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BackgroundEvidence evaluating real-world effectiveness of oral antivirals against Omicron variants is lacking.MethodsAn unselected, territory-wide cohort of all initially non-hospitalized patients with an officially registered diagnosis of SARS-CoV-2 infection between 26th February and 3rd May 2022 during the Omicron BA.2.2 wave in Hong Kong, was identified. We undertook a retrospective cohort design as primary analysis, and case-control design as sensitivity analysis. Outpatient oral antiviral users were matched with controls using 1:10 propensity-score matching. Study outcomes were mortality, COVID-19-related hospitalization, composite outcome of in-hospital disease progression (in-hospital mortality, invasive mechanical ventilation, or intensive care unit admission) and its individual outcomes. Hazard ratios (HR) were estimated by Cox regression, and odds ratios in oral antiviral users compared with non-users by logistic regression. Subgroup analyses evaluated the associations by vaccination status and age.FindingsAmong 1,072,004 non-hospitalized COVID-19 patients, 5,257 and 5,663 were initiated molnupiravir and nirmatrelvir/ritonavir in the community setting with a median follow-up of 42 and 38 days, respectively. Molnupiravir use was associated with lower risks of mortality (HR=0·61, 95%CI=0·46-0·82, pInterpretationAmid the Omicron BA.2.2 wave, early initiation of oral antivirals among non-institutionalised COVID-19 patients was associated with reduced risks of mortality and in-hospital outcomes. Nirmatrelvir/ritonavir use was associated with greater and more consistent protection than molnupiravir.FundingHealth and Medical Research Fund, Food and Health BureauResearch in contextEvidence before this studyOral antivirals have been initiating in non-hospitalized COVID-19 patients to lower their risks of hospitalization and death, and hence to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 25 May 2022 using the search terms “SARS-CoV-2 OR COVID-19” AND “molnupiravir OR Lagevrio OR EIDD-2801” OR “nirmatrelvir OR Paxlovid OR PF-07321332”. Major studies examining the outpatient use of molnupiravir and nirmatrelvir/ritonavir are MOVe-OUT and EPIC-HR trials, respectively. Both have been conducted among unvaccinated, non-hospitalized patients with mild-to-moderate COVID-19 who are at risk of progression to severe disease, during a pandemic wave of SARS-CoV-2 Delta variant. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Considering the real-world evaluation of the two oral antivirals against the currently circulating Omicron variant, only one single-center, retrospective review of solid organ transplant recipients with COVID-19 has been conducted; yet their results are unlikely generalizable to other populations given its specific patient group and small sample size. Real-world effectiveness of oral antivirals is urgently needed to inform their clinical use in COVID-19 patients, considering their vaccination status and the variant of concern.Added value of this studyTo the best of our knowledge, this is one of the first real-world studies exploring the clinical use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. A territory-wide, retrospective cohort study was conducted to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in community-dwelling COVID-19 patients. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset was associated with significant reduction of all-cause mortality risk by 39% and 75%, respectively, compared to not using any oral antivirals. Nirmatrelvir/ritonavir use was also associated with a reduced risk of COVID-19-related hospitalization by 31%, which was consistently observed across age and vaccination status. In terms of disease progression, both oral antivirals were effective in lowering the risk of in-hospital death, which was again more substantial with nirmatrelvir/ritonavir than molnupiravir. Intriguingly, the need for invasive ventilation might be reduced among molnupiravir users compared to matched controls.Implications of all the available evidenceBased on relative efficacy, our findings give support to current guidelines prioritizing nirmatrelvir/ritonavir use over molnupiravir in community-dwelling COVID-19 patients who are at high risk of hospitalization or progression to severe disease, should the former be accessible and clinically appropriate. Amid a pandemic wave of the Omicron variant, real-world effectiveness of oral antivirals in reducing the mortality risk of community-dwelling COVID-19 patients has been demonstrated in this study consisting mostly of the elderly and those who had not been fully vaccinated, extending beyond the evidence demonstrated in clinical trials among those of the Delta variant and who were at risk of severe COVID-19 from being overweight/obese. Several clinical trials (namely RECOVERY and PANORAMIC) and observational studies of the two oral antivirals are ongoing, and further research is needed to confirm our results in other patient populations and healthcare settings.

