Serum antibodies to Vibrio vulnificus biotype 3 lipopolysaccharide and susceptibility to disease caused by the homologous V. vulnificus biotype

In 1996 an outbreak of severe soft tissue infections caused by Vibrio vulnificus unexpectedly erupted in fish consumers in Israel with relatively little morbidity in fish farmers. To test the hypothesis that recurrent exposure of fishermen to the virulent strain may have provided protection against severe or symptomatic disease, we investigated the association between the immune response to V. vulnificus biotype 3 lipopolysaccharide (BT3 LPS) and disease susceptibility in fish farmers and fish consumers. Serum samples were tested for IgA and IgG of anti-BT3 LPS in fishermen and fish consumers who suffered from V. vulnificus BT3 infections and their matched controls. Pre-existing levels of IgG (IgG0) of anti-BT3 LPS were significantly lower in diseased fishermen who developed disease associated with the homologous biotype, compared to controls. In multivariate analysis, levels of IgG0 anti-BT3 LPS remained the only variable significantly associated with disease occurrence in fishermen. Higher levels of pre-existing IgG anti-BT 3 LPS antibodies may be associated with protection against severe or symptomatic disease with the homologous biotype in fishermen but not in subjects from the general public

Chronology with a pinch of salt:Integrated stratigraphy of Messinian evaporites in the deep Eastern Mediterranean reveals long-lasting halite deposition during Atlantic connectivity

The Messinian Salinity Crisis (MSC; 5.97–5.33 Ma) is considered an extreme environmental event driven by changes in climate and tectonics, which affected global ocean salinity and shaped the biogeochemical composition of the Mediterranean Sea. Yet, after more than 50 years of research, MSC stratigraphy remains controversial. Recent studies agree that the transition from the underlying pre-evaporite sediments to thick halite deposits is conformal in the deep Eastern Mediterranean Basin. However, the age of the base and the duration of halite deposition are still unclear. Also disputed is the nature of the intermediate and upper MSC units, which are characterized as periods of increased clastic deposition into the Eastern Mediterranean based on marginal outcrops and seismic data. We provide a multidisciplinary study of sedimentary, geochemical, and geophysical data from industrial offshore wells in the Levant Basin, which recovered a sedimentary record of deep-basin Mediterranean evaporites deposited during the MSC. In combination with previous observations of the MSC throughout the Mediterranean Basin, our results promote the need for a new chronological model. Remarkably, the one-kilometer-thick lower part of the evaporitic unit is composed of essentially pure halite, except for a thin transitional anhydrite layer at its base. The halite is undisturbed and homogeneous, lacking diverse features apparent in more proximal sections, indicating a deep-sea depositional environment. We find that distinct, meters-thick non-evaporitic intervals interbedded with the halite, previously thought to be clastic layers, are diatomites. While XRD analysis confirms an increase in clastic components in these sediments, they are composed primarily of well-preserved marine and freshwater planktonic diatoms. The occurrence of marine planktonic diatoms in these intervals indicates the input of Atlantic waters into the Mediterranean Basin during the deposition of the massive halite unit. Seismic stratigraphy and well-log cyclostratigraphy further support deep basin halite deposition, which started about 300 kyr earlier than widely assumed (~5.97 Ma). We propose that halite deposition in the deep Mediterranean took place during stage 1 of the MSC, rather than being limited to the short 50 kyr MSC acme when sea level was presumably at its lowest. Thus, brine formation, salt precipitation, and faunal extinction occurred at least in part in a deep, non-desiccated basin, with a restricted yet open Mediterranean-Atlantic connection that allowed inflow of oceanic water. We observe an increase in heavy minerals and reworked fauna within the clastic-evaporitic, Interbedded Evaporites of the basinal MSC section, and argue that these settings correspond in the deep basins with a significant sea-level drawdown during stage 2 of the MSC, as observed in the marginal sections. This correlation is corroborated by astrochronology and chemostratigraphic markers, such as the distribution of n-alkanes and biomarker-based thermal maturity indices. The Levant deposits indicate that high sea level and partial connectivity with global oceans promoted the deposition of deep-basin deep-water halite, while sea-level drawdown promoted deposition of reworked and transported material from the margins into deep Mediterranean basins. This study modifies the current understanding of the mechanisms governing salt deposition throughout the MSC with implications for other evaporitic events in the geologic record

Dataset of characteristic remanent magnetization and magnetic properties of early Pliocene sediments from IODP Site U1467 (Maldives platform)

