The genomic basis of parasitism in the Strongyloides clade of nematodes.

Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families--families encoding astacin-like and SCP/TAPS proteins--is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Pesticide regulation, utilization, and retailers' selling practices in Trinidad and Tobago, West Indies: current situation and needed changes Regulación, utilización y prácticas de venta minorista de los pesticidas en Trinidad y Tobago, Indias Occidentales: situación actual y cambios necesarios

OBJECTIVE: To explore pesticide regulation in Trinidad and Tobago, and to ascertain pesticide utilization and retailers' selling practices on Trinidad, which is the larger of twin islands that constitute the republic of Trinidad and Tobago. METHODS: Between February and June 2005, agrochemical retailers in Trinidad were surveyed about the most frequently sold pesticides and their knowledge and practices of pesticide sale. The Poisons and Toxic Chemicals Control Board of the Ministry of Health informed on legislature. RESULTS: Of 107 actively trading licensed pesticide outlets, 97 participated (91% response rate) in the survey. Currently only 2.9% (21) of 720 registered products from four chemical classes are frequently utilized. Paraquat, methomyl, and alpha-cypermethrin (respective trade names are Gramoxone, Lannate, and Fastac) from World Health Organization (WHO) Hazard Classes I and II, and glyphosate isopropylamine (Swiper, Class U) are the most frequently purchased pesticides. Pet shops constitute 39.2% (38) of retail shops selling pesticides. No regulations guide pesticide sale to agriculturists, and children may purchase them. Inadequate human and technical resources render legislative controls ineffective and disciplinary action against offenders is weak. Extensive governmental resources are employed in legislative procedures and product approval for the very low, 2.9% utilization rate, negatively impacting on monitoring pesticide sales. The Poisons Information Centre (PIC) does not liaise with the Poisons and Toxic Chemicals Control Board or provide educational interventions for the community. As a result of this survey, it was possible to develop the first database to include the chemical, brand, and colloquial names of pesticides used in Trinidad and Tobago; WHO classification of approved pesticides; manufacturers; packaging; and antidotes and their availability for use by the Board and health professionals in Trinidad. CONCLUSIONS: Urgent critical evaluation of legislation regarding pesticide imports and use, and partnership with the Rotterdam Convention are recommended for Trinidad and Tobago. A strengthened Poisons Information Centre can provide educational initiatives and information on early management of pesticide exposure.<br>OBJETIVO: Analizar la regulación de los pesticidas en Trinidad y Tobago y verificar la utilización y las prácticas de venta minorista de pesticidas en Trinidad, la mayor de las dos islas que componen la República de Trinidad y Tobago. MÉTODOS: Entre febrero y junio de 2005 se realizó una encuesta a los vendedores minoristas de sustancias químicas de Trinidad sobre los pesticidas más frecuentemente vendidos, así como sobre sus conocimientos y las prácticas de venta de pesticidas. La Junta de Control de Venenos y Sustancias Tóxicas (JCVST) del Ministerio de Salud informó sobre la legislación vigente. RESULTADOS: De 107 tiendas autorizadas que comerciaban activamente con pesticidas, 97 participaron en este estudio (tasa de respuesta de 91%). Solo 21 (2,9%) de los 720 productos registrados de cuatro clases de sustancias se utilizan con frecuencia. Los productos paraquat, metomil y alfacipermetrina (cuyos nombres comerciales respectivos son Gramoxone, Lannate y Fastac) pertenecientes a las clases de riego I y II de la Organización Mundial de la Salud (OMS) y la isopropilamina de glifosato (Swiper, Clase U) son los pesticidas más frecuentemente adquiridos. Las tiendas de mascotas constituyen 39,2% (38 unidades) de las tiendas minoristas que participaron en el estudio. No hay regulaciones que normen la venta de pesticidas a los agricultores y los niños pueden comprarlos. Los recursos humanos y técnicos inadecuados hacen inefectivos los controles legislativos y las medidas disciplinarias contra los infractores son débiles. Se emplean considerables recursos gubernamentales en procedimientos legislativos y en la aprobación de productos de muy baja (2,9%) tasa de utilización, lo que afecta negativamente en el monitoreo de las ventas de pesticidas. El Centro de Información sobre Venenos no coordina sus acciones con la JCVST ni ofrece intervenciones educativas para la comunidad. Como resultado de este estudio, se pudo elaborar la primera base de datos con los nombres químicos, de marcas y vernáculos de los pesticidas utilizados en Trinidad y Tobago; la clasificación de la OMS de los pesticidas aprobados; los productores; los empacadores; y los antídotos y su disponibilidad, tanto para el uso de la Junta como de los profesionales sanitarios de Trinidad. CONCLUSIONES: Se recomienda realizar una urgente evaluación crítica de la legislación relacionada con la importación y el uso de los pesticidas en Trinidad y Tobago, así como la asociación con la Convención de Rotterdam. Un fortalecido Centro de Información sobre Venenos podría promover iniciativas educativas y ofrecer información sobre el tratamiento temprano de las personas expuestas a pesticidas

The impact of premorbid and current intellect in schizophrenia:Cognitive, symptom, and functional outcomes

BACKGROUND: Cognitive heterogeneity among people with schizophrenia has been defined on the basis of premorbid and current intelligence quotient (IQ) estimates. In a relatively large, community cohort, we aimed to independently replicate and extend cognitive subtyping work by determining the extent of symptom severity and functional deficits in each group. METHODS: A total of 635 healthy controls and 534 patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited through the Australian Schizophrenia Research Bank. Patients were classified into cognitive subgroups on the basis of the Wechsler Test of Adult Reading (a premorbid IQ estimate) and current overall cognitive abilities into preserved, deteriorated, and compromised groups using both clinical and empirical (k-means clustering) methods. Additional cognitive, functional, and symptom outcomes were compared among the resulting groups. RESULTS: A total of 157 patients (29%) classified as 'preserved' performed within one s.d. of control means in all cognitive domains. Patients classified as 'deteriorated' (n = 239, 44%) performed more than one s.d. below control means in all cognitive domains except estimated premorbid IQ and current visuospatial abilities. A separate 138 patients (26%), classified as 'compromised,' performed more than one s.d. below control means in all cognitive domains and displayed greater impairment than other groups on symptom and functional measures. CONCLUSIONS: In the present study, we independently replicated our previous cognitive classifications of people with schizophrenia. In addition, we extended previous work by demonstrating worse functional outcomes and symptom severity in the compromised group