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Background Thumb carpometacarpal (CMC) joint arthroplasty is a common procedure in the surgical management of symptomatic thumb basal joint arthritis. Following trapeziectomy, a number of suspensionplasty techniques are often used, but limited comparative evidence exists between these techniques. The central aim of this study was to prospectively compare the outcomes of 2 suspensionplasty techniques following trapeziectomy: suture button (TightRope) versus ligament reconstruction and tendon interposition (LRTI). Methods Prospective data were collected on 112 consecutive patients with Eaton stage III-IV thumb CMC arthritis who underwent open trapeziectomy and suspensionplasty. There were 53 LRTI and 59 TightRope suspensionplasty procedures. Outcomes were measured using the Quick Disabilities of the Arm, Shoulder, and Hand ( QuickDASH) questionnaire, Visual Analogue Scale (VAS) for pain, radiographic analysis, and lateral pinch strength. Patient demographic data and complications were also recorded. Results Patients undergoing TightRope suspensionplasty had significantly higher trapeziometacarpal index and thus less subsidence than the LRTI group at 2 weeks (0.22 vs 0.17 [ P < .0001]) and 3 months (0.17 vs 0.15 [ P < .05]) postoperatively. TightRope suspensionplasty also had a significantly lower QuickDASH score at 2 weeks (64.7 vs 74.6 [ P < .05]), 3 months (20.7 vs 32.5 [ P < .05]), and 1 year postoperatively (7.57 vs 21.5 [ P < .05]) compared with the LRTI group. However, there was no difference in VAS pain, lateral pinch strength, reoperation, or complications at any time point between groups. Conclusions Thumb CMC joint arthroplasty performed with a TightRope suspensionplasty versus LRTI yielded short-term improved resistance to subsidence, long-term greater improvement in clinical outcome by QuickDASH, and no difference in pain or complication rates.

Introduction Increasing abdominal pressures could affect pulmonary compliance and cardiac performance, a fact based on which the aim of the present study to detect the cardiopulmonary burden of multiple retractors application during supine versus lateral abdominal surgeries. We hypothesized that surgical ring multiple retractors application would affect the pulmonary and cardiac functions during both lateral and supine abdominal surgeries. Methods Prospective observational comparative study on forty surgical patients subdivided into two groups twenty each, comparing pulmonary compliance and cardiac performance before, during and after retractors application, group (S) supine position cystectomy surgery, and group (L) lateral position nephrectomy surgery under general anesthesia, Composite 1ry outcome; dynamic compliance C-dyn and cardiac index CI and Other outcome variables ICON cardio-meter were also recorded. Results C-dyn and C-stat were significantly decreased late during retractor application in lateral compared to supine surgery with significant decrease compared to basal values all over the surgical time. CI was significantly increased after retractor removal in both of the study groups compared to basal values. PAWP was significantly increased in -lateral compared to supine surgery -with significant increase compared to basal value all over the surgical time in both of the study groups. significant increase in DO2I compared to basal value during both supine and lateral positions. Conclusion Surgical retraction results in a short-lived significant decreases in lung compliance and cardiac output particularly during the lateral-kidney position than the supine position compliance.

Background Aging affects immunity, potentially altering fever response to infection. We assess effects of biological variables on basal temperature, and during COVID-19 infection, proposing an updated temperature threshold for older adults ≥65 years. Methods Participants were from 4 cohorts: 1 089 unaffected adult TwinsUK volunteers; 520 adults with emergency admission to a London hospital with RT-PCR confirmed SARS-CoV-2 infection; 757 adults with emergency admission to a Birmingham hospital with RT-PCR confirmed SARS-CoV-2 infection and 3 972 adult community-based COVID Symptom Study participants self-reporting a positive RT-PCR test. Heritability was assessed using saturated and univariate ACE models; mixed-effect and multivariable linear regression examined associations between temperature, age, sex, and body mass index (BMI); multivariable logistic regression examined associations between fever (≥37.8°C) and age; receiver operating characteristic (ROC) analysis was used to identify temperature threshold for adults ≥ 65 years. Results Among unaffected volunteers, lower BMI (p = .001), and increasing age (p < .001) was associated with lower basal temperature. Basal temperature showed a heritability of 47% (95% confidence interval 18%–57%). In COVID-19+ participants, increasing age was associated with lower temperatures in Birmingham and community-based cohorts (p < .001). For each additional year of age, participants were 1% less likely to demonstrate a fever ≥37.8°C (OR 0.99; p < .001). Combining healthy and COVID-19+ participants, a temperature of 37.4°C in adults ≥65 years had similar sensitivity and specificity to 37.8°C in adults Conclusions Aging affects temperature in health and acute infection, with significant heritability, indicating genetic factors contribute to temperature regulation. Our observations suggest a lower threshold (37.4°C/97.3°F) for identifying fever in older adults ≥65 years.

An 81-year-old man presented with chronic cough, which did not respond to the initiation of combined bronchodilator/inhaled corticosteroid therapy. CT of the chest revealed calcified nodules throughout the trachea sparing the posterior membrane, and tiny peripheral parenchymal nodules with basal interlobular septal thickening and calcification. Flexible bronchoscopy demonstrated endobronchial nodularity from the proximal trachea to the mid-sections of both main bronchi, sparing the posterior membrane. Histopathology revealed submucosal fibrous connective tissue and benign bone, confirming a diagnosis of tracheobronchopathia osteochondroplastica. CT was consistent with a concurrent diagnosis of dendriform pulmonary ossification. These two rare phenomena often present with non-specific symptoms, and the diagnosis can be made with imaging in both conditions. There is a role for bronchoscopy in the diagnosis of tracheobronchopathia osteochondropastica, and the endobronchial appearance could be diagnostic. The concurrence of both phenomena in our case might represent activity of a common cellular pathway of ossification in both sites.

Growth hormone (GH) is secreted by cells in the anterior pituitary on two time scales: discrete pulses over minutes that occur within a 24-hr pattern. Secretion reflects the balance of stimulatory and inhibitory inputs from the hypothalamus and is influenced by gonadal steroids, stress, nutrition, and sleep/wake states. We propose a novel approach for the analysis of GH data and use this approach to quantify (i) the timing, amplitude and the number of GH pulses and (ii) GH infusion, clearance and basal secretion (i.e., time invariant) rates, using serum GH sampled every 10 minutes during an 8-hour sleep study in 18 adolescents. In our method, we approximate hormonal secretory events by deconvolving GH data via a two-step coordinate descent approach. The first step utilizes a sparse-recovery approach to estimate the timing and amplitude of GH secretory events. The second step estimates physiological parameters. Our method identifies the timing and amplitude of GH pulses and system parameters from experimental and simulated data, with a median R^2 of 0.93, among experimental data. Recovering GH pulses and model parameters using this approach may improve the quantification of GH parameters under different physiological and pathological conditions and the design and monitoring of interventions.

