Sleep characteristics of middle-aged adults with non-alcoholic fatty liver disease: findings from the Shahrekord PERSIAN cohort study.
Several studies have reported short sleep duration in people with non-alcoholic fatty liver disease (NAFLD) but other sleep characteristics have been less studied. We aimed to assess the cross-sectional association of NAFLD with sleep duration and quality in an Iranian population sample. We used data from 9,151 participants in the Shahrekord Prospective Epidemiological Research Studies in Iran (PERSIAN) Cohort Study, including 1,320 that were diagnosed with NAFLD. Log-binomial regression models sequentially adjusted for sociodemographic, lifestyle, clinical and biological variables were used to estimate relative risks (RR) and 95% confidence intervals (95% CI) for the association between NAFLD and sleep characteristics. Participants with NAFLD had shorter sleep duration, later wake-up time and bedtime, worse sleep efficiency, and more frequent daytime napping and use of sleeping pills, in age- and sex-adjusted models. After controlling for sociodemographic, lifestyle, clinical, and biological variables the associations remained strong for sleep efficiency (per 10%, RR = 0.92, 95%CI: 0.88-0.96) and use of sleeping pills (RR = 1.48, 95%CI: 1.17-1.88). The association between NAFLD and sleep efficiency was stronger in participants aged > 60 years (RR = 0.81, 0.70-0.93) and 40-60 years (RR = 0.87, 0.82-0.94), compared with those aged < 40 years (P-heterogeneity < 0.001). More frequent daytime napping in participants with NAFLD, compared with non-NAFLD, was observed in males but not females (P-heterogeneity = 0.007), and in those with body mass index (BMI) < 30 but not in obese participants (P-heterogeneity < 0.001). Diagnosis of NAFLD is associated with several poor sleep characteristics in middle-aged Iranians. Although longitudinal studies would help to clarify the direction of causality, our study shows that poor sleep is an important aspect of NAFLD.


Genital Chlamydia infection in hyperlipidemic mouse models exacerbates atherosclerosis.
Atherosclerosis is a chronic inflammatory disease, and recent studies have shown that infection at remote sites can contribute to the progression of atherosclerosis in hyperlipidemic mouse models. In this report, we tested the hypothesis that genital Chlamydia infection could accelerate the onset and progression of atherosclerosis. Apolipoprotein E (Apoe-/-) and LDL receptor knockout (Ldlr-/-) mice on a high-fat diet were infected intra-vaginally with Chlamydia muridarum. Atherosclerotic lesions on the aortic sinuses and in the descending aorta were assessed at 8-weeks post-infection. Systemic, macrophage, and vascular site inflammatory responses were assessed and quantified. Compared to the uninfected groups, infected Apoe-/- and Ldlr-/- mice developed significantly more atherosclerotic lesions in the aortic sinus and in the descending aorta. Increased lesions were associated with higher circulating levels of serum amyloid A-1, IL-1β, TNF-α, and increased VCAM-1 expression in the aortic sinus, suggesting an association with inflammatory responses observed during C. muridarum infection. Genital infection courses were similar in Apoe-/-, Ldlr-/-, and wild type mice. Further, Apoe-/- mice developed severe uterine pathology with increased dilatations. Apoe-deficiency also augmented cytokine/chemokine response in C. muridarum infected macrophages, suggesting that the difference in macrophage response could have contributed to the genital pathology in Apoe-/- mice. Overall, these studies demonstrate that genital Chlamydia infection exacerbates atherosclerotic lesions in hyperlipidemic mouse and suggest a novel role for Apoe in full recovery of uterine anatomy after chlamydial infection.


Remote magnetic navigation versus manual catheter ablation of atrial fibrillation: A single center long-term comparison.
Data comparing remote magnetic catheter navigation (RMN) with manual catheter navigation (MCN) ablation of atrial fibrillation (AF) is lacking. The aim of the present prospective observational study was to compare the outcome of RMN versus (vs.) MCN ablation of AF with regards to AF recurrence. The study comprised 667 consecutive patients with a total of 939 procedures: 287 patients were ablated using RMN, 380 using MCN. There was no significant difference between the groups at baseline. After 2.3 ± 2.3 years of follow-up, 23% of the patients in the MCN group remained free of AF recurrence compared to 13% in the RMN group (p < .001). After analysis of 299 repeat ablations (133 MCN, 166 RMN) there was a significantly higher reconnection rate of pulmonary veins after RMN ablation p < .001). In multivariable Cox-regression analysis, RMN ablation was an independent risk factor for AF recurrence besides age, persistent AF, number of isolated pulmonary veins, and left atrial diameter. Procedure time, radiofrequency application time and total number of ablation points were higher in the RMN group. Total fluoroscopy time and total fluoroscopy dose were significantly lower for RMN. Complication rates did not differ between groups (p = .842), although the incidence of significant pericardial effusion was higher in the MCN group (seven cases vs. three in RMN group). In our study the AF recurrence rate and pulmonary vein reconnection rate is higher after RMN ablation with a similar complication rate but reduced probability of pericardial effusion when compared to MCN.


Treatment of metastatic renal cell carcinoma and renal pelvic cancer.
A better understanding of the molecular biology of renal cell carcinoma (RCC) and the emergence of molecular targeted drugs have revolutionized the treatment for patients with metastatic RCC (mRCC). Multi-targeted tyrosine kinase inhibitors (sorafenib and sunitinib) and mammalian target of rapamycin inhibitors (temsirolimus and everolimus) have recently shown superiority over interferon-α or placebo. However, while the molecular targeted drugs have demonstrated encouraging results, these drugs have also sometimes induced unexpected adverse events. Control of adverse events is important to obtain the maximum effectiveness and sustain quality of life for patients. Because renal pelvic cancer has many similarities in pathogenesis with urinary bladder cancer, the same chemotherapeutic regimen is often proposed for patients with metastatic renal pelvic cancer. Combined chemotherapy with gemcitabine and cisplatin is now widely considered to be first-line chemotherapy against these metastatic diseases; however, there are still unresolved problems with this treatment, including the limited survival benefit. To select new therapeutic modalities, a more profound understanding of the molecular biology of renal pelvic cancer is crucial. The purpose of this review is to summarize the current evidence supporting the role and activities of new chemotherapeutic agents and to reveal potential future directions in the management of mRCC and renal pelvic cancer.


Mixed epithelial polyps in association with hereditary non-polyposis colorectal cancer providing an alternative pathway of cancer histogenesis.
A member of a hereditary non-polyposis colorectal cancer (HNPCC) family developed two colorectal cancers and multiple polyps within four years of a negative colonoscopic examination. One of the cancers was only 4 mm in diameter and showed the gross and endoscopic appearances of a de novo carcinoma. Microscopic examination of multiple levels revealed a mixed hyperplastic polyp/adenoma (mixed polyp) in contiguity with the cancer. The colon harboured additional polyps of which five were tubular adenomas, seven were hyperplastic polyps and seven were mixed polyps (architecturally compatible with hyperplastic polyps but with atypical cytology). Atypical features of the mixed polyps included tripolar mitoses, bizarre chromatin aggregations and multinucleation. One mixed polyp showed DNA microsatellite instability. Under the influence of the mutator defect, hyperplastic polyps may develop atypical or adenomatous features and show progression to carcinoma. Such an alternative morphogenetic pathway could explain the differing molecular and pathological profiles of cancers showing DNA microsatellite instability.


Incidence and Severity of Postoperative Pharyngolaryngeal Complications following Use of Baska Mask versus Endotracheal Intubation.
Use of Baska Mask, since a supraglottic airway device, could result in low incidence of postoperative pharyngolaryngeal complications. The objectives were to compare the effect of Baska Mask versus endotracheal intubation on the incidence and severity of postoperative sore throat (POST), postoperative hoarseness of voice (POHV), and postoperative cough (POC). This prospective randomized study was conducted in a tertiary care teaching institute in 120 patients undergoing short laparoscopic surgeries. Airway was secured using with low-pressure, high-volume cuffed endotracheal tube in Group T and with Baska Mask in Group B. POST, POC, and POHV were assessed at 2, 6, 12, and 24 h after surgery. Those with Grade III score throat were managed by gargling with dispersible aspirin 75 mg. Pearson's Chi-square test, Fisher's exact test, and independent sample t-test were used as applicable. Group B patients required significantly more attempts at securing airway. Incidence of POST was significantly higher in Group T as compared to that Group B at 2, 6, 12, and 24 h after surgery. POC was significantly more in Group T at 2, 6, and 12 h. No patient in Group B had POC at 12 and 24 h. POHV showed significantly higher incidence in Group T at 2 and 6 h. No patient in Group B had hoarseness at 6, 12, and 24 h. Use of Baska Mask as compared to endotracheal intubation significantly reduces the incidence and severity of pharyngolaryngeal complications such as POST, POC, and POHV in patients undergoing short laparoscopic surgeries.


The relation between "long-term exposure" to lifestyle during youth and young adulthood and risk factors for cardiovascular disease at adult age.
To investigate the relationship between lifestyle (dietary intake of macronutrients, smoking behavior, alcohol consumption and daily physical activity) from 13-29 years of age ("long-term exposure") and cardiovascular disease (CVD) risk factors (lipoprotein levels, blood pressure, body fatness, and body composition) at the age of 29 years. The study was part of the Amsterdam Growth and Health Study, which began in 1977, and in which repeated measurements were carried out over a period of 17 years on 181 subjects (98 females and 83 males). "Long-term exposure" to smoking behavior was inversely related to high density lipoprotein cholesterol (HDL) levels (p = 0.02) and positively to the total cholesterol/HDL ratio (p = 0.05). Both smoking behavior and alcohol consumption were inversely related to blood pressure (p < 0.01). "Long-term exposure" to daily physical activity was inversely related to body fatness (p < 0.01), but for females positively to the waist/hip ratio (p < 0.01). No relationship was found between the dietary intake of macronutrients and the CVD risk factors. When "long-term exposure" was limited to adolescence (13-16 years of age) only the relationship between daily physical activity and the waist/hip ratio for females remained significant (p < 0.01). "Long-term" smoking behavior was related to a high risk profile regarding hypercholesterolemia, but to a low risk profile regarding blood pressure. The latter was also found for "long-term" alcohol consumption. "Long-term" daily physical activity was related to a low risk profile regarding body fatness; but for females, surprisingly, to a high risk profile regarding body fat distribution.


