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Colombia has a high prevalence of mucopolysaccharidosis (MPS) type IVA. Nevertheless, data regarding the mutation spectrum for MPS IVA in this population have not been completely characterized. Forty-seven families and 53 patients from seven different Colombian regions were tested for MPS IVA mutations. We compared the sequences with the N-acetylgalactosamine-6-sulfatase (GALNS) reference sequence NM_000512.4, and gene variants were reported. Bioinformatics analysis was performed using SWISS-MODEL. The mutant proteins were generated by homology from the wild-type GALNS 4FDJ template obtained from the PDB database, and visualization was performed using Swiss-PDBViewer and UCSF Chimera. The predictive analysis was run using different bioinformatic tools, and the deleterious annotation of genetic variants was performed using a neural network. We found that 79% and 21% of the cohort was homozygous and compound heterozygous, respectively. The most frequent mutation observed was p.Gly301Cys (78.3% of alleles), followed by p.Arg386Cys (10.4% of alleles). A novel mutation (p.Phe72Ile) was described and classified in silico as a pathogenic variant. This study reveals the mutation spectrum of MPS IVA in Colombia. The high prevalence of the p.Gly301Cys mutation suggests a founder effect of this variant in the Colombian population that causes diseases in the Andean region (via migration). These data can facilitate genetic counseling, prenatal diagnosis, and the design of therapeutic interventions.

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.

Objective In small for gestational age (SGA) children, catch-up growth could be influenced by methylation of several genes involved in metabolism. Epigenetics may influence the development of metabolic diseases in adulthood. To compare the methylation of leptin (LEP), glucagon-like peptide-2 receptor (GLP2R), insulin receptor substrate-2 (IRS2) in SGA patients with and without catch-up growth. Methods Observational prospective study of SGA children. Demographical and clinical variables were collected from clinical records and parents’ questionnaire. Methylation status of LEP, IRS2, and GLP2R promoters was evaluated in DNA extracted from patient and one parent saliva samples. Results Forty-eight SGA patients were included. Twenty-six (54.2%) had catch-up growth phenotype and 22 (45.8%) did not. The median age was 5.2 years [RIC 4.1-6.8] without difference between groups (p=0.306). The catch-up group had increased appetite (42.3% vs 9.1%, p=0.008), family history of dyslipidemia (42.3% vs 27.3%) and diabetes (34.6% vs 22.7%) compared to non-catch-up group. Catch-up patients had significantly larger waist circumference compared to non-catch-up group (median 55 cm [RIC 52-58] versus median 49.5 cm [RIC46-52]; p

Fusarium graminearum is considered the main causative agent of Fusarium Head Blight in wheat. The fungus produces mycotoxins of the trichothecene family that pose a significant threat to the health of animals and humans. The objective of this work was to analyze the effect of the time of fungicide application on the trichothecene production in 8 inoculated wheat varieties. The fungicide Tebuconazole was applied in two independent stages: immediately after inoculation and after 72 h of the inoculation (infective event derived from 72 h of wetting). The detection of mycotoxins was performed by gas chromatography with electron capture detector and the results were confirmed by gas chromatography coupled to a mass spectrometer. Significant levels of deoxynivalenol were found in all samples and in almost all of them 15 acetyldeoxynivalenol was found in low concentration. Less frequently, 3 acetyldeoxynivalenol was found in higher values. There were not significant differences (p > 0.05) between the time of fungicide application (immediately after inoculation in anthesis and after 72 h) in all wheat varieties studied. The expansion of the fungicide application window for effective control of trichothecenes for 72 h represents an economic advantage for the producer avoiding the use of agrochemicals by preventive applications and minimizing the risk on human health and the environment.

This study incorporates curriculum mapping as a method to assess the effectiveness of approval plans supporting undergraduate psychology courses offered at a large research university. Usage data i...

