Word recognition memory and serum levels of Borna disease virus specific circulating immune complexes in obsessive-compulsive disorder.

BACKGROUND: Borna disease virus 1 (BoDV-1) is a non-segmented, negative-strand RNA virus that persistently infects mammals including humans. BoDV-1 worldwide occurring strains display highly conserved genomes with overlapping genetic signatures between those of either human or animal origin. BoDV-1 infection may cause behavioral and cognitive disturbances in animals but has also been found in human major depression and obsessive-compulsive disorder (OCD). However, the impact of BoDV-1 on memory functions in OCD is unknown. METHOD: To evaluate the cognitive impact of BoDV-1 in OCD, event-related brain potentials (ERPs) were recorded in a continuous word recognition paradigm in OCD patients (n = 16) and in healthy controls (n = 12). According to the presence of BoDV-1-specific circulating immune complexes (CIC), they were divided into two groups, namely group H (high) and L (low), n = 8 each. Typically, ERPs to repeated items are characterized by more positive waveforms beginning approximately 250 ms post-stimulus. This "old/new effect" has been shown to be relevant for memory processing. The early old/new effect (ca. 300-500 ms) with a frontal distribution is proposed to be a neural correlate of familiarity-based recognition. The late old/new effect (post-500 ms) is supposed to reflect memory recollection processes. RESULTS: OCD patients were reported to show a normal early old/new effect and a reduced late old/new effect compared to normal controls. In our study, OCD patients with a high virus load (group H) displayed exactly these effects, while patients with a low virus load (group L) did not differ from healthy controls. CONCLUSION: These results confirmed that OCD patients had impaired memory recollection processes compared to the normal controls which may to some extent be related to their BoDV-1 infection.

Differences in the spatiotemporal expression and epistatic gene regulation of the mesodiencephalic dopaminergic precursor marker PITX3 during chicken and mouse development.

Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral mesencephalon and caudal diencephalon of all tetrapod species studied so far. They are the most prominent DA neuronal population and are implicated in control and modulation of motor, cognitive and rewarding/affective behaviors. Their degeneration or dysfunction is intimately linked to several neurological and neuropsychiatric human diseases. To gain further insights into their generation, we studied spatiotemporal expression patterns and epistatic interactions in chick embryos of selected marker genes and signaling pathways associated with mdDA neuron development in mouse. We detected striking differences in the expression patterns of the chick orthologs of the mouse mdDA marker genes Pitx3 and Aldh1a1, which suggests important differences between the species in the generation/generating of these cells. We also discovered that the sonic hedgehog signaling pathway is both necessary and sufficient for the induction of ectopic PITX3 expression in chick mesencephalon downstream of WNT9A-induced LMX1a transcription. These aspects of early chicken development resemble the ontogeny of zebrafish diencephalic DA neuronal populations, and suggest a divergence between birds and mammals during evolution.

Use Stereoscopic Model in Interventional and Surgical Procedures.

The 3-dimensional (3D) stereoscopic modeling software allows anatomists to create high-resolution 3D models from computed tomography (CT) images. In this paper, we used high resolution CT images from a cadaver and a patient to develop clinically relevant anatomic models that can be used to teach surgical trainees different surgical procedures and approaches. The model facilitates visualization, manipulation, and interaction. It can be presented in stereoscopic 3D in a virtual environment, either in a classroom setting or immediately preceding a surgical procedure.

Expression and function of microRNA-9 in the mid-hindbrain area of embryonic chick.

