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Mitochondria provide the energy to keep cells alive and functioning and they have the capacity to influence highly complex molecular events. Mitochondria are essential to maintain cellular energy homeostasis that determines the course of neurological disorders, including traumatic brain injury (TBI). Various aspects of mitochondria metabolism such as autophagy can have long-term consequences for brain function and plasticity. In turn, mitochondria bioenergetics can impinge on molecular events associated with epigenetic modifications of DNA, which can extend cellular memory for a long time. Mitochondrial dysfunction leads to pathological manifestations such as oxidative stress, inflammation, and calcium imbalance that threaten brain plasticity and function. Hence, targeting mitochondrial function may have great potential to lessen the outcomes of TBI.

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Introduction Dengue, a viral infection transmitted by Aedes mosquitoes, has become a significant global health concern. Its incidence has surged dramatically over the past decades, with severe cases potentially leading to life-threatening conditions such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Despite its prevalence in tropical regions, including India, the clinical manifestations of dengue can vary widely, sometimes presenting atypically. Recent outbreaks, particularly in Northern India, underscore the urgency of understanding and managing this disease. This study focuses on the clinical and laboratory findings of hospitalized dengue fever patients from January 2022 to January 2023, aiming to provide insights for effective patient care and mortality reduction. Methods This was a prospective study at JSS (Jagadguru Sri Shivarathreeshwara) Medical College and Hospital, Mysuru, Karnataka, India (January 2022-January 2023). Blood samples from suspected dengue patients presenting acute febrile symptoms were collected. NS1 antigen and IgM antibody were detected using enzyme-linked immunosorbent assay (ELISA). Patients positive for dengue NS1 antigen and IgM antibodies were included in the study, excluding those with co-infections or comorbidities. Results A nine-month study at JSS Hospital (January 2022-January 2023) screened 1019 samples, identifying 316 dengue cases. Among these, 84.8% were dengue fever and 15.1% were DHF/DSS. Male predominance (60.1%) was noted, with peak incidence in the age groups of 11-20 years (29.11%) and 0-10 years (27.53%). Common symptoms included fever (98.1%), headache (32.91%), myalgia (40.87%), and vomiting (42.7%). Thrombocytopenia was found in 60.6% of cases. NS1 was detected in 56% of patients and IgM was positive in 20.8% of the patients. Comorbidities like type 2 diabetes mellitus (T2DM) (7.59%) and hypertension (7.27%) were observed. Among severe cases, 43.6% had platelet counts <1 lakh/cumm, and 27.5% required intravenous fluids. Seven deaths occurred, primarily in patients with comorbidities and severe dengue. Discussion and conclusion High dengue seropositivity among males (60.12%) compared to females (39.87%) was noted, possibly due to varied exposures. Patients aged 11-20 years had the highest dengue infection, with a peak in admissions during the rainy season. Thrombocytopenia (60.6%) and comorbidities like T2DM and HTN were common, with seven fatalities linked to severe dengue and comorbidities, emphasizing the need for early recognition and management to reduce mortality.

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Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.

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Natural killer cells (NK cells) are the front line of immune cells to combat pathogens and able to influence the subsequent adaptive immune responses. One of the factors contributing to pathogenesis in dengue hemorrhagic fever (DHF) disease is aberrant immune activation during early phase of infection. This study explored the profile of NK cells in dengue infected pediatric patients with different degrees of disease severity. DHF patients contained higher frequency of activated NK cells but lower ratio of CD56dim:CD56bright NK subsets. Activated NK cells exhibited alterations in several NK receptors. Interestingly, the frequencies of NKp30 expressing activated NK cells were more pronounced in dengue fever (DF) than in DHF pediatric patients. In vitro functional analysis indicated that degranulation of NK cells in responding to dengue infected dendritic cells (DCs) required cell-cell contact and type I IFNs. Meanwhile, Interferon gamma (IFN-γ) production initially required cell-cell contact and type I IFNs followed by Interleukin-12 (IL-12), Interleukin-15 (IL-15) and Interleukin-18 (IL-18) resulting in the amplification of IFN-γ producing NK cells over time. This study highlighted the complexity and the factors influencing NK cells responses to dengue virus. Degree of activation, phenotypes of activated cells and the crosstalk between NK cells and other immune cells, could modulate the outcome of NK cells function in the dengue disease.

