Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury.

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.

Corrigendum: Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury.

[This corrects the article DOI: 10.3389/fcell.2021.637270.].

Career Challenges Model Among Female Engineers: PLS-Sem Analysis

@#Women are likely to leave the job sector as a result of the crisis between their commitments to the career with the household interest. In response to this issue, this study aims to build a career challenge model that caters to the demand among women in this century. Hence, this study has identified the key factors to the challenges faced by female engineers in pursuing their career as an engineer through the Delphi Modified Technique. The result shows this study looking into the relationship between four independent constructs namely, life balance, childcare, leaves and gender discrimination. Meanwhile, the dependent construct of this study is career challenges faced by women. The scope of the study comprises female engineers with families and 211 respondents were selected to answer the questionnaire. The data obtained were analysed using the PLS-SEM 2.0 software via the algorithm, bootstrapping and blindfolding method. The construction process of this model involves two tests including the construction of the measurement model and the structure model. Testing the measurement model involves internal consistency namely (a) convergent validity and (b) discriminant validity in which these two validities have six analyses; (i) external loading, (ii) composite reliability, (iii) average variance extracted (AVE), (iv) Fornell-Larcker, (v) cross loading, and (vi) Heterotrait-Monotrait Ratio (HTMT). Meanwhile, the structural model testing involves the analysis of (i) Multicollinearity (Inner VIF), (ii) Path Coefficient, (iii) R square (R2), (iv) size effect (f2), and (v) Predictive Relevance (Q2). The findings indicate that gender discrimination and life balance have significant relationships in influencing career challenges. Hence, this model is expected to contribute to the literature of Human Resource Management.

Seroprevalence of leptospiral antibodies among market workers and food handlers in the central state of Malaysia.

OBJECTIVE: The high prevalence of leptospirosis in humans is of great public health concern, particularly in tropical and subtropical regions. This study aimed to determine the seroprevalence of leptospiral antibodies and distribution of serovars, and to assess the usefulness of enzyme-linked immunosorbent assay (ELISA) as a screening method for leptospiral antibodies in a high-risk healthy community. METHODS: Cross-sectional study of 231 market workers and food handlers in wet markets and food premises from two localities in central Malaysia. Respondents' background information was obtained using a questionnaire. Serum samples were tested for leptospiral antibodies using ELISA and microscopic agglutination test (MAT). RESULTS: Seroprevalence of leptospirosis among healthy workers was 46.3%. Detection of seropositivity was higher by MAT (46%) than ELISA (15%). We observed high seropositivity among local workers (49%), food handlers (49.5%), females (60.8%) and those aged 34 years and older (46.3%). Local strain LEP175 was the predominant serovar, followed by WHO strain Patoc. CONCLUSION: Overall seroprevalence among healthy food handlers and market workers was high in this study. The workplace places susceptible individuals at risk of leptospirosis.

Individual and interpersonal emotion regulation among adults with substance use disorders and matched controls.

OBJECTIVES: Self-report studies show that negative emotional states and ineffective use of emotion regulation strategies are key maintaining factors of substance use disorders (SUD). However, experimental research into emotional processing in adults with SUD is in its infancy. Theoretical conceptualizations of emotion regulation have shifted from a focus on individual (internal) processes to one that encompasses social and interpersonal functions - including the regulation of facial expression of emotion. The purpose of this study was to examine the individual and interpersonal emotion regulation capacity of 35 adults in residential treatment diagnosed with a SUD compared to 35 demographically matched controls (both samples Mage  = 25 years; 37% females). DESIGN AND METHODS: Participants completed a facial emotion expression flexibility task while viewing emotive images, as well as the Difficulties of Emotion Regulation Scale (DERS) and the Social (Emotion) Expectancy Scale (SES). RESULTS: Adults in SUD treatment experienced significantly more emotion regulation difficulties on all DERS subscales than controls. They also reported higher levels of negative self-evaluation and social expectancies not to feel negative emotions (anxiety and depression) compared to controls. Moreover, when viewing emotive images, the treatment sample showed significantly less flexibility of their emotional expression compared to the control sample. CONCLUSIONS: These findings demonstrate that the awareness, expression, and regulation of emotions are particularly difficult for people with SUD and this may maintain their substance use and provide an important target for treatment. PRACTITIONER POINTS: Compared to matched controls, adults with substance use disorders self-report significantly more difficulties with emotional awareness and regulation. Compared to matched controls, adults with substance use disorders report significantly greater expectancies not to show depression and anxiety. When viewing positive and negative images, adults with substance use disorders are significantly less flexible in their facial expression of emotion than matched controls in response to regulatory instructions. Emotion regulation should be measured and addressed as part of substance use disorder treatment.

