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Second, habitat destruction, hunting, and both threats together contributed ~57%, ~37%, and ~6% to overall facet declines, respectively. However, hunting pressure increased where TD and PD declined most strongly, whereas habitat destruction disproportionally contributed to FD declines. Third, just 23% of the Chaco would have to be protected to safeguard the top 17% of all three facets. Our findings uncover a widespread impoverishment of mammal species richness, evolutionary history, and ecological functions across broad areas of the Chaco due to increasing habitat destruction and hunting. Moreover, our results pinpoint key areas that should be preserved and managed to maintain all facets of mammalian diversity across the Chaco. More generally, our work highlights how long-term changes in biodiversity facets can be assessed and attributed to specific threats, to better understand human impacts on biodiversity and to guide conservation planning to mitigate them.This experiment was conducted to study nutrient and mineral utilization in greater one-horned rhinoceros fed season-specific diets. Nine adult greater one-horned rhinoceros (774-2407 kg BW) of Sanjay Gandhi Biological Park, Patna, Bihar, India, were used in this experiment. Three digestion trials of 60-d duration were conducted per animal, out of which 55 days was adaptation period and 5 days was collection period. The amount of concentrate was kept constant during all the trials. Green fodder sources were sugarcane, berseem (Trifolium alexndrinum) and chari (Sorghum bicolor) during trials I, II and III respectively. Green fodders were offered 20% in excess of previous day's intake in the afternoon. Apparent digestibility of dry matter and crude fibre was higher (p less then .01) in group II as compared to other groups. Apparent digestibility of crude protein was lowest (p less then .01) in group I, followed by group III, and the highest value was observed in group II. Apparent digestibility of Ca and P was lower in greater one-horned rhinoceros fed sugarcane and sorghum as green fodder source. In spite of this, sugarcane and sorghum-based diets were able to meet the requirement of Ca, P, Fe and Mn. Berseem supplied Ca in excess of requirement. All the diets were deficient in Zn. Hence, a suitable supplement of Zn should be added to the conventional zoo diet of greater one-horned rhinoceros.

Myocardial bridging (MB) is commonly treated in patients with hypertrophic cardiomyopathy. However, whether and how MB should be treated in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent septal myectomy remain unclear.

A total of 823 adults with HOCM who underwent septal myectomy at the Fuwai Hospital from 2011 to 2017 were retrospectively studied.

Overall, 31 events occurred 24 patients died and 7 had nonfatal myocardial infarction (MI). The 3-year cumulative event-free survival of all-cause death (97.9% vs. 100% vs. 100% vs. 98.4%, p = .89) and cardiovascular death (98.3% vs. 100% vs. 100% vs. 98.4%, p = .63) were similar among the four groups (non-MB, coronary artery bypass grafting [CABG], unroofing, untreated, respectively). However, the 3-year cumulative event-free survival of nonfatal MI (100% vs. find more 97.5% vs. 98.0% vs. 89.9%, p < .001) and combined endpoints (97.9% vs. 97.5% vs. 98.0% vs. 88.4%, p = .02) were significantly lowest in untreated MB (non-MB, CABG, unroofing, untreated, respectively). Cox regression analysis indicated that untreated MB was a significant independent predictor of combined endpoints (hazard ratio 4.06, 95% confidence interval 1.60-10.32, p < .001). Moreover, 49 patients underwent coronary artery computed tomography 1 year after surgery. The patency rate of the saphenous vein graft was significantly higher than that of the left internal mammary artery (13.3% vs. 84.2%, p < .001). link2 No MB was detected in the unroofing group.

Surgical MB treatment could be beneficial and performed safely during septal myectomy. Myocardial unroofing is the recommended treatment for MB, and unroofing when technically possible may be preferable for long-term outcomes.

Surgical MB treatment could be beneficial and performed safely during septal myectomy. Myocardial unroofing is the recommended treatment for MB, and unroofing when technically possible may be preferable for long-term outcomes.

Antiandrogens are effective therapies that block androgen receptor (AR) transactivation and signaling in over 50% of castration-resistant prostate cancer (CRPC) patients. However, an estimated 30% of responders will develop resistance to these therapies within 2 years. JNJ-pan-AR is a broad-spectrum AR antagonist that inhibits wild-type AR as well as several mutated versions of AR that have emerged in patients on chronic antiandrogen treatment. In this work, we aimed to identify the potential underlying mechanisms of resistance that may result from chronic JNJ-pan-AR treatment.

The LNCaP JNJR prostate cancer subline was developed by chronically exposing LNCaP parental cells to JNJ-pan-AR. Transcriptomic and proteomic profiling was performed to identify potential drivers and/or biomarkers of the resistant phenotype.

Several enzymes critical to intratumoral androgen biosynthesis, Aldo-keto reductase family 1 member C3 (AKR1C3), UGT2B15, and UGT2B17 were identified as potential upstream regulators of the JNJ-pan-AR resistant cells. While we confirmed the overexpression of all three enzymes in the resistant cells only AKR1C3 expression played a functional role in driving JNJ-pan-AR resistance. We also discovered that AKR1C3 regulates UGT2B15 and UGT2B17 expression in JNJ-pan-AR resistant cells.

