Preoperative lifestyle modifications combined with a structured exercise protocol on patient outcomes following total knee replacement surgery: A systematic review.

BACKGROUND: Medical guidelines recommend structured prehabilitation protocols consisting of lifestyle modifications and exercise to enhance post-operative outcomes for patients undergoing a total knee replacement (TKR). However, current research showing effectiveness is limited and has primarily focused on outcomes of exercise-based prehabilitation. OBJECTIVES: To investigate whether a structured prehabilitation protocol consisting of exercise and lifestyle modifications improves physical function and patient-reported outcomes following TKR surgery compared with usual care. DESIGN: Systematic review. METHODS: Five databases were searched to identify randomised controlled trials comparing structured prehabilitation programs consisting of lifestyle modifications and exercise, with usual care, for those undergoing a TKR. Methodological quality of included studies was assessed via the RoB 2.0 tool and results synthesis via a Grading of Recommendation Assessment, Development and Evaluation approach was performed to determine the certainty evidence for each outcome. RESULTS/FINDINGS: Four studies were included in this review. Despite a positive trend supporting the inclusion of a structured prehabilitation protocol, additional improvements in post-operative pain, physical function and self-reported function were only seen in one study. Reductions in hospital length of stay were also seen in one study. No additional improvements in post-operative quality of life following prehabilitation were reported. CONCLUSION: Limited evidence supporting prehabilitation reported in our review is likely attributed to the intervention type, intensity, and delivery model of included studies. However, there remains to be strong evidence supporting the use of a structured prehabilitation protocol consisting of lifestyle modifications and exercise to improve post-operative outcome.

The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta-analysis.

OBJECTIVES: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification. METHODS: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747. RESULTS: Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%). CONCLUSION: The likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.

Periplasmic stress contributes to a tradeoff between protein secretion and cell growth in E. Coli Nissile.

Maximizing protein secretion is an important target in the design of engineered living systems. In this paper, we characterize a tradeoff between cell growth and per cell protein secretion in the curli biofilm secretion system of E Coli Nissile 1917. Initial characterization using 24-hour continuous growth and protein production monitoring confirms decreased growth rates at high induction leading to a local maximum in total protein production at intermediate induction. Propidium iodide staining at the endpoint indicates that cellular death is a dominant cause of growth reduction. Assaying variants with combinatorial constructs of inner and outer membrane secretion tags, we find that diminished growth at high production is specific to secretory variants associated with accumulation of protein containing the outer membrane transport tag in the periplasmic space. RNA sequencing experiments indicate upregulation of known periplasmic stress response genes in the highly secreting variant, further implicating periplasmic stress in the growth-secretion tradeoff. Overall, these results motivate additional strategies for optimizing total protein production and longevity of secretory engineered living systems.

Geometric microcanonical theory of two-dimensional truncated Euler flows.

This paper presents a geometric microcanonical ensemble perspective on two-dimensional truncated Euler flows, which contain a finite number of (Fourier) modes and conserve energy and enstrophy. We explicitly perform phase space volume integrals over shells of constant energy and enstrophy. Two applications are considered. In the first part, we determine the average energy spectrum for highly condensed flow configurations and show that the result is consistent with Kraichnan's canonical ensemble description, despite the fact that no thermodynamic limit is invoked. In the second part, we compute the probability density for the largest-scale mode of a free-slip flow in a square, which displays reversals. We test the results against numerical simulations of a minimal model and find excellent agreement with the microcanonical theory, unlike the canonical theory, which fails to describe the bimodal statistics. This article is part of the theme issue 'Mathematical problems in physical fluid dynamics (part 2)'.

Spontaneous MXene monolayer assembly at the liquid-air interface.

Here we report on the spontaneous assembly of Ti3C2Tx MXene flakes into monolayer films at the liquid-air interface. According to X-ray reflectivity and grazing incidence X-ray fluorescence both the structure of the layers and assembly kinetics depends on the pH value of the solution. At pH > 4 MXene flakes form a single ∼1.5 nm thick layer carrying a negative charge, while in the acidic medium the layer contains coordinated anions with the formation of the Braq-/Ti3C2Tx/subphase interface. The surface layer compression allows the assembling of MXene flakes into a dense monolayer films with the surface coverage of up to 96% and surface pressure exceeding 40 mN m-1 in the case of the acidic subphase. The films can readily be transferred onto solid substrates by the conventional Langmuir-Blodgett approach or modified by surfactants to form MXene/surfactant composite films.

Pattern and predictors of medical care received by hepatitis B carriers during pregnancy and after delivery.

OBJECTIVE: The objective of the study is to evaluate the pattern and predictors of medical care received by hepatitis B virus (HBV) carriers during pregnancy and after delivery in Hong Kong. STUDY DESIGN: The study is a retrospective analysis. METHODS: Pregnant HBV carriers and their infants were followed up for 9-12 months after delivery. Face-to-face interviews were conducted to investigate what medical care they received for HBV before, during and after pregnancy. RESULTS: Data were available for 412 HBV carriers. A total of 375 (91.0%) women were known HBV carriers before pregnancy. Routine antenatal screening picked out the remaining 37 (9.0%) HBV carriers; these women were younger, more likely to be smokers and had a lower level of education (P < 0.05) than known HBV carriers. In total, 356 of 412 (86.4%) HBV carriers did not receive any medical care for HBV during pregnancy. Known HBV carrier status, history of medical check-up and the use of antiviral treatment before pregnancy were significant predictors for HBV medical care during pregnancy (P < 0.05). The results show that 217 of 412 (52.6%) HBV carriers did not receive medical care for HBV after delivery. HBV medical care before pregnancy, use of antiviral treatment before pregnancy and a higher level of education were significant predictors for postpartum HBV medical care (P < 0.05). Multivariate analysis showed that HBV medical care before pregnancy (odds ratio [OR], 7.73; 95% confidence interval [CI], 3.21-18.65; P < 0.001) and the use of antiviral treatment (OR, 5.02; 95% CI, 1.41-17.81; P = 0.013) were associated with medical care during pregnancy. Medical care before pregnancy was also associated with postpartum HBV medical care (OR, 5.05; 95% CI, 3.29-7.51; P < 0.001). CONCLUSIONS: A significant proportion of HBV carriers did not receive HBV-related medical check-ups during and after pregnancy in Hong Kong despite the majority being aware of their carrier status. Medical care before pregnancy predicted antenatal and postpartum HBV medical care.

