Obtaining assent for research involving children in Malaysia: a position statement from the Academy of Medicine of Malaysia College of Paediatrics.

The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.

Early-onset sepsis in Malaysian neonatal intensive care units.

OBJECTIVES: To determine the incidence, causative pathogens, morbidities, mortality, and risk factors associated with blood culture-positive early-onset sepsis (EOS, ≤72 hours of age) in symptomatic neonates admitted to the neonatal intensive care units (NICUs) of a middle-income country. STUDY DESIGN: Retrospective cohort study using data submitted prospectively to the Malaysian National Neonatal Registry (MNNR). SETTING: 44 Malaysian NICUs. PARTICIPANTS: All neonates born in 2015- 2020. RESULTS: EOS was reported in 991 neonates. The annual incidence of EOS increased from 0.46 to 0.49/1000 livebirths over the six years. The most common pathogen was Streptococcus agalactiae or Group B haemolytic streptococcus (GBS) (n=388, 39.2%), followed by Escherichia coli (E. coli) (n=80, 8.1%), Klebsiella spp (n=73, 7.4%), coagulase negative staphylococcus (CONS) (n=73, 7.4%), Pseudomonas spp (n=44, 4.4%) and methicillin-sensitive Staphylococcus aureus (n=34, 3.4%). The incidence of EOS due to GBS increased from 0.17 to 0.22/1000 livebirths. Morbidities and mortality were higher in those with EOS than without EOS. Multiple logistic regression analysis showed that Indian ethnic group, chorioamnionitis, gestation≥37weeks, female, spontaneous vaginal delivery, instrumental delivery, and surfactant therapy were significantly associated with increased risk of EOS due to GBS. Four factors were significantly associated with increased risk of non-GBS EOS (outborns, birthweight lt;1000 g, vaginal delivery, and surfactant therapy). Early continuous positive airway pressure was associated with significantly lower risk of EOS. CONCLUSION: The incidence of EOS showed an increasing trend in Malaysian NICUs. GBS was the most common causative pathogen. Several modifiable risk factors associated with EOS have been identified.

Pnictogen-Functionalised C1 Ligands: MC-ARn (n=0, 1, 2, 3).

The chemistry of transition metal carbynes, Ln M≡CR, has historically been dominated by species bearing hydrocarbyl or amino 'R' substituents, with other elements appearing only sporadically. In recent years, carbynes and related 'C1 ' species bearing other main-group substituents, particularly heavier elements of the p-block, have begun to emerge. This review details the chemistry of heavier pnictogen-functionalised C1 ligands, MCARn (A=P, As, Sb, Bi; n=0-3), including their syntheses, properties and reactivities, and how these are distinguished from more traditional carbyne complexes. Recent developments in the closely related phospha-isonitrile Ln M(CPR), cya-phosphide and cya-arside ligands, Ln M(C≡A) (A=P, As), are also discussed.

Haemoglobin Constant Spring (HbA2: c.427T>C) and Haemoglobin Adana (HbA2: c.179G>A) in jaundiced Malaysian term neonates with clinically significant hyperbilirubinemia.

INTRODUCTION: Haemoglobin Constant Spring (Hb CoSp) and Haemoglobin Adana (Hb Adana), are two non-deletion type of α-thalassemia reported in Malaysia. Owing to their structural instability, they cause hemolysis and hyperbilirubinemia. This observational study was part of a large study investigating multiple factors associated with severe neonatal jaundice. In this part we aimed to determine the prevalence of Hb CoSp and Hb Adana and their association with clinically significant neonatal hyperbilirubinemia (SigNH, total serum bilirubin (TSB>290µmol/L)) among jaundiced Malaysian term neonates. MATERIALS AND METHODS: The inclusion criteria were normal term-gestation neonates admitted consecutively for phototherapy. PCR-restriction fragment length polymorphism method was applied on DNA extracted from dry blood spot specimens of each neonate to detect for Hb CoSp and Hb Adana gene. Positive samples were verified by gene sequencing. RESULTS: Of the 1121 neonates recruited (719 SigNH and 402 no-SigNH), heterozygous Hb CoSp gene was detected in only two (0.27%) neonates. Both were SigNH neonates (0.3% or 2/719). No neonate had Hb Adana variant. CONCLUSION: Hb CoSp was not common but could be a risk factor associated with SigNH. No Hb Adana was detected.