SummaryBackgroundEffectiveness of oral antivirals in mild-to-moderate COVID-19 patients is urgently needed. This retrospective cohort study aims to evaluate the clinical and virologic outcomes associated with molnupiravir and nirmatrelvir/ritonavir use in COVID-19 patients during a pandemic wave dominated by the Omicron BA.2 subvariant.MethodsWe analyzed data from a territory-wide retrospective cohort of hospitalized patients with confirmed diagnosis of SARS-CoV-2 infection from 26th February 2022 to 26th April 2022 in Hong Kong. Oral antiviral users were matched with controls using propensity-score matching in a ratio of 1:1. Study outcomes were all-cause mortality, a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], intensive care unit admission, or the need for oxygen therapy) and their individual outcomes, and time to achieving lower viral burden of cycle threshold (Ct) value ≥30 cycles. Hazard ratios (HR) of event outcomes were estimated using Cox regression models.ResultsAmong 40,776 hospitalized patients with SARS-CoV-2 infection over a mean follow-up of 41.3 days with 925,713 person-days, this study included 1,856 molnupiravir users, 890 nirmatrelvir/ritonavir users and 2,746 control patients not initially requiring oxygen therapy at baseline after propensity-score matching. Oral antiviral use was associated with significantly lower risks of all-cause mortality (molnupiravir: HR=0.48, 95%CI=0.40-0.59, pConclusionsAgainst Omicron BA.2, initiation of novel oral antiviral treatment in hospitalized patients not requiring any oxygen therapy was associated with lower risks of all-cause mortality and disease progression, in addition to achieving low viral burden faster. Our findings support the early use of oral antivirals in COVID-19 patients who do not require supplemental oxygen on admission.FundingHealth and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong SARResearch in contextEvidence before this studyThe medical and research community are actively exploring the use of oral antivirals in COVID-19 patients to lower their risks of hospitalization and death, and to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 13th May 2022 using the search terms “SARS-CoV-2 OR COVID-19” AND “molnupiravir OR Lagevrio OR EIDD-2801” OR “nirmatrelvir OR Paxlovid OR PF-07321332”. Major studies examining the safety and efficacy of molnupiravir include MOVe-IN and MOVe-OUT trials conducted in hospitalized and non-hospitalized COVID-19 patients, respectively. Clinical evidence for the use of ritonavir-boosted nirmatrelvir came from the EPIC-HR trial conducted among non-hospitalized adults with COVID-19. While no clinical benefits have been observed with molnupiravir use in the inpatient setting among patients with moderate-to-severe COVID-19, early initiation of molnupiravir or nirmatrelvir/ritonavir within 5 days of symptom onset in non-hospitalized patients with mild-to-moderate COVID-19 and risk factors for progression to severe disease has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Notably, these clinical trials were conducted prior to the prevalence of Omicron variant, and the efficacy of oral antivirals against this current variant of concern can only be inferred from experimental evidence to date. Real-world evidence of oral antiviral use in patients with SARS-CoV-2 infection of Omicron variant is lacking.Added value of this studyTo the best of our knowledge, this is the first real-world study exploring the inpatient use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. We conducted a territory-wide, retrospective cohort study to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in COVID-19 patients who did not require supplemental oxygen on admission in Hong Kong. Early initiation of oral antivirals within 2 days of admission was associated with significantly lower risks of all-cause mortality and disease progression, in addition to achieving low viral burden faster than their respective matched controls. Oral antiviral use was also associated with a reduced need for oxygen therapy than non-use.Implications of all the available evidenceCurrent guidelines are now prioritizing the distribution of oral antivirals to those who do not require supplemental oxygen, but who are at the highest risk of disease progression. Our study cohort reflected such prescription pattern in real-world clinical practice, consisting of mostly the elderly with multiple pre-existing comorbidities and who had not been fully vaccinated. The antiviral effect and mortality benefit observed in this patient cohort support the use of oral antivirals in COVID-19 patients who do not require supplemental oxygen on admission during a pandemic wave of Omicron variant. Ongoing research will inform the safety and effectiveness of oral antivirals in specific patient populations (by vaccination status and viral variants), drug combinations, and different healthcare settings.

