Comparative effectiveness of non-compounded polidocanol 1% endovenous microfoam (Varithena) ablation versus endovenous thermal ablation: A systematic review and network meta-analysis.

OBJECTIVE: We compared the effectiveness and safety of polidocanol 1% endovenous microfoam ablation vs endovenous thermal ablation with radiofrequency or laser energy for treatment of venous insufficiency caused by lower extremity truncal vein incompetence via network meta-analysis of published comparative evidence. METHODS: We conducted a systematic literature review following best practices, including a prospective protocol. We screened studies published in English from 2000 to 2023 for randomized and nonrandomized studies reporting direct or indirect comparisons between polidocanol 1% endovenous microfoam and endovenous thermal ablation. Thirteen studies met our eligibility criteria for the network meta-analysis. The co-primary effectiveness outcomes were the closure rate ≥3 months after procedure and the average change in the Venous Clinical Severity Score. For the subgroup of venous ulcer patients, the ulcer healing rate was the primary effectiveness outcome. The secondary outcomes included safety and patient-reported outcomes. Network meta-analyses were conducted on outcomes having sufficient data. Categorical outcomes were summarized using odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity tests and estimates of network inconsistency were used to investigate the robustness of our meta-analysis. RESULTS: We found that polidocanol 1% endovenous microfoam was not significantly different statistically from endovenous thermal ablation for venous closure (OR, 0.65; 95% CI, 0.36-1.18; P = .16). Although not the primary aim of the study, the network meta-analysis also provided evidence to confirm our supposition that polidocanol 1% endovenous microfoam was significantly differentiated statistically from physician-compounded foam, with higher odds for vein closure (OR, 2.91; 95% CI, 1.58-5.37; P < .01). A sensitivity analysis using the longest available time point for closure in each study, with a minimum of 12 months of follow-up (median, 48 months; range, 12-72 months), showed results similar to those of the main analysis. No association was found between the risk of deep vein thrombosis and the treatment received. The available data were insufficient for a network meta-analysis of Venous Clinical Severity Score improvement and ulcer healing rates. CONCLUSIONS: Polidocanol 1% endovenous microfoam was not significantly different statistically from endovenous thermal ablation for venous closure and deep vein thrombosis risk for chronic venous insufficiency treatment, based on a network meta-analysis of published evidence. Polidocanol 1% endovenous microfoam was significantly differentiated statistically from physician-compounded foam, with higher odds of vein closure. A sensitivity analysis found venous closure findings were robust at follow-up intervals of ≥12 months and for ≤6 years. New evidence meeting the inclusion criteria for this review will be incorporated at regular intervals into a living network meta-analysis.

Viroscope: Plant viral diagnosis from high-throughput sequencing data using biologically-informed genome assembly coverage.

High-throughput sequencing (HTS) methods are transforming our capacity to detect pathogens and perform disease diagnosis. Although sequencing advances have enabled accessible and point-of-care HTS, data analysis pipelines have yet to provide robust tools for precise and certain diagnosis, particularly in cases of low sequencing coverage. Lack of standardized metrics and harmonized detection thresholds confound the problem further, impeding the adoption and implementation of these solutions in real-world applications. In this work, we tackle these issues and propose biologically-informed viral genome assembly coverage as a method to improve diagnostic certainty. We use the identification of viral replicases, an essential function of viral life cycles, to define genome coverage thresholds in which biological functions can be described. We validate the analysis pipeline, Viroscope, using field samples, synthetic and published datasets, and demonstrate that it provides sensitive and specific viral detection. Furthermore, we developed Viroscope.io a web-service to provide on-demand HTS data viral diagnosis to facilitate adoption and implementation by phytosanitary agencies to enable precise viral diagnosis.

Preoperative thrombolysis is associated with improved vein patency and functional outcomes after first rib resection in acute Paget-Schroetter syndrome.

