Cytokinin-like substances and accumulation of labelled metabolites at infection sites of Alternaria brassicicola

Green islands were observed on mustard leaves beneath the infection drops containing germinating conidia of Alternaria brassicicola, when the surrounding uninfected tissue had yellowed due to senescence. Green island formation has been correlated with the secretion of cytokinin-like substances by the pathogens. A. brassicicola secreted cytokinin-like substances in a liquid synthetic medium and their application to detached host leaves evoked the formation of green islands in the dark. ¹⁴C studies confirmed that green islands act as metabolic sinks in which photosynthates are retained or accumulated. Cytokinin-like substances appear to be actively involved in infection and pathogenesis of A. brassicicola.     

Type III DNA restriction and modification systems EcoP1 and EcoP15. Nucleotide sequence of the EcoP1 operon, the EcoP15 mod gene and some EcoP1 mod mutants

This paper presents the nucleotide sequence of the mod-res operon of phage P1, which encodes the two structural genes for the EcoP1 type III restriction and modification system. We have also sequenced the mod gene of the allelic EcoP15 system. The mod gene product is responsible for binding the system-specific DNA recognition sequences in both restriction and modification; it also catalyses the modification reaction. A comparison of the two mod gene product sequences shows that they have conserved amino and carboxyl ends but have completely different sequences in the middle of the molecules. Two alleles of the EcoP1 mod gene that are defective in modification but not in restriction were also sequenced. The mutations in both alleles lie within the non-conserved regions.     

A novel and cost effective methodology for qualitative screening of alkalo-thermophilic cellulase free xylano-pectinolytic microorganisms using agricultural wastes

Qualitative screening of alkalo-thermophilic cellulase free xylano-pectinolytic microorganisms was done on agricultural residues. Since xylan is an expensive substrate for the isolation of xylanase producing microorganisms, the possibility of using wheat bran for screening of these microorganisms was investigated. Screening was carried out on wheat bran for the selection of xylanolytic microorganisms, on waste paper for the evaluation of cellulase free xylanolytic microorganisms, and on citrus peel for screening of pectinolytic microorganisms. Qualitative analysis of xylanase, pectinase and cellulase activities depicted that the zones obtained on nutrient agar medium containing agricultural residues were apparent and comparable with the zones obtained on nutrient agar medium containing commercial substrates. A strategy of using cost effective wheat-bran, wastepaper and citrus-peel for the isolation of cellulase free xylano-pectinolytic microorganisms is a novel and promising method and will ultimately bring down the cost of screening of these enzyme producing microorganisms.     

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

BACKGROUND:Patients receiving in-centre hemodialysis are at high risk of exposure to SARS-CoV-2 and death if infected. One dose of the BNT162b2 SARS-CoV-2 vaccine is efficacious in the general population, but responses in patients receiving hemodialysis are uncertain.METHODS:We obtained serial plasma from patients receiving hemodialysis and health care worker controls before and after vaccination with 1 dose of the BNT162b2 mRNA vaccine, as well as convalescent plasma from patients receiving hemodialysis who survived COVID-19. We measured anti–receptor binding domain (RBD) immunoglobulin G (IgG) levels and stratified groups by evidence of previous SARS-CoV-2 infection.RESULTS:Our study included 154 patients receiving hemodialysis (135 without and 19 with previous SARS-CoV-2 infection), 40 controls (20 without and 20 with previous SARS-CoV-2 infection) and convalescent plasma from 16 patients. Among those without previous SARS-CoV-2 infection, anti-RBD IgG was undetectable at 4 weeks in 75 of 131 (57%, 95% confidence interval [CI] 47% to 65%) patients receiving hemodialysis, compared with 1 of 20 (5%, 95% CI 1% to 23%) controls (p < 0.001). No patient with nondetectable levels at 4 weeks developed anti-RBD IgG by 8 weeks. Results were similar in non-immunosuppressed and younger individuals. Three patients receiving hemodialysis developed severe COVID-19 after vaccination. Among those with previous SARS-CoV-2 infection, median anti-RBD IgG levels at 8 weeks in patients receiving hemodialysis were similar to controls at 3 weeks (p = 0.3) and to convalescent plasma (p = 0.8).INTERPRETATION:A single dose of BNT162b2 vaccine failed to elicit a humoral immune response in most patients receiving hemodialysis without previous SARS-CoV-2 infection, even after prolonged observation. In those with previous SARS-CoV-2 infection, the antibody response was delayed. We advise that patients receiving hemodialysis be prioritized for a second BNT162b2 dose at the recommended 3-week interval.

