Glycerol is not suitable for the cryopreservation of quail semen.

1. This study investigated the potential use of glycerol as a cryoprotectant for quail sperm cells. Its role in maintaining sperm fertilising ability in vivo and in vitro quality parameters, such as motility, was assessed.2. The data showed that the presence of glycerol in semen samples was associated with infertility, which suggested that removal prior to insemination is mandatory. Removal through serial dilution centrifugation was associated with fewer than 5% of motile sperm cells and resulted in no fertility.3. In conclusion, glycerol alone is not suitable for quail semen cryopreservation, and other approaches need to be investigated to develop cryobanking programmes for this species.

Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability.

Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate a mutant form of the TARP family member stargazin, described in an ID patient. Molecular dynamics analyses predicted that the ID-associated stargazin variant, V143L, weakens the overall interface of the AMPAR:stargazin complex and impairs the stability of the complex. Knock-in mice harboring the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects, resembling phenotypes displayed by ID patients. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation, abnormal synaptic transmission and long-term potentiation specifically in basal dendrites, and synaptic ultrastructural alterations. These data suggest a causal role for mutated stargazin in the pathogenesis of ID and unveil a new role for stargazin in the development and function of hippocampal synapses.

The influence of simultaneous pancreas-kidney transplantation on the evolution of diabetic foot lesions and peripheral arterial disease.

PURPOSE: Simultaneous pancreas-kidney transplantation (SPKT) remains the best treatment option in patients with type 1 diabetes and chronic kidney failure. There are only a few studies addressing the potential ischemic deterioration of peripheral arterial disease (PAD) due to blood diverting from the iliac artery to the kidney graft. We aimed to evaluate diabetic foot lesions and PAD evolution in SPKT recipients and investigate if they are more frequent in ipsilateral lower limb of kidney graft. METHODS: We developed a retrospective cohort, including patients submitted to SPKT in our tertiary center, between 2000 and 2017. Diabetic foot lesions and PAD frequencies were compared in the period before and after transplantation. RESULTS: Two hundred and eleven patients were included, 50.2% (n = 106) female, with a median age at transplantation of 35 years (IQR 9). After a median follow-up period of 10 years (IQR 7), patient, kidney, and pancreatic graft survival were 90.5% (n = 191), 83.4% (n = 176), and 74.9% (n = 158), respectively. Before transplant, 2.8% (n = 6) had PAD and 5.3% (n = 11) had history of foot lesions. In post-transplant period, 17.1% (n = 36) patients presented PAD and 25.6% (n = 54) developed diabetic foot ulcers, 47.6% (n = 35) of which in the ipsilateral and 53.3% (n = 40) in the contralateral lower limb of the kidney graft (p = 0.48). Nine patients (4.3%) underwent major lower limb amputation, 3 (30%) ipsilateral and 7 (70%) contralateral to the kidney graft (p = 0.29). CONCLUSIONS: Diabetic foot lesions were not more frequent in the ipsilateral lower limb of the kidney graft, therefore downgrading the 'steal syndrome' role in these patients.

Home administration of biological treatment in severe asthma in real-life experience: impact on asthma control and quality of life.

