A special issue of Biophysical Reviews dedicated to the 20th IUPAB (virtual) Congress “in” Foz do Iguaçu

The 20th IUPAB Congress took place online, together with the annual meetings of the Brazilian Biophysical Society and the Brazilian Society for Biochemistry and Molecular Biology, from the 4th to the 8th of October, 2021. The ten keynote lectures, 24 symposia, two poster sessions, and a series of technical seminars covered the full diversity of current biophysical research and its interfaces with other fields. The event had over 1000 attendees, with an excellent gender balance. Although the Americas dominated, there were also significant numbers of participants from Europe, Asia, and Africa.

The International Union of Pure and Applied Biophysics (IUPAB) came into existence in Stockholm in 1961 and has been a member of the International Science Council since 1966 (Solomon 1968). Its overall objectives aim to foster international collaboration in all aspects of biophysics and related areas and to catalyze the advancement of basic biophysical research as well as its many applications. Although IUPAB is active on many fronts, undeniably one of its showcase events is the IUPAB Congress, traditionally organized every three years in different locations worldwide. In 2021, the event was organized and run from Brazil, albeit for the very first time in a virtual format due to travel restrictions imposed by the COVID-19 pandemic. On this occasion, the Congress was organized in conjunction with the annual meetings of both the Brazilian Biophysical Society (SBBf, in its 45th edition) and the Brazilian Society for Biochemistry and Molecular Biology (SBBq, in its 50th edition). Even with the united forces of these well-established local societies, it turned out to be a bumpy ride to bring the event to fruition.Plans for the 20th Congress began in 2016, almost immediately after the decision to hold the event in Brazil, a cause championed by the then-president of the Brazilian Biophysical Society, Marcelo Morales. The original plans had the meeting to be held in the Cidade Maravilhosa (The Wonderful City) of Rio de Janeiro in October 2020. However, it soon became apparent that the political and economic difficulties that the State of Rio was facing at the time meant that it would be wise to search for an alternative venue. The previous experience of SBBq in organizing similar events in the city of Foz do Iguaçu, on the borders with Argentina and Paraguay, made this an obvious choice. Furthermore, the natural attraction of the spectacular Iguaçu waterfalls seemed to be an ideal compensation for Sugar Loaf Mountain, Copacabana beach, and the statue of Christ the Redeemer on Corcovado Mountain.Then came the pandemic. By mid-2020, it had become apparent that there were too many unknowns to make it possible to proceed with an in-person event in October of that year. It was decided to postpone the congress to 2021 but with a firm belief that things would be “back to normal.” Sweet delusion! As 2020 turned into 2021 and the severity and longevity of the pandemic became clearer and clearer (not to mention the abysmal performance of the Brazilian government in failing to rise to the challenge), the inevitable decision was taken to transform the event into an “on-line” congress. This was a first for both the local organizers and the IUPAB.The move to an online format immediately had an impact on the organization of the Young Scientist Program. This was initially envisaged to be a combination of formal and informal activities aimed at uniting about 40 early carrier scientists and post-docs for a couple of days prior to the main event in a stimulating atmosphere conducive to networking. Skillfully conceived, organized, and executed by Eneida de Paula (Campinas) and Eduardo Reis (São Paulo), this too had to be adapted to a “virtual reality.” The successful solution turned out to be a series of fortnightly thematic webinars, including a talk from a recognized authority in the field followed by three or four short presentations from the participants themselves (Table ​(Table1).1). The standard was extremely high and the YSP ended up being a highly effective warm-up to the congress itself. Furthermore, there was excellent geographical diversity among the participants with Europe, Africa, Asia, the Middle East, and both North and South America represented.Table 1Young Scientist Webinar Program

The Russian invasion of Ukraine: a humanitarian tragedy and a tragedy for science

The Invasion of Ukraine prompts us to support our Ukranian colleagues but also to keep open communication with the Russian scientists who oppose the war.

