JAK inhibitors in refractory dermatomyositis: A case series.

This retrospective cohort study assessed the efficacy and safety of Janus kinase (JAK) inhibitors, tofacitinib and baricitinib, in 14 patients with refractory dermatomyositis (DM), a multisystemic autoimmune disorder with limited therapeutic options. Results demonstrated a significant median decrease of 21 points and a 76% reduction in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, along with a complete resolution of muscular symptoms in 64% of the patients. JAK inhibitors were effective in managing refractory DM across various subtypes with mild and manageable adverse events.

Spermiogenesis and biflagellate spermatozoon of the teleost fish Lampanyctus crocodilus (Myctophiformes, Myctophidae): ultrastructure and characterisation of its sperm basic nuclear proteins.

We undertook an ultrastructural study of the spermiogenesis of the lanternfish Lampanyctus crocodilus (Myctophiformes, Myctophidae) with special emphasis on the condensation of chromatin and the biochemical characterisation of its sperm nuclear basic proteins (SNBPs). The round head of the early spermatid of L. crocodilus develops into a curved conical-shaped head in the spermatozoon. Two flagella, present even in the spermatid, are inserted laterally at the convex side of the sperm head. Both flagella possess an axoneme with a 9 + 0 instead of the typical 9 + 2 axonemal structure. Mitochondria undergo a characteristic redistribution during spermiogenesis. A reduced number of them are present lying away from the centrioles at both ends of the concave side of the sperm head. During the chromatin condensation stages in spermiogenesis, fibrogranular structures with granules of 25 ± 5 and 50 ± 5 nm can be observed in the early spermatid and develop into larger granules of about 150 ± 50 nm in the middle spermatid. The latter granules coalesce during the transition to the advanced spermatid and spermatozoon giving rise to highly condensed chromatin in the sperm cell. Protamines are the main SNBPs associated with this chromatin; however, they are unusually large and correspond to the largest protamines described in fish to date. Small stoichiometric amounts of histones and other basic proteins coexist with these protamines in the spermatozoon.

Complex chromatin condensation patterns and nuclear protein transitions during spermiogenesis: examples from mollusks.

In this paper we review and analyze the chromatin condensation pattern during spermiogenesis in several species of mollusks. Previously, we had described the nuclear protein transitions during spermiogenesis in these species. The results of our study show two types of condensation pattern: simple patterns and complex patterns, with the following general characteristics: (a) When histones (always present in the early spermatid nucleus) are directly replaced by SNBP (sperm nuclear basic proteins) of the protamine type, the spermiogenic chromatin condensation pattern is simple. However, if the replacement is not direct but through intermediate proteins, the condensation pattern is complex. (b) The intermediate proteins found in mollusks are precursor molecules that are processed during spermiogenesis to the final protamine molecules. Some of these final protamines represent proteins with the highest basic amino acid content known to date, which results in the establishment of a very strong electrostatic interaction with DNA. (c) In some instances, the presence of complex patterns of chromatin condensation clearly correlates with the acquisition of specialized forms of the mature sperm nuclei. In contrast, simple condensation patterns always lead to rounded, oval or slightly cylindrical nuclei. (d) All known cases of complex spermiogenic chromatin condensation patterns are restricted to species with specialized sperm cells (introsperm). At the time of writing, we do not know of any report on complex condensation pattern in species with external fertilization and, therefore, with sperm cells of the primitive type (ect-aquasperm). (e) Some of the mollusk an spermiogenic chromatin condensation patterns of the complex type are very similar (almost identical) to those present in other groups of animals. Interestingly, the intermediate proteins involved in these cases can be very different.In this study, we discuss the biological significance of all these features and conclude that the appearance of precursor (intermediate) molecules facilitated the development of complex patterns of condensation and, as a consequence, a great diversity of forms in the sperm cell nuclei

Internal anatomy and ultrastructure of the male reproductive system of the spider crab Maja brachydactyla (Decapoda: Brachyura).

