Evaluating the rate of reversal of fentanyl-induced respiratory depression using a novel long-acting naloxone nanoparticle, cNLX-NP.

Introduction: Fentanyl and fentanyl analogs (F/FA) have become increasingly common adulterants in counterfeit prescription pills and illicit street drug mixtures due to their ease of synthesis and exceedingly high potency. The ongoing epidemic of fatal overdoses fueled by F/FA continues to highlight the need for longer-acting therapies than naloxone (NLX), the current gold-standard for reversing opioid overdoses, which shows limited efficacy to prevent renarcotization associated with F/FA toxicity. A novel opioid reversal agent based on covalent naloxone nanoparticles (cNLX-NP) has been shown to blunt fentanyl-induced respiratory depression out to 48 hr, demonstrating its potential therapeutic utility. The purpose of this study was to characterize how rapidly cNLX-NP reverses fentanyl-induced respiratory effects as well as the duration of its protective effects. Methods: Sprague Dawley male rats (n=6/group) were tested on an oximeter for baseline percent arterial oxygen saturation (%SaO2) challenged with 0.1 mg/kg SC fentanyl and 15 min later given 10 mg/kg IM doses of NLX, nalmefene (NLMF), or cNLX-NP and continuously monitored via oximetry for 10 minutes. One week later the experiment was repeated using a 1:1 mixture of NLX:cNLX-NP as the reversal agent in the rats that previously received NLX alone. Results: While both NLX and NLMF rapidly reversed %SaO2 to baseline within 1 min, rats that received cNLX-NP did not return to >90% SaO2 levels until 9 min after administration. Similarly, heart and breath rates returned to baseline within 1 min of treatment with NLX and NLMF but did not return to baseline until 10 minutes after cNLX-NP administration. In contrast, NLX:cNLX-NP reversed all fentanyl-induced respiratory depressive effects within one minute. Discussion: While cNLX-NP alone may not sufficiently reverse F/FA overdose in a timely manner, mixing free NLX with cNLX-NP can provide a mechanism to both rapidly reverse fentanyl-related effects and maintain extended protection against synthetic opioid toxicity. These data support further development of cNLX-NP as a fast-acting and long-lasting antidote to treat F/FA-induced respiratory depression and overdose, and potentially prevent renarcotization in humans.

Organophosphate Detoxification and Acetylcholinesterase Reactivation Triggered by Zeolitic Imidazolate Framework Structural Degradation.

Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn-L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P-X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate. P-X hydrolysis is accompanied by ZIF structural degradation (Zn-imidazolate bond hydrolysis), with the concomitant release of the imidazolate linkers and zinc ions representing up to 95% of ZIF particle dissolution. The delivered imidazolate nucleophilic attack on the OP@AChE adduct gives rise to the recovery of AChE enzymatic function. P-X bond breakdown, ZIF structural degradation, and AChE reactivation are dependent on imidazolate linker nucleophilicity, framework topology, and particle size. The best performance is obtained for 20 nm nanoparticles (NPs) of Zn(2-methylimidazolate)2 (sod ZIF-8) exhibiting a DIFP degradation half-life of 2.6 min and full recovery of AChE activity within 1 h. 20 nm sod ZIF-8 NPs are not neurotoxic, as proven by in vitro neuroblastoma cell culture viability tests.

T Cell-Induced Colitis Is Exacerbated by Prolonged Stress: A Comparison in Male and Female Mice.

Psychological stress exposure is well recognized to exacerbate inflammatory bowel disease (IBD) but the mechanisms involved remain poorly understood. In this study, chronic T cell-mediated colitis was induced by adoptively transferring CD4+CD45RBhigh splenic T cells from C57BL/6 WT donor mice into Rag1tm1Mom mice. Two weeks after T cell transfer, mice were exposed to a prolonged restraint stressor (RST) for 8 h per day for 6 consecutive days. The colitis phenotype was assessed via histopathology and semi-quantitative rt-PCR at humane endpoints or 10 weeks post-T-cell transfer. Mice that received the T cell transplant developed chronic colitis marked by increases in colonic histopathology and inflammatory cytokines. Colonic histopathology was greater in males than females regardless of RST exposure but RST exposure increased histopathology scores in females such that they reached scores observed in the males. This pattern was consistent with cytokine gene expression and protein levels in the colon (especially for IFN-γ, IL-17A, and TNF-α). Serum cytokine levels were not strongly affected by exposure to the stressor. Using a murine model of chronic T cell-mediated colitis, this study demonstrates that biological sex strongly influences colonic inflammation and exposure to chronic stress has a more pronounced effect in females than in males.

