Topical 1% cyclosporine eyedrops for the treatment of crystalline corneal dystrophy in dogs.

Background: Crystalline corneal dystrophy (CCD) is the most common type of corneal lipidic deposition in dogs. CCD is a primary metabolic disorder of the corneal fibroblast featuring an accumulation of extracellular and intracellular lipid deposits. Corneal lipid deposits create a corneal opacity and modify the interfibrillar collagen distance, inducing light scattering. Corneal vascularization is not usually associated with the disease, but, in case of chronicity, cell death may produce inflammation, and new corneal vessels are developed. To the best of the authors' knowledge, this is the first report of a medical approach for CCD treatment in veterinary medicine. Aim: To evaluate the efficacy of topical 1% cyclosporine eyedrops (1% CsA) for the treatment of CCD in dogs. Methods: Medical records of dogs with CCD were retrospectively reviewed (2009-2020). Corneal opacification description (COD) [size (mm), depth, and opacification degree (0-3)] was evaluated at 0, 3, 6, 9, 12, and 15 months postinitial diagnosis. Dogs were classified into three groups: the control group (G0), the group receiving topical 1% CsA once per day (G1), and the group receiving topical 1% CsA twice daily (G2). Results: Ninety-two client-owned dogs (163 eyes) of different breeds, ages, and gender fulfilled the inclusion criteria. When compared to G0, where the eyes significantly increased COD (p < 0.001), G1 and G2 significantly decreased COD (p < 0.001). In fact, the probability of reducing COD was about three times higher in G2 than in G1, being nearly the same for the right [odds ratio (OR) = 2.94; 95% confidence interval (95% CI) = 0.55-15.78] and left eye (OR = 2.92; 95% CI = 0.49-17.26). In addition, for each additional month of treatment in G2, the probability of reducing COD increased significantly (OR = 1.12; 95%CI = 1.00-1.26 for the right eye and OR = 1.16; 95%CI = 1.02-1.32 for the left eye). Conclusion: Long-term treatment with topical 1% CsA eyedrops significantly improved CCD in dogs, being the probability of reducing COD higher when applying the treatment twice daily.

Follicular conjunctivitis in dogs: A retrospective study (2007-2022).

OBJECTIVE: To evaluate the incidence, clinical features, treatment, and outcome of canine follicular conjunctivitis (CFC). PROCEDURE: Medical records of dogs diagnosed with CFC were reviewed. Data recorded included signalment, duration of clinical signs and treatment details prior to presentation, concurrent ocular/systemic diseases, ocular clinical signs, cytology, treatment, follow-up, and outcome. Blepharospasm, signs of self-trauma, hyperemia, chemosis, ocular discharge, and follicle location and severity (0.5-4) were retrospectively evaluated. Based on severity, treatment consisted of topical 0.1% diclofenac or 0.1% dexamethasone sodium eyedrops. Dogs were classified into young (YD < 18 months) and adult (AD ≥ 18 months). RESULTS: One hundred and fifty-three dogs (276 eyes) were included in the study: 83YD (54%) and 70AD (46%). Males and bilateral disease were over-represented in both groups. Severity was associated with young age (p = .032) and bilaterality (p = .025), and not with dermatological diseases (p > .05). No differences in follicular location were observed except for more frequent involvement of the nictitating membrane (MN) in YD (p = .02). Response to treatment was faster in AD (p = .001), with complete resolution in 80.6% of the eyes (100/124) at 1 month. YD treated with diclofenac showed faster resolution than those treated with 0.1% dexamethasone (p = .009). CONCLUSIONS: Although CFC is a bilateral ocular disease occurring at any age, the clinical presentation is influenced by age. Follicular conjunctivitis in adult dogs is less sever, less commonly affects the NM, and responds more quickly to topical treatment. One month of topical diclofenac may be adequate for mild cases, and 1 month of topical 0.1% dexamethasone is recommended as initial therapy for moderate to severely affected cases.

