Predictors of disease severity in SARS-CoV-2 omicron variant XBB sublineages and variants of interest.

The Omicron variant has been reported to present with milder disease compared with Delta, although this may be due to immunity from vaccination and prior exposure. Predictors of severity with recent strains have not been well characterized. We retrospectively examined consecutive cases of moderate-to-severe COVID-19 (defined as requiring supplemental oxygenation, intensive care or mortality) admitted to seven tertiary hospitals across Singapore in April 2023. Whole genome sequencing was performed on each isolate to determine the sublineage, while baseline clinical, laboratory data and outcomes were tabulated. We reviewed 182 patients with moderate-to-severe illness and 466 controls hospitalized at the same time. Advanced age and presence of chronic kidney disease predicted adverse outcome. Previously reported markers such as radiographic evidence of pneumonia, elevated C-reactive protein and serum creatinine levels at presentation also correlated with adverse outcomes. There were no observable differences in outcomes with any specific Omicron XBB sublineage. We did not find any specific Omicron XBB sublineage that was associated with worse outcomes. Larger multinational studies would be important to track the clinical evolution of the virus in its current endemic state.

Reminder-dependent alterations in long-term declarative memory expression.

The reminder of a previously-learned memory can render that memory vulnerable to disruption or change in expression. Such memory alterations have been viewed as supportive of the framework of memory reconsolidation. However, alternative interpretations and inconsistencies in the replication of fundamental findings have raised questions particularly in the domain of human declarative memory. Here we present a series of related experiments, all of which involve the learning of a declarative memory, followed 1-2 days later by memory reminder. Post-reminder learning of interfering material did result in modulation of subsequent recall at test, but the precise manifestation of that interference effect differed across experiments. With post-reminder performance of a visuospatial task, a quantitative impairment in test recall performance was observed within a visual list-learning paradigm, but not in a foreign vocabulary learning paradigm. These results support the existence of reminder-induced memory processes that can lead to the alteration of subsequent memory performance by interfering tasks. However, it remains unclear whether these effects are reflective of modulation or impairment of the putative memory reconsolidation process.

Predictive factors for successful non-operative treatment and achieving MCID improvement in health-related quality of life in adult spinal deformity.

BACKGROUND: Adult spinal deformity is a spectrum of degenerative spinal diseases with increasing prevalence and healthcare burden worldwide. Identification of patients who are more likely to improve through conservative management may reduce cost and potentially prevent surgery and its associated costs and complications. This study aims to identify predictive factors for MCID in improvement of ODI and SRS-22r questionnaires in patients with adult spinal deformity treated with conservative treatment. METHODS: A prospective, observational cohort study of 46 patients was conducted at a spine specialist clinic. Inclusion criteria were 30-80 years of age, diagnosis of neglected adolescent idiopathic scoliosis, de-novo scoliosis, degenerative spondylolisthesis, and sagittal plane deformities (thoracic hypokyphosis, lumbar hypolordosis), presenting with mechanical back pain with or without radicular leg pain. All patients received conservative management including medication and physiotherapy. Radiological and clinical parameters were measured at baseline and at 1-year follow-up. Primary outcomes were ODI and SRS-22r scores. Secondary outcomes were EQ-5D-5L scores and requiring spine surgery during conservative treatment. Predictors for MCID improvement in ODI and SRS-22r were identified using multivariate regressions and receiver operating characteristic (ROC) analyses. RESULTS: At baseline, patients who reached MCID in ODI and/or SRS-22r showed less comorbidities (diabetes mellitus, hypertension, ischemic heart disease, osteoarthritis, cancer), smaller range of lateral spinal flexion, larger trunk shift, larger pelvic incidence, a higher EQ-5D-5L anxiety/depression dimension score, a lower SRS-22r total score, and presence of spondylolisthesis. Lateral flexion range < 25 degrees, trunk shift > 14 mm, pelvic incidence > 50 degrees, EQ-5D-5L anxiety/depression dimension score > 1, and SRS-22r total score < 3.5 were the cut-off values generated by ROC analysis. CONCLUSIONS: Both radiological and clinical predictive factors for MCID improvement in health-related quality of life were identified. Future research should identify subgroups of patients who are responsive to specific conservative treatment modalities, so as to provide information for personalized medicine. LEVEL OF EVIDENCE: II.