Maternal and neonatal effects of Acinetobacter colonisation in preterm premature rupture of membrane and term labour.

INTRODUCTION: Some anecdotal reports suggest that maternal colonisation with Acinetobacter baumannii during pregnancy is associated with adverse maternal and neonatal effects, including preterm premature rupture of membrane (PPROM). The objective of this study was to compare the maternal and neonatal effects of A. baumannii colonisation in cases with PPROM and those with spontaneous onset of labour at term. METHODS: The recruitment of participants' was carried out at Selayang Hospital, Selangor, Malaysia. Vaginal swabs were prospectively taken from 104 patients of PPROM and 111 with spontaneous onset of labour at term. Swabs were also taken from the axillae and ears of their babies. These swabs were cultured to isolate A. baumannii. Maternal and neonatal adverse outcomes were documented. RESULTS: Sixteen mothers were A. baumannii positive, eight from each group respectively. None of the cases developed chorioamnionitis or sepsis. Those positive were four cases of PPROM and two babies of term labour. None of the babies developed sepsis. CONCLUSIONS: This study does not support the suggestion that A. baumannii colonisation during pregnancy is associated with adverse maternal and neonatal outcomes.

Bi- and Polynuclear Transition-Metal Carbon Tellurides.

The first examples of bi- and polynuclear tellurocarbonyl complexes were obtained from the reactions of [W(≡CTe)(CO)2 (Tp*)]NEt4 (Tp*=hydrotris(dimethylpyrazolyl)borate) with [MCl(PCy3 )]/TlPF6 (M=Cu, Au) or [Au2 Cl2 (µ-dppm)], which afford [WM(µ-CTe)(PCy3 )(CO)2 (Tp*)] (M=Cu, Au) and [WAu2 (µ-CTe)(µ-dppm)(CO)2 (Tp*)]3 (PF6 )3 . In all cases it is specifically the tellurocarbonyl that assumes a bridging, but in each case distinct, role including examples of isotellurocarbonyl, semi-bridging and σ-π coordination and combinations thereof. Tetrametallic complexes bridged by C2 Te and C2 Te2 ligands are also described.

Single shot, large area metal sintering with micrometer level resolution.

- This paper presents the optics design for a microscale Selective Laser Sintering (µ-SLS) system that aims to allow large areas of nanoparticles to be sintered simultaneously while still maintaining micrometer scale feature resolutions in order to improve the throughput of the microscale additive manufacturing process. The optics design is shown to be able to sinter a 2.3 mm by 1.3 mm area of metal nanoparticles that have been spread into a ~400 nm thick layer with a feature resolution of ~3 µm in a single shot. The optical resolution of this system is shown to be ~1.2 µm indicating that only about 2-3 pixels are needed to form a good sintered part. In addition, using the optical design presented in this paper, it is estimated that the µ-SLS system should be able to achieve a volumetric throughput of ~63 mm3/hr, making this process one of the highest throughput processes available today for the microscale additive manufacturing of three-dimensional metal structures.

Limitations of cytochrome oxidase I for the barcoding of Neritidae (Mollusca: Gastropoda) as revealed by Bayesian analysis.

The mitochondrial DNA (mtDNA) cytochrome oxidase I (COI) gene has been universally and successfully utilized as a barcoding gene, mainly because it can be amplified easily, applied across a wide range of taxa, and results can be obtained cheaply and quickly. However, in rare cases, the gene can fail to distinguish between species, particularly when exposed to highly sensitive methods of data analysis, such as the Bayesian method, or when taxa have undergone introgressive hybridization, over-splitting, or incomplete lineage sorting. Such cases require the use of alternative markers, and nuclear DNA markers are commonly used. In this study, a dendrogram produced by Bayesian analysis of an mtDNA COI dataset was compared with that of a nuclear DNA ATPS-α dataset, in order to evaluate the efficiency of COI in barcoding Malaysian nerites (Neritidae). In the COI dendrogram, most of the species were in individual clusters, except for two species: Nerita chamaeleon and N. histrio. These two species were placed in the same subcluster, whereas in the ATPS-α dendrogram they were in their own subclusters. Analysis of the ATPS-α gene also placed the two genera of nerites (Nerita and Neritina) in separate clusters, whereas COI gene analysis placed both genera in the same cluster. Therefore, in the case of the Neritidae, the ATPS-α gene is a better barcoding gene than the COI gene.