INTRODUCTION: Most patients with acute Paget-Schroetter syndrome (PSS) present in one of two manners: (1) thrombosis managed initially with thrombolysis and anticoagulation and then referred for surgery, and (2) initial treatment with anticoagulation only and later referral for surgery. Definitive benefits of thrombolysis in the acute period (the first 2 weeks after thrombosis) over anticoagulation alone have not been well reported. Our goal was to compare patients managed with early thrombolysis and anticoagulation followed by first rib resection (FRR) and later postoperative venography with venoplasty (PTA) with those managed with anticoagulation alone followed by FRR and PTA using vein patency assessed with venography and standardized outcome measures. METHODS: We reviewed a prospectively collected database from 2000 to 2019. Two groups were compared: those managed with early thrombolysis at our institution (Lysis) and those managed with anticoagulation alone (NoLysis). All patients underwent FRR. Venography was routinely performed before and after FRR. Standardized outcome measures included Quick Disability of Arm, Shoulder, and Hand (QuickDASH) scores and Somatic Pain Scale. RESULTS: A total of 50 Lysis and 50 NoLysis patients were identified. Pre-FRR venography showed that thrombolysis resulted in patency of 98% of veins, whereas 78% of NoLysis veins were patent. After FRR, postoperative venography revealed that 46 (92%) patients in the Lysis group and 37 (74%) patients in the NoLysis group achieved vein patency. Thrombolysis was significantly associated with final vein patency (odds ratio: 17 [4-199]; P < .001). Lysis patients had a trend toward lower QuickDASH scores from pre-FRR to post-FRR compared with NoLysis patients with a mean difference of -16.4 (±19.7) vs -5.2 (±15.6) points (P = .13). The difference in reduction of Somatic Pain Scale scores was not statistically significant. CONCLUSIONS: Thrombolysis as initial management of PSS, combined with anticoagulation, followed by FFR and VenoPTA resulted in improved final vein patency and may lead to an improved functional outcome measured with QuickDASH scores. Therefore, clinical protocols using thrombolysis as initial management should be considered when planning the optimal treatment strategy for patients with acute PSS.

A new approach of immunotherapy against Crotalus snakes envenoming: ostrich (Struthio camelus) egg yolk antibodies (IgY-technology) / Un nuevo enfoque de inmunoterapia contra el envenenamiento de serpientes Crotalus: anticuerpos de yema de huevo de avestruz (Struthio camelus) (tecnología IgY)

Abstract Crotalid envenomation is a neglected collective health problem involving many countries in America, which need secure and inexpensive snake anti-venom treatments. Here, high antibody titers (IgY) were raised in the Ostrich (Struthio camelus) egg yolk by immunizing with the venom of Venezuelan venomous Crotalus snakes. Ostriches were immunized with a pool of venoms from common rattlesnake (Crotalus durissus cumanensis), Uracoan rattlesnake (Crotalus vegrandis), Guayana rattlesnake (Crotalus durissus ruruima) and black rattlesnake (Crotalus pifanorum). The anti-snake venom antibodies were prepared from egg yolk by the water dilution method, enriched by the addition of caprylic acid (CA) and precipitation with ammonium sulfate at 30% (W/V). The purity and molecular mass of the final product was satisfactory, yielding a single ∼ 175 kDa band in SDS-PAGE gels ran under non-reducing conditions. In the immunoblot analysis, specific binding of the antivenom was observed with most venom proteins. The LD50 was 16.5 g/mouse (825 μg/kg body weight). High titers of IgY against Crot/pool venom were shown by ELISA. The median effective dose (ED50) was 19.66 mg/2LD50. IgY antibodies neutralized efficiently the Crot/pool venom lethality. As far as we know, this is the first anti-snake venom produced in ostriches, which could make this technology an affordable alternative for low-income countries, since it is likely to produce manteniabout 2-4 g of IgY per ostrich egg. Hence, almost 400 g of IgY can be purified from only one ostrich during a year. In addition, there are enormous differences in the cost of investment in the maintenance of horses, from the points of view of infrastructure, feeding and veterinary care, in which the cost can reach USD 100 per animal per day, compared to a maintenance cost of USD 146 per month per producing bird. These results are encouraging and could easily be extrapolated to the manufacturing of other antivenoms and antitoxins as well, as they could be applied to the manufacturing of potential diagnostic tools.

