A dominant population of optically invisible massive galaxies in the early Universe.

Our current knowledge of cosmic star-formation history during the first two billion years (corresponding to redshift z > 3) is mainly based on galaxies identified in rest-frame ultraviolet light1. However, this population of galaxies is known to under-represent the most massive galaxies, which have rich dust content and/or old stellar populations. This raises the questions of the true abundance of massive galaxies and the star-formation-rate density in the early Universe. Although several massive galaxies that are invisible in the ultraviolet have recently been confirmed at early epochs2-4, most of them are extreme starburst galaxies with star-formation rates exceeding 1,000 solar masses per year, suggesting that they are unlikely to represent the bulk population of massive galaxies. Here we report submillimetre (wavelength 870 micrometres) detections of 39 massive star-forming galaxies at z > 3, which are unseen in the spectral region from the deepest ultraviolet to the near-infrared. With a space density of about 2 × 10-5 per cubic megaparsec (two orders of magnitude higher than extreme starbursts5) and star-formation rates of 200 solar masses per year, these galaxies represent the bulk population of massive galaxies that has been missed from previous surveys. They contribute a total star-formation-rate density ten times larger than that of equivalently massive ultraviolet-bright galaxies at z > 3. Residing in the most massive dark matter haloes at their redshifts, they are probably the progenitors of the largest present-day galaxies in massive groups and clusters. Such a high abundance of massive and dusty galaxies in the early Universe challenges our understanding of massive-galaxy formation.

Pharmacotherapy for ADHD in children and adolescents: A summary and overview of different European guidelines.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries.   Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. What is Known: • There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents. • Pediatricians are often involved in assessment, diagnosis and management of children with ADHD. What is New: • Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents. • Discrepancies exist primarily in terms of selection and sequencing of different medications.

Refining dietary metabolisable energy and crude protein levels in relation to duck performance and behaviour.

1. The study evaluated the effect of dietary metabolisable energy (ME) content and crude protein (CP) level on the growth performance and behaviour of ducks.2. A total of 720, Cherry Valley ducks were allocated to 36 pens in groups of 20 birds. For the initial period, from 1 to 21 d age, six diets, containing a standard (SME), low (LME) and high (HME) ME of 12.14, 11.93 and 12.35 MJ/kg, and standard (SCP) or high (HCP) CP contents of 210 or 220 g/kg diet, respectively, were mixed. For the period from 22 to 42 d age, the diets contained ME of 12.98 (SME), 12.77 (LME), 13.19 (HME) MJ/kg and the levels of CP were 170 (SCP) or 180 (HCP) g/kg, respectively.3. An ME by CP interaction was seen from 1 to 21 d age in ducks fed HME + HCP diet, which had greater weight gain than those fed LME + SCP (P < 0.05). Compared to LME + SCP, dietary HME decrease feeding but increased walking behaviour compared to LME + SCP and SME + SCP (P < 0.05). High CP in LME and SME diets increased drinking behaviour (P < 0.05), but there was no change in HME diet. Compared to LME, feeding HME reduced ground pecking (P < 0.05). Feeding HME reduced feeding behaviour (P < 0.05) from 22 to 42 d age. During the same period, standing behaviour was reduced in HCP + LME (P < 0.05). Drinking was reduced in LME + SCP compared to SME + HCP and HME + HCP (P < 0.05).4. A diet formulated with HME and HCP is effective for enhancing growth performance of ducks aged 1-21 d and saving time for feeding or ground pecking, which may induce spending more time on other activities.

The clinical and geographical characteristics, health-seeking behaviours of ST-segment elevation myocardial infarction patients with their total ischaemic time and short-term cardiac mortality outcomes: a local geographical perspective from a developing country.

