Pre-operative cardiac optimisation: a directed review.

Cardiac events remain the leading cause of peri-operative morbidity and mortality, and patients undergoing major surgery are exposed to significant risks which may be preventable and modifiable. Proper assessment and management of various cardiac conditions in the peri-operative period by anaesthetists can markedly improve patient safety, especially in high-risk patient populations. This involves understanding and applying current evidence-based practice and international guidelines on the main aspects of cardiac optimisation, including management of patients with hypertension, chronic heart failure, valvular heart diseases and cardiac implantable electronic devices. Peri-operative management of antihypertensive drugs in keeping with the current best evidence is discussed. Pre-operative cardiac risk assessment and cardiac biomarkers can be used to help predict and quantify peri-operative adverse cardiac events. There is an increasing need for anaesthetist-led services, including focused transthoracic echocardiography and management of implantable cardiac electronic devices. Anaesthetists should be encouraged to play a proactive role in pre-operative risk stratification and make timely multidisciplinary referrals if necessary. A personalised approach to pre-operative cardiac optimisation enables a safer peri-operative journey for at-risk patients undergoing major surgery.

Solution structure analysis of the periplasmic region of bacterial flagellar motor stators by small angle X-ray scattering.

The bacterial flagellar motor drives the rotation of helical flagellar filaments to propel bacteria through viscous media. It consists of a dynamic population of mechanosensitive stators that are embedded in the inner membrane and activate in response to external load. This entails assembly around the rotor, anchoring to the peptidoglycan layer to counteract torque from the rotor and opening of a cation channel to facilitate an influx of cations, which is converted into mechanical rotation. Stator complexes are comprised of four copies of an integral membrane A subunit and two copies of a B subunit. Each B subunit includes a C-terminal OmpA-like peptidoglycan-binding (PGB) domain. This is thought to be linked to a single N-terminal transmembrane helix by a long unstructured peptide, which allows the PGB domain to bind to the peptidoglycan layer during stator anchoring. The high-resolution crystal structures of flagellar motor PGB domains from Salmonella enterica (MotBC2) and Vibrio alginolyticus (PomBC5) have previously been elucidated. Here, we use small-angle X-ray scattering (SAXS). We show that unlike MotBC2, the dimeric conformation of the PomBC5 in solution differs to its crystal structure, and explore the functional relevance by characterising gain-of-function mutants as well as wild-type constructs of various lengths. These provide new insight into the conformational diversity of flagellar motor PGB domains and experimental verification of their overall topology.

Potential benefits of diagnosis and treatment on health outcomes among elderly people with symptoms of overactive bladder.

OBJECTIVES: This study examined potential benefits of diagnosing and treating elderly adults with overactive bladder (OAB) symptoms. METHODS: Data were analysed from the OAB Re-Contact Study (N = 2750), a cross-sectional, self-reported Internet survey. Elderly respondents (65+ years old) with OAB were identified according to current medication use to control OAB symptoms or by scores > 14 (men) or > 16 (women) on the OAB Awareness Tool. Treated were those currently using prescription medication and never treated were those who never used prescription medication for OAB. Outcome measures included health-related quality of life, activity impairment, OAB-related severity and symptoms, and healthcare resource use (e.g. hospitalisations). Generalised linear models predicted health outcomes as a function of diagnosis or treatment, adjusting for covariates. RESULTS: Diagnosed vs. not diagnosed elderly respondents had higher mental component summary (MCS) scores and SF-6D health utilities, and less activity impairment. Treated vs. never treated elderly respondents had higher MCS and SF-6D health utilities, less activity impairment, fewer OAB symptoms, lower OAB Awareness Tool scores, and lower odds of having bladder problems or incontinence. There were no significant differences in healthcare resource use. Further analysis by age group (middle-aged vs. elderly respondents) revealed significantly greater diagnosis- and treatment-related benefits on MCS (2.93 and 4.49 points more, respectively) and activity impairment (1.24 and 1.37 times as much, respectively) among elderly respondents. CONCLUSIONS: Diagnosis and treatment were each associated with a lower health burden for elderly adults with OAB symptoms. These findings highlighted the importance of diagnosis and treatment in alleviating OAB symptoms and their impact on health outcomes.

A rare cause of severe diarrhoea diagnosed by urine metabolic screening: aromatic L-amino acid decarboxylase deficiency.