Adenoid ameloblastoma with dentinoid is an uncommon benign odontogenic neoplasm, and its unicystic variant seems to be even rarer. A 34-year-old man was referred for evaluation of an asymptomatic swelling in the posterior maxilla. Intraoral examination showed an expansive lesion, soft to palpation, covered by a normal color mucosa. Cone-beam tomography revealed a well-defined unilocular hypodense tumor involving the left maxillary sinus. Histopathological examination of the surgically excised specimen showed a cystic tumor lined by an ameloblastic-like epithelium containing columnar basal cells with hyperchromatic and polarized nuclei. In some areas of the capsule, the tumor showed mural infiltration by sheets of cells containing central whirling structures. Dentinoid material was also observed in association with ameloblastic-like cells. The tumor was BRAF and KRAS wild-type. Collectively, these findings were consistent with the diagnosis of a unicystic variant of adenoid ameloblastoma with dentinoid.

The enzyme 17-β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) catalyzes the biosynthesis of testosterone from Δ4-androstenedione, and plays an important role in the final steps of androgen synthesis. 17β-HSD3 deficiency originates from mutations in the HSD17B gene, causing an autosomal recessive 46, XY sex developmental disorder (DSD). Patients with 46, XY karyotype can exhibit a wide phenotypic spectrum varying from complete external female genitalia to male genitalia with hypospadias. This study reports a case of 17β-HSD3 deficiency diagnosed in the infantile period who was later found to have a novel HSD17B3 gene variation. The 14-month old patient, who exhibited a female phenotype, presented with a bilateral lump in the inguinal area. Imaging revealed bilateral testicular gonads in the inguinal area. Hormonal evaluation showed low levels of basal and stimulated serum testosterone (T), a high level of androstenedione (A), and a low T/A ratio. Chromosomal analysis showed 46, XY karyotype. The patient's sequence analysis of the HSD17B3 gene revealed a c.673_1G>C homozygous class 2 (splice site) variation in intron 9. The father and mother were heterozygous carriers of the same variation. This variation has not been previously reported in the literature. In conclusion, a 46, XY DSD should be considered in patients with a female phenotype who exhibit gonad(s) in the inguinal area at an early age; in patients with insufficient testosterone synthesis and high levels of androstenedione, 17β-HSD3 should be considered, and molecular analysis should be done for a definitive diagnosis and subsequent genetic counseling.

Objective: The objective of this study was to investigate the effects of different degrees of maternal dietary energy restriction on lipid deposition in embryonic tissues during the medium laying period (37 to 39 weeks) in Arbor Acres (AA) broiler breeders.Methods: A single factor design was adopted, and 400 AA broiler breeders (20 weeks of age) with a similar weight were randomly allocated into four groups. The birds in the control group were fed a corn-soybean meal based diet, and those in trial groups were fed diets with 80%, 70%, and 50% energy levels of the basal diet. Incubated eggs from the medium laying period were collected. Samples of developing embryos at various stages were prepared for composition analysis.Results: The embryo weight in the 80% energy group was higher than those of the other groups on embryonic day (E) 13, but at 21 E, they were significantly decreased with decreasing energy intake of the broiler breeders (p

Background For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy. Objective To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy. Design, setting, and participants Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation. Outcome measurements and statistical analysis Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes. Results and limitations Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11–0.79) and UroC tumors (HR 0.37, 95% CI: 0.14–0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response. Conclusions Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC. Patient summary This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.

Anxiety disorders are highly prevalent among individuals with a history of prenatal alcohol exposure (PAE), and adolescent rodents demonstrate anxiety-like behavior following moderate PAE on Gestational Day (G) 12. A likely systemic target of PAE is the stress peptide corticotrophin-releasing factor (CRF), as activation of CRF receptor 1 (CRFR1) in the medial nucleus of the central amygdala (CeM) is known to increase anxiety-like behavior in adults. To determine if CRF-CRFR1 interactions underly PAE-induced anxiety, functional changes in CRF system activity were investigated in adolescent male and female Sprague Dawley rats following G12 PAE. Compared to air-exposed controls, PAE increased basal spontaneous (s) inhibitory post-synaptic current (IPSC) frequency in the CeM of males, but not females. Furthermore, PAE blunted CRFR1-regulated miniature (m) IPSCs in a sex- and dose-specific manner, and only PAE males demonstrated tonic CRFR1 activity in the CeM. It was further determined that G12 PAE decreased CRFR1 mRNA in the CeM of males while increasing regional expression in females. Finally, infusion of a CRFR1 agonist into the CeM of adolescents produced a blunted expression of CRFR1-induced anxiety-like behavior exclusively in PAE males, mirroring the blunted physiology demonstrated by PAE males. Cumulatively, these data suggest that CRFR1 function within the CeM is age- and sex-specific, and PAE not only increases the expression of anxiety-like behavior, but may reduce the efficacy of treatment for PAE-induced anxiety through CRFR1-associated mechanisms. Therefore, future research will be necessary to develop targeted treatment of anxiety disorders in individuals with a history of PAE.

As gender-affirming surgery is becoming more common, it is important for pathologists to recognize potential benign findings to avoid misinterpretation. Cervical transitional cell metaplasia and superficial clusters of small basophilic cells have been described in the context of gender-affirming testosterone therapy; these findings may be misdiagnosed as high-grade squamous intraepithelial lesions or endometrial cells on Pap smears. Prostatic metaplasia has been reported in the surface squamous epithelium of the vagina and the uterine cervix in individuals undergoing gender-affirming androgen therapy; this finding is often associated with NKX3.1-positive basal keratinocytes. The aim of this study was to assess the morphological and immunohistochemical features of the uterine cervix in gender-affirming hysterectomies in comparison with benign hysterectomies from cisgender women.We assessed the morphological and immunohistochemical features of the uterine cervix in 49 gender-affirming hysterectomies as compared with 57 hysterectomies from cisgender patients to establish the relative prevalences of surface prostatic metaplasia, NKX3.1-positive basal keratinocytes, transitional cell metaplasia, and small basophilic cells in the cervical squamous epithelium. The cervical tissue from the gender-affirming therapy cohort showed significantly higher prevalences of NKX3.1-positive basal keratinocytes (86% versus 1.8%), transitional cell metaplasia (80% versus 3.5%), superficial clusters of small basophilic cells (67% versus 7%), and surface prostatic metaplasia (43% versus 3.5%).NKX3.1-positive basal keratinocytes, transitional cell metaplasia, small basophilic cells and surface prostatic metaplasia are all more prevalent in the cervices of individuals receiving gender-affirming testosterone therapy; awareness of this fact allows pathologists to avoid the overdiagnosis of dysplasia or the recommendation of unnecessary follow-up procedures.

Papillary thyroid cancer (PTC) is extremely rare in children. Herein, we present a case diagnosed with PTC at 15 months of age. We conducted a literature review of the published cases with PTC under five years of age. A 1.25-year-old male patient had initially presented with a complaint of progressively enlarging cervical mass that appeared four months earlier. On physical examination, a mass located in the anterior cervical region with the largest measurements of around 3x3 cm was detected. Cervical and thyroid ultrasonography showed a 50x27 mm solid mass in the right lateral neck. Excisional biopsy revealed a follicular variant of PTC with capsular invasion. Subsequently, he underwent a complementary total thyroidectomy. He was diagnosed with intermediate-risk (T3N0M0) PTC. He developed permanent hypoparathyroidism. In the first year of the operation, he was treated with radioiodine ablation (RAI) since basal and stimulated thyroglobulin (Tg) levels tended to increase. Whole-body scintigraphy was normal in the first year of RAI ablation. On levothyroxine sodium (LT4) treatment, levels of thyroid stimulating hormone (TSH) and Tg were adequately suppressed. He is now 8.5-years-old and disease-free on LT4 replacement therapy for seven years and three months. Pediatric PTC has different biological behavior and an excellent prognosis compared to adults. The optimal treatment strategy for pediatric TC is total thyroidectomy, followed by RAI ablation. Post-operative management should include regular follow-up, TSH suppression by adequate LT4 therapy, serial Tg evaluation, and radioiodine scanning when indicated.