BACKGROUND: MiR-9 is a small non-coding RNA that is highly conserved between species and primarily expressed in the central nervous system (CNS). It is known to influence proliferation and neuronal differentiation in the brain and spinal cord of different vertebrates. Different studies have pointed to regional and species-specific differences in the response of neural progenitors to miR-9. METHODS: In ovo and ex ovo electroporation was used to overexpress or reduce miR-9 followed by mRNA in situ hybridisation and immunofluorescent stainings to evaluate miR- expression and the effect of changed miR-9 expression. RESULTS: We have investigated the expression and function of miR-9 during early development of the mid-hindbrain region (MH) in chick. Our analysis reveals a closer relationship of chick miR-9 to mammalian miR-9 than to fish and a dynamic expression pattern in the chick neural tube. Early in development, miR-9 is diffusely expressed in the entire brain, bar the forebrain, and it becomes more restricted to specific areas of the CNS at later stages. MiR-9 overexpression at HH9-10 results in a reduction of FGF8 expression and premature neuronal differentiation in the mid-hindbrain boundary (MHB). Within the midbrain miR-9 does not cause premature neuronal differentiation it rather reduces proliferation in the midbrain. CONCLUSION: Our findings indicate that miR-9 has regional specific effects in the developing mid-hindbrain region with a divergence of response of regional progenitors.

Untranslatable tospoviral NSs fragment coupled with L conserved region enhances transgenic resistance against the homologous virus and a serologically unrelated tospovirus.

Tospoviruses cause severe damages to important crops worldwide. In this study, Nicotiana benthamiana transgenic lines carrying individual untranslatable constructs comprised of the conserved region of the L gene (denoted as L), the 5' half of NSs coding sequence (NSs) or the antisense fragment of whole N coding sequence (N) of Watermelon silver mottle virus (WSMoV), individually or in combination, were generated. A total of 15-17 transgenic N. benthamiana lines carrying individual transgenes were evaluated against WSMoV and the serologically unrelated Tomato spotted wilt virus (TSWV). Among lines carrying single or chimeric transgenes, the level of resistance ranged from susceptible to completely resistant against WSMoV. From the lines carrying individual transgenes and highly resistant to WSMoV (56-63% of lines assayed), 30% of the L lines (3/10 lines assayed) and 11% of NSs lines (1/9 lines assayed) were highly resistant against TSWV. The chimeric transgenes provided higher degrees of resistance against WSMoV (80-88%), and the NSs fragment showed an additive effect to enhance the resistance to TSWV. Particularly, the chimeric transgenes with the triple combination of fragments, namely L/NSs/N or HpL/NSs/N (a hairpin construct), provided a higher degree of resistance (both 50%, with 7/14 lines assayed) against TSWV. Our results indicate that the untranslatable NSs fragment is able to enhance the transgenic resistance conferred by the L conserved region. The better performance of L/NSs/N and HpL/NSs/N in transgenic N. benthamiana lines suggests their potential usefulness in generating high levels of enhanced transgenic resistance against serologically unrelated tospoviruses in agronomic crops.

2-Amino-5-nitro-pyridinium hydrogen oxalate.

In the cation of the title mol-ecular salt, C5H6N3O2 (+)·C2HO4 (-), the dihedral angle between the aromatic ring and the nitro group is 3.5 (3)°; in the anion, the dihedral angle between the CO2 and CO2H planes is 10.5 (2)°. In the crystal, the anions are linked into [100] chains by O-H⋯O hydrogen bonds. The cations cross-link the chains by way of N-H⋯O hydrogen bonds and the structure is consolidated by C-H⋯O inter-actions.

Advancement in biomedical implant materials-a mini review.

Metal alloys like stainless steel, titanium, and cobalt-chromium alloys are preferable for bio-implants due to their exceptional strength, tribological properties, and biocompatibility. However, long-term implantation of metal alloys can lead to inflammation, swelling, and itching because of ion leaching. To address this issue, polymers are increasingly being utilized in orthopedic applications, replacing metallic components such as bone fixation plates, screws, and scaffolds, as well as minimizing metal-on-metal contact in total hip and knee joint replacements. Ceramics, known for their hardness, thermal barrier, wear, and corrosion resistance, find extensive application in electrochemical, fuel, and biomedical industries. This review delves into a variety of biocompatible materials engineered to seamlessly integrate with the body, reducing adverse reactions like inflammation, toxicity, or immune responses. Additionally, this review examines the potential of various biomaterials including metals, polymers, and ceramics for implant applications. While metallic biomaterials remain indispensable, polymers and ceramics show promise as alternative options. However, surface-modified metallic materials offer a hybrid effect, combining the strengths of different constituents. The future of biomedical implant materials lies in advanced fabrication techniques and personalized designs, facilitating tailored solutions for complex medical needs.