Patients with end-stage kidney disease receiving incentre hemodialysis have been uniquely vulnerable during the COVID-19 pandemic. For these patients, unlike for most other people, self-isolation to avoid exposure to SARS-CoV-2 is impossible. Most patients receiving hemodialysis must leave their homes 3 times weekly to receive their life-saving treatments, often in shared spaces for hours at a time. COVID-19 case fatality rates are 20%–30% for patients receiving hemodialysis —10 times higher than in the general population.^1,2 Advanced age, multiple comorbidities and blunted immune response likely all contribute to the high COVID-19 death rates in this population. Some hemodialysis centres have thus prioritized these patients for vaccination.To facilitate wider vaccine distribution during current shortages, ³ the National Advisory Committee on Immunization of Canada has recommended delaying the second dose of the BNT162b2 vaccine from 3 to 16 weeks.⁴ In a randomized controlled trial (RCT), the clinical efficacy of the BNT162b2 was reported to be greater than 80% at 3 weeks after the first dose.⁵ However, no patients receiving hemodialysis were enrolled in this trial.⁵ Patients with end-stage kidney disease receiving hemodialysis often have impairments in both humoral and cellular immune responses⁶ and are noted to have lower antibody responses to other vaccines.⁷ Whether patients receiving hemodialysis develop robust immune responses after vaccination against SARS-CoV-2 remains uncertain.⁸ Data are required to better inform Canadian public health policy on whether second doses of vaccine can be safely delayed in this population.Usually, once clinical trials are completed, antibody levels can be used as surrogate measures of vaccine efficacy, such as with hepatitis B⁹ and influenza.¹⁰ With respect to the novel coronavirus SARS-CoV-2, although there is increasing understanding of the antibodies that best correlate with viral neutralization and T-cell responses,^11,12 assays vary from laboratory to laboratory and as yet there are no internationally accepted standards defining what antibody levels constitute immunity.¹³ The only way to evaluate vaccine efficacy using antibody levels, therefore, is through direct experimental comparison with controls who are known to reliably develop immunity after vaccination (i.e., healthy individuals similar to those enrolled in the RCT showing vaccine efficacy⁵) or who have developed immunity after natural infection (i.e., survivors of COVID-19).We sought to determine whether short-term antibody responses after a single dose of the BNT162b2 mRNA vaccine are comparable between patients receiving hemodialysis and healthy individuals, and how this compares with antibody responses in patients receiving hemodialysis who survived natural infection with SARS-CoV-2.     

UK legislation on analgesic packs: before and after study of long term effect on poisonings

Objective To evaluate the long term effect of legislation limiting the size of packs of analgesics sold over the counter.Design Before and after study.Setting Suicides in England and Wales, data from six liver units in England and Scotland and five general hospitals in England, and UK data on sales of analgesics, between September 1993 and September 2002.Data sources Office for National Statistics; six liver units in England and Scotland; monitoring systems in general hospitals in Oxford, Manchester, and Derby; and Intercontinental Medical Statistics Health UK.Main outcome measures Deaths by suicidal overdose with paracetamol, salicylates, or ibuprofen; numbers of patients admitted to liver units, listed for liver transplant, and undergoing transplantations for paracetamol induced hepatotoxicity; non-fatal self poisonings with analgesics and numbers of tablets taken; and sales figures for analgesics.Results Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths.Conclusion Legislation restricting pack sizes of analgesics in the United Kingdom has been beneficial. A further reduction in pack sizes could prevent more deaths.     

Barriers to Implementing the DSM-5 Cultural Formulation Interview: A Qualitative Study

The Outline for Cultural Formulation (OCF) in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) marked an attempt to apply anthropological concepts within psychiatry. The OCF has been criticized for not providing guidelines to clinicians. The DSM-5 Cultural Issues Subgroup has since converted the OCF into the Cultural Formulation Interview (CFI) for use by any clinician with any patient in any clinical setting. This paper presents perceived barriers to CFI implementation in clinical practice reported by patients (n = 32) and clinicians (n = 7) at the New York site within the DSM-5 international field trial. We used an implementation fidelity paradigm to code debriefing interviews after each CFI session through deductive content analysis. The most frequent patient threats were lack of differentiation from other treatments, lack of buy-in, ambiguity of design, over-standardization of the CFI, and severity of illness. The most frequent clinician threats were lack of conceptual relevance between intervention and problem, drift from the format, repetition, severity of patient illness, and lack of clinician buy-in. The Subgroup has revised the CFI based on these barriers for final publication in DSM-5. Our findings expand knowledge on the cultural formulation by reporting the CFI’s reception among patients and clinicians.     

A dynamic model of motor basal ganglia functions

 Fast aiming movements were measured in a choice reaction paradigm in a healthy control group and in Parkinsonian patients. The patients were tested without (‘off ’) and with 3,4-dihydroxyphenylalanine (‘on’) (L-dopa) medication. The movement trajectories were used to estimate the parameters of a dynamic linear model. The model is based on the functional structure of the basal ganglia-thalamocortical circuit with direct and indirect pathways linking the putamen to the basal ganglia output nuclei (Albin et al. 1989). The output of the circuit is connected to a model for the motor neuron-musculo-skeletal system. The gain k _d for the direct pathway and the gain k _i for the indirect pathway were estimated. They were found to be significantly decreased for Parkinsonian patients in ‘off ’ compared with the control group. L-dopa therapy in Parkinsonian patients increased the gains of the direct and the indirect pathway almost to normal values which implies that the long-term dopamine level in the striatum was excitatory for the direct and for the indirect pathway. This result is restricted to movements of correct size. For movements of diminished size, which are typical for Parkinsonian patients, the model predicts that the dopamine level in the striatum is excitatory for the direct pathway but inhibitory for the indirect pathway. The simulated values for neuronal activities are in agreement with expected values according to the experimental data. The proposed model of the ‘motor’ basal ganglia thalamocortical circuit implies that information about biomechanical properties of the musculo-skeletal system is stored in the ‘motor’ basal ganglia-thalamocortical circuit, and that the basal ganglia are involved in computation of the desired movement amplitude. Received: 24 April 1996/Accepted in revised form: 25 February 1997     

Diurnal variation in stature - Is it more in children or adults?

Stature is the most often used anthropometric measure in the nutritional, growth and development, anthropological and forensic oriented studies. Its estimate is considered to be an important assessment in the identification of unknown human remains and its medico-legal significance is obvious in forensic examinations. Diurnal variation in stature is a biological norm in the human body and its effects can be reflected in the reliability of height data in these studies. We hypothesize that the extent of diurnal variation is more in children as compared to adults in a population.