Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Multiple Osteomas of Mandible in a Patient with Gardner’s Syndrome - Report of a Case

Introduction: Osteomas are benign tumors of the bone usually seen in craniofacial bones which arise from either the cortex or medulla. They are usually asymptomatic with slow painless growth. Multiple osteomas are often associated with Gardners syndrome. Solitary osteomas are typically non syndromic. Case Presentation: The patient presented with remarkable facial asymmetry following the growth in the mandible. Multiple os- teomas were noted which invoked suspicion of a syndrome. On endoscopic evaluation the patient was found to have multiple intestinal polyps, pathgnomonic for Gardners syndrome. Management and prognosis: The lesion was surgically removed under local anaesthesia. as an excisional biopsy and the asymmetry was rectified. Histopathologic examination revealed it to be ivory osteoma with dense compact bone and less mar- row spaces. The jaw lesions would precede the development of colonic polyps and therefore may contribute to early diagnosis of Gardner’s syndrome. There is also a chance of malignant evolution associated with the polyps Conclusion: People with the condition have a higher risk of developing other family adenomatous polyp (FAP)related cancers including pancreatic cancer and liver cancer. The patient should be in close follow up

Total Transit Time and Probiotic Persistence in Healthy Adults: A Pilot Study

Background/Aims@#Motility, stool characteristics, and microbiota composition are expected to modulate probiotics’ passage through the gut but their effects on persistence after intake cessation remain uncharacterized. This pilot, open-label study aims at characterizing probiotic fecal detection parameters (onset, persistence, and duration) and their relationship with whole gut transit time (WGTT). Correlations with fecal microbiota composition are also explored. @*Methods@#Thirty healthy adults (30.4 ± 13.3 years) received a probiotic (30 × 10 9 CFU/capsule/day, 2 weeks; containing Lactobacillus helveticus R0052, Lacticaseibacillus paracasei HA-108, Bifidobacterium breve HA-129, Bifidobacterium longum R0175, and Streptococcus thermophilus HA-110). Probiotic intake was flanked by 4-week washout periods, with 18 stool collections throughout the study. WGTT was measured using 80% recovery of radio-opaque markers. @*Results@#Tested strains were detected in feces ~1-2 days after first intake and persistence after intake cessation was not significantly different for R0052, HA-108, and HA-129 (~3-6 days). We identified 3 WGTT subgroups within this population (named Fast, Intermediate, and Slow), which could be classified by machine learning with high accuracy based on differentially abundant taxa. On average, R0175persisted significantly longer in the intermediate WGTT subgroup (~8.5 days), which was mainly due to 6 of the 13 Intermediate participants for whom R0175 persisted ≥ 15 days. Machine learning classified these 13 participants according to their WGTT cluster (≥ 15 days or < 5 days) with high accuracy, highlighting differentially abundant taxa potentially associated with R0175 persistence. @*Conclusion@#These results support the notion that host-specific parameters such as WGTT and microbiota composition should be considered when designing studies involving probiotics, especially for the optimization of washout duration in crossover studies but also for the definition of enrollment criteria or supplementation regimen in specific populations.

Purtscher-like retinopathy in a patient with COVID-19-associated coagulopathy / Retinopatia tipo Purtscher em paciente com coagulopatia associada ao COVID-19

ABSTRACT The most frequently reported ophthalmic manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is conjunctivitis. We have described a case of Purtscher-like retinopathy in a patient with severe coronavirus disease 2019 (COVID-19)-associated coagulopathy. A young woman with multiple comorbidities was admitted for COVID-19-related acute respiratory distress syndrome. Her course was complicated by fungemia. Ophthalmic examination revealed bilateral posterior pole, intraretinal lesions and fluconazole was added for presumed fungal retinitis. At 1-week follow-up, widespread peripapillary cotton-wool spots and hemorrhages suggestive of Purtscher-like retinopathy were observed. The levels of D-dimers, fibrinogen, and C-reactive protein were markedly elevated prior to our consultation, indicating preceding prothrombotic and pro-inflammatory states. Subsequent venous duplex revealed deep venous thrombosis in the right subclavian and internal jugular veins. Von Willebrand factor indices were markedly elevated, suggesting severe COVID-19-associated coagulopathy. Purtscher-like retinopathy, a rare occlusive microangiopathy has been described in various pro-inflammatory and prothrombotic conditions. To the best of our knowledge, this is the first report of Purtscher-like retinopathy in COVID-19-associated coagulopathy.