Better soon than never: climate change induces strong phenological reassembly in the flowering of a Mediterranean shrub community.

● Flowering is a key process in the life cycle of a plant. Climate change is shifting flowering phenologies in the Northern Hemisphere, but studies with long data series at community level are scarce, and even more so those regarding the consequences of phenological changes for emerging ecological interactions. In the Mediterranean region, the effects of climate change are stronger than the global average and there is an urgent need to understand how biodiversity will be affected in this area. ● In this study we investigated how the entire flowering phenology of a community comprising 51 perennial species from the south of the Iberian Peninsula changed from the decade of the 1980s to the 2020s. Furthermore, we have analysed the consequences of these changes for flowering order and co-flowering patterns. ● We have found that the flowering phenology of the community has advanced by about 20 days, and was coherent with the increasing temperatures related to climate change. Individual species have generally advanced their entire flowering phenology (start and end) and increased their flowering duration. The early flowering has resulted in a re-organisation of the flowering order of the community and generated a new co-flowering assemblages of species, with a slight trend towards an increase of shared flowering time among species. ● The advanced flowering phenology and changes on flower duration reported here were of unprecedented magnitude, showcasing the extreme effects of climate change on Mediterranean ecosystems. Furthermore, the effects were not similar among species, which could be attributed to differences in sensitivities of environmental cues for flowering. One consequence of these changes in flowering times is the ecological mismatches indicated by the changes in flower order and co-flowering between decades. The novel scenario may lead to new competition or facilitation interactions and to the loss or gain of pollinators.

Parásitos en un venado de cola blanca silvestre en Cajamarca, Perú

En el presente estudio se informa sobre los parásitos encontrados en un venado de cola blanca, Odocoileus virginianus peruvianus, capturado en el bosque seco del distrito de Paccha, provincia de Chota, departamento de Cajamarca. El Servicio Nacional Forestal y de Fauna Silvestre recuperó los parásitos de un espécimen macho adulto y las remitió al Centro de Investigación en Medicina Tropical de la Universidad Nacional de Cajamarca para la identificación taxonómica de helmintos y artrópodos, y análisis coproparasitológico. Se identificaron dos metacéstodos correspondientes a Cysticercus tenuicollis. En los análisis coproparasitológicos cualitativos se hallaron huevos de Nematodirus spp. en una carga de 10 por gramo de heces (h.p.g.) y 40 h.p.g. tipo Strongílidos que no pudieron diferenciarse por la baja carga en el coprocultivo. No se detectaron huevos de trematodos en la sedimentación. De ectoparásitos, se identificaron ocho garrapatas duras Rhipicephalus (Boophilus) microplus y cinco piojos chupadores Solenopotes binipilosus. Varios de los ejemplares fueron depositados en el Museo de Historia Natural de la Universidad Nacional Mayor de San Marcos, Lima. Los hallazgos representan el primer reporte formal de la garrapata común del ganado en esta subespecie de cérvido. Además, se registra por primera vez la presencia del piojo Solenopotes binipilosus en territorio peruano.

In the present study, findings regarding parasites discovered in a white-tailed deer, Odocoileus virginianus peruvianus, captured in the dry forest of the Paccha district, Chota province, Cajamarca department, are reported. The Servicio Nacional Forestal y de Fauna Silvestre recovered parasites from an adult male specimen and forwarded them to the Tropical Medicine Research Center at the Universidad Nacional de Cajamarca for taxonomic identification of helminths and arthropods, as well as coproparasitological analysis. Two metacestodes corresponding to Cysticercus tenuicollis were identified. Qualitative coproparasitological analyses revealed Nematodirus spp. eggs at a concentration of 10 eggs per gram of feces (EPG) and 40 EPG of Strongylid type that could not be differentiated due to low counts in the coproculture. No trematode eggs were detected in the sedimentation. Among ectoparasites, eight hard ticks Rhipicephalus (Boophilus) microplus and five sucking lice Solenopotes binipilosus were identified. Several specimens were deposited in the Museo de Historia Natural de la Universidad Nacional Mayor de San Marcos, Lima. These findings represent the first formal report of the common cattle tick in this subspecies of cervid. Additionally, the presence of the Solenopotes binipilosus louse in Peruvian territory is reported for the first time.

