Beyond digestive pathology: endoscopic study in systemic disease.

A 77-year-old male patient with heart disease, kidney disease under study, and quiescent multiple myeloma. He presented a 2 years history of weight loss and digestive symptoms. In the endoscopic study, multiple gastric ulcers were observed, whose histological study ruled out the initial suspicion. The patient died a month later from refractory shock.

Teneurin-3 regulates the generation of non-image-forming visual circuitry and responsiveness to light in the suprachiasmatic nucleus.

Visual system function depends upon the elaboration of precise connections between retinal ganglion cell (RGC) axons and their central targets in the brain. Though some progress has been made in defining the molecules that regulate RGC connectivity required for the assembly and function of image-forming circuitry, surprisingly little is known about factors required for intrinsically photosensitive RGCs (ipRGCs) to target a principal component of the non-image-forming circuitry: the suprachiasmatic nucleus (SCN). Furthermore, the molecules required for forming circuits critical for circadian behaviors within the SCN are not known. We observe here that the adhesion molecule teneurin-3 (Tenm3) is highly expressed in vasoactive intestinal peptide (VIP) neurons located in the core region of the SCN. Since Tenm3 is required for other aspects of mammalian visual system development, we investigate roles for Tenm3 in regulating ipRGC-SCN connectivity and function. Our results show that Tenm3 negatively regulates association between VIP and arginine vasopressin (AVP) neurons within the SCN and is essential for M1 ipRGC axon innervation to the SCN. Specifically, in Tenm3-/- mice, we find a reduction in ventro-medial innervation to the SCN. Despite this reduction, Tenm3-/- mice have higher sensitivity to light and faster re-entrainment to phase advances, probably due to the increased association between VIP and AVP neurons. These data show that Tenm3 plays key roles in elaborating non-image-forming visual system circuitry and that it influences murine responses to phase-advancing light stimuli.

Human Papillomavirus Prevalence and Associated Factors in Indigenous Women in Ecuador: A Cross-Sectional Analytical Study.

Cervical cancer (CC) is the second leading cause of death from malignancy in women in Ecuador. Human papillomavirus (HPV) is the main causative agent of CC. Although several studies have been conducted on HPV detection in Ecuador, there are limited data on indigenous women. This cross-sectional study aimed to analyze the prevalence of HPV and associated factors in women from the indigenous communities of Quilloac, Saraguro and Sevilla Don Bosco. The study included 396 sexually active women belonging to the aforementioned ethnicities. A validated questionnaire was used to collect socio-demographic data, and real-time Polymerase Chain Reaction (PCR) tests were used to detect HPV and other sexually transmitted infections (STIs). These communities are located in the southern region of Ecuador and face geographical and cultural barriers to accessing health services. The results showed that 28.35% of women tested positive for both types of HPV, 23.48% for high-risk (HR) HPV, and 10.35% for low-risk (LR) HPV. Statistically significant associations were found between HR HPV and having more than three sexual partners (OR 1.99, CI 1.03-3.85) and Chlamydia trachomatis infection (OR 2.54, CI 1.08-5.99). This study suggests that HPV infection and other sexually transmitted pathogens are common among indigenous women, highlighting the need for control measures and timely diagnosis in this population.

Myiasis in a Neglected Elderly: Urgent Action Needed in South America.

Background: Myiasis is an infestation by fly larvae. Some species exclusively affect humans, contaminating wounds, mucous membranes, and other tissues. It is a disease with marked socioeconomic connotations. Case Presentation: The current case involves a 95-year-old woman, an inhabitant of the Andean region of Ecuador with a history of resection of basal cell carcinoma in the left zygomatic region and a diagnosis of chronic leukemia. The surgical wound was secondarily infested with Cochliomyia hominivorax fly larvae and the patient was readmitted to the hospital to treat this complication. A marked clinical improvement was observed after surgical debridement, removal of larvae and administration of ivermectin and antibiotics. Conclusion: The determinants of this infestation were advanced age, neglect, and destitution in a patient with an open wound on the face after resection of a basal cell carcinoma. This case illustrates the appalling reality of the marginalized and excluded population of South America. Also of concern is the expansion of myiasis-producing fly populations to areas outside their natural humid and warm habitat. South American governments are called upon to act jointly and effectively against this ominous disease.

