Analysis of the mucosal chemokines CCL28, CXCL14, and CXCL17 in dry eye disease: An in vitro and clinical investigation.

Mucosal chemokines have antimicrobial properties and play an important role in mucosal immunity. However, little is known about their expression on the ocular surface. This study aimed to analyze the expression of the mucosal chemokines CCL28, CXCL14 and CXCL17 in corneal and conjunctival epithelial cells under in vitro dry eye (DE) conditions, and in conjunctival samples from healthy subjects and DE patients. Human corneal epithelial cells (HCE) and immortalized human conjunctival epithelial cells (IM-HConEpiC) were incubated under hyperosmolar (400-500 mOsM) or inflammatory (TNF-α 25 ng/mL) conditions for 6 h and 24 h to measure CCL28, CXCL14, and CXCL17 gene expression by RT-PCR and their secretion by immunobead-based analysis (CCL28, CXCL14) and ELISA (CXCL17). Additionally, twenty-seven DE patients and 13 healthy subjects were included in this study. DE-related questionnaires (OSDI, mSIDEQ and NRS) evaluated symptomatology. Ocular surface integrity was assessed using vital staining. Tactile sensitivity was measured with Cochet-Bonnet esthesiometer, and mechanic and thermal (heat and cold) sensitivity using Belmonte's non-contact esthesiometer. Subbasal nerve plexus and dendritic cell density were analyzed by in vivo confocal microscopy. Conjunctival cells from participants were collected by impression cytology to measure mucosal chemokines gene expression by RT-PCR. Our results showed that HCE and IM-HConEpiC cells increased CCL28, CXCL14, and CXCL17 secretion under hyperosmolar conditions. The gene expression of CCL28 was significantly upregulated in conjunctival samples from DE patients. CCL28 expression correlated positively with symptomatology, corneal staining, heat sensitivity threshold, and dendritic cell density. CXCL14 expression correlated positively with age, ocular pain, conjunctival staining, tactile sensitivity, and image reflectivity. CXCL17 expression correlated positively with corneal staining. These results suggest that corneal and conjunctival epithelial cells could be a source of CCL28, CXCL14, and CXCL17 on the ocular surface and that CCL28 might be involved in DE pathogenesis.

Patterns and predictors of antidepressant prescribing among adults with cancer and depression in ambulatory care settings in the United States.

OBJECTIVE: Despite depression being a common comorbidity among adults with cancer, limited literature is available regarding pharmacologic depression treatment patterns and predictors in this population. This study aims to examine patterns and predictors of antidepressant prescribing among adults with cancer and depression in ambulatory care settings in the United States (US). METHODS: This retrospective, cross-sectional study utilized data collected from the 2014 to 2015 National Ambulatory Medical Care Survey (NAMCS). The study sample consisted of adults (age ≥ 18 years) with cancer and depression (unweighted N = 539; weighted N = 11,361,000). A multivariable logistic regression analysis was used to adjust for individual-level factors to identify predictors of antidepressant prescribing. RESULTS: Most patients were adults aged ≥ 65 years, female, and non-Hispanic whites. Thirty-seven percent of the study sample received antidepressant treatment. Multivariable logistic regression analysis revealed that race/ethnicity, physician specialty, and number of medications were significantly associated with receiving antidepressant(s). For example, non-Hispanic whites were two-and-half times more likely to receive an antidepressant [OR 2.43, 95% confidence interval 1.13-5.23] compared to other race/ethnic groups. Every unit increase in the number of prescribed medications increased the likelihood of receiving an antidepressant by 6% (OR 1.06, 95% CI: 1.01-1.11). CONCLUSION: Among adults with a comorbid cancer and depression diagnosis and a recorded U.S. ambulatory care visit in 2014-2015, 37% received antidepressant treatment. This suggests most patients with cancer and depression do not receive pharmacologic treatment for depression. Future studies are needed to investigate the impact of antidepressant treatment on health outcomes in this patient population.

A histological study of the facial hair follicles in the pygmy sperm whale (Kogia breviceps).

