Heart failure with preserved ejection fraction (HFPEF) is a global health problem of considerable socioeconomic burden. It is projected to worsen with the aging population worldwide. The lack of effective therapies underscores our incomplete understanding of this complex heterogeneous syndrome. A novel paradigm has recently emerged, in which central roles are ascribed to systemic inflammation and generalized endothelial dysfunction in the pathophysiology of HFPEF. In this review, we discuss the role of the endothelium in cardiovascular homeostasis and how deranged endothelial-related signaling pathways contribute to the development of HFPEF. We also review the novel therapies in various stages of research and development that target different components of this signaling pathway.
Animals ; Endothelium, Vascular/*physiopathology ; Heart Failure/diagnosis/metabolism/*physiopathology/therapy ; Humans ; Inflammation/diagnosis/metabolism/*physiopathology/therapy ; Inflammation Mediators/metabolism ; Prognosis ; Risk Factors ; Signal Transduction ; *Stroke Volume ; *Ventricular Function, Left

Aims: This study is to isolate and characterize endophytic bacteria for potential industrial enzymes and antimicrobial activities against some human pathogens. Methodology and results: Mentha spicata, a local medicinal plant, was used to source for endophytes. The roots, stems and leaves of M. spicata were surface-sterilized to isolate the endophytic bacteria. The endophytic bacteria were subsequently characterized based on their 16S rRNA sequences. The endophytic bacteria were screened for both antimicrobial and enzymatic activities. We identified 15 isolates of 4 genus-Pseudomonas (7 species), Bacillus (3 species), Enterobacter (1 species) and Comamonas (1 species) with 97-100% similarity level. Isolates MSS-3 (Pseudomonas putida), MSR-4 (Pseudomonas pictorum), MSS-2 (Bacillus thuringiensis) and MSR-5 (Pseudomonas straminea) showed prominent antimicrobial activities against the pathogens tested with zones of inhibition between 6.3 to 15.3 ± 0.6 mm. All species examined have positive cellulase activities except Comamonas guangdongensis and only isolates of the Bacillus genus, Pseudomonas pictorum and P. argentinensis exhibited amylase activities. Conclusion, significance and impact of study: Our findings revealed potential therapeutic uses of the bioactive compounds of these bacteria endophytes against pathogens. Their enzymatic potential can also be of use in various industries.
Anti-Infective Agents

INTRODUCTIONAtherosclerotic coronary artery thrombosis is the most common cause of acute myocardial infarction.

CLINICAL PICTUREA 30-year-old lady presented with acute peripartum massive anterior ST segment myocardial infarction and cardiogenic shock. This was due to acute Stanford type A aortic dissection with the intimal flap occluding the left coronary ostium. The initial diagnosis was not apparent. Echocardiography confirmed the diagnosis.

TREATMENT AND OUTCOMEShe underwent emergency surgical repair (Bentall procedure). Pathology confirmed underlying idiopathic cystic medial degeneration.

CONCLUSIONA high index of clinical suspicion is required in acute myocardial infarction presenting without traditional cardiovascular risk factors.

Acute Disease ; Adult ; Aneurysm, Dissecting ; complications ; diagnosis ; surgery ; Aortic Aneurysm ; complications ; diagnosis ; surgery ; Echocardiography ; Electrocardiography ; Female ; Humans ; Myocardial Infarction ; etiology ; physiopathology ; Pregnancy ; Pregnancy Complications, Cardiovascular ; Shock, Cardiogenic ; etiology

INTRODUCTIONWaiting times for kidney transplant are long in Singapore. Healthrelated quality of life (HRQoL) of patients might be affected as a result of the stress of the long wait and the uncertainty of being called to undergo a surgical operation. This study aimed to measure the HRQoL of patients on the kidney transplant waiting list and to identify factors which could impact on the HRQoL scores in this group of patients.

MATERIALS AND METHODSThis was a cross-sectional study of kidney transplant waiting list patients managed at a tertiary renal unit using the SF-36. A SF-36 normative calculator was used to generate HRQoL scores for the Singapore general population matched with the study cohort's age, gender and ethnicity.

RESULTSThere were 265 respondents with a response rate was 81%. Our study shows that HRQoL scores for the kidney transplant waiting list patients were lower than the population norms across all subscales and were clinically significant for General Health, Role Physical, Bodily Pain, Social Functioning and Mental Component Summary scores. Factors such as being Chinese, married, employed and undergoing haemodialysis predicted better HRQoL scores after adjusting for possible confounders. Age, gender, educational level, household income, history of kidney transplant, duration on the transplant waiting list and years on dialysis did not significantly influence SF-36 across all subscales scores.

CONCLUSIONKidney transplant waiting list patients had worse HRQoL compared to the general population. Factors such as ethnicity, marital status, employment status, and type of dialysis treatment significantly influenced patients' perception of their HRQoL.

