Variant-specific effects of GBA1 mutations on dopaminergic neuron proteostasis.

Glucocerebrosidase 1 (GBA1) mutations are the most important genetic risk factors for Parkinson's disease (PD). Clinically, mild (e.g., p.N370S) and severe (e.g., p.L444P and p.D409H) GBA1 mutations have different PD phenotypes, with differences in age at disease onset, progression, and the severity of motor and non-motor symptoms. We hypothesize that GBA1 mutations cause the accumulation of α-synuclein by affecting the cross-talk between cellular protein degradation mechanisms, leading to neurodegeneration. Accordingly, we tested whether mild and severe GBA1 mutations differentially affect the degradation of α-synuclein via the ubiquitin-proteasome system (UPS), chaperone-mediated autophagy (CMA), and macroautophagy and differentially cause accumulation and/or release of α-synuclein. Our results demonstrate that endoplasmic reticulum (ER) stress and total ubiquitination rates were significantly increased in cells with severe GBA1 mutations. CMA was found to be defective in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons with mild GBA1 mutations, but not in those with severe GBA1 mutations. When examining macroautophagy, we observed reduced formation of autophagosomes in cells with the N370S and D409H GBA1 mutations and impairments in autophagosome-lysosome fusion in cells with the L444P GBA1 mutation. Accordingly, severe GBA1 mutations were found to trigger the accumulation and release of oligomeric α-synuclein in iPSC-derived dopaminergic neurons, primarily as a result of increased ER stress and defective macroautophagy, while mild GBA1 mutations affected CMA, which is mainly responsible for the degradation of the monomeric form of α-synuclein. Overall, our findings provide new insight into the molecular basis of the clinical variability in PD associated with different GBA1 mutations.

Assessment of CD39 expression in regulatory T-cell subsets by disease severity in adult and juvenile COVID-19 cases.

COVID-19 is a disease characterized by acute respiratory failure and is a major health problem worldwide. Here, we aimed to investigate the role of CD39 expression in Treg cell subsets in COVID-19 immunopathogenesis and its relationship to disease severity. One hundred and ninety COVID-19 patients (juveniles, adults) and 43 volunteers as healthy controls were enrolled in our study. Flow cytometric analysis was performed using a 10-color monoclonal antibody panel from peripheral blood samples. In adult patients, CD39+ Tregs increased with disease severity. In contrast, CD39+ Tregs were decreased in juvenile patients in an age-dependent manner. Overall, our study reveals an interesting profile of CD39-expressing Tregs in adult and juvenile cases of COVID-19. Our results provide a better understanding of the possible role of Tregs in the mechanism of immune response in COVID-19 cases.

Asprosin and Oxidative Stress Level in COVID-19 Patients.

BACKGROUND: The global COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created great problems in healthcare systems throughout the world. Although, just like other respiratory tract viral infections, it is a disease with pathophysiological processes associated in general with cytokine production, inflammation, cell death, and redox imbalance or oxidative stress, very little is known about the pathology. Also, in recent studies, the effect of asprosin, which has an important and complex role on metabolism, on COVID-19 is unknown. The aim of this study is to determine the level of asprosin, a new hormone that has the potential to affect many metabolic pathways such as glucose metabolism, in COVID-19 patients. In addition, it is to determine whether asprosin is associated with oxidative stress in COVID-19 patients. METHODS: Blood samples were taken from 30 patients diagnosed with COVID-19 confirmed with RT-PCR test and 30 healthy control subjects. The serum asprosin level was analyzed with ELISA, and total antioxidant status (TAS) and total oxidant status (TOS) levels with colorimetric analysis. RESULTS: The asprosin and TAS levels were determined to be statistically significantly decreased in the COVID-19 patients, and the TOS and OSI levels were significantly increased. CONCLUSIONS: It can be thought that a decrease in asprosin level in COVID-19 patients causes a decrease in metabolic activity, prevents sufficient energy production in patients, and therefore oxidative stress increases in patients.

Hypothalamic-pituitary-adrenal axis function in traumatic spinal cord injury-related neuropathic pain: a case-control study.

