Helper T cell immunity in humans with inherited CD4 deficiency.

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.

Comparative Analysis of SARS-CoV-2 Antibody Responses across Global and Lesser-Studied Vaccines.

Few data are available on antibody response for some SARS-CoV-2 vaccines, and there is a lack of ability to compare vaccine responses in the same population. This cross-sectional study conducted in Nicaragua examines the SARS-CoV-2 antibody responses in individuals, previously exposed to high infection rates who have received various vaccines. The vaccines under comparison include well-known ones like Pfizer (BNT162b2) and AstraZeneca (ChAdOx1-S), alongside less-studied vaccines including Soberana (Soberana 02), Abdala (CIGB-66), and Sputnik V/Sputnik Light. Overall, 3195 individuals participated, with 2862 vaccinated and 333 unvaccinated. We found that 95% of the unvaccinated were seropositive, with much lower titers than the vaccinated. Among the vaccinated, we found that Soberana recipients mounted the highest anti-spike response (mean difference (MD) = 36,498.8 [20,312.2, 52,685.5]), followed by Abdala (MD = 25,889.9 [10,884.1, 40,895.7]), BNT162b2 (MD = 12,967.2 [7543.7, 18,390.8]) and Sputnik with AstraZeneca as the reference group, adjusting for age, sex, vaccine status, days after last dose, and self-reported COVID-19. In addition, we found that subjects with complete vaccination series had higher antibody magnitude than those with incomplete series. Overall, we found no evidence of waning in the antibody magnitude across vaccines. Our study supports the conclusion that populations with high infection rates still benefit substantially from vaccination.

Antimicrobial Resistance and Extended-Spectrum Beta-Lactamase Genes in Enterobacterales, Pseudomonas and Acinetobacter Isolates from the Uterus of Healthy Mares.

Antibiotic-resistant bacteria are a growing concern for human and animal health. The objective of this study was to determine the antimicrobial resistance and extended-spectrum beta-lactamase genes in Enterobacterales, Pseudomonas spp. and Acinetobacter spp. isolates from the uterus of healthy mares. For this purpose, 21 mares were swabbed for samples, which were later seeded on blood agar and MacConkey agar. The isolates were identified using MALDI-TOF and the antimicrobial susceptibility test was performed using the Kirby-Bauer technique. To characterize the resistance genes, a polymerase chain reaction (PCR) scheme was performed. Of the isolates identified as Gram-negative, 68.8% were Enterobacterales, represented by E. coli, Enterobacter cloacae, Citrobacter spp., and Klebsiella pneumoniae; 28.1% belonged to the genus Acinetobacter spp.; and 3.1% to Pseudomonas aeruginosa. A 9.3% of the isolates were multidrug-resistant (MDR), presenting resistance to antibiotics from three different classes, while 18.8% presented resistance to two or more classes of different antibiotics. The diversity of three genes that code for ESBL (blaTEM, blaCTX-M and blaSHV) was detected in 12.5% of the strains. The most frequent was blaSHV, while blaTEM and blaCTX-M were present in Citrobacter spp. and Klebsiella pneumoniae. These results are an alarm call for veterinarians and their environment and suggest taking measures to prevent the spread of these microorganisms.

Main mites associated with dermatopathies present in dogs and other members of the Canidae family.

Dermatological diseases of parasitic origin are one of the most frequent in the clinical practice of dogs and cats. Mites such as Sarcoptes scabiei, Otodectes cynotis, Demodex canis, and Cheyletiella spp., commonly affect domestic dogs. However, the impact generated by these mites on populations of wildlife animals and the mechanisms involved in their epidemiological dynamics are still not clear. In recent decades, the migration of populations and their interaction with domestic environments and vice versa have generated a worrying threat due to the transmission of some of these ectoparasites. Some reports have suggested that sarcoptic mange represents an emerging threat to wildlife. Given the outbreaks of greater magnitude and geographical extension. The objective of this review is to contribute to the state of the art of the main mites that cause dermatopathies in members of the Canis lupus familiaris family and other members of the Canidae family. For this, a systematic search was carried out in the Embase and PubMed databases. Infections caused by mites, mainly scabies, continue to be diseases with a worldwide distribution, affecting mammals and humans. Although they are long-standing diseases, the effects that are generated in wild canids are still unknown. A comprehensive evaluation is required to generate guidelines in favor of the conservation of some species of foxes and wolves present in different regions of the world.

