In Vitro and In Vivo Characterisation of Lactiplantibacillus plantarum LAB12 in Pea Protein-Alginate Microcapsules.

The susceptibility of probiotics to high temperature and low pH remains a major challenge in food industries. Numerous commercially available probiotic products were reportedly presented with lower probiotic viability than claimed. To confer health benefits to the host, it is essential that probiotic strain remains viable at optimal amount during food processing procedures, storage and passage through the gastrointestinal tract. This study addressed these issues by immobilising Lactiplantibacillus plantarum LAB12 isolated from tempeh (fermented soybean) in a polymeric matrix made up of alginate (Alg, 0.5% w/v) and denatured pea protein isolate (PPi, 1-10% w/v) using the emulsion/acidification technique. Alg supplemented with 10% PPi (Alg-PPi10) appeared to be optimally small (< 350 µm), substantiated by the improved surface smoothness and uniform dispersion of probiotics in the Alg-PPi core. The findings indicated that microencapsulation enhanced thermal stability of L. plantarum LAB12. The microencapsulated L. plantarum LAB12 remained highly viable (80%) despite exposure to 100 °C for 5 min. The microencapsulated cell number during storage at 4 and 25 °C for 8 weeks was greater than 7 log CFU g-1. L. plantarum LAB12 encapsulated in Alg-PPi10 exhibited high viability (96%) in simulated gastric juice (at pH 1.8 for 120 min) and facilitated maximum release of probiotics (> 9 log CFU g-1) in simulated intestinal fluid (at pH 6.8 for 240 min). Whilst retaining their intrinsic cholesterol lowering effect, microencapsulation conferred additional advantages to L. plantarum LAB12 in terms of lowering serum triglyceride and increasing HDL cholesterol in zebrafish fed with high-cholesterol diet (HCD). Overall, our findings strongly imply the potential use of Alg-PPi10 as an effective medium that confers thermal protection and facilitates pH-sensitive release of cholesterol-reducing L. plantarum LAB12. This will allow the diverse applications L. plantarum LAB12 across health, food and agro-feed industries amongst others.

E arly S u p ervised I ncremental R esistance T raining (ESpIRiT) following cardiac surgery via a median sternotomy: a study protocol of a multicentre randomised controlled trial.

INTRODUCTION: There is no consistency in current practice pertaining to the prescription and progression of upper limb resistance exercise following cardiac surgery via median sternotomy. The aim of this study is to investigate whether less restrictive sternal precautions with the addition of early-supervised resistance training exercise improves upper limb function and facilitates recovery following median sternotomy. METHODS AND ANALYSIS: This is double-blind randomised controlled trial, with parallel group, concealed allocation, blinding of patients and assessors, and intention-to-treat analysis. 240 adult participants who had median sternotomy from eight hospitals in Malaysia will be recruited. Sample size calculations were based on the unsupported upper limb test. All participants will be randomised to receive either standard or early supervised incremental resistance training. The primary outcomes are upper limb function and pain. The secondary outcomes will be functional capacity, multidomain recovery (physical and psychological), length of hospital stay, incidence of respiratory complications and quality of life. Descriptive statistics will be used to summarise data. Data will be analysed using the intention-to-treat principle. The primary hypothesis will be examined by evaluating the change from baseline to the 4-week postoperative time point in the intervention arm compared with the usual care arm. For all tests to be conducted, a p value of <0.05 (two tailed) will be considered statistically significant, and CIs will be reported. The trial is currently recruiting participants. ETHICS AND DISSEMINATION: The study was approved by a central ethical committee as well as the local Research Ethics Boards of the participating sites (UKM:JEP-2019-654; Ministry of Health: NMMR-50763; National Heart Centre: IJNREC/501/2021). Approval to start was given prior to the recruitment of participants commencing at any sites. Process evaluation findings will be published in peer-reviewed journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: International Standard Randomised Controlled Trials Number (ISRCTN17842822).

