Case Report: A rare instance of acute appendicitis induced by Balantidium Coli parasitic infection.

Introduction: Acute appendicitis secondary to parasitic infections is uncommon, being detected in less than 1% of cases. Balantidium coli is a parasite found in pigs and primates with zoonotic potential. To date, only three cases of acute appendicitis induced by this parasite have been documented globally. Case: A 7-year-old female patient, who consumed pork daily, presented to the emergency department with a one-day history of abdominal pain in the lower quadrants, described as colic-like, alongside abdominal distension. Initial abdominal radiography led to a diagnosis of intestinal obstruction. Conservative management without therapeutic response necessitated referral to a higher complexity center. Upon admission, an abdominal computed tomography scan diagnosed acute appendicitis and secondary ileus. During surgical intervention, an appendiceal phlegmon formed by loops of the small intestine was mechanically released, revealing a perforated appendix with extensive fecal peritoneal contamination. Pathological analysis identified an inflammatory infiltrate and the presence of Balantidium coli trophozoites. Medical treatment included Piperacillin-Tazobactam and Metronidazole. The patient was discharged after 10 days of medical treatment. Discussion: Acute appendicitis caused by Balantidium coli is a rare occurrence. It is crucial to identify parasites in pathological samples due to their impact on postoperative management. The close contact between humans and pigs, especially in developing countries, suggests that the prevalence of parasitic infection and colonization by Balantidium coli may be higher than currently recognized. Regarding the identification of this patient's specific exposure, the regular consumption of pork suggests the hypothesis that improper processing is linked to the acquisition of the parasitic infection.

Oxidative potential of particulate matter and its association to respiratory health endpoints in high-altitude cities in Bolivia.

Exposure to particulate matter (PM) pollution is a significant health risk, driving the search for innovative metrics that more accurately reflect the potential harm to human health. Among these, oxidative potential (OP) has emerged as a promising health-based metric, yet its application and relevance across different environments remain to be further explored. This study, set in two high-altitude Bolivian cities, aims to identify the most significant sources of PM-induced oxidation in the lungs and assess the utility of OP in assessing PM health impacts. Utilizing two distinct assays, OPDTT and OPDCFH, we measured the OP of PM samples, while also examining the associations between PM mass, OP, and black carbon (BC) concentrations with hospital visits for acute respiratory infections (ARI) and pneumonia over a range of exposure lags (0-2 weeks) using a Poisson regression model adjusted for meteorological conditions. The analysis also leveraged Positive Matrix Factorization (PMF) to link these health outcomes to specific PM sources, building on a prior source apportionment study utilizing the same dataset. Our findings highlight anthropogenic combustion, particularly from traffic and biomass burning, as the primary contributors to OP in these urban sites. Significant correlations were observed between both OPDTT and PM2.5 concentration exposure and ARI hospital visits, alongside a notable association with pneumonia cases and OPDTT levels. Furthermore, PMF analysis demonstrated a clear link between traffic-related pollution and increased hospital admissions for respiratory issues, affirming the health impact of these sources. These results underscore the potential of OPDTT as a valuable metric for assessing the health risks associated with acute PM exposure, showcasing its broader application in environmental health studies.

Case Report: ALPPS hepatectomy, an alternative to liver transplantation in central PRETEXT III hepatoblastomas: a case series.

Introduction: Hepatoblastoma is the most common malignant primary liver tumor in the pediatric population, accounting for 67% of cases in the United States. Surgical resection is the only curative treatment option; however, it can be performed in only 10% of patients with primary tumors. The two most common limitations for resection are the need for extensive resections and tumors in central locations. The therapeutic hypertrophy of healthy tissue achieved with ALPPS (Associating Liver Partition and Portal vein ligation for Staged Hepatectomy) enables larger resections and has been successfully employed in the pediatric population in recent years. Objective: To present three cases of patients with centrally located PRETEXT II or III hepatoblastomas who underwent ALPPS procedure as a viable therapeutic alternative to liver transplantation. Discussion and results: Central PRETEXT III hepatoblastomas are typically indications for liver transplantation. Transplantation offers high five-year survival rates (73%). However, the associated morbidity, healthcare system costs, and limited availability make it necessary to explore alternative options. Series have reported the successful application of the ALPPS procedure in PRETEXT II and PRETEXT III hepatoblastomas in other locations. Therapeutically induced hypertrophy, characterized by an increase in the volume of healthy tissue in unaffected lobes or segments, enabled the resection of previously deemed unresectable lesions. The patients experienced uncomplicated postoperative courses and expected reduction in tumor markers. Chemotherapy selection followed the guidelines outlined in Block C of the SIOPEL IV protocol. Conclusions: ALPPS hepatectomy is a viable therapeutic option for patients with centrally located PRETEXT III or II hepatoblastomas.