PURPOSE: This study aimed to investigate the hypothalamic-pituitary-adrenal (HPA) axis in spinal cord injury (SCI)-related neuropathic pain (NP) using dynamic adrenocorticotropic hormone (ACTH) stimulation tests. METHODS: This case-control study was conducted with 22 patients diagnosed with traumatic chronic spinal cord injury (15 with and 7 without neuropathic pain) and ten age- and sex-matched healthy control subjects. Collected data included socio-demographic variables, SCI characteristics, and level of NP using a numeric rating scale (NRS) and the Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS). HPA axis function was measured via low-dose (1 µg) and standard-dose (250 µg) ACTH tests (LDT and SDT, respectively). RESULTS: No significant differences existed regarding peak cortisol responses or area under the curve (AUC) of cortisol responses between the SCI patients with NP and healthy controls using LDT and SDT. In the SCI patients without pain, cortisol responses were significantly lower than those in the healthy controls for LDT and SDT. Peak cortisol and AUC responses of the LDT and SDT were positively correlated with NRS in SCI patients with NP. CONCLUSIONS: This study demonstrated that, in chronic SCI patients with NP, basal cortisol levels are relatively higher compared to healthy controls, and that HPA axis can be activated with low- and standard-dose ACTH stimulation tests. Although NP following SCI was not significantly associated with hypo- or hypercortisolemia, either after low- or standard-dose ACTH stimulation test, the severity of NP during chronic SCI may be positively associated with HPA axis activity.

Acute intestinal obstruction due to a non-involuted uterus after cesarean section: case report.

The involution of the uterus is influenced by a number of factors such as advanced childbearing age, electrolyte disturbances, multiparity, repeated cesarean sections, and vaginal infections. The authors report the management of a clinical case of a 41-year-old female who presented with acute intestinal obstruction due to a non-involuted uterus after cesarean section.

Nanosecond colloidal quantum dot lasers for sensing.

Low-threshold, gain switched colloidal quantum dot (CQD) distributed-feedback lasers operating in the nanosecond regime are reported and proposed for sensing applications for the first time to the authors' knowledge. The lasers are based on a mechanically-flexible polymeric, second order grating structure overcoated with a thin-film of CQD/PMMA composite. The threshold fluence of the resulting lasers is as low as 0.5 mJ/cm² for a 610 nm emission and the typical linewidth is below 0.3 nm. The emission wavelength of the lasers can be set at the design stage and laser operation between 605 nm and 616 nm, while using the exact same CQD gain material, is shown. In addition, the potential of such CQD lasers for refractive index sensing in solution is demonstrated by immersion in water.

Hyperbolic metamaterials based on quantum-dot plasmon-resonator nanocomposites.

We theoretically demonstrate that nanocomposites made of colloidal semiconductor quantum dot monolayers placed between metal nanoparticle monolayers can function as multilayer hyperbolic metamaterials. Depending on the thickness of the spacer between the quantum dot and nanoparticle layers, the effective permittivity tensor of the nanocomposite is shown to become indefinite, resulting in increased photonic density of states and strong enhancement of quantum dot luminescence. This explains the results of recent experiments [T. Ozel et al., ACS Nano 5, 1328 (2011)] and confirms that hyperbolic metamaterials are capable of increasing the radiative decay rate of emission centers inside them. The proposed theoretical framework can also be used to design quantum-dot/nanoplasmonic composites with optimized luminescence enhancement.

Ultrasound-based airway assessment in obese patients as a valuable tool for predicting difficult airway: an observational study.

BACKGROUND: Difficult airway, characterized by difficult mask ventilation and intubation, is common in obese patients undergoing surgery. The purpose of this study was to evaluate and compare the prognostic efficiency of ultrasound-measured anterior cervical soft tissue parameters as an indicator of difficult airway during anesthesia induction in obese patients. METHODS: This prospective, double-blind, observational study was conducted at Balikesir University Faculty of Medicine Hospital between March 2020 and March 2022. A total of 157 patients age ≥ 18 (BMI ≥ 30 kg.m-2), without previous head and neck surgery were included in the study. Anterior cervical soft tissue measurements were performed at three levels; minimum distance between the hyoid bone and skin at the level of the hyoid bone; (DSHB), distance between the midpoint of the epiglottis and skin at the level of the thyrohyoid membrane; (DSE), distance between the anterior commissure of vocal cords and skin at the vocal cord level; (DSV). The Han scale was used to assess difficult mask ventilation and the Cormack-Lehane scale was used to assess difficult laryngoscopy. RESULTS: In the difficult laryngoscopy group, the mean values of DSHB, DSE and DSV were 18.5 ± 3.5, 18.3 ± 3.8, and 18.6 ± 3.4, respectively. The AUC values for DSHB, DSE, and DSV were 0.845, 0.827, and 0.850, respectively. Anterior cervical measurements showed a better predictive value for difficult laryngoscopy compared to difficult mask ventilation. CONCLUSION: Ultrasonographic measurements were predictive for difficult laryngoscopy and ventilation with better correlation in laryngoscopy.