The morphology and function of the male reproductive system in the spider crab Maja brachydactyla, an important commercial species, is described using light and electron microscopy. The reproductive system follows the pattern found among brachyuran with several peculiarities. The testis, known as tubular testis, consists of a single, highly coiled seminiferous tubule divided all along by an inner epithelium into germinal, transformation, and evacuation zones, each playing a different role during spermatogenesis. The vas deferens (VD) presents diverticula increasing in number and size towards the median VD, where spermatophores are stored. The inner monostratified epithelium exocytoses the materials involved in the spermatophore wall formation (named substance I and II) and spermatophore storage in the anterior and median VD, respectively. A large accessory gland is attached to the posterior VD, and its secretions are released as granules in apocrine secretion, and stored in the lumen of the diverticula as seminal fluids. A striated musculature may contribute to the formation and movement of spermatophores and seminal fluids along the VD. The ejaculatory duct (ED) shows a multilayered musculature and a nonsecretory pseudostratified epithelium, and extrudes the reproductive products towards the gonopores. A tissue attached to the ED is identified as the androgenic gland.

Enfermedad renal crónica: nuevos conceptos e implicaciones en anestesia / No disponible

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La velocidad de onda de pulso, el QKd y la monitorización ambulatoria de presión arterial como indicadores de riesgo vascular en un grupo de pacientes sometidos a diálisis peritoneal continua ambulatoria / Pulse wave velocity, QKd and ambulatory blood pressure monitoring as vascular risk indicators in a group of patients submitted to continuous ambulatory peritoneal dialysis

Introducción, material y métodos. En un intento de estudiar los factores de riesgo cardiovascular en un grupo de 22 pacientes sometidos a diálisis peritoneal continua ambulatoria (DPCA) se practicó en todos una monitorización ambulatoria de la presión arterial (MAPA) de 24 h, junto con la medición del QKd y velocidad de onda de pulso (VOP). Resultados. Como grupo estos pacientes tienen unas presión arterial (PA) diurna normal: PA sistólica (PAS)/PA diastólica (PAD): 126,8 ñ 17,3/80,2 ñ 10,8 mmHg, pero sin variación en el período nocturno: 120,3 ñ 24,7/76,2 ñ 13,2 mmHg; p : no significativa (NS), presentando un patrón no-dipper, lo cual es un factor de riesgo cardiovascular. La VOP se correlaciona con otros parámetros también propios del riesgo cardiovascular, como son: la edad, r = 0,59, p < 0,006. La PP diurna, r = 0,50, p < 0,003, nocturna y 24 h. Positivamente con la variabilidad de la PAS nocturna, r = 0,60, p < 0,005 y variabilidad de la presión diferencial (PP) nocturna, r = 0,56, p < 0,01 y negativamente con las diferencias día/noche de la PAS, r = -0,55, p < 0,009 y la PAD, r = -0,64, p < 0,003. Por otro lado, el QKd nocturno mantiene una correlación negativa con la VOP, r = -0,64, p < 0,009. La QKd y la variabilidad del PP diurno tienen una correlación positiva, r = 0,52, p < 0,02. Entre QKd de 24 h y la frecuencia cardíaca (FC) 24 h se establece una correlación negativa: r = -0,50, p < 0,02.Conclusiones. Los valores de la VOP son mayores que los valores controles de referencia, no así el QKd, que no varía significativamente de sus controles (100;60). En este estudio la VOP nos da más información que el QKd. Ambos definen una serie de correlaciones inherentes al daño cardiovascular. (AU)

Extended exposure to a discriminated, limited-hold temporal schedule does not produce stimulus control.

Four rats were exposed to two different stimuli (either lights or tones), each stimulus being correlated with independent probabilities of water delivery in a temporally defined schedule. The schedule consisted of a 60 s T cycle with 30 s t(D) and t(-) successive subcycles; t(D) was correlated with a probability of water delivery of 1.0 and t(-) was correlated with a probability of water delivery of 0.0. The schedule was maintained during 180 sessions and extended for 25 extra sessions omitting the stimulus in t(-). The four rats showed low frequencies of responding, response frequency being slightly higher in t(-) than in t(D). The percentage of lost reinforcers was independent of response frequency. The rats which lost less reinforcers were those which obtained more water deliveries during the first 15 cycles of each session. These results show that stimulus control does not develop in limited-hold temporal schedules, and that response-reinforcer effectiveness may depend on the initial contact with reinforcers in the first cycles of the session.

Chromatin reorganization during spermiogenesis of the mollusc Thais hemostoma (Muricidae): implications for sperm nuclear morphogenesis in cenogastropods.