Prevalence of Malnutrition and Associated Factors in Older Patients with Rheumatoid Arthritis: A Cross-Sectional Study.

OBJECTIVE: To describe the frequency of malnutrition in older patients with rheumatoid arthritis (RA) and investigate associated risk factors. METHODS: This multicenter, cross-sectional study included participants aged ≥65 years who met the 2010 ACR/EULAR criteria for RA. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF) and based on variables, such as albumin level, the Geriatric Nutritional Risk Index (GNRI), and vitamin D. Data were also collected on epidemiological variables, inflammatory disease activity, quality of life, physical function, and frailty. Multivariate models were used to study factors associated with nutritional status. RESULTS: The study population comprised 76 RA patients aged ≥65 years, of whom 68.4% had a normal nutritional status, and 31.5% had an impaired nutritional status: 28.9% were at risk of malnutrition, and 2.6% were malnourished. Additionally, 10% had albumin levels <3.8 g/L. Patients with impaired nutritional status had poorer quality of life and physical function. The factors associated with compromised nutritional status (OR [95% CI]) were age (1.0 [1.0-1.1]; p = 0.035), DAS28-ESR (1.8 [1.0-3.2]; p = 0.024), and EuroQoL-5D-5L (0.9 [0.9-0.9]; p = 0.040). Furthermore, the GNRI was associated with the MNA score (0.06 [0.0-0.1]; p = 0.014). CONCLUSIONS: Approximately one-third of older patients with RA have impaired nutritional status. Older age, higher inflammatory disease activity, and decreased quality of life are associated with impaired nutritional status. The MNA and GNRI are valuable tools for assessing the nutritional status of patients with RA.

Sarcopenia and Nutrition in Elderly Rheumatoid Arthritis Patients: A Cross-Sectional Study to Determine Prevalence and Risk Factors.

OBJECTIVE: To describe the prevalence of sarcopenia in rheumatoid arthritis (RA) patients aged ≥65 years and identify the risk factors associated with sarcopenia. METHODS: This is a multicenter, controlled, cross-sectional study of 76 RA patients and 76 age- and sex-matched healthy controls. Sarcopenia was defined according to the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Whole-body dual-energy X-ray absorptiometry (DXA) was performed. Binary regression was used to assess the relationship between sarcopenia and sex, age, duration of RA, Mini Nutritional Assessment (MNA) score, and Short Physical Performance Battery (SPPB) score in patients with RA. RESULTS: Nearly 80% of participants were female, and the average age was >70 years. Patients with RA had lower muscle mass and greater adiposity (fat-to-muscle ratio mean [SD] 0.9 [0.2] vs. 0.8 [0.2]; p = 0.017) than controls, mainly in the central area (android/gynoid ratio, median [p25-p75]: 1.0 [0.9-1.2] vs. 0.9 [0.8-1.1]; p < 0.001). Twelve patients (15.8%) and three controls (3.9%) had confirmed sarcopenia (p = 0.014). Sarcopenic obesity was observed in 8/76 patients with RA (10.5%) and in 1/76 controls (1.3%) (p = 0.016). The factors associated with sarcopenia were male sex (OR [95% CI]: 9.3 [1.1-80.4]; p = 0.042), disease duration (OR [95% CI]: 1.1 [1.0-1.2]; p = 0.012), and nutritional status according to the MNA (OR [95% CI]: 0.7 [0.5-0.9]; p = 0.042). CONCLUSIONS: Our results suggest that patients with RA aged ≥65 years may be at increased risk for sarcopenia, adiposity, and malnutrition (especially male patients with long-standing disease) and have poor nutritional status.

Development of novel DNA marker for species discrimination of Fasciola flukes based on the fatty acid binding protein type I gene.