Weakened sympathetic response and lower parasympathetic activity in intimate partner violence perpetrators when empathizing: Influence of autonomous activation in affective approach and prosocial behavior.

The autonomic nervous system (ANS) functioning has been proposed as a relevant method to characterize the therapeutic needs of intimate partner violence (IPV) perpetrators. Nevertheless, research has neglected the influence of the ANS on socio-affective functions in this population. The aim of the present study was to analyze the psychophysiological activity of IPV perpetrators (n = 52) compared to controls (n = 46) following an empathic induction task, performed through negative emotion-eliciting videos. We employed two general ANS markers (heart rate [HR] and respiratory rate [RR]), two sympathetic-related indexes (pre-ejection period [PEP] and skin conductance level [SCL]) and a parasympathetic biomarker (respiratory sinus arrhythmia [RSA]). Additionally, we explored the impact of psychophysiological activity on prosocial behavior using Hare's donation procedure. Compared to controls, IPV perpetrators reported lower HR and SCL following the task, as well as longer PEP, suggesting an attenuated sympathetic response to others' distress. No differences in the RSA response pattern were found, however, IPV perpetrators displayed lower overall RSA levels throughout the protocol, indicative of reduced parasympathetic activity. Besides, while no differences in prosocial performance were observed, greater sympathetic responses and overall parasympathetic activity predicted increased donations across the sample. Thus, a high sympathetic and parasympathetic activity might influence the occurrence of prosocial behavior. The present study provides further evidence supporting that IPV perpetrators cope differently with others' negative emotions. In line with this biopsychosocial perspective, insights are gained on the emotional processing of IPV perpetrators which, in turn, could contribute to improve IPV psychotherapeutic programs.

Baseline serum neurofilament light chain levels differentiate aggressive from benign forms of relapsing-remitting multiple sclerosis: a 20-year follow-up cohort.

BACKGROUND AND OBJECTIVES: Serum biomarkers are emerging as useful prognostic tools for multiple sclerosis (MS); however, long-term studies are lacking. We aimed to evaluate the long-term prognostic value of the serum levels of neurofilament light chain (NfL), total tau, glial fibrillary acidic protein (GFAP), and chitinase 3-like-1 (CHI3L1) measured close to the time of MS onset. METHODS: In this retrospective, exploratory, observational, case and controls study, patients with relapsing-remitting MS (RRMS) with available baseline serum samples and prospectively follow-up in our MS unit for a long time were selected based on their clinical evolution to form two groups: (1) a benign RRMS (bRRMS) group, defined as patients with an Expanded Disability Status Scale (EDSS) score of ≤ 3 at ≥ 10 years of follow-up; (2) an aggressive RRMS (aRRMS) group, defined as patients with an EDSS score of ≥ 6 at ≤ 15 years of follow-up. An age-matched healthy control (HC) group was selected. NfL, total tau, and GFAP serum levels were quantified using a single-molecule array (SIMOA), and CHI3L1 was quantified using ELISA. RESULTS: Thirty-one patients with bRRMS, 19 with aRRMS, and 10 HC were included. The median follow-up time from sample collection was 17.74 years (interquartile range, 14.60-20.37). Bivariate and multivariate analyses revealed significantly higher NfL and GFAP levels in the aRRMS group than in the bRRMS group. A receiver operating characteristic curve analysis identified serum NfL level as the most efficient marker for distinguishing aRRMS from bRRMS. DISCUSSION: This proof-of-concept study comparing benign and aggressive RRMS groups reinforces the potential role of baseline NfL serum levels as a promising long-term disability prognostic marker. In contrast, serum GFAP, total tau, and CHI3L1 levels demonstrated a lower or no ability to differentiate between the long-term outcomes of RRMS.

Liver disorders and celiac disease.

Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten intake. Celiac hepatitis is the most common hepatic manifestation of CD, it usually responds to a gluten-free diet (GFD) and is sometimes the only manifestation in paucisymptomatic CD. Through this descriptive observational study, we determined the prevalence of liver abnormalities upon diagnosis of CD. A total of 140 patients were included. The prevalence of alterations in liver markers at diagnosis of CD was 47%. In 2.9% of patients, liver abnormalities were the only manifestation at diagnosis. A higher prevalence of liver alterations was found in those patients who presented a more severe histological alteration (MARSH 3c).