In the pygmy sperm whale (Kogia breviceps, Blainville 1838), vibrissae are present in neonates, but within a few months the hairs are lost, and the structures remain as empty vibrissal crypts (VCs). In this work, we have studied histologically the facial vibrissal follicles of two juveniles and one adult specimens stranded dead. A few VCs with no visible hairs were found grouped in a row rostral to each eye. The follicular lumen, covered by a simple squamous epithelium, showed invaginations in the most superficial part. Beneath the epithelium, the follicle walls were made of loose connective tissue and were encircled by a thick capsule of dense connective tissue. In juveniles, a dermal papilla was found basally and, from it, a non-keratinized pseudo hair grew upwards but did not reach the skin surface. The VCs were richly innervated and irrigated. Many lamellated corpuscles were identified in the subluminal connective tissue of the crypt walls. A large venous cavernous plexus was located beneath and around the hair papilla. The main differences observed in the adult specimen were the degeneration and calcification of both the dermal papilla and the pseudo hair, and the absence of the venous cavernous plexus, albeit maintaining a rich vascularization and innervation. Our study revealed that VCs of the pygmy sperm whale possess features of fully functional sensory structures, with a microanatomy different from those described in other species. In addition, they undergo a postnatal morphological transformation, which implies functional differences between the VCs of neonates and adults.

Assessment of Harbour Porpoise Bycatch along the Portuguese and Galician Coast: Insights from Strandings over Two Decades.

The Iberian harbour porpoise population is small and fisheries bycatch has been described as one of its most important threats. Data on harbour porpoise strandings collected by the Portuguese and Galician stranding networks between 2000 and 2020 are indicative of a recent mortality increase in the western Iberian coast (particularly in northern Portugal). Overall, in Portugal and Galicia, individuals stranded due to confirmed fishery interaction represented 46.98% of all analysed porpoises, and individuals stranded due to probable fishery interaction represented another 10.99% of all analysed porpoises. Considering the Portuguese annual abundance estimates available between 2011 and 2015, it was possible to calculate that an annual average of 207 individuals was removed from the population in Portuguese waters alone, which largely surpasses the potential biological removal (PBR) estimates (22 porpoises, CI: 12-43) for the same period. These results are conservative and bycatch values from strandings are likely underestimated. A structured action plan accounting for new activities at sea is needed to limit the Iberian porpoise population decline. Meanwhile, there is an urgent need for a fishing effort reorganization to directly decrease porpoise mortality.

Complicaciones hemorrágicas y trombóticas del embarazo: diagnóstico, prevención y tratamiento

Las hemorragias y la enfermedad tromboembólica venosa (ETEV) figuran entre las cinco causas más frecuentes de morbilidad y mortalidad materna en el mundo. Revisamos la evaluación y el manejo actualizado de las causas obstétricas de la hemorragia posparto (HPP), así como el diagnóstico y manejo de condiciones hematológicas que pueden causar o agravar la HPP, por ejemplo: coagulación intravascular diseminada, enfermedad de von Willebrand, trombocitopenia autoinmune y las microangiopatías trombóticas. Revisamos el rol del síndrome antifosfolípido y las trombofilias hereditarias como factores predisponentes a pérdidas fetales recurrentes y la ETEV en el embarazo y las recomendaciones actuales para la prevención de ambas complicaciones. Asimismo, repasamos el abordaje diagnóstico y líneas de manejo de la ETEV. Un objetivo adicional fue enfatizar la importancia del trabajo colaborativo multidisciplinario para lograr el manejo exitoso de las gestantes con las complicaciones obstétricas y hematológicas descritas.

Bleeding and venous thromboembolism (VTE) are among the five most common causes of morbidity and mortality in pregnant women worldwide. This review describes the current evaluation and management of the obstetric causes of postpartum hemorrhage (PPH), as well as the diagnosis and management of hematologic conditions which can cause or worsen PPH, such as disseminated intravascular coagulation, von Willebrand disease, autoimmune thrombocytopenia and the thrombotic microangiopathies. It also describes the role of the antiphospholipid syndrome and inherited thrombophilia as predisposing factors for recurrent pregnancy loses and VTE, and the current recommendations for the prevention of both complications. As well, the current diagnostic approach and management of ETEV are described. An additional objective of this Review is to emphasize the importance of a collaborative multidisciplinary approach for the successful management of the obstetric and hematologic complications herein described.

