Imprinted polymers with cyclodextrin pseudo-polyrotaxanes as pseudo-supports for protein recognition.
We report a novel approach for preparing protein molecularly imprinted polymers (MIPs) with cyclodextrin pseudo-polyrotaxanes (CD-PPRs) as pseudo-supports, which are formed by self-assembling assistant recognition polymer chains with γ-cyclodextrins. The conformation of the CD-PPRs was characterised by 2D-NOESY, TGA and WAXD. To prepare MIPs, template bovine serum albumin (BSA) was first selectively assembled with modified CD-PPRs to form complexes in the presence of Cu ions. These assemblies were then immobilised by the polymerisation of acrylamide as the monomer and N,N'-methylenebisacrylamide as the cross-linker to prepare protein MIPs. The amount of BSA template adsorbed initially increased with the increase in the amount of CD-PPR and then decreased with the further increase in the CD-PPR content. To obtain the specific adsorption protein, MIPs were washed with KCl solutions of different concentrations. The results of sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed that the specific adsorption proteins could be collected with a 0.500 mol L(-1) KCl solution. The recognition specificity to the template relies on the spatial configuration constructed by CD-PPR and metal ions. Finally, this imprinted polymer was used to purify the template from the protein mixtures containing either two (BSA and ovalbumin) or four (BSA, ovalbumin, soybean trypsine inhibitor and lysozyme) different proteins. Both experiments have demonstrated MIPs high selectivity.


Opioid Usage and Prescribing Predictors Following Transoral Robotic Surgery for Oropharyngeal Cancer.
Pain management following transoral robotic surgery (TORS) varies widely. We aim to quantify opioid usage following TORS for oropharyngeal squamous cell carcinoma (OPSCC) and identify prescribing predictors. Retrospective cohort study. A consecutive series of 138 patients undergoing TORS for OPSCC were reviewed from 2016 to 2019. Opioid usage (standardized to morphine milligram equivalents [MME]) was gathered for 12 months post-surgery via prescribing record cross-check with the Massachusetts Prescription Awareness Tool. Of 138 OPSCC TORS patients, 92.8% were human papillomavirus (HPV) positive. Adjuvant therapy included radiation (XRT;67.4%) and chemoradiation (cXRT;6.5%). Total MME usage from start of treatment averaged 1395.7 MMEs with 76.4% receiving three prescriptions or less. Categorical analysis showed age <65, male sex, overweight BMI, lower frailty, former smokers, HPV+, higher T stage, and BOT subsite to be associated with increased MMEs. Adjuvant therapy significantly increased MMEs (TORS+XRT:1646.2; TORS+cXRT:2385.0; TORS alone:554.7 [P < .001]) and 12-month opioid prescription totals (TORS+XRT:3.2; TORS+cXRT:5.5; TORS alone:1.6 [P < .001]). Adjuvant therapy increased time to taper (total MME in TORS alone versus TORS+XRT/cXRT: 0 to 3 months:428.2 versus 845.5, 4 to 6 months:46.8 versus 541.8, 7 to 9 months:12.4 versus 178.6, 10 to 12 months:11.0 versus 4.4,[P < .001]). Positive predictors of opioid prescribing at the 4- to 6-month and 4- to 12-month intervals included adjuvant therapy (odds ratio [OR]:5.56 and 4.51) and mFI-5 score ≥3 (OR:36.67 and 31.94). Following TORS at 6-, 9-, and 12-month, 15.7%, 6.6%, and 4.1% were still using opioids. In OPSCC treated with TORS, opioid use tapers faster for surgery alone versus with adjuvant therapy. Opioid prescribing risks include adjuvant therapy and higher frailty index. 4 Laryngoscope, 131:E1888-E1894, 2021.


High-Frequency Ultrasound Imaging of Tidemark In Vitro in Advanced Knee Osteoarthritis.
High-frequency ultrasound imaging has been widely adopted for assessment of the degenerative changes of articular cartilage in osteoarthritis (OA). Yet, there are few reports on investigating its capability to evaluate subchondral bone. Here, we employed high-frequency ultrasound imaging (25 MHz) to examine in vitro the tidemark in cylindrical osteochondral disks (n = 33) harvested from advanced OA knees of humans. We found good correspondence in morphology observed by ultrasound imaging and micro-computed tomography. Ultrasound roughness index (URI) of tidemark was derived from the raw radiofrequency signals to compare with bone quality factors, including bone volume fraction (BV/TV) and bone mineral density (BMD) measured by micro-computed tomography, using the Spearman correlation (ρ). URI of the tidemark was negatively associated with the subchondral plate BV/TV (ρ = -0.73, p <0.001), BMD (ρ = -0.40, p = 0.020), as well as the underneath trabecular bone BV/TV (ρ = -0.39, p = 0.025) and BMD (ρ = -0.43, p = 0.012). In conclusion, this preliminary study demonstrated that morphology measured by high-frequency ultrasound imaging could reflect the quality of the subchondral bone. High-frequency ultrasound is a promising imaging tool to evaluate the changes of the subchondral bone in addition to those of the overlying cartilage in OA.


Hepatic resection for metastasis from colorectal cancer.
Twenty-five patients who had hepatic metastases from carcinomas of the colon and rectum had resection for cure at Memorial Hospital, with a determinate five-year survival rate of 40 per cent, and 10-year survival rate of 28 per cent. Most of the hepatic metastatic lesions were solitary, small, and peripheral, and were treated with simple wedge resection. These favorable results justify an aggressive approach to solitary metastatic lesions in the liver.


The role of alcohol in oesophageal cancer in non-smokers, and of tobacco in non-drinkers.
Data from a hospital-based case-control study of oesophageal cancer conducted in Northern Italy were used to analyse the risk associated with alcohol in non-smokers and with tobacco in non-drinkers. Out of a total of 250 cases (198 males, 52 females) and 1,089 controls (800 males, 289 females), there were 38 cases and 404 controls who described themselves as lifelong non-smokers. Among these persons, the relative risk was not different for teetotallers and moderate drinkers (less than 4 drinks per day), but increased markedly for higher levels of alcohol consumption. The point estimates were 2.1 for 4 to 8 and 3.6 for over 8 drinks per day, and the trend in risk was statistically significant. Likewise, among 30 cases and 189 controls who were non-drinkers, the point estimates were 2.0, 3.9 and 6.2 for smokers of less than 15, 15-24 and greater than or equal to 25 cigarettes per day, with, again, a statistically significant trend. This study supplies further evidence that both alcohol and tobacco are strongly related to the risk of oesophageal cancer, even in the absence of exposure to the other risk factor. This confirms previous indications from a study in Calvados, France and also provides statistically significant epidemiological evidence of an independent role of exposure to tobacco alone in the aetiology of oesophageal cancer. The relative risks associated with exposure to either of the 2 factors among subjects not exposed to the other were readily comparable to the estimates adjusted for the other factor in the overall data-set, thus further confirming the independent effect of alcohol and tobacco on oesophageal carcinogenesis.


Effect of epinephrine and norepinephrine on immuno-reactive insulin secretion from isolated islets of Langerhans.
Earlier studies have demonstrated the inhibitory nature of epinephrine and norepinephrine on pancreatic insulin release. The present study reports their effect on beta-cell IRI release in an isolated islet system. Results show that epinephrine and norepinephrine inhibit islet-IRI release at the 100-10 microM level. The alpha adrenergic blocker phentolamine (100 microM) but not the beta adrenergic blocker propranolol (100 microM) can reverse this catecholamine induced inhibition of islet-IRI release. This clearly suggests that epinephrine and norepinephrine inhibit insulin release via alpha-adrenergic pathway.


[Studies on the immune status of melanoma patients: cell-mediated immune reactions in intracutaneous and epicutaneous tests in the lymphocyte transformation test and the leukocyte-migration inhibition test before and during BCG immunotherapy (author's transl)].
Active immunotherapy with BCG was carried out postoperatively in 22 patients with malignant melanoma. At the beginning and 6 months after treatment cell-mediated immune reactions were checked by both in vivo tests (intracutaneous test with tuberculin and patchtest with DNCB) and in vitro tests (lymphocyte stimulation and leukocyte migration inhibition with tuberculin and DNCB). The results have shown that stimulation of immune response may be obtained by systemic BCG therapy.


Progesterone receptors in lymphocytes of liver-transplanted and transfused patients.
Previous data have shown that lymphocytes from pregnant women, but not from non-pregnant individuals, displayed progesterone receptors. These receptors are inducible in normal human lymphocytes in vitro by mitogenic or allogeneic stimuli. The present study was designed to test the role of in vivo allogeneic stimulation in inducing progesterone receptors in lymphocytes from transplanted and transfused patients. Receptors were detected by immunohistology using a progesterone receptor-specific MoAb and avidin-biotin system. Peripheral blood lymphocytes from 56 healthy pregnant women, 8 liver-transplanted patients and 15 transfused patients contained significantly more receptor-positive cells (P less than 0.001) than those of non-pregnant individuals. In transplanted and transfused patients no correlation was found between the percentage of positive lymphocytes and age, sex or transplant survival. Our results show that in these three groups the percentage of receptor-bearing lymphocytes was higher than in normal subjects.


Cathepsin B and its endogenous inhibitors: the role in tumor malignancy.
Several lysosomal proteinases including the cysteine proteinase cathepsin B have been implicated in malignant progression of tumors. Many investigators have demonstrated correlations between increased activity of cathepsin B and increased metastatic capability of animal tumors or malignancy of human tumors. Such increases in cathepsin B activity in malignant tumors may reflect alterations in synthesis, in activation and processing, and/or in intracellular trafficking and delivery as well as in the endogenous inhibitors of cathepsin B. Increases in mRNA transcripts for cathepsin B have been observed in both murine and human tumors and multiple transcripts for cathepsin B have been identified, but an association of multiple transcripts with malignancy has not been confirmed. Cathepsin B precursors found in human malignant ascites fluid do not possess mannose-rich carbohydrates suggesting that a defect in the post translational processing of carbohydrate moieties on tumor cathepsin B may be responsible for the release of cathepsin B observed in many tumor systems. However, the intracellular trafficking of cathepsin B responsible for its association with plasma membrane/endosomal systems and for its release will require further study as both latent, precursor forms of cathepsin B and native forms of cathepsin B are involved. We speculate that malignant tumor cells adherent to basement membrane are capable of forming a digestive microenvironment in which lysosomal proteinases such as cathepsin B function optimally, a microenvironment similar to that formed between adherent osteoclasts and bone. One of the endogenous cysteine proteinase inhibitors, stefin A, also is affected by malignancy. Reduced expression (mRNA and protein) of stefin A is found as well as a reduction in its inhibitory capacity against cysteine proteinases. The data to date at both the molecular and protein levels supporting a functional role(s) for cathepsin B and its endogenous inhibitors in cancer progression are only correlative. Experimental approaches utilizing well-defined model systems in conjunction with genetic manipulation of cathepsin B and its endogenous inhibitors are needed to provide convincing evidence that cathepsin B has an important role in cancer.


