Mental health in the COVID-19 pandemic: A longitudinal analysis of the CLoCk cohort study.

BACKGROUND: Little is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP's mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP's mental health trajectories. METHODS AND FINDINGS: A matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (B = 0.11 (per month), 95% CI = 0.09 to 0.12, p < 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (B = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; pinteraction = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias. CONCLUSIONS: Overall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.

Ante-mortem and Post-mortem Diagnosis Modalities and Phylogenetic Analysis of Rabies Virus in Domestic and Wild Animals of Gujarat, India.

In the present study, total of 32 ante-mortem (AM) samples (saliva = 18 and corneal smears = 14) from six animal species (cattle = 5; camel = 1; goat = 1; horse = 1; buffalo = 4; dog = 6) and 28 post-mortem (PM) samples of domestic (cattle = 6; camel = 1; goat = 1; buffalo = 5; dog = 7) and wild animals (lion = 4, mongoose = 2; bear = 1; leopard = 1) were examined for rabies diagnosis in Gujarat, India. Direct fluorescent antibody test (dFAT) and reverse transcriptase polymerase chain reaction (RT-PCR) were applied on AM samples, whereas along with dFAT and RT-PCR, histopathological examination, immunohistochemistry (IHC) and real time PCR (qPCR) were used for PM diagnosis. Nucleotide sequencing of full nucleoprotein (N) and glycoprotein (G) genes were carried out upon representative amplicons. In AM examination, 7/18 saliva and 5/14 corneal impressions samples were found positive in dFAT and 8/18 saliva samples were found positive in RT-PCR. In PM examination, 14/28 samples showed positive results in dFAT and IHC with unusual large fluorescent foci in two samples. In histopathology, 11/28 samples showed appreciable lesion and Negri bodies were visible in 6 samples, only. Out of 23 brain samples examined. 12 samples were found positive in N gene RT-PCR and qPCR, and 10 samples in G gene RT-PCR. Phylogenetic analysis of N gene revealed that test isolates (except sample ID: lion-1; lion, Gir) form a close group with sequence ID, KM099393.1 (Mongoose, Hyderabad) and KF660246.1 (Water Buffalo, Hyderabad) which was far from some south Indian and Sri Lankan isolates but similar to Indian isolates from rest of India and neighboring countries. In G gene analysis, the test isolates form a close group with sequence ID, KP019943.1. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01126-0.

Evaluation of the oncolytic potential of R2B Mukteshwar vaccine strain of Newcastle disease virus (NDV) in a colon cancer cell line (SW-620).

Virotherapy is emerging as an alternative treatment of cancer. Among the candidate oncolytic viruses (OVs), Newcastle disease virus (NDV) has emerged as a promising non-engineered OV. In the present communication, we explored the oncolytic potential of R2B Mukteshwar strain of NDV using SW-620 colon cancer cells. SW-620 cells were xenografted in nude mice and after evaluation of the safety profile, 1 x 107 plaque forming units (PFU) of NDV were inoculated as virotherapeutic agent via the intratumoral (I/T) and intravenous (I/V) route. Tumor growth inhibition was compared with their respective control groups by gross volume and histopathological evaluation. Antibody titer and virus survival were measured by hemagglutination inhibition (HI)/serum neutralization test (SNT) and real-time PCR, respectively. During the safety trial, the test strain did not produce any abnormal symptoms nor weight loss in BALB/c mice. Significant tumor lytic activity was evident when viruses were injected via the I/T route. There was a 43 and 57% tumor growth inhibition on absolute and relative tumor volume basis, respectively, compared with mock control. On the same basis, the I/V route treatment resulted in 40 and 16% of inhibition, respectively. Histopathological examination revealed that the virus caused apoptosis, followed by necrosis, but immune cell infiltration was not remarkable. The virus survived in 2/2 mice until day 10 and in 3/6 mice by day 19, with both routes of administration. Anti-NDV antibodies were generated at moderate level and the titer reached a maximum of 1:32 and 1:64 via the I/T and I/V routes, respectively. In conclusion, the test NDV strain was found to be safe and showed oncolytic activity against the SW-620 cell line in mice.

Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability.

