COVID-19 and tuberculosis coinfection: An overview of case reports/case series and meta-analysis of prevalence studies.
Coronavirus disease 2019 (COVID-19) coinfection with other respiratory pathogens poses a serious concern that can complicate diagnosis, treatment, and prognosis. Since COVID-19 and tuberculosis are both severe respiratory infections, their symptoms may overlap and even increase mortality in case of coinfection. The current study aimed to investigate the coinfection of tuberculosis and COVID-19 worldwide through a systematic review and meta-analysis. A systematic literature search based on the Systematic Reviews and Meta-Analyses" (PRISMA) was performed on September 28, 2021, for original research articles published in PubMed, Web of Science, and Embase databases from December 2019 to September 2021 using relevant keywords. Data analysis was performed using Stata 14 software. The final evaluation included 18 prevalence studies with 5843 patients with COVID-19 and 101 patients with COVID-19 and Mycobacterium tuberculosis (M. tuberculosis). The prevalence of tuberculosis infection was 1.1% in patients with confirmed COVID-19. This coinfection among patients with COVID-19 was 3.6% in Africa, 1.5% in Asia, and 1.1% in America. Eighteen case reports and 57 case series were also selected. Eighty-nine adults (67 men and 22 women) with a mean age of 45.14 years had concurrent infections with tuberculosis. The most common clinical manifestations were fever, cough, and weight loss. A total of 20.83% of evaluated patients died, whereas 65.62% recovered. Lopinavir/ritonavir was the most widely used antiviral drug for 10.41% of patients. COVID-19 has a low prevalence of tuberculosis coinfection, but it remains a critical issue, especially for high-risk individuals. The exact rate of simultaneous tuberculosis in COVID-19 patients could not be reported since we didn't have access to all data worldwide. Therefore, further studies in this field are strongly recommended.


Closure of large defects after microcystic lymphatic malformations using lateral intercostal artery perforator flap.
The surgical treatment of microcystic lymphatic malformations (LMs) has historically been difficult and frustrating because of a high recurrence rate due to incomplete resection. However, complete removal of the multifocal and extensive lesions rely on accurate imaging diagnosis and effective repair methods for the resulting large defect. The purpose of this study was to repair large skin defects due to complete resection of microcystic LMs using lateral intercostal artery perforator (LICAP) flap. Between January 2009 and June 2012, tissue defects in the axillary chest wall region of eight patients aged 13-22 years after microcystic LMs resections were closed using the LICAP flap. Flap donor sites in all patients were closed primarily except in one patient who underwent skin grafting. Before surgery, ultrasound and magnetic resonance imaging (MRI) examination were used to confirm the diagnosis and determine the scope and level of the abnormality for complete resection. All defects after microcystic LM excision were successfully closed using LICAP flaps. The follow-up period ranged from 1 to 3 years (mean 2.1 years). All flaps survived postoperatively. No recurrence occurred. Ultrasound and MRI follow-up also demonstrated flap survival without recurrence of microcystic LMs. No functional loss attributable to the LICAP flap harvest was identified in any case. Surgical resection is necessary for microcystic LMs. Imaging assists in the diagnosis and identification of the scope and level of lesions. The LICAP flap provides good coverage for the large defects and achieves acceptable morphology without functional deficits at flap donor sites. Ultrasound and MRI are safe and accurate diagnostic imaging methods for the pre- and postoperative evaluation of microcystic LMs in patients undergoing surgery.


BECCA.
Created by charity Breast Cancer Care, this app aims to help people with breast cancer adapt to life after hospital treatment ends.


Carcinoma of the oral cavity. Selective management according to site and stage.
The treatment philosophy of carcinoma of the oral cavity is explained. Specific guidelines for therapy of various head and neck sites are offered as a rational approach to formulation of individual treatment programs.


Influence of the environmental tonicity perturbations on the release of model compounds from large unilamellar vesicles (LUVs): A mechanistic investigation.
In this work, the influence of environmental tonicity perturbations on the size and release kinetics of model markers from liposomes (calcein and rhodamine) was investigated. Large unilamellar vesicles (LUVs) were prepared from a mixture composed of organic solvents containing dissolved phosphatidylcholine and phosphate buffered saline (PBS, pH 7.4). Organic phase was removed by rotary evaporation and the obtained liposomal dispersions were extruded to reduce the liposomal sizes to approx. 400 nm. The LUVs were exposed to PBS of different tonicity to induce water migration, and consequently, generate an osmotic pressure on the vesicle membranes. The markers release kinetics were studied by the dialysis method employing Franz diffusion cells. LUVs appeared to be more susceptible to the osmotic swelling than the shrinking and the size changes were significantly more pronounced for calcein-loaded LUVs in comparison to rhodamine-loaded LUVs. The calcein release from LUVs was highly affected by the water influx/efflux, whereas rhodamine release was less affected by the tonicity perturbations. Mechanistically, it appeared that hydrophilic molecules (calcein) followed the water flux, whereas lipophilic molecules (rhodamine) seemed to be more affected by the changes in LUVs size and consequent alteration of the tightness of the phospholipid bilayer (where the lipophilic marker was imbedded in). These results demonstrate that the different tonicity (within the inner core and external environment of vesicles) can enhance/hamper the diffusion of a marker from LUVs and that osmotically active liposomes could be used as a novel controlled drug delivery system.


Desmopressin treatment in nocturia; an analysis of risk factors for hyponatremia.
To explore the incidence, severity, time course, and risk factors of clinically significant hyponatremia in desmopressin treatment for nocturia. Data from three multi-center phase III trials were pooled. Hyponatremia was categorised as borderline (134-130 mmol/L) or significant (<130 mmol/L). Risk factors were explored with logistic regression and subgroup analysis performed to explore threshold values for contra-indication. In total 632 patients (344 men, 288 women) were analyzed. During dose-titration, serum sodium concentration below normal range was recorded in 95 patients (15%) and 31 patients (4.9%) experienced significant hyponatremia. The risk increased with age, lower serum sodium concentration at baseline, higher basal 24-hr urine volume per bodyweight and weight gain at time of minimum serum sodium concentration. Age was the best single predictor. Elderly patients (>or=65 years of age) with a baseline serum sodium concentration below normal range were at high risk (75%). Limiting treatment in elderly with normal basal serum sodium concentration to those below 79 years and with a 24-hr urine output below 28 ml/kg would reduce the risk from 8.1% to 3.0% at the cost of 34% fulfilling the contra-indication. The majority of nocturia patients tolerate desmopressin treatment without clinically significant hyponatremia. However, the risk increases with increasing age and decreasing baseline serum sodium concentration. Treatment of nocturia in elderly patients with desmopressin should only be undertaken together with careful monitoring of the serum sodium concentration. Patients with a baseline serum sodium concentration below normal range should not be treated.


Asymptomatic unruptured intracranial aneurysms in the older people.
Unruptured intracranial aneurysm commonly occurs in the older people. Because the rupture risk increases with age, the factors associated with aneurysms might be different according to age. We aimed to evaluate unruptured intracranial aneurysm characteristics in healthy, symptom-free older patients. Patients who visited the health examination center of two regional university hospitals and underwent computed tomography angiography between March 2001 and March 2017 were included. The putative aneurysm risk factors were identified; the aneurysm size and shape were determined by CT angiography, and measuring the ASPECT and dome/neck ratios. All images were interpreted independently by a neurosurgeon and a neurologist for improving size measurement accuracy. The unruptured intracranial aneurysm prevalence was 2.23% and 2.75% in the patients aged ≤ 60 and > 60 years, respectively. Among the younger group, female sex [odds ratio (OR), 1.85; P = 0.002], age (OR, 1.05; P < 0.001), hypertension (OR, 1.88; P < 0.001), coronary artery disease (OR, 0.26; P < 0.001), smoking (OR, 2.04; P < 0.001), and stroke family history (OR, 1.36; P = 0.047) were independently associated with aneurysm; anterior communicating artery aneurysms were the largest. Among the older group, female sex (OR, 1.76; P = 0.005), hypertension (OR, 2.54; P < 0.001), coronary artery disease (OR, 0.27; P < 0.001), and stroke family history (OR, 1.94; P = 0.003) were independently associated with aneurysm; internal carotid artery aneurysms were the largest. The factors related to unruptured intracranial aneurysm formation varied by age, and coronary artery disease protected against aneurysm formation regardless of age. The factors affecting unruptured intracranial aneurysm formation are different according to age and aneurysm location.


Crosstalk of TLR4, vascular NADPH oxidase, and COVID-19 in diabetes: What are the potential implications?
Toll-like receptor 4 (TLR4) contributes to the pathophysiology of diabetes. This happens, at least in part, because TLR4 modulates the enzyme NADPH oxidase, a primary source of ROS in vascular structures. Increased oxidative stress disrupts key vascular signaling mechanisms and drives the progression of diabetes, elevating the likelihood of cardiovascular diseases. Recently, it has been shown that patients with diabetes are also at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Given the importance of the interaction between TLR4 and NADPH oxidase to the disrupted diabetic vascular system, we put forward the hypothesis that TLR4-mediated NADPH oxidase-derived ROS might be a critical mechanism to help explain why this disparity appears in diabetic patients, but unfortunately, conclusive experimental evidence still lacks in the literature. Herein, we focus on discussing the pathological implications of this signaling communication in the diabetic vasculature and exploring this crosstalk in the context of diabetes-associated severe COVID-19.


Mechanisms of action underlying the immunotherapeutic activity of Allovectin in advanced melanoma.
Allovectin (velimogene aliplasmid) is a cancer immunotherapeutic currently completing a pivotal phase 3 study for metastatic melanoma. Consisting of a bicistronic plasmid encoding both major histocompatibility complex (MHC) class I heavy and light chains (HLA-B7 and β2-microglobulin, respectively) formulated with a cationic lipid-based system, it is designed for direct intratumoral administration. Following injection into a single lesion, the product is intended to induce anti-tumor immune responses against both treated and distal lesions. Both the plasmid and lipid components of Allovectin contribute to the biological activity of the drug product, and its therapeutic activity is hypothesized to derive from multiple mechanisms of actions (MOAs). These include the induction of both cytotoxic T-cell and innate immune responses directed against allogeneic as well as tumor-derived targets, consequences of both an increased MHC class I expression on tumor cells and the induction of a localized immune/inflammatory response. In this paper, we review Allovectin's proposed MOAs, placing their contributions in the context of anti-tumor immunity and highlighting both preclinical and clinical supporting data.


