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Delusional disorders often amaze psychiatrists with their variety of themes. Folie a deux is usually characterised as a shared psychotic or induced delusional disorder between two or more persons in close proximity. It has often been cited in case reports but has not been dealt with in much detail compared with other psychiatric conditions, and folie a trois has had even less attention. Only a small percentage of reported cases involve families and an even smaller fraction of these involve siblings. We hereby describe and discuss a case of folie a famille involving 3 unmarried sisters living together in isolation. This demonstrates how the one sister, who had schizophrenia, induced the other sisters to share the same delusional beliefs. We managed to separate the secondary cases using hospitalisation and medications and achieved improvement and recovery. [ABSTRACT FROM AUTHOR]

Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. While there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation have been lacking. Here we describe the in vitro functional and structural characterization of PrnC, a flavin-dependent halogenase that can act on free-standing pyrroles. Computational modeling and site mutagenesis studies identified three key residues in the catalytic pocket. A moderate resolution map using single-particle cryogenic electron microscopy reveals PrnC to be a dimer. This native PrnC can halogenate a library of structurally diverse pyrrolic heterocycles in a site-selective manner and be applied in the chemoenzymatic synthesis of a chlorinated analog of the agrochemical fungicide Fludioxonil., (© 2024. The Author(s).)

Laccase from Trametes versicolor was found to oxidize non-phenolic arenes and enable the trifluoromethylation of arenes in the presence of in situ generated CF 3 radicals at a catalyst loading as low as 0.0034%. The biocatalytic trifluoromethylation proceeded under mild conditions and could increase the yield by up to 12 fold, compared to the control.

RadH is one of the flavin-dependent halogenases that has previously exhibited promising catalytic activity towards hydroxycoumarin, hydroxyisoquinoline, and phenolic derivatives. Here, we evaluated new functional homologs of RadH and expanded its specificities for the halogenation of non-tryptophan-derived, heterocyclic scaffolds. Our investigation revealed that RadH could effectively halogenate hydroxyquinoline and hydroxybenzothiophene. Assay optimization studies revealed the need to balance the various co-factor concentrations and where a GDHi co-factor recycling system most significantly improves the conversion and efficiency of the reaction. A crystal structure of RadH was also obtained with a resolution of 2.4 Å, and docking studies were conducted to pinpoint the binding and catalytic sites for substrates.

Background: Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19., Methods: In the present study, we evaluated various transmission control measures that were imposed in 10 global urban cities and provinces in 2021- Bangkok, Gauteng, Ho Chi Minh City, Jakarta, London, Manila City, New Delhi, New York City, Singapore, and Tokyo., Findings: Based on our analysis, we herein propose the population-level Swiss cheese model for the failures and pitfalls in various strategies that each of these cities and provinces had. Furthermore, whilst all the evaluated cities and provinces took a different personalized approach to managing the pandemic, what remained common was dynamic enforcement and monitoring of breaches of each barrier of protection. The measures taken to reinforce the barriers were adjusted continuously based on the evolving epidemiological situation., Interpretation: How an individual city or province handled the pandemic profoundly affected and determined how the entire country handled the pandemic since the chain of transmission needs to be broken at the very grassroot level to achieve nationwide control., Funding: The present study did not receive any external funding., Competing Interests: The authors declare no conflicts of interests with regards to the present study. Authors did not receive any external funding for the study., (© 2022 The Author(s).)

Background: Elective surgery is the treatment of choice for symptomatic giant hiatus hernia (GHH), and quality of life (QoL) has become an important outcome measure following surgery. The aim of this study is to review the literature assessing QoL following repair of GHH., Methodology: A systematic literature search was performed by two reviewers independently to identify original studies evaluating QoL outcomes after GHH surgery. MeSH terms such as paraoesophageal; hiatus hernia; giant hiatus hernia and quality of life were used in the initial search. Original studies in English language using validated questionnaires on humans were included. Review articles, conference abstracts and case reports and studies with duplicate data were excluded., Results: Two hundred and eight articles were identified on initial search, of which 38 studies (4404 patients) were included. Studies showed a significant heterogeneity in QoL assessment tools, surgical techniques and follow-up methods. All studies assessing both pre-operative and post-operative QoL (n = 31) reported improved QoL on follow-up after surgical repair of GHH. Improvement in QoL following GHH repair was not affected by patient age, surgical technique or the use of mesh. Recurrence of GHH after surgery may, however, adversely impact QoL., Conclusion: Surgical repair of GHH improved QoL scores in all the 38 studies. The impact of recurrence on QoL needs further assessment. The authors also recommend uniform reporting of surgical outcomes in future studies., Competing Interests: None