Endogenous TSG-6 modulates corneal inflammation following chemical injury.

PURPOSE: Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) is upregulated in various pathophysiological contexts, where it has a diverse repertoire of immunoregulatory functions. Herein, we investigated the expression and function of TSG-6 during corneal homeostasis and after injury. METHODS: Human corneas, eyeballs from BALB/c (TSG-6+/+), TSG-6+/- and TSG-6-/- mice, human immortalized corneal epithelial cells and murine corneal epithelial progenitor cells were prepared for immunostaining and real time PCR analysis of endogenous expression of TSG-6. Mice were subjected to unilateral corneal debridement or alkali burn (AB) injuries and wound healing assessed over time using fluorescein stain, in vivo confocal microscopy and histology. RESULTS: TSG-6 is endogenously expressed in the human and mouse cornea and established corneal epithelial cell lines and is upregulated after injury. A loss of TSG-6 has no structural and functional effect in the cornea during homeostasis. No differences were noted in the rate of corneal epithelial wound closure between BALB/c, TSG-6+/- and TSG-6-/- mice. TSG-6-/- mice presented decreased inflammatory response within the first 24 h of injury and accelerated corneal wound healing following AB when compared to control mice. CONCLUSION: TSG-6 is endogenously expressed in the cornea and upregulated after injury where it propagates the inflammatory response following chemical injury.

Oxidized organic molecules in the tropical free troposphere over Amazonia.

New particle formation (NPF) in the tropical free troposphere (FT) is a globally important source of cloud condensation nuclei, affecting cloud properties and climate. Oxidized organic molecules (OOMs) produced from biogenic volatile organic compounds are believed to contribute to aerosol formation in the tropical FT, but without direct chemical observations. We performed in situ molecular-level OOMs measurements at the Bolivian station Chacaltaya at 5240 m above sea level, on the western edge of Amazonia. For the first time, we demonstrate the presence of OOMs, mainly with 4-5 carbon atoms, in both gas-phase and particle-phase (in terms of mass contribution) measurements in tropical FT air from Amazonia. These observations, combined with air mass history analyses, indicate that the observed OOMs are linked to isoprene emitted from the rainforests hundreds of kilometers away. Based on particle-phase measurements, we find that these compounds can contribute to NPF, at least the growth of newly formed nanoparticles, in the tropical FT on a continental scale. Thus, our study is a fundamental and significant step in understanding the aerosol formation process in the tropical FT.

Los cuidados enfermeros de San Juan de Dios según el Modelo de las necesidades humanas de Henderson / Cuidados de enfermagem de São João de Deus segundo o modelo de necessidades humanas de Henderson / Nursing care of Saint John of God according to Henderson's model of human needs

Consulting manuals of the History of Nursing, it can be appreciated how it is from Nightingale when considering the birth of modern or professional Nursing. However, this belief could be a black legend, because before the 19th century there was already awareness of Nursing as a profession, being this initiated by Juan de Dios, the one from Granada, in the Spanish 16th century. For this reason, in this article we have set the objective of describing the care of Juan de Dios following the model of human needs described by Henderson, together with care in agony and post-mortem. To do this, we use the historiographical methodology following the current of the history of mentalities, so that we can go from the past to the present, and vice versa. In the documentary analysis we have been able to observe how what we find today systematized in a theoretical way was already carried out at the beginning of the nursing reform of the Spanish 16th century, being a valid model for current Nursing, since it is found in its being, knowing , and doing, the concepts of the current nursing metaparadigm, although not explicitly, since its intention, more than theoretical, was care, although behind it there was a corpus of doctrine independent of other socio-health disciplines.(AU)

Consultando manuales de Historia de la Enfermería, se puede apreciar cómo es a partir de Nightingale cuando se considera el nacimiento de la Enfermería moderna o profesional. Sin embargo, esta creencia podría ser leyenda negra, pues antes del S. XIX ya existía conciencia de Enfermería como profesión, siendo esta iniciada por Juan de Dios, el de Granada, en el S. XVI español. Por ello, en el presente artículo hemos marcado como objetivo el describir los cuidados de Juan de Dios siguiendo el modelo de necesidades humanas descritas por Henderson, junto con los cuidados en la agonía y post-mortem. Para ello, utilizamos la metodología historiográfica siguiendo la corriente de la historia de las mentalidades, de manera que podamos ir del pasado al presente, y viceversa. En el análisis documental hemos podido observar cómo lo que hoy encontramos sistematizado de manera teórica, ya se realizaba en el inicio de la reforma enfermera del S. XVI español, siendo un modelo válido para la Enfermería actual, pues se encuentra en su ser, saber, y hacer, los conceptos del metaparadigma enfermero actuales aunque no de manera explícita, puesto que su intención, más que teórica, era asistencial, aunque detrás de ella hubo un corpus doctrinal independiente a otras disciplinassocio-sanitarias.(AU)