Resumen El envenenamiento por crotálidos es un problema de salud colectiva desatendido, que involucra a muchos países del continente americano, los cuales necesitan tratamientos seguros y económicos. En este trabajo, se obtuvieron títulos altos de anticuerpos (IgY) producidos en yema de huevo de avestruz (Struthio camelus) mediante la inmunización con el veneno de serpientes venezolanas del genero Crotalus. Se inmunizaron avestruces con una colección de veneno de serpientes de cascabel común (Crotalus durissus cumanensis), cascabel de Uracoa (Crotalus vegrandis), cascabel de Guayana (Crotalus durissus ruruima) y cascabel negra (Crotalus pifanorum). Los anticuerpos anti-veneno de serpiente se prepararon a partir de yema de huevo por el método de dilución en agua, enriquecidos mediante la adición de ácido caprílico (CA), seguido de una precipitación con sulfato de amonio al 30% (P/V). La pureza y masa molecular de los anticuerpos (IgY) se definieron mediante ensayos de SDS-PAGE nativos y las masas moleculares se establecieron electroforéticamente, obteniéndose una única banda de IgY de ∼ 175 kDa. El análisis de inmunotransferencia mostró la unión específica del antiveneno con la mayoría de las proteínas del veneno. La DL50 fue de 16,5 μg/ratón (825 μg / kg de peso corporal); Se mostraron títulos altos de IgY contra el veneno de Crot / pool mediante ELISA. La dosis mediana efectiva (DE50) fue de 19,66 mg/2 LD50. Los anticuerpos IgY neutralizaron eficazmente la letalidad del veneno de Crot / pool. Hasta donde sabemos, se trata del primer antídoto de serpiente producido en avestruces, lo que podría abaratar la producción de este tratamiento en países del tercer mundo. Ya que es probable que se obtengan alrededor de 2-4 g de IgY por huevo de avestruz. Por lo tanto, se podrían purificar casi 400 g de IgY de un solo avestruz durante un año. Asimismo, debido a las enormes diferencias en el costo de inversión en el mantenimiento de los caballos desde el punto de vista de infraestructura, alimentación y atención veterinaria, en los que el costo puede llegar a los 100 USD por día, frente a los 146 USD por mes de mantenimiento de la producción de aves. Estos resultados abren un campo terapéutico, para la fabricación de otros antivenenos contra un amplio espectro de toxinas y también como probables herramientas de diagnóstico.

Evaluation of health outcomes after the implementation of rotational thromboelastometry in patients undergoing cardiac surgery.

BACKGROUND: Viscoelastic tests (rotational thromboelastometry, ROTEM®), together with the implementation of a specific algorithm for coagulation management in cardiac surgery, enable perioperative coagulopathy to be better controlled. METHODS: Retrospective cohort study including 675 patients who underwent cardiac surgery with cardiopulmonary bypass. The incidence of allogeneic blood transfusions and clinical postoperative complications were analyzed before and after ROTEM® implementation. RESULTS: Following viscoelastic testing and the implementation of a specific algorithm for coagulation management, the incidence of any allogeneic blood transfusion decreased (41.4% vs 31.9%, p = .026) during the perioperative period. In the group monitored with ROTEM®, decreased incidence of transfusion was observed for packed red blood cells (31.3% vs 19.8%, p = .002), fresh frozen plasma (9.8% vs 3.8%, p = .008), prothrombin complex concentrate administration (0.9% vs 0.3%, p = .599) and activated recombinant factor VII (0.3% vs 0.0%, p = .603). Increased incidence was observed for platelet transfusion (4.8% vs 6.8%, p = .530) and fibrinogen concentrate (0.9% vs 3.5%, p = .066), tranexamic acid (0.0% vs 0.6%, p = .370) and protamine administration (0.6% vs 0.9%, p = .908). Similar results were observed in the postoperative period, but with a decreased incidence of platelet transfusion (4.8% vs 3.8%, p = .813). In addition, statistically significant reductions were detected in the incidence of postoperative bleeding (9.5% vs 5.3%, p = .037), surgical reexploration (6.0% vs 2.9%, p = .035), and length of Intensive Care Unit (ICU) stay (6.0 days vs 5.3 days, p = .026). CONCLUSIONS: The monitoring of hemostasis by ROTEM® in cardiac surgery, was associated with decreased incidence of allogeneic blood transfusion, clinical hematologic postoperative complications and lengths of ICU stay.

Increased climate pressure on the agricultural frontier in the Eastern Amazonia-Cerrado transition zone.