Background: COVID-19 has stressed healthcare systems and workers worldwide. GPs, as first points of contact between suspected cases and the healthcare system, have assumed frontline roles in this crisis. While the prevalence of mental health problems and illnesses arising in healthcare workers (HCWs) from tertiary care settings during the COVID-19 pandemic is well-examined, 1 the impact on GPs remains understudied., Aim: To describe the prevalence and predictors of anxiety, burnout, depression, and post-traumatic stress disorder (PTSD) among GPs during the COVID-19 pandemic., Design & Setting: Survey of GPs operating in Singapore primary care clinics., Method: GPs completed a survey that comprised of four validated psychometric instruments. Open-ended questions asked about responders' challenges and their envisaged support. Data were analysed with multiple logistic regression with demographic data as covariates; concepts of grounded theory were used to analyse the qualitative responses., Results: A total of 257 GPs participated. Fifty-five (21.4%) met the scales' criteria for anxiety, 211 (82.1%) for burnout, 68 (26.6%) for depression, and 23 (8.9%) for PTSD. Multivariate regression analysis showed working in a public primary care setting was associated with anxiety and depression. Qualitative analyses uncovered possible stressors: changes to clinical and operational practices; increased workloads; and financial difficulties., Conclusion: Mental health issues were found to be present in Singaporean GPs during the pandemic. Prevalence of anxiety, burnout, and depression were found to be higher than those reported pre-COVID-19. The findings also provide determinants of the issues that serve as possible foci for targeted interventions., (Copyright © 2021, The Authors.)

The ability of corals to withstand changes in their surroundings is a critical survival mechanism for coping with environmental stress. While many studies have examined responses of the coral holobiont to stressful conditions, its capacity to reverse responses and recover when the stressor is removed is not well-understood. In this study, we investigated among-colony responses of Pocillopora acuta from two sites with differing distance to the mainland (Kusu (closer to the mainland) and Raffles Lighthouse (further from the mainland)) to heat stress through differential expression analysis of target genes and quantification of photophysiological metrics. We then examined how these attributes were regulated after the stressor was removed to assess the recovery potential of P. acuta . The fragments that were subjected to heat stress (2 °C above ambient levels) generally exhibited significant reduction in their endosymbiont densities, but the extent of recovery following stress removal varied depending on natal site and colony. There were minimal changes in chl a concentration and maximum quantum yield (Fv/Fm, the proportion of variable fluorescence (Fv) to maximum fluorescence (Fm)) in heat-stressed corals, suggesting that the algal endosymbionts' Photosystem II was not severely compromised. Significant changes in gene expression levels of selected genes of interest (GOI) were observed following heat exposure and stress removal among sites and colonies, including Actin , calcium/calmodulin-dependent protein kinase type IV ( Camk4 ), kinesin-like protein ( KIF9 ), and small heat shock protein 16.1 ( Hsp16.1 ). The most responsive GOIs were Actin , a major component of the cytoskeleton, and the adaptive immune-related Camk4 which both showed significant reduction following heat exposure and subsequent upregulation during the recovery phase. Our findings clearly demonstrate specific responses of P. acuta in both photophysiological attributes and gene expression levels, suggesting differential capacity of P. acuta corals to tolerate heat stress depending on the colony, so that certain colonies may be more resilient than others.