Nazarov reagents for convergent and expedient synthesis of new steroids.
[reaction: see text] A new methodology for the convergent synthesis of tetracyclic compounds was developed. Two new bicyclic Nazarov reagents of type II were synthesized, and their cycloaddition with 2-carbomethoxy-2-cyclohexenone I was studied. This cycloaddition afforded new interesting steroidal backbones.


Genetic diversity of groEL and msp4 sequences of Anaplasma ovis infecting camels from Tunisia.
To date, no information is available regarding the infection of camels (Camelus dromedarius) by Anaplasma ovis in North African region. Several animal species can be infected by A. ovis which further complicates its natural infection cycle. In this paper, we investigated the occurrence and the genetic diversity of A. ovis in camels and ticks collected from them in Tunisia and the risk factor analysis. Camel blood samples (n = 412) and tick (n = 300) samples, identified as Hyalomma dromedarii (n = 149, 49.6%), H. impeltatum (n = 142, 47.3%) and H. excavatum (n = 9, 3%), were analyzed by conventional PCR followed by the sequencing of msp4 and groEL genes. A. ovis DNA was identified in five camels (1.2%), but not in infesting ticks (0%). The microscopic examination revealed the specific infection of camel erythrocytes by Anaplasma inclusions. The msp4 and groEL typing confirmed the natural infection of camels by A. ovis and revealed two different msp4 genotypes earlier detected in Tunisian small ruminants and their infested ticks, and five different and novel groEL genetic variants forming a separately sub-cluster within A. ovis cluster. The occurrence of different A. ovis strains specific to camels associated with a low prevalence of this Anaplasma species in camels may enrich knowledge regarding the distribution and the transmission cycle of this bacterium in arid and Saharan areas of Tunisia.


Audiogram of the big brown bat (Eptesicus fuscus).
The audiograms of three big brown bats (Eptesicus fuscus) were determined using a conditioned avoidance procedure. The average audiogram ranged from 0.850 kHz at 106 dB to 120 kHz at 83 dB SPL, with a best threshold of 7 dB at 20 kHz and a distinct decrease in sensitivity at 45 kHz. The results confirm those of a previous study by Dalland (1965a) that the big brown bat has good high-frequency hearing coupled with poor low-frequency hearing. Comparative analysis suggests that the bat's good high-frequency hearing initially evolved for passive sound localization and that it was later coopted for use in echolocation. In addition, the restricted low-frequency hearing of the big brown bat is typical of mammals with good high-frequency hearing.


Familial psychiatric illness and obstetric complications in early-onset affective disorder. A case-control study.
Early-onset affective disorder is associated with obstetric complications and a high familial risk of psychiatric illness, in particular psychosis. In a matched case-control study, we investigated 47 adult in-patients with major depressive disorder or bipolar 1 disorder, who had earlier in life presented to a child psychiatry department. Cases were matched on sex, social class and ethnic group with 47 controls, who were admitted to hospital for affective disorders in adult life but had no psychiatric contact before the age of 21. We found that both psychiatric disorder in first-degree relatives and a history of obstetric complications were associated with early onset. Childhood symptoms did not predict the type of adult affective disorder.


Perioperative cerebral perfusion in aortic arch surgery: a potential link with neurological outcome.
The aim of this study was to examine whether perioperative changes in cerebral blood flow (CBF) relate to postoperative neurological deficits in patients undergoing aortic arch surgery involving antegrade selective cerebral perfusion (ASCP). We retrospectively analysed data from patients who underwent aortic arch surgery involving ASCP and perioperative transcranial Doppler assessments. Linear mixed-model analyses were performed to examine perioperative changes in mean bilateral blood velocity in the middle cerebral arteries, reflecting changes in CBF, and their relation with neurological deficits, i.e. ischaemic stroke and/or delirium. Logistic regression analyses were performed to explore possible risk factors for postoperative neurological deficits. In our study population (N = 102), intraoperative blood velocities were lower compared to preoperative levels, and lowest during ASCP. Thirty-six (35%) patients with postoperative neurological deficits (ischaemic stroke, n = 9; delirium, n = 25; both, n = 2) had lower blood velocity during ASCP compared to patients without (25.4 vs 37.0 cm/s; P = 0.002). Logistic regression analyses revealed lower blood velocity during ASCP as an independent risk factor for postoperative neurological deficits (odds ratio = 0.959; 95% confidence interval: 0.923, 0.997; P = 0.037). Lower intraoperative CBF during ASCP seems independently related to postoperative neurological deficits in patients undergoing aortic arch surgery. Because CBF is a modifiable factor during ASCP, our observation has significant potential to improve clinical management and prevent neurological deficits.


Convolutional Neural Network for Predicting Thyroid Cancer Based on Ultrasound Elastography Image of Perinodular Region.
We aimed to develop deep learning models based on perinodular regions' shear-wave elastography (SWE) images and ultrasound (US) images of thyroid nodules (TNs) and determine their performances in predicting thyroid cancer. A total of 1747 American College of Radiology Thyroid Imaging Reporting & Data System 4 (TR4) thyroid nodules (TNs) in 1582 patients were included in this retrospective study. US images, SWE images, and 2 quantitative SWE parameters (maximum elasticity of TNs; 5-point average maximum elasticity of TNs) were obtained. Based on US and SWE images of TNs and perinodular tissue, respectively, 7 single-image convolutional neural networks (CNN) models [US, internal SWE, 0.5 mm SWE, 1.0 mm SWE, 1.5 mm SWE, 2.0 mm SWE of perinodular tissue, and whole SWE region of interest (ROI) image] and another 6 fusional-image CNN models (US + internal SWE, US + 0.5 mm SWE, US + 1.0 mm SWE, US + 1.5 mm SWE, US + 2.0 mm SWE, US + ROI SWE) were established using RestNet18. All of the CNN models and quantitative SWE parameters were built on a training cohort (1247 TNs) and evaluated on a validation cohort (500 TNs). In predicting thyroid cancer, US + 2.0 mm SWE image CNN model obtained the highest area under the curve in 10 mm < TNs ≤ 20 mm (0.95 for training; 0.92 for validation) and TNs > 20 mm (0.95 for training; 0.92 for validation), while US + 1.0 mm SWE image CNN model obtained the highest area under the curve in TNs ≤ 10 mm (0.95 for training; 0.92 for validation). The CNN models based on the fusion of SWE segmentation images and US images improve the radiological diagnostic accuracy of thyroid cancer.


Delta-aminolevulinate dehydratase enzyme activity and the oxidative profile of pregnant women being treated for acute toxoplasmosis.
The aim of this study was to investigate the clinical and oxidative profile, including the activity of the enzyme delta-aminolevulinate dehydratase (δ-ALA-D), in women who acquired toxoplasmosis during pregnancy and used the triple regimen (sulfadiazine + pyrimethamine + folinic acid [SPFA]) as treatment. These parameters have not been evaluated in pregnant women with toxoplasmosis who used the triple regimen. A total of 53 pregnant women were recruited and divided into two groups: control (C; n = 27) and acute toxoplasmosis (AT; n = 26). Clinical data and blood samples were obtained from all patients. The clinical profile was analyzed by checking parameters such as body mass index, blood pressure, and complete blood count. Oxidative stress was evaluated by quantifying protein (P-SH) and non-protein (NP-SH) thiol groups, vitamin C, plasma iron reduction capacity (FRAP), δ-ALA-D enzyme activity, reactive substances to thiobarbituric acid (TBARS), and nitric oxide (NO). Changes in hematological parameters (increased red cell distribution width and decreased hemoglobin and mean corpuscular hemoglobin concentration), increased antioxidant system (P-SH, NP-SH, FRAP, δ-ALA-D enzyme activity), as well as damage markers (TBARS and NO), were significantly elevated in pregnant women with toxoplasmosis, compared to those in the control group. Pregnant women treated for this acute infection showed increased damage markers, as well as a significant increase in the antioxidant system, including the activity of the δ-ALA-D enzyme. Given this evidence, it is suggested that these changes occur as a form of compensation, with a possible contribution from drug therapy.


Color appearance depends on the variance of surround colors.
The perceived color at each point in a visual scene depends on the relationship between light signals from that point, and light signals from surrounding areas of the scene. In the well known phenomenon of simultaneous color contrast, changing the overall brightness or hue of an object's surround induces a complementary shift in the perceived brightness or hue of the object's color. Color contrast is thought to contribute to color constancy with changes in illumination. We report a new type of simultaneous color contrast, in which changing only the variance (i.e. contrasts and saturations), but not the mean, of colors in a test spot's surround induces a complementary shift in the perceived contrast and saturation of the test spot's color. Objects appear much more vivid and richly colored against low-contrast, gray surrounds than against high-contrast, multicolored surrounds. Color appearance depends not just on the mean color of the surround, but also on the distribution of surround colors about the mean. This novel form of simultaneous color contrast is inconsistent with a variety of models of color appearance, including those based on sensitivity regulation at the receptor level, and those in which the effects of complex surrounds on color appearance can be reduced to adaptation to the illuminant or induction from a homogeneous 'equivalent surround'. It tends to normalize the gamut of perceived colors in each visual scene and may also contribute to color constancy under viewing conditions that affect contrast.


[Direct fluorescent and indirect immunofluorescent assay in buffy coat for candidemia diagnosis in pediatric patients: a comparative study].
The diagnosis of candidemia by blood culture has poor sensitivity; therefore, immunossupresed patients and those with risk factors may receive empirical antifungal therapy, wich is potentially toxic. Fluorescent tests have been developed to obtain an early and more sensitive diagnosis than blood culture. The aim of this study was to compare indirect immunofluorescence vs direct calcofluor white fluorescence in buffy coat for candidemia diagnosis. Sensitivity, specificity, predictive values, of positive and negative samples were 60%, 86%, 33%, 95% and 90%, 80%, 35%, 99%, for indirect immunofluorescence and calcofluor white, respectively.


