Oral immunotherapy in alpha-gal red meat allergy: Could specific IgE be a potential biomarker in monitoring management?

BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergies. Our aim was to establish the long-term safety and efficacy of a novel red meat (RM) OIT in galactose-alpha-1,3-galactose (alpha-gal) allergy in adults. METHODS: Out of 20 patients with confirmed RM allergy, five (41.66%) underwent an early OIT, seven (58.33%) underwent a delayed protocol and eight patients who were not desensitized formed the patient control group. 15 and 27 day RM OIT for early-onset and delayed-onset alpha-gal allergy were administered, respectively. Desensitized patients were recommended to continue eating at least 100 g RM every day for 6 months and every other day in the following 6 months. After a year, the consumption was recommended 2/3 times in a week. Patients were followed up with skin tests with commercial beef and lamb extracts, fresh raw/cooked beef and lamb and cetuximab and also with serum alpha-gal specific Immunoglobulin-E (sIgE) in the first and fifth years. RESULTS: All patients who underwent OIT became tolerant to RM. During the 5 year follow-up, the median alpha-gal sIgE concentration gradually decreased in nine patients who consumed RM uneventfully while remained unchanged in the control group (p = .016). In two patients, rare tick bites acted as inducers of hypersensitivity reactions with concomitant elevation of alpha-gal sIgE concentrations whereas one patient with low follow-up alpha-gal sIgE concentrations consumed RM uneventfully after frequent tick bites. CONCLUSIONS: Our study showed the long-term safety and efficacy of alpha-gal OIT. Additionally, alpha-gal sIgE seems to be a potential biomarker to monitor OIT.

The Safe Surgical Margin for the Testis Sparing Surgery in Testicular Cancer.

BACKGROUND: Testis sparing surgery (TSS) has an important role in preserving the functional capacity of testicular cancer (TC). Germ cell neoplasia in situ (GCNIS) lesions in the remaining testis have a significant risk for local recurrence. AIM: We aimed to evaluate the presence of satellite GCNIS lesions around the primary tumor and to measure the distance of the furthest GCNIS lesion to the primary tumor. SUBJECT AND METHODS: The radical orchiectomy specimens of patients (n = 37) with a tumor size of ≤3 cm were reevaluated by the same pathologist. The satellite GCNIS lesions located around the primary tumor were detected, and the furthest GCNIS lesion distance to the primary tumor was measured under light microscopy. RESULTS: The mean tumor size was 1,9 ± 0,6 cm. The mean furthest GCNIS distance to the primary tumor was 5,08 ± 2,77 mm. A total of 19 (51,4%) patients had the furthest GCNIS lesions <5 mm, and 28 (75,6%) patients had the furthest GCNIS lesions <7 mm away from the primary lesion. CONCLUSIONS: Leaving a 5 mm safety margin during TSS would lead to excise the satellite GCNIS lesions in half of the patients. Increasing the safety margin to 7 mm would lead to excise the satellite GCNIS lesions at 75% of the patients.

Facial masculinity does not appear to be a condition-dependent male ornament and does not reflect MHC heterozygosity in humans.

Recent studies have called into question the idea that facial masculinity is a condition-dependent male ornament that indicates immunocompetence in humans. We add to this growing body of research by calculating an objective measure of facial masculinity/femininity using 3D images in a large sample (n = 1,233) of people of European ancestry. We show that facial masculinity is positively correlated with adult height in both males and females. However, facial masculinity scales with growth similarly in males and females, suggesting that facial masculinity is not exclusively a male ornament, as male ornaments are typically more sensitive to growth in males compared with females. Additionally, we measured immunocompetence via heterozygosity at the major histocompatibility complex (MHC), a widely-used genetic marker of immunity. We show that, while height is positively correlated with MHC heterozygosity, facial masculinity is not. Thus, facial masculinity does not reflect immunocompetence measured by MHC heterozygosity in humans. Overall, we find no support for the idea that facial masculinity is a condition-dependent male ornament that has evolved to indicate immunocompetence.

Bottleneck and selection in the germline and maternal age influence transmission of mitochondrial DNA in human pedigrees.