Racial Differences in Manipulation Under Anesthesia Rates Following Total Knee Arthroplasty.
Despite the extensive literature on racial disparities in care and outcomes after total knee arthroplasty (TKA), data on manipulation under anesthesia (MUA) is lacking. We aimed to determine (1) the relationship between race and rate of (and time to) MUA after TKA, and (2) annual trends in racial differences in MUA from 2013 to 2018. This retrospective cohort study (using 2013-2018 Medicare Limited Data Set claims data) included 836,054 primary TKA patients. The primary outcome was MUA <1 year after TKA; time from TKA to MUA in days was also recorded. A mixed-effects multivariable model measured the association between race (White, Black, Other) and odds of MUA. Odds ratios (OR) and 95% confidence intervals (CI) were reported. A Cochran Armitage Trend test was conducted to assess MUA trends over time, stratified by race. MUA after TKA occurred in 1.7%, 3.2% and 2.1% of White, Black, and Other race categories, respectively (SMD = 0.07). After adjustment for covariates, (Black vs White) patients had increased odds of requiring an MUA after TKA: odds ratio (OR) 1.97, 95% confidence intervals (CI) 1.86-2.10, P < .0001. Moreover, White (compared to Black) patients had significantly shorter time to MUA after TKA: 60 days (interquartile range [IQR] 46-88) versus 64 days (interquartile range [IQR] 47-96); P < .0001. These disparities persisted from 2013 through 2018. Continued racial differences exist for rates and timing of MUA following TKA signifying the continued need for efforts aimed toward understanding and eliminating inequalities that exist in total joint arthroplasty (TJA) care.


Mechanisms and consequences of Jak-STAT signaling in the immune system.
Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced breakneck growth in the quarter century since its discovery and has yielded a stream of basic and clinical insights that have profoundly influenced modern understanding of human health and disease, exemplified by the bench-to-bedside success of Jak inhibitors ('jakinibs') and pathway-targeting drugs. Here we review recent advances in Jak-STAT biology, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.


Development of an International Classification of Functioning, Disability and Health (ICF)-based standard set to describe the impact of joint contractures on participation of older individuals in geriatric care settings.
Joint contractures are characterized as impairment of the physiological movement of joints due to deformity, disuse or pain and have major impact especially for older individuals in geriatric care. Some measures for the assessment of the impact of joint contractures exist. However, there is no consensus on which aspects should constantly be measured. Our objective was to develop a standard-set based on the ICF for describing functioning and disability in older individuals with joint contractures in geriatric care settings, giving special emphasis to activities and participation. The ICF-based standard set was developed in a formal decision-making and consensus process and based on an adapted version of the protocol to develop ICF Core Sets. These are sets of categories from the ICF, serving as standards for the assessment, communication and reporting of functioning and health for clinical studies, clinical encounters and multi-professional comprehensive assessment and management. Twenty-three experts from Germany and Switzerland selected 105 categories of the ICF component Activities and Participation for the ICF-based standard set. The largest number of categories was selected from the chapter Mobility (50 categories, 47.6%). The standard set for older individuals with joint contractures provides health professionals with a standard for describing patients' activity limitations and participation restrictions. The standard set also provides a common basis for the development of patient-centered measures and intervention programs. The preliminary version of the ICF-based standard set will be tested in subsequent studies with regard to its psychometric properties.


A Rare Presentation of Thyroid Mass as Tubercular Abscess: A Case Report.
Isolated thyroid gland tuberculosis is a rare disease, while even rarer is its presentation as an acute abscess. Here we present the case of a 65-year-old female who presented with a neck swelling which progressed to an abscess with multiple discharging sinuses which was proven to be tubercular abscess on histopathology.


Of mice and men on MDMA: A translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy').
MDMA (3,4-methylendioxymethamphetamine), also known as Ecstasy, is a stimulant drug recreationally used by young adults usually in dance clubs and raves. Acute MDMA administration increases serotonin, dopamine and noradrenaline by reversing the action of the monoamine transporters. In this work, we review the studies carried out over the last 30 years on the neuropsychobiological effects of MDMA in humans and mice and summarise the current knowledge. The two species differ with respect to the neurochemical consequences of chronic MDMA, since it preferentially induces serotonergic dysfunction in humans and dopaminergic neurotoxicity in mice. However, MDMA alters brain structure and function and induces hormonal, psychomotor, neurocognitive, psychosocial and psychiatric outcomes in both species, as well as physically damaging and teratogen effects. Pharmacological and genetic studies in mice have increased our knowledge of the neurochemical substrate of the multiple effects of MDMA. Future work in this area may contribute to developing pharmacological treatments for MDMA-related disorders.


Urine α-Glutathione S-transferase, systemic inflammation and arterial function in juvenile type 1 diabetes.
Despite marked improvement in therapy and monitoring of patients with insulin-dependent (type 1) diabetes, diabetic nephropathy remains a serious complication, with subsequent end-stage renal disease in about 20% of cases. To investigate in young patients with type 1 diabetes whether urine α-Glutathione S-transferase to creatinine ratio (α-GST:crea) relates to markers of systemic inflammation and subclinical vasculopathy. Children and adolescents (median age and diabetes duration 14 and 6 years, respectively) with type 1 diabetes screened in a previous study for proximal tubular (urine α-GST:crea ratio) and renal (plasma creatinine, cystatin C glomerular filtration rate (GFR), and timed urine albumin excretion rate (AER)) function were, within the same timeframe, also investigated for vascular (blood pressure, carotid artery intima-media thickness (IMT) and compliance (CAC), brachial artery flow-mediated dilatation (FMD) and plasma cyclic guanosine monophosphate (cGMP) and inflammatory (C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α)) profiles. Exposure to environmental tobacco smoke (ETS) was assessed through questionnaire (n=67 respondents). None of the patients (n=69) had overt renal insufficiency. AER correlated with age (p=0.01, r=0.3), diabetes duration (p=0.02, r=0.3), FMD (p=0.04, r=-0.3, n=52), CAC (p=0.03, r=-0.3, n=62) and cGMP (p=0.01, r=-0.3, n=59). α-GST:crea was lower (p=0.03) in patients than in controls. α-GST:crea appeared to be particularly lower in older patients (p=0.004, r=-0.34 vs age), in those with worse diabetic control (p=0.03, r=-0.26 vs HbA1c), and in those with lower carotid artery elasticity (p=0.017, r=0.3 vs CAC). Although ETS had no direct significant impact on α-GST:crea, α-GST:crea correlated with FMD only in patients with ETS (r=0.5, p=0.009, n=13). α-GST:crea showed positive association with TNF-α (p=0.01, r=0.3). In children and adolescents with type 1 diabetes, lower levels of urine excretion of α-GST:crea appear to be associated with decreasing elasticity and endothelial vasomotor function of peripheral arteries, especially in patients with ETS. In contrast, higher levels of α-GST:crea are more common in patients with elevated markers of systemic inflammation. Large scale prospective studies are needed to clarify the meaning and mechanisms of this association.


Structural studies of metal-organic frameworks under high pressure.
Over the last 10 years or so, the interest and number of high-pressure studies has increased substantially. One area of growth within this niche field is in the study of metal-organic frameworks (MOFs or coordination polymers). Here we present a review on the subject, where we look at the structural effects of both non-porous and porous MOFs, and discuss their mechanical and chemical response to elevated pressures.


Investigation of the functional brain-derived neurotrophic factor gene variant Val66MET in migraine.
Experimental studies and investigations of the cerebrospinal fluid in migraineurs have suggested an involvement of brain-derived neurotrophic factor (BDNF) in migraine pathophysiology. In a case-control study approach, the functional Val66MET polymorphism (rs6265) of the BDNF gene was investigated in 265 migraine patients and 153 controls. Genotype and allele frequencies did not differ between healthy subjects and migraineurs. A subgroup analysis for the occurrence of aura or clinical characteristics, including the number of attacks, did not reveal a positive association for the investigated polymorphism. Our data argue against a role of this well characterized BDNF gene variant as a risk factor in migraine.


Association between timing of speech and language therapy initiation and outcomes among post-extubation dysphagia patients: a multicenter retrospective cohort study.
Post-extubation dysphagia (PED) is recognized as a common complication in the intensive care unit (ICU). Speech and language therapy (SLT) can potentially help improve PED; however, the impact of the timing of SLT initiation on persistent PED has not been well investigated. This study aimed to examine the timing of SLT initiation and its effect on patient outcomes after extubation in the ICU. We conducted this multicenter, retrospective, cohort study, collecting data from eight ICUs in Japan. Patients aged ≥ 20 years with orotracheal intubation and mechanical ventilation for longer than 48 h, and those who received SLT due to PED, defined as patients with modified water swallowing test scores of 3 or lower, were included. The primary outcome was dysphagia at hospital discharge, defined as functional oral intake scale score < 5 or death after extubation. Secondary outcomes included dysphagia or death at the seventh, 14th, or 28th day after extubation, aspiration pneumonia, and in-hospital mortality. Associations between the timing of SLT initiation and outcomes were determined using multivariable logistic regression. A total of 272 patients were included. Of them, 82 (30.1%) patients exhibited dysphagia or death at hospital discharge, and their time spans from extubation to SLT initiation were 1.0 days. The primary outcome revealed that every day of delay in SLT initiation post-extubation was associated with dysphagia or death at hospital discharge (adjusted odds ratio (AOR), 1.09; 95% CI, 1.02-1.18). Similarly, secondary outcomes showed associations between this per day delay in SLT initiation and dysphagia or death at the seventh day (AOR, 1.28; 95% CI, 1.05-1.55), 14th day (AOR, 1.34; 95% CI, 1.13-1.58), or 28th day (AOR, 1.21; 95% CI, 1.07-1.36) after extubation and occurrence of aspiration pneumonia (AOR, 1.09; 95% CI, 1.02-1.17), while per day delay in post-extubation SLT initiation did not affect in-hospital mortality (AOR, 1.04; 95% CI, 0.97-1.12). Delayed initiation of SLT in PED patients was associated with persistent dysphagia or death. Early initiation of SLT may prevent this complication post-extubation. A randomized controlled study is needed to validate these results.