Ao consultar os manuais da História da Enfermagem, podese apreciar como é a partir de Nightingale quando se considera o nascimento da Enfermagem moderna ou profissional. No entanto, esta crença pode ser uma lenda negra, pois antes do século XIX já existia a consciência da Enfermagem como profissão, sendo esta iniciada por Juan de Dios, o de Granada, no século XVI espanhol. Por isso, neste artigo estabelecemos o objetivo de descrever o cuidado de Juan de Dios seguindo o modelo de necessidades humanas descrito por Henderson, juntamente com o cuidado em agonia e post-mortem. Para isso, utilizamos a metodologia historiográfica seguindo a corrente da história das mentalidades, para que possamos ir do passado ao presente e vice-versa. Na análise documental pudemos observar como o que encontramos hoje sistematizado de forma teórica já foi realizado no início da reforma da enfermagem espanhola do século XVI, sendo um modelo válido para a Enfermagem atual, uma vez que se encontra em seu ser, saber e fazer, os conceitos do atual metaparadigma da enfermagem, ainda que não explicitamente, pois sua intenção, mais do que teórica, era o cuidado, embora por trás dele houvesse um corpus de doutrina independente de outras disciplinas sócio-sanitárias.(AU)

Age related changes in hyaluronan expression leads to Meibomian gland dysfunction.

The prevalence of dry eye disease (DED) ranges from ∼5 to 50 % and its associated symptoms decrease productivity and reduce the quality of life. Approximately 85 % of all DED cases are caused by Meibomian gland dysfunction (MGD). As humans and mice age, their Meibomian glands (MGs) undergo age-related changes resulting in age related-MGD (ARMGD). The precise cause of ARMGD remains elusive, which makes developing therapies extremely challenging. We previously demonstrated that a hyaluronan (HA)-rich matrix exists surrounding the MG, regulating MG morphogenesis and homeostasis. Herein, we investigated whether changes to the HA matrix in the MG throughout life contributes towards ARMGD, and whether altering this HA matrix can prevent ARMGD. For such, HA synthase (Has) knockout mice were aged and compared to age matched wild type (wt) mice. MG morphology, lipid production, PPARγ expression, basal cell proliferation, stem cells, presence of atrophic glands and MG dropout were analyzed at 8 weeks, 6 months, 1 year and 2 years of age and correlated with the composition of the HA matrix. We found that as mice age, there is a loss of HA expression in and surrounding the MGs of wt mice, while, in contrast, Has1-/-Has3-/- mice present a significant increase in HA expression through Has2 upregulation. At 1 year, Has1-/-Has3-/- mice present significantly enlarged MGs, compared to age-matched wt mice and compared to all adult mice. Thus, Has1-/-Has3-/- mice continue to develop new glandular tissue as they age, instead of suffering MG atrophy. At 2 years, Has1-/-Has3-/- mice continue to present significantly larger MGs compared to age-matched wt mice. Has1-/-Has3-/- mice present increased lipid production, increased PPARγ expression and an increase in the number of proliferating cells when compared to wt mice at all-time points analyzed. Taken together, our data shows that a loss of the HA matrix surrounding the MG as mice age contributes towards ARMGD, and increasing Has2 expression, and consequently HA levels, prevents ARMGD in mice.

Characterization of Dengue Virus Serotype 2 Cosmopolitan Genotype Circulating in Colombia.