Arabidopsis cell death in compatible and incompatible interactions with Alternaria brassicicola.
Two strains of necrotrophic Alternaria brassicicola, Ab40857 and Ab42464, are virulent on Korean cabbage and several wild types of Arabidopsis thaliana. Interaction between Ab42464 and Col-0 was compatible, whereas interaction between Ab40857 and Col-0 was incompatible. The loss of defense, no death (dnd) 1 function abrogated the compatibility between Ab42464 and Col-0, and the accelerated cell death (acd) 2 mutation attenuated the Col-0's resistance against Ab40857. These two fungal strains induced PR1 transcription in Col-0. Ab40857 accelerated transcription of PDF1.2, THI2.1, CAT, and POX by 12 h compared to those challenged with Ab42464. More abundant cell death was observed in Col-0 infected with Ab42464, however, callose deposition was evident in the incompatible interaction. Remarkably, Ab40857-infected areas of acd2-2 underwent rampant cell death and Ab42464 triggered callose production in dnd1-1. Furthermore, the incompatibility between Ab40857 and Col-0 was nullified by the coronatine-insensitive 1 (coi1) and phytoalexin-deficient 3 (pad3) mutations but not by nonexpresser of PR genes (npr1) and pad4. Ab40857 induced abundant cell death in pad3. Taken together, cell death during the early infection stage is a key determinant that discriminates between a compatible interaction and an incompatible one, and the resistance within Col-0 against Ab40857 is dependent on a defense-signaling pathway mediated by jasmonic acid and PAD3.


Sudden cardiac death in persons with normal (or near normal) hearts.
I have tried to provide a broad overview of the problem of cardiac arrest in the absence of structural heart disease or in the presence of minimal disease, as well as those disease states that are difficult to recognize. Exciting progress in this field has been made in recent years and I anticipate that we will continue to make progress in the future.


Adoptive cellular therapy for cytomegalovirus infection following allogeneic stem cell transplantation using virus-specific T cells.
Adoptive transfer of virus-specific T cells offers the potential for accelerating reconstitution of antigen-specific immunity and limiting the morbidity and mortality of viral infections following allogeneic haematopoietic stem cell transplantation. However, the logistics of producing virus-specific T cells and the risk of inducing graft-versus-host disease secondary to the infusion of alloreactive clones have limited the application of cellular therapies. We report the results in patients of pre-emptive and prophylactic therapy with cytomegalovirus-specific T cells. Cells were administered at early time points following transplantation (when the risk of GVHD is greatest) either prophylactically or following the detection of CMV DNA by a PCR-based surveillance technique. Massive in vivo expansions of CMV-specific cytotoxic T-lymphocytes (3-5 log) were observed in patients within days of adoptive transfer. Viral titers were decreasing within 5 days, in some patients the T-cell receptor CDR3 lengths of CMV-specific CTL expanding in vivo were identical to those of the transferred cells. A low incidence of late cytomegalovirus reactivation was seen and no significant toxicities were observed. Our findings indicate that application of cell lines generated by either short-term in vitro cultures or by direct selection using gamma-capture, which allow expansion of both CD4(+) and CD8(+) virus-specific T cells, is both feasible and effective in a clinical environment. These simple in vitro methodologies should allow widespread application of adoptive transfer of virus-specific T cells.


Production of ultra-low-sulfur gasoline: an equilibrium and kinetic analysis on adsorption of sulfur compounds over Ni/MMS sorbents.
High performance nickel-based micro-mesoporous silica (Ni/MMS) sorbent was prepared by incipient wetness impregnation with ultrasonic aid (IWI-u) for adsorptive desulfurization (ADS) of commercial gasoline and simulated fuels. The sorbents were characterized with BET, XRD, TPR, SEM, HRTEM and TG/DTG. These results show that 20 wt%Ni/MMS (IWI-u) can still retain the framework of MMS and nickel particles were homogeneously distributed in the MMS channels without any aggregation, which improved significantly the ADS performance of the sorbents. The studies on the ADS kinetics indicate that the adsorption behavior of thiophene (T), benzothiophene (BT) and dibenzothiophene (DBT) over 20 wt%Ni/MMS (IWI-u) can be described appropriately by pseudo second-order kinetic model. The intraparticle diffusion model verified that the steric hindrance and intraparticle diffusion were the rate controlling step of the adsorption process of DBT molecules. Langmuir model can be used to describe the adsorption isotherms for T, BT and DBT due to low coverage. The regeneration sorbent maintains the sulfur removal efficiency of 85.9% for 6 cycles.


Coronary heart disease in mothers and fathers of adult children with alcohol use disorders.
Having a family member with an alcohol use disorder (AUD) may negatively affect a person's health. Our aim was to study the long-term risk of coronary heart disease (CHD) in parents who have an offspring with AUD. Cohort study with Cox regression models and co-sibling analyses. Sweden. From population registers, we selected all parent-offspring pairs in which the parent was born in Sweden between 1945 and 1965. Baseline was set when the offspring was 15 years old and AUD was assessed from medical and criminal registers. The parents were followed for CHD during a mean follow-up of 18 years. Hazard ratios (HRs) in mothers and fathers were calculated and adjusted for potential confounders (year of birth, age at childbirth, sex of the child, parent' AUD, educational level, and marital status). In mothers, the adjusted HR for CHD was 1.24 (95% CI = 1.19-1.28) in relation to having a child with AUD. In fathers, the HR for CHD was lower than in mothers but still increased; the adjusted HR was 1.08 (95% CI = 1.05-1.12). In the co-sibling analyses, the HRs for mothers were similar to the HRs estimated from the population-based sample, but in fathers the association did not remain significant (HR = 0.98 [0.90-1.06]). In Sweden, there appears to be an association between having an offspring with alcohol use disorder and increased risk of developing coronary heart disease. For fathers, the association did not remain in co-sibling analyses.


Intrapartum nipple stimulation therapy for labor induction: a randomized controlled external pilot study of acceptability and feasibility.
Nipple stimulation is purported as a natural and inexpensive method for inducing labor, but its use is understudied. We aimed to assess whether conducting a large randomized controlled trial comparing intrapartum nipple stimulation therapy with oxytocin infusion is feasible and acceptable to patients and obstetrical care providers. This single-center parallel-group randomized controlled external pilot study (ClinicalTrials.gov Identifier NCT04756089) included women at ≥36 weeks of gestation who were planned to receive exogenous oxytocin for their labor induction. Women who were <18 years old, non-English speaking, or with fetuses at increased risk of neonatal intensive care were excluded. Stratified by parity, women were randomized 3:1 to intrapartum nipple stimulation therapy or immediate receipt of oxytocin. Women assigned to nipple stimulation therapy were asked to stimulate with an electric breast pump or by hand for periods of at least 30 minutes, with breaks as needed for up to 15 minutes at a time, for at least a cumulative 2 hours before considering initiation of oxytocin, and to complete intrapartum diaries. Labor characteristics and outcomes were examined. Validated questionnaires were used to assess the participants' pain level during the intervention, their sense of control during childbirth, and their breastfeeding success. Primary outcome measures were recruitment, adherence to study protocol and follow-up, and crossover rates. A total of 620 women underwent labor induction from March 13, 2021 to June 23, 2021. Of 557 potentially eligible women, 53 were approached by available research staff. Of the 53 women, 24 (45%) consented and enrolled: 18 randomized to nipple stimulation and 6 randomized to oxytocin. Moreover, 1 woman assigned to nipple stimulation withdrew because of delay of clinical care and received oxytocin (crossover rate of 1/24 [4%]), and 1 woman assigned to oxytocin did not receive it because of spontaneous labor progress. All other participants followed their assigned intervention. The 17 women who performed nipple stimulation stimulated for a median duration of 198 (interquartile range, 125-291) minutes and required a median of 69 (interquartile range, 21-80) minutes of stimulation before achieving at least 3 contractions in a 10-minute window, averaged >30 minutes (also known as "adequate" contractions). Among those assigned to nipple stimulation therapy, 15 of 17 women (88%) later received oxytocin infusion before delivery. The median times from intervention start to delivery were 16.4 (interquartile range, 0.6-28.2) hours for women assigned to nipple stimulation and 20.6 (interquartile range, 14.2-23.4) hours for women assigned to oxytocin infusion. Of note, 12 women (50%) completed their postpartum study questionnaires. Random assignment to either intrapartum nipple stimulation therapy or oxytocin infusion for labor induction was feasible and acceptable to patients and obstetrical care providers.


Improved capacity for influenza surveillance in the WHO Eastern Mediterranean Region: Progress in a challenging setting.
The World Health Organization Regional Office for Eastern Mediterranean has partnered with the United States Centers for Disease Control and Prevention (CDC) to strengthen pandemic influenza preparedness and response in the Region since 2006. This partnership focuses on pandemic preparedness planning, establishing and enhancing influenza surveillance systems, improving laboratory capacity for detection of influenza viruses, estimating the influenza disease burden, and providing evidence to support policies for the introduction and increased use of seasonal influenza vaccines. Various published and unpublished data from public and WHO sources, programme indicators of the CDC cooperative agreement and Pandemic Influenza Preparedness Framework were reviewed and analysed. Analyses and review of the programme indicators and published articles enabled us to generate information that was unavailable from only WHO sources. Most (19/22) countries of the Region have established influenza surveillance system; 16 countries in the Region have designated National Influenza Centres. The Region has seen considerable improvement in geographic coverage of influenza surveillance and influenza detection. Virus sharing has improved and almost all of the participating laboratories have achieved a 100% efficiency score in the WHO external quality assessment programme. At least seven countries have estimated their influenza disease burden using surveillance data and at least 17 are now using seasonal influenza vaccines as a control strategy for influenza illness. The Region has achieved substantial progress in surveillance and response to seasonal influenza, despite the adverse effects to the health systems of many countries due to acute and protracted emergencies and other significant challenges.


Functional and oximetric assessment of patients after lung reduction surgery.
The goal of this study was to clarify the issue of functional oxygen requirement by regimented exercise oximetry in patients undergoing lung reduction surgery. Thirty-seven patients underwent lung reduction surgery and were followed up for at least 3 months. Patients routinely completed a 6-week program of cardiopulmonary rehabilitation. Preoperative and postoperative spirometry, dyspnea scores, 6-minute walk distances, respiratory mechanics, and exercise oximetry were recorded. After the operation, patients had a 37% increase in forced vital capacity and a 59% increase in forced expiratory volume in 1 second. Six-minute walk distance increased from 913 +/- 310 feet before the lung reduction operation to 1202 +/- 274 feet 6 months after the operation (p < 0.001). Maximal inspiratory and expiratory pressures were significantly increased in 16 patients after lung reduction surgery. Perceived dyspnea was significantly improved. Exercise pulse oximetry demonstrated that 83% of patients met American Thoracic Society criteria for supplemental oxygen use before lung reduction surgery. After the operation, 70% of patients continued to meet American Thoracic Society criteria for supplemental oxygen use. Notably, 10 patients with exertional desaturation while breathing room air discontinued supplemental oxygen use because of a reduction in dyspnea. These findings demonstrate significant subjective and functional improvements related to lung reduction surgery. Exercise-induced hypoxia was not reversed by lung reduction surgery. Discontinuance of supplemental oxygen use owing to reduction in dyspnea and improved physical performance may not be warranted in lieu of continued exertional desaturation.