In the eyes of the civilized world, Russia has already lost the war: politically, it is becoming ever more isolated; economically as the sanctions take an enormous toll; militarily as the losses of the Russian army mount. In contrast, the courage of Ukrainian people fighting for their independence has united the Western world that is providing enormous support for those Ukrainians who fight the Russian invasion and those who have fled their war‐torn country. Once this war is over, Ukraine will have to heal the wounds of war, reunite families, restore its economy, reestablish infrastructure, and rebuild science and education. Russia will have to restore its dignity and overcome its self‐inflicted isolation.Europe’s unity in condemning Russia’s war of aggression and showing its solidarity with Ukraine has been impressive. This includes not the least welcoming and accommodating millions of refugees. We, the scientific community in Europe, have a moral obligation to help Ukrainian students and colleagues by providing safe space to study and to continue their research. First, European research organizations and funding agencies should develop strategies to support them in the years to come. Second, efforts by EMBO, research funders, universities, and research institutions to support Ukrainian students and scientists are necessary. As a first priority, dedicated and unbureaucratic short‐term scholarship and grant programs are required to accommodate Ukrainian scientists; such programs have been already initiated by many organizations, for example, by EMBO, Volkswagen Stiftung, Max Planck Society, and the ERC among others. These help Ukrainian scientists to stay connected to research and become integrated into the European research landscape. In the long‐term and after the war, this aid should be complemented by funding for research centers of excellence in Ukraine, to which scientists could then return.Even though the priority must be to help Ukrainians, we must also think of students and colleagues in Russia who oppose the war and are affected by the sanctions. As the Iron Curtain closes again, we have to think differently about our ongoing and future collaborations. Although freezing most, if not all, research collaborations with official Russian organizations is justified, it would be a mistake to extend these sanctions to all scientists and students. There is already an exodus of Russian and Belarusian scholars, which will only accelerate in the next months and years, and accepting scientists who ask for political asylum will be beneficial for Europe.The fraction of Russian society in open opposition to the war is, unfortunately, smaller than that officially in support of it. At the beginning of the war, a number of Russian scientists published an open letter on the internet, in which they condemn this war (https://t‐invariant.org/2022/02/we‐are‐against‐war/). They clearly state that "The responsibility for unleashing a new war in Europe lies entirely with Russia. There is no rational justification for this war”, and “demand an immediate halt to all military operations directed against Ukraine". At the same time, other prominent Russian science and education officials signed the “Statement of the Russian Union of University Rectors (Provosts)”, which expressed unwavering support for Russia, its president and its Army and their goal to “to achieve demilitarization and denazification of Ukraine and thus to defend ourselves from the ever‐growing military threat” (https://www.rsr‐online.ru/news/2022‐god/obrashchenie‐rossiyskogo‐soyuza‐rektorov1/).Inevitably, Russian scientists must decide themselves how to live and continue their scientific work under the increasingly tight surveillance of the Kremlin regime. History is repeating itself. Not long ago, during the Cold War, Soviet scientists were largely isolated from the international research community and worked in government‐controlled research. In some fields, no one knew what they were working on or where. However, even in those dark times, courageous individuals such as Andrei Sakharov spoke out against the regime and tried to educate the next generation about the importance of free will. Many Soviet geneticists had been arrested under Stalin’s regime of terror and as a result of Lysenkoism and were executed or sent to the Gulag or had to emigrate, such as Nikolaj Timofeev‐Resovskij, one of the great geneticists of his time and an opponent of communism. As a result of sending dissident scientists to Siberia, great educational institutions were created in the region, which trained many famous scientists. History tells us that it is impossible to kill free will and the search for truth.The Russian invasion of Ukraine is a major humanitarian tragedy and a tragedy for science at many levels. Our hope is that the European science community, policymakers, and funders will be prepared to continue and expand support for our colleagues from Ukraine and eventually help to rebuild the bridges with Russian science that have been torn down.This commentary has been endorsed and signed by the EMBO Young Investigators and former Young Investigators listed below.

All signatories are current and former EMBO Young Investigators and endorse the statements in this article.

A conifer genome spruces up plant phylogenomics

The Norway spruce genome provides key insights into the evolution of plant genomes, leading to testable new hypotheses about conifer, gymnosperm, and vascular plant evolution.In the past year a burst of plant genome sequences have been published, providing enhanced phylogenetic coverage of green plants (Figure ​(Figure1)1) and inclusion of new agricultural, ecological, and evolutionary models. Collectively, these sequences are revealing some extraordinary structural and evolutionary attributes in plant genomes. Perhaps most surprising is the exceptionally high frequency of whole-genome duplication (WGD): nearly every genome that has been analyzed has borne the signature of one or more WGDs, with particularly notable events having occurred in the common ancestors of seed plants, of angiosperms, and of core eudicots (the latter ''WGD'' represents two WGDs in close succession) [1,2]. Given this tendency for plant genomes to duplicate and then return to an essentially diploid genetic system (an example is the cotton genomes, which have accumulated the effects of perhaps 15 WGDs [3]), the conservation of genomes in terms of gene number, chromosomal organization, and gene content is astonishing. From the publication of the first plant genome, Arabidopsis thaliana [4], the number of inferred genes has been between 25,000 and 30,000, with many gene families shared across all land plants, although the number of members and patterns of expansion and contraction vary. Furthermore, conserved synteny has been detected across the genomes of diverse angiosperms, despite WGDs, diploidization, and millions of years of evolution.Open in a separate windowFigure 1Simplified phylogeny of land plants, showing major clades and their component lineages. Asterisks indicate species (or lineage) for which whole-genome sequence (or sequences) is (are) available. Increases and decreases in genome size are shown by arrows.Despite the proliferation of genome sequences available for angiosperms, genome-level data for both ferns (and their relatives, collectively termed monilophytes; Figure ​Figure1)1) and gymnosperms have been conspicuously lacking - until recently, with the publication of the genome sequence of the gymnosperm Norway spruce (Picea abies) [5]. The large genome sizes for both monilophytes and gymnosperms have discouraged attempts at genome sequencing and assembly, whereas the smaller genome size of angiosperms has resulted in more genome sequences being available (Table ​(Table1)1) [6]. Because of this limited phylogenetic sample, our understanding of the timing and phylogenetic positions of WGDs, the core number of plant genes, possible conserved syntenic regions, and patterns of expansion and contraction of gene families across both tracheophytes (vascular plants) and across all land plants is imperfect. This sampling problem is particularly acute in analyses of the genes and genomes of seed plants; many hundreds of genes are present in angiosperms that are not present in mosses or lycophytes, but whether these genes arose in the common ancestor of seed plants or of angiosperms cannot be determined without a gymnosperm genome sequence. The Norway spruce genome therefore offers tremendous power, not only for understanding the structure and evolution of conifer genomes, but also as a reference for interpreting gene and genome evolution in angiosperms.