Geographical distribution and genetic characterization of pfhrp2 negative Plasmodium falciparum parasites in the Peruvian Amazon.

Malaria rapid diagnostic tests (RDTs) have been evaluated in the Peruvian Amazon region and their performance has been variable. This region is known for being the first with documented evidence of wild Plasmodium falciparum parasites lacking pfhrp2 and pfhrp3 genes, leading to false-positive results with HRP2-based RDTs. In our attempt to further characterize the deletion pattern of these genes and their evolutionary relationship, 93 P. falciparum samples, collected in different communities from the Peruvian Amazon region between 2009 and 2010, were analyzed in this study. Genomic DNA was used to amplify 18S rRNA, pfmsp2 and pfglurp to confirm the diagnosis and DNA quality, respectively; pfhrp2, pfhrp3, and their flanking genes were amplified by PCR to assess the pattern of the gene deletions. In addition, microsatellite analysis were performed using seven neutral microsatellites (MS) and five microsatellite loci flanking pfhrp2. The data showed the absence of pfhrp3 gene in 53.76% (50/93) of the samples, reflecting a higher frequency than the proportion of pfhrp2 gene deletions (33.33%; 31/93). Among the flanking genes, the highest frequency of deletion was observed in the PF3D7_0831900 gene (78.49%; 73/93) for pfhrp2. MS marker analysis showed the presence of 8 P. falciparum lineages. The lineage Bv1 was the most prevalent among parasites lacking pfhrp2 and pfhrp3 genes. Additionally, using MS flanking pfhrp2 gene, the haplotypes α and δ were found to be the most abundant in this region. This study confirms the presence in this area of field isolates with deletions in either pfhrp2, pfhrp3, or both genes, along with their respective flanking regions. Our data suggest that some pfhrp2/pfhrp3 deletion haplotypes, in special the lineage Bv1, are widely dispersed within the Peruvian Amazon. The persistence of these haplotypes ensures a proportion of P.falciparum parasites lacking the pfhrp2/pfhrp3 genes in this area, which ultimately leads to false-negative results on PfHRP2-detecting malaria RDTs. However, additional studies are needed to not only confirm this hypothesis but also to further delineate the origin and genetic basis for the pfhrp2- and pfhrp3 gene deletions in wild P. falciparum parasites.

Evidence-Based Malaria Control and Elimination in the Amazon: Input from the International Center of Excellence in Malaria Research Network in Peru and Brazil.

Malaria remains endemic in 17 countries in the Americas, where 723,000 cases were reported in 2019. The majority (> 90%) of the regional malaria burden is found within the Amazon Basin, which includes nine countries and territories in South America. Locally generated evidence is critical to provide information to public health decision makers upon which the design of efficient and regionally directed malaria control and elimination programs can be built. Plasmodium vivax is the predominant malaria parasite in the Amazon Basin. This parasite species appears to be more resilient to malaria control strategies worldwide. Asymptomatic Plasmodium infections constitute a potentially infectious reservoir that is typically missed by routine microscopy-based surveillance and often remains untreated. The primary Amazonian malaria vector, Nyssorhynchus (formerly Anopheles) darlingi, has changed its behavior to feed and rest predominantly outdoors, reducing the efficiency of core vector control measures such as indoor residual spraying and distribution of long-lasting insecticide-treated bed nets. We review public health implications of recent field-based research carried out by the Amazonia International Center of Excellence in Malaria Research in Peru and Brazil. We discuss the relative role of traditional and novel tools and strategies for better malaria control and elimination across the Amazon, including improved diagnostic methods, new anti-relapse medicines, and biological larvicides, and emphasize the need to integrate research and public health policymaking.

Malaria Resilience in South America: Epidemiology, Vector Biology, and Immunology Insights from the Amazonian International Center of Excellence in Malaria Research Network in Peru and Brazil.