Affinity capture in bottom-up protein analysis - Overview of current status of proteolytic peptide capture using antibodies and molecularly imprinted polymers.
Antibody-based affinity capture has become the gold standard in sample preparation for determination of low-abundance protein biomarkers in biological matrices prior to liquid chromatography-mass spectrometry (LC-MS) determination. This comprises both capture of intact proteins prior to the digestion step and capture of proteolytic peptides after digestion of the sample. The latter can be performed both using antibodies specifically developed to capture target proteolytic peptides, as well as by the less explored use of anti-protein antibodies to capture the proteolytic epitope peptide. Molecularly imprinted polymers (MIPs), also called plastic antibodies are another affinity-based approach emerging as sample preparation technique in LC-MS based protein biomarker analysis. The current review gives a critical and comprehensive overview of proteolytic peptide capture using antibodies and MIPs in LC-MS based protein biomarker determination during the last five years. The main emphasis is on capture of non-modified peptides, while a brief overview of affinity capture of peptides containing post-translational modifications (PTMs) is provided.


The hand of the musician: the kinematics of the bidigital finger system with anatomical restrictions.
Tendons of the fingers are frequently interconnected by anatomic structures that limit the displacements of these tendons relative to each other. In this paper a bidigital finger system in which such interconnections between tendons are present is kinematically modelled. Using this model, an exhaustive description of the effects on finger movement of connections between the different tendons of the fingers is given. The study provides a context for the interpretation of typical difficulties of finger coordination in musicians, especially in pianists and string players.


The Psychosocial Impact of the COVID-19 Pandemic on Chronic Care Patients.
The COVID-19 pandemic has had a profound and pervasive impact on psychosocial health and disrupted care systems world-wide. Our research aims to assess the psychosocial impact of the pandemic and related changes in chronic care provision on patients with chronic obstructive pulmonary disease (COPD) and heart failure. A qualitative survey using semi-structured interviews was held among patients with COPD and heart failure. Using randomized sampling, 23 patients with COPD, heart failure, or both were recruited to participate in semi-structured interviews. Interviews were held by phone or videocall. The survey was held during the summer of 2021, when strict national containment strategies were widely implemented but gradually loosened and vaccination was ongoing. Inductive coding using Gioia's approach was used to analyze the data in Atlas.Ti 9.1 software. Using an iterative approach, the data were synthesized in a data structure and data table, which was analyzed using an interpretative approach. We found 3 aggregate dimensions in which the COVID-19 pandemic has a negative impact on psychosocial health of patients with chronic disease: (1) perceived vulnerability to disease, (2) influence of health policy, and (3) a mismatch of supply and demand of health care. In these dimensions, the impact of the COVID-19 crisis was found to have a negative impact on psychosocial well-being, compounded by national strategies to contain the pandemic and a disruption of chronic care for patients. Health care providers should be aware of a multidimensional nature of psychosocial distress for chronic disease patients due to the COVID-19 crisis. Future practice and health policy could be improved by increasing awareness among health care providers, promote regular attention for psychosocial well-being of patients, provision of clear information related to the pandemic, and strategies to secure continuity of care. Results of this study might be further explored in larger studies.


Differentiating challenge reactivity from psychomotor activity in studies of children's psychophysiology: considerations for theory and measurement.
Current methods of assessing children's physiological "stress reactivity" may be confounded by psychomotor activity, biasing estimates of the relation between reactivity and health. We examined the joint and independent contributions of psychomotor activity and challenge reactivity during a protocol for 5- and 6-year-old children (N = 338). Measures of parasympathetic reactivity (respiratory sinus arrhythmia [RSA]) and sympathetic reactivity (preejection period [PEP]) were calculated for social, cognitive, sensory, and emotional challenge tasks. Reactivity was calculated relative to both resting and a paired comparison task that accounted for psychomotor activity effects during each challenge. Results indicated that comparison tasks themselves elicited RSA and PEP responses, and reactivity adjusted for psychomotor activity was incongruent with reactivity calculated using rest. Findings demonstrate the importance of accounting for confounding psychomotor activity effects on physiological reactivity.


Nutrient modulation based process engineering strategy for improved butanol production from Clostridium acetobutylicum.
The present study demonstrates a process engineering strategy to achieve high butanol titer and productivity from wild type Clostridium acetobutylicum MTCC 11274. In the first step, two different media were optimized with the objectives of maximizing the biomass and butanol productivity, respectively. In the next step, attributes of these two media compositions were integrated to design a two-stage fed-batch process which resulted in maximal butanol productivity of 0.55 g L-1 h-1 with titer of 13.1 g L-1 . Further, two-stage fed-batch process along with combinatorial use of magnesium limitation and calcium supplementation resulted in the highest butanol titer and productivity of 16.5 g L-1 and 0.59 g L-1 h-1 , respectively. Finally, integration of the process with gas stripping and modulation of feeding duration resulted in a cumulative butanol titer of 54.3 g L-1 and productivity of 0.58 g L-1 h-1 . The strategy opens up possibility of developing a viable butanol bioprocess. © 2019 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2771, 2019.


Screening siRNAs against host glycosylation pathways to develop novel antiviral agents against hepatitis B virus.
Hepatitis B virus (HBV) relies on glycosylation for crucial functions, such as entry into host cells, proteolytic processing and protein trafficking. The aim of this study was to identify candidate molecules for the development of novel antiviral agents against HBV using an siRNA screening system targeting the host glycosylation pathway. HepG184.108.40.206 cells that consistently produce HBV were employed for our in vitro study. We investigated the effects of siRNAs that target 88 different host glycogenes on hepatitis B surface antigen (HBsAg) and HBV DNA secretion using the siRNA screening system. We identified four glycogenes that reduced HBsAg and/or HBV DNA secretion; however, the observed results for two of them may be due to siRNA off-target effects. Knocking down ST8SIA3, a member of the sialyltransferase family, significantly reduced both HBsAg and HBV DNA secretion. Knocking down GALNT7, which transfers N-acetylgalactosamine to initiate O-linked glycosylation in the Golgi apparatus, also significantly reduced both HBsAg and HBV DNA levels. These results showed that knocking down the ST8SIA3 and GALNT7 glycogenes inhibited HBsAg and HBV DNA secretion in HepG188.8.131.52 cells, indicating that the host glycosylation pathway is important for the HBV life cycle and could be a potential target for the development of novel anti-HBV agents.


Disentangling spatial conflicts in mental perspective taking.
The present experiment was conducted to examine the cognitive processes underlying mental perspective taking in remembered environments. Participants learned a layout of everyday objects from multiple randomly chosen perspectives. They were then blindfolded and tested for their spatial knowledge by having them point to unseen object locations from imagined perspectives. The acoustic display of a first object name informed participants about the to-be-imagined position, a second object name about the to-be-imagined heading, before a third object name identified the target they should point to with a joystick. The choice of object triplets allowed for independent variation of head-direction disparity (HDD), i.e., the difference in heading direction between real and imagined perspective, and object direction disparity (ODD), i.e., the egocentric shift of target object direction between real and imagined perspectives. Results revealed a consistent pattern of monotonic increasing detrimental effects of HDD (0°, 60°, 120°, 180°) and ODD (0-45°, 46-90°, 91-135°, 136-180°). The independent variation of HDD and ODD disclosed a third source of extra processing costs that could be traced back to allocentric differences in target object direction (ODDallo). A SOA-interval (1, 3, or 5 s) before target presentation allowed participants to save on overall pointing times and errors but did not allow them to reduce incremental costs from HDD, ODDego, or ODDallo. The present results reveal that multiple overlapping spatial interference conflicts between real and imagined spatial perspectives are the most important source of additional processing costs in mental perspective taking in remembered environments.


Advance Directives for Medical Decisions.
Patients can determine in advance how they want to be treated in a certain situation, and in particular, situations in which they reject treatment. The provisions to be observed for the preparation and practical implementation of a living will under German law are presented and discussed. The chapter also describes the principles according to which a decision is to be made if no living will has been drafted. Additionally, it is recommended that a trusted person should be granted power of attorney, since the future course of an illness (including cancer) cannot be predicted in every detail.


Rapid magnetic enrichment and sensitive detection of Sudan pollutants with nanoscale zero valent iron-based nanomaterials in combination with liquid chromatography-ultraviolet detector.
In present work, we reported a new nanomaterial nano Fe0 decorated with SiO2 and dopamine by self-assembly method (Fe@SiO2@PDA). A sensitive method for determination of Sudan pollutants in aqueous samples was developed using Fe@SiO2@PDA as magnetic solid phase extraction adsorbents prior to high-performance liquid chromatography with variable wavelength detector. The possible parameters which would affect the enrichment have been optimized. The best parameters were as follows: elutent, 4.5 mL methanol; adsorbent dosage, 30 mg; adsorption time, 20 min; elution time, 18 min; sample pH 7; sample volume, 40 mL. The experimental results demonstrated that Fe@SiO2@PDA exhibited good adsorption properties to Sudan Red dyes. The established method provided excellent linear ranges over 0.01-50 μg L-1 and detection limits ranged from 2.0 to 5.1 ng L-1 for Sudan red I-IV. The developed method was also evaluated with real water samples and the results demonstrated that it was of applicative value owing to its merits including robustness, easy operation, fastness, cheapness and high enrichment efficiency, and had great prospect in environmental fields.


Acute onset of hematometra associated with endometritis and cervical stenosis. A case report.
The possible cause of hematometra is incomplete cervical stenosis which inhibits the passage of blood due to acute endometritis.