Background COVID-19 infection is known to cause a wide array of clinical chronic sequelae, but little is known regarding the long-term cardiac complications. We aim to report echocardiographic follow-up findings and describe the changes in left (LV) and right ventricular (RV) function that occur following acute infection. Methods Patients enrolled in the World Alliance Societies of Echocardiography-COVID study with acute COVID-19 infection were asked to return for a follow-up transthoracic echocardiogram. Overall, 198 returned at a mean of 129 days of follow-up, of which 153 had paired baseline and follow-up images that were analyzable, including LV volumes, ejection fraction (LVEF), and longitudinal strain (LVLS). Right-sided echocardiographic parameters included RV global longitudinal strain, RV free wall strain, and RV basal diameter. Paired echocardiographic parameters at baseline and follow-up were compared for the entire cohort and for subgroups based on the baseline LV and RV function. Results For the entire cohort, echocardiographic markers of LV and RV function at follow-up were not significantly different from baseline (all P > .05). Patients with hyperdynamic LVEF at baseline (>70%), had a significant reduction of LVEF at follow-up (74.3% ± 3.1% vs 64.4% ± 8.1%, P < .001), while patients with reduced LVEF at baseline (−20%) at baseline had significant improvement at follow-up (−15.2% ± 3.4% vs −17.4% ± 4.9%, P = .004). Patients with abnormal RV basal diameter (>4.5 cm) at baseline had significant improvement at follow-up (4.9 ± 0.7 cm vs 4.6 ± 0.6 cm, P = .019). Conclusions Overall, there were no significant changes over time in the LV and RV function of patients recovering from COVID-19 infection. However, differences were observed according to baseline LV and RV function, which may reflect recovery from the acute myocardial injury occurring in the acutely ill. Left ventricular and RV function tends to improve in those with impaired baseline function, while it tends to decrease in those with hyperdynamic LV or normal RV function.

With the increasing practice of gender-affirming mastectomy as a therapeutic procedure in the setting of gender dysphoria, there has come a profusion of literature on the pathologic findings within these specimens. Findings reported in over 1500 patients have not included either prostatic metaplasia or pilar metaplasia of breast epithelium. We encountered both of these findings in the course of routine surgical pathology practice and therefore aimed to analyze these index cases together with a retrospective cohort to determine the prevalence, anatomic distribution, pathologic features, and associated clinical findings of prostatic metaplasia and pilar metaplasia in the setting of gender-affirming mastectomy. In addition to the 2 index cases, 20 additional archival gender-affirming mastectomy specimens were studied. Before mastectomies, all but 1 patient received testosterone cypionate, 6/22 patients received norethindrone, and 21/22 practiced breast binding. Prostatic metaplasia, characterized by glandular proliferation along the basal layer of epithelium in breast ducts, and in one case, within lobules, was seen in 18/22 specimens; 4/22 showed pilar metaplasia, consisting of hair shafts located within breast ducts, associated with squamoid metaplasia resembling hair matriceal differentiation. By immunohistochemistry, prostatic metaplasia was positive for PSA in 16/20 cases and positive for NKX3.1 in 15/20 cases. Forty-three reduction mammoplasty control cases showed no pilar metaplasia and no definite prostatic metaplasia, with no PSA and NKX3.1 staining observed. We demonstrate that prostatic metaplasia and pilar metaplasia are strikingly common findings in specimens from female-assigned-at-birth transgender patients undergoing gender-affirming mastectomy. Awareness of these novel entities in the breast is important, to distinguish them from other breast epithelial proliferations and to facilitate accrual of follow-up data for better understanding their natural history.

A common clinical phenotype of several neurodegenerative and systemic disorders including Alzheimer’s disease and atherosclerosis is the abnormal accumulation of extracellular material, which interferes with routine cellular functions. Similarly, patients with age-related macular degeneration (AMD), the leading cause of vision loss among the aged population, present with extracellular lipid- and protein-filled basal deposits in the back of the eye. While the exact mechanism of growth and formation of these deposits is poorly understood, much has been learned from investigating their composition, providing critical insights into AMD pathogenesis, prevention, and therapeutics. We identified human osteopontin (OPN), a phosphoprotein expressed in a variety of tissues in the body, as a newly discovered component of basal deposits in AMD patients, with a distinctive punctate staining pattern. OPN expression within these lesions, which are associated with AMD disease progression, were found to co-localize with abnormal calcium deposition. Additionally, OPN puncta colocalized with an AMD risk-associated complement pathway protein, but not with apolipoprotein E or vitronectin, two other well-established basal deposit components. Mechanistically, we found that retinal pigment epithelial cells, cells vulnerable in AMD, will secrete OPN into the extracellular space, under oxidative stress conditions, supporting OPN biosynthesis locally within the outer retina. Finally, we report that OPN levels in plasma of aged (non-AMD) human donors were significantly higher than levels in young (non-AMD) donors, but were not significantly different from donors with the different clinical subtypes of AMD. Collectively, our study defines the expression pattern of OPN in the posterior pole as a function of disease, and its local expression as a potential histopathologic biomarker of AMD.

Spontaneous recovery after a stroke accounts for a major part of the neurological recovery in patients. However limited, the spontaneous recovery is mechanistically driven by axonal restorative processes for which several molecular cues have been previously described. We report the acceleration of spontaneous recovery in a preclinical model of ischemia/reperfusion in rats via a single intracerebroventricular administration of extracellular vesicles released from primary cortical astrocytes. We used MRI, confocal and multiphoton microscopy to correlate the structural remodeling of the corpus callosum and striatocortical circuits with neurological performance over 21 days. We also evaluated the functionality of the corpus callosum by repetitive recordings of compound action potentials to show that the recovery facilitated by astrocytic extracellular vesicles was both anatomical and functional. Our data provide compelling evidence that astrocytes can hasten the basal recovery that naturally occurs post-stroke through the release of cellular mediators contained in extracellular vesicles.

We have studied morphofunctional state of esophageal mucosa in 57 patients with gastroesophageal reflux disease (GERD) with normal (body mass index (BMI) — 18.5–24.9 kg/m2) and excessive (BMI over 25 kg/m2) body weight. A histologic and morphometric study of esophageal mucosa, immunohistochemical analysis of the expression of apoptosis marker CD95 and inflammatory marker cyclooxygenase-2 (COX-2) were carried out. In reflux esophagitis, most characteristic are changes in multilayered epithelium — hyperkeratosis, parakeratosis, proliferation of basal cells and acanthosis. At that, significant differences in morphometric characteristics of patients with normal BMI and overweight were not found. The development of reflux esophagitis was associated with violations of pro-apoptotic ability of esophageal mucosa cells and increased expression of COX-2, most significant in patients with high BMI. Detected disorders may determine the mechanisms of complicated course of GERD in these patients.