Carbon-chalcogen wires: alkynyltellurolatocarbynes.

The reactions of [W(CBr)(CO)2(Tp*)] (Tp* = tris(dimethylpyrazolyl)borate) with LiTeCCR (R = SiMe3, SiiPr3, iPr, nBu, tBu, Ph, C6H4Me-4, methylimidazol-2-yl) afford the first alkynyltellurolatocarbynes [W(CTeCCR)(CO)2(Tp*)]. Both the WC and CC multiple bonds are prone to metal addition as exemplified by treatment with [MCl(SMe2)] (M = Cu, Au) to afford the hexametallic complex [W2Cu4(µ-CTeCCSiiPr3)2Cl4(CO)4(Tp*)2] and [WAu(µ-CTeCCSiMe3)Cl(CO)2-(Tp*)] which evolves to the unusual hypervalent [WAu(µ-CTeCl4)(SMe2)(CO)2(Tp*)].

Spodium bonding in bis(alkynyl)mecurials.

The new bis(alkynyl)mercurial Hg{CCSeCW(CO)2(Tp*)}2 (Tp* = tris(dimethylpyrazolyl)borate) forms adducts with fluoride and phenathroline, the structures of which are interpreted in the context of two-coordinate mercury presenting a σ-torroid for spodium bonding.

The development and validation of the treatment of autoimmune bullous disease quality of life questionnaire, a tool to measure the quality of life impacts of treatments used in patients with autoimmune blistering disease.

BACKGROUND: Treatments for autoimmune blistering diseases have significant risk of medical complications and quality of life impacts during treatment, and it is difficult to differentiate these impacts from disease burden or the effects of treatment. OBJECTIVES: To develop a quality of life instrument specific to the effects of treatments used in patients with autoimmune bullous disease (AIBD). METHODS: A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL, selecting only those questions pertaining to the treatment effects. This pilot Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaire was administered to 70 patients, before factor analysis was performed to yield the final questionnaire of 17 questions. Validity and reliability were evaluated across a range of indices. RESULTS: Face and content validity were established through a comprehensive patient interview process, expert review and summaries of treatments used. The questionnaire was found to have appropriate correlation with the Dermatology Life Quality Index (r = 0.64) and the level of treatments used (P < 0.01), and was found to be responsive to overall variations in treatment burden. The TABQOL was also found to be a reliable instrument as evaluated by internal consistency (Cronbach α = 0.892) and test-retest reliability (r = 0.99). CONCLUSIONS: We have shown that the TABQOL questionnaire is a valid and reliable instrument that may to be used to measure treatment burden in AIBD and serve as an end point in clinical trials.

Research and clinical applications of cancer genome sequencing.

PURPOSE OF REVIEW: To highlight the recent advances in cancer genome research and its clinical applications made possible by next-generation sequencing (NGS), with particular emphasis on gynecological and breast cancers is the purpose of the review. RECENT FINDINGS: Through advances in NGS technologies, whole-exome sequencing and whole-genome sequencing (WGS) have been performed on various cancers, identifying in the process numerous recurrent mutations and highly mutated genes. These cancers include uterine serous carcinomas, high-grade serous ovarian adenocarcinomas and breast cancer. In contrast to identifying somatic mutations in sporadic cancers, a far smaller number of studies using NGS have been conducted to identify new causal mutations or genes for hereditary cancer syndromes. In addition to research discovery, diagnostic applications of NGS have also become increasingly evident. Thus, WGS has been applied in a diagnostic context to identify a complex chromosomal rearrangement in a patient with acute myeloid leukemia of unclear subtype. Similarly, the targeted sequencing of panels of known cancer genes using NGS has demonstrated its robustness in the context of identifying known pathological mutations. SUMMARY: The research and clinical applications of cancer genome sequencing have progressed at an unprecedented pace over the last few years, and this promises to be accelerated with new developments of high-throughput NGS technologies and robust analytical tools.

Independent and Joint Associations of Age, Pre-pregnancy BMI, and Gestational Weight Gain with Adverse Pregnancy Outcomes in Gestational Diabetes Mellitus.