Non-operative management of solid organ injuries in a middle-income country, how does it stack up?

INTRODUCTION: The first trauma surgery unit in Malaysia was established in 2011. After 10 years, we examine our experience in the management, and outcomes of blunt liver, spleen, and kidney injuries. METHODS: This is a cross-sectional study of patients with blunt liver, spleen, and kidney injuries in a level 1 trauma centre in Malaysia between January 2018 to June 2021. Patients' characteristics, new injury severity score, organ-specific AAST injury score, type of primary management (operative management [OM], non-operative management [NOM]), causes of failed NOM, management of failed NOM, and outcome of treatment were recorded and analysed. RESULTS: Among 448 patients, 83.9% were male and in the working-age range of 15-64 years old (93.5%). Road traffic crashes made up 92.0% of blunt trauma resulting in 65.5% of isolated organ injuries and 34.5% combined injuries. An overwhelming 84.2% of the patients had major trauma (NISS>15). Three hundred and thirty-four patients (74.6%) underwent initial non-operative management. Patients in the OM group showed lower mean GCS scores (p = 0.022) and higher NISS scores (p < 0.001). High-grade liver and kidney injuries were mostly treated with NOM (p < 0.001). In contradistinction, patients with high-grade spleen injuries had more OM performed (p < 0.001). NOM had been successful in 325 patients (97.3%) with 9 failures. Underlying causes for NOM failure were hemodynamic instability due to secondary bleeding and infectious complications. Overall mortality was 11.2%, which was significantly higher in the OM group (23.7%) than in the NOM group (6.9%). CONCLUSION: This study represents one of the largest single centre experiences on the blunt liver, spleen, and kidney injuries in Malaysia and South-East Asia. With good selection and adequate resources, non-operative management of blunt liver, spleen, and kidney injuries is a safe and effective therapeutic approach with a high success rate of 97.3%, avoiding the morbidity of unnecessary laparotomies.

Molecular and Epigenetic Basis of Extracellular Vesicles Cell Repair Phenotypes in Targeted Organ-specific Regeneration.

Extracellular vesicles (EVs), which are released by most of the cells, constitute a new system of cell-cell communication by transporting DNA, RNA, and proteins in various vesicles namely exosomes, apoptotic bodies, protein complexes, high-density lipid (HDL) microvesicles, among others. To ensure accurate regulation of somatic stem cell activity, EVs function as an independent metabolic unit mediating the metabolic homeostasis and pathophysiological of several diseases such as cardiovascular diseases, metabolic diseases, neurodegenerative diseases, immune diseases, and cancer. Whist examining the EV biomolecules cargos and their microenvironments that lead to epigenetic alteration of the cell in tissue regeneration, studies have gained further insights into the biogenesis of EVs and their potential roles in cell biology and pathogenicity. Due to their small size, non-virulence, flexibility, and ability to cross biological barriers, EVs have promising therapeutic potentials in various diseases. In this review, we describe EV's mechanism of action in intercellular communication and transfer of biological information as well as some details about EVinduced epigenetic changes in recipient cells that cause phenotypic alteration during tissue regeneration. We also highlight some of the therapeutic potentials of EVs in organ-specific regeneration.

Molecular Regulatory Roles of Long Non-coding RNA HOTTIP: An Overview in Gastrointestinal Cancers.