Wastewater-based epidemiology (WBE) for the SARS-CoV-2 virus in wastewater treatment plants (WWTPs) has emerged as a cost-effective and unbiased tool for population-level testing in the community. In the present study, we conducted a 6-month wastewater monitoring campaign from three WWTPs of different flow rates and catchment area characteristics, which serve 28 % (2.1 million people) of Hong Kong residents in total. Wastewater samples collected daily or every other day were concentrated using ultracentrifugation and the SARS-CoV-2 virus RNA in the supernatant was detected using the N1 and E primer sets. The results showed significant correlations between the virus concentration and the number of daily new cases in corresponding catchment areas of the three WWTPs when using 7-day moving average values (Kendall's tau-b value: 0.227-0.608, p0.001). SARS-CoV-2 virus concentration was normalized to a fecal indicator using PMMoV concentration and daily flow rates, but the normalization did not enhance the correlation. The key factors contributing to the correlation were also evaluated, including the sampling frequency, testing methods, and smoothing days. This study demonstrates the applicability of wastewater surveillance to monitor overall SARS-CoV-2 pandemic dynamics in a densely populated city like Hong Kong, and provides a large-scale longitudinal reference for the establishment of the long-term sentinel surveillance in WWTPs for WBE of pathogens which could be combined into a city-wide public health observatory.

The environment has always been a major determinant of health. More than half of the world’s population is now living in urban areas. The positive contribution of cities and urban centres in economic and sociological advances are well recognized, but this contrasts with the historical findings in the epidemiological and public health literature of unfavourable health effects of cities and urban life termed the ‘urban penalty’. Urban environment as opposed to rural surroundings presents unique challenges and opportunities for health promotion. Health risks of particular concern in cities include environmental pollution and unhealthy lifestyles leading to rising levels of non-communicable diseases, over-crowdedness facilitating the spread of epidemic diseases and inequity of health care provision among people with different socio-economic status. The upside of course is concentration of specialist and emergency medical service easily accessible in terms of location if not necessarily in price. The city also provides ample opportunity for cost-effective health education activities. Indeed, on average, urban dwellers enjoy better health than their rural counterparts. Looking forward, healthy urban living in the future can be fostered by city planning and building design with health enhancement in mind. Finally, the evolving COVID-19 pandemic exposes the difficulties and benefits of infection control in an urban environment that will have significant impact on public health strategy.

The release of microplastics from sewage treatment works (STWs) into the oceans around coastal cities is well documented. However, there are fewer studies on the microplastic abundance in stormwater drains and their emissions into the coastal marine environment via sewage and stormwater drainage networks. Here, we comprehensively investigated microplastic abundance in 66 sewage and 18 sludge samples collected from different process stages at three typical STWs and 36 water samples taken from six major stormwater drains during the dry and wet seasons in Hong Kong, which is a metropolitan city in south China. The results showed that microplastics were detected in all the sewage and stormwater samples, with the abundance ranging from 0.07 to 91.9 and from 0.4 to 36.48 particles/L, respectively, and in all the sludge samples with the abundance ranging from 167 to 936 particles/g (d. w.). There were no significant seasonal variations in the microplastic abundance across all samples of sewage, sludge, and stormwater. For both waterborne sample types, a smaller size (0.02-0.3 mm) and fiber shape were the dominant characteristics of the microplastics. Polyethylene terephthalate (PET) and polypropylene (PP) were the most abundant polymer types in the sewage samples, while polyethylene (PE), PET, PP, and PE-PP copolymer were the most abundant polymer types in the stormwater samples. The estimated range of total daily microplastic loads in the effluent from STWs in Hong Kong is estimated to be 4.48 × 10

Successful external cephalic version (ECV) for breech presenting fetus reduces the need for Caesarean section (CS). We aimed to compare the success rate of ECV with either spinal anaesthesia (SA) or i.v. analgesia using remifentanil.In a double-phased, stratified randomized blinded controlled study we compared the success rates of ECV, performed under spinal anaesthesia (SA), i.v. analgesia (IVA) using remifentanil or no anaesthetic interventions. In phase I, 189 patients were stratified by parity before randomization to ECV, performed by blinded operators, under SA using either hyperbaric bupivacaine 9 mg with fentanyl 15 µg, i.v. remifentanil infusion 0.1 µg kg min(-1), or Control (no anaesthetic intervention). Operators performing ECV were blinded to the treatment allocation. In phase 2, patients in the Control group in whom the initial ECV failed were further randomized to receive either SA (n=9) or IVA (n=9) for a re-attempt. The primary outcome was the incidence of successful ECV.The success rate in Phase 1 was greatest using SA [52/63 (83%)], compared with IVA [40/63 (64%)] and Control [40/63 (64%)], (P=0.027). Median [IQR] pain scores on a visual analogue scale (range 0-100), were 0 [0-0] with SA, 35 [0-60] with IVA and 50 [30-75] in the Control group (P0.001). Median [IQR] VAS sedation scores were highest with IVA [75 (50-80)], followed by SA, [0 (0-50)] and Control [0 (0-0)]. In phase 2, 7/9 (78%) of ECV re-attempts were successful with SA, whereas all re-attempts using IVA failed (P=0.0007). The incidence of fetal bradycardia necessitating emergency CS within 30 min, was similar among groups; 1.6% (1/63) in the SA and IVA groups and 3.2% (2/63) in the Control group.SA increased the success rate and reduced pain for both primary and re-attempts of ECV, whereas IVA using remifentanil infusion only reduced the pain. There was no significant increase in the incidence of fetal bradycardia or emergency CS, with ECV performed under anaesthetic interventions. Relaxation of the abdominal muscles from SA appears to underlie the improved outcomes for ECV.

