Load-dependent kinetics of myosin-V can explain its high processivity.
Recent studies provide strong evidence that single myosin class V molecules transport vesicles and organelles processively along F-actin, taking several 36-nm steps, 'hand over hand', for each diffusional encounter. The mechanisms regulating myosin-V's processivity remain unknown. Here, we have used an optical-tweezers-based transducer to measure the effect of load on the mechanical interactions between rabbit skeletal F-actin and a single head of mouse brain myosin-V, which produces its working stroke in two phases. We found that the lifetimes of the first phase of the working stroke changed exponentially and about 10-fold over a range of pushing and pulling forces of +/- 1.5 pN. Stiffness measurements suggest that intramolecular forces could approach 3.6 pN when both heads are bound to F-actin, in which case extrapolation would predict the detachment kinetics of the front head to slow down 50-fold and the kinetics of the rear head to accelerate respectively. This synchronizing effect on the chemo-mechanical cycles of the heads increases the probability of the trail head detaching first and causes a strong increase in the number of forward steps per diffusional encounter over a system with no strain dependence.


Prevention of asthma in genetically susceptible children: a multifaceted intervention trial focussed on feasibility in general practice.
Although the effectiveness of the multifaceted allergen-reducing interventions for the prevention of asthma in susceptible children was showed to be proven, the feasibility was not clear. The research question of the PREVention of asthma in susceptible children (PREVASC) trial was focused on the assessment of the effectiveness and feasibility of a multifaceted intervention on the prevention of allergic asthma in general practice. The effectiveness and feasibility of an intervention aimed at the simultaneous reduction in the environmental exposures to inhalant- and food allergens in susceptible children was investigated. A total of 476 children susceptible for developing asthma were initially included during pregnancy and were randomly divided over an intervention group of n = 222 children whose parents were offered a multifaceted environmental exposure-reducing intervention. Controls (n = 221) received usual care. The main outcome was 'diagnosis of allergic asthma at age 6'. A significant reduction in inhalant allergen exposure levels of house dust mite [(Der p1), p = 0.043], cat [(Fel d1), p = 0.037], and dog [(Can f1), p = 0.012] was reached. Significantly more intervention group children started using cow's milk and solids after the age of 6 months (p ≤ 0.001). No statistical difference, however, was reached between groups on the duration of breast-feeding (p = 0.635) and the reduction in smoke exposure (p = 0829). At age 6, the intervention had no influence on the development of main outcome allergic asthma (OR = 1.010 (CI 0.580-1.758). Other primary preventive asthma-reducing interventions were shown to be effective in reducing the occurrence of asthma for at least the first 7-8 yr of life. The multifaceted PREVASC allergic asthma primary preventive intervention was effective in reducing the exposure to inhalant and food allergens, but was not feasible for the parents. A lack of sufficient room for improvement focus on stimulating adherence seemed to be involved. It is suggested that a multifaceted environmental exposure-reducing intervention may have to be adapted to the personal circumstances of patients at baseline.


Engineered high-strength biohydrogel as a multifunctional platform to deliver nucleic acid for ameliorating intervertebral disc degeneration.
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain. The strategy of using functional materials to deliver nucleic acids provides a powerful tool for ameliorating IVDD. However, the immunogenicity of nucleic acid vectors and the poor mechanical properties of functional materials greatly limit their effects. Herein, antagomir-204-3p (AM) shows low immunogenicity and effectively inhibits the apoptosis of nucleus pulposus cells. Moreover, a high-strength biohydrogel based on zinc-oxidized sodium alginate-gelatin (ZOG) is designed as a multifunctional nucleic acid delivery platform. ZOG loaded with AM (ZOGA) exhibits great hygroscopicity, antibacterial activity, biocompatibility, and biodegradability. Moreover, ZOGA can be cross-linked with nucleus pulposus tissue to form a high-strength collagen network that improves the mechanical properties of the intervertebral disc (IVD). In addition, ZOGA provides an advantageous microenvironment for genetic expression in which AM can play an efficient role in maintaining the metabolic balance of the extracellular matrix. The results of the radiological and histological analyses demonstrate that ZOGA restores the height of the IVD, retains moisture in the IVD, and maintains the tissue structure. The ZOGA platform shows the sustained release of nucleic acids and has the potential for application to ameliorate IVDD, opening a path for future studies related to IVD.


Insight into Adsorption Performance and Mechanism on Efficient Removal of Methylene Blue by Accordion-like V2CTx MXene.
Dye-bearing wastewaters leading to the water pollution and ecological upset is a crucial issue in the textile industry. Herein, we report a facile method using two-dimensional transition metal carbides (MXenes) for the removal of the methylene blue (MB) in the water. The accordion-like V2CTx MXene is originally demonstrated to have high and spontaneous adsorption capacity of MB at 111.11 mg·g-1, thrice over that of Ti3C2Tx as previously reported. The wide lamellar space of V2CTx is certain to have large accommodation for MB. The electrostatic interaction effect and hydrogen bond between V2CTx and MB not only promote the efficient adsorption process but also provide the selectivity between anionic and cationic dyes. Combined with good reusability, we anticipate that the V2CTx MXene is a promising candidate for the removal of cationic dyes from textile-dye-bearing wastewaters.


Fluorescent microplate cell assay to measure uptake and metabolism of glucose in normal human lung fibroblasts.
This is the first report of a fluorimetric microplate assay to assess glucose uptake and metabolism in eukaryotic cells. The assay was carried out incubating normal human lung fibroblasts in the wells of microtiter trays with a fluorescent D-glucose derivative, 2-N-7-(nitrobenz-2-oxa-1,3-diazol-4-yl)amino-2-deoxy-D-glucose (2-NBDG). This dye could be incorporated by glucose transporting systems in living cells. Substrate uptake was determined by analysing the data obtained with a fluorescence microplate reader. Variables studied in the development of the assay included dye concentration and incubation period. We found that this cell assay is very sensitive, reproducible, provides fast results and graphical display of data. It requires small sample volumes and allows handling of a large number of samples simultaneously. Okadaic acid was used to assess this microplate assay in the field of cytotoxicity. This diarrhetic shellfish toxin is a tumour promoter and a specific inhibitor of protein phosphatases 1 and 2A. The exposition of cells to okadaic acid (0.1 nM-1 microM) at different time intervals causes a decrease in intracellular glucose (40-50% over controls). Results obtained with okadaic acid are the starting point to evaluate application of the method to routine toxicity probes.


Improvement of chronic epiphora symptoms after surgery in patients with different preoperative schirmer-test values.
To compare improvement of epiphora symptoms after surgery between patients who had different preoperative basal Schirmer test values. Retrospective comparative case-series study. Twenty-two consecutive patients (one eye/patient) undergoing surgery for chronic epiphora symptoms resistant to ≥ 6 months of medical treatments (who incidentally had a preoperative basal [oxybuprocain-HCL 0.4 %] Schirmer-test and a postoperative one-year follow-up) were ranked according to their preoperative basal Schirmer test values and divided into two groups of equal size: group I, patients with lower (0 to 6 mm) and group II, patients with higher (7 to 25 mm) Schirmer test values. Combination of Piffaretti's endocanlicular endoscopic lacrimal drainage (22 patients), lacrimal intubation (8 patients), lacrimal punctoplasty (22 patients), lateral canthoplasty (18 patients), and/or conjunctivochalasis (8 patients) surgical procedures. Subjective self-perceptions of improvement of their epiphora symptoms was made by the patients one-year after surgery. While between groups I and II mean (± SD) preoperative basal Schirmer test values significantly differed (4 ± 3 mm/ 5 min vs. 10 ± 6 mm/ 5 min, p ≤ 0.001, Mann-Whitney rank sum test), the mean postoperative improvement of epiphora symptoms did not (82 ± 30 % vs. 76 ± 34 %, p = 0.92) and no significant (rho = -0.11, p = 0.62, Spearman rank correlation coefficient) correlation between Schirmer test values and symptoms improvement was found. In both groups > 70 % of patients reported ≥ 70 % (satisfactory) postoperative improvement. In the present study, patients who had different preoperative basal Schirmer test values reported having very similar epiphora symptoms improvement one-year after surgery.


Does PBL deliver constructive collaboration for students in interprofessional tutorial groups?
Training health professional students in teamwork is recognized as an important step to create interprofessional collaboration in the clinical workplace. Interprofessional problem-based learning (PBL) is one learning approach that has been proposed to provide students with the opportunity to develop the necessary skills to work collaboratively with various health professionals. This study aimed to explore the extent to which students in interprofessional tutorial groups demonstrate constructive collaboration during group discussions. Students (N = 52) from the Medical, Midwifery and Nursing programmes took part in the study. Video-recordings were made of interprofessional PBL discussions (N = 40) in five groups, eight videos per group. Over a period of 4 weeks, participants discussed four scenarios concerned with the reproductive system. The resulting 67 h of video data were analysed qualitatively. To ensure inter-rater reliability, two tutors assessed the students' constructive, collaborative activities using the Maastricht Peer-Activity Rating Scale (MPARS). Finally, to gain an understanding of students' perceptions of their performance and participation in the interprofessional PBL tutorial, we organized three uni-professional focus groups (FGs) at the end of pilot project. The translated MPARS was reliable (Kappa coefficient 0.01-0.20 and p < 0.05). Students were actively involved in the discussion and contributed to a better understanding regardless of their professional background. Group members from different professions complemented one another in solving learning issues. They were open, feeling free to question and argue from the viewpoint of their own profession, and also understood their strengths and limitations. The statistical test of the scores for constructive and collaborative activities indicated a significant difference between students and the various healthcare professionals, p = 0.000, with medical students scoring highest on both activities. Focus groups further clarified some of the observed dynamics. Implementing interprofessional PBL could motivate students to engage collaboratively in co-constructing knowledge to solve the patients' problem. Medical students scored highest on constructive and collaborative activities.


