Effects of individual and work-related factors on incidence of shoulder pain in a large working population.
The aim of this study was to assess the effects of individual and work-related factors on the incidence of shoulder pain in a large French working population. A total of 3,710 workers of a French region were randomly included in a cross-sectional study between 2002 and 2005. They completed a self-administered questionnaire about musculoskeletal symptoms, individual factors and exposure to work constraints. In 2007, 2,332 responded to a follow-up questionnaire. The Nordic questionnaire was used both times to assess shoulder pain during the preceding 7 days. Associations between incident shoulder pain and individual and work-related factors at baseline were studied by multivariate logistic regression for both genders. A total of 946 men and 709 women without shoulder pain at baseline were eligible for the analyses. At follow-up, 105 men (11.1%) and 145 women (20.5%) reported shoulder pain. For men, age (OR 3.3, 95% CI, 1.7-6.5 for ≥50 yr), working with arms above the shoulder (1.5; 1.0-2.3) and high perceived physical exertion (1.6; 1.0-2.5) increased the risk of incident shoulder pain. For women, the factors associated with incident shoulder pain were age (2.9; 1.5-5.8 for ≥50 yr), obesity (2.5; 1.4-4.5), temporary employment (2.1; 1.1-3.7), high perceived physical exertion (2.2; 1.4-3.5) and low decision latitude (1.6; 1.0-2.3). Age was the strongest predictor of incident shoulder pain in both genders. BMI and biomechanical and psychosocial factors were also identified as risk factors, whereas no factor related to work organization remained in the final models.


XBP1 Activation Reduces Severity of Polycystic Kidney Disease due to a Nontruncating Polycystin-1 Mutation in Mice.
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in Pkd1 and Pkd2. They encode the polytopic integral membrane proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively, which are expressed on primary cilia. Formation of kidney cysts in ADPKD starts when a somatic second hit mechanism inactivates the wild-type Pkd allele. Approximately one quarter of families with ADPDK due to Pkd1 have germline nonsynonymous amino acid substitution (missense) mutations. A subset of these mutations is hypomorphic, retaining some residual PC1 function. Previous studies have shown that the highly conserved Ire1 α -XBP1 pathway of the unfolded protein response can modulate levels of functional PC1 in the presence of mutations in genes required for post-translational maturation of integral membrane proteins. We examine how activity of the endoplasmic reticulum chaperone-inducing transcription factor XBP1 affects ADPKD in a murine model with missense Pkd1 . We engineered a Pkd1 REJ domain missense murine model, Pkd1 R2216W , on the basis of the orthologous human hypomorphic allele Pkd1 R2220W , and examined the effects of transgenic activation of XBP1 on ADPKD progression. Expression of active XBP1 in cultured cells bearing PC1 R2216W mutations increased levels and ciliary trafficking of PC1 R2216W . Mice homozygous for Pkd1 R2216W or heterozygous for Pkd1 R2216Win trans with a conditional Pkd1 fl allele exhibit severe ADPKD following inactivation in neonates or adults. Transgenic expression of spliced XBP1 in tubule segments destined to form cysts reduced cell proliferation and improved Pkd progression, according to structural and functional parameters. Modulating ER chaperone function through XBP1 activity improved Pkd in a murine model of PC1, suggesting therapeutic targeting of hypomorphic mutations.


Protein acetylation and deacetylation in plant-pathogen interactions.
Protein acetylation and deacetylation catalysed by lysine acetyltransferases (KATs) and deacetylases (KDACs), respectively, are major mechanisms regulating various cellular processes. During the fight between microbial pathogens and host plants, both apply a set of measures, including acetylation interference, to strengthen themselves while suppressing the other. In this review, we first summarize KATs and KDACs in plants and their pathogens. Next, we introduce diverse acetylation and deacetylation mechanisms affecting protein functions, including the regulation of enzyme activity and specificity, protein-protein or protein-DNA interactions, subcellular localization and protein stability. We then focus on the current understanding of acetylation and deacetylation in plant-pathogen interactions. Additionally, we also discuss potential acetylation-related approaches for controlling plant diseases.


Nodular melanoma serendipitously detected by airport full body scanners.
Nodular melanoma is the most dangerous form of melanoma and often evades early detection. We present a frequently traveling businessman whose nodular melanoma was detected by airport full body scanners. For about 20 flights over 2 months, the airport full body scanners singled out an area on his left lower leg for a pat-down. Dermatologic examination discovered a nodular melanoma in this area, and after surgical excision, the man traveled without incident. This case raises the possibility of using full body imaging in the detection of melanomas, especially of the nodular subtype. In its current form, full body scanning would most likely not be sensitive or specific enough to become a recommended screening tool. Nonetheless, for travelers with areas repeatedly singled out by the machines without a known justification, airport scanners could serve as incidental free screening for suspicious nodular lesions that should prompt dermatologist referral.


Consensus recommendations for the use of anti-egfr therapies in metastatic colorectal cancer.
In January 2010, a panel of Canadian oncologists with particular expertise in colorectal cancer (crc) gathered to develop a consensus guideline on the use of therapies against the epidermal growth factor receptor (egfr) in the management of metastatic crc (mcrc). This paper uses a case-based approach to summarize the consensus recommendations developed during that meeting.These are the consensus recommendations:Testing for the KRAS status of the tumour should be performed as soon as an egfr inhibitor is being considered as an option for treatment.Anti-egfr therapies are not recommended for the treatment of patients with tumours showing mutated KRAS status.For a patient with wild-type KRAS and an Eastern Cooperative Oncology Group status of 0-2, whose mcrc has previously been treated with a fluoropyrimidine, irinotecan, and oxaliplatin, switching to an egfr inhibitor is a recommended strategy.Cetuximab, cetuximab plus irinotecan, and panitumumab are all options for third-line therapy in patients with wild-type KRAS, provided that tolerability is acceptable.


The effect of kinesio taping on calf pain and extensibility immediately after its application and after a duathlon competition.
A sample of 34 duathlete volunteers was recruited from the competitors in a duathlon sprint. Calf pain and extensibility measures were obtained at baseline, immediately after taping, and 10-15 minutes after competition. Kinesio tape (KT) was applied on the calf of duathletes 20-90 minutes before the competition, only on one of their legs, with the other leg acting as a control. Repeated measures ANOVA results on calf extensibility did not show statistically significant differences [F(2) = 0.180; p = 0.836]. Nevertheless, Friedman test results on calf pain showed statistically significant differences [χ(2)(2) = 10.111; p = 0.006]. Additionally, post hoc pairwise comparison showed statistically significant differences from baseline to after competition (p = 0.006). Applying KT on calves seems to reduce muscle pain produced by the competition among duathletes with no apparent musculoskeletal disorder. Kinesio tape (KT) application, however, does not affect the calf extensibility immediately and after a duathlon competition.


Dosimetry of combined intracavitary and external irradiation of carcinoma of the uterine cervix.
Dose distribution around intracavitary applicators (Stockholm technique) has been investigated. The gradient of dose around the combination of intrauterine and vaginal applicators used is steep. The position of the uterus with and without the radium applicators inserted varies. Together with the steep dose gradient this implies that external irradiation following intracavitary treatment involves a risk for overdosage to tissues in the vicinity of the uterus and underdosage to the parametrium.


Timing of exposure to gonadotropins has differential effects on the conceptus: evidence from a mouse model†.
Superovulation with gonadotropins alters the hormonal milieu during early embryo development and placentation, and may be responsible for fetal and placental changes observed after in vitro fertilization (IVF). We hypothesized that superovulation has differential effects depending on timing of exposure. To test our hypothesis, we isolated the effect of superovulation on pre- and peri-implantation mouse embryos. Blastocysts were obtained from either natural mating or following superovulation and mating, and were transferred into naturally mated or superovulated pseudopregnant recipient mice. Fetal weight was significantly lower after peri-implantation exposure to superovulation, regardless of preimplantation exposure (p = 0.006). Placentas derived from blastocysts exposed to superovulation pre- and peri-implantation were larger than placentas derived from natural blastocysts that are transferred into a natural or superovulated environment (p < 0.05). Fetal-to-placental weight ratio decreased following superovulation during the pre- or peri-implantation period (p = 0.05, 0.01, respectively) and these effects were additive. Peg3 DNA methylation levels were decreased in placentas derived from exposure to superovulation both pre- and peri-implantation compared with unexposed embryos and exposure of the preimplantation embryo only. Through RNA sequencing on placental tissue, changes were identified in genes involved in immune system regulation, specifically interferon signaling, which has been previously implicated in implantation and maintenance of early pregnancy in mice. Overall, we found that the timing of exposure to gonadotropin stimulation can have differential effects on fetal and placental growth. These findings could impact clinical practice and underscores the importance of dissecting the role of procedures utilized during IVF on pregnancy complications.


2,2,2-Tris(pyrazol-1-yl)ethanol.
The title compound TPE, C(11)H(12)N(6)O, was prepared by slow evaporation from diethyl ether. In the crystal, there is a hydrogen bond between the alcohol H atom and an N in the pyrazole ring of a neighboring mol-ecule.


Better representing transgender patients in the electronic health record.
In an effort to represent transgender patients more adequately in our electronic health record, we convened a multidisciplinary team to customize a new electronic Social History module based on our vendor's design. This Social History module will better serve our transgender patients and their health care providers.


Correlates of susceptibility to hepatitis B among people who inject drugs in Sydney, Australia.
Despite a safe, effective vaccine, hepatitis B virus (HBV) vaccination coverage remains low among people who inject drugs (PWID). Characteristics of participants screened for a trial investigating the efficacy of financial incentives in increasing vaccination completion among PWID were examined to inform targeting of vaccination programs. Recruitment occurred at two health services in inner-city Sydney that target PWID. HBV status was confirmed via serological testing, and questionnaires elicited demographic, drug use, and HBV risk data. Multinomial logistic regression was utilized to determine variables independently associated with HBV status. Of 172 participants, 64% were susceptible, 17% exposed (HBV core antibody-positive), and 19% demonstrated evidence of prior vaccination (HBV surface antibody ≥ 10 mIU/ml). Compared with exposed participants, susceptible participants were significantly more likely to be aged less than 35 years and significantly less likely to be receiving current opioid substitution therapy (OST) and to test hepatitis C antibody-positive. In comparison to vaccinated participants, susceptible participants were significantly more likely to be male and significantly less likely to report daily or more frequent injecting, current OST, and prior awareness of HBV vaccine. HBV vaccination uptake could potentially be increased by targeting younger, less frequent injectors, particularly young men. In addition to expanding vaccination through OST, targeting "at risk" youth who are likely to have missed adolescent catch-up programs may be an important strategy to increase coverage. The lack of an association between incarceration and vaccination also suggests increasing vaccination uptake and completion in adult and juvenile correctional facilities may also be important.