Gastrointestinal (GI) cancers presented an alarmingly high number of new cancer cases worldwide and are highly characterised by poor prognosis. The poor overall survival is mainly due to late detection and emerging challenges in treatment, particularly chemoresistance. Thus, the identification of novel molecular targets in GI cancer is highly regarded as the main focus. Recently, long non-coding RNAs (lncRNAs) have been discovered as potential novel molecular targets for combating cancer, as they are highly associated with carcinogenesis and have a great impact on cancer progression. Amongst lncRNAs, HOTTIP has demonstrated a prominent oncogenic regulation in cancer progression, particularly in GI cancers, including oesophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. This review aimed to present a focused update on the regulatory roles of HOTTIP in GI cancer progression and chemoresistance, as well as deciphering the associated molecular mechanisms underlying their impact on cancer phenotypes and chemoresistance and the key molecules involved. It has been reported that it regulates the expression of various genes and proteins in GI cancers that impact cellular functions, including proliferation, adhesion, migration and invasion, apoptosis, chemosensitivity, and tumour differentiation. Furthermore, HOTTIP was also discovered to have a higher diagnostic value as compared to existing diagnostic biomarkers. Overall, HOTTIP has presented itself as a novel therapeutic target and potential diagnostic biomarker in the development of GI cancer treatment.

Relationship between Mean Platelet Volume and Critical Limb Ischemia in Diabetes Mellitus Patients.

The prevalence of diabetes mellitus continues to increase from year to year. Critical limb ischemia (CLI) is one of the complications of diabetes mellitus with a high mortality rate and requires amputation if not treated properly. Mean platelet volume (MPV) is an indicator of platelet activation and is expected to be a predictor of CLI in diabetes mellitus patients. This article investigates the relationship between MPV and the incidence of CLI in diabetes mellitus patients. This case-control study was conducted using the vascular registry of Dr. Sardjito Hospital, Yogyakarta, Indonesia, from January 2016 to December 2016. The relationship between MPV and the incidence of CLI was analyzed using bivariate and multivariate analysis. There was a significant association between MPV and incidence of CLI in diabetes mellitus patient both on bivariate analysis ( p = 0.035) and multivariate analysis ( p = 0.029). Diabetes mellitus patients with MPV values of ≥ 9.8 fl had a protective effect to prevent the incidence of CLI (bivariate analysis: odds ratio [OR] = 0.366, 95% confidence interval [CI] = 0.142-0.943; multivariate analysis: adjusted OR = 0.288, 95% CI = 0.09-0.88). Confounding factors such as sex, age, obesity, and use of antiplatelet agents were not associated with the incidence of CLI ( p > 0.05). Meanwhile, history of dyslipidemia as a confounding factor was significantly associated with the incidence of CLI ( p < 0.05). Low MPV was found to be significantly associated with the incidence of CLI in diabetes mellitus patients.

Effectiveness of Colorectal Cancer Screening Promotion Using E-Media Decision Aids: A Systematic Review and Meta-Analysis.

Colorectal cancer (CRC)-screening reduces mortality, yet remains underutilized. The use of electronic media (e-media) decision aids improves saliency and fosters informed decision-making. This systematic review aimed to determine the effectiveness of CRC-screening promotion, using e-media decision aids in primary healthcare (PHC) settings. Three databases (MEDLINE, Web of Science, and the Cochrane Library) were searched for eligible studies. Studies that evaluated e-media decision aids compared to usual care or other conditions were selected. Quality was assessed by using Cochrane tools. Their effectiveness was measured by CRC-screening completion rates, and meta-analysis was conducted to calculate the pooled estimates. Ten studies involving 9393 patients were included in this review. Follow-up durations spanned 3-24 months. The two types of decision-aid interventions used were videos and interactive multimedia programs, with durations of 6-15 min. Data from nine feasible studies with low or some risk of bias were synthesized for meta-analysis. A random-effects model revealed that CRC-screening promotion using e-media decision aids were almost twice as likely to have screening completion than their comparisons (OR 1.62, 95% CI: 1.03-2.62, p < 0.05). CRC-screening promotion through e-media has great potential for increasing screening participation in PHC settings. Thus, its development should be prioritized, and it should be integrated into existing programs.

Effect of Intracanal Medicaments on the Bond Strength of Bioceramic Root Filling Materials to Oval Canals.