Novel opioid peptide amidorphin: characterization and distribution of amidorphin-like immunoreactivity in bovine, ovine, and porcine brain, pituitary, and adrenal medulla.
We have recently isolated from bovine adrenal medulla a novel C-terminally amidated opioid peptide, amidorphin, which derives from proenkephalin A. Amidorphin revealed a widespread distribution in bovine, ovine, and porcine tissue. Particularly high concentrations of amidorphin immunoreactivity were detected in adrenal medulla, posterior pituitary, and striatum, similar to the major gene products of proenkephalin A. In the adrenal medulla of each species, authentic amidorphin was the predominant immunoreactive form. Pituitary and brain, however, contained predominantly putative N-terminally shortened fragments of amidorphin of a slightly lower molecular weight and shorter retention times on HPLC. In addition, in ovine adrenal medulla, a putative high-molecular-weight form of amidorphin was detected. These findings are indicative of a tissue-specific processing of the proenkephalin A precursor, leading predominantly to authentic amidorphin in the adrenal medulla and further processing to smaller C-terminal fragments in the brain and pituitary.


Expression of matrix metalloproteinases (MMP)-12 by myofibroblasts during alkali-burned corneal wound healing.
The purpose of this study was to determine the expression of MMP-12 by myofibroblasts during the healing of alkali-burned rabbit corneas (ARC), thus implicating its role in ECM remodeling. Rabbit corneas during alkali burn were examined for MMP-12 mRNA expression by RT-PCR. Immunohistochemistry was used to determine the presence of alpha-SMA, MMP-12 protein, and macrophages. In situ hybridization was performed to identify MMP-12 mRNA expressing cells. RT-PCR showed that MMP-12 mRNA was expressed in the alkali-burned corneas from one week after the injury. Immunohistochemistry showed myofibroblasts positive for MMP-12 expression. In situ hybridization revealed that MMP-12 mRNA was expressed by myofibroblasts. Our results indicate that, in alkali-burned corneas, myofibroblasts express both MMP-12 mRNA and protein. We suggest that MMP-12 may disintegrate some components of the ECM released after severe alkali burn, which may be involved in the ECM remodeling.


Comparing mechanical, barrier and antimicrobial properties of nanocellulose/CMC and nanochitosan/CMC composite films.
Nano-chitosan (NCH), nano-cellulose (NCL) and cellulose derivative are biodegradable biopolymer. Nano-chitosan or nano-cellulose at different concentrations (0.1, 0.5 and 1%) incorporated in carboxymethyl cellulose (CMC) film solution using casting methods. Both CMC/NCH and NCL decreased physical properties (water solubility, moisture content and moisture absorption) especially in concentration of 1%. However, these properties in CMC/NCH were significantly (p < 0.05) lower than CMC/NCL. Water vapor permeability of polymer and nanofiller decreased when nanocomposite concentration increased. Tensile strength and Elongation at break improved in nanocomposite film by increasing concentration. Thermal properties of CMC/NCH were significantly (p < 0.05) lower than CMC/NCL. Emersion of crystalline peaks in X-ray analyses certified the presence of nanofiller in polymer. However, in high content (1%) cause to create aggregation of nanofiller in CMC film. Finally antibacterial activity against five pathogens was studied and good effective inhibition on CMC/NCH was observed while CMC/NCL had no inhibitory effect. These results show that use of CMC/NCH as a biocompatible film has more advantages than CMC/NCL biopolymer.


A survival score for patients with metastatic spinal cord compression from prostate cancer.
This study aimed to develop and validate a survival scoring system for patients with metastatic spinal cord compression (MSCC) from prostate cancer. Of 436 patients, 218 patients were assigned to the test group and 218 patients to the validation group. Eight potential prognostic factors (age, performance status, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits) plus the fractionation regimen were retrospectively investigated for associations with survival. Factors significant in the multivariate analysis were included in the survival score. The score for each significant prognostic factor was determined by dividing the 6-month survival rate (%) by 10. The total score represented the sum of the scores for each factor. The prognostic groups of the test group were compared to the validation group. In the multivariate analysis of the test group, performance status, ambulatory status, other bone metastases, visceral metastases, and interval from cancer diagnosis to radiotherapy were significantly associated with survival. Total scores including these factors were 20, 21, 22, 24, 26, 28, 29, 30, 31, 32, 33, 35, 37, or 39 points. In the test group, the 6-month survival rates were 6.5% for 20-24 points, 44.6% for 26-33 points, and 95.8% for 35-39 points (p < 0.0001). In the validation group, the 6-month survival rates were 7.4%, 45.4%, and 94.7%, respectively (p < 0.0001). Because the survival rates of the validation group were almost identical to the test group, this score can be considered valid and reproducible.


Psychopathology in Children and Adolescents in Lebanon Study (PALS): a national household survey.
Psychiatric disorders are among the leading causes of disability in children and adolescents globally. In Lebanon, a country that has endured a prolonged history of conflict and economic and political uncertainty, mental health surveys in children and adolescents have been limited to specific disorders or specific settings or cities. PALS (Psychopathology in Children and Adolescents in Lebanon Study) is the first study to screen a nationally representative sample of children and adolescents for psychiatric disorders and estimate the national prevalence of children and adolescents at risk of having a psychiatric disorder. A nationally representative household sample of 1517 children and adolescents (aged 5 years 0 months to 17 years 11 months) was recruited through a multi-stage stratified proportionate sampling technique between February 2018 and November 2018. Parents and adolescents completed a battery of self-reported scales including the Strengths and Feelings Questionnaire (SDQ), Mood and Feelings Questionnaire (MFQ), Screen for Child Anxiety and Emotional Related Disorders (SCARED), the Peer Relations Questionnaire (PRQ), General Health Questionnaire (GHQ), and Conflict Behavior Questionnaire (CBQ), Child Revised Impact of Events Scale (CRIES), and a demographic/clinical information questionnaire. Logistic regression models were used to examine the correlates of screening positive for psychiatric disorders. About a third of children and adolescents (32.7%, n = 497) screened positive for at least one psychiatric disorder, of whom only 5% (n = 25) reported ever seeking professional mental health help. Academic performance, having a chronic physical illness, higher parental GHQ scores, and involvement in bullying were associated with a higher odds of screening positive for a psychiatric disorder. Higher family income was negatively associated with screening positive for a psychiatric disorder. This first national study shows a high prevalence of psychiatric symptoms in Lebanese children and adolescents and an alarming treatment gap. School-based primary prevention programs or screening in primary care settings are key for early detection and management of psychiatric symptoms, and prevention of psychiatric disorders.


Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex-vivo skin tests.
GHK-Cu and HA are two commonly used skin care ingredients, both of which were reported to enhance collagen synthesis. This work aims to investigate their co-effect on collagen regulation. In cell experiments, human dermal fibroblasts were treated by a series of GHK-Cu and HA combinations, and the expressions of collagen I, IV, and VII were measured by qRT-PCR. The best formula screened out from cell experiments were further studied by ex-vivo skin model, and the content of collagen IV was quantified by immunofluorescence method. The combination GHK-Cu and HA was found to promote the generation of collagen I, IV, and VII. Especially, they form a synergy on collagen IV. At the ratio of 1:9, GHK-Cu and LMW HA deliver the strongest effect to elevate collagen IV synthesis by 25.4 times in cell test and 2.03 times in ex-vivo skin test. The co-effect of GHK-Cu and HA was revealed. Their synergy brings an insight to anti-aging technology: choosing proper molecular weight of HA and managing its ratio with GHK-Cu could enhance DEJ health via stimulating collagen IV synthesis.


Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study.
The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg with twice-daily salmeterol/fluticasone (SFC) 50/500 μg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up. IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75-0.93), ≥2 exacerbations (RR: 0.85, 95% CI: 0.70-1.03) and ≥2 exacerbations or ≥1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74-1.00). Prolonged time-to-first exacerbation was observed in all the groups according to exacerbation history. Moderate/severe exacerbations decreased with IND/GLY versus SFC, independent of previous treatment. IND/GLY significantly reduced rates of moderate/severe exacerbations treated with antibiotics (RR: 0.79, 95% CI: 0.67-0.93) and systemic corticosteroids and antibiotics (RR: 0.80, 95% CI: 0.70-0.91); rates of exacerbations treated with systemic corticosteroids alone were comparable (RR: 0.99, 95% CI: 0.80-1.22). Overall, IND/GLY demonstrated consistent beneficial effects versus SFC on moderate/severe exacerbations, independent of prior exacerbation history or treatment. The efficacy of IND/GLY on exacerbation prevention was superior to SFC for exacerbations treated with antibiotics with/without systemic corticosteroids and was similar for exacerbations treated with systemic corticosteroids alone.


Corrigendum: Co-infection of Phlebotomus papatasi (Diptera: Psychodidae) gut bacteria with Leishmania major exacerbates the pathological responses of BALB/c mice.
[This corrects the article DOI: 10.3389/fcimb.2023.1115542.].


Hospital Readmission and Social Risk Factors Identified from Physician Notes.
To evaluate the prevalence of seven social factors using physician notes as compared to claims and structured electronic health records (EHRs) data and the resulting association with 30-day readmissions. A multihospital academic health system in southeastern Massachusetts. An observational study of 49,319 patients with cardiovascular disease admitted from January 1, 2011, to December 31, 2013, using multivariable logistic regression to adjust for patient characteristics. All-payer claims, EHR data, and physician notes extracted from a centralized clinical registry. All seven social characteristics were identified at the highest rates in physician notes. For example, we identified 14,872 patient admissions with poor social support in physician notes, increasing the prevalence from 0.4 percent using ICD-9 codes and structured EHR data to 16.0 percent. Compared to an 18.6 percent baseline readmission rate, risk-adjusted analysis showed higher readmission risk for patients with housing instability (readmission rate 24.5 percent; p < .001), depression (20.6 percent; p < .001), drug abuse (20.2 percent; p = .01), and poor social support (20.0 percent; p = .01). The seven social risk factors studied are substantially more prevalent than represented in administrative data. Automated methods for analyzing physician notes may enable better identification of patients with social needs.