A 15-year-old Chinese male with infantile-onset hypotonia, developmental delay, ptosis, and oculogyric episodes presented with a history of chronic diarrhoea since the age of 5 years. At presentation, he had an exacerbation of diarrhoeal symptoms resulting in dehydration and malnutrition with a concurrent severe chest infection. In view of his infantile-onset hypotonia, oculogyric crises, and protracted diarrhoea, an autonomic disturbance related to neurotransmitters was suspected. Urine organic acid profiling was compatible with aromatic L-amino acid decarboxylase deficiency. The diagnosis was confirmed based on cerebrospinal fluid analysis and genetic mutation analysis. The patient was treated with a combination of bromocriptine, selegiline, and pyridoxine; a satisfactory reduction in diarrhoea ensued. Our report highlights the importance of urine organic acid screening in infantile-onset hypotonia, especially when accompanied by oculogyric crises, and severe diarrhoea which could manifest as a result of autonomic disturbance.

Integrated Assessment of Nickel Electroplating Industrial Wastewater Effluent as a Renewable Resource of Irrigation Water Using a Hydroponic Cultivation System.

Nickel, a micronutrient essential for plant growth and development, has been recognized as a metallic pollutant in wastewater. The concentration of nickel ions in the water course, exceeding the maximum tolerable limit, has called for an alarming attention, due to the bioaccumulative entry in the water-plant-human food chain, leaving a burden of deteriorative effects on visible characteristics, physiological processes, and oxidative stress response in plants. In this work, the renewable utilization of nickel electroplating industrial wastewater effluent (0, 5, 10, 25, 50, and 100%) as a viable source of irrigation water was evaluated using a hydroponic cultivation system, by adopting Lablab purpureus and Brassica chinensis as the plant models, in relation to the physical growth, physiological and morphological characteristics, photosynthetic pigments, proline, and oxidative responses. The elongation of roots and shoots in L. purpureus and B. chinensis was significantly inhibited beyond 25 and 5% of industrial wastewater. The chlorophyll-a, chlorophyll-b, total chlorophyll, and carotenoid contents, accompanied by alterations in the morphologies of xylem, phloem, and distortion of stomata, were recorded in the industrial wastewater-irrigated groups, with pronounced toxicity effects detected in B. chinensis. Excessive proline accumulation was recorded in the treated plant models. Ascorbate peroxidase (APX), guaiacol peroxidase (POD), and catalase (CAT) scavenging activities were drastically altered, with a profound upregulation effect in the POD activity in L. purpureus and both POD and APX in B. chinensis, predicting the nickel-induced oxidative stress. Conclusively, the diluted industrial wastewater effluent up to the optimum concentrations of 5 and 25%, respectively, could be feasibly reused as a renewable resource for B. chinensis and L. purpureus irrigation, verified by the minimal or negligible phytotoxic implications in the plant models. The current findings have shed light on the interruption of nickel-contaminated industrial wastewater effluent irrigation practice on the physical and biochemical features of food crops and highlighted the possibility of nutrient recycling via wastewater reuse in a sustainable soilless cultivation.

Healthcare workers acquired COVID-19 disease from patients? An investigation by phylogenomics.

The increasing number of coronavirus disease 2019 (COVID-19) cases in the community has posed a significant epidemic pressure on healthcare settings. When healthcare workers (HCWs) acquire COVID-19, contact tracing and epidemiological investigation might not be adequate for determining the source of transmission. Here, we report a phylogenetic investigation involving two infected HCWs and nine patients to determine whether patient-to-HCW transmission had occurred in a hospital without a previous COVID-19 outbreak. This is the first study to apply phylogenomics to investigate suspected nosocomial transmission in a region with low prevalence of COVID-19. Our results do not support the occurrence of direct patient-to-HCW transmission.

Endothelial cell injury initiates glomerular sclerosis in the rat remnant kidney.