Several large-scale drivers of both anthropogenic and natural environmental changes are interacting nonlinearly in the transition zone between eastern Amazonia and the adjacent Cerrado, considered to be another Brazilian agricultural frontier. Land-use change for agrobusiness expansion together with climate change in the transition zone between eastern Amazonia and the adjacent Cerrado may have induced a worsening of severe drought conditions over the last decade. Here we show that the largest warming and drying trends over tropical South America during the last four decades are observed to be precisely in the eastern Amazonia-Cerrado transition region, where they induce delayed wet-season and worsen severe drought conditions over the last decade. Our results evidence an increase in temperature, vapor pressure deficit, subsidence, dry-day frequency, and a decrease in precipitation, humidity, and evaporation, plus a delay in the onset of the wet season, inducing a higher risk of fire during the dry-to-wet transition season. These findings provide observational evidence of the increasing climatic pressure in this area, which is sensitive for global food security, and the need to reconcile agricultural expansion and protection of natural tropical biomes.

Elective Resection of Symptomatic Arteriovenous Fistulae and Grafts in Patients with Functioning Renal Allografts at A High Volume Transplant Hospital.

OBJECTIVE: Patients with functioning renal allografts may need ligation of pre-existing hemodialysis conduits. Chronic immunosuppression for renal allografts may adversely affect wound healing and perioperative complications following these procedures. We sought to analyze outcomes following elective ligation and resection of symptomatic arteriovenous (AV) access in immunosuppressed patients with renal allografts no longer requiring dialysis at a high-volume renal transplant hospital. METHODS: We retrospectively reviewed procedure codes for hemodialysis access resection and revision from 2014-2020 at a single academic tertiary care hospital. Patients who underwent complete or subtotal dialysis access resection with a functioning renal allograft were included for analysis of preoperative, operative, and postoperative outcomes. We performed descriptive statistics, and student's t-test using Microsoft Excel. RESULTS: Thirty-four patients met inclusion criteria. The majority were male, 56%, and the most common causes of renal failure were hypertension and diabetes, respectively. Ligation and resection of proximal upper extremity access was performed in 68%. The mean operative time was 126 minutes with pain being the most common indication for intervention. Four patients required arterial reconstruction. Mean postoperative follow-up was 13 months. Arm pain and swelling resolved in 100% and 88% of patients following AV access resection, respectively. No impairment in mean postoperative glomerular filtration rates were noted. One patient required hemodialysis and died three months after fistula resection following complications from treatment of a newly diagnosed neuroendocrine tumor and subsequent fungemia, CONCLUSION: Elective operative resection of symptomatic AV access may be performed safely in immunosuppressed patients with functioning renal transplants. The risk of allograft impairment and/or failure as a result of AV access resection in our series was low. Elective ligation and resection can be achieved with low mortality, excellent symptomatic relief, and few wound complications despite chronic immunosuppression.

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder.

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.

Fisheries interactions and the challenges for target and nontargeted take on shark conservation in the Mexican Pacific.

Sharks have been of great cultural and socioeconomic importance in Mexico since the late 19th century, when the first fisheries were prosecuted in the Gulf of California to export fins to China. Mexican shark and ray fisheries are classified mainly by the size of the fishing vessel and include small- (7.5-10m), medium- (10-27m), and large-sized (>27m) fisheries. All are multispecies fisheries that use longline or gillnet gear, with their relative productivity varying over time. Off the Pacific coast, early shark small size vessel fisheries in the Gulf of California were driven by the need for vitamin A from livers, especially during World War II. As this fishery declined, new shark fishing opportunities arose because of government support and the development of the medium-sized fishery, which was capable of farther offshore excursions. Shark meat became an important part of the diets of poor and impoverished citizens during the 1950s and 1960s. The establishment of a Mexican Exclusive Economic Zone in 1976 pushed foreign vessels from Asia out of Mexican waters and led to the development of the large-sized vessel fishery to exploit pelagic sharks in offshore waters. By the early 1980s, Mexico shark fisheries were among the most productive in the world; however, a national economic crisis reduced effort and landings until the late 1980s, when several new fisheries emerged. Landings from Pacific states fluctuated between ~13,000 and 24,000t (dressed weight) during 1987-2012 but expanded steadily thereafter because of government support and offshore fleet expansion. Shark fisheries landings from the Mexican Pacific are currently at their highest recorded levels, exceeding 31,000t; however, a lack of species-specific landings and life history information has precluded population assessments of targeted stocks. In addition, though several recent management measures have been enacted to protect Mexican shark and ray fishery resources, the enforcement of these regulations is severely lacking. Therefore, the long-term sustainability of current fishing levels is unknown but should engender concern based on anecdotal evidence of serial depletion among historical elasmobranch targets in the Mexican Pacific.

