Transmission of SARS-CoV-2 in standardised first few X cases and household transmission investigations: A systematic review and meta-analysis.

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for "Unity-aligned" First Few X cases (FFX) and HHTIs published 1 December 2019 to 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review; 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%-71%; I 2 = 99.7%); I 2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

Long-term outcomes of Guillain-Barré syndrome possibly associated with Zika virus infection.

BACKGROUND: This prospective cohort investigation analyzed the long-term functional and neurologic outcomes of patients with Zika virus-associated Guillain-Barré syndrome (GBS) in Barranquilla, Colombia. METHODS: Thirty-four Zika virus-associated GBS cases were assessed a median of 17 months following acute GBS illness. We assessed demographics, results of Overall Disability Sum Scores (ODSS), Hughes Disability Score (HDS), Zung Depression Scale (ZDS), and Health Related Quality of Life (HRQL) questionnaires; and compared outcomes indices with a normative sample of neighborhood-selected control subjects in Barranquilla without GBS. RESULTS: Median age at time of acute neurologic onset was 49 years (range, 10-80); 17 (50%) were male. No deaths occurred. At long-term follow-up, 25 (73%) patients had a HDS 0-1, indicating complete / near complete recovery. Among the group, HDS (mean 1.4, range 0-4), ODSS (mean 1.9, range 0-9) and ZDS score (mean 34.4, range 20-56) indicated mild / moderate ongoing disability. Adjusting for age and sex, Zika virus-associated GBS cases were similar to a population comparison group (n = 368) in Barranquilla without GBS in terms of prevalence of physical or mental health complaints, though GBS patients were more likely to have an ODSS of ≥ 1 (OR 8.8, 95% CI 3.2-24.5) and to suffer from moderate / moderate-severe depression (OR 3.89, 95% CI 1.23-11.17) than the comparison group. CONCLUSIONS: Long-term outcomes of Zika virus-associated GBS are consistent with those associated with other antecedent antigenic stimuli in terms of mortality and ongoing long-term morbidity, as published in the literature. Persons with Zika virus-associated GBS more frequently reported disability and depression after approximately one year compared with those without GBS.

Estimating the numbers of pregnant women infected with Zika virus and infants with congenital microcephaly in Colombia, 2015-2017.

BACKGROUND: Colombia experienced a Zika virus (ZIKV) outbreak in 2015-2016. To assist with planning for medical and supportive services for infants affected by prenatal ZIKV infection, we used a model to estimate the number of pregnant women infected with ZIKV and the number of infants with congenital microcephaly from August 2015 to August 2017. METHODS: We used nationally reported cases of symptomatic ZIKV disease among pregnant women and information from the literature on the percent of asymptomatic infections to estimate the number of pregnant women with ZIKV infection occurring August 2015-December 2016. We then estimated the number of infants with congenital microcephaly expected to occur August 2015-August 2017. To compare to the observed counts of infants with congenital microcephaly due to all causes reported through the national birth defects surveillance system, the model was time limited to produce estimates for February-November 2016. FINDINGS: We estimated 1140-2160 (interquartile range [IQR]) infants with congenital microcephaly in Colombia, during August 2015-August 2017, whereas 340-540 infants with congenital microcephaly would be expected in the absence of ZIKV. Based on the time limited version of the model, for February-November 2016, we estimated 650-1410 infants with congenital microcephaly in Colombia. The 95% uncertainty interval for the latter estimate encompasses the 476 infants with congenital microcephaly reported during that approximate time frame based on national birth defects surveillance. INTERPRETATION: Based on modeled estimates, ZIKV infection during pregnancy in Colombia could lead to 3-4 times as many infants with congenital microcephaly in 2015-2017 as would have been expected in the absence of the ZIKV outbreak. FUNDING: This publication was made possible through support provided by the Bureau for Global Health, U.S. Agency for International Development under the terms of an Interagency Agreement with Centers for Disease Control and Prevention.

The Arabidopsis sickle Mutant Exhibits Altered Circadian Clock Responses to Cool Temperatures and Temperature-Dependent Alternative Splicing.

The circadian clock allows plants to anticipate and respond to daily changes in ambient temperature. Mechanisms establishing the timing of circadian rhythms in Arabidopsis thaliana through temperature entrainment remain unclear. Also incompletely understood is the temperature compensation mechanism that maintains consistent period length within a range of ambient temperatures. A genetic screen for Arabidopsis mutants affecting temperature regulation of the PSEUDO-RESPONSE REGULATOR7 promoter yielded a novel allele of the SICKLE (SIC) gene. This mutant, sic-3, and the existing sic-1 mutant both exhibit low-amplitude or arrhythmic expression of core circadian clock genes under cool ambient temperature cycles, but not under light-dark entrainment. sic mutants also lengthen free running period in a manner consistent with impaired temperature compensation. sic mutant alleles accumulate LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) splice variants, among other alternatively spliced transcripts, which is exacerbated by cool temperatures. The cca1-1 lhy-20 double mutant is epistatic to sic-3, indicating the LHY and CCA1 splice variants are needed for sic-3 circadian clock phenotypes. It is not expected that SIC is directly involved in the circadian clock mechanism; instead, SIC likely contributes to pre-mRNA metabolism, and the splice variants that accumulate in sic mutants likely affect the circadian clock response to cool ambient temperature.