Wheat is one of the most important crops in Argentina and worldwide. One of the major diseases affecting the crop is the Fusarium Head Blight (FHB). It is an endemic disease caused mainly by Fusarium graminearum, the most common agent of FHB around the world. The infection is strongly influenced by environmental parameters and occurs mostly when there are favourable conditions of moisture and temperature during wheat anthesis or flowering. This destructive disease affects wheat, barley and other small grains and has the capability of destroying crops, causing great economic losses due to reduced grain quality, and the accumulation of significant levels of mycotoxins such as trichothecenes. The aim of this study was to evaluate the influence of temperature on mycotoxin biosynthesis, on three strains of F. graminearum of 15-ADON genotype and one of 3-ADON genotype, with different capacity of synthesizing DON, 3-ADON and 15-ADON. Trichothecene production of the strains at different temperatures (5, 10, 15, 20, 25, 30 and 35 °C) was evaluated after 7, 14, 21, 28 and 35 d of incubation. The optimum temperature to produce DON and 3-ADON was between 25 and 30 °C, but the maximum production of 15-ADON occurred at a lower temperature (10 °C) for all the strains. Conversely, the minimum production of DON and 3-ADON was recorded between 5 and 10 °C and of 15-ADON between 30 and 35 °C. A possible explanation for the similar accumulation of both acetyl derivatives by strains of different chemotype and genotypes could be that the acetyl derivatives biosynthesis is regulated by temperature. Fil: Ramirez Albuquerque, Lady Diana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Micología y Botánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Micología y Botánica; Argentina Fil: Patriarca, Andrea Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Micología y Botánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Micología y Botánica; Argentina Fil: Fernández Pinto, Virginia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Micología y Botánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Micología y Botánica; Argentina

Our aim was to characterize the phenotype and genotype of individuals with Noonan syndrome in Colombia. There are published cohorts of Noonan individuals from several countries in Latin America including Brazil, Chile, and Argentina, but none from Colombia. We described 26 individuals with NS from a single large referral center in the South West of Colombia using an established database in the genetics department and hospital records search using ICD-10 codes. All patients included in this study were evaluated by a medical geneticist and have molecular confirmation of NS diagnosis. The median age at referral was 3.5 years (range, 0-39), and at molecular diagnosis was 5 years (range, 0-40). Patients mostly originated from the southwest region of Colombia (19/26, 73%). Pathogenic variants in PTPN11 are the most common cause of NS in Colombian individuals followed by SHOC2 and SOS1 variants. The prevalence of cardiomyopathy was low in this population compared to other populations. Further research is needed with a larger sample size and including different regions of Colombia to correlate our findings. This study provides new information about time to diagnosis of NS in Colombia, genotypes, and provides important information to help develop guidelines for diagnosis and management of this disease in the region.

Background: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population.Methods: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921.Findings: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [Interpretation: Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke.Funding: National Health and Medical Research Council of Australia.

Background:The uptake of smartphones as external compensatory memory aids following an acquired brain injury (ABI) in rehabilitation settings is low. Potential reasons for this include professionals not having evidence-based guidelines regarding the best methods to train smartphone use and prospective users not being familiar with technology and/or having memory and learning difficulties. This paper describes the protocol of a study that aims to compare the efficacy of three training methods (Systematic Instruction, Error-based Learning and Trial-and-Error) for training the use of a smartphone reminder app, in people with ABI presenting with memory complaints.Methods/Design:This is a three-armed, assessor-blinded, Phase II randomised controlled trial. The estimated sample size is 51 participants aged >18 years, who are equally randomised to one of the three training groups. They are seen across four sessions: one to conduct baseline measures; one for training the use of an app and two for follow-up assessments (1- and 6-weeks post-training). The main outcome measure is proficiency of performance in tasks with the trained app. Secondary outcomes include generalisation of skills to other apps, number of errors committed while attempting the tasks, frequency of smartphone usage in general and as a memory aid and confidence in smartphone use and memory self-efficacy. Outcome measures are collected by an independent blinded assessor. Proficiency of performance, generalisation of skills and error commission are measured immediately post-training and at the two follow-up sessions. The other secondary measures are taken pre-intervention and at the two follow-up sessions.Discussion:This study will provide initial evidence regarding the efficacy of three different methods to train ABI survivors with memory difficulties in how to use smartphone apps as compensatory memory aids. The results could inform a larger Phase III trial and advance knowledge concerning the advantages or disadvantages of using error-reducing and trial-and-error techniques. Further, the findings could determine the potential of error-based learning as an emerging training method for people with memory impairment within rehabilitation.