Effects of quantum size on the thermoelectric properties of bismuth.
First principles and the Boltzmann transport equation have been combined to investigate the effects of quantum size L/λ, the ratio of quantum confinement length L to thermal de Broglie wavelength λ, on the thermoelectric properties of 2D β-bismuth. It is revealed that the thermoelectric properties of 2D β-bismuth are highly influenced by quantum size, especially when the L/λ is less than 0.1. Specifically, the Seebeck coefficients of both electrons and holes decrease as the L/λ ratio increases, while the electrical and thermal conductivity show the opposite trend. The results also show that 2D bismuth with three or more layers has semimetal properties, with the first observation of a semiconductor-semimetal transition in 2D bismuth. Moreover, the electron affinity, ionization energy, and work function of 2D β-bismuth do not exhibit a significant variation or trend with quantum size effects. The detailed electronic structures provide a fundamental understanding of the thermoelectric properties of bismuth, and the obtained results may provide a deep understanding of the relationship between the quantum size and the thermoelectric properties of 2D β-bismuth.


A fatal case of bone marrow embolism of unknown cause masquerading clinically as dengue shock syndrome.
Bone marrow fat embolism usually occurs following multiple bone fractures, intraosseous surgical procedures, following vigorous cardiac resuscitation, ecclampsia, sickle cell anemia, malignancies, etc. We present a case of 70-year-old male who presented with fever, cough with expectoration, respiratory distress, altered sensorium, hypotension and thrombocytopenia, and diagnosed to have dengue shock syndrome and expired within 1 day of admission. Postmortem lung biopsy revealed bone marrow fat embolism.


Development and evaluation of a dimensionless mechanistic pan coating model for the prediction of coated tablet appearance.
A mathematical, mechanistic tablet film-coating model has been developed for pharmaceutical pan coating systems based on the mechanisms of atomisation, tablet bed movement and droplet drying with the main purpose of predicting tablet appearance quality. Two dimensionless quantities were used to characterise the product properties and operating parameters: the dimensionless Spray Flux (relating to area coverage of the spray droplets) and the Niblett Number (relating to the time available for drying of coating droplets). The Niblett Number is the ratio between the time a droplet needs to dry under given thermodynamic conditions and the time available for the droplet while on the surface of the tablet bed. The time available for drying on the tablet bed surface is critical for appearance quality. These two dimensionless quantities were used to select process parameters for a set of 22 coating experiments, performed over a wide range of multivariate process parameters. The dimensionless Regime Map created can be used to visualise the effect of interacting process parameters on overall tablet appearance quality and defects such as picking and logo bridging.


Binary and ternary combinations of anti-HIV protease inhibitors: effect on gene expression and functional activity of CYP3A4 and efflux transporters.
The purpose of this study is to identify the effect of binary and ternary combinations of anti-HIV protease inhibitors (PIs) on the expression of metabolizing enzyme (CYP3A4) and efflux transporters [multidrug resistance-associated protein 2 (MRP2), P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)] in a model intestinal cell line (LS-180). LS-180 cells were treated with various combinations of PIs (amprenavir, indinavir, saquinavir and lopinavir), and the mRNA expression levels of metabolizing enzyme and efflux transporters were measured using quantitative reverse transcription polymerase chain reaction. The alteration of gene expression was further correlated to the expression of nuclear hormone receptor PXR. Uptake of fluorescent and radioactive substrates was carried out to study the functional activity of these proteins. Cytotoxicity and adenosine triphosphate (ATP) assays were carried out to measure stress responses. Binary and ternary combinations of PIs appeared to modulate the expression of CYP3A4, MRP2, P-gp and BCRP in a considerable manner. Unlike the individual PIs, their binary combinations showed much greater induction of metabolizing enzyme and efflux proteins. However, such pronounced induction was not observed in the presence of ternary combinations. The observed trend of altered mRNA expression was found to correlate well with the change in expression levels of PXR. The gene expression was found to correlate with activity assays. Lack of cytotoxicity and ATP activity was observed in the treatment samples, suggesting that these alterations in expression levels were probably not stress responses. In the present study, we demonstrated that combinations of drugs can have serious consequences toward the treatment of HIV infection by altering their bioavailability and disposition.


Comparison of different methods assessing alcohol contribution to emergency room visits.
The main objective of research was to compare different methods of assessing alcohol's contribution to injuries and medical conditions treated in ER in Poland. Four methods are discussed, including breathalyzer reading, clinical appraisal following Y91 codes of ICD 10, interviewer's observation and self-report. In two Polish sites Warsaw and Sosnowiec probability samples of patients admitted to ER were selected and interviewed face-to-face by trained interviewers. Almost 1.5 thousand patients were interviewed with response rate of 67%. To identify injuries and medical conditions associated with drinking (preceded by alcohol consumption) four methods were used: clinical observations made by nurses trained in applying Y91 codes of ICD-10 (in the Sosnowiec ER only), observations by interviewers who did not receive such a training, breathalyzer readings and patient self-reports of drinking within six hours prior to the event. A breathalyzer reading identified 4.5% under the influence of alcohol among all patients, and 5.7% among those who were breathalyzed. Clinical assessment in Sosnowiec and interviewers' observations in both cites identified almost the same proportion: 5.1% and 4.7%, respectively and self-reports almost 10%. All four measures for identifying potentially alcohol related ER visits found a total of 11.5% cases among sampled patients.


Performance Evaluation of Commercial Dengue Diagnostic Tests for Early Detection of Dengue in Clinical Samples.
The shattering rise in dengue virus infections globally has created a need for an accurate and validated rapid diagnostic test for this virus. Rapid diagnostic test (RDT) and reverse transcription-polymerase chain reaction (RT-PCR) diagnostic detection are useful tools for diagnosis of early dengue infection. We prospectively evaluated the diagnostic performance of nonstructural 1 (NS1) RDT and real-time RT-PCR diagnostic kits in 86 patient serum samples. Thirty-six samples were positive for dengue NS1 antigen while the remaining 50 were negative when tested with enzyme-linked immunosorbent assay (ELISA). Commercially available RDTs for NS1 detection, RTK ProDetect™, and SD Bioline showed high sensitivity of 94% and 89%, respectively, compared with ELISA. GenoAmp® Trioplex Real-Time RT-PCR and RealStar® Dengue RT-PCR tests presented a comparable kappa agreement with 0.722. The result obtained from GenoAmp® Real-Time RT-PCR Dengue test showed that 14 samples harbored dengue virus type 1 (DENV-1), 8 samples harbored DENV-2, 2 samples harbored DENV-3, and 1 sample harbored DENV-4. 1 sample had a double infection with DENV-1 and DENV-2. The NS1 RDTs and real-time RT-PCR tests were found to be a useful diagnostic for early and rapid diagnosis of acute dengue and an excellent surveillance tool in our battle against dengue.


Inhibitory effect of acetylcholine on muscular tonus of the small intestine of a lizard.
The present report concerns the effects of cholinergic agonists on the isometric tension of "in vitro" preparations of the esophagus and distal part of the small intestine of the lizard Liolaemus gravenhorsti. Acetylcholine (Ach) and carbachol elicited a dose-related increase of isometric tension in the esophagus, whereas the small intestine was slowly relaxed by these drugs. Eserine induced a synergistic action on the cholinergic responses of both organs, and atropine completely antagonized the respective effects. The esophagus and the intestine showed different thresholds for the cholinergic evoked responses, the former being about 30 times more sensitive than the intestine. Assessment of cholinesterase activity revealed that Ach is hydrolyzed at a significant lesser speed in the intestine than in the esophagus. The results do not provide information about the nature of the chemical mediator causing the inhibitory effect observed in the intestine. The eventual role of an adrenergic mechanism mediated by muscarinic receptors is under study in our laboratory.


[Mucocele from concha bullosa with invasion of the orbit].
We present a case of a 44-year-old man that came to the clinic with exophthalmus and frontal headaches. TC and MRI showed a fronto-sphenoidal mass with extension to the cribiform plate involving the orbit and pushing the eyeball forward. The mass was completely excised through intranasal endoscopic surgery and it was found out to be a mucocele from concha bullosa.


Wear and microhardness of different resin composite materials.
This study determined the three-body abrasive wear resistance of two packable composites (P-60; Solitaire 2), an ion-releasing composite (Ariston AT), a hybrid composite (Tetric Ceram) and an ormocer (Admira). The study also looked at the correlation between wear resistance and hardness of the composites. Three-body wear testing was performed using an ACTA wear machine with 15 N contact force using millet seed as the third body. Wear depth (microm) was measured by profilometry after 200,000 cycles. The hardness test was performed using a digital microhardness tester (load: 500 g; dwell time: 15 seconds). The data were analyzed by using Kruskal Wallis (p < 0.05). There were statistically significant differences among the three body abrasive wear of the composites. The ranking from least to most were as follows: Filtek P-60 < Solitaire 2 < Ariston AT < Tetric Ceram < Admira. Filtek P-60 showed the highest microhardness value. No other significant differences in hardness were observed among the different resin composites (P-60 > AristonAT = Tetric Ceram = Solitaire 2 = Admira). The results of this study indicate that there are significant differences in the wear resistance of the resin composites. The correlation between hardness and wear was significant with a correlation coefficient of r:-0.91. A significant negative correlation exists between hardness and three-body wear of resin composites.