INTRODUCTION: To explore the independent and combined effects of maternal age, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG) on pregnancy outcomes in gestational diabetes mellitus (GDM). METHODS: A total of 2171 pregnant women with GDM attending the Women's Hospital of Zhejiang University were retrospectively included. We compared pregnancy outcomes in different age, BMI, and GWG groups after adjusting for confounding variables. RESULTS: Results showed that (1) advanced maternal age increased the risk of primary Cesarean section and hypertensive disorders of pregnancy (HDP) in normal weight; (2) independent of age and GWG, high BMI significantly increased the risk of HDP, primary Cesarean section, and macrosomia; (3) Women with excessive GWG had a higher risk of primary Cesarean section and HDP, even they were ≤ 29 years old or normal weight, respectively; (4) Pregnant women with inadequate GWG had a higher risk of preterm birth and a lower risk of macrosomia in both the 30-34 age group and the normal weight group; (5) BMI was a better predictor of HDP than GWG among women younger than 30. CONCLUSIONS: Among the GDM population, women over the age of 35, overweight and obese, or with an excessive GWG were more prone to adverse pregnancy outcomes, especially primary Cesarean delivery and HDP.

A systematic review of spinal cord injury and cerebrospinal fluid drainage after thoracic aortic endografting.

BACKGROUND: The use of thoracic endovascular aneurysm repair (TEVAR) is increasing. Similar to open repair, TEVAR carries a risk of spinal cord ischemia (SCI). We undertook a systematic review to determine whether preoperative cerebrospinal fluid (CSF) drainage reduces SCI. METHODS: PubMed, the Cochrane Library, and conference abstracts were searched using the keywords thoracic endovascular aortic repair, cerebrospinal fluid, spinal cord ischaemia, TEVAR, and aneurysm. Studies reporting SCI rates and CSF drain rates for TEVAR patients were eligible for inclusion. SCI rates across studies were pooled using random-effects modeling. Study quality was evaluated using the Downs and Black score. RESULTS: Study quality was generally poor to moderate (median Downs and Black score, 9). The systematic review identified 46 eligible studies comprising 4936 patients; overall, SCI affected 3.89% (95% confidence interval, 2.95.05%-4.95%). Series reporting routine prophylactic drain placement or no prophylactic drain placement reported pooled SCI rates of 3.2% and 3.47%, respectively. The pooled SCI rate from 24 series stating that prophylactic drainage was used selectively was 5.6%. CONCLUSIONS: Spinal chord injury is uncommon after TEVAR. The role of prophylactic CSF drainage is difficult to establish from the available literature. High-quality studies are required to determine the role of prophylactic CSF drainage in TEVAR.

Dealing with malignancy involving the inferior vena cava in the 21st century.

INTRODUCTION: Malignancies involving the inferior vena cava (IVC) have historically been considered not amendable to surgery. More recently, involvement of the IVC by neoplastic processes in the kidney, liver or in the retroperitoneum can be managed successfully. EVIDENCE ACQUISITION: In this systematic review we summarize the current evidence regarding the surgical management of the IVC in cases of involvement in neoplastic processes. Current literature was searched, and studies selected on the base of the PRISMA guidelines. Evidence was synthesized in narrative form due to heterogeneity of studies. EVIDENCE SYNTHESIS: Renal cell carcinoma accounts for the greatest proportion of studied patients and can be managed with partial or complete vascular exclusion of the IVC, thrombectomy and direct closure or patch repair with good oncological prognosis. Hepatic malignancies or metastases may involve the IVC, and the joint expertise of hepatobiliary and vascular surgeons has developed various strategies, according to the location of tumor and the need to perform a complete vascular exclusion above the hepatic veins. In retroperitoneal lymph node dissection, the IVC can be excised en-block to guarantee better oncological margins. Also, in retroperitoneal sarcomas not arising from the IVC a vascular substitution may be required to improve the overall survival by clearing all the neoplastic cells in the retroperitoneum. Leiomyoma can have a challenging presentation with involvement of the IVC requiring either thrombectomy, partial or complete substitution, with good oncological outcomes. CONCLUSIONS: A multidisciplinary approach with specialist expertise is required when dealing with IVC involvement in surgical oncology. Multiple techniques and strategies are required to deliver the most efficient care and achieve the best possible overall survival. The main aim of these procedures must be the complete clearance of all neoplastic cells and achievement of a safe margin according to the perioperative treatment strategy.