This study supports the rationale to further investigate the benefits of AKR1C3 inhibition in combination with antiandrogens to prevent CRPC disease progression.

This study supports the rationale to further investigate the benefits of AKR1C3 inhibition in combination with antiandrogens to prevent CRPC disease progression.

As the survival of castration-resistant prostate cancer (CRPC) remains poor, and the nuclear factor-κB (NF-κB) pathways playkey roles in prostate cancer (PC) progression, several studies have focused on inhibiting the NF-κB pathway through generating inhibitory κB kinase subunitα (IKKα) small molecule inhibitors. However, the identification of prognostic markers able to discriminate which patients could benefit from IKKα inhibitors is urgently required. The present study investigated the prognostic value of IKKα, IKKα phosphorylated at serine 180 (p-IKKα S180) and threonine 23 (p-IKKα T23), and their relationship with the androgen receptor (AR) and Ki67 proliferation index to predict patient outcome.

A cohort of 115 patients with hormone-naïve PC (HNPC) and CRPC specimens available were used to assess tumor cell expression of proteins within both the cytoplasm and the nucleus by immunohistochemistry. The expression levels were dichotomized (low vs high) to determine the associations between IKKα, AR, Ki67d crosstalk between IKKα and members of the canonical NF-κB pathway in the nucleus of HNPC. Otherwise, IKKα phosphorylated by noncanonical NF-κB and Akt pathways correlated with members of the canonical NF-κB pathway in CRPC.

The present study reports that patients with CRPC expressing high levels of nuclear IKKα or cytoplasmic p-IKKα S180, which associated with a lower time to death from recurrence, may benefit from IKKα inhibitors.

The present study reports that patients with CRPC expressing high levels of nuclear IKKα or cytoplasmic p-IKKα S180, which associated with a lower time to death from recurrence, may benefit from IKKα inhibitors.

Fetal aneuploidy risk increases with maternal age, but the majority of pregnancies complicated by trisomy 21 occur in younger women. It has been suggested that grandmaternal and/or paternal age may also play a role.

To assess the association between grandmaternal and paternal age and trisomy 21.

For the grandmaternal assessments, we included all offspring with trisomy 21 in a statewide birth defects surveillance system (1995-2015) that could be linked to 3-generation matrilineal pedigrees in the Utah Population Database. Ten sex/birth year-matched controls were selected for each case (770 cases and 7700 controls). link3 For the paternal assessments, our cohort included all trisomy 21 cases (1995-2015) where both the mother and father resided in Utah at the time of birth (1409 cases and 14090 controls). Ages were categorised by 5-year intervals (reference 25-29years). Conditional logistic regression, adjusting for potential confounding factors, was used to model the association between grandmaternal and paternat that young paternal age is also associated with trisomy 21, after taking into account maternal age and race/ethnicity.Pemphigus vulgaris (PV) is an autoimmune intraepithelial bullous disease. Associations with the class II human leukocyte antigen (HLA) alleles and pemphigus vulgaris have been described. Furthermore, an association between the single nucleotide polymorphism of the ST18 gene and pemphigus vulgaris has been reported. We report two pairs of siblings from two unrelated Italian families affected by pemphigus vulgaris, characterizing their genetic and immunological profile. In order to assess the genetic background, HLA-DQA1, HLA-DQB1, HLA-DRB1 and a relevant ST18 polymorphism were investigated. As for the immunological profiles, anti-desmoglein antibodies were analyzed. In family A, the two pemphigus vulgaris patients had the same HLA genetic profile HLA-DQA1 *0104/*0301, HLA-DQB1 *0302/*0503 and HLA-DRB1 *0402/*1401. The male patient was heterozygous for the ST18 mutation while the female patient had a wild genotype. In family B, the two pemphigus vulgaris patients were both wild type for the ST18 mutation and showed the same HLA genotype HLA-DQA1 *0301/*0508, HLA-DQB1 *0301/*0303 and HLA-DRB1 *0402/*1101. Our data show a relevant relationship between the HLA profile and pemphigus vulgaris in our Italian families. In family A, all six alleles are frequently associated with pemphigus vulgaris and were expressed only in the two pemphigus patients; and in family B, two of the six alleles are frequently associated with pemphigus vulgaris. No relevant relationship was found between ST18 polymorphism and pemphigus disease.

Orofacial clefts (OFC) have multifactorial aetiology. Established risk factors explain a small proportion of cases.

To evaluate OFC risk by maternal rural residence and race/ethnicity, and test whether these associations changed after US-mandated folic acid fortification.

This population-based case-control study included all non-syndromic OFC cases among Washington State singleton livebirths between 1989-2014 and birth year-matched controls. Data sources included birth certificates and hospital records. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for OFC by maternal rural-urban residence (adjusted for maternal race/ethnicity) and by maternal race/ethnicity. We evaluated additive and multiplicative effect measure modification by time of folic acid fortification (before vs. after). Probabilistic quantitative bias analysis accounted for potential differential case ascertainment for infants born to Black mothers.

The overall non-syndromic OFC birth prevalence was 1.0 per 1000 livebirths (n=2136 cases).

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