RESUMO A manifestação oftálmica mais frequentemente re­latada da infecção por SARS-CoV-2 é a conjuntivite. Trata-se de estudo de caso de retinopatia tipo Purtscher em uma paciente com coagulopatia grave associada ao COVID-19. Uma jovem com múltiplas comorbidades foi admitida por síndrome do desconforto respiratório agudo relacionado ao COVID-19. Seu quadro foi complicado pela fungemia. O exame oftálmico revelou pólo posterior bilateral, lesões intraretinianas e o fluconazol foi adicionado para tratar a retinite fúngica presumida. No decorrer de uma semana, manchas largas peripapilares de algodão e hemorragias sugestivas de retinopatia tipo Purtscher foram observadas. Os dímeros D, o fibrinogênio e a proteína c-reativa estavam acentuadamente elevados antes da nossa consulta, indicando um estado pró-trombótico e pró-inflamatório precedente. O duplex venoso subsequente revelou trombose venosa profunda nas veias subclávia direita e jugular interna. Os índices de fatores von Willebrand estavam marcadamente elevados, sugerindo coagulopatia grave associada ao COVID-19. A retinopatia tipo Purtscher, uma microangiopatia oclusiva rara foi descrita em várias condições pró-inflamatórias e pró-trombóticas. Para nosso conhecimento, este é o primeiro relatório de retinopatia tipo Purtscher com coagulopatia associada ao COVID-19.

Isolation and Characterization of Microbes of Different Kinds of Street Food and Determination of Antibiotic Susceptibility of the Isolates

Aim: Improper personal hygiene can facilitate the transmission of the pathogenic microorganisms found in environment and on people抯 hands via food to humans. The present study was undertaken to investigate the microbiological quality of different street food and determining the antibiotic susceptibility of the isolated microorganisms. Study Design: Collection of food samples for isolation of Pathogenic Microorganisms, to identify them by using Biochemical test, molecular test (16sr RNA typing), Antibiotic susceptibility was done by using different antibiotics against the isolates. Place and Duration of Study: Food samples were collected from street vendors of Sainkpuri area, work was done from December 2020 to April 2021 at Microbiology Department, St. Francis College for Women, Hyderabad. Methodology: Five samples of street food were collected in sterilized bottles, tested for the presence of microorganisms by following standard microbiological method used for isolation of microorganisms. The organisms were identified by carrying out various biochemical test according to Bergey抯 Manual of Systematic Bacteriology. The Molecular characterization was done based on 16sr RNA typing. Determining the sensitivity of the isolates against different Antibiotics by employing Kirby Bauer technique. Results: The organisms isolated from Manchuria and Ragada samples: Lactobacillus delbrueckii; Lactobacillus casei, Klebsiella pneumonia, Enterococcus faecalis and Vibrio spp respectively; Samosa and bonda: Staphylococcus aureus, Lactobacillus delbrueckii and Pantoea dispersa; Pani puri water: Staphylococcus aureus and Providencia vermicola. Antibiotic susceptibility tests showed that most of the isolated microorganisms were sensitive to Ciproflaxin. Conclusion: Hence the quality of street food is found to be low due to following factor: lack hygiene conditions in the food preparation, ingredients may also affect quality of the food, and presence of air borne microorganisms in the surrounding areas of service points.

Problems and puzzles in echinoderm demography / Problemas y acertijos en la demografía de los equinodermos

Introduction: There are problems and puzzles in understanding reproduction, growth and mortality in echinoderm life cycles. Objective: Explore problems and puzzles in life cycles that are important and challenging. Methods: The literature is used to elucidate problems associated with all life stages. Results: Sources of larvae that settle at a site are explored using oceanographic modelling and genetic methods. There are few studies that have estimated larval mortality in the plankton under field conditions and results differ from experimental results or patterns of settlement. In a small number of studies, mortality rate of newly settled larvae appears to change rapidly as individuals grow. There are problems measuring size, and measurement bias that interferes with many tagging methods used to estimate growth. There also are problems with the use of natural growth lines and commonly used software to estimate both growth and mortality from size-frequency data. An interesting puzzle is that echinoderms may show negative senescence with mortality rate decreasing with size. There is a problem in fertilization success based on density so there should not be rare species where sexes are separate with free spawning of gametes yet there seem to be rare echinoderms. Conclusions: All parts of echinoderm life cycles provide problems and puzzles that are important and challenging.