INTRODUCTION: Ischaemic heart disease including ST-segment elevation myocardial infarction (STEMI) is the leading cause of death among Malaysians. Total ischaemic time (TIT) which consists of patient delay and systemic delay is a strong predictor of cardiovascular outcome in STEMI. Primary percutaneous coronary intervention (PPCI) is superior to medical thrombolysis in improving STEMI patients' survival outcomes. Our study aims to provide an insight into the clinical and geographical characteristics of STEMI patients, their health-seeking behaviour, TIT, interventions received and short-term cardiac mortality outcomes in the effort to improve the existing coronary care service. MATERIALS AND METHODS: This is a descriptive study looking into patients who were diagnosed with STEMI and presented to or were referred to Sarawak Heart Centre between 1st July 2022 and 31st December 2022. RESULTS: A total of 183 patients were recruited and 33.3% were <50 years old. The majority were in a different division during symptom onset from where the local PPCI centre is located and some underwent one or two transits before arrival at the revascularisation centre. More presented outof- hour and they were more likely to present within the PPCI window. The median TIT for the study population was 3.3 hours. The short-term cardiac mortalities were 9.3% and only the Killip class was found to have a significant association. In this study, TIT was not significantly associated with short-term mortalities but those who died had a longer median TIT. CONCLUSION: A local STEMI network should be set up using the 'Hub-and-Spoke' model in a staged-wise approach to reduce TIT given that PPCI is now the gold standard of treatment alongside continuous effort in patient education.

Navigating an unexpected diagnosis - experience of a tertiary referral centre with two cases of intraplacental choriocarcinoma.

Intraplacental choriocarcinoma is a rare tumour, with approximately 62 reported cases. It may manifest as a spectrum of disease ranging from an incidental lesion diagnosed on routine placental examination to disseminated maternal and/or neonatal disease. In this case series, we presented two rare cases of intraplacental choriocarcinoma with extremely varied clinical presentations. The extremely varied clinical presentations of both patients described in the case series complicated the process of arriving at the diagnosis. In both cases, subsequent investigations showed no maternal or neonatal metastasis, and maternal serum beta-hCG levels downtrended with conservative management. We aim to highlight the importance of performing a detailed physical examination and evaluation of the patient and multidisciplinary management with oncology opinion. A detailed examination of the placenta should also be considered when faced with obstetric complications so that early diagnosis and the required management can be executed in a prompt fashion.

Characteristics of patients with tuberculosis and the associated factors with TB-related mortality in a rural setting in Sarawak, Malaysia: A single-centre study.

INTRODUCTION: Tuberculosis (TB) in Malaysia has estimated incidence and mortality rates of 81 cases per 100,000 people-year and 4.9 per 100,000 populations, respectively. This study aimed to study the characteristics of rural TB patients and their mortality outcomes. MATERIALS AND METHODS: This is a retrospective observational study involving real-world data analysis, looking into TB patients in Lubok Antu Health Clinic by obtaining data through clinic cards, from 1 January 2019 till 31 December 2020. Statistical significance was p < 0.05. RESULTS: Eighty-four patients were included. Fifty-two (61.9%) were male. Median age was 58.5 (39-67). Forty-six (54.8%) had smear-positive TB. Seventy-eight (92.9%) were alive at treatment completion. Fifteen (17.9%) experienced adverse drug reactions. Estimated prevalence and mortality rate were 7.1% and 10.7 per 100,000 populations, respectively. Regression analyses revealed that drug reaction was significantly associated with compliance [OR = 8.38 (95% CI: 1.26, 55.53), p = 0.029]. Patients compliant with treatment were more likely to survive [OR = 12.5 (95% CI: 1.61, 97.34), p = 0.028]. CONCLUSION: Compliance with TB treatment should be emphasised to reduce TB-related mortality.

Factors associated with in-hospital mortality among infective endocarditis patients.

INTRODUCTION: Despite recent advancements in the diagnosis and management of infective endocarditis (IE), it is associated with substantial morbidity and mortality. Our study objective is to determine the factors associated with in-hospital mortality in IE patients among the local population. MATERIALS AND METHODS: All IE patients who were diagnosed with definite or possible IE and were treated at Sarawak Heart Centre from 1st January 2020 to 31st December 2022 were recruited. We examined the demographic features of the subjects and the factors that contributed to in-hospital mortality. Multivariate logistic regression was used to analyse the associated factors and in-hospital mortality. RESULTS: Our study population comprised a total of 37 patients with a mean age of 46.4 years and male predominance. The in-hospital mortality rate of IE in this study was 44.4%. Haemodynamic instability and anaemia were found to be strong predictors of IE survival outcome, with an odds ratio of 51.5 and 35.7 respectively. Patients with vascular phenomenon and heart failure were at 10.5- and 6.0-times higher odds of dying, however, these two associations were found to be not statistically significant. CONCLUSION: The in-hospital mortality due to IE in our study was among the highest in developing countries. Factors of hypotension and optimal response to individual hemodynamic parameters may confer lower mortality. While anaemia is demonstrable as a risk factor for inpatient mortality, a target has yet to be reasonably established.