Effect of COVID-19 pandemic on general surgery trauma surgeries: a single-center, retrospective cross-sectional study.

OBJECTIVE: This study aims to assess the impact of trauma surgeries performed in our clinic before and during the COVID-19 pandemic on surgical indications, procedure types, perioperative course, and final outcomes. PATIENTS AND METHODS: We conducted a retrospective single-center clinical study. The study group (n=88) comprised trauma patients who presented to the emergency department during the COVID-19 pandemic and underwent emergency surgeries. The control group (n=115) consisted of trauma patients who sought emergency care and underwent surgeries in the same period of the previous year, before the pandemic. We compared the number of patients, demographic data, clinical findings, diagnoses, and surgical interventions. RESULTS: The study group exhibited a 13.3% decrease in the number of patients compared to the control group during the COVID-19 pandemic. The study group and control group had similar age and gender distributions. The study group had a lower rate of surgical intervention. Among the study group, liver laceration was the most common diagnosis in 19 patients (7.4%), compared to 30 patients (11.7%) in the control group. Mortality rates were 1.0% in the study group and 2.0% in the control group. There were no significant differences in mortality (p=0.632) or patient diagnoses (p=0.357) between the COVID-19 pandemic and control periods. CONCLUSIONS: This study demonstrates a decline in the number of trauma patients admitted to the hospital and undergoing surgery during the COVID-19 pandemic. The pandemic has affected the management of patients requiring urgent surgical intervention, resulting in a lower rate of surgical procedures in the study group. However, despite the preference for medical treatment in trauma patients, surgical interventions remain necessary for appropriate indications.

Spatial angle dependent lasing from a dye-doped two-dimensional hexagonal photonic crystal made of holographic polymer-dispersed liquid crystals.

The observation of spatial angle dependent lasing from a dye-doped two-dimensional photonic crystal (2D PC) holographic polymer dispersed liquid crystals made of hexagonal lattice structure is reported. With the increasing output angle of the laser beam in the plane perpendicular to the 2D PC, the lasing wavelength is red-shifted. By analyzing the lasing oscillation trace, we found that the effective lattice constant changes with the output angle, causing the spatial angle dependent lasing.

Evaluating the effect of tumor size and sidedness on prognosis in stage 2 colon cancer: a retrospective population study.

OBJECTIVE: In this study, we aimed to evaluate the effect of tumor size and tumor sidedness on prognosis in patients with stage 2 colon cancer. PATIENTS AND METHODS: Data of 501 patients diagnosed with stage 2 colon cancer were evaluated retrospectively. It was evaluated whether the patients' age, gender, tumor differentiation, tumor node metastasis (TNM) stage, overall survival rate, and disease-free survival rate had any correlation with horizontal tumor diameter and tumor sidedness. In the ROC analysis performed to determine the cut-off value for the tumor diameter, which we think will predict survival, no significant results were obtained with maximum sensitivity and specificity. Therefore, the median value of the tumor diameter, which is 5 cm, was accepted as the cut-off value.  Kaplan-Meier method and Cox regression analysis were used for survival analysis and determination of prognostic factors. RESULTS: When the patients were evaluated in terms of tumor localization, 189 (37.7%) patients had right colon tumors and 312 (62.3%) patients had left colon tumors. There was no statistically significant difference in terms of disease-free survival and overall survival according to tumor localization. When the patients were analyzed by dividing them into two groups according to the horizontal tumor size (<5 cm and ≥5 cm), no statistically significant difference was found between the groups in terms of disease-free survival (DFS) and overall survival (OS) p=0.085, p=0.699, respectively. CONCLUSIONS: Our results suggest that the management of patients with stage 2 colon cancer requires a better understanding of tumor biology rather than features such as tumor size and localization.

The Age-Dependent Role of Th22, Tc22, and Tc17 Cells in the Severity of Pneumonia in COVID-19 Immunopathogenesis.