AIM: This study aimed to evaluate the effect of the prior application of intracanal medicaments on the bond strength of OrthoMTA (mineral trioxide aggregate) and iRoot SP to the root dentin. MATERIALS AND METHODS: Thirty single-rooted mandibular premolars were standardized and prepared using ProTaper rotary files. The specimens were divided into a control group and two experimental groups receiving Diapex and Odontopaste medicament, either filled with iRoot SP or OrthoMTA, for 1 week. Each root was sectioned transversally, and the push-out bond strength and failure modes were evaluated. The data were analyzed using Kruskal Wallis and Mann-Whitney U post hoc test. RESULTS: There was no significant difference between the bond strength of iRoot SP and OrthoMTA without medicaments and with the prior placement of Diapex (p value > 0.05). However, iRoot SP showed significantly higher bond strength with the prior placement of Odontopaste (p value < 0.05). Also, there was no association between bond strength of OrthoMTA with or without intracanal medicament (p value > 0.05) and between failure mode and root filling materials (p value > 0.05). The prominent failure mode for all groups was cohesive. CONCLUSION: Prior application of Diapex has no effect on the bond strength of iRoot SP and OrthoMTA. However, Odontopaste improved the bond strength of iRoot SP. CLINICAL SIGNIFICANCE: Dislodgment resistance of root canal filling from root dentin could be an indicator of the durability and prognosis of endodontic treated teeth.

Tuberculosis Incidence and Factors Associated With Mortality Among Health Care Workers in Malaysia.

This study aims to determine tuberculosis incidence, all-cause mortality, and its associated factors among health care workers (HCWs) registered in 2012 to 2014 with the Malaysian National Tuberculosis (MyTB) Surveillance Registry. Regression analysis was used to determine factors associated with all-cause mortality. Incidence rates ranged from 135.18 to 156.50/100 000 and were higher for HCWs compared with the general population (risk ratio = 1.70-1.96). The mean age at notification was 34.6 ± 10.55 years; 68.9% were female. Most were paramedics (44.3%) followed by other HCWs (41.9%) and doctors (13.8%). Nearly a quarter (23.8%) had extrapulmonary tuberculosis. There were 23 deaths giving a case fatality rate of 2.4%. Factors associated with death were older age (odds ratio [OR] =1.05; confidence interval [CI] =1.01-1.10), diabetes (OR = 3.83; CI = 1.32-11.08), HIV positivity (OR = 18.16; CI = 4.60-71.68), and not receiving directly observed therapy (DOTS) (OR = 10.97; CI = 3.61-33.38). It is important for HCWs to be aware of these increased risks and for authorities to implement protective measures.

Resistencia a los medicamentos del Mycobacterium Leprae detectados en cultivo de almohadilla plantar de ratón entre 1997 y 2013 en Malasia / No disponible

Antecedentes: Después de tres décadas de implementación de la multiterapia (MDT), consistente en una combinación de rifampicina, dapsona y clofazimina, en Malasia la aparición de resistencia farmacológica del Mycobacterium leprae constituye una preocupación, ya que puede llevar al fracaso del tratamiento y la recidiva de la enfermedad. Objetivos: Determinar el modelo de resistencia farmacológica del M. leprae en Malasia. Métodos: Se analizaron los cultivos en almohadilla plantar de ratón (MFP) de todas las biopsias cutáneas de pacientes con lepra borderline lepromatosa y lepra lepromatosa enviados a la Unidad de la Lepra, Laboratorio Nacional de Salud Publica, Sungai Buloh, Malasia, entre 1997-2013. Resultados: Se realizaron 651 cultivos MFP. La edad media de los pacientes fue de 41 anos (rango: 6-88). La proporción varón/hembra era de 3·8:1. Cuatrocientos cuarenta y cuatro pacientes (69·1%) eran malayos. La proporción de M. leprae positivo en cultivo era del 66·6% (433 of 651). El Índice Bacteriologico (IB) y el Índice Morfológico (IM) promedios para los cultivos positivos fue de 3·7 and 2·8 respectivamente. El IB y el IM de los que no crecieron en la MFP eran significativamente menores que los que presentaban cultivos positivos (P < 0·001). La dapsona presento el mayor índice de resistencia del 55% (238 of 433). Sin embargo, el elevado grado de resistencia a la dapsona (0·01%) fue de 6·24%. Hubo 407 MFP con rifampicina 0·003% y 12 (2·9%) resultaron resistentes a la misma. La clofazimina presento el menor grado de resistencia intermedia (0·001%) que fue del 0·2% (1 of 429). No había diferencias significativas entre el patrón de resistencia y género o nacionalidad de los pacientes. Conclusiones: Mas de la mitad de los cultivos MFP presentaron resistencia de baja intensidad a la dapsona; menos del 3% eran resistentes a la rifampicina y la resistencia a la clofazimina resulto muy baja