Genomics reveals the role of admixture in the evolution of structure among sperm whale populations within the Mediterranean Sea.

In oceanic ecosystems, the nature of barriers to gene flow and the processes by which populations may become isolated are different from the terrestrial environment, and less well understood. In this study we investigate a highly mobile species (the sperm whale, Physeter macrocephalus) that is genetically differentiated between an open North Atlantic population and the populations in the Mediterranean Sea. We apply high-resolution single nucleotide polymorphism (SNP) analysis to study the nature of barriers to gene flow in this system, assessing the putative boundary into the Mediterranean (Strait of Gibraltar and Alboran Sea region), and including novel analyses on structuring among sperm whale populations within the Mediterranean basin. Our data support a recent founding of the Mediterranean population, around the time of the last glacial maximum, and show concerted historical demographic profiles in both the Atlantic and the Mediterranean. In each region there is evidence for a population decline around the time of the founder event. The largest decline was seen within the Mediterranean Sea where effective population size is substantially lower (especially in the eastern basin). While differentiation is strongest at the Atlantic/Mediterranean boundary, there is also weaker but significant differentiation between the eastern and western basins of the Mediterranean Sea. We propose, however, that the mechanisms are different. While post-founding gene flow was reduced between the Mediterranean and Atlantic populations, within the Mediterranean an important factor differentiating the basins is probably a greater degree of admixture between the western basin and the North Atlantic and some level of isolation between the western and eastern Mediterranean basins. Subdivision within the Mediterranean Sea exacerbates conservation concerns and will require consideration of what distinct impacts may affect populations in the two basins.

Long-term outcomes of transanal total mesorectal excision for rectal cancer: what could we do to improve them?

BACKGROUND: Long-term outcomes of transanal mesorectal excision are still controversial. The aim of this study was to analyze long-term oncological and functional results of TaTME. METHODS: Fifty patients with mid-low rectal cancer were included: 20 underwent TaTME and 30 laparoscopic total mesorectal excision. Clinical characteristics of patients and tumors and quality indicators for rectal surgery were described. Long-term functional outcomes were compared in two groups (TaTME vs. laTME). Local recurrence rate was calculated. Kaplan-Meier curves were performed for disease-free and overall survival and log-rank test was used to compare two groups. RESULTS: There were not significant differences between two groups in sex, age ASA Score, neoadjuvant therapy, tumor stage and quality indicators of rectal surgery. After a median follow-up of 46 (41-51) months functional outcomes were significantly worse in TaTME group in terms of rates of maior low anterior resection syndrome score (10% vs. 0%, P=0.009), faucal incontinence (15% vs. 3%, P=0.017), urinary disfunction (10% vs. 0%, P=0.009) and sexual disfunction (15% vs. 13%, P=0.047). Only one patient presented local recurrence (TaTME group, ypT3N0). Overall survival at 1 and 3 years were 92.6% and 90% respectively and disease-free survival at 1 and 3 years were 96% and 90% respectively. There were not significant differences in overall survival and disease-free survival between two groups. CONCLUSIONS: Overall survival and disease-free survival after TaTME for rectal cancer were similar to laparoscopic total mesorectal excision. However functional outcomes were worse after TaTME.

Engineered rHDL Nanoparticles as a Suitable Platform for Theranostic Applications.

