Laser treatment for adverse reactions to injectable facial filling: a systematic review.

Facial filling is widespread in society, albeit associated with inherent risks. This review analyzes clinical studies using laser therapy for filler complications to assess its safety and efficacy as an alternative treatment. A literature search was conducted up until April 2023, encompassing five different databases: PubMed, Scopus, Embase, Web of Science, and Medline, to find clinical trials addressing patients who underwent laser treatment for adverse reactions to injectable facial filling. The outcome variables were the clinical assessment of the lesion and the occurrence of post-intervention complications/sequelae. The risk of bias was assessed using the ROBINS-I tool. In total, six studies were included, all classified as having a "moderate risk" of bias. A total of 533 patients underwent laser treatment for adverse reactions to injectable facial fillers. The diode laser was the most frequently utilized equipment, with positive results reported in five studies. Among all treated patients, 96.24% achieved partial or complete resolution, 0.22% experienced some sequelae or complications, and only 0.01% showed no improvement. Laser treatment can eliminate the necessity for surgical intervention for adverse reactions to injectable facial fillers, resulting in partial or complete improvement of the condition.

The Tumor Microenvironment: An Introduction to the Development of Microfluidic Devices.

The tumor microenvironment (TME) is like the Referee of a soccer match who has constant eyes on the activity of all players, such as cells, acellular stroma components, and signaling molecules for the successful completion of the game, that is, tumorigenesis. The cooperation among all the "team members" determines the characteristics of tumor, such as the hypoxic and acidic niche, stiffer mechanical properties, or dilated vasculature. Like in soccer, each TME is different. This heterogeneity makes it challenging to fully understand the intratumor dynamics, particularly among different tumor subpopulations and their role in therapeutic response or resistance. Further, during metastasis, tumor cells can disseminate to a secondary organ, a critical event responsible for approximately 90% of the deaths in cancer patients. The recapitulation of the rapidly changing TME in the laboratory is crucial to improve patients' prognosis for unraveling key mechanisms of tumorigenesis and developing better drugs. Hence, in this chapter, we provide an overview of the characteristic features of the TME and how to model them, followed by a brief description of the limitations of existing in vitro platforms. Finally, various attempts at simulating the TME using microfluidic platforms are highlighted. The chapter ends with the concerns that need to be addressed for designing more realistic and predictive tumor-on-a-chip platforms.

Effects of increased doses of lysine in a rumen-protected form on plasma amino acid concentration and lactational performance of dairy cows fed a lysine-deficient diet.

The objective of these studies was to determine the effects of feeding a novel rumen-protected Lys (RP-Lys) product on plasma AA, lactational performance, and Lys bioavailability. To evaluate RP-Lys on lactation performance a corn-based diet (42.5% of corn silage and 21.9% of corn and corn by-products, on DM basis) was formulated to be Lys deficient but adequate in Met, energy, and metabolizable protein. Thirty-six lactating Holstein cows were fed either a Lys-deficient control diet (CON) with no added RP-Lys, or diets containing 0.3% of RP-Lys (0.3RP-Lys) or 0.6% of RP-Lys (0.6RP-Lys) for 8 wk. There were no effects on dry matter intake (mean ± SD; 26.1 ± 0.58 kg/d), milk yield (37.9 ± 0.72 kg/d), or milk composition to the RP-Lys supplementation. No effect was observed on plasma AA concentrations except for His. Plasma His was linearly reduced by Lys feeding (42.6, 41.2, 30.0 ± 4.09 µM, for CON, 0.3RP-Lys, and 0.6RP-Lys, respectively). Calculated efficiency of Lys utilization decreased linearly with RP-Lys supplementation. In the companion study, 3 rumen-cannulated lactating dairy cows were used in a 3 × 3 Latin square design to assess the bioavailability of the RP-Lys. Free Lys (HCl-Lys), RP-Lys, and water were administered separately by postruminal bolus dosing. The Lys bioavailability was assessed by the ratio of area under the curve of Lys plasma concentration for RP-Lys compared with HCl-Lys and discounted for the area under the curve for water bolus dose. The estimated bioavailability of the RP-Lys was 24.4% ± 4.61. In summary, increased supplemental doses of Lys had no effect on Lys plasma concentration and lactational performance when fed to dairy cows on a corn-based diet, although altered Lys as % of essential AA was observed. However, the lack of effects should be considered in light of the lower-than-expected bioavailability of the RP-Lys.