Cross-Sectional Studies ; Female ; Health Status ; Humans ; Kidney Transplantation ; Male ; Quality of Life ; Surveys and Questionnaires ; Waiting Lists

We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient's disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.
Brain ; Chelation Therapy ; Cognition ; Extremities ; Gait Apraxia ; Humans ; Iron ; Movement Disorders

INTRODUCTIONChronic kidney disease (CKD) is a major public health problem in Singapore. Efforts are being made to right-site CKD care (stage 1 to 3) from specialist outpatient clinics (SOCs) to general practitioners (GPs) to ease congestion. This study aims to identify factors influencing screening and management of CKD among GPs in Singapore.

MATERIALS AND METHODSA survey was conducted among the 1202 GPs between April and September 2010. The survey questionnaire was developed in collaboration with experts in nephrology and general practice, it included questions about screening, awareness and management of CKD.

POPULATION STUDIEDGPs registered with the National Healthcare Group General Practitioner (NHG GP) partner database.

RESULTSThree hundred and two GPs completed the survey. A total of 70% of the respondents were males and with their median years of practice as 18. A total of 86% of them reported screening for CKD while 50% of GPs were confident of managing patients with CKD stage 1; and 38% of GPs are aware of CKD guidelines. Majority of GPs (64%) agreed that right-siting of early CKD patients would ease congestion at SOCs. Some of the obstacles in CKD management listed by the GPs were lack of patient trust, experience and communication with the specialist and the inability of the patient to pay.

CONCLUSIONGPs screen patients for CKD, however their awareness of guidelines is limited. Opportunities exist for improving physician recognition of CKD, awareness of CKD guidelines, improving collaborative care and reimbursement for the patient and the provider. This study has identified factors which when addressed could lead to wider acceptance of CKD right-siting by both the patients and the GPs.

Ambulatory Care Facilities ; utilization ; Female ; General Practice ; Health Care Surveys ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Practice Patterns, Physicians' ; statistics & numerical data ; Renal Insufficiency, Chronic ; diagnosis ; therapy ; Singapore

Background & Objective: Association between HLA-B*1502 and carbamazepine-induced StevenJohnson syndrome/toxic epidermal necrolysis (CBZ-SJS/TEN) was reported in many Southeast Asian populations but not in Indonesian. The purpose of this study was to evaluate the association between HLA-B*1502 andCBZ-SJS/TEN in an Indonesian population. Methods: Patients with history of CBZ-SJS/TEN are recruited as cases and those who tolerated CBZ as controls. HLA-B typing was performed. Results: We recruited 14 cases with CBZ-SJS/TEN and 53 controls. Positive HLA-B*1502 was found in 8 (57.1%) cases and 14 (26.4%) controls (OR 3.7, 95% CI 1.09-12.61, p=0.035). Conclusion: HLA-B*1502 is associated with CBZ-SJS/TEN patients in Indonesian.

Hyponatraemia with rapid correction of serum sodium may cause an osmotic demyelination syndrome (ODS) with damage to pontine and/or extrapontine areas of the brain. The prognosis of ODS can range from complete recovery to death; at present, our ability to predict clinical outcome is very limited. We describe here a patient with ODS and increased signal intensity in the striatum on diffusion-weighted MRI, with corresponding low apparent diffusion coeffi cient values (indicating restricted water diffusion). This case provides a further example of the typical MRI appearance of extrapontine ODS and suggests the potential value of diffusion-weighted MRI in predicting prognosis in ODS.

Introduction:Cutaneous adverse drug reactions are one of the most common adverse drug reactions. Publicationson clinical correlation between cutaneous presentations and causative agents are limited among thelocal population. This study aims to determine the clinical presentations of cutaneous adverse drugreactions and the causative drugs in the local population.Methods:A retrospective, cross sectional study was conducted from the pharmacy cutaneous adverse drugreaction database from January 2014 to December 2016 in Tawau, Keningau & Queen Elizabeth (KotaKinabalu) Hospitals.Results:A total of 859 cases of cutaneous adverse drug reactions were identified. Out of these, 53.3% (n=458)were females and 46.7% (n=401) were males. The mean age was 36 years old. Majority of patients were20-29 years old (16.6%) followed by 50-59 years old (15.1%). Most of the cases were reported amongthe Chinese community (16.4%), followed by the Malay (15.9%), Dusun (14.7%) and Bajau (14.0%)populations. The most common cutaneous manifestations were urticaria and or angioedema (49%, n=421) and maculopapular rash (39.6%, n=340). Severe cutaneous adverse reactions (SCAR) constituted2.8% in total. The major causative agent was antibiotic which accounted for 55.1% (n=473), followedby nonsteroidal anti-inflammatory drugs (NSAIDs), 28.1% (n=241) and analgesics, 10.8% (n=93).Conclusion:The types of cutaneous manifestations and causative drugs in Sabah are similar to those reported inother states of the country and abroad. This study provides evidence of local cutaneous adverse drugreaction characteristics in different ethnic group.