BACKGROUND: Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks. METHOD: One hundred and twenty two drug-free children aged 7-15 with hyperkinetic disorder and IQ 30-69 were recruited to a double-blind, placebo-controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1 week each of low (0.5 mg/kg/day), medium (1.0 mg/kg/day) and high dose (1.5 mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI-I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat. TRIAL REGISTRATION: ISRCTN 68384912. RESULTS: Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure. CONCLUSIONS: Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group.

Natural course of health and well-being in non-hospitalised children and young people after testing for SARS-CoV-2: a prospective follow-up study over 12 months.

Background: Despite high numbers of children and young people (CYP) having acute COVID, there has been no prospective follow-up of CYP to establish the pattern of health and well-being over a year following infection. Methods: A non-hospitalised, national sample of 5086 (2909 SARS-COV-2 Positive; 2177 SARS-COV-2 Negative at baseline) CYP aged 11-17 completed questionnaires 6- and 12-months after PCR-tests between October 2020 and March 2021 confirming SARS-CoV-2 infection (excluding CYP with subsequent (re)infections). SARS-COV-2 Positive CYP was compared to age, sex and geographically-matched test-negative CYP. Findings: Ten of 21 symptoms had a prevalence less than 10% at baseline, 6- and 12-months post-test in both test-positives and test-negatives. Of the other 11 symptoms, in test-positives who had these at baseline, the prevalence of all symptoms declined greatly by 12-months. For CYP first describing one of these at 6-months, there was a decline in prevalence by 12-months. The overall prevalence of 9 of 11 symptoms declined by 12-months. As many CYP first described shortness of breath and tiredness at either 6- or 12-months, the overall prevalence of these two symptoms in test-positives appeared to increase by 6-months and increase further by 12-months. However, within-individual examination demonstrated that the prevalence of shortness of breath and tiredness actually declined in those first describing these two symptoms at either baseline or 6-months. This pattern was also evident for these two symptoms in test-negatives. Similar patterns were observed for validated measures of poor quality of life, emotional and behavioural difficulties, poor well-being and fatigue. Moreover, broadly similar patterns and results were noted for the sub-sample (N = 1808) that had data at baseline, 3-, 6- and 12-months post-test. Interpretation: In CYP, the prevalence of adverse symptoms reported at the time of a positive PCR-test declined over 12-months. Some test-positives and test-negatives reported adverse symptoms for the first time at six- and 12-months post-test, particularly tiredness, shortness of breath, poor quality of life, poor well-being and fatigue suggesting they are likely to be caused by multiple factors. Funding: NIHR/UKRI (ref: COVLT0022).

Antibiotic Susceptibility Pattern of Canine Coagulase Positive and Coagulase Negative Staphylococcus spp. in a Hot and Dry Region of India.

The emergence of antimicrobial resistance among Staphylococcus spp. isolated from clinical cases of canines should be continuously monitored hence the present study was formulated to ascertain the antibiotypes and methicillin resistance in coagulase positive and coagulase negative staphylococci of canine skin and associated mucous membrane affections from a hot and dry region of India. A total of 165 clinical samples were collected and Staphylococcus aureus was identified by conventional bacteriological methods and PCR. Antibiotic susceptibility test was done against commercially available antibiotic impregnated discs as per Clinical and Laboratory Standards Institute (CLSI) method. Methicillin resistance was determined by plate methods and then via PCR of mecA gene. These 165 samples yielded, 88 (53.33%) isolates of genus Staphylococcus and 46 S. aureus and 51/88 (57.95%) isolates were coagulase positive staphylococci. Total 55 (62.5%) isolates showed susceptibility to Ceftriaxone/Sulbactum, 37 (42.05%) to Ciprofloxacin, 26 (29.55%) to Oxacillin, 24 (27.27%) to Penicillin, and 10 (11.36%) to Gentamicin. Total 21 methicillin-resistant S. aureus (MRSA) and 12 methicillin-resistant coagulase negative staphylococci (MRCoNS) were found on phenotypic basis whereas the mecA gene was detected in 6/21 MRSA and 2/12 MRCoNS isolates. Staphylococcus spp. showed increased level of resistance against commonly used antibiotics. The higher prevalence of methicillin resistance found with phenotypic methods than to mecA PCR indicates toward additional mechanisms responsible for emergence of MRS, especially in CoNS.