The development of progressive glomerulosclerosis in the renal ablation model has been ascribed to a number of humoral and hemodynamic events, including the peptide growth factor, transforming growth factor-beta 1 (TGF-beta 1). An important role has also been attributed to angiotensin II (AII), which, in addition to its hemodynamic effects, can stimulate transcription of TGF-beta 1. We postulated that increased glomerular production of AII, resulting from enhanced intrinsic angiotensinogen expression, stimulates local TGF-beta 1 synthesis, activating glomerular matrix protein synthesis, and leads to sclerosis. Using in situ reverse transcription, the glomerular cell sites of alpha-1 (IV) collagen, fibronectin, laminin B1, angiotensinogen, and TGF-beta 1 mRNA synthesis were determined at sequential periods following renal ablation. The early hypertrophic phase was associated with global, but transient, increases in the mRNA for alpha-1 (IV) collagen. No changes were noted for fibronectin, TGF-beta 1, and angiotensinogen mRNAs. At 24 d after ablation, at which time sclerosis is not evident, endothelial cells, particularly in the dilated capillaries at the vascular pole, expressed angiotensinogen and TGF-beta 1 mRNAs, as well as fibronectin and laminin B1 RNA transcripts. By 74 d after ablation angiotensinogen and TGF-beta 1 mRNAs were widely distributed among endothelial and mesangial cells, and were particularly prominent in regions of evolving sclerosis. These same regions were also notable for enhanced expression of matrix protein mRNAs, particularly fibronectin. All receptor blockade inhibited angiotensinogen, TGF-beta 1, fibronectin, and laminin B1 mRNA expression by the endothelium. We conclude that, as a result of hemodynamic changes, injured or activated endothelium synthesizes angiotensinogen, triggering a cascade of TGF-beta 1 and matrix protein gene expression with resultant development of the segmental glomerular sclerotic lesion.

Serodiagnosis of dengue virus infection using commercially available antibody and NS1 antigen ELISAs.

Accuracy of the InBios DENV Detect IgM, IgG and NS1 antigen (Ag) ELISAs (Seattle, WA) for detection of dengue virus (DENV) infection were evaluated using 100 retrospectively selected sera from acutely febrile patients presenting to a Singapore hospital. The InBios DENV NS1, IgM and IgG ELISAs had an overall sensitivity of 83.6%, 40% and 58.2% and an overall specificity of 97.8%, 97.8% and 55.6%, respectively. Simultaneous testing for NS1 and IgM-antibodies yielded a sensitivity and specificity of 85.5% and 95.5%, respectively, which did not significantly differ from testing for NS1 Ag alone. Using sera positive for IgM- or IgG-class antibodies to six common arboviruses, the InBios IgM and IgG ELISAs showed an overall analytic specificity of 89.2% and 66.4%, respectively. This study suggests that recent DENV infection can reliably be detected by the InBios NS1 Ag ELISA alone and that InBios DENV IgG reactivity should be interpreted with caution.

Y-chromosome STR haplotype diversity in three ethnic populations in Singapore.

In this study, 12 Y-STR loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438 and DYS439) were genotyped in the three major ethnic populations in Singapore, namely the Chinese, Malay and Indian. Allele frequency distribution, locus diversity, haplotype diversity and discrimination capacity were estimated. Analysis of molecular variance between the three ethnic populations indicated that 87.71% of the haplotypic variation is found within population and 12.29% is between populations (Fixation Index FST=0.123, p=0.000). Population pairwise comparisons showed significant Phist values between all population pairs, with the lowest (RST=0.05) for Chinese-Malay and the highest (RST=0.19) for Chinese-Indian.

Menstruation among adolescent girls in Malaysia: a cross-sectional school survey.

INTRODUCTION: The onset of menstruation is part of the maturation process. However, variability in menstrual cycle characteristics and menstrual disorders are common. The purpose of this study was to determine the menstrual characteristics of adolescent females and factors associated with it. METHODS: This is a cross-sectional descriptive study carried out on 2,411 secondary school adolescent females in Negeri Sembilan, Malaysia. Data were collected using a self-administered structured questionnaire on menstruation in Bahasa Malaysia. RESULTS: Abnormal cycle length (menstrual cycle longer than 35 days or cycle length between 14 to 20 days or irregular pattern) was common and affected 37.2 percent of subjects. The majority (74.6 percent) experienced premenstrual syndrome and 69.4 percent had dysmenorrhoea. About 18 percent reported excessive menstrual loss (use two pads at a time to prevent blood from soaking through or confirmed by doctor to be anaemic due to heavy menstrual flow). Only 11.1 percent of schoolgirls seeked medical consultation for their menstrual disorders. Mothers remained the most important source of information (80 percent). Menstrual disorders were significantly more common in female adolescents who smoke and have suicidal behaviours (p-value is less than 0.05). CONCLUSION: Menstrual problems among adolescent female are common. They are influenced by certain modifiable factors.

Premarital sexual intercourse among adolescents in Malaysia: a cross-sectional Malaysian school survey.

