage of the upper extremities are not consistently symmetric. Functional nodal drainage as demonstrated by lymphoscintigraphy shows less symmetry than anatomic studies of lymphatic channels using ICG. Symmetric lymphatic anatomy does not appear to correlate with hand dominance. These findings challenge the prevailing assumption of left-right lymphatic symmetry.

Nanoparticle Augmentation of Adhesive Systems: Impact on Tensile Strength in Fiberglass Post Placement within Root Dentin.

BACKGROUND Modification of the glass fiber post (GFP) with titanium dioxide or silver particles can improve the durability and reliability of dental treatments for ensuring long-term success. This research assessed the tensile bond strength (TBS) of an adhesive system used for cementing GFPs into root dentin following the incorporation of nanoparticles of titanium dioxide (NTiO2) and silver (NAg). MATERIAL AND METHODS Sixty human maxillary canines were prepared to create a 10-mm intra-radicular space for post placement from the cementoenamel junction. The specimens were randomly allocated into 2 groups (a non-thermocycling group and a thermocycling group). Each group was divided into 3 subgroups (10 samples each) according to the adhesive system used (adhesive system devoid of any addition, adhesive system including 1% NAg, and adhesive system infused with 1% NTiO2). TBS tests were conducted and recorded in MPa using a Universal Testing Machine, with an axial load applied at a rate of 0.5 mm/min until failure. The TBS for both groups (non-thermocycling and thermocycling) was measured in megapascals (MPa), and the failure type was recorded. The data were statistically analyzed using one-way analysis of variance (ANOVA) and Tukey's test with P.

Second twin outcome at birth: retrospective analysis in a single tertiary centre in Malaysia.

OBJECTIVES: To investigate factors associated with outcome of second twin during labour. METHODS: The study was a retrospective cohort study in a single tertiary centre in Malaysia from 2014 until 2018 involving all twin pregnancies delivered at or more than 24 weeks of gestation. RESULTS: Total of 409 twin pregnancies were included. Dichorionic twin comprises of 54.5 % (n=223) and 45.5 % (n=186) are monochorionic. Women with dichorionic pregnancies are significantly older (p<0.001), have more pre-existing medical disorders (p=0.011) and fetal structural anomalies (p=0.009). Monochorionic pregnancies are significantly more amongst Malay (p=0.01) and conceived spontaneously (p<0.001). There are significantly more fetuses both in cephalic presentation (p=0.026), birthweight discrepancy more than 20 % (p=0.038) and shorter mean inter-twin delivery duration (p=0.048) in monochorionic pregnancies. Second twin delivered with Apgar score <7 is significantly more in dichorionic pregnancies (p=0.006). The second twin is associated with lower birthweight, small for gestational age and arterial cord pH<7.25. Within the group of women who delivered both fetuses vaginally, there was significantly more second twins with intertwin delivery duration less than 30 min who were delivered vaginally without instrumentation (p=0.018). There was significantly more second twin with intertwin delivery duration of 30 min and more with arterial cord pH<7.25 (p=0.045). Those who delivered spontaneously had inter-twin delivery duration within 15-29 min. The outcome of second twin is not influenced by type of twin, gestational age at delivery, inter-twin delivery duration, mode of delivery and presentation at birth. CONCLUSIONS: The neonatal outcome for the second twin at birth is not influenced by type of twin, gestational age at delivery, inter-twin delivery duration, mode of delivery and presentation at birth in a cohort managed with non-active management of the second twin in Malaysia.

Role of optically pumped magnetometers in presurgical epilepsy evaluation: Commentary of the American Clinical Magnetoencephalography Society.