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Itaconyl-CoA hydratase in Pseudomonas aeruginosa (PaIch) converts itaconyl-CoA to (S)-citramalyl-CoA upon addition of a water molecule, a part of an itaconate catabolic pathway in virulent organisms required for their survival in humans host cells. Crystal structure analysis of PaIch showed that a unique N-terminal hotdog fold containing a 4-residue short helical segment α3-, named as an "eaten sausage", followed by a flexible loop region slipped away from the conserved ß-sheet scaffold, whereas the C-terminal hotdog fold is similar to all MaoC. A conserved hydratase motif with catalytic residues provides mechanistic insights into catalysis, and existence of a longer substrate binding tunnel may suggest the binding of longer CoA derivatives.

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Dengue and leptospirosis are frequently discussed separately, with dengue causing rash and leptospirosis causing jaundice. Currently, there are more and more reports of coinfections. The comparable clinical symptoms of both infections make it challenging to distinguish between leptospirosis and dengue. Differentiating between leptospirosis and dengue is crucial since leptospirosis has a more favorable prognosis with early antibiotic therapy, whereas dengue does not have a specific treatment, although early detection is essential for close monitoring and cautious fluid management. Here, we highlight a case of dengue virus and leptospirosis coinfection in a female who presented with acute febrile illness, dyspnea, and altered sensorium, which progressed to multiorgan dysfunction syndrome, involving the neurological, respiratory, hepatic, and hematological systems.

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Dengue, a prevalent arboviral disease, has witnessed a resurgence in India, with outbreaks frequently reported. However, dengue-associated oral (oro-pharyngeal) candidiasis (DAOC) was never reported. We present two severe dengue cases with oral/oro-pharyngeal pseudomembranous candidiasis. Case 1 of a young man without any comorbidities or abuse or immunosuppression presented with fever, headache, altered sensorium, throat pain on recovery, and laboratory reports confirmed dengue with leukopenia, thrombocytopenia, and severe hepatic involvement with oro-pharyngeal candidiasis. Similarly, case 2 of a middle-aged man with a history of smoking and diabetes presented with fever, gum bleeding, and throat pain, later confirmed to be dengue NS1 positive with thrombocytopenia, and mild-moderate hepatic involvement along with oral-oro-pharyngeal candidiasis. Both cases showed improvement with conservative management and oral nystatin suspension. These cases prompt consideration of superadded candida infections in dengue patients, emphasizing the need for further study and clinical vigilance.

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Vascular dementia (VD) is a degenerative cerebrovascular disorder associated with progressive cognitive decline. Previous reports have shown that 7,8-dihydroxyflavone (7,8-DHF), a well-known TrkB agonist, effectively ameliorates cognitive deficits in several disease models. Therefore, this study investigated the protective effects of 7,8-DHF against 2-VO-induced VD. VD was established in rats using the permanent bilateral carotid arteries occlusion (two-vessel occlusion, 2-VO) model. 7,8-DHF (5, 10, and 20 mg/kg) and Donepezil (10 mg/kg) were administered for 4 weeks. Memory function was assessed by the novel objective recognition task (NOR) and Morris water maze (MWM) tests. Inflammatory (TNF-α, IL-1ß, and NF-kß), oxidative stress, and apoptotic (BAX, BCL-2, caspase-3) markers, along with the activity of choline acetylcholinesterase (AChE) was assessed. p-AKT, p-CREB, BDNF, and neurotransmitter (NT) (GLU, GABA, and ACh) levels were also analyzed in the hippocampus of 2-VO rats. Our results show that 7,8-DHF effectively improved memory performance and cholinergic dysfunction in 2-VO model rats. Furthermore, 7,8-DHF treatment also increased p-AKT, p-CREB, and BDNF levels, suppressed oxidative, inflammatory, and apoptotic markers, and restored altered NT levels in the hippocampus. These findings imply that 7, 8-DHF may act via multiple mechanisms and as such serve as a promising neuroprotective agent in the context of VD.

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BACKGROUND: Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of Erα. These findings demonstrated that TrkB activation in the presence of Erα comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of Erα-dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period. METHODS: In this study, we used a unilateral hypoxic ischemic (HI) mouse model. Erα+/+ or Erα-/- mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for 7 days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety-like behavior. The brains were then assessed for tissue damage using immunohistochemistry. RESULTS: Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking Erα. The female-specific improved recognition and location memory outcomes in adulthood conferred by DHF therapy after neonatal HI tended to be or were Erα-dependent, respectively. Interestingly, DHF triggered anxiety-like behavior in both sexes only in the mice that lacked Erα. When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of Erα significantly reduced overall HI-associated mortality in both sexes. CONCLUSIONS: These observations provide evidence for a therapeutic role for DHF in which TrkB-mediated sustained recovery of recognition and location memories in females are Erα-associated and dependent, respectively. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner.