Adjunctive berberine reduces antipsychotic-associated weight gain and metabolic syndrome in patients with schizophrenia: a randomized controlled trial.

AIM: The aim of this study was to evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic-associated weight gain and metabolic syndrome. METHODS: One hundred thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome were recruited. They were randomly assigned to berberine (600 mg/d, n = 58) or placebo (n = 55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight. Secondary outcomes included body mass index, waist circumference, serum glucose and lipid profiles, and the severity of psychotic symptoms. RESULTS: Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD], -0.75; 95% CI, -1.42 to -0.07 [P = 0.031, d = 0.41]) and 12 weeks (MD, -1.08; 95% CI, -1.76 to -0.40 [P = 0.002, d = 0.59]). Patients who received berberine also showed statistically significant improvements in end point in body mass index (MD, -0.41; 95% CI, -0.65 to -0.17 [P = 0.001, d = 0.64]), total cholesterol (MD, -0.58; 95% CI, -0.74 to -0.41 [P < 0.001, d = 1.31]), low-density lipoprotein (MD, -0.52; 95% CI, -0.68 to -0.35 [P < 0.001, d = 1.19]), and glycated hemoglobin (MD, -0.09; 95% CI, -0.18 to 0 [P = 0.05, d = 0.37]). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo. CONCLUSION: The findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and metabolic syndrome.

Aviremic organ transplant dengue virus transmission - A case report.

Dengue virus (DENV), a mosquito-borne pathogen, causes systemic infections. There are no clear guidelines regarding the screening of donor blood is used in endemic countries to prevent blood transfusion or transplant-associated dengue. DENV has been shown to be detected in urine samples even when DENV viremia is undetectable. We describe an incident of transplant-associated dengue where the donor tested negative for DENV viremia but positive for DENV viuria resulting in the transmission of DENV to our two kidney recipients. Both recipients resolved DENV infection uneventfully, with no adverse impact on the renal graft. Our findings raise the consideration for revised screening recommendations in endemic countries to include DENV RT-PCR in the urine.

Cytomegalovirus-associated pseudomembranous colitis in a kidney transplant recipient.

Pseudomembranous colitis (PMC) is classically associated with Clostridium difficile infection. We report a rare case of cytomegalovirus (CMV)-associated PMC in a 52-year-old female patient who had undergone kidney transplantation more than 20 years ago and was on low dose prednisolone and ciclosporin. She presented with an acute history of fever, lethargy, vomiting and diarrhoea on admission. Computed tomography of the abdomen showed extensive colitis, and colonoscopy revealed extensive pseudomembrane formation. Multiple tests for Clostridium difficile and other common microbiological causes of colitis were negative. CMV DNAemia and colonic biopsies confirmed the diagnosis of CMV colitis. The patient responded to prompt CMV treatment, as demonstrated by clinical, endoscopic, and histological response. While CMV is a common pathogen in the solid organ transplant population that is familiar to most transplant physicians, it may present atypically as PMC. Here, we review the literature on CMV-associated PMC and its relevance to solid organ transplant recipients. To our knowledge, this is the first reported case of CMV-associated PMC in a kidney transplant recipient.

Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial.

OBJECTIVES: An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL. METHODS: Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points. RESULTS: Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ = 4.010, P = 0.045) and menstrual resumption (χ = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups. CONCLUSIONS: Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).

Implementing electronic handover: interventions to improve efficiency, safety and sustainability.