Mortality under early access to antiretroviral therapy vs. Eswatini's national standard of care: the MaxART clustered randomized stepped-wedge trial.

OBJECTIVES: Current WHO guidelines recommend the treatment of all HIV-infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others. MaxART is the first implementation trial of this strategy embedded within a government-managed health system, and assesses mortality as a secondary outcome. Because primary findings strongly supported scale-up of the 'treat all' strategy (hereafter Treat All), this analysis examines mortality as an additional indicator of its impact. METHODS: MaxART was conducted in 14 Eswatinian health clinics through a clinic-based stepped-wedge design, by transitioning clinics from then-national standard of care (SoC) to the Treat All intervention. All-cause, disease-related, and HIV-related mortality were analysed using the Cox proportional hazards model, censoring SoC participants at clinic transition. Median follow-up time among study participants was 292 days. There were 36/2034 deaths in SoC (1.77%) and 49/1371 deaths in Treat All (3.57%). RESULTS: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and Treat All interventions, respectively, the multivariable-adjusted 12-month all-cause mortality rates were 1.42% [95% confidence interval (CI): 0.66-2.17] and 1.60% (95% CI: 0.78-2.40), disease-related mortality rates were 1.02% (95% CI: 0.40-1.64) and 1.10% (95% CI: 0.46-1.73), and HIV-related mortality rates were 1.03% (95% CI: 0.40-1.65) and 0.99% (95% CI: 0.40-1.58). Treat All had no impact on all-cause [hazard ratio (HR) = 1.12, 95% CI: 0.58-2.18, P = 0.73], disease-related (HR = 1.04, 95% CI: 0.52-2.11, P = 0.90), or HIV-related mortality (HR = 0.93, 95% CI: 0.46-1.87, P = 0.83). CONCLUSION: There was no immediate benefit of the Treat All strategy on mortality, nor evidence of harm. Longer follow-up of participants is needed to establish long-term consequences.

Reflection from the strong gravity regime in a lensed quasar at redshift z = 0.658.

The co-evolution of a supermassive black hole with its host galaxy through cosmic time is encoded in its spin. At z > 2, supermassive black holes are thought to grow mostly by merger-driven accretion leading to high spin. It is not known, however, whether below z ≈ 1 these black holes continue to grow by coherent accretion or in a chaotic manner, though clear differences are predicted in their spin evolution. An established method of measuring the spin of black holes is through the study of relativistic reflection features from the inner accretion disk. Owing to their greater distances from Earth, there has hitherto been no significant detection of relativistic reflection features in a moderate-redshift quasar. Here we report an analysis of archival X-ray data together with a deep observation of a gravitationally lensed quasar at z = 0.658. The emission originates within three or fewer gravitational radii from the black hole, implying a spin parameter (a measure of how fast the black hole is rotating) of a = 0.87(+0.08)(-0.15) at the 3σ confidence level and a > 0.66 at the 5σ level. The high spin found here is indicative of growth by coherent accretion for this black hole, and suggests that black-hole growth at 0.5 ≤ z ≤ 1 occurs principally by coherent rather than chaotic accretion episodes.

Collagen-based bioinks for hard tissue engineering applications: a comprehensive review.