BACKGROUND: Multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) for nuclear phosphoenolpyruvate carboxykinase (pepck) and polymerase delta (pold), respectively, have been used to differentiate Fasciola hepatica, F. gigantica, and hybrid Fasciola flukes. However, discrimination errors have been reported in both methods. This study aimed to develop a multiplex PCR based on a novel nuclear marker, the fatty acid binding protein type I (FABP) type I gene. METHODS: Nucleotide sequence variations of FABP type I were analyzed using DNA samples of F. hepatica, F. gigantica, and hybrid Fasciola flukes obtained from 11 countries in Europe, Latin America, Africa, and Asia. A common forward primer for F. hepatica and F. gigantica and two specific reverse primers for F. hepatica and F. gigantica were designed for multiplex PCR. RESULTS: Specific fragments of F. hepatica (290 bp) and F. gigantica (190 bp) were successfully amplified using multiplex PCR. However, the hybrid flukes contained fragments of both species. The multiplex PCR for FABP type I could precisely discriminate the 1312 Fasciola samples used in this study. Notably, no discrimination errors were observed with this novel method. CONCLUSIONS: Multiplex PCR for FABP type I can be used as a species discrimination marker in place of pepck and pold. The robustness of the species-specific primer should be continuously examined using a larger number of Fasciola flukes worldwide in the future since nucleotide substitutions in the primer regions may cause amplification errors.

Advancing humanized monoclonal antibody for counteracting fentanyl toxicity towards clinical development.

Innovative therapies to complement current treatments are needed to curb the growing incidence of fatal overdoses related to synthetic opioids. Murine and chimeric monoclonal antibodies (mAb) specific for fentanyl and its analogs have demonstrated pre-clinical efficacy in preventing and reversing drug-induced toxicity in rodent models. However, mAb-based therapeutics require extensive engineering as well as in vitro and in vivo characterization to advance to first-in-human clinical trials. Here, novel murine anti-fentanyl mAbs were selected for development based on affinity for fentanyl, and efficacy in counteracting the pharmacological effects of fentanyl in mice. Humanization and evaluation of mutations designed to eliminate predicted post-translational modifications resulted in two humanized mAbs that were effective at preventing fentanyl-induced pharmacological effects in rats. These humanized mAbs showed favorable biophysical properties with respect to aggregation and hydrophobicity by chromatography-based assays, and thermostability by dynamic scanning fluorimetry. These results collectively support that the humanized anti-fentanyl mAbs developed herein warrant further clinical development for treatment of fentanyl toxicity.

[Therapeutic approach to attention deficit hyperactivity disorder]. / Enfoque terapéutico del trastorno por déficit de atención e hiperactividad.

Attention deficit hyperactivity disorder (ADHD) is the most prevalent and frequent neurodevelopmental disorder in neuropediatrics, child psychiatry and child psychology consultations. The greater awareness of this condition, the information and, above all, the socio-cultural acceptance, has led to an earlier diagnosis, leading to more timely and effective treatment. Individualizing each case through systematic tools such as neuropsychological studies and their neuroanatomical and neurobiochemical correlation, related to ADHD, together with algorithms that analyze executive functions, is essential to indicate the optimal pharmacological treatment, together with the application of appropriate non-pharmacological therapies. Multimodal treatment, with cognitive behavioral intervention and pharmacological treatment, is the most effective therapeutic approach.

El trastorno por déficit de atención e hiperactividad (TDAH) es el trastorno del neurodesarrollo más prevalente y frecuente en las consultas de neuropediatría, psiquiatría y psicología infantiles. La mayor sensibilización ante esta condición, la información y sobre todo la aceptación socio cultural, ha provocado que se diagnostique más precozmente, implicando ello un tratamiento más oportuno y eficaz. El individualizar cada caso mediante herramientas sistemáticas como los estudios neuropsicológicos y su correlación neuroanatómica y neurobioquímica, relacionados con el TDAH, junto con los algoritmos que analizan las funciones ejecutivas, es primordial para indicar el tratamiento farmacológico óptimo, unido a la aplicación de las terapias no farmacológicas apropiadas. El tratamiento multimodal, con intervención cognitivo conductual y tratamiento farmacológico, es el enfoque terapéutico más efectivo.

