TBS correlates with bone density and microstructure at trabecular and cortical bone evaluated by HR-pQCT.

INTRODUCTION: Trabecular bone score (TBS) estimates bone microstructure, which is directly measured by high-resolution peripheral quantitative computed tomography (HRpQCT). We evaluated the correlation between these methods and TBS influence on fracture risk assessed by FRAX. MATERIALS AND METHODS: We evaluated 129 individuals (82 women, 43 postmenopausal) 20 to 82.3 years without prevalent clinical or non-clinical morphometric vertebral fractures, using DXA (spine and hip), HR-pQCT at distal radius (R) and tibia (T) and TBS which classifies bone microarchitecture as normal (TBS ≥ 1.350), partially degraded (1.200 < TBS < 1.350), or degraded (TBS ≤ 1.200). RESULTS: Spine and hip BMD and HR-pQCT parameters at cortical bone: area (T), density (R,T) thickness (T) and trabecular bone: density (R,T), number (T) and thickness (R) were significantly better in the 78 individuals with normal TBS (group 1) versus the 51 classified as partially degraded (n = 42) or degraded microarchitecture (n = 9) altogether (group 2). TBS values correlated with age (r = - 0.55), positively with spine and hip BMD and all cortical and trabecular bone density and microstructure parameters evaluated, p < 0.05 all tests. Binary logistic regression defined age (p = 0.008) and cortical thickness (p = 0.018) as main influences on TBS, while ANCOVA demonstrated that HR-pQCT data corrected for age were not different between TBS groups 1 and 2. TBS adjustment increased FRAX risk for major osteoporotic fractures and hip fractures. CONCLUSION: We describe significant association between TBS and both trabecular and cortical bone parameters measured by HR-pQCT, consistent with TBS influence on fracture risk estimation by FRAX, including hip fractures, where cortical bone predominates.

Levitating the noise performance of ultra-stable laser cavities assisted by a deep neural network: the non-intuitive role of the mirrors.

The most precise measurand available to science is the frequency of ultra-stable lasers. With a relative deviation of 4 × 10-17 over a wide range of measuring times between one second and 100 seconds, the smallest effects in nature can thus be made measurable. To enable cutting-edge precision, the laser frequency is stabilized to an external optical cavity. This complex optical device must be manufactured to the highest standards and shielded from environmental influences. Given this assumption, the smallest internal sources of perturbation become dominant, namely the internal noise of the optical components. In this work, we present the optimization of all relevant noise sources from all components of the frequency-stabilized laser. We discuss the correlation between each individual noise source and the different parameters of the system and discover the significance of the mirrors. The optimized laser offers a design stability of 8 × 10-18 for an operation at room temperature for measuring times between one second and 100 seconds.

Morning serum cortisol role in the adrenal insufficiency diagnosis with modern cortisol assays.

PURPOSE: To investigate the accuracy of cutoff values of the morning serum cortisol (MSC) using the cortisol stimulus test (CST) insulin tolerance test (ITT) and 250 mcg short Synacthen test (SST) as the reference standard tests, to better define its clinical role as a tool in the diagnostic investigation of adrenal insufficiency (AI) AI. METHODS: An observational study was conducted with a retrospective analysis of MSC in adult patients who had been submitted to a CST to investigate AI between January 2014 and December 2020. The normal cortisol response (NR) to stimulation was defined based on the cortisol assay. RESULTS: 371 patients underwent CST for suspected AI, 121/371 patients (32.6%) were diagnosed with AI. ROC curve analysis showed an area under the curve (AUC) for MSC of 0.75 (95% CI 0.69 - 0.80). The best MSC cutoff values to confirm AI were < 3.65, < 2.35 and < 1.5 mcg/dL with specificity of 98%, 99%, and 100%, respectively. MSC > 12.35, > 14.2 and > 14.5 mcg/dL had sensitivity of 98%, 99%, and 100%, respectively, being the best cutoff values to exclude AI. Almost 25% of patients undergoing CST for possible AI had MSC values between < 3.65 mcg/dL (6.7% of patients) and > 12.35 mcg/dL (17.5% of patients), making the formal CST testing unnecessary if we consider these cutoff values. CONCLUSION: With the most modern cortisol assays, MSC could be used as a diagnostic tool, with high accuracy to confirm or exclude AI, avoiding unnecessary CST; thus, reducing expenses and safety risks during AI investigation.

