Concomitant Occurrence of Hepatitis A and a Pyogenic Liver Abscess: A Pediatric Case.

Pyogenic liver abscess (PLA) and hepatitis A are common in developing countries. As there is an overlap of clinical features, a diagnosis of dual infection can be missed. Here, we present the case of a five-year-old male who presented with abdominal pain, fever, and jaundice diagnosed as a complicated liver abscess with concurrent hepatitis A. To our knowledge, this is the first case where a PLA co-existed with hepatitis A. Simultaneous infection should be considered when a patient with liver abscess presents with jaundice, especially in areas where both diseases are endemic. Early diagnosis of both is crucial as PLA is a potentially fatal disease and co-infection with hepatitis A may worsen clinical outcomes.

Palatal bone block: A predictable bone augmentation technique for restricted maxillary defect.

Bone grafting for implant dentistry depends on bone quality, quantity, and biological principles for good outcome. Autogenous bone as donor remains the gold standard among all the available materials. However, it carries unpredictable morbidity and need for different surgical sites. In our report, we describe a simplified approach in bone augmentation for restricted maxillary atrophic defect within the same surgical site as a harvesting site. The method can be an alternative for different intraoral surgical harvesting sites. The patient's left maxillary central incisor before treatment had a large bony defect which was reconstructed though single site approach of augmentation. The implant-supported restoration with healthy periodontium around even after 2 years of review looks promising. The approach can be an alternative for different intraoral surgical sites.

FSTL1-knockdown improves neural oscillation via decreasing neuronal-inflammation regulating apoptosis in Aß1-42 induced AD model mice.

Follistatin like protein 1 (FSTL1) is a famous growth regulatory protein. FSTL1 has been noticed in many diseases, including heart and lung ischemia, cerebral ischemia, glioma, schizophrenia, and Autism. The role of FSTL1 has been declared in the genetics and development of the central nervous system. Therefore, we designed this study to investigate the function and the role of FSTL1 in Alzheimer's disease. Firstly, we noticed upregulated expression level of FSTL1 among four to six-month-old 5XFAD AD mice. Accordingly, we hypothesized that FSTL1-Knockdown improved AD model mice's cognitive function and recover from Alzheimer's disease. Thus, AD model mice were made by single intracerebroventricular injections of Aß1-42 peptides in FSTL1+/- and CON mice. Next, our results concluded that FSTL1-knockdown effectively improved cognitive functions. FSTL1-knockdown enhanced the pattern of neural oscillations, and synaptic plasticity in Aß1-42 treated FSTL1-Knockdown mice compared to Aß1-42 induced AD model mice. Next, FSTL1-Knockdown inhibited the activation of microglia and binding of TLR-4 with microglia. Further, inactivated microglia stopped the formation of MyD88. Thus, our data revealed that FSTL1-Knockdown is slowing down the caspase/BAX/Bcl-2/TLR-4 regulating apoptosis pathway, and the expression of inflammatory cytokines in the hippocampus of Aß1-42 inserted FSTL1-Knockdown mice. Overall, all these data illuminate the clinical significance role of down-regulated FSTL1. FSTL1-Knockdown reduced the amyloid-beta by affecting microglia, neural-inflammation and apoptosis in AD-like model mice. Finally, down regulation of FSTL1 improved synaptic plasticity, neural oscillations, and cognitive behaviours in the Aß1-42 induced AD model mice.

Analyzing mouse neural stem cell and progenitor cell proliferation using EdU incorporation and multicolor flow cytometry.

This protocol describes an ex vivo approach to identify and quantify the proportions of proliferating neural stem cells and progenitors of the mouse subventricular zone. It uses ethynyl deoxyuridine (EdU) incorporation to identify dividing cells, combined with multicolor flow cytometry for 4 cell surface antigens to distinguish between 8 phenotypically distinct mouse neural progenitors and stem cells. It has been optimized for wild-type neonatal mice but can be used on mice of any postnatal age. For complete details on the use and execution of this profile, please refer to Kumari et al. (2020).

Modestly increasing systemic interleukin-6 perinatally disturbs secondary germinal zone neurogenesis and gliogenesis and produces sociability deficits.