Objectives: To evaluate comparative outcomes of laparoscopic repair of groin hernia with and without mesh fixation., Methods: MEDLINE; EMBASE; CINAHL; CENTRAL; the World Health Organization International Clinical Trials Registry; ClinicalTrials.gov; ISRCTN Register, and bibliographic reference lists were systematically checked. Combination of free text and controlled vocabulary search adapted were applied to thesaurus headings, search operators and limits in each of the above databases. Post-operative pain, procedure time, conversion rate, length of hospital stay, time taken to normal activities, overall complications, seroma formation, cost and recurrence were the outcome parameters. Combined overall effect sizes were calculated using fixed-effect or random-effects models. The work has been reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. This protocol was registered at the International Prospective Register of Systematic Reviews (registration number: CRD42019139564)., Results: We identified 13 randomized controlled trials reporting a total of 1731 patients (2021 groin hernia) evaluating outcomes of laparoscopic hernia repair with mesh fixation using stapler or tacker (n = 853 patients, 999 hernia) and without mesh fixation (n = 878 patients, 1022 hernia). Mesh Fixation was associated with significantly higher post-operative pain assessed by visual analogue scale (VAS) (MD: 0.59; 95% CI, 0.05-1.13, P = 0.03) and longer procedure time (MD: 2.00; 95% CI, 0.98-3.02, P = 0.0001), compared to no fixation technique. However, there was no significant difference in length of hospital stay (MD:0.09; 95% CI, -0.05-0.23, P = 0.19), time to normal activities, (MD: 0.12; 95% CI, -0.37-0.61, P = 0.69), overall complications (OR: 1.05; 95% CI, 0.77-1.43, P = 0.76), seroma formation (OR: 0.63; 95% CI, 0.39-1.00, P = 0.05) and recurrence rate (RD: 0.00; 95% CI, -0.01-0.01, P = 0.84) between two groups., Conclusions: Avoiding mesh fixation with a stapler or tacker during laparoscopic groin hernia repair may reduce postoperative pain and procedure time. Future studies are encouraged to evaluate cost effectiveness of each approach., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Introduction: People who have a mental illness and who are stable on their current treatment may be suitable for follow-up care with a community-based general practitioner. A general practitioner-partnership programme was designed in an institute in Singapore to facilitate the transition to community services. However, the rates of successful referrals were low., Methods: Our study followed the format of a quality improvement project, and used administrative data from April 2014 to June 2016 to gauge the impact of the interventions chosen to improve uptake of referrals. Three potential areas of improvement were found based on interviews with 25 service users., Results: During the 11 months of pre-intervention period (April 2014 to February 2015), 64% of potentially suitable service users (152 of 238 referrals) transitioned to community services. Low transition was linked to 3 identified causes and consequently, case managers developed personalised financial counselling for service users, assisted in the application for financial supports, and dispelled misconceptions about service provider inability to treat mental illness. Over the 16 months of intervention period (March 2015 to June 2016), the follow-up rate for referrals rose to 92% (260 / 283 referrals)., Conclusion: Given that financial support entitlements change, it is important for case managers to remain aware of changing policy. Misconceptions of service provider qualifications may have a great impact on service user's willingness to seek services from primary care providers.

Background: Studies worldwide indicate that people with intellectual disability have high risks of physical and mental morbidities, and poor quality of health care. This study was aimed at determining general practitioners' perceptions on barriers in clinical assessment and training needs with regard to the healthcare of community-dwelling people with intellectual disability., Methods: A survey questionnaire was developed specifically for the study through focus group discussions and a literature review. The study was conducted as a cross-sectional anonymous survey of private general practitioners practicing in Singapore. The survey contained questions on their experience and training needs in assessing and treating patients with intellectual disability., Results: Forty-nine of the 272 questionnaires sent out were returned. The respondents were predominantly male general practitioners working in "solo" practices. For most general practitioners, the proportion of patients with intellectual disability ranged from 1% to 5%. Nearly 90% of general practitioners identified problems in communicating with such patients as an important barrier that affected the quality of assessment of their health conditions. Other barriers identified were behavioral issues and sensory impairments. Only one-third of the general practitioners were confident that they had sufficient knowledge of physical and mental health conditions related to patients with intellectual disability. Three-fourths of the general practitioners believed that further training in this area would be beneficial., Conclusion: Appropriate interventions to address barriers in assessment and management of patients with intellectual disability with further training for general practitioners may improve the standard of healthcare provided to this population group.

Over the last few decades, resveratrol has gained significance due to its impressive array of biological activities; however, its true potential as a drug has been severely constrained by its poor bioavailability. Indeed, several studies have implicated this bioavailability trait as a major road-block to resveratrol's potential clinical applications. To mitigate this pharmacokinetic issue, we envisioned a tactical bioisosteric modification of resveratrol to bicyclo[1.1.1]pentane (BCP) resveratrol. Relying on the beneficial bioisosteric potential demonstrated by the BCP-scaffold, we hypothesized that BCP-resveratrol would have an inherently better in vivo PK profile as compared to its natural counterpart. To validate such a hypothesis, it was necessary to secure a synthetic access to this novel structure. Herein we describe the first synthesis of BCP-resveratrol and disclose its PK properties.