Deep learning assisted design of high reflectivity metamirrors.

The advent of optical metasurfaces, i.e. carefully designed two-dimensional nanostructures, allows unique control of electromagnetic waves. To unlock the full potential of optical metasurfaces to match even complex optical functionalities, machine learning provides elegant solutions. However, these methods struggle to meet the tight requirements when it comes to metasurface devices for the optical performance, as it is the case, for instance, in applications for high-precision optical metrology. Here, we utilize a tandem neural network framework to render a focusing metamirror with high mean and maximum reflectivity of Rmean = 99.993 % and Rmax = 99.9998 %, respectively, and a minimal phase mismatch of Δϕ = 0.016 % that is comparable to state-of-art dielectric mirrors.

Blood biomarkers associated with inflammation predict poor prognosis in cerebral venous thrombosis:: a multicenter prospective observational study.

BACKGROUND AND PURPOSE: Experimental studies suggest inflammation can contribute to blood barrier disruption and brain injury in cerebral venous thrombosis (CVT). We aimed to determine whether blood biomarkers of inflammation were associated with the evolution of brain lesions, persistent venous occlusion or functional outcome in patients with CVT. METHODS: Pathophysiology of Venous Infarction-Prediction of Infarction and Recanalization in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Evaluation of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) concentrations in peripheral blood samples was performed at admission in 62 patients. Additional quantification of interleukin (IL)-6 was performed at day 1, 3 and 8 in 35 patients and 22 healthy controls. Standardized magnetic resonance imaging was performed at day 1, 8 and 90. Primary outcomes were early evolution of brain lesion, early recanalization and functional outcome at 90 days. RESULTS: Interleukin-6 levels were increased in patients with CVT with a peak at baseline. IL-6, NLR and CRP levels were not related with brain lesion outcomes or early recanalization but had a significant association with unfavourable functional outcome at 90 days (IL-6: OR = 1.28, 95% CI: 1.05-1.56, P = 0.046; NLR: OR = 1.39, 95% CI: 1.4-1.87, P = 0.014; CRP: OR = 1.756, 95% CI: 1.010-3.051, P = 0.029). Baseline IL-6 had the best discriminative capacity, with an area under the receiver operating characteristic curve to predict unfavourable functional outcome of 0.74 (P = 0.031). CONCLUSIONS: Increased baseline levels of NLR, CRP and IL-6 may serve as new predictive markers of worse functional prognosis at 90 days in patients with CVT. No association was found between inflammatory markers and early evolution of brain lesion or venous recanalization.

Adrenal incidentaloma as a novel independent predictive factor for periodontitis.

PURPOSE: There are no data regarding periodontal derangements in patients with adrenal incidentalomas (AI). We assessed the frequency and severity of periodontitis in patients with AI [non-functioning adrenal incidentaloma (NFAI) and possible autonomous cortisol secretion (ACS)] and compared with individuals with normal adrenal. METHODS: A cross-sectional study evaluated thirty-five individuals with AI and 26 controls. NFAI and possible ACS diagnosis was based on the current guidelines: NFAI [cortisol levels after 1 mg dexamethasone suppression test (1 mg-DST) ≤ 1.8 µg/dL (≤ 50 nmol/L)]; possible ACS [cortisol levels after 1 mg-DST 1.9-5.0 µg/dL (51-138 nmol/L)]. Sociodemographic data were collected, and a full-mouth periodontal evaluation was performed. RESULTS: There was no significant difference between groups regarding age, sex, income, ethnicity, education level, smoking, body mass index, dysglycemia, and arterial hypertension. Patients with AI exhibited worse periodontal conditions than controls for the following periodontal clinical parameters: mean percentage of probing pocket depth (PPD) and clinical attachment level (CAL) ≥ 5 mm (p < 0.001 and p = 0.006, respectively). Patients with NFAI and possible ACS showed higher gingival bleeding index (p = 0.014), bleeding on probing (p < 0.001), and CAL (p < 0.001) means compared to controls. The frequencies of periodontitis were 72.7% in patients with NFAI, 84.6% in possible ACS, and 30.8% in controls (p = 0.001). Periodontitis was more severe in patients with possible ACS than NFAI and controls. Patients with NFAI and possible ACS exhibited odds ratio for periodontitis of 4.9 (p = 0.016) and 8.6 (p = 0.02), respectively. CONCLUSION: Patients with AI have higher frequency and severity of periodontitis than controls. The presence of AI was an independent predictive factor for periodontitis.