Reconstituted high-density lipoproteins (rHDLs) can transport and specifically release drugs and imaging agents, mediated by the Scavenger Receptor Type B1 (SR-B1) present in a wide variety of tumor cells, providing convenient platforms for developing theranostic systems. Usually, phospholipids or Apo-A1 lipoproteins on the particle surfaces are the motifs used to conjugate molecules for the multifunctional purposes of the rHDL nanoparticles. Cholesterol has been less addressed as a region to bind molecules or functional groups to the rHDL surface. To maximize the efficacy and improve the radiolabeling of rHDL theranostic systems, we synthesized compounds with bifunctional agents covalently linked to cholesterol. This strategy means that the radionuclide was bound to the surface, while the therapeutic agent was encapsulated in the lipophilic core. In this research, HYNIC-S-(CH2)3-S-Cholesterol and DOTA-benzene-p-SC-NH-(CH2)2-NH-Cholesterol derivatives were synthesized to prepare nanoparticles (NPs) of HYNIC-rHDL and DOTA-rHDL, which can subsequently be linked to radionuclides for SPECT/PET imaging or targeted radiotherapy. HYNIC is used to complexing 99mTc and DOTA for labeling molecules with 111, 113mIn, 67, 68Ga, 177Lu, 161Tb, 225Ac, and 64Cu, among others. In vitro studies showed that the NPs of HYNIC-rHDL and DOTA-rHDL maintain specific recognition by SR-B1 and the ability to internalize and release, in the cytosol of cancer cells, the molecules carried in their core. The biodistribution in mice showed a similar behavior between rHDL (without surface modification) and HYNIC-rHDL, while DOTA-rHDL exhibited a different biodistribution pattern due to the significant reduction in the lipophilicity of the modified cholesterol molecule. Both systems demonstrated characteristics for the development of suitable theranostic platforms for personalized cancer treatment.

Cytokine profile of human limbal myofibroblasts: Key players in corneal antiviral response.

BACKGROUND: Corneal transparency may be compromised by viral infections causing corneal scarring, edema, and neovascularization. Ocular injury results from collateral damage induced by exacerbated immune response in corneal stroma. Myofibroblasts play a key role in this process by producing a disorganized extracellular matrix and inflammatory mediators. However, the immune response profile of myofibroblasts during viral infections is still under study. The aim of this work was to analyze the cytokine profile of human limbal myfibroblasts (HLMs) stimulated with the double-stranded RNA analog polyinosinic:polycytidylic acid (poly I:C) and to identify their signaling pathways. METHODS: HLMs were isolated from cadaveric sclera-corneal rims and stimulated with poly I:C (10 µg/ml) for 12 h. The secretion of 36 cytokines was measured using the Human Cytokine Array Panel A. The secretion of IFN-ß was quantified by ELISA. The expression of pattern recognition receptors (PRRs) such as TLR3, RIG-1 and MDA5 were analyzed by western blot assays. Furthermore, translocation of the nuclear factors NF-κB, IRF3, and IRF7 was assessed by fluorescence staining. In addition, the differentially expressed cytokines were analyzed using the Core Analysis Tool of the Ingenuity Pathway Analysis IPA software. RESULTS: HLMs stimulated with poly I:C increased (fold change > 2) the secretion of G-CSF, sTREM-1, CXCL1, CCL1, CXCL8, CXCL10, CXCL11, CCL2, CCL5, IL-13, IL-6, IL-1ra, and IFN-ß compared with HLMs under basal conditions. Poly I:C stimulation also induced the expression of RIG-1 (p < 0.001), but the expression of TLR3 and MDA5 was unmodified. Finally, HLMs increased nuclear translocation of NF-κB, IRF3, and IRF7 after poly I:C stimulation. Bioinformatic analysis identified canonical signaling pathways associated with cell adhesion and diapedesis, chemokine signaling, and activation of IRFs by cytosolic pattern recognition receptors. CONCLUSIONS: These results demonstrate that HLMs secrete cytokines involved in immune cell activation and chemotaxis. The data suggest a key role for HLMs during viral infections in cornea and extend our knowledge about the signaling pathways they trigger.

Distribution and genetic diversity of Anisakis spp. in cetaceans from the Northeast Atlantic Ocean and the Mediterranean Sea.

Parasite biodiversity in cetaceans represents a neglected component of the marine ecosystem. This study aimed to investigate the distribution and genetic diversity of anisakid nematodes of the genus Anisakis sampled in cetaceans from the Northeast Atlantic Ocean and the Mediterranean Sea. A total of 478 adults and pre-adults of Anisakis spp. was identified by a multilocus genetic approach (mtDNA cox2, EF1 α - 1 nDNA and nas 10 nDNA gene loci) from 11 cetacean species. A clear pattern of host preference was observed for Anisakis spp. at cetacean family level: A. simplex (s.s.) and A. pegreffii infected mainly delphinids; A. physeteris and A. brevispiculata were present only in physeterids, and A. ziphidarum occurred in ziphiids. The role of cetacean host populations from different waters in shaping the population genetic structure of A. simplex (s.s.), A. pegreffii and A. physeteris was investigated for the first time. Significant genetic sub-structuring was found in A. simplex (s.s.) populations of the Norwegian Sea and the North Sea compared to those of the Iberian Atlantic, as well as in A. pegreffii populations of the Adriatic and the Tyrrhenian Seas compared to those of the Iberian Atlantic waters. Substantial genetic homogeneity was detected in the Mediterranean Sea population of A. physeteris. This study highlights a strong preference by some Anisakis spp. for certain cetacean species or families. Information about anisakid biodiversity in their cetacean definitive hosts, which are apex predators of marine ecosystems, acquires particular importance for conservation measures in the context of global climate change phenomena.