We describe a rare case of newly discovered pulmonary metastases and surgical confirmation 12 years after initial surgery for a pheochromocytoma. A 61-year-old asymptomatic man was referred because of an abnormal shadow in the right lung field upon chest radiography. Computed tomography (CT) showed two well-demarcated tumors in the basal segment of the right lung. Twelve years previously, he underwent right adrenalectomy and was pathologically diagnosed as having a benign pheochromocytoma. Thereafter, he received a medical check-up annually. To confirm the diagnosis of two pulmonary tumors, video-assisted thoracic surgery was done and wedge resection of the right lower lobe completed. Pathology studies revealed these tumors as pulmonary metastases from the pheochromocytoma, which indicated that the true diagnosis was a malignant pheochromocytoma. Patients with a benign pheochromocytoma should continue to undergo careful monitoring for a long time after the initial surgical procedure. Thoracic surgeons should be aware of the possibility of pulmonary metastases even if >10 years have passed since initial resection of a benign pheochromocytoma.

Background: Breast cancer is a collection of diseases defined by distinct pathological (e.g., ductal, lobular, mucinous) and molecular characteristics (e.g., ER and PR, HER2 amplification, and more recently transcriptome-based classifications such as luminal and basal cancers). Molecular subtyping is beneficial for the diagnosis and individualized treatment of breast cancer.MRI is a supplemental technique to mammography and ultrasonography for the evaluation of breast lesions and to predict molecular subtypes of breast cancer. Studies have highlighted the value of DCE-MRI in reflecting the anatomic and functional properties of tumors and facilitating treatment. Objectives: The aim of this work was to assess the utility of MRI as an accurate method for detection of molecular subtypes of breast cancer. Patients and Methods: a retrospective clinical study of 2-years enrollment duration. The study was conducted at Radiology Department, Assuit University Hospitals on 50 lesions, patient age ranging from 23 to 66 years old with mean age was (46.9 ± SD) years. MR imaging studies were performed using a 1.5 T Magnetom Vision scanner with dedicated bilateral phased-array breast coil (Siemens, Erlangen, Germany). MRI sequences were 1. Axial T1WI. 2. Axial T2WI. 3. Axial STIR. 4. Axial DWI and ADC. 5. DCE-MRI. Results: The study included 50 lesions; 21 lesions were Luminal A, 15 lesions were Luminal B, 10 lesions were HER2+, and 4 lesions were TN. Histopathology 39 lesions were IDC-NOS, 1 lesion was IDC (medullary type), 7 lesions were mixed pathology IDC + DCIS, and 3 lesions were ILC. As regard the correlation between the histopathological type and grade, both were specific in differentiation between the molecular subtypes. According to the MRI findings it was found that T2 Intratumoral signal intensity, STIR, and the margin of the lesion were highly specific in differentiation, both L.N status and number were found that they were highly specific in differentiation (p

Patients with idiopathic nonischemic cardiomyopathy (NICM) and near-normal left ventricular ejection fraction (LVEF) may develop ventricular tachycardia (VT).The purpose of this study was to describe procedural characteristics and outcomes in patients requiring ablation for NICM-related VT with near-normal LVEF compared to impaired LVEF.Over 8 years, 77 consecutive patients with NICM-related VT underwent catheter ablation. Of these patients, 47 had idiopathic NICM (20 near-normal LVEF, 27 impaired LVEF). Procedural characteristics and outcomes were compared.Mean age was 64 ± 12years, mean LVEF was 40% ± 14%, and 75% were male. In the near-normal LVEF group compared to the impaired LVEF group, LVEF was higher (54% ± 5% vs 30 ± 8%; P .001), scar was predominantly located in the perivalvular left ventricle (LV) and basal septum (15/20 [75%]), was smaller in size [bipolar: 9.7 (6.2-32.4) cmIdiopathic NICM-related VT with near-normal LVEF was associated with discrete areas of arrhythmogenic, predominantly intramural, scar in the perivalvular LV and basal septum. Despite smaller scar, patients required similar ablation amounts and experienced comparable long-term outcomes compared to patients with idiopathic NICM-related VT and impaired LVEF. These findings underscore the "three-dimensionality" of substrate, whereby the intramural basal septum forms the third dimension and impacts ablation outcomes.

The increased detection and treatment of early stage breast cancer as well as ductal carcinoma in situ (DCIS) has not led to significant survival benefits. Therefore, the current standard treatment of DCIS is questionable. An informed evidence-based treatment strategy, and likely de-escalation from the current standards requires new prognostic models built from more comprehensive characterization with objective criteria. Parallel profiling of the molecular landscape and micro-environment in pure DCIS remains challenging due to histological heterogeneity and the inevitable reliance on small archived specimens. Leveraging recent methodological advances, we characterized the mutational, transcriptional, histological and microenvironmental landscape across multiple micro-dissected regions from 39 cases to generate a multi-modal breast precancer atlas. The histological architecture was associated with grade, adiposity, and intrinsic expression subtypes. Similar to previous findings, high-grade lesions had higher mutational burden, including TP53 mutations, while low-grade lesions had more frequent 16q losses and GATA3 mutations. Multi-region analysis revealed most somatic alterations, including whole genome duplication events, were clonal, but genetic divergence increased with distance between regions. In 7/12 evaluable cases, somatic mutations in putative driver genes affected a subset of regions only. This genetic heterogeneity often accompanied phenotypic heterogeneity and regions with low risk features (Normal-like, Luminal A) occurred earlier than those with high-risk features (Her2-like, Basal or necrosis) according to the phylogenetic analysis. The immune-environment was evaluated using multiplex immuno-histochemistry to measure relative stromal and epithelial densities of B lymphocyte (B-cell), T lymphocyte (T-cell) and regulatory T cells (T-reg) and identify 3 immune-states: Active, Suppressed and Excluded (lower epithelial density). All states included both DCIS and adjacent benign regions, and none associated with intrinsic subtypes. The Excluded state was enriched in high-grade DCIS and, compared to benign areas, more likely acquired in DCIS, showing transcriptional evidence of stronger immune-suppression and possible evasion. The breast pre-cancer atlas therefore reveals correlated levels of phenotypic and genotypic heterogeneity, including at sub-histological resolution. These uniquely integrated observations will help scope future studies, prioritize candidate markers for progression risk modelling and identify functional similarities in precursor lesions from other types of adenocarcinomas.