Dengue virus (DENV) is the etiological agent of dengue fever (DF), which is among the most prevalent vector-borne diseases in the tropics. In 2022, the Colombian health surveillance system reported more than 69,000 cases of DF. As part of a hospital-based fever surveillance study, acute-phase sera were collected from 4,545 patients with suspected dengue between 2020 and 2023 in three municipalities of Colombia. Combined reverse transcription-polymerase chain reaction and antigen rapid testing confirmed that 376 patients (8.3%) had DF. The virus was isolated in cell culture from 166 of these patients (44.1%), and genome sequencing was performed successfully on 122 (73.5%). Three DENV serotypes (1, 2, and 3) were identified. Phylogenetic analyses of the DENV-2 sequences revealed that 42 of 50 of the isolates (84%) belonged to the DENV-2 cosmopolitan genotype lineage, clustering with sequences from Asia, Peru, and Brazil. We report the detection, isolation, and whole-genome sequencing (11 Kb) of the DENV-2 cosmopolitan genotype and its recent introduction to Colombia.

Recent advances in age-related meibomian gland dysfunction (ARMGD).

Meibomian glands (MGs), located within the tarsal plate of the eyelid, secrete meibum which is the lipid-rich secretion necessary for stabilizing the tear film and preventing tear evaporation. Changes in the quality and quantity of meibum produced causes MG dysfunction (MGD), the leading cause of evaporative dry eye disease (EDED). MGD is an underdiagnosed disease and it is estimated that, in the US, approximately 70 % of the population over 60 have MGD. Three forms of MGD occur based on their meibum secretion: hyposecretory, obstructive, and hypersecretory MGD. The pathophysiology of MGD remains poorly understood, however aging is the primary risk factor. With age, MGs undergo various age-related changes, including decreased acinar basal cell proliferation, hyperkeratinization, MG atrophy, and eventual MG drop-out, leading to age-related MGD (ARMGD). Additionally, studies have suggested that MGs can suffer inflammatory cell infiltration and changes innervation patterns with aging, which could also contribute towards ARMGD. This review focuses on how the aging process affects the MG, and more importantly, how age-related changes to the MG can lead to MG atrophy and MG drop-out, ultimately leading to ARMGD. This review also highlights the most recent developments in potential therapeutic interventions for ARMGD.

Biological treatment interruption in inflammatory bowel disease: Motivation and predictive factors / Interrupción del tratamiento biológico en la enfermedad inflamatoria intestinal: causas y factores predictores

Background: Loss-of-response and adverse events (AE) to biologics have been linked to HLA-DQA1*05 allele. However, the clinical factors or biologic used may influence treatment duration. Our objective was to evaluate the influence of clinical and therapeutic factors, along with HLA, in biological treatment discontinuation. Methods: A retrospective study of consecutive IBD patients treated with biologics between 2007 and 2011 was performed. Main outcome was treatment discontinuation due to primary non-response (PNR), secondary loss of response (SLR) or AE. HLA-DQA1 genotyping was done in all patients. Regression analyses were used to assess risk factors of treatment discontinuation. Results: One hundred fifty patients (61% male) with 312 biologic treatments were included. 147 (47%) were discontinued with a cumulative probability of 30%, 41% and 56% at 1, 2 and 5 years. The use of infliximab (p=0.006) and articular manifestations (p<0.05) were associated with treatment discontinuation. Considering cause of withdrawal, Ulcerative Colitis (UC) had a higher proportion of PNR (HR=4.99; 95% CI=1.71–14.63; p=0.003), SLR was higher if biologics had been indicated due to disease flare (HR=2.32; 95% CI=1.05–5.09; p=0.037) while AE were greater with infliximab (HR=2.46; 95% CI=1.48–4.08; p<0.001) or spondylitis (HR=2.46; 95% CI=1.78–6.89; p<0.001). According to the biological drug, HLA-DQA1*05 with adalimumab showed more SLR in cases with Crohn's disease (HR=3.49; 95% CI=1.39–8,78; p=0.008) or without concomitant immunomodulator (HR=2.8; 95% CI=1.1–6.93; p=0.026). Conclusions: HLA-DQ A1*05 was relevant in SLR of IBD patients treated with adalimumab without immunosupression. In patients treated with other biologics, clinical factors were more important for treatment interruption, mainly extensive UC or extraintestinal manifestations and having indicated the biologic for flare. (AU)

