Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation

During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior–posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3^−/− embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.     

Is there a role for pericytic cells in the vascular bed of infantile hemangioendothelioma of the liver?

Electron microscopic examination of an infantile hemangioendothelioma (IHE) type I of the liver, appearing in a five month old child, showed a high density of pericytes in the walls of the neoplastic vessels. These vessels, in part of the IHE patients, establish an important arteriovenous shunt leading to high output, congestive cardiac failure. It is unclear whether functions ascribed to pericytes, such as participation in microvascular contractility or as suppressors of endothelial cell proliferation are involved in two noteworthy aspects of the present case. The child exhibited no congestive heart failure and the multiple nodular lesions underwent spontaneous regression.     

Patterns of exochorion ornaments on eggs of seven South American species of Lutzomyia sand flies (Diptera: Psychodidae)

The patterns of exochorion ornaments on eggs of seven South American Lutzomyia sand fly species were analyzed by scanning electron microscopy (SEM): Lutzomyia (Lutzomyia) cruzi (Mangabeira 1938), Lutzomyia (Micropygomyia) evandroi (Costa Lima and Antunes 1936), L. (Nyssomyia) intermedia (Lutz and Neiva 1912), L. longipalpis (Lutz and Neiva 1912), L. migonei (Franca 1920), L. (Nyssomyia) neivai (Pinto 1926), and L. renei (Martins, Falcao, and Silva 1957). Different patterns were observed, which showed the distinction between some species. Egg ornaments in L. cruzi and L. longipalpis appear as single, parallel, unconnected ridges, whereas eggs of L. migonei appear as single, parallel, connected ridges. Eggs of L. (Nyssomyia) intermedia and L. (N.) neivai present a new variation of the single, unconnected, parallel ridges pattern: small tubercles are present, distributed between the ridges. Eggs of L. renei present an elliptical pattern, with most structures connected by straight ridges. Eggs of L. (M.) evandroi present a polygonal pattern, with alternate rows of small and large hexagons. Our data emphasize the advantages of the SEM approach in the study of the exochorion patterns of Lutzomyia eggs and in the distinction of the sand fly species.     

Interpopulation variability among Panstrongylus megistus (Hemiptera: Reduviidae) from Brazil

Comparisons were made among Panstrongylus megistus (Burmeister) from three areas of Brazil (Bahia, Minas Gerais, and Santa Catarina), where populations differ with regard to their degree of association with human dwellings. The following characters were studied: morphology of the eggs and the male genitalia; morphometry of the head and thorax; isoenzyme profile; enzymatic activity of the alpha-glycerophosphate dehydrogenase (alpha-GPDH); and cytogenetics. In general, differences were observed in the weight, diameter, and length of the egg among Bahia, Minas Gerais, and Santa Catarina populations. Differences were not observed in the architecture of the egg exochorion. The size of the median process of the pygophore of the male genitalia of individuals from Bahia differed from the other two populations. The Minas Gerais population presented the largest number of denticles in the endosome process. The morphometry of the head and thorax differentiated Santa Catarina from the Bahia and Minas Gerais populations. Phosphoglucomutase (EC 5.4.2.2., PGM) was the only enzyme out of 11 that showed polymorphism; the population from Minas Gerais was most polymorphic, whereas the population from Santa Catarina was monomorphic. Study of the alpha-GPDH activity and cytogenetics did not reveal differences among the three populations. Analysis of all the characters studied together with information on these three populations from previous publications allowed a phenogram to be constructed. Two distinct groups were evident, one represented by Santa Catarina and the other by Bahia and Minas Gerais. Considering the greater variability of the Minas Gerais and Bahia populations, we propose the inclusion of these states within the area of origin of P. megistus.     