PROBLEM: Effective handovers are critical for patient care and safety. Electronic handover tools are increasingly used today to provide an effective and standardized platform for information exchange. The implementation of an electronic handover system in tertiary hospitals can be a major challenge. Previous efforts in implementing an electronic handover tool failed due to poor compliance and buy-in from end-users. A new electronic handover tool was developed and incorporated into the existing electronic medical records (EMRs) for medical patients in Singapore General Hospital (SGH). INITIAL ASSESSMENT: There was poor compliance by on-call doctors in acknowledging electronic handovers, and lack of adherence to safety rules, raising concerns about the safety and efficiency of the electronic handover tool. Urgent measures were needed to ensure its safe and sustained use. SOLUTION: A quality improvement group comprising stakeholders, including end-users, developed multi-faceted interventions using rapid PDSA (P-Plan, D-Do, S-Study, A-Act ) cycles to address these issues. IMPLEMENTATION: Innovative solutions using media and online software provided cost-efficient measures to improve compliance. EVALUATION: The percentage of unacknowledged handovers per day was used as the main outcome measure throughout all PDSA cycles. Doctors were also assessed for improvement in their knowledge of safety rules and their perception of the electronic handover tool. LESSONS LEARNT: An electronic handover tool complementing daily clinical practice can be successfully implemented using solutions devised through close collaboration with end-users supported by the senior leadership. A combined 'bottom-up' and 'top-down' approach with regular process evaluations is crucial for its long-term sustainability.

Improved outcomes after technical modifications in tubularized incised plate urethroplasty for mid-shaft and proximal hypospadias.

PURPOSE: To investigate and compare the outcomes after tubularized incised plate (TIP) urethroplasty in mid-shaft and proximal hypospadias using a standard and a modified technique. METHODS: We conducted a retrospective study in 104 consecutive children who underwent mid-shaft or proximal TIP repairs from Jan 2007 to Sept 2015. Patients in Cohort One had dorsal dartos (DD) neourethral coverage while patients in Cohort Two had either de-epithelialized split preputial (DESP) or tunica vaginalis (TV) flap coverage. TV flap was used only when DESP flap was not sufficient to cover the neourethra. RESULTS: There were 52 patients each in Cohort One (DD, n = 52) and Cohort Two (DESP, n = 38; TV, n = 14) with no difference in ratio of mid-shaft/proximal between the two cohorts. At a median follow-up of 28 months, 36 patients (34.6 %) developed 47 complications including fistula (n = 19; 18.3 %) and neourethral dehiscence (n = 4; 3.8 %). Cohort One patients had significantly more fistula (28.8 vs 7.7 %; p = 0.005) and neourethral dehiscence (7.7 vs 0 %; p = 0.04) than Cohort Two. There was no difference between the two cohorts in the complication rates of meatal stenosis, recurrent ventral curvature and neourethral stricture. CONCLUSIONS: Both DESP and TV flap appear to be superior to DD in preventing fistula and neourethral dehiscence in non-distal TIP repairs.

18beta-glycyrrhetinic acid induces apoptosis in pituitary adenoma cells via ROS/MAPKs-mediated pathway.

The purpose of the present study was to evaluate the anti-tumor effects of 18beta-glycyrrhetinic acid (GA), a natural compound extracted from liquorice, against pituitary adenoma and its underlying mechanisms in cultured cells and mouse model of xenografted tumor. GA induced cellular damage in rat pituitary adenoma-derived MMQ and GH3 cells, manifested as reduced cell viability, increased lactate dehydrogenase release, elevated intracellular reactive oxygen species (ROS) and Ca(2+) concentration. GA also caused G0/G1 phase arrest, increased apoptosis rate and increased mitochondrial membrane permeabilization by suppressing the mitochondrial membrane potential and down-regulating a ratio of B cell lymphoma 2 (Bcl-2) and Bax. GA activated calcium/calmodulin-dependent protein kinase II (CaMKII), c-Jun N-terminal kinase (JNK) and P38; but these activating effects were attenuated by pretreatment with N-acetyl-L-cysteine, a ROS inhibitor. Pretreatment with KN93, a CaMKII inhibitor, also abolished the GA activation of JNK and P38. GA remarkably inhibited growth of pituitary adenoma grafted on nude mice. These results suggest that the anti-pituitary adenoma effect of GA is associated with its apoptotic actions by activating mitochondria-mediated ROS/mitogen-activated protein kinase pathways in particular CaMKII that may serve a linkage between ROS accumulation and the activation of JNK and P38. This study provides experimental evidence in the support of further developing GA as a chemotherapeutic agent for pituitary adenoma.

From laparoscopic to open Kasai portoenterostomy: the outcome after reintroduction of open Kasai portoenterostomy in infant with biliary atresia.