Design of a syndemic based intervention to facilitate care for men who have sex with men with high risk behaviour: the syn.bas.in randomized controlled trial.
Men who have sex with men (MSM) constitute a risk group for sexual transmitted infections (STIs), including HIV. Despite counselling interventions, risk behaviour remains high. Syndemic theory holds that psychosocial problems often co-occur, interact and mutually reinforce each other, thereby increasing high risk behaviours and co-occurring diseases. Therefore, if co-occurring psychosocial problems were assessed and treated simultaneously, this might decrease high risk behaviour and disease. An open label randomized controlled trial will be conducted among 150 MSM with high risk behaviour recruited from the STI clinic of Amsterdam. Inclusion criteria are: HIV negative MSM with two STI and/or PEP treatment in the last 24 months, or HIV positive MSM with one STI in the last 24 months. All participants get questionnaires on the following syndemic domains: ADHD, depression, anxiety disorder, alexithymia and sex- and drug addiction. Participants in the control group receive standard care: STI screenings every three months and motivational interviewing based counselling. Participants in the experimental group receive standard care plus feedback based on the results of the questionnaires. All participants can be referred to co-located mental health or addiction services. The primary outcome is help seeking behaviour for mental health problems and/or drug use problems. The secondary outcomes are STI incidence and changes in sexual risk behaviour (i.e. condom use, number of anal sex partners, drug use during sex). This study will provide information on syndemic domains among MSM who show high risk behaviour and on the effect of screening and referral on help seeking behaviour and health (behaviour) outcomes. Trial Registration at clinicaltrail.gov, identifier NCT02859935 .


Antihyperglycemic and insulin-releasing effects of beta-sitosterol 3-beta-D-glucoside and its aglycone, beta-sitosterol.
The effect of beta-sitosterol 3-beta-glucoside (antihyperglycemic principle isolated from the aerial part of Centaurea seridis L. var. maritima Lge.) and its aglycone on plasma insulin and glucose levels in normo- and hyperglycemic rats was investigated. The results indicate that oral treatment with the glycoside or with the beta-sitosterol increased the fasting plasma insulin levels. There was a corresponding decrease in fasting glycemia when beta-sitosterol was administered orally. In addition, these compounds improved the oral glucose tolerance test with an increase in glucose-induced insulin secretion. But when these products were administered orally, the effect of glycoside, either on fasting insulinemia or on glucose-induced insulin secretion, lasted longer than that of aglycone. The present study compared these effects with those of glibenclamide. It can be assumed that beta-sitosterol 3-beta-D-glucoside acts by increasing circulating insulin levels, and that this effect is due to their aglycone: beta-sitosterol.


Strategies for reporting health plan performance information to consumers: evidence from controlled studies.
To assess whether presentation approaches designed to be more meaningful result in greater weighting of quality information in decisions. An emerging body of research indicates that the way information is presented affects how it is interpreted and how it is weighted in decisions. Comparative health plan performance reports are not being used by consumers possibly because the information presented is difficult to use. The next generation of these reports should be designed to support decision making. The study uses a controlled experimental design. Participants (n = 162) were randomly assigned to different conditions and asked to complete tasks related to using quality information and making health plan selections. Dependent variables included the amount of weight given to quality information in choices and decision accuracy. Some presentation approaches make it easier for users to process and integrate quality data into their choices. However, other presentation formats influence consumers' decisions in ways that undermine their self-interest. Findings indicate that presenting quality data in a more evaluable format increases the weight it carries in consumer decisions. Every change made in the presentation of comparative data has the potential to influence decisions. Those who disseminate information have a responsibility to be aware of how they use that influence and to direct it in productive and defensible ways. The alternative is to manipulate people in ways that are unknown, are not thought out, or are not defensible, but are no less manipulative.


Ultrafine Molybdenum Carbide Nanoparticles Composited with Carbon as a Highly Active Hydrogen-Evolution Electrocatalyst.
The replacement of platinum with non-precious-metal electrocatalysts with high efficiency and superior stability for the hydrogen-evolution reaction (HER) remains a great challenge. Herein, we report the one-step synthesis of uniform, ultrafine molybdenum carbide (Mo2C) nanoparticles (NPs) within a carbon matrix from inexpensive starting materials (dicyanamide and ammonium molybdate). The optimized catalyst consisting of Mo2C NPs with sizes lower than 3 nm encapsulated by ultrathin graphene shells (ca. 1-3 layers) showed superior HER activity in acidic media, with a very low onset potential of -6 mV, a small Tafel slope of 41 mV dec(-1), and a large exchange current density of 0.179 mA cm(-2), as well as good stability during operation for 12 h. These excellent properties are similar to those of state-of-the-art 20% Pt/C and make the catalyst one of the most active acid-stable electrocatalysts ever reported for HER.


Pulmonary arterial hypertension in critically ill elderly patients.
To assess the incidence, possible risk factors and prognosis of pulmonary arterial hypertension (PAH) in critically ill elderly patients. We selected 122 cases admitted to the ICU, ages 60-93 years old. An echocardiography examination was performed within four days after admission to the ICU. PAH is usually suspected if the patient's pulmonary artery systolic pressure ≥ 40 mmHg. We collected echocardiography data, relevant clinical data and routine laboratory data; we then used a statistical method to analyze the risk factors for PAH in critically ill elderly patients and examined its impact on the prognosis. Total 51 patients were diagnosed with PAH. The prevalence of critically ill elderly patients with PAH was 41.8%. The ANOVA analysis showed that if patients had COPD (P = 0.031) and/or respiratory failure (P = 0.021), they were more prone to PAH. An enlarged left atrium (P = 0.038) and/or right ventricle (P = 0.029), a declining left ventricle fractional shortening rate (P = 0.038), and an elevated amount of the brain natriuretic peptides (P = 0.046) were all associated with the occurrence of PAH. Multivariate regression analysis showed that the left atrial diameter (P = 0.045) was the risk factor in critically ill elderly patients with PAH. The 30-day mortality rate was 33.3% for elderly patients with PAH, which is statistically significant (P = 0.035) when compared with the mortality rate of patients with normal pulmonary artery pressure. Our multivariate regression analysis also showed that, for critically ill elderly patients admitted in the ICU, PAH (P = 0.039) is risk factor for increased mortality. A higher incidence of PAH occurs in critically ill elderly patients. PAH is more likely to occur in patients with an enlarged left atrium, and these problems adversely impact the prognosis.


Mouse hepatitis coronavirus A59 nucleocapsid protein is a type I interferon antagonist.
The recent emergence of several new coronaviruses, including the etiological cause of severe acute respiratory syndrome, has significantly increased the importance of understanding virus-host cell interactions of this virus family. We used mouse hepatitis virus (MHV) A59 as a model to gain insight into how coronaviruses affect the type I alpha/beta interferon (IFN) system. We demonstrate that MHV is resistant to type I IFN. Protein kinase R (PKR) and the alpha subunit of eukaryotic translation initiation factor are not phosphorylated in infected cells. The RNase L activity associated with 2',5'-oligoadenylate synthetase is not activated or is blocked, since cellular RNA is not degraded. These results are consistent with lack of protein translation shutoff early following infection. We used a well-established recombinant vaccinia virus (VV)-based expression system that lacks the viral IFN antagonist E3L to screen viral genes for their ability to rescue the IFN sensitivity of the mutant. The nucleocapsid (N) gene rescued VVDeltaE3L from IFN sensitivity. N gene expression prevents cellular RNA degradation and partially rescues the dramatic translation shutoff characteristic of the VVDeltaE3L virus. However, it does not prevent PKR phosphorylation. The results indicate that the MHV N protein is a type I IFN antagonist that likely plays a role in circumventing the innate immune response.


Bilateral digitally-aided tooth autotransplantation: A 2-year case report.
Tooth autotransplantation is an effective treatment to replace missing teeth. Digital planning can facilitate successful autotransplantation. Guiding templates are highly recommended when performing cases in healed ridges in the posterior area to reduce excessive bone subtraction and increase the chances of fitting of the donor tooth in the new socket. This case report highlights the use of three-dimensional planning tools and fully-guided drilling templates for successful tooth autotransplantation in the posterior area. Two tooth autotransplantations were performed in a 51-year-old patient using lower wisdom teeth to replace hopeless lower molars. Root canal treatments were carried out before the surgeries and different alveoloplasty techniques were used in each recipient area. The prosthetic phase was carried out after 9 months. Both teeth were asymptomatic, functional, and exhibited no signs of resorption or apical radiolucency and complete regeneration of the periodontal apparatus at the 2-year follow-up.


Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons.
Removal of synaptic AMPA receptors is important for synaptic depression. Here, we characterize the roles of individual subunits in the inducible redistribution of AMPA receptors from the cell surface to intracellular compartments in cultured hippocampal neurons. The intracellular accumulation of GluR2 and GluR3 but not GluR1 is enhanced by AMPA, NMDA, or synaptic activity. After AMPA-induced internalization, homomeric GluR2 enters the recycling pathway, but following NMDA, GluR2 is diverted to late endosomes/lysosomes. In contrast, GluR1 remains in the recycling pathway, and GluR3 is targeted to lysosomes regardless of NMDA receptor activation. Interaction with NSF plays a role in regulated lysosomal targeting of GluR2. GluR1/GluR2 heteromeric receptors behave like GluR2 homomers, and endogenous AMPA receptors show differential activity-dependent sorting similar to homomeric GluR2. Thus, GluR2 is a key subunit that controls recycling and degradation of AMPA receptors after internalization.


A novel binding protein of single-minded 2: the mitotic arrest-deficient protein MAD2B.
Single-minded 2 (Sim2) gene, located at the Down syndrome (DS) critical region, is thought to be particularly important because of its critical role in the development of the central nervous system (CNS) and its overexpression resulting in impairment of learning and memory which is similar to that in DS. However, its exact role in DS still remains elusive. Using a yeast two-hybrid interaction trap, we identified the mitotic arrest-deficient protein MAD2B as a novel Sim2 binding protein. Through confocal laser scanning microscopy, we found that Sim2 and MAD2B colocalized in rat cortex neurons. This interaction between Sim2 and MAD2B was also confirmed by co-immunoprecipitation. Moreover, levels of mRNA and protein of both Sim2 and MAD2B were regulated during nervous development as detected by quantitative RT-PCR and western blot analysis. We also found that overexpression of Sim2 affected the distribution of MAD2B in primary culture neurons. The results of confocal laser scanning microscopy and co-immunoprecipitation indicated that in neurons, MAD2B interacted with clathrin light chain A, which is best known for its role in endocytosis. In addition, it was found that overexpression of Sim2 or MAD2B caused deficits in clathrin-mediated endocytosis. Furthermore, overexpression of both MAD2B and Sim2 exacerbates their own inhibitory effect on transferrin uptake. These results suggest that MAD2B may mediate Sim2 function during development in CNS and thereby play a critical role in pathophysiological mechanisms in DS.