Summary: Introduction. Several biological agents for the treatment of severe asthma have been approved for self-administration on an outpatient basis in the last years. However, data on the impact of home administration in outcomes such as asthma control and quality of life in real-life settings are sparse. Being this knowledge crucial for clinical practice, this study aimed to assess asthma control and quality of life in patients who transitioned from day hospital administration of biological therapy to home administration. Methods. A single-center prospective analysis of 33 patients treated with biologics for severe asthma, who switched from hospital to home treatment was performed. Asthma Control Test (ACT), Control of Allergic Rhinitis and Asthma Test (CARAT), Asthma Life Quality (ALQ) and the number of exacerbations were assessed 3 months before and 3 and 6 months after of home-use. Results. ACT and CARAT did not show statistical differences comparing to the baseline values (21.8 ± 2.7 and 23.8 ± 5.5) within 3 months (22.1 ± 2.4, p = 0.609; 23.2 ± 5.3, p = 0.572) or 6 months (23.4 ± 0.9, p = 0.553; 23.7 ± 6.2, p = 0.149) of home administration. Also, ALQ score did not show meaningful variations between baseline (9.5 ± 3.2) and after 3 months (11.2 ± 4.4, p = 0.275) and 6 months (10.3 ± 3.8, p = 0.209) of home-use. Regarding asthma exacerbations, we did not record a significant difference comparing to the baseline values of 3 months/patient exacerbations (0.2 ± 0.4) and after 3 months (0.2 ± 0.5, p = 0.786) or 6 months (0.2 ± 0.4, p = 1.000) of change in modality treatment. There was no cases of anaphylaxis or other serious adverse effects in those patients treated at home. Conclusions. Transition of day hospital administration of biologic treatment for severe asthma to home administration did not lead to any deterioration of asthma control or quality of life. Our results emphasized the efficacy and safety of home administration of biologic treatment and provide support on changing the paradigm of the administration of biological treatment in severe asthma.

Avian sperm-borne RNAs: optimisation of a new isolation protocol.

1. Sperm-borne RNAs are involved in sperm and embryonic protein translation, the regulation of early development and the epigenetic inheritance of the paternal phenotype. Sperm-borne RNA purification protocols generally include a cell purification stage to discard contamination by somatic cells. In avian species, no protocol is currently available to isolate all the populations composing sperm-borne RNAs.2. This study evaluated the presence of somatic cells in semen samples of chickens and quails using visual examination after fluorescent nuclei staining. The efficiency of somatic cell lysis buffer (SCLB) on chicken liver cells and its impacts on chicken sperm cell integrity was explored. Three different approaches were tested to isolate RNA: two developed for mammalian sperm cells and a commercial kit for somatic cells. The efficiency and reliability of each approach was determined based on RNA quality and purity. Eventually, the presence of miRNA and mRNA in purified avian sperm-borne RNAs was investigated by RT-(q)PCR.3. No somatic cells were found in chicken and quail semen. The SCLB totally lysed chicken liver cells but also induced sperm cell necrosis. Consequently, this treatment wasn't performed on samples prior to RNA isolation. Among the tested RNA purification protocols, the commercial one was the least variable and isolated RNA with the highest purity levels. No DNA contamination was observed. Furthermore, the samples contained miRNA and mRNA already known as present in mammalian sperm cells (gga-miR-100-5p, gga-miR-191-5p, GAPDH and PLCZ1), but mRNAs associated with leucocytes (CD4) and Sertoli cells (SOX4, CLDN11) were not detected. This protocol was successfully applied to quail sperm cells.4. Altogether, the study reveals that it is unnecessary to pre-treat samples to remove somatic cell contamination before RNA purification and successfully describes an isolation protocol for sperm-borne RNAs, including small non-coding and long coding RNAs, in two distinct avian species highly valuable as biological models.

Strength of a Zirconia- Reinforced Glass-Ceramic After Diamond Bur Adjustment.

INTRODUCTION: Adjustments with diamond burs on the ceramic surface can affect its roughness and decrease flexural strength. This study evaluated the effect of polishing or glazing on the surface roughness and biaxial flexural strength of a zirconia-reinforced lithium silicate glass-ceramic upon adjustment with diamond burs. METHODS: Seventy disks were prepared according to ISO 6872 and divided into seven groups (n = 10) according to different adjustments and finishing processes. Surface roughness was measured prior to biaxial flexural strength testing. The topography was analyzed using an atomic force microscope , fracture markings were identified using a stereomicroscope and representative specimens were analyzed using scanning electron microscopy. RESULTS: The use of diamond burs significantly increased the surface roughness and decreased the strength of the evaluated ceramic (p⟨0.05). Polishing reduced the ceramic's roughness but resulted in flexural strength similar to that of the groups with wear (p⟩0.05). The glaze-treated specimens showed flexural strength statistically similar to the control group (p>0.05) but higher roughness, similar to those with wear. CONCLUSIONS: Polishing reduced the surface roughness but did not affect the biaxial flexural strength of the ZLS ceramic. At the same time, the application of glaze after wear increased the strength.