PURPOSE: Apparently superior result was observed after open Kasai portoenterostomy in infant with biliary atresia. Our institute stopped performing laparoscopic portoenterostomy since 2007. We aimed to investigate the outcome after reintroduction of open portoenterostomy. METHODS: 27 non-syndromic infants underwent open Kasai portoenterostomy from 2007 to 2012. The age and the sex of the patient, the bilirubin level before the operation, the early clearance of jaundice (total bilirubin <20 µmol/L within 6 month of portoenterostomy), the native liver survival at 2 years after the operation were reviewed. The results were retrospectively compared with all 16 infants who underwent laparoscopic Kasai portoenterostomy before 2007. RESULTS: All infants had type III biliary atresia. No statistical difference was observed regarding the age at operation and the pre-operative bilirubin level. The early clearance of jaundice rate was 81% (22/27) after open operation and was 50% (8/16) after laparoscopic operation (p = 0.03). At 2 years after the operation, the native liver survival was 81% (22/27) after open operation and was 50% (8/16) after laparoscopic operation (p = 0.03). CONCLUSION: Reintroduction of open Kasai portoenterostomy was associated with superior early clearance of jaundice rate and 2-year native liver survival rate.

Abridging the CMOS Technology II.

As silicon CMOS devices approach their physical and technological miniaturization limits, Moore's Law is expected to persist for several more cycles, thanks to innovative, more compact layout structures [...].

Comment on "Bipolar Resistive Switching in Lanthanum Titanium Oxide and an Increased On/Off Ratio Using an Oxygen-Deficient ZnO Interlayer".

The Mott-based resistive switching random access memory (RRAM) has been considered as a promising candidate for next-generation nonvolatile mass storage. Its performance relies on the oxygen migration process. In ACS Appl. Mater. Interfaces 2022, 14, 17682-17690, Wang et al. demonstrated that inserting a ZnO layer between the top tungsten electrode and the lanthanum titanium oxide (LTO) layer can improve the ON/OFF current ratio of the RRAM. This improvement was attributed to the increased oxygen vacancies in the ZnO layer. We argue their interpretation with the role, significance, and statistics of the oxygen vacancy in the samples. Our experimental evidence contradicts their claim, and we propose that hydroxy groups should be the responsible candidate for their claimed oxygen vacancy peak at around 531-532 eV in the O 1s photoelectron spectroscopy observed in their samples. We thus propose an alternative mechanism for the ON/OFF ratio enhancement with the ZnO interlayer: the ZnO layer prevents the LTO oxygen and hydroxy groups migration and from reacting with the multivalent tungsten electrode.

Contacts at the Nanoscale and for Nanomaterials.

Contact scaling is a major challenge in nano complementary metal-oxide-semiconductor (CMOS) technology, as the surface roughness, contact size, film thicknesses, and undoped substrate become more problematic as the technology shrinks to the nanometer range. These factors increase the contact resistance and the nonlinearity of the current-voltage characteristics, which could limit the benefits of the further downsizing of CMOS devices. This review discusses issues related to the contact size reduction of nano CMOS technology and the validity of the Schottky junction model at the nanoscale. The difficulties, such as the limited doping level and choices of metal for band alignment, Fermi-level pinning, and van der Waals gap, in achieving transparent ohmic contacts with emerging two-dimensional materials are also examined. Finally, various methods for improving ohmic contacts' characteristics, such as two-dimensional/metal van der Waals contacts and hybrid contacts, junction doping technology, phase and bandgap modification effects, buffer layers, are highlighted.

Rapid management of Serratia marcescens outbreak in neonatology unit in Singapore: Risk factors and infection control measures.