Heteroplasmy-the presence of multiple mitochondrial DNA (mtDNA) haplotypes in an individual-can lead to numerous mitochondrial diseases. The presentation of such diseases depends on the frequency of the heteroplasmic variant in tissues, which, in turn, depends on the dynamics of mtDNA transmissions during germline and somatic development. Thus, understanding and predicting these dynamics between generations and within individuals is medically relevant. Here, we study patterns of heteroplasmy in 2 tissues from each of 345 humans in 96 multigenerational families, each with, at least, 2 siblings (a total of 249 mother-child transmissions). This experimental design has allowed us to estimate the timing of mtDNA mutations, drift, and selection with unprecedented precision. Our results are remarkably concordant between 2 complementary population-genetic approaches. We find evidence for a severe germline bottleneck (7-10 mtDNA segregating units) that occurs independently in different oocyte lineages from the same mother, while somatic bottlenecks are less severe. We demonstrate that divergence between mother and offspring increases with the mother's age at childbirth, likely due to continued drift of heteroplasmy frequencies in oocytes under meiotic arrest. We show that this period is also accompanied by mutation accumulation leading to more de novo mutations in children born to older mothers. We show that heteroplasmic variants at intermediate frequencies can segregate for many generations in the human population, despite the strong germline bottleneck. We show that selection acts during germline development to keep the frequency of putatively deleterious variants from rising. Our findings have important applications for clinical genetics and genetic counseling.

Evaluation of IL-17A expressions in high-grade glial tumors receiving radiotherapy.

Aim: In this study, we aimed to investigate the interleukin-17A (IL-17A) levels in patients with high-grade glial tumors before receiving radiotherapy, immediately after radiotherapy, and 3 months after radiotherapy. Patients and Methods: A total of 33 patients who applied to Adana City Training and Research Hospital, Department of Radiation Oncology between December 2016 and May 2018 was included in this study. A total of three blood samples was taken from each patient to assess IL-17A levels before and after radiotherapy and 3 months after the completion of radiotherapy. Results: The differences in IL-17A levels between genders were not statistically significant. IL-17A levels progressively decreased after the radiotherapy and 3 months after the radiotherapy as compared to the levels before radiotherapy. However, this was not statistically significant. IL-17A levels in the non-surviving patients were high before and after radiotherapy as compared to the surviving ones, but this was also not statistically significant. Conclusion: As compared to the period before radiotherapy, IL-17A levels tend to decrease in the period of acute and chronic phases of radiotherapy in all patient groups.

Correction: Investigating the case of human nose shape and climate adaptation.

[This corrects the article DOI: 10.1371/journal.pgen.1006616.].

Effects of combined the trendelenburg and passive leg raising positions on the cross-sectional area of the right internal jugular vein.

OBJECTIVE: The primary aim of this study was to assess the effects of a combination of the passive leg raising (PLR) and Trendelenburg positions on the cross-sectional area (CSA) of the right internal jugular vein (RIJV) using ultrasound measurement in awake patients. METHODS: This prospective observational cross-over study measured the CSA of RIJV in patients in supine (Supine-I), Trendelenburg, Trendelenburg with passive leg raising (T + PLR position), and repeated supine position (Supine-II). The CSA and vertical and horizontal diameters of the RIJVs were compared before and after each position. RESULTS: A total of 120 adult patients were enrolled in the study. The mean CSA of the RIJV significantly increased from 91.2 ± 31.7 mm2 to 110.4 ± 38.2 mm2 in the Trendelenburg position compared to the supine position (P < 0.05). However, there were no statistically significant differences in CSA were observed between the Trendelenburg and Trendelenburg + PLR positions. CONCLUSION: Although the PLR + Trendelenburg position increased the jugular vein diameter relative to the supine position, its clinical usefulness is limited as this increase was still lower than that achieved with the Trendelenburg position alone.

Clinical comparison of patients with angiography: Negative perimesencephalic and nonperimesencephalic subarachnoid hemorrhages.