Identifying social cognition subgroups in euthymic patients with bipolar disorder: a cluster analytical approach.

BACKGROUND: Bipolar disorder (BD) is associated with social cognition (SC) impairments even during remission periods although a large heterogeneity has been described. Our aim was to explore the existence of different profiles on SC in euthymic patients with BD, and further explore the potential impact of distinct variables on SC. METHODS: Hierarchical cluster analysis was conducted using three SC domains [Theory of Mind (ToM), Emotional Intelligence (EI) and Attributional Bias (AB)]. The sample comprised of 131 individuals, 71 patients with BD and 60 healthy control subjects who were compared in terms of SC performance, demographic, clinical, and neurocognitive variables. A logistic regression model was used to estimate the effect of SC-associated risk factors. RESULTS: A two-cluster solution was identified with an adjusted-performance group (N = 48, 67.6%) and a low-performance group (N = 23, 32.4%) with mild deficits in ToM and AB domains and with moderate difficulties in EI. Patients with low SC performance were mostly males, showed lower estimated IQ, higher subthreshold depressive symptoms, longer illness duration, and poorer visual memory and attention. Low estimated IQ (OR 0.920, 95% CI 0.863-0.981), male gender (OR 5.661, 95% CI 1.473-21.762), and longer illness duration (OR 1.085, 95% CI 1.006-1.171) contributed the most to the patients clustering. The model explained up to 35% of the variance in SC performance. CONCLUSIONS: Our results confirmed the existence of two discrete profiles of SC among BD. Nearly two-thirds of patients exhibited adjusted social cognitive abilities. Longer illness duration, male gender, and lower estimated IQ were associated with low SC performance.

A computer vision chemometric-assisted approach to access pH and glucose influence on susceptibility of Candida pathogenic strains.

Microorganisms adapt to environmental conditions as a survival strategy for different interactions with the environment. The adaptive capacity of fungi allows them to cause disease at various sites of infection in humans. In this study, we propose digital images as responses of a complete factorial 23. Furthermore, we compared two experimental approaches: the experimental design (3D) and the checkerboard assay (2D) to know the influence of pH, glucose, and fluconazole concentration on different strains of the genus Candida. The digital images obtained from the factorial 23 were used as input in the PCA-ANOVA to analyze the results of this experimental design. pH modification in the culture medium modifies the susceptibility in some species less adapted to this type of modification. For the first time, to the best of our knowledge, digital images were used as input to PCA-ANOVA to obtain information on Candida spp.. Therefore, a higher concentration of antifungals is needed to inhibit the same strain at a lower pH. In short, we present an alternative with less use of reagents and time. In addition, the use of digital images allows obtaining information about fungal susceptibility with three or more factors.

Water dynamics in human cancer and non-cancer tissues.

Normal-to-malignant transformation is a poorly understood process associated with cellular biomechanical properties. These are strongly dependent on the dynamical behaviour of water, known to play a fundamental role in normal cellular activity and in the maintenance of the three-dimensional architecture of the tissue and the functional state of biopolymers. In this study, quasi-elastic neutron scattering was used to probe the dynamical behaviour of water in human cancer specimens and their respective surrounding normal tissue from breast and tongue, as an innovative approach for identifying particular features of malignancy. This methodology has been successfully used by the authors in human cells and was the first study of human tissues by neutron scattering techniques. A larger flexibility was observed for breast versus tongue tissues. Additionally, different dynamics were found for malignant and non-malignant specimens, depending on the tissue: higher plasticity for breast invasive cancer versus the normal, and an opposite effect for tongue. The data were interpreted in the light of two different water populations within the samples: one displaying bulk-like dynamics (extracellular and intracellular/cytoplasmic) and another with constrained flexibility (extracellular/interstitial and intracellular/hydration layers).