Characterization of a Ferryl Flip in Electronically Tuned Nonheme Complexes. Consequences in Hydrogen Atom Transfer Reactivity.

Two oxoiron(IV) isomers (R 2a and R 2b) of general formula [FeIV (O)(R PyNMe3 )(CH3 CN)]2+ are obtained by reaction of their iron(II) precursor with NBu4 IO4 . The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R 2a and R 2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R 2a reacts one order of magnitude faster than R 2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R 2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.

Comparison of Sequential Dalbavancin With Standard-of-Care Treatment for Staphylococcus aureus Bloodstream Infections.

Background: Dalbavancin (DAL) is a long-acting lipoglycopeptide with activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). This study investigates DAL as sequential therapy in S. aureus bloodstream infections (BSIs). Methods: We conducted a retrospective cohort study from 2014 to 2021 comparing sequential DAL with standard-of-care therapy (SoC) for S. aureus BSI. The primary outcome was 90-day clinical failure (90-day all-cause mortality or 90-day recurrence). Secondary outcomes were incidence of acute kidney injury, creatinine phosphokinase elevations, catheter-related thrombosis, and hospital-acquired infections. Analyses were adjusted using inverse probability of treatment weighting (IPTW). Results: Overall, 225 patients (45 DAL, 180 SoC) were included. DAL patients had a higher incidence of community-acquired infection and persons who use drugs; SoC patients had more comorbidities and a longer duration of bacteremia. MRSA incidence was similar between the DAL and SoC groups. The median length of stay was 16 days among DAL recipients compared with 24 days among SoC recipients. Central catheter placement was 17.8% compared with 57.2% in the SoC group. Ninety-day clinical failure occurred in 13.3% and 18.3% of participants in the DAL and SOC groups, respectively. In IPTW-adjusted analysis, sequential DAL was not associated with 90-day clinical failure (adjusted odds ratio, 0.94; 95% CI, 0.333-2.32). Conclusions: This study provides preliminary evidence that select patients with S. aureus BSI treated with sequential DAL have similar clinical failure rates, with significant reductions in catheter placement and hospital length of stay compared with SoC. Further prospective evaluation is needed.

Antifungal susceptibility of Malassezia pachydermatis isolated from the external auditive conduct from dogs, in central Chile.

Background: External otitis is common in dogs, and one of the main agents involved is Malassezia pachydermatis, a yeast belonging to the otic microbiota. Empirical treatment can fail; therefore, it is essential to know the antifungal susceptibility profile to prescribe appropriate treatment, a fact scarcely reported in Chile. Aim: This study aimed to determine the antifungal sensitivity of M. pachydermatis isolated from the external auditory canal of dogs in central Chile. Methods: Ear swabs from 30 dogs (15 healthy and 15 with external otitis) were used. Samples were subjected to cytology and fungal culture. The antifungal susceptibility was determined according to clinical and laboratory standards institute (CLSI) document M44A-2 using the disk diffusion test from amphotericin B, Caspofungin, fluconazole, nystatin, clotrimazole, and voriconazole were used. Results: The prevalence of M. pachydermatis was 66.7% from 8 healthy dogs and 12 with otitis. While fungal culture was not associated with the patient's clinical condition (p = 0.24), the yeast count by cytology was significantly higher in dogs with otitis (p = 0.003). The strains were sensitive to all antifungals except for Caspofungin, where 55% of the strains were resistant. Conclusion: Malassezia pachydermatis is isolated more frequently in dogs with otitis, and the ear cytological examination is useful to differentiate colonized dogs versus dogs with otitis. In addition, most antifungals in vitro are active against this yeast, except Caspofungin, an antifungal used in human medicine. This situation should be further monitored in epidemiological programs to evaluate the possible impact on Chilean public health.

Isolation and Identification of Staphylococcus Species Obtained from Healthy Companion Animals and Humans.

The close contact between people and their pets has generated the exchange of skin microbiota, accompanied by bacteria that present resistance to antibiotics. Staphylococcus spp., opportunistic pathogens present in the skin and mucosa of mammals, have had their importance recognized in human and veterinary medicine. The objectives of this study were to identify Staphylococcus spp. present in isolates from the nostrils of healthy humans, dogs and cats as well as to determine their phenotype of resistance to methicillin. Strain identification was performed by MALDI-TOF mass spectrometry and antimicrobial susceptibility was determined using a disk diffusion assay for 12 antibiotics. Sixty humans (veterinary and technicians), sixty dogs and sixty cats were sampled; of them, 61.6%, 56.6% and 46.6%, respectively, carried Staphylococcus spp. in their nostrils, and only two people carried two different species of Staphylococcus in the only anatomical site sampled. A methicillin-resistant phenotype was present in 48.7% of the humans, 26.5% of the dogs and 57.1% of the cats, and sampled. These results demonstrate the presence of Staphylococcus spp. strains resistant to methicillin in personnel who work in contact with animals, as well as in dogs and cats that entered the same hospital or veterinary clinic, which alerts us to the potential transfer of these strains to or between people, dogs and/or cats.

