Community-Based Approach to Promote Rational Use of Antibiotics in Indonesia: The Development and Assessment of an Education Program for Cadres.

BACKGROUND: Cadres play an important part in providing community-based education. This study developed and assessed an education program for cadres in Malang, Indonesia, as 'change agents' to promote rational antibiotic use. METHODS: In-depth-interviews with stakeholders (N = 55) and a subsequent group discussion with key personnel (N = 5) were conducted to develop a relevant education tool for cadres. This was followed with a pilot study with cadres (N = 40) to assess the effectiveness and acceptability of the new tool. RESULTS: Consensus was reached on the education tool media: an audio-recording (containing full information) with a pocketbook (containing key information) as a supplement. A pilot study on the new tool reported its effectiveness in improving knowledge (p < 0.001) and demonstrated a high acceptability (all respondents stated 'Strongly Agree' or 'Agree' on all statements). CONCLUSION: This study has created a model for an education tool which can potentially be implemented for cadres to educate their communities about antibiotics in the Indonesian context.

Outcome of acute ischaemic stroke patients after intravenous alteplase in Hospital Universiti Sains Malaysia.

INTRODUCTION: Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) is effective in treating acute ischaemic stroke. Our primary objective is to assess the outcome of these acute ischaemic stroke (AIS) patients after IV alteplase with the modified Rankin scale (mRS). METHODS: This is a cross-sectional study in which patients receiving IV alteplase in Hospital Universiti Sains Malaysia, from January 2017 to April 2020 were recruited. Demographical data, National Institutes of Health Stroke Scale (NIHSS) scores, door-to-needle time were recorded. Modified Rankin scale (mRS) scores were evaluated at 90 days after initial therapy. Good and poor functional outcomes were defined as 0-2 and 3-6, respectively. RESULTS: A total of 30 patients were included in the study with a mean age of 59±11.47 years old. 76.7% of them were male and the rest were female. From the study, onset-toneedle time was 197.47±51.74 minutes, whereas door-toneedle time was 120.93±53.63 minutes. Seventeen (56.3%) patients achieved a favourable score of 0-2 on the mRS at 90 days after treatment. Haemorrhagic transformation occurred in eight (26.7%) of the patients with a mortality rate of 13.3%. CONCLUSION: 56.7% of our patients showed improvement in the mRS at 90 days post thrombolysis for AIS. Higher baseline NIHSS scores and diabetes mellitus were associated with poorer functional outcomes after thrombolysis.

Expression of oestrogen-α receptor in papillary thyroid carcinoma and its association with metastasis.

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the ninth most common malignancy among women. Although the disease prognosis is good, less favourable outcomes are predicted in those with higher disease stages and nodal metastasis. Oestrogen- α (ER-α) expression has been associated with aggressive presentation and greater disease progression and has been proposed as a predictor for lymph node metastases. The objective of this study was to evaluate the association between ER expression and clinicopathological features i.e. lymph node metastasis, tumour size, extrathyroidal extension, histological variants of PTC , age groups , ethnic and gender. METHODS: We studied ER-α expression in 84 cases of PTC obtained within an eight-year period (2011-2018) by immunohistochemical technique (IHC). Associations between ER-α expression and clinicopathological features were evaluated using Fisher's exact test. The statistical significance was set at p < 0.05. RESULTS: ER-α was expressed in 13.1% of all the PTC cases examined (n=11/84). There were no associations observed between ER-α expression and lymph node metastasis (p=1.000), tumour size (p=0.970), extrathyroidal extension (p=0.677), variants of PTC (p=1.000), age groups (p=0.188), gender (p=0.725) or race (p=0.920). CONCLUSION: There was no evidence in this study to support the application of ER-α as prediction marker for lymph node metastasis or disease aggressiveness in PTC. Given that the scope of this study was limited to the protein expression of ER- α, we also propose the inclusion of molecular analysis of ESR1 gene expression, as well as inclusion of detailed clinical and radiological findings in future research investigating the role of ER-α in prognostication of PTC.

Guidance to improve the effectiveness of process safety management systems in operating facilities.

The Process Safety Management (PSM) systems at the operating facilities in the Oil & Gas and in Chemical manufacturing industries have matured over the years and have become, at most facilities, very robust and sophisticated. These programs are administrated by Process Safety (PS) teams at both the corporate business units and plant levels and have been effective in reducing the number and severity of PS events across the industries over the past 25 years or so. Incidents however are occurring at a regular interval and in recent times several noteworthy PS events have occurred in the United States which have brought into question the effectiveness of the PSM programs at play. These facilities have been applying their PSM programs with the expectation that the number and severity of PS events would decrease over time. The expected result has not been realized, especially in context to those facilities that have undergone the recent incidents. Current paper reviews a few publicly available PS performance reports of Oil & Gas and Chemical manufacturing industries. The authors identified a few factors at play that have led to these PS events based on their experience, literature review, and incident investigation reports. Most of the factors are intertwined with multiple PSM elements and it requires a holistic approach to address them. Each of the factors is described and the path forward is proposed to improve the effectiveness of PSM programs.