Hypnotizability and dissociativity in sexually abused girls.
Research on the relation between hypnotizability and clinical dissociation has led to contradictory findings. Measures of hypnotizability and dissociation are only weakly correlated in general population samples, but studies of posttraumatic stress and dissociative disorders patients have found elevated levels of clinical dissociation and hypnotizability respectively. This study assesses the relationships among hypnotizability, clinical dissociation and traumatic antecedents in 54 sexually abused girls, ages 6-15 years, and 51 matched controls. Hypnotizability was assessed on initial evaluation and again in matched subsamples at one year using the Stanford Hypnotic Clinical Scale for Children. Clinical dissociation was assessed using the Child Dissociative Checklist. Abuse variables were extracted from Child Protective Services reports. There were no significant differences in hypnotizability between abuse and control subjects. There were significant differences in clinical dissociation initially and on 1-year retest. Hypnotizability and clinical dissociation were only weakly correlated (r(105) = .118, p = NS). However, in the abuse group, highly hypnotizable subjects were significantly more dissociative. Higher levels of clinical dissociation were associated with abuse by multiple perpetrators and co-presence of physical abuse independent of the sexual abuse. A small subgroup of "double dissociative" subjects, high in both hypnotizability and dissociativity, was identified. Double dissociation was associated with multiple perpetrators and earlier onset of sexual abuse.


Face-lifting the surface of LiNi0.8Co0.15Al0.05O2cathode via Y(PO3)3to form anin situtriple composite Li-ion conductor coating layer with the enhanced electrochemical performance.
Due to the assets such as adequate discharge capacity and rational cost, LiNi0.8Co0.15Al0.05O2(NCA), a high-nickel ternary layered oxide, is regarded to be a favorable cathode contender for lithium-ion batteries. However, the superior commercial application is restricted by the surface residual alkaline lithium salt (LiOH or/and Li2CO3) of nickel-rich cathode materials, which will expedite the disintegration of the structure and the engendering of gas (CO2). Therefore, in this paper, we devise and fabricate a Y(PO3)3modified LiNi0.8Co0.15Al0.05O2(NCA), intending to optimize the surface residual alkaline lithium salt (antecedent deportation of H2O and CO2) while forming anin situtriple composite Li-ion conductor coating (Y(PO3)3-Li3PO4-YPO4) to enhance the electrochemical behavior. Under this method, the 2 mol% Y(PO3)3modified NCA electrode reveals exceptional rate capability (5 C/156.3 mAh g-1) and extraordinary cycle stability after 200 cycles (2 C/88.3%), whereas the original sample is only 5 C/123.1 mAh g-1and 2 C/71.2% after 200 cycles. Conspicuously, even under the draconian circumstances of the high temperature and the high rate at 55 °C/1 C, the 2 mol% Y(PO3)3modified NCA electrode sustains a high reversible capacity, with an admirable capacity retention rate of 89.4% after 100 cycles. These contented results signify that the surface remodeling tactic presents a viable scheme for ameliorating high-nickel materials' performance and appropriateness.


Opioid Use and Risk of Nonvertebral Fractures in Adults With Rheumatoid Arthritis: A Nested Case-Control Study Using Administrative Databases.
To assess the risk of nonvertebral fractures in patients with rheumatoid arthritis (RA) who were exposed to opioids. A population-based, nested case-control study was conducted using health services administrative databases (Quebec, Canada) from 1997 to 2012. Among RA patients, cases of nonvertebral fractures from 2007 to 2012 were identified using a validated algorithm. The date of the first fracture was the index date for the case and his/her matched control. Controls were selected using incidence density sampling and were matched 5:1 to cases for age, sex, and date of RA diagnosis. Opioid exposure was classified as current use, recent past use, remote past use, and nonuse. Conditional logistic regression was used to assess the association of nonvertebral fractures with opioid exposure, adjusting for comorbidity, indicators of RA severity, drugs influencing fracture risk, and health care utilization. In total, 1,723 cases and 8,046 controls were identified. Among these patients, 2,595 (722 cases and 1,873 controls) had been exposed to opioids. Current use (versus nonuse) increased the risk of nonvertebral fracture. Cumulative current use of opioids according to the quartile distribution was also associated with the risk of nonvertebral fracture: for continuous use for 1-20 days before the index date, odds ratio (OR) 11.49 (95% confidence interval [95% CI] 8.81-14.99); for 21-155 days, OR 1.75 (95% CI 1.31-2.33); for 156-355 days, OR 1.54 (95% CI 1.17-2.04); and for ≥356 days, OR 1.73 (95% CI 1.31-2.30). No association between the risk of nonvertebral fractures and recent past use or remote past use of opioids was observed. Among RA patients, the risk of nonvertebral fracture is increased in those treated with opioids.


Preparation of Surface Adsorbed and Impregnated Multi-walled Carbon Nanotube/Nylon-6 Nanofiber Composites and Investigation of their Gas Sensing Ability.
We have prepared electrospun Nylon-6 nanofibers via electrospinning, and adsorbed multi-walled carbon nanotubes (MWCNTs) onto the surface of Nylon-6 fibers using Triton(®) X-100 to form a MWCNTs/Nylon-6 nanofiber composite. The dispersed MWCNTs have been found to be stable in hexafluoroisopropanol for several months without precipitation. A MWCNTs/Nylon-6 nanofiber composite based chemical sensor has demonstrated its responsiveness towards a wide range of solvent vapours at room temperature and only mg quantities of MWCNTs were expended. The large surface area and porous nature of the electrospun Nylon-6/MWCNT nanofibers facilitates greater analyte permeability. The experimental analysis has indicated that the dipole moment, functional group and vapour pressure of the analytes determine the magnitude of the responsiveness.


Ancestries of a recombining diploid population.
We derive the exact one-step transition probabilities of the number of lineages that are ancestral to a random sample from the current generation of a bi-parental population that is evolving under the discrete Wright-Fisher model with n diploid individuals. Our model allows for a per-generation recombination probability of r . When r = 1, our model is equivalent to Chang's (Adv Appl Probab 31:1002-1038, 1999) model for the karyotic pedigree. When r = 0, our model is equivalent to Kingman's (Stoch Process Appl 13:235-248, 1982) discrete coalescent model for the cytoplasmic tree or sub-karyotic tree containing a DNA locus that is free of intra-locus recombination. When 0 < r < 1 our model can be thought to track a sub-karyotic ancestral graph containing a DNA sequence from an autosomal chromosome that has an intra-locus recombination probability r . Thus, our family of models indexed by r ∈ [0, 1] connects Kingman's discrete coalescent to Chang's pedigree in a continuous way as r goes from 0 to 1. For large populations, we also study three properties of the ancestral process corresponding to a given r ∈ (0, 1): the time Tn to a most recent common ancestor (MRCA) of the population, the time Un at which all individuals are either common ancestors of all present day individuals or ancestral to none of them, and the fraction of individuals that are common ancestors at time Un. These results generalize the three main results of Chang's (Adv Appl Probab 31:1002-1038, 1999). When we appropriately rescale time and recombination probability by the population size, our model leads to the continuous time Markov chain called the ancestral recombination graph of Hudson (Theor Popul Biol 23:183-201, 1983) and Griffiths (The two-locus ancestral graph, Institute of Mathematical Statistics 100-117, 1991).


Interleukin-33 attenuates doxorubicin-induced cardiomyocyte apoptosis through suppression of ASK1/JNK signaling pathway.
Interleukin-33 (IL-33), a new member of the IL-1 cytokine family, has cardiac protective effect in many circumstances. The aims of present study are to assess whether IL-33 can protect cardiomyocytes from doxorubicin (DOX)-induced apoptosis and the mechanism involved in the protection. Cardiomyocytes derived from either wild-type or c-Jun N-terminal kinase deficient (JNK-/-) mice were challenged with DOX (1 μM) with or without IL-33 (10 ng/ml). Myocyte apoptosis was assessed by measuring Caspase 3 activity, fragmented DNA and the TUNEL staining. In addition, cardiomyocyte reactive oxygen species (ROS) was assessed by measuring 2',7'-dichlorofluorescin diacetate (DCFDA); apoptosis signal-regulating kinase 1(ASK1) and JNK phosphorylation were assessed with western blot analysis. Treatment of cardiomyocyes with DOX resulted in ROS generation, ASK1 and JNK phosphorylation and myocyte apoptosis. IL-33 inhibited the DOX-induced ROS, prevented ASK1 and JNK phosphorylation and attenuated the DOX-induced myocyte apoptosis. Genetic inhibition of ASK1 (ASK1 siRNA transfection) and JNK (JNK-/-) ameliorated the cardiac-protective effect of IL-33. Moreover, inhibition of ASK1 prevented the DOX-induced phosphorylation of JNK, while inhibition of JNK showed no effect on DOX-induced ASK1 phosphorylation. Our study indicates that: 1) ASK1/JNK signaling pathway is involved in DOX-induced cardiomyocyte apoptosis; 2) IL-33 protects cardiomyocytes from DOX-induced myocyte apoptosis through inhibition of the ASK1/JNK signaling pathway. IL-33 may have therapeutic potential for DOX-induced cardiac injury.


Role of hippocalcin in mediating Aβ toxicity.
Alzheimer's disease (AD) is the most common cause of dementia, and amyloid-β (Aβ) plaques and tau-containing tangles are its histopathological hallmark lesions. These do not occur at random; rather, the neurodegenerative process is stereotyped in that it is initiated in the entorhinal cortex and hippocampal formation. Interestingly, it is the latter brain area where the calcium-sensing enzyme hippocalcin is highly expressed. Because calcium deregulation is a well-established pathomechanism in AD, we aimed to address the putative role of hippocalcin in human AD brain and transgenic mouse models. We found that hippocalcin levels are increased in human AD brain and in Aβ plaque-forming APP23 transgenic mice compared to controls. To determine the role of hippocalcin in Aβ toxicity, we treated primary cultures derived from hippocalcin knockout (HC KO) mice with Aβ and found them to be more susceptible to Aβ toxicity than controls. Likewise, treatment with either thapsigargin or ionomycin, both known to deregulate intracellular calcium levels, caused an increased toxicity in hippocampal neurons from HC KO mice compared to wild-type. We found further that mitochondrial complex I activity increased from 3 to 6months in hippocampal mitochondria from wild-type and HC KO mice, but that the latter exhibited a significantly stronger aging phenotype than wild-type. Aβ treatment induced significant toxicity on hippocampal mitochondria from HC KO mice already at 3months of age, while wild-type mitochondria were spared. Our data suggest that hippocalcin has a neuroprotective role in AD, presenting it as a putative biomarker.