[Gastrointestinal stromal tumours: clinico-morphological features, pathogenesis and modern treatment strategies].
Gastrointestinal stromal tumours (GIST) are the commonest mesenchymal tumours of gastrointestinal organs accounting for 1-3% of all gastrointestinal neoplasms and almost 5% of all soft tissue sarcomas. Most GIST (95%) express transmembrane receptor KIT or CD117, CD34 (70%), vimentin (80%), specific smooth muscle and neurogenic markers (with different frequency). Up to 85% of the stromal tumours have mutations in the KIT gene (exones 9, 11, 13, 17) and 3-18% in the PDGFRA (platelet-derived growth factor receptor-alpha) gene (exones 12, 14, 18). Mutations are absent in 5% of KITand PDGFRA genes. Mutational status, mitotic index, size and location of the tumour are the most informative criteria for the choice of treatment strategy and prognosis of the disease.


Venetoclax Cooperates with Ionizing Radiation to Attenuate Diffuse Midline Glioma Tumor Growth.
Tumor relapse after radiotherapy is a major hurdle in treating pediatric H3K27M-mutant diffuse midline gliomas (DMG). Radiotherapy-induced stress increases association of BCL2 family of proteins with BH3 pro-apoptotic activators preventing apoptosis. We hypothesized that inhibition of radiotherapy-induced BCL2 with a clinically relevant inhibitor, venetoclax, will block BCL2 activity leading to increased apoptosis. BCL2 has never been implicated in DMG as a radiotherapy-induced resistant mechanism. We performed an integrated genomic analysis to determine genes responsible for radioresistance and a targeted drug screen to identify drugs that synergize with radiation in DMG. Effect of venetoclax on radiation-naïve and 6 Gy radiation on cells was evaluated by studying cell death, changes in BCL2 phosphorylation, reactive oxygen species (ROS), and apoptosis, as well as BCL2 association with BH3 apoptosis initiators. The efficacy of combining venetoclax with radiation was evaluated in vivo using orthotopic xenograft models. BCL2 was identified as a key regulator of tumor growth after radiation in DMGs. Radiation sensitizes DMGs to venetoclax treatment independent of p53 status. Venetoclax as a monotherapy was not cytotoxic to DMG cells. Postradiation venetoclax treatment significantly increased cell death, reduced BCL2-BIM association, and augmented mitochondrial ROS leading to increased apoptosis. Combining venetoclax with radiotherapy significantly enhanced the survival of mice with DMG tumors. This study shows that venetoclax impedes the antiapoptotic function of radiation-induced BCL2 in DMG, leading to increased apoptosis. Results from these preclinical studies demonstrate the potential use of the BCL2 inhibitor venetoclax combined with radiotherapy for pediatric DMG.


Molecular cloning of coat protein gene of cucumber mosaic virus, CMV-U strain.
RNA isolation from purified cucumber mosaic virus, CMV-U strain and cDNA synthesis was carried out. The coat protein gene (RNA4) region was amplified selectively by polymerase chain reaction (PCR) with CMV RNA4-specific primers. Double-stranded cDNA was cloned in PRT103 vector at Xho1/Kpn1 site and about 1kb insert obtained. The insert was partly sequenced which showed 50% sequence homology with CMV-Q, C and WL strains.


Catalyzed oxidative corrosion of porous silicon used as an optical transducer for ligand-receptor interactions.
Biosensors fabricated on the nanoscale offer exciting new avenues in the quest for better understanding and characterization of biological systems. Porous silicon is an ideal nanostructured material for the construction of optical transducer matrices because it is easily functionalized with biomolecular probes and displays strong optical interferences. Here, we show that certain transition metal complexes, including nickel(II)cyclam, are able to induce corrosion in porous silicon films rapidly, generating a strong optical interferometric signal that originates from the porous layer. We subsequently exploit this effect to design a transducer for ligand-receptor recognition. With a nickel(II)cyclam derivative as a catalytic label, DNA- and avidin-binding events are detected by time-lapse interferometric reflectance spectroscopy in a fast, simple, and inexpensive fashion.


[Osseous changes in Hodgkin's disease and cellular bone marrow infiltrations].
In 83 patients (40 females and 43 males) aged from 17 to 69 years belonging to 190 cases of Hodgkin's disease treated as inpatients in the Institute of Haematology in Warsaw in the years 1966-1974 radiological investigations of the skeletal system were done. In 17 cases (20.4%) bone changes were demonstrated appearing as rarefaction (9 cases), sclerosis (6 cases) or mixed (2 cases) changes. The changes were located most frequently in the spine, less frequently in the epiphyses of long bones and flat bones. All 17 cases with bone changes were qualified as IV clinical stage of disease progression. Radiological osseous changes were not pathognomonic and it was difficult to draw conclusions as to the mode of spread. Bone pains were present in 8 patients, including 7 with spinal changes. In some cases treated postmortem specific infiltrations were found in bone marrow.


Search for Unstable Sterile Neutrinos with the IceCube Neutrino Observatory.
We present a search for an unstable sterile neutrino by looking for a resonant signal in eight years of atmospheric ν_{μ} data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (stable) three-neutrino and the 3+1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with p values of 2.8% and 0.81%, respectively, we do not observe evidence for 3+1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are Δm_{41}^{2}=6.7_{-2.5}^{+3.9} eV^{2}, sin^{2}2θ_{24}=0.33_{-0.17}^{+0.20}, and g^{2}=2.5π±1.5π, where g is the decay-mediating coupling. The preferred regions of the 3+1+decay model from short-baseline oscillation searches are excluded at 90% C.L.


FK506 may reduce early liver injury following living related liver transplantation.
We investigated the influence of FK506 which has been used frequently after transplant surgery as an immunosuppressant, on liver injury after partial hepatectomy by comparing laboratory data from donors and recipients after liver transplantation. Seventeen donors and respective recipients who underwent living related donor liver transplantation were included in the present study. Serum levels of transaminases and cytokines were measured and compared preoperatively and in the early period after the operation. Serum level of asparaginic acid aminotransferase in the postoperative day 1 was significantly higher in the donor group. Serum levels of alanine aminotransferase in the early period after the operation were significantly higher in the donor group. Serum levels of interferon y and soluble Fas ligand in the early period after the operation were significantly higher in the donor group. Steroid doses administered were significantly higher in the recipient group. FK506 administration and steroid administration in larger doses were thought to reduce serum transaminase levels of the recipient group. These findings might suggest that cell-mediated immunity weigh heavier than the operation time of ischemia-reperfusion injury as a cause of liver injury after partial hepatectomy.


On the "Born" term used in thermodynamic models for electrolytes.
In the literature, many expressions for the Helmholtz or Gibbs energy of electrolyte solutions have included a term that takes into account the variation of the solution permittivity with the composition of solution (e.g., within the statistical-associated fluid theory formalism). This contribution is often called the "Born" term because it was inspired by the classic expression established by Born to describe the solvation energy of an ion. The present work is an attempt to get more physical insight into this semiempirical "Born" term. The way in which it has been used in the literature is briefly examined, and its typical magnitude is evaluated. Next, it is proposed to use the nonprimitive mean spherical approximation model to calculate the chemical potential of an ion in a solution composed of charged hard spheres (HSs) (the ions) and dipolar HSs (the solvent). The cation and the anion are monovalent monoatomic ions of equal diameter. The dipoles have a different size and mimic water molecules. The theoretical expressions for this model were found to fulfill the Gibbs-Duhem relation, which suggests that they are correct. A rescaled ion-dipole contribution is introduced, in a form that is suitable for inclusion in electrolyte models. It is compared with a "Born" term expressed in the same framework. It is found that the former is in general not well estimated by the latter. The two might even be of opposite signs in the case of ions of sufficiently small size.


Lytic replication of Human herpesvirus 8 and induction of apoptosis.
Although many viruses can induce apoptosis in infected cells, large DNA viruses, such as poxviruses, herpesviruses and adenoviruses, usually exhibit the ability to suppress the induction of apoptosis in the infected cells. We investigated the ability of Human herpesvirus 8 (HHV-8) to protect cells from apoptosis induced by the virus. HHV-8 has been shown to harbor genes with anti-apoptotic capacity. However, we demonstrate here that a lytic replication of HHV-8 resulted in induction of apoptosis using different techniques to detect apoptosis. Therefore, despite the presence of anti-apoptotic genes in its genome, HHV-8 could complete its cycle of productive infection while inducing apoptosis in infected cells. This finding might have implications for the pathobiology of HHV-8 and other gamma herpesviruses in vivo.


Genes and/or jeans?: Genetic and socio-cultural contributions to risk for eating disorders.
Eating disorders are prevalent among young adult females and pose serious psychological and medical risks. Notwithstanding important advances, efforts to develop effective means of preventing and treating eating disorders have been limited by an incomplete understanding of their multifactorial etiology. Whereas epidemiologic data strongly suggest the influence of socio-cultural context in moderating risk, many hypotheses about how these effects are exerted have remained empirically unevaluated. Specifically, experimental and observational data suggest that social transition (e.g., transnational migration, urbanization, modernization), Western media exposure, and certain peer environments (involving social comparison and teasing) may all contribute to risk. With respect to genetic influences on etiology, family and twin studies have supported a genetic diathesis to eating disorders. Whereas, molecular genetic studies have generated interesting leads- with the most promising findings emerging for genes related to the function of serotonin-they have yet to identify well-replicated susceptibility loci. This paper reviews the data supporting both socio-cultural and genetic contributions for eating disorders and suggests productive future strategies for continuing to unravel their likely multiple and complex interactions.