One of the major challenges of modern epileptology is the underutilization of epilepsy surgery for treatment of patients with focal, medication resistant epilepsy (MRE). Aggravating this distressing failure to deliver optimum care to these patients is the underuse of proven localizing tools, such as magnetoencephalography (MEG), a clinically validated, non-invasive, neurophysiological method used to directly measure and localize brain activity. A sizable mass of published evidence indicates that MEG can improve identification of surgical candidates and guide pre-surgical planning, increasing the yield of SEEG and improving operative outcomes. However, despite at least 10 common, evidence supported, clinical scenarios in MRE patients where MEG can offer non-redundant information and improve the pre-surgical evaluation, it is regularly used by only a minority of USA epilepsy centers. The current state of the art in MEG sensors employs SQUIDs, which require cooling with liquid helium to achieve superconductivity. This sensor technology has undergone significant generational improvement since whole head MEG scanners were introduced around in 1990s, but still has limitations. Further advances in sensor technology which may make ME G more easily accessible and affordable have been eagerly awaited, and development of new techniques should be encouraged. Of late, optically pumped magnetometers (OPMs) have received considerable attention, even prompting some potential acquisitions of new MEG systems to be put on hold, based on a hope that OPMs will usher in a new generation of MEG equipment and procedures. The development of any new clinical test used to guide intracranial EEG monitoring and/or surgical planning must address several specific issues. The goal of this commentary is to recognize the current state of OPM technology and to suggest a framework for it to advance in the clinical realm where it can eventually be deemed clinically valuable to physicians and patients. The American Clinical MEG Society (ACMEGS) strongly supports more advanced and less expensive technology and looks forward to continuing work with researchers to develop new sensors and clinical devices which will improve the experience and outcome for patients, and perhaps extend the role of MEG. However, currently, there are no OPM devices ready for practical clinical use. Based on the engineering obstacles and the clinical tradeoffs to be resolved, the assessment of experts suggests that there will most likely be another decade relying solely on "frozen SQUIDs" in the clinical MEG field.

Seizure outcome of pediatric magnetic resonance-guided laser interstitial thermal therapy versus open surgery: A matched noninferiority cohort study.

OBJECTIVE: Minimally invasive magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been proposed as an alternative to open epilepsy surgery, to address concerns regarding the risk of open surgery. Our primary hypothesis was that seizure freedom at 1 year after MRgLITT is noninferior to open surgery in children with drug-resistant epilepsy (DRE). The secondary hypothesis was that MRgLITT has fewer complications and shorter hospitalization than surgery. The primary objective was to compare seizure outcome of MRgLITT to open surgery in children with DRE. The secondary objective was to compare complications and length of hospitalization of the two treatments. METHODS: This retrospective multicenter cohort study included children with DRE treated with MRgLITT or open surgery with 1-year follow-up. Exclusion criteria were corpus callosotomy, neurostimulation, multilobar or hemispheric surgery, and lesion with maximal dimension > 60 mm. MRgLITT patients were propensity matched to open surgery patients. The primary outcome was seizure freedom at 1 year posttreatment. The difference in seizure freedom was compared using noninferiority test, with noninferiority margin of -10%. The secondary outcomes were complications and length of hospitalization. RESULTS: One hundred eighty-five MRgLITT patients were matched to 185 open surgery patients. Seizure freedom at 1 year follow-up was observed in 89 of 185 (48.1%) MRgLITT and 114 of 185 (61.6%) open surgery patients (difference = -13.5%, one-sided 97.5% confidence interval = -23.8% to ∞, pNoninferiority  = .79). The lower confidence interval boundary of -23.8% was below the prespecified noninferiority margin of -10%. Overall complications were lower in MRgLITT compared to open surgery (10.8% vs. 29.2%, respectively, p < .001). Hospitalization was shorter for MRgLITT than open surgery (3.1 ± 2.9 vs. 7.2 ± 6.1 days, p < .001). SIGNIFICANCE: Seizure outcome of MRgLITT at 1 year posttreatment was inferior to open surgery. However, MRgLITT has the advantage of better safety profile and shorter hospitalization. The findings will help counsel children and parents on the benefits and risks of MRgLITT and contribute to informed decision-making on treatment options.

Impact of hydroxyurea on lymphocyte subsets in children with sickle cell anemia.