In the last few years, additive manufacturing (AM) has been gaining great interest in the fabrication of complex structures for soft-to-hard tissues regeneration, with tailored porosity, and boosted structural, mechanical, and biological properties. 3D printing is one of the most known AM techniques in the field of biofabrication of tissues and organs. This technique opened up opportunities over the conventional ones, with the capability of creating replicable, customized, and functional structures that can ultimately promote effectively different tissues regeneration. The uppermost component of 3D printing is the bioink, i.e. a mixture of biomaterials that can also been laden with different cell types, and bioactive molecules. Important factors of the fabrication process include printing fidelity, stability, time, shear-thinning properties, mechanical strength and elasticity, as well as cell encapsulation and cell-compatible conditions. Collagen-based materials have been recognized as a promising choice to accomplish an ideal mimetic bioink for regeneration of several tissues with high cell-activating properties. This review presents the state-of-art of the current achievements on 3D printing using collagen-based materials for hard tissue engineering, particularly on the development of scaffolds for bone and cartilage repair/regeneration. The ultimate aim is to shed light on the requirements to successfully print collagen-based inks and the most relevant properties exhibited by the so fabricated scaffolds. In this regard, the adequate bioprinting parameters are addressed, as well as the main materials properties, namely physicochemical and mechanical properties, cell compatibility and commercial availability, covering hydrogels, microcarriers and decellularized matrix components. Furthermore, the fabrication of these bioinks with and without cells used in inkjet printing, laser-assisted printing, and direct in writing technologies are also overviewed. Finally, some future perspectives of novel bioinks are given.

Incidence of cardiovascular risk factors in female patients with systemic lupus erythematosus: a 3-year follow-up cohort.

Objectives To evaluate the incidence and variability of traditional coronary artery disease (CAD) risk factors in a cohort of lupus patients and to investigate if prednisone use predicts an increase in the number of risk factors. Methods A total of 151 women, 37.8 ± 11.1 (mean ± SD) years old at baseline, were reevaluated after a median period of 39 (interquartile range 36.5-42.0) months. The cumulative incidence of traditional risk factors, the incidence rate (with 95% confidence interval) of hypertension, diabetes, dyslipidemia and hypertriglyceridemia, and the frequency of the risk factors' disappearance were calculated. Metabolic syndrome (MetS) and Framingham risk score (FRS) were computed. Logistic regression was used to investigate if maximum or cumulative prednisone dose used during follow-up predicted an increase in the cardiometabolic risk factors' number. Results The cumulative incidence of risk factors varied from 39.1% (abdominal obesity) to zero (smoking), and the incidence rate varied from 133.2 (87.8-178.6) per 1000 person-years (dyslipidemia) to 10.4 (1.3-19.5) per 1000 person-years (diabetes). The cumulative incidence for MetS was 18.8%, and 11.7% of 143 patients with low FRS at baseline (T1) were classified in the high-risk category at the end of the study (T2). Dyslipidemia was the most variable risk factor, with 43.5% disappearance at T2. The maximum prednisone dose used during follow-up was borderline ( p = 0.050) for prediction of an increase in the number of cardiometabolic risk factors in an adjusted model for antimalarial use, modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and age. Conclusion The authors described high incidence and variability of CAD risk factors in female lupus patients, with higher prednisone dose being borderline for an increase in the number of cardiometabolic risk factors.

Cervical dilatation over time is a poor predictor of severe adverse birth outcomes: a diagnostic accuracy study.

OBJECTIVE: To assess the accuracy of the World Health Organization (WHO) partograph alert line and other candidate predictors in the identification of women at risk of developing severe adverse birth outcomes. DESIGN: A facility-based, multicentre, prospective cohort study. SETTING: Thirteen maternity hospitals located in Nigeria and Uganda. POPULATION: A total of 9995 women with spontaneous onset of labour presenting at cervical dilatation of ≤6 cm or undergoing induction of labour. METHODS: Research assistants collected data on sociodemographic, anthropometric, obstetric, and medical characteristics of study participants at hospital admission, multiple assessments during labour, and interventions during labour and childbirth. The alert line and action line, intrapartum monitoring parameters, and customised labour curves were assessed using sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and the J statistic. OUTCOMES: Severe adverse birth outcomes. RESULTS: The rate of severe adverse birth outcomes was 2.2% (223 women with severe adverse birth outcomes), the rate of augmentation of labour was 35.1% (3506 women), and the caesarean section rate was 13.2% (1323 women). Forty-nine percent of women in labour crossed the alert line (4163/8489). All reference labour curves had a diagnostic odds ratio ranging from 1.29 to 1.60. The J statistic was less than 10% for all reference curves. CONCLUSIONS: Our findings suggest that labour is an extremely variable phenomenon, and the assessment of cervical dilatation over time is a poor predictor of severe adverse birth outcomes. The validity of a partograph alert line based on the 'one-centimetre per hour' rule should be re-evaluated. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development (USAID), UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), and WHO (A65879). TWEETABLE ABSTRACT: The alert line in check: results from a WHO study.