Propionic acidemia (PA) is a severe autosomal recessive metabolic disease caused by deficiency of propionyl-CoA carboxylase (PCC). We studied PA transgenic (Pat) mice that lack endogenous PCC but express a hypoactive human PCCA cDNA, permitting their survival. Pat cohorts followed from 3 to 20 weeks of age showed growth failure and lethal crises of lethargy and hyperammonemia, commoner in males (27/50, 54%) than in females (11/52, 21%) and occurring mainly in Pat mice with the most severe growth deficiency. Groups of Pat mice were studied under basal conditions (P-Ba mice) and during acute crises (P-Ac). Plasma acylcarnitines in P-Ba mice, compared to controls, showed markedly elevated C3- and low C2-carnitine, with a further decrease in C2-carnitine in P-Ac mice. These clinical and biochemical findings resemble those of human PA patients. Liver acyl-CoA measurements showed that propionyl-CoA was a minor species in controls (propionyl-CoA/acetyl-CoA ratio, 0.09). In contrast, in P-Ba liver the ratio was 1.4 and in P-Ac liver, 13, with concurrent reductions of the levels of acetyl-CoA and other acyl-CoAs. Plasma ammonia levels in control, P-Ba and P-Ac mice were 109 ± 10, 311 ± 48 and 551 ± 61 μmol/L respectively. Four-week administration to Pat mice, of carglumate (N-carbamyl-L-glutamic acid), an analogue of N-carbamylglutamate, the product of the only acyl-CoA-requiring reaction directly related to the urea cycle, was associated with increased food consumption, improved growth and absence of fatal crises. Pat mice showed many similarities to human PA patients and provide a useful model for studying tissue pathophysiology and treatment outcomes.

Diagnosis of salivary gland neoplasms can be challenging for surgical pathologists due to low incidence of tumors as well as overlapping histologic features. On small biopsy, the most important information to be conveyed for clinical management is the distinction between a benign/low grade tumor and a high grade carcinoma. This review will discuss the differential diagnosis of salivary gland tumors based on four broad morphologic patterns: basaloid/tubular/cribriform, (micro)cystic/secretory/mucinous, solid-nested/clear-spindled, and oncocytic/oncocytoid. With the assistance of immunohistochemistry, demonstration of the number of cell types (mainly epithelial versus myoepithelial/basal) can further subclassify tumors within these morphologic categories. Additional tumor-specific immunomarkers are useful in some cases. Underlying tumor-specific genetic anomalies can be of value, however, immunohistochemical correlates are only available for some. When used judiciously, in the correct morphologic context, and with knowledge of their limitations, immunohistochemical stains can aid in differentiating tumors with similar morphology.

Objectives In this study, we aimed to investigate the correlation between SUVmax of primary tumor and prognostic factors/molecular subtype in ductal breast cancer patients. Materials and methods We retrospectively reviewed 150 female patients with pathologically proven invasive ductal breast cancer from January 2015 to October 2019 who underwent 18F-FDG PET/CT for initial staging. Histopathological prognostic features of the primary tumor (histological grade, hormone receptor status, Ki-67 index, vb.) were obtained from the tru-cut biopsy report. In 18F-FDG PET/CT studies, the maximum standardized uptake value (SUVmax) of the primary breast tumor was calculated and compared with the presence of axillary lymphadenopathy and/or distant metastases, histopathological prognostic factors and molecular subtype. Results The high SUVmax of primary breast tumors is significantly correlated with the clinicopathological factors: high tumor size, high histologic grade, high Ki-67 index, axillary lymph node positivity and distant metastasis. SUVmax value was significantly higher in patients with basal subtype than patients with Luminal A subtype (8,14 ± 3,71 and 4,64 ± 2,45, p = 0,002). Correlation analysis revealed a low correlation between Ki-67 index and SUVmax (r = 0,276, p = 0,001) and moderate correlation between tumor size and SUVmax (r = 0,470, p = 0,001). In multivariate linear regression analysis, Ki-67 index and tumor size had a statistically significant effect on SUVmax values. As these parameters increase, it is seen that it increases SUVmax values (p = 0,004, Std Beta: 0,228, 95% CI:0,010–0,055 and p = 0,001, Std Beta:0,374, 95% CI:0,55–0,136, respectively). Conclusion High SUVmax value is associated with factors suggesting poor prognosis. Pretreatment 18F-FDG PET/CT can be used as a tool to predict prognosis in breast cancer.

Objectives To evaluate the treatment outcomes and patient satisfaction following the use of fixed, immediately loaded, basal implant- reconstructive prostheses in a cohort of patients who underwent marginal mandibulectomy. Methods Ninety-seven Basal Cortical Screw implants (BCS®1; Dr. Ihde Dental AG, Gommiswald, Switzerland) were inserted in 15 marginal mandibulectomy patients. Clinical, radiographic, and prosthetic parameters, as well as patient satisfaction, were evaluated at 1 week and 3, 6, 9, 12, 18, 24, 36, 48, and 60- months after implant insertion. Clinical evaluations included measurement of the plaque (PI) and modified gingival indices (MGI), and the probable pocket depth (PPD). Implant survival and implant success were assessed using the James–Misch implant health quality scale and the Albrektsson criteria for implant success. Results The implants showed optimum health with 100 % survival and success rates. None of the implants were mobile, lost, or fractured. There was a non-significant increase in the PI at 3, 6, 9, 12, 18 months, a significant difference at 24, 36, 48, 60-months follow-up visits, and a significant decrease in the MGI and PPD. Radiographic findings showed an increase in bone‒implant contact and peri-implant bone level. Evaluation of the prostheses revealed some manageable complications. All patients were satisfied and reported that they would choose the same treatment modality again. Conclusions Basal implant- reconstructive prostheses provide optimum clinical and radiographic success, with 100 % implant survival and success rates, and patient satisfaction in marginal mandibulectomy cases.

Background Although remission is a priority target in psychosis, reported rates show a marked variation across studies and instability over time. Such variability, partly due to methodology, emphasizes the need to define the optimal assessment procedure, as well as to identify reliable predictors. This study aims to: 1. longitudinally compare remission status according to different criteria; 2. identify predictors of duration and stability. Methods 112 patients with schizophrenia or schizoaffective disorder underwent comprehensive clinical evaluations, with 24-month follow-up. Remission was assessed using three criteria: Remission in Schizophrenia Working Group (RSWG) vs Positive and Negative Syndrome Scale (PANSS) positive and negative scales (PANSS-PN) vs total score (PANSS-T). Kaplan-Meier survival analysis was used for longitudinal comparison, regression models to identify predictors of duration and stability. Results At enrolment 50% of patients were in remission according to RSWG, while only 23.2% reached the other criteria. PANSS-T cumulative remission rates showed the greatest stability. Stable remission according to RSWG criteria was predicted by negative symptoms, while no significant predictors emerged for PANSS-T. Remission duration was predicted by negative, positive and cognitive symptoms and treatment dosage for RSWG criteria, while for PANSS-T the predictors were cognitive symptoms and duration of illness. Conclusion Results are in line with previous literature on remission rates and further support the role of basal clinical predictors. In addition, this study shows that more stringent criteria are more stable over time, suggesting their predictive value and the relevance of their use to optimize evaluations also in clinical settings.