Epidemiologic studies have demonstrated that infections during pregnancy increase the risk of offspring developing Schizophrenia, Autism, Depression and Bipolar Disorder and have implicated interleukin-6 (IL-6) as a causal agent. However, other cytokines have been associated with the developmental origins of psychiatric disorders; therefore, it remains to be established whether elevating IL-6 is sufficient to alter the trajectory of neural development. Furthermore, most rodent studies have manipulated the maternal immune system at mid-gestation, which affects the stem cells and progenitors in both the primary and secondary germinal matrices. Therefore, a question that remains to be addressed is whether elevating IL-6 when the secondary germinal matrices are most active will affect brain development. Here, we have increased IL-6 from postnatal days 3-6 when the secondary germinal matrices are rapidly expanding. Using Nestin-CreERT2 fate mapping we show that this transient increase in IL-6 decreased neurogenesis in the dentate gyrus of the dorsal hippocampus, reduced astrogliogenesis in the amygdala and decreased oligodendrogenesis in the body and splenium of the corpus callosum all by âˆ¼ 50%. Moreover, the IL-6 treatment elicited behavioral changes classically associated with neurodevelopmental disorders. As adults, IL-6 injected male mice lost social preference in the social approach test, spent âˆ¼ 30% less time socially engaging with sexually receptive females and produced âˆ¼ 50% fewer ultrasonic vocalizations during mating. They also engaged âˆ¼ 50% more time in self-grooming behavior and had an increase in inhibitory avoidance. Altogether, these data provide new insights into the biological mechanisms linking perinatal immune activation to complex neurodevelopmental brain disorders.

Tacrine accelerates spatial long-term memory via improving impaired neural oscillations and modulating GAD isomers including neuro-receptors in the hippocampus of APP/PS1 AD mice.

Tacrine (Amino tetrahydroacridine hydrochloride hydrate) is a non-competitive and reversible inhibitor of acetylcholine esterase, and butylcholinesterase. Alzheimer's disease (AD) shows multiple types of pathological pathway in which cholinergic neuron deficiency is 95 % popular and the oldest pathological mechanism. However, the effect of tacrine on the hippocampal dependent memory is not yet known. In this study, we did verify that tacrine induced recovery of the specific pattern associated memory along with long-term memory through the improvement in the pattern of neural oscillation from deficits condition in the hippocampus of 6th month old AD mice. Our results showed that tacrine improved the performance of Morris water maze related spatial cognitive functions, and enhanced LTP in AD-TAC mice. Furthermore, our results implied that tacrine strongly improve the patterns of neural oscillations, and hippocampal synaptic plasticity in the 6th month old APP-PS1 double transgenic AD-TAC mice via changing the theta and alpha power spectra including with the improvement in theta, alpha and gamma synchronization. Moreover, tacrine generated the improvement in the theta cross spectra, theta-gamma phase-phase synchronization and theta-gamma phase-amplitude coupling. Besides, the data represented that tacrine accelerated the expression of NR2B, SYP and GAD65 while it caused deceleration on the expression of GAD67 neurotransmitter and Aß. Thus, our results infer that tacrine works as a strong causative agent for improving the specific pattern-associated spatial long-term memory in the AD mice without showing any side effect.

Developmental IL-6 Exposure Favors Production of PDGF-Responsive Multipotential Progenitors at the Expense of Neural Stem Cells and Other Progenitors.

Interleukin-6 (IL-6) is increased in maternal serum and amniotic fluid of children subsequently diagnosed with autism spectrum disorders. However, it is not clear how increased IL-6 alters brain development. Here, we show that IL-6 increases the prevalence of a specific platelet-derived growth factor (PDGF)-responsive multipotent progenitor, with opposite effects on neural stem cells and on subsets of bipotential glial progenitors. Acutely, increasing circulating IL-6 levels 2-fold above baseline in neonatal mice specifically stimulated the proliferation of a PDGF-responsive multipotential progenitor accompanied by increased phosphorylated STAT3, increased Fbxo15 expression, and decreased Dnmt1 and Tlx expression. Fate mapping studies using a Nestin-CreERT2 driver revealed decreased astrogliogenesis in the frontal cortex. IL-6-treated mice were hyposmic; however, olfactory bulb neuronogenesis was unaffected. Altogether, these studies provide important insights into how inflammation alters neural stem cells and progenitors and provide new insights into the molecular and cellular underpinnings of neurodevelopmental disorders associated with maternal infections.

U1 snRNA over-expression affects neural oscillations and short-term memory deficits in mice.