Education librarians are receiving an increasing number of requests to help researchers with systematic reviews. Systematic reviews are evidence syntheses that require comprehensive, reproducible s...

Smartphones are useful compensatory memory aids, yet training on how to use them is seldom offered as part of rehabilitation for acquired brain injuries (ABIs). We aimed to explore the experience and acceptability of a smartphone training intervention in 26 people with ABI who participated in a pilot randomized controlled trial comparing three skills training approaches. Participants completed questionnaire ratings and a semi-structured interview, six weeks post-training. Most participants rated the training as enjoyable (80.8%) and reasonable in duration (88.5%). Others reported that more than one training session was needed to learn the app (34.6%). Five themes were identified from qualitative data through thematic analysis: (1) Attitudes and pre-existing factors, (2) Experiencing the intervention, (3) Tailoring the intervention to the individual, (4) Facilitators and barriers to implementation and (5) Enhancing smartphone use in everyday life. These themes were juxtaposed with a theoretical framework of acceptability, which indicated that some elements (e.g., having a structured session and a supportive trainer) contributed to the acceptability of the intervention by minimizing training burden and increasing self-efficacy. Tailoring the training to the individual's technological skills and lifestyle, providing post-training resources and involving family members were identified as factors that could improve intervention acceptability.

Background Elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV HD) is the leading cause of death in captive Asian elephant calves in Asia, North America, and Europe with a mortality rate of ~ 65% in calves that are under human care. Although EEHV HD was first found in elephant camps, more recently it was identified in wild populations which poses a greater threat to the elephant population. Deaths due to EEHV HD have been seen in wild elephants, but the in-situ prevalence and mortality rate is unknown. We report the first EEHV HD cases in Malaysia from 3 wild born endangered Bornean elephant calves from Sabah with known typical clinical signs. Case presentation The first calf died within 24 h of the onset of clinical signs; the second calf died within 12 h of the onset of clinical signs. The third calf succumbed within 72 h. Necropsies revealed that all 3 calves had similar presentations of EEHV HD but in the third calf with less severity. We conducted conventional polymerase chain reaction (cPCR) assays and found EEHV DNA at all 7 loci in the 3 calves; it was identified as EEHV1A, the virus type that has been found in most other reported cases. Conclusion Typical EEHV HD clinical signs and the molecular confirmation of EEHV by cPCR and sequencing point to EEHV as the cause of death. Further genetic investigation of the strain is in progress.

This study aimed to compare the efficacy of three skills training methods (Trial and error TEL; systematic instruction SI; and error-based learning EBL) for training the use of a smartphone reminder app in individuals with an acquired brain injury. Participants (

Case Description: We report the case of a one-year-old girl who was diagnosed with Wiedemann-Steiner Syndrome based on the identification of a novel de novo frameshift mutation in the KMT2A gene by whole exome sequencing and supported by her clinical features. Clinical Findings: KMT2A mutations cause Wiedemann-Steiner Syndrome, a very rare genetic disorder characterized by congenital hypertrichosis, short stature, intellectual disability, and distinct facial features. Treatment and Outcome: Whole exome sequencing identified a novel frameshift variant: c. 4177dupA (p.Ile1393Asnfs * 14) in KMT2A ; this change generates an alteration of the specific binding to non-methylated CpG motifs of the DNA to the protein. The genotype and phenotype of the patient were compared with those of earlier reported patients in the literature. Clinical Relevance: In diseases with low frequency, it is necessary to establish a genotype-phenotype correlation that allows the establishment of therapeutic and follow-up goals. The phenotype comparation with other reported cases did not show differences attributable to sex or age among patients with Wiedemann-Steiner Syndrome. Whole exome sequencing allows identifying causality in conditions with high clinical and genetic heterogeneity like hypertrichosis.

