Effect of hyperbaric oxygen in hepatopulmonary syndrome: an innovative experimental study.

OBJECTIVE: This study aimed to analyze the effect of hyperbaric oxygen treatment (HBOT) in hepatopulmonary syndrome (HPS). MATERIALS AND METHODS: Five-month-old female Wistar-Albino rats were randomly divided into three groups: Group I, the control group; Group II, the cirrhosis group; and Group III, the cirrhosis group + HBOT group. Rats were exposed to HBO sessions (2.4 atm./60 min) for 20 days. Animals were sacrificed 24 hours after the last HBO session. Biochemical analysis, oxygenation parameters, NO and NO synthase (NOS) levels, histopathological changes in the liver and lungs, and pulmonary artery diameter were measured. RESULTS: A total of 24 rats (10 rats were included in Group I, six rats in Group II, and eight rats in Group III) weighing 220-250 g were included in the study. Significant differences were observed for NO and NOS (9.10±1.05 to 12.17±1.85 µmol/L, p<0.05 and 0.46±0.31 to 1.17±0.39 U/ml, p<0.05, respectively) at baseline and day 36 only in group II. Inflammatory cell infiltration and bronchial injury were significantly increased in group II compared to group I (p=0.007 and p=0.008, respectively) but not in group III (p=0.266 and p=0.275, respectively). Pulmonary artery diameter was significantly lower in group III compared with group II at all sites in both lungs (p<0.05). CONCLUSIONS: HBOT may be a promising treatment for HPS by reducing NO and NOS activity, perialveolar arteriolar dilation, lung inflammation, and injury and guiding future clinical trials.

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.

Interpreting SNP heritability in admixed populations.

SNP heritability (hsnp2) is defined as the proportion of phenotypic variance explained by genotyped SNPs and is believed to be a lower bound of heritability (h2), being equal to it if all causal variants are known. Despite the simple intuition behind hsnp2, its interpretation and equivalence to h2 is unclear, particularly in the presence of population structure and assortative mating. It is well known that population structure can lead to inflation in h/np2 estimates. Here we use analytical theory and simulations to demonstrate that hsnp2 estimated with genome-wide restricted maximum likelihood (GREML) can be biased in admixed populations, even in the absence of confounding and even if all causal variants are known. This is because admixture generates linkage disequilibrium (LD), which contributes to the genetic variance, and therefore to heritability. GREML implicitly assumes this component is zero, which may not be true, particularly for traits under divergent or stabilizing selection in the source populations, leading under- or over-estimates of hsnp2 relative to h2. For the same reason, GREML estimates of local ancestry heritability (hγ2) will also be biased. We describe the bias in h/np2 and h^γ2 as a function of admixture history and the genetic architecture of the trait and discuss its implications for genome-wide association and polygenic prediction.

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 genetic and phenotypic correlates of mtDNA copy number in a multi-ancestry cohort.

Mitochondrial DNA copy number (mtCN) is often treated as a proxy for mitochondrial (dys-) function and disease risk. Pathological changes in mtCN are common symptoms of rare mitochondrial disorders, but reported associations between mtCN and common diseases vary across studies. To understand the biology of mtCN, we carried out genome- and phenome-wide association studies of mtCN in 30,666 individuals from the Penn Medicine BioBank (PMBB)-a diverse cohort of largely African and European ancestry. We estimated mtCN in peripheral blood using exome sequence data, taking cell composition into account. We replicated known genetic associations of mtCN in the PMBB and found that their effects are highly correlated between individuals of European and African ancestry. However, the heritability of mtCN was much higher among individuals of largely African ancestry (h2=0.3) compared with European ancestry individuals(h2=0.1). Admixture mapping suggests that there are undiscovered variants underlying mtCN that are differentiated in frequency between individuals with African and European ancestry. We show that mtCN is associated with many health-related phenotypes. We discovered robust associations between mtDNA copy number and diseases of metabolically active tissues, such as cardiovascular disease and liver damage, that were consistent across African and European ancestry individuals. Other associations, such as epilepsy and prostate cancer, were only discovered in either individuals with European or African ancestry but not both. We show that mtCN-phenotype associations can be sensitive to blood cell composition and environmental modifiers, explaining why such associations are inconsistent across studies. Thus, mtCN-phenotype associations must be interpreted with care.

Cost-Effective Laboratory Matrix Projection Micro-Lithography System.