Table 1

Genome sizes in land plants

Economic Benefits of Investing in Women’s Health: A Systematic Review

Background

Globally, the status of women’s health falls short of its potential. In addition to the deleterious ethical and human rights implications of this deficit, the negative economic impact may also be consequential, but these mechanisms are poorly understood. Building on the literature that highlights health as a driver of economic growth and poverty alleviation, we aim to systematically investigate the broader economic benefits of investing in women’s health.

Methods

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we systematically reviewed health, gender, and economic literature to identify studies that investigate the impact of women’s health on micro- and macroeconomic outcomes. We developed an extensive search algorithm and conducted searches using 10 unique databases spanning the timeframe 01/01/1970 to 01/04/2013. Articles were included if they reported on economic impacts stemming from changes in women’s health (table of outcome measures included in full review,

Does an Eye-Hand Coordination Test Have Added Value as Part of Talent Identification in Table Tennis? A Validity and Reproducibility Study

This study investigated the added value, i.e. discriminative and concurrent validity and reproducibility, of an eye-hand coordination test relevant to table tennis as part of talent identification. Forty-three table tennis players (7–12 years) from national (n = 13), regional (n = 11) and local training centres (n = 19) participated. During the eye-hand coordination test, children needed to throw a ball against a vertical positioned table tennis table with one hand and to catch the ball correctly with the other hand as frequently as possible in 30 seconds. Four different test versions were assessed varying the distance to the TotalNationalRegionalLocalTotal43131119Boys268810Girls17539Age (years)10.4±1.410.9±1.510.4±1.510.1±1.47 year olds1--18 year olds51139 year olds3-3-10 year olds1232711 year olds1151512 year olds11443Length (cm)149±11150±12150±12148±10Weight (kg )38±837±737±738±9Right-handed359917Left-handed8422Training (hours*week-1)6 (0–20)11 (7–20)7 (4–11)2 (0–3)Competition (points)173 (−52–430)297 (144–430)188 (72–317)36 (−52–130)Open in a separate windowData are frequencies, except for age, length and weight (years±SD), and training and competition (mean (range)).     

Vasoconstricción cerebral fatal,presentación inusual de una enfermedad inusual

The reversible cerebral vasoconstriction syndrome is a variable, segmental, and multifocal constriction of brain arteries, usually with a benign course.We describe the case of a 49-year-old woman who presented with headaches, visual symptoms, and seizures. Three days after admission, vasoconstriction areas were found in at least two vascular territories in two segments of the same arteries.The patient was admitted to the intensive care unit where her blood pressure was monitored and she received medical treatment. Surprisingly, the patient presented an unpredicted evolution in developing malignant cerebral edema on the seventh day after admission. She then suffered brain death and was taken to organ donation. A guided nervous system necropsy was later performed. The pathology discarded vasculitis and exhibited hemorrhage areas in the cerebral convexity.Herein, we discuss the most relevant aspects of cases with fulminant evolution reported in the literature. The reversible cerebral vasoconstriction syndrome is usually associated with fatal outcomes when patients exhibit focalization, their first neuroimaging typically shows disturbances, and a rapid clinical deterioration occurs. It is crucial to identify factors linked to poor prognosis and set intervention strategies and early prevention.Key words: stroke, brain hemorrhage, vasoconstriction, mortality, prognosis

El síndrome de vasoconstricción cerebral reversible se produce por una vasoconstricción variable, segmentaria y multifocal, de las arterias cerebrales (1).Esta condición patológica es más común en mujeres entre los 10 y los 76 años, con un pico a los 42 años (2). Hasta en el 70% de los pacientes puede haber factores precipitantes (3), entre los cuales se han mencionado estrés emocional y físico, actividad sexual, puerperio, trauma, maniobra de Valsalva, y uso de sustancias vasoactivas o de inhibidores selectivos de la recaptación de serotonina (4-6).Los hallazgos clínicos son diversos, pero se sabe que la forma más común de presentación clínica es la cefalea “en trueno” (7). La principal herramienta diagnóstica es la angiografía cerebral, considerada la prueba de referencia, aunque no es el único estudio de imagenología que se puede utilizar como método de evaluación (3,8).A pesar de que muchos casos se resuelven de forma espontánea, algunos pacientes pueden desarrollar complicaciones como hemorragia, convulsiones e infartos cerebrales (3), e incluso, se han reportado casos fatales asociados con este síndrome (9-12).Se presenta el caso de una paciente que falleció. Se describe la secuencia de eventos clínicos que llevaron a su muerte, haciendo énfasis en aquellos factores que deben alertar sobre un posible curso fulminante.     