This data article describes data of magnetic stratigraphy and anisotropy of isothermal remanent magnetization (AIRM) from "Magnetic properties of early Pliocene sediments from IODP Site U1467 (Maldives platform) reveal changes in the monsoon system" [1]. Acquisition of isothermal magnetization on pilot samples and anisotropy of isothermal remanent magnetization are reported as raw data; magnetostratigraphic data are reported as characteristic magnetization (ChRM).info:eu-repo/semantics/publishedVersio

New Modularity of DAP-Kinases: Alternative Splicing of the DRP-1 Gene Produces a ZIPk-Like Isoform

DRP-1 and ZIPk are two members of the Death Associated Protein Ser/Thr Kinase (DAP-kinase) family, which function in different settings of cell death including autophagy. DAP kinases are very similar in their catalytic domains but differ substantially in their extra-catalytic domains. This difference is crucial for the significantly different modes of regulation and function among DAP kinases. Here we report the identification of a novel alternatively spliced kinase isoform of the DRP-1 gene, termed DRP-1β. The alternative splicing event replaces the whole extra catalytic domain of DRP-1 with a single coding exon that is closely related to the sequence of the extra catalytic domain of ZIPk. As a consequence, DRP-1β lacks the calmodulin regulatory domain of DRP-1, and instead contains a leucine zipper-like motif similar to the protein binding region of ZIPk. Several functional assays proved that this new isoform retained the biochemical and cellular properties that are common to DRP-1 and ZIPk, including myosin light chain phosphorylation, and activation of membrane blebbing and autophagy. In addition, DRP-1β also acquired binding to the ATF4 transcription factor, a feature characteristic of ZIPk but not DRP-1. Thus, a splicing event of the DRP-1 produces a ZIPk like isoform. DRP-1β is highly conserved in evolution, present in all known vertebrate DRP-1 loci. We detected the corresponding mRNA and protein in embryonic mouse brains and in human embryonic stem cells thus confirming the in vivo utilization of this isoform. The discovery of module conservation within the DAPk family members illustrates a parsimonious way to increase the functional complexity within protein families. It also provides crucial data for modeling the expansion and evolution of DAP kinase proteins within vertebrates, suggesting that DRP-1 and ZIPk most likely evolved from their ancient ancestor gene DAPk by two gene duplication events that occurred close to the emergence of vertebrates

Early Miocene Intensification of the North African Hydrological Cycle: Multi-Proxy Evidence From the Shelf Carbonates of Malta

During the Miocene (23.0–5.3 Ma) North Africa experienced both humid and arid intervals, but the underlying cause of these transitions is unknown. Earth's climate was characterized by a unipolar icehouse with a dynamic Antarctic ice sheet, which may have influenced regional hydrology through atmospheric teleconnections. However, the Miocene also witnessed the restriction of the Mesopotamian Seaway, which may have had significant climatic impacts. The Maltese il-Blata section (Central Mediterranean) comprises Late Oligocene to Early Miocene marine deposits previously used to constrain the timing of the Mesopotamian Seaway restriction using the εNd tracer. The location of this section also makes it sensitive to climatic changes in the North African region, and biogeochemical changes in the central Mediterranean. Here, we present lithological and geochemical records of the il-Blata section. We find a marked shift in lithology and an increase in sedimentation rate coeval with the Early Miocene (∼19–20 Ma) restriction of the Mesopotamian Seaway. Concomitant changes in bulk sediment CaCO3, Sr/Ca, K/Al, Ti/Al, Zr/Al, and Si/Ti support a major humid climate transition and associated intensification of river systems over western North Africa. We propose that these changes in North African hydroclimate reflect either a tipping point effect in a gradually warming global climate, or are the result of the initial restriction of the Mesopotamian Seaway, perhaps through consequent changes in Atlantic Meridional Overturning Circulation and the West African Monsoon. We also suggest the restriction of the Mesopotamian Seaway inhibited phosphorite deposition at low latitudes

Control de cambios / Rastrea los cambios / El camino cambia: Reflexiones sobre un mundo en transformación

“Track changes: Reflecting on a transforming world” was the theme chosen to invite panels, papers, posters and alternative presentations to be part of the 2019 international congress of SIEF that was held in Santiago de Compostela, Galicia (Spain). This introduction includes a description of the content of the congress, the rationale of the choice of plenaries and some reflections about the outcomes of the congress.El lema elegido para presentar paneles, ponencias, posters y presentaciones en formatos alternativos para el congreso internacional 2019 de SIEF -que tuvo lugar en Santiago de Compostela, Galicia (España)- fue “Track changes: Reflecting on a transforming world”. Esta introducción incluye una descripción del contenido del congreso, la idea para la elección de las plenarias y algunas reflexiones sobre los resultados del congreso. &nbsp