Debunking myths in headache diagnosis for the pain practitioner.

With headache being one of the most common chief complaints, it is essential for pain practitioners to interpret and differentiate a variety of headache characteristics to accurately diagnose and treat specific headache disorders. Certain misconceptions often lead to misdiagnosis. This article presents and discusses six myths about several common headache disorders (migraine, tension-type headache, cluster headache, cervicogenic headache, sinus headache, and occipital neuralgia) often encountered in clinical practice. The discussion is based primarily on the International Classification of Headache Disorders, 3rd edition and the latest studies. Recognizing and understanding the intricacies behind key headache diagnoses will help providers devise appropriate plans to better care for their patients.

Anti-bacterial and arsenic remediation insights in aqueous systems onto heterogeneous metal oxide (Cu0.52Al0.1Fe0.47O4)/rGO hybrid: an approach towards airborne microbial degradation.

Copper-based ternary metal oxide (i.e., Cu0.52Al0.01Fe0.47O4) impregnated reduced graphene oxide nanohybrid is verified for microbial and arsenic treatment. Growth inhibition of colonies are observed around 99.99% (E. coli), and 99.83% (S. aureus) at 10-20 µg/mL of hybrid dosage, respectively. The inhibition rates for both the colonies are increased to 99.9998% at 80 µg/mL. TEM images have shown insight of cell-content/lipid leakage behavior after inoculating with the hybrid. The efficient hindrance towards microbial colony growth is attributed to better charge transfer, reactive oxygen species generation, and metal-ion release. Maximum arsenic sorption capacities are observed around 248 and 314 mg/g for As(III), and As(V), respectively (Ci ~ 500 ppm). Surface morphology studies onto arsenic adsorption are reported with atomic force microscope, and FT-IR/Raman analysis. A detailed discussion onto individual spectra of As 3d spectra confirmed the occurrence of redox transformation in arsenic species [As(III)]. The variation in the quantity (at. %) of oxygen functional groups in O1s spectra (i.e., M-O, M-OH, and -OH2) onto the hybrid supported the ligand-exchange behavior. Cyclic voltammetry study in arsenic electrolytes (10 µM - 1 mM) provides the occurrence of various in-situ electrochemical reactions supporting the redox activity. A significant electromagnetic wave absorption characteristics of the present hybrid is proposed with plausible airborne antimicrobial-agent abilities.

Antimicrobial efficacy of a hemilabile Pt(II)-NHC compound against drug-resistant S. aureus and Enterococcus.

Three platinum(II)-N-heterocyclic carbene (NHC) compounds [Pt(L1)Cl](PF6) (1), [Pt(L2)(COD)](PF6)2 (2) and [Pt(L2)Cl2] (3) were synthesized bearing pyridyl-functionalized butenyl-tethered (L1H) and n-butyl tethered (L2H) NHC ligands, and their antibacterial activity against clinically relevant human pathogens was evaluated. Complex 1 was designed to have one of its metal coordination sites masked with a hemilabile butenyl group. The antibacterial activity spectrum against the ESKAPE panel of pathogens shows superior activity of 1 compared to 2 and 3 against the Gram-positive S. aureus pathogen. Complex 1 showed equipotent activity against clinical drug-resistant S. aureus and Enterococcus isolates. Furthermore, 1 demonstrated concentration-dependent bactericidal activity with a long post-antibiotic effect, eradicated preformed S. aureus biofilm and synergized with gentamicin and minocycline for combinatorial antimicrobial therapy. Under in vivo conditions, 1 displayed potent activity in reducing bacterial load in a murine thigh infection model, similar to vancomycin, albeit at 2.5× less dosage. An array of experiments reveals key characteristics for the hemilabile complex 1 as a potential anti-staphylococcal drug.