This paper presents a home-built projection lithographer designed to transfer the image from a DLP (digital light processing) projector MEMS matrix onto the microscope objective's field of view, where a photoresist-covered substrate is placed. The photoresist is exposed using blue light with a wavelength of 450 nm. To calibrate the device and adjust focal lengths, we utilize a red light that does not affect the photoresist. The substrate is located on a movable platform, allowing the exposure field to be shifted, enabling the exposure of designs with lateral sizes of 1 × 1 cm2 at a resolution of a few micrometers. Our setup showcases a 2 µm resolution for the single frame 200 × 100 µm2, and a 5 µm resolution for 1 × 1 cm2 with field stitching. The exposure speed, approximately 1 mm2/100 s, proves to be sufficient for a variety of laboratory prototyping needs. This system offers a significant advantage due to its utilization of easily accessible and budget-friendly components, thereby enhancing its accessibility for a broader user base. The exposure speed and resolution meet the requirements for laboratory prototyping in the fields of 2D materials, quantum optics, superconducting microelectronics, microfluidics, and biology.

The value of potential immunohistochemical biomarkers and clinicopathological findings in predicting response to neoadjuvant chemotherapy in breast cancer.

OBJECTIVE: Following neoadjuvant chemotherapy (NAC) in breast cancer (BC), complete treatment response is achieved in some patients, while treatment response is limited in others. Predicting non-responder patients can prevent exposure to adverse effects associated with chemotherapeutic agents and delays in selecting other treatment modalities. In this study, we aimed at identifying predictive factors related to tumor regression in patients with BC who received NAC. PATIENTS AND METHODS: This single-center cohort included 91 patients with BC who underwent surgery following NAC based on pretreatment tumor biopsy. According to BC molecular subtype, tumor regression grade (TRG) was determined using the Miller-Payne scoring system in patients who received standard NAC. Immunohistochemical stainings for VEGFR3 and CD44 were applied to needle core biopsies obtained prior to NAC in these patients. RESULTS: Pathological complete response (pCR) was achieved in 20 patients (22%). In univariate analysis, high Ki-67 expression, ER negativity, and HER2 positivity were determined to be predictive factors of TRG (p < 0.05). In multivariate analysis, Ki-67 was the single independent predictor of TRG, with a 1.05-fold effect size. CD44 and VEGFR3 levels did not affect TRG or survival (p > 0.05). There was a significant difference in TRG according to molecular subtype of BC (p < 0.001). The treatment response was 5.5-fold higher in HER2-positive patients compared with HER2-negative patients. CONCLUSIONS: pCR rates were significantly higher in TNBC, HER2, and luminal HER2+ subtypes when compared with luminal HER2- subtype. Ki-67 >25% and ER negativity had a favorable effect on TRG after NAC. CD44 and VEGFR3 were not effective in predicting treatment response.

The Impact of COVID-19 on the Psychological Well-Being of Surgeons in Pakistan: A Multicenter Cross-Sectional Study.

Introduction The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic left a profound and pervasive impact on the healthcare infrastructure on a global scale. Since its onset, the pattern of reported cases and its associated mortality had shown variability with intermittent peaks causing a significant effect on the psychological well-being of the surgeons of Pakistan. The aim of this study was to assess the effects of the COVID-19 pandemic on the mental well-being of surgeons in Pakistan. Methods This multicenter cross-sectional study was carried out to assess the impact of COVID-19 on the psychological well-being of surgeons in Pakistan. The validated Self-Reporting Questionnaire-20 (SRQ-20) tool was circulated electronically via Google Forms (Google, Inc., Mountain View, CA, USA) in the practicing surgical fraternity across all five regions of Pakistan, i.e., Sindh, Punjab, Baluchistan, Khyber Pakhtunkhwa (KPK), and Azad Jammu and Kashmir (AJK). Results This study showed that the female gender, having fewer years of working experience, non-satisfaction with the available personal protective equipment (PPE), and working in the public sector were the factors affecting the psychological well-being of surgeons during the pandemic. Conclusion Considering the continuous rise in new cases during the ongoing pandemic, the mental health of surgeons working in low- and middle-income countries (LMIC) such as Pakistan has been significantly affected. There is an undeniable need to pay close attention to their psychological well-being. Measures need to be undertaken to ensure their physical and mental health and wellness.

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.

Comparison of clinical features and the impact of reproductive factors on by age at diagnosis young and elderly breast cancer patients in the middle Anatolian region of Turkey.