Bis(7)-tacrine, a promising anti-Alzheimer's dimer, has been shown to have multiple neuroprotective activities in vitro. Here, we investigate whether bis(7)-tacrine attenuates focal cerebral ischemic impairment in vivo. Cerebral ischemia was induced in Sprague-Dawley rats by transient (2 h) middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Bis(7)-tacrine administered intraperitoneally 15 min after ischemia dose-dependently improved neurological behavior deficits and reduced both cerebral infarct volume and edema. The TUNEL staining assay showed that bis(7)-tacrine attenuated neuronal apoptosis in the penumbral region. Compared with that for memantine, a moderately effective N-methyl-D-aspartate (NMDA) receptor antagonist with a similar affinity and potency to bis(7)-tacrine in blocking NMDA receptors, the therapeutic window for bis(7)-tacrine was wider and lasted up to 6 h after the onset of ischemia. Bis(7)-tacrine did not affect physiological parameters or regional cerebral blood flow during either the occlusion period or the early reperfusion stage. In conclusion, bis(7)-tacrine close- and time-dependently protected against acute focal cerebral ischemic insults, possibly through the drug's anti-apoptotic effects during multiple events in the ischemic cascade. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Early-trimester human fetal pancreas is a promising potential source of pancreatic progenitor cells. However, the ethical controversy associated with the source of these cells, and technical difficulties associated with their differentiation into insulin-producing cells have limited both their availability and utility. This study aimed to characterize a population of pancreatic progenitor cells (PPCs) isolated from human fetus and describe the effects of a novel factor, PDZ-domain containing-2 (PDZD2), and its secreted form (sPDZD2), on PPC proliferation and differentiation. In particular, we examined and characterized the expression of several stem cell (nestin, ABCG2, c-kit), growth and differentiation markers (GLP-1R, c-met, erbB1), and PDZD2 in PPCs by RT-PCR, Western blot, and immunocytochemistry. We also examined the effects of sPDZD2 on PPC proliferation and differentiation by examining BrdU incorporation, MTT, cell number, and real-time PCR as well as ELISA. PPCs were isolated, cultured and characterized from human fetal pancreas. PDZD2 and sPDZD2 were detected at high levels in both human fetal pancreas and in PPCs. sPDZD2 acted as a potent mitogen on PPCs, and inhibited the differentiation of PPC-derived islet-like cell-clusters (ICCs), evidenced by the downregulation of Isl-1, Pdx-1, and insulin mRNA levels. sPDZD2 treatment also reduced levels of C-peptide in ICCs. These results show that a novel pancreatic developmental factor, PDZD2, is sufficient to promote the proliferation of human fetal PPCs while limiting differentiation of ICCs into islet/endocrine cells. Findings from this study will contribute to the development of improved methods for islet transplantation therapy in the treatment of diabetes.

The chemical degradation of the endocrine disrupting chemical, butylated hydroxyanisole (BHA), was investigated by different treatment processes including ultraviolet (UV) irradiation, ozonation (O(3)), and UV/O(3). O demethylation, dimerization, and oxidation have been found to be the main degradation mechanisms. A systematic decay pathway was proposed based on ten identified intermediates in the studied processes, including a unique pathway leading to the formation of precipitates in the ozonation process. An unconventional minimum-type variation of BHA decay rate constants from acidic to caustic range has been found for both ozonation and UV/O(3) processes. The precipitates formed during ozonation can be removed during the process to optimize the treatment, while the UV/O(3) process can offer a relatively fast and clean process to degrade BHA and its associated intermediates.