ROTAVAC® does not interfere with the immune response to childhood vaccines in Indian infants: A randomized placebo controlled trial.
A phase III randomized double-blind placebo-controlled trial was conducted in the urban neighborhoods of Delhi to assess whether Oral Rotavirus Vaccine ROTAVAC® interferes with the immune response to childhood vaccines when coadministered. Infants aged 6 weeks were randomized to receive three doses of either ROTAVAC® or placebo along with childhood vaccines: Oral Polio Vaccine and vaccines against Diphtheria, Pertussis, Tetanus, Hepatitis B and Haemophilus influenza type b given as Pentavalent at 6, 10, 14 weeks of age. Blood specimens were collected from all infants at baseline and 4 weeks post dose 3 to assess the immune response to antigens in Oral Polio Vaccine, Pentavalent and ROTAVAC® vaccines. Non-inferiority of immune response to all vaccine components of the childhood vaccines when ROTAVAC® was administered concurrently was demonstrated. Non-inferior immune responses to childhood vaccines were evaluated based on the seroprotective levels of antibodies against polio types 1, 2, and 3, Diphtheria toxoid, Tetanus toxoid, Haemophilus influenza type b anti- polyribosyl ribitol phosphate antibodies and Hepatitis B antibodies; and the Geometric Mean Concentration for Pertussis. The proportion of infants who seroconverted (≥4 fold rise) was 38.6% in the ROTAVAC® group and 12.2% in the placebo group. The frequency and severity of immediate adverse events, adverse events and serious adverse events were similar in both groups. None of the five reported deaths were considered to be related to the ROTAVAC® and no case of intussusception meeting Brighton Diagnostic Certainty Level I criteria was reported. This study demonstrated that ROTAVAC® can be safely administered with childhood vaccines without interfering with the immune response to the antigens contained in these vaccines.


Metabolism of biliverdin. Biliary excretion of bile pigments after intravenous injection of biliverdin isomers.
14C-labelled biliverdins IX alpha, beta, gamma and delta have been prepared in vitro from haemoglobin obtained from duck erythrocytes incubated with 5-amino[4-14C]-laevulinic acid. When injected intravenously into rats with biliary fistulae, about 60% of the label was recovered in the bile in 24 h after the alpha isomer was given, while approximately 10% was recovered with injection of the beta isomer. The gamma and delta isomers gave intermediate values. In each experiment, most of the recovered isotope was found in association with conjugated bile pigment. Thus, the metabolic pathway for bile pigment excretion in the rat handles the IX alpha isomer preferentially but is not specific for it.


Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics.
Thymoquinone is a natural product known for its anticancer activity. Preclinical studies indicated numerous mechanisms of action by which thymoquinone exerts its effects on cancer cells. Recent evidence has indicated that thymoquinone can modulate epigenetic machinery, like modifying histone acetylation and deacetylation, DNA methylation and demethylation, which are among the major epigenetic changes that can contribute to carcinogenesis. Moreover, thymoquinone can alter the genetic expression of various noncoding RNAs, such as miRNA and lncRNA, which are the key parts of cellular epigenetics. This review focuses on cellular epigenetic systems, epigenetic changes responsible for cancer and the counteraction of thymoquinone to target epigenetic challenges, which might be among the mechanisms of the thymoquinone effect in cancer cells.


Anomalous differential polarized phase angles for two-photon excitation with isotropic depolarizing rotations.
We describe frequency-domain measurements of the anisotropy decay of 1,6-diphenylhexatriene resulting from one- and two-photon excitation. For two-photon excitation, the phase shifts (Δ) between the horizontally and vertically polarized components of the decay exceed the absolute maximum of 30° possible for one-photon excitation, and values of Δ as large as 37° were observed for 1,6-diphenylhexatriene in triacetin. These results are explained by the increased orientation of the photoselected population for two- as compared to one-photon excitation.


Bovine colostrum as a fortifier to human milk in very preterm infants - A randomized controlled trial (FortiColos).
Human milk for very preterm infants need fortification for optimal growth and development but the optimal fortification product remains to be identified. To investigate feasibility, safety and preliminary efficacy on growth and blood biochemistry when using intact bovine colostrum (BC) as a fortifier to human milk in very preterm infants. In an open-label, multicenter, randomized controlled pilot trial (infants 26-31 weeks' gestation), mother's own milk or donor human milk was fortified with powdered BC (n = 115) or a conventional fortifier (CF, bovine-milk-based, n = 117) until 35 weeks' postmenstrual age. Fortifiers and additional micronutrients were added to human milk according to local guidelines to achieve optimal growth (additional protein up to +1.4 g protein/100 mL human milk). Anthropometry was recorded weekly. Clinical morbidities including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) were recorded. Clinical biochemistry included plasma amino acid (AA) levels to assess protein metabolic responses to the new fortifier. A total of 232 infants, gestational age (GA) 28.5 ± 1.4 (weeks + days), fulfilled inclusion criteria. Birthweight, GA and delta Z scores from birth to end of intervention on weight, length or head circumference did not differ between groups, nor between the subgroups of small for gestational age infants. Likewise, incidence of NEC (BC: 3/115 vs. CF: 5/117, p = 0.72, unadjusted values), LOS (BC: 23/113 vs. CF: 14/116, p = 0.08) and other morbidities did not differ. BC infants received more protein than CF infants (+10%, p < 0.05) and showed several elevated AA levels (+10-40%, p < 0.05). Infants fortified with BC showed similar growth but received more protein and showed a moderate increase in plasma AA-levels, compared with CF. Adjustments in protein composition and micronutrients in BC-based fortifiers may be required to fully suit the needs for very preterm infants.


Magnetic Resonance T1w/T2w Ratio in the Putamen and Cerebellum as a Marker of Cognitive Impairment in MSA: a Longitudinal Study.
The exact pathophysiology of cognitive impairment in multiple system atrophy (MSA) is unclear. In our longitudinal study, we aimed to analyze (I) the relationships between cognitive functions and some subcortical structures, such as putamen and cerebellum assessed by voxel-based morphometry (VBM) and T1-weighted/T2-weighted (T1w/T2w) ratio, and (II) the neuroimaging predictors of the progression of cognitive deficits. Twenty-six patients with MSA underwent a comprehensive neuropsychological battery, motor examination, and brain MRI at baseline (T0) and 1-year follow-up (T1). Patients were then divided according to cognitive status into MSA with normal cognition (MSA-NC) and MSA with mild cognitive impairment (MCI). At T1, we divided the sample according to worsening/non worsening of cognitive status compared to baseline evaluation. Logistic regression analysis showed that age (β = - 9.45, p = .02) and T1w/T2w value in the left putamen (β = 230.64, p = .01) were significant predictors of global cognitive status at T0, explaining 65% of the variance. Logistic regression analysis showed that ∆-values of WM density in the cerebellum/brainstem (β = 2188.70, p = .02) significantly predicted cognitive worsening at T1, explaining 64% of the variance. Our results suggest a role for the putamen and cerebellum in the cognitive changes of MSA, probably due to their connections with the cortex. The putaminal T1w/T2w ratio may deserve further studies as a marker of cognitive impairment in MSA.


A Microbial Piñata: Bacterial Endosymbionts of Trichomonas vaginalis Come in Different Flavors.
The protozoan parasite Trichomonas vaginalis causes trichomoniasis, a prevalent human urogenital infection with significant morbidity that is commonly associated with vaginal dysbiosis. Exacerbation of T. vaginalis pathogenicity has been related to endosymbionts, including mycoplasma, and thought for a while to be solely attributable to Mycoplasma hominis. In a recent publication, Margarita and colleagues (https://journals.asm.org/doi/10.1128/mbio.00918-22) showed that endosymbiosis extends to a second species of mycoplasma known as "Candidatus Mycoplasma girerdii." Those authors confirmed the strong association of T. vaginalis with both species of mycoplasma by reassessing clinical samples. Additionally, they showed that in vitro symbiosis of protozoa and bacteria resulted in the modulation of gene expression of T. vaginalis and enhancement of parasite cytoadhesion and hemolytic activity in culture assays. In this commentary, we portray T. vaginalis as a synergistically interacting multimicrobe organism-a "microbial piñata"-whose endosymbionts contribute significantly to the pathophysiology of this medically important protozoan parasite.


Mediating roles of adherence attitude and patient education on antidepressant use in patients with depression.
The purpose of this study was to examine the roles of adherence attitude to antidepressants and patient education as mediators in mediating patients' attitudes toward antidepressant use. A sample of 201 outpatients, 50 years of age or older, with major depressive disorder, completed a drug use questionnaire, attitudes toward and patient education about antidepressants questionnaire, and Adherence Attitude Inventory. Attitudes toward antidepressants were positively associated to antidepressant use, an association explained by the mediating variable, patient education about antidepressants. Adherence attitudes to antidepressants were a mediator that accounted to a significant degree for the causal relationship between attitudes toward antidepressants and antidepressant use. Adequate patient education and an understanding of patients' adherence attitude to antidepressant use are needed in nursing practice to reduce patients' uncertainty about treatment and increase successful treatment.


A novel bioanalytical method for the quantification of pemigatinib in rat plasma by UPLC-MS/MS.
Pemigatinib is an oral, selective, potent, competitive inhibitor acting on fibroblast growth factor receptor (FGFR)1, FGFR2, and FGFR3, which has obtained accelerated approval in the USA through a test approved by the USA FDA. It is not only significant in the therapy of adult recurrent, unresectable, metastatic or locally advanced cholangiocarcinoma, but also plays an important role in treating adult patients with FGFR2 fusion or other rearrangements. The aim of our research was to establish and verify a reliable and quick ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay to determine the level of pemigatinib in rat plasma. The analyte was prepared using a simple and convenient approach with acetonitrile for protein crash, and then separated from the matrix on a Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) in a gradient elution program, where the mobile phase was consisted of acetonitrile and 0.1 % formic acid in water and was set at 0.40 mL/min flow rate. Selective reaction monitoring (SRM) was used to conducted for UPLC-MS/MS dectection with ion transitions at m/z 488.01 → 400.98 for pemigatinib and m/z 447.00 → 361.94 for erdafitinib (Internal standard, IS), respectively. This method had good linearity in a 0.5-1000 ng/mL calibration range for pemigatinib, where the lower limit of quantification (LLOQ) was validated at 0.5 ng/mL. The precision of pemigatinib for intra- and inter-day was less than 13.3 %, and the accuracy was determined to be from -4.8%-11.2%. During the assay in plasma samples, the analyte was found to be stable. Besides, matrix effect and recovery of the analyte and IS were acceptable. The novel optimized UPLC-MS/MS assay was also suitable for determining the concentration level of pemigatinib in a pharmacokinetic study after a single dose of 1.35 mg/kg pemigatinib orally to the rats.