Interaction between KIR3DL1 and HLA-B*57 supertype alleles influences the progression of HIV-1 infection in a Zambian population

KIR and HLA loci are both highly polymorphic, and some HLA class 1 products bind and trigger cell-surface receptors specified by KIR genes. We examined whether KIR genes act in concert with HLA-B locus to control HIV-1 infection in a sample of Zambian patients. DNA samples from 88 Zambian patients with HIV-1 were examined. Patients were classified as either slow progressors (SP; n = 54) or rapid progressors (RP; n = 34) to AIDS. All were typed for HLA-B and KIR genes. Our results reveal an association between B*57 supertype (B*57s, which includes B*57 and B*58 alleles) and delayed progression to AIDS (p = 0.0007 by pc = 0.015; OR = 5.25). We also observed an increase incidence of Bw4-I80 in patients with slow progression (p = 0.001 by pc = 0.003, OR = 5). This increase was found to be secondary to B*57s. The presence of both KIR3DL1 and B*57S has a significant effect on progression to AIDS (p = 0.0008; OR = 5.61). B*57s genotypes with another HLA-B allele different from those in the trans position, which also had a specificity different to Bw4-I80 (Bw4-T80 or Bw6), was also greater in the SP than in the RP group (p = 0.00003; OR = 10.11). The presence of the inhibitory allele KIR3DL1 in combination with the HLA-B*57s alleles that contain the Bw4-I80 epitope, has a highly protective effect against progression to AIDS in Zambian patients.     

Multiple macrodontic multituberculism

Ekman-Westborg and Julin [1974: Oral Surg 38:217-222], described multiple macrodontia and multituberculism affecting the teeth without other anomalies (E-WJ). We describe a Chilean case in a 12-year-old with the typical dental alterations and with histopathologic findings that include absence of predentin layer and prominent reduced enamel epithelium. E-WJ is not a syndrome and we propose "multiple macrodontic multituberculism" as a better name for this anomaly of uncertain etiology affecting only the crowns of the teeth.     

Is choledochoduodenostomy in the treatment of stones in the common bile duct an obsolete technique?

The complex pathogenesis of bile duct stones, the anatomical properties of the biliary tree, the patient's age, associated diseases, as well as the technical devices available, may explain the great variety of procedures and preferences of different groups in the treatment of choledocholithiasis. Since no technique is infallible or free of complications, it seems unfair to argue that procedures whose efficacy has been proven by many authors are obsolete. This is the case of choledochoduodenostomy (CDS) in the treatment of common bile duct (CBD) stones. The complications associated with CDS, (ascending cholangitis, and sump syndrome) have been overemphasized and have led CDS to be rejected by many surgeons. Our experience with this technique is good and concurs with that of Madden and others.Data on 125 patients with CBD stones treated with CDS between 1968 and 1982 are analyzed. Sixty-eight of them were female and the mean age was 61.4 years; 73.6% were more than 50 years old. There were frequent accompanying diseases, especially cardiovascular ones. More than half of the patients had a previous operation on the biliary tree. The duct diameter was always greater than 20 mm and it was frequently associated with stenosis of the distal choledochus. Floercken's technique of CDS was the most frequently used, after Kocher's maneuver had been performed. There was no intraoperative mortality. Postoperative mortality was 3.2% and is analyzed in detail. The incidence of postoperative complications was 42.4%. Most were septic complications or those ascribed to accompanying diseases. Late operative cholangitis was present in 1.6% of patients, comparable with reports of other authors. We encourage the use of CDS in the treatment of CBD stones provided that: (a) careful attention is paid to its clinical indications, considering that the patient may benefit from alternative techniques, for example, duodenoscopic papillotomy; and (b) choledochal dilatation is greater than 20 mm in diameter and the choledochal and duodenal walls are normal. We specifically recommend CDS as the primary operation for patients with choledochal funnel syndrome. The operation is simple, restores normal digestive function, and almost always resolves the problems of CBD stones in high-risk patients.