Objective To determine the relationship between gestational age and the ultrasonic measurement of umbilical coiling index (UCI), and to assess the ability of second-trimester ultrasonic measurements of UCI to predict the true UCI, determined at birth. Subjects/methods Five hundred and thirty-one consecutive women with uncomplicated pregnancies, booking for delivery with a singleton pregnancy, were recruited during a routine second-trimester fetal morphology scan. Multiple ultrasonographic measurements of the intercoil distance were performed between two to three coils of the umbilical cord, along its entire visible length. Three hundred and seventy-four patients (70%) were followed until delivery when the true UCI was measured. Results An adequate portion of umbilical cord for assessment of coiling was visualized in 99% of cases. Adequate ultrasonographic visibility rates for the fetal, middle and placental regions of the cord were different. All three regions of the umbilical cord could only be visualized adequately in 10% of cases, and two regions were visible in 75%. The UCI progressively decreased along the cord from the fetal insertion to the placental insertion. The mean decrease in UCI with increasing gestational age was similar in all parts of the cord before the 23rd week (160 days) of pregnancy, and plateaued off after this point, except in measurements performed near the fetal insertion. The sensitivity of second-trimester ultrasound examination for predicting hypercoiling at birth was 17.3% and for predicting hypocoiling was 9.1%. Discussion Whilst UCI can be measured easily and reliably in the second trimester these estimates do not accurately reflect the UCI at term. Our original assumption that umbilical coiling does not alter after the initial formation of coils in the first trimester is incorrect; mixed patterns occurred in about 25% of cases. These patterns develop during the second and third trimesters, presumably due to snarls in the cord, and influence the final coiling number and therefore the relationship between the two measurements of UCI. Copyright © 2002 International Society of Ultrasound in Obstetrics and Gynecology

Objective The purpose of this study was to examine if depressive symptomatology in pregnancy is associated with adverse obstetric and neonatal outcomes. Method In a prospective observational study, 959 women were followed up longitudinally from early pregnancy to postpartum. The level of depression was measured at baseline (first antepartum visit) and in late pregnancy using the Beck Depression Inventory (BDI). Adverse obstetric and neonatal outcomes were recorded at delivery. Results Depression in late pregnancy was associated with increased risk of epidural analgesia (33% vs. 19%, p =.01, adjusted RR = 2.56, 95% CI 1.24-5.30), operative deliveries (caesarean sections and instrumental vaginal deliveries) (39% vs. 27%, p =.02, adjusted RR = 2.28, 95% CI 1.15-4.53), and admission to neonatal care unit (24% vs. 19%, p =.03, adjusted RR = 2.18, 95% CI 1.02-4.66). These effects remained significant even when controlled for potential confounders, such as antepartum complications. Conclusion Previous studies have shown that antepartum anxiety or stress was associated with growth retardation, premature delivery, and epidural analgesia. Our findings add to this body of evidence, which together suggest an adverse impact of antepartum psychological morbidity on maternal and neonatal well-being.

A model to establish customised birthweight standards for the Chinese population was developed, using data from a cohort of 1564 Chinese women with normal singleton pregnancies. Multiple regression analysis was performed using maternal height, weight, parity, gestation at delivery and fetal sex as independent (predictor) variables. From this, a customised ideal birthweight for each baby can be estimated, and the normality of the actual birthweight can be evaluated according to this, rather than from population standards. The results of this study show that birthweights are strongly influenced by maternal characteristics, confirming conclusions from similar studies in other ethnic populations. The overall mean birthweight at 280 days of gestation was 3252 g, which was smaller than that of the Caucasian population. Birthweight increased with maternal height (5.1 g/cm), maternal booking weight (10.2 g/kg) and gestation at delivery (18.3 g/day from 280 days). Babies from women who had two previous deliveries weighed 145.2 g more than the nulliparous. Male babies were 84.8 g heavier than females. Adjustment using these results produces a customised ideal birthweight for each baby. When compared with population based standards, customised birthweight standards identified significantly fewer small for gestational age (SGA - birthweight below 10th centile, McNemar Chi square = 19.1, p < 0.01) and fewer large for gestational age (LGA - birthweight above 90th centile, McNemar Chi square = 23.7, p < 0.01) cases.