Surgery in ovarian cancer - Brazilian Society of Surgical Oncology consensus.

Surgical management in epithelial ovarian cancer (EOC) has a significant impact in overall survival and progression-free survival. The Brazilian Society of Surgical Oncology (BSSO) supported a taskforce of experts to reach a consensus: experienced and specialised trained surgeons, in cancer centres, provide the best EOC surgery. Laparoscopic and/or radiological staging prognosticates the possibility of complete cytoreduction (CC0) and helps to reduce unnecessary laparotomies. Surgical techniques were reviewed. Multidisciplinary input is essential for treatment planning. Quality assurance criteria are proposed and require national consensus. Genetic testing is mandatory. This consensus states the final recommendations from BSSO for management of EOC. TWEETABLE ABSTRACT: Brazilian Society of Surgical Oncology consensus for surgery in epithelial ovarian cancer patients.

Mitochondrial genome analysis in penile carcinoma.

Penile cancer is a rare neoplasm that seems to be linked to socio-economic differences. Mitochondrial genome alterations are common in many tumors types and are reported as regulating oxidative metabolism and impacting tumorigenesis. In this study, we evaluate for the first time the mitochondrial genome in penile carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA) mutational load and mtDNA content in Penile tumors. Using next generation sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and 12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and heteroplasmy. We further evaluated variant's pathogenicity using Mutpred predictive software and calculated mtDNA content using quantitative PCR. Mitochondrial genome sequencing revealed an increase number of non-synonymous variants in the tumor tissue, along with higher frequency of heteroplasmy and mtDNA depletion in penile tumors, suggesting an increased mitochondrial instability in penile tumors. We also described a list of mitochondrial variants found in penile tumor and normal tissue, including five novel variants found in the tumoral tissue. Our results showed an increased mitochondrial genome instability in penile tumors. We also suggest that mitochondrial DNA copy number (mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function in PeCa. The better understanding of mitochondrial biology can bring new insights on mechanisms and open a new field for therapy in PeCa.

The expression of clock genes cry1 and cry2 in human colorectal cancer and tumor adjacent tissues correlates differently dependent on tumor location.

Colorectal cancer (CRC) exhibits differences in its features depending on the location of the tumor. The role of the circadian system in carcinogenesis is accepted, and many studies report different clock gene expression in tumors compared to healthy tissue. However, little attention is given to the changes in clock genes in tumors arising from various locations across the colon and rectum. The aim of our study was to investigate the expression of the clock genes cry1 and cry2 in human CRC tissue and tissue adjacent to colorectal tumors in a cohort of 64 patients by real time PCR. Expression of cry1 in the entire patient cohort was higher in tumors compared to adjacent tissues in the right-sided colon but not in the left-sided colorectum. Difference in cry1 expression between tumor and adjacent tissue in the right-sided colon was preserved in women and a trend was observed in men. Higher expression of cry1 in the right-sided colon tumor tissue was associated with worse survival in women and the expression of cry1 in the left-sided colorectum was significantly higher in the adjacent tissue compared to tumor in men but not in women. Expression of cry2 was lower in the tumor than in adjacent tissue in both the right and left-sided colorectum. This trend was generally preserved, but the difference reached significance level only in the male left-sided colon, and cry2 expression in the tumor tissue significantly correlated with location of the tumor in men with grade 2 cancer. Finally, we detected significant correlation between tumor location and cry1 expression in the adjacent tissue and the combined results establish that tumor influence on adjacent tissue is dependent on tumor location. Changed clock gene expression should therefore be considered in specific CRC patient sub-groups.

Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for non-vaccination; two systematic reviews.

BACKGROUND: Despite effective national immunisation programmes in Europe, some groups remain incompletely or un-vaccinated ('under-vaccinated'), with underserved minorities and certain religious/ideological groups repeatedly being involved in outbreaks of vaccine preventable diseases (VPD). Gaining insight into factors regarding acceptance of vaccination of 'under-vaccinated groups' (UVGs) might give opportunities to communicate with them in a trusty and reliable manner that respects their belief system and that, maybe, increase vaccination uptake. We aimed to identify and describe UVGs in Europe and to describe beliefs, attitudes and reasons for non-vaccination in the identified UVGs. METHODS: We defined a UVG as a group of persons who share the same beliefs and/or live in socially close-knit communities in Europe and who have/had historically low vaccination coverage and/or experienced outbreaks of VPDs since 1950. We searched MEDLINE, EMBASE and PsycINFO databases using specific search term combinations. For the first systematic review, studies that described a group in Europe with an outbreak or low vaccination coverage for a VPD were selected and for the second systematic review, studies that described possible factors that are associated with non-vaccination in these groups were selected. RESULTS: We selected 48 articles out of 606 and 13 articles out of 406 from the first and second search, respectively. Five UVGs were identified in the literature: Orthodox Protestant communities, Anthroposophists, Roma, Irish Travellers, and Orthodox Jewish communities. The main reported factors regarding vaccination were perceived non-severity of traditional "childhood" diseases, fear of vaccine side-effects, and need for more information about for example risk of vaccination. CONCLUSIONS: Within each UVG identified, there are a variety of health beliefs and objections to vaccination. In addition, similar factors are shared by several of these groups. Communication strategies regarding these similar factors such as educating people about the risks associated with being vaccinated versus not being vaccinated, addressing their concerns, and countering vaccination myths present among members of a specific UVG through a trusted source, can establish a reliable relationship with these groups and increase their vaccination uptake. Furthermore, other interventions such as improving access to health care could certainly increase vaccination uptake in Roma and Irish travellers.

Triggering the activation of Activin A type II receptor in human adipose stem cells towards tenogenic commitment using mechanomagnetic stimulation.

Stem cell therapies hold potential to stimulate tendon regeneration and homeostasis, which is maintained in response to the native mechanical environment. Activins are members of the mechano-responsive TGF-ß superfamily that participates in the regulation of several downstream biological processes. Mechanosensitive membrane receptors such as activin can be activated in different types of stem cells via magnetic nanoparticles (MNPs) through remote magnetic actuation resulting in cell differentiation. In this work, we target the Activin receptor type IIA (ActRIIA) in human adipose stem cells (hASCs), using anti-ActRIIA functionalized MNPs, externally activated through a oscillating magnetic bioreactor. Upon activation, the phosphorylation of Smad2/3 is induced allowing translocation of the complex to the nucleus, regulating tenogenic transcriptional responses. Our study demonstrates the potential remote activation of MNPs tagged hASCs to trigger the Activin receptor leading to tenogenic differentiation. These results may provide insights toward tendon regeneration therapies.

Effects of treatment of preweaning dairy calves with recombinant bovine somatotropin on immune responses and somatotropic axis.