A biologically active hydrophobic T-1-conotoxin from the venom of Conus spurius.
A major, very hydrophobic peptide, sr5a, was purified from the venom duct of Conus spurius specimens collected in the Yucatan Channel, Mexico. Its amino acid sequence (IINWCCLIFYQCC; calculated monoisotopic mass assuming two disulfide bridges 1616.68 Da) was determined by automatic Edman degradation after reduction and alkylation, and confirmed by mass spectrometry (ESI monoisotopic mass, 1616.60; MALDI monoisotopic mass 1616.42 Da). The primary structure of sr5a showed the pattern that characterizes the family of the T-1-conotoxins, which belong to the T-superfamily of conotoxins. The disulfide bonds were determined by partial reduction and alkylation with N-ethylmaleimide, followed by total reduction and alkylation with 4-vinylpyridine, and automatic Edman sequencing. The connectivity of the Cys residues (I-III, II-IV) is the same as that found in the T-1-conotoxin family. When injected intracranially (2.0 nmol) into mice, peptide sr5a caused depressed behavioral activity.


Introduction to the Toxins' Special Issue on Evaluation of Cytotoxicity and Cytoprotection Effects of Natural Toxins.
The lifestyle associated with good nutritional quality of food is well known for its widely recognized health benefits, especially when rich in bioactive compounds [...].


Experimental results of cancellous autografts and frozen allografts transplanted into the canine frontal sinus.
Autograft and frozen allograft cancellous bone were each placed into one of the canine frontal sinus cavities of eight animals and analyzed by radiographic and histologic methods after one year. Complete and equal bony obliteration was demonstrated. Thus no advantage was seen in using an autograft over a frozen allograft in obliterating the frontal sinus cavity.


Oral benzquinamide in the treatment of nausea and vomiting.
The clinical antiemetic effect of bezquinamide by oral route at a dosage of 100 mg 3 times daily was evaluated by a controlled double-blind method in 183 studies of patients treated with 5-fluorouracil. The incidence of nausea and vomiting in benzquinamide-treated patients was equal to that in placebo-treated patients and significantly higher than that in patients treated with prochlorperazine, 10 mg 3 times daily. Sedation was the only significant side effect observed, and this occurred at essentially equal rates in benzquinamide- and prochlorperazine-treated patients.


A retroviral peptide encoded by mutated env p15E gene is recognized by specific CD8+ T lymphocytes on drug-treated murine mastocytoma P815.
Highly immunogenic ("xenogenized") tumour variants appear after treatment of murine mastocytoma P815 with the triazene derivative DTIC, a phenomenon associated with the appearance of structurally abnormal p15E env proteins in the variant cells. In the present study, we have isolated and sequenced several p15E cDNA gene fragments amplified by means of polymerase chain reaction (PCR) from parental (P815) and xenogenized (P815/DTIC) tumour cells. Compared to known p15E sequences in parental cells, one p15E sequence from xenogenized cells presented three distinct nucleotide changes, one of which was apparently unique to P815/DTIC DNA and cDNA upon single-nucleotide primer extension assay. One major histocompatibility complex (MHC) class I-binding peptide, corresponding to a putative mutation in the p15E sequence, was tested in parallel with the parental peptide for recognition by P815/DTIC-specific cytotoxic T cells in vitro. The results suggested that the amino acid substitution at the relevant position of the p15E protein may produce an antigenic T cell epitope. By skin test assay of mice primed with either the synthetic peptide or P815/DTIC cells, evidence was obtained that the mutated peptide is immunogenic in vivo, and that the neoepitope is expressed by P815/DTIC cells. In accordance with previous data in the L5178Y/DTIC tumour model system, these findings reinforce the notion that xenogenization of tumour cells may result in the expression of class I-binding mutated peptides of retroviral origin.


Effect of sodium salicylate, sodium oxalate, and sodium chloride on the micellization and adsorption of sodium deoxycholate in aqueous solutions.
The salicylate ion increases the rate of bile flow (choleretic effect) and bile salts are known to affect the colonic absorption of oxalate. Owing to this physiological relevance of salicylate and oxalate ions, critical micelle concentration (cmc) values of sodium deoxycholate (NaDC) were determined in aqueous sodium oxalate, sodium salicylate, and sodium chloride solutions by using surface tension, fluorescence, and EMF methods. The results indicate, besides a counterion effect, the influence of coanions on the cmc. In the range from 25 to 40 °C, cmc increases almost linearly with temperature. In the temperature range from 30 to 40 °C, the counterion binding constant β of NaDC micelles has the same value (0.17±0.01) in the presence of sodium chloride and sodium salicylate. On the other hand, in sodium oxalate solution β=0.05±0.02 when oxalate concentration is less than or equal to c* and β=0.48±0.04 above c*, where c*≈0.038 mol kg(-1). EMF measurements also supported this type of counterion binding to NaDC micelles in sodium oxalate solutions. In sodium oxalate solution, at c* a change in the shape of deoxycholate micelles is expected to take place. Salicylate, oxalate, and chloride coanions have a similar effect on the adsorption of NaDC. This study reveals that the choleretic effect of salicylate is not due to the influence of salicylate ions on the micellization of NaDC.


Dual-Interface-Reinforced Flexible Perovskite Solar Cells for Enhanced Performance and Mechanical Reliability.
Two key interfaces in flexible perovskite solar cells (f-PSCs) are mechanically reinforced simultaneously: one between the electron-transport layer (ETL) and the 3D metal-halide perovskite (MHP) thin film using self-assembled monolayer (SAM), and the other between the 3D-MHP thin film and the hole-transport layer (HTL) using an in situ grown low-dimensional (LD) MHP capping layer. The interfacial mechanical properties are measured and modeled. This rational interface engineering results in the enhancement of not only the mechanical properties of both interfaces but also their optoelectronic properties holistically. As a result, the new class of dual-interface-reinforced f-PSCs has an unprecedented combination of the following three important performance parameters: high power-conversion efficiency (PCE) of 21.03% (with reduced hysteresis), improved operational stability of 1000 h T90 (duration at 90% initial PCE retained), and enhanced mechanical reliability of 10 000 cycles n88 (number of bending cycles at 88% initial PCE retained). The scientific underpinnings of these synergistic enhancements are elucidated.


Association of HLA-DR/DQ polymorphism with myasthenia gravis in Tunisian patients.
Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction. MG has been shown to be associated with many human leukocyte antigens (HLA) in different populations. The aim of this study was to investigate the probable association between HLA-DR/DQ alleles and MG in Tunisian patients. HLA DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers (PCR-SSP) with 48 MG patients and 100 healthy individuals serving as the control group. Myasthenia gravis in Tunisian patients was found to be associated with the following alleles (p(c) denotes Bonferroni corrected probability values): HLA-DRB1*03 (p(c)<10(-3)), DRB1*04 (p(c)=0.005), DQB1*02 (p(c)=0.002) and, DQB1*03 (p(c)=0.007). Our data demonstrated a new HLA-MG predisposition with DRB1*04. The DRB1*03, DRB1*04, DQB1*02, and DQB1*03 alleles also could be predisposing genetic factors for MG in the Tunisian population.


Enamel demineralization during clear aligner orthodontic treatment compared with fixed appliance therapy, evaluated with quantitative light-induced fluorescence: A randomized clinical trial.
The objective of this prospective randomized clinical trial was to investigate the relationship between clear aligner (CA) therapy and the development of white spot lesions and compare it with orthodontic fixed appliance (FA) therapy. This was a prospective randomized clinical trial. The setting was the postgraduate orthodontic clinic at Jordan University of Science and Technology. A total of 49 patients (39 female, 10 male; mean age ± standard deviation, 21.25 ± 3 years) who required orthodontic treatment with either FAs or CAs were randomly allocated into 1 of 2 study groups. Eligibility criteria included healthy patients of both sexes (age range 17-24 years), Class I malocclusion with mild-to-moderate crowding (≤5 mm), nonextraction treatment plan, and optimum oral hygiene before treatment as determined by clinical examination. The participants were randomly assigned to a study group according to a simple randomization method using a coin toss by the patient; the text or tail side of the coin indicated treatment with CA (group 1), and the head side of the coin indicated orthodontic treatment with FA (group 2). Blinding was applicable for outcome assessment only. CA therapy was performed for group 1 and FA for group 2. Quantitative light-induced fluorescence (QLF) images were taken before treatment (T0) and 3 months later (T1). The QLF images were then analyzed to assess the research outcomes. The main outcome was the mean amount of fluorescence loss (ΔF). Number of newly developed lesions, deepest point in the lesion (ΔFMax), lesion area (pixels), and plaque surface area (ΔR30) were measured as secondary outcomes. Descriptive statistics and comparison within and between groups were calculated. In total, 42 of the 49 participants recruited completed the study (19 in the CA group and 23 in the FA group). The mean amount of fluorescence loss was 0.4% for the CA group (P = 0.283) and 1.2% for the FA group (P = 0.013). The difference between the 2 groups was significant (confidence interval [CI], -1.8 to -0.4; P = 0.002). The mean increase in lesion area was 82.2 pixels for the CA group (P <0.001) and 9.3 pixels for the FA group (P = 0.225). The difference between the 2 groups was significant (CI, -117 to -75.0; P <0.001). ΔR30 was 1.2% for the CA group and 10.9% for the FA group (CI, 6.847-12.479; P <0.001). The number of newly developed lesions in the CA group was 6 lesions/patient and 8.25 in the FA group (P = 0.039). No serious harm on the oral health of the participants in the 2 study groups was observed other than mild gingivitis associated with plaque accumulation. No serious harm was reported by any of the participants. Orthodontic treatment with CAs and FAs caused enamel demineralization. The CA group developed larger but shallower white spot lesions, whereas the FA group developed more new lesions with greater severity, but they were smaller in area. More plaque accumulation was found in the FA group compared with the CA group. NCT04107012. The protocol was published after trial commencement.


