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The impact of an outbreak of bovine viral diarrhea (BVD) on reproductive performance and milk production was investigated in 28 Spanish dairy herds using an observational study design. Mean calving to conception interval (CCI), mean number of inseminations per conception (AI/P) and mean daily milk yield were recorded from herds affected by outbreaks. Infection was confirmed by evidence of viral transmission to young stock (heifers 9-24 months) and persistently infected animals, after previous BVD-free status. Fifteen herds did not use vaccines (G1) whereas the remaining 13 received modified live BVD virus (BVDV) vaccines (G2). In G1 herds, a significant increase in CCI (13.8 days; 95% CI, 0.4-27.3 days; P = 0.050) was observed during the BVD outbreak compared to the year before the outbreak. In G2 herds, there was a not a significant increase in CCI (3.0 days; 95% CI, -1.2-7.2 days; P = 0.558). Changes in AI/P between periods were not significant in any of the herds. In G1 herds, there was an increase of 0.09 units (P > 0.05) during the outbreak, whereas in G2 herds, AI/P decreased 0.08 units (P > 0.05). Compared to milk production in the year before the BVD outbreak, there was no significant change in G1 herds throughout the study period (P > 0.05), but there were significant increases in G2 herds over the study period (P1-P2, 1.4 kg/day increase, P = 0.019; P1-P3, 2.0 kg/day increase, P = 0.007). These results indicate that BVDV infection affected reproductive performance, which is critical in maintaining dairy herd profitability., (Copyright © 2021. Published by Elsevier Ltd.)

TIF1 (transcriptional intermediary factor 1) proteins are encoded by an expanding family of developmental and physiological control genes that are conserved from flies to man. These proteins are characterized by an N-terminal RING-B box-coiled-coil (RBCC) motif and a C-terminal PHD finger/bromodomain unit, and have been implicated in epigenetic mechanisms of transcriptional repression involving histone modifiers and heterochromatin-binding proteins. We describe here the isolation and functional characterization of a fourth murine TIF1 gene, TIF1delta. The predicted TIF1delta protein displays all the structural hallmarks of a bona fide TIF1 family member and resembles the other TIF1s in that it can exert a deacetylase-dependent silencing effect when tethered to a promoter region. Moreover, like TIF1alpha and TIF1beta, TIF1delta can homodimerize and contains a PXVXL motif necessary and sufficient for HP1 (heterochromatin protein 1) binding. Although TIF1alpha and TIF1beta also bind nuclear receptors and Kruppel-associated boxes specifically and respectively, TIF1delta appears to lack nuclear receptor- and Kruppel-associated box binding activity. Furthermore, TIF1delta is unique among the TIF1 family proteins in that its expression is largely restricted to the testis and confined to haploid elongating spermatids, where it associates preferentially with HP1 isotype gamma (HP1gamma) and forms discrete foci dispersed within the centromeric chromocenter and the surrounding nucleoplasm. Collectively, these data are consistent with specific, nonredundant functions for the TIF1 family members in vivo and suggest a role for TIF1delta in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis.

Objective: To evaluate the usefulness of Ki67 expression in the biopsy specimens, to predict the biochemical progression of the prostate cancer after radical prostatectomy., Material and Methods: We analyse the Ki67 expression in the biopsy specimens of 103 patients treated with radical prostatectomy. The mean follow up is 3.4 years (1.3-8.8 years). We correlate the biochemical progression with traditional prognostic factors as the PSA (> 10/< or = 10), Gleason (> or = 7/< 7), pT classification (pT3/pTO-2) and immunohistochemical factor Ki67 (> 3%/< or = 3%)., Results: Of all 103 patients, in 71 (69%) biochemical progression was not detected and in 32 (31%) biochemical progression was detected. The mean of preoperative PSA is 10.07 ng/ml in the patients without progression and 20.90 ng/ml in the patients with biochemical progression (p=0.0001). The mean of Gleason score in 6.03 in the patients without progression and 6.75 in the patients with biochemical progression (p=0.0001). The percentage of Ki67 expression is 3.95% in the patients without progression and 5.05% in the patients with biochemical progression (p=0.030). The tumors pT0-2 progressed 12/67 (17.9%) and the tumors pT3 progressed 20/36 (55.6%) (p=0.0001). Multivariant regression analysis indicate that it does not exist a statistically significant relation between Ki67 (> 3%/< or = 3%) expression in the biopsy specimens and the biochemical progression of the prostate cancer after radical prostatectomy (p=0.204)., Conclusions: The immunohistochemical factor Ki67 (> 3%/< or = 3%) in the biopsy specimens, is less effective than the classic factors, PSA (> 10/< or = 10), Gleason (> or = 7/< 7) and pT classification (pT3/pT0-2), to predict the biochemical progression of the prostate cancer after radical prostatectomy.