Protein-PAINT: Superresolution microscopy with signaling proteins.

Superresolution techniques have advanced our understanding of complex cellular structures and processes but require the attachment of fluorophores to targets through tags or antibodies, which can be bulky and result in underlabeling. To overcome these limitations, we developed a technique to visualize the nanoscale binding locations of signaling proteins by taking advantage of their native interaction domains. Here, we demonstrated that pPAINT (protein point accumulation in nanoscale topography) is a new, single-molecule localization microscopy (SMLM) technique and used it to investigate T cell signaling by visualizing the Src homology 2 (SH2) domain, which is common in signaling molecules. When SH2 domain-containing proteins relocate to the plasma membrane, the domains selectively, transiently, and reversibly bind to preferred phosphorylated tyrosine residues on receptors. This transient binding yields the stochastic blinking events necessary for SMLM when observed with total internal reflection microscopy and enables quantification of binding coefficients in intact cells. We used pPAINT to reveal the binding sites of several T cell receptor-proximal signaling molecules, including Zap70, PI3K, Grb2, Syk, Eat2, and SHP2, and showed that the probes could be multiplexed. We showed that the binding half-life of the tandem SH2 domain of PI3K correlated with binding site cluster size at the immunological synapses of T cells, but that longer binding lifetimes were associated with smaller clusters for the monovalent SH2 domain of Eat2. These results demonstrate the potential of pPAINT for investigating phosphotyrosine-mediated signaling processes at the plasma membrane.

Characterization of microbial communities and predicted metabolic pathways in the uterus of healthy mares.

Background: Culture-independent techniques have made it possible to expand the knowledge about the composition of bacterial communities present in the healthy uterus and their role in health and disease, mainly in humans. However, in animals like mares, there is a dearth of information regarding this area. Aim: To narrow this knowledge gap, the objective of this study was to identify and characterize the composition and function of the uterine microbiome of a group of Chilean purebred mares (CPM), an equine breed with the oldest genealogical record in South America and an economical important reproductive industry. Methods: From uterine biopsy samples obtained during estrus, DNA extraction and targeted sequencing were performed to investigate the bacterial diversity and its probable metabolic function. Results: CPM biopsy samples were characterized by having a varied microbial composition, where the four most relatively abundant phyla were Proteobacteria (69.6%), Firmicutes (21.1%), Bacteroidetes (7.8%), and Actinobacteria (1.06%); which made up 99.6% of the total identified phyla. In contrast, Actinobacteria and Fusobacteria were the phyla not identified in all samples. Of a total of 59 genera identified across all samples, Staphylococcus was the most abundant genus with an average relative abundance of 18.88%, followed by Pseudomonas (17.9%), Escherichia/Shigella (10.42%), and Klebsiella (9.92%). Conclusion: These findings contribute to the knowledge of microbes' presence in the uterus, while future studies are required to demonstrate the role of these microorganisms in health and disease.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Cold-Shock Test Is a Practical Method for Selecting Boar Ejaculates Yielding Appropriate Seminal Plasma for Post-Thawing Supplementation.

Artificial insemination (AI) with cryopreserved semen is still unreliable for extensive pig industry application. Adding seminal plasma (SP) could improve post-thawing quality, but its suitability could vary. We applied a simple cold-shock test (CST, 5 min at 0 °C) on neat semen for classifying ejaculates (n = 63) as resistant or sensitive, obtaining two SP pools (CST-resistant: SPr, sensitive: SPs). Subsequently, frozen/thawed spermatozoa from six boars were incubated (37 °C) in MR-A® extender (control), 20% SPr, or 20% SPs, and analyzed at 0, 2, and 4 h. SP improved total and progressive motility, with a higher effect for SPr and STR (p < 0.05), decreasing kinematic parameters VCL and VAP, ALH, and BCF. Sperm viability was unaffected. SP increased apoptotic and membrane disorder ratios, and acrosomal damage, not affecting the chromatin structure (DNA fragmentation and immaturity by SCSA), protamination (CMA3), or disulfide levels (mBBr). However, the proportion of spermatozoa with elevated free thiols (disulfide bridges reduction) significantly increased. Results support a stimulatory role of SP on thawed semen, with additional benefits from SPr. The effect of SP and especially SPr after AI should be tested since CST could be a practical test for selecting suitable ejaculates in AI centers.