Influence of soft tissue thickness on marginal bone level around dental implants: A systematic review with meta-analysis and trial-sequential analysis.

OBJECTIVES: The aim of the present review and meta-analysis was to evaluate the influence of soft tissue thickness on initial bone remodeling after implant installation. MATERIALS AND METHODS: A literature search was conducted by two independent reviewers on electronic databases up to May 2022. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) performed on human subjects were included. The risk of bias was evaluated using Cochrane Collaboration's tool. Meta-analysis and Trial Sequential Analysis (TSA) were performed on the selected articles. The primary outcome was marginal bone loss. RESULTS: After screening, 6 studies were included in the final analysis, with a total of 354 implants, and a follow-up from 10 to 14 months. 194 implants were placed in a ≥ 2 mm soft tissue thickness, while 160 had <2 mm soft tissue thickness before implant placement. The included studies had a high level of heterogeneity (I2  > 50%). The meta-analysis indicated a statistically significant difference between the two groups (0.54; p = .027) and the TSA analysis confirmed the results, despite the limited number of dental implants. Additional analysis showed that age and follow-up parameters were not statistically significant factors influencing the bone loss (p = .22 and p = .16, respectively). CONCLUSIONS: Based on the available RCTS and CCTs, initial soft tissue thickness seems to influence marginal bone loss after a short follow-up period. Based on TSA analysis, further studies are needed to assess the influence of the soft tissue thickness on marginal bone loss. PROSPERO registration number: CRD42021235324.

A chromosome-level genome assembly enables the identification of the follicule stimulating hormone receptor as the master sex-determining gene in the flatfish Solea senegalensis.

Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis.

Consultas por sospecha de abuso sexual infantojuvenil en la sección de Ginecología de un hospital pediátrico: variaciones prepandemia e intrapandemia de COVID-19 / Consultations due to suspected child and adolescent sexual abuse at the Department of Gynecology of a children's hospital: pre- and intra-COVID-19 pandemic

Introducción. Se ha postulado que el aislamiento social debido a la pandemia de la enfermedad por el coronavirus 2019 (COVID-19, por su sigla en inglés) aumentaría la incidencia de abuso sexual infantojuvenil (ASIJ). Objetivo. Comparar la incidencia y las características de las consultas realizadas en Ginecología en relación con ASIJ antes y durante la pandemia de COVID-19. Materiales y métodos. Se realizó un estudio descriptivo, observacional y comparativo entre las situaciones de sospecha de ASIJ ocurridas durante la pandemia de COVID-19 en relación con las del mismo período del año previo en un hospital pediátrico de alta complejidad. Resultados. Se consignaron 122 consultas por sospecha de ASIJ, 78 en el período previo a la pandemia y 44 en la pandemia. El motivo de consulta al hospital más frecuente, en ambos grupos, fue el relato de ASIJ y, al Servicio de Ginecología en particular, la evaluación de genitales externos. La mayor parte presentó un examen físico normal. Se observó una mayor prevalencia de infecciones de transmisión sexual (ITS) en el grupo de pandemia. Se realizaron más internaciones y denuncias para protección de víctimas en dicho grupo. Se registró que el agresor era conocido de la víctima en casi el 90 % de las víctimas de ambos grupos. Conclusiones. Durante la pandemia se evidenció una disminución en el número total de consultas a Ginecología, de modo que aquellas por sospecha de ASIJ representaron un mayor porcentaje. Sin embargo, las características en relación con la presencia de lesiones graves, infecciones de transmisión sexual o embarazo no se vieron modificadas

