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Dengue is the most rapidly spreading mosquito-borne disease and has become a major public health threat, particularly for tropical and subtropical countries including Bangladesh. This comprehensive review aims to summarize the overall scenario of dengue, including disease burden, clinical spectrum, seroprevalence, circulating serotypes/genotypes, and spatial distribution since the first recorded outbreak in Bangladesh. Since the first recorded outbreak in 2000, dengue epidemiology has shown the typical epidemic pattern with more frequent and bigger outbreaks and gradual geographic expansion to non-endemic regions in Bangladesh. For instance, highly confined Rohingya refugee camps that provide shelters to nearly 1.2 million forcibly displaced vulnerable Myanmar nationals in Cox's Bazar district confronted a massive outbreak in 2022. Recent major outbreaks are found to be associated with the emergence of serotype DENV-3, which was undetected for a long time. Consequently, changes in serotypes might be attributed to increased severity in clinical manifestation in recent years. The existing weak surveillance and risk management systems are inadequate to deal with impending dengue risks. The healthcare system, particularly at the district level, is not prepared to manage impending large-scale dengue outbreaks in Bangladesh. Our findings would contribute to the development of strategies for dengue control and management in Bangladesh as well as other similar settings elsewhere in the world., (© 2023. The Author(s).)

Establishing reliable early warning models for severe dengue cases is a high priority to facilitate triage in dengue-endemic areas and optimal use of limited resources. However, few studies have identified the complex interactive relationship between potential risk factors and severe dengue. This research aimed to assess the potential risk factors and detect their high-order combinative effects on severe dengue. A structured questionnaire was used to collect detailed dengue outbreak data from eight representative hospitals in Dhaka, Bangladesh, in 2019. Logistic regression and machine learning models were used to examine the complex effects of demographic characteristics, clinical symptoms, and biochemical markers on severe dengue. A total of 1,090 dengue cases (158 severe and 932 non-severe) were included in this study. Dyspnoea (Odds Ratio [OR] = 2.87, 95% Confidence Interval [CI]: 1.72 to 4.77), plasma leakage (OR = 3.61, 95% CI: 2.12 to 6.15), and hemorrhage (OR = 2.33, 95% CI: 1.46 to 3.73) were positively and significantly associated with the occurrence of severe dengue. Classification and regression tree models showed that the probability of occurrence of severe dengue cases ranged from 7% (age >12.5 years without plasma leakage) to 92.9% (age ≤12.5 years with dyspnoea and plasma leakage). The random forest model indicated that age was the most important factor in predicting severe dengue, followed by education, plasma leakage, platelet, and dyspnoea. The research provides new evidence to identify key risk factors contributing to severe dengue cases, which could be beneficial to clinical doctors to identify and predict the severity of dengue early., Competing Interests: The authors report there are no competing interests to declare., (Copyright: © 2023 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background Major depressive disorder (MDD) is a persistent psychiatric condition and one of the leading causes of global disease burden. In a previous study, we investigated the effects of a five-week intervention consisting of rhythmic gamma frequency (30-70 Hz) vibroacoustic stimulation in 20 patients formally diagnosed with MDD. In that study, the findings suggested a significant clinical improvement in depression symptoms as measured using the Montgomery-Asberg Depression Rating Scale (MADRS), with 37% of participants meeting the criteria for clinical response. The goal of the present research was to examine possible changes from baseline to posttreatment in resting-state electroencephalography (EEG) recordings using the same treatment protocol and to characterize basic changes in EEG related to treatment response. Materials and methods The study sample consisted of 19 individuals aged 18-70 years with a clinical diagnosis of MDD. The participants were assessed before and after a five-week treatment period, which consisted of listening to an instrumental musical track on a vibroacoustic device, delivering auditory and vibrotactile stimulus in the gamma-band range (30-70 Hz, with particular emphasis on 40 Hz). The primary outcome measure was the change in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to posttreatment and resting-state EEG. Results Analysis comparing MADRS score at baseline and post-intervention indicated a significant change in the severity of depression symptoms after five weeks (t = 3.9923, df = 18, p = 0.0009). The clinical response rate was 36.85%. Resting-state EEG power analysis revealed a significant increase in occipital alpha power (t = -2.149, df = 18, p = 0.04548), as well as an increase in the prefrontal gamma power of the responders (t = 2.8079, df = 13.431, p = 0.01442). Conclusions The results indicate that improvements in MADRS scores after rhythmic sensory stimulation (RSS) were accompanied by an increase in alpha power in the occipital region and an increase in gamma in the prefrontal region, thus suggesting treatment effects on cortical activity in depression. The results of this pilot study will help inform subsequent controlled studies evaluating whether treatment response to vibroacoustic stimulation constitutes a real and replicable reduction of depressive symptoms and to characterize the underlying mechanisms., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Mosabbir et al.)