Summary Objective: To examine the relationship between signs and symptoms associated with threatened abortion and viability of the pregnancy. Design: A prospective observational study Setting: A university teaching hospital Participants: One thousand consecutive women presenting with a threatened abortion. Intervention: A structured history and an examination were performed as initial clinical assessment. These were followed by transvaginal sonography to determine the status of the pregnancy. Main outcomes: The relationship between individual signs and symptoms and the status of the pregnancy was determined. Logistic regression was performed to determine which signs or symptoms were independent predictors of spontaneous abortion. Results: A history of having passed a tissue mass, the presence of products of conception in the vagina and an open cervix were the only sign or symptom associated with a greater than 90% chance that the pregnancy was non-viable. Logistic regression of signs and symptoms at presentation indicated that maternal age greater than 35 years, a history of passing clots vaginally, vaginal bleeding similar to normal menstruation, increasing vaginal bleeding and discrepancy of 4 or more weeks between the uterine size on examination and that which would have been expected by menstrual dates were significant predictors of nonviable pregnancy. A history of vomiting was predictive of a viable pregnancy. Conclusion: The clinical assessment of threatened abortion is unreliable in most cases and should be superseded by ready access to sonographic assessment.

Objective: To compare obstetric outcomes in two socio-economically distinct populations; illegal immigrants, who travelled across the Chinese border near term to deliver in Hong Kong between 1994 and 1996, and local Hong Kong residents. Methods: We identified two obstetric populations in our hospital with distinct social characteristics and patterns of antenatal care. A retrospective study of pregnancy outcome was conducted in these women. Results: When compared with Hong Kong residents, the illegal immigrants had a significantly lower incidence of antenatal complications, a lower requirement for obstetric intervention, and comparable obstetric outcome with the exception of a higher rate of delivery before arrival at hospital. Conclusion: Our findings were in contrast to previous reports, and contrary to our expectations. Obstetric outcome is multifactorial and previous assumptions about unbooked or socially disadvantaged patients should be re-evaluated.

Summary: We performed a retrospective analysis to assess the content and accuracy of operative and anaesthetic records for Caesarean section in a large unit. The obstetric record was considered adequate if it included patient identification, participating doctors, operative date, title, details and findings and a signature. The anaesthetic record was evaluated by The Australian and New Zealand College of Anaesthetists guidelines. We analysed 104 operative and 101 anaesthetic records. There was inadequate identification in 17 (16.3%) of the operative records. Documentation of a previous scar or the presence or absence of intraabdominal adhesions was incomplete in 22 of the 35 patients (63%) with a previous laparotomy. Sixty per cent of records had incomplete skin closure information. Common anaesthetic record deficiencies were patient position, patient airway, investigation results and postoperative plan. Our findings identified deficiencies that could lead to inadequate medical care and indicate the need for improved standards of perioperative records.

Alchemical molecular dynamics simulations are performed to determine the difference in the free energy of binding of the tyrosine substrate between the wild type of tyrosyl-tRNA synthetase (TyrRS) from Bacillus stearothermophilus and the mutant Tyr169-->Phe. The results are of general interest because the Tyr169 hydroxyl group interacts with the ammonium group of the substrate in a manner corresponding to that found in other amino acid binding proteins (e.g. the Asp receptor of the chemotactic bacterium Salmonella typhimurium and class I major histocompatibility complex molecules). The calculated free-energy change due to the Tyr169-->Phe mutation is 3.4 kcal/mol (the statistical error is +/- 0.5 kcal/mol) in satisfactory agreement with the experimental value of 3(+/- 0.5) kcal/mol. By use of thermodynamic integration, the contribution of the different terms to the free energy change are estimated. The path dependence of such a decomposition is discussed and it is suggested that the alchemical choice is of primary interest for understanding the interactions involved. There are large protein contributions to the alchemical free energy difference of the bound and free enzyme that cancel in the overall result. Due to this cancellation, the essential interactions contributing to the free-energy change are those between the OH group of Tyr169 and water in the free enzyme and those between the OH group of Tyr169 and the ammonium group of the substrate in the bound system. The results thus support simple models based on a balance of hydrogen bonding interactions.

We present an evaluation of the diagnosis, management and outcome of a pair of heterokaryotypic monozygotic dichorionic twins. The heterokaryotype was an incidental finding from an amniocentesis performed for prenatal diagnosis of β-thalassaemia major in a pair of dichorionic twins. Monozygocity was revealed by QF-PCR showing identical short tandem repeat markers on chromosomes 21, 18, 13, X and Y. The twins were heterokaryotypic for duplication chromosome 2q13-q23.3, as shown by array comparative genomic hybridization. Selective foeticide was performed. This case demonstrates that heterokaryotypic monozygotic dichorionic twins are a genetic possibility that does occur.