Periods of low oxygen delivery and blood flow to the brains of newborns are known to cause life-long impairments to their cognitive ability as adults. Interestingly, male newborns are more susceptible to this injury than females. The mechanisms causing this sex difference are poorly understood. Here we test the role of the nerve growth factor receptor tyrosine kinase B (TrkB) in providing long-term neuroprotection following neonatal hypoxia­ischemia (HI) in mice. We have previously shown that when mice are treated with the TrkB agonist 7,8-dihydroxyflavone (DHF) in the days following neonatal HI, the result is short-term neuroprotection only in females and this protection is dependent on the presence of the estrogen receptor alpha receptor ([Formula: see text]). In this study, we extend these observations by subjecting mice either with or without [Formula: see text] to HI. Some of the mice were then treated with DHF immediately after HI. As adults, we performed tests to assess the mice's memory and anxiety-like behavior. At the end of these tests, we assessed the brains for tissue loss. Our results show that as adults the DHF treatment following HI in neonatal mice preserved memory only in females and this effect was dependent on the presence of [Formula: see text]. In addition, DHF therapy triggered anxiety-like behavior in mice lacking [Formula: see text]. We also show that this neuroprotection is not dependent on preservation of brain tissue following the injury. These results provide insight into the mechanisms behind the female resistance to hypoxic ischemic episodes as newborns.

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Whey protein-derived carbon nanodots (WCND) were synthesized using the microwave irradiation method, and its amine-rich surface functionality was crosslinked with covalently bound Iodine functionalized 2,5-dimethoxy-2,5-dihydrofuran (DHFI) to produce WCND-DHFI. The physicochemical characterization of both WCND and WCND-DHFI was performed and compared to comprehend the consequence of iodination on the characteristics of WCND. The suitability of CND in biological environments was evaluated through in vitro cytocompatibility and Chorioallantoic Membrane (CAM) assay, as well as a hemocompatibility study. WCND-DHFI has shown enhanced cell viability against WCND. Further, the antibacterial properties of both CNDs were studied against both gram-positive and gram-negative bacterial strains, representing an enhancement in antibacterial activity after DHFI crosslinking. WCND-DHFI has depicted a stable and prominent bacteriostatic activity for up to 6 h for both strains of bacteria. WCND-DHFI has denoted a 99.996% and 99.999% loss of bacterial viability for gram-positive and negative strains, respectively. Novel surface functionalization portrays an improvement in antibacterial activity. Transmission and scanning electron microscopy represent the cell wall rupturing by the WCND-DHFI, resulting in bacterial death. The ROS-mediated bacteriostatic mechanism of WCND-DHFI has been explored through assessing lipid peroxidation and protein oxidation assay. Moreover, the oxidative damage of DNA also has been explored. WCND-DHFI is performing as a promising cytocompatible and hemocompatible material for antibacterial applications.

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Background: Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of ERα. These findings demonstrated that TrkB activation in the presence of ERα comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of ERα-dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period. Methods: In this study we used a unilateral hypoxic ischemic (HI) mouse model. ERα+/+ or ERα-/- mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for seven days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety like behavior. The brains were then assessed for tissue damage using immunohistochemistry. Results: Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking ERα. Thus, the female-specific and ERα-dependent neuroprotection conferred by DHF therapy after neonatal HI was associated with improved learning and memory outcomes in adulthood. Interestingly, DHF triggered anxiety like behavior in both sexes only in the mice that lacked ERα. When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of ERα significantly reduced overall HI-associated mortality in both sexes. Conclusions: These observations provide evidence for a therapeutic role for DHF in which sustained recovery of memory in females is TrkB-mediated and ERα-dependent. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner.

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The recent emergence and re-emergence of viral infections transmitted by vectors, Zika, chikungunya, dengue, and others, is a cause for international concern. Here, we provide a summary of the current understanding of the transmission, clinical features, diagnosis, global burden, and the likelihood of future epidemics by these viruses. Arboviruses transmitted by mosquitoes are challenging to diagnose and can have surprising clinical complications. Dengue, chikungunya, and Zika are the most important diseases caused by arboviruses worldwide, especially in tropical and subtropical regions. These are transmitted to humans by day-biting Aedes aegypti and Aedes albopictus mosquitoes. In India, the increase in the incidence of dengue and chikungunya cases is primarily linked to the dissemination of Aedes aegypti. A rapid and accurate diagnosis is paramount for effectively controlling dengue outbreaks. As there is no vaccination or specific treatment available for these viruses, vector control is the only comprehensive solution available.