Mortalidad causada por animales venenosos en Venezuela (2000-2009): nuevo patrón epidemiológico

IntroducciónLos accidentes causados por animales venenosos ocurren con mucha frecuencia en comunidades pobres con acceso limitado a los servicios de salud. Se les consideran enfermedades desatendidas y son una de las causas importantes de morbimortalidad en varias naciones del mundo, incluida Venezuela.ObjetivoEvaluar la mortalidad por contacto traumático con animales venenosos (serie X20-X29) en Venezuela en el periodo de 2000 a 2009.Materiales y métodosLos datos se obtuvieron de los anuarios de mortalidad del Ministerio de Salud.ResultadosSe registraron 759 decesos, la mayoría de ellos en el 2009. La primera causa fue la mordedura de serpientes (n=323; 42,6%), seguida por la picadura de himenópteros (n=170; 22,4%), la mordedura de centípedos (n=106; 14,0%) y la picadura de escorpiones (n=76; 10,0%). La mediana de la tasa de mortalidad general para el periodo fue de 0,285 fallecidos por 100.000 habitantes, en tanto que, por grupo específico, fue de 0,120 para ofidios, de 0,065 para himenópteros, de 0,035 para centípedos y de 0,025 para escorpiones.ConclusiónAl comparar estos datos con los antecedentes históricos, se evidenció la modificación del patrón de mortalidad en el país caracterizada por un aumento significativo de los decesos por centípedos, tercera causa de muerte, lo que reubica la picadura de escorpiones como la cuarta causa de mortalidad.Palabras clave: serpientes, himenópteros, escorpiones, mortalidad, epidemiología     

Inserción “velamentosa”, encefalopatía hipóxico-isquémica y rehabilitación neurológica: reporte de caso

La encefalopatía hipóxico-isquémica es una causa frecuente e importante de daño neurológico en recién nacidos a término y prematuros. Un evento centinela de esta condición es la vasa previa, específicamente cuando existe anormalidad de la placenta como la inserción “velamentosa” del cordón umbilical. Algunos reportes evidencian la asociación entre estas dos condiciones, pero son escasos los que dan cuenta del proceso de recuperación y del pronóstico neurológico de los niños afectados por ellas.Se presenta el caso de un paciente, con antecedentes de inserción “velamentosa” del cordón umbilical y encefalopatía hipóxico-isquémica, que recibió hipotermia terapéutica (cool cap). Se describe su proceso de rehabilitación neurológica y se calculó el porcentaje de probabilidad de presentar esta condición frente a la población sin estos factores. El niño tenía cinco años y el puntaje en su prueba de Apgar fue de 0 al minuto y de 2 a los 15 minutos. Desarrolló encefalopatía hipóxico-isquémica grave secundaria a una inserción “velamentosa” del cordón umbilical sin diagnóstico prenatal, con gran compromiso neurológico y multisistémico inicial. El proceso de recuperación incluyó el manejo inicial multidisciplinario en la unidad de cuidados intensivos neonatales y el inicio temprano de habilitación neurológica.Hoy el niño está escolarizado y en terapia integral, no presenta deficiencias motoras ni sensoriales en el examen físico, aunque la prueba neuropsicológica sugiere un riesgo de trastorno por déficit de atención e hiperactividad. Habitualmente, los niños con encefalopatía hipóxico-isquémica grave presentan discapacidad por deficiencias motoras, cognitivas o conductuales. El haber recibido hipotermia terapéutica y un manejo estructurado de rehabilitación redujo en gran medida las deficiencias esperadas y ha promovido un satisfactorio desarrollo físico y neurológico.Palabras clave: cordón umbilical, hipoxia-isquemia encefálica, hipotermia inducida, rehabilitación neurológica     

Perioperative Opioid Counseling Reduces Opioid Use Following Primary Total Joint Arthroplasty

BackgroundPreoperative counseling may reduce postoperative opioid requirements; however, there is a paucity of randomized controlled trials (RCTs) demonstrating efficacy. The purpose of this study was to perform an interventional, telehealth-based RCT evaluating the effect of peri-operative counseling on quantity and duration of opioid consumption following primary total joint arthroplasty (TJA).MethodsParticipants were randomized into three groups: 1. Control group, no perioperative counseling; 2. Intervention group, preoperative educational video; 3. Intervention group, preoperative educational video and postoperative acceptance and commitment therapy (ACT). Opioid consumption was evaluated daily for 14 days and at 6 weeks postoperatively. Best-case and worse-case intention to treat analyses were performed to account for non-responses. Bonferroni corrections were applied.Results183 participants were analyzed (63 in Group 1, 55 in Group 2, and 65 in Group 3). At 2 weeks postoperatively, there was no difference in opioid consumption between Groups 1, 2, and 3 (p>0.05 for all). At 6 weeks postoperatively, Groups 2 and 3 had consumed significantly less opioids than Group 1 (p=0.04, p<0.001) (VariableGroupp-value1. Control2. Video OnlyVideo + ACTSex (n, % female)39 (62%)32 (58%)40 (62%)0.90Surgery (n, % THA)26 (41%)21 (38%)31 (47%)0.56Age (mean ± SD; years)59 ± 1159 ± 1158 ± 9Overall: 0.83
1v2: 0.98
2v3: 0.65
2v3: 0.56Prolonged Opioid Use > 60 mo. (n, %)000-Opioid Use Within 3 mo. of Index Surgery (n, %)0 (14%)4 (7%)5 (8%)0.34Open in a separate windowSD – standard deviation.Table 2.Quantity of Opioid Consumption at 2 Weeks Postoperatively, Best-Case Scenario