The oxidation of fresh and saline wastewater containing an endocrine disrupting chemical (butylated hydroxyanisole, BHA) under different reaction conditions by ozonation and O(3)/H(2)O(2) was investigated at various pH levels. The observed pseudo-first-order reaction kinetics was justified through a combined direct ozone and indirect radical oxidation approach for the ozonation process. The BHA decay rates increased with the increase of the solution pH, but decreased as the NaCl concentration increased because of the consumption of ozone by chloride. A kinetic model was therefore derived for predicting BHA degradation at various initial pH levels and NaCl concentrations. For the O(3)/H(2)O(2) and O(3)/H(2)O(2)/Cl(-) processes, the rate of BHA removal was investigated at hydrogen peroxide concentration ranged from 0.5 to 5mM at pH 7. Different optimal H(2)O(2) dosages and decay rates were found for both processes due to the participation of reactions among O(3), H(2)O(2), OH* and Cl(-) as discussed in the paper.

This review provide an update on antenatal screening and diagnosis of thalassaemia disorders.The topics covered are the effectiveness of antenatal screening programmes for thalassaemia, its prenatal diagnosis, molecular basis and laboratory findings, ultrasound screening for haemoglobin Bart's disease, and non-invasive prenatal diagnosis of thalassaemia.Universal antenatal screening for thalassaemia carriers should be implemented in populations with a high prevalence of this condition. The appropriate measure to screen for alpha and beta thalassaemias remains mean cell haemoglobin (27 pg) or mean corpuscular volume (80 fl). A haemoglobin pattern and iron profile should follow if the red cell indices are low. In a population where alpha thalassaemia is prevalent, it is advisable to check the partner's mean cell haemoglobin or mean corpuscular volume as well. Further cascades of investigations will depend on these results and the prevalence of other haemoglobinopathies in that population. Invasive prenatal diagnosis remains the gold standard for diagnosis in high-risk couples. Provided expertise is available, ultrasound measurement of the cardiothoracic ratio appears a good screening tool for alpha thalassaemia major. Non-invasive prenatal diagnosis by identification of a paternal mutation in maternal plasma, although currently at the experimental stage, may be an option in the future.

BACKGROUND: Hydrosalpinx fluid may be toxic to sperm and early embryo growth. Information concerning the effect of hydrosalpinx fluid on embryo development during organogenesis is lacking. METHODS: Rat embryos at gestational day 9.5 were cultured for 48 h with 80% rat serum and 20% of either hydrosalpinx fluid (study group) or lactated Ringer’s solution (control group). Embryos were scored for growth and development at the end of the culture period. RESULTS: Hydrosalpinx fluid, collected from 10 patients, was tested for embryotoxicity individually. Median total morphological scores were significantly lower in embryos exposed to hydrosalpinx fluid from three of the 10 patients (43.0 versus 47.0, P = 0.01; 36.0 versus 45.0, P < 0.001; 36.0 versus 46.5, P = 0.003). This was accompanied by a significant reduction in median yolk sac diameter (4.0 versus 5.2 mm, P < 0.001 and 4.0 versus 5.0 mm, P < 0.001) and somite number (17.5 versus 22.5, P < 0.001 and 17.0 versus 21.5, P = 0.008) in the latter two patients. CONCLUSIONS: Hydrosalpinx fluid in some patients may contain toxin(s) that is potentially teratogenic.

Two cases of uterine leiomyosarcoma associated with pregnancy are reported. The outcome of the pregnancies were either second-trimester abortion or premature labor. Although the placentas were considered to be complete, both patients had foul-smelling vaginal discharge and tissue mass found at cervical os at the time of presentation. Both were treated initially by evacuation, followed later by total abdominal hysterectomy. One patient remained clinically well with no evidence of recurrence, while the other died 1 month after the diagnosis was made.

BACKGROUND: Naproxen is one of the most common non-steroidal anti-inflammatory drugs used by women of reproductive age. Naproxen is known to be teratogenic in animals. The aim of this study was to investigate the placental transfer of naproxen in the first trimester of human pregnancy, and to determine the amount of the drug in different embryonic compartments. METHODS: Twenty-eight patients who requested surgical termination of pregnancy in the first trimester were given two oral 500 mg doses of naproxen before the surgical procedure. Four biological samples, maternal venous blood, coelomic fluid, amniotic fluid and fetal tissue, were collected from each patient for drug analyses by high performance liquid chromatography. RESULTS: Naproxen was detected in all samples. The mean ( SD) concentrations were 69.5 12.2 µg/ml, 6.4 2.4 µg/g, 1.85 1.03 µg/ml and 0.14 0.11 µg/ml in maternal serum, fetal tissue, coelomic fluid and amniotic fluid respectively. The mean amniotic fluid/ maternal drug ratio and fetal/maternal drug ratio were 0.002 (range 0.0005–0.0064) and 0.092 (range 0.022–0.155) respectively. There was a positive correlation between the fetal drug concentration (r 0.59, P 0.001), amniotic fluid drug concentration (r 0.47, P 0.013), amniotic fluid/maternal ratio (r 0.536, P 0.003) and fetal/ maternal ratio (r 0.72, P < 0.001) with advancing gestational age. CONCLUSIONS: Although naproxen can cross the placenta readily in the first trimester of human pregnancy, only a small amount was present in fetal tissues. Since there is no information on whether this small amount of naproxen would be teratogenic or not, women of reproductive age who are taking naproxen regularly should be warned of the possible fetal side-effects.