Gallbladder agenesis (GA) is a rare congenital abnormality with an incidence of 0.01-0.09%. Majority of GA exist alone although it can be associated with other systemic malformations involving the gastrointestinal, genitourinary, cardiovascular and skeletal systems. It is thought that biliary and pancreatic pathologies coexist and this is the second case reported in the literature of GA presenting with pancreatitis., (2016 BMJ Publishing Group Ltd.)

Background: Gastroesophageal reflux disease (GERD) is a prevalent disease caused by multiple facets of factors. Current Western Medicine treatment of GERD focuses mainly on symptom alleviation. Although proton-pump inhibitors are known to alleviate symptoms in most patients, a significant portion of patients continue to present GERD., Objective: Given multiple factors, including the involvement of psychosocial influences, that contribute to the pathogenesis of GERD, we sought to look beyond the current available treatments for a multitargeting therapy to combat this disease. Traditional Chinese Medicine, with a history of more than 2000 years, is known for its holistic approach in the treatment of human body., Methods: In this article, we aim to review the ancient Traditional Chinese Medicine literature and current Traditional Chinese Medicine studies related to GERD, thereby presenting the understanding of GERD from a TCM perspective., (Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Both converted and difficult laparoscopic cholecystectomies (LC) have impact on operating time and training of juniors. The aim of this study is to evaluate parameters that predict difficult LC or conversion (C), and find predictive values for different cut-off points of C-reactive protein (CRP) for conversion., Materials and Methods: A retrospective cohort study of cholecystectomies performed from January 2011 to December 2012 at NHS trust was undertaken. Association of intra-operative difficulties or conversion with the following factors was studied: Age, gender, CRP, white blood cell count (WBC), history of pancreatitis, and endoscopic retrograde cholangiopancreatography (ERCP)., Results: Two hundred and ninety one patients were analysed (222 laparoscopic, 45 difficult LC and 24 C). Only 141 patients had a recorded CRP. Median CRP was highest for patients who were converted (286.20) compared to those who had difficult LC (67.40) or LC (7.05). Those patients who did not have preoperative CRP (8/150, 5.3%) had less chance of conversion than those who had CRP (16/141, 11.34%) (P = 0.063). Patients with CRP of ≤220 (3/91, 3.2%) had significantly less chance of conversion than those with CRP >220 (13/21, 61.9%) (P < 0.001). High preoperative CRP, WBC count and ERCP, were predictors of conversion. These factors were only marginally better than CRP alone in predicting conversion., Conclusion: CRP can be a strong predictor of conversion of LC. Further validation of the results is needed.

Exploration of novel chemical space, a modern trend in medicinal chemistry, is heavily reliant on synthetic access to new and interesting building blocks. In this direction, the following work describes an expedient synthesis of one such moiety, 3-fluorobicyclo[1.1.1]pentan-1-amine, by employing radical fluorination.

Introduction: The recurrence rate of giant hiatus hernias (GHH) following repair is high (30%) and increases with the hernia size and previous revision surgery. The mechanism of recurrence is poorly understood., Methods: This is a retrospective cohort study of all consecutive patients who underwent repair of giant hiatus hernia in a tertiary upper GI referral centre from November 2000 to November 2014. Patients who underwent redo surgery were identified and data on intra-operative findings and procedure performed at primary and redo surgery from their operation notes were collected., Results: A total of 81 patients underwent primary repair of GHH over the 14 year study period. 10 (12.3%) had symptomatic/radiological recurrence of which 4 were found to have the distal stomach herniating into the chest despite having an intact intra-abdominal wrap/gastropexy. To prevent migration of the distal stomach into the chest, distal gastropexy - fixing the antrum to the anterior abdominal wall, was added to 'conventional' gastropexy in 5 subsequent cases, in whom the antrum was in the chest preoperatively. These cases have no evidence of recurrence at the end of 6 months follow up., Conclusion: Securing the antrum of stomach to the anterior abdominal wall may prevent migration of the distal stomach and other infracolic organs into the chest and thus reduce recurrence of some GHH where antrum had been in chest previously., (Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