Administration of low doses of the 5-HT1A receptor agonist 8-OH-DPAT attenuates the discriminative signal of amphetamine in the conditioned taste aversion procedure.

Several studies have reported that low doses of the 5-HT1A receptor agonist 8-OH-DPAT reduce cocaine-induced locomotor activity. However, it has also been reported that high doses of 8-OH-DPAT do not substitute for or alter the discriminative signal of cocaine (COC) or amphetamine (AMPH). This study aimed to evaluate the effects of low and high doses of the 5-HT1A agonist 8-OH-DPAT on the discriminative signal of AMPH using conditioned taste aversion as a drug discrimination procedure. Additionally, to establish a correlation between the behavioral effects in drug discrimination and changes in dopamine (DA) and gamma-aminobutyric acid (GABA) concentrations, we evaluated the effect of systemic administration of low or high doses of the 5-HT1A receptor agonist 8-OH-DPAT and of the 5-HT1A receptor antagonist WAY100135 on DA and GABA extracellular concentrations in the nucleus accumbens (nAcc) and ventral tegmental area (VTA), respectively, using cerebral microdialysis. The behavioral results showed that low but not high doses of 8-OH-DPAT produced a reduction in the AMPH-induced discriminative signal, while WAY100135 administration prevented such effects. The microdialysis results showed that a low dose of 8-OH-DPAT decreased extracellular DA concentrations in the nAcc and increased GABA concentrations in the VTA. Pretreatment with WAY100135 prevented these effects. These data support the hypothesis that 5-HT1A receptors modulate the behavioral effects of psychostimulant drugs, such as AMPH, through somatodendritic 5-HT1A autoreceptors in the raphe nucleus indicating that 5-HT1A receptors may be an important target for the development of pharmacological treatments for psychostimulant addiction.

Temporal and latitudinal comparisons of reproductive parameters in a heavily exploited shark, the bonnethead, Sphyrna tiburo (L. 1758), in the southern Gulf of Mexico.

In the southern Gulf of Mexico, the bonnethead shark, Sphyrna tiburo, is one of the most frequently captured species in landings of small-scale fisheries. Based on the analysis of two fishery-dependent sampling periods (1993-1994 and 2007-2014), this study aimed to determine reproductive parameters and identify temporal differences between the two time periods. In the first sampling period, 776 males and 352 females with a size range of 28.0-120.0 cm total stretched length (LT ) were analysed, and in the second sampling period, 387 males and 432 females with a size range of 28.0-122.0 cm LT were analysed. The size at 50% maturity in the second sampling period was significantly different between sexes, 82.6 cm LT for females and 73.8 cm LT for males (no estimation was possible for the first sampling period). The size at 50% maternity was not different between sampling periods, 97.3 cm LT for the first sampling period and 99.0 cm LT for the second sampling period. Litter size varied from 3 to 19 embryos and the average was not statistically different in both periods, 10.1 (S.D. = 3.8) for the first sampling period and 11.3 (S.D. = 3.5) for the second sampling period. The female reproductive cycle is asynchronous, and it seems to be annual, with a gestation period of 5-6 months, and a consecutive ovarian cycle and gestation period. Temporal (between sampling periods) and latitudinal (southern Gulf versus northern regions) variations occur in the synchronicity of the reproductive cycle, temporal variation in the relationship between maternal length and litter size, and latitudinal variation in average size of mature sharks.

Short- and intermediate-term clinical outcome comparison between laparoscopic and robotic-assisted median arcuate ligament release.