Seroprevalence of Bovine ephemeral fever virus in Gujarat State of India.

Bovine ephemeral fever (BEF) virus (BEFV) is an arthropod borne virus that causes bovine ephemeral fever or three­day sickness in cattle and buffaloes. This is the first report on seroprevalence of BEF in cattle and buffaloes in Gujarat, India. Total of 92 animals, 78 cattle and 14 buffaloes from three regions (districts) of Gujarat state of India, were screened for the presence of anti­BEF antibodies. A total of 27 out of 92 animals were found positive and overall seroprevalence detected was 29.34% (95% CI 20.0­38.6%). A total of 19 out of 78 cattle and 8 out of 14 buffalo's samples were found positive BEFV antibodies. Species­wise seroprevalence in cattle and buffaloes was 24.35% (95% CI 14.8­33.8%) and 57.1% (95% CI 31.2­83.0%), respectively. There was a statistically significant (p < 0.05) species effect based on the seroprevalence. In cattle, location­wise seroprevalence was observed to be 26.82% (95% CI 13.2­40.3%) and 21.62% (95% CI 8.3­34.8%) in Navsari and Banaskantha districts, respectively. The effect of location is not statistically significant (p < 0.05). Cytopathic effect of Vero cells was characterized by rounding, granulation of the cytoplasm within 48­72 hrs of post infection. This was the first report demonstrating the presence of BEFV in Gujarat state.

A retrospective audit of referrals of 16-17 year olds with reference to substance abuse.

BACKGROUND: Emerge is an innovative Child and Adolescent Mental Health Service that provides support for 16-17 year olds. The team provide a community based multi-disciplinary, open access model, texting young people and travelling to locations convenient to them. There is an enhanced duty system providing a rapid flexible response within working hours. AIMS: To examine the referral data as part of the ongoing annual audit cycle and to establish prevalence of alcohol, cigarettes and substance use among young people referred to the service. METHOD: Data from the case notes was analysed using Statistical Package for Social Science. Demographic details, referrer profession, reason for referral, other services involved and substance use were examined. RESULTS: There were 437 patients referred to Emerge between 1/4/2010 and 31/3/2011, and 387 patients were accepted while 50 were signposted on. Cases were not accepted if they fell outside the age and geographical area, or were not in need of a mental health service. Overall, 24% of young people were reported to consume alcohol, 19% used cannabis and 9% reported using cigarettes. In all categories there were areas where documentation was not complete, and we suggest that these figures are an underestimate. CONCLUSION: This data has been fed back to the team, a full morning of teaching regarding drugs and alcohol has been delivered. Emerge often works with young people who are marginalised and may be harder to reach, consequently early sessions require neutral and supportive questions, thus if young people do not return after the first appointment, histories may be incomplete. The team will be reflecting on the lessons learned and considering ways to optimise their work.

VP2 gene sequencing based Geno-grouping of infectious bursal disease viruses isolated from Gujarat and Maharashtra state (India).

Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), has recently been reported in chickens vaccinated with classical or intermediate types of vaccines from various regions of India due to the emergence of novel very virulent strains of infectious bursal disease virus (vvIBDV). In the present study, suspected samples of IBD were collected from poultry flocks of districts of Gujarat and Nagpur (Maharashtra), identified using PCR and grouped as per traditional and new genogrouping pattern. Out of 54 bursa samples, 21 (38.89%) yielded the expected amplicon of 743 bp (701-1444 bp), and were found positive for IBDV. Among these 21 positive flocks, 11 (52.38%) were already vaccinated. Upon nucleotide sequencing of amplicon and its deduction into amino acids, it was found that all the sequences of present study were related to vvIBDV according to old classification pattern. Considering the new genogrouping pattern, nine and four sequences of this study fell within G3a and G3b lineage, respectively. These sequences revealed important differences at key amino acid positions with respect to classical (G1 genogroup), variant (G2 genogroup) type of IBDV and classical vaccines. Further divergence from prototypic vvIBDV strains was revealed as, D-N at 212 position (N = 9) and 279 position (N = 1). In sequences from Maharashtra (group 2 of G3a lineage), occurrence of V instead of P/T/A at 222 position was recorded as a novel and conspicuous substitution in the immunodominant peak A of VP2 hypervariable region. Additional changes at 270 (3 sequences) and 272 positions (4 sequences) could be attributed to reverse mutation or recombination with vaccine strains. In conclusion, both point mutation and genetic reassortment with intermediate type of vaccines were found to be responsible for generation of novel vvIBDV strains in this area which belonged to G3a and G3b genogroups.