Background: After three decades of implementing multidrug therapy (MDT) consisting of rifampicin, dapsone and clofazimine in Malaysia, the drug resistance pattern of Mycobacterium leprae is a growing concern as it may lead to failure of treatment and relapse of disease. Objective: To determine the drug resistance patterns of M. leprae in Malaysia. Methods: Mouse footpad (MFP) culture of all skin biopsy samples from patients with borderline lepromatous and lepromatous leprosy sent to the Leprosy Unit, National Public Health Laboratory, Sungai Buloh, Malaysia between 1997-2013 were retrospectively studied. Results: There were 651 MFP cultures performed. The mean age of patients was 41 years old (range: 6-88). The male: female ratio was 3·8:1. Four hundred and forty four patients (69·1%) were Malaysian. The rate of positive M. leprae culture was 66·6% (433 of 651). The mean Bacteriological Index (BI) and median Morphological Index (MI) for those with positive culture were 3·7 and 2·8 respectively. The mean BI and MI of those which failed to grow in the MFP were significantly lower than those with positive cultures (P < 0·001). Dapsone has the highest resistance rate of 55% (238 of 433). Nevertheless, high degree dapsone resistance (0·01%) was 6·24%. There were 407 MFP tests using rifampicin 0·003% and 12 (2·9%) were resistant to it. Clofazimine has the lowest intermediate degree (0·001%) resistance rate of 0·2% (1 of 429). There were no significant differences between the drug resistance pattern and the gender or the nationality of the patients. Conclusion: More than half of our positive MFP cultures showed low-level resistance to dapsone; less than 3% were resistant to rifampicin, and clofazimine resistance remained very low

Paratesticular aggressive angiomyxoma: A rare case.

Aggressive angiomyxoma (AAM) particularly testicular origin is a rare benign mesenchymal myxoid tumor which is locally aggressive, blatant for local recurrence, and may metastasize. It occurs mostly in females of childbearing age and extremely rare in males. AMM particular testicular origin is not reported in literature yet. This is a 65-year-old man who had a right scrotal swelling. Ultrasound scrotum showed a soft tissue tumor of the right testis. The patient underwent radical right orchidectomy of which histopathologically confirmed to be a paratesticular AAM with clear resection margins. There were no signs of local recurrence or metastasis 2 years postsurgical resection.

Counting in the dark: non-intrusive laser scanning for population counting and identifying roosting bats.

Population surveys and species recognition for roosting bats are either based on capture, sight or optical-mechanical count methods. However, these methods are intrusive, are tedious and, at best, provide only statistical estimations. Here, we demonstrated the successful use of a terrestrial Light Detection and Ranging (LIDAR) laser scanner for remotely identifying and determining the exact population of roosting bats in caves. LIDAR accurately captured the 3D features of the roosting bats and their spatial distribution patterns in minimal light. The high-resolution model of the cave enabled an exact count of the visibly differentiated Hipposideros larvatus and their roosting pattern within the 3D topology of the cave. We anticipate that the development of LIDAR will open up new research possibilities by allowing researchers to study roosting behaviour within the topographical context of a cave's internal surface, thus facilitating rigorous quantitative characterisations of cave roosting behaviour.