Introduction: Headaches are a frequent cause of children's visits to different health care services but the epidemiological profile varies widely according to whether the sample is taken from among visits to hospital clinics, neuropaediatric units or emergency services., Aims: The aim of this study was to analyse the aetiologies of the cases of headache attended in a paediatric emergency service., Patients and Methods: We conducted a retrospective analysis of patient records with headache as the main reason for visiting over a six month period at the Paediatric Emergency Department at the Centro Hospitalario Pereira Rossell. Aetiologies were classified according to International Headache Society (IHS) criteria and the information was completed by telephone if the medical records contained insufficient data., Results: The records of 185 children were studied, which represented 0.58% of the total number of visits. The most common aetiologies were non-cranial infections (43.1%), migraines (14.6%), tension-type headaches (9.2%), traumatic injury (8.1%) and sinusitis (5.4%). Serious causes constituted 4.9% of the total, with a predominance of tumours and infections of the central nervous system. The low percentage of viral meningitis in our series (1%) leads us to suspect an underdiagnosis of this disorder, given the scant number of cases in which the cerebrospinal fluid was examined., Conclusions: Our study confirmed the existence of a wide and varied range of aetiologies causing headaches, with a clear predominance of extracranial disorders and a low percentage of serious intracranial causes. Non-classifiable headaches made up 10.8% of the sample. Brain imaging studies were performed in 9.7% of cases, which is a considerably lower percentage than that of other series and demonstrates a rational use of this resource.

Haploinsufficiency of the NSD1 gene is a hallmark of Sotos syndrome, and rearrangements of this gene by translocation can cause acute myeloid leukemia. The NSD1 gene product is a SET-domain histone lysine methyltransferase that has previously been shown to interact with nuclear receptors. We describe here a novel NSD1-interacting protein, Nizp1, that contains a SCAN box, a KRAB-A domain, and four consensus C2H2-type zinc fingers preceded by a unique finger derivative, referred to herein as the C2HR motif. The C2HR motif functions to mediate protein-protein interaction with the cysteine-rich (C5HCH) domain of NSD1 in a Zn(II)-dependent fashion, and when tethered to RNA polymerase II promoters, represses transcription in an NSD1-dependent manner. Mutations of the cysteine or histidine residues in the C2HR motif abolish the interaction of Nizp1 with NSD1 and compromise the ability of Nizp1 to repress transcription. Interestingly, converting the C2HR motif into a canonical C2H2 zinc finger has a similar effect. Thus, Nizp1 contains a novel type of zinc finger motif that functions as a docking site for NSD1 and is more than just a degenerate evolutionary remnant of a C2H2 motif.

The beta-thymosins are a family of actin monomer-sequestering proteins widely distributed among vertebrate classes. The most abundant beta-thymosins in mammalian species are thymosin beta(4) (Tbeta(4)) and thymosin beta(10) (Tbeta(10)), two small peptides (43 amino acids) sharing a high degree of sequence homology. In the present work, we have analyzed the distribution of Tbeta(4) and Tbeta(10) in the developing and adult rat cerebellum using in situ hybridization and immunohistochemistry techniques. Our results show that the temporal and cellular patterns of expression of both beta-thymosins are different. In the young (7 and 18 postnatal days) and adult (1 and 4 months old) rat cerebellum, Tbeta(4) was mainly expressed in the glia (microglia, Golgi epithelial cells and oligodendrocytes), neurons (granule cells and Purkinje cells), and in the capillaries. In 14-month-old rats, the Tbeta(4) immunoreactivity was only detected in some microglia cells. In young and adult animals, most of the Tbeta(10) immunoreactivity was localized in several types of neuronal cells including granule cells, Golgi neurons and Purkinje cells. In old animals, a faint Tbeta(10) signal could be detected in a few Purkinje cells. Our results suggest that each beta-thymosin could play a different function in the control of actin dynamics.