3D modelling of the pathogenic Leptospira protein LipL32: A bioinformatics approach.

Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira species (Leptospiraceae). LipL32 is an abundant lipoprotein from the outer membrane proteins (OMPs) group, highly conserved among pathogenic and intermediate Leptospira species. Several studies used LipL32 as a specific gene to identify the presence of leptospires. This research was aimed to study the characteristics of LipL32 protein gene code, to fill the knowledge gap concerning the most appropriate gene that can be used as antigen to detect the Leptospira. Here, we investigated the features of LipL32 in fourteen Leptospira pathogenic strains based on comparative analyses of their primary, secondary structures and 3D modeling using a bioinformatics approach. Furthermore, the physicochemical properties of LipL32 in different strains were studied, shedding light on the identity of signal peptides, as well as on the secondary and tertiary structure of the LipL32 protein, supported by 3D modelling assays. The results showed that the LipL32 gene was present in all the fourteen pathogenic Leptospira strains used in this study, with limited diversity in terms of sequence conservation, hydrophobic group, hydrophilic group and number of turns (random coil). Overall, these results add basic knowledge to the characteristics of LipL32 protein, contributing to the identification of potential antigen candidates in future research, in order to ensure prompt and reliable detection of pathogenic Leptospira species.

Efficiency of newly formulated camptothecin with ß-cyclodextrin-EDTA-Fe3O4 nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug.

Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE3O4), a composite nanoparticle of magnetic iron oxide (Fe3O4), and ß-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT's solubility and bioavailability for cancer cells. The use of magnetically responsive anti-cancer formulation is highly advantageous in cancer chemotherapy. The chemical characterisation of CPT-CEF was studied here. The ability of this nano-compound to induce apoptosis in HT29 colon cancer cells and A549 lung cancer cells was evaluated. The dose-dependent cytotoxicity of CPT-CEF was shown using MTT. Propidium iodide and Annexin V staining, mitochondrial membrane depolarisation (JC-1 dye), and caspase-3 activity were assayed to detect apoptosis in CPT-CEF-treated cancer cells. Cell cycle analysis also showed G1 phase arrest, which indicated possible synergistic effects of the nano-carrier. These study results show that CPT-CEF causes a dose-dependent cell viability reduction in HT29 and A549 cells and induces apoptosis in colon cancer cells via caspase-3 activation. These data strongly suggest that CPT could be used as a major nanocarrier for CPT to effectively treat colon cancer.

Experience of a rapid access falls and syncope service at a teaching hospital in Kuala Lumpur.

No abstract available.

Leptospirosis: Molecular trial path and immunopathogenesis correlated with dengue, malaria and mimetic hemorrhagic infections.

Immuno-pathogenesis of leptospirosis can be recounted well by following its trail path from entry to exit, while inducing disastrous damages in various tissues of the host. Dysregulated, inappropriate and excessive immune responses are unanimously blamed in fatal leptospirosis. The inherent abilities of the pathogen and inabilities of the host were debated targeting the severity of the disease. Hemorrhagic manifestation through various mechanisms leading to a fatal end is observed when this disease is unattended. The similar vascular destructions and hemorrhage manifestations are noted in infections with different microbes in endemic areas. The simultaneous infection in a host with more than one pathogen or parasite is referred as the coinfection. Notably, common endemic infections such as leptospirosis, dengue, chikungunya, and malaria, harbor favorable environments to flourish in similar climates, which is aggregated with stagnated water and aggravated with the poor personal and environmental hygiene of the inhabitants. These factors aid the spread of pathogens and parasites to humans and potential vectors, eventually leading to outbreaks of public health relevance. Malaria, dengue and chikungunya need mosquitoes as vectors, in contrast with leptospirosis, which directly invades human, although the environmental bacterial load is maintained through other mammals, such as rodents. The more complicating issue is that infections by different pathogens exhibiting similar symptoms but require different treatment management. The current review explores different pathogens expressing specific surface proteins and their ability to bind with array of host proteins with or without immune response to enter into the host tissues and their ability to evade the host immune responses to invade and their affinity to certain tissues leading to the common squeal of hemorrhage. Furthermore, at the host level, the increased susceptibility and inability of the host to arrest the pathogens' and parasites' spread in different tissues, various cytokines accumulated to eradicate the microorganisms and their cellular interactions, the antibody dependent defense and the susceptibility of individual organs bringing the manifestation of the diseases were explored. Lastly, we provided a discussion on the immune trail path of pathogenesis from entry to exit to narrate the similarities and dissimilarities among various hemorrhagic fevers mentioned above, in order to outline future possibilities of prevention, diagnosis, and treatment of coinfections, with special reference to endemic areas.