Social sciences librarians have an interest in supporting systematic reviews, but the available guidance is focused on health sciences settings. This study contributes guidance specifically for social sciences librarians using the Campbell Collaboration’s standards to evaluate the search methods reported in systematic reviews on K–12 mathematics education. After searching ERIC (EBSCO), Education Source (EBSCO), Academic Search Ultimate (EBSCO), and Compendex (Engineering Village) in April 2018, we included 40 systematic reviews. The reviews were evaluated on the transparency of the reporting and the comprehensiveness of the search as required by the standards. The findings revealed deficiencies in search processes and reporting of search methods. We conclude by discussing the implications of these findings for librarians collaborating with social sciences researchers.

Lorena Díaz-Ordóñez,1– 3 Diana Ramírez-Montaño,1– 3 Estephania Candelo,2– 4 Carolina González-Restrepo,1 Sebastián Silva-Peña,1 Carlos Arturo Rojas,5 Mario Sepulveda Copete,5 Hector Raul Echavarria,6 Harry Pachajoa1– 3 1Basic Medical Science Department, Faculty of Health Sciences, Universidad Icesi, Cali, Colombia; 2Clinical Genetic Department, Fundación Valle del Lili, Cali, Colombia; 3Research Centre in Rare Diseases and Congenital Abnormalities (CIACER), Universidad Icesi, Cali, Colombia; 4Research Centre, Fundación Valle de Lili, Cali, Colombia; 5Gastroenterology Department, Fundacion Valle del Lili, Cali, Colombia; 6Centro Medico Imbanaco, Cali, ColombiaCorrespondence: Estephania Candelo Calle 18 122-135, Cali, 76003, ColombiaTel +57 2 5552334Fax + 57 2 555 1441Email ecandelo@icesi.edu.coBackground: CYP2C19 is a highly polymorphic gene that encodes an enzyme with the same name and whose function is associated with the metabolism of many important drugs, such as proton pump inhibitors (such as esomeprazole, which is used for the treatment of acid peptic disease). Genetic variants in CYP2C19 alter protein function and affect drug metabolism. This study aims to genotypically and phenotypically characterize the genetic variants in the CYP2C19 gene in 12 patients with acid peptic disorders and different therapeutic profiles to proton pump inhibitor (PPI) drugs. The patients were randomly selected from a controlled, randomized and blinded clinical pilot trial of 33 patients. We determined the presence and frequency of single nucleotide polymorphisms (SNPs) within exons 1– 5 and 9, the intron-exon junctions, and a fragment in the 3ʹ UTR region of the CYP2C19 gene using Sanger sequencing. Undescribed polymorphisms were analyzed by free online bioinformatics tools to evaluate the potential molecular effects of these genetic variants.Results: We identified nine polymorphisms, six of which had no reported functions. One of these genetic variants, with a functional impact, not yet reported (p.Arg132Trp) was predicted by bioinformatic tools as potentially pathogenic. This finding suggests that p.Arg132Trp could be related to poor metabolizers of drugs metabolized by CYP2C19.Conclusion: We identified the genotype spectrum of variants in CYP2C19. The genotype spectrum of variants in CYP2C19 could predict the treatment response and could support to evaluate clinical efficacy in patients treated with esomeprazole.Keywords: single nucleotide polymorphism, cytochrome P450 CYP2C19, pharmacogenetics, computational biology, treatment failure, proton pump inhibitors

The legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (> 50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families—Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In the light of recent reports of coronaviruses including a SARS-CoV-2-related virus in Sunda pangolins in China, the lack of any coronavirus detection in our ‘upstream’ market chain samples suggests that these detections in ‘downstream’ animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally.