Coronavirus disease 2019 (COVID-19) has clinical manifestations ranging from mild symptoms to respiratory failure, septic shock, and multi-organ failure. Lymphocytes are divided into different subtypes based on their cytokine production pattern. In this study, we investigated the role of cytokine expressions of CD4+ T (T helper [Th]1, Th2, Th17, Th22) and CD8+ T cell subtypes (T cytotoxic [Tc]1, Tc2, Tc17, Tc22) in the pathogenesis of COVID-19. Peripheral blood mononuclear cells (PBMCs) were extracted with Ficoll by density gradient centrifugation from blood samples of 180 COVID-19 patients (children and adults) and 30 healthy controls. PBMCs were stimulated with PMA and Ionomycin and treated with Brefeldin A in the fourth hour, and a 10-colored monoclonal antibody panel was evaluated at the end of the sixth hour using flow cytometry. According to our findings, the numbers of Th22 (CD3+, CD4+, and interleukin [IL]-22+) and Tc22 (CD3+, CD8+, IL-22+) cells increased in adult patients regardless of the level of pneumonia (mild, severe, or symptom-free) as compared with healthy controls (p < 0.05). In addition, the number of Tc17 (CD3+, CD8+, and IL-17A+) cells increased in low pneumonia and severe pneumonia groups compared with the healthy controls (p < 0.05). Both IL-22 and IL-17A production decreased during a follow-up within 6 weeks of discharge. Our findings suggest that the increase in only IL-22 expressed Tc22 cells in the 0-12 age group with a general symptom-free course and higher levels of Th22 and Tc22 in uncomplicated adult cases may indicate the protective effect of IL-22. On the contrary, the association between the severity of pneumonia and the elevation of Tc17 cells in adults may reveal the damaging effect of IL-22 when it is co-expressed with IL-17.

Improved performance of organic light-emitting diodes with MoO3 interlayer by oblique angle deposition.

We fabricated and demonstrated improved organic light emitting diodes (OLEDs) in a thin film architecture of indium tin oxide (ITO)/ molybdenum trioxide (MoO3) (20 nm)/N,N'-Di(naphth-2-yl)-N,N'-diphenyl-benzidine (NPB) (50 nm)/ tris-(8-hydroxyquinoline) (Alq3) (70 nm)/Mg:Ag (200 nm) using an oblique angle deposition technique by which MoO3 was deposited at oblique angles (θ) with respect to the surface normal. It was found that, without sacrificing the power efficiency of the device, the device current efficiency and external quantum efficiency were significantly enhanced at an oblique deposition angle of θ=60° for MoO3.

Free-standing ZnO-CuO composite nanowire array films and their gas sensing properties.

A modified hydrothermal method was developed to synthesize ZnO-CuO composite nanostructures. A free-standing film made of ZnO-CuO nanostructures was assembled on the surface of the hydrothermal solution with a smooth surface on one side and a spherical surface on the other side. The structure, growth mechanism and the optical properties of the composite nanostructures were studied. Structural characterizations indicate that the composite nanostructure mainly consisted of two single-crystal phases of CuO and ZnO. The sensitivity for CO gas detection was significantly improved for the composite CuO-ZnO nanostructure film. This method offers a possible route for the fabrication of free-standing nanostructure films of different functional composite oxides.

Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis).

OBJECTIVE: To identify genetic causes of COACH syndrome BACKGROUND: COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). METHODS: In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. RESULTS: 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). CONCLUSIONS: Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L.

Control of mushroom sciarid fly Lycoriella ingenua populations with insect growth regulators applied by soil drench.

Mushroom sciarid fly Lycoriella ingenua (Dufour, 1839) comb. nov., is one of the most common fly pests affecting the cultivation of Agaricus bisporus (Lange) Imbach in Turkey. In this study, eight insect growth regulators (IGRs)--diflubenzuron, flufenoxuron, lufenuron, methoprene, novaluron, pyriproxyfen, teflubenzuron, and triflumuron-were tested for their potential to control L. ingenua populations in two successive growing periods. Treatments were targeted at larvae as soil drenches; treatment efficacy was evaluated by assessing adult emergence and larval damage. These products were compared with a control treated with water (negative control) and a conventional chemical insecticide (chlorpyrifos ethyl) (positive control). Treatments with the IGRs caused significant reductions in emerging adult numbers and sporophore damage rates compared with the water-treated control over the two growing periods. Of the IGRs tested, novaluron, diflubenzuron, and teflubenzuron had significantly lower numbers of emerging adults than the rest of the IGRs and chlorpyrifos ethyl-treated control in both periods. Treatments with teflubenzuron, pyriproxyfen, novaluron, and diflubenzuron resulted in significantly lower sporophore damage rates than all other treatments. Compared with negative control, there were no significant yield reductions due to applications of selected IGRs. The results suggest that all the IGRs tested can be used as alternatives to conventional pesticides in controlling L. ingenua populations on mushroom.

Rehabilitation results of patients with acute transverse myelitis.