3-Deazaneplanocin A (DzNep) is a potential epigenetic drug for the treatment of various cancers. DzNep has been reported to deplete histone methylations, including oncogenic EZH2 complex, giving rise to epigenetic modifications that reactivate many silenced tumor suppressors in cancer cells. Despite its promise as an anticancer drug, little is known about the structure-activity relationships of DzNep in the context of epigenetic modifications and apoptosis induction. In this study, a number of analogues of DzNep were examined for DzNep-like ability to induce synergistic apoptosis in cancer cells in combination with trichostatin A, a known histone deacetylase (HDAC) inhibitor. The structure-activity relationship data thus obtained provide valuable information on the structural requirements for biological activity. The studies identified three compounds that show similar activities to DzNep. Two of these compounds show good pharmacokinetics and safety profiles. Attempts to correlate the observed synergistic apoptotic activities with measured S-adenosylhomocysteine hydrolase (SAHH) inhibitory activities suggest that the apoptotic activity of DzNep might not be directly due to its inhibition of SAHH., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gallbladder duplication is a rare congenital abnormality first described by Boyden in 1926. Pre-operative diagnosis is essential in identifying anatomical abnormalities in order to avoid biliary injuries at the time of surgery or performance of an incomplete operation. We present a case of a duplex gallbladder and review of the literature., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This article introduces the Layer Analysis Method of the Yellow Emperor's Inner Classic text to revive its use in modern acupuncture and medicine. This is a crucial concept, especially for the diagnosis and treatment of diseases by acupuncture. First, the rise and decline of this method is explored. Second, the differentiation of this method is described by symptoms, the affected organs, and the stage of the disease. Third, the treatment method is summarized into four categories: (1) equipment, (2) technique, (3) acupoint, and (4) pathology. The resemblance of the Layer Analysis Method to modern clinical applications is worth examining. The sinew layer is especially fascinating with its similarity to the Anatomy Trains' track. The skin, vessel, muscle, and bone layers have their respective resemblances to their counterparts in modern medicine. The holism concept of traditional Chinese medicine (TCM) is demonstrated throughout the Layer Analysis Method theory. In addition, the Layer Analysis Method of the Yellow Emperor's Inner Classic should be reconsidered and complemented by channel-collateral pattern differentiation for acupuncturists to achieve better clinical results. Future research on acupuncture should consider this theory with the channel-collateral pattern differentiation theory., (Copyright © 2014. Published by Elsevier B.V.)

Biomimetic in vitro intestinal models are becoming useful tools for studying host-microbial interactions. In the past, these models have typically been limited to simple cultures on 2-D scaffolds or Transwell inserts, but it is widely understood that epithelial cells cultured in 3-D environments exhibit different phenotypes that are more reflective of native tissue, and that different microbial species will preferentially adhere to select locations along the intestinal villi. We used a synthetic 3-D tissue scaffold with villous features that could support the coculture of epithelial cell types with select bacterial populations. Our end goal was to establish microbial niches along the crypt-villus axis in order to mimic the natural microenvironment of the small intestine, which could potentially provide new insights into microbe-induced intestinal disorders, as well as enabling targeted probiotic therapies. We recreated the surface topography of the small intestine by fabricating a biodegradable and biocompatible villous scaffold using poly lactic-glycolic acid to enable the culture of Caco-2 with differentiation along the crypt-villus axis in a similar manner to native intestines. This was then used as a platform to mimic the adhesion and invasion profiles of both Salmonella and Pseudomonas, and assess the therapeutic potential of Lactobacillus and commensal Escherichia coli in a 3-D setting. We found that, in a 3-D environment, Lactobacillus is more successful at displacing pathogens, whereas Nissle is more effective at inhibiting pathogen adhesion.

From a medicinal chemistry perspective, bicyclo[1.1.1]pentan-1-amine (1) has served as a unique and important moiety. Synthetically, however, this compound has received little attention, and only one scalable route to this amine has been demonstrated. Reduction of an easily available and potentially versatile intermediate, 1-azido-3-iodobicyclo[1.1.1]pentane (2), can offer both a flexible and scalable alternative to this target. Herein, we describe our scrutiny of this reportedly elusive transformation and report our ensuing success with this endeavor.