Harbour Porpoise Abundance in Portugal over a 5-Year Period and Estimates of Potential Distribution.

The Iberian porpoise population is small and under potentially unsustainable removal by fisheries bycatch. Recently, a marine Site of Community Importance (SCI) was legally approved in Portugal, but no measures ensued to promote porpoise conservation. Information about porpoise abundance and distribution is fundamental to guide any future conservation measures. Annual aerial surveys conducted between 2011 and 2015 show a low overall porpoise abundance and density (2254 individuals; 0.090 ind/km2, CV = 21.99%) in the Portuguese coast. The highest annual porpoise estimates were registered in 2013 (3207 individuals, 0.128 ind/km2), followed by a sharp decrease in 2014 (1653 individuals, 0.066 ind/km2). The porpoise density and abundance estimated in 2015 remained lower than the 2013 estimates. A potential distribution analysis of the Iberian porpoise population was performed using ensembles of small models (ESMs) with MaxEnt and showed that the overall habitat suitability is particularly high in the Portuguese northern area. The analysis also suggested a different pattern in porpoise potential distribution across the study period. These results emphasize the importance of further porpoise population assessments to fully understand the spatial and temporal porpoise habitat use in the Iberian Peninsula as well as the urgent need for on-site threat mitigation measures.

Minimally invasive treatment of an amebic empyema secondary to the transdiaphragmatic rupture of a liver abscess: a case report.

Liver abscesses are a common complication in patients with amebiasis. Rarely, these will rupture across the diaphragm causing life-threatening empyemas. Evidence justifies performing surgical debridement or decortication for their treatment, given the better overall performance in comparison to open surgeries. However, no current guideline specifies which is the best approach. This report presents the case of a 39-year-old male with clinical, radiographical and microbiological evidence of an amebic empyema secondary to an amebic liver abscess, who received treatment by video-assisted thoracoscopy. The case description highlights the surgical technique, findings and operative outcomes that could be taken into consideration by other physicians to timely manage similar cases. The latter is especially relevant in underdeveloped and developing countries, where the burden of amebiasis appears to be greater. To the best of the authors' knowledge, this is the first description of a transdiaphragmatic amebic infection treated in a minimally invasive fashion.

Mechanical triangular esophagogastrostomy: Technical aspects and initial results.

INTRODUCTION: Esophageal cancer represents the eighth neoplasm worldwide. The therapeutic approach is interdisciplinary, with surgery being the most effective option. Several techniques have been proposed to perform esophagogastrostomy after esophagectomy, among them mechanical triangular esophagogastrostomy (MT), with a little experience published in the Western literature on the latter. The objective of this study is to describe the technical aspects and initial results of MT anastomosis. METHODS: A retrospective review of the patients who underwent esophagectomy according to the McKeown technique was performed, those in which MT anastomosis was implemented, between October 2017 and March 2020 in our hospital. RESULTS: 14 patients were included, with a mean age of 63 years. The mean operative time was 436 min (360-581), being diagnosed of anastomotic leak (AL) 3 of the 14 patients (21.4%), as well as 3 patients presented anastomotic stenosis (AS). The median stay was 20 days, without any death in the series. DISCUSSION: Multiple publications suggest the superiority in terms of AL and AS of the mechanical triangular anastomosis, which was also observed in our series, in which despite the small sample, a rapid improvement was observed in the indicators after the first cases. Therefore, this type of anastomosis may be a safe option for performing esophagogastric anastomosis after esophagectomy, being necessary more definitive conclusive studies.