Fusion of Tumor-Derived Exosomes with Long-Circulating and pH-Sensitive Liposomes Loaded with Doxorubicin for the Treatment of Breast Cancer.

Doxorubicin (DOX) is a chemotherapeutic agent that has been used in the treatment of breast cancer. However, serious toxic effects have limited its use, mainly cardiotoxicity. To minimize the adverse effects, liposomal preparations containing DOX have been developed. These preparations can reach the target in the tumor region as well as bypass the resistance-related problems. An alternative to increased therapeutic efficacy may be the fusion of liposomes with exosomes released from tumor cells to facilitate membrane and fusion interactions, achieving greater cell uptake. Thus, the purpose of this study was the fusion of exosomes derived from breast tumor cells with long-circulating and pH-sensitive liposomes loading DOX (ExoSpHL-DOX) for the treatment of breast cancer. The mean diameter of ExoSpHL-DOX was 100.8 ± 7.8 nm, the polydispersity index was 0.122 ± 0.004, and the encapsulated DOX content was equal to 83.5 ± 2.5%. The fusion of exosomes with long-circulating and pH-sensitive liposomes was confirmed by Fourier transform infrared spectroscopy, Raman spectroscopy, and nano-flow cytometry. The physicochemical characteristics of ExoSpHL-DOX were maintained for 60 days, at 4 °C. The study of the release of DOX from ExoSpHL-DOX in dilution media with different pH values showed the pH sensitivity characteristic of the nanosystem, since 96.6 ± 0.2% of DOX was released from ExoSpHL-DOX at pH 5.0, while at pH 7.4, the release was 70.1 ± 1.7% in the medium. The cytotoxic study against the breast cancer cell line demonstrated that ExoSpHL-DOX treatment significantly reduced the cancer cell viability.

Computational methods for 2D materials modelling.

Materials with thickness ranging from a few nanometers to a single atomic layer present unprecedented opportunities to investigate new phases of matter constrained to the two-dimensional plane. Particle-particle Coulomb interaction is dramatically affected and shaped by the dimensionality reduction, driving well-established solid state theoretical approaches to their limit of applicability. Methodological developments in theoretical modelling and computational algorithms, in close interaction with experiments, led to the discovery of the extraordinary properties of two-dimensional materials, such as high carrier mobility, Dirac cone dispersion and bright exciton luminescence, and inspired new device design paradigms. This review aims to describe the computational techniques used to simulate and predict the optical, electronic and mechanical properties of two-dimensional materials, and to interpret experimental observations. In particular, we discuss in detail the particular challenges arising in the simulation of two-dimensional constrained fermions and quasiparticles, and we offer our perspective on the future directions in this field.

Aspergillus fumigatus and aspergillosis: From basics to clinics.

The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A. fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP 51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP 51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A. fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A. fumigatus. This review paper comprehensively discusses the current clinical challenges caused by A. fumigatus and provides insights on how to address them.

Chronic skin disease and levels of physical activity in 17 777 Spanish adults: a cross-sectional study.

BACKGROUND: To date there is limited literature on the prevalence of chronic skin conditions and its association with levels of physical activity (PA) in Spain. AIM: To determine the prevalence of chronic skin disease and to compare levels of PA between people with and without chronic skin disease in a large representative sample of Spanish adults aged 15-69 years. METHODS: Data from the Spanish National Health Survey 2017 were analysed. Chronic skin disease was assessed using a yes/no question. PA was measured using the short form of the International Physical Activity Questionnaire. Total PA metabolic equivalent of task min/week were calculated, and PA was included in the analyses as a continuous and a five-category variable. RESULTS: This cross-sectional study included 17 777 adult participants (52.0% women; mean ± SD age 45.8 ± 14.1 years), of whom 940 (5.3%) had chronic skin disease. After adjusting for several potential confounders, there was a negative association between chronic skin disease and PA (OR = 0.87, 95% CI 0.76-1.00, P = 0.05), which was significant for men (OR = 0.76, 95% CI 0.62-0.93, P = 0.01) but not for women (OR = 0.97, 95% CI 0.81-1.16, P = 0.72). CONCLUSIONS: In this large representative sample of Spanish adults, the prevalence of chronic skin disease was low. Levels of PA were lower in men with than in men without chronic skin conditions, but this association was not seen in women.