Probiotic characterization of Lactiplantibacillus plantarum HOM3204 and its restoration effect on antibiotic-induced dysbiosis in mice.

The purpose of this study was to evaluate the probiotic characteristics of Lactiplantibacillus plantarum HOM3204 isolated from homemade pickled cabbage and to examine its restoration effect on antibiotic-induced dysbiosis in mice. Lact. plantarum HOM3204 tolerated simulated gastric and intestinal juices with a 99·38% survival rate. It also showed strong adhesion ability (3·45%) to Caco-2 cells and excellent antimicrobial activity against foodborne pathogens in vitro. For safety (antibiotic susceptibility) of this strain, it was susceptible to all the tested seven antibiotics. Lact. plantarum HOM3204 had good stability during storage, especially in cold and frozen conditions. Furthermore, Lact. plantarum HOM3204 significantly restored the gut microbiota composition by increasing the abundance of Lactobacilli and Bifidobacteria and decreasing Enterococci, and improved antioxidative function by raising the concentrations of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in serum of antibiotic-induced dysbiosis in mice. These results suggest that Lact. plantarum HOM3204 could be a potential probiotic as a functional food ingredient.

Physical exertion exacerbates decline in the musculature of an animal model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. It remains unresolved whether increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle's disrupted contractile machinery. This knowledge has important implications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. Recently we showed how burrowing dystrophic (dys-1) C. elegans recapitulate many salient phenotypes of DMD, including loss of mobility and muscle necrosis. Here, we report that dys-1 worms display early pathogenesis, including dysregulated sarcoplasmic calcium and increased lethality. Sarcoplasmic calcium dysregulation in dys-1 worms precedes overt structural phenotypes (e.g., mitochondrial, and contractile machinery damage) and can be mitigated by reducing calmodulin expression. To learn how dystrophic musculature responds to altered physical activity, we cultivated dys-1 animals in environments requiring high intensity or high frequency of muscle exertion during locomotion. We find that several muscular parameters (e.g., size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion, regardless of effort duration. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insight into the pathology of the disease as well as the initial assessment of potential treatment strategies.

Effective recycling of disposable medical face masks for sustainable green concrete via a new fiber hybridization technique.

Global public response to the COVID-19 (SARS-CoV-2) pandemic is highly focused on human health. However, conservationists have cautioned of unprecedented threats to the natural environment from a new type of non-biodegradable microplastic waste resulting from extensive use of disposable medical face masks (DMFMs). Thus, this waste must be recycled in an eco-friendly manner on an urgent basis. In this research, we developed a new environmentally friendly recycling technique using waste DMFMs in sustainable green concrete. More explicitly, a new fiber hybridization approach has been introduced in which two types of fibers namely DMFM fiber and basalt fiber (BF) were incorporated into fiber reinforced recycled aggregate concrete (FRAC). The volume fractions of DMFM fiber were 0%, 0.1%, and 0.2% and the volume fractions of BF were 0%, 0.25%, and 0.5%. In addition, two mineral admixtures (fly ash and ground granulated blast furnace slag) were also used. Test results indicated increase of approximately 12% in compressive strength, 26% in split tensile strength, and 60% in flexural strength of FRAC containing hybrid fibers and mineral admixtures. The density and ultra-sonic pulse velocity (UPV) of DMFM fiber- and BF-modified FRAC ranged from 2406-2433 kg/m3 and 4502-4541 m/s, respectively, which meets structural concrete requirements. The water absorption rate gradually increased with an increase in the volume fractions of fibers but remained within the allowable water absorption limit for construction materials. Lastly, the microstructure investigation indicated excellent concrete quality, improved interfacial transition zones (ITZs), and good compatibility of host concrete matrix with both DMFM fiber and BF that correlates well with the experimental results reported in this study.

Clinical utility of Pandy test in the face of quantitative CSF total protein and albumin: A retrospective study and literature review.