Immortalization of neuronal progenitors using SV40 large T antigen and differentiation towards dopaminergic neurons.

Transplantation is common in clinical practice where there is availability of the tissue and organ. In the case of neurodegenerative disease such as Parkinson's disease (PD), transplantation is not possible as a result of the non-availability of tissue or organ and therefore, cell therapy is an innovation in clinical practice. However, the availability of neuronal cells for transplantation is very limited. Alternatively, immortalized neuronal progenitors could be used in treating PD. The neuronal progenitor cells can be differentiated into dopaminergic phenotype. Here in this article, the current understanding of the molecular mechanisms involved in the differentiation of dopaminergic phenotype from the neuronal progenitors immortalized with SV40 LT antigen is discussed. In addition, the methods of generating dopaminergic neurons from progenitor cells and the factors that govern their differentiation are elaborated. Recent advances in cell-therapy based transplantation in PD patients and future prospects are discussed.

Identification and Genome Analysis of an Arsenic-Metabolizing Strain of Citrobacter youngae IITK SM2 in Middle Indo-Gangetic Plain Groundwater.

Whole-genome sequencing (WGS) data of a bacterial strain IITK SM2 isolated from an aquifer located in the middle Indo-Gangetic plain is reported here, along with its physiological, morphological, biochemical, and redox-transformation characteristics in the presence of dissolved arsenic (As). The aquifer exhibits oxidizing conditions relative to As speciation. Analyses based on 16S rRNA and recN sequences indicate that IITK SM2 was clustered with C. youngae NCTC 13708T and C. pasteuri NCTC UMH17T. However, WGS analyses using the digital DNA-DNA hybridization and Rapid Annotations using Subsystems Technology suggest that IITK SM2 belongs to a strain of C. youngae. This strain can effectively reduce As(V) to As(III) but cannot oxidize As(III) to As(V). It exhibited high resistance to As(V) [32,000 mg L-1] and As(III) [1,100 mg L-1], along with certain other heavy metals typically found in contaminated groundwater. WGS analysis also indicates the presence of As-metabolizing genes such as arsC, arsB, arsA, arsD, arsR, and arsH in this strain. Although these genes have been identified in several As(V)-reducers, the clustering of these genes in the forms of arsACBADR, arsCBRH, and an independent arsC gene has not been observed in any other Citrobacter species or other selected As(V)-reducing strains of Enterobacteriaceae family. Moreover, there were differences in the number of genes corresponding to membrane transporters, virulence and defense, motility, protein metabolism, phages, prophages, and transposable elements in IITK SM2 when compared to other strains. This genomic dataset will facilitate subsequent molecular and biochemical analyses of strain IITK SM2 to identify the reasons for high arsenic resistance in Citrobacter youngae and understand its role in As mobilization in middle Indo-Gangetic plain aquifers.

Clinico-Radiological-Pathologic Profile and Outcomes of Lung Transplant in Post-COVID-19 Phenotype: A Single Center Experience.

BACKGROUND: Lung transplantation (LTx) has come as hope for select patients with post-COVID acute respiratory distress syndrome (ARDS). It has a different phenotype with unique challenges. We aimed to bring out our experience with and outcomes of LTx for post-COVID ARDS. METHODS: This study is retrospective case series from a single center in India. All the patients with post-COVID end stage lung disease (ESLD) who underwent bilateral LTx between 1st May 2020 and 30th August 2021 were included. LTx was performed following no improvement with optimal medical management with adequate time provided for recovery. Information relating to demographics, comorbidities, pretransplant status, perioperative parameters, gross and histopathological findings of explanted lungs, posttransplant morbidity, and mortality were analyzed. RESULTS: This study included 23 patients. The median age of the patients in this study was 42 years and 20 participants were men (87%). The mean duration of intensive care unit stay was 15.83 ± 6.61 days. Mortality was observed among 8 participants (34.78%). Mean survival time was 34.54 weeks. Among the 8 patients who expired, the cause of death was sepsis for 6 patients (75.0%), neurologic cerebrovascular accident for 1 patient (12.5%), and cytomegalovirus for 1 patient (12.5%). All the deaths were reported in primary graft dysfunction grade 2 & 3 category. No rejections were observed on first and third month surveillance biopsies. CONCLUSIONS: LTx is the definitive option for survival in select patients with severe post-COVID-19-associated ESLD. This study brings out various challenges involved in such phenotypes and also observations in postoperative recovery.