Introducción: Existen problemas y acertijos en la comprensión de la reproducción, el crecimiento y la mortalidad en los ciclos de vida de los equinodermos. Objetivo: Explorar los problemas y acertijos en los ciclos de vida que son importantes y desafiantes. Métodos: La literatura es usada para dilucidar los problemas asociados con todas las etapas de vida. Resultados: Las fuentes de larvas que se asientan en un sitio se exploran usando modelos oceanográficos y métodos genéticos. Existen pocos estudios que han estimado la mortalidad larval del plancton bajo condiciones de campo y los resultados difieren de los resultados experimentales o los patrones de asentamiento. En un número pequeño de estudios, la tasa de mortalidad de las larvas recién asentadas parece cambiar rápidamente a medida que los organismos crecen. Existen problemas para medir tamaños y el sesgo de medición interfiere con el uso de muchos métodos de marcado para estimar el crecimiento. También hay problemas con el uso de las líneas de crecimiento natural y con los programas comúnmente usados para estimar tanto el crecimiento como la mortalidad a partir de datos de frecuencia de tamaño. Un acertijo interesante es que los equinodermos pueden mostrar senescencia negativa con una tasa de mortalidad que disminuye con el tamaño. Existe un problema con el éxito de la fertilización basado en la densidad, por lo que no debería haber especies raras cuando los sexos están separados y existe un desove libre de gametos, sin embargo, parece haber equinodermos raros. Conclusiones: Todas las partes de los ciclos de vida de los equinodermos proveen problemas y acertijos que son importantes y desafiantes.

Can a low-cost exercise monitor provide useful heart rate monitoring for use in low-resource emergency departments?

Objective@#Our objective was to study the clinical monitoring capabilities of a low-cost fitness wristband while measuring patient satisfaction with a mobility permitting device in the emergency department. @*Methods@#Patients enrolled were on continuous three-lead telemetry monitoring in a high acuity zone of the emergency department. Patients were given a fitness band to wear while simultaneously monitored with standard three-lead monitor. A brief survey was conducted upon study end, and data was compared between wristband and three-lead telemetry. Median heart rate (HR) values were calculated, a Bland-Altman plot was generated, and sensitivity and specificity were calculated for comparison of the formal telemetry and the inexpensive wristband. @*Results@#Thirty-four patients with an average age of 61.5 years were enrolled. From June to October 2019, over 100 hours of data were collected. In comparison for comfort, participants scored 9.5 of 10, preferring wristband over telemetry. Using a correlation coefficient graph, we found a significant disparity of HR readings within a telemetry range of 40 to 140 beats/min. An R-value of 0.36 was detected. Using a Bland-Altman plot, we observed a significant difference in HR between the telemetry monitor and the wristband. The sensitivity and specificity of the wristband to detect bradycardia (HR 100 beats/min) were 92% and 51%, respectively. @*Conclusion@#Inexpensive fitness bands cannot be a suitable tool for monitoring patient’s HR because of inaccuracy in detecting bradycardia or tachycardia.

Genomics and epidemiology of the P 1 SARS-CoV-2 lineage in Manaus, Brazil

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Can a low-cost exercise monitor provide useful heart rate monitoring for use in low-resource emergency departments?

Objective@#Our objective was to study the clinical monitoring capabilities of a low-cost fitness wristband while measuring patient satisfaction with a mobility permitting device in the emergency department. @*Methods@#Patients enrolled were on continuous three-lead telemetry monitoring in a high acuity zone of the emergency department. Patients were given a fitness band to wear while simultaneously monitored with standard three-lead monitor. A brief survey was conducted upon study end, and data was compared between wristband and three-lead telemetry. Median heart rate (HR) values were calculated, a Bland-Altman plot was generated, and sensitivity and specificity were calculated for comparison of the formal telemetry and the inexpensive wristband. @*Results@#Thirty-four patients with an average age of 61.5 years were enrolled. From June to October 2019, over 100 hours of data were collected. In comparison for comfort, participants scored 9.5 of 10, preferring wristband over telemetry. Using a correlation coefficient graph, we found a significant disparity of HR readings within a telemetry range of 40 to 140 beats/min. An R-value of 0.36 was detected. Using a Bland-Altman plot, we observed a significant difference in HR between the telemetry monitor and the wristband. The sensitivity and specificity of the wristband to detect bradycardia (HR 100 beats/min) were 92% and 51%, respectively. @*Conclusion@#Inexpensive fitness bands cannot be a suitable tool for monitoring patient’s HR because of inaccuracy in detecting bradycardia or tachycardia.