Thais is a cenogastropod mollusc belonging to the Muricidae family. The sperm nuclear morphogenesis of Thais develops in two well-defined and peculiar steps. In the first one, the round early spermatidyl nucleus is penetrated by an endonuclear channel, which arranges as a helix at the inner nuclear surface and organizes the condensing chromatin all around. In the second step, the spiral channel stretches, dragging along the associated chromatin and leading to a definitive cylinder-shaped sperm nucleus. Simultaneously with these changes in nuclear shape, the chromatin is sequentially organized in granules, fibres, lamellae, and, finally, in a very condensed structure, whereas the spermiogenic DNA-associated proteins become more basic and simple. The sperm nucleus contains a small group of protamines consisting of only four types of amino acid (lysine, arginine, glycine, and serine). The most remarkable fact on nuclear spermiogenesis in Thais is that, whereas the chromatin condensation process, the nuclear proteins, and the final shape of sperm nucleus are very similar to those in other muricidae studied, the pathway of nuclear morphogenesis is completely different. We propose an independent genetic control for those two spermiogenic events (chromatin condensation and nucleomorphogenesis). Finally we discuss briefly the main traits of nucleomorphogenesis of muricid molluscs.

Effects of auditory stimuli correlated with different probabilities of water delivery in a limited-hold temporal schedule.

Four rats were exposed to two different tone frequencies, each tone being correlated with independent probabilities of water delivery in a temporally defined schedule. The schedule consisted of a 60-s T cycle, with 30-s t(D) and t(Delta) succesive subcycles. t(D) and t(Delta) were assigned complementary probabilities of water delivery (1.0-0, 0.75-0.25, 0.5-0.5 and 1.0-0) in succesive phases. Each of the first three experimental phases was followed by five consecutive probe sessions using the same probability values, and in which water was delivered independently of responding at the end of each subcycle. Three additional rats were exposed to the same conditions, except that only one tone was used in t(D) and t(Delta). The highest frequencies of responding were observed in two of the rats exposed to differential tone frequencies, an effect that was correlated with lower percentages of lost water deliveries, shorter response latencies, and less variability in the intervals between successive water presentations. In the last phase in which probabilities of water delivery in t(D) and t(Delta) were 1.0 and 0, respectively, response frequency was always higher in t(Delta). These results suggest that the number of water deliveries obtained in the early cycles of every session were responsible for the total number of responses and its correlated effects.

DNA-interacting proteins in the spermiogenesis of the mollusc Murex brandaris.

Sperm chromatin of Murex brandaris (a neogastropod mollusc) undergoes a series of structural transitions during spermiogenesis. The DNA-interacting proteins responsible for these changes as well as the mature protamines present in the ripe sperm nucleus have been characterized. The results reveal that spermiogenic nuclear proteins are protamine precursors that are subjected to a substantial number of small N-terminal deletions that gradually modify their overall charge. The composition of mature protamines is remarkably simple in turn, promoting an efficient and extremely tight packaging of DNA. The pattern of spermiogenic chromatin condensation in M. brandaris clearly departs from that corresponding to vertebrate chromatin.

Automated peritoneal dialysis: a Spanish multicentre study.

BACKGROUND: A prospective sequential study on continuous ambulatory peritoneal dialysis (CAPD) and three techniques of automated peritoneal dialysis (APD) was conducted to assess peritoneal clearances, the influence of peritoneal permeability on nocturnal APD clearances and the suitability of the peritoneal equilibration test (PET) for predicting clearances on APD. METHODS: After performing a PET, a series of clinical, biochemical and dialysis adequacy markers were evaluated after 2 months on CAPD, continuous cycling peritoneal dialysis (CCPD) and tidal volume peritoneal dialysis (TPD) with 50% and 25% tidal volumes. Forty five patients participated and 33 completed the study. RESULTS: Serum urea and creatinine decreased significantly whereas haemoglobin and glucose increased. Mean peritoneal urea clearance (1/week) was 55.40+/-8.76 on CAPD, 74.82+/-12.62 on CCPD, 69.20+/-14.63 on TPD (tidal 50%) and 66.89+/-13.23 on TPD (tidal 25%); mean creatinine clearance (1/week/1.73 m2) was 42.80 +/- 9.95, 52.19 +/- 11.11, 51.31 +/- 13.3 and 49.17 +/- 11.83, respectively. Both clearances were significantly lower on CAPD than on APD (P<0.001). CCPD was the automated technique that provided the best nocturnal urea clearance (P<0.01). Nocturnal creatinine clearance did not show significant differences between CCPD and TPD (tidal 50%), being better with both techniques than with TPD (tidal 25%). There were statistically significant differences between nocturnal dialysate to plasma (D/P) ratios and those corresponding to the nearest times in the PET. The urea D/P ratio at 180 min and the creatinine D/P ratio at 240 min of the PET were the parameters that better estimated nocturnal clearances on APD. CONCLUSIONS: This study confirms that TPD does not improve the results of CCPD. Significant differences between D/P ratios during actual nocturnal cycles and PETs were observed.