Cortisol level after dexamethasone suppression test in patients with non-functioning adrenal incidentaloma is positively associated with the duration of reactive hyperemia response on microvascular bed.

PURPOSE: Data on endothelial derangements in patients with non-functioning adrenal incidentaloma (NFAI) are scarce. METHODS: We investigated if NFAI patients present clinical, biochemical and endothelial alterations compared to individuals without an adrenal lesion and also the associations among these variables. Forty-two NFAI and 40 controls were evaluated. NFAI diagnosis and controls were defined according to the current guidelines and based on a normal adrenal imaging exam, respectively. Body composition was evaluated by dual emission X-ray absorptiometry. Endothelial reactivity was assessed by two methods: tonometry (Endo-PAT®) and laser speckle contrast imaging (LSCI). RESULTS: There were no differences between groups regarding age, gender, ethnicity, smoking status, and statin use. The frequency of metabolic syndrome according to the International Diabetes Federation criteria was 69% and 57.9%, respectively in NFAI and controls (p = 0.36), whereas the atherosclerotic cardiovascular disease (ASCVD) risk was 63.4% and 66.7% (p = 0.81). The clinical, laboratory, and anthropometric characteristics, as well as body composition, were similar between the groups. Additionally, any differences between groups were observed on endothelial reactivity tests. Nevertheless, we noted an association between cortisol levels after 1 mg-dexamethosone suppression test (1 mg-DST) and the duration of post-occlusive reactive hyperemia tested on microcirculation (r = 0.30; p = 0.03). NFAI patients require more antihypertensive drugs to achieve blood pressure control (p = 0.04). The number of antihypertensive drugs used to control blood pressure correlated with cortisol levels after 1 mg-DST (r = 0.29; p = 0.03). CONCLUSIONS: Since both groups herein investigated had a high frequency of metabolic syndrome and ASCVD risk, it might explain similarities observed on endothelial reactivity. Nevertheless, prolonged reactive hyperemia response on microcirculation was correlated with cortisol levels under suppression.

A conserved haplotype in Wagyu cattle contains RAB4A whose encoded protein regulates glucose trafficking in muscle and fat cells.

The Wagyu breed of taurine cattle possess favourable genetics for intramuscular fat (IMF) but genomic loci associated with the trait remain under characterised. Here, we report the identification of a previously unidentified genomic region possessing a particular haplotype structure in Wagyu. Through deployment of a genome-wide haplotype detection analysis that captures regions conserved in a target population but not other populations we screened 100 individual Wagyu and contrasted them with 100 individuals from two independent comparison breeds, Charolais and Angus, using high-density SNPs. An extreme level of Wagyu conservation was assigned to a single genomic window (spanning genomic coordinates BTA28:41 088-300 265 bp). In fact, a five-SNP region spanning 27 096 bp is almost perfectly conserved among the 100 Wagyu individuals assayed and partially overlaps RAB4A. Focussing in, two consecutive SNPs (genomic coordinates 236 949 and 239 950) are apparently fixed within the Wagyu (BB and AA respectively), but at mixed frequencies in the other two breeds. These SNPs are located in the two introns straddling exon 7. In a separate analysis using the 1000 Bulls database, we found that, coincident with exon 7 of RAB4A first allele frequencies were highest in the high IMF Japanese Native (Wagyu) breeds (0.78) and lowest in the low IMF indicine breeds (Nelore and Brahman), with intermediate marbling breeds (Angus and Charolais) assigned intermediate rankings (0.42). RAB4A is known to encode a protein that regulates intracellular trafficking of the insulin-regulated glucose transporter GLUT4. RAB4A can be considered an attractive new positional candidate for IMF development.

Is there bacterial infection in the intact crowns of teeth with pulp necrosis of sickle cell anaemia patients? A case series study nested in a cohort.