Introducción: Estudios previos han observado una asociación entre el HLA-DQA1*05 y la pérdida de respuesta a biológicos y el desarrollo de efectos adversos (EA). Hay factores clínicos y biológicos que podrían influir en la duración del tratamiento. El objetivo del estudio fue evaluar la influencia del HLA, de factores clínicos y terapéuticos en la interrupción del tratamiento biológico. Métodos: Se realizó un estudio retrospectivo de pacientes con enfermedad inflamatoria intestinal (EII) tratados con biológicos entre 2007 y 2011. Los principales eventos analizados fueron la suspensión del tratamiento por fallo de respuesta primaria (PRP), secundaria (PRS) o EA. Se realizó un tipaje del HLA-DQA1*05 y se evaluaron los factores de riesgo de interrupción del tratamiento mediante un análisis de regresión logística. Resultados: Se incluyeron 150 pacientes y 312 tratamientos, de los cuales se suspendieron 147 (47%) en el seguimiento. El infliximab (p=0,006) y las manifestaciones articulares (p<0,05) se relacionaron con la interrupción del tratamiento. La colitis ulcerosa (CU) presentó mayor PRP (HR: 4,99; IC 95%: 1,71-14,63; p=0,003), el brote como indicación de tratamiento se asoció a más PRS (HR: 2,32; IC 95%: 1,05-5,09; p=0,037); el uso de infliximab (HR: 2,46; IC 95%: 1,48-4,08; p<0,001) y la espondilitis (HR: 2,46; IC 95%: 1,78-6,89; p<0,001) a la suspensión por EA. El HLA-DQA1*05 fue un factor de riesgo de PRS en los pacientes tratados con adalimumab (ADA) con enfermedad de Crohn (HR: 3,49; IC 95%: 1,39-8,78; p=0,008) o con EII sin inmunosupresor asociado (HR: 2,8; IC 95%: 1,1-6,93; p=0,026). Conclusiones: El HLA-DQA1*05 se asoció al cese del tratamiento con ADA por PRS en los pacientes con EII sin inmunosupresor asociado. Respecto a otros biológicos, la suspensión se debió más a factores como la CU, las manifestaciones articulares y la indicación para remisión de brote intestinal. (AU)

Characterization of the Limbal Epithelial Stem Cell Niche.

Purpose: Limbal epithelial stem cells (LESCs) reside within a LSC niche (LSCN). We recently identified that hyaluronan (HA) is a major constituent of the LSCN, and that HA is necessary for maintaining LESCs in the "stem cell" state, both in vitro and in vivo. Herein, we characterized the LSCN to identify key components of the HA-specific LSCN. Methods: The cornea and limbal rim were dissected from mouse corneas, subjected to mRNA extraction, and sequenced using a NextSeq 500 (Illumina) and data processed using CLC Genomics Workbench 20 (Qiagen) and the STRING database to identify key components of the LSCN. Their expression was confirmed by real-time PCR, Western blotting, and immunohistochemistry. Furthermore, the differential expression of key compounds in different corneal cell types were determined with single-cell RNA sequencing. Results: We identified that the hyaladherins inter-alpha-inhibitor (IαI), TSG-6 and versican are highly expressed in the limbus. Specifically, HA/HC complexes are present in the LSCN, in the stroma underlying the limbal epithelium, and surrounding the limbal vasculature. For IαI, heavy chains 5 and 2 (HC5 and HC2) were found to be the most highly expressed HCs in the mouse and human limbus and were associate with HA-forming HA/HC-specific matrices. Conclusions: The LSCN contains HA/HC complexes, which have been previously correlated with stem cell niches. The identification of HA/HC complexes in the LSCN could serve as a new therapeutic avenue for treating corneal pathology. Additionally, HA/HC complexes could be used as a substrate for culturing LESCs before LESC transplantation.

ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing.

A buildup of reactive oxygen species (ROS) occurs in virtually all pathological conditions. Hyaluronan (HA) is a major extracellular matrix component and is susceptible to oxidation by reactive oxygen species (ROS), yet the precise chemical structures of oxidized HA products (oxHA) and their physiological properties remain largely unknown. This study characterized the molecular weight (MW), structures, and physiological properties of oxHA. For this, high-molecular-weight HA (HMWHA) was oxidized using increasing molar ratios of hydrogen peroxide (H2O2) or hypochlorous acid (HOCl). ROS lead to the fragmentation of HA, with the oxHA products produced by HOCl exhibiting an altered chemical structure while those produced by H2O2 do not. HMWHA promotes the viability of human corneal epithelial cells (hTCEpi), while low MWHA (LMWHA), ultra-LMWHA (ULMWHA), and most forms of oxHA do not. HMWHA and LMWHA promote hTCEpi proliferation, while ULMWHA and all forms of oxHA do not. LMWHA and some forms of oxHA promote hTCEpi migration, while HMWHA does not. Finally, all native forms of HA and oxHA produced by HOCl promote in vivo corneal wound healing, while oxHA produced by H2O2 does not. Taken together, our results show that HA fragmentation by ROS can alter the physiological activity of HA by altering its MW and structure.

