What our children lost and gained at the time of school closure during the Covid-19 pandemic: a study on psychological distress, behavioural concerns and protective factors of resilience among preschool children in Kerala, India.

BACKGROUND: The pandemic has put at risk the social and emotional development of children on account of the paucity of arenas for social interaction. This study from Kerala, India was conducted to assess the resilience factors, behavioural concerns, psychological distress symptoms among the children aged 3 to 5 years. We also tried to look into the lost opportunities that could have aided the social and emotional development of children like peer interaction, child care hours. METHODS: The cross-sectional study was conducted among the children aged 3 to 5 years. A total of 535 children attending the immunisation clinics were enrolled by consecutive sampling. Devereux Early Childhood Assessment P2 (DECA P2) questionnaire was used to assess the levels of resilient factors and behavioural concerns in the study population. RESULTS: We observed a high proportion of children in the area of need category of protective factors under DECA P2. The proportion of children falling under area of concern was 64.5%, 49%, 68.4% for attachment/relationship, self-regulation, and initiative respectively. 24.9% study subjects have a behavioural concern score that puts them in the area of need category. The logistic regression model we created identified 'Male Gender,' 'Mothers could spend only less time for child care' and 'electronic devices used as pacifier' as significant predictors for belonging to Area of need Behavioural Concerns T score category. CONCLUSION: A large proportion of children aged between 3 to 5 years with reported behavioural concerns and lack of protective factors for socioemotional development. This can be attributed partly to the ongoing pandemic and its associated restrictions. The increased child care hours invested by parents or grandparents could have sized down the full impact that the pandemic would have had on the socio emotional development of the child. Increased time spent using electronic devices coupled with dwindled opportunities for interaction with peers have been notable challenges.

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis.

BACKGROUND: Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. METHODS AND RESULTS: A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband's mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. CONCLUSIONS: We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases.

The Covid-19 pandemic in low- and middle-income countries, who carries the burden? Review of mass media and publications from six countries.

During the Covid-19 pandemic, rich countries employed lockdown and physical distancing policies for transmission control. However, the question still remains whether these measures are also suitable in countries with a fragile economy, which rests mainly on the informal sector. The impacts of lockdown measures in disadvantaged population strata in six low- and middle-income countries (LMICs) were reviewed using i) 93 media reports and ii) 17 published scientific papers. This review showed that those who suffered the most from the lockdown were migrants, workers in the large informal sector, small businesses, slum dwellers, women and elderly, revealing the social, cultural and economic inequalities of societies. Financial and food support for the poor was inadequate and sometimes mismanaged. In the better organized societies, the resilience was stronger (South Korea, Kerala/India) but here also the poor had to suffer the most. It is strongly recommended that outbreak response strategies should particularly focus on the poor and vulnerable population.

FOLFOX alternated with FOLFIRI as first-line chemotherapy for metastatic colorectal cancer.

BACKGROUND: 5-fluorouracil (5-FU), irinotecan, and oxaliplatin are the most active drugs in advanced colorectal cancer (CRC), and survival is improved with patient exposure to all of them. The efficacy and safety of an alternating schedule of continuous-infusion 5-FU with leucovorin (LV) plus oxaliplatin (ie, FOLFOX regimen) or irinotecan (ie, FOLFIRI regimen) was assessed in the first-line setting. PATIENTS AND METHODS: Seventy-nine patients with previously untreated, unresectable CRC were included. Treatment consisted of 5-FU/LV (de Gramont schedule) plus oxaliplatin (85 mg/m2) alternated biweekly with the same 5-FU/LV regimen plus irinotecan (180 mg/m2). Treatment was maintained until tumor progression or unacceptable toxicity was noted. RESULTS: Median age was 62 years. Performance status was 0/1 in 91% of patients, 63% had 1 organ involved, and 80% had liver metastases. A median of 6 courses per patient (range, 1-9) and a total of 952 infusions were given. The most frequent grade 3/4 toxic events were neutropenia (32%), diarrhea (26%), and asthenia (7%). Grade 1/2 neurotoxicity was seen in 59% of cases, but no grade 3/4 neurotoxicity was observed. There were no toxic deaths. An objective response rate of 54% (4 complete responses plus 39 partial responses) was attained. Median time to progression and overall survival were 13 months and 18 months, respectively. CONCLUSION: This alternating schedule is active, with efficacy results similar to those seen with sequential protocols, the advantages of less toxicity, and 100% patient exposure to irinotecan and oxaliplatin.