While laparoscopic median arcuate ligament (MAL) release remains the most common approach, robotic-assisted MAL release has been increasingly performed by several institutions. This study aims to compare surgical outcomes between laparoscopic and robotic-assisted MAL release. This is a retrospective study of patients undergoing laparoscopic and robotic-assisted MAL release in a teaching hospital from January 1999 to December 2018. Intraoperative and postoperative outcomes as well as short- and intermediate-term clinical outcomes were compared between the two groups. A total of 16 laparoscopic and 18 robotic cases were included. Demographics and baseline characteristics were similar between the two comparison groups. Median operative time was shorter in the robotic group [179.5 (IQR 127.3-225) vs. 106 (IQR 80.8-122.8) minutes; p < 0.001]. The rates of conversion to open operation were similar in both groups (6.3% vs. 5.6%, p = 0.99). Conversions to laparotomy were performed due to bleeding and extensive adhesions in one laparoscopic case and due to technical difficulties in a patient with narrow body habitus in the robotic group. Postoperative complication rates were similar (12.5% vs. 16.7%, p = 0.99), all in grade I and II. Complete pain resolution rates (37.5% vs. 44.4%, p = 0.93), symptom recurrence rates (37.5% vs. 27.8%, p = 0.93), and overall clinical improvement at last follow-up (87.5% vs. 77.8%, p = 0.66) were not statistically different. Both laparoscopic and robotic-assisted MAL release offer similar short- and intermediate-term clinical outcomes. A shortened operative time may be achieved by incorporating the robot platform.

Factors Associated with Symptomology of Celiac Artery Compression and Outcomes following Median Arcuate Ligament Release.

BACKGROUND: This study aims to identify potential risk factors for becoming symptomatic in patients with radiographic celiac artery compression (CAC) as well as prognostic factors for patients with median arcuate ligament syndrome (MALS) who underwent surgical ligament release. METHODS: This is a retrospective cohort study of patients with findings of CAC on computed tomography or magnetic resonance angiography (CT/MRA) who were asymptomatic and who were diagnosed with MALS at a single university hospital between January 2001 and 2018. RESULTS: Following a review of 1,330 CT/MRA reports, a total of 109 patients were identified as having radiographically apparent CAC. Among these, 48 (44.0%) patients were symptomatic. Univariate comparison between those with and without symptoms showed that symptomatic patients were more commonly younger than 30 years old [17/48 (35.4%) vs. 8/61 (13.1%), P = 0.006], had a history of prior abdominal surgery [25/48 (52.1%) vs. 18/61 (29.5%), P = 0.017], and had high-grade stenosis [32/43 (74.4%) vs. 25/61 (41.0%), P = 0.001]. Among 41 included patients who underwent surgical release of the median arcuate ligament including open, laparoscopic, and robotic approaches, 82.9% reported overall clinical improvement, 5/41 (12.2%) reported persistent pain, and 13/36 (36.0%) experienced pain recurrence. The only identified risk factor associated with symptom recurrence was American Society of Anesthesiologists class III [7/13 (53.8%) vs. 4/23 (17.4%), P = 0.029]. CONCLUSIONS: The severity of stenosis and prior abdominal surgery both contributed to symptom development in patients with radiographically apparent CAC from the median arcuate ligament.

Mutacytin-1, a New C-Type Lectin-Like Protein from the Venezuelan Cuaima (Lachesis muta muta Linnaeus, 1766) (Serpentes: Viperidae) Snake Venom Inducing Cardiotoxicity in Developing Zebrafish (Danio rerio) Embryos.

Envenomation by the Venezuelan bushmaster snake (Lachesis muta muta) (Serpentes: Viperidae) is characterized by local and cardiac alterations. This study investigates the in vivo cardiac dysfunction, tissue destruction, and cellular processes triggered by Lachesis muta muta snake crude venom and a C-type lectin (CTL)-like toxin named Mutacytin-1 (MC-1). The 28 kDa MC-1 was obtained by molecular exclusion, ion exchange, and C-18 (checking pureness) reverse-phase chromatographies. N-terminal sequencing of the first eight amino acids (NNCPQ LLM) revealed 100% identity with Mutina (CTL-like) isolated from Lachesis stenophrys, which is a Ca2+-dependent-type galactoside-binding lectin from Bothrops jararaca and CTL BpLec from Bothrops pauloensis. The cardiotoxicity in zebrafish of MC-1 was evaluated by means of specific phenotypic expressions and larvae behavior at 5, 15, 30, 40 and 60 min post-treatment. The L. muta muta venom and MC-1 also produced heart rate/rhythm alterations, circulation modifications, and the presence of thrombus and apoptotic phenomenon with pericardial damages. Acridine orange (100 µg/mL) was used to visualize apoptosis cellular process in control and treated whole embryos. The cardiotoxic alterations happened in more than 90% of all larvae under the action of L. muta muta venom and MC-1. The findings have demonstrated the potential cardiotoxicity by L. muta muta venom, suggesting the possibility of cardiovascular damages to patients after bushmaster envenoming.