The Differences in the Susceptibility Patterns to Triclabendazole Sulfoxide in Field Isolates of Fasciola hepatica Are Associated with Geographic, Seasonal, and Morphometric Variations.

Triclabendazole (TCBZ) resistance is an emerging problem in fascioliasis that is not well understood. Studies including small numbers of parasites fail to capture the complexity of susceptibility variations between and within Fasciolahepatica populations. As the first step to studying the complex resistant phenotype−genotype associations, we characterized a large sample of adult F. hepatica with diverging TCBZ susceptibility. We collected parasites from naturally infected livestock slaughtered in the Cusco and Cajamarca regions of Peru. These parasites were exposed to TCBZ sulfoxide (TCBZ.SO) in vitro to determine their susceptibility. We used a motility score to determine the parasite's viability. We titrated drug concentrations and times to detect 20% non-viable (susceptible conditions) or 80% non-viable (resistant conditions) parasites. We exposed 3348 fully motile parasites to susceptible (n = 1565) or resistant (n = 1783) conditions. Three hundred and forty-one (21.8%) were classified as susceptible and 462 (25.9%) were classified as resistant. More resistant parasites were found in Cusco than in Cajamarca (p < 0.001). Resistant parasites varied by slaughterhouse (p < 0.001), month of the year (p = 0.008), fluke length (p = 0.016), and year of collection (p < 0.001). The in vitro susceptibility to TCBZ.SO in wildtype F. hepatica was associated with geography, season, and morphometry.

High mortality among hospitalized adult patients with COVID-19 pneumonia in Peru: A single centre retrospective cohort study.

BACKGROUND: Peru is the country with the world's highest COVID-19 death rate per capita. Characteristics associated with increased mortality among adult patients with COVID-19 pneumonia in this setting are not well described. METHODS: Retrospective, single-center cohort study including 1537 adult patients hospitalized with a diagnosis of SARS-CoV-2 pneumonia between May 2020 and August 2020 at a national hospital in Lima, Peru. The primary outcome measure was in-hospital mortality. RESULTS: In-hospital mortality was 49.71%. The mean age was 60 ± 14.25 years, and 68.38% were males. We found an association between mortality and inflammatory markers, mainly leukocytes, D-dimer, lactate dehydrogenase, C-reactive protein and ferritin. A multivariate model adjusted for age, hypertension, diabetes mellitus, and corticosteroid use demonstrated that in-hospital mortality was associated with greater age (RR: 2.01, 95%CI: 1.59-2.52) and a higher level of oxygen requirement (RR: 2.77, 95%CI: 2.13-3.62). Conclusions: In-hospital mortality among COVID-19 patients in Peru is high and is associated with greater age and higher oxygen requirements.

Stressor-Induced Increases in Circulating, but Not Colonic, Cytokines Are Related to Anxiety-like Behavior and Hippocampal Inflammation in a Murine Colitis Model.

Stressor exposure increases colonic inflammation. Because inflammation leads to anxiety-like behavior, we tested whether stressor exposure in mice recovering from dextran-sulfate-sodium (DSS)-induced colitis enhances anxiety-like behavior. Mice received 2% DSS for five consecutive days prior to being exposed to a social-disruption (SDR) stressor (or being left undisturbed). After stressor exposure, their behavior was tested and colitis was assessed via histopathology and via inflammatory-cytokine measurement in the serum and colon. Cytokine and chemokine mRNA levels in the colon, mesenteric lymph nodes (MLNs), hippocampus, and amygdala were measured with RT-PCR. SDR increased anxiety-like behaviors, which correlated with serum and hippocampal IL-17A. The stressor also reduced IL-1ß, CCL2, and iNOS in the colonic tissue, but increased iNOS, IFNγ, IL-17A, and TNFα in the MLNs. A network analysis indicated that reductions in colonic iNOS were related to elevated MLN iNOS and IFNγ. These inflammatory markers were related to serum and hippocampal IL-17A and associated with anxiety-like behavior. Our data suggest that iNOS may protect against extra-colonic inflammation, and when suppressed during stress it is associated with elevated MLN IFNγ, which may coordinate gut-to-brain inflammation. Our data point to hippocampal IL-17A as a key correlate of anxiety-like behavior.