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Dengue is a viral infection transmitted by mosquitoes that causes fever, headache, joint pain, nausea, vomiting, and pain behind the eyes. In severe cases, it can progress to dengue hemorrhagic fever and dengue shock syndrome, which can be life-threatening. Armenia has not reported a single case of dengue to date and is non-endemic for this disease. However, it has been found that the vector of the disease, Aedes albopictus, is present in Armenia since 2016. The aim of this report is to present the imported case of suspected dengue hemorrhagic fever. A 23-year-old female who was admitted to the University Hospital experienced symptoms of general weakness, fever, joint pain, and chills after her return from Bali and had a three-day febrile period. A thorough examination revealed mosquito bites on her skin. On the fourth day of hospitalization, the patient's condition deteriorated. She started experiencing vaginal bleeding. On the same day, the patient noted a small petechiae rash sized 1-2 mm in diameter in the upper and lower extremities. The patient deteriorated, with progressive leukopenia and thrombocytopenia, and hypertransaminasemia. Screening tests for HIV and hepatitis A, B, C, and E were performed, and the results showed that the anti-hepatitis C antibody was positive, while the hepatitis C virus polymerase chain reaction was negative. The case was reported to the National Center for Disease Control and Prevention as an imported case of hemorrhagic fever. Unfortunately, no lab test was available there for confirmation of the diagnosis. The patient received IV infusion and symptomatic treatment. Her condition improved, and upon discharge, she was in a state of recovery. This case report highlights the importance of early diagnosis and appropriate treatment for hemorrhagic fevers, particularly dengue fever. The unavailability of diagnostic kits for dengue in Armenia highlights the need to invest in improving their availability. It also emphasizes the importance of maintaining dengue surveillance in non-endemic nations and carefully evaluating and monitoring febrile patients who have returned from dengue-endemic countries.

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Dengue virus infection, a highly prominent health concern, has caused many health complications, positive cases, and deaths in Bangladesh in previous years. However, the prevalence of this infection and fatality rates in 2022 has shattered all prior records. The dengue virus vector, mosquitoes, found a high prevalence of infection due to the weather's favorable conditions for breeding in the months of June and July. While there is presently no particular vaccination for dengue infection, awareness of its epidemiology, pathogenesis, signs, and symptoms may aid in the development of improved diagnostic and treatment strategies. The government should also improve the infrastructure of cities to make prevent mosquito breeding and the spread of dengue infection.

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Introduction: Growth-associated protein 43 (GAP-43) is known as a neuronal plasticity protein because it is widely expressed at high levels in neuronal growth cones during axonal regeneration. GAP-43 expressed in mature adult neurons is functionally important for the neuronal communication of synapses in learning and memory. Brain-derived neurotrophic factor (BDNF) is closely related to neurodegeneration and synaptic plasticity during the aging process. However, the molecular mechanisms regulating neurodegeneration and synaptic plasticity underlying the pathogenesis and progression of Alzheimer's disease (AD) still remain incompletely understood. Methods: Remarkably, the expressions of GAP-43 and BDNF perfectly match in various neurons in the Human Brain Atlas database. Moreover, GAP-43 and BDNF are highly expressed in a healthy adults' hippocampus brain region and are inversely correlated with the amyloid beta (Aß), which is the pathological peptide of amyloid plaques found in the brains of patients with AD. Results: These data led us to investigate the impact of the direct molecular interaction between GAP-43 and BDNF in hippocampal neuron fate. In this study, we show that GAP-43 and BDNF are inversely associated with pathological molecules for AD (Tau and Aß). In addition, we define the three-dimensional protein structure for GAP-43 and BDNF, including the predictive direct binding sites via analysis using ClusPro 2.0, and demonstrate that the deprivation of GAP-43 and BDNF triggers hippocampal neuronal death and memory dysfunction, employing the GAP-43 or BDNF knock-down cellular models and 5XFAD mice. Conclusion: These results show that GAP-43 and BDNF are direct binding partners in hippocampal neurons and that their molecular signaling might be potential therapeutic targets for AD.

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This article constructs a new model based on multivariate adaptive generalized Poisson regression splines (MAGPRS) and geographically weighted generalized Poisson regression (GWGPR), which is known as multivariate adaptive geographically weighted generalized Poisson regression splines (MAGWGPRS). The article elaborates the steps of weighted maximum likelihood estimation (weighted-MLE) to obtain the estimated values of its parameters. MAGWGPRS and MAGPRS were applied to the number of dengue hemorrhagic fever (DHF) cases in 119 districts or cities in Java, Indonesia, in 2020, to compare their performance. The fitted value plot versus actual data and a comparison of the mean square error (MSE) value demonstrate the goodness of the two models. The best MAGWGPRS model for each location was obtained, and only one the best MAGPRS model for all locations was acquired. Based on the plot results of the fitted value with the actual data and MSE value, MAGWGPRS is determined to be superior to MAGPRS.