INTRODUCTION: Sexual intercourse among Malaysian adolescents is a major concern, especially with the worry of HIV/AIDS. This study was done to determine the prevalence of sexual intercourse among secondary school students aged 12 to 19 years in Negeri Sembilan, Malaysia. METHODS: This is a cross-sectional school survey conducted on 4,500 adolescent students based on a structured questionnaire. Data were collected using the self-administered questionnaire (translated version of the Youth Risk Behaviour Surveillance in Bahasa Malaysia). RESULTS: The study showed that 5.4 percent of the total sample were reported to have had sexual intercourse. The proportion among male students who had had sex was higher (8.3 percent) compared with female students (2.9 percent). The mean age at first sexual intercourse was 15 years. One percent of students reported that they had been pregnant or had made someone else pregnant. Adolescent sexual intercourse was significantly associated with (1) socio-demographical factors (age, gender); (2) environmental factors (staying with parents); and (3) substance use (alcohol use, cigarette smoking, drug use), even after adjustment for demographical factors. The survey showed that 20.8 percent of respondents had taken alcohol, 14.0 percent had smoked cigarettes, 2.5 percent had tried marijuana, 1.2 percent had tried ecstasy pills, 2.6 percent had tried glue sniffing, 0.7 percent had tried heroin, and 0.7 percent had intravenous drugs. CONCLUSION: Prevalence of sexual intercourse among Malaysian adolescents was relatively low compared to developed countries. However, certain groups of adolescents tend to be at higher risk of engaging in sexual intercourse. This problem should be addressed early by targeting these groups of high-risk adolescents.

Backbone dynamics of a short PU.1 ETS domain.

The resonance assignments, secondary structure and backbone dynamics of the ETS domain of the transcription factor PU.1 have been determined for the free protein in solution by NMR spectroscopy. The secondary structure for the free ETS domain is similar to that observed in the crystal structure of the PU.1 protein complexed with DNA, except that helix alpha2 and recognition helix alpha3 are shorter for the free protein in solution. Backbone dynamics of the protein have been examined using amide hydrogen-deuterium exchange and (15)N laboratory-frame spin relaxation measurements. A significant probability of local unfolding of helix alpha2, which precedes the loop-helix-loop DNA recognition domain, is inferred from the very fast hydrogen-deuterium exchange for amide protons in this helix. The (15)N relaxation measurements indicate that the protein is partially oligomerized at a concentration of 2.5 mM, but monomeric at a concentration of 0.3 mM. The (15)N relaxation data for the low concentration sample were interpreted, using the model-free formalism, to provide insight into protein dynamics on picosecond-nanosecond and microsecond-millisecond time scales. High flexibility of the protein backbone is observed for the residues in the loop between alpha2 and alpha3. This loop is variable in length and in structure within the class of winged helix proteins and is partially responsible for binding to DNA. The dynamic properties observed for alpha2, alpha3 and the intervening loop may indicate a correlation between protein plasticity in particular structural elements and recognition of specific DNA sequences.

Portfolio as a learning tool: students' perspective.

Portfolio writing is a method of encouraging reflective learning among professionals. Although portfolio-based learning is popular among educators, not many studies have been done to determine students' perceptions of portfolio as a learning tool. A questionnaire survey was conducted among 143 medical students to find out their perceptions of the portfolio as a learning tool. A majority of the students felt that the portfolio is a good learning tool. However, they also perceived that it is stressful and time-consuming to develop a proper portfolio. The study indicates that students need appropriate guidance from the academic staff for the system to succeed.

Smoking among secondary school students in Negeri Sembilan, Malaysia.

This study was done to determine the prevalence of smoking and factors influencing cigarette smoking among secondary school students in Negeri Sembilan, Malaysia. This is a cross-sectional school survey conducted on 4500 adolescent students based on a structured questionnaire. Data was collected using the supervised self-administered questionnaire the Youth Risk Behaviour Surveillance in the Malaysian National Language Bahasa Malaysia. The prevalence of smoking among the students was 14.0%. About a third of the students (37.8%) started smoking at 13 to 14 years of age. The prevalence of smoking among the male students was higher (26.6%) compared to the female students (3.1%). Adolescent smoking was associated with (1) sociodemographic factors (age, ethnicity, rural/urban status); (2) environmental factors (parental smoking, staying with parents); (3) behavioural factors (playing truant and risk-taking behaviours such as physical fighting, drug use, alcohol use, sexual activity, lack of seatbelt use, riding with a drunk driver); (4) lifestyle behaviours (being on diet and lack of exercise); (5) personal factors (feeling sad and suicidal behaviours). In conclusion, smoking is a major problem among Malaysian adolescents. Certain groups of adolescents tend to be at higher risk of smoking. This problem should be curbed early by targeting these groups of high risk adolescents.