IDF Diabetes Atlas: A review of studies utilising retinal photography on the global prevalence of diabetes related retinopathy between 2015 and 2018.

AIMS: The purpose of this study is to assess the prevalence of diabetic retinopathy (DR) world-wide from articles published since 2015 where the assessment of the presence and severity of DR was based on retinal images. METHODS: A total of 4 databases were searched for the MESH terms diabetic retinopathy and prevalence. Of 112 publications 32 studies were included and individual data pooled for analysis. The presence of any DR or diabetic macular edema (DME) was recorded and severity as mild, moderate or severe non-proliferative DR (NPDR), proliferative DR (PDR) and DME and/or clinically significant macular edema (CSME). The level of severity of DR reported refer to persons with diabetes and not individual eyes. RESULTS: The global prevalence of DR and DME, for the period 2015 to 2019 were 27.0% for any DR comprising of 25.2%, NPDR, 1.4% PDR and 4.6% DME. The lowest prevalence was in Europe at 20.6% and South East Asia at 12.5% and highest in Africa at 33.8%, Middle East and North Africa 33.8%, and the Western Pacific region at 36.2%. CONCLUSIONS: This study illustrated difficulties in deriving a meaningful global prevalence rate for DR and DME due to the lack of uniformity in defining the study populations, methodological differences, retinal image capture and grading criteria. Therefore, international consensus is required using a minimal data set for future studies.

Damage control resuscitation: A case of thoraco-abdominal impalement.

Damage Control Resuscitation and Surgery is the concept of controlled hypotension, haemostatic resuscitation and abbreviated surgical procedures following severe trauma; the practice of which has resulted in improved mortality and morbidity. We describe a rare case of thoraco-abdominal impalement successfully managed based on the concept of Damage Control Resuscitation.

Damage control resuscitation: A case of thoraco abdominal impalement

Damage Control Resuscitation and Surgery is the concept of controlled hypotension, haemostatic resuscitation and abbreviated surgical procedures following severe trauma; the practice of which has resulted in improved mortality and morbidity. We describe a rare case of thoraco-abdominal impalement successfully managed based on the concept of Damage Control Resuscitation.

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

Current status of percutaneous PFO closure.

The clinical significance of persistent patent foramen ovale (PFO) is not well defined. Empirically, PFO has been associated with many clinical conditions. In cryptogenic stroke, migraine, and orthodeoxia/platypnea, a plausible biologic mechanism exists to support PFO closure as a possible treatment. Although transcatheter closure of PFO has been available for over 2 decades, it has remained controversial due to a paucity of evidence to guide patient and device selection. Contemporary studies investigating PFO closure as treatment for patients with these conditions have been published recently and longitudinal data regarding the safety and efficacy of the devices is now available. In this review, we aim to describe the potential clinical significance of a patent foramen in the adult, appraise the newest additions to the body of evidence, and discuss the safety, benefit, patient selection, and future of transcatheter treatment of PFO.

2,3,9,10,15,16-Hexaaza-tetra-cyclo-[6.6.2.0(4,16).0(11,15)]hexa-decane dihydrate.

The four six-membered fused rings in the title compound, C(10)H(20)N(6)·2H(2)O, adopt chair conformations; the H atoms of the four secondary N atoms occupy axial positions. Hydrogen bonds of the types N-H⋯N, N-H⋯O and O-H⋯N link the organic and water mol-ecules into a three-dimensional network.

Comparative evaluation of microleakage among three different glass ionomer types.

OBJECTIVES: This study compared the microleakage and adaptation of Class V cavity preparations restored with three types of glass-ionomer materials as a function of time. METHODS AND MATERIALS: A total of 144 sound, freshly-extracted human premolars were used for the study. One clinician prepared all the teeth for Class V-type cavities on the buccal surface of each tooth. The preparations measured 3 mm long, 2 mm wide and 1.5 mm deep, with the gingival margin in dentin and the occlusal margin in enamel. All the prepared teeth were randomly divided into three groups of 48 teeth, according to the type of glass-ionomer material used: Group (A): Ketac N100 glass ionomer, Group (B): Vitremer glass ionomer and Group (C): Photac Fil Quick glass ionomer. The restorative materials were used according to their manufacturers' recommendations. The teeth were placed in one increment and photocured for 40 seconds. All of the restored teeth were then stored in artificial saliva. Each group was subdivided into three subgroups according to the testing periods (7, 30, 60 days). Next, they were thermocycled at 5°C­55°C for 100 cycles. The teeth used for the dye penetration test were immersed in 1%methylene blue solution for eight hours. They were then sectioned longitudinally in a bucco-lingual direction. The extent of dye penetration at the occlusal and gingival margins of each restoration was studied under a stereomicroscope at 25× magnification. Randomly selected samples from each group were prepared for scanning electron microscopic evaluation. Dye penetration scores were analyzed using the SAS program, cross tabulation and Chi square test. RESULTS: The difference among the three groups was significant after immersion for 30 days at the occlusal margin. Statistical analysis also revealed significant differences between group (A) and the other groups at the occlusal margin after immersion for 60 days (p<0.05). At the gingival margin, statistical analysis revealed significant differences between group (C) and the other groups at the gingival margin after immersion for 60 days (p<0.05). CONCLUSION: The light-curing nanofilled glass ionomer (Ketac N100) showed the least microleakage.