Monitoring bovine tick fever on a dairy farm: An economic proposal for rational use of medications.

In this study, we evaluated the monitoring of tick fever (TF) in a Brazilian dairy farm in the Minas Gerais state, Brazil, from July 10 to August 4, 2018. We aimed to identify diagnostic and treatment flaws in the protocol adopted by the farm, and to establish a novel and accurate TF monitoring protocol based on precision dairy farming and rational use of antimicrobials and antiparasitic drugs, while evaluating the economic benefits of the proposed strategy. We monitored TF in 395 heifer calves aged between 3 and 14 mo. According to the farm's standard protocol, all calves with an increase of 0.5°C in rectal temperature compared with the previous week's measurement were treated for Anaplasma spp. and Babesia spp. Blood smears were collected from the tail tip of the treated calves. During the last week of the study, we prepared blood smears of all calves regardless of treatment indication. Economic analysis was performed. The results indicated that at least 56.86% (261/459) of the calves did not require treatment for TF, whereas only 23.09% (106/459) had treatment indications. Negative blood smears (45.97%; 211/459) indicated the possibility of calves being affected by another disease or a condition that was not being adequately treated or those not necessarily sick. These results demonstrate the excessive use of medications, representing a direct economic loss, in addition to potentially favoring the occurrence of resistance to antimicrobials. In contrast, 9.42% (26/276) of calves had no treatment indication based on rectal temperature but had treatment indications based on blood smears. Only 5.73% (42/735) of blood smears had co-infection with hemopathogens, and none had triple co-infection. Therefore, we proposed the monitoring of TF using rectal temperature and microscopic analysis. If implemented, this strategy would result in a direct annual savings of approximately $22,638.96 (77.99%) related to medication for the treatment of TF. Therefore, implementing the proposed protocol would be cheaper than treatment based only on rectal temperatures. The currently implemented TF protocols overestimate the occurrence of TF, resulting in overtreatment. Thus, implementing a TF monitoring protocol based on a microscopy tool is justified, with benefits including rational use of medication, potential to generate savings, and reduced morbidity and mortality rates, in addition to enabling other diagnoses.

Single Layer and Double Layer Duraplasty for the Management of Persistent Cerebrospinal Fluid Rhinorrhea Following Frontal Sinus Trauma: A Retrospective Study.

ABSTRACT: Persistent cerebrospinal fluid (CSF) rhinorrhea is an infrequent complication of frontal sinus trauma. It often require craniotomy for dural repair and obliteration of sinus with well vascularized pericranial flap. The multilayer vascularized techniques have gained popularity over the years owing to low rate of postoperative CSF leaks. The study retrospectively analyzed 25 frontal sinus trauma patients (20 males, 5 females) of mean age 32 ±â€Š10.23 years with persistent CSF rhinorrhea from January 2011 to December 2018. All patients underwent frontal craniotomy and duraplasty was done with pericranial flap alone in 14 patients (Group I) and in combination with fascia lata graft in 11 patients (Group II). The clinical outcomes of single and double layer dural reconstruction techniques in management of CSF leak were analyzed. The size of defects ranged between 3 to 28 mm. Significant association was present between defect size and reconstruction technique with large defects underwent double layer repair. Two patients developed CSF leak following repair with pericranial flap alone. The rate of successful closure of CSF fistula was 100% with double layer reconstruction technique. However, statistically no significant association was noted between postoperative CSF leak and reconstruction technique. There was no evidence of meningitis, subdural hematoma, intracranial abscess, and mucocele formation in all patients during follow-up of 50.7 ±â€Š23.6 months. To conclude, pericranial flap is a reliable reconstruction material for management of post traumatic frontal sinus CSF leaks. Dual flap technique that combine the use of fascia lata provides comprehensive solution of CSF fistula repair.