BACKGROUND: In this study, we aimed to evaluate the efficacy of rehabilitation in patients with acute transverse myelitis (ATM). METHOD: The patients were included in rehabilitation program in the rehabilitation unit. Spasticity of the patients was evaluated by modified Ashworth scale at baseline and at the end of treatment. The functional independence measurement (FIM), Barthel index and functional ambulatory scale (FAS) values were as well evaluated at baseline and at the end of the treatment, and the results were compared to evaluate the efficacy of the rehabilitation program. RESULTS: A total of 13 patients (6 males, 7 females) with transverse myelitis were included in the study. The mean +/- SD of age of the patients was 14.30 +/- 3.14. The mean +/- SD of duration of disease was 4.5 +/- 1.85 weeks. There was statistically significant difference in modified Ashworth scale, FIM, and FAS values when the baseline and after treatment values were compared, which indicated improvement due to treatment (p < 0.05). CONCLUSIONS: We concluded that in patients with ATM, rehabilitation of patients contributes to clinical and functional improvement of the disease (Tab. 2, Fig. 1, Ref. 23).

Prognostic role of pre-operative serum ferritin level in stage 2 colon cancer.

OBJECTIVE: In this study, we aimed to evaluate the prognostic value of preoperative serum ferritin level in patients with stage 2 colon cancer who underwent curative surgery. PATIENTS AND METHODS: The data of 120 patients who were stage 2 after curative surgery and whose ferritin levels were measured at the time of diagnosis without starting any treatment were analyzed. Demographic data such as age and gender, histopathological characteristics such as tumor size, lymphovascular invasion (LVI), perineural invasion (PNI), number of removed lymph nodes, tumor grade, and clinical and laboratory data were retrieved from the hospital medical charts or electronic medical records. In the survival analysis, the cut-off level of ferritin was accepted as 150 ng/ml, which is the upper limit determined by the World Health Organization (WHO), as a prognostic factor. RESULTS: Fifty (41.7%) of the patients were female, 70 (58.3%) were male, and the median age was 63.5 (range 24-90) years. There was no significant difference between the low and high ferritin groups regarding age, gender, T stage, tumor localization, histological subtype, PNI, LVI, removal of less than 12 lymph nodes, and tumor size. Disease-free survival and overall survival of patients with high ferritin levels were worse than patients with low ferritin levels, but this difference did not reach statistical significance. CONCLUSIONS: Serum ferritin level is an easily monitored, cost-effective, and reproducible marker. In this study we found that high ferritin level was associated with poor survival, although it was not statistically significant.

The diagnostic utility of maspin in the distinction between malignant mesothelioma and pulmonary adenocarcinoma.

Immunohistochemistry is frequently employed to differentiate between malignant mesothelioma (MM) and pulmonary adenocarcinoma (AC) infiltrating the pleura, but there is uncertainty as to which antibodies are most useful. The present study investigated the presence of the serine protease, maspin, in epithelioid MMs and evaluated the diagnostic utility of maspin for the differential diagnosis between epithelioid MM and pulmonary AC with pleural involvement. The results showed more frequent maspin immunostaining among AC cases compared with MM cases. Maspin positivity was significantly higher among AC cases with respect to both the extent and intensity of staining. A significant difference also existed between the two tumour types with respect to the overall maspin score. Despite these findings, the sensitivity and specificity of maspin positivity to detect AC were only 59% and 73%, respectively, indicating that detection of maspin is of no value for the differential diagnosis of AC and MM.

Clinicopathologic and prognostic evaluation of invasive breast carcinoma molecular subtypes and GATA3 expression.

PURPOSE: recently, molecular subclassification of breast carcinomas has been proposed as a new prognostic parameter. METHODS: we classified 222 invasive breast carcinoma cases in 5 molecular subtypes by using tissue microarray (TMA) and immunohistochemistry methods. These subtypes were luminal A (estrogen receptor/ER and/or progesterone receptor/ PR positive), luminal B (ER and/or PR positive + HER2 positive), HER2-expressing type (ER and PR negative, HER2 positive), basal-like type (ER, PR and HER2 negative, positive with at least one of these myoepithelial markers: CK5/6, CK14, EGFR) and null type (ER, PR, HER2 and myoepithelial markers negative). We compared these subtypes according to their clinicopathological features and GATA3 expression. RESULTS: luminal A was the most frequent subtype. According to overall survival rates, HER2-expressing and basal- like types had the worst prognosis, while luminal A had the best. However, luminal B had the worst prognosis according to disease free survival. Most of the squamous differentiated metaplastic carcinomas were basal-like type. Tubular and mucinous carcinomas were luminal A. Most basal-like tumors were grade III. The majority of grade I tumors were luminal A. GATA3 positivity was associated with low grade tumors and luminal A subtype. CONCLUSION: molecular classification can be accepted as an independent prognostic factor for invasive breast carcinomas. GATA3 expression was associated with luminal A and low histological grade. However, it wasn't shown as an independent parameter.