Rational design and synthesis of lumican stapled peptides for promoting corneal wound healing.

PURPOSE: Lumican is a major extracellular matrix (ECM) component in the cornea that is upregulated after injury and promotes corneal wound healing. We have recently shown that peptides designed based on the 13 C-terminal amino acids of lumican (LumC13 and LumC13C-A) are able to recapitulate the effects of lumican on promoting corneal wound healing. Herein we used computational chemistry to develop peptide mimetics derived from LumC13C-A with increased stability and half-life that are biologically active and non-toxic, thereby promoting corneal wound healing with increased pharmacological potential. METHODS: Different peptides staples were rationalized using LumC13C-A sequence by computational chemistry, docked to TGFßRI and the interface binding energies compared. Lowest scoring peptides were synthesized, and the toxicity of peptides tested using CCK8-based cell viability assay. The efficacy of the stapled peptides at promoting corneal wound healing was tested using a proliferation assay, an in vitro scratch assay using human corneal epithelial cells and an in vivo murine corneal debridement wound healing model. RESULTS: Binding free energies were calculated using MMGBSA algorithm, and peptides LumC13C and LumC13S5 displayed superior binding to ALK5 compared to the non-stapled peptide LumC13C-A. The presence of the hydrocarbon staple in LumC13C enhances the stability of the α-helical conformation, thereby facilitating more optimal interactions with the ALK5 receptor. The stapled peptides do not present cytotoxic effects on human corneal epithelial cells at a 300 nM concentration. Similar to lumican and LumC13C-A, both C13C and LumC13S5 significantly promote corneal wound healing both in vitro and in vivo. CONCLUSIONS: Highly stable and non-toxic stapled peptides designed based on LumC13, significantly promote corneal wound healing. As a proof of principle, our data shows that more stable and pharmacologically relevant peptides can be designed based on endogenous peptide sequences for treating various corneal pathologies.

La irrigación transanal como opción terapéutica para los pacientes con incontinencia y estreñimiento crónico severo refractarios a primera línea / Transanal irrigation as a therapeutic option for patients with incontinence and severe chronic constipation refractory to first line treatment

Introducción: El objetivo es evaluar la utilidad de la irrigación transanal como tratamiento de la incontinencia y estreñimiento crónico severo refractario a primera línea terapéutica, y valorar su impacto en la sintomatología y calidad de vida. Métodos: Estudio retrospectivo descriptivo de pacientes con incontinencia y estreñimiento crónico que han iniciado irrigación transanal en dos hospitales de la región. Se recogen variables sociodemográficas, comorbilidades, tratamientos previos, pruebas realizadas, parámetros e incidencias durante la irrigación, puntuación en las escalas de gravedad de incontinencia y estreñimiento de la Cleveland Clinic y calidad de vida EuroQol-5D antes y después del tratamiento. Resultados: Un total de 40 pacientes, 20 con incontinencia y 20 con estreñimiento crónico. Tras una media de 9 meses de tratamiento, en 14 pacientes con incontinencia hemos objetivado una media de mejoría de 7,45 puntos pre-post tratamiento en la escala de gravedad de incontinencia de la Cleveland Clinic, y una media de mejoría en la calidad de vida de 23 puntos pre-post tratamiento en la escala EQ5D (p<0,001); y en 16 pacientes con estreñimiento una media de mejoría de 7,6 puntos pre-post tratamiento en la escala de gravedad de estreñimiento de la Cleveland Clinic, y una media de mejoría en la calidad de vida de 31,5 puntos pre-post tratamiento en la escala EQ5D (p<0,001). Conclusiones: La irrigación transanal es una terapia efectiva para pacientes con incontinencia y estreñimiento crónico no respondedores a primera línea terapéutica. Es sencilla, autoadministrable y segura. Cuando el paciente aprende a emplearla, mejora su sintomatología y calidad de vida. (AU)