BACKGROUND: Hydroxyurea (HU) has beneficial effects in the management of sickle cell anemia (SCA), but there is a paucity of data on the effect of HU on immune cells in SCA. Herein we aimed to evaluate the effect of HU on immune profiles of Egyptian children with SCA. METHODS: This was a controlled prospective cohort study conducted in 30 children with SCA and 30 healthy age-matched controls. Flow cytometry was used to evaluate lymphocyte profiles, including CD8+ T, CD19+ B, CD3+, CD4+, natural killer (NK), NK T, T helper 1 (Th1), Th2, T cytotoxic (Tc1), and Tc2 cells, prior to and after 1 year of treatment with HU. RESULTS: HU treatment led to significant increases in hemoglobin (Hb), red blood cell, and hematocrit counts and a significant decrease in the percentage of sickle Hb, with subsequent improvement in SCA complications. Compared with baseline values, CD3+, CD4+, Th1, and CD8+ T cells were significantly increased, while NK, Th2, and Tc2 cells were significantly decreased, with a resulting increase in the Th1/Th2 and Tc1/Tc2 ratios. CONCLUSIONS: HU has the beneficial effect of restoring the abnormally elevated immune parameters in children with SCA. IMPACT: Hydroxyurea treatment restores the abnormal immune parameters in children with sickle cell anemia. HU treatment led to significantly increased CD3+, CD4+, Th1, and CD8+ T cells, while NK, Th2, and Tc2 cells were significantly decreased, with a resulting increase in the Th1/Th2 and Tc1/Tc2 ratios. Our study showed the impact of HU therapy on immune parameters in children with SCA.

Vitamin D protects against depression: Evidence from an umbrella meta-analysis on interventional and observational meta-analyses.

Meta-analyses of interventional and observational studies investigating the efficacy and the relationship between vitamin D and depression provided inconsistent results. The current umbrella meta-analysis was conducted to assess the available evidence and provide a conclusive outcome in this regard. The following international databases were systematically searched till March 2022: PubMed, Scopus, Embase, Web of Science, and Google Scholar. Random-effects model was carried out to calculate the pooled point estimates and their respective 95 % confidence intervals (CI). Ten meta-analyses of randomised controlled trials (RCTs) revealed significant reduction in depression symptoms comparing participants on vitmain D supplements to those on placebo (Pooled standardised mean difference: - 0.40; 95 % CI: - 0.60, - 0.21, p < 0.01: I2 = 89.1 %, p < 0.01). Four meta-analyses of cohort studies (with one having two subgroups) revealed that participants with lower levels of serum vitamin D were at increased odds of depression than those with higher levels of serum vitamin D (Pooled odds ratio: 1.60; 95 % CI: 1.08, 2.36, p < 0.01; I2 = 91.3 %, p < 0.01). The present umbrella meta-analysis confirms the potential benefits of vitamin D supplementation and higher serum vitamin D levels in reducing the development and symptoms of depression.

A Hybrid Stacked CNN and Residual Feedback GMDH-LSTM Deep Learning Model for Stroke Prediction Applied on Mobile AI Smart Hospital Platform.

Artificial intelligence (AI) techniques for intelligent mobile computing in healthcare has opened up new opportunities in healthcare systems. Combining AI techniques with the existing Internet of Medical Things (IoMT) will enhance the quality of care that patients receive at home remotely and the successful establishment of smart living environments. Building a real AI for mobile AI in an integrated smart hospital environment is a challenging problem due to the complexities of receiving IoT medical sensors data, data analysis, and deep learning algorithm complexity programming for mobile AI engine implementation AI-based cloud computing complexities, especially when we tackle real-time environments of AI technologies. In this paper, we propose a new mobile AI smart hospital platform architecture for stroke prediction and emergencies. In addition, this research is focused on developing and testing different modules of integrated AI software based on XAI architecture, this is for the mobile health app as an independent expert system or as connected with a simulated environment of an AI-cloud-based solution. The novelty is in the integrated architecture and results obtained in our previous works and this extended research on hybrid GMDH and LSTM deep learning models for the proposed artificial intelligence and IoMT engine for mobile health edge computing technology. Its main goal is to predict heart-stroke disease. Current research is still missing a mobile AI system for heart/brain stroke prediction during patient emergency cases. This research work implements AI algorithms for stroke prediction and diagnosis. The hybrid AI in connected health is based on a stacked CNN and group handling method (GMDH) predictive analytics model, enhanced with an LSTM deep learning module for biomedical signals prediction. The techniques developed depend on the dataset of electromyography (EMG) signals, which provides a significant source of information for the identification of normal and abnormal motions in a stroke scenario. The resulting artificial intelligence mHealth app is an innovation beyond the state of the art and the proposed techniques achieve high accuracy as stacked CNN reaches almost 98% for stroke diagnosis. The GMDH neural network proves to be a good technique for monitoring the EMG signal of the same patient case with an average accuracy of 98.60% to an average of 96.68% of the signal prediction. Moreover, extending the GMDH model and a hybrid LSTM with dense layers deep learning model has improved significantly the prediction results that reach an average of 99%.