INTRODUCTION: Qualitative Pandy test has long been used to indicate raised globulins in the cerebrospinal fluid (CSF). Despite its shortfalls and the availability of quantitative CSF protein assays, Pandy test continues to be performed in clinical laboratories across Malaysia. OBJECTIVES: (1) Compare diagnostic performance of Pandy test to CSF total protein and albumin; (2) Conduct literature review on clinical utility of Pandy test. MATERIALS AND METHODS: This is a retrospective, cross-sectional study involving 890 inpatients of all ages with CSF biochemistry analysed in Hospital Pulau Pinang over a period of 7 months. Patient demographics, clinical diagnosis and CSF total protein, albumin and Pandy results were collected and analysed using Mann-Whitney U test, Spearman rank-order correlation coefficient, Chi Square test and receiver operating characteristic (ROC) curve analysis. RESULTS: CSF total protein, CSF albumin, CSF protein-albumin difference and age showed significantly higher median values in patients with positive Pandy compared to negative Pandy. Significant associations were found between positive Pandy test with clinical diagnosis (Cramers V 0.443, p<0.01), sample haemolysis (Phi 0.326, p<0.01), CSF protein-albumin difference (Spearman 0.727, p<0.001), CSF total protein (Spearman 0.710, p<0.001) and CSF albumin (Spearman 0.662, p<0.01). All three quantified CSF parameters showed comparably good sensitivity and specificity in determining positive Pandy. DISCUSSION AND CONCLUSION: Good correlation with CSF proteins, analytical issues and reagent hazards indicate no added clinical value of Pandy test in the face of quantified CSF total protein and albumin. Abolishing the test saves resources, reduces occupational hazards and shortens turnaround time without compromising diagnosis.

Prognostic significance of bone marrow 2-[18F]-fluoro-2-deoxy-d-glucose uptake in diffuse large B-cell lymphoma: relation to iliac crest biopsy results.

AIM: To investigate the prognostic significance of bone marrow (BM) 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake in relation to posterior iliac crest BM biopsy (BMB) results in diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Pretreatment integrated positron-emission tomography(PET)/computed tomography (CT) images of 512 DLBCL patients who underwent BMB and received rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy were analysed retrospectively. BM uptake was assessed visually and by maximum standard uptake value (SUVmax). Associations with lymphoma-specific survival (LSS) were assessed using Kaplan-Meier and Cox regression analyses. RESULTS: FDG(+) BM was observed in 64 cases (41 focal, 12 heterogeneous, 11 diffuse). This finding distinguished iliac crest involvement (positive in 59 and negative in 453) with 89.6% accuracy (459/512) and 93.6% specificity (424/453). In BMB(+) patients, BM-to-liver SUVmax ratio >1.8 concurred perfectly with FDG(+) BM. During 52 months of follow-up, there were 156 lymphoma-related deaths. In the entire population, multivariate analysis revealed high International Prognostic Index (IPI; p<0.001), old age (p=0.003), bulky disease (p=0.011), BMB(+) (p=0.028), and FDG(+) BM (p=0.019) as independent predictors of worse LSS. In the BMB(+) subgroup, high National Comprehensive Cancer Network-revised IPI (NCCN-IPI; p=0.029) and FDG(+) BM (p=0.008) were significant independent predictors. Among BMB(+) patients with low to low-intermediate NCCN-IPI, FDG(+) BM was associated with significantly worse 2-year LSS (33.3% versus 100%; p=0.017). The same was true among those with high-intermediate NCCN-IPI (34.7% versus 76.9%.; p=0.026). CONCLUSION: Increased BM FDG in DLBCL is a predictor of worse LSS independent of BMB results and other prognostic variables including IPI/NCCN-IPI.

A case study exploring the 'real world' process of 'naturalizing' school playgrounds.

Background: The aim of this study was to examine the lived experiences of teachers and administrators at two schools (one elementary Kindergarten-Grade 5 and one middle school, grades 6-8) following the 'naturalizing' of a portion of their schoolyard. Methods: A qualitative case study design was used. Focus groups and interviews allowed participants to express their rationale, identify implementation facilitators and barriers and critical processes/steps for realizing their naturalization goals. Researcher questions explored (1) factors which led to naturalizing the schoolyard, (2) key planning and process steps (3) challenges and successes experienced, and, (4) lessons learned. Findings: Six themes were identified as rationale for naturalizing including: re-integration of outdoor play into children's daily lives, pro-active mental health, opportunity for inclusion, nature as a positive space for learning, it fit with our values and principles, we had a need. Implementation was facilitated by having champions and support from multiple levels, adopting a phased approach, resources and having the buy-in to persevere over time. Significant challenges and 'how to' steps were also identified. Conclusions: Naturalizing schoolyards does not happen without a supportive context, significant time and effort. Implementation steps and issues were those commonly found in other school-based health promotion efforts.