The role of the left end of the H-2b haplotype in the male-specific cytotoxic T cell response.
The male-specific cytotoxic T cell response was tested in various mouse strains. We found that priming with 10(7) nonirradiated or 2 x 10(7) X-irradiated cells (2000 Rad) was similarly effective in B6 mice. We have avoided possible allogeneic effects due to priming F1 hybrids with parental cells and tested all mice after the same time interval for generation of male-specific cytotoxic T lymphocytes in vitro. Under these conditions, we found an absolute requirement for H-2b gene products, encoded left of B, in order to see male-specific responses.


Interleukin-10 gene polymorphisms influence susceptibility to cachexia in patients with low-third gastric cancer in a Chinese population.
Interleukin (IL)-10 is a pleiotropic cytokine that can both stimulate and suppress the immune response. Previous studies have reported that IL-10 production was significantly elevated in cachectic patients, and it has been confirmed that polymorphisms of the IL10 gene could influence its expression. Therefore, we designed this study to investigate whether polymorphisms of the IL10 gene were associated with cachexia in patients with low-third gastric cancer in a Chinese population. 190 patients with low-third gastric cancer were included in this study. The serum levels of IL-10 were measured by radioimmunoassay. The single nucleotide polymorphisms (SNPs) at positions -1082A/G, -819T/C, and -592A/C in the IL10 gene promoter were analyzed using polymerase chain reaction (PCR) restriction fragment length polymorphism (PCR-RFLP). The serum levels of IL-10 were significantly higher in patients with cachexia than in those without (Z = -10.66, p < 0.001). Single SNP analysis showed that the frequency of the IL10 -1082G allele was increased in patients with cachexia (p = 0.02). The -1082AG and -819CC genotypes were observed to be associated with an increased risk of cachexia. In a logistic regression analysis adjusted for actual weight and carcinoma stage, the -1082AG genotype was associated with an odds ratio (OR) of 2.45 (95% CI 1.21, 4.96; p = 0.01), and the -819CC genotype was associated with an OR of 3.70 (95% CI 1.20, 11.39; p = 0.02) for cachexia. Furthermore, haplotype analysis of the -1082A/G, -819T/C, and -592A/C SNPs revealed that at least five haplotypes (ATA, ACC, GCC, ACA, and ATC) were present in this Chinese population, and the -1082G/-819C/-592C (GCC) haplotype was associated with a significantly increased risk of cachexia as compared with the ATA haplotype (OR = 2.42; 95% CI 1.17, 5.00; p = 0.02). Our results indicate that genetic polymorphisms of IL-10 may influence susceptibility to cachexia in patients with low-third gastric cancer in this Chinese population.


An unusual case of eosinophilia, myalgia and skin contractures: Shulman's disease revisited.
Shulman's disease (eosinophilic fasciitis) is a very rare autoimmune disorder with an unknown etiopathogenesis. During the initial period of disease, it usually causes limb and trunk edema followed by collagenous thickening of the subcutaneous fascia. Eosinophilia is a predominant laboratory finding during the initial phase of the disease and less prominent in the later phases. Patients may also present with arthritis, myositis, peripheral neuropathy, and rarely pleuropericarditis. Here, we are reporting a case of eosinophilic fasciitis presenting with vague constitutional symptoms, fever, and peripheral blood eosinophilia followed by rapidly evolving skin tightening with joint contractures and muscle stiffness, which misled the treating team toward Scleroderma and its overlap syndromes. The diagnosis was finally clinched by a full-thickness skin biopsy along with underlying fascia and muscle tissue from an effected area, with a gratifying treatment response to standard immune suppression.


A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families.
The RAD51C gene has been recently proposed as a high-penetrance breast and ovarian cancer gene. However, early replication studies have failed to confirm the finding. Thus, further studies in larger cohorts should be conducted in order to clarify the role of RAD51C as a cancer susceptibility gene. Here, we describe a high-resolution melting analysis (HRMA)-based method developed for presequence screening of RAD51C sequence variants. We have screened RAD51C sequence variants by HRMA in 492 breast cancer patients with family history of breast and/or ovarian cancer that were previously tested negative for BRCA1/2. All variants were confirmed by direct sequencing. We have detected 12 different RAD51C germ-line sequence variants, including eight transitions, two transversion, and two indels (insA, and delT). All these variants generated melting profiles which differ from wild type homozygous controls. Interestingly, we have identified one clearly pathogenic mutation (c.774delT) in the subset of 101 breast and ovarian cancer families, supporting that RAD51C is a human breast and ovarian cancer susceptibility gene.


Analysis of carries in signed digit expansions.
The number of positive and negative carries in the addition of two independent random signed digit expansions of given length is analyzed asymptotically for the (q, d)-system and the symmetric signed digit expansion. The results include expectation, variance, covariance between the positive and negative carries and a central limit theorem. Dependencies between the digits require determining suitable transition probabilities to obtain equidistribution on all expansions of given length. A general procedure is described to obtain such transition probabilities for arbitrary regular languages. The number of iterations in von Neumann's parallel addition method for the symmetric signed digit expansion is also analyzed, again including expectation, variance and convergence to a double exponential limiting distribution. This analysis is carried out in a general framework for sequences of generating functions.


Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing.
Steroidal resource occupies a vital proportion in the pharmaceutical industry attributing to their important therapeutic effects on fertility, anti-inflammatory and antiviral activities. Currently, microbial transformation from phytosterol has become the dominant strategy of steroidal drug intermediate synthesis that bypasses the traditional chemical route. Mycobacterium sp. serve as the main industrial microbial strains that are capable of introducing selective functional modifications of steroidal intermediate, which has become an indispensable platform for steroid biomanufacturing. By reviewing the progress in past two decades, the present paper concentrates mainly on the microbial rational modification aspects that include metabolic pathway editing, key enzymes engineering, material transport pathway reinforcement, toxic metabolic intermediates removal and byproduct reconciliation. In addition, progress on omics analysis and direct genetic manipulation are summarized and classified that may help reform the industrial hosts with more efficiency. The paper provides an insightful present for steroid biomanufacturing especially on the current trends and prospects of mycobacteria.


The Complexity of Two Colouring Games.
We consider two variants of orthogonal colouring games on graphs. In these games, two players alternate colouring uncoloured vertices (from a choice of m ∈ N colours) of a pair of isomorphic graphs while respecting the properness and the orthogonality of the partial colourings. In the normal play variant, the first player unable to move loses. In the scoring variant, each player aims to maximise their score, which is the number of coloured vertices in their copy of the graph. We prove that, given an instance with partial colourings, both the normal play and the scoring variant of the game are PSPACE-complete. An involution σ of a graph G is strictly matched if its fixed point set induces a clique and v σ ( v ) ∈ E ( G ) for any non-fixed point v ∈ V ( G ) . Andres et al. (Theor Comput Sci 795:312-325, 2019) gave a solution of the normal play variant played on graphs that admit a strictly matched involution. We prove that recognising graphs that admit a strictly matched involution is NP-complete.


Highly Selective and Quantitative Point-of-Care Diagnostic Method for Adrenaline.
Adrenaline, also known as epinephrine, is a neurotransmitter/hormone that is an important target in diagnostics. Development of an effective method for detecting it in the presence of other neurotransmitters is a challenging task. The electrochemical and fluorescent techniques commonly used have low selectivity in distinguishing among catecholamines. Herein, a small-molecule organic probe with an activated furfural moiety is reported to exploit the nucleophilicity of epinephrine to generate a bright-colored donor-acceptor Stenhouse adduct. Among nine common neurotransmitters or their analogues, only epinephrine was found to generate a unique colour change discernible with the naked eye, whereas the other ones remain unaffected. Under various in-field detection conditions, including solution, droplet, and paper strip-based detection, the colour change were also noticeable. The low detection limit of 1.37 nM and a limit of quantitation of 4.37 nM were achieved with simple UV/Vis methods in addition to the sub-ppm level sensing under visual conditions with naked eyes. The probe could be used for practical colorimetric measurements as a point-of-care tool without any complex and expensive machinery, making this approach accessible to all. In addition, using a simple smartphone, the determination of epinephrine concentrations is possible by using machine-learning techniques.


Cervical osteophytes: a cause of potentially life-threatening laryngeal spasms. Case report.
This 80-year-old woman presented with acute breathing difficulty during neck flexion when cyanosis also developed. The only potential causes were detected on cervical magnetic resonance imaging: two large anterior cervical osteophytes compressing the retropharyngeal space. Excision of these osteophytes resulted in resolution of the symptoms.


Glucose turnover in the young chicken (Gallus domesticus) using variously labeled (3H, U-14C) glucose tracers.
1. Various parameters of glucose metabolism--glucose replacement rate, percent recycling, mean transit time, and glucose mass were examined using various double labeled glucose tracers--2T-, U-14C; 3T-, U-14C; 4T-, U-14C; 5T-, U14C; and 6T-, U-14C. 2. Estimates of replacement rate were greatest for 2T-glucose (21.4 mg/min/kg), with 3T-, 4T-, 5T-, and 6T-glucose all having similar values (15.8, 15.6, 17.0, 16.0 mg/min/kg, respectively). 3. Calculated glucose mass based on all tritiated tracers (734-1086 mg/kg body weight) agreed closely with a direct determination of body glucose (969 mg/kg). 4. Reincorporation of tritium from 3H2O into glucose did not occur to any significant degree. 5. The young chick was found to have a very rapid rate of glucose turnover and high percent recycling compared to mammals.


The effects of nimodipine on cerebral blood flow and metabolism.
Nimodipine, a calcium entry blocker, was administered in increasing doses of 0.1-3.0 micrograms kg-1 min-1 to six dogs after they had recovered consciousness from a surgical preparation that was conducted under general anesthesia and while they were under the influence of total spinal anesthesia. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Nimodipine did not influence either CBF or CMRO2. There was a decrease in the cortical pyruvate level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with six control dogs. It has previously been reported that nimodipine increases the CBF in global ischemia with a potentially beneficial effect on the neurological outcome. With no effect on normal CBF or metabolism, this suggests that nimodipine may be useful in a variety of ischemic situations without fear of either a steal phenomenon or untoward effects on intracranial pressure.