AIMS: This study aimed to compare the clinical courses, complications, and clinical outcome scores of patients with perimesencephalic (PM) and nonperimesencephalic (n-PM) subarachnoid hemorrhage (SAH) with no vascular pathology observed on cerebral angiography. MATERIALS AND METHODS: This retrospective study included 52 of 310 patients who underwent cerebral digital subtraction angiography for SAH between October 2016 and April 2018. The patients were categorized into PM and n-PM groups based on the type of hemorrhage observed on brain CT. The patients Fischer's grades, Glasgow Coma Scale scores, and World Federation of Neurosurgical Societies SAH grades were recorded. Hydrocephalus, vasospasm findings in both groups, and modified Rankin scale (mRS) scores were assessed, and vascular pathology factors (diabetes mellitus, hypertension, and smoking) were compared between the patient groups. RESULTS: The PM group included 30 patients, the n-PM group 22 patients. Minimal hydrocephalus was observed in two patients in the PM group and six patients developed apparent hydrocephalus in the n-PM group. Angiographic vasospasm was observed in four patients in the n-PM group but none of the patients in the PM group. On discharge, all patients in the PM group had mRS scores of 0. One patient in the n-PM group become exitus and 18 patients were discharged mRS 0, 2 for two patients, and 3 for one patient. CONCLUSION: The patients with PM SAH experienced a benign course, whereas those with n-PM SAH showed a higher risk of vasospasm and hydrocephalus as well as worse exit scores.

Hybrid molecules based on fullerene C60 and 5Z,9Z-dienoic acids: Synthesis and cytotoxic activity.

The present research project details synthesis of new hybrid methanofullerenes based on acetylene and triazole esters of malonic acid containing 5Z,9Z-dienoic acids and fullerene C60 under Bingel-Hirsch conditions, including study of the cytotoxic activity with respect to Jurkat, K562, U937 and HL60 tumor cell lines. Hybrid methanofullerenes containing acetylenic fragments, unlike triazole substituents, were found to exhibit higher cytotoxicity, but are characterized by lower selectivity of action in relation to healthy cells.

Investigating the case of human nose shape and climate adaptation.

The evolutionary reasons for variation in nose shape across human populations have been subject to continuing debate. An import function of the nose and nasal cavity is to condition inspired air before it reaches the lower respiratory tract. For this reason, it is thought the observed differences in nose shape among populations are not simply the result of genetic drift, but may be adaptations to climate. To address the question of whether local adaptation to climate is responsible for nose shape divergence across populations, we use Qst-Fst comparisons to show that nares width and alar base width are more differentiated across populations than expected under genetic drift alone. To test whether this differentiation is due to climate adaptation, we compared the spatial distribution of these variables with the global distribution of temperature, absolute humidity, and relative humidity. We find that width of the nares is correlated with temperature and absolute humidity, but not with relative humidity. We conclude that some aspects of nose shape may indeed have been driven by local adaptation to climate. However, we think that this is a simplified explanation of a very complex evolutionary history, which possibly also involved other non-neutral forces such as sexual selection.

Endoscopic treatment of suprasellar arachnoid cysts indenting third ventricle with obstructive hydrocephalus in children: Thirteen cases.

AIMS: The present study aimed to evaluate the clinical usefulness of endoscopic treatment of suprasellar arachnoid cysts indenting the third ventricle with obstructive hydrocephalus and discuss the clinical features and outcomes of thirteen children treated at our institution. METHOD: We treated thirteen pediatric cases of suprasellar arachnoid cysts indenting the third ventricle with obstructive hydrocephalus between January 2012 and September 2018. Five female and eight male patients were enrolled in the study. The patients had increased intracranial pressure symptoms due to hydrocephaly. Endoscopic treatment was performed in all cases. RESULTS: The patients were followed-up for an average of 36.8 months. The postoperative intracranial pressure findings improved. There was a reduction in the size of the cyst and ventricles and enlargement of the cortical sulci. One patient suffered transient oculomotor nerve deficit. No further surgical interventions, such as shunt placement, were required during the follow-up period. The head circumference of two of the patients with macrocephaly were stable during the follow-up. There were no postoperative recurrences detected. CONCLUSIONS: Endoscopic cyst fenestration and third ventriculostomy are less invasive, safer, and more effective ways to treat suprasellar arachnoid cysts indenting the third ventricle with obstructive hydrocephalus in children with hydrocephaly.

Comparison of 1-year results of single transforaminal epidural steroid injection among patients with different spinal pathologies-related radicular pain.