Diclofenac is a commonly used non-steroidal anti-inflammatory drug in women of reproductive age. It has teratogenic effects in animals. The aim of this study was to investigate the placental transfer of diclofenac in the first trimester of human pregnancy. Thirty patients undergoing surgical termination of pregnancy between 8 and 12 weeks gestation were given two doses of diclofenac before the procedure. Corresponding samples of maternal serum, amniotic fluid, coelomic fluid and fetal tissue were analysed by high-performance liquid chromatography. Diclofenac was detectable in all fetal tissue samples, with a concentration similar to that found in maternal venous samples. However, diclofenac was detectable in only 56.7 and 23.3% of the coelomic and amniotic fluid samples respectively, and the highest concentration attained was 80 and 5% of the maternal concentration respectively. In summary, we confirmed that diclofenac crosses the human placenta readily during the first trimester. Further studies are required to investigate the potential teratogenic effect of diclofenac in human embryos.

Summary: A retrospective analysis of the obstetric database between January, 1995 and December, 1996 was conducted to establish the rate of preterm birth and the incidence of babies with low birth-weight amongst Hong Kong Chinese in an obstetric teaching unit in Hong Kong, and to investigate possible risk factors for spontaneous preterm deliveries. In the series of 13,641 Chinese women who delivered during the study period, the incidence of preterm births before 37 weeks'gestation was 7.4% while the incidence of low birth-weight infants (

Apart from predisposing to the formation of atherosclerosis in the coronary and cerebrovascular circulation, the menopause is also associated with an increased risk of developing peripheral vascular disease. The aim of this observational study was to determine whether the administration of hormone replacement therapy (HRT) had any effect on peripheral flow velocity in postmenopausal women. Changes in peripheral resistance were recorded in 11 healthy postmenopausal women using Doppler ultrasound. The pulsatility index (PI) of the brachial, radial, dorsalis pedis and popliteal arteries was measured before treatment and every 2 months after the commencement of HRT for 6 months. There was a significant decrease in the PI of the radial and dorsalis pedis arteries after HRT, and there were also reductions in the PI of the brachial and popliteal arteries which were not statistically significant. These changes persisted over the complete study period. Our findings suggest that the administration of HRT will have a beneficial effect on peripheral flow velocity in postmenopausal woman. These changes require confirmation in a larger controlled trial.

Significant vaginal discharge of clear fluid after Wertheim-Taussig hysterectomy with bilateral salpingo-oophorectomy is most often due to urinary fistula. Rarely, the same symptom may be caused by lymphatic fistula, which has not been reported previously. The differentiation between lymph and urine is simple. If this rare complication is not suspected, patients may undergo unnecessary invasive diagnostic procedures of the urinary tract.

The value of adjunctive penile block for analgesia, after circumcision in children using 0.5 percent bupivacaine has been evaluated in this randomized, prospective trial. Significantly more children without nerve block were found to require analgesics, administered by injection orally, in the first 12 hour period when compared with children given the nerve block. Penile block is a procedure that is safe, simple to achieve, free from complications, and covers the postoperative period when analgesia is much needed.

Microprocessor-controlled, optical diagnostic instrumentation systems are being developed at Mississippi State University for the U.S. Department of Energy's (DOE) magnetohydrodynamic (MHD) program and other fossil energy technologies. Three of these instrumentation techniques are described. The sensitivity of the temperature gradient of the combustion flame to a change in stoichiometry indicates a possible optical stoichiometric control technique. A microprocessor-controlled, packaged optical instrument for non-intrusive measurement of nitric oxide (NO) concentration in a combustion gas is described. Experimental results are presented using coherent anti-Stokes Raman spectroscopy (CARS) for spatially and temporally resolved temperature measurements in a simulated coal-fired envi ronment.