Second-order discrimination in humans: the roles of explicit instructions and constructed verbal responding.

In two experiments, university students were trained on a conditional discrimination task (second-order matching to sample) involving various types of stimulus presentations and experimenter-provided instructions. The students' acquisition of conceptual behavior was assessed during transfer tests defined at the intramodal, extramodal and extrarelational levels. On each transfer trial, subjects had to construct their own verbal description of the stimulus being chosen and of the stimulus relation controlling their current choice. The main finding was that conceptual behavior during test trials developed largely independently of the training conditions. The acquisition of conceptual behavior in these experiments may be attributed to the subjects' constructing their own verbal descriptions on each transfer trial. These findings are discussed in relation with the notions of problem solving, generalized responding, and rule-governance.

Retroviral properties inherent to viral erythrocytic infection in sea bass.

The characterization of the aetiological agent of viral erythrocytic infection (VEI) of sea bass suggests a retroviral origin of the disease. RNA from viral erythrocytic infection virus (VEIV) and DNA from blood and organs of VEI-affected fish hybridized to a specific retrovirus cDNA probe. Sequences homologous to retrovirus genome were also detected in non-infected SBL cells (a sea bass cell line), however, Southern blot analysis showed that the DNA restriction patterns in VEI-affected erythrocytes differed from those of SBL cells. RNA-dependent DNA polymerase activity was detected in VEI-affected sea bass blood. This reverse transcription was strongly Mn(2+)-dependent and is the first report of its occurrence in a marine fish and in fish blood samples. Nucleic acid sequences homologous to retrovirus RNA were detected in chromatographic fractions exhibiting reverse transcriptase activity and the presence of virus-like particles, 125-150 mm in diameter. The density of VEIV in sucrose was 1.17-1.18 g/cm3. The symptomatology of VEI is not far from those described for some retroviral diseases.

Characterization of chromatin-condensing proteins during spermiogenesis in a neogastropod mollusc (Murex brandaris).

During the process of chromatin condensation in the spermiogenesis of the neogastropod mollusc Murex brandaris, the nuclear protein complement undergoes a complex series of changes. These changes lead to the appearance of three small protamines in the ripe sperm nuclei. We have characterized this system electrophoretically and at the compositional level, as well as through the analysis of crossreactions with antibodies elicited against a specific spermatozoan protamine. Our results indicate that the complex pattern of chromatin condensation during spermiogenesis in this species (M. brandaris) may be modulated by a series of post-translational (and intranuclear) modifications of DNA-interacting proteins, such as precursors to the sperm protamines. The amino acid composition of each sperm protamine is remarkably simple (lys + arg + gly > or = 96 mol%). This system of spermiogenic/spermatozoal proteins in the neogastropod M. brandaris clearly differs from that in patellogastropods and archaeogastropods, and it may be helpful in understanding evolutionary changes in the chromatin condensation pattern during the spermiogenesis of gastropod molluscs.

Chromosomal Proteins of the Sperm of a Cephalochordate (Branchiostoma floridae) and an Agnathan (Petromyzon marinus): Compositional Variability of the Nuclear Sperm Proteins of Deuterostomes.