A retrospective record review of tuberculous infections in rheumatoid arthritis patients on biologics in Malaysia.

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.

Time-Series Forecasting of Hemodialysis Population in the State of Qatar by 2030.

BACKGROUND: There are few statistics on dialysis-dependent individuals with end-stage kidney disease (ESKD) in Qatar. Having access to this information can aid in better understanding the dialysis development model, aiding higher-level services in future planning. In order to give data for creating preventive efforts, we thus propose a time-series with a definitive endogenous model to predict ESKD patients requiring dialysis. METHODS: In this study, we used four mathematical equations linear, exponential, logarithmic decimal, and polynomial regression, to make predictions using historical data from 2012 to 2021. These equations were evaluated based on time-series analysis, and their prediction performance was assessed using the mean absolute percentage error (MAPE), coefficient of determination (R2), and mean absolute deviation (MAD). Because it remained largely steady for the population at risk of ESKD in this investigation, we did not consider the population growth factor to be changeable. (FIFA World Cup 2022 preparation workforce associated growth was in healthy and young workers that did not influence ESKD prevalence). RESULT: The polynomial has a high R2 of 0.99 and is consequently the best match for the prevalence dialysis data, according to numerical findings. Thus, the MAPE is 2.28, and the MAD is 9.87%, revealing a small prediction error with good accuracy and variability. The polynomial algorithm is the simplest and best-calculated projection model, according to these results. The number of dialysis patients in Qatar is anticipated to increase to 1037 (95% CI, 974-1126) in 2022, 1245 (95% CI, 911-1518) in 2025, and 1611 (95% CI, 1378-1954) in 2030, with a 5.67% average yearly percentage change between 2022 and 2030. CONCLUSION: Our research offers straightforward and precise mathematical models for predicting the number of patients in Qatar who will require dialysis in the future. We discovered that the polynomial technique outperformed other methods. Future planning for the need for dialysis services can benefit from this forecasting.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore.

OBJECTIVE: To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. METHODS: A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. RESULTS: The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. CONCLUSION: At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

Enhanced Neonatal Pulse Oximetry Sounds for the First Minutes of Life: A Laboratory Trial.

OBJECTIVE: Auditory enhancements to the pulse oximetry tone may help clinicians detect deviations from target ranges for oxygen saturation (SpO2) and heart rate (HR). BACKGROUND: Clinical guidelines recommend target ranges for SpO2 and HR during neonatal resuscitation in the first 10 minutes after birth. The pulse oximeter currently maps HR to tone rate, and SpO2 to tone pitch. However, deviations from target ranges for SpO2 and HR are not easy to detect. METHOD: Forty-one participants were presented with 30-second simulated scenarios of an infant's SpO2 and HR levels in the first minutes after birth. Tremolo marked distinct HR ranges and formants marked distinct SpO2 ranges. Participants were randomly allocated to conditions: (a) No Enhancement control, (b) Enhanced HR Only, (c) Enhanced SpO2 Only, and (d) Enhanced Both. RESULTS: Participants in the Enhanced HR Only and Enhanced SpO2 Only conditions identified HR and SpO2 ranges, respectively, more accurately than participants in the No Enhancement condition, ps < 0.001. In the Enhanced Both condition, the tremolo enhancement of HR did not affect participants' ability to identify SpO2 range, but the formants enhancement of SpO2 may have attenuated participants' ability to identify tremolo-enhanced HR range. CONCLUSION: Tremolo and formant enhancements improve range identification for HR and SpO2, respectively, and could improve clinicians' ability to identify SpO2 and HR ranges in the first minutes after birth. APPLICATION: Enhancements to the pulse oximeter tone to indicate clinically important ranges could improve the management of oxygen delivery to the neonate during resuscitation in the first 10 minutes after birth.