Prospective comparison of cirrus and stratus optical coherence tomography for quantifying retinal thickness.
To compare Cirrus Fourier-domain optical coherence tomography (OCT) with Stratus time-domain OCT for imaging retinal diseases and quantifying retinal thickness (RT) of all nine OCT zones, central macular thickness, and average macular thickness in eyes with and without macular edema. Prospective comparison between two OCT systems. RT measurements were performed in 120 eyes of 60 patients suspected of having increased retina thickness using both Stratus and Cirrus OCT on the same day. Twenty-one eyes had both 512 x 128 and 200 x 200 Cirrus cube scans done. Data from 101 eyes (53 patients) were analyzed; 46 eyes (45.5%) had macular edema on clinical examination (Group 1), whereas 55 eyes (54.4%) had no clinical evidence of macular edema (Group 2). There was modest correlation between all thickness measurements in 909 zones and each group (range of Pearson correlation, 0.51 to 0.89) and average value was significantly greater when measured with Cirrus OCT for all eyes (mean difference, 43.2 microm; P < .0001). There were few measurement differences between different resolution Cirrus cube scans. Cirrus OCT measures RT approximately 43 microm greater than Stratus OCT, which is likely attributable to Cirrus OCT detection of the outer band of the retinal pigment epithelium vs Stratus OCT detection of the inner/outer segment photoreceptor junction. All zones showed a wide degree of variability in correlation. Both Cirrus cube scans provide similar data. Future studies comparing these systems might consider utilizing average macular thickness values, which reflect macular volume and may provide more consistent measurements.


Predictors of Long-Term Exercise Engagement in Patients With Obsessive-Compulsive Disorder: The Role of Physical Activity Enjoyment.
Most U.S. adults, even more so those with psychiatric conditions like obsessive-compulsive disorder (OCD), do not engage in the recommended amount of physical activity (PA), despite the wide array of physical and mental health benefits associated with exercise. Therefore, it is essential to identify mechanistic factors that drive long-term exercise engagement so they can be targeted. Using the science of behavior change (SOBC) framework, this study examined potential predictors of long-term exercise engagement as a first step towards identifying modifiable mechanisms, in individuals with OCD, such as PA enjoyment, positive or negative affect, and behavioral activation. Fifty-six low-active patients (mean age = 38.8 ± 13.0, 64% female) with a primary diagnosis of OCD were randomized to either aerobic exercise (AE; n = 28) or health education (HE; n = 28), and completed measures of exercise engagement, PA enjoyment, behavioral activation, and positive and negative affect at baseline, postintervention, and 3-, 6-, and 12-month follow-up. Significant predictors of long-term exercise engagement up to 6-months postintervention were baseline PA (Estimate = 0.29, 95%CI [0.09, 0.49], p = .005) and higher baseline PA enjoyment (Estimate = 1.09, 95%CI [0.30, 1.89], p = .008). Change in PA enjoyment from baseline to postintervention was greater in AE vs. HE, t(44) = -2.06, p = .046, d = -0.61, but endpoint PA enjoyment did not predict follow-up exercise engagement above and beyond baseline PA enjoyment. Other hypothesized potential mechanisms (baseline affect or behavioral activation) did not significantly predict exercise engagement. Results suggest that PA enjoyment may be an important modifiable target mechanism for intervention, even prior to a formal exercise intervention. Next steps aligned with the SOBC framework are discussed, including examining intervention strategies to target PA enjoyment, particularly among individuals with OCD or other psychiatric conditions, who may benefit most from long-term exercise engagement's effects on physical and mental health.


Detection of elevated amounts of urinary pseudouridine in cancer patients by use of a monoclonal antibody.
Preparation of anti-pseudouridine monoclonal antibodies (MoAbs) and their applications for the quantitation of urinary pseudouridine in cancer patients are described. Seven MoAbs were selected. Five MoAbs were specific for pseudouridine and two MoAbs were cross-reactive with uridine. The most specific antibody, APU-6, was used in an enzyme-linked immunosorbent assay (ELISA) to determine urinary pseudouridine. Sensitivity was in the picomole range and the accuracy was nearly equal to that of the high performance liquid chromatography (HPLC) assay. The amount of pseudouridine in the urine of 28 healthy donors was 31.17 +/- 9.94 nmol/mumol creatinine. In 55% (35/63) of patients with cancer, urinary pseudouridine was elevated above the normal mean + 2 SD (51.04 nmol/mumol creatinine). Particularly, all of the patients (15/15) with leukemia and lymphoma had elevated levels of pseudouridine. These results suggest that urinary pseudouridine might be useful as a marker for leukemia and lymphoma.


Osteoporosis in primary care: an opportunity to approach risk factors.
Climacteric women are susceptible to a number of changes, among them osteoporosis. Osteoporosis is a disease characterized by low bone mass and susceptibility to fracture. Currently, this disease is a public health issue, being necessary to recognize its risk factors. Identify risk factors related to osteoporosis in women attending PROPIS/PROEX/UFMA, tracing a socio-demographic characterization and considering community lifestyles. This is a transversal retrospective clinical with a quantitative approach study conducted between March and June 2013 in São Luís-MA with 107 women treated at the Programa de Práticas de Integralidade em Saúde (PROPIS - Integrality Health Practice Program). The study was approved by the University Hospital Ethics Committee of UFMA under opinion no. 362/07. Data were tabulated and analyzed in the epidemiological Epi-Info(®) software, version 3.4.1. The brown color was predominant, consensual relationships proved to be a protective factor and low education was a risk factor. The average age of the group with menopause was 54.1 years and without menopause was 31.3 years (p<0.0001). The average age of menopause was 43.7 years. The irregular menstrual cycle was a protective factor. The average number of pregnancies was 4.56 for the group with menopause and 2.45 for the group without menopause, with most births occurring normally (p<0.0001). Smoking, physical inactivity and caffeine intake were risk factors, while the absence of alcoholism and of soda intake were protective factors for the disease. The patients followed the socioeconomic and demographic profile of Maranhão. Most had menarche and menopause in appropriate periods, showed no positive family history of osteoporosis, did not usually drink alcohol, were sedentary and the caffeine intake was high.


Factors associated with severity of symptoms in patients with chronic unexplained muscular aching.
Subjects with chronic, diffuse, unexplained muscular aching were recruited--21 from a primary care practice, nine from a rheumatology practice, and two from a pain clinic. No additional criteria were used to select subjects. Subjects with mild or moderate symptoms differed from those with severe symptoms with respect to the following characteristics: the presence of fatigue on awakening, the number of tender points, difficulty in sleeping, and the degree of tenderness in typical fibromyalgia areas as measured by a dolorimeter. These findings suggest that muscular aching is likely to be of greater severity if other symptoms or signs of fibromyalgia are also present.


Severe anemia is associated with increased short-term and long-term mortality in patients hospitalized with cirrhosis.
The relationship between anemia and the outcome of patients with cirrhosis is not completely clear. Therefore, we performed this large-scale epidemiological study to investigate the prevalence and severity of anemia in patients with cirrhosis and acute decompensation or liver injury and how anemia impacts short-term and long-term outcomes. Patients with cirrhosis and acute decompensation (AD) or acute liver injury (ALI) were enrolled in the Chinese AcuTe on CHronic LIver FailurE (CATCH-LIFE) studies, which consisted of two large, multicenter, prospective, observational cohorts between January 2015 and December 2016 and July 2018 and January 2019. We conducted data analysis on the prevalence of anemia and determined the relationship between anemia and prognosis. Among 1979 patients, 1389 (70.2%) had anemia, among whom 599 (41.3%) had mild anemia, 595 (15.8%) had moderate anemia and 195 (2.4%) had severe anemia. A linear association between hemoglobin level and 90-day or 1-year LT-free mortality was shown, and a 10 g/L decrease in hemoglobin level was associated with a 6.8% extra risk of 90-day death and a 5.7% extra risk of 1-year death. Severe anemia was an independent risk factor for 90-day [HR=1.649 (1.100, 2.473), p=0.016] and 1-year LT-free mortality [HR=1.610 (1.159, 2.238), p=0.005]. Multinomial logistic regression analysis further identified that severe anemia was significantly associated with post-28-day mortality but not within-28-day mortality. Anemia is common in patients with cirrhosis admitted for acute events. Severe anemia was associated with poor 90-day and 1-year prognoses in these patients.


Enterogenous cyst of the third ventricle.
We present the second case of an enterogenous cyst of the third ventricle. This is a 28-year-old woman who presented with a 2 year history of progressive headaches and memory loss. A cystic lesion of the anterior third ventricle was noted on MRI. The cyst was resected via a transcallosal approach and demonstrated simple cystic morphology lined by ciliated cuboidal epithelium with numerous goblet cells. The presentation was unusual with signs of memory loss presumably due to a mass effect on the fornices. Although uncommon, this entity should be considered in the differential diagnosis of a cystic lesion of the third ventricle.


Enhanced fresh-keeping capacity of printed surimi by Ca2+-nano starch-lutein and its nondestructive freshness monitoring based on 4D printed anthocyanin.
To solve undiscernible freshness changes of printed functional surimi while maintaining printed shape, 4D printable color-changing material were prepared. Firstly, based on results of printing properties and fresh-keeping of Ca2+-NS-L-surimi, it showed better printing effects (enhanced mechanical strength) and good preservation (inhibition of amino acids decomposition, bacterial growth). However, freshness changes of printed Ca2+-NS-L-surimi were not distinguished directly. To avoid that, 4D printable color-changing material-anthocyanin-hydroxypropyl methyl cellulose-xanthan gum-carrageenan (AHXK) was prepared for indicating freshness through discoloration. Printing results showed AHX with 5 % K had the most suitable mechanical strength (appropriate gel strength, texture, rheology) for printing. Based on that, AHXK had stable color (ΔE fluctuation <5) and was sensitive to pH and ammonia (obvious discoloration; ΔE > 10). Actual freshness monitoring results (co-printing of AHXK-surimi) exhibited significant discolorations, especially for HXK with 0.75 % A. It became green during refrigeration of 3-5 d (keeping fresh, ΔE < 4), brighter green at 7 d (decreased freshness, ΔE > 6), turned yellow at 9 d (spoilage, ΔE > 16), which were distinguished significantly with naked eyes rather than traditional freshness determining. In conclusion, printed AHXK-functional surimi exhibited good printing, preservation and nondestructive freshness monitoring, facilitating application of 3D printed functional surimi.


A SAS procedure for exact probability testing of difference between sample and population proportion.
Statistical testing of the hypothesis that the proportion of subjects in a defined population having a certain attribute (proportion of "positives" in a population, P) is equal to some specified value (P0) is frequently encountered in biomedical research. For example, a study might be carried out to statistically test whether the postoperative wound infection rate in patients having undergone an operation with a "new" surgical procedure is 20%, the same value that has been observed for the "established" surgical procedure. The significance test for this hypothesis (e.g., test H0: P = 0.20 against HA: P not equal to 0.20) is usually based on the normal theory approximation method. However, when the sample size is "small", especially if P0 is close to 0 or 1, the normal theory method can yield grossly unreliable results. In contrast, the significance test based on the exact binomial probability procedure always yields reliable results. A computer program coded in SAS is described herein to perform this exact probability test procedure.


