Early auditory processing abnormalities alter individual learning trajectories and sensitivity to computerized cognitive training in schizophrenia.

BACKGROUND: Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a 'bottom up' intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown. METHODS: Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10-12 weeks later. RESULTS: SZ patients were deficient in APS at baseline (d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis (d = 1.75, p = 0.002) and time (d = 1.04, p < 0.001), and a diagnosis × time interaction (d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients (d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT (r = 0.51, p = 0.02) in SZ. CONCLUSIONS: TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.

Bidirectional Multiphoton Communication between Remote Superconducting Nodes.

Quantum communication test beds provide a useful resource for experimentally investigating a variety of communication protocols. Here we demonstrate a superconducting circuit test bed with bidirectional multiphoton state transfer capability using time-domain shaped wave packets. The system we use to achieve this comprises two remote nodes, each including a tunable superconducting transmon qubit and a tunable microwave-frequency resonator, linked by a 2 m-long superconducting coplanar waveguide, which serves as a transmission line. We transfer both individual and superposition Fock states between the two remote nodes, and additionally show that this bidirectional state transfer can be done simultaneously, as well as being used to entangle elements in the two nodes.

Clarifying directional dependence among measures of early auditory processing and cognition in schizophrenia: leveraging Gaussian graphical models and Bayesian networks.

BACKGROUND: Research using latent variable models demonstrates that pre-attentive measures of early auditory processing (EAP) and cognition may initiate a cascading effect on daily functioning in schizophrenia. However, such models fail to account for relationships among individual measures of cognition and EAP, thereby limiting their utility. Hence, EAP and cognition may function as complementary and interacting measures of brain function rather than independent stages of information processing. Here, we apply a data-driven approach to identifying directional relationships among neurophysiologic and cognitive variables. METHODS: Using data from the Consortium on the Genetics of Schizophrenia 2, we estimated Gaussian Graphical Models and Bayesian networks to examine undirected and directed connections between measures of EAP, including mismatch negativity and P3a, and cognition in 663 outpatients with schizophrenia and 630 control participants. RESULTS: Chain structures emerged among EAP and attention/vigilance measures in schizophrenia and control groups. Concerning differences between the groups, object memory was an influential variable in schizophrenia upon which other cognitive domains depended, and working memory was an influential variable in controls. CONCLUSIONS: Measures of EAP and attention/vigilance are conditionally independent of other cognitive domains that were used in this study. Findings also revealed additional causal assumptions among measures of cognition that could help guide statistical control and ultimately help identify early-stage targets or surrogate endpoints in schizophrenia.

Effects of Memantine on the Auditory Steady-State and Harmonic Responses to 40 Hz Stimulation Across Species.

BACKGROUND: Click trains elicit an auditory steady-state response (ASSR) at the driving frequency (1F) and its integer multiple frequencies (2F, 3F, etc.) called harmonics; we call this harmonic response the steady-state harmonic response (SSHR). We describe the 40 Hz ASSR (1F) and 80 Hz SSHR (2F) in humans and rats and their sensitivity to the uncompetitive NMDA antagonist memantine. METHODS: In humans (healthy control participants, n = 25; patients with schizophrenia, n = 28), electroencephalography was recorded after placebo or 20 mg memantine in a within-participant crossover design. ASSR used 1 ms, 85-dB clicks presented in 250 40/s 500-ms trains. In freely moving rats (n = 9), electroencephalography was acquired after memantine (0, 0.3, 1, 3 mg/kg) in a within-participant crossover design; 65-dB click trains used 5-mV monophasic, 1-ms square waves (40/s). RESULTS: Across species, ASSR at 1F generated greater evoked power (EP) than the 2F SSHR. 1F > 2F intertrial coherence (ITC) was also detected in humans, but the opposite relationship (ITC: 2F > 1F) was seen in rats. EP and ITC at 1F were deficient in patients and were enhanced by memantine across species. EP and ITC at 2F were deficient in patients. Measures at 2F were generally insensitive to memantine across species, although in humans the ITC harmonic ratio (1F:2F) was modestly enhanced by memantine, and in rats, both the EP and ITC harmonic ratios were significantly enhanced by memantine. CONCLUSIONS: ASSR and SSHR are robust, nonredundant electroencephalography signals that are suitable for cross-species analyses that reveal potentially meaningful differences across species, diagnoses, and drugs.

First detection of Varicella Zoster Virus clade 9 cases in India during mpox surveillance.

