Cell non-autonomous control of autophagy and metabolism by glial cells.

Glia are the protectors of the nervous system, providing neurons with support and protection from cytotoxic insults. We previously discovered that four astrocyte-like glia can regulate organismal proteostasis and longevity in C. elegans. Expression of the UPRER transcription factor, XBP-1s, in these glia increases stress resistance, and longevity, and activates the UPRER in intestinal cells via neuropeptides. Autophagy, a key regulator of metabolism and aging, has been described as a cell autonomous process. Surprisingly, we find that glial XBP-1s enhances proteostasis and longevity by cell non-autonomously reprogramming organismal lipid metabolism and activating autophagy. Glial XBP-1s regulates the activation of another transcription factor, HLH-30/TFEB, in the intestine. HLH-30 activates intestinal autophagy, increases intestinal lipid catabolism, and upregulates a robust transcriptional program. Our study reveals a novel role for glia in regulating peripheral lipid metabolism, autophagy, and organellar health through peripheral activation of HLH-30 and autophagy.

Host lipids regulate multicellular behavior of a predator of a human pathogen.

As symbionts of animals, microbial eukaryotes benefit and harm their hosts in myriad ways. A model microeukaryote (Capsaspora owczarzaki) is a symbiont of Biomphalaria glabrata snails and may prevent transmission of parasitic schistosomes from snails to humans. However, it is unclear which host factors determine Capsaspora's ability to colonize snails. Here, we discovered that Capsaspora forms multicellular aggregates when exposed to snail hemolymph. We identified a molecular cue for aggregation: a hemolymph-derived phosphatidylcholine, which becomes elevated in schistosome-infected snails. Therefore, Capsaspora aggregation may be a response to the physiological state of its host, and it may determine its ability to colonize snails and exclude parasitic schistosomes. Furthermore, Capsaspora is an evolutionary model organism whose aggregation may be ancestral to animals. This discovery, that a prevalent lipid induces Capsaspora multicellularity, suggests that this aggregation phenotype may be ancient. Additionally, the specific lipid will be a useful tool for further aggregation studies.

Comparación de la actividad antimicrobiana de cementos selladores en endodoncia / Comparison of the antimicrobial activity of sealing cements in endodontics

Introducción: la persistencia de microorganismos en los conductos radiculares es uno de los principales factores del fracaso endodóncico. Por ello la importancia de conocer las propiedades antimicrobianas de los distintos tipos de selladores. Objetivo: realizar una comparación con base en la evidencia disponible sobre la actividad antimicrobiana de los diferentes cementos selladores en endodoncia. Material y métodos: la información fue recopilada de las bases de datos PubMed y Google Académico en el idioma inglés y español, publicados en el periodo 2014-2023. Resultados: un gran número de microorganismos se encuentran presentes en los diferentes tipos de infecciones de origen endodóncico, se han identificado más de 500 especies microbianas, entre ellas bacterias, hongos, arqueas y virus. Los cementos selladores se pueden clasificar según su composición química, en cementos a base de óxido de zinc-eugenol, hidróxido de calcio, a base de ionómero de vidrio, silicona, resina y biocerámicos. Conclusión: los cementos selladores que mostraron mayor actividad antimicrobiana contra los microorganismos persistentes fueron los cementos a base de óxido de zinc-eugenol, resina y biocerámicos. Sin embargo, se identificó que cada autor utilizó diferentes métodos y tiempos, por lo tanto, no es posible lograr definir con exactitud qué cemento sellador posee la mejor capacidad antimicrobiana (AU)

Introduction: the persistence of microorganisms in root canals is one of the main factors of endodontic failure. Therefore, the importance of knowing the antimicrobial properties of the different types of sealants. Objective: to make a comparison based on the available evidence on the antimicrobial activity of the different endodontics sealers. Material and methods: the information was collected from PubMed and Google Academic databases in English and Spanish, published in the period 2014-2023. Results: a large number of microorganisms are present in the different types of infections of endodontic origin, more than 500 microbiological species have been identified, including bacteria, fungi, archaea and viruses. Sealer cements can be classified according to their chemical composition, into cements based on zinc oxide-eugenol, calcium hydroxide, based on glass ionomer, silicone, resin and bioceramics. Conclusion: sealer cements that showed the highest antimicrobial activity against persistent microorganisms were zinc oxide-eugenol, resin, and bioceramic-based cements. However, it was identified that each author used different methods and times, therefore, it is not possible to accurately define which sealer cement has the best antimicrobial capacity (AU)

Feline minor salivary gland adenocarcinoma: retrospective case series and literature review.