Widespread Distribution of Cell Defense against d-Aminoacyl-tRNAs

Several l-aminoacyl-tRNA synthetases can transfer a d-amino acid onto their cognate tRNA(s). This harmful reaction is counteracted by the enzyme d-aminoacyl-tRNA deacylase. Two distinct deacylases were already identified in bacteria (DTD1) and in archaea (DTD2), respectively. Evidence was given that DTD1 homologs also exist in nearly all eukaryotes, whereas DTD2 homologs occur in plants. On the other hand, several bacteria, including most cyanobacteria, lack genes encoding a DTD1 homolog. Here we show that Synechocystis sp. PCC6803 produces a third type of deacylase (DTD3). Inactivation of the corresponding gene (dtd3) renders the growth of Synechocystis sp. hypersensitive to the presence of d-tyrosine. Based on the available genomes, DTD3-like proteins are predicted to occur in all cyanobacteria. Moreover, one or several dtd3-like genes can be recognized in all cellular types, arguing in favor of the nearubiquity of an enzymatic function involved in the defense of translational systems against invasion by d-amino acids.Although they are detected in various living organisms (reviewed in Ref. 1), d-amino acids are thought not to be incorporated into proteins, because of the stereospecificity of aminoacyl-tRNA synthetases and of the translational machinery, including EF-Tu and the ribosome (2). However, the discrimination between l- and d-amino acids by aminoacyl-tRNA synthetases is not equal to 100%. Significant d-aminoacylation of their cognate tRNAs by Escherichia coli tyrosyl-, tryptophanyl-, aspartyl-, lysyl-, and histidyl-tRNA synthetases has been characterized in vitro (3–9). Recently, using a bacterium, transfer of d-tyrosine onto tRNA^Tyr was shown to occur in vivo (10).With such misacylation reactions, the resulting d-aminoacyl-tRNAs form a pool of metabolically inactive molecules, at best. At worst, d-aminoacylated tRNAs infiltrate the protein synthesis machinery. Although the latter harmful possibility has not yet been firmly established, several cells were shown to possess a d-tyrosyl-tRNA deacylase, or DTD, that should help them counteract the accumulation of d-aminoacyl-tRNAs. This enzyme shows a broad specificity, being able to remove various d-aminoacyl moieties from the 3′-end of a tRNA (4–6, 11). Such a function makes the deacylase a member of the family of enzymes capable of editing in trans mis-aminoacylated tRNAs. This family includes several homologs of aminoacyl-tRNA synthetase editing domains (12), as well as peptidyl-tRNA hydrolase (13, 14).Two distinct deacylases have already been discovered. The first one, called DTD1, is predicted to occur in most bacteria and eukaryotes (see d-amino acids, including d-tyrosine (6). In fact, in an E. coli Δdtd strain grown in the presence of 2.4 mm d-tyrosine, as much as 40% of the cellular tRNA^Tyr pool becomes esterified with d-tyrosine (10).

TABLE 1

Distribution of DTD1 and DTD2 homologs in various phylogenetic groupsHomologs of DTD1 and DTD2 were searched for using a genomic Blast analysis against complete genomes in the NCBI Database (www.ncbi.nlm.nih.gov). Values in the table are number of species. For instance, E. coli is counted only once in γ-proteobacteria despite the fact that several E. coli strains have been sequenced.

Cognitive Manic Symptoms in Bipolar Disorder Associated with Polymorphisms in the DAOA and COMT Genes

Introduction

Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.

Methodology

Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Bipolar disorder type 1 [n]488Men [n (%)]209 (43)Talkativeness [n (%)]373 (76)Distracibility [n (%)]269 (55)Thought disorder [n (%)]372 (76)Cognitive manic symptoms^* [n (%)]215 (44)Men [n (%)]81 (39)Non-Cognitive manic symptoms [n (%)]248 (51)Men [n (%)]117 (56)Unknown [n (%)]25 (5)Men [n (%)]11 (44)Anonymous blood donors (ABD)1044Men [n (%)]616 (59)Open in a separate window^*having all three symptoms: talkativeness, distractibility, and tought disorder.

Results

The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (BP1 CMSBP1 non-CMSABDBP1 CMS vs. non-CMS^b BP1 CMS vs. ABD controls^b GeneSNP^a aa/ab/bbaa/ab/bbaa/ab/bbpEMP1^c EMP2^d OR [95% CI] ^e pEMP1^c EMP2^d OR [95% CI] ^e DAOA rs3916967 (C/T)32/88/8950/118/77177/494/3610.0180.0180.210.72 [0.55–0.93]0.0290.0260.280.78 [0.66–1.0] DAOA rs2391191 (A/C)28/75/7939/111/70179/487/3570.0550.0390.500.75 [0.57–1.0]0.0200.0190.210.75 [0.63–1.0] DAOA rs1935062 (C/A)26/67/8935/102/86146/460/4050.120.120.780.80 [0.58–1.0]0.0690.0660.520.80 [0.65–1.0] COMT rs5993883 (T/G)33/120/5371/112/57269/510/2230.0250.0300.270.73 [0.56–0.95]0.0017^* 1.0E^{−4 *} 0.021^* 0.68 [0.91–1.4] COMT rs165599 (G/A)29/94/8725/93/12687/443/5010.0930.0940.691.27 [1.0–1.8]0.0140.0170.161.34 [1.1–1.7]Open in a separate window^aSNP (minor allele(a)/major allele(b)).^bgender and rs1718119 as covariate.^cpoint-wise p-value from 10,000 pemutations with no covarite (EMP1).^dcorrected empirical p-value by max (T) permutation.^eodds ratio (OR), the proportion of minor versus major allele affected (cognitive manic symptoms factor)/proportion of minor versus major allele unaffected (non-cognitive manic symptoms factor or ABD controls).^*significant after correction for multiple testing by max (T) permutation.