Introduction. It has been suggested that the social isolation due to the coronavirus disease 2019 (COVID-19) may increase the incidence of child and adolescent sexual abuse (CASA). Objective. To compare the incidence and characteristics of medical consultations made to the Department of Gynecology due to CASA before and during the COVID-19 pandemic. Materials and methods. Descriptive, observational, and comparative study about suspected CASA events occurred during the COVID-19 pandemic compared to those occurred in the previous year at a tertiary care children's hospital. Results. One hundred and twenty-two medical consultations due to suspected CASA were recorded; 78 before and 44 during the pandemic. In both groups, the most common reason for consultation at the hospital was an account of CASA and, at the Department of Gynecology in particular, the external genitalia examination. Most subjects had a normal physical examination. There was a higher prevalence of STI in the pandemic group. In addition, there were also more hospitalizations and police reports for victims protection in this group. The abuser was known to the victim in almost 90% of cases in both groups. Conclusions. During the pandemic, the total number of medical consultations to the Department of Gynecology decreased so the percentage of those due to suspected CASA was higher. However, the presence of severe lesions, STIs or pregnancy did not change

Consultations due to suspected child and adolescent sexual abuse at the Department of Gynecology of a children's hospital: pre- and intra-COVID-19 pandemic. / Consultas por sospecha de abuso sexual infantojuvenil en la sección de Ginecología de un hospital pediátrico: variaciones prepandemia e intrapandemia de COVID-19.

INTRODUCTION: It has been suggested that the social isolation due to the coronavirus disease 2019 (COVID-19) may increase the incidence of child and adolescent sexual abuse (CASA). OBJECTIVE: To compare the incidence and characteristics of medical consultations made to the Department of Gynecology due to CASA before and during the COVID-19 pandemic. MATERIAL AND METHODS: Descriptive, observational, and comparative study about suspected CASA events occurred during the COVID-19 pandemic compared to those occurred in the previous year at a tertiary care children's hospital. RESULTS: One hundred and twenty-two medical consultations due to suspected CASA were recorded; 78 before and 44 during the pandemic. In both groups, the most common reason for consultation at the hospital was an account of CASA and, at the Department of Gynecology in particular, the external genitalia examination. Most subjects had a normal physical examination. There was a higher prevalence of STI in the pandemic group. In addition, there were also more hospitalizations and police reports for victims protection in this group. The abuser was known to the victim in almost 90% of cases in both groups. CONCLUSIONS: During the pandemic, the total number of medical consultations to the Department of Gynecology decreased so the percentage of those due to suspected CASA was higher. However, the presence of severe lesions, STIs or pregnancy did not change.

Introducción. Se ha postulado que el aislamiento social debido a la pandemia de la enfermedad por el coronavirus 2019 (COVID-19, por su sigla en inglés) aumentaría la incidencia de abuso sexual infantojuvenil (ASIJ). OBJETIVO: Comparar la incidencia y las características de las consultas realizadas en Ginecología en relación con ASIJ antes y durante la pandemia de COVID-19. Materiales y métodos. Se realizó un estudio descriptivo, observacional y comparativo entre las situaciones de sospecha de ASIJ ocurridas durante la pandemia de COVID-19 en relación con las del mismo período del año previo en un hospital pediátrico de alta complejidad. RESULTADOS: Se consignaron 122 consultas por sospecha de ASIJ, 78 en el período previo a la pandemia y 44 en la pandemia. El motivo de consulta al hospital más frecuente, en ambos grupos, fue el relato de ASIJ y, al Servicio de Ginecología en particular, la evaluación de genitales externos. La mayor parte presentó un examen físico normal. Se observó una mayor prevalencia de infecciones de transmisión sexual (ITS) en el grupo de pandemia. Se realizaron más internaciones y denuncias para protección de víctimas en dicho grupo. Se registró que el agresor era conocido de la víctima en casi el 90 % de las víctimas de ambos grupos. CONCLUSIONES: Durante la pandemia se evidenció una disminución en el número total de consultas a Ginecología, de modo que aquellas por sospecha de ASIJ representaron un mayor porcentaje. Sin embargo, las características en relación con la presencia de lesiones graves, infecciones de transmisión sexual o embarazo no se vieron modificadas.