Late referral for dialysis: improving the management of chronic renal disease.
Timely nephrological referral of patients with chronic renal failure (CRF) is important, but referral at a late stage of disease is common. To investigate whether late referral of patients is avoidable, and where the missed opportunities lie. Prospective ascertainment of new cases and comprehensive review of pre-end stage history. Patients admitted to Bristol and Portsmouth renal units for chronic RRT between June 1997 and May 1998 were identified from computer databases. Data were collected from case notes and hospital records, and a self-administered patient questionnaire. Late referral, defined as dialysis within 4 months of first referral to a dialysing nephrologist, was categorized by algorithm as unavoidable or avoidable. Of 250 patients, 96 (38%) were referred late. Forty-three (45%) had definite avoidable reasons: 35 (37%) with raised serum creatinine for a median 3.7 years (IQR 1.5-8.2) before referral, and eight (8%) with risk factors for renal disease but scant assessment of renal function; 12/43 (31%) had a diagnosis of diabetic nephropathy. Late referred patients were less likely to receive standard renal therapies for chronic renal failure, were in a poorer clinical state at start of RRT, and more often required emergency dialysis, compared to patients referred early. Late referrals were as likely from a hospital as a primary care physician. A significant proportion of patients are avoidably referred to a dialysing renal unit at a very late stage. Guidelines on referral should be developed by nephrologists, primary and secondary care physicians, and patient groups, and further research is needed into the cost-effectiveness of early referral strategies.


Attack of radicals and protons on ladderane lipids: quantum chemical calculations and biological implications.
Quantum chemical calculations on possible decomposition processes for ladderane lipids are described. Based on the results of these calculations, it is proposed that hydrogen atom abstraction next to the ladderane core can lead to opening of the cyclobutane rings comprising the ladderane substructure, and protonation leads directly to fragmentation. Potential biological implications of these processes are discussed.


Survey of SNPs Associated with Total Number Born and Total Number Born Alive in Pig.
Reproductive productivity depend on a complex set of characteristics. The number of piglets at birth (Total number born, Litter size, TNB) and the number of alive piglets at birth (Total number born alive, NBA) are the main indicators of the reproductive productivity of sows in pig breeding. Great hopes are pinned on GWAS (Genome-Wide Association Studies) to solve the problems associated with studying the genetic architecture of reproductive traits of pigs. This paper provides an overview of international studies on SNP (Single nucleotide polymorphism) associated with TNB and NBA in pigs presented in PigQTLdb as "Genome map association". Currently on the base of Genome map association results 306 SNPs associated with TNB (218 SNPs) and NBA (88 SNPs) have been identified and presented in the Pig QTLdb database. The results are based on research of pigs such as Large White, Yorkshire, Landrace, Berkshire, Duroc and Erhualian. The presented review shows that most SNPs found in chromosome areas where candidate genes or QTLs (Quantitative trait locus) have been identified. Further research in the given direction will allow to obtain new data that will become an impulse for creating breakthrough breeding technologies and increase the production efficiency in pig farming.


Time out for surgeons: when is the attending surgeon too tired?
Pediatric surgical subspecialty workforce shortages are here to stay without any expected solution for the short-term. Individual surgeons, hospital administrators, risk management and patient-safety teams need to recognize that patient safety must take precedence over clinical productivity and financial "bottom lines." Pushing attending surgeon work hours beyond the limits of exhaustion impairs patient safety. Just as resident surgeon work hours have been appropriately curtailed in the name of patient safety, so must attending surgeon work hours. This issue needs to be addressed by hospital patient safety committees, professional societies, and by state and national regulating authorities.


Induction of lymphosarcoma in sheep by bovine leukemia virus.
Newborn sheep inoculated with phytohemagglutinin (PHA)-treated short-term, cultures of lymphocytes from cattle infected with bovine leukemia virus (BLV) or with a BLV- infected long-term culture of bovine leukemic lymphocytes became persistently infected with BLV. Fifty percent or more of the sheep died with histologically confirmed lymphosarcomas. Cytogenetic studies of representative cases demonstrated that the tumors did not result from the progressive growth of neoplastic lymphocytes in the inoculum but rather from the neoplastic transformation of the recipients lymphoid cells. Neither BLV infection nor lymphosarcoma was observed in control uninoculated sheep or in sheep given injections of PHA-treated cultures of lymphocytes from BLV-free cows. The virus recovered from the tumorous sheep was indistinguishable from BLV morphologically, antigenically, and biologically, and its reverse transcriptase had the same cation preference and immunologic properties as the BLV enzyme. Persistent BLV infection and lymphosarcoma were also observed in a group of sheep inoculated neonatally with BLV-containing cell-free culture supernatants. These results extend previous observations on the high susceptibility of sheep to BLV infection and provide definitive evidence that BLV is a tumor-inducing virus.


Hang-Time HAR: A Benchmark Dataset for Basketball Activity Recognition Using Wrist-Worn Inertial Sensors.
We present a benchmark dataset for evaluating physical human activity recognition methods from wrist-worn sensors, for the specific setting of basketball training, drills, and games. Basketball activities lend themselves well for measurement by wrist-worn inertial sensors, and systems that are able to detect such sport-relevant activities could be used in applications of game analysis, guided training, and personal physical activity tracking. The dataset was recorded from two teams in separate countries (USA and Germany) with a total of 24 players who wore an inertial sensor on their wrist, during both a repetitive basketball training session and a game. Particular features of this dataset include an inherent variance through cultural differences in game rules and styles as the data was recorded in two countries, as well as different sport skill levels since the participants were heterogeneous in terms of prior basketball experience. We illustrate the dataset's features in several time-series analyses and report on a baseline classification performance study with two state-of-the-art deep learning architectures.


Spectrum of PAH gene mutations and genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey.
The aim of our study was to define the genotype-phenotype correlations of mutations in the PAH gene among the Turkey's Central Anatolian region. Demographic characteristics of 108 patients with hyperphenylalaninemia (HPA) and 94 patients whose diagnosis was confirmed by PAH gene analysis (Sanger DNA Sequence Analysis and Next-Generation Sequencing) were determined retrospectively. Blood phenylalanine levels were analyzed using the high-performance liquid chromatography method. Mild HPA-not-requiring-treatment (NT) was found in 50.9% of the patients, and a classical phenylketonuria (PKU) phenotype was found in 25.9%. Forty-seven types of variants were identified. The predominant variants were p.Ala403Val (9.9%), p.Ala300Ser (9.4%), and c.1066-11G>A (splicing) (9.4%). Missense mutations accounted for 68% of mutations and attenuated the clinical impact; splice variations were found in 14.8% of cases with severe features. The p.Thr380Met allele was specific to the mild HPA-NT group. The c.1066-11G>A (splicing) allele was associated with classical PKU, whereas the p.Arg408Trp allele was linked to severe symptoms. Three variations of unknown clinical significance were discovered: c.706+4A>T (splicing), c.843-5T>C (splicing), and p.Thr323=. Of these variants, the patient who was homozygous for the c.843-5T>C (splicing) allele related to the classical PKU phenotype. 70% of the patients who underwent tetrahydrobiopterin (BH4) test were responsive. Phenotypes that responded to BH4 treatment were mostly mild phenotypes. The PAH genotype is the main factor that determines the phenotype of PKU. Establishing the relationship between the identified genetic mutations and phenotypic characteristics will provide very important data for each patient in terms of the specific management style.


Vaccination of Sheep with a Methanogen Protein Provides Insight into Levels of Antibody in Saliva Needed to Target Ruminal Methanogens.
Methane is produced in the rumen of ruminant livestock by methanogens and is a major contributor to agricultural greenhouse gases. Vaccination against ruminal methanogens could reduce methane emissions by inducing antibodies in saliva which enter the rumen and impair ability of methanogens to produce methane. Presently, it is not known if vaccination can induce sufficient amounts of antibody in the saliva to target methanogen populations in the rumen and little is known about how long antibody in the rumen remains active. In the current study, sheep were vaccinated twice at a 3-week interval with a model methanogen antigen, recombinant glycosyl transferase protein (rGT2) formulated with one of four adjuvants: saponin, Montanide ISA61, a chitosan thermogel, or a lipid nanoparticle/cationic liposome adjuvant (n = 6/formulation). A control group of sheep (n = 6) was not vaccinated. The highest antigen-specific IgA and IgG responses in both saliva and serum were observed with Montanide ISA61, which promoted levels of salivary antibodies that were five-fold higher than the second most potent adjuvant, saponin. A rGT2-specific IgG standard was used to determine the level of rGT2-specific IgG in serum and saliva. Vaccination with GT2/Montanide ISA61 produced a peak antibody concentration of 7 × 1016 molecules of antigen-specific IgG per litre of saliva, and it was estimated that in the rumen there would be more than 104 molecules of antigen-specific IgG for each methanogen cell. Both IgG and IgA in saliva were shown to be relatively stable in the rumen. Salivary antibody exposed for 1-2 hours to an in vitro simulated rumen environment retained approximately 50% of antigen-binding activity. Collectively, the results from measuring antibody levels and stablility suggest a vaccination-based mitigation strategy for livestock generated methane is in theory feasible.


[A level of social support and intensity of anxiety in patients with AIDS].
The article is devoted to psychological aspects of functioning of patients with AIDS. The issue may be analysed from different perspectives. The article focuses on two of them. The first--a point of view of the person directly affected by the new illness and the second--a perspective of social phenomena accompanying AIDS. The empirical research have been carried out on the basis of a synthesis of the above mentioned areas and they have made it possible to describe relations between them. The inquiries have concerned mainly the connection between the social support given to the ills and the anxiety experienced by them, resulting from emotional uneasiness. The independent variable, which was social support, has been formulated in a qualitive way, by referring to such subjective measures like: feeling of support, its perceived availability, adequacy. The survey pattern has been prepared on the basis of the claim of existence of the so called main effect i.e. direct relationship between social support and individual's psychophysical comfort. The investigated variables have been measured using the following research tools: The Inventory for Measuring Anxiety as a State and as a Feature, elaborated by C.D. Spielberger and The Scale of Social Support Deficit by K. Kmiecik-Baran. The achieved results have clearly shown the dependence between a level of social support and intensity of the anxiety experienced by the ills with AIDS. Apart from a cognitive value of the fact it is worth to pay attention to a possibility of its practical application.


[Iatrogenic pathology in the cardiovascular field].
The possible iatrogenic effects of some drugs commonly employed in heart cases (digitalis, quinidine, procainamide, antihypertensives, etc.) and the possible risks of electrical stimulation techniques are described. Attention is also given to the dangers associated with erroneous laboratory data, or the mistaken interpretation of correct data by the physician. Some illustrative cases are presented.