CASE SERIES SUMMARY: Salivary gland adenocarcinoma, of major or minor salivary gland origin, is an uncommon tumor in cats. This article describes the clinical features, morbidity and survival rates of four cats with salivary gland adenocarcinoma arising from minor salivary gland tissue. Medical records from a private multicenter dentistry and oral surgery practice were reviewed for the period between 2007 and 2021. Four cats were included in this retrospective case series study, with oral masses on either the right or left caudal mandibular labial buccal mucosa. The inclusion criteria included a diagnosis of salivary gland adenocarcinoma in an anatomical location with lack of involvement of a major salivary gland, complete medical history and a follow-up of at least 6 months. The age range of the cats was 9-15 years; three of the cats were castrated males and one was a spayed female. Curative intent surgery was performed in three cats, whereas palliative surgery (debulking) owing to extensive soft tissue invasion was performed in one cat. Survival times were in the range of 210-1730 (mean 787) days. All four cats were euthanized owing to local recurrence and decreased quality of life, regardless of treatment modality. RELEVANCE AND NOVEL INFORMATION: There are limited documented studies reporting the prevalence of salivary gland neoplasia affecting minor disseminated glands in the oral cavity of feline patients. Salivary gland adenocarcinoma should be a differential in cats presenting with caudal labial masses. Surgical resection has been the recommended treatment for salivary gland neoplasia of major salivary gland origin. According to this current case series, we propose that early aggressive surgical treatment with wide surgical margins should be performed for cats with salivary gland adenocarcinoma of minor salivary gland origin. Surgery increased the quality and duration of life; however, each patient was euthanized owing to local recurrence and morbidity.

Adaptación cultural y confiabilidad del instrumento Five-part questionnaire on hypermobility al contexto peruano / Cultural adaptation and reliability of the instrument Five-part questionnaire on hypermobility to the Peruvian context

Introducción Para el diagnóstico de hiperlaxitud articular se emplea comúnmente el Test de Beighton que requiere de un profesional para la exploración física. Por su parte, el instrumento es una herramienta autoadministrada que permite identificar de forma temprana la presencia de hiperlaxitud articular. Objetivos Realizar la adaptación cultural y confiabilidad test-retest del instrumento The Five-part questionnaire on hypermobility al contexto peruano, por medio de la traducción al español, adaptación lingüística y verificación de la confiabilidad test--retest en estudiantes de 13 a 17 años y docentes/administrativos de 24 a 60 años. Métodos Se realizó una traducción-retrotraducción con dos traductores, dos retrotraductores y la adaptación lingüística con 10 expertos. Obtenida la versión adaptada del cuestionario, se aplicó un análisis de comprensibilidad a 50 sujetos. Finalmente se estimó la confiabilidad test-retest en dos grupos: en adolescentes de 13 a 17 años y en adultos de 24 a 60 años. Resultados Se obtuvo la versión traducida del cuestionario, el cual pasó por un proceso de adaptación lingüística donde 10 expertos realizaron un análisis de concordancia (Coeficiente V de Aiken = 1) y un análisis de comprensibilidad con una escala de 0 a 10 que obtuvo una media de 10 puntos. Posteriormente, esta versión fue retro traducida y cotejada con el original. En el análisis de confiabilidad, los resultados de la aplicación del test-retest encontraron una confiabilidad alta entre el puntaje total de ambas aplicaciones tanto para el grupo de 65 adultos (Kappa 0,795; intervalo de confianza al 95%: de 0,777 a 0,819) y el de 71 adolescentes (Kappa 0,946; intervalo de confianza al 95%: de 0,908 a 0,982). Conclusiones Se adaptó el instrumento traducido cuestionario corto al contexto cultural de Perú y se encontró alta confiabilidad para los grupos de estudio de 13 a 17 años y de 24 a 60 años. Se recomienda la validación concurrente para considerar su aplicación en clínica y en investigación.