Healing of Wounds Treated with Chitosan Hydrogels with Extracts from Aloe vera and Calendula officinalis / Cicatrización de Heridas Tratadas con Hidrogeles de Quitosano con Extractos de Aloe vera y Calendula officinalis

ABSTRACT This project's purpose was to evaluate the healing effects of chitosan (CS) hydrogels loaded with extracts from Aloe vera (CS+AV) and Calendula officinalis (CS+CO) on wounds of diabetic and non-diabetic Wistar rats. A total of 24 rats were used; animals were randomly divided into three diabetic and three non-diabetic groups (one control and two treated groups) and monitored for 13 days. A biopsy on the wound site was recovered to assess the collagen and n-acetyl glucosamine content. The wound area ratio was reduced since day 1 on both non-diabetic treated groups. A similar effect was observed on the diabetic group treated with CS+AV, while the diabetic group treated with CS+CO showed a reduction in wound area compared to the diabetic control until day 11 after being wounded. Collagen and n-acetyl glucosamine content were higher in every treated group. Further studies are needed to clarify the underlying mechanisms through which they promote wound healing. These results suggest that the hydrogels prepared are potential material to be used as wound dressings.

RESUMEN El propósito de este proyecto fue evaluar los efectos curativos de los hidrogeles de quitosano con extractos de Aloe vera (CS + AV) y Calendula officinalis (CS + CO) en heridas en ratas Wistar diabéticas y no diabéticas. Se utilizaron un total de 24 ratas; los animales fueron divididos aleatoriamente en tres grupos diabéticos y tres no diabéticos (un grupo control y dos tratados) y se monitorearon durante 13 días. Se recuperó una biopsia del sitio de la herida para evaluar el contenido de colágeno y n-acetilglucosamina. El área de la herida se redujo desde el día 1 en ambos grupos no diabéticos tratados. Se observó un efecto similar en el grupo diabético tratado con CS + AV, mientras que el grupo diabético tratado con CS + CO mostró una reducción del área de la herida en comparación al control diabético hasta el día 11 después de la creación de la herida. El contenido de colágeno y n-acetilglucosamina fue mayor en todos los grupos tratados. Se necesitan más estudios para aclarar los mecanismos subyacentes a través de los cuales estos tratamientos promueven la cicatrización de heridas. Estos resultados sugieren que los hidrogeles preparados son materiales con potencial para usarse como apósitos para heridas.

Urrets-Zavalia syndrome following cataract surgery in dogs: A case series.

Background: In human medicine, Urrets-Zavalia syndrome (UZS) is a well-recognized but uncommon postoperative complication characterized by a fixed dilated pupil, accompanied by iris atrophy and glaucoma. Although it was originally reported in 1963 after penetrating keratoplasty surgery for keratoconus, it has been associated with various ophthalmic procedures such as cataract surgery. The condition has not been previously published in the veterinary literature. Case Description: Three client-owned diabetic dogs that developed UZS´s triad after cataract surgery are described. Despite uneventful phacoemulsification in the six eyes, five developed moderate-to-severe postoperative ocular hypertension. Although intraocular pressure (IOP) spikes were initially controlled, fixed dilated pupils accompanied by iris atrophy and chronic ocular hypertension were seen in the five affected eyes. Aggressive medical and surgical management maintained vision in three of those eyes. In one eye, uncontrolled IOP led to blindness. Conclusion: This is the first published description of UZS in dogs, occurring after phacoemulsification. Although no exact, demonstrable causative element could be determined, we believe that should be considered a triggering condition for this syndrome, as it directly affects the ocular blood flow autoregulation and intrinsic uveal tissue integrity. Until the contrary is proved, diabetes mellitus might be considered as a risk factor for developing this syndrome after cataract surgery in dogs.