BACKGROUND: The multi-country mpox outbreak across the globe has led to the systematic surveillance of mpox cases in India. During the surveillance of mpox, we encountered cases of Varicella Zoster Virus (VZV) in suspected mpox cases amongst children & adults. This study focused on the genomic characterization of VZV in India. METHODS: A total of 331 mpox suspected cases were tested for VZV through real-time PCR, and the positive samples were subjected to next-generation sequencing to retrieve the whole genome of VZV using CLC genomics software. Phylogenetic analysis has been done in MEGA 11.0 software to identify circulating clades. RESULT: Of the 331 suspected cases, 28 cases with vesicular rashes were found to be positive for VZV. The maximum genome could be retrieved from the clinical specimens of 16 cases with coverage greater than 98% when mapped with reference strain Dumas (NC 001348). The phylogenetic analyses of these sequences determined the circulation of clades 1, 5, and 9 in India. Further, the sequence analysis demonstrated non-synonymous single nucleotide polymorphism (SNPs) among specific ORF of VZV including ORF 14, ORF 22, ORF 36, ORF 37 and ORF 51. Although clade 1 and 5 has been reported earlier, the circulation of clade 9 of VZV has been determined for the first time in India. CONCLUSION: Although the circulation of different clades of VZV was reported from India, the presence of clade 9 was detected for the first time during the mpox surveillance.

Reporting Rigor of Cancer Rehabilitation Interventions: Application of the CReDECI-2 Guidelines.

ABSTRACT: Clear reporting of cancer rehabilitation interventions is critical for interpreting and translating research into clinical practice. This study sought to examine the completeness of intervention reporting of cancer rehabilitation interventions addressing disability and to identify which elements are most frequently missing. This was a secondary analysis of randomized controlled trials included in two systematic reviews examining effectiveness of cancer rehabilitation interventions that address cancer-related disability, including functional outcomes. Eligible trials were reviewed for intervention reporting rigor using the Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 checklist. Intervention descriptions for cancer rehabilitation interventions were generally incomplete. Approximately 85% ( n = 157) of trials described ≤50% of Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 checklist items. Commonly underreported items included description of the intervention's underlying theoretical basis, fidelity, description of process evaluation or external conditions influencing intervention delivery, and costs or required resources for intervention delivery. The findings reveal that cancer rehabilitation intervention descriptions lacked necessary detail in this body of literature. Poor descriptions limit the translation of research to clinical practice. To ensure higher-quality study design and reporting, future intervention research should incorporate an intervention reporting checklist to ensure more complete descriptions for research and practice.

Mismatch negativity predicts initial auditory-based targeted cognitive training performance in a heterogeneous population across psychiatric disorders.

Auditory-based targeted cognitive training (ATCT) programs are emerging pro-cognitive therapeutic interventions which aim to improve auditory processing to attenuate cognitive impairment in a "bottom up" manner. Biomarkers of early auditory information processing (EAIP) like mismatch negativity (MMN) and P3a have been used successfully to predict gains from a full 40 h course of ATCT in schizophrenia (SZ). Here we investigated the ability of EAIP biomarkers to predict ATCT performance in a group of subjects (n = 26) across SZ, MDD, PTSD and GAD diagnoses. Cognition was assessed via the MATRICS Consensus Cognitive Battery (MCCB) and MMN/P3a were collected prior to completing 1 h of "Sound Sweeps," a representative ATCT exercise. Baseline and final performance over the first two levels of cognitive training served as the primary dependent variables. Groups had similar MMN, but the SZ group had attenuated P3a. MMN and MCCB cognitive domain t-scores, but not P3a, were strongly correlated with most ATCT performance measures, and explained up to 61% of variance in ATCT performance. Diagnosis was not a significant predictor for ATCT performance. These data suggest that MMN can predict ATCT performance in heterogeneous neuropsychiatric populations and should be considered in ATCT studies across diagnostically diverse cohorts.

Comparative pathogenicity of BA.2.12, BA.5.2 and XBB.1 with the Delta variant in Syrian hamsters.

Omicron variant is evolving into numerous sub variants with time and the information on the characteristics of these newly evolving variants are scant. Here we performed a pathogenicity evaluation of Omicron sub variants BA.2.12, BA.5.2 and XBB.1 against the Delta variant in 6-8-week-old Syrian hamster model. Body weight change, viral load in respiratory organs by real time RT-PCR/titration, cytokine mRNA quantification and histopathological evaluation of the lungs were performed. The intranasal infection of the BA.2.12, BA.5.2 and XBB.1 variants in hamster model resulted in body weight loss/reduced weight gain, inflammatory cytokine response and interstitial pneumonia with lesser severity compared to the Delta variant infection. Among the variants studied, BA.2.12 and XBB.1 showed lesser viral shedding through the upper respiratory tract, whereas the BA.5.2 showed comparable viral RNA shedding as that of the Delta variant. The study shows that the Omicron BA.2 sub variants may show difference in disease severity and transmissibility amongst each other whereas the overall disease severity of the Omicron sub variants studied were less compared to the Delta variant. The evolving Omicron sub variants and recombinants should be monitored for their properties.