Using Structural Analysis In Silico to Assess the Impact of Missense Variants in MEN1.
Despite the rapid expansion in recent years of databases reporting either benign or pathogenic genetic variations, the interpretation of novel missense variants remains challenging, particularly for clinical or genetic testing laboratories where functional analysis is often unfeasible. Previous studies have shown that thermodynamic analysis of protein structure in silico can discriminate between groups of benign and pathogenic missense variants. However, although structures exist for many human disease‒associated proteins, such analysis remains largely unexploited in clinical laboratories. Here, we analyzed the predicted effect of 338 known missense variants on the structure of menin, the MEN1 gene product. Results provided strong discrimination between pathogenic and benign variants, with a threshold of >4 kcal/mol for the predicted change in stability, providing a strong indicator of pathogenicity. Subsequent analysis of seven novel missense variants identified during clinical testing of patients with MEN1 showed that all seven were predicted to destabilize menin by >4 kcal/mol. We conclude that structural analysis provides a useful tool in understanding the effect of missense variants in MEN1 and that integration of proteomic with genomic data could potentially contribute to the classification of novel variants in this disease.


Anaerobic co-digestion of solid waste: Effect of increasing organic loading rates and characterization of the solubilised organic matter.
The impact of stepwise increase in OLR (up to 7.5kgVS/m(3)d) on methane production, reactor performance and solubilised organic matter production in a high-loading reactor were investigated. A reference reactor operated at low OLR (<2.0kgVS/m(3)d) was used solely to observe the methane potential of the feed substrate. Specific methane yield was 0.33lCH(4)/gVS at the lowest OLR and dropped by about 20% at the maximum OLR, while volumetric methane production increased from 0.35 to 1.38m(3)CH(4)/m(3)d. At higher loadings, solids hydrolysis was affected, with consequent transfer of poorly-degraded organic material into the drain solids. Biodegradability and size-fractionation of the solubilised COD were characterized to evaluate the possibility of a second stage liquid reactor. Only 18% of the organics were truly soluble (<1kD). The rest were in colloidal and very fine particulate form which originated from grass and cow manure and were non-biodegradable.


BPDE exposure promotes trophoblast cell pyroptosis and induces miscarriage by up-regulating lnc-HZ14/ZBP1/NLRP3 axis.
Environmental Benzo(a)pyrene (BaP) and its ultimate metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) are typical persistent organic pollutants and endocrine disrupting chemicals. BaP/BPDE exposure might cause human trophoblast cell dysfunctions and induce miscarriage. However, the underlying mechanisms remain largely elusive. In this study, we found that BPDE exposure induced human trophoblast cell pyroptosis by up-regulating NLRP3/Caspase1/GSDMD pathway. We also identified that lnc-HZ14 was highly expressed in BPDE-exposed trophoblast cells and in recurrent miscarriage (RM) vs healthy control (HC) villous tissues. Lnc-HZ14 promoted trophoblast cell pyroptosis by promoting IRF1-mediated ZBP1 transcription, increasing METTL3-mediated m6A methylation on NLRP3 mRNA and its stability, and also enhancing ZBP1/NLRP3 protein interactions. Knockdown of lnc-HZ14/ZBP1/NLRP3 axis could efficiently alleviate BPDE-induced trophoblast cell pyroptosis. Higher level of pyroptosis, as indicated by the up-regulation of lnc-HZ14/ZBP1/NLRP3 axis, was found in RM vs HC villous tissues. In BaP-exposed mouse model, BaP exposure induced placental tissue pyroptosis and miscarriage by up-regulating murine Zbp1/Nlrp3 axis, and knockdown of Nlrp3 could efficiently reduce placenta pyroptosis and alleviate BaP-induced mouse miscarriage. Serum IL-1β protein level might act as a promising indicator to predict the risk of miscarriage. These findings provided new insights into BaP/BPDE-induced trophoblast cell pyroptosis and miscarriage and might be helpful for further assessment of the toxicological effects of BaP/BPDE on the female reproduction.


Cardiac Lymphoma.
Lymphoma of the heart and pericardium may develop in up to 25% of patients with disseminated nodal disease, but primary cardiac lymphoma is rare. The majority are diffuse large B-cell lymphomas, which arise in immunocompetent older individuals, men twice as often as women. Subsets are found in immunocompromised patients, including those with HIV-AIDS or allograft recipients. Cardiac lymphomas tend to arise in the wall of the right heart, especially right atrium, with contiguous infiltration of epicardium and pericardium. Pericardial implants and effusions are common. The disease is often multifocal in the heart, but cardiac valves are usually spared.


Hemophilic arthropathy of the temporomandibular joint: review of the literature, a case report, and discussion.
Hemarthrosis of extremity joints in patients with hemophilia has been well documented. However, hemarthrosis of the temporomandibular joint in patients with coagulopathies appears to be rare. Consequently, management of a temporomandibular joint hemarthrosis is difficult because of the lack of treatment guidelines. The purpose of this article is to review the pathophysiology of hemophilic arthropathy and its management. A case of temporomandibular joint hemophilic arthropathy in a patient with a factor XI deficiency will be presented. A brief review of factor XI deficiency and a hypothetical pathophysiological mechanism for internal derangement induced by myofascial pain dysfunction are included.


Benchtop-NMR and MRI--a new analytical tool in drug delivery research.
During the last years, NMR spectroscopy and NMR imaging (magnetic resonance imaging, MRI) have been increasingly used to monitor drug delivery systems in vitro and in vivo. However, high installation and running costs of the commonly used superconducting magnet technology limits the application range and prevents the further spread of this non-invasive technology. Benchtop-NMR (BT-NMR) relaxometry uses permanent magnets and is much less cost intensive. BT-NMR relaxometry is commonly used in the food and chemical industry, but so far scarcely used in the pharmaceutical field. The paper shows on several examples that the application field of BT-NMR relaxometry can be extended into the field of drug delivery, including the characterisation of emulsions and lipid ingredients (e.g. the amount and physicochemical state of the lipid) and the monitoring of adsorption characteristics (e.g. oil binding of porous ingredients). The most exciting possibilities of BT-NMR technology are linked with the new development of BT-instruments with imaging capability. BT-MRI examples on the monitoring of hydration and swelling of HPMC-based monolayer and double-layer tablets are shown. BT-MRI opens new MRI opportunities for the non-invasive monitoring of drug delivery processes.


Physical modelling of the arterial wall. Part 1: Testing of tubes of various materials.
Tubes of various elastic materials were tested using a purpose-built apparatus to select those most appropriate for physical simulation of the arterial wall. The influences of temperature and longitudinal stress were measured in selected tubes. It was found that the static elasticity of latex tubes is close to that of the arterial wall for intraluminal pressures corresponding to the lower range of intra-arterial pressures.


Complete Genome Sequence of Bovine Polyomavirus Type 1 from Aborted Cattle, Isolated in Belgium in 2014.
The complete and fully annotated genome sequence of a bovine polyomavirus type 1 (BPyV/BEL/1/2014) from aborted cattle was assembled from a metagenomics data set. The 4,697-bp circular dsDNA genome contains 6 protein-coding genes. Bovine polyomavirus is unlikely to be causally related to the abortion cases.


Dual mechanisms of green tea extract (EGCG)-induced cell survival in human epidermal keratinocytes.
Beneficial effects attributed to green tea, such as its anticancer and antioxidant properties, may be mediated by (-)-epigallocatechin-3-gallate (EGCG). In this study, the effects of EGCG on cell proliferation and UV-induced apoptosis were investigated in normal epidermal keratinocytes. When topically applied to aged human skin, EGCG stimulated the proliferation of epidermal keratinocytes, which increased the epidermal thickness. In addition, this topical application also inhibited the UV-induced apoptosis of epidermal keratinocytes. EGCG was found to increase the phosphorylation of Bad protein at the Ser112 and Ser136. Moreover, EGCG-induced Erk phosphorylation was found to be critical for the phosphorylation of Ser112 in Bad protein, and the EGCG-induced activation of the Akt pathway was found to be involved in the phosphorylation of Ser136. Furthermore, EGCG increased Bcl-2 expression but decreased Bax expression, causing an increase in the Bcl-2-to-Bax ratio. In addition, we demonstrate the differential growth inhibitory effects of EGCG on cancer cells. In conclusion, this study demonstrates that EGCG promotes keratinocyte survival and inhibits the UV-induced apoptosis via two mechanisms: by phosphorylating Ser112 and Ser136 of Bad protein through Erk and Akt pathways, respectively, and by increasing the Bcl-2-to-Bax ratio. Moreover, these two proposed mechanisms of EGCG-induced cell proliferation may differ kinetically to promote keratinocyte survival.


Treatment of gasoline-contaminated waters by advanced oxidation processes.
In this study, the efficiency of advanced oxidative processes (AOPs) was investigated toward the degradation of aqueous solutions containing benzene, toluene and xylenes (BTX) and gasoline-contaminated waters. The results indicated that BTX can be effectively oxidized by near UV-assisted photo-Fenton process. The treatment permits almost total degradation of BTX and removal of more than 80% of the phenolic intermediates at reaction times of about 30 min. Preliminary investigations using water contaminated by gasoline suggest a good potentiality of the process for the treatment of large volumes of aqueous samples containing these polluting species. Heterogeneous photocatalysis and H2O2/UV system show lower degradation efficiency, probably due to the heterogeneous character of the TiO2-mediated system and lost of photonic efficiency of the H2O2/UV system in the presence of highly colored intermediated.


Psychology and mind in Aquinas.
This article stresses the main lines of Thomas Aquinas's philosophy on the nature of the body-soul union. Following Aristotle, Aquinas sees the soul as a 'principle of life' which is intimately bound to a body. Together they form a non-contingent composition. In addition, the distinctive feature of the human soul is rationality, which implies that a human needs a mind to be what it is. However, this is not to say, as Descartes proposes, that the reason that I am a human is that I am fully self-conscious. On the contrary, I will show that self-consciousness is not necessarily a key to defining a human being. To that aim, and based on Aquinas's views, I draw a distinction between what I will call 'egos' and selves'.