Standard-based method for proton-electron double resonance imaging of oxygen.
Proton-electron double resonance imaging (PEDRI) has been utilized for indirect determination of oxygen concentrations in aqueous samples and living systems. Due to the complexity of the problem, there are seven oxygen related parameters that need to be measured to determine the distribution of oxygen. We present an improved approach in which image intensities from only two PEDRI acquisitions with different EPR irradiation powers are required to determine the distribution of a paramagnetic probe and oxygen in an analyzed sample. This is achieved using three reference samples with known concentrations of a paramagnetic probe and oxygen placed inside the resonator together with the measurement sample. An EPR-off image, which has low signal intensity at low magnetic field (0.02 T) is not required for the calculations, significantly reducing the total time of the experiments and the noise while enhancing the accuracy of these oxygen measurements. The Finland trityl radical was used as the paramagnetic probe and oxygen concentrations could be accurately measured and imaged over the physiological range from 0 to 240 μM.


Right hemicolectomy - from laparoscopic facilitated technique to robotic intracorporeal anastomosis.
Several different operative techniques have been applied in minimally invasive right colectomy. Data reported in literature confirm the advantages of laparoscopic approach, however, there is no sure evidence of which one is the best. The pure laparoscopic technique with intracorporeal anastomosis seems to show some advantages compared to the other laparoscopic and open procedures, although for the price of technical difficulty and a longer operating time.


Inhibition of cyclin-dependent kinases by olomoucine and roscovitine reduces lipopolysaccharide-induced inflammatory responses via down-regulation of nuclear factor kappaB.
Initiation and maintenance of pro-inflammatory reactions elicited by bacterial lipopolysaccharide and/or cytokines in the macrophage lineage have been reported to play a crucial role in acute and chronic pathogenic effects. Whether pro-inflammatory responses triggered by lipopolysaccharide in growth arrested cells differ from those in proliferating cells remains unanswered. Olomoucine and roscovitine are cyclin-dependent kinase (CDK) inhibitors that prevent progression through the cell cycle. After treatment with CDK inhibitors, expression of pro-inflammatory genes was analysed by reverse transcriptase-polymerase chain reaction. Protein levels of inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-kappaB) were determined by Western blotting. Promoter activity of iNOS was measured by the luciferase activity assay. In this study we have demonstrated that both olomoucine and roscovitine inhibit cell proliferation and diminish nitric oxide production and cytokine gene expression, in lipopolysaccharide-stimulated murine RAW264.7 macrophages. In addition, olomoucine reduces iNOS promoter activity and alleviates NF-kappaB transcription activation. After co-transfection with E2F1 interference RNA, suppression of lipopolysaccharide-mediated iNOS promoter activity and NF-kappaB activation was observed. Furthermore, we demonstrated that olomoucine-induced growth arrested cells reduce expression of the p65 subunit of NF-kappaB. The findings of this study suggest that inhibition of cell-cycle progression is capable of reducing pro-inflammatory responses via down-regulation of NF-kappaB.


Dynamic Navigation in Implant Dentistry: A Systematic Review and Meta-analysis.
Dynamic navigation is a technique that allows for the placement of dental implants using a computer-guided approach according to preoperative planning. Its accuracy has been assessed in several previous studies. The purpose of this study was to summarize data on implant placement accuracy using dynamic navigation, to synthesize the frequency of intraoperative complications and implant failures, and to compare this technique with static computer-guided surgery and a freehand approach. Electronic and manual literature searches until December 2019 were performed. The outcome variables were implant placement accuracy using dynamic navigation, accuracy differences between dynamic and static techniques and between dynamic and freehand techniques, intraoperative complications, and implant failures. Random-effects meta-analyses were performed. A total of 32 studies were included; 29 reported accuracy values (2,756 implants), and 10 focused on complications and implant failures (1,039 implants). The pooled mean implant placement errors were 0.81 (95% CI: 0.677 to 0.943) mm at the entry point and 0.910 (95% CI: 0.770 to 1.049) mm at the apical point. The pooled mean vertical and angular deviations were 0.899 (95% CI: 0.721 to 1.078) mm and 3.807 (95% CI: 3.083 to 4.530) degrees. The navigation group showed significantly lower implant placement errors with respect to the freehand technique (P < .01) and similar accuracy values (P ≥ .05) compared with the static technique. The pooled prevalence of failures was 1% (95% CI: 0.00% to 2%). Dynamic navigation provided small implant placement errors, comparable with those obtained using static computer-guided surgery, and can be considered a more accurate technique than conventional freehand surgery.


Early outcome of Frey's procedure for chronic pancreatitis: Nepalese tertiary center experience.
Chronic pancreatitis is a progressive and persistent inflammatory disease resulting in pancreatic insufficiency leading to diabetes and steatorrhea. Abdominal pain is the most debilitating feature and is often refractory to treatment. Medical management with adequate analgesia and replacement of pancreatic enzyme supplements is the first line in management of chronic pancreatitis. Surgery is reserved for those who fail medical management. The choice of surgical procedure and timing of surgery is a topic of debate. The objective of this study was to analyze surgical safety along with short- and long- term outcomes of Frey's procedure for patients suffering from chronic pancreatitis. This was a retrospective review of cases of chronic pancreatitis who underwent Frey's procedure from 2016 January to 2019 February at Tribhuvan University Teaching Hospital. Demographics, intraoperative findings, perioperative outcomes, and short- and long-time outcomes were analyzed. Total of 26 patients (age ranged 17-52, male - 14) underwent Frey's procedure in the study period. Alcohol was etiology in six patients while the majority (76.9%) were nonalcoholic. Half of the patients had tropical pancreatitis. Intractable pain was present in all cases along with pseudocyst in three and pseudoaneurysm in one case. The mean preoperative Izbicki scores were 53.4 ± 17.6. Six patients had diabetes and two patients had steatorrhea. Major complications were seen in 11.5% of cases while mortality was in one patient. The median duration of the hospital stay was seven days. Over a median follow up of 17 months (range, 3-38), there were significantly lower pain scores postoperatively and 92% were pain-free. Only one new case of diabetes developed postoperatively. Our early experiences suggests that Frey's procedure can be a safe option for patients with chronic pancreatitis, with acceptable perioperative morbidity with adequate pain relief without worsening of pancreatic endocrine and exocrine function.


Training modalities: over-reaching and over-training in athletes, including a study of the role of hormones.
An imbalance between the overall strain experienced during exercise training and the athlete's tolerance of such an effort may induce over-reaching (OR) or over-training syndrome (OTS). OR is characterized by an unexpected drop in performance despite increased training load or may lead to OTS, a complex state of exhaustion and persistent fatigue. As it is important to adapt training modalities to the athletes' needs, and as there is still a lack of objective parameters suitable for the prevention and diagnosis of OTS, we studied 11 male elite cyclists, analysing the impact of training modalities ('training high-living low'; 'training low-living low') on exercise performance as well as on variable hormonal responses in order to detect early and sensitive markers for OR and/or OTS. Although the variable hormones varied quite substantially among the two training groups, two ratios--free testosterone/cortisol (FTCR) and insulin-like growth factor-I/cortisol (IGF-I/C)--did not differ at all. This is important because athletes' final aim is to improve in an anabolic way. In addition, IGF-binding protein 3 (IGF-BP3) might be a useful screening factor for OR and OTS. First, from a critical review of the existing over-training research, it must be concluded that there has been little improvement in recent years in the tools available for the diagnosis of OTS. Second, as variable training modalities do have a major impact on isolated hormones in circulation, hormonal ratios such as FTCR and IGF-I/C have to be calculated. These ratios might be useful parameters in the early detection of a imbalance between anabolic and catabolic metabolism.


Nuclear Mechanics and Cancer Cell Migration.
As a cancer cell invades adjacent tissue, penetrates a basement membrane barrier, or squeezes into a blood capillary, its nucleus can be greatly constricted. Here, we examine: (1) the passive and active deformation of the nucleus during 3D migration; (2) the nuclear structures-namely, the lamina and chromatin-that govern nuclear deformability; (3) the effect of large nuclear deformation on DNA and nuclear factors; and (4) the downstream consequences of mechanically stressing the nucleus. We focus especially on recent studies showing that constricted migration causes nuclear envelope rupture and excess DNA damage, leading to cell cycle suppression, possibly cell death, and ultimately it seems to heritable genomic variation. We first review the latest understanding of nuclear dynamics during cell migration, and then explore the functional effects of nuclear deformation, especially in relation to genome integrity and potentially cancerous mutations.


Silver-stained nucleolar organizer regions and immunoglobulins in cutaneous squamocellular tumors.
This study was conducted to elucidate the biological activity of epidermal cells in cutaneous squamocellular tumors by counting the number of silver-stained nucleolar organizer regions (AgNORs), to estimate the quantity of Ig-producing cells and the inflammatory cellular infiltrate (ICI), and to achieve a comparative evaluation. Twenty cases of actinic keratosis (AK), 20 in situ squamous cell carcinomas (ISC), and 20 invasive squamous cell carcinomas (SCCs) were assessed using a silver colloid technique. Ig-producing or binding cells and ICI were also investigated immunohistochemically. In all samples, AgNORs, Ig-producing cells, and ICI increased in proportion to the degree of malignancy. With regard to AgNORs values, a statistically significant difference was confirmed between AK and ISC (p<0.01), AK and SCC (p<0.001), and ISC and SCC (p<0.05). IgG-producing cells predominated in each case. Furthermore, a linear correlation was detected between ICI and AgNORs in AK and ISC. The significant difference in the number of AgNORs among the 3 stages of involution of SCC reinforces the value of AgNORs as a marker for malignant potential. Despite the absence of a correlation between AgNORs and the proportion of Ig-producing cells, the association between ICI and AgNORs in AK and ISC was obvious.