Los biomarcadores cardiacos e inflamatorios se asocian con un empeoramiento en los outcomes renales en pacientes con diabetes mellitus tipo 2: observaciones del estudio SAVOR-TIMI 53 / Cardiac and inflammatory biomarkers are associated with worsening renal outcomes in patients with type 2 diabetes mellitus: observations from SAVOR-TIMI 53

Antecedentes: Las enfermedades cardiaca y renal se manifiestan comunmente con interacciones bidireccionales. Nuestra hipotesis es que los biomarcadores cardiacos e inflamatorios pueden ser utiles en la identificacion de pacientes con diabetes mellitus tipo 2 (DM2) de alto riesgo de deterioro de la funcion renal. Métodos: En el presente analisis exploratorio del estudio SAVOR-TIMI 53, las concentraciones de troponina T cardiaca de alta sensibilidad (TnT-us), propeptido natriuretico cerebral N-terminal (NT-proBNP) y proteina C-reactiva de alta sensibilidad (PCR-us) fueron medidas en muestras basales de suero de 12.310 pacientes. El punto final primario para este analisis fue una disminucion mayor al 40% en la tasa de filtracion glomerular estimada (TFGe) al final del tratamiento (FdT) en una mediana de seguimiento de 2,1 anos. Las relaciones entre los biomarcadores y el punto final se modelaron utilizando regresion logistica ajustada y regresion de Cox. Resultados: Despues de la regresion logistica ajustada, incluyendo la funcion renal basal, cada biomarcador se asocio independientemente con mayor riesgo de una disminucion mayor o igual al 40% en la TFGe al FdT [Cuartil (Q) Q4 vs Q1: cociente de probabilidades (CP) ajustado de TnT-us fue 5,63 (IC 95%, 3,49-9,10); para NTproBNP CP ajustado, 3,53 (IC 95%, 2,29-5,45); OR ajustado para PCR-us, 1,84 (IC 95%, 1,27-2,68); todos los valores con p≤0,001]. Ademas, cada biomarcador se asocio de manera independiente con mayor riesgo de empeoramiento en la categoria de la relacion albumina/ creatinina urinaria (RACu) (p≤0,002 en todos los casos). Los analisis de sensibilidad en pacientes sin insuficiencia cardiaca y TFGe >60 mL/min demostraron resultados similares. En un modelo ajustado de marcadores multiples (multi-marcador), TnT-us y NT-proBNP se mantuvieron significativamente asociados con ambos puntos finales renales (p<0,01 en todos los casos). Conclusiones: TnT-us, NT-proBNP y PCR-us se asociaron con el empeoramiento de la funcion renal [reduccion de la TFGe (≥40%) y deterioro en la categoria de RACu] en pacientes con DM2 de alto riesgo. Los pacientes con biomarcadores cardiacos o inflamatorios elevados deben ser tratados no solo por su riesgo de resultados cardiovasculares, sino tambien monitoreados en cuanto a su deterioro renal.