Serum Magnesium Measurements After Parathyroidectomy for Primary Hyperparathyroidism: Should It be Routine?

BACKGROUND: Parathyroidectomy is the treatment of choice in primary hyperparathyroidism (PHPT). Following surgery, significant changes in bone and mineral metabolism may follow, but routine magnesium monitoring is not standard practice. The occurrence of significant clinical events linked to hypomagnesaemia in 3 patients after parathyroidectomy led to our evaluation of magnesium levels after surgery for PHPT. METHODS: Serum magnesium levels before and after parathyroidectomy for PHPT were prospectively evaluated in a single centre over a year. The incidence and severity of hypomagnesaemia and its correlation with other biochemical variables were assessed. RESULTS: A total of 138 patients underwent parathyroidectomy for PHPT. Pre-operative and day 1 post-operative serum magnesium levels were available in 57/138 (41.3%) and 99/138 (71.7%) patients, respectively. Serum magnesium decreased significantly after surgery (mean ± SD of 0.85 ± 0.08 and 0.75 ± 0.11 mmol/L, respectively, p < 0.001). On the day after parathyroidectomy, 31/99 (31.3%) patients had hypomagnesaemia (<0.70 mmol/L); in 3 of whom it was severe (<0.50 mmol/L). Patients with hypomagnesaemia had lower pre-operative magnesium (mean ± SD of 0.78 ± 0.06 and 0.87 ± 0.07 mmol/L, p < 0.001), higher pre-operative calcium [median (IQR) of 2.83 (2.71-2.99) and 2.71 (2.63-2.80) mmol/L, p = 0.001] and higher post-operative calcium [median (IQR) of 2.41 (2.30-2.51) and 2.35 (2.28-2.43) mmol/L, p = 0.046] compared to those with normomagnesaemia. In addition, these patients demonstrated higher drop in calcium levels after surgery (0.44 ± 0.20 and 0.35 ± 0.18 mmol/L, p = 0.033). Magnesium levels after surgery correlated positively with pre-operative magnesium (r = 0.561, p < 0.001) and post-operative PTH (r = 0.210, p = 0.037) and negatively with pre-operative adjusted calcium (r = - 0.389, p < 0.001). CONCLUSIONS: Serum magnesium decreased significantly following parathyroidectomy for PHPT and nearly a third of patients developed post-operative, mostly mild hypomagnesaemia. Whilst routine serum magnesium measurements could facilitate prompt recognition and treatment of this electrolyte disturbance, further research needs to establish the clinical importance of mild hypomagnesaemia in these clinical settings and, if indicated, to devise optimal treatment strategies.

Health information needs of 1000 midlife Singaporean women.

OBJECTIVES: Due to demographic changes, aging is a health priority. We aimed to identify midlife women's perceived health information needs and the preferred method(s) of information delivery. METHODS: A questionnaire was offered to women, aged 45-69 years, attending gynecological clinics during April/May 2016, collecting age and ethnicity data. Participants were asked to indicate important midlife health topics out of 26 topics, including 'other'. For each topic, six delivery options were offered. Age was stratified by 5-year intervals. Associations with age and ethnicity were examined using Pearson's chi-square tests (p < 0.05); analyses were performed with SPSS version 22.0. RESULTS: The top health topics chosen were gynecological cancer (66.0%), joint/muscle aches and pain (64.4%), bone health (63.2%), breast screening (55.9%), and heart health (55.3%). Adjusted results from the logistic regression model found that the odds of choosing the topics gynecological cancer, cervical screening, and complementary and alternative medicine for menopausal symptoms were significantly lower in age groups 55-59, 60-64 and 65-69 years compared to age group 45-49 years. Both Malay and Indian women were less likely to report bone health as important (odds ratio = 0.59, 95% confidence interval = 0.41-0.86) and (odds ratio = 0.64, 95% confidence interval = 0.42-0.98), respectively. Written leaflets were chosen by the majority (84.7%). CONCLUSION: This study of over 1000 midlife Asian women found that holistic health information is desired and requires tailoring by age, not ethnicity. Written information was preferred over support groups. These findings will guide clinical health services in delivering patient-centered information resources for midlife women.