Repressing the activity of protein kinase CK2 releases the brakes on mitochondria-mediated apoptosis in cancer cells.

Execution of the mitochondrial death signaling is paramount to an effective response of cancer cells to chemotherapeutic intervention. Therefore, factors that inhibit the engagement of the mitochondrial amplification pathway, such as the expression of the anti-apoptotic proteins of the Bcl2 family or inactivation of inducers of mitochondrial permeability, play a critical role in the acquisition of the resistant phenotype. Protein kinase CK2 (CK2) is a ubiquitous serine/threonine kinase that is highly conserved in eukaryotic cells. This multifunctional protein kinase has been shown to impact cell growth and proliferation, as numerous growth-related proteins are substrates of CK2. More importantly, experimental evidence linking increased expression and activity of the kinase to human cancers, underscores the relevance of CK2 biology to cellular transformation and carcinogenesis. Of note, among the many cellular substrates of CK2 are proteins involved in the efficient execution of the mitochondria-dependent cell death signaling, such as Bid, caspase-2, ARC and others. Supporting this, recent reports have demonstrated that genetic manipulation of CK2 expression as well as pharmacological inhibition of its enzymatic activity sensitizes cancer cells to apoptotic stimuli. Due to the critical regulatory role that this kinase plays in cell fate determination in cancer cells, there is a tremendous increase in activity geared at the development of CK2-specific therapies. Here we provide a brief review of CK2-mediated inhibition of mitochondrial death signaling in cancer cells and its implications for the design of novel target specific therapeutic strategies.

Casein Kinase II: an attractive target for anti-cancer drug design.

Casein Kinase II (CK2) is a ubiquitous serine/threonine kinase that is highly conserved in eukaryotic cells. CK2 has been shown to impact cell growth and proliferation, as numerous growth-related proteins are substrates of CK2. More importantly, experimental evidence linking increased expression and activity of CK2 to human cancers underscores the relevance of CK2 biology to cellular transformation and carcinogenesis. Due to the critical regulatory role CK2 plays in cell fate determination in cancer cells, there is a tremendous interest in the development of CK2-specific therapies. Supporting this, recent reports have demonstrated that genetic manipulation of CK2 expression as well as pharmacological inhibition of its enzymatic activity sensitizes cancers to apoptotic stimuli. Here we provide a succinct account of the biology of CK2, its cellular substrates, its pro-survival and pro-proliferation activity, and highlight evidence for its involvement in human cancer.

Resveratrol inhibits drug-induced apoptosis in human leukemia cells by creating an intracellular milieu nonpermissive for death execution.

Efficient apoptotic signaling is a function of a permissive intracellular milieu created by a decrease in the ratio of superoxide to hydrogen peroxide and cytosolic acidification. Resveratrol (RSV) triggers apoptosis in some systems and inhibits the death signal in others. In this regard, the inhibitory effect on hydrogen peroxide-induced apoptosis is attributed to its antioxidant property. We provide evidence that exposure of human leukemia cells to low concentrations of RSV (4-8 micro M) inhibits caspase activation, DNA fragmentation, and translocation of cytochrome c induced by hydrogen peroxide or anticancer drugs C2, vincristine, and daunorubicin. Interestingly, at these concentrations, RSV induces an increase in intracellular superoxide and inhibits drug-induced acidification. Blocking the activation of NADPH oxidase complex neutralized RSV-induced inhibition of apoptosis. Furthermore, our results implicate intracellular hydrogen peroxide as a common effector mechanism in drug-induced apoptosis that is inhibited by preincubation with RSV. Interestingly, decreasing intracellular superoxide with the NADPH oxidase inhibitor diphenyliodonium reversed the inhibitory effect of RSV on drug-induced hydrogen peroxide production. These data show that low concentrations of RSV inhibit death signaling in human leukemia cells via NADPH oxidase-dependent elevation of intracellular superoxide that blocks mitochondrial hydrogen peroxide production, thereby resulting in an intracellular environment nonconducive for death execution.