Tumor del saco vitelino primario de vagina en una niña. A propósito de un caso / Primary vaginal yolk sac tumor in a girl. Case report

Las neoplasias ginecológicas en niñas son raras. Representan menos del 5 % de todos los cánceres en pediatría. No existen estadísticas sobre la incidencia de tumores de vagina en esta etapa de la vida. Se presenta el caso de una niña de 9 meses con sangrado por genitales. La ecografía evidencia una masa sólida en vagina, y la vaginoscopia, un tumor friable. Presenta valores de α-fetoproteína elevados, por lo que se diagnostica tumor de saco vitelino, confirmado por biopsia. Se realiza tratamiento quimioterápico. A menos de 1 año del diagnóstico, se encuentra en remisión completa. Este caso resulta de interés no solo por la rareza, sino también porque el diagnóstico rápido de tumor de saco vitelino permite mejorar los resultados y la sobrevida de las pacientes

Gynecological neoplasms in girls are rare and represent only less than 5 % of all childhood tumors. There are no statistics on the incidence of vaginal tumors at this stage in life. We present a 9-month-old girl evaluated for genital bleeding. Ultrasound reveals a vaginal solid mass and vaginoscopy reports a friable tumor. AFP is elevated. A yolk sac tumor is confirmed by biopsy she receives chemotherapy. Within a year after diagnosis, she remains tumor-free. This is a case of interest, not only because of its rarity, but also because a rapid diagnosis of a yolk sac tumor improves outcomes and patient's survival rates.

[Primary vaginal yolk sac tumor in a girl. Case report]. / Tumor del saco vitelino primario de vagina en una niña. A propósito de un caso.

Gynecological neoplasms in girls are rare and represent only less than 5 % of all childhood tumors. There are no statistics on the incidence of vaginal tumors at this stage in life. We present a 9-month-old girl evaluated for genital bleeding. Ultrasound reveals a vaginal solid mass and vaginoscopy reports a friable tumor. AFP is elevated. A yolk sac tumor is confirmed by biopsy she receives chemotherapy. Within a year after diagnosis, she remains tumor-free. This is a case of interest, not only because of its rarity, but also because a rapid diagnosis of a yolk sac tumor improves outcomes and patient's survival rates.

Las neoplasias ginecológicas en niñas son raras. Representan menos del 5 % de todos los cánceres en pediatría. No existen estadísticas sobre la incidencia de tumores de vagina en esta etapa de la vida. Se presenta el caso de una niña de 9 meses con sangrado por genitales. La ecografía evidencia una masa sólida en vagina, y la vaginoscopia, un tumor friable. Presenta valores de α-fetoproteína elevados, por lo que se diagnostica tumor de saco vitelino, confirmado por biopsia. Se realiza tratamiento quimioterápico. A menos de 1 año del diagnóstico, se encuentra en remisión completa. Este caso resulta de interés no solo por la rareza, sino también porque el diagnóstico rápido de tumor de saco vitelino permite mejorar los resultados y la sobrevida de las pacientes.

Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: A structured summary of a randomised controlled trial.

OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y León, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. INCLUSION CRITERIA: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients' medical records. EXCLUSION CRITERIA: - Oxygen desaturation below 93% or P02 < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title "OUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE" with EudraCT number 2020-001622-64 , registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Prevalence of UGT1A1 (TA)n promoter polymorphism in Panamanians neonates with G6PD deficiency.

A relationship between the polymorphism in promoter region of the UGT1A1 gene and the development of jaundice has been demonstrated recently. This polymorphism leads to 30% of normal rate transcription initiation of UGT1A1 gene, thus decreasing the bilirubin glucuronidation. The combination of the G6PD deficiency and polymorphism in neonates and adults may causepronounced hyperbilirubinaemias. The aim of this study was to analyse the variations in the UGT1A1 gene promoter in Panamanians neonates with G6PD deficiency and its association with neonatal jaundice (NJ). We identified five different genotypes of TA repeats, in 17 neonates (42.5%) the normal variant TA6/TA6 and in the other 57.5% of the subjects: TA7/TA7 (12.5%), TA6/TA7 (40%), TA6/TA8 (2.5%) and TA6/TA5 (2.5%). Additionally 75% of the 16 newborns that showed NJ had an abnormal variant in the promotersequence, although, there was no significant difference (P = 0.068). The risk of jaundice in neonates with TA7 variant was thrice higher in subjects than with other alleles (P = 0.093, CI: 0.81-11.67). The TA7 allele frequency in this study (0.325) was consistent with the global frequency and similar to Caucasians. The results proved that there is no significant relationship between promoter polymorphism in UGT1A1 and NJ in G6PD deficient Panamanian newborns. Further studies with a greater number of subjects would determine the exact relationship between marked NJ and UGT1A promoter variations.