BACKGROUND: We describe the investigations for control of two consecutive Serratia marcescens outbreaks in neonatology unit of Singapore General Hospital. METHODS: Epidemiological investigations, environmental sampling and risk-factors analysis were performed to guide infection control measures. Active surveillance sampling of nasopharyngeal aspirate and/or stool from neonates was conducted during both outbreaks. Whole-genome-sequencing was done to determine clonal links. Retrospective case-control study was conducted for second outbreak to identify risk factors for S marcescens acquisition. RESULTS: In 2022, two genetically unrelated S marcescens outbreaks were managed involving five neonates in March 2022 (outbreak 1) and eight neonates in November 2022 (outbreak 2). A link to positive isolates from sinks in intensive care units and milk preparation room was identified during outbreak 1. Neonatal jaundice (aOR, 16.46; p-value= 0.023) and non-formula milk feeding (aOR, 13.88; p-value= 0.02) were identified as risk factors during second outbreak. Multiple interventions adopted were cohorting of positive cases, carriage-screening, enhanced environmental cleaning, and emphasis on alcohol-based handrubs for hand-hygiene. CONCLUSION: The two outbreaks were likely due to infection prevention practices lapses and favourable environmental conditions. Nosocomial S marcescens outbreaks in neonatology units are difficult to control and require multidisciplinary approach with strict infection prevention measures to mitigate risk factors.

Paeoniflorin, a natural neuroprotective agent, modulates multiple anti-apoptotic and pro-apoptotic pathways in differentiated PC12 cells.

Numerous studies have shown robust neuroprotective effects of paeoniflorin (PF), a natural compound derived from the herbal medicine Paeony radix. In the present study, we determined associations of PF neuroprotection with its modulation of various apoptotic and anti-apoptotic pathways. PF (50-400 µM) pretreatment significantly improved viability of differentiated PC12 cells exposed to methyl-4-phenylpyridine ion (MPP(+)), a neurotoxin, and inhibited over-release of lactate dehydrogenase, a biomarker of neuronal cell death. PF also ameliorated MPP(+)-induced nuclear and mitochondrial apoptotic alteration and intracellular calcium overload. PF treatment reversed MPP(+) suppression of activity of B cell lymphoma-extra large, which is a mitochondrial membrane molecule that protects cells from DNA damage-induced apoptosis, and strikingly inhibited the enhanced level of cleaved poly(ADP-ribose)polymerase, which is involved in the process of apoptosis. PF alone and coadministration with MPP(+) enhanced phospho activation of extracellular signal-regulated kinases, Akt, and its downstream element glycogen synthase kinase-3, but the effects were completely abolished in the presence of their blockers PD98059 and LY294002. The presence of the blockers also diminished the potency of PF in improving viability of MPP(+)-exposed cells. These results indicate that neuroprotective effects of PF are related to its modulation of multiple anti-apoptotic and pro-apoptotic pathways, including blockade of intracellular calcium overload, prevention of mitochondrial membrane integrity, inhibition of pro-apoptotic molecules, and up-regulation of anti-apoptotic proteins associated with cell survival and proliferation. The study provides evidence supporting PF as a potential therapeutic agent used for the treatment of neurodegenerative diseases and neural injury.

Poole-Frenkel (PF)-MOS: A Proposal for the Ultimate Scale of an MOS Transistor.

This work reports, for the first time, the phenomenon of lateral Poole-Frenkel current conduction along the dielectric/Si interface of a silicon nanowire metal-oxide semiconductor (MOS) transistor. This discovery has a great impact on the study of device characteristic modeling and device reliability, leading to a new kind of electronic device with a distinct operation mechanism for replacing the existing MOS transistor structure. By measuring the current-voltage characteristics of silicon nanowire MOS transistors with different nanowire widths and at elevated temperatures up to 450 K, we found that the current level in the conventional ohmic region of MOS transistors, especially for the transistors with a nanowire width of 10 nm, was significantly enhanced and the characteristics are no longer linear or in an ohmic relationship. The enhancement strongly depended on the applied drain voltage and strictly followed the Poole-Frenkel emission characteristics. Based on this discovery, we proposed a new type of MOS device: a Poole-Frenkel emission MOS transistor, or PF-MOS. The PF-MOS uses the high defect state Si/dielectric interface layer as the conduction channel and is expected to possess several unique features that have never been reported. PF-MOS could be considered as the ultimate MOS structure from a technological point of view. In particular, it eliminates the requirement of a subnanometer gate dielectric equivalent oxide thickness (EOT) and eradicates the server mobility degradation issue in the sub-decananometer nanowires.