Epigenetic modifications in the motor cortex caused by exercise or pharmacological inhibition of histone deacetylases (HDACs) after intracerebral hemorrhage (ICH).
Epigenetic regulation is expected to provide an enriched platform for neurorehabilitation of post-stroke patients. Acetylation of specific lysine residues in histones is a potent epigenetic target essential for transcriptional regulation. Exercise modulates histone acetylation and gene expression in neuroplasticity in the brain. This study sought to examine the effect of epigenetic treatment using a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaB), and exercise on epigenetic markers in the bilateral motor cortex after intracerebral hemorrhage (ICH) to identify a more enriched neuronal condition for neurorehabilitation. Forty-one male Wistar rats were randomly divided into five groups: sham (n = 8), control (n = 9), NaB, exercise (n = 8), and NaB and exercise (n = 8). Intraperitoneal administration of an HDAC inhibitor (300 mg/kg NaB) and treadmill exercise (11 m/min for 30 min) was conducted five days a week for approximately-four weeks. ICH specifically decreased the acetylation level of histone H4 in the ipsilateral cortex, and HDAC inhibition with NaB increased the acetylation level of histone H4 over the sham level, accompanied by an improvement in motor function as assessed by the cylinder test. Exercise increased the acetylation levels of histones (H3 and H4) in the bilateral cortex. Synergistic effects of exercise and NaB were not observed during histone acetylation. Pharmacological treatment with a HDAC inhibitor and exercise can provide an enriched epigenetic platform for neurorehabilitation in an individual manner.


Effects of vaginal delivery, cesarean section and exposure to labor on endothelial function of pregnant women.
This study was undertaken to assess the influence of labor and cesarean section on endothelial function. Flow-mediated vasodilatation (FMD) was measured before and after delivery for an assessment of endothelial function in three groups: (1) the Vaginal delivery group (with spontaneous labor or induction of labor, n = 48), (2) the Elective C/S group (with a cesarean planned, n = 20), and (3) the C/S after FP group (scheduled for vaginal delivery but required to have an emergency cesarean section because of failure in progress, n = 11). There were statistically significant changes between the antepartum and postpartum FMD values in the Vaginal delivery group and the Elective C/S group but not in the C/S after FP group (P < 0.001, P = 0.023 and P = 0.22 respectively). These observations suggest that labor may enhance endothelial function and that cesarean section may impair endothelial function.


Apomorphine-induced motor behavior in rats exposed prenatally to alcohol.
We psychopharmacologically examined dopamine function in rats exposed to ethanol prenatally. Pregnant rats received liquid diets of 35% or 0% ethanol-derived calories (EDC), or ad lib lab chow (LC). Twenty-eight-day-old offspring received systemic doses of apomorphine chosen to stimulate predominantly presynaptic (0.02 or 0.1 mg/kg) or postsynaptic dopamine receptors (2.0 or 5.0 mg/kg). Behavior was scored automatically for 60 min in an "open field." For males, prenatal ethanol exposure resulted in a dose-response shift to the left for locomotor activity. Females exposed to the liquid diet, with or without ethanol, showed less of an increase in locomotor activity following the 5.0 mg/kg dose of apomorphine than did LC controls. There were no effects of prenatal treatment on repetitious motor behavior in the automated "open field" or on stereotypy scored by direct observation in separate groups of rats. The results are consistent with an hypothesis that prenatal ethanol exposure alters the sensitivity of postsynaptic (perhaps mesolimbic) dopamine systems important to locomotor activity in young male rats.


Hepatic actinomycosis mimicking an isolated tumor recurrence.
Actinomyces species has been described as an opportunistic pathogen, particularly in the oral cavity; however, in rare cases these bacteria can cause actinomycosis which is characterized by formation of abscesses in the mouth, lungs, or gastrointestinal tract. Actinomycosis was commonly present in the pre-antibiotic era; however, it has a low prevalence now days. It has been recognized since 150 years ago, but because of its variable clinical presentation and indolent course, its recognition is difficult and patients are often misdiagnosed. Here we present a case of primary hepatic actinomycosis presenting as a metastatic liver tumor.


Effects of oral digoxin on ventricular ectopy and its relation to left ventricular function.
The ventricular antiarrhythmic properties of oral digoxin were examined in 13 patients with chronic ventricular ectopy using serial 24-hour electrocardiographic monitoring. Mean premature ventricular complex frequency (per 1,000 normal beats) decreased from 56 +/- 47 during the placebo period to 40 +/- 27 (p = not significant [NS]) and 25 +/- 17 (p less than 0.05) during daily administration of digoxin, 0.25 and 0.375 mg. Digoxin had no significant effect on the qualitative occurrence of complex ventricular arrhythmia patterns (multiformity, bigeminy, couplets, ventricular tachycardia). Radionuclide left ventricular (LV) ejection fraction was measured during the placebo period. Seven patients had normal (ejection fraction greater than 50%) and 6 abnormal global LV performance. In the normal group, the mean premature ventricular complex frequency decreased from 69 +/- 58 to 20 +/- 18 (p less than 0.05) and the mean couplet frequency decreased from 0.59 +/- 0.85 to 0.07 +/- 0.06 (p less than 0.04) during the placebo and 0.375 mg digoxin dosing periods, respectively. In contrast, no significant changes in either variable occurred after digoxin in subjects with depressed LV function. This study indicates that oral digoxin is moderately effective in suppressing premature ventricular complexes, and that its effects are greatest in patients with normal overall LV performance.


Hyperspectral imaging: a novel approach for plant root phenotyping.
Root phenotyping aims to characterize root system architecture because of its functional role in resource acquisition. RGB imaging and analysis procedures measure root system traits via colour contrasts between roots and growth media or artificial backgrounds. In the case of plants grown in soil-filled rhizoboxes, where the colour contrast can be poor, it is hypothesized that root imaging based on spectral signatures improves segmentation and provides additional knowledge on physico-chemical root properties. Root systems of Triticum durum grown in soil-filled rhizoboxes were scanned in a spectral range of 1000-1700 nm with 222 narrow bands and a spatial resolution of 0.1 mm. A data processing pipeline was developed for automatic root segmentation and analysis of spectral root signatures. Spectral- and RGB-based root segmentation did not significantly differ in accuracy even for a bright soil background. Best spectral segmentation was obtained from log-linearized and asymptotic least squares corrected images via fuzzy clustering and multilevel thresholding. Root axes revealed major spectral distinction between center and border regions. Root decay was captured by an exponential function of the difference spectra between water and structural carbon absorption regions. Fundamentals for root phenotyping using hyperspectral imaging have been established by means of an image processing pipeline for automated segmentation of soil-grown plant roots at a high spatial resolution and for the exploration of spectral signatures encoding physico-chemical root zone properties.


α-syn and SNP rs356219 as a potential biomarker in blood for Parkinson's disease in Mexican Mestizos.
Clinical criteria diagnose Parkinson's disease (PD), therefore, it is crucial to find biological elements that could support diagnosis or even act as prognostic tools of PD. The SNCA gene codifies a protein called α - synuclein; several studies associate genetic and biochemical factors of SNCA with PD, including transcript and plasmatic protein levels, however, contradictory evidence indicates inconclusive results. We aim to compare SNCA mRNA expression, plasmatic α-syn protein and rs356219 SNP between PD cases and a control group, and to identify a potential biomarker in Mexican mestizos', focusing on these three components determined in blood. We included 88 PD patients and 88 age-matched controls. We observed higher α-syn protein and decreased SNCA mRNA levels in PD subjects, compared to control group (p = 0.044 and p < 0.001, respectively). A statistically significant difference was found in allelic and genotypic frequencies of SNP rs356219 between PD patients and normal subjects (p = 0.006 and p = 0.023, respectively). Logistic regression analysis determined as optimal predictors of PD the GG genotype of SNP rs356219 (OR 2.49; p = 0.006) in a recessive model and α-syn protein (OR 1.057; p = 0.033). Furthermore, the G allele of SNP rs356219 was associated with higher plasmatic α-syn and mRNA levels in PD subjects. The receiver operating curves (ROC) distinguished PD from healthy controls with good sensitivity and specificity considering the plasmatic α-syn protein (AUC = 0.693, Sensitivity = 66.7 %, Specificity = 63.9 %) or a predictive probability of plasmatic α-syn protein and SNP rs356219 in a single model (AUC = 0.692, Sensitivity = 62.3 %, Specificity = 62.5 %). The performance of this classifier model in PD at early stage (n = 31) increase the discriminant power in both, plasmatic α-syn protein (AUC = 0.779, Sensitivity = 72.7 %, Specificity = 73.9 %) and predictive probability (AUC = 0.707, Sensitivity = 63.6 %, Specificity = 62.5 %). We propose that α-syn protein and SNP rs356219 together may work as a good signature of PD, and they can be suggested as a non-invasive biomarker of PD risk.


Objective optical assessment of tear-film quality dynamics in normal and mildly symptomatic dry eyes.
To evaluate and compare the tear-film dynamics in normal eyes and in eyes with mild dry-eye symptoms using a new noninvasive optical method based on a double-pass instrument. Hospital Universitario Virgen de la Arrixaca, Murcia, Spain. Evaluation of diagnostic test or technology. Dynamic recording of double-pass retinal images during unforced tear-film breakup was performed in eyes with mild dry-eye symptoms (study group) and in an asymptomatic control group. Series of consecutive retinal images were recorded every 0.5 seconds while the patient avoided blinking. Measurements were performed under low-light conditions to naturally increase pupil diameter and maximize the method's sensitivity. Additional clinical tests were performed for comparison and included tear breakup time (TBUT), Schirmer I tests, and a normalized questionnaire (McMonnies). From the retinal images, a quality metric, the intensity distribution index, was calculated. An objective TBUT value was estimated in each eye when the intensity distribution index surpassed a defined threshold value compared with the initial baseline. The study group comprised 20 eyes and the control group, 18 eyes. Symptomatic dry eyes had a typical exponential increase in the intensity distribution index with time. The objective TBUT values in the study group were comparable to the clinical TBUT estimates. The new objective optical method to evaluate the quality and stability of the tear film was sensitive in detecting mild symptoms of dry eye and differentiating from normal cases. The procedure may allow early detection and follow-up of patients' tear film-related complaints.