Auditory Sequences Presented With Spearcons Support Better Multiple Patient Monitoring Than Single-Patient Alarms: A Preclinical Simulation.

OBJECTIVE: A study of auditory displays for simulated patient monitoring compared the effectiveness of two sound categories (alarm sounds indicating general risk categories from international alarm standard IEC 60601-1-8 versus event-specific sounds according to the type of nursing unit) and two configurations (single-patient alarms versus multi-patient sequences). BACKGROUND: Fieldwork in speciality-focused high dependency units (HDU) indicated that auditory alarms are ambiguous and do not identify which patient has a problem. We tested whether participants perform better using auditory displays that identify the relevant patient and problem. METHOD: During simulated patient monitoring of four patients in a respiratory HDU, 60 non-clinicians heard either (a) IEC risk categories as single-patient alarm sounds, (b) event-specific categories as single-patient alarm sounds, (c) IEC risk categories in multi-patient sequences or (d) event-specific categories in multi-patient sequences. Participants performed a perceptual-motor task while monitoring patients; after detecting abnormal events, they identified the patient and the event. RESULTS: Participants hearing multi-patient sequences made fewer wrong patient identifications than participants hearing single-patient alarms. Advantages of event-specific categories emerged when IEC risk category sounds indicated more than one potential event. Even when IEC and event-specific sounds indicated the same unique event, spearcons supported better event identification than did auditory icon sounds. CONCLUSION: Auditory displays that unambiguously convey which patient is having what problem dramatically improve monitoring performance in a preclinical HDU simulation. APPLICATION: Time-compressed speech assists development of detailed risk categories needed in specific HDU contexts, and multi-patient sound sequences allow multiple patient wellbeing to be monitored.

Attention to Changes on a Head-Worn Display: Two Preclinical Studies with Healthcare Scenarios.

OBJECTIVE: In two experiments, we examined how quickly different visual alerts on a head-worn display (HWD) would capture participants' attention to a matrix of patient vital sign values, while multitasking. BACKGROUND: An HWD could help clinicians monitor multiple patients, regardless of where the clinician is located. We sought effective ways for HWDs to alert multitasking wearers to important events. METHODS: In two preclinical experiments, university student participants performed a visuomotor tracking task while simultaneously monitoring simulated patient vital signs on an HWD to detect abnormal values. Methods to attract attention to abnormal values included highlighting abnormal vital signs and imposing a white flash over the entire display. RESULTS: Experiment 1 found that participants detected abnormal values faster with high contrast than low contrast greyscale highlights, even while performing difficult tracking. In Experiment 2, a white flash of the entire screen quickly and reliably captured attention to vital signs, but less so on an HWD than on a conventional screen. CONCLUSION: Visual alerts on HWDs can direct users' attention to patient transition events (PTEs) even under high visual-perceptual load, but not as quickly as visual alerts on fixed displays. Aspects of the results have since been tested in a healthcare context. APPLICATION: Potential applications include informing the design of HWD interfaces for monitoring multiple processes and informing future research on capturing attention to HWDs.

Microneedle-Based Vaccine Delivery: Review of an Emerging Technology.

Vaccination has produced a great improvement to the global health by decreasing/eradicating many infectious diseases responsible for significant morbidity and mortality. Thanks to vaccines, many infections affecting childhood have been greatly decreased or even eradicated (smallpox, measles, and polio). That is why great efforts are made to achieve mass vaccination against COVID-19. However, developed vaccines face many challenges with regard to their safety and stability. Moreover, needle phobia could prevent a significant proportion of the population from receiving vaccines. In this context, microneedles (MNs) could potentially present a solution to address these challenges. MNs represent single dose administration systems that do not need reconstitution or cold-chain storage. Being self-administered, pain-free, and capable of producing superior immunogenicity makes them a more attractive alternative. This review explores microneedles' types, safety, and efficacy in vaccine delivery. Preclinical and clinical studies for microneedle-based vaccines are discussed and patent examples are included.

Co-expression of candidate genes regulating growth performance and carcass traits of Barki lambs in Egypt.