Weaning may be associated with negative energy balance and body weight loss when calves are still immunologically immature, predisposing them to infectious diseases. The aim of the present experiment was to investigate the effects of treatment of preweaning dairy calves with recombinant bovine somatotropin (rbST) on the somatotropic axis, selected immune parameters, and hematology of calves around weaning. Thirty-six Holstein female calves were randomly assigned to receive 1.5 to 1.8 mg of rbST (Posilac, Elanco Animal Health, Greenfield, IN) per kilogram of body weight or to receive injections of saline (saline solution 0.9%, Valley Vet Supply, Marysville, KS) every 7 d from 21 to 63 d of life. Calves were fed milk replacer ad libitum from birth to 38 d of age (d -11), when progressive weaning started, and calves were weaned at 49 d of age (d 0). Calves were weighed at birth and weekly from 21 to 63 d of age, when wither height also was measured. Calves were vaccinated with 0.5 mg of ovalbumin on study d -28 and -7. Blood samples were collected on d -28, -25, -21, -11, 0, 3, 7, and 14. Polymorphonuclear leukocytes were isolated and challenged ex vivo with Escherichia coli to determine phagocytosis and oxidative burst capacity. Additionally, expression of cluster of differentiation (CD)62L and CD18 by granulocyte, lymphocyte, and CD14+ monocyte were determined. Blood samples were also used to determine hematological parameters and concentrations of growth hormone, insulin-like growth factor-1, insulin, glucose, fatty acids, ß-hydroxybutyrate, haptoglobin, and anti-ovalbumin IgG. Calves treated with rbST had greater concentrations of growth hormone and insulin-like growth factor-1 from d -25 to 14 than control calves, whereas insulin, fatty acid, and ß-hydroxybutyrate concentrations did not differ. On d -11, glucose concentration was greater for rbST-treated calves. Treatment did not affect polymorphonuclear lymphocyte phagocytosis and oxidative burst, but intensity of expression of CD62L and CD18 by granulocytes tended to be increased by rbST treatment. Treatment did not affect the concentration of anti-ovalbumin IgG in serum. Haptoglobin concentration was reduced in rbST treated calves on d 3 and we noted a tendency for hematocrit to be lower in rbST-treated calves. Treatment did not affect body weight, wither height, and average daily gain, despite the fact that rbST-treated calves had lower daily milk replacer intake. The relatively minor improvements in immune responses resulting from rbST treatment of weaning calves may not be sufficient to reduce the incidence of infectious diseases.

Biofunctional Ionic-Doped Calcium Phosphates: Silk Fibroin Composites for Bone Tissue Engineering Scaffolding.

The treatment and regeneration of bone defects caused by traumatism or diseases have not been completely addressed by current therapies. Lately, advanced tools and technologies have been successfully developed for bone tissue regeneration. Functional scaffolding materials such as biopolymers and bioresorbable fillers have gained particular attention, owing to their ability to promote cell adhesion, proliferation, and extracellular matrix production, which promote new bone growth. Here, we present novel biofunctional scaffolds for bone regeneration composed of silk fibroin (SF) and ß-tricalcium phosphate (ß-TCP) and incorporating Sr, Zn, and Mn, which were successfully developed using salt-leaching followed by a freeze-drying technique. The scaffolds presented a suitable pore size, porosity, and high interconnectivity, adequate for promoting cell attachment and proliferation. The degradation behavior and compressive mechanical strengths showed that SF/ionic-doped TCP scaffolds exhibit improved characteristics for bone tissue engineering when compared with SF scaffolds alone. The in vitro bioactivity assays using a simulated body fluid showed the growth of an apatite layer. Furthermore, in vitro assays using human adipose-derived stem cells presented different effects on cell proliferation/differentiation when varying the doping agents in the biofunctional scaffolds. The incorporation of Zn into the scaffolds led to improved proliferation, while the Sr- and Mn-doped scaffolds presented higher osteogenic potential as demonstrated by DNA quantification and alkaline phosphatase activity. The combination of Sr with Zn led to an influence on cell proliferation and osteogenesis when compared with single ions. Our results indicate that biofunctional ionic-doped composite scaffolds are good candidates for further in vivo studies on bone tissue regeneration.

Geriatric nutritional risk index as a nutritional and survival risk assessment tool in stable outpatients with systolic heart failure.