[Late onset Ondine syndrome: literature review on a case report].
Ondine syndrome is the central congenital hypoventilation syndrome (CCHS) caused by the mutation of the PHOX2B gene. In late onset cases, the symptomatology often appears after an acute event (infection, general anesthesia, drug intake), increasing hypoventilation. We report a case of late onset Ondine curse in a 9-year-old girl. The diagnosis was made based on a hypercapnic coma complicating a respiratory infection caused by Mycoplasma pneumoniae and was confirmed by genetic testing. In the patient's history we found symptoms that had not been noted (e.g., enuresis, morning headache, adynamia), attesting to chronic hypoventilation. Through this observation, we review the literature on CCHS, notably late onset cases, which are rare and insidious, emphasizing the pre-existing hypoventilation symptoms in this child. This case underlines the need for all practitioners not to trivialize these symptoms so as to decrease the current delay in diagnosis for late onset CCHS and to introduce optimal care as soon as possible.


MAS dependent sensitivity of different isotopomers in selectively methyl protonated protein samples in solid state NMR.
Sensitivity and resolution together determine the quality of NMR spectra in biological solids. For high-resolution structure determination with solid-state NMR, proton-detection emerged as an attractive strategy in the last few years. Recent progress in probe technology has extended the range of available MAS frequencies up to above 100 kHz, enabling the detection of resolved resonances from sidechain protons, which are important reporters of structure. Here we characterise the interplay between MAS frequency in the newly available range of 70-110 kHz and proton content on the spectral quality obtainable on a 1 GHz spectrometer for methyl resonances. Variable degrees of proton densities are tested on microcrystalline samples of the α-spectrin SH3 domain with selectively protonated methyl isotopomers (CH3, CH2D, CHD2) in a perdeuterated matrix. The experimental results are supported by simulations that allow the prediction of the sensitivity outside this experimental frequency window. Our results facilitate the selection of the appropriate labelling scheme at a given MAS rotation frequency.


Signal transduction for formation/release of interleukin-8 caused by a PAR2-activating peptide in human lung epithelial cells.
Proteinase-activated receptor-2 (PAR2) plays a dual role in the respiratory system, being pro- and anti-inflammatory. In human lung epithelial cells (A549), PAR2 activation causes release of interleukin-8 (IL-8) in addition to prostaglandin E(2) (PGE(2)). In the present study, we thus investigated PAR2-triggered signal transduction pathways causing IL-8 formation in A549 cells. SLIGRL-NH(2), a PAR2-activating peptide, but not LSIGRL-NH(2), a scrambled peptide, elicited release of IL-8 from A549 cells for 18 h, as measured by the ELISA method, an effect being suppressed by inhibitors of MEK, JNK, EGF receptor-tyrosine kinase (EGFR-TK), Src, pan-tyrosine kinases and protein kinase C, but not p38 MAP kinase or cyclooxygenase. SLIGRL-NH(2) also up-regulated IL-8 at protein and mRNA levels, as determined by Western blotting and RT-PCR, respectively. The PAR2-triggered up-regulation of IL-8 protein and mRNA was blocked by an inhibitor of MEK, but not clearly by inhibitors of JNK and EGFR-TK. SLIGRL-NH(2) actually phosphorylated JNK as well as ERK, the JNK activation being resistant to inhibitors of Src, pan-tyrosine kinases, protein kinase C and EGFR-TK. Our data suggest that PAR2-triggered IL-8 formation involves transcriptional up-regulation of IL-8 via the MEK-ERK pathway, while the JNK and EGF receptor pathways might rather contribute to a post-transcriptional process for the release of IL-8.


Percutaneous Common Carotid Artery Access for Cardiac Interventions in Infants Does Not Acutely Change Cerebral Perfusion.
Pediatric cardiac interventions via percutaneous common carotid artery (CCA) access have been shown to be safe and effective. However, the impact of placement of a sheath in the carotid artery for interventions on cerebral perfusion is unknown. In this study we used cerebral near-infrared spectroscopy (NIRS) to analyze the effects of percutaneous CCA access for cardiac interventions on cerebral perfusion. This study is a retrospective chart review carried out at a tertiary care center on all pediatric patients who underwent percutaneous cardiac catheterization via carotid artery access from January 2010 to January 2020. All patients who had ipsilateral NIRS recorded on the side of carotid artery access were included. Patients with only partial or no ipsilateral NIRS data were excluded. The primary outcome measure was the change in NIRS upon CCA access; the mean NIRS for 15 min before obtaining access was compared to the mean NIRS during the procedure and to the mean NIRS 15 min after removal of the CCA sheath. We hypothesized that there would be a significant drop in NIRS values on the side of CCA access. There were 48 catheterizations in the study period where percutaneous CCA was accessed. Of those, 21 catheterizations had complete data and were included in the study. 13 (62%) were of males. The median age was 23 days (IQR 7-79). The indications for CCA access were patent ductus arteriosus stent implantation (n = 13; 62%), aortic valvuloplasty (n = 5; 24%), balloon angioplasty of coarctation of aorta (n = 2; 10%), and renal artery angioplasty (n = 1; 4%). In 16 patients (72%), the left common carotid artery was accessed. The median weight of the patients was 3.3 kg (IQR 2.8-2.9). The most common sheath size used was 4F, in 16 patients (72%). The mean NIRS prior to the procedure was 67 ± 15%, during the procedure was 68 ± 20%, and after removal of sheath was 68 ± 21%. Paired t test of cerebral NIRS before, during, and after the procedure showed no significant change with CCA access (P = 0.08). No patient in the series had a documented neurologic deficit following the procedure. Percutaneous CCA access was not associated with a decrease in NIRS on the side of the access during the procedure, suggesting there was no significant acute change in cerebral perfusion with CCA access.


The Generalized Entropy Ergodic Theorem for Nonhomogeneous Bifurcating Markov Chains Indexed by a Binary Tree.
In this paper, we study the generalized entropy ergodic theorem for nonhomogeneous bifurcating Markov chains indexed by a binary tree. Firstly, by constructing a class of random variables with a parameter and the mean value of one, we establish a strong limit theorem for delayed sums of the bivariate functions of such chains using the Borel-Cantelli lemma. Secondly, we prove the strong law of large numbers for the frequencies of occurrence of states of delayed sums and the generalized entropy ergodic theorem. As corollaries, we generalize some known results.


Towards safer non-volatile tissue fixatives: Evaluation of choline-based ionic liquids for fixing ocular tissues.
Volatile organic chemicals (VOCs) are routinely used for processing biological tissue samples in clinical laboratories. Recognizing their serious health and environmental impacts, a few non-volatile green solvents (choline based ionic liquids, ILs) were evaluated as tissue fixatives here. Microscopic evaluation of histo-morphology, fixation and staining quality, and macromolecular integrity (DNA and proteins) were assessed in human eye tissues (sclera, choroid, retinal layers and retinal pigmented epithelium, eyelid and orbit) after IL-fixation. Formalin-fixed tissues were used as standard reference. Microscopic examination revealed favorable histomorphology, tissue fixation and staining characteristics in most tissues immersed in ILs. Time taken to fix, and stability over a period of time (24 h, 48 h, 1 week, 1 month) was also recorded. Electrophoretic analysis revealed stability of cellular proteins and nucleic acids in IL-fixed scleral tissues. Heterogeneity in tissue fixation property relative to the type of ocular tissue, duration of fixation and storage, warrant further design and optimization of ILs to fix biological tissues. The simple cholinium salts based ILs tested here show favorable potential for tissue fixation application, and as an alternative approach to the use of VOCs, towards sustainable biomedical practice.


Two-component ribonucleotidyl transferase from Escherichia coli. III. Effect of nucleoside diphosphates on synthesis and pyrophosphorolysis of polyribonucleotides by the enzyme.
1. The capacity of two-component ribonucleotidyl transferase to catalyze pyrophosphorolysis of polyribonucleotides is studied. 2. It is shown that nucleoside diphosphates (NDP), not being substrates for the enzyme, activate both the synthesis and pyrophosphorolysis of polynucleotides by the enzyme. The concentration of NDP is important for this effect: with an increase of NDP concentration the rate of synthesis increases and reaches a plateau at 10(-5) M NDP, while the rate of pyrophosphorolysis, attaining maximal values at 10(-5)--10(-3) M NDP, decreases with a further increase of NDP concentration. 3. The possible biological role of two-component ribonucleotidyl transferase is discussed.


Phenotypical modifications of immune cells are enhanced by extracellular matrix.
Immune cells not only constitute tumour microenvironment but they may even affect disease prognosis as a result of dual functional roles that they may play in tumour tissues. Two frequently used established immune cell lines (lymphocytic Jurkat and monocytic THP-1) were used to test whether microenvironmental factors, especially molecular components of extracellular matrix, can shape the phenotype of immune cells. Proliferation, morphological and phenotypical analyses were applied to compare behaviour of the immune cells, typically cultured as suspensions in culture medium, with their behaviour in collagen type I-based and Matrigel-based 3D cultures. Density of both immune cell types in routine suspension cultures affected their subsequent proliferation in extracellular matrices. THP-1 cells appeared to be more sensitive to their surrounding microenvironment as judged from extracellular matrix type-dependent changes in their cell doubling times and from slight increase in their diameters in both extracellular matrix-containing cell cultures. Moreover, even chemically uninduced monocytic THP-1 cells were present in a minor fraction as CD68 positive cell population in collagen type I matrix indicating their partial differentiation to macrophages. Observed modifications of immune cells by microenvironmental factors may have profound implications for their roles in healthy and pathological tissues.


Suppression of Tescalcin inhibits growth and metastasis in renal cell carcinoma via downregulating NHE1 and NF-kB signaling.
Renal cell carcinoma (RCC) is the most common form of kidney cancer. Recent studies reported that Tescalcin was overexpressed in various tumor types. However, the status of Tescalcin protein expression in RCC and its biological function is uncertain. This study was designed to investigate the expression of Tescalcin in human RCC and its biological function. shRNA transfection was performed to abrogates the expression of Tescalcin. Quantitative real time PCR and western blotting assays were used to determine mRNA and protein expression levels, respectively. The cell viability was analyzed by MTT and colony formation. Cell flow cytometry was used to assess pHi value and cell apoptosis. Cell invasive and migratory ability was measured with modified Boyden chamber assay. Xenograft model was setup to evaluate tumor growth. Tescalcin was overexpressed in RCC tissues compared with matched normal tissues. It was also overexpressed in RCC cell lines relative that of normal cells. Suppression Tescalcin with specific shRNA resulted in the inhibition of cell proliferation, migration, invasion and apoptosis of RCC cells. Additionally, silencing of Tescalcin also caused the inhibition of the tumor growth in nude mice. Mechanistic study showed that Tescalcin regulated cell proliferation, migration and invasion via NHE1/pHi axis as well as AKT/NF-κB signaling pathway. These findings demonstrate that atopic expression of Tescalcin facilitates the survival, migration and invasion of RCC cells via NHE1/pHi axis as well as AKT/ NF-κB signaling pathway, providing new perspectives for the future study of Tescalcin as a therapeutic target for RCC.