Competing Interests: The authors have declared that no competing interests exist.

Background: Thalassaemia, a hereditary haemoglobin disorder, is a major public health concern in some parts of the world. Although Bangladesh is in the world's thalassaemia belt, the information on this disease is scarce. Additionally, the awareness of this life threatening, but potentially preventable disease is surprisingly poor. However, mass awareness is pivotal for the development of an effective preventive strategy. In this context, the understanding of parental perspectives is essential to grasp the magnitude of the problem. Therefore, this study aimed to investigate the parental knowledge gaps and perceptions regarding thalassemia, the barriers confronted by the parents for caring for their thalassaemic children and their attitude to prenatal screening and prenatal diagnosis., Methods: This cross-sectional study was conducted between January 2018 and December 2018 at a dedicated thalassemia hospital located in Dhaka. A structured questionnaire was used for face-to-face interviews with parents of thalassaemic children. Descriptive statistics were used to analyse data., Results: Of 365 respondents, nearly all respondents (97%) had not heard about the term, 'thalassemia' before the disease was diagnosed in their children; all (100%) were unscreened for carrier status prior to marriage. Mean knowledge scores were significantly higher in respondents with higher income and education. Most respondents (~ 91%) had a guilty feeling for not undergoing premarital screening. Only around 36% of them had heard about prenatal diagnosis. Approximately 25% participants would consider prenatal diagnosis in a future pregnancy, while 70% of them were unsure and only ~ 5% would decline prenatal diagnosis. Only 9.3% mothers had prenatal diagnosis in a previous pregnancy. Nearly 80% of the parents faced difficulty for obtaining blood donors regularly and a similar proportion (~ 81%) of them did not receive support from any organized blood clubs. More than 40% of the parents reported they felt socially stigmatized., Conclusion: This study suggests poor parental knowledge regarding thalassaemia including prenatal diagnosis and the challenges faced while caring for their children. These findings would be of paramount importance in planning and devising effective prevention and intervention strategies in Bangladesh as well as other countries with similar sociocultural setting., (© 2021. The Author(s).)

Protein-based systems for light directed migration of cells have been demonstrated up to distances of several hundred microns, but larger distances in the centimeter scale would allow new possible applications. Light activated migration in mammalian cells can be achieved by cells expressing channelrhodopsin-2 and an engineered Ca 2+ sensitive Rac1 protein called RACer. In this study, light was used to induce wound healing, localize cells into a region of interest, and move cells over centimeter scale distances. Given the spatially complex organization of different types of cells in real tissue, light directed migration over the centimeter scale could potentially organize cell type arrangement to help develop more realistic tissues for transplantation.

Background: Chikungunya virus causes mosquito-transmitted infection that leads to extensive morbidity affecting substantial quality of life. Disease associated morbidity, quality of life, and financial loss are seldom reported in resources limited countries, such as Bangladesh. We reported the acute clinical profile, quality of life and consequent economic burden of the affected individuals in the recent chikungunya outbreak (May to September 2017) in Dhaka city, Bangladesh., Methods: We conducted a cross-sectional study during the peak of chikungunya outbreak (July 24 to August 5, 2017) to document the clinical profiles of confirmed cases (laboratory test positive) and probable cases diagnosed by medical practitioners. Data related to clinical symptoms, treatment cost, loss of productivity due to missing work days, and quality of life during their first two-weeks of symptom onset were collected via face to face interview using a structured questionnaire. World Health Organization endorsed questionnaire was used to assess the quality of life., Results: A total of 1,326 chikungunya cases were investigated. Multivariate analysis of major clinical variables showed no statistically significant differences between confirmed and probable cases. All the patients reported joint pain and fever. Other more frequently reported symptoms include headache, loss of appetite, rash, myalgia, and itching. Arthralgia was polyarticular in 56.3% of the patients. Notably, more than 70% patients reported joint pain as the first presenting symptom. About 83% of the patients reported low to very low overall quality of life. Nearly 30% of the patients lost more than 10 days of productivity due to severe arthropathy., Conclusions: This study represents one of the largest samples studied so far around the world describing the clinical profile of chikungunya infection. Our findings would contribute to establish an effective syndromic surveillance system for early detection and timely public health intervention of future chikungunya outbreaks in resource-limited settings like Bangladesh., Competing Interests: The authors have declared that no competing interests exist.