Comparative study on the different techniques for the preparation of sustained-release hydrophobic matrices of a highly water-soluble drug.

The objective of the present study was to control the release of freely water-soluble salbutamol sulphate (SS) over a prolonged period of time by embedding the drug into slowly eroding waxy matrix materials such as Precirol® ATO5, Compritol® 888 ATO, beeswax, paraffin wax, carnauba wax, and stearyl alcohol. The matrices were prepared by either direct compression or hot fusion techniques. The compatibility of the drug with the various excipients was examined using differential scanning calorimetry (DSC). A factorial design was employed to study the effect of polymer type, polymer concentration (15% and 35%), and filler type (Avicel® PH101 and dibasic calcium phosphate dehydrate (DCP) on the in vitro drug release at 6 h. Results of DSC confirmed drugexcipient compatibility. Increasing the polymer ratio resulted in a significant retardation of drug release. The use of DCP resulted in significant retardation and incomplete drug release while the use of Avicel did not. The hot fusion method was found to be more effective than the direct compression method in retarding SS release. A Precirol formulation, prepared using the hot fusion technique, had the slowest drug release, releasing about 31.3% of SS over 6 h. In contrast, Compritol, prepared using the direct compression technique, had the greatest retardation, providing sustained release of 59.3% within 6 h. A hydrophobic matrix system is thus a useful technique for prolonging the release of freely water-soluble drugs such as salbutamol sulphate.

Systemic polyarteritis nodosa mimicking pyoderma gangrenosum in a rare association with small lymphocytic leukaemia/chronic lymphocytic leukaemia.

A 48-year-old patient presented with a nonhealing leg ulcer and a raised white blood cell count. He was diagnosed with pyoderma gangrenosum (PG) and small lymphocytic leukaemia/chronic lymphocytic leukaemia (SLL/CLL). Eight months later, after undergoing treatment with chlorambucil for the SLL/CLL, and prednisone, ciclosporin and intravenous immunoglobulin for the PG, the patient developed livedo reticularis and palpable purpura, and was diagnosed with systemic polyarteritis nodosa (PAN). The case highlights the difficulty in establishing a diagnosis of PAN by biopsy of cutaneous ulcers alone, and that a diagnosis of PG should raise suspicion of another aetiology.

The incretin hormones GIP and GLP-1 in diabetic rats: effects on insulin secretion and small bowel motility.

Incretin hormones often display inhibitory actions on gut motility. The aim of this study was to investigate if altered responsiveness to glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) as regards insulin release and small bowel motility could bring further clarity to the pathophysiology of diabetes in the Goto-Kakizaki (GK) rat. The isolated perfused pancreas was studied in male GK and Wistar rats (controls) under euglycemic and hyperglycemic conditions. Glucose-dependent insulinotropic peptide (10 nmol L(-1)) or GLP-1 (10 nmol L(-1)) were added to the medium and perfusate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar electrodes in the small bowel and myoelectric activity was recorded during intravenous administration of GIP (1-400 pmol kg(-1) min(-1)) or GLP-1 (0.1-20 pmol kg(-1) min(-1)). Finally, tissue was collected from GK and Wistar rats for RNA extraction. Under euglycemia, GIP and GLP-1 stimulated the initial insulin response by 10-fold in GK rats (P < 0.05). At later hyperglycemia, the insulin response to GIP and GLP-1 was blunted to about one-third compared with controls (P < 0.05). In the bowel GLP-1 was about 2.6-16.7 times more potent than GIP in abolishing the migrating myoelectric complex in the GK and control rats. Polymerase chain reaction (PCR) showed GIP and GLP-1 receptor gene expression in pancreatic islets and in small bowel. The initially high, but later low insulin responsiveness to stimulation with GIP and GLP-1 along with inhibition of small bowel motility in the GK rat indicates a preserved incretin response on motility in diabetes type 2.

Physical performance and muscular characteristics in different stages of COPD.