Table 3

Haplotype association of haplotype group 1 in bipolar 1 patients with cognitive manic symptoms (CMS) compared with non-CMS patients or ABD controls in the DAOA gene.

Antimicrobial Activity of Simulated Solar Disinfection against Bacterial,Fungal, and Protozoan Pathogens and Its Enhancement by Riboflavin

Riboflavin significantly enhanced the efficacy of simulated solar disinfection (SODIS) at 150 watts per square meter (W m⁻²) against a variety of microorganisms, including Escherichia coli, Fusarium solani, Candida albicans, and Acanthamoeba polyphaga trophozoites (>3 to 4 log₁₀ after 2 to 6 h; P < 0.001). With A. polyphaga cysts, the kill (3.5 log₁₀ after 6 h) was obtained only in the presence of riboflavin and 250 W m⁻² irradiance.Solar disinfection (SODIS) is an established and proven technique for the generation of safer drinking water (11). Water is collected into transparent plastic polyethylene terephthalate (PET) bottles and placed in direct sunlight for 6 to 8 h prior to consumption (14). The application of SODIS has been shown to be a simple and cost-effective method for reducing the incidence of gastrointestinal infection in communities where potable water is not available (2-4). Under laboratory conditions using simulated sunlight, SODIS has been shown to inactivate pathogenic bacteria, fungi, viruses, and protozoa (6, 12, 15). Although SODIS is not fully understood, it is believed to achieve microbial killing through a combination of DNA-damaging effects of ultraviolet (UV) radiation and thermal inactivation from solar heating (21).The combination of UVA radiation and riboflavin (vitamin B₂) has recently been reported to have therapeutic application in the treatment of bacterial and fungal ocular pathogens (13, 17) and has also been proposed as a method for decontaminating donor blood products prior to transfusion (1). In the present study, we report that the addition of riboflavin significantly enhances the disinfectant efficacy of simulated SODIS against bacterial, fungal, and protozoan pathogens.Chemicals and media were obtained from Sigma (Dorset, United Kingdom), Oxoid (Basingstoke, United Kingdom), and BD (Oxford, United Kingdom). Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633), Candida albicans (ATCC 10231), and Fusarium solani (ATCC 36031) were obtained from ATCC (through LGC Standards, United Kingdom). Escherichia coli (JM101) was obtained in house, and the Legionella pneumophila strain used was a recent environmental isolate.B. subtilis spores were produced from culture on a previously published defined sporulation medium (19). L. pneumophila was grown on buffered charcoal-yeast extract agar (5). All other bacteria were cultured on tryptone soy agar, and C. albicans was cultured on Sabouraud dextrose agar as described previously (9). Fusarium solani was cultured on potato dextrose agar, and conidia were prepared as reported previously (7). Acanthamoeba polyphaga (Ros) was isolated from an unpublished keratitis case at Moorfields Eye Hospital, London, United Kingdom, in 1991. Trophozoites were maintained and cysts prepared as described previously (8, 18).Assays were conducted in transparent 12-well tissue culture microtiter plates with UV-transparent lids (Helena Biosciences, United Kingdom). Test organisms (1 × 10⁶/ml) were suspended in 3 ml of one-quarter-strength Ringer''s solution or natural freshwater (as pretreated water from a reservoir in United Kingdom) with or without riboflavin (250 μM). The plates were exposed to simulated sunlight at an optical output irradiance of 150 watts per square meter (W m⁻²) delivered from an HPR125 W quartz mercury arc lamp (Philips, Guildford, United Kingdom). Optical irradiances were measured using a calibrated broadband optical power meter (Melles Griot, Netherlands). Test plates were maintained at 30°C by partial submersion in a water bath.At timed intervals for bacteria and fungi, the aliquots were plated out by using a WASP spiral plater and colonies subsequently counted by using a ProtoCOL automated colony counter (Don Whitley, West Yorkshire, United Kingdom). Acanthamoeba trophozoite and cyst viabilities were determined as described previously (6). Statistical analysis was performed using a one-way analysis of variance (ANOVA) of data from triplicate experiments via the InStat statistical software package (GraphPad, La Jolla, CA).The efficacies of simulated sunlight at an optical output irradiance of 150 W m⁻² alone (SODIS) and in the presence of 250 μM riboflavin (SODIS-R) against the test organisms are shown in Table ​Table1.1. With the exception of B. subtilis spores and A. polyphaga cysts, SODIS-R resulted in a significant increase in microbial killing compared to SODIS alone (P < 0.001). In most instances, SODIS-R achieved total inactivation by 2 h, compared to 6 h for SODIS alone (Table ​(Table1).1). For F. solani, C. albicans, ands A. polyphaga trophozoites, only SODIS-R achieved a complete organism kill after 4 to 6 h (P < 0.001). All control experiments in which the experiments were protected from the light source showed no reduction in organism viability over the time course (results not shown).