Computer tomographic assessment of gastric volume in major trauma patients: impact of pre-hospital airway management on gastric air.
Gastric dilation is frequently observed in trauma patients. However, little is known about average gastric volumes comprising food, fluids and air. Although literature suggests a relevant risk of gastric insufflation when endotracheal intubation (ETI) is required in the pre-hospital setting, this assumption is still unproven. Primary whole body computed tomographic (CT) studies of 315 major trauma patients admitted to our Level 1 Trauma Centre Salzburg during a 7-year period were retrospectively assessed. Gastric volumes were calculated employing a CT volume rendering software. Patients intubated in the pre-hospital setting by emergency physicians (PHI, N = 245) were compared with spontaneously breathing patients requiring ETI immediately after arrival in the emergency room (ERI, N = 70). The median (range) total gastric content and air volume was 402 (26-2401) and 94 (0-1902) mL in PHI vs. 466 (59-1915) and 120 (1-997) mL in ERI patients (p = .59 and p = .35). PHI patients were more severely injured when compared with the ERI group (injury severity score (ISS) 33 (9-75) vs. 25 (9-75); p = .004). Mortality was higher in the PHI vs. ERI group (26.8% vs. 8.6%, p = .001). When PHI and ERI patients were matched for sex, age, body mass index and ISS (N = 50 per group), total gastric content and air volume was 496 (59-1915) and 119 (0-997) mL in the PHI vs. 429 (36-1726) and 121 (4-1191) mL in the ERI group (p = .85 and p = .98). Radiologic findings indicative for aspiration were observed in 8.1% of PHI vs. 4.3% of ERI patients (p = .31). Gastric air volume in patients who showed signs of aspiration was 194 (0-1355) mL vs. 98 (1-1902) mL in those without pulmonary CT findings (p = .08). In major trauma patients, overall stomach volume deriving from food, fluids and air must be expected to be around 400-500 mL. Gastric dilation caused by air is common but not typically associated with pre-hospital airway management. The amount of air in the stomach seems to be associated with the risk of aspiration. Further studies, specifically addressing patients after difficult airway management situations are warranted.


The Rhodopseudomonas viridis photosynthetic membrane: arrangement in situ.
The organization of photosynthetic membranes in the cytoplasm of the photosynthetic bacterium Rh. viridis has been examined by several techniques for electron microscopy. Thin sections of membrane stacks show that the regular lattice of membrane subunits reported in other studies can be observed in thin section. Tilting of sections in the electron microscope shows that the regular lattices of several membranes overlap in a way that suggests they are in register with each other. This observation can be confirmed by freeze-fracture images in which a regular arrangement of membrane lattices can be observed, each perfectly aligned. Analysis of the spacings of membrane pairs shows that the photosynthetic membranes of Rh. viridis are very closely apposed. The mean diameter of two membranes is 160A, and the average space between two such membranes is only 42A. When a recently developed atomic level model of Rh. viridis reaction center is superimposed against these spacings, each reaction center extends from the surface of its respective membrane far enough to make contact with an apposing membrane. The limited free space between membranes and regular alignment of lattices has a number of implications for how this membrane is organized to carry out the process of energy transfer.


Unprotected sidewalls of implantable silicon-based neural probes and conformal coating as a solution.
Silicon-based implantable neural devices have great translational potential as a means to deliver various treatments for neurological disorders. However, they are currently held back by uncertain longevity following chronic exposure to body fluids. Conventional deposition techniques cover only the horizontal surfaces which contain active electronics, electrode sites, and conducting traces. As a result, a vast majority of today's silicon devices leave their vertical sidewalls exposed without protection. In this work, we investigated two batch-process silicon dioxide deposition methods separately and in combination: atomic layer deposition and inductively-coupled plasma chemical vapor deposition. We then utilized a rapid soak test involving potassium hydroxide to evaluate the coverage quality of each protection strategy. Focused ion beam cross sectioning, scanning electron microscopy, and 3D extrapolation enabled us to characterize and quantify the effectiveness of the deposition methods. Results showed that bare silicon sidewalls suffered the most dissolution whereas ALD silicon dioxide provided the best protection, demonstrating its effectiveness as a promising batch process technique to mitigate silicon sidewall corrosion in chronic applications.


Automatic method for classifying COVID-19 patients based on chest X-ray images, using deep features and PSO-optimized XGBoost.
The COVID-19 pandemic, which originated in December 2019 in the city of Wuhan, China, continues to have a devastating effect on the health and well-being of the global population. Currently, approximately 8.8 million people have already been infected and more than 465,740 people have died worldwide. An important step in combating COVID-19 is the screening of infected patients using chest X-ray (CXR) images. However, this task is extremely time-consuming and prone to variability among specialists owing to its heterogeneity. Therefore, the present study aims to assist specialists in identifying COVID-19 patients from their chest radiographs, using automated computational techniques. The proposed method has four main steps: (1) the acquisition of the dataset, from two public databases; (2) the standardization of images through preprocessing; (3) the extraction of features using a deep features-based approach implemented through the networks VGG19, Inception-v3, and ResNet50; (4) the classifying of images into COVID-19 groups, using eXtreme Gradient Boosting (XGBoost) optimized by particle swarm optimization (PSO). In the best-case scenario, the proposed method achieved an accuracy of 98.71%, a precision of 98.89%, a recall of 99.63%, and an F1-score of 99.25%. In our study, we demonstrated that the problem of classifying CXR images of patients under COVID-19 and non-COVID-19 conditions can be solved efficiently by combining a deep features-based approach with a robust classifier (XGBoost) optimized by an evolutionary algorithm (PSO). The proposed method offers considerable advantages for clinicians seeking to tackle the current COVID-19 pandemic.


In situ, one step removal of ammonia from onshore and offshore formation water of petroleum production fields.
Fish, crustaceans and other living organisms are threatened due to disposal of harmful contaminants in sea water. Ammonia is considered one of harmful contaminants due to industrial activities of oil companies, where excess ammonia in the formation water is discharged into sea water. Electrochemical treatment (EC) was used in one step for total removal of ammonia and remediation of other contaminants. Three working electrodes were examined EC cell, aluminum, iron and modified electrode (Ti/IrO2). Graphite electrode was used as counter electrode in all processes of binary system. Both ionized and unionized ammonia of onshore (5.54 mg L-1) and off shore (110 mg L-1) were totally undetected after one step using all types of electrodes. The study was extended also to check the removal efficiency of other contaminants, where the analysis indicated the alleviation of them. Total suspended solid (TSS) of both onshore 64 mg L-1 and offshore 228 mg L-1 samples was reduced to 4 mg L-1. Total dissolved solids (TDS), chemical oxygen demand (COD) and biological oxygen demand (BOD) of high values, 232,000, 8500 and 2442 mg L-1 were also reduced to lower levels 18,400, 4000 and 1600 mg L-1, respectively. The formed sludge after EC treatment was also investigated using XRD.


Experience with the new pneumatic nasal tampon in cases of critical nasal bleeding.
A pneumatic nasal tube is recommended to control serious bleeding in the nasal cavity and nasopharynx. This is easily administered and tightly seals the nasal cavity and nasopharynx. The tube allows reduced nasal respiration with sufficient sealing. It is available in three sizes and has been proven useful by the authors.


EGF receptor phosphorylation is affected by ionizing radiation.
Eukaryotic cells respond to ionizing radiation with cell cycle arrest, activation of DNA repair mechanisms, and lethality. However, little is known about the molecular mechanisms that constitute these responses. Here we report that ionizing radiation enhances epidermal growth factor (EGF) receptor tyrosine phosphorylation in intact cells as well as in isolated membranes of A431 cells. Phosphoamino acid analysis revealed that ionizing radiation preferentially enhances tyrosine phosphorylation, while EGF enhances the phosphorylation of all three phosphoamino acids (serine, threonine and tyrosine) of the EGF receptor. In addition, radiation reduces the turnover rate of the EGF receptor, while EGF increases the rate of the receptor turnover and down-regulation. Moreover, the confined radiation-induced phosphorylation of tyrosine residues is inhibited by genistein, indicating that this phosphorylation of EGF receptor is due to protein tyrosine kinase activation. These studies provide novel insights into the capacity of radiation to modulate EGF receptor phosphorylation and function. The radiation-induced elevation in the EGF receptor tyrosine phosphorylation and the receptor's slower rate of turnover are discussed in terms of their possible role in cell growth and apoptosis modulation.


Gestational environment programs adult depression-like behavior through methylation of the calcitonin gene-related peptide gene.
Early life exposure to specific environmental factors can increase risk for developing psychopathology including major depression in adulthood. However, the molecular pathways and epigenetic mechanisms that mediate the effects of early environments on adult mood remain poorly understood. We examined the effects of different gestational and rearing conditions on adult anxiety- and depression-like behavior using a combined reciprocal outcrossing and cross-fostering design in Balb/cJ (cJ) and C57BL/6J (B6) mouse strains. First filial (F1) hybrid offspring, which were gestated by B6 or cJ dams and then reared by either strain, were evaluated for behavior and whole-genome hippocampal gene expression during adulthood. Adult hybrid mice gestated by B6 dams showed increased depression-like behavior in the forced swim and sucrose preference tests, increased hippocampal expression of alpha calcitonin gene-related peptide (αCGRP) transcripts, and decreased methylation of the αCGRP promoter compared with those gestated by cJ dams. Differential expression of αCGRP in adulthood did not result from genomic imprinting, and differences between B6 and cJ mitochondrial DNA were not responsible for behavioral phenotypes observed. Finally, central administration of αCGRP to adult hybrid mice increased depression-like behavior, whereas the CGRP1 receptor antagonist CGRP8-37 reduced depression-like behavior in the forced swim test. Our findings suggest that gestational factors influence adult depression-like behavior through methylation of the αCGRP gene.


Distance Education During COVID-19 Pandemic: A College of Pharmacy Experience.
This study aimed at describing the experience of academic staff and students with distance education, during the COVID-19 pandemic, at a college of pharmacy in Saudi Arabia. This study used a mixed-method approach. The first phase implemented a survey that targeted both academic staff and students to evaluate their experiences with distance education during the COVID-19 pandemic. Then, a focus group discussion was conducted to explore, in-depth, their experience. The survey consisted of five domains as follows: readiness for the shift to distance education during the full and partial lockdown, perception towards distance education, barriers against distance education, and the acquisitions due to distance education. A five-point Likert scale was used to assess participants' responses to the different domains (mean score ± standard deviation). Seventy-eight percent of the academic staff and 65% of the students responded to the survey. Participants' views were positive for readiness for the shift to distance education during the full lockdown (3.89±0.42 for academic staff and 3.82±0.50 for students) with almost similar evaluation for the readiness during the blended learning period (3.91±0.44 for staff and 3.83±0.59 for students). The findings showed a generally positive perception towards distance education (3.59± 0.67 for academic staff and 3.47±0.64 for students). The acquisitions due to distance education were also positive (3.95±0.72 for academic staff and 3.78±0.77 for students). Nonetheless, some barriers that affected distance education were raised with an overall neutral view from both academic staff (3.31±0.72) and students (3.31±0.64), with different responses for the individual items. Qualitative findings from the focus group discussions explored the strengths, weaknesses, opportunities, and challenges, with emphasis on the areas for improvement. Although the shift for distance education was out of a sudden, participants showed overall positive views about their experience with distance education and highlighted areas for improvement.