Introduction: The aim is to evaluate the utility of transanal irrigation such as treatment of incontinence and severe chronic constipation which is refractory to first-line therapy, and to assess its impact into the symptomatology and quality of life. Methods: Observational retrospective study of patients with incontinence and chronic constipation that had initiated transanal irrigation in two hospitals of the region. We collect sociodemographic variables, comorbidity, previous treatments, tests, parameters and incidences during the irrigation, and punctuation in the Cleveland Clinic Incontinence and Constipation Scores and EuroQol-5D Quality Of Life Scale before and after the treatment. Results: 40 patients, 20 with incontinence and 20 with chronic constipation. After an average period of 9 months of treatment, in 14 patients with incontinence we have observed a mean clinical improvement of 7,45 points before-after treatment measured with Cleveland Clinic Incontinence Score, and a mean improvement of 23 points in their quality of life before-after treatment measured with EQ5D Scale (p<0.001); and in 16 patients with constipation a mean clinical improvement of 7,6 points before-after treatment measured with Cleveland Clinic Constipation Score, and a mean improvement of 31,5 points in their quality of life before-after treatment measured with EQ5D Scale (p<0.001). Conclusions: Transanal irrigation is an effective therapy for patients with incontinence and chronic constipation that are refractory to first-line therapies. It's an easy, self-administered and safe procedure. When the patient learns how to use it, the symptomatology and quality of life are improved. (AU)

Assessment of the oxidative status in mother-child couples from Seville (Spain): A prospective cohort study.

Pregnancy requires a high demand of energy, which leads to an increase of oxidative stress. The aim of this study was to assess the oxidative status in 200 couples of pregnant women-newborns at the time of delivery, for the first time, who gave birth in two University Hospitals from the province of Seville. Recruited women filled an epidemiological questionnaire with their demographic characteristics and dietary habits during pregnancy. At the time of delivery, both maternal and cord blood samples were collected. Protein oxidation, superoxide dismutase, and catalase levels were measured to assess the oxidative status of these women, together with the levels of vitamins D, B12, Zn, Se, and Cu. Our results showed a tendency for all biomarkers measured to be higher in cord blood than in maternal blood. For the correlations established between the OS markers and sociodemographic characteristics, only significant differences for carbonyl groups values were found on both maternal and cord blood, relating these higher values to the use of insecticides in the women's homes. For newborns, only a significant correlation was detected between antioxidant enzymes and the newborn's weight, specifically for superoxide dismutase activity. Additionally, the higher values obtained in cord blood might suggest metabolization, while a higher production of ROS and antioxidant enzymes might be required to maintain the balance. Measured levels for Se were similar in both maternal and cord blood, unlike Cu and Zn, where higher levels were found for maternal blood than cord blood, indicating a correlation between maternal Se values and SOD as OS biomarker. Furthermore, vitamin D levels were around the optimum values established, finding a relationship between vitamin D and new-born's height, unlike for vitamin B12 values, where a correlation with maternal food consumption characteristics was established. Overall values were inside normal ranges and consistent for our population.

Barreras y facilitadores en la implementación de una investigación observacional sobre SARS-CoV-2 en una red de escuelas centinela de Cataluña / Barriers and facilitators in the implementation of an observational research on SARS-CoV-2 in a Sentinel School Network in Catalonia

El presente artículo describe las barreras y facilitadores identificadas durante laplementación en campo de un proyecto de investigación observacional sobre SARS-CoV-2 realizado en una red de escuelas centinela de Cataluña durante los cursos escolares 2020-21 y 2021-22. Los objetivos del proyecto Escoles Sentinella aquí descritos son monitorizar la dinámica de la infección y sus determinantes a través de recogida de muestras biológicas, así como describir los conocimientos, actitudes y conductas del alumnado, personal docente y no docente sobre la infección por SARS-CoV-2 a través de cuestionarios bioconductuales. La experiencia desarrollada demostró que, a pesar de las dificultades operativas ante un contexto pandémico cambiante y con presión social y mediática, el estudio fue viable y contó con la aceptabilidad de gran parte de la comunidad educativa. Las lecciones aprendidas de esta experiencia en campo podrían ser útiles y aplicables en la implementación de otros estudios de investigación en situaciones epidemiológicas similares. (AU)

This article describes the barriers and facilitators identified during the implementation in the field of an observational research project about SARS-CoV-2 and carried out in different schools in Catalonia during 2020-21 and 2021-22 school years. The objectives of Escoles Sentinella project here described are to monitor the dynamics of the infection and its determinants through collection of biological samples, and to describe the knowledge, attitudes, and behaviours of students, teaching, and non-teaching staff about the infection by SARS-CoV-2 through biobehavioral questionnaires. The experience developed showed that, despite the operational difficulties due to the changing pandemic context and the social and media pressure, the study was viable and had the acceptability of a large part of the educational community. Lessons learned from this field experience could be useful and applicable in the implementation of other research studies in similar epidemiological situations. (AU)