Evaluation of the salivary function of patients in treatment with radiotherapy for head and neck cancer submitted to photobiomodulation.

BACKGROUND: Head and neck radiotherapy is typically associated with toxicities that can have profound effects on the patient's quality of life. Xerostomia, which may or may not be related to hypofunction of the salivary gland, leading to negative consequences, mainly in quality of life, leaving patients more susceptible to the development of oral mucositis, dental caries, oral infection and difficulties in speech is one of the most common side effects of such treatment. The aim of the present study was to evaluate salivary function of patients in treatment with radiotherapy for head and neck cancer submitted to photobiomodulation. MATERIAL AND METHODS: A cross-sectional study with a quantitative approach was carried out in the Dentistry Department of the Hospital de Câncer de Pernambuco between February and September 2019. RESULTS: The study sample comprised 23 patients of both genders, treated with radiotherapy for cancer in the head and neck region. The patients were submitted to photobiomodulation with infrared laser, as intraoral applications in order to prevent mucositis and extraoral applications to stimulate salivary glands. The applications were undertaken three times a week on alternate days throughout the radiotherapy period. The following parameters were used: Intraoral 15mW, 12J / cm2, 10s / point, 2.4 J / point, and extraoral 30mW, 7.5J / cm2, 10s / point, 0.3J / point, both with a wavelength of 830nm and area of 0.028cm². Subjective and objective symptoms were evaluated by measuring the unstimulated salivary flow (USF) using the spitting technique before, during and after radiotherapy treatment. For statistical analysis, a significance level of 5% was adopted. Most patients were male (70%) with 60 years of age on average. At the beginning of treatment, 22 patients had USF > 0.2 ml / min (grade 1), at the end of which 15 patients remained unchanged and only 3 patients progressed to grade 3. As for the subjective classification, most (52%) remained in grade 1 (absence of disability) throughout the treatment. CONCLUSION: Based upon the results of this study it was possible to conclude that the use of photobiomodulation did not significantly interfere with the xerostomia complaint of patients in treatment with radiotherapy, however, it does seem to prevent patients from reaching higher degrees of xerostomia taking into account salivary flow measures.

Frailty and risk of complications in head and neck oncologic surgery. Systematic review and dose-response meta-analysis.

BACKGROUND: There is emerging evidence that frail individuals present a decreased physiological reserve, decreased ability to maintain homeostasis, and increased vulnerability to stressors. The concept of frailty has become increasingly recognized as a valuable measure in oncological surgical patients, including those with head and neck cancer. Preoperative screening for frailty may provide an individualized risk assessment that can be used by an interdisciplinary team for preoperative counseling and to improve outcomes. The aim of this meta-analysis was to evaluate the relationship between frailty and the risk of major postoperative complications in frail individuals submitted to head and neck oncologic surgery. MATERIAL AND METHODS: PubMed, SCOPUS, Web of Science, Google Scholar and OpenThesis were systematically searched to identify studies that evaluated the risk of major postoperative complications in frail individuals undergoing head and neck oncologic surgery. The search was performed on August 31, 2020, without language or date restrictions. Two independent investigators screened the searched studies based on each paper's title and abstract. Relevant studies were read in full and selected according to the eligibility criteria. Frailty was assessed by modified Frailty Index (mFI-11) and major postoperative complications were measured by the Clavien-Dindo classification. We performed a categorical and dose-response meta-analysis using a random-effects model to evaluate the association between frailty and the risk of major postoperative complications in patients submitted to head and neck oncologic surgery. The results of the meta-analysis were expressed as relative risk (RR) and 95% confidence interval (95% CI). The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Four studies (9,947 patients) were included in this systematic review and meta-analysis. Frail patients presented an increased risk of life-threatening complications requiring intensive care unit (ICU) admission (RR = 4.67; 95% CI 1.54-14.10) and 30-day mortality (RR = 8.10; 95% CI 2.30-28.57) compared to non-frail patients. We found evidence of dose-response trend between mFI-11 and major postoperative complications. CONCLUSIONS: Higher frailty scores are associated with a significant increase in ICU-level complications and 30-day mortality after head and neck oncologic surgery.