Background: Chronic renal failure in women is frequently associated with endocrine disturbances leading to menstrual disorders. However, most studies on renal osteodystrophy have not taken into account the possible role of these hormonal disturbances on the pathogenesis of bone alterations seen in these patients. In the present study, we evaluated bone mineral metabolism in a group of young hemodialyzed women with persistent amenorrhea and compared them with similar women with regular menstruation., Methods: We studied 74 women who were further subdivided into 43 women with regular menstrual periods and 31 women with persistent amenorrhea, defined as the absence of menstrual bleeding for more than six months. In all patients, we performed a bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, intact parathyroid hormone (iPTH), sexual hormone determinations that included total estradiol, follicle-stimulating (FSH), and luteinizing hormone and markers of bone resorption such as the procollagen type 1 cross-linked carboxy-terminal telopeptide (ICTP)., Results: Serum calcium, phosphorus, and iPTH were similar in both groups. Serum alkaline phosphatase was higher in amenorrheic women. Although the total serum estradiol concentration was normal in the amenorrheic women when compared with nonuremic women, the values were significantly lower than those in regularly menstruating women. Serum FSH and ICTP values were significantly higher in the amenorrheic women. Trabecular BMD in the lumbar spine was also significantly lower in the amenorrheic women compared with regularly menstruating dialysis patients. Lumbar spine BMD and total estradiol levels correlated significantly in the amenorrheic group., Conclusions: These studies show that persistent amenorrheic young women on dialysis have lower trabecular BMD and evidence of increased bone resorption when compared with normal menstruating women on dialysis. The possible impact of these results in the natural history of the uremic osteodystrophy remains to be determined.

Although the distribution of cholinergic cells is remarkably similar across the vertebrate species, no data are available on more primitive species, such as cartilaginous fishes. To extend the evolutionary analysis of the cholinergic systems, we studied the distribution of cholinergic neurons in the brain and rostral spinal cord of Scyliorhinus canicula by immunocytochemistry using an antibody against the enzyme choline acetyltransferase (ChAT). Western blot analysis of brain extracts of dogfish, sturgeon, trout, and rat showed that this antibody recognized similar bands in the four species. Putative cholinergic neurons were observed in most brain regions, including the telencephalon, diencephalon, cerebellum, and brainstem. In the retrobulbar region and superficial dorsal pallium of the telencephalon, numerous small pallial cells were ChAT-like immunoreactive. In addition, tufted cells of the olfactory bulb and some cells in the lateral pallium showed faint immunoreactivity. In the preoptic-hypothalamic region, ChAT-immunoreactive (ChAT-ir) cells were found in the preoptic nucleus, the vascular organ of the terminal lamina, and a small population in the caudal tuber. In the epithalamus, the pineal photoreceptors were intensely positive. Many cells of the habenula were faintly ChAT-ir, but the neuropil of the interpeduncular nucleus showed intense ChAT immunoreactivity. In the pretectal region, ChAT-ir cells were observed only in the superficial pretectal nucleus. In the brainstem, the somatomotor and branchiomotor nuclei, the octavolateral efferent nucleus, and a cell group just rostral to the Edinger-Westphal (EW) nucleus contained ChAT-ir neurons. In addition, the trigeminal mesencephalic nucleus, the nucleus G of the isthmus, some locus coeruleus cells, and some cell populations of the vestibular nuclei and of the electroreceptive nucleus of the octavolateral region exhibited ChAT immunoreactivity. In the reticular areas of the brainstem, the nucleus of the medial longitudinal fascicle, many reticular neurons of the rhombencephalon, and cells of the nucleus of the lateral funiculus were immunoreactive to this antibody. In the cerebellum, Golgi cells of the granule cell layer and some cells of the cerebellar nucleus were also ChAT-ir. In the rostral spinal cord, ChAT immunoreactivity was observed in cells of the motor column, the dorsal horn, the marginal nucleus (a putative stretch-receptor organ), and in interstitial cells of the ventral funiculus. These results demonstrate for the first time that cholinergic neurons are distributed widely in the central nervous system of elasmobranchs and that their cholinergic systems have evolved several characteristics that are unique to this group., (Copyright 2000 Wiley-Liss, Inc.)