Ophthalmologic findings associated with Rhodococcus equi bronchopneumonia in foals.

OBJECTIVE: To describe ocular findings associated with Rhodococcus equi bronchopneumonia in foals, and to determine whether severity of the ocular lesions is related with outcome. ANIMALS STUDIED: Foals diagnosed with R equi infection at the VTH-UAB from January 2002 to December 2017. PROCEDURE: Rhodococcus equi infection was diagnosed by means of clinical signs, radiographic/ultrasonographic findings, and/or positive culture. In all the foals, a complete ophthalmic examination by a boarded ophthalmologist was performed and ocular signs were recorded and graded (0-4). RESULTS: Thirty-nine foals were included in the study, from which 12 showed signs of bilateral anterior uveitis (30.8%). Among these, three foals were classified as mildly uveitis-affected (MUA:7.7%) and nine as severely uveitis-affected (SUA:23.1%). Five SUA foals showed green aqueous flare (5/9;55.5%). Despite the systemic treatment, 9/39 sick foals died (23.1%), the fatality rate being different between groups: SUA (4/9;44.4%), MUA (0/3; 0%) and nonuveitis-affected foals (5/27;18.5%). Among SUA foals, only one with green aqueous flare died (1/5;20%). CONCLUSION: Bilateral anterior uveitis is highly prevalent in foals with R equi pneumonia (30.8%). The severity of anterior uveitis might be considered a nonsurvival prognostic factor and, until proven otherwise, green aqueous flare could be taken as a strongly suggestive ocular sign of the disease. Findings of this study remark the clinical relevance of performing a complete ophthalmic examination in sick foals, in order to help in the diagnosis and prognosis of uveal diseases, as well as to guaranteeing visual soundness.

Clinical and Economic Value of p16INK4a for the Differential Diagnosis of Morphologic Cervical Intraepithelial Neoplasia 2.

The detection of high-grade intraepithelial lesions requires highly sensitive and specific methods that allow more accurate diagnoses. This contributes to a proper management of preneoplastic lesions, thus avoiding overtreatment. The purpose of this study was to analyze the value of immunostaining for p16 in the morphologic assessment of cervical intraepithelial neoplasia 2 lesions, to help differentiate between low-grade (p16-negative) and high-grade (p16-positive) squamous intraepithelial lesions. The direct medical cost of the treatment of cervical intraepithelial neoplasia 2 morphologic lesions was estimated. A retrospective observational cross-sectional study was carried out. This study analyzed 46 patients treated with excisional procedures because of cervical intraepithelial neoplasia 2 lesions, using loop electrosurgical excision procedures. Immunostaining for the biomarker was performed. For the estimation of overtreatment, percentages (%) and their 95% confidence interval were calculated. Of the 41 patients analyzed, 32 (78%) showed overexpression of p16 and 9 (22%) were negative (95% confidence interval, 11%-38%). Mean follow-up was 2.9 years, using cervical cytology testing (Pap) and colposcopy. High-risk human papillomavirus DNA tests were performed in 83% of patients. These retrospective results reveal the need for larger biopsy samples, which would allow a more accurate prediction of lesion risk. Considering the cost of p16 staining, and assuming the proper management of the low-grade lesion, an average of US$919 could be saved for each patient with a p16-negative result, which represents a global direct cost reduction of 10%.

Corneal thickness, endothelial cell density, and morphological and morphometric features of corneal endothelial cells in goats.