Background: Cardiac and renal diseases commonly occur with bidirectional interactions. We hypothesized that cardiac and inflammatory biomarkers may assist in identification of patients with type 2 diabetes mellitus (T2DM) at high risk of worsening renal function. Methods: In this exploratory analysis from SAVOR-TIMI 53, concentrations of high-sensitivity cardiac troponin T (hs-TnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP) were measured in baseline serum samples of 12310 patients. The primary end point for this analysis was a ≥40% decrease in estimated glomerular filtration rate (eGFR) at end of treatment (EOT) at a median of 2.1 years. The relationships between biomarkers and the end point were modeled using adjusted logistic and Cox regression. Results: After multivariable adjustment including baseline renal function, each biomarker was independently associated with an increased risk of ≥40% decrease in eGFR at EOT [Quartile (Q) Q4 vs Q1: hs-TnT adjusted odds ratio (OR), 5.63 (3.49-9.10); NT-proBNP adjusted OR, 3.53 (2.29-5.45); hs-CRP adjusted OR, 1.84 (95% CI, 1.27-2.68); all P values ≤0.001]. Furthermore, each biomarker was independently associated with higher risk of worsening of urinary albumin-to-creatinine ratio (UACR) category (all P values ≤0.002). Sensitivity analyses in patients without heart failure and eGFR >60 mL/min provided similar results. In an adjusted multimarker model, hs- TnT and NT-proBNP remained significantly associated with both renal outcomes (all P values <0.01). Conclusions: hs-TnT, NT-proBNP, and hs-CRP were each associated with worsening of renal function [reduction in eGFR (≥40%) and deterioration in UACR class] in high-risk patients with T2DM. Patients with high cardiac or inflammatory biomarkers should be treated not only for their risk of cardiovascular outcomes but also followed for renal deterioration.

Bone scan positivity in non-metastatic, castrate-resistant prostate cancer: external validation study

ABSTRACT Introduction: Tables predicting the probability of a positive bone scan in men with non-metastatic, castrate-resistant prostate cancer have recently been reported. We performed an external validation study of these bone scan positivity tables. Materials and Methods: We performed a retrospective cohort study of patients seen at a tertiary care medical center (1996-2012) to select patients with non-metastatic, castrate-resistant prostate cancer. Abstracted data included demographic, anthropometric, and disease-specific data such as patient race, BMI, PSA kinetics, and primary treatment. Primary outcome was metastasis on bone scan. Multivariable logistic regression was performed using generalized estimating equations to adjust for repeated measures. Risk table performance was assessed using ROC curves. Results: We identified 6.509 patients with prostate cancer who had received hormonal therapy with a post-hormonal therapy PSA ≥2ng/mL, 363 of whom had non-metastatic, castrate-resistant prostate cancer. Of these, 187 patients (356 bone scans) had calculable PSA kinetics and ≥1 bone scan. Median follow-up after castrate-resistant prostate cancer diagnosis was 32 months (IQR: 19-48). There were 227 (64%) negative and 129 (36%) positive bone scans. On multivariable analysis, higher PSA at castrate-resistant prostate cancer (4.67 vs. 4.4ng/mL, OR=0.57, P=0.02), shorter time from castrate-resistant prostate cancer to scan (7.9 vs. 14.6 months, OR=0.97, P=0.006) and higher PSA at scan (OR=2.91, P <0.0001) were significantly predictive of bone scan positivity. The AUC of the previously published risk tables for predicting scan positivity was 0.72. Conclusion: Previously published risk tables predicted bone scan positivity in men with non-metastatic, castrate-resistant prostate cancer with reasonable accuracy.

Procurement, storage and utilization trends of eye banks in India

Purpose: To study the trends in collection, storage and utilization of donor corneas in eye banks in India. Methods: The data was collected from 12 eye banks in India that collected more than 1000 corneas per year. The retrospective analysis of the parameters like characteristics of the donor and the host, storage media used, number of eyes collected, number of eyes utilized, causes of non-utilization of the tissue and the procedures performed was done. Results: A total of 20,564 eyes were collected by the 12 eye banks during the year 2013–2014. Voluntary eye donation (VED), and hospital cornea retrieval program (HCRP) contributed to 59.6% and 40.4% of tissue procurement respectively. Whole globe enucleation (52.3%) was more commonly performed as compared to in-situ excision of the donor corneas. The most commonly used storage media at all eye banks was McCarey-Kaufman (MK) media (83.3%). The utilization rate of the donor eyes was 50.5%. The most frequent indication for corneal transplantation was infection (active infection - 33.13%, healed infection - 10.78%) followed by Pseudophakic bullous keratopathy (PBK) (13.57%). Full thickness keratoplasty (optical penetrating keratoplasty - 47.23%, therapeutic penetrating keratoplasty - 31.74%) was performed most often followed by endothelial keratoplasty (12.41%) in the developing country. Conclusion: VED still contributes to majority of the donor tissue retrieval in India. The majority of the eye banks still utilize whole globe enucleation technique and store tissues in MK media. Trends from previous years showed a change towards HCRP, in-situ excision technique and preservation in the long-term storage media.