C5a inhibitory peptide combined with gabexate mesilate is a clinically available candidate for preventing the instant blood-mediated inflammatory reaction.
The instant blood-mediated inflammatory reaction, characterized by activation of both the coagulation and complement cascades, is a serious obstacle to successful islet engraftment. No attractive protocol is clinically available as yet. The objective of the present study was to examine whether complementary peptide against an active region of C5a in combination with a clinically available anticoagulant could provide an effective protocol for suppression of the instant blood-mediated inflammatory reaction. Three islet equivalents per gram of syngeneic rat grafts were transplanted intraportally into 6 pairs of rats with streptozotocin-induced diabetes. Islets from the same donor were transplanted into each pair. In each pair, one rat was treated with C5a inhibitory peptide in addition to continuous intravenous infusion of gabexate mesilate and the other rat, injected with equivalent amount of saline solution, served as the control. In addition, 6 rats that received transplants from irrelevant donors were treated with the same dose of gabexate mesilate. We evaluated the cure rate, time to normoglycemia, liver insulin concentration in recipients, and results of in vivo glucose tolerance tests. The cure rate was remarkably improved and the time to normoglycemia in cured animals was significantly shortened with C5a inhibitor plus gabexate treatment. In six rats that received only gabexate mesilate, normoglycemia was not restored during the study. These data suggest that C5a inhibitory peptide combined with gabexate mesilate could be an attractive drug candidate without adverse effects to control the detrimental innate immune responses induced in clinical islet transplantation.


In vivo studies on DNA repair and turnover with age.
Since the capacity for DNA repair relative to other cellular processes should be an important parameter of mutagenesis, carcinogenesis, and also aging, this capacity should preferably be studied in intact animals. Thus, we developed autoradiographic techniques for measuring DNA repair directly in vivo. By these methods unscheduled DNA synthesis (UDS) was detected quantitatively as silver grains on epithelial cells of mouse skin after treatment with chemical carcinogens or UV irradiation, and on cerebral ganglion cells of aquarium fish after treatment with various chemical carcinogens. Several interesting findings so far obtained are presented. Possible age-related change in the UDS response was examined by the skin technique with mice of 2 and 18 months old. Similar dose-dependent induction of UDS was observed in mice of both ages after treatment with 4-hydroxyaminoquinoline 1-oxide; their levels of UDS at each dose were not significantly different. The dose-response curves for young and aged animals after UV irradiation showed similar increases to a plateau at low doses, but their responses to high doses were very different: in aged mice the UDS level decreased markedly with increase in the dose, whereas in young mice it remained at the same level. This suggests that in aged animals, high doses of UV irradiation cause deterioration of DNA repair systems, and that aged animals cannot repair extensive DNA damage efficiently. It is generally thought that DNA has a stable structure and a much slower turnover than other cellular components. Although the effect of DNA repair on DNA turnover may be insignificant, accumulation of repaired DNA in cells should result in detectable DNA turnover. Therefore, we investigated DNA turnover in postmitotic ganglion cells of rat retina. However, careful autoradiographic studies on pairs of eyes showed no detectable DNA turnover up to nearly their median life span (2 years). This result suggests that the DNA of post-mitotic cells, which are not replaced throughout the life span of the animal, is very stable and is possibly protected in some special way.


Comparison of dexmedetomidine and propofol for sedation in awake craniotomy: A meta-analysis.
Awake craniotomy (AC) is the preferred option for the resection of tumors adjacent to eloquent cortical areas and in cases of intractable epilepsy. It is mostly used to maintain the integrity of the brain during intracranial neurosurgical procedures. Awake craniotomy requires the use of ideal anesthetics, hypnotics, and analgesics to balance sedation, prompt the reversal of sedation, and prevent respiratory depression while maintaining communication between patient and medical team. Although a wide variety of anesthetics and hypnotics have been used for awake craniotomy over the past several decades, the optimal drug for the procedure has yet to be determined. The purpose of this meta-analysis was to compare dexmedetomidine and propofol in terms of intraoperative adverse events (i.e., hypertension, hypotension, nausea, vomiting, respiratory depression), patient and surgeon satisfaction, and procedure duration. We searched PubMed, Google Scholar, and the Cochrane Library for relevant articles published between the inception of these databases and April of 2022. The systematic search yielded 781 articles. After screening, we excluded 778 articles. The remaining three articles reporting 138 patients were selected for meta-analysis. This meta-analysis showed no statistically significant difference between propofol and dexmedetomidine related to intraoperative adverse events, patient satisfaction, or procedure duration. The only statistically significant result was surgeon satisfaction, which appeared to be higher in the dexmedetomidine group. Further high-quality randomized and controlled trials are needed to find a preferred agent for intraoperative sedation in awake craniotomy.


Optimizing the aryl-triazole of cjoc42 for enhanced gankyrin binding and anti-cancer activity.
Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play a key role in regulating cell proliferation, cell growth, and cell migration. These roles are largely due to gankyrin's protein-protein interaction with the 26S proteasome. We previously published a study exploring the aryl sulfonate ester of cjoc42 in an effort to enhance gankyrin binding and inhibit cancer cell proliferation. In order to further improve the gankyrin binding ability of the cjoc42 scaffold, an extensive SAR for the aryl-triazole moiety of cjoc42 was developed. Our cjoc42 derivatives exhibited enhanced gankyrin binding, as well as enhanced antiproliferative activity against Hep3B, HepG2, A549, and MDA-MB-231 cancer cell lines.


Specific incorporation of selenium into lysine- and glutamate- accepting tRNAs from Escherichia coli.
Amino acid transfer nucleic acids (tRNAs) that contain selenium-modified bases are synthesized by Escherichia coli in the presence of low levels (0.1-0.5 microM) of [75Se]selenite or [75Se]selenate. The amount of selenium incorporated (1-2 g atoms/100 mol of tRNA) was unchanged by 10-20-fold variations in selenium or sulfate concentrations or by the addition of 1 mM cysteine, sulfide, or sulfite. Specific incorporation of selenium (as opposed to nonspecific substitution for sulfur) was further indicated by the different reversed phase chromatographic elution patterns of 35S- and 75Se-labeled tRNAs isolated from cells labeled with 35SO2-4 and 75SeO2-4. Also, E. coli mutants unable to synthesize an abundant sulfur-modified base, 4-thiouracil, nevertheless produced normal levels of selenium-modified tRNAs. Two different methods of distinguishing between aminoacylated and nonaminoacylated tRNA, one which examined mobility during reversed phase chromatography and another which employed anti-AMP antibodies, indicated that over 50% of the selenium-containing tRNA had lysine or glutamate acceptor activity.


Fully-automated synthesis of 177Lu labelled FAPI derivatives on the module modular lab-Eazy.
To the best of our knowledge, manually production of [177Lu]Lu-FAPI radiopharmaceutical derivatives has been only described in literature. In this work, a fully-automated [177Lu]Lu-FAPI synthesis has been well designed for the first time using commercially available synthesis module. In addition to the development of an automated system with disposable cassette, quality control (QC) and stability studies were comprehensively presented. A fully automated synthesis of [177Lu]Lu-FAPI derivatives was achieved on the Modular Lab Eazy (ML Eazy) with high radiochemical yield ([177Lu]Lu-FAPI-04; 88% ± 3, [177Lu]Lu-FAPI-46; 86% ± 3). Chromatographic analysis indicated the formation of radiosynthesis with an absolute radiochemical purity (99%). Stability experiments clarified the durability of the products within 4 days. All obtained specifications are consistent to European Pharmacopoeia. A fully automated synthesis of [177Lu]Lu-FAPI radiopharmaceuticals was accomplished regarding quality control standards and quality assurance by using commercially available a modular approach namely ML Eazy with disposable customized cassette and template.


Outcome study of protective services: comparison of interviews and records as data sources.
This study explores a complex area for research, and yields, despite the problems, distinct indicators for fruitful further research.


Retear After Arthroscopic Rotator Cuff Repair Results in Functional Outcome Deterioration Over Time.
This study aimed to evaluate the effect of retear on long-term functional outcomes and glenohumeral joint osteoarthritis (OA) progression after arthroscopic rotator cuff repair (ASRCR). We retrospectively reviewed 201 patients who underwent ASRCR and were followed up for at least 5 years. Rotator cuff tendon structural integrity was evaluated using magnetic resonance imaging and/or ultrasonography. Pain, active range of motion, and the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) were evaluated for functional outcomes. To evaluate deterioration over time, the minimal clinically important difference value of pain and ASES were used. The mean follow-up period was 8.6 ± 2.2 years and overall retear rate was 21.4%. OA progression was strongly associated with retear (odds ratio 5.1, P < .001). Functional outcomes at the 2-year postoperative follow-up significantly improved compared to the preoperative status (all P < .017), regardless of retear. However, the retear group presented worse functional outcomes at the final follow-up (pain: 3.1 ± 2.6; ASES: 72.0 ± 17.4) than at the 2-year postoperative follow-up (pain: 1.2 ± 2.3, P = .014; ASES: 91.1 ± 9.9, P= .015) than the healed tendon group at final follow-up (pain: .6 ± 1.7; P < .001; ASES 95.5 ± 11.8; P < .001). The time for deterioration of pain (healed group vs. retear group: 5.5 ± 0.5 vs. 10.6 ± 0.4 years; P < .001) and ASES (healed group vs. retear group: 7.5 ± 0.5 vs. 12.8 ± 0.2 years; P < .001) decreased in the retear group. The functional status improved after ASRCR in short- and long-term follow-up, regardless of retear. However, retear was strongly associated with OA progression, and long-term functional outcomes deteriorated over time in retear cases, which was not observed during short-term follow-up. III, retrospective cohort study.


Multiple subdural hematomas associated with breakdancing.
A 17-year-old, previously healthy, male breakdancer presented with a three-month history of crescendo headache and newly identified papilledema. The patient was found to have four separate, unilateral extracranial collections. At surgery, three were subdural hematomas, and one was a probable arachnoid cyst containing a hematoma. These were removed, and the patient made an uneventful recovery with no neurosurgical sequelae. The possibility of serious head injury must be considered when evaluating headache in youngsters who engage in this new and apparently popular dance form.