Post-COVID-19 Fungal Infection in the Aged Population.

Coronavirus disease 2019 (COVID-19) infection is currently a great cause of concern for the healthcare sector around the globe. SARS-CoV-2 is an RNA virus that causes a serious infection that is associated with numerous adverse effects and multiple complications associated with different organs and systems during its pathogenic cycle in humans. Individuals affected by COVID-19, especially elderly populations and immunocompromised people, are greatly vulnerable to opportunistic fungal pathogens. Aspergillosis, invasive candidiasis, and mucormycosis are widespread fungal coinfections in COVID-19 patients. Other fungal infections that are rare but are exhibiting increased incidence in the current scenario include infections caused by Pneumocystis jirovecii, Histoplasma sp., Cryptococcus sp., etc. By producing virulent spores, these pathogens increase the severity of the disease and increase the morbidity and fatality rates in COVID-19 patients globally. These infections generally occur in patients recovering from COVID-19 infection, resulting in rehospitalization. Older and immunocompromised individuals are at higher risk of developing opportunistic fungal infections. This review focuses on understanding the opportunistic fungal infections prevalent in COVID-19 patients, especially elderly people. We have also highlighted the important preventive methods, diagnostic approaches, and prophylactic measures for fungal infections.

Thermoresponsive Conductivity of Graphene-Based Fibers.

Smart materials are versatile material systems which exhibit a measurable response to external stimuli. Recently, smart material systems have been developed which incorporate graphene in order to share on its various advantageous properties, such as mechanical strength, electrical conductivity, and thermal conductivity as well as to achieve unique stimuli-dependent responses. Here, a graphene fiber-based smart material that exhibits reversible electrical conductivity switching at a relatively low temperature (60 °C), is reported. Using molecular dynamics (MD) simulation and density functional theory-based non-equilibrium Green's function (DFT-NEGF) approach, it is revealed that this thermo-response behavior is due to the change in configuration of amphiphilic triblock dispersant molecules occurring in the graphene fiber during heating or cooling. These conformational changes alter the total number of graphene-graphene contacts within the composite material system, and thus the electrical conductivity as well. Additionally, this graphene fiber fabrication approach uses a scalable, facile, water-based method, that makes it easy to modify material composition ratios. In all, this work represents an important step forward to enable complete functional tuning of graphene-based smart materials at the nanoscale while increasing commercialization viability.

Preliminary Evidence that Memantine Enhances Prepulse Effects on Startle Magnitude and Latency in Patients with Alzheimer's Disease.

BACKGROUND: The uncompetitive NMDA antagonist, memantine (MEM), enhances prepulse inhibition of startle (PPI) across species. MEM is used to treat Alzheimer's disease (AD); conceivably, its acute impact on PPI might be used to predict a patient's sensitivity to MEM's therapeutic effects. OBJECTIVE: To begin to test this possibility, we studied MEM effects on PPI and related measures in AD patients. METHODS: 18 carefully screened individuals with AD (mean age = 72.8 y; M:F=9 : 9) completed double-blind order-balanced testing with MEM (placebo versus 20 mg), assessing acoustic startle magnitude, habituation, PPI, and latency. RESULTS: Fifteen out of 18 participants exhibited reliable startle responses. MEM did not significantly impact startle magnitude or habituation. Compared to placebo responses, PPI was significantly increased after MEM (p < 0.04; d = 0.40); this comparison reached a large effect size for the 60 ms interval (d = 0.62), where maximal MEM effects on PPI were previously detected. Prepulses reduced peak startle latency ("latency facilitation") and this effect was amplified after MEM (p = 0.03; d = 0.41; for 60 ms intervals, d = 0.69). No effects of MEM were detected on cognition, nor were MEM effects on startle associated with cognitive or clinical measures. CONCLUSION: MEM enhances prepulse effects on startle magnitude and latency in AD; these changes in PPI and latency facilitation with MEM suggest that these measures can be used to detect an AD patient's neural sensitivity to acute MEM challenge. Studies in progress will determine whether such a "biomarker" measured at the outset on treatment can predict sensitivity to MEM's therapeutic effects.

Cholinergic Functioning, Cognition, and Anticholinergic Medication Burden in Schizophrenia.