Introduction Takayasu's arteritis is a panarteritis, characterized by chronic inflammation, that affects large vessels, especially the Aorta and its main branches. This pathology is extremely rare, has a higher incidence in Japan, presenting low incidence in Latin America. Case description We present the case of a young adult, with no significant medical history, who presents a 3 months of evolution intense headache initially classified as trigeminal neuralgia and cluster headache. Asymmetric pulses and variation in blood pressure between both upper extremities where observed which allowed several presumptive diagnoses to be considered. In the complementary examinations, the patient showed sustained elevation of acute phase reactants. Our patient met four diagnostic criteria of the American College of Rheumatology for Takayasu arteritis and the diagnosis was confirmed by magnetic Angio resonance of the neck, chest and abdomen, where involvement of the entire route of the aorta was observed. In context to treatment, the first-line therapy is high-dose steroids. In patients in whom the suspension of steroids is difficult, combined therapy with immunosuppressive agents is used. In the case of our patient, combined therapy with prednisone and methotrexate was chosen, which presented a favorable evolution. Conclusion Takayasu arteritis is an infrequent vasculitis, however, it is important to make an early diagnosis and treatment in order to improve the prognosis, stop the progression of the disease and improve the quality of life of patients suffering from this pathology.

Objective: In small for gestational age (SGA) children, catch-up growth could be influenced by methylation of several genes involved in metabolism. Epigenetics may influence the development of metabolic diseases in adulthood. To compare the methylation of leptin (LEP), glucagon-like peptide-2 receptor (GLP2R), insulin receptor substrate-2 (IRS2) in SGA patients with and without catch-up growth. Methods: Observational prospective study of SGA children. Demographical and clinical variables were collected from clinical records and parents’ questionnaire. Methylation status of LEP, IRS2, and GLP2R promoters was evaluated in DNA extracted from patient and one parent saliva samples. Results: Forty-eight SGA patients were included. Twenty-six (54.2%) had catch-up growth phenotype and 22 (45.8%) did not. The median age was 5.2 years [RIC 4.1-6.8] without difference between groups (p=0.306). The catch-up group had increased appetite (42.3% vs 9.1%, p=0.008), family history of dyslipidemia (42.3% vs 27.3%) and diabetes (34.6% vs 22.7%) compared to non-catch-up group. Catch-up patients had significantly larger waist circumference compared to non-catch-up group (median 55 cm [RIC 52-58] versus median 49.5 cm [RIC46-52]; p

Low-resistivity pay reservoirs have been described in many basins around the world. Technical information available explains the causes related to hydrocarbon bearing zones, represented by low resistivity values. These causes are mainly associated with mineralogy and complex pore structures. All the wells drilled and produced in the Johanna Este field in Ecuador have met the condition of pay zones with high resistivity values in relation to the well-known water formation resistivity. A step change in the understanding of the main reservoir M1 sandstone occurred after drilling the horizontal well JE34H. The first half of the lateral section was drilled with resistivity values close to water resistivity. Vertical variations in the resistivity were confirmed in the second half of the well, with no lithologic barriers between both zones observed in the logs. The oil production obtained from this well was recognized as a field record, and the first time it was associated with low resistivity values. After an exhaustive review of the available information including LWD electrical logs, the tool functioning, and cuttings description, it was possible to explain the low-resistivity pay within the M1 sandstone reservoir at the mineralogical level. The density-neutron cross-plots used for lithology identification show that the reservoir is mainly quartz with some mineral mixture. The target zone is mainly made up of medium-to-coarse grain with no visible matrix in the composition, showing no evidence of compaction or cement in density-neutron logs. Macroscopic anisotropy was also discarded as the reason for the decrease in the measured resistivity. In addition, structural compartments and preferential pathways for water invasion created by faults and/or fractures were discarded based on the azimuthal density image interpretation. The possible causes for the low resistivity pay were microporosity, presence of disseminated clay, and presence of conductive minerals. Special analysis (cores, magnetic resonance, capillary pressure, SEM) are required in order to understand the mineralogy and porosity distribution. A low-resistivity pay within the M1 has opened a door for future analysis by means of conventional or special open hole and cased hole logs in order to identify reserves that could be bypassed.

The legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (>50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families – Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In light of recent reports of coronaviruses including a SARS-CoV-2 related virus in Sunda pangolins in China, the lack of any coronavirus detection in our ‘upstream’ market chain samples suggests that these detections in ‘downstream’ animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally.

Background Chagas disease, caused by the parasite Trypanosoma cruzi, once considered a disease confined to Mexico, Central America, and South America, is now an emerging global public health problem. An estimated 300 000 immigrants in the United States are chronically infected with T. cruzi. However, awareness of Chagas disease among the medical community in the United States is poor. Methods We review our experience managing 60 patients with Chagas disease in hospitals throughout the New York City metropolitan area and describe screening, clinical manifestations, EKG findings, imaging, and treatment. Results The most common country of origin of our patients was El Salvador (n = 24, 40%), and the most common detection method was by routine blood donor screening (n = 21, 35%). Nearly half of the patients were asymptomatic (n = 29, 48%). Twenty-seven patients were treated with either benznidazole or nifurtimox, of whom 7 did not complete therapy due to side effects or were lost to follow-up. Ten patients had advanced heart failure requiring device implantation or organ transplantation. Conclusions Based on our experience, we recommend that targeted screening be used to identify at-risk, asymptomatic patients before progression to clinical disease. Evaluation should include an electrocardiogram, echocardiogram, and chest x-ray, as well as gastrointestinal imaging if relevant symptoms are present. Patients should be treated if appropriate, but providers should be aware of adverse effects that may prevent patients from completing treatment.

Objective: \ud \ud The α1D-adrenoreceptor (α1D-AR) is involved in angiotensin II-induced vascular remodeling and hypertension. Whether α1D-AR plays a role in hypertension-associated cardiac hypertrophy is unclear. Here we investigated effects of BMY 7378, a selective α1D-AR antagonist, on cardiac status in aged spontaneously hypertensive rats (SHR).\ud \ud Methods: \ud \ud Male SHR were studied during the phase of developing hypertension (5 and 10 weeks old) and once hypertension was established (20 and 30 weeks old) to assess the evolution of cardiac hypertrophy. Age-matched WKY rats were studied as controls. Thirty-week-old SHR were treated for 4 weeks with BMY 7378 (10 mg/kg per day, o.a.), or captopril (angiotensin-converting enzyme inhibitor, 40 mg/kg per day, o.a.) (as a positive control). Blood pressure and cardiac function were measured in vivo, cardiac hypertrophy by histology, and α1D-AR protein expression by immunofluorescence.\ud \ud Results: \ud \ud By 30 weeks of age, SHR exhibited significant hypertension and cardiac hypertrophy. BMY 7378 and captopril decreased blood pressure and improved hemodynamic parameters and cardiac function in treated SHR vs. untreated SHR (P < 0.05). Histology showed increased cardiomyocyte size, fibrosis, and left ventricular hypertrophy in SHR hearts. BMY 7378 ameliorated fibrosis and cardiac hypertrophy, but had no effect on cardiomyocyte size in SHR. Effects of BMY 7378 were associated with increased α1D-AR protein expression in SHR.\ud \ud Conclusion: \ud \ud Our data indicate that pharmacological antagonism of α1D-AR reduces blood pressure and associated cardiac hypertrophy in aged SHR. These findings suggest that the α1D-AR plays a pathophysiological role in the development of hypertension and cardiac target organ damage in SHR.