Paroxetine treatment in children and adolescents with major depressive disorder: a randomized, multicenter, double-blind, placebo-controlled trial.
To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating Scale-Revised total score at week 8 last observation carried forward). Safety was primarily assessed by spontaneous reporting of adverse events. A total of 206 patients (intent to treat) were randomized to paroxetine (n = 104) or placebo (n = 102). Week 8 Children's Depression Rating Scale-Revised total score adjusted mean changes from baseline for patients receiving paroxetine and placebo were -22.58 (SE 1.47) and -23.38 points (SE 1.60), respectively (0.80, 95% confidence interval -3.09 to 4.69, p = 0.684). Increased cough (5.9% versus 2.9%), dyspepsia (5.9% versus 2.9%), vomiting (5.9% versus 2.0%), and dizziness (5.0% versus 1.0%) occurred in >or=5% of the paroxetine group and at least twice that of the placebo group. Six of 104 (5.8%) paroxetine patients reported serious adverse events compared to 1 placebo patient (1.0%). The incidence of adverse events of suicidal behavior and/or ideation while taking study medication (excluding taper) was 1.92% (2/104) for paroxetine versus 0.98% (1/102) for placebo. Paroxetine was not shown to be more efficacious than placebo for treating pediatric major depressive disorder.


Effect of interleukin-1 and insulin like growth factor-1 on the release of proteoglycan components and hyaluronan from pig articular cartilage in explant culture.
The turnover of proteoglycans was investigated in articular cartilage in explant culture by analysing the components released into the culture medium. The effect of IL-1 alpha on the release of fragments derived from different proteoglycan domains and hyaluronan (HA) was determined over 4 days in culture. The effect of IGF-1 (100 ng/ml) on matrix degradation of proteoglycan and its ability to inhibit the effects of IL-1 (10 ng/ml) was also assessed. The rate of release of G1 and G2 globular domains of proteoglycans into the culture medium was determined by radioimmunoassay. In unstimulated control cartilage there was a greater release of proteoglycan G2 domain than of G1 domain suggesting that cleavage occurred between them and that some G1 was preferentially retained bound in the matrix. Compared with control cartilage IL-1 stimulated the release of all proteoglycan components and hyaluronan. IL-1 had a greater effect on the release of G1 than on G2 domain, but also resulted in some net loss of these proteins (approximately 45% as detected in the immunoassays). In explants treated with both IL-1 and IGF-1 there was much less release of proteoglycan fragments and evidence for less extensive degradation. IGF-1 was particularly affective in preventing any increase in HA release and also preventing the apparent loss of G1 and G2 domains. It also partially inhibited the release of G1 and G2 domains and the sulphated glycosaminoglycan fragments. IGF-1 was therefore an effective antagonist of IL-1 action on cartilage. It is not known at what level it blocks the chondrocyte response to IL-1, but it clearly results in the suppression of matrix degradative activity.


Evaluation of osteogenic potential of Cissus quadrangularis on mandibular alveolar ridge distraction.
This randomized clinical trial was designed to evaluate osteogenic potential of Cissus quadrangularis in alveolar distraction to facilitate implant installation. Twenty patients with atrophic ridge were treated by alveolar distraction. After completing distractor activation, patients were randomly divided into two equal groups according to administered drug (placebo and Cissus quadrangularis group). After a consolidation period, distractors were removed and implants were inserted. Clinical evaluation was done to assess wound healing, and distractor and implant stability. Histological evaluation was performed at time of implant insertion. Radiographic evaluation was performed to assess bone volume and density after distraction, as well as, density and bone loss around implant. Radiographic and histological results showed that bone formation and maturation of study group were faster than that of control group. There was a significant increased bone density in distracted area and around implant in study group than control group. A significant bone loss at end of consolidation period, and around implant at end of the study was reported in control group than study group. Cissus quadrangularis administration during the consolidation period is associated with increased osteogenic potential of distracted bone. The histological and radiographic findings of current study proved that Cissus quadrangularis not only enhances rate of new bone formation, but also bone density to withstand the biomechanical requirements of implant placement in a shorter time. Trial registration This study was retrospectively registered on www.ClinicalTrial.gov : NCT04669795-17\12\2020.


Persistent sciatic artery.
Persistent sciatic artery (PSA) is a very uncommon congenital malformation. Its incidence is estimated to be 0.025-0.04%. If it is accompanied by hypoplasia of the femoral artery system, its presence is essential for perfusion of the limbs. The usual form of presentation is as an aneurysm (25-58%) and/or its complications (thrombosis, distal remobilization, local compression). A 66-year-old woman presented with a painful mass of several months' progression. After performing angio-computed tomography, a fusiform aneurysmal dilation was observed in the left gluteal mass dependent on the left obturator artery, which was identified as the left lower gluteal artery. For this reason, we decided to perform therapeutic embolization. During the angiogram, a left aneurysmal PSA with distal thrombosis was observed. In view of these findings, a bypass from the superficial femoral artery to the tibioperoneal trunk was performed, with a contralateral inverted saphenous vein. The PSA was subsequently embolized with an occluder (AGA Medical IZASA, Plymouth, MN). The patient was discharged after checking complete exclusion of the aneurysm by ultrasound, with distal pulses during follow-up. Combined treatment using embolization, before surgical revascularization of the limb, markedly decreases the morbidity and mortality by avoiding the pelvic approach by the posterior route.


Characteristics and correlates of electronic cigarette product attributes and undesirable events during e-cigarette use in six countries of the EUREST-PLUS ITC Europe Surveys.
This study assessed characteristics and correlates associated with e-cigarette product attributes and identified correlates of experiencing undesirable events during e-cigarette use among adult smokers across six European Union (EU) Members States (MS) prior to the implementation of the Tobacco Products Directive (TPD) in 2016. We conducted a cross-sectional survey with a nationally representative sample of adult cigarette smokers from six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) reporting e-cigarette use; randomly selected through a multistage cluster sampling design from June to September 2016. Stepwise logistic regressions were used to identify factors associated with use of flavors, noticing health warnings, mixing e-liquids, experiencing 'dry puff', e-liquid leaking during use and e-liquid spilling during refill. Current daily or weekly prevalence of e-cigarette use among this sample of adult smokers was 7.5%. The most common attributes of e-cigarettes used included those that are flavored, contain nicotine, and are of tank style. Noticing health warnings on e-cigarette packaging and leaflets, respectively, was low (10.2% and 28%, respectively). Use of e-liquid refill nozzle caps, described as easy for a child to open, was associated with spilling during refill (OR=6.73; 95% CI: 2.02-22.37). Participants who adjusted occasionally or regularly the power (voltage) or temperature of their e-cigarette had greater odds of ever experiencing a 'dry puff' (OR=6.01; 95% CI: 2.68-13.46). Mixing different e-liquids was associated with leaking during use (OR=7.78; 95% CI: 2.45-24.73) and spilling during refill (OR=8.54; 95% CI: 2.29-31.88). Ongoing evaluation of factors associated with e-cigarette attributes and of the correlates of experiencing e-cigarette undesirable events during use, related to product design, is crucial to monitoring the impact of the implementing Acts of the EU TPD.


Obesity Progression Between Young Adulthood and Midlife and Incident Arthritis: A Retrospective Cohort Study of US Adults.
To examine the association between weight change from young adulthood to midlife and the risk of incident arthritis. Using data from the National Health and Nutrition Examination Survey, we categorized participants into weight-change categories based on their recalled weight during young adulthood and midlife. We estimated the association of weight change and developing an arthritis condition over 10 years using adjusted Cox models. Findings were extrapolated to the US population to determine the proportion of incident arthritis cases that could be averted if the entire population maintained a normal body mass index (BMI) in young adulthood and midlife. Among our sample of adults who were ages 40-69 years at their midlife weight measure (n = 13,669), 3,603 developed an arthritis condition. Compared with adults who maintained a normal-normal BMI, the normal-overweight, normal-obese, overweight-obese, and obese-obese groups had a significantly elevated risk of incident arthritis conditions. The obese-overweight group had a lower risk of incident arthritis conditions compared with the obese-obese group and a comparable risk to the overweight-overweight group. Nearly one-fourth of incident arthritis cases, corresponding to 2.7 million individuals, would have been averted under the hypothetical scenario where all individuals maintained normal weight from young adulthood to midlife. Weight loss from young adulthood to midlife was associated with a substantially reduced risk of developing an arthritis condition. We found no evidence of residual risk from having been heavier earlier in life. Our findings highlight the critical need to expand obesity treatment and prevention to achieve meaningful reductions in the burden of arthritis.


Uracil-DNA glycosylase activity in chronic lymphoproliferative disorders.
The activity of uracil-DNA glycosylase, a repair enzyme for the excision of uracil from DNA, was studied in patients with chronic lymphoproliferative disorders and with malignant plasma cell dyscrasias. The biochemical assay was performed on mononuclear cells, isolated by density gradient centrifugation from peripheral blood, from bone marrow or from both. The activity of the uracil-DNA glycosylase of peripheral blood cells in 8/8 cases of myeloma and in 3/3 cases of Waldenström's macroglobulinemia was in the same range as in 22 non-hematological control patients, i.e. 2.4-25.1 U/mg of protein. Higher activities were found in 9/12 cases of chronic lymphocytic leukemia (CLL), in 2/4 cases of hairy cell leukemia (HCL), in 2/2 cases of chronic T-cell lymphocytosis and in the only case of small cell lymphocytic lymphoma. Follow-up of some CLL and HCL patients revealed that uracil-DNA glycosylase activity was fairly stable during the course of the disease. We conclude that malignant cells in chronic lymphoproliferative disorders are characterized by a normal or even increased capability to repair DNA, as exemplified by uracil-DNA glycosylase in this study.