Introduction For the diagnosis of joint hypermobility, the Beighton test is commonly used; this requires a professional for the physical examination. The "Five- part questionnaire on hypermobility" is a self- administered tool that allows early identification of joint hypermobility. Objective To carry out the cultural adaptation and test- retest reliability of the "Five- part questionnaire on hypermobility" to the Peruvian context through translation into spanish, linguistic adaptation, and verification of test- retest reliability in students from 13 to 17 years of age and teachers/ad-ministrators from 24 to 60 years of age. Methods A translation and back- translation were performed with two translators and two back- translators, followed by a linguistic adaptation with ten experts. Once the adapted version of the question-naire was obtained, a comprehensibility analysis was carried out with 50 subjects. Finally, test- retest reliability was estimated in two groups: adolescents aged 13 to 17 and adults aged 24 to 60. Results The translated version of the questionnaire was obtained and underwent a linguistic adaptation process in which ten experts performed a concordance analysis (Aiken's V coefficient = 1), and a comprehensibility analysis with a scale of zero to ten obtained an average of ten points. Subsequently, this version was back- translated and checked against the original. In the reliability analysis, the results of the test- retest application found high reliability between the total score of both applications for both the group of 65 adults (Kappa 0.795; 95% CI: 0.777 to 0.819) and the group of 71 adolescents (Kappa 0.946; 95% CI: 0.908 to 0.982). Conclusions The translated instrument "Five- part questionnaire (5pq) on hypermobility" was adapted to the Peruvian cultural context, and high reliability was found for the study groups 13 to 17 years and 24 to 60 years. Concurrent validation is recommended to consider its application in clinical and research settings.

The Continued Need for the Routine Assessment of Folate Status.

OBJECTIVE: The Choosing Wisely initiative recommended cessation of folate measurement, suggesting folate supplementation in macrocytic anemia. This study reviewed the need for continued blood folate testing at a large SafetyNet county teaching hospital. METHODS: Red blood cell (RBC) folate, vitamin B12, iron, ferritin, and hemoglobin results were obtained for utilization review. RESULTS: Of the 593 RBC folate results, 69 (11.7%) were deficient and 30 (5%) had high values. Collectively, 369 (73.9%) had normal vitamin B12 levels, 342 (70%) had low hemoglobin, 184 (62.5) had normal and 57 (19.4%) had low ferritin, 122 (38.2%) had normal and 188 (59%) had low iron levels. A total of 41 (12%) had normal folate, low ferritin, low hemoglobin, and low iron, suggestive of iron deficiency anemia. There were 11 patients who exhibited low folate, low or normal ferritin, low hemoglobin, and low iron levels, suggesting combined folate and iron deficiency anemias. CONCLUSION: This study highlights the need for institutions to assess the applicability of national recommendations to their local population.

Cultural adaptation and reliability of the instrument Five-part questionnaire on hypermobility to the Peruvian context. / Adaptación cultural y confiabilidad del instrumento Five-part questionnaire on hypermobility al contexto peruano.