The 1990s saw the rapid reemergence of malaria in Amazonia, where it remains an important public health priority in South America. The Amazonian International Center of Excellence in Malaria Research (ICEMR) was designed to take a multidisciplinary approach toward identifying novel malaria control and elimination strategies. Based on geographically and epidemiologically distinct sites in the Northeastern Peruvian and Western Brazilian Amazon regions, synergistic projects integrate malaria epidemiology, vector biology, and immunology. The Amazonian ICEMR's overarching goal is to understand how human behavior and other sociodemographic features of human reservoirs of transmission-predominantly asymptomatically parasitemic people-interact with the major Amazonian malaria vector, Nyssorhynchus (formerly Anopheles) darlingi, and with human immune responses to maintain malaria resilience and continued endemicity in a hypoendemic setting. Here, we will review Amazonian ICEMR's achievements on the synergies among malaria epidemiology, Plasmodium-vector interactions, and immune response, and how those provide a roadmap for further research, and, most importantly, point toward how to achieve malaria control and elimination in the Americas.

Epidemiological characteristics of P. vivax asymptomatic infections in the Peruvian Amazon.

Introduction: Herein, we tested the hypothesis that Asymptomatic P. vivax (Pv) infected individuals (Asym) feature different epidemiological, clinical and biochemical characteristics, as well as hematological parameters, potentially predictive of clinical immunity in comparison to symptomatic Pv infected individuals (Sym). Methodology: Between 2018 - 2021, we conducted 11 population screenings (PS, Day 0 (D0)) in 13 different riverine communities around Iquitos city, in the Peruvian Amazon, to identify Pv Sym and Asym individuals. A group of these individuals agreed to participate in a nested case - control study to evaluate biochemical and hematological parameters. Pv Asym individuals did not present common malaria symptoms (fever, headache, and chills), had a positive/negative microscopy result, a positive qPCR result, reported no history of antimalarial treatment during the last month, and were followed-up weekly until Day 21 (D21). Control individuals, had a negative malaria microscopy and qPCR result, no history of antimalarial treatment or malaria infections during the last three years, and no history of comorbidities or chronic infections. Results: From the 2159 individuals screened during PS, data revealed a low but heterogeneous Pv prevalence across the communities (11.4%), where most infections were Asym (66.7%) and submicroscopic (82.9%). A total of 29 Asym, 49 Sym, and 30 control individuals participated in the nested case - control study (n=78). Ten of the individuals that were initially Asym at D0, experienced malaria symptoms during follow up and therefore, were included in the Sym group. 29 individuals remained Asym throughout all follow-ups. High levels of eosinophils were found in Asym individuals in comparison to Sym and controls. Conclusion: For the first-time, key epidemiological, hematological, and biochemical features are reported from Pv Asym infections from the Peruvian Amazon. These results should be considered for the design and reshaping of malaria control measures as the country moves toward malaria elimination.

Insights into Plasmodium vivax Asymptomatic Malaria Infections and Direct Skin-Feeding Assays to Assess Onward Malaria Transmission in the Amazon.

Understanding the reservoir and infectivity of Plasmodium gametocytes to vector mosquitoes is crucial to align strategies aimed at malaria transmission elimination. Yet, experimental information is scarce regarding the infectivity of Plasmodium vivax for mosquitoes in diverse epidemiological settings where the proportion of asymptomatically infected individuals varies at a microgeographic scale. We measured the transmissibility of clinical and subclinical P. vivax malaria parasite carriers to the major mosquito vector in the Amazon Basin, Nyssorhynchus darlingi (formerly Anopheles). A total of 105 participants with natural P. vivax malaria infection were recruited from a cohort study in Loreto Department, Peruvian Amazon. Four of 18 asymptomatic individuals with P. vivax positivity by blood smear infected colony-grown Ny. darlingi (22%), with 2.6% (19 of 728) mosquitoes infected. In contrast, 77% (44/57) of symptomatic participants were infectious to mosquitoes with 51% (890 of 1,753) mosquitoes infected. Infection intensity was greater in symptomatic infections (mean, 17.8 oocysts/mosquito) compared with asymptomatic infections (mean, 0.28 oocysts/mosquito), attributed to parasitemia/gametocytemia level. Paired experiments (N = 27) using direct skin-feeding assays and direct membrane mosquito-feeding assays showed that infectivity to mosquitoes was similar for both methods. Longitudinal studies with longer follow-up of symptomatic and asymptomatic parasite infections are needed to determine the natural variations of disease transmissibility.