This research was conducted with the aim of evaluating the effect of wheatgrass, which contains chlorophyll and a high percentage of antioxidants such as Vitamin C and selenium in addition to some minerals such as calcium, iron, and magnesium on the biological efficiency and the immune system in white rats. In the present study, 40 rats were divided into 8 groups, each of 5 rats, and it was divided into two experiments I and II with each trial four groups. In Experiment I, 5 rats were fed the basic meal and were used as a negative control group. The other 15 rats are divided into 3 sub-groups (1, 2 and 3) each fed on the main meal plus wheatgrass at rates of 100,150, and 200 mg, respectively, and then a method of suppressing the immune system was performed at the end of the trial period. In experiment II, animals were immune suppressed by stress treatment as done in experiment I then divided into 4 groups (5 rats each). The first group was served as positive control [Co. (+) ] and fed basal diet only, while the other three groups (4, 5 and 6 ) were served as experimental groups and were fed basal diet and wheatgrass (100, 150 and 200mg). All groups recorded stability in weight at the beginning and at the end of the experiment and in their acquired increase in their weight gained, food efficiency, intake of food as compared to the control negative group, while groups 4, 5 and 6 had the lowest average rate of food intake compared to the positive control. All groups were found to have no change in the relative weight of their spleen and liver. All the experimental groups recorded no change in the percentage of hemoglobin, red blood cells and hematocrit compared to the control group. Also, they showed a decrease in the MCV rate and MCH compared to the control groups. All groups recorded no change in the rate of MCHC and an increase in the rate of RDW% compared to the control. Groups 1, 2 and 3 showed a significant decrease in urea and uric acid compared to the control group. While groups 4, 5 and 6 showed a significant increase in urea compared to the control group. All the experimental groups showed an increase in the level of creatinine compared to the control group.

Background Although isolated cardiac sarcoidosis (CS) is not uncommon, little is known about the prognosis. We aimed to clarify clinical features and clinical outcomes in patients with isolated CS. Methods Two-hundred eighty-six patients with suspected CS were enrolled. Systemic CS (SCS) was diagnosed by histological or clinical confirmation of sarcoidosis according to the guidelines. Isolated CS was diagnosed by histological or clinical confirmation in the heart alone. The endpoint was cardiac death, hospitalization for heart failure, or fatal ventricular arrhythmia. Results Twenty-one patients were diagnosed with isolated CS, and 63 were diagnosed with SCS. The frequencies of diagnostic criteria, such as high-grade atrioventricular block or fatal ventricular arrhythmia, basal thinning of the ventricular septum, left ventricular contractile dysfunction, positive myocardial uptake of gallium-67 citrate scintigraphy or fluorine-18 fluorodeoxyglucose positron emission tomography, and delayed contrast enhancement of cardiac magnetic resonance, were higher or equivalent in patients with isolated CS, compared to those with SCS. Over a median follow-up of 31 months (range: 1–175 months), cardiac death, hospitalization for heart failure, or fatal ventricular arrhythmia occurred in 14 (67%) patients with isolated CS, 24 (38%) patients with SCS, and 63 (31%) patients without CS. The rate of cardiac events was higher in patients with isolated CS (log-rank test, p = 0.01). Cox proportional hazard analysis showed that isolated CS, age, and New York Heart Association functional class were independently associated with cardiac events. Conclusions Patients with isolated CS have clinical features compatible with SCS, and have cardiac events at a higher rate.

The investigational trials were conducted on day-old, total ninety chicks of broilers and indigenous (IND) poultry breeds in controlled conditions to analyze some hematological parameters. Water and basal diet were provided ad libitum. The experiment was carried out for 20 weeks. A total of 40 blood samples 20 for each breed were collected in a randomized manner through a brachial cut at the end of the trial. Hematological parameters, i.e., RBCs (106/μl), WBCs (103/μL), Lymphocytes (103/μL), Monocytes (103/μL), PLTs (103/μL), Hb (g/dL), Ht (%), MCV (fL), MCH (pg), and MCHC (g/dL) were analyzed. Two-tailed Student t-test was applied to compare the means (p 0.05) noted in both breeds in Ht, MCV, MCH, and MCHC parameters.

Objectives This study sought to describe the electrophysiologic characteristics, diagnostic maneuvers, and treatment of a series of arrhythmias using concealed nodoventricular (cNV) or His-ventricular (cHV) pathways. Background Confirming the presence and participation of cNV or cHV pathways in tachyarrhythmias is challenging. Methods We present 4 cases of tachycardias with a participatory cNV or cHV pathway. Results The first patient had a narrow complex tachycardia with ventriculoatrial dissociation. Findings of an entrainment pacing from the right ventricle and fused premature ventricular complexes suggested cNV pathway involvement. The second patient had nonsustained narrow complex tachycardia with more ventricular than atrial complexes. The tachycardia exhibited an anterograde His-right bundle (RB) activation sequence and normal His-ventricular (HV) interval and consistently terminated with fused ventricular extra stimuli, suggesting cNV pathway participation. The third patient had a wide complex tachycardia (WCT) with either a right or left bundle branch block pattern. The WCT showed an eccentric His-RB activation sequence and short HV interval and terminated with fused premature ventricular complexes, suggesting a cHV (or concealed fasciculoventricular) pathway involvement. The fourth patient had a WCT with alternating bundle branch block morphologies with a short HV interval. Entrainment from the basal right ventricle demonstrated fusion and a short postpacing interval, suggesting cHV (or fasciculoventricular) pathway involvement. Ablation at the proximal RB rendered the tachycardia noninducible. Conclusions A structured approach can help diagnose and treat cNV or cHV pathways. We emphasize the importance of evaluating both the His-RB activation pattern and HV interval during sinus rhythm and tachycardia as well as the ventricular pacing study.

Objective To evaluate whether or not embryo transfer day has an effect on the rates of clinical pregnancy (CPR) and live birth (LBR) in in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) treatment. Material and Methods A total of 757 patients who had undergone IVF-ICSI treatment between 2012 and 2017 were included in this study. The participants were stratified according to embryo transfer day as Group 1 (day 2 transfer; n= 43), Group 2 (day 3 transfer; n=633), and Group 3 (day 5 (blastocyst) transfer; n=81). Basal parameters and IVF-ICSI outcomes were compared between the groups. Results Groups 1 and 2 patients were older, had a higher BMI, worse responder rate, lower antral follicle count, lower peak E2 levels, and less endometrial thickness, and required an increased total gonadotropin dose than the other transfer day groups. In addition, the number of oocytes and MII oocytes, fertilization rate, and 2 PN were statistically different between the groups and the CPR (19.5% vs 36.9% vs 39.0%, respectively) and LBR (14.6% vs 30.4% vs 35.1%, respectively) were lower in group 1 than groups 2 and 3 (p

Aims To distinguish between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM) using cardiac magnetic resonance feature tracking (CMR‐FT) left ventricle (LV) diastolic time–strain curve patterns and myocardial strain. Methods and Results A total of 32 CP patients, 27 RCM patients, and 25 control subjects were examined by CMR‐FT and analysed for global strain, segmental strain, and LV time–strain curve patterns in the longitudinal, circumferential, and radial directions. Speckle tracking echocardiography (STE) strain imaging was performed in some cases. The peak global longitudinal strain (GLS) and global circumferential strain (GCS) of the RCM group were lower than those of the CP group. GLS [median (interquartile range) CP vs. RCM: −11.15 (−12.85, −9.35) vs. −6.5 (−8.75, −4.85), P

Hymenoptera venom anaphylaxis is the most frequent cause of anaphylaxis and responsible for about 20% of all fatal anaphylaxis cases in adults. We report two cases of fatal hymenoptera venom anaphylaxis with undiagnosed underlying mastocytosis and review the risk factors for severe or fatal hymenoptera venom anaphylaxis, as well as the specificities of its association with mastocytosis. As hymenoptera venom allergic patients with underlying clonal mast cell disorder generally lack typical skin lesions of mastocytosis, its diagnosis can easily be missed, underscoring the importance and need for diagnostic strategies in order to correctly identify these patients. Predominant cardiovascular symptoms in the absence of urticaria or angioedema following an insect sting are suggestive of underlying clonal mast cell disorder, and should be distinguished from panic attack or vasovagal syncope. Similarly, an unexplained syncope or an "idiopathic" anaphylaxis might reveal mastocytosis or hereditary alpha-tryptasemia. Acute and basal serum tryptase measurements should always be integrated in the diagnostic work-up of an insect sting reaction or unexplained syncope or shock of any origin.