AIMS: This study aims to investigate the effectiveness of transforaminal epidural steroid injection (TFESI) in patients with lumbar radicular pain or radiculopathy caused by different spinal pathologies. METHODS: One hundred and seventy seven patients who underwent single transforaminal epidural steroid injection were included in the study group and divided into 3 subgroups (central spinal stenosis + lateral recess stenosis, foraminal stenosis, lumbar disc herniation) according to existing spinal pathology. Patients' visuel analogue scale (VAS) measures and Oswestry Disability Index (ODI) scores were recorded and the patients who give favourable response to treatment were called respondents and who were not called as non-respondents. Subgroups were compared statistically at the end of 12 months. RESULTS: Sixty patients (33.9%) were considered as respondents and 117 patients (66.1%) were non-respondents in the entire study group. Patients with foraminal stenosis included the vast majority of the respondents and showed better results of pain relief as opposed to patients of other groups at the end of 12 months (P < 0.001). CONCLUSION: TFESI was an effective treatment modality for pain relief and functional improvement in patients with foraminal stenosis. However, it could not produce the same results in patients with central spinal stenosis and lumbar disc herniations.

Postpartum depression and affecting factors in primary care.

AIM: The aim of this study was to determine the frequency and affecting factors of postpartum depression (PPD) in Edirne city center. This cross-sectional study was conducted among 111 pregnant women in their third trimester in Family Health Centers in Edirne, Turkey. MATERIALS AND METHODS: The participants filled out a questionnaire on sociodemographic factors developed by the researchers along with the Beck Depression Inventory for Primary Care (BDI-PC) before childbirth. Women with a probability of depression, determined with the BDI-PC, were excluded, and the remaining 100 participants were applied the Edinburgh postpartum depression scale (EPDS) in the first and second months after childbirth. RESULTS: The frequency of PPD was 14% (n = 14) in the first month and 17% (n = 17) in the second month of delivery. Thus, 24 different mothers out of 100 were determined to have PPD in the first two months after childbirth. The probability of PPD, measured with EPDS, was significantly higher among younger mothers, mothers with unemployed husbands, mothers with lower income, mothers with a health problem of the child, and mothers who do not breastfeed. There was no significant relationship between PPD and mother's education status, marriage age, the age of first labor, PPD after previous childbirth, psychiatric disorders in first-degree relatives, higher number of children, method of delivery, and unwanted pregnancies. CONCLUSION: PPD is an important community problem. Thus, it is useful to monitor the risky mothers in primary care and screen them with the practical EPDS in order to prevent the negative effects on the baby and the mother.

No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Modeling 3D facial shape from DNA.

Human facial diversity is substantial, complex, and largely scientifically unexplained. We used spatially dense quasi-landmarks to measure face shape in population samples with mixed West African and European ancestry from three locations (United States, Brazil, and Cape Verde). Using bootstrapped response-based imputation modeling (BRIM), we uncover the relationships between facial variation and the effects of sex, genomic ancestry, and a subset of craniofacial candidate genes. The facial effects of these variables are summarized as response-based imputed predictor (RIP) variables, which are validated using self-reported sex, genomic ancestry, and observer-based facial ratings (femininity and proportional ancestry) and judgments (sex and population group). By jointly modeling sex, genomic ancestry, and genotype, the independent effects of particular alleles on facial features can be uncovered. Results on a set of 20 genes showing significant effects on facial features provide support for this approach as a novel means to identify genes affecting normal-range facial features and for approximating the appearance of a face from genetic markers.

Amputation predictors in diabetic foot ulcers treated with hyperbaric oxygen.

OBJECTIVE: Although hyperbaric oxygen therapy (HBOT) has long been used for diabetic foot ulcers (DFUs), its effectiveness is still controversial. The aim of this study was to investigate the efficacy of HBOT in the management of DFUs and identify amputation predictors. METHOD: Patients with chronic DFUs (Wanger grade 2-5) were included in the study, which took place between January 2010 and December 2012. HBOT, 100% oxygen, 2.4 atmosphere absolute (ATA) for 120 minutes, was administered to all patients in addition to standard treatment. DFUs were monitored for at least 3 years, or until healing or amputation occurred. RESULTS: Patients with a total of 146 chronic DFUswere recruited. Complete healing (69.6%) and significant improvement (17.9%) was observed in 87.5% of the patients. The cases with no improvement resulted in amputation (minor amputation: 15.0%; major amputation: 8.2%). The duration of diabetes (p=0.037), new wound formation (p=0.045), C-reactive protein (p=0.001) and Wagner grade (p=0.0001) were correlated with amputation in multiple regression analysis. Mortality was higher in the amputation group than in the non-amputation group (47.1 % versus 21.4 %, p=0.007). CONCLUSION: The inclusion of HBOT with standard treatment and a multidisciplinary approach may be useful in the treatment of DFUs. We found the most important predictors of amputation to be Wagner grade and wound infection. Multicentre, prospective, randomised studies are needed to provide more evidence.