The damaging and degenerative effects in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn's disease often manifests as the formation of lesions that feature a high local concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF along with other pro-inflammatory factors form a positive feedback loop that ultimately perpetuate the lesions. Hence, to engineer chemotaxis to GM-CSF, we created a new chimeric GM-CSF receptor alpha subunit (GMRchi) that was coupled with a previously engineered Ca 2+ -activated RhoA. When these proteins were expressed in mammalian cells, it allowed migration to chemical and cellular sources of GM-CSF. As a possible therapeutic intervention, we further implemented the mechanism of cell-cell membrane fusion and subsequent death. Since the microenvironment of lesions is more than just GM-CSF secretion, the further ability to recognize a combination of other features such as tissue markers will be needed for greater specificity. Nonetheless, this work represents a first step to enable cell-based therapy of autoimmune lesions., (© 2017 Wiley Periodicals, Inc.)

As monoclonal antibodies have two epitopes for their target ligand, they should theoretically dimerize target receptors upon binding. In particular, the dimerization of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) stimulates early events occurring within minutes (e.g. Ca 2+ signal generation) and late events occurring over hours and days (e.g. cell migration in angiogenesis). Although studies have noted that antibodies targeting VEGFR2 (anti-VEGFR2) inhibited cell migration in angiogenesis, we show in this paper that an anti-VEGFR2 stimulus nevertheless triggered a Ca 2+ signal in VEGFR2 expressing cells. This Ca 2+ signal was then re-wired to promote cell migration by co-expressing an engineered Ca 2+ activated RhoA (called CaRQ), thereby engineering the opposite anticipated effect of an anti-VEGFR2 antibody. In these cells, the anti-VEGFR2 antibody stimulus induced cellular blebbing, migration across a membrane, and in vitro scratch wound healing. This work expands the utility of monoclonal antibodies to induce tailored responses in engineered cells such as changes in cell fluorescence via Ca 2+ reporters or migration patterns via CaRQ.

Magnetoreception can be generally defined as the ability to transduce the effects of a magnetic field into a cellular response. Magnetic stimulation at the cellular level is particularly attractive due to its ability for deep penetration and minimal invasiveness, allowing remote regulation of engineered biological processes. Previously, a magnetic-responsive genetic circuit was engineered using the transient receptor potential vanilloid 1 (TRPV1) and the iron containing ferritin protein (i.e., the TF circuit). In this study, we combined the TF circuit with a Ca 2+ activated RhoA protein (CaRQ) to allow a magnetic field to remotely regulate cell migration. Cells expressing the TF circuit and CaRQ exhibited consistent dynamic protrusions, leading to migration along a porous membrane, directed spreading in response to a magnetic field gradient, as well as wound healing. This work offers a compelling interface for programmable electrical devices to control the migration of living systems for potential applications in cell-based therapy.

Challenges of cell-based cancer therapy include effectively homing therapeutic cells to the disease site and producing a controlled response in recognition of the microenvironment. While stem cells have been intensively studied for treating cancer as they naturally home towards sites of injury, they have drawbacks due to their pluripotency. In this paper we have shown that a stable HEK293 cell line expressing VEGFR2 and CarQ (an engineered Ca 2+ -sensitive RhoA) can home towards a cell colony expressing VEGF. Upon VEGF binding to VEGFR2, a Ca 2+ signal is produced that in turn activates CarQ-mediated cell blebbing. With the addition of VSVG, these homing cells can further initiate pH-dependent fusion upon reaching the cell colony. This protein system can form the basis of engineering cells for therapeutic intervention by homing and inhibiting tumour growth by pH-dependent fusion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Disease sites in atherosclerosis and cancer feature cell masses (e.g., plaques/tumors), a low pH extracellular microenvironment, and various pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). The ability to engineer a cell to seek TNFα sources allows for targeted therapeutic delivery. To accomplish this, here we introduced a system of proteins: an engineered TNFα chimeric receptor (named TNFR1chi), a previously engineered Ca 2+ -activated RhoA (named CaRQ), vesicular stomatitis virus glycoprotein G (VSVG), and thymidine kinase. Upon binding TNFα, TNFR1chi generates a Ca 2+ signal that in turn activates CaRQ-mediated non-apoptotic blebs that allow migration toward the TNFα source. Next, the addition of VSVG, upon low pH induction, causes membrane fusion of the engineered and TNFα source cells. Finally, after ganciclovir treatment cells undergo death via the thymidine kinase suicide mechanism. Hence, we assembled a system of proteins that forms the basis of engineering a cell to target inflammatory disease sites characterized by TNFα secretion and a low-pH microenvironment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To use HIV-1 based lentivirus components to produce gene integration and the formation of a stable cell line in the packaging cell line without viral infection., Results: A co-transfection of a Human Embryonic Kidney (HEK) 293 packaging cell line with Gag-pol (GP) and a transfer vector, without the envelope vector, produces a stable cell line after 2 weeks of selection. Furthermore, a matrix protein deficient GP in the packaging vector enhances this integration. This supports that, in theory, unexported lentiviral cores produced within the packaging cell can infect itself without requiring the release of any lentiviral particles., Conclusion: If the packaging cell is also the target cell, then gene integration leading to a stable cell line can be accomplished without viral particle infection.