Cytokine IP-10 and GM-CSF are prognostic biomarkers for severity in secondary dengue infection.

Dengue virus (DENV) infection is mostly prevalent in tropical and sub-tropical regions of the world. Though most DENV infections are self-limiting febrile like-illness, a small proportion of secondary infection is fatal, if untreated symptomatically. Among various factors involved in severe dengue, immune enhancement by cytokine is the major one. The objective of the study is to elucidate serum cytokine expression among primary and secondary infection and determine if any signature cytokine is correlated with disease severity. Seventy-six serum samples at acute time points were collected during the 2017 DENV outbreak in Madurai, Tamil Nadu. Among the 76 serum samples, 49 belong to primary and 27 to secondary DENV infection. Interestingly, a large number of primary infection presented with DHF/DSS symptoms and, children were found prone to DHF and DSS in secondary infection. The serum samples were analysed for inflammatory cytokines, namely IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IFN-γ, TNF-α, IP-10 and GM-CSF using ELISA assay as well as mRNA analysis using qPCR. Among the 12 inflammatory cytokines analysed IP-10 and GMCSF mRNA and protein shows significant upregulation in secondary infection. Similarly, a strong correlation was observed between GM-CSF and IP-10 with thrombocytopenia, ascites, serous effusion and spontaneous bleeding. Based on the observations, GM-CSF and IP-10 could be a potential prognostic biomarkers for secondary DENV infection.

Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile.

Dengue virus (DENV) infection is prevalent in tropical and subtropical regions of the world, which is fatal if untreated symptomatically. Emergence of new genotype within serotypes led to enhanced severity. The objective of the study is to identify the molecular characteristics of the DENV circulated during 2017 outbreak in Tamil Nadu, India, and to investigate the role of inflammatory cytokines in different "serotypes" and in "dengue severity". A total of 135 suspected samples were tested for DENV infection using IgM, IgG, and qPCR assay; where 76 samples were positive for DENV and analyzed for 12 inflammatory cytokines using ELISA. Serotyping shows 14 DENV-1, 22 DENV-2, 7 DENV-3, and 33 DENV-4, where DENV-4 was predominant. Among 76, 42 isolates were successfully sequenced for C-prM region and grouped. A lineage shift was observed in DENV-4 genotype. Irrespective of serotypes, IFNγ was significantly elevated in all serotypes than control as well as in primary infection than secondary, indicating its role in immune response. GM-CSF and IP-10 were significantly elevated in secondary infection and could be used as prognostic biomarkers for secondary infection. Our observation shows differential cytokine expression profile varied with each serotype, indicating serotype/genotype-specific viral proteins might play a major role in dengue severity. DENV-4 as dominant serotype was reported in Tamil Nadu for the first time during an outbreak with a mixed Th1/Th17 cytokine expression profile that correlated with disease severity. We conclude it is essential to identify circulating viral genotype and their fitness by mutational analysis to correlate with disease severity and immune status, as this correlation will be helpful in diagnostics and therapeutics applications.

Impact of COVID-19 on an Academic Pain Fellowship Program.

BACKGROUND: While the COVID-19 pandemic still rages on in the United States, leaving in its wake hundreds of thousands of infected patients, families shattered by the untimely death of their loved ones, an economy in free fall that hit all-time highs barely a few months ago, and a fearful citizenry unsure of what the future holds, the effect it has had on residency and fellowship training programs across the country may appear inconsequential to the general populace. However, if you are a graduating trainee confronted with this unusual set of circumstances, fear of the virus is not the only thing that is foremost in your mind. METHODS: Literature review. RESULTS: We discuss the unique challenges our pain fellowship program continues to deal with during this pandemic and particularly its impact on our fellows. It is entirely likely these concerns are mirrored in academic programs all over the United States. LIMITATIONS: A narrative review with paucity of literature.