Multicenter performance evaluation of a new TaqMan PCR assay for monitoring human immunodeficiency virus RNA load.
A TaqMan real-time PCR assay, the COBAS TaqMan human immunodeficiency virus (HIV) (HPS-CTMHIV) PCR assay, recently developed for the quantification of HIV type 1 RNA in plasma, was evaluated in comparison with the licensed COBAS AMPLICOR HIV-1 MONITOR (CAHIM) assay. In this study, we have analyzed the tests' sensitivities, precisions, and linearities using multiple replicates of a standard panel of HIV RNA covering a 7-logarithm range of concentrations, as well as serial threefold dilutions of high-titer clinical samples. The subtype inclusivity was also investigated, using a panel of subtypes A to H, while a collection of 160 clinical samples was analyzed to assess the tests' specificities and the systems' similarities. The results of these experiments showed that the HPS-CTMHIV assay has a sensitivity of 53 copies/ml (95% hit rate), 100% specificity, and good intra- and interassay precision. The results of the HPS-CTMHIV assay were linear in the 50- to 10(7)-copies/ml range, with a correlation coefficient (R) for expected versus observed results of 0.98. Compared to the CAHIM assay, the HPS-CTMHIV assay showed a high correlation (R=0.99) across the dynamic range of RNA concentrations that, for the CAHIM assay, requires two different sample preparations. Equivalent performances were also observed for the two systems in the detection and quantification of HIV subtypes A to H. These data indicate that the HPS-CTMHIV assay may be one of the tests of choice for monitoring viral load throughout the course of HIV infection and during highly active antiretroviral therapy.


Subsequent somatic axis and bone tissue metabolism responses to a low-zinc diet with or without phytase inclusion in broiler chickens.
Zinc is required for normal bone development and cartilage formation. The purpose of this study was to assess the effect of with adding organic Zn (alone or phytase inclusion) at the reduced dose to growing male Ross 308 chickens on somatic axis and bone tissue metabolism. 200 one-day old broilers were divided into the negative control group fed diet without Zn or phytase inclusion, positive control group receiving Zn in the 100% of daily recommended dose from ZnO, and two experimental groups fed diet introduced Zn in 25% of daily recommendation as a glycine chelate (Zn-Gly) with or without phytase inclusion (500 FTU·kg-1). Supplemental organic Zn increased bone Zn and Mg content, serum IGF-1, growth hormone and leptin concentration. Additional phytase inclusion increased body weight gain, blood plasma Ca, Fe, Zn and osteocalcin concentration and tibia ash percentage when compared to the Zn-deprived control. Bone geometry, yield and ultimate strengths were enhanced in both organic Zn supplemented groups, and the overall mechanical strength parameters of bone were better in these groups than in the positive control group supplemented with standard dose of inorganic Zn. Also marked improvements in the thickness of articular and the growth plate cartilages as well as real bone volume and thickness of metaphyseal trabeculae were achieved in all broilers fed Zn-supplemented diet irrespective of phytase inclusion, however, the highest cancellous bone mass and the best trabecular structure were noted after ZnO supplementation. In concludion, although dietary organic Zn given to growing broilers in 25% of daily recommended dose improved general bone properties and mechanical strength, the obtained results do not allow to unambiguously state that organic Zn supplementation at this level, even after phytase inclusion, is sufficient for proper bone development.


Smooth muscle tumor of uncertain malignant potential (STUMP): a case-based analysis.
The present study aimed to analyze of uterine smooth muscle tumors of uncertain malignant potential (STUMP) and the outcomes of patients with STUMP. In this retrospective study, the data of patients diagnosed with STUMP in a single tertiary center between January 2005-January 2020 were reviewed. We assessed the demographic variables, treatment outcomes, time until recurrence, disease-free and overall survival of the patients. Twenty-five patients diagnosed with STUMP were included in the study. The mean age of the patients was 43.2 ± 10.3 years. Thirteen of the 25 patients (52%) were treated by myomectomy, others received diagnoses following hysterectomy. The median follow-up time was 45.2 months. Recurrence was observed in three cases (12%), two of which were followed up without hysterectomy, and the third patient died by peritonitis carcinomatosa 60 months after diagnosis although she received cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment. This study evaluates the data of patients with STUMP. Our results reveal a STUMP recurrence of 12%, like those previously reported in the literature. Despite the possibility of malignant recurrence, fertility-preserving treatment with close follow-up should be tried, because of the relatively early age at diagnosis.


Teaching surgical technologists.
Teaching of any kind can be a rewarding career option for a perioperative nurse. Whether it is teaching patients, the public, other nurses, surgical technologists, or ancillary staff members, the result can still be the same: a feeling of satisfaction in doing an important job. This article explores one nurse's perioperative career and examines how that career evolved into the expanded role of clinical instructor for surgical technology at the college level.


Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism.
Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation.


Colchicine binding to tubulin monomers: a mechanistic study.
The kinetic and thermodynamic parameters for colchicine-tubulin and deacetamidocolchicine-tubulin interaction, under the condition where tubulin is predominantly in its dissociated state (approximately 80% monomer), have been determined. We observe that the kinetic parameters exihibit marked change when colchicine interacts with the monomeric form of tubulin rather than with the dimeric form of tubulin. The reaction of colchicine with tubulin monomers is characterized by an enhanced association rate which is a consequence of the lowering of activation energy. Colchicine-tubulin interaction, which is only poorly reversible, becomes partially reversible under this condition. Differences were also noticed in the thermodynamic parameters: the reaction of colchicine with tubulin monomers is enthalpy driven with small positive entropy, while with tubulin dimers a large positive entropy change was reported. However, no such changes in the binding parameters were observed for the reaction involving deacetamidocolchicine (a colchicine analog devoid of a side chain at the C-7 position of B-ring) with tubulin monomers. We therefore conclude that a single subunit of tubulin is capable of binding colchicine and that the unusual properties of colchicine-tubulin interactions such as the slow association rate, high activation energy, and the poor reversibility are due to the possible contact(s) of the C-7 substituent (in the B-ring) of colchicine with the other subunit of tubulin.


Evaluation of indocyanine green retention and aminopyrine breath tests in patients with malignant biliary obstruction.
Impaired hepatic function is a major contributory factor to the high incidence of postoperative morbidity and mortality in patients with malignant biliary obstruction. Dynamic hepatic function tests such as indocyanine green (ICG) retention and aminopyrine breath tests were evaluated in such patients to define whether they were clinically useful for prediction of postoperative morbidity and mortality. Forty-four patients with malignant biliary obstruction undergoing surgery for relief of obstructive jaundice were recruited into the study. Indocyanine green retention and aminopyrine breath tests were carried out in all patients pre-operatively and repeated in 36 patients postoperatively. The ICG retention was abnormal in all patients before surgery and there was significant improvement 2 weeks after surgery (32.8 +/- 2.5% vs 18.3 +/- 2.8%, P = 0.001). The change in ICG retention levels correlated with the serum bilirubin levels but the pre-operative ICG retention value could not predict postoperative morbidity and mortality. The aminopyrine breath test was abnormal in all but one patient. It correlated with pre-operative prothrombin time of the patients before surgery but it did not improve significantly after surgery and was not predictive of postoperative outcome. It is concluded that both ICG retention and aminopyrine breath tests have limited clinical value in the pre-operative evaluation of patients with malignant biliary obstruction.


High extracellular pressure promotes gastric cancer cell adhesion, invasion, migration and suppresses gastric cancer cell differentiation.
Slightly increased pressure stimulates tumor cell adhesion and proliferation. In the present study, we aimed to evaluate the effects of high pressure on gene expression and the biological behavior of gastric cancer cells. After incubation for 30 min at 37˚C under ambient and increased pressure, one portion of SGC7901 cells was used for cell proliferation and apoptosis assays, cell cycle analysis, adhesion invasion or migration assays. The other portion of cells was harvested for detection of matrix metalloproteinase-2 (MMP-2), inhibitor of DNA binding-1 (ID1), sonic Hedgehog (SHH) and E-cadherin expression by western blotting or RT-PCR. In addition, we investigated the effects of high pressure on SGC7901 cell ultrastructure by transmission electron microscopy. We found that the adhesion fold under increased pressure of 760 and 1,520 mmHg was 2.39±1.05 (P<0.05) and 2.47±0.85 (P<0.01) as compared with the control, respectively. The invasion fold was 3.42±2.06 (P<0.05) and 5.13±2.49 (P<0.01) as compared with the control, respectively. The migration was 1.65±0.20 (P<0.001) and 2.53±0.50 (P<0.001) as compared with the control, respectively. At increased pressure, MMP-2 and ID1 expression increased significantly, while the expression of SHH decreased significantly. However, we did not find significant change in proliferation, apoptosis, cell cycle or ultrastructure of the SGC7901 cells under high pressure. In conclusion, high pressure promoted the adhesion, invasion and migration of SGC7901 cells. Moreover, the present study suggests that the pressure-augmented invasion and migration may be related to the increase in MMP-2 expression. Moreover, high pressure may suppress SGC7901 cell differentiation, which may result from the change in SHH and ID1 expression.


Perfluoroalkyl substances in the Maltese environment - (I) surface water and rain water.
The presence of perfluoroalkyl substances (PFASs) in rain water on the Maltese Islands is reported here for the first time and an extensive survey of these substances in surface water also reported. The Maltese archipelago lies at the centre of the Mediterranean Sea and consists of three main inhabited islands: Malta, Gozo and Comino. Surface water was collected from 41 valleys during the months of February and March 2015 at the peak of the wet season. Rain water was collected during the months of December 2014, February, August, September and October 2015. PFASs were extracted from the water samples using solid phase extraction and the extracts were then analysed using ultra performance liquid chromatography coupled to mass spectrometry in tandem (UPLC-MS/MS). All surface and rain water samples were contaminated with at least one PFAS. PFOS (<LOD - 8.6ng/L) and PFOA (ND - 16ng/L) were the two major PFASs being detected in 100% and 95% of the surface waters respectively. The ΣPFAS concentrations in rain water ranged between 0.38ng/L (1st October 2015) and 6ng/L (21st February 2015). The Maltese archipelago is surrounded by sea and disconnected from any other mainland; therefore the results confirm that remote environments can become contaminated by PFASs from rain events depending on wind prevailing trajectories.