Rhizoma Coptidis (RC), commonly known as huanglian, is a herb frequently used in Traditional Chinese Medicine (TCM) prescriptions. Known to have "clearing damp-heat, quenching fire and counteracting poison" properties, it was widely used in the Chinese community in Singapore. Berberine, an alkaloid isolated from RC, is known to have a wide array of therapeutic effects including antimicrobial, antineoplastic, and hepatoprotective effects. In 1978, RC was implicated in causing neonatal jaundice (NNJ) and kernicterus in neonates suffering from glucose-6-phosphate dehydrogenase (G6PD) deficiency, leading to the banning of RC and berberine in Singapore. More than three decades later, accumulating evidence-based studies pointing to the safety of RC for general public and better understanding of G6PD deficiency, the Health Sciences Authority (HSA) in Singapore reviewed and lifted the prohibition on RC and berberine, turning a brand new chapter in the history of TCM in Singapore. This paper aims to review the safety of RC and berberine, using the prohibition of use and subsequent lifting of ban on RC and berberine in Singapore as an illustration to highlight the importance of evidence-based studies in Traditional Chinese Medicine (TCM).

The research on acupuncture has increased steadily over the years and regular review and revision of the direction of future acupuncture research are necessary. This paper aims to review and explore the significance of acupuncture depth in modern acupuncture research. Searches conducted in Science Direct and China National Knowledge Infrastructure (CNKI) databases reflected a lack of focus on depth of acupuncture. We propose that the research trends of acupuncture should progress to the depth of insertion. It is suggested that future acupuncture research, especially randomized controlled trials (RCTs), should take into consideration the depth of insertion. Comparison between databases using different language of medium suggests the need for international collaboration of researchers from the same field. It is also crucial to inherit and innovate traditional medicine (TM) through modern technology. The use of bibliometric method is also suitable for development of TM research trends. Acupuncture and depth should be considered as one of the future directions of acupuncture research.

3-Deazaneplanocin A (DzNep), a global histone methylation inhibitor, has attracted significant interest in epigenetic research in recent years. The molecular mechanism of action and the cellular off-targets of DzNep, however, are still not well-understood. Our aim was to develop novel DzNep-derived small-molecule probes suitable to be used in live mammalian cells for identification of potential cellular targets of DzNep under physiologically relevant settings. In the current study, we have successfully designed, synthesized, and tested one such probe, called DZ-1. DZ-1 is a 'clickable' affinity-based probe (AfBP) derived from DzNep with minimal structural modifications. The probe was found to be highly cell-permeable, and possessed similar anti-apoptotic activities as DzNep in MCF-7 mammalian cells. Two additional control probes were made as negative labeling/pull-down probes in order to minimize false identification of background proteins due to unavoidable, intrinsic nonspecific photo-crosslinking reactions. All three probes were subsequently used for in-situ proteome profiling in live mammalian cells, followed by large-scale pull-down/LC-MS/MS analysis for identification of potential cellular protein targets that might interact with DzNep in native cellular environments. Our LC-MS/MS results revealed some highly enriched proteins that had not been reported as potential DzNep targets. These proteins might constitute unknown cellular off-targets of DzNep. Though further validation experiments are needed in order to unequivocally confirm these off-targets, our findings shed new light on the future use of DzNep as a validated chemical probe for epigenetic research and as a potential drug candidate for cancer therapy., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background/purpose: Total esophagogastric dissociation has been described as both a primary and a rescue procedure for patients with severe gastroesophageal reflux. Although most commonly used in the neurologically impaired, it has also been used in those with no neurological impairment. The main objective of this study was to determine morbidity and mortality for this procedure., Methods: All published cases of esophagogastric dissociation in children were identified. Series were updated where possible by personal communication with the author. Patient characteristics, indications, morbidity, and mortality were analyzed., Results: One hundred eighty-one cases were identified. One hundred seventeen were primary operations and 64 were rescue procedures. There were 29 (16.0%) early complications and 28 (15.5%) late complications with 6 (3.3%) deaths related to the procedure of a total of 35 deaths. Twenty-one patients (11.6%) required re-operation in the study periods., Conclusions: Esophagogastric dissociation has an acceptable morbidity and mortality. It is useful as both a primary and a rescue procedure., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Infectious diseases are the leading causes of death worldwide. The development of efficient and low cost prophylactics to prevent pathogenic infection is given high priority in the twenty-first century. Commensal bacteria are largely seen as harmless and can survive symbiotically (in many cases) in niches throughout the human body. Advances in genetic engineering and understanding of pathogenesis have revealed many potential strategies to develop engineered bacteria for prophylaxis purposes: including live vaccines and anti-infective agents. In this review, we discuss recent advances and potentialities of prophylaxis with engineered bacteria., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: At the Institute of Mental Health/Woodbridge Hospital, 55% of the long-stay patients are on more than two antipsychotics for treatment of chronic schizophrenia. Our aim was to reduce antipsychotic polypharmacy (APP) among chronic schizophrenia inpatients at the long-term wards at the Institute of Mental Health, Singapore from 2006 to 2008., Methodology: Using Clinical Practice Improvement Program (CPIP) methodology and using a Plan, Do, Study, Act approach, we surveyed patients, physicians, and nurses for responses regarding reducing the amount of APP for psychiatric patients. The first CPIP (CPIP1) was conducted from August 2006 to January 2007, and focused on psychogeriatric chronic schizophrenia inpatients. This methodology was spread to a second CPIP (CPIP2) from April 2008 to October 2008, which focused on adult chronic schizophrenia inpatients., Results: Both CPIPs were successful in the reduction of APP within the geriatric and adult long-term patients. For CPIP1, eight patients had their antipsychotics reduced. There was a reduction of an average chlorpromazine-equivalent dose per day from 375 mg per patient to 170 mg. For CPIP2, the average number of antipsychotics was reduced from 2.9 to 2.27 from July 2008 to October 2008. There was a reduction of an average chlorpromazine-equivalent dose per day from 1523 mg per patient to 1246 mg. There was no documented relapse within six months of implementation of both the projects., Conclusion: APP in long-term patients suffering from chronic schizophrenia can be safely reduced with proper clinical titration, aided by guidelines and protocols.