A novel sequencing-based vaginal health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis.

The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a woman's reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive vaginal health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 31 bacterial taxa of clinical importance, including Lactobacillus, Sneathia, Gardnerella, and 3 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, reference ranges were determined in a group of 50 self-reported healthy women. The HPV sequencing portion of the test was evaluated against the digene High-Risk HPV HC2 DNA test. For hrHPV genotyping, agreement was 95.3% with a kappa of 0.804 (601 samples); after removal of samples in which the digene hrHPV probe showed cross-reactivity with lrHPV types, the sensitivity and specificity of the hrHPV genotyping assay were 94.5% and 96.6%, respectively, with a kappa of 0.841. For lrHPV genotyping, agreement was 93.9% with a kappa of 0.788 (148 samples), while sensitivity and specificity were 100% and 92.9%, respectively. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.

Effect of coadministration of the GABAB agonist baclofen and the 5-HT2C agonist Ro60-0175 on the expression of amphetamine-induced locomotor sensitization.

GABAB and 5-HT2C agonists are effective in attenuating the behavioral effects of psychostimulants. However, they induce adverse side effects when used in high doses. The previous evidence has suggested that the 5HT2C receptor activation effect could be produced by an increased release of GABA in the ventral tegmental area (VTA) and the consequent activation of GABAergic receptors. Therefore, the objective of this study was to evaluate the effects of joint administration of an intermediate dose of the GABAB agonist baclofen (3.0 mg/kg) with different doses of the 5HT2C agonist Ro60-0175 (0.3, 1.0, and 3.0 mg/kg) on the locomotor sensitization expression induced by the repeated administration of amphetamine (1.0 mg/kg). Our results showed an attenuation of the expression of sensitization in a dose-dependent manner with both agonists. In both cases, we observed a complete blockade at the highest dose. In addition, the intermediate dose of baclofen increased the effects of the three doses of Ro60-0175. These results support the role of the joint action of GABAB and 5-HT2C receptors in the effects of psychostimulants. However, it remains to be explored whether the observed effect can be attributed to receptors located in the VTA or the nucleus accumbens.

Spatio-temporal patterns of thermal anomalies and drought over tropical forests driven by recent extreme climatic anomalies.

The recent 2015-2016 El Niño (EN) event was considered as strong as the EN in 1997-1998. Given such magnitude, it was expected to result in extreme warming and moisture anomalies in tropical areas. Here we characterize the spatial patterns of temperature anomalies and drought over tropical forests, including tropical South America (Amazonia), Africa and Asia/Indonesia during the 2015-2016 EN event. These spatial patterns of warming and drought are compared with those observed in previous strong EN events (1982-1983 and 1997-1998) and other moderate to strong EN events (e.g. 2004-2005 and 2009-2010). The link between the spatial patterns of drought and sea surface temperature anomalies in the central and eastern Pacific is also explored. We show that indeed the EN2015-2016 led to unprecedented warming compared to the other EN events over Amazonia, Africa and Indonesia, as a consequence of the background global warming trend. Anomalous accumulated extreme drought area over Amazonia was found during EN2015-2016, but this value may be closer to extreme drought area extents in the other two EN events in 1982-1983 and 1997-1998. Over Africa, datasets disagree, and it is difficult to conclude which EN event led to the highest accumulated extreme drought area. Our results show that the highest values of accumulated drought area over Africa were obtained in 2015-2016 and 1997-1998, with a long-term drying trend not observed over the other tropical regions. Over Indonesia, all datasets suggest that EN 1982-1983 and EN 1997-1998 (or even the drought of 2005) led to a higher extreme drought area than EN2015-2016. Uncertainties in precipitation datasets hinder consistent estimates of drought severity over tropical regions, and improved reanalysis products and station records are required.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.

Robotic-assisted laparoscopic median arcuate ligament release: 7-year experience from a single tertiary care center.