[Myelodysplastic syndromes].
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic diseases with inefficient hematopoiesis. Diagnosis is based on the persistence of at least one cytopenia for more than 6 months, together with cytological and cytogenetic bone marrow abnormalities, a variety of other diagnosis being discarded. Most patients will die from the consequences of cytopenias. These diseases can progress to acute leukemia. The last WHO classification (2008) distinguishes 6 MDS types. An International Prognostic Scoring System (IPSS) based on the percentage of blast cells in the bone marrow, the cytogenetic abnormalities and the number of cytopenias completes the WHO classification. The patient care depends of the disease severity, cytogenetic abnormalities, age and performance status. Supportive care is required in all cases. In low risk patients, drugs are possibly used to correct cytopenias whereas in high risk patients, the treatment aims to increase survival through induction of a complete response. MDS classification may become molecular in the coming years, based on the genetic abnormalities that lead either to apoptosis of blood cell progenitors in the bone marrow or the accumulation of blast cells that precedes acute leukemia.


Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg2+/curcumin from injectable self-healing hydrogels.
Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.


Dialectical behavioral therapy informed treatment with deaf mental health consumers: an Australian pilot program.
This paper outlines the process of implementation of a dialectical behavioral therapy (DBT) informed treatment for Australian Deaf mental health consumers. The pilot project team members adapted DBT materials for the Australian Deaf population. Feedback was obtained from the pilot participants and modifications made during the pilot. Participant progress and therapeutic alliance were monitored using culturally valid tools. The DBT informed therapy approach was well received by this target group, with the observation and self report of improved interpersonal skills and emotional regulation. While labor intensive, the process of developing a DBT informed treatment program for Australian Deaf mental health consumers appears to be beneficial for this group. Culturally valid, objective measures of skill attainment need to be developed and further studies comparing different adapted therapeutic approaches would be useful.


Midazolam and fat-emulsion diazepam as intramuscular premedication. A double-blind clinical trial.
Sixty female patients were given, in random order, under double-blind conditions, either midazolam or fat-emulsion diazepam, intramuscularly, as premedication, 1 h before general anaesthesia. The dose of midazolam used was 0.13 mg/kg and that of diazepam 0.17 mg/kg. The degree of sedation, mood of the patient, and time at which onset of effect was perceptible were assessed before induction of anaesthesia, together with skin temperature and concentrations of midazolam or diazepam in plasma. Patients were interviewed postoperatively to discover their subjective evaluation of the premedication and to assess its amnesic effects. Midazolam was significantly superior (P less than 0.05) to diazepam as regards sedation. There were no differences in effects on mood of the patients between the two groups. Sixteen patients in the diazepam group and four in the midazolam group had no perception of onset of effect. The difference is significant (P less than 0.01). The skin temperature was, on average, 2 degrees C higher in the midazolam group than in the diazepam group (P less than 0.005). The mean plasma concentration was 67.8 +/- 24.5 micrograms/l in the midazolam group and 44.8 +/- 25.7 micrograms/l in the diazepam group. In only two cases was the concentration of diazepam above 100 micrograms/l (arbitrarily defined as the minimum sedative concentration). Subjective evaluation of efficacy significantly (P less than 0.002) favoured midazolam. Local pain was evident in two patients in the diazepam group, and three patients experienced nausea immediately after administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)


Effective atomic number and electron density of some biologically important lipids for electron, proton, alpha particle and photon interactions.
X-ray, γ-ray and charged particle interaction parameters of biomolecules are useful in medical diagnosis and radiation therapy as exposure to radiations can cause energy of photons and charged particles to be deposited in body through various interaction processes. With this in view, the effective atomic number (Zeff) and electron density (Neff) of some biologically important lipids for X-ray, γ-ray and charged particle interactions were studied in the energy range 10 keV-500 MeV using logarithmic interpolation method. A non-monotonic variation in Zeff values was observed for protons and alpha particles in low and intermediate energy regions respectively whereas a sudden increase in Zeff was observed for electron interaction in higher energy region. Zeff values were maximum in higher energy region for total electron interactions whereas maximum values of Zeff for total alpha particle interactions were at relatively lower energies. Highest Zeff values were found at lower energy region of photoelectric absorption dominance for photon interactions. Variation in Neff seems to be similar to variation in Zeff as they are inter-related.


Off with their heads: the need to criminalize some forms of scientific misconduct.
Improvement in policy for the management of scientific misconduct has been slow. While assurance of due process at the ORI level is now in place, similar protections at the institutional level and institutional responsibility for further oversight and a workplace where the responsible conduct of research can be practiced have not yet been addressed. In contrast, policy regarding human subject protection has evolved rapidly to reflect firmer norms, with decisive priority given to subject protection over scientific or social needs. Perhaps because scientific misconduct policy has the potential to harm the careers of individual scientists and harms to individual subjects are thought to be indirect, the scientific community has been successful in blocking every move toward testing more rigorous regulation. The mantras that scientists can discipline their own, and the price of competitive science is some level of scientific misconduct are not persuasive. The standards by which science is judged should not be an exception to those governing others who deal with the public's money and have a duty to the public interest.


Exosome-derived microRNAs in oral squamous cell carcinomas impact disease prognosis.
microRNA (miRNA) expression patterns have provided new insight as biomarkers of prognosis as well as novel therapeutic targets for several neoplasms. However, the role of exosomal miRNA in the prognosis of oral squamous cell carcinoma (OSCC) has not yet been completely clarified. Paired primary tumor and normal oral epithelial cells from OSCC patients were obtained, and the exosomal miRNA profiles between them were compared by miRNA microarray analysis. The miRNA levels in the serum exosomes of OSCC patients were verified by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Finally, the biological functions and the potential as a prognostic marker of the selected miRNA candidates were analyzed in the OSCC cells and patients, respectively. Exosomal miR-155 and miR-21 were significantly upregulated, and exosomal miR-126 was dramatically downregulated in the primary OSCC cells and the serum of OSCC patients. In the analysis of oncogenic behaviors, coculture with either miR-155-rich or miR-21-rich exosomes could promote cell proliferation and invasion accompanied with downregulation of PTEN and Bcl-6 tumor suppressors. Moreover, treatment with miR-126-rich exosomes inhibited oncogenic behaviors and oncogene EGFL7 expression in OSCC cells. Finally, exosomal miR-126 was reduced in the serum of the late-staged OSCC patients, and downregulation of blood exosomal miR-126 was associated with poor survival in OSCC patients. Exosomal miR-155 and miR-21 are oncogenic miRNAs which suppress PTEN and Bcl-6 expression, and exosomal miR-126 acts as a tumor suppressor which downregulates EGFL7 in OSCC. Furthermore, blood exosomal miRNAs may serve as biomarkers for the diagnosis and prognosis of OSCC.


Identification of robust diagnostic and prognostic gene signatures in different grades of gliomas: a retrospective study.
Gliomas are the most common primary tumors of the central nervous system. The complexity and heterogeneity of the tumor makes it difficult to obtain good biomarkers for drug development. In this study, through The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), we analyze the common diagnostic and prognostic moleculer markers in Caucasian and Asian populations, which can be used as drug targets in the future. The RNA-seq data from Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) were analyzed to identify signatures. Based on the signatures, the prognosis index (PI) of every patient was constructed to predict the prognostic risk. Also, gene ontology (GO) functional enrichment analysis and KEGG analysis were conducted to investigate the biological functions of these mRNAs. Glioma patients' data in the CGGA database were introduced to validate the effectiveness of the signatures among Chinese populations. Excluding the previously reported prognostic markers of gliomas from this study, the expression of HSPA5 and MTPN were examined by qRT-PCR and immunohistochemical assay. In total, 20 mRNAs were finally selected to build PI for patients from TCGA, including 16 high-risk genes and four low-risk genes. For Chinese patients, the log-rank test p values of PI were both less than 0.0001 in two independent datasets. And the AUCs were 0.831 and 0.907 for 3 years of two datasets, respectively. Moreover, among these 20 mRNAs, 10 and 15 mRNAs also had a significant predictive effect via univariate COX analysis in CGGA_693 and CGGA_325, respectively. qRT-PCR and Immunohistochemistry assay indicated that HSPA5 and MTPN over-expressed in Glioma samples compared to normal samples. The 20-gene signature can forecast the risk of Glioma in TCGA effectively, moreover it can also predict the risks of Chinese patients through validation in the CGGA database. HSPA5 and MTPN are possible biomarkers of gliomas suitable for all populations to improve the prognosis of these patients.


Development of a one-step synthesized red emission fluorescent probe for sensitive detection of viscosity in vitro and in vivo.
Diseases caused by metabolic abnormalities, such as inflammation and fatty liver, which are characterized by high viscosity, so it is necessary to detect the change of viscosity in vivo and in vitro. Due to the advantages of high sensitivity, noninvasive detection, high selectivity and real-time imaging, fluorescence imaging has become an effective means to detect biological parameters of biomolecules and life systems. Therefore, we have prepared a red emitting fluorescent probe NBI-V with easy synthesis which can ensure that the probe can be developed for the widely used to detection of viscosity changes in vivo and in vitro. The probe NBI-V has good stability, high response times, selectivity, and good biocompatibility. As the viscosity of a water-glycerol system increased from 1.29 cp to 937.48 cp, the fluorescence of NBI-V was increased by about 77 times. Biological experiments showed that the probe NBI-V can target mitochondria, and the Pearson correlation coefficient was as high as 0.89. What's more, it can distinguish normal liver from fatty liver, and can detect the viscosity changes caused by inflammation in mice.