Efficient few-shot machine learning for classification of EBSD patterns.
Deep learning is quickly becoming a standard approach to solving a range of materials science objectives, particularly in the field of computer vision. However, labeled datasets large enough to train neural networks from scratch can be challenging to collect. One approach to accelerating the training of deep learning models such as convolutional neural networks is the transfer of weights from models trained on unrelated image classification problems, commonly referred to as transfer learning. The powerful feature extractors learned previously can potentially be fine-tuned for a new classification problem without hindering performance. Transfer learning can also improve the results of training a model using a small amount of data, known as few-shot learning. Herein, we test the effectiveness of a few-shot transfer learning approach for the classification of electron backscatter diffraction (EBSD) pattern images to six space groups within the [Formula: see text] point group. Training history and performance metrics are compared with a model of the same architecture trained from scratch. In an effort to make this approach more explainable, visualization of filters, activation maps, and Shapley values are utilized to provide insight into the model's operations. The applicability to real-world phase identification and differentiation is demonstrated using dual phase materials that are challenging to analyze with traditional methods.


Computer assisted analysis of ferritin-insulin receptor sites on adipocytes and the effects of cytochalasin B on groups of insulin receptor sites.
A computerized quantitative technique was used to analyze the distribution of ferritininsulin receptor sites on rat adipocytes and the effects of cytochalasin B on groups of receptor sites. Computer analysis of separation distances between receptor sites established that insulin receptor sites on adipocytes did not have a random distribution but have a distinct tendency to exist in groups with a maximum separation distance between particles of 400 A. A peak in the distribution of separation distances occurred at 100-200 A. Cytochalasin B, but not cytochalasin D, treatment of adipocytes resulted in a decrease in the number of large groups of receptor sites and a corresponding increase in single and paired receptor sites without affecting the separation distance between the remaining grouped receptors. This suggested that when cytochalasin B disrupted the bond holding receptor sites together, it caused complete disruption. These observations provided additional information on the ultrastructural characteristics of the insulin receptor. Further application of these techniques to the analysis of insulin receptors may provide the necessary structural correlates to the biochemically observed differences in insulin action in other tissues and diseased states.


Tinnitus and insomnia.
Sleep problems are common in individuals with tinnitus but it is not known if they can be seen as a reaction to the acoustic percept of tinnitus disturbing normal sleep, or if there are common causes. Sleep problems further impair the quality of life of individuals with tinnitus and the impairment correlates with the severity of the tinnitus. However the nature of the relationship between tinnitus and disturbed sleep in individuals with tinnitus is not clearly understood. Preliminary studies suggest that chronically disturbed sleep (insomnia) in individuals with tinnitus that is not caused by organic disorders exists unrelated to the tinnitus. We studied the relationship between tinnitus and insomnia in a retrospective sleep study of 13 hospitalized patients with insomnia and tinnitus. Patients with sleep apnea, periodic leg movements, or a severe psychiatric disorder were excluded. We collected physiologic sleep measures (EEG, EOG, EMG, and respiration) and subjective sleep information from a morning protocol during two nights. We also obtained information about performance in sustained attention tasks and the scores of self-rated depression scale and self-rated daytime-tiredness scale. Thirteen age- and sex-matched inpatients with primary insomnia who did not have tinnitus served as controls. There were no significant differences between the physiologic data obtained in patients with tinnitus and in the controls. Both groups had low sleep efficiency but the patients with both insomnia and tinnitus had longer subjective sleep latencies than insomnia patients without tinnitus (controls). No differences were found in sustained attention tasks, subjective daytime tiredness, and depression rating scores between the two groups. Similarities between the results from these two groups suggest that sleep specific psychotherapeutic methods, which are established for treating insomnia, should be further developed for the use in patients with insomnia and tinnitus.


Age-related changes in correlation between behavioral and biochemical parameters in Lewis rats.
This study evaluated aging by using a correlational analysis of behavior and biochemistry in young (4 months old) and old (24 months old) Lewis rats. The rats were subjected to different learning tasks (spatial discrimination learning in the Morris task and cone-field task, temporal discrimination learning, one-trial inhibitory avoidance task) and noncognitive tests (emotional reactivity, motor coordination, and food motivation) and the relation between the various parameters was assessed. In the learning tasks, except for the inhibitory avoidance task, the first part of the learning curve was taken as an index of learning. Blood glucose (baseline and blood glucose regulation) and hippocampal choline acetyltransferase (ChAT) activity were also measured. There was no correlation between the different parameters of learning in young and old rats. This indicates that there are individual differences in performance in different learning and memory tasks. Measures of noncognitive behavior (food motivation, emotional reactivity, and motor performance) did not predict performance in the learning tasks. Hippocampal ChAT activity did not correlate with learning performance in old rats, whereas blood glucose level was found to correlate with spatial learning in old rats. These results suggest that an impaired regulation of blood glucose may be related to cognitive performance in aging.


Is the polio virus responsible for late central nervous system tumors?
A hypothesis is advanced concerning the relationship of poliomyelitis viruses and late developing neoplasia in the central nervous system. The literature is surveyed, and several experimental approaches based upon known evidence of viral and neoplastic behaviour are advanced. The present status of world polio incidence is discussed as it applies to this possible relationship.


Carbon sequestration for high-quality sludge-based carbon preparation via K/Na bi-molten salts pyrolysis.
Pyrolysis carbonization of sewage sludge is employed to achieve carbon sequestration and access carbon resources, while the quality of the obtained sludge-based carbon (SBC) is poor due to high ash contents and volatile organic matter. Here, carbonization in KOH/Na2CO3 (K/Na) bi-molten salts was developed for SBC preparation, improvement of carbon exploitation from biomass, and to reduce the contents of ash and volatile organic matter. The results showed that the surface area and pore volume of SBC under optimized conditions reached 1631 m2 g-1 and 1.312 cm3 g-1 at 700 °C, respectively, with a K/Na bi-molten salts/sludge ratio of 2:1 (K:Na = 5:5). Moreover, over fivefold the higher surface area and 43.61% amount of carbon element could be obtained, with a decrease in the mass loss rate for sludge pyrolysis of 25%. The mechanism behind the higher surface area of the SBC was identified and divided into three stages: intense dehydration and dehydrogenation caused by molten salt-enhanced polycondensation of protein and polysaccharide (200-400 °C), strongly reduced carbon-oxygen structure after deoxygenation reactions (400-600 °C), aromatization and cyclization of long-chain fatty acids triggered by deamidation of tar catalyzed by molten salts (600-900 °C). Eventually, 14.63% carbon was sequestered for the high-surface-area SBC prepared by K/Na bi-molten salts system.


Validation of the Pain Resilience Scale in a Chronic Pain Sample.
Psychosocial factors that protect against negative outcomes for individuals with chronic pain have received increased attention in recent years. Pain resilience, or the ability to maintain behavioral engagement and regulate emotions as well as cognitions despite prolonged or intense pain, is one such factor. A measure of pain-specific resilience, the Pain Resilience Scale, was previously identified as a better predictor of acute pain tolerance than general resilience. The present study sought to validate this measure in a chronic pain sample, while also furthering understanding of the role of pain resilience compared with other protective factors. Participants with chronic pain completed online questionnaires to assess factors related to positive pain outcomes, pain vulnerability, pain intensity, and quality of life. A confirmatory factor analysis confirmed the 2-factor structure of the Pain Resilience Scale previously observed among respondents without chronic pain, although one item from each subscale was dropped in the final version. For this chronic pain sample, structural equation modeling showed that pain resilience contributes unique variance to a model including pain acceptance and pain self-efficacy in predicting quality of life and pain intensity. Further, pain resilience was a better fit in this model than general resilience, strengthening the argument for assessing pain resilience over general resilience. A modified version of the Pain Resilience Scale retained the original factor structure when tested in a chronic pain sample. Construct validity was supported by expected relationships with pain-related protective and vulnerability measures. Further, a model including positive pain constructs showed that pain resilience accounts for unique variability when predicting quality of life and pain intensity.


Association between DNA methylation and coronary heart disease or other atherosclerotic events: A systematic review.
The aim of this study was to perform a systematic review of the association between DNA methylation and coronary heart disease (CHD) or related atherosclerotic traits. A systematic review was designed. The condition of interest was DNA methylation, and the outcome was CHD or other atherosclerosis-related traits. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). A functional analysis was undertaken using the Ingenuity Pathway Analysis software. In total, 51 articles were included in the analysis: 12 global methylation, 34 candidate-gene and 11 EWAS, with six studies using more than one approach. The results of the global methylation studies were inconsistent. The candidate-gene results were consistent for some genes, suggesting that hypermethylation in ESRα, ABCG1 and FOXP3 and hypomethylation in IL-6 were associated with CHD. The EWAS identified 84 genes showing differential methylation associated with CHD in more than one study. The probability of these findings was <1.37·10-5. One third of these genes have been related to obesity in genome-wide association studies. The functional analysis identified several diseases and functions related to these set of genes: inflammatory, metabolic and cardiovascular disease. Global DNA methylation seems to be not associated with CHD. The evidence from candidate-gene studies was limited. The EWAS identified a set of 84 genes highlighting the relevance of obesity, inflammation, lipid and carbohydrate metabolism in CHD. This set of genes could be prioritized in future studies assessing the role of DNA methylation in CHD.


The Implications of Intergenerational Relationships for Minority Aging: a Review of Recent Literature.
This study aims to understand how intergenerational relationships impact minority aging in the USA. We reviewed studies published in the last 5 years that examine both familial and non-familial intergenerational relationships. Intergenerational relationships can have positive and negative implications for minority aging. Minority older adults benefit most from these relationships when they increase social interaction and/or offer social support by reducing acculturative stress, providing emotional closeness, or increasing access to tangible resources. At the same time, these relationships can be sources of strain as they lead to burden among already disadvantaged groups. Future studies should explore the impact of intergenerational relations among more diverse subgroups of older adults and identify mechanisms linking intergenerational relationships to health-related outcomes among minority older adults. Further, longitudinal cohort studies and randomized trials are needed to test mechanisms and evaluate the effectiveness of promising intergenerational interventions.