Consolidation of the Neonatal Screening Program as a Public Health Program in Paraguay

Abstract In Paraguay, neonatal screening for congenital hypothyroidism (CH) and phenylketonuria (PKU) started in October 1999, in 2005 cystic fibrosis (CF) was selectively incorporated. The National Program for Neonatal Screening has a centralized laboratory that encompasses 1.132 Sample Collecting Sites (SCS) distributed in the 18 Health Regions, with over 80% coverage of live births; the incidence of CH being 1:2.060, HPA/PKU 1:6.328 and CF 1:5.671 newborns. The newborn screening program headed by the Ministry of Public Health and Social Welfare in Paraguay has been consolidated itself as a public health program. This publication describes the historic 20-year process, the strategies and activities carried out as well as the results and achievements, among which it is important to point out the achievement of newborns screening laws that make mandatory to detect, diagnose and treat those affected, as well as the human resources committed to newborn screening.

The Role of Anxiety in the Relationship between Self-efficacy and Math Achievement / El papel de la ansiedad en la relación entre la competencia percibida y el rendimiento en matemáticas

This study aims to improve current understanding of how the relationship between perceived math ability and math achievement may be mediated or moderated by levels of anxiety about math, considering intellectual abilities, gender, and school year. In this study, participants were 2,245 Spanish students (7th to 10th grade). All completed the FennemaSherman Mathematics Attitudes Scales and the Sternberg Triarchic Abilities Test. The main results showed that (I) perceivedcompetence is a potent predictor of achievement (the higher the perceived competence, the better the performance in mathematics), (II) anxiety about mathematics significantly mediates the relationship between perceived competence and math achievement (although the effect is small), and (III) levels of anxiety condition the intensity of the effect of perceived competence on math achievement (at high levels of anxiety the effect size of the relationship between perceived competence and achievement is large, whereas at low levels of anxiety the effect is small)

El estudio tiene como objetivo mejorar el conocimiento actual sobre cómo la relación entre la capacidad matemática percibida y el rendimiento matemático puede estar mediada, o moderada, por el nivel de ansiedad ante las matemáticas, teniendo en cuenta las habilidades intelectuales, el género y el curso escolar. En el estudio participaron 2,245 estudiantes españoles de 7º a 10º grado. Todos completaron las Escalas de Actitudes Matemáticas Fennema-Sherman y la Escalade Inteligencia Triárquica de Sternberg. Los principales resultados mostraron que (I) la competencia percibida es un potente predictor de rendimiento matemático (cuanto mayor es la competencia percibida mejor es el rendimiento en matemáticas), (II) la ansiedad ante las matemáticas media significativamente la relación entre la competencia percibida y el rendimiento matemático (aunque el efecto sea pequeño) y (III) el nivel de ansiedad condiciona la intensidad del efecto de la competencia percibida en el rendimiento matemático (a un nivel de ansiedad elevado el tamaño del efecto de la relación entre la competencia percibida y el logro es grande, mientras que a un nivel bajo el efecto es pequeño)

Age-dependent manifestations and case definitions of paediatric Zika: a prospective cohort study.