Introduction: For the diagnosis of joint hypermobility, the Beighton test is commonly used; this requires a professional for the physical examination. The "Five- part questionnaire on hypermobility" is a self- administered tool that allows early identification of joint hypermobility. Objective: To carry out the cultural adaptation and test- retest reliability of the "Five- part questionnaire on hypermobility" to the Peruvian context through translation into spanish, linguistic adaptation, and verification of test- retest reliability in students from 13 to 17 years of age and teachers/ad-ministrators from 24 to 60 years of age. Methods: A translation and back- translation were performed with two translators and two back- translators, followed by a linguistic adaptation with ten experts. Once the adapted version of the question-naire was obtained, a comprehensibility analysis was carried out with 50 subjects. Finally, test- retest reliability was estimated in two groups: adolescents aged 13 to 17 and adults aged 24 to 60. Results: The translated version of the questionnaire was obtained and underwent a linguistic adaptation process in which ten experts performed a concordance analysis (Aiken's V coefficient = 1), and a comprehensibility analysis with a scale of zero to ten obtained an average of ten points. Subsequently, this version was back- translated and checked against the original. In the reliability analysis, the results of the test- retest application found high reliability between the total score of both applications for both the group of 65 adults (Kappa 0.795; 95% CI: 0.777 to 0.819) and the group of 71 adolescents (Kappa 0.946; 95% CI: 0.908 to 0.982). Conclusions: The translated instrument "Five- part questionnaire (5pq) on hypermobility" was adapted to the Peruvian cultural context, and high reliability was found for the study groups 13 to 17 years and 24 to 60 years. Concurrent validation is recommended to consider its application in clinical and research settings.

Introducción: Para el diagnóstico de hiperlaxitud articular se emplea comúnmente el Test de Beighton que requiere de un profesional para la exploración física. Por su parte, el instrumento es una herramienta autoadministrada que permite identificar de forma temprana la presencia de hiperlaxitud articular. Objetivos: Realizar la adaptación cultural y confiabilidad test-retest del instrumento The Five-part questionnaire on hypermobility al contexto peruano, por medio de la traducción al español, adaptación lingüística y verificación de la confiabilidad test--retest en estudiantes de 13 a 17 años y docentes/administrativos de 24 a 60 años. Métodos: Se realizó una traducción-retrotraducción con dos traductores, dos retrotraductores y la adaptación lingüística con 10 expertos. Obtenida la versión adaptada del cuestionario, se aplicó un análisis de comprensibilidad a 50 sujetos. Finalmente se estimó la confiabilidad test-retest en dos grupos: en adolescentes de 13 a 17 años y en adultos de 24 a 60 años. Resultados: Se obtuvo la versión traducida del cuestionario, el cual pasó por un proceso de adaptación lingüística donde 10 expertos realizaron un análisis de concordancia (Coeficiente V de Aiken = 1) y un análisis de comprensibilidad con una escala de 0 a 10 que obtuvo una media de 10 puntos. Posteriormente, esta versión fue retro traducida y cotejada con el original. En el análisis de confiabilidad, los resultados de la aplicación del test-retest encontraron una confiabilidad alta entre el puntaje total de ambas aplicaciones tanto para el grupo de 65 adultos (Kappa 0,795; intervalo de confianza al 95%: de 0,777 a 0,819) y el de 71 adolescentes (Kappa 0,946; intervalo de confianza al 95%: de 0,908 a 0,982). Conclusiones: Se adaptó el instrumento traducido cuestionario corto al contexto cultural de Perú y se encontró alta confiabilidad para los grupos de estudio de 13 a 17 años y de 24 a 60 años. Se recomienda la validación concurrente para considerar su aplicación en clínica y en investigación.

HIV and Sexually Transmitted Infections Among Persons with Monkeypox - Eight U.S. Jurisdictions, May 17-July 22, 2022.

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.

Correlation Between Radiographic and Histopathologic Findings Associated with Unerupted Teeth in Dogs.

An association between unerupted teeth and dentigerous cysts is well known,1- 4 however little is known about the presence of disease and histopathologic changes in unerupted teeth without radiographic evidence of cyst formation. Forty-two dogs representing 25 breeds, ranging in age from 5 months to 12 years were selected based on radiographic evidence of an unerupted tooth or teeth, either as a primary complaint or incidental finding. Dogs meeting the study criteria were presented to a private dental referral practice within a period of eighteen months from December 2016 through May 2018. Patients were treated with conservative en bloc resection of the unerupted tooth and overlying bone as well as debridement of any cystic structure and biopsy of the samples collected. Radiographs were evaluated using criteria previously established to assess for evidence of a cyst.1, 5- 7 A total of 68 unerupted teeth were identified; 63 (92.7%) were mandibular first premolar teeth. Of the 63 unerupted mandibular first premolar teeth, 28 (44.4%) had radiographic evidence of a cystic structure. Histopathology revealed that 21 of 28 (75.0%) had evidence of non-keratinizing stratified squamous epithelium consistent with a cyst lining. Of the remaining 35 of 63 (55.6%) mandibular first premolar teeth with no radiographic evidence of a cyst, 27 (77.1%) had no histologic evidence of epithelium associated with the impacted tooth. Notably however, the remaining 8 of 35 (22.9%) unerupted teeth without radiographic evidence of a cyst did have histologic evidence of non-keratinizing stratified squamous epithelium associated with the impacted tooth.