Phylogenetic analyses of endoparasitic Acanthocephala based on mitochondrial genomes suggest secondary loss of sensory organs.
The metazoan taxon Syndermata (Monogononta, Bdelloidea, Seisonidea, Acanthocephala) comprises species with vastly different lifestyles. The focus of this study is on the phylogeny within the syndermatan subtaxon Acanthocephala (thorny-headed worms, obligate endoparasites). In order to investigate the controversially discussed phylogenetic relationships of acanthocephalan subtaxa we have sequenced the mitochondrial (mt) genomes of Echinorhynchus truttae (Palaeacanthocephala), Paratenuisentis ambiguus (Eoacanthocephala), Macracanthorhynchus hirudinaceus (Archiacanthocephala), and Philodina citrina (Bdelloidea). In doing so, we present the largest molecular phylogenetic dataset so far for this question comprising all major subgroups of Acanthocephala. Alongside with publicly available mt genome data of four additional syndermatans as well as 18 other lophotrochozoan (spiralian) taxa and one outgroup representative, the derived protein-coding sequences were used for Maximum Likelihood as well as Bayesian phylogenetic analyses. We achieved entirely congruent results, whereupon monophyletic Archiacanthocephala represent the sister taxon of a clade comprising Eoacanthocephala and monophyletic Palaeacanthocephala (Echinorhynchida). This topology suggests the secondary loss of lateral sensory organs (sensory pores) within Palaeacanthocephala and is further in line with the emergence of apical sensory organs in the stem lineage of Archiacanthocephala.


Assessment of the psychometric properties of the Italian version of the New Freezing of Gait Questionnaire (NFOG-Q-IT) in people with Parkinson disease: a validity and reliability study.
Freezing of gait (FOG) in Parkinson's disease (PD) is a challenging clinical symptom to assess, due to its episodic nature. A valid and reliable tool is the New FOG Questionnaire (NFOG-Q) used worldwide to measure FOG symptoms in PD. The aim of this study was to translate, to culturally adapt, and to test the psychometric characteristics of the Italian version of the NFOG-Q (NFOG-Q-It). The translation and cultural adaptation was based on ISPOR TCA guidelines to finalize the 9-item NFOG-Q-It. Internal consistency was assessed in 181 Italian PD native speakers who experienced FOG using Cronbach's alpha. Cross-cultural analysis was tested using the Spearman's correlation between the NFOG-Q-It and the Modified Hoehn-Yahr Scale (M-H&Y). To assess construct validity, correlations among NFOG-Q-It, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Falls Efficacy Scale-International (FES-I), the 6-min Walking Test (6MWT), the Mini Balance Evaluation System Test (Mini-BESTest) and the Short Physical Performance Battery (SPPB) were investigated. The Italian N-FOGQ had high internal consistency (Cronbach's α = 0.859). Validity analysis showed significant correlations between NFOG-Q-IT total score and M-H&Y scores (r = 0.281 p < 0.001), MDS-UPDRS (r = 0.359 p < 0.001), FES-I (r = 0.230 p = 0.002), Mini BESTest (r = -0.256 p = 0.001) and 6MWT (r = -0.166 p = 0.026). No significant correlations were found with SPPB, MOCA and MMSE. The NFOG-It is a valuable and reliable tool for assessing FOG symptoms, duration and frequency in PD subjects. Results provide the validity of NFOG-Q-It by reproducing and enlarging previous psychometric data.


Benchmark datasets of immune receptor-epitope structural complexes.
The development of accurate epitope prediction tools is important in facilitating disease diagnostics, treatment and vaccine development. The advent of new approaches making use of antibody and TCR sequence information to predict receptor-specific epitopes have the potential to transform the epitope prediction field. Development and validation of these new generation of epitope prediction methods would benefit from regularly updated high-quality receptor-antigen complex datasets. To address the need for high-quality datasets to benchmark performance of these new generation of receptor-specific epitope prediction tools, a webserver called SCEptRe (Structural Complexes of Epitope-Receptor) was created. SCEptRe extracts weekly updated 3D complexes of antibody-antigen, TCR-pMHC and MHC-ligand from the Immune Epitope Database and clusters them based on antigen, receptor and epitope features to generate benchmark datasets. SCEptRe also provides annotated information such as CDR sequences and VDJ genes on the receptors. Users can generate custom datasets based by selecting thresholds for structural quality and clustering parameters (e.g. resolution, R-free factor, antigen or epitope sequence identity) based on their need. SCEptRe provides weekly updated, user-customized comprehensive benchmark datasets of immune receptor-epitope structural complexes. These datasets can be used to develop and benchmark performance of receptor-specific epitope prediction tools in the future. SCEptRe is freely accessible at http://tools.iedb.org/sceptre .


A family with Duane anomaly and distal limb abnormalities: a further family with the arthrogryposis-ophthalmoplegia syndrome.
A two-generation family is reported in which three members have Duane anomaly and distal limb abnormalities. All three affected have photopic electroretinogram responses that are abnormal or at the lower limit of the normal range with normal scotopic responses. Two affected family members also have hearing loss. The likeliest diagnosis is the syndrome listed as "arthrogryposis-ophthalmoplegia syndrome" on the London Dysmorphology Database or as "arthrogryposis with oculomotor limitation and electroretinal abnormalities" or "oculomelic aplasia" in OMIM [MIM 108145]. In view of the similarities with Okihiro syndrome, a search for mutations within the SALL4 gene was undertaken, but none were identified.


Epidemiologic and Molecular Investigation of a MRSA Outbreak Caused by a Contaminated Bathtub for Carbon Dioxide Hydrotherapy and Review of the Literature.
We conducted an outbreak investigation and performed a molecular typing of the outbreak strains with pulsed-field gel electrophoresis (PFGE). In addition, we reviewed PubMed and the Outbreak Database for MRSA outbreaks related to hydrotherapy or other bathing activities. Four patients acquired nosocomial MRSA during the 4-week outbreak period. Environmental sampling revealed the presence of MRSA in the bathtub used for hydrotherapy. The environmental and the patients' isolates showed an indistinguishable restriction pattern in the PFGE. Subsequent discontinuation of bathing stopped the outbreak. The literature search found 9 MRSA outbreak reports related to bathing activities or hydrotherapy. The epidemiologic outbreak investigation together with the molecular findings suggests monoclonal spread of MRSA due to surface contamination of the bathtub. After enhancing the disinfection and cleaning process accompanied by staff training with respect to hand hygiene, no further cases occurred. Standardized and best practice cleaning and disinfection protocols are crucial, especially in critical facilities such as hydrotherapy units. Regular environmental sampling is helpful to monitor these processes and to detect potential contamination.


Metamorphic variations in the hemoglobins of Bombina variegata (L.).
1. The electrophoretic pattern of the anuran Bombina variegata presents one band only until the end of premetamorphosis. Afterwards three new bands appear which substitute the larval band within 15-18 days of metamorphosis. 2. The gradual change of larval and adult hemoglobin, correlated with the development, has been reported in a diagram. 3. In Bombina variegata the hemoglobin change is total, like in most amphibians, but starts earlier and develops slower than in most other species.


Skeletal metastasis in renal cell carcinoma: current and future management options.
Metastasis to the skeleton is common in advanced renal cancer and leads to debilitating skeletal complications including severe pain, increased fracture rate and spinal cord compression. The incidence of renal cell carcinoma is increasing by around 2% per year and recent advances in targeted anti-angiogenic therapy for advanced disease are expected to lead to longer survival times. The clinical management of metastatic bone disease in renal cell carcinoma therefore merits greater focus than hitherto. Bone metastases arising from renal cancer are highly osteolytic and particularly destructive. Fortunately, the continuing development of anti-resorptive drugs is revolutionising the medical management of metastatic bone disease across many tumour types and making a major impact on quality of life. The bisphosphonate zoledronic acid is now licensed for use in advanced renal cell carcinoma and appears to yield a greater benefit in terms of reduction in skeletal related events than in bone metastases arising from other tumour types. Drugs which are directed at specific targets in the bone metastasis pathway are in development, including denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor kappa B ligand, which has recently been licensed in the United States for use in renal cell carcinoma, with European licensing expected soon. This review examines the increasing options for treatment of metastatic bone disease in renal cell carcinoma, with a focus on drug-based advances and progress in the development of existing and new biomarkers to support clinical management.


Spatial and temporal patterns of malaria incidence in Mozambique.
The objective of this study is to analyze the spatial and temporal patterns of malaria incidence as to determine the means by which climatic factors such as temperature, rainfall and humidity affect its distribution in Maputo province, Mozambique. This study presents a model of malaria that evolves in space and time in Maputo province-Mozambique, over a ten years period (1999-2008). The model incorporates malaria cases and their relation to environmental variables. Due to incompleteness of climatic data, a multiple imputation technique is employed. Additionally, the whole province is interpolated through a Gaussian process. This method overcomes the misalignment problem of environmental variables (available at meteorological stations--points) and malaria cases (available as aggregates for every district--area). Markov Chain Monte Carlo (MCMC) methods are used to obtain posterior inference and Deviance Information Criteria (DIC) to perform model comparison. A Bayesian model with interaction terms was found to be the best fitted model. Malaria incidence was associated to humidity and maximum temperature. Malaria risk increased with maximum temperature over 28 °C (relative risk (RR) of 0.0060 and 95% Bayesian credible interval (CI) of 0.00033-0.0095) and humidity (relative risk (RR) of 0.00741 and 95% Bayesian CI 0.005141-0.0093). The results would suggest that additional non-climatic factors including socio-economic status, elevation, etc. also influence malaria transmission in Mozambique. These results demonstrate the potential of climate predictors particularly, humidity and maximum temperature in explaining malaria incidence risk for the studied period in Maputo province. Smoothed maps obtained as monthly average of malaria incidence allowed to visualize months of initial and peak transmission. They also illustrate a variation on malaria incidence risk that might not be related to climatic factors. However, these factors are still determinant for malaria transmission and intensity in the region.