Understanding the habenula: A major node in circuits regulating emotion and motivation.
Over the last decade, the understanding of the habenula has rapidly advanced from being an understudied brain area with the Latin name 'habena" meaning "little rein", to being considered a "major rein" in the control of key monoaminergic brain centers. This ancient brain structure is a strategic node in the information flow from fronto-limbic brain areas to brainstem nuclei. As such, it plays a crucial role in regulating emotional, motivational, and cognitive behaviors and has been implicated in several neuropsychiatric disorders, including depression and addiction. This review will summarize recent findings on the medial (MHb) and lateral (LHb) habenula, their topographical projections, cell types, and functions. Additionally, we will discuss contemporary efforts that have uncovered novel molecular pathways and synaptic mechanisms with a focus on MHb-Interpeduncular nucleus (IPN) synapses. Finally, we will explore the potential interplay between the habenula's cholinergic and non-cholinergic components in coordinating related emotional and motivational behaviors, raising the possibility that these two pathways work together to provide balanced roles in reward prediction and aversion, rather than functioning independently.


Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation of characteristics.
Pyridostigmine bromide (3-[[(dimethylamino)-carbonyl]oxy]-1-methylpyridinium bromide), a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid) microcapsules (PPNMCs) were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine. The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium. The optimal volume ratio of inner phase to external phase, poly(lactic acid) concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm. Compared with free pyridostigmine, PPNMCs showed an initial burst release and a subsequent very slow release in vitro. The release profiles for the PPNMCs in four different types of dissolution medium were fitted to the Ritger-Peppas and Weibull models. The similarity between pairs of dissolution profiles for the PPNMCs in different types of medium was statistically significant, and the difference between the release curves for PPNMCs and free pyridostigmine was also statistically significant. PPNMCs prepared by the optimized protocol described here were in the nanometer range and had good uniformity, with significantly slower pyridostigmine release than from free pyridostigmine. This novel sustained-release delivery nanosystem for pyridostigmine might alleviate the need to identify new acetylcholinesterase inhibitors.


In Vitro/In Vivo Hepatoprotective and Antioxidant Effects of Defatted Extract and a Phenolic Fraction Obtained from Phlomis Tuberosa.
An in vitro/in vivo hepatotoxicity and hepatoprotection evaluation of a defatted extract and a phenolic fraction from Phlomis tuberosa, administered alone and in a carbon tetrachloride (CCl4)-induced metabolic bioactivation model, was performed. The extract and the phenolic fraction were analysed by high performance liquid chromatography (HPLC) to determine the total flavonoid content, to identify flavonoids and to quantify verbascoside. In addition, total polyphenolics in the samples were expressed as gallic acid equivalents. Applied alone, the extract and the fraction (5, 10 and 50 µg/mL) did not show a statistically significant hepatotoxic effect on isolated rat hepatocytes in vitro. In a CCl4-induced hepatotoxicity model, the samples exhibited a concentration-dependent, statistically significant hepatoprotective effect, which was most pronounced at 50 µg/mL for both. The phenolic fraction exhibited a more pronounced hepatoprotective effect compared to the extract. Data from the in vitro study on the effects of the extract were also confirmed in the in vivo experiment conducted in a CCl4-induced hepatotoxicity model in rats. A histopathological study showed that the animals treated with CCl4 and the extract had an unaltered histoarchitecture of the liver. The effects of the extract were the same as those of silymarin.


Novel Insights into the Influence of Seed Sarcotesta Photosynthesis on Accumulation of Seed Dry Matter and Oil Content in Torreya grandis cv. "Merrillii".
Seed oil content is an important trait of nut seeds, and it is affected by the import of carbon from photosynthetic sources. Although green leaves are the main photosynthetic organs, seed sarcotesta photosynthesis also supplies assimilates to seed development. Understanding the relationship between seed photosynthesis and seed development has theoretical and practical significance in the cultivation of Torreya grandis cv. "Merrillii." To assess the role of seed sarcotesta photosynthesis on the seed development, anatomical and physiological traits of sarcotesta were measured during two growing seasons in the field. Compared with the attached current-year leaves, the sarcotesta had higher gross photosynthetic rate at the first stage of seed development. At the late second stage of seed development, sarcotesta showed down-regulation of PSII activity, as indicated by significant decrease in the following chlorophyll fluorescence parameters: the maximum PSII efficiency (Fv/Fm ), the PSII quantum yield (Φ PSII ), and the photosynthetic quenching coefficient (qP). The ribulose 1, 5-bisphosphate carboxylase (Rubisco) activity, the total chlorophyll content (Chl(a+b)) and nitrogen content in the sarcotesta were also significantly decreased during that period. Treatment with DCMU [3-(3,4-dichlorophenyl)-1,1-dimethylurea] preventing seed photosynthesis decreased the seed dry weight and the oil content by 25.4 and 25.5%, respectively. We conclude that seed photosynthesis plays an important role in the dry matter accumulation at the first growth stage. Our results also suggest that down-regulation of seed photosynthesis is a plant response to re-balance the source-sink ratio at the second growth stage. These results suggest that seed photosynthesis is important for biomass accumulation and oil synthesis of the Torreya seeds. The results will facilitate achieving higher yields and oil contents in nut trees by selection for higher seed photosynthesis cultivars.


[3-dimensional scintigraphy of the brain: single photon emission computerized tomography].
Both IMP and HMPAO are lipophilic substances with high blood brain barrier permeability and sufficiently long constant retention in the brain parenchyma to enable SPECT to be carried out with a computer controlled Gamma camera. Both tracers are almost completely cleared from the blood during a single passage through the brain. Hence, the regional distribution of activity in the brain is proportional to the regional cerebral blood flow. Computerized acquisition and data processing result in 16 mm thick tomograms at a spatial resolution of 12 mm, which enable clinicians to detect and characterize the pathogenesis and the development of cerebral disorders in terms of altered function. At present, SPECT can be used in daily clinical routine (final SPECT images are available 30 min after the investigation) in cerebrovascular diseases and, because of the coupling of metabolism to cerebral blood flow, in disturbances of cerebral blood flow due to pathological changes of brain metabolism, i.e. in epilepsy and in degenerative disorders. The forthcoming application of physiologically highly specific tracers (e.g. receptor ligands) as a means of studying the distribution of receptors and drugs in the brain will further enlarge the eventual role of SPECT in clinical management.


Tenckhoff catheter insertion by nephrologists: open dissection technique.
The practice of Tenckhoff catheter insertion by nephrologists remains uncommon in most countries. ♢ We report our single-center experience of Tenckhoff catheter insertion by nephrologists using the open dissection surgical technique in a dedicated ward-based procedure room. ♢ Between November 2005 and September 2008, 250 peritoneal catheters were inserted by 6 nephrologists with varying levels of experience. Surgical dissection followed by exposure of the peritoneum under direct vision was performed under local anesthesia. Primary catheter failure, as defined by catheters that failed to function within 1 month after insertion, occurred in 2.8% of cases. Within 1 month of catheter insertion, 20 patients developed infectious complications: 9 (3.6%) peritonitis, and 11 (4.4%) exit-site infections; none of these complications led to catheter removal. Mean technique survival for the catheters was 41.2 months (95% confidence interval: 39.5 months to 42.9 months). Catheter survival rates at 1 and 2 years were 92.7% and 87.2% respectively. ♢ We reported an encouraging outcome for Tenckhoff catheters inserted by nephrologists in an open surgical manner, with a 2-year catheter survival of 87.2% and a good safety profile.


A registry of patients with severe deficiency of alpha 1-antitrypsin. Design and methods. The Alpha 1-Antitrypsin Deficiency Registry Study Group.
The Registry of Patients with Severe Deficiency of Alpha 1-Antitrypsin (A1AT) is a multicenter natural history study, with 37 participating clinical centers in the United States (36 centers) and Canada (1 center). The study has enrolled 1,129 individuals aged > or = 18 years with severe deficiency of A1AT (serum level < or = 11 microM), and will follow them longitudinally for up to 7 years, characterizing the clinical course of the disease, regardless of whether they are receiving augmentation therapy. Primary outcomes of interest are the yearly decline in FEV1 and mortality. This article describes the design and structure of the Registry.


Transplantation in obese patient.
Obesity is a worldwide epidemic leading to severe comorbidity that damages end-organ function. Overall transplant outcomes in this population are inferior to those in nonobese patients. Large population studies show decreased patient and graft survival in obese kidney transplant patients. Despite the poorer outcomes, kidney transplantation is considered because of the survival benefit as compared with the wait-listed dialysis patients. In liver transplantation, the benefit to transplantation as compared with remaining on the list is obvious, as there is no viable liver dialysis at this time. Obesity in potential organ donors impacts both medical and surgical issues. Obesity-related kidney disease affects both the remaining and transplanted kidney. Pancreas donor organs are associated with decreased early graft survival. Liver donor organs with significant steatosis lead to an increased risk for delayed or nonfunction of the organ. Immunosuppressive drugs with variable lipophilicity and altered volume of distribution can greatly affect the therapeutic usefulness of these drugs. Transplant candidates benefit from a multidisciplinary team approach to their care. As the epidemic progresses and less-invasive treatments for metabolic surgery evolve, we are likely to require more patients to lose weight prior to transplantation as we continue to strive for improved outcomes.