High Prevalence of Slow Transit Constipation in Patients With Gastroparesis

BACKGROUND/AIMS: Current evidence suggests the presence of motility or functional abnormalities in one area of the gastrointestinal tract increases the likelihood of abnormalities in others. However, the relationship of gastroparesis to chronic constipation (slow transit constipation and dyssynergic defecation) has been incompletely evaluated. METHODS: We retrospectively reviewed the records of all patients with chronic dyspeptic symptoms and constipation who underwent both a solid gastric emptying scintigraphy and a high-resolution anorectal manometry at our institution since January 2012. When available, X-ray defecography and radiopaque marker colonic transit studies were also reviewed. Based on the gastric emptying results, patients were classified as gastroparesis or dyspepsia with normal gastric emptying (control group). Differences in anorectal and colonic findings were then compared between groups. RESULTS: Two hundred and six patients met the inclusion criteria. Patients with gastroparesis had higher prevalence of slow transit constipation by radiopaque marker study compared to those with normal emptying (64.7% vs 28.1%, P = 0.013). Additionally, patients with gastroparesis had higher rates of rectocele (88.9% vs 60.0%, P = 0.008) and intussusception (44.4% vs 12.0%, P = 0.001) compared to patients with normal emptying. There was no difference in the rate of dyssynergic defecation between those with gastroparesis vs normal emptying (41.1% vs 42.1%, P = 0.880), and no differences in anorectal manometry findings. CONCLUSIONS: Patients with gastroparesis had a higher rate of slow transit constipation, but equal rates of dyssynergic defecation compared to patients with normal gastric emptying. These findings argue for investigation of possible delayed colonic transit in patients with gastroparesis and vice versa.

Statin Exposure Is Not Associated with Reduced Prevalence of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: Statins have been postulated to lower the risk of colorectal neoplasia. No studies have examined any possible chemopreventive effect of statins in patients with inflammatory bowel disease (IBD) undergoing colorectal cancer (CRC) surveillance. This study examined the association of statin exposure with dysplasia and CRC in patients with IBD undergoing dysplasia surveillance colonoscopies. METHODS: A cohort of patients with IBD undergoing colonoscopic surveillance for dysplasia and CRC at a single academic medical center were studied. The inclusion criteria were IBD involving the colon for 8 years (or any colitis duration if associated with primary sclerosing cholangitis [PSC]) and at least two colonoscopic surveillance exams. The exclusion criteria were CRC or high-grade dysplasia (HGD) prior to or at enrollment, prior colectomy, or limited ( < 30%) colonic disease. The primary outcome was the frequency of dysplasia and/or CRC in statin-exposed versus nonexposed patients. RESULTS: A total of 642 patients met the inclusion criteria (57 statin-exposed and 585 nonexposed). The statin-exposed group had a longer IBD duration, longer follow-up period, and more colonoscopies but lower inflammatory scores, less frequent PSC and less use of thiopurines and biologics. There were no differences in low-grade dysplasia, HGD, or CRC development during the follow-up period between the statin-exposed and nonexposed groups (21.1%, 5.3%, 1.8% vs 19.2%, 2.9%, 2.9%, respectively). Propensity score analysis did not alter the overall findings. CONCLUSIONS: In IBD patients undergoing surveillance colonoscopies, statin use was not associated with reduced dysplasia or CRC rates. The role of statins as chemopreventive agents in IBD remains controversial.

Multimorbidity and care for hypertension, diabetes and HIV among older adults in rural South Africa

Objective To examine how multimorbidity might affect progression along the continuum of care among older adults with hypertension,diabetes and human immunodeficiency virus (HIV) infection in rural South Africa.Methods We analysed data from 4447 people aged 40 years or older who were enrolled in a longitudinal study in Agincourt sub-district. Household-based interviews were completed between November 2014 and November 2015. For hypertension and diabetes (2813 and 512 people, respectively), we defined concordant conditions as other cardiometabolic conditions, and discordant conditions as mental disorders or HIV infection. For HIV infection (1027 people) we defined any other conditions as discordant. Regression models were fitted to assess the relationship between the type of multimorbidity and progression along the care continuum and the likelihood of patients being in each stage of care for the index condition (four stages from testing to treatment).Findings People with hypertension or diabetes plus other cardio metabolic conditions were more like to progress through the care continuum for the index condition than those without cardiometabolic conditions (relative risk, RR: 1.14, 95% confidence interval, CI: 1.09­1.20, and: 2.18, 95% CI: 1.52­3.26, respectively). Having discordant comorbidity was associated with greater progression in care for those with hypertension but not diabetes. Those with HIV infection plus cardiometabolic conditions had less progress in the stages of care compared with those without such conditions (RR: 0.86, 95% CI: 0.80­0.92).Conclusion Patients with concordant conditions were more likely to progress further along the care continuum, while those with discordant multimorbidity tended not to progress beyond diagnosis

Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation

BACKGROUND/AIMS: Visceral pain and hypothalamic-pituitary-adrenal axis (HPA) dysregulation is a common characteristic in irritable bowel syndrome (IBS) patients. Previously, we reported that a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) prevents chronic stress-mediated brain function abnormalities by attenuating the HPA axis response. Here, we compared the effect between different probiotic treatments on the perception of visceral pain during colorectal distension (CRD) following a chronic stress and the consequences to the activity of the HPA axis. METHODS: After a 2-week treatment with a combined probiotic formulation, or L. helveticus or B. longum alone in stressed mice, the visceral pain in response to CRD was recorded. The expression of glucocorticoid receptors was determined in the different brain areas involved in the stress response (hypothalamus, hippocampus, and prefrontal cortex). The plasma levels of stress hormones were also measured. RESULTS: A pretreatment using the combination of probiotic formulation significantly reduces the chronic stress-induced visceral hypersensitivity respectively at 0.06, 0.08, and 0.10 mL CRD volume. However, a single probiotic (B. longum or L. helveticus) administration is less effective in reducing visceral pain in stressed mice. Moreover, the expression of the glucocorticoid receptor mRNA was consistently up-regulated in several brain areas after pretreatment with a combined probiotic, which correlated with the normalization of stress response compared to the inconsistent effects of a single probiotic. CONCLUSION: The combination of L. helveticus and B. longum is more effective in regulating glucocorticoid negative feedback on the HPA axis than probiotic alone and subsequently in treating stress-induced visceral pain.

External morphology, postcranial and appendicular osteology of three southwestern Atlantic flatfishes ( Paralichthys, Paralichthyidae), and comparisons with other congeneric species

Comparisons of the external morphology and analysis of osteological features of the postcranial and appendicular skeletons of three southwestern Atlantic flatfish species of the genus Paralichthys (P. isosceles, P. orbignyanus and P. patagonicus) were carried out. Bones are described, and detailed morphological, morphometric and meristic characteristics of these flounders are given in order to provide information about the external and internal morphology of three species of Paralichthys occurring in the south-west Atlantic waters that add new information and will help regarding within the framework of a phylogenetic study of the group. Interspecific differences were found in the number of vertebrae and intermuscular bones, as well as in the morphology and morphometry of vertebrae, caudal skeletons, pectoral and pelvic girdle bones. Relationships between bones are discussed and bone characteristics compared with those found in other species of Paralichthys and in other pleuronectiform species. The position of Paralichthys isosceles within Paralichthys is discussed, along with other congeners such as P. triocellatus and P. oblongus.(AU)

Se llevaron a cabo comparaciones de la morfología externa y el análisis de las características osteológicas de los esqueletos postcraneal y apendicular de tres especies de peces planos del Atlántico sudoccidental del género Paralichthys (P. isosceles, P. orbignyanus y P. patagonicus). Se describen los huesos, y se proporcionan características morfológicas, morfométricas y merísticas detalladas de estos lenguados con el fin de aportar información sobre la morfología externa e interna de tres especies de Paralichthys presentes en el Atlántico sudoccidental. Esta nueva información contribuirá al marco de un estudio filogenético del grupo. Se encontraron diferencias interespecíficas en el número de vértebras y huesos intermusculares, así como en la morfología y morfometría de las vértebras, los esqueletos caudales, los huesos de las cinturas pectoral y pélvica. Se discuten las relaciones entre los huesos y las características óseas en comparación con las encontradas en otras especies de Paralichthys y de otros Pleuronectiformes. Se discute la posición de Paralichthys isosceles dentro del género Paralichthys, junto con otros congéneres como P. oblongus y P. triocellatus.(AU)

Trivalent M-related protein as a component of next generation group A streptococcal vaccines