MiR-9 and the Midbrain-Hindbrain Boundary: A Showcase for the Limited Functional Conservation and Regulatory Complexity of MicroRNAs.

MicroRNAs regulate gene expression at post-transcriptional levels. Some of them appear to regulate brain development and are involved in neurodevelopmental disorders. This has led to the suggestion that the role of microRNAs in neuronal development and function may be more central than previously appreciated. Here, we review the data about miR-9 function to depict the subtlety, complexity, flexibility and limited functional conservation of this essential developmental regulatory system. On this basis we propose that species-specific actions of miR-9 could underlie to a large degree species differences in brain size, shape and function.

A biphasic nanohydroxyapatite/calcium sulphate carrier containing Rifampicin and Isoniazid for local delivery gives sustained and effective antibiotic release and prevents biofilm formation.

Long term multiple systemic antibiotics form the cornerstone in the treatment of bone and joint tuberculosis, often combined with local surgical eradication. Implanted carriers for local drug delivery have recently been introduced to overcome some of the limitations associated with conventional treatment strategies. In this study, we used a calcium sulphate hemihydrate (CSH)/nanohydroxyapatite (nHAP) based nanocement (NC) biomaterial as a void filler as well as a local delivery carrier of two standard of care tuberculosis drugs, Rifampicin (RFP) and Isoniazid (INH). We observed that the antibiotics showed different release patterns where INH showed a burst release of 67% and 100% release alone and in combination within one week, respectively whereas RFP showed sustained release of 42% and 49% release alone and in combination over a period of 12 weeks, respectively indicating different possible interactions of antibiotics with nHAP. The interactions were studied using computational methodology, which showed that the binding energy of nHAP with RFP was 148 kcal/mol and INH was 11 kcal/mol, thus varying substantially resulting in RFP being retained in the nHAP matrix. Our findings suggest that a biphasic ceramic based drug delivery system could be a promising treatment alternative to bone and joint TB.

Genome Sequence of Bacillus subtilis subsp. subtilis Strain IITK SM1, Isolated from Kitchen Waste Compost.

We report here the complete genome sequence of Bacillus subtilis subsp. subtilis strain IITK SM1, isolated from kitchen waste compost. We have sequenced the whole genome of this strain to identify and characterize the enzymes that participate in efficient composting activity.

In vitro analysis of synthetic peptides in blocking the entry of dengue virus.

Dengue fever is the most prevalent arthropod-borne viral disease, and no specific therapeutic or promising antiviral drug is available for its treatment. Peptide inhibitors are less toxic than synthetic compounds and have found proven effective against viral infections. Here, three peptides that mimic part of the E protein of the dengue virus (DENV) were synthesized and evaluated for their inhibitory activity against four serotypes of DENV in African green monkey kidney (Vero) and rhesus macaque (Macaca mulatta) monkey kidney (LLC-MK2) cell lines. The three peptides, Pep1, Pep2, and Pep3 are located in domains I, II, and III of the E protein respectively. All three peptides effectively reduced >80% of focus forming units in the virus treated mammalian cell lines than control and exhibited their IC50 in the range of 10-33 µM. Pep1 was found effective against DENV-2, DENV-3, and DENV-4 (IC80 below 50 µM). Pep2 showed the highest inhibitory activity against all four serotypes (IC50 below 20 µM). Pep3 reduced the 80% focus forming units in all serotypes at the concentration of 40 µM. Evaluation of peptides at different time points of viral infection in the mammalian cell lines revealed that the peptides inhibited viral infection by binding to the virus and not by binding to cellular receptors and blocking viral entry. The peptides assumedly exert their inhibitory effects by binding to the E protein and repressing its conformational changes; this prevents the virus from binding to cellular receptors, thereby inhibiting viral entry. Hence, these peptides might limit viral spread and reduce the virus's ability to infect.