Different Risk Factors for Erosive Tooth Wear in Rural and Urban Nepal: A National Study.
Erosive tooth wear (ETW) is of growing concern, but data on ETW among Nepalese children are scarce. The main aim of the study was to investigate the prevalence and severity of ETW among Nepalese schoolchildren. We also aimed to analyse the risk indicators for ETW according to location (rural/urban) and the role of obesity in the risk for ETW. This national study was conducted among 5-15-year-old Nepalese schoolchildren from different regions. Altogether, 1137 out of 1151 schoolchildren participated in both a clinical examination and a survey. ETW was recorded using the Basic Erosive Wear Examination. The prevalence of ETW was 65%. One-fifth of the examined subjects were in need of preventive or restorative treatment. Living in an urban area and studying in a private school were protective factors for ETW, whereas consuming fruits frequently and using charcoal for tooth cleaning increased the odds for ETW. Central obesity was the strongest risk indicator for ETW among urban residents. ETW of low severity is common among Nepalese children and adolescents. Socio-demographic factors influence the prevalence of ETW in Nepal and there seems to be different factors that play a role in the ETW process according to location of residence.


Cytophotometric DNA analysis of rectal mucosa of patients with ulcerative colitis.
Cytophotometric DNA analysis of rectal mucosa was carried out in 11 patients with ulcerative colitis, in attempt to determine the proliferative activity of rectal mucosa. There was no significant difference in the mean DNA value, modal DNA value, total variation of DNA content and population of over 3c cells of rectal mucosa between controls and the patients. However, the differential determination of the proliferative activity in the upper, middle and lower thirds of the crypt disclosed that a population of over 3c cells in the upper and middle thirds of the crypt was significantly larger in the patients with longstanding disease than in the controls.


White matter lucencies in multi-infarct dementia: a somatosensory evoked potentials and CT study.
White matter low attenuation (WMLA) on computed tomography (CT) and the central conduction time (CCT) measured by median nerve-somatosensory evoked potentials were examined in 12 multi-infarct dementia (MID) patients, 10 patients with multiple infarcts (MI) without dementia and 11 age-matched controls. Patients with deep vascular lesions without cortical infarcts on CT were included. In MID, prolongation of CCT and moderate to severe WMLA were observed. The CCT and WMLA in MI patients were intermediate. The CCT was longer when the WMLA was more extensive. The result suggests that white matter disease in MID is concerned to the occurrence of dementia by disturbing axonal conduction.


Towards a carbon-neutral economy: The dynamics of factor substitution in Germany.
This paper investigates the elasticity of substitution between four inputs-capital, labor, energy, and material-with the translog cost approach for a wide range of industries in Germany by incorporating the slow adjustment process in factor substitution. To this end, we take advantage of EU KLEMS database covering a wide range of industries and consider two models. The first is the static model, in which instantaneous and complete substitution adjustments are assumed. The other model, referred to as dynamic, takes into account the slow adjustment process and applies this to the cost share equations which are estimated using Zellner's seemingly unrelated regression. The empirical results suggest that (i) the dynamic models have greater explanatory power than the static models; (ii) the production process at the national or industry level in Germany is mainly characterized by a complementarity or weak substitutability between energy and other inputs, which limits German government's ability to reduce energy use through factor substitution; (iii) among four factor prices, energy demand seems to be more sensitive to changes in the price of material, followed by labor. Hence, an increase in energy prices can be efficient to some extent in order to reduce energy use; (iv) there is a substantial industry heterogeneity in Germany in terms of both input substitution and its adjustment process. Therefore, strategies to mitigate CO2 emissions through input substitution channel should be designed at the industry level based on the industry-specific needs and peculiarities. It is because well-designed comprehensive policies that consider different structures of industries could help to achieve a carbon-neutral economy for Germany.


A surgical treatment of thrombosed external hemorrhoids.
An anatomically based method for the surgical treatment of thrombosed external hemorrhoids has been described. It involves a circumferential incision over the thrombosed hemorrhoidal sinus and removes the thrombi from involved veins.


Targeting Mutant p53 for Cancer Treatment: Moving Closer to Clinical Use?
Mutant p53 is one of the most attractive targets for new anti-cancer drugs. Although traditionally regarded as difficult to drug, several new strategies have recently become available for targeting the mutant protein. One of the most promising of these involves the use of low molecular weight compounds that promote refolding and reactivation of mutant p53 to its wild-type form. Several such reactivating drugs are currently undergoing evaluation in clinical trials, including eprenetapopt (APR-246), COTI-2, arsenic trioxide and PC14586. Of these, the most clinically advanced for targeting mutant p53 is eprenetapopt which has completed phase I, II and III clinical trials, the latter in patients with mutant TP53 myelodysplastic syndrome. Although no data on clinical efficacy are currently available for eprenetapopt, preliminary results suggest that the drug is relatively well tolerated. Other strategies for targeting mutant p53 that have progressed to clinical trials involve the use of drugs promoting degradation of the mutant protein and exploiting the mutant protein for the development of anti-cancer vaccines. With all of these ongoing trials, we should soon know if targeting mutant p53 can be used for cancer treatment. If any of these trials show clinical efficacy, it may be a transformative development for the treatment of patients with cancer since mutant p53 is so prevalent in this disease.


Octyl-functionalized hybrid silica monolithic column for reversed-phase capillary electrochromatography.
Hybrid silica monolithic stationary phase functionalized with octyl groups was synthesized by a two-step acid/base-catalyzed hydrolysis/co-condensation of tetraethoxysilane (TEOS) and n-octyltriethoxysilane (C(8)-TEOS). The influences of determining factors in the sol-gel process such as the monomer ratio and water content on the monolith formation were systematically investigated. An increase in the TEOS/C(8)-TEOS ratio in the polymerization mixture shifted the pore size distribution towards smaller pore diameter with larger pore volume. The optimal TEOS/C(8)-TEOS volume ratio was found to be 90/50, under which condition the median pore diameter of the monolith was around 1.0 microm with pore volume of 3.25 cm(3)/g. The chromatographic characteristics of the monolithic column prepared with the optimized fabrication condition were studied. Some aromatic compounds including alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs) and phenols were successfully separated on the octyl-functionalized silica monolithic column with high column efficiency up to 180,000 plates/m.


[Measurement of 75Se-SeHCAT abdominal retention in the initial diagnosis of Bile Acid Absorption (BAM)].
To evaluate the usefulness of the (75)SeHCAT abdominal retention (AR) measurement in the early diagnosis of diarrhea syndrome (DS). Thirty-seven patients with diarrhea syndrome within the first month of evolution were prospectively evaluated. The (75)Se-SeHCAT abdominal retention was measured 4 and 7 days post-administration of 0.01 mCi of (75)SeHCAT. The test was performed prior to treatment and at 3 months when the baseline study was positive. The test was considered positive if the RA was <25% at 4(th) and <10% on the 7th day. The patients were visited at 3 months. Depending on the response, 3 groups were established: a) complete response: normalization of stool frequency, b) partial response, decrease of frequency or c) no response. Group A: The AR of (75)Se-SEHCAT was normal in 21 patients. Six were diagnosed of colonic diverticulosis, 8 of irritable bowel syndrome, 1 of lymphocytic colitis, 1 of post-gastroenteritis syndrome, 1 of celiac disease and 1 of stenosis of the cardia. Four are still under study. Group B: The AR of (75)Se-SEHCAT decreased in 16 patients. All showed abnormal AR at day 7 and all but 1 at day 4. Following administration of cholestyramine resin, 8 (50%) presented partial response and 8 (50%) complete response. At 3 months, AR had increased at day 4 and 9 at day 7. The measurement of (75)SEHCAT abdominal retention allows the early diagnosis of bile acid malabsorption in 43% of the patients with DS. Measurement at 7 days seems more accurate than that at 4 days.


The effect of women's status and community on the gender differential in children's nutrition in India.
This study uses the third National Family Health Survey (2005-06) in India to investigate whether differences in women's status, both at the individual and community levels, can explain the persistent gender differential in nutritional allocation among children. The results show that girls are less likely than boys to receive supplemental food and more likely to be malnourished. In general it appears that higher women's status within a community, as well as higher maternal status, have beneficial effects on a daughter's nutritional status. Further, the moderating effects of community appear to be more consistent and stronger than the individual-level characteristics. A positive relationship between the percentage of literate women in a community and the gender differential in malnutrition appears to be an exception to the general findings regarding the beneficial nature of women's status on a daughter's well-being, showing the need for more than just basic adult literacy drives in communities to overcome the problem of daughter neglect.


Rapid and sensitive streptavidin-biotin amplified fluorogenic enzyme-linked immunosorbent-assay for direct detection and identification of dengue viral antigens in serum.
Each of the four serotypes of dengue viruses is responsible for a spectrum of illnesses that range from nonspecific febrile syndrome with good prognosis to dengue haemorrhagic fever or dengue shock syndrome. Definite diagnosis of dengue is provided by the detection of virus in acute-phase sera of patients. Virus isolation can be accomplished with mosquito cell lines or mosquito inoculations. However, these methods are time consuming and labour intensive. The reverse-transcriptase polymerase chain reaction (RT-PCR) provides a potential means of rapid diagnosis but requires specialised facilities and equipment and is expensive. Therefore a rapid, simple, sensitive, and economical method for direct detection of viral antigens in viraemic sera is needed for clinical and epidemiological investigations. An amplified fluorogenic enzyme-linked immunosorbent assay (F-ELISA) is described for the detection and identification of dengue-3 viruses in serum specimens. This assay utilizes biotinylated mouse IgG antibody directed against dengue antigens captured by anti-dengue monoclonal antibody coated onto polystyrene microplate wells. It takes advantage of the high affinity of biotin for the multivalent binding sites of streptavidin-labelled beta-galactosidase, and combines the amplification effect of biotin-streptavidin interaction with the high sensitivity of fluorogenic detection methods. Following optimisation of the procedure by reducing non-specific binding of proteins and enhancing the specific binding of antigens, F-ELISA was tested on 259 sera submitted routinely to our laboratory for confirmation of dengue diagnosis. The sensitivity of the F-ELISA was 90%, the specificity was 99% and the agreement rate was 98% between F-ELISA and virus isolation results.