Rigid barriers are prevalent structure countermeasures for mitigating granular flow hazards in mountainous areas. To reduce maintenance for barriers, a basal clearance is commonly set between the base of the barrier and the channel base. A rational design of the clearance is still an important and open issue. In this study, the interactions between a dry granular flow and rigid barriers with different basal clearances are investigated through discrete element modeling of flume tests. The numerical model is firstly validated by comparing the numerical results with the experimental data reported in the literature. This model is further employed to evaluate the influence of basal clearance and slope angle on the flow–barrier interactions. The ratio between the clearance size and particle diameter is varied from 0 to 4, and the slope angle is varied from 15 to 40°. Based on the numerical results, the value of the clearance size that causes clogging of the clearance is identified. The influences of basal clearance and slope angle on the outflow rate, energy-breaking efficiency, and retention efficiency are quantified. The obtained results can provide some insights into the design of basal clearance for a rigid barrier.

Objective: To analyze the effects of neuromuscular electrical stimulation of the femoral quadriceps associated or not with whey protein supplementation on the electromyographic activity and body mass distribution in volunteers undergoing anterior cruciate ligament reconstruction. Methods: 24 volunteers were randomly divided into three groups: basal control, whey protein in association with neuromuscular electrical stimulation, and neuromuscular electrical stimulation alone. Results: In the postoperative evaluation, during the mini squat, the basal group showed a decrease in the electromyographic activity of the vastus medialis (p = 0.005, eyes open; p = 0.003, eyes closed), vastus lateralis (p = 0.005, eyes open; p = 0.020; eyes closed) and rectus femoris (p = 0.075, eyes open; p = 0.074, eyes closed) and of body mass distribution in the injured limb (p < 0.001, eyes open; p < 0.001, eyes closed), and in the healthy limb (p < 0.001, eyes open; p < 0.001, eyes closed). Conclusion: The early use of neuromuscular electrical stimulation of the quadriceps femoris maintained the electromyographic activity of the vastus medialis and vastus lateralis muscles and prevented asymmetries in body mass distribution 15 days after anterior cruciate ligament reconstruction. Level of Evidence I, High quality randomized trial. RESUMO Objetivo: Analisar os efeitos da estimulação elétrica neuromuscular do quadríceps femoral associado ou não à suplementação com whey protein na atividade eletromiográfica e distribuição de massa corporal em voluntários submetidos à reconstrução do ligamento cruzado anterior. Métodos: 24 voluntários foram divididos em três grupos: controle basal, whey protein associado com estimulação elétrica neuromuscular e estimulação elétrica neuromuscular isolada. Resultados: Na avaliação pós-operatória, durante o miniagachamento, o grupo controle basal demonstrou diminuição da atividade eletromiográfica do vasto medial (p = 0,005, olhos abertos; p = 0,003, olhos fechados), vasto lateral (p = 0,005, olhos abertos; p = 0,020, olhos fechados) e reto femoral (p = 0,075, olhos abertos; p = 0,074, olhos fechados) e da distribuição de massa corporal no membro operado (p < 0,001, olhos abertos; p < 0,001, olhos fechados) e membro lesionado (p < 0,001, olhos abertos; p < 0,001, olhos fechados). Conclusão: O uso precoce de estimulação elétrica neuromuscular do quadríceps femoral, independentemente do uso de whey protein, foi eficaz para manter a atividade eletromiográfica dos músculos vasto medial e vasto lateral, e prevenir assimetrias na distribuição de massa corporal 15 dias após a reconstrução do ligamento cruzado anterior. Nível de Evidência I, Ensaio randomizado de alta qualidade.

Recent evidence shows a greater facilitating effect of beta-adrenergic receptors (β-ARs) on long-term synaptic plasticity in the ventral versus the dorsal hippocampus. Here, using field potentials from the CA1 area and a ten-pulse stimulation train of varying frequency we show that activation of β-ARs by isoproterenol preferentially facilitates the output from the dorsal hippocampus at the frequency range of 3–40 Hz without affecting short-term synaptic plasticity. Furthermore, isoproterenol increases basal synaptic transmission in the dorsal hippocampus only and enhances basal neuronal excitation more in the dorsal than the ventral hippocampus. These results suggest that β-AR-modulation of short-term neuronal dynamics differs along the longitudinal axis of the hippocampus, thereby contributing to functional specialization along the same axis., Highlights • We studied the effects of isoproterenol (ISO) in dorsal (DH) and ventral (VH) hippocampus. • ISO increased synaptic transmission and population spike more in DH than VH. • ISO modulated short-term changes of population spike in the dorsal hippocampus only. • ISO did not affect short-term changes of synaptic transmission in DH or VH. • β adrenergic receptors modulate short-term changes in excitation in DH only.

Objective To describe our current understanding of hereditary α-tryptasemia (HαT), how HαT fits into the evolutionary context of tryptases and contemporary framework of mast cell–associated disorders, and to discuss the future clinical and therapeutic landscape for symptomatic individuals with HαT. Data Sources Primary peer-reviewed literature. Study Selections Basic, clinical, and translational studies describing tryptase gene composition, generation, secretion, and elevation and the associated clinical impacts of HαT and treatment of such individuals were reviewed. Results HαT is a common autosomal dominant genetic trait caused by increased TPSAB1 copy number encoding α-tryptase. Approximately 1 in 20 White individuals have HαT, making it by far the most common cause for elevated basal serum tryptase levels. Although many individuals with HαT may not manifest associated symptoms, the prevalence of HαT is increased in patients with clonal and nonclonal mast cell–associated disorders wherein it is linked to more prevalent and/or severe anaphylaxis and increased mast cell mediator-associated symptoms. Increased generation of mature α/β-tryptase heterotetramers, and their unique physiochemical properties, may be responsible for some of these clinical findings. Conclusion HαT is a common modifier of mast cell–associated disorders and reactions. Nevertheless, whether HαT may be an independent cause of clinical phenotypes with which it has been associated remains unproven. Correct identification of HαT is critical to accurate interpretation of serum tryptase levels in the clinical evaluation of patients. Beyond HαT, we foresee tryptase genotyping as an important parameter in the standard workup of patients with mast cell–associated disorders and development of therapeutic modalities targeting these patients and associated clinical phenotypes.