BACKGROUND: Paedeatric Zika remains an understudied topic. WHO and the Pan American Health Organization (PAHO) Zika case definitions have not been assessed in children. We aimed to characterise clinical profiles and evaluate the diagnostic performance of the WHO and PAHO case definitions in a large cohort of paediatric Zika cases. METHODS: From January, 2016 to February, 2017, encompassing the major 2016 Zika epidemic, participants in the Pediatric Dengue Cohort Study (PDCS) in Managua, Nicaragua, were encouraged to visit the study health centre at first indication of any illness. PDCS participants were aged 2-14 years, healthy at enrolment, and recruited before the initiation of the present study. Molecular and serological assays were used to test participants exhibiting any of four broad clinical profiles suspected of resulting from a symptomatic Zika virus infection. These clinical profiles were: fever and at least two of headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations, and leukopenia; fever and at least two of nausea or vomiting, rash, aches and pains, positive tourniquet test, leukopenia, and any dengue warning sign; undifferentiated fever without evident cause, with or without any other clinical finding; and afebrile rash with or without any other clinical finding. We characterised acute clinical findings (signs, symptoms, and complete blood counts) in both Zika cases and non-Zika cases. FINDINGS: We prospectively followed a cohort of about 3700 children, of which 1110 were deemed eligible for inclusion. Four participants with laboratory-confirmed Zika (three co-infections with dengue virus, one missing complete blood count data) and two participants who were non-Zika cases (missing complete blood count data) were excluded from analysis. We analysed 556 laboratory-confirmed Zika and 548 non-Zika cases. The WHO case definition captured 176 confirmed Zika cases, and the PAHO definition 109 confirmed Zika cases, who presented with the most clinical findings and a dengue-like clinical profile. The remaining two thirds of Zika cases, principally characterised by undifferentiated fever or afebrile rash, were missed. Among Zika cases, rash (n=440)-particularly generalised erythematous rash (n=334)-fever (n=333), leukopenia (n=217), and headache (n=203) were most common and peaked within 3 days of illness onset. The most common Zika presentation over the first week of illness was rash only (n=80). The sensitivity of Zika case definitions increased across paediatric age (from 11·3% to 56·1% for the WHO case definition and from 6·0% to 36·6% for the PAHO case definition), as the prevalence of most clinical findings (particularly arthralgia) increased with age, irrespective of previous dengue virus infection. Consequently, Zika manifested differently across paediatric age; older Zika cases presented with a dengue-like clinical profile while younger Zika cases presented with undifferentiated fever or afebrile rash. INTERPRETATION: We provide the most thorough description of paediatric Zika to date. Most paediatric Zika cases go undetected under the WHO and PAHO case definitions, suggesting that current standards for Zika case ascertainment require revision. Zika manifests with mild but differing clinical profiles across paediatric age, presenting major challenges to diagnosis, surveillance, and efforts to control future Zika epidemics. FUNDING: US National Institutes of Health.

Peer Victimization in Overweight Adolescents and Its Effect on Their Self-Esteem and Peer Difficulties.

This study has three objectives: to examine whether adolescents who perceive themselves as overweight differ from others in terms of offline victimization at school, cybervictimization, self-esteem, and difficulties relating to peers; to examine the possible effects of offline and cybervictimization on self-esteem and difficulties relating to peers; and to examine the possible moderating role of perceiving oneself as overweight on those effects. Previously validated questionnaires were applied to a sample of 3145 adolescents in Asturias (Spain). Descriptive, inferential, correlational, and structural equation analyses were performed. Adolescents who perceived themselves as overweight reported being victims of both offline victimization and most forms of cybervictimization to a greater extent than those who did not perceive themselves as overweight. They also reported lower self-esteem and more peer difficulties (shyness or social anxiety). In both groups of adolescents, victimization and cybervictimization were correlated with each other, both types of victimization had direct, negative effects on self-esteem, and self-esteem in turn had a direct, negative effect on peer difficulties. Furthermore, offline victimization had a direct, positive effect on peer difficulties. Perceiving oneself as overweight moderated the effect of self-esteem on peer difficulties. In adolescents perceiving themselves as overweight, low self-esteem was a stronger risk factor of peer difficulties than in the rest of the adolescents. With high overall self-esteem there were no significant differences in peer difficulties between the adolescents perceiving themselves as overweight and the rest of the adolescents.

An ethnographic study of 'touristic escapism' and health vulnerability among Dominican male tourism workers.

Health research on tourism has expanded over the past two decades, focusing on understanding how the social, economic, and political configuration of tourism zones might contribute to health vulnerabilities among the diverse populations that interact in these areas. While there are few studies of HIV and drug use interactions in the region, research has indicated that these two outcomes are often interwoven in tourism zones, potentially producing 'syndemics' of HIV infection and problematic drug use. One framework that has been used in public health research on tourism is one that we refer to as touristic escapism or situational disinhibition that may be heightened for some tourists while on vacation, potentially leading to the abandonment of normative constraints on behaviour and contributing to health risks such as unprotected sex or binge drinking. In this article, we draw upon tourism theory and ethnographic research with male tourism workers employed in two popular tourist areas of the Dominican Republic to explore whether touristic escapism offers insights in understanding health vulnerabilities within tourism spaces.

Granulocyte-monocyte apheresis: an alternative combination therapy after loss of response to anti-TNF agents in ulcerative colitis.