Micro-anatomical changes in major blood vessel caused by dengue virus (serotype 2) infection.

Dengue virus (DENV) has emerged as a major economic concern in developing countries, with 2.5 billion people believed to be at risk. Vascular endothelial cells (ECs) lining the circulatory system from heart to end vessels perform crucial functions in the human body, by aiding gas exchange in lungs, gaseous, nutritional and its waste exchange in all tissues, including the blood brain barrier, filtration of fluid in the glomeruli, neutrophil recruitment, hormone trafficking, as well as maintenance of blood vessel tone and hemostasis. These functions can be deregulated during DENV infection. In this study, BALB/c mice infected with DENV serotype 2 were analyzed histologically for changes in major blood vessels in response to DENV infection. In the uninfected mouse model, blood vessels showed normal architecture with intact endothelial monolayer, tunica media, and tunica adventitia. In the infected mouse model, DENV distorted the endothelium lining and disturbed the smooth muscle, elastic laminae and their supporting tissues causing vascular structural disarrangement. This may explain the severe pathological illness in DENV-infected individuals. The overall DENV-induced damages on the endothelial and it's supporting tissues and the dysregulated immune reactions initiated by the host were discussed.

Impact of dengue virus (serotype DENV-2) infection on liver of BALB/c mice: A histopathological analysis.

In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host.

Enhanced sensitization to animal, interpersonal, and intergroup fear-relevant stimuli (but no evidence for selective one-trial fear learning).

Selective sensitization has been proposed as an alternative explanation for enhanced responding to animal fear-relevant stimuli--snakes and spiders--during extinction of Pavlovian fear conditioning. The current study sought to replicate the phenomenon using a shock workup procedure as the sensitizing manipulation and to extend it to interpersonal and intergroup fear-relevant stimuli--angry faces and other-race faces. Assessment of selective sensitization was followed by a one-trial fear learning procedure. Selective sensitization, larger electrodermal responses to fear-relevant than to control stimuli after sensitization, or a larger increase in electrodermal responding to fear-relevant than to control stimuli after sensitization was observed across stimulus domains. However, the one-trial fear learning procedure failed to provide evidence for enhanced fear conditioning to fear-relevant stimuli. One-trial fear learning was either absent or present for fear-relevant and nonfear-relevant stimuli. The current study confirms that electrodermal responses to fear-relevant stimuli across stimulus domains are subject to selective sensitization.

Modality-specific attentional startle modulation during continuous performance tasks: a brief time is sufficient.

Attentional startle modulation has been found to be modality specific in continuous performance tasks (CPTs) and modality nonspecific in trial-structured tasks. Experiment 1 investigated whether attentional blink modulation in a CPT would change if a trial structure was imposed. Participants performed a visual CPT either continuously (CONT), or during brief periods of time signaled by a change in screen color with stimuli either presented all the time (MIXED) or only during the trial segments (DISC). Contrary to expectation, evidence for modality-specific attentional startle modulation-smaller acoustic startle during targets than during nontargets-was strongest in Groups MIXED and DISC. Experiment 2 confirmed that this pattern of results was present during the first stimulus of the task period in group DISC. This suggests that the continuous nature of a task is not critical in determining the attentional mechanisms engaged.

Startle blink facilitation during the go signal of a reaction time task is not affected by movement preparation or attention to the go signal.

Startle reflex eliciting stimuli presented at the onset of the go signal in a simple forewarned reaction time (RT) task (at a SOA of 0 ms) elicit larger blink reflexes than do stimuli presented later (e.g., at a SOA of 150 ms) or during inter trial intervals. The present study investigated whether this facilitation is affected by attention to the go signal or motor preparation. Participants performed a forewarned reaction time task that crossed the requirements for a speeded response (Hold versus Move) and for a discrimination task performed with the go signal (Report versus No report). Relative to control reflexes, blinks elicited at a SOA of 0 ms were facilitated and blinks elicited at a SOA of 150 ms were inhibited. RTs were slower on trials that required attention to the go signal and in both attention conditions and at both SOAs shortened in the presence of a blink-eliciting stimulus. However, neither attention to the go signal nor motor preparation affected blink facilitation at the 0 ms SOA. This finding suggests that the blink reflex facilitation observed at a SOA of 0 ms with the onset of a go signal reflects on the summation of sub- and supra-threshold activations of the startle pathway.

Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio.

BACKGROUND: Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines. RESULTS: Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 +/- 0.026 microg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC50 obtained was higher compared to the IC50 for HepG2 cells (> 10 microg/ml). The extent of DNA fragmentation was evaluated by the Tdt-mediated dUTP nick end labelling assay which showed that, zerumbone significantly increased apoptosis in HepG2 cells in a time-course manner. In detail, the apoptotic process triggered by zerumbone involved the up-regulation of pro-apoptotic Bax protein and the suppression of anti-apoptotic Bcl-2 protein expression. The changes that occurred in the levels of this antagonistic proteins Bax/Bcl-2, was independent of p53 since zerumbone did not affect the levels of p53 although this protein exists in a functional form. Western blotting analysis for Bax protein was further confirmed qualitatively with an immunoassay that showed the distribution of Bax protein in zerumbone-treated cells. CONCLUSION: Therefore, zerumbone was found to induce the apoptotic process in HepG2 cells through the up and down regulation of Bax/Bcl-2 protein independently of functional p53 activity.

Racial disparity in the prevalence of thyroid disorder during pregnancy.

A study to determine the prevalence of goitre and abnormal thyroid status during pregnancy in Malaysian women was conducted. Two hundred and three women (Malay = 85, Chinese = 47 and Indian = 71) in the third trimester and with no known thyroid disease were studied. There was a marked racial disparity in the prevalence of goitre: Indian 61%, Malay 28% and Chinese 29% (p = 0.001). The serum thyrotropic hormone (TSH) was significantly higher in Indians (median: 1.36 uIU/ml) compared to Malays (1.14 uIU/ml, p = 0.009). The serum albumin was also significantly lower in Indians (mean +/- sd; 36.12 +/- 3.9 mmol/l) compared to Malays (39.3 +/- 4.8 mmol/l) or Chinese (39.1 +/- 5.2) (p < 0.001). Thyroid antibody was detected in 14.6% of these women with no significant racial difference in its prevalence. Three women were found to be thyrotoxic but none were hypothyroid. This study found a high prevalence of goitre among the pregnant Indian women, probably related to the protein malnutrition state. The high prevalence of positive thyroid antibody in our population indicates that a high percentage of women are at risk of developing postpartum thyroiditis.

Painful thyroiditis in postpartum period.

Destructive thyroiditis commonly occurs during the postpartum period, with a prevalence rate of 5% to 16%, and is mainly due to postpartum autoimmune thyroiditis (PPT) and, very rarely, to subacute thyroiditis. The thyroiditis is similar to Hashimoto's thyroiditis and is generally painless in nature, although cases with painful thyroiditis have been described. We report a case of painful destructive thyroiditis occurring during the postpartum period, which was clinically and biochemically indistinguishable from the variant of painful PPT or subacute thyroiditis. Fine needle aspiration cytology showed multi-nucleated giant cells diagnostic of subacute thyroiditis.

Iodine content in drinking water not an important determinant of endemic goitre.

The prevalence of goitre was determined in several communities in rural parts of Pahang. Urine specimens were collected randomly among the participants. Drinking water from various sources such as river and spring, and water from gravity feed systems was also collected to determine the iodine content by using the ashing method. The results were compared to that of Kuala Lumpur City. lt was found that the prevalence of goitre in rural areas was between 20 and 70% depending on village, ethnic group, age and gender. The interior parts of the jungle where Aborigines lived was moderately endemic with goitre prevalence of goitre more than 20% and urinary iodine content 2.0-5.0 µg I/dl). A nearby Malay traditional village which was studied had mild endemia (prevalence 10-30% and urinary iodine content 5.0-10.0 µg I/dl) while a Felda Malay resettlement scheme and Kuala Lumpur City did not have endemic goitre. Endemic goitre in rural areas was associated with low iodine content in drinking water. Even though Kuala Lumpur had low iodine content in its drinking water there was no endemic goitre, indicating that other factors were more important.