IntroductionFlaviviridae family belongs to the Spondweni serocomplex, which is mainly transmitted by vectors from the Aedes genus. Zika virus (ZIKV) is part of this genus. It was initially reported in Brazil in December 2014 as an unknown acute generalized exanthematous disease and was subsequently identified as ZIKV infection. ZIKV became widespread all over Brazil and was linked with potential cases of microcephaly.Case reportWe report a case of a 28-year-old Colombian woman, who came to the Obstetric Department with an assumed conglomerate of fetal abnormalities detected via ultrasonography, which was performed at 29.5 weeks of gestation. The patient presented with multiple abnormalities, which range from a suggested Arnold–Chiari malformation, compromising the lateral and third ventricles, liver calcifications, bilateral pyelocalic dilatations, other brain anomalies, and microcephaly. At 12 weeks of gestation, the vertical transmission of ZIKV was suspected. At 38.6 weeks of gestation, the newborn was delivered, with the weight in the 10th percentile (3,180 g), height in the 10th percentile (48 cm), and cephalic circumference under the 2nd percentile (31 cm). Due to the physical findings, brain magnetic resonance imaging (MRI) was performed, revealing a small and deviated brain stem, narrowing of the posterior fossa, a giant posterior fossa cyst with ventricular dilatation, a severe cortical and white matter thinning, cerebellar vermis with hypoplasia, and superior and lateral displacement of the cerebellum. In addition, hydrocephalus was displayed by the axial sequence, and the cerebral cortex was also compromised with lissencephaly. Schizencephaly was found with left frontal open-lip, and no intracranial calcifications were found. Two novel heterozygous nonsense mutations were identified using whole-exome sequencing, and both are located in exon 8 under the affection of ZIKV congenital syndrome (CZS) that produced a premature stop codon resulting in the truncation of the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) protein.ConclusionWe used molecular and microbiological assessments to report the initial case of vertically transmitted ZIKV infection with congenital syndrome associated with a neurological syndrome, where a mutation in the CDK5RAP2 gene was also identified. The CDK5RAP2 gene encodes a pericentriolar protein that intervenes in microtubule nucleation and centriole attachment. Diallelic mutation has previously been associated with primary microcephaly.

Background Achondrogenesis type IA (ACG1A) is a rare, lethal autosomal recessive chondrodysplasia affecting endochondral bone ossification and differentiation, causing intrauterine growth restriction, narrow thorax, and short limbs. Mutations in TRIP11, which encodes Golgi microtubule-binding protein 210 in the Golgi apparatus, alter protein transport in tissues. Case presentation A 28-week gestation male fetus was diagnosed with ACG1A by clinical, radiological, histologic, and molecular findings. Results Whole exome sequencing was performed on fetal DNA and parental blood. Two fetal heterozygous novel variants of TRIP11, c.2304_2307delTCAA (p.Asn768Lysfs*7) and c.2128_2129delAT (p.lle710Cysfs*19), were inherited from the mother and father, respectively. Both variants created a reading frameshift leading to a premature stop codon and loss of protein function. Conclusion To our knowledge, this is the first Latin American report with clinical, radiographic, and molecular diagnosis of ACG1A. Clinical and molecular diagnosis in utero is essential for genotype–phenotype correlation and is useful for providing better genetic counseling.

Introduction Mutations in ABCC9 are associated with Cantu syndrome (CS), a very rare genetic disorder characterized by congenital hypertrichosis, acromegaloid facial appearance (AFA), cardiomegaly, and skeletal anomalies. Case report We report an 8-year-old female patient with congenital generalized hypertrichosis and coarse facial appearance but without cardiovascular or skeletal compromise. Whole exome sequencing revealed a novel de novo heterozygous mutation in ABCC9. In addition, the genotype and phenotype of the patient were compared with those of the patients reported in the literature and with other related conditions that include AFA, hypertrichosis and AFA, and CS. Conclusion This is the first report of a South-American patient with mutation in ABCC9. We propose that her phenotype is a part of a spectrum of features associated with congenital hypertrichosis and mutations in ABCC9, which differs from CS and related disorders. Whole exome sequencing enabled the identification of the causality of this disease characterized by high clinical and genetic heterogeneity.