Beta-glucan has been shown to have a beneficial effect on gastrointestinal health. This experiment was conducted to investigate the effects of β-glucan isolated from Agrobacterium sp. ZX09 on growth performance and intestinal health of weaning pigs. A total of 108 weaned pigs (21 d of age; 6.05 ± 0.36 kg) were randomly divided into 3 groups (6 pens/group; 6 pigs/pen), and the groups were each treated with the following diets: 1) basal diet, 2) basal diet supplemented with 20 mg/kg olaquindox, 3) basal diet supplemented with 200 mg/kg β-glucan, for 21 d. Compared with the control group, pigs fed with 200 mg/kg β-glucan had greaterBW, average daily gain and duodenal villus height to crypt depth ratio (P

BACKGROUND Pancreatic carcinoma carries a devastating prognosis and is the 4th leading cause for cancer related death in the US and most European countries. Apart from imaging and CA 19-9, pancreatic carcinoma is still lacking reliable markers to assess tumor dynamics and to monitor treatment response over time. The aim of this study was to evaluate the feasibility of cell free tumor-DNA (cft-DNA), respectively KRAS mutation in peripheral blood, detection as a prognostic and predictive value for chemotherapy monitoring. METHODS Serial plasma samples from 42 patients with KRAS mutated pancreatic cancer were prospectively collected and the ctKRAS Mutation Assay (Idylla™, Biocartis, Mechelen, Belgium) of cft-DNA was performed on 29 patients that did not receive curative surgery and went on to palliative chemotherapy. To monitor cft-DNA KRAS mutation levels during treatment quantitative assessment of cft-DNA was performed at baseline and during follow up at predetermined times. RESULTS All 29 patients included in our analyses had a detected KRAS mutation in the tumor biopsy. In almost half (48.2%) of patients a KRAS mutation could also be detected in peripheral plasma. Patients with detectable KRAS mutations before treatment start in plasma had a significantly worse survival (16.8 months vs not reached, p

Penile melanosis is an uncommon but benign condition. Its appearance, however, can cause significant distress to patients. We report a case of a patient presenting with hyperpigmented annular penile macules, with a fibrillar pattern seen on dermoscopy. Histopathological examination revealed basal keratinocyte hyperpigmentation with no melanocytic proliferation or atypia, confirming our diagnosis of penile melanosis. The patient was managed conservatively. We also reviewed the literature surrounding the clinical assessment and management of penile melanosis. Future reports on this topic with clinical-dermoscopic-pathological correlations will aid further understanding of this seldom reported condition.

Background/aimTo evaluate the safety and efficacy of ruthenium-106 (Ru-106) plaque brachytherapy in managing invasive ocular surface squamous neoplasia (OSSN).MethodsThis is a retrospective, non-comparative, interventional case series of 42 eyes with OSSN with histopathologically-proven corneal stromal and/or scleral invasion that underwent Ru-106 plaque brachytherapy. Main outcome measures were tumour regression, eye salvage, final visual acuity, treatment complications and metastasis.ResultsAt presentation, the mean tumour basal diameter was 9.3 mm (range 5–26 mm) and thickness 3.1 mm (range 1.5–11 mm). Prior treatment included excision biopsy in two patients (5%), incision biopsy and topical interferon in one each (2%). Following excision with 4 mm clinically clear margins, corneal stromal and/or scleral invasion of OSSN was confirmed in all 42 cases, with the excised base showing invasive squamous cell carcinoma. A total dose of 5000 cGy over a mean duration of 19.7 hours (range 7–41 hours) was provided to an axial depth of 2 mm using Ru-106 surface plaque. Over a mean follow-up of 36.9 months (range 22.3–72 months), complete tumour regression was achieved in all eyes (100%). Two eyes (5%) showed conjunctival tumour growth remote from the site of prior treatment. Visual acuity was maintained at ≥20/200 in 35 eyes (83%), with a loss of >2 Snellen lines in 1 eye (2%). There was no evidence of regional lymph node or systemic metastasis.ConclusionHistopathology-guided use of Ru-106 surface plaque brachytherapy is a safe and an effective adjuvant therapy in the management of corneal stromal and/or scleral invasion of OSSN.

We examined the sensitivity of the neurons in the inferior colliculus (IC) in male and female rats to the interaural time differences (ITDs) conveyed in electrical pulse trains. Using bipolar pairs of electrodes that selectively activate the auditory nerve fibers at different intracochlear locations, we assessed whether the responses to electrical stimulation with ITDs in different frequency regions were processed differently. Most well-isolated single units responded to the electrical stimulation in only one of the apical or basal cochlear regions, and they were classified as either apical or basal units. Regardless of the cochlear stimulating location, more than 70% of both apical and basal units were sensitive to ITDs of electrical stimulation. However, the pulse rate dependence of neural ITD sensitivity differed significantly depending on the location of the stimulation. Moreover, ITD discrimination thresholds and the relative incidence of ITD tuning type markedly differed between units activated by apical and basal stimulations. With apical stimulation, IC neurons had a higher incidence of peak-type ITD function, which mostly exhibited the steepest position of the tuning curve within the rat's physiological ITD range of ±160 μs and, accordingly, had better ITD discrimination thresholds than those with basal stimulation. These results support the idea that ITD processing in the IC might be determined by functionally segregated frequency-specific pathways from the cochlea to the auditory midbrain.

In oil palm plantations, Basal Stem Rot (BSR) disease has been acknowledged by many researchers worldwide to be a core and consistent danger. Given this problem, the early evaluation of the disease...

Objectives This study aimed to assess the success rate and the amount of suture separation after the miniscrew-assisted rapid palatal expansion (MARPE) procedure in relation to the chronological age and sex of the patients. Materials and methods The periapical radiographs of 215 subjects (95 male; 120 female; range, 6–60 years) who had undergone MARPE treatment were retrospectively analyzed. The success of suture separation was determined and, in suture-separated subjects, the amount of suture separation was evaluated by suture separation ratio calculated from the periapical radiograph obtained after active expansion. Association tests were performed using linear-by-linear association, the Jonckheere-Terpstra test, Fisher’s exact test, and the Mann–Whitney U test, and linear regression models were also developed. Results The success rate of suture separation was 61.05% in male, 94.17% in female, and 79.53% in both sexes. There was a statistically significant association between older age and suture nonseparation in male (p p = 0.221). In suture-separated subjects, there was a statistically significant trend toward a low amount of suture separation with older age subgroups in both sexes (p Conclusions Older patients treated with MARPE, particularly in male, may have a reduced likelihood of both success in suture separation and sufficient basal bone expansion. Clinical relevance This study demonstrates that clinicians should consider that the success rate of MARPE and the amount of suture separation may depend on chronological age and sex.

Bayesian modelling of radiocarbon dates directly integrates information obtained through archaeological analysis. Here, I explain how to add known information/reasonable assumptions about the length of a deposition phase, using the example of date sequences from two Early Neolithic communities in the Aegean whose dating has been hotly debated, i.e. basal Knossos (Crete) and Nea Nikomedeia (Northern Greece). The consequences of the re-evaluation of their dates are discussed for the broader picture of the Neolithisation in the Aegean and for the chronology of the regional use of stamps.