Sheep are considered one of the main sources of animal protein in Egypt and the producers of sheep mutton eagers to find biological criteria for selecting fast-growing lambs that reach market weight early. Therefore, the present study aimed to find a link between the expression profile of selected candidate genes with growth performance and carcass traits of Barki lambs. Thirty-eight Barki lambs were kept and fed individually after weaning till 12 months of age and were divided into 3 groups according to growth performance (fast, intermediate, and slow-growing). Three samples were taken from different body tissues (eye muscle, liver, and fat tail) of each group, directly during slaughtering and stored at - 80 °C until RNA isolation. Real-time PCR was used to profile selected candidate genes (RPL7, CTP1, FABP4, ADIPOQ, and CAPN3) and GAPDH was used as a housekeeping gene. The results indicated that the final body weight was significantly (P ≤ 0.05) greater in the fast (49.9 kg) and intermediate (40.7 kg) compared to slow-growing animals (30.8 kg). The hot carcass weight was heavier (P ≤ 0.05) in the fast and intermediate-growing (24.57 and 19.07 kg) than slow-growing lambs (15.10 kg). The blood profiles of T3 and T4 hormones in addition to other parameters such as total protein, total lipids, and calcium level showed no clear variations among different experimental groups. At the molecular level, our data demonstrated upregulation of genes involved in protein biosynthesis (RPL7), fatty acid oxidation (CPT1), and lipolysis (FABP4) in the fast and intermediate-growing lambs in all studied tissues which facilitate protein accretion, energy expenditure, and fatty acid partitioning required for muscle building up. Moreover, the expression profile of the gene involved in muscle development (CAPN3) was increased in fast and intermediate-growing compared to slow-growing lambs in order to support muscle proper development. On the other hand, a candidate gene involved in lipogenesis (ADIPOQ) was expressed similarly in fat and liver tissues; however, its expression was increased in muscles of fast and intermediate-growing lambs compared to slow-growing animals. In conclusion, the current study indicated that the expression profile of genes involved in metabolic activities of liver, muscle, and adipose tissue is linked with the growth performance of lambs although no variations were detected in blood parameters. This provides an evidence for the importance of co-expression of these genes in body tissues to determine the final body weight and carcass characteristics of Barki sheep.

Factors associated with severe envenomation of snakebite cases at emergency department, Hospital Sultan Abdul Halim, Kedah, Malaysia.

INTRODUCTION: Snakebite envenomation is a medical emergency and cases continue to be encountered in Malaysian hospitals. This study aims to determine the prevalence of snakebite presentations and the associated factors with severe envenomation of snakebite in Sungai Petani, Kedah, Malaysia. MATERIALS AND METHODS: This was a retrospective, crosssectional study involving snakebite patients presented at the Emergency Department (ED), Hospital Sultan Abdul Halim (HSAH), Kedah from 1 July 2015 to 30 June 2019. The cases were extracted from the computerized system and the case records of patients were retrieved from the Medical Record Unit. Patients that met the study criteria were included and their sociodemographic features, clinical presentations including use of anti-venom were collected. Logistic regression analysis was performed to determine the factors associated with severe envenomation. RESULTS: A total of 220 snakebite cases with the mean age of patients was 39.66 (SD±21.79) years old. Majority of them were Malay and males. 41.4% of snakebite cases occurred in late evenings and the mean time-lapsed to arrive at HSAH was 108.6 minutes. 81.4% of snakebite cases occurred while engaging in outdoor activities and 43.6% of the snakebite cases involved work-related incidents. 58.2% of the patients were bitten in the lower limb. 78.6% of patients were bitten by the identified snake species, predominantly from Viperidae family. The prevalence of severe envenomation was 50.9%. Malay ethnicity (adj. OR =2.549, 95% CI =1.277,5.089), bite to the upper limb (adj. OR =2.125, 95% CI =1.192, 3.790), and bite by snakes from Viperidae family (adj. OR =3.017, 95% CI =1.613, 5.642) were found to have significant associations with severe envenomation of snakebite. CONCLUSION: The prevalence of severe envenomation was more than 50% of snakebite cases. Malay ethnicity, upper limb snake bites, and snakebite from a Viperidae family had a higher chance of severe envenomation.