Анализ факторов, определяющих развитие послеоперационной боли у пациентов, перенесших эндопротезирование коленных и тазобедренных суставов

Chronic postoperative pain (POP) is a serious complication of total replacement (TR) of the knee (KJ) and hip (HJ) joints.Objective: to determine the factors associated with POP in patients after TR of KJ or HJ.Patients and methods. The study group consisted of 124 patients with knee osteoarthritis or hip osteoarthritis (age 63.6±9.9 years, 63% women and 37% men) who underwent TR of KJ or HJ. POP was defined as pain ≥40 mm on a numerical rating scale persistent for ≥3 months. Its presence was assessed after 3 and 6 months by telephone survey. Comparison of patients with POP and without it was carried out for a number of factors identified before surgery.Results and discussion. The incidence of POP was 27.4%. There was no difference in the incidence of POP in patients after TR of KJ or HJ: 28.1% and 26.9% (p=0.88). POP was statistically significantly associated with parameters such as higher body mass index (BMI); the intensity of pain at rest; general assessment of impairment; WOMAC index pain, stiffness and overall; severity of symptoms of neuropathic pain (PainDETECT); signs of depression and anxiety (HADS).The risk of POP was significantly higher (p<0.05) with BMI >30 kg/m2 (odds ratio, OR 2.755; 95% confidence interval, CI 1.053–7.206), rest pain ≥40 mm on a visual analog scale (OR 1.349; 95% CI 0.478–3.803), PainDETECT scores ≥13 (OR 3.598; 95% CI 1.048–12.36) and HADS depression ≥8 (OR 2.193; 95% CI 0.745–6.454), presence of ≥2 sources of pain (OR 6.996; 95% CI 2.358–20.756).Conclusion. It was found that the risk of POP after TR of KJ and HJ is higher in patients with overweight, severe preoperative pain, signs of neuropathic pain and depression, as well as in the presence of several sources of pain (except for the affected joint, that was replaced surgically).Хроническая послеоперационная боль (ПОБ) – серьезное осложнение тотального эндопротезирования (ТЭ) коленного (КС) и тазобедренного (ТБС) суставов.Цель исследования – определение факторов, ассоциирующихся с ПОБ у пациентов, перенесших ТЭ КС или ТБС.Пациенты и методы. Исследуемую группу составили 124 пациента с ОА КС или ТБС (возраст 63,6±9,9 года, 63% женщины и 37% мужчины), которым было проведено ТЭ КС или ТБС. ПОБ определяли как боль ≥40 мм по числовой рейтинговой шкале, персистирующую ≥3 мес. Ее наличие оценивалось через 3 и 6 мес путем телефонного опроса. Проведено сопоставление пациентов с ПОБ и ее отсутствием по ряду факторов, выделенных до операции.Результаты и обсуждение. Частота ПОБ составила 27,4%. Не выявлено различия в частоте ПОБ у пациентов после ТЭ КС или ТБС: 28,1 и 26,9% (р=0,88). ПОБ статистически значимо была связана с такими параметрами, как более высокие индекс массы тела (ИМТ); интенсивность боли в покое; оценка нарушения самочувствия; индекс WOMAC боль, скованность и общий; выраженность симптомов невропатической боли (PainDETECT); признаки депрессии и тревожности (HADS).Риск ПОБ был значимо выше (p<0,05) при ИМТ >30 кг/м2 (отношение шансов, ОШ 2,755; 95% доверительный интервал, ДИ 1,053–7,206), боли в покое ≥40 мм по визуальной аналоговой шкале (ОШ 1,349; 95% ДИ 0,478–3,803), показателях PainDETECT ≥13 (ОШ 3,598; 95% ДИ 1,048–12,36) и HADS депрессия ≥8 (ОШ 2,193; 95% ДИ 0,745–6,454), наличии ≥2 источников боли (ОШ 6,996; 95% ДИ 2,358–20,756).Заключение. Выявлено, что риск ПОБ после ТЭ КС и ТБС выше у пациентов с избыточной массой тела, выраженной предоперационной болью, признаками невропатической боли и депрессии, а также при наличии нескольких источников боли (кроме пораженного сустава, подлежащего ТЭ)

Antidepressant Response in Major Depressive Disorder: A Meta-Regression Comparison of Randomized Controlled Trials and Observational Studies