OBJECTIVE To determine corneal thickness (CT), endothelial cell density (ECD), and morphological and morphometric features of caprine eyes and to assess effects of aging on these variables. SAMPLE 27 healthy eyes of 19 Murciano-Granadina goats. PROCEDURES Goats were classified into 2 age groups (kids, 14 months old [14 eyes]; and adults, 7 to 10 years old [13 eyes]). The ECD and CT were calculated in the central cornea and 4 peripheral quadrants. Mean cell area (MCA), pleomorphism (percentage of hexagonal cells), and polymegathism were evaluated in the central cornea. RESULTS Median values for kids were determined for ECD (3,831 cells/mm2; inter-quartile [25th to 75th percentile] range [IQR], 3,669 to 4,011 cells/mm2), CT (608 µm; IQR, 573 to 655 µm), MCA (255 µm2; IQR, 243 to 272 µm2), pleomorphism (80.53%; IQR, 78.83% to 83.30%), and polymegathism (19; IQR, 18 to 22). Median values for adults were determined for ECD (2,101 cells/mm2; IQR, 1,966 to 2,251 cells/mm2), CT (706 µm; IQR, 670 to 730 µm), MCA (466 µm2; IQR, 425 to 507 µm2), pleomorphism (67.80%; IQR, 65.50% to 70.00%), and polymegathism (21; IQR, 15 to 26). Values differed significantly between the 2 groups for all variables, except polymegathism. For both groups, the dorsal and temporal quadrants were the thickest and thinnest, respectively. Ventral ECD was the lowest for both groups. CONCLUSIONS AND CLINICAL RELEVANCE ECD decreased with age, whereas MCA, pleomorphism, and CT increased. Moreover, differences among regions of the cornea indicated that the central cornea should not be considered as representative of the entire cornea.

A dose-escalation ex vivo study on the effects of intracameral benzalkonium chloride in rabbits.

BACKGROUND: Rabbits are currently not a good model for studying diseases of the corneal endothelium because their corneal endothelial cells (CECs) maintain a high proliferative capacity throughout almost all their life. Addressing this particular feature might allow the use of this species for such a purpose. The aim of this study was to evaluate the corneal endothelial injury after intracameral benzalkonium chloride (BAC) injection into rabbit eyes ex vivo, and to establish the most suitable starting dose for an in vivo study aimed at developing an animal model of corneal endothelial disease. RESULTS: Forty rabbit eyes obtained postmortem by transconjunctival enucleation were divided into 8 groups according to the injected compound: Control (no injection), BSS, and increasing BAC concentrations (0.005%, 0.01%, 0.025%, 0.05%, 0.1% and 0.2%). At 0, 6, 24 and 48 h, ophthalmologic examination of the anterior segment, pachymetry and specular microscopy were performed, and corneas were finally vital-stained and observed under the light microscope to assess the CECs morphology and mortality rate. When compared to BSS, CECs density started to decrease significantly at 0.025% BAC concentration, while mean cell area, corneal edema and corneal thickness began to increase significantly at 0.05%, 0.005% and 0.1% BAC concentrations, respectively. Concentrations of 0.05% BAC and above caused significant increases in CECs pleomorphism (decreased hexagonality) and mortality, compared to control and BSS. CONCLUSIONS: Ex vivo intracameral BAC injection induces corneal endothelial toxicity in rabbits. However, confirmatory in vivo studies are required to develop the desired model, with 0.05% BAC being a suggested starting point.

Varenicline in smokers with severe or very severe COPD after 24 weeks of treatment. A descriptive analysis: VALUE study.