Components of Oranta-AO software expert system for innovative application of blood pressure monitors.
The authors developed and substantiated the original methods of arterial oscillography, which were implemented in the developed Oranta-AO information system. The methods of application to the arterial oscillogram registered at measurement of arterial pressure gives the possibility to carry out the supplementary systematic assessment of health, functional state of cardiovascular system, its reserve possibilities etc. The authors also developed an Expert System (based on machine-learning methods) for the differential diagnosis of risks of heart, lung, mental illness and prognosis of some blood parameters. Oranta-AO software system was created based on research results due to methods and algorithms that were innovate. For the mathematical modeling of arterial oscillograms used cyclic random processes. Methods of arterial oscillograms processing based on its model in the form of a cyclic random process was developed. The method of evaluation of the rhythm function of arterial oscillograms and statistical methods for estimating the probabilistic characteristics of arterial oscillograms were developed. To solve the clustering problem, the Python k-means and k-means++ algorithm were used. Oranta-AO information system consists of three interrelated parts: mobile application, computing kernel and web system. Computing kernel and web system are deployed on AWS servers and have been tested already. The developed environment aims to be integrated into every new model of electronic meters in the world. Certification (EN 62304:2014, ISO 13485: 2018) in Ukraine is completed, PCT priority is completed. The next step will be to establish cooperation with manufacturers of electronic pressure monitors, patenting and certification in world.


Evidence for the glycoprotein nature of vitamin K-dependent carboxylase from rat liver.
The ability of the rat liver microsomal vitamin K-dependent carboxylase and microsomal precursors of prothrombin and other vitamin K-dependent proteins to bind to lectin gels has been determined. Under denaturing conditions which dissociate precursor substrates from the carboxylase enzyme, prothrombin precursors and microsomal proteins labeled in gamma-carboxyglutamate residues with [14C]bicarbonate were nearly quantitatively bound to concanavalin A gels. When lentil lectin gels were used, only about one third of these proteins were bound, suggesting a heterogeneity of this glycoprotein pool. Under non-denaturing conditions, both precursor proteins and vitamin K-dependent carboxylase activity were retained on either concanavalin A or lentil lectin gels. These data are consistent with an increase in lectin binding determinants in the precursor-carboxylase complex and are evidence for the glycoprotein nature of this microsomal enzyme.


Defining Asthma-Chronic Obstructive Pulmonary Disease Overlap.
Much interest has been given to the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) in the past 2 decades, but the condition is still ill-defined. There is general agreement that a patient with longstanding asthma who develops fixed airflow obstruction after years of smoking has ACO although defining asthma in the face of COPD can be challenging. Many features of asthma are also found in patients with COPD without indicating an overlap and no consensus exists on which characteristics should be included in the definition of ACO. Nevertheless, some guidance has been issued to help clinicians and researchers to make a diagnosis of ACO and these will be reviewed here.


Radiological approach for the newly incorporated T staging factor, depth of invasion (DOI), of the oral tongue cancer in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual: assessment of the necessity for elective neck dissection.
The 8th edition of American Joint Committee on Cancer's (AJCC) Cancer Staging Manual was modified by incorporating depth of invasion (DOI) in the T categorization of oral cavity cancer. This is because DOI is strongly associated with cervical lymph node metastasis, which is the most important negative prognostic factor of oral cavity cancer. This major change in the AJCC Cancer Staging Manual caused re-staging of T category in several cases. Although, the DOI on MRI and CT (radiological DOI; r-DOI) strongly correlated with pathological DOI (p-DOI), it is often 2-3 mm larger than p-DOI. Due to this variance, estimation of p-DOI based on r-DOI may not be accurate. However, when a lesion is undetectable on MRI, p-DOI was often smaller than 4 mm. On the other hand, when MRI depicts lesions with styloglossus and hyoglossus muscle invasion, p-DOI was always larger than 4 mm. These correlations between MRI findings and p-DOI are important when assessing the need for elective neck dissection, as the National Comprehensive Cancer Network (NCCN) recommends elective neck dissection in cases with DOI greater than 4 mm.


The proline-rich myticalins from Mytilus galloprovincialis display a membrane-permeabilizing antimicrobial mode of action.
Bivalve mollusks are continuously exposed to potentially pathogenic microorganisms living in the marine environment. Not surprisingly, these filter-feeders developed a robust innate immunity to protect themselves, which includes a broad panel of antimicrobial peptides. Among these, myticalins represent a recently discovered family of linear cationic peptides expressed in the gills of Mytilus galloprovincialis. Even though myticalins and insect and mammalian proline-rich antimicrobial peptides (PrAMPs) share a similar amino acid composition, we here show that none of the tested mussel peptides use a non-lytic mode of action relying on the bacterial transporter SbmA. On the other hand, all the tested myticalins perturbed and permeabilized the membranes of E. coli BW25113, as shown by flow-cytometry and atomic force microscopy. Circular dichroism spectra revealed that most myticalins did not adopt recognizable secondary structures in the presence of amphipathic environments, such as biological membranes. To explore possible uses of myticalins for biotech, we assessed their biocompatibility with a human cell line. Non-negligible cytotoxic effects displayed by myticalins indicate that their optimization would be required before their further use as lead compounds in the development of new antibiotics.


Investigations of Lipid Binding to Acyl-CoA-Binding Proteins (ACBP) Using Isothermal Titration Calorimetry (ITC).
Isothermal titration calorimetry (ITC) is a quantitative, biophysical method to investigate intermolecular binding between biomolecules by directly measuring the heat exchange in the binding reaction. The assay is carried out in solution when the molecules interact in vitro. This allows to determine values for binding affinity (Kd), binding stoichiometry (n), as well as changes in Gibbs free energy (ΔG), entropy (ΔS), and enthalpy (ΔH). This method also addresses the kinetics of enzymatic reactions for a substrate during conversion to a product. ITC has been used to study the interactions between proteins and ligands such as those of acyl-CoA-binding proteins (ACBPs) and acyl-CoA thioesters or ACBPs with protein partners. ITC has also been used in investigating interactions between antiserum and antigen, as well as those involving RNA and DNA and other macromolecules. We describe the methods used to isolate and purify a recombinant rice ACBP (OsACBP) for ITC. To study OsACBP binding to long-chain acyl-CoA thioesters, a microcalorimeter was used at 30 °C, and the ligand (acyl-CoA thioesters or a protein partner in the first cell), was mixed with the ACBP protein solution in a second cell, for more than 40 min comprising 20 injections. Subsequently, the binding parameters including the heat-release data were analyzed and various thermodynamic parameters were calculated.


Genetic Analysis in Anal and Cervical Cancer: Exploratory Findings About Radioresistance in the ProfiLER Database.
This study aimed to describe genomic alterations on squamous cell cervical and anal carcinomas. From 2013 to 2019, 3,269 patients were included in the molecular screening ProfiLER trial. Only patients with non-metastatic cervical or anal cancer, and those initially treated with radiotherapy in a curative intent were selected. Genetic analyses were performed by next generation sequencing (NGS). Genomic alterations were observed in most patients: 5 patients out of 15 (33.3%) had at least one mutation on NGS and 4 out of 15 (26.7%) had at least one aberration of the number of copies of genes in the comparative genomic hybridation (CGH) analysis. The most common mutated gene was PIK3CA. All omic approaches must be integrated in the locally advanced cancer setting by new clinical trial design to develop two routes in the treatment strategy: intensification or de-escalation treatment strategy according to omic markers.


A stapled p53 helix overcomes HDMX-mediated suppression of p53.
Cancer cells neutralize p53 by deletion, mutation, proteasomal degradation, or sequestration to achieve a pathologic survival advantage. Targeting the E3 ubiquitin ligase HDM2 can lead to a therapeutic surge in p53 levels. However, the efficacy of HDM2 inhibition can be compromised by overexpression of HDMX, an HDM2 homolog that binds and sequesters p53. Here, we report that a stapled p53 helix preferentially targets HDMX, blocks the formation of inhibitory p53-HDMX complexes, induces p53-dependent transcriptional upregulation, and thereby overcomes HDMX-mediated cancer resistance in vitro and in vivo. Importantly, our analysis of p53 interaction dynamics provides a blueprint for reactivating the p53 pathway in cancer by matching HDM2, HDMX, or dual inhibitors to the appropriate cellular context.


Ultrafast extraction of uranium from seawater using photosensitized biohybrid system with bioinspired cascaded strategy.
The highly effective utilization of uranium resources in global seawater is a viable method to satisfy the rising demands for fueling nuclear energy industry. Herein, inspired by the multi-mechanisms of the marine bacteria for uranium immobilization, CdS nanoparticles are deposited on the cell of marine bacterial strain Bacillus velezensis UUS-1 to create a photosensitized biohybrid system UUS-1/CdS. This system achieves high uranium extraction efficiency using a cascaded strategy, where the bacterial cells guarantee high extraction selectivity and the photosensitive CdS nanoparticles realize cascading photoreduction of high soluble U(VI) to low soluble U(IV) to enhance extraction capacity. As one of the fastest-acting adsorbents in natural seawater, a high extraction capacity for uranium of 7.03 mg g-1 is achieved with an ultrafast extraction speed of 4.69 mg g-1 d-1. The cascaded strategy promisingly improves uranium extraction performance and pioneers a new direction for the design of adsorbents to extract uranium from seawater.


Microwave-assisted frozen section diagnosis. A comparison between conventional cryostat technique and the combination of freezing and microwave-stimulated fixation.
The study evaluates the morphology of frozen tissue sections treated by microwave-stimulated fixation compared with unfixed cryostat sections. Furthermore, microwave fixation has been compared with fixation at room temperature. Improved preservation of nuclear structures (chromatin pattern and nucleoli) was found with the microwave combination, while other parameters were indistinguishable from the unfixed cryostat sections. Fixation at room temperature showed no difference compared with the unfixed cryostat sections. The combined method might be useful in rapid diagnosis of mesenchymal tumors, lymphoid proliferations and tumors of the CNS.


Indications for and results of operative treatment of spondylitis and spondylodiscitis.
We present a retrospective follow-up study of 24 patients with spondylitis or spondylodiscitis whose treatment included surgical intervention. Tuberculous spondylitis was diagnosed in 14 patients and 10 suffered from non-specific spondylitis. The average age of the patients was 50.2 years and average follow-up was 3 years. All patients were asymptomatic at the time of examination and showed radiographic evidence of solid fusion. We recommend radical debridement and spinal fusion through a ventral approach in patients with destruction of the ventral vertebral body, progressive neurological impairment, septicaemia and antibiotic-resistant, symptomatic infections of the spine. In the elderly patient, even in reduced states of health, early surgical intervention can be particularly valuable. Although surgical intervention should be reserved for specific indications, we were able to document favourable results in all 24 patients treated with debridement and spinal fusion.