To compare response to antidepressants between randomized controlled trials (RCTs) and observational trials.Published and unpublished studies (from 1989 to 2009) were searched for by 2 reviewers on Medline, the Cochrane library, Embase, clinicaltrials.gov, Current Controlled Trial, bibliographies and by mailing key organisations and researchers. RCTs and observational studies on fluoxetine or venlafaxine in first-line treatment for major depressive disorder reported in English, French or Spanish language were included in the main analysis. Studies including patients from a wider spectrum of depressive disorders (anxious depression, minor depressive episode, dysthymia) were added in a second analysis. The main outcome was the pre-/post-treatment difference on depression scales standardised to 100 (17-item or 21-item Hamilton Rating Scale for Depression or Montgomery and Åsberg Rating Scale) in each study arm. A meta-regression was conducted to adjust the comparison between observational studies and RCTs on treatment type, study characteristics and average patient characteristics. 12 observational studies and 109 RCTs involving 6757 and 11035 patients in 12 and 149 arms were included in the main analysis. Meta-regression showed that the standardised treatment response in RCTs is greater by a magnitude of 4.59 (2.61 to 6.56). Study characteristics were related to standardised treatment response, positively (study duration, number of follow-up assessments, outpatients versus inpatients, per protocol analysis versus intention to treat analysis) or negatively (blinded design, placebo design). At patient level, response increased with baseline severity and decreased with age. Results of the second analysis were consistent with this.Response to antidepressants is greater in RCTs than in observational studies. Observational studies should be considered as a necessary complement to RCTs

BRCA1 is an essential regulator of heart function and survival following myocardial infarction

The tumour suppressor BRCA1 is mutated in familial breast and ovarian cancer but its role in protecting other tissues from DNA damage has not been explored. Here we show a new role for BRCA1 as a gatekeeper of cardiac function and survival. In mice, loss of BRCA1 in cardiomyocytes results in adverse cardiac remodelling, poor ventricular function and higher mortality in response to ischaemic or genotoxic stress. Mechanistically, loss of cardiomyocyte BRCA1 results in impaired DNA double-strand break repair and activated p53-mediated pro-apoptotic signalling culminating in increased cardiomyocyte apoptosis, whereas deletion of the p53 gene rescues BRCA1-deficient mice from cardiac failure. In human adult and fetal cardiac tissues, ischaemia induces double-strand breaks and upregulates BRCA1 expression. These data reveal BRCA1 as a novel and essential adaptive response molecule shielding cardiomyocytes from DNA damage, apoptosis and heart dysfunction. BRCA1 mutation carriers, in addition to risk of breast and ovarian cancer, may be at a previously unrecognized risk of cardiac failure

Локальная инъекционная терапия в комплексном лечении болезней костно-мышечной системы: основные принципы использования, доказательная база, безопасность

Local injection therapy (LIT)  is an important component of the complex treatment of musculoskeletal disorders (MSD), which is widely used in real clinical practice. Glucocorticoids, hyaluronic acid drugs (HA), autologous cell drugs, botulinum toxin type A, radioactive isotopes, etc. are used for LIT.  LIT makes it possible to achieve a pronounced symptomatic effect, while in some cases, for example, repeated HA treatments in patients with osteoarthritis, the possibility of slowing the progression of the disease and reducing the need for surgical treatment is discussed.The performance of LIT requires special skills and abilities of the physician, careful compliance with the rules of asepsis and antisepsis, and instrumental visualization. LIT can be associated with serious complications and therefore must be performed according to strict indications.The Expert Council was devoted to defining the basic principles of LIT. The indications for the use of certain types of this therapies, the evidence base for its efficacy and safety, the order of application of different drugs, and the need to combine LIT with other drug and non-drug treatments of MSD were reviewed.Локальная инъекционная терапия (ЛИТ)  – важная составляющая комплексного лечения болезней костно-мышечной системы (БКМС), широко используемая в реальной клинической практике. Для ЛИТ применяются глюкокортикоиды, препараты гиалуроновой кислоты (ГлК), аутологичные клеточные препараты, ботулинический токсин типа А, радиоактивные изотопы и др. ЛИТ позволяет добиться выраженного симптоматического эффекта, при этом в ряде случаев, например при проведении повторных курсов лечения ГлК у пациентов с остеоартритом, обсуждается возможность замедления прогрессирования заболевания и снижения потребности в хирургическом лечении.Проведение ЛИТ требует специальной компетенции и навыков врача, тщательного соблюдения правил асептики и антисептики, инструментальной визуализации.  ЛИТ  может быть сопряжена с серьезными осложнениями, поэтому должна выполняться по строгим показаниям.Совет экспертов был посвящен определению основных принципов ЛИТ. Были рассмотрены показания для применения тех или иных видов данной терапии,  доказательная база ее эффективности и безопасности, последовательность использования различных препаратов, а также необходимость комбинации ЛИТ с другими медикаментозными и немедикаментозными методами лечения БКМС