This study has examined exercise capacity and muscle morphology in patients with different severities of chronic obstructive pulmonary disease (COPD). Twenty-three patients and 12 healthy matched controls were recruited. Based on the severity of airflow obstruction, patients were divided into two subgroups. Exercise capacity was determined using a 6-min walk test. Muscle fiber composition, fiber area and number of satellite cells/muscle fiber were determined in muscle biopsies using immunohistochemistry. A progressive decline in exercise capacity was noted with ascending disease severity. Furthermore, a correlation between reduction in exercise capacity and changes in muscle fiber composition was observed in COPD. The group with severe and very severe COPD had a lower proportion of type I and a higher proportion of type IIa fibers compared with the other groups. In severe and very severe COPD, a reduction in fiber area of type IIa fibers was also seen. The number of satellite cells/muscle fiber did not differ between the groups. In conclusion, a decline in exercise capacity occurs already in mild and moderate COPD, indicating that the 6-min walk test is a reliable indicator of disease severity. Furthermore, changes in skeletal muscle morphology are associated with disease severity while muscle regenerative capacity is not altered.

Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with chronic obstructive pulmonary disease.

BACKGROUND: A significant number of patients with chronic obstructive pulmonary disease (COPD) exhibit skeletal muscle wasting and decreased capillary area formation, which correlate with increased mortality. AIM: To determine the molecular mechanisms mediating decreased capillary formation in COPD. METHODS: 24 patients with COPD and 12 matching controls were recruited. Patients with COPD were classified into mild, moderate and severe groups according to GOLD (global initiative for chronic obstructive lung disease) criteria. Biopsy specimens were obtained from the tibialis anterior muscle. Fibre typing and capillary formation, together with messenger RNA (mRNA) expression of hypoxia-inducible factors (HIF1alpha and HIF3alpha), vascular endothelial growth factors (VEGF-A, VEGF-B and VEGF-C isoforms) and von Hippel-Lindau (VHL) protein, were determined. VHL expression and localisation were further studied by immunohistochemistry. RESULTS: Skeletal muscle capillary formation decreased significantly with increasing disease severity. Compared with controls, a tendency to mRNA overexpression of HIF1alpha, HIF3alpha and VEGF isoforms was observed in mild and moderate COPD, which decreased at the severe stage. In contrast, skeletal muscle biopsy samples from patients with COPD exhibited significant overexpression of VHL at both the mRNA and protein level by immunohistochemistry. VHL protein was further determined to be localised to satellite cells. CONCLUSIONS: Overexpression of VHL was identified in the skeletal muscle of patients with COPD. Increased VHL activity may have a negative effect on transduction of the hypoxic signal and may contribute to decreased capillarisation in skeletal muscles of patients with COPD.

Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis--a randomized controlled, cross-over trial.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function. AIM: To determine the efficacy of adding ranitidine at bedtime to control nocturnal acid breakthrough (NAB) and GERD in patients with systemic sclerosis already prescribed high-dose omeprazole. METHODS: Patients with systemic sclerosis and GERD symptoms (n = 14) were treated with omeprazole 20 mg b.d. and either placebo or ranitidine 300 mg at bedtime for 6 weeks in a randomized, cross-over, placebo controlled study. At the end of each period a 24 h pH-study with intragastric and oesophageal pH measurement was performed. RESULTS: Pathological acid reflux occurred in eight patients with omeprazole/placebo and in seven with omeprazole/ranitidine (P = ns) with technically adequate oesophageal pH-studies (n = 13). NAB was present in eight patients with omeprazole/placebo and six with omeprazole/ranitidine (P = ns) in whom technically adequate gastric pH-studies were obtained (n = 10). The addition of ranitidine had no consistent effect on patient symptoms or quality of life. CONCLUSION: Many patients with systemic sclerosis experienced NAB and pathological oesophageal acid exposure despite high-dose acid suppression with omeprazole b.d. Adding ranitidine at bedtime did not improve NAB, GERD or quality of life in this population.

Preparation of an ultra fast binding cement from calcium silicate-based mixed oxide nanoparticles.

Building construction takes time, in part because the binding process of cement is based on the slow re-crystallization and precipitation of calcium silicate species. Since the material's reactivity is surface area limited, a reduction in particle size of Portland cements has been used to prepare faster binding formulations. The present work investigates a new and direct, one-step preparation of calcium silicate-based nanoparticles of a typical Portland cement composition by flame spray synthesis. Isothermal calorimetry revealed that the hardening of this new nano-cement corroborated a more than tenfold increase of initial reactivity with different reaction kinetics if compared to conventionally prepared cements. At present, the unfavourably high porosity of nano-cements, however, underlines the need for additional improvements of chemical composition and formulation to make these highly reactive materials applicable to modern construction work, where load-bearing strength is of importance.