Aims: DNA fingerprinting of Salmonella enterica serotype Paratyphi B isolated in Malaysia during 1982-83, 1992 and 1996-2002 was carried out by pulsed-field gel electrophoresis (PFGE), antimicrobial susceptibility tests and D-tartrate utilization tests to assess the extent of genetic diversity of these isolates in Malaysia., Methods and Results: Eighty-six human isolates and one food isolate of Salm. Paratyphi B were analysed by PFGE, antimicrobial susceptibility tests and D-tartrate utilization tests. Sixty-five strains were D-tartrate-negative (dT-) while 22 strains were D-tartrate-positive (dT+). Thirty-seven per cent of the Salm. Paratyphi B strains were resistant to one or more antimicrobial agents. PFGE analysis clearly distinguished the dT- and dT+ strains into two clusters based on the unweighted pair group average method (UPGMA). Twenty-two XbaI-pulsotypes were observed among the 65 dT- strains while 17 XbaI-pulsotypes were observed among the 22 isolates of Salm. Paratyphi B dT+., Conclusions: The present study showed that PFGE was very discriminative with 33.7% of the strains yielding distinct fingerprints. Paratyphoid fever in Malaysia is probably caused by one predominant, endemic clone of Salm. Paratyphi B dT- with various subtypes. There was no association between the pulsotypes and the severity of the disease indicating that the severity of the disease is probably multifactorial., Significance and Impact of the Study: The findings of the present study verify the usefulness of PFGE in characterizing strains of Salm. Paratyphi B. This is the first report on the application of PFGE on a large collection of Salm. Paratyphi B in Malaysia.

Pulsed-field gel electrophoresis (PFGE) of XbaI-digested chromosomal DNA was performed on 133 strains of Salmonella enterica serovar Typhi obtained from Papua New Guinea, with the objective of assessing the temporal variation of these strains. Fifty-two strains that were isolated in 1992 and 1994 were of one phage type, D2, and only two predominant PFGE profiles, X1 and X2, were present. Another 81 strains isolated between 1997 and 1999 have shown divergence, with four new phage types, UVS I (n = 63), UVS (n = 5), VNS (n = 4), and D1 (n = 9), and more genetic variability as evidenced by the multiple and new PFGE XbaI profiles (21 profiles; Dice coefficient, F = 0.71 to 0.97). The two profiles X1 and X2 have remained the stable, dominant subtypes since 1992. Cluster analysis based on the unweighted pair group method using arithmetic averages algorithm identifies two main clusters (at 87% similarity), indicating that the divergence of the PFGE subtypes was probably derived from some genomic mutations of the X1 and X2 subtypes. The majority of isolates were from patients with mild and moderate typhoid fever and had various XbaI profiles. A single isolate from a patient with fatal typhoid fever had a unique X11 profile, while four of six isolates from patients with severe typhoid fever had the X1 pattern. In addition, 12 paired serovar Typhi isolates recovered from the blood and fecal swabs of individual patients exhibited similar PFGE patterns, while in another 11 individuals paired isolates exhibited different PFGE patterns. Three pairs of isolates recovered from three individuals had different phage types and PFGE patterns, indicating infection with multiple strains. The study reiterates the usefulness of PFGE in assessing the genetic diversity of S. enterica serovar Typhi for both long-term epidemiology and in vivo stability and instability within an individual patient.