Pathogenic variants in WAC are uncommon causes of developmental delay and neurobehavioral phenotypes. The clinical features associated with WAC haploinsufficiency include recognizable dysmorphic facial features that were recently delineated as DeSanto-Shinawi syndrome (DESSH; OMIM 616708). Additional clinical features include hypotonia, hearing and vision abnormalities, gastrointestinal problems, and behavioral difficulties. Here, we report a case of a 4-year-old Colombian male patient with typical dysmorphic facial features, developmental delay, hyperactivity, and recurrent respiratory infections. His immune workup revealed hypogammaglobulinemia, and clinical exome sequencing revealed a novel intronic variant in WAC (c.1437+1G>A). To the best of our knowledge, this is the first case of DESSH in South America, underlining the accumulating evidence of the significant role of WAC haploinsufficiency in neurobehavioral phenotypes. Although this report suggested the potential involvement of WAC in immune regulation, additional reports are required to confirm our observations.

Los defectos congénitos de la glicosilación (CDG) son un grupo de errores innatos del metabolismo de las glicoproteínas con manifestaciones multisistémicas heterogéneas. Se han reportado más de 100 tipos diferentes de CDG. La forma que involucra el gen de la glicosilación ligada a asparagina (ALG13) comunmente ligada al X, es una enfermedad infrecuente.Objetivo: Describir las manifestaciones clínicas de un paciente con CDG relacionado con ALG13 y comparararlo con los casos reportados previamente.Caso Clínico: paciente varon de 11 años de edad, hijo de padres consanguíneos, con antecedentes de hipotonía, retardo del desarrollo psicomotor severo, déficit cognitivo y problemas de alimentación desde los 5 meses de vida. Presentaba además microcefalia, cardiopatía congénita (ductus arterioso persistente e insuficiencia mitral) sin trastorno convulsivo ni compromiso de la coagulación. Se realizaron estudios metabólicos los cuales no fueron concluyentes, incluyendo estudios de N-glicosilación en plasma normales, por lo que se decidió realizar secuenciación de Exoma completo que identificó una variante no reportada anteriormente en el gen ALG13: c.428C > T (p.P143L) en hemicigosis, confirmada por secuenciación Sanger, la madre fue portadora de la misma variante.Conclusión: Se presenta el primer paciente reportado en Colombia con CDG-Is sin epilepsia, los hallazgos amplían el espectro fenotípico de CDG-Is conocido hasta el momento y soportan que los transtornos de la N-glicosilacion pueden presentarse con estudios bioquímicos normales. Sin embargo, se necesitan estudios funcionales para demostrar estos hallazgos. La secuenciación de exoma es una tecnología costo-efectiva que permite la identificación de mutaciones responsables de los fenotipos en enfermedades con gran heterogeneidad genotípica y fenotípica.

Undergraduate research is one of the most valuable activities an undergraduate can engage in because of its benefits, and studies have shown that longer experiences are more beneficial. However, prior research has illuminated that undergraduates encounter challenges that may cause them to exit research prematurely. These studies have been almost exclusively conducted at research-intensive (R1) institutions, and it is unclear whether such challenges are generalizable to other institution types. To address this, we extended a study previously conducted at public R1 institutions. In the current study, we analyze data from 1262 students across 25 public R1s, 12 private R1s, 30 master's-granting institutions, and 20 primarily undergraduate institutions (PUIs) to assess 1) to what extent institution type predicts students' decisions to persist in undergraduate research and 2) what factors affect students' decisions to either stay in or consider leaving their undergraduate research experiences (UREs) at different institution types. We found students at public R1s are more likely to leave their UREs compared with students at master's-granting institutions and PUIs. However, there are few differences in why students enrolled at different institution types consider leaving or choose to stay in their UREs. This work highlights the importance of studying undergraduate research across institutions.