Bioprocess optimization of glutathione production by Saccharomyces boulardii: biochemical characterization of glutathione peroxidase.

The well-known probiotic GRAS Saccharomyces boulardii (CNCM I-745) was used for the first time to produce glutathione (GSH). The culture conditions affecting GSH biosynthesis were screened using a Plackett-Burman design (PBD). Analyzing the regression coefficients for 12 tested variables, yeast extract, glucose, peptone, cysteine, temperature and agitation rate had a positive significant effect on GSH production with a maximum yeild 192 mg/L. The impact of kinetics of adding cysteine was investigated in 19 experiments during the growth time course (0-36 h), and the maximum yield of glutathione (235 mg/L) was obtained by addition of cysteine after 8 h post-inoculation. The most significant variables were further explored at five levels using central composite rotatable design (CCRD), giving a maximum production of GSH (552 mg/L). Using baffled flasks, the yield of GSH was increased to 730 mg/L, i.e., 1.32-fold increment. The two rate-limiting genes of GSH biosynthesis "γ-glutamyl cysteine synthetase (GSH1) and GSH-synthetase (GSH2)" were amplified and sequenced to validate the GSH biosynthetic potency of S. boulardii. The sequences of genes showed 99% similarity with GSH1 and GSH2 genes of S. cerevisiae. Glutathione peroxidase was purified and characterized from S. boulardii with molecular mass and subunit structure of 80 kDa and 35 kDa as revealed from native and SDS-PAGE, ensuring its homodimeric identity. The activity of GPx was reduced by 2.5-fold upon demetallization confirming its metalloproteinic identity. The GPx was strongly inhibited by hydroxylamine and DTNB, ensuring the implication of surface lysine and cysteine residues on the enzyme active site domains.

Experience of SARS-CoV-2 infection in two kidney transplant recipients living with HIV-1 infection.

There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.

Vitamin D in gestational diabetes mellitus and its association with hyperglycaemia, insulin sensitivity and other factors.

We investigated if vitamin D is independently associated with hyperglycaemia in gestational diabetes mellitus (GDM). Serum 25 hydroxy vitamin D (25OHD), fasting blood glucose (FBG), HbA1c, fructosamine, insulin sensitivity (QUICKI equation), body mass index, clothing style and outdoor activity were measured in 58 pregnant women with GDM during the third trimester. 25OHD was also measured in 20 women with normal pregnancies. There was no significant difference in mean 25OHD concentrations between GDM (14.43 ± 5.27 ng/ml) and normal (15.45 ± 5.29 ng/ml) pregnancies, p = .354. However, a higher percentage of GDM subjects had 25OHD concentration <19.8 ng/ml (86 versus 65%, p = .003). 25OHD did not correlate with FBG, HbA1c, fructosamine, insulin sensitivity or insulin dosage (p > .05). On multivariate analysis, only ethnicity (p = .006) and outdoor activity (p = .004) were associated with 25OHD. We conclude that the lower 25OHD levels in our GDM patients were related to ethnicity and outdoor activity (Study FF-2017-111, National University of Malaysia, 16 March 2017).IMPACT STATEMENTWhat is already known on this subject? Vitamin D deficiency in pregnancy is widespread and particularly in certain ethnic groups. Low vitamin D levels may be an aetiological factor for gestational diabetes mellitus (GDM) but previous studies provide conflicting results perhaps due to confounding factors.What do the results of this study add? In this study of pregnant women with GDM from different ethnic backgrounds, we analysed serum 25-hydroxy vitamin D (25OHD) levels together with other confounding factors, that is, body mass index, ethnicity and sunlight exposure. Furthermore, instead of using consensus values, we determined cut-offs for different vitamin D status from normal pregnancies matched for gestational age and ethnicity. We found that a higher percentage of GDM subjects had lower vitamin D status but there was no correlation with hyperglycaemia or insulin sensitivity. The study showed that lower vitamin D levels in GDM was associated with ethnicity and less outdoor activity.What the implications are of these findings for clinical practice and/or further research? In GDM patients, low vitamin D levels may be modifiable by supplementation or lifestyle change. Longitudinal studies are needed to determine whether this would impact on the occurrence of GDM.