Comparison of two different optical coherence tomography angiography devices in detecting healthy versus glaucomatous eyes - an observational cross-sectional study.

BACKGROUND: To understand the differences between two different optical coherence tomography angiography (OCTA) devices in detecting glaucomatous from healthy eyes by comparing their vascular parameters, diagnostic accuracy and test-retest reliability. METHODS: A cross-sectional observational study was performed on healthy and glaucoma subjects, on whom two sets of OCTA images of optic disc and macula were acquired using both AngioVue (Optovue, USA) and Swept Source (Topcon, Japan) OCTA devices during one visit. A novel in-house software was used to calculate the vessel densities. Diagnostic accuracy of the machines in differentiating healthy versus glaucomatous eyes was determined using area under the receiver operating characteristic curve (AUROC) and test-retest repeatability of the machines was also evaluated. RESULTS: A total of 80 healthy and 38 glaucomatous eyes were evaluated. Glaucomatous eyes had reduced mean vessel density compared to healthy controls in all segmented layers of the optic disc and macula using AngioVue (p ≤ 0.001). However, glaucomatous eyes had higher mean vessel density on optic disc scans using Swept Source, with lack of statistically significant difference between healthy and glaucomatous eyes. The AUROC showed better diagnostic accuracy of AngioVue (0.761-1.000) compared to Swept Source (0.113-0.644). The test-retest reliability indices were generally better using AngioVue than Swept Source. CONCLUSIONS: AngioVue showed better diagnostic capability and test-retest reliability compared to Swept Source. Further studies need to be undertaken to evaluate if there is any significant difference between the various machines in diagnosing and monitoring glaucoma.

Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases.

Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.

Angiosarcoma - a rare fatal cause of recurrent pericardial effusions.

A 40-year-old man presented to the Hospital Sultanah Bahiyah, Alor Setar, Kedah, with constitutional and respiratory symptoms. Physical examination and echocardiogram demonstrated massive pericardial effusion. Patient required multiple attempts of pericardiocentesis due to recurrent pericardial effusion. Initial workup including pericardial fluids examination and computed tomography imaging did not reveal any apparent cause. Magnetic resonance imaging showed a suspicious mass infiltrating into the right atrium. Autoimmune screening was negative. Patient was subsequently treated as having tuberculous pericarditis. However, his disease progressed rapidly and he eventually passed away due to right atrial rupture. Postmortem revealed a ruptured right atrial tumour leading to massive haemothorax. Histopathological examination confirmed the diagnosis of primary pericardial angiosarcoma.

Wilms tumour with poor response to pre-operative chemotherapy: A report of 2 cases.

INTRODUCTION: Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy. CASE REPORT: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up. DISCUSSION: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.

Tailoring the homing capacity of human Tregs for directed migration to sites of Th1-inflammation or intestinal regions.

Cell-based therapy with CD4+ FOXP3+ regulatory T cells (Tregs) is a promising strategy to limit organ rejection and graft-vs-host disease. Ongoing clinical applications have yet to consider how human Tregs could be modified to direct their migration to specific inflammation sites and/or tissues for more targeted immunosuppression. We show here that stable, homing-receptor-tailored human Tregs can be generated from thymic Tregs isolated from pediatric thymus or adult blood. To direct migration to Th1-inflammatory sites, addition of interferon-γ and IL-12 during Treg expansion produced suppressive, epigenetically stable CXCR3+ TBET+ FOXP3+ T helper (Th)1-Tregs. CXCR3 remained expressed after injection in vivo and Th1-Tregs migrated efficiently towards CXCL10 in vitro. To induce tissue-specific migration, addition of retinoic acid (RA) during Treg expansion induced expression of the gut-homing receptors α4ß7-integrin and CCR9. FOXP3+ RA-Tregs had elevated expression of the functional markers latency-associated peptide and glycoprotein A repetitions predominant, increased suppressive capacity in vitro and migrated efficiently to healthy and inflamed intestine after injection into mice. Homing-receptor-tailored Tregs were epigenetically stable even after long-term exposure to inflammatory conditions, suppressive in vivo and characterized by Th1- or gut-homing-specific transcriptomes. Tailoring human thymic Treg homing during in vitro expansion offers a new and clinically applicable approach to improving the potency and specificity of Treg therapy.