The time of day effects of warm temperature on flowering time involve PIF4 and PIF5.

Warm temperature promotes flowering in Arabidopsis thaliana and this response involves multiple signalling pathways. To understand the temporal dynamics of temperature perception, tests were carried out to determine if there was a daily window of enhanced sensitivity to warm temperature (28 °C). Warm temperature applied during daytime, night-time, or continuously elicited earlier flowering, but the effects of each treatment were unequal. Plants exposed to warm night (WN) conditions flowered nearly as early as those in constant warm (CW) conditions, while treatment with warm days (WD) caused later flowering than either WN or CW. Flowering in each condition relied to varying degrees on the activity of CO , FT , PIF4 , and PIF5 , as well as the action of unknown genes. The combination of signalling pathways involved in flowering depended on the time of the temperature cue. WN treatments caused a significant advance in the rhythmic expression waveform of CO, which correlated with pronounced up-regulation of FT expression, while WD caused limited changes in CO expression and no stimulation of FT expression. WN- and WD-induced flowering was partially CO independent and, unexpectedly, dependent on PIF4 and PIF5 . pif4-2, pif5-3, and pif4-2 pif5-3 mutants had delayed flowering under all three warm conditions. The double mutant was also late flowering in control conditions. In addition, WN conditions alone imposed selective changes to PIF4 and PIF5 expression. Thus, the PIF4 and PIF5 transcription factors promote flowering by at least two means: inducing FT expression in WN and acting outside of FT by an unknown mechanism in WD.

Tratamiento regional del sarcoma y melanoma localmente avanzado de la extremidad mediante la perfusión aislada con tumor necrosis factor α y melfalan asociada a hipertermia / Tumor necrosis factor α and melfalan-based hyperthermic isolated limb perfusion in locally advanced extremity soft tissue sarcomas and melanomas

Introducción El objetivo del estudio fue evaluar el número de amputaciones evitables en pacientes con sarcomas y melanomas localmente avanzados de las extremidades mediante la perfusión aislada de la extremidad (PAE) con melfalán y tumor necrosis factor α (PAE-MT) en condiciones de hipertermia. Material y métodos Se revisó a todos los pacientes con sarcoma y melanoma localmente avanzados de la extremidad que fueron tratados en nuestro centro con PAE-MT durante el periodo comprendido entre noviembre de 2001 y febrero de 2010. Se evaluó el porcentaje de respuestas, las amputaciones evitadas, la toxicidad del tratamiento, las complicaciones, el intervalo libre de enfermedad y la supervivencia global. Resultados Treinta pacientes (19 mujeres y 11 varones), con una mediana de edad de 60 años (14-82), fueron tratados con esta técnica. Tras un seguimiento medio de 23 meses, el porcentaje de respuestas globales fue del 93,4% (completas, 46,7%; parciales 46,7%). La mediana de duración de la respuesta fue de 5 meses (0-62) y la mediana de supervivencia global de 13,5 meses (rango 1-62). Se evitó la amputación en el 86,7% de los casos. En la actualidad, once pacientes (5 sin enfermedad, 2 con enfermedad residual en tratamiento, 2 con progresión local y 2 con progresión sistémica) están vivos. Conclusión Mediante la PAE hemos logrado evitar la amputación de 26 miembros afectos de melanoma y sarcoma localmente avanzados. La PAE es factible y segura en un entorno multidisciplinar (AU)

Introduction The aim of the study is to evaluate the limb salvage rate achieved by treating locally advanced extremity sarcoma and melanoma by hyperthermic isolated limb perfusion with melphalan and (..) (AU)

[Tumor necrosis factor α and melfalan-based hyperthermic isolated limb perfusion in locally advanced extremity soft tissue sarcomas and melanomas]. / Tratamiento regional del sarcoma y melanoma localmente avanzado de la extremidad mediante la perfusión aislada con tumor necrosis factor α y melfalan asociada a hipertermia.

INTRODUCTION: The aim of the study is to evaluate the limb salvage rate achieved by treating locally advanced extremity sarcoma and melanoma by hyperthermic isolated limb perfusion with melphalan and TNF-α (ILP-MT). MATERIAL AND METHODS: A retrospective study was conducted on patients suffering from locally advanced soft tissue sarcoma and melanoma of the limb and treated by means of ILP-MT between November 2001 and February 2010. The response rate, toxicity, complications, disease free intervals, overall survival and limb salvage rate were evaluated. RESULTS: A total of 30 patients (19 females and 11 males) with a median age of 60 years (14-82) were treated by this technique. The overall response rate was 93.4% (complete, 46.7%; partial 46.7%); the mean follow-up was 23 months. The median duration of response was 5 months (0-62), The median overall survival was 13.5 months (range 1 - 62). Limb salvage rate was 86.7%. Eleven patients are currently alive (5 without disease, 2 with residual disease on treatment, 2 with local progression and 2 with systemic progression). CONCLUSION: With the use of ILP-MT we have avoided the amputation of 26 limbs affected by locally advanced sarcoma or melanoma. ILP-MT is feasible and safe in a multidisciplinary environment.

Abdomen agudo en una paciente con cáncer de mama tratada con quimioterapia / Acute abdomen in a chemotherapy treated breast cancer patient

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