Acetylcholine (ACh) signaling is critical for central nervous function and is known to be abnormal in schizophrenia (SZ), a chronic neuropsychiatric disorder in which cognitive deficits persist, despite treatment. This review provides a summary of the clinical evidence linking ACh abnormalities to SZ-associated cognitive deficits, an overview of ACh-based pro-cognitive strategies attempted in SZ, and a survey of recent studies that describe the impact of anticholinergic medication burden on cognitive outcomes in SZ. Methodological challenges that currently limit more substantial investigation of ACh in SZ patients and future directions are also discussed.

Omicron BA.2 lineage predominance in severe acute respiratory syndrome coronavirus 2 positive cases during the third wave in North India.

Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India. Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7. Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men. Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant.

Genomic profile of SARS-CoV-2 Omicron variant and its correlation with disease severity in Rajasthan.

Background: Omicron, a new variant of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), was first detected in November 2021. This was believed to be highly transmissible and was reported to evade immunity. As a result, an urgent need was felt to screen all positive samples so as to rapidly identify Omicron cases and isolate them to prevent the spread of infection. Genomic surveillance of SARS-CoV-2 was planned to correlate disease severity with the genomic profile. Methods: All the SARS-CoV-2 positive cases detected in the state of Rajasthan were sent to our Lab. Samples received from 24 November 2021 to 4 January 2022 were selected for Next-Generation Sequencing (NGS). Processing was done as per protocol on the Ion Torrent S5 System for 1,210 samples and bioinformatics analysis was done. Results: Among the 1,210 samples tested, 762 (62.9%) were Delta/Delta-like and other lineages, 291 (24%) were Omicron, and 157 (12.9%) were invalid or repeat samples. Within a month, the proportion of Delta and other variants was reversed, 6% Omicron became 81%, and Delta and other variants became 19%, initially all Omicron cases were seen in international travelers and their contacts but soon community transmission was seen. The majority of patients with Omicron were asymptomatic (56.7%) or had mild disease (33%), 9.2% had moderate symptoms, and two (0.7%) had severe disease requiring hospitalization, of which one (0.3%) died and the rest were (99.7%) recovered. History of vaccination was seen in 81.1%, of the previous infection in 43.2% of cases. Among the Omicron cases, BA.1 (62.8%) was the predominant lineage followed by BA.2 (23.7%) and B.1.529 (13.4%), rising trends were seen initially for BA.1 and later for BA.2 also. Although 8.9% of patients with Delta lineage during that period were hospitalized, 7.2% required oxygen, and 0.9% died. To conclude, the community spread of Omicron occurred in a short time and became the predominant circulating variant; BA.1 was the predominant lineage detected. Most of the cases with Omicron were asymptomatic or had mild disease, and the mortality rate was very low as compared to Delta and other lineages.

Delta variant SARS-CoV-2 infections in pediatric cases during the second wave in India.

BACKGROUND: During October 2020, Delta variant was detected for the first time in India and rampantly spread across the globe. It also led to second wave of pandemic in India which affected millions of people. However, there is limited information pertaining to the SARS-CoV-2 strain infecting the children in India. METHODS: Here, we assessed the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n = 583) aged 0-18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021. RESULTS: Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. CONCLUSION: Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS-CoV-2 infection even amongst children.

Zika a Vector Borne Disease Detected in Newer States of India Amidst the COVID-19 Pandemic.

Background: During the second wave of the COVID-19 pandemic, outbreaks of Zika were reported from Kerala, Uttar Pradesh, and Maharashtra, India in 2021. The Dengue and Chikungunya negative samples were retrospectively screened to determine the presence of the Zika virus from different geographical regions of India. Methods: During May to October 2021, the clinical samples of 1475 patients, across 13 states and a union territory of India were screened and re-tested for Dengue, Chikungunya and Zika by CDC Trioplex Real time RT-PCR. The Zika rRTPCR positive samples were further screened with anti-Zika IgM and Plaque Reduction Neutralization Test. Next generation sequencing was used for further molecular characterization. Results: The positivity was observed for Zika (67), Dengue (121), and Chikungunya (10) amongst screened cases. The co-infections of Dengue/Chikungunya, Dengue/Zika, and Dengue/Chikungunya/Zika were also observed. All Zika cases were symptomatic with fever (84%) and rash (78%) as major presenting symptoms. Of them, four patients had respiratory distress, one presented with seizures, and one with suspected microcephaly at birth. The Asian Lineage of Zika and all four serotypes of Dengue were found in circulation. Conclusion: Our study indicates the spread of the Zika virus to several states of India and an urgent need to strengthen its surveillance.