Student-Authored Scientist Spotlights: Investigating the Impacts of Engaging Undergraduates as Developers of Inclusive Curriculum through a Service-Learning Course.

Scientist Spotlights-curricular materials that employ the personal and professional stories of scientists from diverse backgrounds-have previously been shown to positively influence undergraduate students' relatability to and perceptions of scientists. We hypothesized that engaging students in authoring Scientist Spotlights might produce curricular materials of similar impact, as well as provide a mechanism for student involvement as partners in science education reform. To test this idea and investigate the impact of student-authored Scientist Spotlights, we developed a service-learning course in which teams of biology students partnered with an instructor to develop and implement Scientist Spotlights in a biology course. Results revealed that exposure to three or four student-authored Scientist Spotlights significantly shifted peers' perceptions of scientists in all partner courses. Interestingly, student-authored Scientist Spotlights shifted peers' relatability to scientists similarly among both white students and students of color. Further, student authors themselves showed increases in their relatability to scientists. Finally, a department-wide survey demonstrated significant differences in students' perceptions of scientist representation between courses with and without student-authored Spotlights. Results suggest that engaging students as authors of inclusive curricular materials and partners in reform is a promising approach to promoting inclusion and addressing representation in science.

An outbreak of canine schistosomiasis in Utah: Acquisition of a new snail host (Galba humilis) by Heterobilharzia americana, a pathogenic parasite on the move.

Parasites with complex life cycles engaging multiple host species living among different environments well-exemplify the value of a cross-cutting One Health approach to understanding fundamental concerns like disease emergence or spread. Here we provide new information regarding a pathogenic schistosome trematode parasite of both wild and domestic mammals that has recently expanded its known range from mesic/wet environments of the southeastern United States to the arid southwest. In 2018, 12 dogs living near a man-made pond in Moab, Utah, were found positive for Heterobilharzia americana, the most westerly report of this endemic North American schistosome, and the first from Utah. Raccoon scats collected near the pond were positive for H. americana eggs, and snails living near the pond's water line identified as Galba humilis shed H. americana cercariae, the first indication of natural infections in this widespread North American snail species. The susceptibility of G. humilis to H. americana was confirmed experimentally. Our studies support the existence of two variants of H. americana and emphasize the need for further investigations of lymnaeids and their compatibility with H. americana, to better define the future potential for its spread. Capture of a new species of intermediate host vector snail and construction of man-made habitats suitable for this snail have created the potential for a much more widespread animal health problem, especially for dogs and horses. H. americana will prove difficult to control because of the role of raccoons in maintaining transmission and the amphibious habits of the snail hosts of this pathogenic schistosome.

Meningeal B Cell Clusters Correlate with Submeningeal Pathology in a Natural Model of Multiple Sclerosis.

Multiple sclerosis (MS) is an idiopathic demyelinating disease in which meningeal inflammation correlates with accelerated disease progression. The study of meningeal inflammation in MS has been limited because of constrained access to MS brain/spinal cord specimens and the lack of experimental models recapitulating progressive MS. Unlike induced models, a spontaneously occurring model would offer a unique opportunity to understand MS immunopathogenesis and provide a compelling framework for translational research. We propose granulomatous meningoencephalomyelitis (GME) as a natural model to study neuropathological aspects of MS. GME is an idiopathic, progressive neuroinflammatory disease of young dogs with a female bias. In the GME cases examined in this study, the meninges displayed focal and disseminated leptomeningeal enhancement on magnetic resonance imaging, which correlated with heavy leptomeningeal lymphocytic infiltration. These leptomeningeal infiltrates resembled tertiary lymphoid organs containing large B cell clusters that included few proliferating Ki67+ cells, plasma cells, follicular dendritic/reticular cells, and germinal center B cell-like cells. These B cell collections were confined in a specialized network of collagen fibers associated with the expression of the lympho-organogenic chemokines CXCL13 and CCL21. Although neuroparenchymal perivascular infiltrates contained B cells, they lacked the immune signature of aggregates in the meningeal compartment. Finally, meningeal B cell accumulation correlated significantly with cortical demyelination reflecting neuropathological similarities to MS. Hence, during chronic neuroinflammation, the meningeal microenvironment sustains B cell accumulation that is accompanied by underlying neuroparenchymal injury, indicating GME as a novel, naturally occurring model to study compartmentalized neuroinflammation and the associated pathology thought to contribute to progressive MS.