Human mesenchymal stroma/stem cells exchange membrane proteins and alter functionality during interaction with different tumor cell lines.
To analyze effects of cellular interaction between human mesenchymal stroma/stem cells (MSC) and different cancer cells, direct co-cultures were performed and revealed significant growth stimulation of the tumor populations and a variety of protein exchanges. More than 90% of MCF-7 and primary human HBCEC699 breast cancer cells as well as NIH:OVCAR-3 ovarian adenocarcinoma cells acquired CD90 proteins during MSC co-culture, respectively. Furthermore, SK-OV-3 ovarian cancer cells progressively elevated CD105 and CD90 proteins in co-culture with MSC. Primary small cell hypercalcemic ovarian carcinoma cells (SCCOHT-1) demonstrated undetectable levels of CD73 and CD105; however, both proteins were significantly increased in the presence of MSC. This co-culture-mediated protein induction was also observed at transcriptional levels and changed functionality of SCCOHT-1 cells by an acquired capability to metabolize 5'cAMP. Moreover, exchange between tumor cells and MSC worked bidirectional, as undetectable expression of epithelial cell adhesion molecule (EpCAM) in MSC significantly increased after co-culture with SK-OV-3 or NIH:OVCAR-3 cells. In addition, a small population of chimeric/hybrid cells appeared in each MSC/tumor cell co-culture by spontaneous cell fusion. Immune fluorescence demonstrated nanotube structures and exosomes between MSC and tumor cells, whereas cytochalasin-D partially abolished the intercellular protein transfer. More detailed functional analysis of FACS-separated MSC and NIH:OVCAR-3 cells after co-culture revealed the acquisition of epithelial cell-specific properties by MSC, including increased gene expression for cytokeratins and epithelial-like differentiation factors. Vice versa, a variety of transcriptional regulatory genes were down-modulated in NIH:OVCAR-3 cells after co-culture with MSC. Together, these mutual cellular interactions contributed to functional alterations in MSC and tumor cells.


[The pharmacokinetics and bioequivalence of acipimox sustained-release tablets after a single and multiple oral administration in healthy dogs].
To study the pharmacokinetics and bioequivalence of acipimox sustained-release tablets (SRT) after a single and multiple oral dose in healthy dogs. The plasma concentrations of of SRT and reference capsules with a single and multiple oral doses. The drug concentration-time profiles fitted to a noncompartment model. After a single dose administration of sustained-release tablets and capsules, the pharmacokinetic parameters were as follows: AUC were (158 +/- 30) and (147 +/- 37) microg x h x mL(-1); Tmax were (4.3 +/- 0.8) and (2.6 +/- 1.3) h; Cmax were (29 +/- 6) and (42 +/- 10) microg x mL(-1); T(1/2) were (2.3 +/- 0.7) and (1.60 +/- 0.10) h; MRT were (6.0 +/- 0.8) and (3.9 +/- 0.7) h, respectively. The relative bioavailability of the sustained-release tablet was (108 +/- 16) %. After a multiple oral administration of sustained-release tablets and capsules, the pharmacokinetic parameters were as follows: AUC were (209 +/- 23) and (195 +/- 26) microg x h x mL(-1); Tmax were (6.3 +/- 0.8) and (3.4 +/- 1.5) h; Cmax were (27 +/- 4) and (36 +/- 5) microg x mL(-1); Cmmin were (2.2 +/- 1.0) and (0.20 +/- 0.20) microg x mL(-1); Cav were (8.7 +/- 1.0) and (8.1 +/- 1.1) micro x mL(-1); FI were (293 +/- 73) % and (448 +/- 91) % , respectively. The relative bioavailability of the sustained-release tablet was (114 +/- 19) %. The results of two one-side test from single dose administration shown that two preparations were bioequivalent. The Cmax of sustained-release tablet was lower than that of capsules, while the Tmax and MRT of sustained-release tablet were higher than that of capsule, which indicating a good retarding effect. The results from multiple dose administration also shown that two preparations were bioequivalent and the DF of sustained-release tablet was significant lower than that of capsule.


Penile Inflammatory Skin Disorders and the Preventive Role of Circumcision.
Penile inflammatory skin conditions such as balanitis and posthitis are common, especially in uncircumcised males, and feature prominently in medical consultations. We conducted a systematic review of the medical literature on PubMed, EMBASE, and Cohrane databases using keywords "balanitis," "posthitis," "balanoposthitis," "lichen sclerosus," "penile inflammation," and "inflammation penis," along with "circumcision," "circumcised," and "uncircumcised." Balanitis is the most common inflammatory disease of the penis. The accumulation of yeasts and other microorganisms under the foreskin contributes to inflammation of the surrounding penile tissue. The clinical presentation of inflammatory penile conditions includes itching, tenderness, and pain. Penile inflammation is responsible for significant morbidity, including acquired phimosis, balanoposthitis, and lichen sclerosus. Medical treatment can be challenging and a cost burden to the health system. Reducing prevalence is therefore important. While topical antifungal creams can be used, usually accompanied by advice on hygiene, the definitive treatment is circumcision. Data from meta-analyses showed that circumcised males have a 68% lower prevalence of balanitis than uncircumcised males and that balanitis is accompanied by a 3.8-fold increase in risk of penile cancer. Because of the high prevalence and morbidity of penile inflammation, especially in immunocompromised and diabetic patients, circumcision should be more widely adopted globally and is best performed early in infancy.


Efficient Active Learning for Electronic Medical Record De-identification.
Electronic medical records are often de-identified before disseminated for secondary uses. However, unstructured natural language records are challenging to de-identify while utilizing a considerable amount of expensive human annotation. In this investigation, we incorporate active learning into the de-identification workflow to reduce annotation requirements. We apply this approach to a real clinical trials dataset and a publicly available i2b2 dataset to illustrate that, when the machine learning de-identification system can actively request information to help create a better model from beyond the system (e.g., a knowledgeable human assistant), less training data will be needed to maintain or improve the performance of trained models in comparison to the typical passive learning framework. Specifically, with a batch size of 10 documents, it requires only 40 documents for an active learning approach to reach an F-measure of 0.9, while passive learning needs at least 25% more data for training a comparable model.


Eating disorders: challenges in the later phases of the recovery process: a qualitative study of patients' experiences.
Scand J Caring Sci; 2013; 27; 92-98 Eating disorders: challenges in the later phases of the recovery process Little is known about how patients experience the later recovery phases of eating disorders. The aim of this study was to describe such experiences using an explorative and descriptive design based on content analysis. Thirteen female patients participated in qualitative interviews. The analysis resulted in four main categories, that is, (i) realising negative consequences, (ii) searching for alternative coping, (iii) searching for normality and identity and (iv) accepting the losses. The categories represent normal psychological processes related to grief, commitment and reconciliation. Such processes may be functionally or dysfunctionally resolved. The clinical implication is that patients in the later recovery phases may need professional help or counselling to accomplish a functional resolving. While in the initial phases of illness and recovery, a focus is on controlling symptoms and the changing of overvalued ideas about weight and shape, therapy in the later recovery phases should focus on the psychological management of the challenges represented in the four categories resulting from the present study.


Glycated hemoglobin in insulinoma.
To determine whether preoperative levels of glycated hemoglobin (GHb) are lower in patients with functioning insulinoma and, if so, whether a distinct separation of GHb values from those in control subjects might serve for diagnosis. We examined preoperative GHb in consecutive patients (who had this measurement done) with surgically confirmed insulinoma for the period 1983 (when the current method became available for routine use) through 1996. Hemoglobin A(1) (HbA(1)) was measured by the Isolab Glyc-Affin Test System (normal range, 4 to 7%). We studied 64 patients with insulinoma (40 women and 24 men; median age, 47.5 years; age range, 21 to 79) and 38 control subjects (25 women and 13 men; median age, 42.5 years; age range, 20 to 83) considered not to have a hypoglycemic disorder on the basis of normal results of a supervised 72-hour fast. HbA(1) was significantly lower in patients with insulinoma (median, 4.7%; range, 2.7 to 6.9%) than in control subjects (median, 5.3%; range, 4.1 to 6.4%) (P<0.001, two-tailed rank sum test). Among 15 patients with insulinoma treated with diazoxide preoperatively, HbA(1) was higher (median, 4.8%; range, 4.2 to 6.9%) than in patients not treated with diazoxide (median, 4.6%; range, 2.7 to 5.7%), although the difference was not statistically significant (P = 0.08). Because of considerable overlap in HbA(1) values, no GHb value was diagnostic for insulinoma; however, 16 of 64 patients (25%) with insulinoma had HbA(1) values below the lowest value (4.1%) in control subjects. Thus, HbA(1) values less than 4.1% in patients with possible insulinoma are strongly indicative of that disorder.


Interaction of type IV collagen with the isolated integrins alpha 1 beta 1 and alpha 2 beta 1.
The triple-helical cyanogen-bromide-derived fragment CB3[IV] of collagen IV, located 100 nm from the N-terminus of the molecule, contains the binding sites for the integrins alpha 1 beta 1 and alpha 2 beta 1. To investigate the interaction of these integrins and collagen IV, we performed solid-phase and inhibition assays using as receptor isolated alpha 1 beta 1 and alpha 2 beta 1. The ligands used were the binding-site-bearing trimeric peptide CB3[IV] and its shorter tryptic fragments F1-F4. Using titration curves, in which the binding of soluble receptors to coated ligands and the binding of soluble ligands to coated receptors were analyzed, the binding sites for alpha 1 beta 1 and alpha 2 beta 1 were in different but adjacent areas of CB3[IV]. Triple-helical conformation and distinct primary structures were required for the interaction. Dissociation constants (Kd), for the affinity of integrins for collagen IV, were determined in the 1-nM range in the presence of Mn2+ and Mg2+. In the absence of Mn2+, the Kd values indicated a 30-60-fold decrease in the affinities, which for alpha 2 beta 1 was further reduced by adding Ca2+. In the presence of Ca2+ and Mg2+ the affinity of collagen IV for alpha 1 beta 1 was four-times higher than for alpha 2 beta 1.


Balancing Biases and Preserving Privacy on Balanced Faces in the Wild.
There are demographic biases present in current facial recognition (FR) models. To measure these biases across different ethnic and gender subgroups, we introduce our Balanced Faces in the Wild (BFW) dataset. This dataset allows for the characterization of FR performance per subgroup. We found that relying on a single score threshold to differentiate between genuine and imposters sample pairs leads to suboptimal results. Additionally, performance within subgroups often varies significantly from the global average. Therefore, specific error rates only hold for populations that match the validation data. To mitigate imbalanced performances, we propose a novel domain adaptation learning scheme that uses facial features extracted from state-of-the-art neural networks. This scheme boosts the average performance and preserves identity information while removing demographic knowledge. Removing demographic knowledge prevents potential biases from affecting decision-making and protects privacy by eliminating demographic information. We explore the proposed method and demonstrate that subgroup classifiers can no longer learn from features projected using our domain adaptation scheme. For access to the source code and data, please visit https://github.com/visionjo/facerec-bias-bfw.