Age dependence of freezable and nonfreezable water content of normal human lenses.

The cortex, intermediate zone, and nucleus of 19 normal human lenses between the ages of 3 and 77 yr were investigated. The freezable water content of the lenses was obtained by differential scanning calorimetry. The total water content was measured by vacuum dehydration. The nonfreezable water content was calculated from these two measurements. The total water content of the nucleus and intermediate layers decrease with age, while that of the cortex does not vary appreciably. The nonfreezable water content of all three regions of normal human lenses decreases with age.

Ultrastructure of acetylcholine receptor aggregates parallels mechanisms of aggregation.

BACKGROUND: Acetylcholine receptors become aggregated at the developing neuromuscular synapse shortly after contact by a motorneuron in one of the earliest manifestations of synaptic development. While a major physiological signal for receptor aggregation (agrin) is known, the mechanism(s) by which muscle cells respond to this and other stimuli have yet to be worked out in detail. The question of mechanism is addressed in the present study via a quantitative examination of ultrastructural receptor arrangement within aggregates. RESULTS: In receptor rich cell membranes resulting from stimulation by agrin or laminin, or in control membrane showing spontaneous receptor aggregation, receptors were found to be closer to neighboring receptors than would be expected at random. This indicates that aggregation proceeds heterogeneously: nanoaggregates, too small for detection in the light microscope, underlie developing microaggregates of receptors in all three cases. In contrast, the structural arrangement of receptors within nanoaggregates was found to depend on the aggregation stimulus. In laminin induced nanoaggregates receptors were found to be arranged in an unstructured manner, in contrast to the hexagonal array of about 10 nm spacing found for agrin induced nanoaggregates. Spontaneous aggregates displayed an intermediate amount of order, and this was found to be due to two distinct population of nanoaggregates. CONCLUSIONS: The observations support earlier studies indicating that mechanisms by which agrin and laminin-1 induced receptor aggregates form are distinct and, for the first time, relate mechanisms underlying spontaneous aggregate formation to aggregate structure.

Genetic variations in CCK2 receptor in PVG hooded and Sprague-Dawley rats and its mRNA expression on cat exposure.

This study examined differential freezing behavior, mediated by cholecystokinin-2 (CCK2) receptors (J. M. Farook et al., 2001), in PVG hooded and Sprague-Dawley (SD) rats exposed to a predator. The authors confirmed by reverse transcription polymerase chain reaction that CCK2 receptor expression in the PVG rats was increased in the hippocampus and cerebral cortex compared with that of SD rats. In addition, 4 variations in the coding region of the CCK2 receptor gene were detected between the PVG hooded and SD rats: 1 in Exon 4, 1 in Intron 2, and 2 in Intron 3. Acute treatment with a CCK2 agonist (CCK-4) or antagonist (LY225910) did not alter the level of CCK2 receptor expression, indicating no difference between the 2 strains in sensitivity of the CCK2 receptor to drugs.

Insulin-like growth factor-I promotes successful fetal pancreas transplantation in the intramuscular site.

BACKGROUND: Fetal pancreas (FP) has the capacity for exuberant proliferation and engrafts in the safe, accessible intramuscular site. These characteristics make FP transplantation an attractive approach to the treatment of diabetes mellitus. Insulin-like growth factor-I (IGF-I) is an important mediator of growth and maturation of many tissues and has been shown to induce fetal islet proliferation. METHODS: IGF-I was locally administered at a rate of 69 micrograms/kg/day to 0, 2, 4, 8, or 16 FP isografts placed into the thigh muscle of streptozotocin-induced diabetic Lewis rats (blood glucose > 350 mg/dl). RESULTS: Diabetes was reversed in eight of eight animals receiving 16 FP and treated with IGF-I. One of seven animals receiving 16 FP without IGF-I treatment became euglycemic (p = 0.003). Similar improved conversion rates were seen in groups of animals receiving either eight, four, or two FP and treated with IGF-I, compared to groups receiving eight, four, or two FP without IGF-I treatment. Euglycemic recipients had physiologic glucose tolerance. The interval to conversion increased inversely in proportion to the amount of FP tissue transplanted. CONCLUSIONS: These results show that local delivery of IGF-I has potent trophic effects on FP transplanted to the intramuscular site.