BACKGROUND AND AIMS: Malnutrition is frequent in heart failure (HF). However, the best tool for evaluating malnutrition in geriatric patients with HF with reduced ejection fraction (HFrEF) is unknown. This study aimed to evaluate the incremental prognostic value of the geriatric nutritional risk index (GNRI) in stable geriatric outpatients with HFrEF compared with a clinical/laboratory prognostic model. METHODS AND RESULTS: A total of 143 outpatients with HFrEF, aged >65 years, a LVEF <40%, and who were stable and on optimal therapy were studied. Follow-up lasted 3 years. The outcome was all-cause death. The GNRI was calculated as follows: [(1.489 × serum albumin (g/L)) + (41.7 × (current body weight/ideal weight)]. The 3-year death rate was 36.4% and 16 (11.2%) patients were at risk of malnutrition (GNRI ≤98). Deceased patients had a lower GNRI (113.6 ± 9.1 vs. 105.6 ± 9.2; p < 0.001) than did survivors. Greater values of the GNRI (hazard ratio = 0.93, 95% confidence interval [CI] = 0.90-0.95; p < 0.001) and GNRI >98 (hazard ratio = 0.29, 95% CI 0.15-0.57; p < 0.001) were associated with better survival. These factors remained significant after adjustment of significant confounders. The GNRI was a better discriminator of death than weight and albumin. Adding the GNRI to the clinical/laboratory predictor survival model significantly increased the c-statistics from 0.93 to 0.95 (p < 0.001) and the chi-square likelihood ratio test from 106.15 to 119.9. CONCLUSION: The risk of malnutrition, as assessed by the GNRI, in stable geriatric outpatients with HFrEF is a strong independent predictor of survival. The GNRI adds significant prognostic information to the clinical/laboratory model.

Mutational profile of TP53 in esophageal squamous cell carcinoma associated with chagasic megaesophagus.

Chaga's disease is an important communicable neglected disease that is gaining wider attention due to its increasing incidence worldwide. Achalasia due to chagasic megaesophagus (CM), a complication of this disease, is a known-yet, poorly understood-etiological factor for esophageal squamous cell carcinoma (ESCC) development. In this study, we aimed to perform the analysis of TP53 mutations in a series of Brazilian patients with ESCC that developed in the context CM (ESCC/CM), and to compare with the TP53 mutation profile of patients with benign CM and patients with nonchagasic ESCC. Additionally, we intended to correlate the TP53 mutation results with patient's clinical pathological features. By polymerase chain reaction (PCR) followed by direct sequencing of the hotspot regions of TP53 (exon 5 to 8), we found that TP53 mutations were present in 40.6% (13/32) of the ESCC/CM group, 45% (18/40) of the nonchagasic ESCC group, and in only 3% (1/33) of the benign CM group. Missense mutations were the most common in the three groups, yet, the type and mutated exon mutation varied significantly among the groups. Clinically, the groups exhibited distinct features, with both cancer groups (ESCC and ESCC/CM) been significantly associated higher consumption of alcohol and tobacco, older age, worse Karnofsky performance status, poor outcome than the patients with benign CM. No significant association was found between TP53 mutation profile and clinical-pathological features in any of the three groups. We describe first the time the analysis of TP53 mutations in ESCC that developed in the context of CM, and the observed high frequency of mutations, suggest that TP53 also plays an important role in the tumorigenic process of this unexplored etiological condition.

Expression of hepatic genes related to energy metabolism during the transition period of Holstein and F1 Holstein-Gir cows.