A large number of COPD patients are smokers. The particular characteristics of this group as well as their need to quit usually require psychological counselling and pharmacological treatment to achieve abstinence and, often, intensively. Little information is available about this issue.  The main objective of the study was to evaluate the effectiveness of varenicline after 24 weeks of treatment, with continuous abstinence between weeks 9 and 24.  This study was a post-authorization, open label, observational study of prospective follow-up. Patients included were smokers with severe or very severe COPD criteria who were treated with varenicline for 24 weeks, i.e. with a 12-week extension over the usual treatment.  The outcomes in the population of subjects completing 24 weeks of follow-up were at week 24: continuous abstinence 36.8%, 7 days point prevalence abstinence 65.7%, and continuous smoking 31.5%.The outcomes in the intention-to-treat population included at baseline were: continuous abstinence 17.7% of patients, 7 days point prevalence abstinence 31.6%, continuous smoking 15.1% and not valid/unknown 51.8%.  The mean CAT score at week 24 was 15 and reduction from the baseline was 3.77 (paired T test, p<0.01). The most common adverse events reported were nausea, vivid dreams, stomach ache, insomnia, headache and vomiting.  Patients included in VALUE were active smokers despite all of them had a severe COPD which suggests a very high degree of dependence. Although the study do not allow to infer the results to the global population of smokers with severe COPD, the outcomes have shown that, at 24 weeks follow up 36.8% of the patients were successful in quitting but from 79 patients enrolled initially only 17.7% quit.

A Swine Model of Selective Geographic Atrophy of Outer Retinal Layers Mimicking Atrophic AMD: A Phase I Escalating Dose of Subretinal Sodium Iodate.

PURPOSE: To establish the dose of subretinal sodium iodate (NaIO3) in order to create a toxin-induced large animal model of selective circumscribed atrophy of outer retinal layers, the retinal pigment epithelium (RPE), and photoreceptors, by spectral-domain optical coherence tomography (SD-OCT) and immunocytochemistry. METHODS: Fifteen male and female healthy Yorkshire pigs received unilateral subretinal escalating doses of NaIO3 under general anesthesia. In all the animals, volumes of 0.1 to 0.2 mL NaIO3 were injected into the subretinal space of the area centralis through a 23/38-gauge subretinal cannula. Control SD-OCTs were performed 1 and 2 months after the surgery, at which time pigs were euthanized and eyes enucleated. Globes were routinely processed for histologic and immunohistochemical evaluation. RESULTS: Spectral-domain OCT and immunohistochemistry revealed circumscribed and well-demarcated funduscopic lesions, limited to the outer retinal layers in pigs treated with 0.01 mg/mL subretinal sodium iodate. CONCLUSIONS: The swine model of a controlled area of circumscribed retinal damage, with well-delimited borders, and selectively of the outer layers of the retina presented herein shows several clinical and histologic features of geographic atrophy in AMD. Therefore, it may represent a valuable tool in the investigation of new emerging regenerative therapies that aim to restore visual function, such as stem cell transplantation or optogenetics.

Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.

This updated Good Publication Practice (GPP) guideline, known as GPP3, builds on earlier versions and provides recommendations for individuals and organizations that contribute to the publication of research results sponsored or supported by pharmaceutical, medical device, diagnostics, and biotechnology companies. The recommendations are designed to help individuals and organizations maintain ethical and transparent publication practices and comply with legal and regulatory requirements. These recommendations cover publications in peer-reviewed journals and presentations (oral or poster) at scientific congresses. The International Society for Medical Publication Professionals invited more than 3000 professionals worldwide to apply for a position on the steering committee, or as a reviewer, for this guideline. The GPP2 authors reviewed all applications (n = 241) and assembled an 18-member steering committee that represented 7 countries and a diversity of publication professions and institutions. From the 174 selected reviewers, 94 sent comments on the second draft, which steering committee members incorporated after discussion and consensus. The resulting guideline includes new sections (Principles of Good Publication Practice for Company-Sponsored Medical Research, Data Sharing, Studies That Should Be Published, and Plagiarism), expands guidance on the International Committee of Medical Journal Editors' authorship criteria and common authorship issues, improves clarity on appropriate author payment and reimbursement, and expands information on the role of medical writers. By following good publication practices (including GPP3), individuals and organizations will show integrity; accountability; and responsibility for accurate, complete, and transparent reporting in their publications and presentations.