Timed up and go test predicts mortality in older adults in Peru: a population-based cohort study.

BACKGROUND: While there is evidence about stablished risk factors (e.g., raised blood pressure) and higher mortality risk in older population, less has been explored about other functional parameters like the Timed Up and Go test and the Gait Speed in older people at low- and middle-income countries. We aimed to study these mobility tests as predictors of mortality in a population of older people in Peru. METHODS: Population-based prospective cohort study (2013-2020). Random sampling of people aged 60+ years in a community of Lima, Peru. Geriatricians conducted all clinical evaluations and laboratory tests were conducted in the local hospital. Participants were sought in the national vital registration system, and we collated cause (ICD-10) and date of death. We conducted a nested forward multivariate Cox proportional hazard model to identify all potential predictors of all-cause, communicable and non-communicable diseases mortality. RESULTS: At baseline, there were 501 older people (mean age 70.6 and 62.8% were women), complete follow-up information was available from 427 people. Mean follow-up time was 46.5 months (SD = 25.3). In multivariate models, the Timed Up and Go test was associated with higher risk of all-cause mortality (HR = 1.05; 95% CI: 1.02-1.09). For cause-specific mortality, history of heart disease (HR = 2.25; 95% CI: 1.07-4.76) and age in years (HR = 1.05; 95% CI: 1.01-1.09) were predictors of non-communicable diseases mortality. CONCLUSIONS: In addition to established risk factors for mortality in older population, the Timed Up and Go test, a functional parameter, raised as a relevant predictor of all-cause mortality.

A novel series of pyrazole derivatives toward biological applications: experimental and conceptual DFT characterization.

A new series of 13 pyrazole-derivative compounds with potential antifungal activity were synthetized with good yields. The series have the (E)-2-((1-(R)-3,5-dimethyl-1H-pyrazol-4-yl)diazenyl)phenol general structure and were characterized by means of X-ray diffraction, UV-Vis, FTIR, 1H-NMR, 13C-NMR, and two-dimensional NMR experiments. This experimental characterization was complemented by DFT simulations. A deep insight regarding molecular reactivity was accomplished employing a conceptual DFT approach. In this sense, dual descriptors were calculated at HF and DFT level of theory and GGV spin-density Fukui functions. The main reactive region within the molecules was mapped through isosurface and condensed representations. Finally, chemical descriptors that have previously shown to be close related to biological activity were compared within the series. Thus, higher values of chemical potential ω and electrophilicity χ obtained for compounds 10, 9, 8, 6 and 7, in this order, suggest that these molecules are the better candidates as biological agents.

The Effect of an Abdominal Binder on Postoperative Pain After Laparoscopic Incisional Hernia Repair­A Multicenter, Randomized Pilot Trial (ABIHR-I) of the Intraperitoneal Onlay-Mesh Technique.

BACKGROUND: Incisional hernias with apertures measuring less than 7 cm can generally be treated adequately with the laparoscopic intraperitoneal onlay-mesh (IPOM) technique. The wearing of an abdominal binder after surgery is often recommended in order to promote wound healing and prevent recurrent herniation. We carried out a multicenter, randomized pilot trial to evaluate the utility of abdominal binders. METHODS: The trial was conducted from May 2019 to December 2020. Persons with a laparoscopic IPOM procedure for treatment of an incisional hernia were included in the trial and randomized preoperatively (1:1). The patients in the abdominal binder group wore an abdominal binder during the day for 14 days after surgery, while those in the control group wore no binder. The primary endpoint was pain at rest on postoperative days 1, 2, and 14, as measured on a visual analog scale. The secondary endpoints were overall subjective well-being, the rates of wound infection, recurrence, and complications, mobility, and the rate and size of postoperative seromas (on postoperative days 1, 2, and 14). RESULTS: Forty patients were included. Three were excluded because of conversion to an open surgical technique. The biometric and perioperative data of the abdominal binder group (n = 18) and the control group (n = 19) did not differ to any statistically significant extent. The patients in the binder group had significantly less postoperative pain (F [dfn, dfd]) 4.44, 95% confidence interval [1; 35]; p = 0.042).The patients in the binder group also had better overall subjective well-being and a higher rate of postoperative seroma formation, but these differences did not reach statistical significance. There was less limitation of mobility than in the control group; however, this difference also did not attain statistical significance. CONCLUSION: An abdominal binder may reduce pain after incisional hernia repair with the IPOM technique. The postoperative use of analgesic medication was not measured.