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Resumen La compleja patogenia de los cálculos del colédoco, las propiedades anatómicas del árbol biliar, la edad del paciente, las patologías asociadas y otros factores, junto con la disponibilidad de diversos elementos técnicos, explican la gran variedad de procedimientos y de preferencias por parte de los cirujanos en el tratamiento y de preferencias por parte de los cirujanos en el tratamiento de la litiasis biliar. Puesto que ninguna técnica operatoria es infalible ni totalmente libre de complicaciones, parece injusto argumentar que procedimientos cuya eficacia ha sido comprobada por muchos autores sean calificados como obsoletos. Tal es el caso de la coledocoduodenostomía (CDS) en el tratamiento de los cálculos del colédoco. Las complicaciones asociadas con la CDS (colangitis ascendente y el sindrome del segmento distal ciego) han sido exageradas, lo cual ha llevado a muchos cirujanos a rechazar la CDS. Nuestra experiencia con esta técnica es buena y está de acuerdo con la de Madden y de otros. Se analizaron los datos en 125 pacientes con cálculos del colédoco tratados con CDS entre 1968 y 1982. Sesenta y ocho eran mujeres y la edad promedio fué de 61.4 años; 73.6% eran mayores de cincuenta años. Otras enfermedades asociadas fueron halladas con frecuencia, especialmente las cardiovasculares. Más de la mitad de los pacientes tenían historia de una operación previa sobre el árbol biliar. El diámetro del colédoco fué superior a 20 mm en todos los casos y con frecuencia se encontró estenosis árbol de la porción distal. La técnica de Floercken fué la más frecuentemente utilizada, una vez realizada la maniobra de Kocher. No hubo mortalidad intraoperatoria. La mortalidad postoperatoria fué de 3.2% y se analiza en detalle. La tasa de complicaciones postoperatorias fué de 42.4%, incluyendo las sistematicas y las locales, leves y severas, habiéndose observado predominancia de las complicaciones sépticas y de aquellas relativas a patologiás asociadas. La colangitis operatoria tardía ocurrió en el 1.6% de los pacientes, tasa comparable a la informada por otros autores. Nosotros preconizamos el uso de la CDS en el tratamiento de los cálculos del colédoco siempre que: (a) se preste atención cuidadosa a sus indicaciones clínicas, considerando que el paciente puede beneficiarse con otras alternativas, por ejemplo la papilotomía duodenoscópica; y (b) la dilatación del colédoco sea de un diámetro superior a 20 mm y que las paredes tanto del colédoco como del duodeno sean normales. Específicamente recomendamos la CDS como la operación primaria para pacientes con el síndrome del embudo coledociano (estenosis distal con dilatación proximal). La operación es sencilla, restaura la función digestiva normal y en forma casi uniforme resuelve los problemas que producen los cálculos del colédoco en pacientes de alto riesgo.