TABLE 1.

Efficacies of simulated SODIS for 6 h alone and with 250 μM riboflavin (SODIS-R)

Detection and Identification of tdh- and trh-Positive Vibrio parahaemolyticus Strains from Four Species of Cultured Bivalve Molluscs on the Spanish Mediterranean Coast

Presented here is the first report describing the detection of potentially diarrheal Vibrio parahaemolyticus strains isolated from cultured bivalves on the Mediterranean coast, providing data on the presence of both tdh- and trh-positive isolates. Potentially diarrheal V. parahaemolyticus strains were isolated from four species of bivalves collected from both bays of the Ebro delta, Spain.Gastroenteritis caused by Vibrio parahaemolyticus has been reported worldwide, though only sporadic cases have been reported in Europe (7, 14). The bacterium can be naturally present in seafood, but pathogenic isolates capable of inducing gastroenteritis in humans are rare in environmental samples (2 to 3%) (15) and are often not detected (10, 19, 20).The virulence of V. parahaemolyticus is based on the presence of a thermostable direct hemolysin (tdh) and/or the thermostable direct hemolysin-related gene (trh) (1, 5). Both are associated with gastrointestinal illnesses (2, 9).Spain is not only the second-largest producer in the world of live bivalve molluscs but also one of the largest consumers of bivalve molluscs, and Catalonia is the second-most important bivalve producer of the Spanish Autonomous Regions. Currently, the cultivation of bivalves in this area is concentrated in the delta region of the Ebro River. The risk of potentially pathogenic Vibrio spp. in products placed on the market is not assessed by existing legislative indices of food safety in the European Union, which emphasizes the need for a better knowledge of the prevalence of diarrheal vibrios in seafood products. The aim of this study was to investigate the distribution and pathogenic potential of V. parahaemolyticus in bivalve species exploited in the bays of the Ebro delta.Thirty animals of each species of Mytilus galloprovincialis, Crassostrea gigas, Ruditapes decussatus, and Ruditapes philippinarum were collected. They were sampled from six sites of the culture area, three in each bay of the Ebro River delta, at the beginning (40°37′112"N, 0°37′092"E [Alfacs]; 40°46′723"N, 0°43′943"E [Fangar]), middle (40°37′125"N, 0°38′570"E [Alfacs]; 40°46′666"N, 0°45′855"E [Fangar]), and end (40°37′309"N, 0°39′934"E [Alfacs]; 40°46′338"N, 0°44′941"E [Fangar]) of the culture polygon. Clams were sampled from only one site per bay as follows: in the Alfacs Bay from a natural bed of R. decussatus (40°37′44"N, 0°38′0"E) and in the Fangar Bay from an aquaculture bed of R. philippinarum (40°47′3"N, 0°43′8"E). In total, 367 samples were analyzed in 2006 (180 oysters, 127 mussels, 30 carpet shell clams, and 30 Manila clams) and 417 samples were analyzed in 2008 (178 oysters, 179 mussels, 30 carpet shell clams, and 30 Manila clams).All animals were individually processed and homogenized, and 1 ml of the homogenate was inoculated into 9 ml of alkaline peptone water (Scharlau, Spain). Following a 6-h incubation at 37°C, one loopful of the contents of each tube of alkaline peptone water was streaked onto CHROMagar vibrio plates (CHROMagar, France) and incubated for 18 h at 37°C. Mauve-purple colonies were purified, and each purified isolate was cryopreserved at −80°C (135 isolates in 2006 and 96 in 2008). From the initial homogenate portion, 100 μl was inoculated onto marine agar (Scharlau, Spain) and onto thiosulfate citrate-bile salts-sucrose agar (Scharlau, Spain) for total heterotrophic marine bacteria counts and total vibrio counts, respectively (Table ​(Table11).

TABLE 1.

Vibrio parahaemolyticus isolates, serotypes, and origins and total number of vibrios/heterotrophic bacteria contained in the bivalve^a

Diminished Susceptibility to Cefoperazone/Sulbactam and Piperacillin/Tazobactam in Enterobacteriaceae Due to Narrow-Spectrum β-Lactamases as Well as Omp Mutation

Cefoperazone/sulbactam (CSL) and piperacillin/tazobactam (TZP) are commonly used in clinical practice in China because of their excellent antimicrobial activity. CSL and TZP-nonsusceptible Enterobacteriaceae are typically resistant to extended-spectrum cephalosporins such as ceftriaxone (CRO). However, 11 nonrepetitive Enterobacteriaceae strains, which were resistant to CSL and TZP yet susceptible to CRO, were collected from January to December 2020. Antibiotic susceptibility tests and whole-genome sequencing were conducted to elucidate the mechanism for this rare phenotype. Antibiotic susceptibility tests showed that all isolates were amoxicillin/clavulanic-acid resistant and sensitive to ceftazidime, cefepime, cefepime/tazobactam, cefepime/zidebactam, ceftazidime/avibactam, and ceftolozane/tazobactam. Whole-genome sequencing revealed three of seven Klebsiella pneumoniae strains harbored bla_SHV-1 only, and four harbored bla_SHV-1 and bla_TEM-1B. Two Escherichia coli strains carried bla_TEM-1B only, while two Klebsiella oxytoca isolates harbored bla_OXY-1-3 and bla_OXY-1-1, respectively. No mutation in the β-lactamase gene and promoter sequence was found. Outer membrane protein (Omp) gene detection revealed that numerous missense mutations of OmpK36 and OmpK37 were found in all strains of K. pneumoniae. Numerous missense mutations of OmpK36 and OmpK35 and OmpK37 deficiency were found in one K. oxytoca strain, and no OmpK gene was found in the other. No Omp mutations were found in E. coli isolates. These results indicated that narrow spectrum β-lactamases, TEM-1, SHV-1, and OXY-1, alone or in combination with Omp mutation, contributed to the resistance to CSL and TZP in CRO-susceptible Enterobacteriaceae.Antibiotic susceptibility tests