BACKGROUND: Despite previous reports of robotic-assisted laparoscopic release for median arcuate ligament syndrome (MALS), the safety and efficacy profile of this approach has been difficult to establish due to the rarity of this diagnostic entity. We aim to present our experience from a tertiary minimally invasive surgery referral center. METHODS: A case series was performed whereby all patients who underwent robotic-assisted MAL release from July 2010 to July 2017 at our institution were included. Diagnosis of MALS was made based on consideration of symptom presentation, celiac artery duplex ultrasound, and corresponding findings on Computed Tomography (CT) or Magnetic Resonance Angiography (MRA). Outcomes up until the most recent clinic follow-up were reviewed. RESULTS: A total of 13 patients underwent robotic-assisted MAL release. Patients' age ranged from 16 to 71 years (mean 38 years) and consisted primarily of females (76.9%). Most common presenting symptoms included postprandial pain (76.9%), weight loss (76.9%), nausea and vomiting (76.9%). Mean symptom duration was 3 years (range 1-10 years). No intraoperative complications. None required conversion to open surgery. One case required a conversion back to laparoscopy due to anatomical complexity. The mean operative time for successfully completed robotic cases was 94.6 min (range 52-120 min), and for all cases including converted case was 103.5 min (52-210 min). Mean follow-up duration was 19.7 months (range 1-77 months). During subsequent follow-up, a 30-day readmission rate of 23.1% was observed. All but one of the patients experienced prompt symptom improvement. Four patients had symptom recurrence during follow-up. CONCLUSIONS: Our experience demonstrates that the robotic-assisted approach to MAL release may be safe and efficacious in selected patients. Prospective comparative studies are required to further evaluate its outcomes against conventional laparoscopic approach, the current gold standard.

Differentiation of Ecuadorian National and CCN-51 cocoa beans and their mixtures by computer vision.

BACKGROUND: Ecuador exports two major types of cocoa beans, the highly regarded and lucrative National, known for its fine aroma, and the CCN-51 clone type, used in bulk for mass chocolate products. In order to discourage exportation of National cocoa adulterated with CCN-51, a fast and objective methodology for distinguishing between the two types of cocoa beans is needed. RESULTS: This study reports a methodology based on computer vision, which makes it possible to recognize these beans and determine the percentage of their mixture. The methodology was challenged with 336 samples of National cocoa and 127 of CCN-51. By excluding the samples with a low fermentation level and white beans, the model discriminated with a precision higher than 98%. The model was also able to identify and quantify adulterations in 75 export batches of National cocoa and separate out poorly fermented beans. CONCLUSION: A scientifically reliable methodology able to discriminate between Ecuadorian National and CCN-51 cocoa beans and their mixtures was successfully developed. © 2017 Society of Chemical Industry.

Efficacy of Distal Perfusion Cannulae in Preventing Limb Ischemia During Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

To date, no consensus exists regarding indication, technique, or efficacy of distal perfusion cannulae (DPC) in preventing limb ischemia among patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). We aim to examine the available literature and report association between DPC and risk of limb ischemia. PubMed/Medline, Scopus, Cochrane Central Register of Controlled Trials, Google Scholar, and bibliographies of included studies were searched from database inception until August 2016. Original studies describing the DPC placement technique and incidence of limb ischemia following DPC placement among VA-ECMO patients were included for systematic review. Studies with a comparison group of patients without DPC were included for meta-analysis. Two authors independently screened title/abstracts, reviewed full texts, and extracted data from the eligible studies. Meta-analysis was performed using the Mantel-Haenszel method under a random-effects model. Statistical heterogeneity was examined with the I2 statistic (RevMan Version 5.3). Of 542 title/abstracts screened, 62 full text articles were selected for review, yielding 22 retrospective observational studies, for a total of 779 patients with 132 limb ischemia events. There was significant variation in DPC indication, cannula type, and placement technique among the studies. Compared to no DPC, the presence of a DPC was associated with at least a 15.7% absolute reduction in the incidence of limb ischemia (9.74 vs. 25.42%; risk ratio 0.41; 95% confidence interval 0.26-0.65, P < 0.01; heterogeneity statistic I2 = 28%). There was no statistically significant difference in mortality in the pooled dataset comparing DPC versus no DPC. In adults treated with VA-ECMO, DPC placement was associated with a lower incidence of limb ischemia. Currently no consensus guidelines exist regarding indication for DPC placement. Given the association described in this analysis, future prospective trials are warranted to establish a causal relationship and optimal technique for the use of DPC in patients treated with VA-ECMO.