Choledochoduodenostomy with LAMS (Hot-Axios type) for malignant obstructive jaundice - An increasingly used technique.

An 82-year-old woman who presented with obstructive jaundice and constitutional syndrome was diagnosed with pancreatic adenocarcinoma. Palliative management was decided with endoscopic ultrasound drainage as it was impossible to perform ERCP due to anatomical alterations, a consequence of the neoplastic lesion.

Impact of a Systematic Pharmacist-Initiated Antibiotic Time-Out Intervention for Hospitalized Adults.

INTRODUCTION: Antibiotic time-outs (ATO) are a recommended antimicrobial stewardship action, but data assessing their impact are lacking. This study investigated the impact of a systematic, pharmacist initiated ATO intervention. METHODS: This pre-post study included inpatients on hospitalist and intensivist services receiving empiric antibiotics for ≥48 hours. The ATO was initiated by pharmacists after 48 hours of empiric therapy and the outcome was documented including antibiotic indication, plan, and duration. An electronic medical record (EMR) alert facilitated ATO completion and pharmacists and prescribers received education prior to implementation. The primary outcome was EMR documentation of an antibiotic plan by 72 hours. Secondary outcomes included antibiotic utilization and antibiotic therapy modifications by 2 hours. RESULTS: 399 patients were included, 199 pre- and 200 post-intervention. The most common indications were pneumonia (32%), intra-abdominal infection (20%) and urinary tract infection (19%), with no between-group differences. EMR documentation of an antibiotic plan significantly improved in the post-intervention group (19% vs. 79%, p<0.0001) as did modifications to antibiotic therapy. The median duration of in-hospital antibiotic therapy was similar between groups (4.0 vs. 4.0 days, p = 0.2499). Approximately 45% of patients in each group received discharge antibiotics and median duration of discharge antibiotic therapy prescribed was reduced (7 vs. 5 days in the pre- and post-intervention groups, respectively; p = 0.0140). DISCUSSION: Implementation of pharmacist initiated ATO was associated with improvements in supporting EMR documentation and antibiotic therapy modifications. These findings highlight an important role in which pharmacists can serve as part of a collaborative antibiotic stewardship team.

Occlusal polygon area of the molars in six Colombian ethnic groups / Área del polígono oclusal de molares en seis grupos étnicos de Colombia

SUMMARY: Descriptive observational cross-sectional study to determine the AOP of the second molars (55, 65, 75, 85) and the first permanent molars (16, 26, 36 and 46) in 459 study models corresponding to six ethnic groups in Colombia, Embera indigenous of Alto Baudó (Chocó), Caucasoid mestizos of Cali (Valle del Cauca), African descent of Cali (Valle del Cauca), Misak indigenous of Silvia (Cauca), Nasa indigenous of Morales (Cauca), and indigenous of Leticia (Amazonas). There were no significant differences of AOP among the six ethnic groups except when compared to the Amazon Indians with African descent of Cali, Embera indigenous and Nasa indigenous. There was no sexual dimorphism except tooth 65 for all ethnic groups. There was bilateral symmetry except between teeth 16 and 26. The distance matrix showed that Caucasoid mestizos of Cali were grouped with microdont populations, Amazon indigenous, Embera indigenous, Misak indigenous and Nasa indigenous, and African descendants of Cali were grouped with mesodont populations. The Embera and Amazon indigenous had the highest values of OAP associated with the relative isolation and less mestizaje. Overall, there was no sexual dimorphism or bilateral asymmetry. This study coincides with the different theories about reducing the size of the teeth as evolutionary characteristic of hominids.