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The title compounds Si(C4H5O)4 (1) and Ge(C4H5O)4 (2) are di-hydro-furyl compounds of silicon and germanium and are useful building blocks for the functionalization of these elements. Both structures crystallize in space group P21/n in the monoclinic crystal system with two mol-ecules in the asymmetric unit: the Si and Ge atoms adopt slightly distorted tetra-hedral geometries, while the C4H5O moieties exhibit shallow envelope conformations. Through a Hirshfeld surface analysis of the structures, inter-actions within the crystal packing could be elucidated: compound 1 features a polymeric chain in the (101) plane via C-H⋯O hydrogen bonds whereas in 2 C-H⋯O hydrogen bonds create a polymeric chain in the (010) plane.

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A systematic review was conducted to investigate the relationship between aminotransferases and the severity of dengue infection, which is a prevalent and significant infection in tropical and subtropical regions. Aminotransferases are enzymes that are often elevated in dengue due to the liver's physiological and immunological response to the infection. This review focused on analyzing various studies that examined the correlation between aminotransferase levels and the severity of dengue. Extensive literature searches were performed using ("dengue*" OR "dengue fever*" OR "dengue haemorrhagic fever*" OR "dengue shock syndrome*") AND ("alanine aminotransferase*" OR "aspartate aminotransferase*") on PubMed. The selected articles were thoroughly reviewed, encompassing epidemiology, pathogenesis, and clinical manifestations of dengue. The consistent findings across the studies indicated that aminotransferases can serve as predictive markers for dengue severity. Therefore, early assessment of liver enzyme levels is crucial in dengue cases, and elevated levels should be closely monitored to prevent adverse outcomes.

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Biallelic mutations in the gene encoding WFS1 underlie the development of Wolfram syndrome (WS), a rare neurodegenerative disorder with no available cure. We have previously shown that Wfs1 deficiency can impair the functioning of the renin-angiotensin-aldosterone system (RAAS). The expression of two key receptors, angiotensin II receptor type 2 (Agtr2) and bradykinin receptor B1 (Bdkrb1), was downregulated both in vitro and in vivo across multiple organs in a rat model of WS. Here, we show that the expression of key RAAS components is also dysregulated in neural tissue from aged WS rats and that these alterations are not normalized by pharmacological treatments (liraglutide (LIR), 7,8-dihydroxyflavone (7,8-DHF) or their combination). We found that the expression of angiotensin II receptor type 1a (Agtr1a), angiotensin II receptor type 1b (Agtr1b), Agtr2 and Bdkrb1 was significantly downregulated in the hippocampus of WS animals that experienced chronic experimental stress. Treatment-naïve WS rats displayed different gene expression patterns, underscoring the effect of prolonged experiment-induced stress. Altogether, we posit that Wfs1 deficiency disturbs RAAS functioning under chronic stressful conditions, thereby exacerbating neurodegeneration in WS.

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India is an endemic country for dengue. The incidence of hemophagocytic lymphohistiocytosis (HLH) with dengue in children has been well-reported. However, central nervous system (CNS) HLH associated with dengue has not been described in the literature yet. We hereby report a novel case of CNS HLH triggered by dengue infection. An eight-month-old, well-grown male infant with uneventful antenatal, perinatal, and neonatal history was admitted with a history of febrile illness associated with cough, cold, vomiting, and loose motions and one episode of hematochezia and hepatosplenomegaly on examination. Investigations revealed bi-cytopenia, hyper-ferritinemia, deranged coagulation profile, liver function test, and hypo-fibrinogenemia. Dengue non-structural protein 1 ( NS1) antigen was positive. The child was given dexamethasone and continued supportive care with a diagnosis of dengue shock syndrome. The child showed an overall transient improvement, however, he had rebound fever followed by right focal convulsion on Day 9 of steroids. MRI brain revealed areas of diffusion-restricted embolic infarcts with diffuse leptomeningeal enhancement and mild cerebral edema, and CSF showed a total leukocyte count of 80 cells with 75% lymphocytic picture, histiocytes with hemophagocytosis, confirmatory of CNS HLH. Intrathecal methotrexate, hydrocortisone, and intravenous (IV) etoposide were started. However, the child succumbed to his illness. CNS involvement in dengue-triggered HLH needs to be suspected despite subtle neurological signs and aggressively managed following a multi-departmental approach to ensure the best clinical and neuro-developmental outcomes.