Small nuclear RNAs (snRNAs) and other RNA spliceosomal components are involved in neurological and psychiatric disorders. U1 snRNA has recently been demonstrated to be altered in pathology in some neurodegenerative diseases, but whether it has a causative role is not clear. Here we have studied this by overexpressing U1 snRNA in mice and measured their hippocampal oscillatory patterns and brain functions. Novel object recognition test showed that the recognition index was significantly decreased in the U1 snRNA over-expression mice compared to that in the C57BL mice. U1 snRNA over-expression regulated not only the pattern of neural oscillations but also the expression of neuron excitatory and inhibitory proteins. Here we show that U1 snRNA over-expression contains the shrinkage distribution of theta-power, theta-phase lock synchronization, and theta and low-gamma cross-frequency coupling in the hippocampus. The alternations of neuron receptors by the U1 snRNA overexpression also modulated the decreasing of recognition index, the energy distribution of theta power spectrum with the reductions of theta phase synchronization and phase-amplitude coupling between theta and low-gamma. Linking these all together, our results suggest that U1 snRNA overexpression particularly causes a deficit in short-term memory. These findings make a bedrock of our research that U1 snRNA bridges the gap about the mechanism behind short-term memory based on the molecular and mesoscopic level.

Insulin-like Growth Factor II: An Essential Adult Stem Cell Niche Constituent in Brain and Intestine.

Tissue-specific stem cells have unique properties and growth requirements, but a small set of juxtacrine and paracrine signals have been identified that are required across multiple niches. Whereas insulin-like growth factor II (IGF-II) is necessary for prenatal growth, its role in adult stem cell physiology is largely unknown. We show that loss of Igf2 in adult mice resulted in a ∼50% reduction in slowly dividing, label-retaining cells in the two regions of the brain that harbor neural stem cells. Concordantly, induced Igf2 deletion increased newly generated neurons in the olfactory bulb accompanied by hyposmia, and caused impairments in learning and memory and increased anxiety. Induced Igf2 deletion also resulted in rapid loss of stem and progenitor cells in the crypts of Lieberkühn, leading to body-weight loss and lethality and the inability to produce organoids in vitro. These data demonstrate that IGF-II is critical for multiple adult stem cell niches.

Molecular events leading to death of Leishmania donovani under spermidine starvation after hypericin treatment.

We have previously reported that the hypericin treatment caused spermidine starvation and death of Leishmania parasite. Here, we report different molecular events under spermidine starvation and potential role of spermidine in processes other than redox homeostasis of the parasite. We have analyzed changes in expression of several genes by using quantitative gene expression analysis. Further, these changes at molecular level were also confirmed by using biochemical and cellular studies. Altered expression of several genes involved in redox metabolism, hypusine modification of eIF5A, DNA repair pathway and autophagy was observed. There was decrease in Sir2RP expression after hypericin treatment and this decrease has been found to be associated with induced ROS due to hypericin treatment as it has been rescued by either trypanothione or spermidine supplementation. Translation initiation in the parasite was decreased upon spermidine starvation. We also observed increased AMPK expression upon hypericin treatment. The increase in intracellular ATP and NAD+ levels as well as decrease in Sir2RP expression of the parasite are cytoprotective mechanism towards generated ROS due to hypericin treatment possibly by inducing autophagy as indicated by increase in autophagy related gene expression and acridine orange staining. However, the autophagy needs to be established using more rigorous methodologies.

Unmasking the responses of the stem cells and progenitors in the subventricular zone after neonatal and pediatric brain injuries.

There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone (SVZ). However, a comprehensive understanding of SVZ cell responses to brain injuries has been hindered by the lack of sensitive approaches to study the cellular composition of this niche. Here we review progress being made in deciphering the cells of the SVZ gleaned from the use of a recently designed flow cytometry panel that allows SVZ cells to be parsed into multiple subsets of progenitors as well as putative stem cells. We review how this approach has begun to unmask both the heterogeneity of SVZ cells as well as the dynamic shifts in cell populations with neonatal and pediatric brain injuries. We also discuss how flow cytometric analyses also have begun to reveal how specific cytokines, such as Leukemia inhibitory factor are coordinating SVZ responses to injury.

Traumatic globe luxation: A case report.

Globe luxation is a rare clinical event. Most of the cases are usually traumatic, although spontaneous globe luxation has also been reported. The majority of the posttraumatic cases are usually associated with the injury or fracture of the bony orbit. We report here a case of globe luxation that occurred per se without any injury to the orbital or maxillo-facial bony structures.

Ocular tilt reaction, internuclear ophthalmoplegia, and torsional nystagmus following mitral commissurotomy.

Ocular tilt reaction, a type of skew deviation, and unilateral internuclear ophthalmoplegia with torsional nystagmus resulting from an ischemic event may result from unilateral disruption of otolithic pathways in the medial longitudinal fasciculus. A subset of skew deviations is known to simulate superior oblique palsy; however, none have been reported with a coexisting internuclear ophthalmoplegia. The present report documents the rare occurrence of an ocular tilt reaction simulating a left superior oblique palsy from involvement of left medial longitudinal fasciculus at the level of interstitial nucleus of Cajal.