Environmental Isolates of Burkholderia pseudomallei in Ceará State,Northeastern Brazil

Melioidosis has been considered an emerging disease in Brazil since the first cases were reported to occur in the northeast region. This study investigated two municipalities in Ceará state where melioidosis cases have been confirmed to occur. Burkholderia pseudomallei was isolated in 26 (4.3%) of 600 samples in the dry and rainy seasons.Melioidosis is an endemic disease in Southeast Asia and northern Australia (2, 4) and also occurs sporadically in other parts of the world (3, 7). Human melioidosis was reported to occur in Brazil only in 2003, when a family outbreak afflicted four sisters in the rural part of the municipality of Tejuçuoca, Ceará state (14). After this episode, there was one reported case of melioidosis in 2004 in the rural area of Banabuiú, Ceará (14). And in 2005, a case of melioidosis associated with near drowning after a car accident was confirmed to occur in Aracoiaba, Ceará (11).The goal of this study was to investigate the Tejuçuoca and Banabuiú municipalities, where human cases of melioidosis have been confirmed to occur, and to gain a better understanding of the ecology of Burkholderia pseudomallei in this region.We chose as central points of the study the residences and surrounding areas of the melioidosis patients in the rural areas of Banabuiú (5°18′35″S, 38°55′14″W) and Tejuçuoca (03°59′20″S, 39°34′50′W) (Fig. ​(Fig.1).1). There are two well-defined seasons in each of these locations: one rainy (running from January to May) and one dry (from June to December). A total of 600 samples were collected at five sites in Tejuçuoca (T1, T2, T3, T4, and T5) and five in Banabuiú (B1, B2, B3, B4, and B5), distributed as follows (Fig. ​(Fig.2):2): backyards (B1 and T1), places shaded by trees (B2 and T2), water courses (B3 and T3), wet places (B4 and T4), and stock breeding areas (B5 and T5).Open in a separate windowFIG. 1.Municipalities of Banabuiú (5°18′35″S, 38°55′14″W) and Tejuçuoca (03°59′20″S, 39°34′50″W).Open in a separate windowFIG. 2.Soil sampling sites in Banabuiú and Tejuçuoca.Once a month for 12 months (a complete dry/rainy cycle), five samples were gathered at five different depths: at the surface and at 10, 20, 30 and 40 cm (Table ​(Table1).1). The samples were gathered according to the method used by Inglis et al. (9). Additionally, the sample processing and B. pseudomallei identification were carried out as previously reported (1, 8, 9).

TABLE 1.

Distribution of samples with isolates by site and soil depth

Costos directos de la infección adquirida en la comunidad por neonatos a término con bajo riesgo al nacer,Cundinamarca, Colombia

IntroducciónEl 50% de los episodios de sepsis neonatal se originan en la comunidad, con un gran porcentaje de mortalidad y complicaciones.ObjetivoEstimar los costos directos de la hospitalización por infección neonatal adquirida en la comunidad en neonatos a término con bajo riesgo al nacer.Materiales y métodosSe utilizó la perspectiva del tercer pagador y la técnica de microcosteo; el horizonte de tiempo fue la duración de la hospitalización. La determinación de las situaciones generadoras de costos se obtuvo por medio de un consenso de expertos y se cuantificaron con base en la factura detallada de la atención de 337 neonatos hospitalizados. Los costos de los medicamentos se calcularon con base en el Sistema de Información de Precios de Medicamentos (SISMED) y, el de los procedimientos, según los manuales tarifarios ISS 2001 con porcentaje de ajuste y el seguro obligatorio de accidentes de tráfico (SOAT). Para incorporar la variabilidad de la información en la estimación, se obtuvo una distribución de los costos usando el método de bootstrapping.ResultadosSe incluyeron las facturas por la atención de 337 recién nacidos. El promedio de costos directos de la atención por paciente fue de COL$ 2’773.965 (desviación estándar, DE=$ 198.813,5; IC_95%: $ 2’384.298 - $ 3’163.632). Las principales categorías generadoras de costos fueron la internación en la unidad de cuidados intensivos y las tecnologías en salud. Los costos siguieron una una distribución logarítmica normal (log-normal).ConclusionesLas categorías con mayor impacto en los costos fueron la internación en la unidad neonatal y las tecnologías en salud. Los costos se ajustaron a una distribución logarítmica normal.Palabras clave: sepsis neonatal, costos y análisis de costo, recién nacido, unidades de cuidado intensivo neonatal, mortalidad infantil