PURPOSE: There is a need to broaden protective coverage of M protein–based vaccines against group A streptococci (GAS) because coverage of the current 30-valent M protein vaccine does not extend to all emm types. An additional GAS antigen and virulence factor that could potentially extend vaccine coverage is M-related protein (Mrp). Previous work indicated that there are three structurally related families of Mrp (MrpI, MrpII, and MrpIII) and peptides of all three elicited bactericidal antibodies against multiple emm types. The purpose of this study was to determine if a recombinant form containing Mrp from the three families would evoke bactericidal antiserum and to determine if this antiserum could enhance the effectiveness of antisera to the 30-valent M protein vaccine. MATERIALS AND METHODS: A trivalent recombinant Mrp (trMrp) protein containing N-terminal fragments from the three families (trMrp) was constructed, purified and used to immunize rabbits. Anti-trMrp sera contained high titers of antibodies against the trMrp immunogen and recombinant forms representing MrpI, MrpII, and MrpIII. RESULTS: The antisera opsonized emm types of GAS representing each Mrp family and also opsonized emm types not covered by the 30-valent M protein–based vaccine. Importantly, a combination of trMrp and 30-valent M protein antiserum resulted in higher levels of opsonization of GAS than either antiserum alone. CONCLUSION: These findings suggest that trMrp may be an effective addition to future constructs of GAS vaccines.

Substrate-dependent activity of ERK and MEK proteins in breast cancer [MCF7], and kidney embryonic [Hek-293] cell lines, cultured on different substrates

Background: Breast cancer has been one of the most common types of cancer, as the leading cause of women death in world. Breast cancer has known as a heterogenic disease that the clinical path in different patients would be very different. Since the current classification has not covered the diverse clinical course of breast cancer, lots of efforts has done to find new biological markers. Integrins are hetero dimmer proteins of alpha and beta subunits on cell membrane. After binding to extra cellular matrix [ECM], integrins activate MAPK pathway that regulated different activities like survival, differentiation, migration, immunologic response. The interaction of integrins and ECM have a key role in cancer cell activities like survival and metastasis

Objectives: In this study the expression alpha[v]beta[3] integrin, substrate-dependent morphology and ERK and p-ERK activation was compared in MCF7 and Hek-293 cells lines

Materials and Methods: The expression alpha[v]beta[3] integrin was assayed by flow cytometry. These cell lines were cultured on pre-covered plates with fibronectin [FN], fibrinogen [Fg] or collagen [Col] and the expression of ERK and p-ERK proteins was assessed in attached and free cells for each substrate after 1 hour incubation. The morphology of the cells have examined under an inverted phase contrast microscope at 15 min, 1 hour, 3 hours, 5 hours and 1 day of incubation

Results: Different substrate induced the expression ERK or p-ERK differently in the two cell lines. In MCF7 cells, substrates induced the expression of ERK in all the attached cells but free cells in BSA, collagen and Fg showed a lower expression of ERK. In comparison with Hek-293 cells althought all the attached cells have expressed ERK peotein but only free cells in collagen plates showed the expression of ERK. None of the cell lines has shown any expression of ERK and p-ERK in attached or free cells except for the Hek-293 free cells in collagen platees that have shown a weak signal for p-ERK

Conclusions: Overall the breast cancer cell lines MCF7 and Hek-293 cells have differently responded on similar substrates regarding morphology or ERK and MEK expressions

Aplicaciones de la ultrasonografía en cadera / Ultrasound Applications on Hip

Ultrasonography (US) in the last decade has gained interest for the study of the hip, with its known advantages over other imaging techniques, although the acoustic window of this joint is small. It is useful to differentiate pathology intra of extra-articular, guide local corticosteroid infiltration and monitoring of the response to systemic or local treatment. It has application in patients with hip osteoarthritis, rheumatoid arthritis and spondyloarthritis, also the prosthetic hip.

La ultrasonografía (US) en la última década ha cobrado interés para el estudio de la cadera, con sus conocidas ventajas sobre otras técnicas de imagen, a pesar de que la ventana acústica de esta articulación sea pequeña. Es de gran utilidad para diferenciar patología intra de la extra articular, guiar la infiltración local de glucocorticoides y monitoreo de la respuesta a tratamiento sistémico o local. Tiene aplicación tanto en la cadera de pacientes con osteoartritis, artritis reumatoide y espondiloartritis como en la cadera protésica.