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

Insulin resistance negatively affects bone quality not quantity: the relationship between bone and adipose tissue.

The present study suggests that insulin resistance has no association with bone quantity, but quality. INTRODUCTION: The literature has contradictory results concerning the influence of insulin resistance on bone. The present study sought to evaluate the association of insulin resistance and adipose tissue with either bone mineral density or the trabecular bone score. METHODS: The study included 56 individuals (36 women and 20 men): age = 46.6 ± 14.2 years, weight = 67.8 ± 10.9 kg, height = 1.65 ± 0.10 m and BMI = 24.8 ± 3.9 kg/m2. The investigational protocol included biochemical determinations and bone assessment by dual X-ray absorptiometry for evaluation of bone mineral density and trabecular bone score. Magnetic resonance was employed to estimate visceral, subcutaneous and bone marrow adipose tissues, as well as intrahepatic lipids. RESULTS: The bone mineral density of the lumbar spine, femoral neck and total hip were not associated with insulin resistance-related parameters [visceral adipose tissue, intrahepatic lipids and homeostatic model assessment of insulin resistance (HOMA-IR)]. In contrast, there was a negative relationship between the trabecular bone score and all these components. The association between the trabecular bone score and HOMA-IR was reinforced after adjustment for age and BMI. Marrow adipose tissue was negatively associated with both bone mineral density and trabecular bone score. CONCLUSIONS: The present study shows that the trabecular bone score is negatively associated with marrow adipose tissue, insulin resistance, visceral adipose tissue and intrahepatic lipid measurements. Additionally, there was a negative relationship between saturated lipids in marrow adipose tissue and the trabecular bone score. These results encourage further studies to investigate the role of the trabecular bone score exam in the clinical evaluation of osteoporosis in conditions of insulin resistance.

Synthetic Biology of Cannabinoids and Cannabinoid Glucosides in Nicotiana benthamiana and Saccharomyces cerevisiae.

Phytocannabinoids are a group of plant-derived metabolites that display a wide range of psychoactive as well as health-promoting effects. The production of pharmaceutically relevant cannabinoids relies on extraction and purification from cannabis (Cannabis sativa) plants yielding the major constituents, Δ9-tetrahydrocannabinol and cannabidiol. Heterologous biosynthesis of cannabinoids in Nicotiana benthamiana or Saccharomyces cerevisiae may provide cost-efficient and rapid future production platforms to acquire pure and high quantities of both the major and the rare cannabinoids as well as novel derivatives. Here, we used a meta-transcriptomic analysis of cannabis to identify genes for aromatic prenyltransferases of the UbiA superfamily and chalcone isomerase-like (CHIL) proteins. Among the aromatic prenyltransferases, CsaPT4 showed CBGAS activity in both N. benthamiana and S. cerevisiae. Coexpression of selected CsaPT pairs and of CHIL proteins encoding genes with CsaPT4 did not affect CBGAS catalytic efficiency. In a screen of different plant UDP-glycosyltransferases, Stevia rebaudiana SrUGT71E1 and Oryza sativa OsUGT5 were found to glucosylate olivetolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid. Metabolic engineering of N. benthamiana for production of cannabinoids revealed intrinsic glucosylation of olivetolic acid and cannabigerolic acid. S. cerevisiae was engineered to produce olivetolic acid glucoside and cannabigerolic acid glucoside.