RESUMEN: Estudio observacional descriptivo de corte transversal en el que se determinó el APO de los segundos molars deciduos (55, 65, 75, 85) y de los primeros molares permanentes (16, 26, 36, 46) en 459 modelos de estudio correspondientes a seis grupos étnicos de Colombia: Indígenas embera del Alto Baudó (Chocó), mestizos caucasoides de Cali (Valle del Cauca), afrodescendientes de Cali (Valle del Cauca), indígenas misak de Silvia (Cauca), indígenas nasa de Morales (Cauca) e indígenas de Leticia (Amazonas). No se encontraron diferencias significativas en el APO de los seis grupos étnicos, excepto entre indígenas del Amazonas y de afrodescendientes de Cali, e indígenas embera e indígenas nasa. No se evidenció dimorfismo exual en ninguno de los seis grupos. Hubo simetría bilateral, excepto entre los dientes 16 y 26. La matriz de distancias demostró que los mestizos caucasoides de Cali se agrupan con poblaciones microdontes, indígenas del amazonas, indígenas embera, indígenas misak e indígenas nasa; mientras que los afrodescendientes de Cali se agrupan con poblaciones mesodentes. Los indígenas embera y del Amazonas presentaron altos valores del APO, asociado a su aislamiento relativo y bajo mestizaje. En términos generales, no hubo dimorfismo sexual ni asimetría bilateral. Los resultados de este estudio concuerdan con diferentes teorías sobre la reducción del tamaño dental como una característica evolutiva de los himínidos.

Extracorporeal CO2 removal and renal replacement therapy in acute severe respiratory failure in COVID-19 pneumonia: Case report.

The COVID-19 pandemic significates an enormous number of patients with pneumonia that get complicated with severe acute respiratory distress syndrome (ARDS), some of them with refractory hypercapnia and hypoxemia that need mechanical ventilation (MV). Those patients who are not candidate to extracorporeal membrane oxygenation (ECMO), the extracorporeal removal of CO2 (ECCO2 R) can allow ultra protective MV to limit the transpulmonary pressures and avoid ventilatory induced lung injury (VILI). We report a first case of prolonged ECCO2 R support in 38 year male with severe COVID-19 pneumonia refractory to conventional support. He was admitted tachypneic and oxygen saturation 71% without supplementary oxygen. The patient's clinical condition worsens with severe respiratory failure, increasing the oxygen requirement and initiating MV in the prone position. After 21 days of protective MV, PaCO2 rise to 96.8 mmHg, making it necessary to connect to an ECCO2 R system coupled continuous veno-venous hemodialysis (CVVHD). However, due to the lack of availability of equipment in the context of the pandemic, a pediatric gas exchange membrane adapted to CVVHD allowed to maintain the removal of CO2 until completing 27 days, being finally disconnected from the system without complications and with a satisfactory evolution.

Lenvatinib in severe hypoglycemia associated with hepatocellular carcinoma.

We present the case of a 24-year-old male with multicentric hepatocellular carcinoma (HCC) over HBV-related compensated liver cirrhosis, on treatment with sorafenib and tenofovir. He had multiple admissions in recent months for severe hypoglycemia episodes with neurological symptoms.

PvMSP8 as a Novel Plasmodium vivax Malaria Sero-Marker for the Peruvian Amazon.

The measurement of recent malaria exposure can support malaria control efforts. This study evaluated serological responses to an in-house Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) expressed in a Baculovirus system as sero-marker of recent exposure to P. vivax (Pv) in the Peruvian Amazon. In a first evaluation, IgGs against PvMSP8 and PvMSP10 proteins were measured by Luminex in a cohort of 422 Amazonian individuals with known history of Pv exposure (monthly data of infection status by qPCR and/or microscopy over five months). Both serological responses were able to discriminate between exposed and non-exposed individuals in a good manner, with slightly higher performance of anti-PvMSP10 IgGs (area under the curve AUC = 0.78 [95% CI = 0.72-0.83]) than anti-PvMSP8 IgGs (AUC = 0.72 [95% CI = 0.67-0.78]) (p = 0.01). In a second evaluation, the analysis by ELISA of 1251 plasma samples, collected during a population-based cross-sectional survey, confirmed the good performance of anti-PvMSP8 IgGs for discriminating between individuals with Pv infection at the time of survey and/or with antecedent of Pv in the past month (AUC = 0.79 [95% CI = 0.74-0.83]). Anti-PvMSP8 IgG antibodies can be considered as a good biomarker of recent Pv exposure in low-moderate transmission settings of the Peruvian Amazon.