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Résumé La pathogénie complexe de la lithiase biliaire, les caractères anatomiques des voies biliaires ainsi que l'âge des malades, les affections associées et la grande variété des méthodes techniques expliquent la grande diversité des procédés de traitement de la lithiase choledocienne employés par les différentes équipes chirurgicales. Aucune technique n'étant infaillible ou exempte de complications, il paraît inconsidéré d'abandonner toute méthode qui a fait ses preuves. Il en est ainsi de la choledocoduodénostomie. Les complications attribuées à ce type d'intervention comme l'angiocholite ascendante, et le syndrome du moignon sous-anastomotique ont été exagérées conduisant de nombreux chirurgiens à l'écarter de leur pratique. Notre expérience de la choledocoduodénostomie est bonne et coincide avec celle de Madden et d'autres auteurs. Les données recueillies chez 125 malades qui présentaient des calculs de la V.B.P. et qui furent traités par la choledocoduodénostomile de 1968 à 1982 ont été étudiées. Soixante-huit étaient des femmes. La moyenne d'âge était de 61.4 ans, 73.6% étaient âgés de plus de 50 ans. Les affections associées étaient fréquentes en particulier les affections cardiovasculaires. Plus de la moitié de nos opérés avaient déjà subi une intervention sur la voie biliaire. Le diamètre de la voie biliaire a toujours été supérieur à 20 mm et la dilatation se trouvait souvent au dessus d'un rétrécissement du bas cholédoque. La technique de Floercken fut le plus souvent employée après le décollement du bloc duodénopancréatique. Il n'y eu aucun décès peropératoire. La mortalité postopératoire s'est élevée à 3.2% et a été étudiée avec précision. Le taux des complications postopératoires a atteint 42.4%, dont les infections et les désordres secondaires aux affections associées occupent la première place. Le taux de l'angiocholite postopératoire tardive s'est élevé à 1.6%, identique à celui rapporté par d'autres auteurs. Notre expérience nous permet de recommander la choledocoduodénostomie à condition (a) d'apporter une attention particulière aux indications après avoir pris en considération la possibilité de traiter la lithiase par une autre méthode, la sphinctérotomie endoscopique par exemple; et (b) de la réserver aux cas où le diamètre de la V.B.P. est supérieur à 20 et ou les parois de la voie biliaire et du duodénum sont normales. Nous considérons qu'elle est particulièrement indiquée en présence du syndrome du cholédoque en entonnoir. L'intervention est simple, restaure la fonction digestive normale et résoud le problème des calculs de la V.B.P. chez les malades de haut risque.

     

Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice

Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.     

Household Food Insecurity,Lung Function,and COPD in US Adults

Increasing epidemiological evidence suggests that optimal diet quality helps to improve preservation of lung function and to reduce chronic obstructive pulmonary disease (COPD) risk, but no study has investigated the association of food insecurity (FI) and lung health in the general population. Using data from a representative sample of US adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2012 cycles, we investigated the association between FI with lung function and spirometrically defined COPD in 12,469 individuals aged ≥ 18 years of age. FI (high vs. low) was defined using the US Department of Agriculture’s Food Security Scale). Population-weighted adjusted regression models were used to investigate associations between FI, and forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), their ratio, and spirometrically defined restriction (FVC below the lower limit of normal) and airflow obstruction (COPD). The prevalence of household FI was 13.2%. High household FI was associated with lower FVC (adjusted β-coefficient −70.9 mL, 95% CI −116.6, −25.3), and with higher odds (OR) of spirometric restriction (1.02, 95% CI 1.00, 1.03). Stratified analyses showed similar effect sizes within specific ethnic groups. High FI was associated with worse lung health in a nationally representative sample of adults in the US.     

Proposals for person‐centred care in the COVID‐19 era. Delphi study

BackgroundIn this COVID‐19 era, we need to rethink the criteria used to measure the results of person‐centred care strategies.ObjectiveTo identify priorities, and criteria that health services can use to pursue actually the goal of achieving person‐centred care.DesignThree‐phase online qualitative study performed during May–July of 2020 using the Delphi technique.Setting and ParticipantsAn online platform was used for a consensus meeting of 114 participants, including health planning experts, health‐care institution managers, clinicians and patients.Main Outcome MeasuresCriteria and indicators for the achievement of person‐centred care.Main ResultsThe first round began with 125 proposals and 11 dimensions. After the second round, 28 ideas reached a high level of consensus among the participants. Ultimately, the workgroup agreed on 20 criteria for goals in the implementation of person‐centred care during the COVID‐19 era and 21 related indicators to measure goal achievement.DiscussionNine dimensions and 28 priorities were identified. These priorities are also in accordance with the quadruple aim approach, which emphasizes the need for care for health‐care professionals, without whom it is impossible to achieve a better quality of care.ConclusionsPerson‐centred care continues to be a key objective. However, new metrics are needed to ensure its continued development during the restoration of public health services beyond the control of COVID‐19.Patient or Public ContributionTwelve professionals and patient representatives participated voluntarily in the construction of the baseline questionnaire and in the selection of the criteria and indicators using an online platform for consensus meetings.