AIM: To evaluate the presence of bacteria in permanent teeth with intact crowns (without caries, periodontal disease or dental trauma) in patients with sickle cell anaemia (HbSS genotype) by analysing their clinical, imaging and microbiological parameters. METHODOLOGY: This is a case series study nested in a cohort. In the first follow-up of this cohort study (Journal of Endodontics, 2013, 39, 177), 10 HbSS patients with at least one tooth with an intact crown and clinically diagnosed with pulp necrosis by pulse oximetry adapted for dentistry and a cold pulp sensitivity test (n = 27 teeth) were selected. Changes in the pulp chamber, root and periodontal ligament were identified in the tomographic analysis. Bacterial culture, staining for live and dead bacteria, and real-time polymerase chain reaction with 16S rRNA primers were used to identify the presence of bacteria. Culture sample collection was performed immediately after access to the pulp chamber. The microbiome was analysed with a MiSeq sequencer (Illumina, San Diego, CA). RESULTS: The diagnosis of pulp necrosis was confirmed clinically in 82% (22/27) of the teeth. The amount of bacterial load identified was less than 100 copies µL-1 in 23% (5/22) of the teeth with intact crowns and pulp necrosis. Thirteen bacterial species were identified that are commonly found in urinary tract infections, septicaemia and infective endocarditis. Only one of these species, Granulicatella adjacens, has also be found in primary endodontic infections. CONCLUSION: Prospective clinical, imaging and microbiological analyses suggest that pulp necrosis of teeth with intact crowns in HbSS patients is not associated with the presence of bacteria.

The role of immune checkpoint inhibitor therapy in advanced adrenocortical carcinoma revisited: review of literature.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare disease with few therapeutic options. There is an urgency of new effective therapeutic options for these patients. The role of immune checkpoint inhibitors (ICI) in advanced ACC patients is still unclear. METHODS: We conducted a MEDLINE search using the following string: adrenocortical carcinoma and immunotherapy or checkpoint inhibitors. RESULTS: We found four case series comprising 10 patients, and four prospective studies totaling 115 patients. The response rate (RR) in the group of 10 patients was 1 complete response, 3 partial response (PR), 4 stable disease (SD), and 2 progressive disease (PD). The median progression-free survival (mPFS) ranged from 2 to 31 months and the median overall survival (mOS) ranged from 4.3 to 31 months. The results in the 115 patients from prospective trials was variable, the PR ranged from 6 to 23%, the SD ranged from 18 to 50% and overall disease control rate ranged from 30 to 64%. The mPFS reported varied from 1.8 to 2.6 months while the mOS varied from 10.6 to 24.9 months. There were five patients with sustained response for more than 24 months. The most common treatment-related adverse event (TRAE) was the increase in liver enzymes. No treatment-related deaths were reported. Better results in terms of RR and survival were observed in studies that used pembrolizumab. No predictive biomarker of response was found up to now. CONCLUSION: ICI, mainly pembrolizumab, is a potential therapeutic option, which is safe and associated with prolonged OS benefit, in selected patients with advanced ACC.

Evaluation of body composition using dual-energy X-ray absorptiometry in patients with non-functioning adrenal incidentalomas and an intermediate phenotype: Is there an association with metabolic syndrome?

PURPOSE: Metabolic syndrome (MS) and sarcopenia are associated with increased cardiovascular risk. No studies using dual-energy x-ray absorptiometry (DXA) have evaluated association between body composition (BC) changes and MS in adrenal incidentaloma (AI). Our aim was to analyse BC in non-functioning AI (NFAI) and intermediate phenotype (IP) relative to controls and to correlate with cortisol levels. METHODS: Cross-sectional study with 44 NFAI (serum cortisol ≤ 50 nmol/L after the overnight 1 mg dexamethasone suppression test), 27 IP (cortisol 51-138 nmol/L), and 41 controls (normal adrenal on imaging examination) using DXA. Autonomic cortisol secretion (cortisol > 138 nmol/L) was excluded from the study. BC data were compared using criteria for MS (World Health Organization, National Cholesterol Education Program-Adult Treatment Panel-III, American Association of Clinical Endocrinologists (AACE), and International Diabetes Federation). RESULTS: There was no significant difference in clinical data and body mass index (BMI) among the three groups. Waist circumference (WC) was larger in AI vs. controls (p < 0.01). Waist-to-hip ratio was higher in NFAI vs. controls and waist-to-height ratio was higher in IP vs. controls (p = 0.03 and p = 0.02, respectively). The frequency of MS was higher in AI vs. controls. BC was not different among the groups. Patients with AI there was a significant association of MS with both an increase in total fat and body fat index (all criteria), and a significant difference between MS and smaller BMI-adjusted lean mass (AACE, p = 0.036). No correlation of cortisol after 1 mg dexamethasone test with BC or MS. AI and WC were independently associated with MS. CONCLUSIONS: AI presented high frequency of MS and was independently associated with MS. Possible deleterious effects of cortisol secretion seem to initially affect the muscular system.