A Novel Seed-Dressing Formulation Based on an Improved Mutant Strain of Trichoderma virens, and Its Field Evaluation.

Using gamma-ray-induced mutagenesis, we have developed a mutant (named G2) of Trichoderma virens that produced two- to three-fold excesses of secondary metabolites, including viridin, viridiol, and some yet-to-be identified compounds. Consequently, this mutant had improved antibiosis against the oomycete test pathogen Pythium aphanidermatum. A transcriptome analysis of the mutant vis-à-vis the wild-type strain showed upregulation of several secondary-metabolism-related genes. In addition, many genes predicted to be involved in mycoparasitism and plant interactions were also upregulated. We used tamarind seeds as a mass multiplication medium in solid-state fermentation and, using talcum powder as a carrier, developed a novel seed dressing formulation. A comparative evaluation of the wild type and the mutant in greenhouse under high disease pressure (using the test pathogen Sclerotium rolfsii) revealed superiority of the mutant over wild type in protecting chickpea (Cicer arietinum) seeds and seedlings from infection. We then undertook extensive field evaluation (replicated micro-plot trials, on-farm demonstration trials, and large-scale trials in farmers' fields) of our mutant-based formulation (named TrichoBARC) for management of collar rot (S. rolfsii) in chickpea and lentil (Lens culinaris) over multiple locations in India. In certain experiments, other available formulations were included for comparison. This formulation consistently, over multiple locations and years, improved seed germination, reduced seedling mortality, and improved plant growth and yield. We also noticed growth promotion, improved pod bearing, and early flowering (7-10 days) in TrichoBARC-treated chickpea and lentil plants under field conditions. In toxicological studies in animal models, this formulation exhibited no toxicity to mammals, birds, or fish.

Disinhibited Attachment Disorder in UK Adopted Children During Middle Childhood: Prevalence, Validity and Possible Developmental Origin.

We investigate the prevalence, specificity and possible aetiology of Disinhibited Attachment Disorder (DAD) in adopted children without a history of institutional care. Sixty children adopted from UK out-of-home care (AD; mean age 102 months, 45 % male); 26 clinic-referred children with externalizing disorder (ED; mean age 104 months, 77 % male) but no history of maltreatment or disrupted care; and 55 matched low-risk comparison controls (LR; mean age 108 months, 49 % male) were assessed for DAD using a triangulation of parent, teacher, and research observations. Maltreatment history and child psychiatric symptoms were obtained from parent report and child language development was assessed. DAD was identified in 49 % of AD, 4 % of ED and 6 % of LR children. Seventy-two percent of AD children had suffered maltreatment. DAD was not associated with degree of risk exposure, demographics, or language. A significant association with ADHD did not explain variance in DAD prevalence across groups. DAD was significantly more common in children first admitted to out-of-home care between 7 and 24 months, independent of maltreatment severity, age at adoption and number of care placements. Implications for developmental theory, adoption policy and clinical application are discussed.

Autism Spectrum Disorder in Children Adopted After Early Care Breakdown.

Syndromic autism has been described in children adopted after orphanage rearing. We investigated whether the same existed in children adopted after family breakdown. Families of 54/60 adopted children aged 6-11 years (mean 102 months; SD 20; 45% male) returned screening questionnaires for autism spectrum disorder (ASD); 21/54 (39%) screened positive. Detailed in-person phenotyping of screen positive cases showed ASD in 6/54 (11%), Broad ASD (sub threshold traits) in 10/54 (18.5%); 5/54 (9%) screened false positive. The ASD group showed impairments across both social communication and restrictive repetitive behaviour domains, Broad ASD was more mixed. These rates, much higher than population prevalence, are comparable with institutionalised samples. There are implications for developmental science, and assessment, treatment and policy for adopted children.