Balloon embolectomy catheter-induced arterial injury: a comparison of four catheters.
This study compared four brands of balloon embolectomy catheters with respect to their mechanical characteristics and the histologic responses they elicit. Seventy-two 4F Becton-Dickinson, Edwards, Electro-Catheter, and Shiley catheters were studied. In vitro studies of penetration forces demonstrated that the forces required for arterial puncture were greatest for Shiley (295 +/- 22 gm) and least for Edwards catheter tips (217 +/- 11 gm) (p less than 0.05). This indicates that the Shiley catheter is least likely to puncture vessels in patients. Studies of balloon eccentricity showed that none of the balloons distended with excessive eccentricity. Studies of balloon emptying time demonstrated that the silicon Becton-Dickinson balloon required more than two times as long (5.7 +/- 1.2 seconds) as all other balloons to empty. Balloon emptying time reflects the ability of the surgeon to rapidly adapt the balloon to changing vessel diameter in patients. Shear forces were studied in cylindrical segments of arteries in vitro. Initial shear forces were significantly different among all catheters, Becton-Dickinson greater than Edwards greater than Shiley greater than Electro-Catheter (p less than 0.05). In contrast, during catheter withdrawal dynamic shear forces were similar among the four brands of catheters. Balloon embolectomies were performed in vivo in the common carotid and common femoral arteries in 18 anesthetized dogs. Histologic examinations of the vessels exposed to 50, 100, and 200 gm shear forces showed that myointimal hyperplasia increased with rising shear forces for all catheters (p less than 0.05), but that there were no differences in the degree of myointimal hyperplasia elicited by the different brands of catheters.(ABSTRACT TRUNCATED AT 250 WORDS)


Alteration of the expression of adenosine triphosphate-binding cassette transporters associated with bile acid and cholesterol transport in the rat liver and intestine during cholestasis.
Multidrug resistance protein 2 (Mrp2), Mrp3, adenosine triphosphate-binding cassette transporter g5 (Abcg5) and adenosine triphosphate-binding cassette transporter g8 (Abcg8) have been identified as bile acid or cholesterol transporter in the enterocytes as well as hepatocytes. The purpose of the present study was to evaluate intestinal and hepatic adenosine triphosphate-binding cassette transporter expressions during cholestasis. Experiment 1: Rats were subjected to bile duct ligation or sham operation. Blood, liver and small intestines were obtained 24 and 72 h after operation. Experiment 2: Rats were divided into four groups as follows: (i) control group; (ii) diosgenin group (fed with diosgenin in diet [1%(wt/wt)] for 7 days); (iii) ethinyl estradiol group (received ethinyl estradiol [5 mg/kg daily] for 5 days); and (iv) diosgenin-ethinyl estradiol group (received ethinyl estradiol and diosgenin). After treatment, blood, bile, liver and intestines were obtained. The mRNA related to lipid and bile acid metabolism was analyzed by reverse transcription polymerase chain reaction. Intestinal Mrp2 and Abcg5/Abcg8 mRNA expression remarkably decreased 24 h after bile duct ligation (43% and 61%/54% of sham operation) and recovered 72 h after bile duct ligation (103% and 95%/83% of sham operation). Intestinal Mrp3 mRNA expression did not change after bile duct ligation. Intestinal Mrp2 mRNA expression was remarkably increased in diosgenin and diosgenin-ethinyl estradiol groups in comparison with the control group. There were no significant differences in intestinal Mrp3 mRNA expression among the four groups. Hepatic Mrp3 mRNA expression was remarkably increased in the D, EE and DE groups in comparison with the control group (531%, 321% and 1160% of control, respectively, P < 0.01). Hepatic Abcg5 and Abcg8 mRNA expression decreased in ethinyl estradiol and diosgenin-ethinyl estradiol groups compared with the control group and there were no differences in intestinal Abcg5 and Abcg8 mRNA expressions among the four groups. Bile duct ligation affects not only hepatic but also the intestinal Mrp2 and Abcg5 and Abcg8 expressions. Intestinal Mrp2 mRNA level was regulated by factor in the lumen (e.g. diosgenin feeding). Cholestasis by ethinyl estradiol treatment was enhanced by diosgenin and the increase in hepatic Mrp3 mRNA level might affect the enhancement.


Electron diffraction analysis of the M412 intermediate of bacteriorhodopsin.
High resolution electron diffraction data have been recorded for glucose-embedded purple membrane specimens in which bacteriorhodopsin (bR) has been trapped by cooling slowly to below--100 degrees C under continuous illumination. Thin films (OD approximately 0.7) of glucose-embedded membranes, prepared as a control, showed virtually 100% conversion to the M state, and stacks of such thin film specimens gave very similar x-ray diffraction patterns in the bR568 and the M412 state in most experiments. To be certain that any measured differences in diffraction intensity would be real, two independent sets of electron diffraction intensities were recorded for near-equatorial, i.e. (hkO), reflections. Little correlation was indeed observed between these two sets for delta F values at low resolution (15-5.0 A, 49 reflections), but the correlation coefficient is approximately 0.3 at high resolution (5.0-3.3 A, 218 reflections). Thus, while most of the measured difference is error, the mean delta F and the correlation coefficient can be used to estimate the smaller, true delta F due to structural changes occurring in the M state. The magnitude of this estimated true mean delta F is equal to what would be produced if approximately five to seven nonhydrogen atoms were moved to structurally uncorrelated (i.e., new) positions in the M state. Movements of a few amino acid side chains, and repositioning of atoms of the retinal group and the associated lysine side chain after trans-cis isomerization, are the most probable causes of the observed intensity changes in the M state. The difference Fourier map, calculated in projection at 3.5-A resolution, shows only very small peaks, the largest of which are confined, however, to the region of the protein.


[Evidence on the effects of crisis resolution teams, home treatment and assertive outreach for people with mental disorders in Germany, Austria and Switzerland - a systematic review].
Based on international randomized controlled trials (RCT) the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) recommends acute treatment in the domestic environment (AHU) and intensive outreach treatment (IAB) with the highest level of evidence; however, due to large differences in national healthcare systems the transference of results from international studies to the healthcare systems in Germany, Austria and Switzerland could be limited. Evaluation of studies on outreach psychiatric treatment forms in Germany, Austria and Switzerland and discussion of the results in the light of international evidence. A systematic literature search for clinical trials on outreach community treatment from Germany, Austria and Switzerland was conducted in the PubMed database. A total of 19 publications were identified which could be assigned to 5 publications on 4 studies with 2857 patients on AHU and 14 publications on 10 studies with 3207 patients on IAB. The studies on AHU showed this treatment form to be superior regarding the duration of inpatient stay and healthcare costs. The studies on IAB showed more positive outcomes in comparison to controls regarding symptoms, severity of illness, substance abuse, functioning level, remission, satisfaction with treatment, quality of life, healthcare costs, work and housing situations. The studies from Germany, Austria, and Switzerland suggest that outreach community treatment is superior regarding several outcome parameters. Thus, there are no indications suggesting that international evidence could not be valid for these countries. Additionally, with one RCT for AHU and one for IAB the requirements for an evidence level of 1b for outreach community treatment in the healthcare systems in question are fulfilled.


Combined kidney and liver transplantation for familial haemolytic uraemic syndrome.
Recurrent haemolytic uraemic syndrome (HUS) is a genetic form of thrombotic microangiopathy that is mostly associated with low activity of complement factor H. The disorder usually develops in families, leads to end stage renal disease, and invariably recurs after kidney transplantation. We did a simultaneous kidney and liver transplantation in a 2-year-old child with HUS and a mutation in complement factor H to restore the defective factor H, with no recurrence of the disease. The operation was successful, and at discharge, the child had healthy kidney and liver function, with no sign of haemolysis.


Mitochondrial adaptation decreases drug sensitivity of persistent triple negative breast cancer cells surviving combinatory and sequential chemotherapy.
Triple negative breast cancer (TNBC) is an aggressive malignancy for which chemotherapy remains the standard treatment. However, between 3 and 5 years after chemotherapy, about half patients will relapse and it is essential to identify vulnerabilities of cancer cells surviving neoadujuvant therapy. In this study, we established persistent TNBC cell models after treating MDA-MB-231 and SUM159-PT TNBC cell lines with epirubicin and cyclophosphamide, and then with paclitaxel, for a total of 18 weeks. The resulting chemo-persistent cell lines were more proliferative, both in vitro and in xenografted mice. Interestingly, MDA-MB-231 persistent cells became less sensitive to chemotherapeutic drugs, whereas SUM159-PT persistent cells kept similar sensitivity compared to control cells. The reduced sensitivity to chemotherapy in MDA-MB-231 persistent cells was found to be associated with an increased oxidative phosphorylation (OXPHOS) and modified levels of tricarboxylic acid cycle (TCA) intermediates. Integration of data from proteomics and metabolomics demonstrated TCA cycle among the most upregulated pathways in MDA-MB-231 persistent cells. The absence of glucose and pyruvate impeded OXPHOS in persistent cells, while the absence of glutamine did not. In contrast, OXPHOS was not modified in control cells independently of TCA substrates, indicating that MDA-MB-231 persistent cells evolved towards a more pyruvate dependent profile. Finally, the inhibition of pyruvate entry into mitochondria with UK-5099 reduced OXPHOS and re-sensitized persistent cells to therapeutic agents. Together, these findings suggest that targeting mitochondrial pyruvate metabolism may help to overcome mitochondrial adaptation of chemo-persistent TNBC.


Botulinum Toxin Type A for Painful Temporomandibular Disorders: Systematic Review and Meta-Analysis.
This systematic review investigated the effectiveness and safety of botulinum toxin type A (BTX-A) for painful temporomandibular disorders. We searched for randomized controlled trials (RCTs) in 10 databases, from inception to February 12, 2019 (MEDLINE, EMBASE, CENTRAL, LILACS, BBO, Web of Science, Scopus, ClinicalTrials.gov, WHO and OpenGrey). We included 12 RCTs that compared BTX-A versus inactive or active interventions. BTX-A was slightly more effective than placebo for pain reduction at 1 month: mean difference -1.74 points (0-10 scale), 95% confidence interval -2.94 to -.54, 3 RCTs, 60 participants, I-square (I2) = 0%. However, there were no significant differences at 3 and 6 months. BTX-A was similar to no treatment for pain reduction at 3 and 6 months. BTX-A was more effective than conventional treatment and low-level laser therapy for pain reduction at 1, 6, and 12 months, but less effective than facial manipulation for pain reduction at 3 months. BTX-A was not associated with a significant increase in the risk of adverse events. The quality of the evidence was low, and results are insufficient to support the use of BTX-A for painful temporomandibular disorders. High-quality RCTs are needed to increase confidence in effect estimates. PERSPECTIVE: BTX-A for painful temporomandibular disorders appears to be well tolerated. For pain reduction, BTX-A is slightly more effective than placebo only at 1 month; conventional treatment and low-level laser at 1, 6, and 12 months. Low-quality evidence limits the applicability of these findings and precludes recommendations for practice.