Genomic clues of the evolutionary history of Bos indicus cattle.

Together with their sister subspecies Bos taurus, zebu cattle (Bos indicus) have contributed to important socioeconomic changes that have shaped modern civilizations. Zebu cattle were domesticated in the Indus Valley 8000 years before present (YBP). From the domestication site, they expanded to Africa, East Asia, southwestern Asia and Europe between 4000 and 1300 YBP, intercrossing with B. taurus to form clinal variations of zebu ancestry across the landmass of Afro-Eurasia. In the past 150 years, zebu cattle reached the Americas and Oceania, where they have contributed to the prosperity of emerging economies. The zebu genome is characterized by two mitochondrial haplogroups (I1 and I2), one Y chromosome haplogroup (Y3) and three major autosomal ancestral groups (Indian-Pakistani, African and Chinese). Phenotypically, zebu animals are recognized by their hump, large ears and excess skin. They are rustic, resilient to parasites and capable of bearing the hot and humid climates of the tropics. Many resources are available to study the zebu genome, including commercial arrays of SNP, reference assemblies and publicly available genotypes and whole-genome sequences. Nevertheless, many of these resources were initially developed to support research and subsidize industrial applications in B. taurus, and therefore they can produce bias in data analysis. The combination of genomics with precision agriculture holds great promise for the identification of genetic variants affecting economically important traits such as tick resistance and heat tolerance, which were naturally selected for millennia and played a major role in the evolution of B. indicus cattle.

Socio-environmental profile of child and adolescents sensitized by house dust mite in northeast of Brazil.

INTRODUCTION: The association regarding the atopic sensitization to mite aeroallergens and the socio-environmental features is still inconsistent. OBJECTIVES: We analyzed the role played by socioeconomic and environmental factors in the prevalence of sensitization to house dust mite (HDM) allergens, and associated with the risk of developing asthma symptoms. PATIENTS AND METHODS: This is a case-control study conducted with 108 patients, aged 1-17. We inquired about family habits, socioeconomic and environmental features. We applied the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: We observed patients sensitized to all HDM tested, Derp (42%), Derf (37%) and Blot (33%). Middle family income (OR: 2.74; CI95%: 1.127-6.684), exposure to dog (OR: 3.758, CI95%: 1.127-6.684) and artificial climatization (OR: 4.319, CI95%: 1.398-13.348) were associated with sensitization to Derp. We also observed protective factors, such as sharing of dormitories, washing cycle for bedspreads and the presence of basic sanitation. An increased risk of sensitization to Derf was associated with Blot sensitization (OR: 3.172, CI95%: 1.083-9.292) and presence of mold on the walls (OR: 3.095, CI95%: 1.063-9.008). A protective factor was dormitory sharing. For sensitization to Blot, we observed an increase in the risk associated with Derp sensitization (OR: 3.462, CI95%: 1.191-10.061) and exposure to dog (OR: 3.255, CI95%: 0.987-10.736). In addition, sensitization to Blot increases the risk of developing asthma symptoms (OR: 2.732, CI95%: 0.981-7.606). CONCLUSION: Our data show distinct sociodemographic and environmental relations that lead to HDM sensitization and increased probability of development of allergic diseases.

3D printing anatomical models of head bones.