Ribavirin monotherapy for the treatment of chronic hepatitis E in an immunosuppressed patient.

We herein report the case of a 54-year-old male patient with a human immunodeficiency virus 1 (HIV-1) infection, usually with low viral loads and CD4 cells < 200-100/mm3 due to thymic exhaustion. He was referred to our clinic because of hypertransaminasemia and cholestasis of a duration of 58 months and liver cirrhosis on FibroScan® without esophageal varices. Nonspecific manifestations included weight loss. Liver disease stigmata and generalized amyotrophy were also present.

Ribbed mussel in an urban waterway filters bacteria introduced by sewage.

The ribbed mussel has been demonstrated to tolerate high levels of urban pollution and inhabits intertidal regions of the New York City estuary. The ability of this bivalve to filter bacteria raises the question of whether it can remove from the water column the fecal bacteria introduced to urban waterways by septic system leakage or sewer overflow. The study here addresses the hypothesis that ribbed mussel filters bacteria introduced by combined sewer overflow (CSO) discharge. Mussels and water were collected from a highly polluted region of the NYC estuary in order to conduct two sets of five trials for filtration of coliform and coccoid fecal indicator bacteria, respectively, Escherichia coli and Enterococcus species. Mussels and water samples were collected in proximity to a major CSO outfall within 1-2 days of a rainfall event to ensure high baseline values of bacterial contamination for filtration trials. For any given Enterococcus or E. coli trial, equal volume water samples were serially distributed across aerated tanks either containing a mussel or not. Comparison of with-mussel versus no-mussel tank water contamination across pooled trials showed significant (P < 0.05) reduction in water exposed to mussel filtration for both, Enterococcus and E. coli trials. For Enterococcus trials, measures of turbidity (suspended particle density) were taken concurrently with measures of bacterial contamination. Regression of contamination against turbidity, with measures standardized across trials, yielded a significant positive association (n = 50, P < 0.0001) across all tank water with a mussel. Thus, contamination reduction was associated with particle removal by mussel filtration.

Malaria Situation in the Peruvian Amazon during the COVID-19 Pandemic.

The Peruvian Ministry of Health reports a near absence of malaria cases in the Amazon region during the COVID-19 pandemic. However, the rapid increase in SARS-CoV-2 infections has overwhelmed the Peruvian health system, leading to national panic and closure of public medical facilities, casting doubt on how accurately malaria cases' numbers reflect reality. In the Amazon region of Loreto, where malaria cases are concentrated, COVID-19 has led to near-complete closure of the primary healthcare system, and diagnosis and treatment of acute febrile illnesses, including malaria, has plummeted. Here, we describe the potential association of COVID-19 with a markedly reduced number of reported malaria cases due to the reduced control activities carried out by the Peruvian Malaria Zero Program, which could lead to malaria resurgence and an excess of morbidity and mortality.

Diagnosis of Plasmodium vivax by Loop-Mediated Isothermal Amplification in Febrile Patient Samples from Loreto, Perú.

Plasmodium vivax is co-endemic with Plasmodium falciparum in Peru, and optimum management requires distinguishing these two species in the blood of patients. For the differential identification of P. vivax and other Plasmodium spp., the LoopampTM Malaria Pan Detection Kit in combination with the Loopamp Malaria Pv Detection Kit (Eiken Chemical Co. Ltd., Tokyo, Japan) was used to evaluate 559 whole blood samples collected in 2017 from febrile patients with suspected malaria attending different health facilities in the Loreto region. The Loopamp Malaria Pan Detection Kit showed a sensitivity of 87.7% (95% CI: 83.5-91.9) and a specificity of 94.4% (95% CI: 91.9-96.9) and good agreement with PCR (Cohen's kappa 0.8266, 95% CI: 0.7792-0.874). By comparison, the Loopamp Malaria Pv Detection Kit showed a similar sensitivity (84.4%, 95% CI: 79.0-89.7) and specificity (92.4%, 95% CI: 89.7-95.0) and substantial agreement with PCR (Cohen's kappa: 0.7661, 95% CI: 0.7088-0.8234).