Background: Many studies have assessed the relationship of depression and anxiety with Parkinson's disease (PD), as well as examining restless leg syndrome (RLS) with depression and anxiety. Nonetheless, there has not been an extensive effort to show how the prevalence of RLS affects both depression and anxiety in PD patients. The objective of this study was to examine how the prevalence of RLS in PD patients affects the prevalence and severity of depression and anxiety and how they compare with each other. This study is the first of its kind that examines the effects of the combination of the two neurological conditions with depression and anxiety as well as comparing their prevalence and severity to each other., Methods: The study included 27 PD patients who also suffered from RLS, 27 PD patients not suffering from RLS, and 27 gender-matched healthy individuals. All were evaluated for caseness and severity of both anxiety and depression using the Hospital Anxiety and Depression Scale (HADS); HADS-A and HADS-D, respectively., Results: PD patients with RLS reported having the highest prevalence of both anxiety and depression. The least reported cases for both anxiety and depression were in the control group. In comparison, the results for severity of anxiety and depression within the three groups showed that PD patients with and without RLS had significantly higher severity scores for both anxiety and depression than the control group, but the scores did not significantly differ between the two PD patient groups., Conclusion: The presence of RLS in PD patients may increase the occurrence of both anxiety and depression, but the severity of the symptoms is not significant in the two groups of the PD patients.

Protein splicing is mediated by inteins that auto-catalytically join two separated protein fragments with a peptide bond. Here we engineered a genetically encoded synthetic photoactivatable intein (named LOVInC), by using the light-sensitive LOV2 domain from Avena sativa as a switch to modulate the splicing activity of the split DnaE intein from Nostoc punctiforme. Periodic blue light illumination of LOVInC induced protein splicing activity in mammalian cells. To demonstrate the broad applicability of LOVInC, synthetic protein systems were engineered for the light-induced reassembly of several target proteins such as fluorescent protein markers, a dominant positive mutant of RhoA, caspase-7, and the genetically encoded Ca2+ indicator GCaMP2. Spatial precision of LOVInC was demonstrated by targeting activity to specific mammalian cells. Thus, LOVInC can serve as a general platform for engineering light-based control for modulating the activity of many different proteins.

Objective: Action tremor (AT) and resting tremor (RT) have been widely cited in many studies with Parkinson's disease (PD) patients, but studies looking at the association between the two tremor types are few and show inconsistent results. This study will look at the prevalence and association of AT and RT in a large sample of idiopathic PD patients, and will put the results into context with the literature., Methods: A retrospective chart review analysis of 332 patients with idiopathic PD was performed. Prevalence rates of particular tremor types were noted. The presence of AT was analyzed relative to the presence and severity of RT., Results: Nearly all individuals with AT also had RT. The concurrence of the two tremor types was found to be highly significant by statistical analysis (P < 0.0001). The severity of RT, measured by its laterality, may also be of importance, albeit to a much smaller extent if at all. Neither presence of tremor nor type of tremor present was influenced by patient gender, age, or Hoehn and Yahr stage of PD., Conclusions: The results indicate that AT has extensive presence in PD. This and its seemingly close relationship to RT suggest that AT may be considered a variant of RT, particularly in PD patients. The degree of association between RT and AT needs to be further analyzed in PD, as well as in essential tremor (ET) and ET-PD.