Esofagogastrostomía triangular mecánica: aspectos técnicos y resultados iniciales / Mechanical triangular esophagogastrostomy: Technical aspects and initial results

IntroducciónEl cáncer de esófago representa la octava neoplasia a nivel mundial. El abordaje terapéutico es interdisciplinar y la cirugía es la opción más eficaz. Se han planteado varias técnicas para la realización de la esofagogastrostomía posterior a la esofagectomía, entre ellas, la esofagogastrostomía triangular mecánica, con muy poca experiencia publicada en la literatura occidental. El objetivo de este estudio es describir los aspectos técnicos y los resultados iniciales de la instauración de anastomosis triangular mecánica.MétodosSe realizó una revisión retrospectiva de los pacientes tratados mediante esofaguectomía según la técnica de McKeown, en los cuales se realizó anastomosis triangular mecánica entre octubre de 2017 y marzo de 2020 en nuestro hospital.ResultadosFueron incluidos 14 pacientes, con una media de edad de 63 años. El tiempo operatorio promedio fue de 436 min (360-581); fueron diagnosticados de fuga anastomótica 3 de los 14 pacientes (21,4%) y otros 3 pacientes presentaron estenosis anastomótica. La mediana de estancia fue de 20 días, sin ningún fallecimiento en la serie.ConclusionesMúltiples publicaciones señalan la superioridad en términos de fuga anastomótica y estenosis anastomótica de la anastomosis triangular mecánica. Esto también se observa en nuestra serie, en la cual, a pesar de lo reducido de la muestra, se observó una rápida mejoría en los indicadores posterior a los primeros casos, por lo que este tipo de anastomosis puede ser una opción segura para la confección de la anastomosis esofagogástrica posterior a la esofaguectomía. Son necesarios más estudios para alcanzar conclusiones definitivas (AU)

IntroductionEsophageal cancer represents the eighth neoplasm worldwide. The therapeutic approach is interdisciplinary, with surgery being the most effective option. Several techniques have been proposed to perform esophagogastrostomy after esophagectomy, among them mechanical triangular esophagogastrostomy, with a little experience published in the Western literature on the latter. The objective of this study is to describe the technical aspects and initial results of triangular esophagogastrostomy anastomosis.MethodsA retrospective review of the patients who underwent esophagectomy according to the McKeown technique was performed, those in which triangular esophagogastrostomy anastomosis was implemented, between October 2017 and March 2020 in our hospital.ResultsA total of 14 patients were included, with a mean age of 63 years. The mean operative time was 436minutes (360-581), being diagnosed of anastomotic leak 3 of the 14 patients (21.4%), as well as 3 patients presented anastomotic stenosis. The median stay was 20 days, without any death in the series.ConclusionsMultiple publications suggest the superiority in terms of anastomotic leak and anastomotic stenosis of the mechanical triangular anastomosis, which was also observed in our series, in which despite the small sample, a rapid improvement was observed in the indicators after the first cases. Therefore, this type of anastomosis may be a safe option for performing esophagogastric anastomosis after esophagectomy, being necessary more definitive conclusive studies (AU)

Influence of the Specific Surface Area of Graphene Nanoplatelets on the Capacity of Lithium-Ion Batteries.

In order to understand the influence of the morphological properties of graphene materials on the electrochemical performance of electrodes for lithium-ion batteries, three different graphene nanoplatelets with the increasing specific surface area (NP1: 296 m2 g-1, NP2: 470 m2 g-1, and NP3: 714 m2 g-1) were added in the electrode formulation in different ratios. Higher specific surface area graphene nanoplatelets (NP3) exhibit reversible capacity up to 505 mA h g-1 in the first discharge cycle (29.5% higher than that of graphite). Although significant irreversible capacity is shown for NP3, still higher reversible capacity is obtained compared to that of graphite electrode. The presence of micropores in the graphene structure benefits the lithiation. C-rate capability tests also show better performance of the graphene-based electrode. In this work, we demonstrate that graphene nanoplatelets with high specific surface area (714 m2 g-1) improve the electrochemical performance of Li-ion battery electrodes. The relationship between specific surface area, the presence of defects, and porosity is discussed.