Objective: To evaluate the effectiveness and safety of the combination of granulocyte-monocyte apheresis (GMA) after loss of response (LOR) to anti-tumor necrosis factor (TNF) agents in ulcerative colitis (UC). Materials and methods: A retrospective, multicenter study was performed in 11 inflammatory bowel disease (IBD) Units. Clinical remission was defined as a partial Mayo score ≤2. The effectiveness of the treatment was evaluated by the partial Mayo score and the rate of anti-TNF intensification, switch, swap or colectomy. Results: Forty-seven patients with ulcerative colitis were included (mean age 35 years, mean disease duration 52 months, 66% male and 59% extensive colitis). Twenty-three subjects were receiving infliximab, eighteen adalimumab and six golimumab. GMA was combined after a primary non-response (49%) or secondary loss of response (51%) to anti-TNF therapy. We observed a significant decrease in partial Mayo score and fecal calprotectin after GMA. Fifteen patients (32%) responded to the combination therapy without anti-TNF intensification, switch, swap or colectomy. Eight patients (17%) underwent colectomy. Two patients (4%) presented adverse events related to the technique. Conclusions: Combination of GMA and anti-tumor necrosis factor is a safe and effective treatment after the loss of response to these biologic agents, with a significant decrease of the clinical disease activity and biomarkers, in a population with limited therapeutic alternatives.

Incidencia de la fibrosis quística en Paraguay / Incidence of cystic fibrosis in Paraguay

Introducción: Fibrosis quística (FQ) patología genética, autosómica recesiva por mutaciones en el gen de la proteína reguladora de la conductancia transmembrana (CFTR cystic fibrosis transmembrane regulator). En una enfermedad multisistémica, afecta el aparato respiratorio, sistema digestivo, glándulas sudoríparas y conducto deferente. En Paraguay la detección, diagnóstico y tratamiento es obligatoria y gratuita para todo recién nacidos (RN). El tamizaje neonatal es realizado a través del dosaje de la tripsinainmuno reactiva (TIR) y la confirmación diagnóstica con el test del sudor. Objetivo: Reportar la incidencia de la FQ en la población de RN de Paraguay. Es un Materiales y Métodos: trabajo descriptivo, retrospectivo de corte trasversal, donde se analizaron los datos del Programa Nacional de Detección Neonatal (PNDN), de enero del 2015 a diciembre del 2017, para el análisis de la base de datos se utilizó una planilla Excel. Resultados: En el 2015 un 91% (79.093/87.181) de las muestras ingresadas al Programa reunieron los criterios (edad y calidad de la muestra) para el estudio de la TIR, arrojando una incidencia de 1 en 6.591 RN. Para el 2016, esto correspondió a un 97% (83.525/86.094) con una incidencia de 1 en 4.176 RN y por último en el 2017, se tuvo un 97% (87.075/90.037) con una incidencia de 1 en 5.112 RN. Conclusión: La incidencia de la FQ en la población de recién nacidos del Paraguay, en los tres años que abarca este estudio, no presentan entre sí diferencias significativas, tampoco con las reportadas para la población hispánica.

Introduction: Cystic fibrosis (CF), is an autosomal recessive genetic pathology that is caused by mutations in the transmembrane conductance regulatory protein (CFTR cystic fibrosis transmembrane regulator) gene. As a multisystem disease, it affects the respiratory system, digestive system, sweat glands and vas deferens. In Paraguay, detection, diagnosis and treatment is mandatory and free for all newborns (NB). Neonatal screening is performed by the immunoreactive trypsinogen assay (IRT) and diagnostic confirmation is performed by the sweat test. Objective: To report the incidence of CF in the NB population of Paraguay. Materials and Methods: This was a descriptive, retrospective, cross-sectional study, where data from the National Neonatal Screening Program (NNSP) were analyzed, from January 2015 to December 2017. To analyze the database, we used an Excel spreadsheet. Results: In 2015, 91% (79,093 / 87,181) of the samples sent to the Program met the criteria (age and sample quality) for the IRT study, with an incidence of 1 in 6,591 NB. In 2016, 97% (83,525 / 86,094) met criteria, with an incidence of 1 in 4,176 NB, while in 2017, 97% (87,075 / 90,037) met criteria, with an incidence of 1 in 5,112 NB. Conclusion: The incidence of CF in the newborn population of Paraguay, during the three years of this study, did not show significant differences between years, nor with those reported for the Hispanic population.