Risk for Alzheimer's disease: A review of long-term episodic memory encoding and retrieval fMRI studies.
Many risk factors have been identified that predict future progression to Alzheimer's disease (AD). However, clear links have yet to be made between these risk factors and how they affect brain functioning in early stages of AD. We conducted a narrative review and a quantitative analysis to better understand the relationship between nine categories of AD risk (i.e., brain pathology, genetics/family history, vascular health, head trauma, cognitive decline, engagement in daily life, late-life depression, sex/gender, and ethnoracial group) and task-evoked fMRI activity during episodic memory in cognitively-normal older adults. Our narrative review revealed widespread regional alterations of both greater and lower brain activity with AD risk. Nevertheless, our quantitative analysis revealed that a subset of studies converged on two patterns: AD risk was associated with (1) greater brain activity in frontal and parietal regions, but (2) reduced brain activity in hippocampal and occipital regions. The brain regions affected depended on the assessed memory stage (encoding or retrieval). Although the results clearly indicate that AD risks impact brain activity, we caution against using fMRI as a diagnostic tool for AD at the current time because the above consistencies were present among much variability, even among the same risk factor.


Long-term lung cancer survivors have permanently decreased quality of life after surgery.
Retrospective evaluation of the long-term health-related quality of life (HRQoL) among survivors after non-small-cell lung cancer (NSCLC) surgery. A total of 586 patients underwent surgery for NSCLC in Helsinki University Central Hospital between January 2000 and June 2009. Two validated quality-of-life questionnaires, the 15D and the EORTC QLQ-C30 with its lung cancer-specific module, QLQ-LC13, were sent to the 276 patients alive in June 2011. Response rate was 83.3%. Results of the 15D were compared with those of an age- and gender-standardized general population. Median follow-up was 5 years. Compared with a general population, our patients had a significantly lower 15D total score, representing their total HRQoL and scores for dimensions of mobility, breathing, usual activities, depression, distress, and vitality. The patients, however, scored significantly higher on vision, hearing, and mental function. NSCLC survivors may suffer postoperatively from permanently reduced long-term HRQoL compared to an age- and gender-matched general population. This is essential patient information as more patients are surviving longer.


Evidence for perinatal and child health care guidelines in crisis settings: can Cochrane help?
It is important that healthcare provided in crisis settings is based on the best available research evidence. We reviewed guidelines for child and perinatal health care in crisis situations to determine whether they were based on research evidence, whether Cochrane systematic reviews were available in the clinical areas addressed by these guidelines and whether summaries of these reviews were provided in Evidence Aid. Broad internet searches were undertaken to identify relevant guidelines. Guidelines were appraised using AGREE and the clinical areas that were relevant to perinatal or child health were extracted. We searched The Cochrane Database of Systematic Reviews to identify potentially relevant reviews. For each review we determined how many trials were included, and how many were conducted in resource-limited settings. Six guidelines met selection criteria. None of the included guidelines were clearly based on research evidence. 198 Cochrane reviews were potentially relevant to the guidelines. These reviews predominantly addressed nutrient supplementation, breastfeeding, malaria, maternal hypertension, premature labour and prevention of HIV transmission. Most reviews included studies from developing settings. However for large portions of the guidelines, particularly health services delivery, there were no relevant reviews. Only 18 (9.1%) reviews have summaries in Evidence Aid. We did not identify any evidence-based guidelines for perinatal and child health care in disaster settings. We found many Cochrane reviews that could contribute to the evidence-base supporting future guidelines. However there are important issues to be addressed in terms of the relevance of the available reviews and increasing the number of reviews addressing health care delivery.


Oral squamous cell carcinoma: epidemiological study and risk factor assessment based on a 39-year series.
Oral squamous cell carcinoma (OSCC) remains a challenge for head and neck surgeons, with low 5-year survival rates despite improvements in diagnostic techniques and therapies. This retrospective observational study was performed to evaluate the epidemiology and risk factors in a cohort of 666 patients with invasive OSCC over a 39-year period. Risk factors assessed were age, sex, toxic habits, premalignant lesions, tumour location and size, and neck involvement, and pathological factors such as surgical margins, tumour thickness, perineural invasion, and bone invasion. These factors were analysed over time, and their influence on recurrence and survival rates examined. Results were compared with those of current epidemiological studies in the literature. This series showed a tendency to diagnosis at older ages (P<0.001) and decreased differences in sex distribution (P<0.001) over time. Regarding risk factors, tobacco and alcohol drinking increased significantly in females, but remained stable in males. Forty percent of the patients developed recurrences during follow-up; the relapse rate did not improve over time (45.6% in the 1980s to 36.1% in 2010-2017). The 5-year survival rate also remained stable over time, ranging from 62.7% (1980s) to 71.7% (2010-2017). This epidemiological study analysed trends across four decades in a stable cohort, with results that may be extrapolated to the populations of European countries. The results confirmed that recurrence rates and survival rates have not improved over time, despite better surgical treatments and new therapies. Further studies are needed to improve knowledge about genetics and tumour behaviour in oral cancer.


Inverted conversions: reading the Bible and writing the lesbian subject in Oranges are not the only fruit.
The prominence of the Bible as intertext in Oranges Are Not the Only Fruit, both a coming-of-age and a coming-out story, has puzzled readers. This paper argues that Winterson's articulation of a lesbian subject is actually inseparable from her revisionary engagement of the Bible. By repeatedly turning and re-turning several types of narrative about the origins of identity and story-making. Winterson reconstructs both some biblical texts and a hallmark of the gay and lesbian literary tradition as precursors for the prophetic voice of the main character.


Cross-study comparisons of self-reported alcohol consumption in four clinical groups.
Clinical research on the chronic effects of alcohol has been difficult to evaluate and compare because of the failure by investigators to quantify self-reported alcohol consumption. The authors describe four diverse groups of patients who were treated for alcohol and/or drug abuse. After devising a procedure for comparing the data from these studies, they found that patient self-reports of alcohol consumption may be less distorted than commonly assumed. The present findings are consistent with current research indicating that self-reports of alcohol use are reliable and clinically consistent. The authors also discuss the relationship between neuropsychological impairment and measures of alcohol and drug abuse.


Circular RNA profiling reveals that circCOL3A1-859267 regulate type I collagen expression in photoaged human dermal fibroblasts.
Production of type I collagen declines is a main characteristic during photoaging, but the mechanism is still not fully understood. Circular RNAs (circRNAs) are a class of newly identified non-coding RNAs with regulatory potency by sequestering miRNAs like a sponge. It's more stable than linear RNAs, and would be a useful tool for regulation of gene expression. However, the role of circRNAs in collagen expression during photoaging is still unclear. Here we performed deep sequencing of RNA generated from UVA irradiated and no irradiated human dermal fibroblasts (HDFs) and identified 29 significantly differentially expressed circRNAs (fold change ≥ 1.5, P < 0.05), 12 circRNAs were up-regulated and 17 circRNAs were down-regulated.3 most differentially expressed circRNAs were verified by qRT-PCR and the down-regulated circCOL3A1-859267 exhibited the most significantly altered in photoaged HDFs. Overexpression of circCOL3A1-859267 inhibited UVA-induced decrease of type I collagen expression and silencing of it reduced type I collagen intensity. Via a bioinformatic method, 44 miRNAs were predicted to binding with circCOL3A1-859267, 5 of them have been confirmed or predicted to interact with type I collagen. This study show that circCOL3A1-859267 regulate type I collagen expression in photoaged HDFs, suggesting it may be a novel target for interfering photoaging.


Chromosome location of four genes in Leishmania.
Chromosome-sized DNA molecules from Leishmania isolates (L. mexicana amazonensis, L. mexicana mexicana, L. chagasi, L. major, L. donovani, and L. braziliensis) were separated by orthogonal field alternation gel electrophoresis. The chromosome locations of four genes were mapped. The alpha-tubulin and rRNA genes each mapped to a single chromosome size class. The beta-tubulin and the 5'-spliced-leader-sequence genes were found on more than one chromosome size class and showed variation of hybridization profiles across species.


Effect of probiotics on hemodynamic changes and complications associated with cirrhosis: A pilot randomized controlled trial.
Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance. To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial. This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis; 24 patients received probiotics (Saccharomyces boulardii) for 3 mo, and 16 patients received a placebo over the same period. Liver function and the systemic hemodynamic status were evaluated pre- and post-intervention. Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators. Cardiac output and systemic vascular resistance were calculated. Following a 3-mo course of probiotics in comparison to the control group, we observed amelioration of hyperdynamic circulation [a decrease in cardiac output (P = 0.026) and an increase in systemic vascular resistance (P = 0.026)] and systemic inflammation [a decrease in serum C-reactive protein levels (P = 0.044)], with improved liver function [an increase in serum albumin (P = 0.001) and a decrease in the value of Child-Pugh score (P = 0.001)] as well as a reduction in the severity of ascites (P = 0.022), hepatic encephalopathy (P = 0.048), and cholestasis [a decrease in serum alkaline phosphatase (P = 0.016) and serum gamma-glutamyl transpeptidase (P = 0.039) activity] and an increase in platelet counts (P < 0.001) and serum sodium level (P = 0.048). Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.


Application and control of flexible alternating current transmission system devices for voltage stability enhancement of renewable-integrated power grid: A comprehensive review.
This paper presents a comprehensive review on the application and control of Flexible Alternating Current Transmission Systems (FACTS) devices in order to improve voltage stability of power grid with high share of renewable energy systems. The rise in the development of renewable energy technologies is driven by the attempts to mitigate the effects of global warming. In addition, global energy demand continues to rise as new electricity-driven systems such as electric vehicles are being developed and as remote locations are being connected to the grid. These changes in the power grid formation comes with attendant challenges which must be addressed. One of these challenges is voltage stability issues. This paper therefore explores the applications of FACTS devices for voltage stability improvement and points out the future research direction in the area of voltage stability enhancement by FACTS devices for modern power grids characterized by increasing levels of renewable energy penetration.