A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage.

Somatic cells age and die, but the germ-cell lineage is immortal. In Caenorhabditis elegans, germline immortality involves proteostasis renewal at the beginning of each new generation, when oocyte maturation signals from sperm trigger the clearance of carbonylated proteins and protein aggregates. Here, we explore the cell biology of this proteostasis renewal in the context of a whole-genome RNAi screen. Oocyte maturation signals are known to trigger protein-aggregate removal via lysosome acidification. Our findings suggest that lysosomes are acidified as a consequence of changes in endoplasmic reticulum activity that permit assembly of the lysosomal V-ATPase, which in turn allows lysosomes to clear the aggregates via microautophagy. We define two functions for mitochondria, both of which appear to be independent of ATP generation. Many genes from the screen also regulate lysosome acidification and age-dependent protein aggregation in the soma, suggesting a fundamental mechanistic link between proteostasis renewal in the germline and somatic longevity.

Malakoplakia in the Urinary Bladder of 4 Puppies.

Malakoplakia in humans most often affects the urinary bladder and is characterized by inflammation with von Hansemann-type macrophages, with or without Michaelis-Gutmann bodies, and is frequently associated with Escherichia coli infection. We describe the microscopic features of malakoplakia in the urinary bladder of 4 puppies. In all cases, the lamina propria of the urinary bladder was markedly expanded by sheets of large, round to polygonal macrophages with intracytoplasmic, periodic acid-Schiff-positive granules and granular inclusions, and rare Prussian blue-positive inclusions. Macrophages were positive for CD18 and Iba1. In 2 cases, Michaelis-Gutmann bodies were detected with hematoxylin and eosin stain and were best demonstrated with von Kossa stain. E. coli infection was confirmed in 2 cases with bacterial culture or polymerase chain reaction (PCR) and sequencing of the bacterial 16S ribosomal RNA gene. Transmission electron microscopy of one case demonstrated macrophages with abundant lysosomes, phagolysosomes, and rod-shaped bacteria. Microscopic features were similar to human cases of malakoplakia. In dogs, the light microscopic characteristics of malakoplakia closely resemble granular cell tumors and histiocytic ulcerative colitis.

Clinical, histopathologic, and immunohistochemical features of 13 cases of canine gallbladder neuroendocrine carcinoma.

In this retrospective descriptive study, we characterized the clinical, histologic, and immunohistochemical features of 13 cases of canine gallbladder neuroendocrine carcinoma (GB-NEC). Immunohistochemical stains for neuroendocrine (neuron-specific enolase [NSE], chromogranin A, synaptophysin) and gastrin markers were evaluated, and clinicopathologic and follow-up data were obtained for all cases. The average age at diagnosis was 8.9 y, and breeds included 6 Boston Terriers, 2 Bichon Frise, 1 Poodle, 1 English Bulldog, 1 French Bulldog, and 2 mixed-breed dogs. Boston Terriers were overrepresented in this cohort, and therefore a breed predilection is possible. Most dogs were presented with emesis and elevated liver enzyme activities: 13 of 13 had elevated alanine aminotransferase and alkaline phosphatase activities; 8 of 13 had elevated aspartate aminotransferase activity; 7 of 13 had elevated gamma-glutamyl transferase activity. Abdominal ultrasound and/or exploratory surgery revealed a gallbladder mass. All neoplasms had similar histologic features and positive immunoreactivity for NSE, chromogranin A, synaptophysin, and gastrin. Vascular invasion was noted in 8 of 13 neoplasms, and metastasis was present in 6 of 13 cases (4 hepatic and 2 pulmonary metastases). The median survival time was 3.7 y in patients who died; 5 of 8 deaths were directly attributed to the GB-NEC, 3 of which had metastatic spread. GB-NECs have the potential to metastasize; however, surgical excision may be curative in a subset of dogs.