OBJECTIVE: Reproductive risk factors have been shown to influence breast cancer etiology for women of different origin worldwide; most studies in young/older patients have been limited to analyzing survival or tumor characteristics within their age group. This study aimed to compare the clinicopathological characteristics, treatment regimens, survival outcomes, and the impact of reproductive risk factors on young and elderly breast cancer patients. PATIENTS AND METHODS: The data were collected retrospectively between October 2015 and March 2021, where 77 young patients (≤ 40 years) and 107 elderly patients (>65 years) were included out of a total of 567 patients undergoing treatment at Kayseri City Training and Research Hospital General Surgery Clinic, Turkey. Logistic regression analysis was performed to assess the impact of risk factors according to age. RESULTS: Luminal-like tumors were in the majority in both age groups; there was no difference in diagnostic stages and survival between groups. The nulliparity ratio, total breastfeeding duration, number of biological children, first full-term pregnancy age, body mass index (BMI), and breast density distribution were significantly statistically different between groups. According to the multiple binary logistic regression analysis results for age, the most significant factors with risk effects were variables age of menarche OR= 3.36 (95% CI: 1.44-7.86) and child number OR= 2.58 (95% CI: 1.75-3.79), respectively. CONCLUSIONS: The importance of looking at the impact of different risk factors on breast cancer risk lies in the potential to develop valid risk prediction models that can allow targeted screening and preventive interventions for high-risk women. By identifying more influential risk factors in different geographical profiles, risk-based screening, and targeted prevention efforts can be encouraged, and these factors can be included in risk prediction models.

The magnetic resonance imaging assessment of optic nerve sheath diameter in pediatric acute liver failure patients.

OBJECTIVE: To evaluate the diagnostic value of optic nerve sheath diameter (ONSD) using brain MRI in the pretransplantation period in the pediatric acute liver failure patients, and correlate the ONSD with clinical grade of hepatic encephalopathy (HE) and MRI findings. PATIENTS AND METHODS: Forty acute liver failure patients and 40 control group patients were retrospectively analyzed. The high signal intensities in T2W (T2-weighted image), FLAIR (Fluid Attenuated Inversion Recovery) and DWI (diffusion-weighted imaging) sequences were evaluated and ONSD was measured. The patients were grouped first into 5 according to their West Haven score, and HE grade 0 and grade 1 were accepted as low grade HE, HE grade 2, 3 and 4 were accepted as high grade HE. The patients were grouped to 2 according to the MRI findings as low grade and high grade MRI group. RESULTS: The mean value of ONSD was 6.0 ± 1.80 and 4.94 ± 1.27 in the all patients and in the control group, respectively. There was statistically significant difference between both the ONSD and the low grade-high grade HE groups (p=0.01), and between the ONSD and the low grade-high grade MRI groups (p<0.001). CONCLUSIONS: Although high ONSD values do not make the diagnosis of cerebral edema, it may cause suspicion in the early period. MRI can be helpful in the diagnoses of increased intracranial pressure like ultrasound. Our study is the first study to compare ONSD and MRI findings in addition to HE grades. The widespread use of MRI in children in recent years may help determine the normal range of ONSD values.

Micromask Lithography for Cheap and Fast 2D Materials Microstructures Fabrication.

The fast and precise fabrication of micro-devices based on single flakes of novel 2D materials and stacked heterostructures is vital for exploration of novel functionalities. In this paper, we demonstrate a fast high-resolution contact mask lithography through a simple upgrade of metallographic optical microscope. Suggested kit for the micromask lithography is compact and easily compatible with a glove box, thus being suitable for a wide range of air-unstable materials. The shadow masks could be either ordered commercially or fabricated in a laboratory using a beam lithography. The processes of the mask alignment and the resist exposure take a few minutes and provide a micrometer resolution. With the total price of the kit components around USD 200, our approach would be convenient for laboratories with the limited access to commercial lithographic systems.

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.

High-throughput phenotyping methods for quantifying hair fiber morphology.

Quantifying the continuous variation in human scalp hair morphology is of interest to anthropologists, geneticists, dermatologists and forensic scientists, but existing methods for studying hair form are time-consuming and not widely used. Here, we present a high-throughput sample preparation protocol for the imaging of both longitudinal (curvature) and cross-sectional scalp hair morphology. Additionally, we describe and validate a new Python package designed to process longitudinal and cross-sectional hair images, segment them, and provide measurements of interest. Lastly, we apply our methods to an admixed African-European sample (n = 140), demonstrating the benefit of quantifying hair morphology over classification, and providing evidence that the relationship between cross-sectional morphology and curvature may be an artefact of population stratification rather than a causal link.

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.

Demographic history mediates the effect of stratification on polygenic scores.

Population stratification continues to bias the results of genome-wide association studies (GWAS). When these results are used to construct polygenic scores, even subtle biases can cumulatively lead to large errors. To study the effect of residual stratification, we simulated GWAS under realistic models of demographic history. We show that when population structure is recent, it cannot be corrected using principal components of common variants because they are uninformative about recent history. Consequently, polygenic scores are biased in that they recapitulate environmental structure. Principal components calculated from rare variants or identity-by-descent segments can correct this stratification for some types of environmental effects. While family-based studies are immune to stratification, the hybrid approach of ascertaining variants in GWAS but reestimating effect sizes in siblings reduces but does not eliminate stratification. We show that the effect of population stratification depends not only on allele frequencies and environmental structure but also on demographic history.

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.

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.