Heterobimetallic µ2-halocarbyne complexes.

The halocarbyne complexes [M(CX)(CO)2(Tp*)] (M = Mo, W; X = Cl, Br; Tp* = hydrotris(dimethylpyrazolyl)borate) react with [AuCl(SMe2)], [Pt(η2-H2CCH2)(PPh3)2] or [Pt(η2-nbe)3] (nbe = norbornene) to furnish rare examples of µ2-halocarbyne complexes [MAu(µ2-CX)Cl(CO)2(Tp*)], [MPt(µ2-CCl)(CO)2(PPh3)2(Tp*)] and [W2Pt(µ2-CCl)2(CO)4(Tp*)2]. The complex [WPt(µ2-CCl)(CO)2(PPh3)2(Tp*)] spontaneously rearranges to the µ2-carbido complex [WPt(µ2-C)Cl(CO)2(PPh3)2(Tp*)] during silica-gel chromatography. One phosphine ligand of [WPt(µ2-CCl)(CO)2(PPh3)2(Tp*)] is readily substituted by CO to afford [WPt(µ2-CCl)(CO)3(PPh3)(Tp*)]. These µ2-halocarbyne complexes have been interrogated by spectroscopic, crystallographic and computational methods, the latter by reference to data for terminal halocarbyne precursors [M(CX)(CO)2(Tp*)].

A brief structured education programme enhances self-care practices and improves glycaemic control in Malaysians with poorly controlled diabetes.

We assessed the effectiveness of a brief structured diabetes education programme based on the concept of self-efficacy on self-care and glycaemic control using single-blind study design. One hundred and sixty-four participants with poorly controlled diabetes from two settings were randomized using computer-generated list into control (n = 82) and intervention (n = 82) groups, of which 151 completed the study. Monthly interventions over 12 weeks addressed the self-care practices of diet, physical activity, medication adherence and self-monitoring of blood glucose (SMBG). These self-care practices were assessed at Weeks 0 and 12 using pre- and post-questionnaires in both groups together with glycated haemoglobin A1c (HbA1c) and diabetes knowledge. In the intention-to-treat analysis (n = 164), the intervention group improved their SMBG (P = <0.001), physical activity (P = 0.001), HbA1c (P = 0.03), diabetes knowledge (P = <0.001) and medication adherence. At Week 12, HbA1c difference adjusted for SMBG frequency, medication adherence and weight change remained significant (P = 0.03) compared with control group. For within group comparisons, diabetes knowledge (P = <0.001), HbA1c level (P = <0.001), SMBG (P = <0.001) and medication adherence (P = 0.008) improved from baseline in the intervention group. In the control group, only diabetes knowledge improved (P = <0.001). These findings can contribute to the development of self-management diabetes education in Malaysia.

Phylogenetic study and barcoding of the blood cockle, Tegillarca granosa, found on the west coast of peninsular Malaysia using the COI gene.

Blood cockles are among the most economically important brackish water invertebrates found in Malaysia. However, our knowledge of blood cockle phylogeny and systematics is rudimentary, especially for the species Tegillarca granosa. It is unclear, for instance, whether the cockles occurring on the west coast of peninsular Malaysia constitute a single species, or multiple, phylogenetically distinct species. We performed the first DNA molecular phylogenetic analysis of T. granosa to distinguish it from other related species found in other parts of the world and to create a DNA database for the species. An approximately 585-nucleotide fragment of the mitochondrial DNA (cytochrome oxidase I, COI) was sequenced for 150 individual cockles, representing 10 populations: three from the north, four from the central part and three from the southern part of peninsular Malaysia. Phylogenetic analyses of the resulting dataset yielded tree topologies that not only showed the relationship between T. granosa and its closest relatives but its position in the evolutionary tree. Three mitochondrial clades were evident, each containing an individual genus. Using the mutation rate of the COI gene, the divergence time between T. granosa and its closest related species was estimated to be 460 thousand years ago. This study provides a phylogenetic framework for this ecologically prominent and commercially important cockle species.