PURPOSE: In many medical schools, the study of Anatomy is becoming increasingly theoretical owing to the difficulty of having human body parts available, rather than offering the students the possibility of a more realistic and practical approach. We developed a project where we use a 3D printer to produce models of the human skull bones, with high quality and quantity to satisfy the needs for Anatomy classes and to be available for request to study at home. METHODS: We selected regular and well-shaped bones of the head upon which we based the 3D models. These bones were scanned using a 64-channel Computed Tomography (high-resolution volumetric acquisition) and the resulting images were then processed with a segmentation software to isolate and reconstruct the structures of interest. The final digital three-dimensional objects were converted into a printable file that the 3D printer could read. We used two filament extrusion type 3D printers, the Prusa i3 and the Zortrax M200. RESULTS: We have printed successfully several models of the skull bones, such as the temporal, occipital, and sphenoid. All the models have obtained good anatomical detail, thus demonstrating the practicality of this technology. Key aspects of the CT image post-processing are discussed. The production process is cost-effective and technically accessible. CONCLUSIONS: These results confirm the potential of 3D printing to create more complex models (e.g. regional, vascular, nervous system structures) that would allow a similar experience compared with a dissection.

Pre- and post-puberty expression of genes and proteins in the uterus of Bos indicus heifers: the luteal phase effect post-puberty.

Progesterone signaling and uterine function are crucial in terms of pregnancy establishment. To investigate how the uterine tissue and its secretion changes in relation to puberty, we sampled tissue and uterine fluid from six pre- and six post-pubertal Brahman heifers. Post-pubertal heifers were sampled in the luteal phase. Gene expression of the uterine tissue was investigated with RNA-sequencing, whereas the uterine fluid was used for protein profiling with mass spectrometry. A total of 4034 genes were differentially expressed (DE) at a nominal P-value of 0.05, and 26 genes were significantly DE after Bonferroni correction (P < 3.1 × 10-6 ). We also identified 79 proteins (out of 230 proteins) that were DE (P < 1 × 10-5 ) in the uterine fluid. When we compared proteomics and transcriptome results, four DE proteins were identified as being encoded by DE genes: OVGP1, GRP, CAP1 and HBA. Except for CAP1, the other three had lower expression post-puberty. The function of these four genes hypothetically related to preparation of the uterus for a potential pregnancy is discussed in the context of puberty. All DE genes and proteins were also used in pathway and ontology enrichment analyses to investigate overall function. The DE genes were enriched for terms related to ribosomal activity. Transcription factors that were deemed key regulators of DE genes are also reported. Transcription factors ZNF567, ZNF775, RELA, PIAS2, LHX4, SOX2, MEF2C, ZNF354C, HMG20A, TCF7L2, ZNF420, HIC1, GTF3A and two novel genes had the highest regulatory impact factor scores. These data can help to understand how puberty influences uterine function.

Effects of cryolipolysis on abdominal adiposity of women.

　　BACKGROUND: The cryolipolysis is on the spotlight as a non-invasive method which reduces fat layer thickness with no damage to surrounding tissues. OBJECTIVE: This study aims to verify the effectiveness of cryolipolysis in the reduction of localized adiposity in women. MATERIALS AND METHODS: This is an experimental study, without a control group, with pre- and post- treatment evaluation through a single application on the lower abdominal area. SETTING: Research conducted in the period from July to December 2015 at the University Potiguar. PARTICIPANTS: A group of 15 women, age between 25-50 years. The cryolipolysis was used in the following parameters: temperature (-7 degree C); suction power (30 kPa), and application time (60 min). MEASUREMENTS: After the cryolipolysis was performed, a follow-up of 2 months was conducted to verify the changes related to weight, body circumference, fat layer thickness, which were evaluated by ultrasonography and photogrammetry. RESULTS: From data analysis, the reductions observed on perimeter (p=0.03) and ultrasonography (p=0.03) showed significant results, considering p <0.05. As of body weight results (p=0.57), the average value varied during the study; however, at the end of the research, no significant weight increase or decrease was reported, as it is known that this method does not interfere with this variable. Additionally, quantitative data were satisfactory. The photogrammetry analysis showed that cryolipolysis positively affected subjects' results. CONCLUSION: A change in body contouring, especially in individuals with lower body mass, reinforces the idea that the parameters must be suitable for individual needs.

Ipilimumab-induced hypophysitis: review of the literature.