The incidence of food-borne salmonellosis due to Salmonella enterica serotype Weltevreden is reported to be on the increase in Malaysia. The pulsed-field gel electrophoresis (PFGE) subtyping method was used to assess the extent of genetic diversity and clonality of Salmonella serotype Weltevreden strains from humans and the environment. PFGE of XbaI-digested chromosomal DNA from 95 strains of Salmonella serotype Weltevreden gave 39 distinct profiles with a wide range of Dice coefficients (0.27 to 1.00), indicating that PFGE is very discriminative and that multiple clones of Salmonella serotype Weltevreden exist among clinical and environmental isolates. Strains of one dominant pulsotype (pulsotype X1/X2) appeared to be endemic in this region, as they were consistently recovered from humans with salmonellosis between 1996 and 2001 and from raw vegetables. In addition, the sharing of similar PFGE profiles among isolates from humans, vegetables, and beef provides indirect evidence of the possible transmission of salmonellosis from contaminated raw vegetables and meat to humans. Furthermore, the recurrence of PFGE profile X21 among isolates found in samples of vegetables from one wet market indicated the persistence of this clone. The environment in the wet markets may represent a major source of cross-contamination of vegetables with Salmonella serotype Weltevreden. Antibiotic sensitivity tests showed that the clinical isolates of Salmonella serotype Weltevreden remained drug sensitive but that the vegetable isolates were resistant to at least two antibiotics. To the best of our knowledge, this is the first study to compare clinical and environmental isolates of Salmonella serotype Weltevreden in Malaysia.

Aims: Subtyping of Salmonella Paratyphi A isolates from India, Pakistan, Indonesia and Malaysia was carried out by pulsed-field gel electrophoresis (PFGE) to assess the extent of genetic diversity of these isolates from different endemic countries., Methods and Results: A total of 39 human isolates of Salmonella Paratyphi A from Pakistan, India, Indonesia and Malaysia were studied using PFGE analysis following digestion of chromosomal DNA with XbaI. Seven isolates from Pakistan were resistant to ampicillin, tetracycline and cotrimoxazole. It was noted that Salmonella Paratyphi A isolates obtained from outbreaks in India had limited genetic diversity and probably belonged to closely related clones. Significant genetic homogeneity was observed among antimicrobial-resistant isolates from Pakistan and antimicrobial-sensitive isolates from Pakistan and Indonesia, respectively., Conclusions: PFGE was a useful subtyping technique to differentiate Salmonella Paratyphi A from different endemic countries. However, it fails to differentiate the antimicrobial-resistant and -sensitive strains., Significance and Impact of the Study: The findings of the present study verify the usefulness of PFGE in characterizing and comparing strains of Salmonella Paratyphi A. Our study suggests that a limited number of clones are responsible for paratyphoid fever in these countries.

A representative sample of 20 isolates of Salmonella weltevreden strains from stool cultures of patients admitted at the University Hospital, Kuala Lumpur, Malaysia were analyzed. All the strains were susceptible to ampicillin, ceftriaxone, ciprofloxacin, chloramphenicol, tetracycline, trimethoprim, gentamicin and co-trimoxazole. Ribosomal RNA gene restriction pattern analysis of PstI-digested DNA gave three ribotypes while pulsed-field gel electrophoresis (PFGE) analysis of XbaI-digested DNA gave ten distinct profiles. PFGE was more discriminative than ribotyping in distinguishing the strains. The majority of the strains analyzed were very closely related with similarity coefficient values ranging from 0.8 to 1.0. Both PFGE and ribotyping could distinguish one of the strains which was obtained from a patient following a bone marrow transplant for beta-thalassemia major, indicating that this particular strain was unrelated to the rest of the strains from patients with acute gastroenteritis.