A case report of metastasis of malignant mesothelioma to the retromolar trigone.

BACKGROUND: Malignant mesothelioma is a rare and aggressive tumor with a poor prognosis. Distant metastases are very rare, and the oral cavity metastases are exceedingly rare. Only a few cases with metastasis to oral gingiva are reported. To our knowledge, this is the first case report of pleural mesothelioma metastasized to the retromolar trigone. CASE PRESENTATION: A 59-year-old male was referred with a painless growth at retromolar trigone area. It had been present for 2 months and had increased in size during this period of time. Past medical history revealed a malignant mesothelioma. Intraoral examination showed a soft, haemorrhagic, ulcerated lesion at the right retromolar trigone area. There was no destruction of the bony architecture. An incisional biopsy was performed under local anaesthesia. Based on the histopathological and immunohistochemical findings, a final diagnosis of metastatic mesothelioma was made. The patient was informed about the possibility of multiple metastases within the body, but he succumbed after 45 days following deterioration of his medical condition. CONCLUSIONS: Biopsy, history of the patient and clinical picture were provided to the clinicians to make an efficient differential diagnosis. Differential diagnosis must be performed with other oral cancers, because the management is totally different.

The conditioning of intervention effects on early adolescent alcohol use by maternal involvement and dopamine receptor D4 (DRD4) and serotonin transporter linked polymorphic region (5-HTTLPR) genetic variants.

Data drawn from the in-home subsample of the PROSPER intervention dissemination trial were used to investigate the moderation of intervention effects on underage alcohol use by maternal involvement and candidate genes. The primary gene examined was dopamine receptor D4 (DRD4). Variation in this gene and maternal involvement were hypothesized to moderate the influence of intervention status on alcohol use. The PROSPER data used were drawn from 28 communities randomly assigned to intervention or comparison conditions. Participating youth were assessed in five in-home interviews from sixth to ninth grades. A main effect of sixth-grade pretest maternal involvement on ninth-grade alcohol use was found. Neither intervention status nor DRD4 variation was unconditionally linked to ninth-grade drinking. However, moderation analyses revealed a significant three-way interaction among DRD4 status, maternal involvement, and intervention condition. Follow-up analyses revealed that prevention reduced drinking risk, but only for youth with at least one DRD4 seven-repeat allele who reported average or greater pretest levels of maternal involvement. To determine if this conditional pattern was limited to the DRD4 gene, we repeated analyses using the serotonin transporter linked polymorphic region site near the serotonin transporter gene. The results for this supplemental analysis revealed a significant three-way interaction similar but not identical to that found for DRD4.

Cesarean scar pregnancy and early placenta accreta share common histology.

OBJECTIVE: To determine, by evaluation of histological slides, images and descriptions of early (second-trimester) placenta accreta (EPA) and placental implantation in cases of Cesarean scar pregnancy (CSP), whether these are pathologically indistinguishable and whether they both represent different stages in the disease continuum leading to morbidly adherent placenta in the third trimester. METHODS: The database of a previously published review of CSP and EPA was used to identify articles with histopathological descriptions and electronic images for pathological review. When possible, microscopic slides and/or paraffin blocks were obtained from the original researchers. We also included from our own institutions cases of CSP and EPA for which pathology specimens were available. Two pathologists examined all the material independently and, blinded to each other's findings, provided a pathological diagnosis based on microscopic appearance. Interobserver agreement in diagnosis was determined. RESULTS: Forty articles were identified, which included 31 cases of CSP and 13 cases of EPA containing histopathological descriptions and/or images of the pathology. We additionally included six cases of CSP and eight cases of EPA from our own institutions, giving a total of 58 cases available for histological evaluation (37 CSP and 21 EPA) containing clear definitions of morbidly adherent placenta. In the 29 cases for which images/slides were available for histopathological evaluation, both pathologists attested to the various degrees of myometrial and/or scar tissue invasion by placental villi with scant or no intervening decidua, consistent with the classic definition of morbidly adherent placenta. Based on the reviewed material, cases with a diagnosis of EPA and those with a diagnosis of CSP showed identical histopathological features. Interobserver correlation was high (kappa = 0.93). CONCLUSIONS: EPA and placental implantation in CSP are histopathologically indistinguishable and may represent different stages in the disease continuum leading to morbidly adherent placenta in the third trimester.