Implantación intraabdominal de un injerto renal con dos arterias renales en un receptor pediátrico de bajo peso. Primer caso reportado en el Paraguay / Intra-abdominal implantation of a kidney graft with two renal arteries in a low-weight pediatric recipient. First case reported in Paraguay

El trasplante renal de órganos provenientes de donantes adultos implantados en una cavidad anatómica estrecha en pacientes pediátricos de bajo peso, ofrece importantes desafíos médicos y quirúrgicos a ser considerados. En esta publicación reportamos el primer caso en el Paraguay de un riñón con dos arterias renales injertado a la aorta y vena cava inferior, dentro de la cavidad abdominal de un paciente pediátrico de 12 kilogramos de peso, evaluando las dificultades médicas, anatómicas y quirúrgicas enfrentadas, así como las opciones de tratamiento instituidas para llevar a cabo este procedimiento de manera exitosa

Kidney transplantation of organs from adult donors implanted into a narrow anatomical cavity in underweight pediatric patients offers significant medical and surgical challenges to be considered. In this publication we report the first case in Paraguay of a kidney with two renal arteries, grafted to the aorta and inferior vena cava within the abdominal cavity, on a 12 kilogram pediatric patient, evaluating the medical, anatomical and surgical conditions faced, as well as the treatment options instituted to successfully carry out this procedure

A Rare Etiology of Unilateral Pseudo-Pulmonary Fibrosis in a Puerto Rican Child.

Congenital unilateral pulmonary hypoplasia of a pulmonary artery is considered a rare congenital anomaly in the pediatric and adult population. With an estimated prevalence of one in 200,000, it can range from partial to near-total lung underdevelopment. The diagnosis of lung and pulmonary artery hypoplasia is challenging in adults as they can easily be mistaken for more common diseases. Many survive into adulthood with minimal or no symptoms, which makes their identification challenging. We present the case of a 14-year-old female with a previous diagnosis of 3-methylglutaconic aciduria (3-MGA-uria) with a history of chronic wet cough andrecurrent respiratory tract infections (RTIs) that led to multiple hospitalizations throughout her childhood. After further evaluation, the patient was diagnosed with hypoplasia of the right-sided pulmonary artery system and its branches. This case report highlights the importance of early identification of congenital unilateral pulmonary hypoplasia of a pulmonary artery to prevent pulmonary complications like recurrent RTIs in pediatric patients with rare diseases.

Polyethylene Glycol 3350 Changes Stool Consistency and the Microbiome but not Behavior of CD1 Mice.

OBJECTIVES: Polyethylene Glycol 3350 (PEG3350) is a laxative commonly used to treat constipation in children. The Food and Drug Administration has received reports of increased anxiety, aggression, and obsessive--compulsive behaviors in children administered PEG3350. Thus, we assessed whether daily administration of PEG3350 leads to anxiety-like behavior in mice. METHODS: Outbred CD-1 IGS mice were administered either a high or a low dose of PEG3350 via daily oral gavage for 2 weeks. As a laxative comparison and control, additional mice were given a high or low dose of magnesium citrate or vehicle (water). Weight and stool consistency were assessed after each gavage to determine laxative effectiveness. Anxiety-like behaviors were assessed using light/dark, open field, and elevated plus maze (EPM) tests at baseline, after 2 weeks of daily gavage, and after a 2 week washout in experiment 1, and after 2 weeks of daily gavage in experiment 2. Stool samples were collected for microbiome analysis in experiment 2 at baseline, after 2 weeks of daily gavage, and after 2 weeks washout. RESULTS: PEG3350 and magnesium citrate significantly changed stool consistency, as well as microbiome alpha and beta diversity. Anxiety-like behaviors were not, however, different in mice administered low or high doses of PEG3350 or magnesium citrate. CONCLUSIONS: Although changes in stool consistency and the gut microbiome occurred, administration of PEG3350 did not alter anxiety-like behaviors.