The aim of this study was to investigate the expression of genes encoding enzymes and other factors involved with carbohydrate and lipid metabolism in the liver of 2 genetic groups of dairy cows during the transition period. We analyzed the expression of glucose-6-phosphatase (G6PC), cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), methylmalonyl-CoA mutase (MUT), ß-hydroxybutyrate dehydrogenase-2 (BDH2), acetyl-CoA carboxylase (ACC), carnitine palmitoyltransferase-2 (CPT2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), glucose transporter-2 (SLC2A2), and the transcription factor peroxisome proliferator-activated receptor α (PPARA). Blood concentrations of glucose, nonesterified fatty acids, and ß-hydroxybutyrate were also determined. Liver biopsies and blood samples were taken at d 15 prepartum and at d 6, 21, 36, 51, and 66 postpartum from Holsteins (n = 6) and F1 Holstein-Gir (n = 6) cows. Cows were kept under the same prepartum and postpartum management conditions. The results showed that the expression of G6PC, PEPCK-C, BDH2, ACC, CPT2, HMGCR, SLC2A2, and PPARA genes did not differ between genetic groups. Except for PEPCK-C, no interaction between genetic groups and the experimental period was observed. Within both groups of cows, G6PC and PEPCK-C gene expression decreased when comparing prepartum gene expression with 21 and 36 DIM, and increased in d 51 postpartum. MUT mRNA levels differed between the 2 genetic groups and displayed a significant increase after d 36 postpartum, whereas mRNA levels of HMGCR tended to increase when comparing d 21 and 36 to d 51 postpartum. Glucose concentrations also differed between genetic groups, being significantly higher in the plasma of F1 Holstein-Gir cows than in Holstein cows, but no differences were found within each group during the analysis period. ß-Hydroxybutyrate and nonesterified fatty acid concentrations did not differ between genetic groups, but displayed increased levels from prepartum to d 6 and 21 postpartum. Our results indicated that expression in the liver of genes involved with glucose and fatty acid metabolism were similar in both groups of cows and significant differences were observed between the 2 groups in the expression of MUT, a gene involved in propionate metabolism.

Parent Training Programs for Ethnic Minorities: a Meta-analysis of Adaptations and Effect.

This meta-analysis focuses on parent training programs for ethnic minority families and reports on (i) the adaptation of program content and (ii) the process that informs these adaptations. Relevant studies are reviewed to determine the adaptations made and the impact of the adaptations on parenting and child outcomes. Studies were eligible for inclusion if they enrolled predominantly ethnic minority parents with children aged 0-12 years, used a randomized controlled trial design with post-intervention assessments, focused on group-based parent training programs and on prevention of parenting problems, and reported parenting behavior outcomes. A total of 18 studies were included in the analysis. The results show that parent training programs targeting ethnic minority parents have a small but significant effect on improving parenting behavior (k = 18, Cohen's d = 0.30), child outcomes (k = 16, Cohen's d = 0.13), and parental perspectives (k = 8, Cohen's d = 0.19). Most of the programs made adaptations related to surface and deep structure sensitivity. Programs with cultural adaptations, especially deep structure sensitivity (k = 7, Cohen's d = 0.54), are more effective in improving parenting behavior. Because only a third of the included studies provided details on the processes that guided the adaptations made, additional studies are needed to provide information on the process of adaptation; this will enable others to learn from the procedures that can be undertaken to culturally adapt interventions.

New species of the miniature genus Gelanoglanis (Siluriformes: Auchenipteridae) from the Tocantins River basin (Brazil) and osteological description of G. nanonocticolus.

A new species of Gelanoglanis is described based on specimens collected in the Tocantins River, a tributary of the Amazon Basin. The new species is distinguished from congeners by unusual features to the genus such as the pelvic fin falling short of the urogenital opening by a distance larger than the anal-fin length, the first unbranched dorsal and pectoral-fin rays not ossified as spines, the dorsal-fin spinelet absent and the adipose fin in adults preceded by a long fleshy ridge. The new species is further distinguished from congeners by its soft, sinuous snout tip and morphometric proportions of the body and head. The new species shares most putative synapomorphies of the genus, as well as the miniaturized condition evidenced by a diminutive body size and reduced ossifications and lateral sensory system. An elongate dorsal process of the cleithrum is posited as an additional synapomorphy for the genus. An osteological description of Gelanoglanis nanonocticolus based on high-resolution X-ray computed tomography is also provided. http://zoobank.org/urn:lsid:zoobank.org:pub:BA3FE72D-FEF84-7A7-B751-2A15EA52C203.