Immunohistochemical detection of hepatocellular carcinoma in the setting of ongoing necrosis after radiofrequency ablation.
After radiofrequency ablation (RFA), hepatocellular carcinoma undergoes complete necrosis and an ongoing necrosis that is irreversible and characterized histologically by disrupted cell outlines, homogenous cytoplasmic eosinophilia, and preserved nuclear staining, with the cells appearing quite distinct from viable cancer cells. Antibody to detect single-stranded DNA (ssDNA) specifically labeled nuclei in the setting of ongoing necrosis, but not viable tumor cells, whereas human mitochondrial antibody labeled the cytoplasm of viable cells but not cells of ongoing necrosis. The results demonstrate that RFA causes denaturation of both DNA and proteins and that the immunohistochemistry of ssDNA and mitochondrial protein is useful in detection of ongoing necrosis after RFA and provides pathological information on the validity of this procedure.


The effects of tiadenol, clofibrate and clofibride on bile composition in the rat.
Biliary secretion was studied in normolipidemic rats after a 7 day treatment with the hypolipidemic drugs, tiadenol (bis-(hydroxyethylthio)-1,10-decane), clofibrate and clofibride (chloro-4-phenoxy-2-methyl-2-propionate of dimethylcarbamoyl-3-propyl). All three drugs decreased blood cholesterol and total lipids, increased liver weight and liver catalase content, and decreased biliary excretion of cholesterol. The biliary concentrations of bile salts, phospholipids and cholesterol decreased to a variable extent, in such a way that the ratio of bile salts + phospholipids to cholesterol was increased by the drugs. The bile salt independent fraction was increased. The effects were qualitatively similar for all three drugs tested, but quanitative differences appeared for some of the parameters.


Iron depletion in HCT116 cells diminishes the upregulatory effect of phenethyl isothiocyanate on heme oxygenase-1.
Some of the health-promoting properties of cruciferous vegetables are thought to be partly attributed to isothiocyanates. These phytochemicals can upregulate the expression of certain cytoprotective stress genes, but it is unknown if a particular nutrient is involved. Herein, the objective was to ascertain if adequate iron is needed for enabling HCT116 cells to optimally express heme oxygenase-1 (HO-1) when induced by phenethyl isothiocyanate (PEITC). PEITC increased HO-1 expression and also nuclear translocation of Nrf2, which is a transcription factor known to activate the HO-1 gene. However, in HCT116 cells that were made iron-deficient by depleting intracellular iron with deferoxamine (DFO), PEITC was less able to increase HO-1 expression and nuclear translocation of Nrf2. These suppressive effects of DFO were overcome by replenishing the iron-deficient cells with the missing iron. To elucidate these findings, it was found that PEITC-induced HO-1 upregulation can be inhibited with thiol antioxidants (glutathione and N-acetylcysteine). Furthermore, NADPH oxidase inhibitors (diphenyleneiodonium and apocynin) and a superoxide scavenger (Tiron) each inhibited PEITC-induced HO-1 upregulation. In doing so, diphenyleneiodonium was the most potent and also inhibited nuclear translocation of redox-sensitive Nrf2. Collectively, the results imply that the HO-1 upregulation by PEITC involves an iron-dependent, oxidant signaling pathway. Therefore, it is concluded that ample iron is required to enable PEITC to fully upregulate HO-1 expression in HCT116 cells. As such, it is conceivable that iron-deficient individuals may not reap the full health benefits of eating PEITC-containing cruciferous vegetables that via HO-1 may help protect against multiple chronic diseases.


Structural Origins of Silk Piezoelectricity.
Uniaxially oriented, piezoelectric silk films were prepared by a two-step method that involved: (1) air drying aqueous, regenerated silk fibroin solutions into films, and (2) drawing the silk films to a desired draw ratio. The utility of two different drawing techniques, zone drawing and water immersion drawing were investigated for processing the silk for piezoelectric studies. Silk films zone drawn to a ratio of λ= 2.7 displayed relatively high dynamic shear piezoelectric coefficients of d(14) = -1.5 pC/N, corresponding to over two orders of magnitude increase in d(14) due to film drawing. A strong correlation was observed between the increase in the silk II, β-sheet content with increasing draw ratio measured by FTIR spectroscopy (C(β)∝ e(2.5) (λ)), the concomitant increasing degree of orientation of β-sheet crystals detected via WAXD (FWHM = 0.22° for λ= 2.7), and the improvement in silk piezoelectricity (d(14)∝ e(2.4) (λ)). Water immersion drawing led to a predominantly silk I structure with a low degree of orientation (FWHM = 75°) and a much weaker piezoelectric response compared to zone drawing. Similarly, increasing the β-sheet crystallinity without inducing crystal alignment, e.g. by methanol treatment, did not result in a significant enhancement of silk piezoelectricity. Overall, a combination of a high degree of silk II, β-sheet crystallinity and crystalline orientation are prerequisites for a strong piezoelectric effect in silk. Further understanding of the structural origins of silk piezoelectricity will provide important options for future biotechnological and biomedical applications of this protein.


On the validity of single tests, two-test combinations and the full Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in detecting patients with cognitive impairment.
The international standard to screen for cognitive impairment in multiple sclerosis (MS) is BICAMS (Brief International Cognitive Assessment for MS). However, with an application time of approximately 20 minutes, the battery might be too time consuming from a pragmatic perspective of a routine examination. To examine the relative sensitivity and specificity of a BICAMS short version and its validity compared to the total battery. The German BICAMS version was applied comprising the Symbol Digit Modalities Test (SDMT), the Brief Visuospatial Memory Test-Revised (BVMT-R) and the Rey Auditory Verbal Learning Test (RAVLT; German VLMT). Single tests and two-test combinations were compared regarding conformity with the total battery. Examining 1320 MS patients, the two-test combination of SDMT-BVMT-R was the most sensitive (92.7%) to impairment and showed the strongest agreement with the total battery (κ = 0.95). Performing binary logistic regression analyses, this combination was also validated by its association with employment status. Application of the total BICAMS battery should be the goal to strive for. However, in time-restricted clinical settings, the combined application of SDMT and BVMT-R is a recommendable alternative with an application time of 10 minutes, while single tests alone are not sufficiently sensitive.


β-catenin and Smad3 regulate the activity and stability of myocardin-related transcription factor during epithelial-myofibroblast transition.
Injury to the adherens junctions (AJs) synergizes with transforming growth factor-β1 (TGFβ) to activate a myogenic program (α-smooth muscle actin [SMA] expression) in the epithelium during epithelial-myofibroblast transition (EMyT). Although this synergy plays a key role in organ fibrosis, the underlying mechanisms have not been fully defined. Because we recently showed that Smad3 inhibits myocardin-related transcription factor (MRTF), the driver of the SMA promoter and many other CC(A/T)-rich GG element (CArG) box-dependent cytoskeletal genes, we asked whether AJ components might affect SMA expression through interfering with Smad3. We demonstrate that E-cadherin down-regulation potentiates, whereas β-catenin knockdown inhibits, SMA expression. Contact injury and TGFβ enhance the binding of β-catenin to Smad3, and this interaction facilitates MRTF signaling by two novel mechanisms. First, it inhibits the Smad3/MRTF association and thereby allows the binding of MRTF to its myogenic partner, serum response factor (SRF). Accordingly, β-catenin down-regulation disrupts the SRF/MRTF complex. Second, β-catenin maintains the stability of MRTF by suppressing the Smad3-mediated recruitment of glycogen synthase kinase-3β to MRTF, an event that otherwise leads to MRTF ubiquitination and degradation and the consequent loss of SRF/MRTF-dependent proteins. Thus β-catenin controls MRTF-dependent transcription and emerges as a critical regulator of an array of cytoskeletal genes, the "CArGome."


Polycystic Liver Disease: Advances in Understanding and Treatment.
Polycystic liver disease (PLD) is a group of genetic disorders characterized by progressive development of cholangiocyte-derived fluid-filled hepatic cysts. PLD is the most common manifestation of autosomal dominant and autosomal recessive polycystic kidney diseases and rarely occurs as autosomal dominant PLD. The mechanisms of PLD are a sequence of the primary (mutations in PLD-causative genes), secondary (initiation of cyst formation), and tertiary (progression of hepatic cystogenesis) interconnected molecular and cellular events in cholangiocytes. Nonsurgical, surgical, and limited pharmacological treatment options are currently available for clinical management of PLD. Substantial evidence suggests that pharmacological targeting of the signaling pathways and intracellular processes involved in the progression of hepatic cystogenesis is beneficial for PLD. Many of these targets have been evaluated in preclinical and clinical trials. In this review, we discuss the genetic, molecular, and cellular mechanisms of PLD and clinical and preclinical treatment strategies.


Patterns of synaptic contact upon individually labeled large cells of the dorsal lateral geniculate nucleus of the cat.
Four large geniculate cells that were densely filled with horseradish peroxidase have been studied in detail, at first light microscopically, to define the shape and distribution of the dendritic arbors, and then electron microscopically, to define the pattern of synaptic contacts upon their surfaces. Three of the cells had the morphological characteristics of a class 1 cell, and one cell was intermediate between class 1 and 2. All of these cells had few of the characteristic grape-like appendages, thought to receive retinal input within synaptic glomeruli. Retinal afferents were mainly distributed around proximal juxtasomatic dendritic segments and dendritic branch points. Some retinal afferents made simple axodendritic contacts, while others formed a part of a synaptic glomerulus. None of the retinal afferents forming synapses near the perikaryon were involved in glomeruli. Within the glomeruli involving class 1 cells, retinal terminals can relate both to dendritic segments, particularly near branch points, as well as to dendritic appendages. The few singly placed grape-like appendages were always contacted by retinal afferents, but not necessarily in a glomerular arrangement. Terminals interpreted as cortico-geniculate were seen most commonly upon peripheral dendritic segments, while those containing pleomorphic vesicles (F) were distributed more or less evenly over all parts of the dendritic and perikaryal surface. The perikaryon itself was contacted by F-type terminals but was not contacted by retino-geniculate or cortico-geniculate terminals. A class of slender axonal terminal, containing round synaptic vesicles and few or no mitochondria, was found contacting two of the four perikarya, but the origin of these slender axons is unknown. It is concluded that the surfaces of geniculate class 1 cells can be separated into several functionally distinct zones on the basis of the synaptic contacts they receive.