Impact of umbilical cord length on fetal circulatory system by Doppler assessment.

INTRODUCTION: Numerous studies have revealed the impact of umbilical cord (UC) length on fetal perfusion; abundant data implicate abnormal UC length to neurological delay and subsequent poor prognoses for fetuses and newborns. Indeed, our group previously developed theoretical approximations that contributed to formulas capable of explaining the impact of UC length on cardiac output. METHODS: We performed an observational study that measured the pulsatility index and flow velocity in umbilical arteries. A special Doppler measured proximal and distal indexes in both arteries. After birth, medical staff measured complete UC length. We obtained maternal and neonatal outcomes from clinical records. RESULTS: Our study enrolled 20 pregnant mothers. We found that flow velocities in the two edges were different: fetal edges exhibited greater velocity in the majority of cases; but, when we compared pressure differentials (ΔP), the pulsatility index was significantly related to umbilical cord length. CONCLUSIONS: Fetal perfusion, welfare, and viability are related to UC function as the conveyor of all fetal volemia. Excessive UC length affects cardiac dynamics and increases peripheral vascular resistance. Further studies could validate routine use of the differential proximal and distal measurements proposed in this article, and their implications in in utero fetal heart function. We also hope that early diagnosis or UC alterations could alert neonatologists and obstetricians to clinical conditions of the fetus.

Lysosomal recycling of amino acids affects ER quality control.

Recent work has highlighted the fact that lysosomes are a critical signaling hub of metabolic processes, providing fundamental building blocks crucial for anabolic functions. How lysosomal functions affect other cellular compartments is not fully understood. Here, we find that lysosomal recycling of the amino acids lysine and arginine is essential for proper ER quality control through the UPRER. Specifically, loss of the lysine and arginine amino acid transporter LAAT-1 results in increased sensitivity to proteotoxic stress in the ER and decreased animal physiology. We find that these LAAT-1-dependent effects are linked to glycine metabolism and transport and that the loss of function of the glycine transporter SKAT-1 also increases sensitivity to ER stress. Direct lysine and arginine supplementation, or glycine supplementation alone, can ameliorate increased ER stress sensitivity found in laat-1 mutants. These data implicate a crucial role in recycling lysine, arginine, and glycine in communication between the lysosome and ER.

UPRER promotes lipophagy independent of chaperones to extend life span.

Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPRER) specifically in neurons is sufficient to enhance organismal stress resistance and extend life span. Here, we find that this activation not only promotes chaperones but also facilitates ER restructuring and ER function. This restructuring is concomitant with lipid depletion through lipophagy. Activation of lipophagy is distinct from chaperone induction and is required for the life-span extension found in this paradigm. Last, we find that overexpression of the lipophagy component, ehbp-1, is sufficient to deplete lipids, remodel ER, and promote life span. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the proteostasis arm through protein chaperones and metabolic changes through lipid depletion mediated by EH domain binding protein 1 (EHBP-1).

Radiography and ultrasonography of pneumatosis intestinalis in a cat.

An adult cat was presented for acute history of vomiting and collapse. Radiographs showed the presence of air within small intestinal walls and arborizing gas patterns within the liver, compatible with pneumatosis intestinalis and presumed portal venous gas, respectively. An abdominal ultrasound the following day was suggestive of gas within the intestinal wall, however, gas within the hepatic vasculature, parenchyma, or biliary tree was not evident. Due to progressive clinical deterioration of the patient, the owners elected humane euthanasia. Necropsy revealed severe necrotizing hemorrhagic enterotyphlocolitis secondary to Clostridium difficile toxin.