The effect of unilateral tubal block diagnosed by hysterosalpingogram on clinical pregnancy rate in intrauterine insemination cycles: systematic review and meta-analysis.

BACKGROUND: Fallopian tube occlusion is a common cause of infertility, but the effect of unilateral tubal block (UTB) on pregnancy rates (PR) after controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) remains controversial. OBJECTIVE: To evaluate PR after COH-IUI among infertile women with proximal and distal UTB diagnosed by hysterosalpingogram (HSG), compared against women with bilateral patent tubes experiencing unexplained infertility. SEARCH STRATEGY: We searched EMBASE, MEDLINE, Google Scholar, Cochrane Library, and PUBMED from inception to 14 January 2018. SELECTION CRITERIA: Studies that report PR/cycle or cumulative PR among women with UTB and controls were included. DATA COLLECTION AND ANALYSIS: Two authors independently selected and extracted study characteristics and data. Methodological quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. MAIN RESULTS: Among 2965 patients and 5749 IUI cycles across ten studies, no significant difference in PR/cycle (odds ratio, OR = 0.88; 95% confidence interval, 95% CI = 0.69-1.12) and cumulative PR (OR = 0.80, 95% CI = 0.62-1.04) was observed. Patients with proximal UTB demonstrated similar PR/cycle (OR = 1.06, 95% CI = 0.68-1.66) and cumulative PR (OR = 1.10, 95% CI = 0.75-1.62), compared with controls, whereas patients with distal UTB had significantly lower cumulative PR (OR = 0.49, 95% CI = 0.25-0.97, P = 0.04). Patients with proximal block also demonstrated significantly improved cumulative PR, compared with patients with distal block (OR=2.41, 95% CI = 1.37-4.25, P = 0.002). CONCLUSION: Infertile patients with proximal UTB diagnosed by HSG can expect similar pregnancy rates after COH-IUI, compared with those with bilateral tubal patency and unexplained infertility, whereas patients with distal UTB have lower odds of pregnancy. These differences may reflect inherent diagnostic limitations of HSG or differences in underlying pathologies. TWEETABLE ABSTRACT: Meta-analysis evaluates pregnancy outcomes after COH-IUI in women with unilateral tubal block diagnosed by HSG.

Converse Smith-Martin cell cycle kinetics by transformed B lymphocytes.

Recent studies using direct live cell imaging have reported that individual B lymphocytes have correlated transit times between their G1 and S/G2/M phases. This finding is in contradiction with the influential model of Smith and Martin that assumed the bulk of the total cell cycle time variation arises in the G1 phase of the cell cycle with little contributed by the S/G2/M phase. Here we extend these studies to examine the relation between cell cycle phase lengths in two B lymphoma cell lines. We report that transformed B lymphoma cells undergo a short G1 period that displays little correlation with the time taken for the subsequent S/G2/M phase. Consequently, the bulk of the variation noted for total division times within a population is found in the S/G2/M phases and not the G1 phase. Models that reverse the expected source of variation and assume a single deterministic time in G1 followed by a lag + exponential distribution for S/G2/M fit the data well. These models can be improved further by adopting two sequential distributions or by using the stretched lognormal model developed for primary lymphocytes. We propose that shortening of G1 transit times and uncoupling from other cell cycle phases may be a hallmark of lymphocyte transformation that could serve as an observable phenotypic marker of cancer evolution.

The first pilot study of expanded newborn screening for inborn errors of metabolism and survey of related knowledge and opinions of health care professionals in Hong Kong.

INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

The role of the endometrial receptivity array (ERA) in patients who have failed euploid embryo transfers.

PURPOSE: Endometrial receptivity issues represent a potential source of implantation failure. The aim of this study was to document our experience with the endometrial receptivity array (ERA) among patients with a history of euploid blastocyst implantation failure. We investigated whether the contribution of the endometrial factor could be identified with the ERA test and if actionable results can lead to improved outcomes. METHODS: A retrospective review was performed for 88 patients who underwent ERA testing between 2014 and 2017. Reproductive outcomes were compared for patients undergoing frozen embryo transfer (FET) using a standard progesterone protocol versus those with non-receptive results by ERA and subsequent FET according to a personalized embryo transfer (pET) protocol. RESULTS: Of patients with at least one previously failed euploid FET, 22.5% had a displaced WOI diagnosed by ERA and qualified for pET. After pET, we found that implantation and ongoing pregnancy rates were higher (73.7 vs. 54.2% and 63.2 vs. 41.7%, respectively) compared to patients without pET, although differences were not statistically significant. CONCLUSIONS: Our experience demonstrates that a significant proportion of patients with a history of implantation failure of a euploid embryo have a displaced WOI as detected by the ERA. For these patients, pET using a modified progesterone protocol may improve the outcomes of subsequent euploid FET. Larger randomized studies are required to validate these results.

Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

BACKGROUND: Beta-interferon (IFN-ß) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. METHODS: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-ß and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. RESULTS: We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. CONCLUSIONS: Meta-analyses confirmed that IFN-ß and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.