Neuropsychopharmacology at the new millennium: new industry directions.
Rapid advances in modern gene seeking techniques and the sequence data evolving from related genome research should provide both new targets for drug discovery and new insights into risk factors for many neurological and psychiatric disorders. Coupled with the high speed synthetic capabilities available in many companies, high-throughput screening is identifying potential novel drug candidates at extraordinary rates. This enables the drug discoverer to be more precise in the biological specificity of drugs taken to human trials thereby reducing the potential side-effect profile of clinical candidates. The ability to create large libraries of compounds also allows researchers to focus on metabolism and pharmacokinetics at an earlier stage in the drug development process to minimize drug-drug interactions via common sites of metabolism and optimize duration of action for particular indications. An emerging bottleneck in psychopharmacological drug discovery is the relative paucity of preclinical behavioral models predictive of clinical efficacy and the need to carry out early clinical trials to demonstrate therapeutic utility. However, through the use of recently developed chip technology, coupled with data bases of information about single nucleotide polymorphisms in potential candidate genes or risk factors for psychiatric disorders, it should be possible in the near future to stratify clinical populations genetically for inclusion in specific drug treatment trials. The ultimate goal of this research is to obtain homogeneous populations for trials and to predict risk before the phenotype of the disorder is manifest.


Depressive symptoms and functional impairment among amyotrophic lateral sclerosis patients in South Korea.
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease, resulting in physical and psychological distress. Little is known about the health of ALS patients in South Korea. The purpose of this study was to assess the degree of functional impairment and depressive symptoms and their interrelationships in Korean ALS patients. In this cross-sectional descriptive study, a convenience sample of 62 ALS patients was recruited. Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and Beck Depression Inventory (BDI) were used. The mean score of ALSFRS was 18.98 and 24.50 for BDI. Severity of depressive symptoms was associated with gender, employment, perceived health status, and ALS type. A greater functional impairment was associated with greater depressive symptoms. This study reports high prevalence of depressive symptoms in ALS patients. The findings add to the body of knowledge on emotional health and provide motives for interventions to promote mental health of these patients.


Conservative management of esophageal perforation after a fall.
Esophageal perforation in the setting of blunt trauma is rare, and diagnosis can be difficult due to atypical signs and symptoms accompanied by distracting injury. We present a case of esophageal perforation resulting from a fall from height. Unexplained air in the soft tissues planes posterior to the esophagus as well as subcutaneous emphysema in the absence of a pneumothorax on CT aroused clinical suspicions of an injury to the aerodigestive tract. The patient suffered multiple injuries including bilateral first rib fractures, C6 lamina fractures, C4-C6 spinous process fractures, a C7 right transverse process fracture with associated ligamentous injury and cord contusion, multiple comminuted nasal bone fractures, and a right verterbral artery dissection. Esophageal injury was localized using a gastrograffin esophagram to the cervical esophagus and was most likely secondary to cervical spine fractures. Because there were no clinical signs of sepsis and the esophagram demonstrated a contained rupture, the patient was thought to be a good candidate for a trial of conservative management consisting of broad spectrum intravenous antibiotics, oral care with chlorhexadine gluconate, NPO, and total parenteral nutrition. No cervical spine fixation or procedure was performed during this trial of conservative management. The patient was received another gastrograffin esophagram on hospital day 14 and demonstrated no evidence of contrast extravasation. Early diagnosis and control of the infectious source are the cornerstones to successful management of esophageal perforation from all etiologies. Traditionally, esophageal perforation relied on a high index of clinical suspicion for early diagnosis, but the use of CT scan for has proved to be highly effective in diagnosing esophageal perforation especially in patients with atypical presentations. While aggressive surgical infection control is paramount in the majority of esophageal perforations, a select subset of patients can be successfully managed non-operatively. In the setting of blunt trauma, esophageal perforation is rare and is associated with a high morbidity. In select patients who do not show any clinical signs of sepsis, contained perforations can heal with non-operative management consisting of broad spectrum antibiotics, strict oral hygiene, NPO, and total parenteral nutrition.


Silica mitigated calcium mineral scaling in brackish water reverse osmosis.
Although the autopsies of reverse osmosis (RO) membranes from full-scale, brackish water desalination plants identify the co-presence of silica and Ca-based minerals in scaling layers, minimal research exists on their formation process and mechanisms. Therefore, combined scaling by silica and either gypsum (non-alkaline) or amorphous calcium phosphate (ACP, alkaline) was investigated in this study for their distinctive impacts on membrane performance. The obtained results demonstrate that the coexistence of silica and Ca-based mineral salts in feedwaters significantly reduced water flux decline as compared to single type of Ca-based mineral salts. This antagonistic effect was primarily attributed to the silica-mediated alleviation of Ca-based mineral scaling. In the presence of silica, silica skins were immediately established around Ca-based mineral precipitates once they emerged. Sheathing by the siliceous skins hindered the aggregation and thus the morphological evolution of Ca-based mineral species. Unlike sulfate precipitates, ACP precipitates can induce the formation of dense and thick silica skins via an additional condensation reaction. Such a phenomenon rationalized the notion concerning a stronger mitigating effect of silica on ACP scaling than gypsum scaling. Meanwhile, coating by silica skins altered the surface chemistries of Ca-based mineral precipitates, which should be fully considered in regulating membrane surface properties for combined scaling control. Our findings advance the mechanistic understanding on combined mineral scaling of RO membranes, and may guide the appropriate design of membrane surface properties for scaling-resistant membrane tailored to brackish water desalination.


Volumetric extrusive rates of silicic supereruptions from the Afro-Arabian large igneous province.
The main phase of silicic volcanism from the Afro-Arabian large igneous province preserves some of the largest volcanic eruptions on Earth, with six units totaling >8,600 km3 dense rock equivalent (DRE). The large volumes of rapidly emplaced individual eruptions present a case study for examining the tempo of voluminous silicic magma generation and emplacement. Here were report high-precision 206Pb/238U zircon ages and show that the largest sequentially dated eruptions occurred within 48 ± 34 kyr (29.755 ± 0.023 Ma to 29.707 ± 0.025 Ma), yielding the highest known long-term volumetric extrusive rate of silicic volcanism on Earth. While these are the largest known sequential silicic supereruptions, they did not cause major global environmental change. We also provide a robust tie-point for calibration of the geomagnetic polarity timescale by integrating 40Ar/39Ar data with our 206Pb/238U ages to yield new constraints on the duration of the C11n.1r Subchron.


Objective Assessment of Cough: An Early Marker of Response to Biological Therapies in Asthma?
Cough is an important symptom of asthma. The objective assessment of chronic cough has been enhanced by the development of ambulatory cough monitoring systems. Mepolizumab has been demonstrated to reduce exacerbations in eosinophilic asthmatics long-term. We evaluate the utility of objective cough count as an outcome measure in severe eosinophilic asthma treated with mepolizumab. Consecutive, consenting patients initiated on treatment with mepolizumab had a 24-h cough count recorded at baseline; this was repeated at 1, 3 and 6 months. Asthma control questionnaire (ACQ) scores and exacerbation frequency were also recorded. The mean 24-h cough count in 11 subjects (8 females, mean age 53.6 years) was 172.4 at baseline; at 1, 3 and 6 months following initiation of treatment this decreased to 101.4, 92 and 70.8, respectively (p < 0.02). Significant improvements were also observed in mean ACQ score (3-1.6, p < 0.01) and exacerbation frequency (5.5 per year - 1.3, p < 0.01). Objective cough measurement could be used as an early, precise and clinically relevant endpoint in assessing response to asthma therapy.


Controlled register-based study of road traffic accidents in 12,651 Finnish cancer patients during 2013-2019.
Little controlled evidence exists on road traffic accident (RTA) risk among patients diagnosed with cancer, while clinicians are often requested to comment their ability to drive. The aim of this study was to evaluate RTA risk in a population-based cohort of cancer patients living in Southwest Finland. All adult patients diagnosed with cancer in 2013-2019 were included. Acute appendectomy/cholecystectomy and actinic keratosis patients without cancer were selected from the same region as the control cohort. Participants were cross-referenced to a national driving licence database, yielding 12,651 cancer and 6334 control patients with a valid licence. Due to marked differences in their clinical presentation, the cancer cohort was divided into nine cancers of interest (breast, prostate, colorectal, lung, melanoma, head & neck, primary brain tumours, gynaecological and haematological malignancies). The nationwide law-regulated motor liability insurance registry was searched for all RTAs leading to injury with claims paid to not- or at-fault participants. At-fault drivers were verified based on sex and birth year. During a median follow-up of 34 months, 167 persons were at-fault drivers in RTAs leading to injury. Among the nine cancers of interest, RTA risk did not differ from the control cohort. Among cancer patients, multivariable regression suggested male sex and opioid use, but not advanced cancer stage or given systemic therapy, as the most influential risk factors for RTA. Cancer diagnosis itself was not associated with increased RTA risk, but other associated symptoms, medications, comorbidities or specific cancer subgroups may.


Intraoperative Ultrasound Technology in Neuro-Oncology Practice-Current Role and Future Applications.
Surgery for cranial and spinal tumors has evolved tremendously over the years. Not only have neuro-oncologists been able to better understand tumor biology and thereby improve multimodality therapy, but advances in surgical techniques have also directly equipped neurosurgeons with the armamentarium necessary to achieve more radical resections safely. Intraoperative imaging tools are one such adjunct. Though intraoperative magnetic resonance (MR) has emerged as the "gold standard" among these, logistical challenges make it difficult to implement across all centers. On the other hand, the use of ultrasound (US) intraoperatively predates the use of MR. Over the past 4 decades, technologic improvements have refined and expanded the scope and application of intraoperative US technology. Strategies to maximize its efficacy and overcome the various limitations have evolved. A large volume of clinical experience has accumulated with respect to its role as an adjunct specifically in tumor surgery. We performed a literature review to evaluate the role of IOUS in tumor surgery. This review traces the evolution of intraoperative US over the years and reviews the current scope and applications with respect to neuro-oncologic surgery, as well as potential future applications. IOUS has evolved over the years since its introduction. Advances in technology have provided real-time navigated and 3-D techniques, which overcome many of the limitations of older IOUS techniques. This has shown to be very useful in not only localization of lesions, but also in improving resection rates as well as survival. IOUS is a powerful and versatile multipurpose intraoperative adjunct in tumor surgery, especially for resection control. The learning curve is relatively easy to climb and future improvements in technology are likely to widen the scope of its use.