We have isolated and characterized for the first time the chromosomal proteins from the nucleus of the sperm of a lancelet (amphioxus) Branchiostoma floridae (Hubbs, 1922) (Phylum Chordata: Subphylum Cephalochordata) and of a lamprey Petromyzon marinus (Linnaeus, 1758) (Phylum Chordata: Subphylum Vertebrata: Class Agnatha). In the first case, the major protein component of the sperm-chromatin of a lancelet is a highly specialized protamine-like (PL) protein that has structural and compositional features similar to those of PL-III from bivalve mollusks. In contrast, the chromatin of the sperm of the lamprey has a structural arrangement and protein composition (histones) very similar to that found in the somatic cells of all eukaryotic organisms. Among the deuterostomes, chromosomal protein variability is considerably greater in representatives of the Phylum Chordata than in echinoderms. The possible evolutionary significance of these findings is discussed.

Fine structure of the spermatozoa of Crassostrea gigas (Mollusca, Bivalvia).

We describe sperm ultrastructure and acrosome differentiation during spermiogenesis in Crassostrea gigas (Mollusca Bivalvia). The sperm cell is a uniflagellated cell of the primitive type. The head region contains a rounded or conical nucleus surmounted by small acrosome. This organelle consists of a membrane-bound acrosomal granule, the contents of which have a homogeneous density, except in the anterior region, which is positive for PTA. The acrosome also surrounds the perforatorium, which includes oriented fibrillar elements: this is the axial body. The middle piece contains four mitochondria encircling two perpendicular centrioles. The distal centriole is provided with a system of mechanical fixation to the plasma membrane, consisting of nine fibers in radial arrangement. The tail flagellum, about 50 microns long, contains the usual microtubular axoneme.

Differences in chromatin condensation during spermiogenesis in two species of fish with distinct protamines.

The sperm cells of Mullus surmuletus (family Mullidae, order Perciformes) and Dicentrarchus labrax (family Percichthyidae, order Perciformes) belong respectively to "type I" and "type II" spermiogenesis categorized by Mattei ('70). The protein content in their sperm nuclei consists of two histone-like proteins (Mullus surmuletus) and one typical protamine (D. labrax). In order to correlate the molecular characteristics of these proteins with their function, we have analyzed the molecules in detail and studied at the ultrastructural level the condensation of chromatin during the spermiogenesis in both species. D. labrax has a true protamine of 34 amino acid residues and its sequence (PR4QASRPVR5TR2STAER5V2R4) contains four arginine clusters. The sperm proteins of M. surmuletus contain 110 and 115 amino acid residues and , by their composition (23-24% Lys, 21-22% Arg, 11-12% Ala), they are similar to protamine-like molecules from sperm of molluscs. During the spermiogenesis of D. Labrax, chromatin condensation progresses from small fibro-granular structures (25 +/- 5 nm in diameter), to larger granules (150 +/- 50 nm diameter). M. surmuletus accumulates 25 +/- 5 nm diameter structures in the basal pole of the nucleus; these structures grow till they reach a diameter of 50 +/- 10 nm and finally go through a process of fusion that changes the condensation of chromatin in sperm nuclei, acquiring a homogeneous aspect. These observations show that during spermiogenesis in the studied types, the last stages of chromatin condensation are dependent on the type of nuclear proteins.

The growth of the first metatarsal bone.

This study presents a common finding in the first metatarsal bone of a distal epiphyseal cartilage which is considered as a physis. This growth center is omitted in the classic anatomical descriptions of the bone. Analyses of the growth of this physis relates to the metatarsal formula of the adult foot. It may result in a first metatarsal "index-plus," where the first metatarsal is longer than the second, depending upon the duration of the activity of the physis. The presence of this physis may be related, in some cases, to: 1) Hallux rigidus. The conformation of index-plus anatomically predisposes the development of such degeneration. 2) Kohler's metatarsal disease. Disturbance in the arterial vascularity of the epiphyseal-metaphyseal type may, in theory, cause osteonecrosis of the first metatarsal head, although no cases have been reported in the literature. 3) Osteochondritis dissecans. Our finding that disorders of epiphyseal ossification may lead to the development of osteochondritis dissecans.

Pneumomediastinum following a surgical renal biopsy.

A case of pneumomediastinum, which appeared after a biopsy of the right kidney by minimal lumbotomy, is reported. The anatomicopathological condition of the renal fragment obtained was judged to be focal and segmental hyalinosis. We wish to emphasize the rarity of such a complication, the type of electrocardiographic changes observed, and the rapid and spontaneous recuperation of the patient without further repercussions.