PURPOSE: Ipilimumab is a human monoclonal antibody against cytotoxic T-lymphocyte antigen 4 available as an immunotherapy mainly for advanced melanoma. It induces an activation of T cells, resulting in an immune-mediated anti-tumor response and also immune-related adverse events, including hypophysitis. The aim of this review is to identify and discuss features concerning ipilimumab-induced hypophysitis (IIH). DESIGN: A MEDLINE research of all years of publication of IIH was conducted. We gathered information regarding clinical, radiologic and laboratory features of 71 cases recorded in the literature. RESULTS: In our review, IIH was more frequent among older and male patients. Fatigue and headache were the most frequent initial clinical manifestations of IIH and enlargement of the pituitary gland at MRI was present in the majority of patients. Those who received more than 3 cycles of ipilimumab had more fatigue (p = 0.04) and arthritis (p = 0.04). Adrenal insufficiency was more prevalent in men (p = 0.007). Glucocorticoid therapy and hormone replacement were required in most patients and pituitary function recovery was uncommon. Low prolactin at diagnosis tended to predict permanent pituitary dysfunction (p = 0.07). CONCLUSION: Hypopituitarism as a consequence of IIH, if not promptly recognized, can lead to potentially fatal events, such as adrenal insufficiency. IIH can be easily managed with glucocorticoids and hormonal replacement; therefore, physicians should be familiar with the key aspects of this condition. More studies to develop screening protocols and therapeutic intervention algorithms should be performed to decrease morbidity related to IIH.

Genetic and non-genetic factors that increase the risk of non-syndromic cleft lip and/or palate development.

OBJECTIVES: We investigated the relationship between non-syndromic cleft lip/palate (NSCLP) and polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and RFC1, as well as the corresponding interactions with environmental factors. SUBJECTS AND METHODS: One hundred and forty NSCLP patients and their mothers, as well as 175 control individuals and their mothers, were recruited. Information regarding smoking and alcohol consumption was recorded. Blood samples were obtained in order to measure serum folate and cobalamin, as well as, plasma total homocysteine concentrations and to extract DNA. Polymorphisms in MTHFR(677C>T and 1298A>C), MTR(2756A>G), MTR(66A>G), and RFC1(80A>G) were analyzed by PCR-restriction fragment length polymorphism. RESULTS: Among the patients, 59.5% had cleft lip and palate, 22.0% had cleft palate, and 18.5% had cleft lip only. Maternal alcohol consumption and reduced folic acid concentrations in both children and mothers (P < 0.001 and P = 0.003, respectively) were risk factors for NSCLP. Patients and their mothers carrying the MTHFR 667T allele showed lower serum folate than CC (P = 0.011 and P = 0.030, respectively). Mothers who carried the MTHFR 1298C allele exhibited increased risk of having a child with NSCLP, after adjusting for alcohol consumption (OR: 1.75, 95% CI: 1.03-2.99, P = 0.038). CONCLUSIONS: Reduced folic acid levels, alcohol consumption, and the MTHFR 677T and 1298C alleles may have contributed to NSCLP development in this sample population from Rio Grande do Norte.

Improving plant transformation using Agrobacterium tumefaciens.

Here, we report a quick and low-cost method to improve plant transformation using Agrobacterium tumefaciens. This method involves the use of physical wounding, ultrasound, and an increase in exposure time to the bacteria. We show how the transformation rate increased from 0 to 14% when an ultrasound pulse of 10 s was used in conjunction with 96 h of bacterial exposure in Eclipta alba explants.

Physical mapping of 18S and 5S rDNA loci and histone H3 gene in grasshopper species of the subfamily Gomphocerinae (Acrididae).

In this study, fluorescence in situ hybridization (FISH) analysis was used to determine and compare the numbers and chromosomal locations of two multigene families (rDNA and histone H3) in four Neotropical species of gomphocerine grasshoppers. FISH using the 18S rDNA probe identified a single site on the S9 chromosome of Amblytropidia sp and Cauratettix borelli, a single site on chromosome M6 of Compsacris pulcher, and two sites (chromosomes L1 and L2) in Orphulella punctata. By contrast, FISH with a 5S rDNA probe identified dispersion of this sequence in the genomes of the four species, with evidence of intraspecific variations. Amblytropidia sp had six to eight FISH signals on autosomal chromosomes, while C. pulcher exhibited a signal only on the M5 bivalent. The histone H3 gene was less variable and was restricted to a single pair in all species. The conservation of the numbers and locations of 18S rDNA and H3 genes in conjunction with data from the literature was useful for evaluating karyotype evolution in this subfamily. The variation in the number and sizes of 5S rDNA sites indicates a process of recent dispersion that might have been mediated by transposition.