Therapeutic climbing in Parkinson's disease: Differences in self-reported health and well-being, feasibility and clinical changes.
Therapeutic climbing (TC) is a whole-body workout that stimulates and improves physical and psychosocial abilities. It has been used in neurological rehabilitation, but there is scarce evidence of specific benefits for people with Parkinson's (PwP). To investigate and evaluate self-reported differences in health and well-being among trial participants, the overall feasibility of TC and clinical changes caused as a rehabilitation measure for PwP. A 3-level Likert scale survey was completed by 26 PwP (100% response rate) after a TC course (mean 16 sessions) at the Neurological Rehabilitation Center assessing self-perceived differences in health and well-being in terms of physical, psychological, and social parameters. We investigated the feasibility of TC in terms of adherence, practicability and acceptability during a multidisciplinary inpatient rehabilitation program and determined several clinical outcomes (10-meter distance and 2-minute duration walking tests, Functional Gait Assessment, Nine-Hole-Peg tests, and Tinetti Assessment Tool). Improvements are based on self-reported perceptions of PwP. We observed an improvement of overall physical (average 65%), psychological (average 59%) and social (average 39%) aspects after TC. PwP improved strength (96%), balance (88%), range of motion (88%), body awareness (85%), physical well-being (77%), and fatigue (75%). Furthermore, they self-reported admiration in their social surrounding (42%) and felt more sociable and outgoing (40%). Concerning adherence, practicability and acceptability, TC seems to be feasible for PwP. Treatment adherence was 100%, 70% declared motivation to continue TC, and 96% intended to recommend TC to peers. Furthermore, PwP showed statistically significant improvements in 10-meter walking tests (T0: 7.5 (1.1-13.9), T1: 6.5 (0.1-12.9); p < .01; n = 16), 2-minute walking tests (T0: 149.5 (-111.0-410.0), T1: 177.0 (-140.7-494.7); p < .01; n = 19), Functional Gait Assessment (T0: 26.0 (-24.8-76.8), T1: 28.0 (2.6-53.4); p < .01; n = 15), and Nine-Hole-Peg tests (left: T0: 26.5 (24.3-28.7), T1: 24.1 (22.0-26.3); p < .01; n = 15; right: T0: 26.7 (24.1-29.2), T1: 23.3 (20.8-25.7); p < .01; n = 15). The preliminary findings suggest that TC offers an effective and feasible training method that may positively affect PwP overall perceptions of physical and psychosocial health status. The methodological limitations and small sample size limit the study's interpretability. More research is needed to definitely show the scientifically significant benefits of TC to PwP.


[Dynamics of the antiprotease system and ventilation indicators during treatment of chronic bronchitis].
The relationship between the antitryptic activity of the blood serum, bronchoalveolar secretion and ventilatory indices of the external respiration function in 85 patients with chronic bronchitis in the process of treatment is described. The above findings allow to recommend antibiotics for wide use only in exacerbations of purulent bronchitis while in other clinical variants reduction of drug loads result in increased therapeutic efficiency.


Effects of physical activity and immobilization on plasma digoxin concentration and renal digoxin clearance.
Plasma digoxin concentration and renal digoxin clearance were determined during 2 hr of normal physical activity and during 2 hr of complete immobilization in eight healthy subjects on steady-state digoxin dosing. Mean plasma digoxin concentration rose from 0.64 +/- 0.13 ng/ml during physical activity to 1.04 +/- 0.19 ng/ml (63%) after 2 hr of rest. Resumption of physical activity resulted in gradual decline of plasma digoxin, and subsequent strenuous exercise reduced the value to preimmobilization level. Mean renal digoxin clearance was reduced from 168.4 +/- 18.7 ml/min during physical activity to 137.2 +/- 32.7 ml/min during rest whereas creatinine clearance was unchanged. The rise in plasma digoxin during rest is presumed to be due to changes in the binding of the drug to tissues such as skeletal muscles. Our findings indicate that attention should be given to the state of physical activity when kinetic studies are performed or when digoxin therapy is monitored by means of plasma digoxin analysis.


Rapid assessment of polycyclic aromatic hydrocarbon (PAH) exposure in decapod crustaceans by fluorimetric analysis of urine and haemolymph.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and potentially harmful contaminants of the coastal and marine environment. Studies of their bioavailability, disposition and metabolism in marine organisms are therefore important for environmental monitoring purposes. Detecting PAH compounds in the biological fluids of marine organisms provides a measure of their environmental exposure to PAHs. In the present study, the shore crab Carcinus maenas was exposed to waterborne pyrene for 48h. Urine and haemolymph samples were analysed by direct fluorimetry utilising both fixed wavelength (FF) and synchronous scanning fluorescence (SFS) techniques. Samples from exposed crabs exhibited fluorescence due to 1-OH pyrene equivalents, whilst samples from control crabs did not. Levels of equivalents were exposure dependent. Urine was shown to be a more suitable medium for the analysis of PAH equivalents. In a separate experiment, depuration of pyrene equivalents in urine was monitored over time. Urinary levels reached a maximum 2-4 days after initial exposure and decreased steadily thereafter. No unchanged parent pyrene was detected in samples from exposed crabs. While fluorimetric techniques could discriminate between 1-OH pyrene equivalents and parent pyrene, identification of specific metabolites was only possible with HPLC/F analysis. This revealed crabs had bio-transformed pyrene into 3 major conjugates of 1-OH pyrene, which were excreted in the urine. While such biotransformation of PAH is well documented in fish and several crustaceans, this is the first study to use direct fluorimetry to detect PAH equivalents in exposed crustacean urine. Fluorimetric results correlated well with those obtained by HPLC/F and ELISA techniques. The technique has great potential as a rapid, inexpensive and non-destructive technique for field biomonitoring of PAH exposure in crustaceans.


[The importance of isolating septic patients in an autonomous unit in orthopedic surgery and traumatology].
To examine whether Sepsis Containment Units are presently in use by French Orthopedic surgeons in a number of hospitals and the subsequent efficacy of these measures in the prevention of risks linked to methicillin resistant Staphylococcus aureus (MRSA), MRSA was used as an example because it is the bacteria most frequently associated with infection in orthopedics. The transient carriage of MRSA on the hands of hospital personnel is the most common mechanism of patient to patient transmission. Consequently, the incidence of nosocomial MRSA in patients can be used to assess the quality of infection control. The orthopaedic surgery department (104 beds) of a 1. 228 bed, university affiliated public hospital located in eastern France (Besançon). First: a questionnaire was sent out to 71 French university orthopedic departments to investigate the practice in place. Second: to establish whether a significant correlation exists between the colonisation pressure exerted by real imported MRSA, and the number of cases of real acquired MRSA since we know that colonisation pressure of bacteria is a major factor in the prognosis of clinical infection. Third: our orthopedic surgery department was redesigned to study the risks of colonisation pressure with or without Sepsis Containment Units. First: among the 71 orthopedic departments studied, only 11 used a Sepsis Containment Unit. Second: there is a definite, linear relationship between the colonisation pressure exerted in a unit by real imported MRSA and the number of cases of real acquired clinical infection. Third: in the absence of Sepsis Containment Units, the risk of MRSA infections is increased by 160%. Debat: the classical clinical arguments concerning the dangers of hand or aerobic MRSA transmission are confirmed by our figures. The strict use of Sepsis Containment Units prevents contamination of septics by septics. Inversely, the rigorous concentration of means in the Sepsis Containment Units also prevents cross contamination of septics. At question are the psychological and financial inconveniences of Sepsis Containment Units. The results of this experiment, performed in orthopedic surgery, show that the use of Sepsis Containment Units is just as critical in other surgical units: vascular, thoracic, etc., nor should they be overlooked in outpatient and emergency care--often the first step in orthopedic surgery. Sepsis Containment Units are essential and merit further development.


Plastid RNA polymerases, promoters, and transcription regulators in higher plants.
Plastids are semiautonomous plant organelles exhibiting their own transcription-translation systems that originated from a cyanobacteria-related endosymbiotic prokaryote. As a consequence of massive gene transfer to nuclei and gene disappearance during evolution, the extant plastid genome is a small circular DNA encoding only ca. 120 genes (less than 5% of cyanobacterial genes). Therefore, it was assumed that plastids have a simple transcription-regulatory system. Later, however, it was revealed that plastid transcription is a multistep gene regulation system and plays a crucial role in developmental and environmental regulation of plastid gene expression. Recent molecular and genetic approaches have identified several new players involved in transcriptional regulation in plastids, such as multiple RNA polymerases, plastid sigma factors, transcription regulators, nucleoid proteins, and various signaling factors. They have provided novel insights into the molecular basis of plastid transcription in higher plants. This review summarizes state-of-the-art knowledge of molecular mechanisms that regulate plastid transcription in higher plants.


IL-6 levels decrease with SSRI treatment in patients with major depression.
Some evidence indicates that an immune response with an increased production of proinflammatory cytokines often accompanies major depression. The objective of this study was to examine the serum levels of IL-6 in patients with major depression and the changes occurring in IL-6 levels during treatment with selective serotonin reuptake inhibitors (SSRI). Twenty-three patients with a DSM-IV diagnosis of major depressive disorder and 23 healthy matched controls were included in the study. The severity of depression was measured with the Hamilton rating scale for depression. Blood samples for IL-6 levels were obtained at baseline and at week 6 of treatment and IL-6 concentrations were evaluated using a solid phase sandwich enzyme immunoassay. All patients were treated with an SSRI. The IL-6 levels showed no statistically significant difference between the patients and the controls at baseline. However, IL-6 levels after treatment with SSRIs were significantly lower compared with the baseline IL-6 levels of both the patients and the controls. The results of this study suggest that proinflammatory cytokines show some changes during the course of treatment of major depression. These findings might also be considered as supporting the hypothesis of a modulatory role of antidepressants on the immune system.


Hearing Rehabilitation in Patients With Neurofibromatosis Type 2: The Quebec's Experience With Auditory Implants.
To review a single-center experience with hearing rehabilitation in patients with neurofibromatosis type 2 (NF2) and to describe the auditory outcomes of cochlear implants (CIs) and auditory brainstem implants (ABI) in this population. Retrospective case series. Tertiary referral center. Twelve adult patients with NF2 who received a CI (n = 10) and/or an ABI (n = 5) between 2000 and 2021. Insertion of a CI and/or an ABI in NF2 patients with bilateral vestibular schwannomas (VSs). Patients' demographic data, treatment history, hearing evolution, hearing rehabilitation methods, implant details, and auditory outcomes after implantation. Among those who received a CI, five patients had a stable untreated VS, one patient underwent a cochlear nerve preserving surgery, and four patients received radiotherapy treatments. Six patients became regular users of their device. The median open-set sentence recognition scores were as follows: 0.5% preoperatively, 60% at 1 year postoperatively, and 80% on the most recent audiological evaluation. All patients with an ABI were implanted concomitantly with VS surgical excision, and three of them also received radiotherapy treatments. The median open-set sentence recognition scores were as follows: 4% preoperatively, 26% at 1 year postoperatively, and 0% on the most recent evaluation. Three patients became regular ABI users. Despite major technological advances, auditory outcomes with ABIs remain deceiving. Considering the overall improvement in postoperative auditory performances provided by CIs compared with ABIs, cochlear implantation standouts as a primary mean of hearing rehabilitation in NF2 patients.