Cue salience of the use of an electronic nicotine delivery system (ENDS) device marketed to women.
Passive exposure to the use of electronic nicotine delivery systems (ENDS or e-cigarettes) has been shown to generalize as a smoking cue. As young adult women in particular are increasingly targeted by ENDS distributors, the present study examined whether passive exposure to the use of a female-marketed ENDS product selectively enhanced smoking urge, cigarette and e-cigarette desire, and smoking behavior among women (vs men) smokers. Using a mixed design, young adult smokers (n = 64; mean age 28.2 yrs.; ≥5 cigarettes/day) observed a study confederate drink bottled water (control cue) and then vape a female-marketed tank-based ENDS (active cue). Main measures were the Brief Questionnaire of Smoking Urges (BQSU) and visual analog scales (VAS) for cigarette and e-cigarette desire pre- and post-cue exposure, followed by a smoking latency task. Compared to the control cue, the female-marketed ENDS cue increased smoking urge and desire for cigarettes and e-cigarettes to a similar extent in women and men. It also affected subsequent smoking behavior similarly between the sexes, with 68% of men and 58% of women opting to smoke (vs. obtaining monetary reinforcers). Both women and men were sensitive to the use of the female-marketed ENDS as a smoking cue. Consistent with prior work by our group, findings demonstrate the cue salience of ENDS, which may be attributable to the aspects of vaping that resemble traditional smoking (e.g. hand-to-mouth and inhalation and exhalation behaviors).


Radiomics for pseudoprogression prediction in high grade gliomas: added value of MR contrast agent.
Our aim is to define the capabilities of radiomics in predicting pseudoprogression from pre-treatment MR images in patients diagnosed with high-grade gliomas using T1 non-contrast-enhanced and contrast-enhanced images. In this retrospective IRB-approved study, image segmentation of high-grade gliomas was semi-automatically performed using 3D Slicer. Non-contrast-enhanced T1-weighted images and contrast-enhanced T1-weighted images were used prior to surgical therapy or radio-chemotherapy. Imaging data was split into a training sample and an independent test sample at random. We extracted 107 radiomic features by use of PyRadiomics. Feature selection and model construction were performed using Generalized Boosted Regression Models (GBM). Our cohort included 124 patients (female: n = 53), diagnosed with progressive (n = 61) and pseudoprogressive disease (n = 63) of primary high-grade gliomas. Based on non-contrast-enhanced T1-weighted images of the independent test sample, the mean area under the curve (AUC), mean sensitivity, mean specificity and mean accuracy of our model were 0.651 [0.576, 0.761], 0.616 [0.417, 0.833], 0.578 [0.417, 0.750] and 0.597 [0.500, 0.708] to predict the development of pseudoprogression. In comparison, the independent test data of contrast-enhanced T1-weighted images yielded significantly higher values of AUC = 0.819 [0.760, 0.872], sensitivity = 0.817 [0.750, 0.833], specificity = 0.723 [0.583, 0.833] and accuracy = 0.770 [0.687, 0.833]. Our findings show that it is possible to predict pseudoprogression of high-grade gliomas with a Radiomics model using contrast-enhanced T1-weighted images with comparatively good discriminatory power. The use of a contrast agent results in a clear added value.


Transcriptional activation of p21 by Tranilast is mediated via transforming growth factor beta signal pathway.
Tranilast, an antiallergic medication, is a very promising inhibitor of restenosis after balloon angioplasty. Tranilast can prevent the proliferation and migration of smooth muscle cells by activating the gene expression of p21, a strong cyclin/cyclin-dependent kinase (CDK) inhibitor, and by arresting cell growth at the G0/G1 phase. The signaling pathway of Tranilast in regulating p21 is to our best interest and is elucidated in the present study. The major emphasis was weighted on exploring the regulatory effects of Tranilast on promoter activity of p21. By serial deletion analysis, the sequence between -74 and -83 bp of the p21 promoter, previously identified as the transforming growth factor-beta (TGF-beta)-response element, was found sufficient, where as most of the promoter region 5' to -111 bp was found unnecessary for the transcriptional activation of p21 by both TGF-beta1 and Tranilast. Tranilast was also found to induce phosphorylation of Smad2 (a cytoplasmic signaling molecule essential for mediating TGF-beta signal transduction). Transfection of DeltakTbetaRII, a truncated form of TGF-beta type II receptor known to exert a dominant-negative effect on TGF-beta signaling, was found to suppress the signaling of both Tranilast and TGF-beta1 to a similar extent. These results suggested that induction of p21 by Tranilast might be closely related to TGF-beta signal transduction pathway.


Physical Activity Scaled to Preferred Walking Speed as a Predictor of Walking Difficulty in Older Adults: A 2-Year Follow-up.
The usual accelerometry-based measures of physical activity (PA) are dependent on physical performance. We investigated the associations between PA relative to walking performance and the prevalence and incidence of early and advanced walking difficulties compared to generally used measures of PA. Perceived walking difficulty was evaluated in 994 community-dwelling participants at baseline (age 75, 80, or 85 years) and 2 years later over 2 km (early difficulty) and 500 m (advanced difficulty). We used a thigh-mounted accelerometer to assess moderate-to-vigorous PA, daily mean acceleration, and relative PA as movement beyond the intensity of preferred walking speed in a 6-minute walking test (PArel). Self-reported PA was assessed using questionnaires. The prevalence and incidence were 36.2% and 18.9% for early and 22.4% and 14.9% for advanced walking difficulty, respectively. PArel was lower in participants with prevalent (mean 42 [SD 45] vs 69 [91] min/week, p < .001) but not incident early walking difficulty (53 [75] vs 72 [96] min/week, p = .15) compared to those without difficulty. The associations between absolute measures of PA and incident walking difficulty were attenuated when adjusted for preferred walking speed. The variation in habitual PA may not explain the differences in the development of new walking difficulty. Differences in physical performance explain a meaningful part of the association of PA with incident walking difficulty. Scaling of accelerometry to preferred walking speed demonstrated independence on physical performance and warrants future study as a promising indicator of PA in observational studies among older adults.


Changes in nocturia from medical treatment of benign prostatic hyperplasia: secondary analysis of the Department of Veterans Affairs Cooperative Study Trial.
We evaluate the efficacy of medical therapy on nocturia in men with benign prostatic hyperplasia (BPH). We performed a secondary analysis of data from the VA Cooperative Study Program Trial in which 1,229 men with BPH 45 to 80 years old were randomly assigned to receive terazosin, finasteride, combination or placebo. The 1,078 men who completed 12 months of the trial are included in this study. Of those men 1,040 (96.5%) had at least 1 episode of nocturia at baseline and 38 (3.5%) had less than 1 episode (baseline nocturia is an average of 2 measures). Of those 1,040 men 788 (75.8%) had 2 or more nocturia episodes. Overall, nocturia decreased from a baseline mean of 2.5 to 1.8, 2.1, 2.0 and 2.1 episodes in the terazosin, finasteride, combination and placebo groups, respectively. Of men with 2 or more episodes of nocturia 50% reduction in nocturia was seen in 39%, 25%, 32% and 22% in the terazosin, finasteride, combination and placebo groups, respectively. Changes in nocturia were correlated with changes in reported bother from nocturia (Pearson correlation 0.48), BPH impact index (0.32) and overall satisfaction with urinary symptoms (0.33). Terazosin and combination therapy reduced nocturia in men with BPH, yet the net advantage of terazosin over placebo was a net reduction of 0.3 nocturia episode. For a person to reach a 50% or greater reduction in nocturia, the advantage of terazosin over placebo was 17 percentage points. Changes in nocturia had a moderate impact on symptom specific quality of life measures.


Short-term Evaluation of Negative Pressure Applied by the Multi-Pressure Dial System to Lower Nocturnal IOP: A Prospective, Controlled, Intra-subject Study.
The purpose of this study was to investigate the short-term safety and feasibility of negative pressure application by the Multi-Pressure Dial (MPD) System to lower nocturnal intraocular pressure (IOP) in subjects with open-angle glaucoma (OAG). A prospective, controlled, intra-subject study of 22 eyes from 11 subjects at a single site was performed. All subjects had a history of OAG and were currently using a topical prostaglandin. For each subject, the eye with the highest IOP in the supine position was selected as the treatment eye (TE) and the contralateral eye served as the control eye (CE). The negative pressure for the TE was set to 60% of the baseline IOP value with no negative pressure in the CE. IOP measurements were collected at three prespecified time points overnight in the supine position with active negative pressure. The primary outcome measure was mean IOP with the application of negative pressure. At the three overnight time points, the mean (± standard deviation) baseline IOP prior to negative pressure application was 22.2 ± 2.5 mmHg in the TE and 21.8 ± 2.5 mmHg in the CE. With the application of 60% negative pressure to the TE and no active negative pressure to the CE, the mean IOP was 14.2 ± 2.2 and 19.5 ± 2.4 mmHg, respectively. The mean percentage IOP reduction in the TE was 35% (p < 0.001). There were two minor adverse events, both unrelated to device wear, and there were no IOP spikes ≥ 10 mmHg. The MPD can safely and effectively lower nocturnal IOP in the supine position. The MPD holds promise as a potential new, non-invasive treatment option for the control of nocturnal IOP.


Synthesis and biological evaluation of novel acenaphthene derivatives as potential antitumor agents.
Twelve novel acenaphthene derivatives have been synthesized. The structures of all compounds were confirmed by ¹H-NMR, MS and elemental analysis. Their antitumor activities were evaluated in six human solid tumor cell lines, namely non-small cell lung cancer (H460), human colon adenocarcinoma (SW480), human breast cancer cell (MDA-MB-468 and SKRB-3), human melanoma cell (A375) and human pancreatic cancer (BxPC-3). Among them, compound 3c shows the best antitumor activity against SKRB-3 cell line, as high as the positive control adriamycin.


Larval development of the shell and the shell gland inMytilus (Bivalvia).
In the newly hatched larva ofMytilus galloprovincialis the larval shell field almost totally invaginates to form a shell gland. Only very few cells remain outside and they meet at one point. Only these cells secrete the pellicle, which in the beginning is protected by the glycocalyx and the microvilli of the surrounding cells. The invaginated cells do not participate in pellicle secretion. The secretion partly passes through infoldings of the apical cell membrane. Mineralization of each valve begins along the hinge line, continues to the valve margins and includes the valve centre.


Chromosomal mosaicism in the fetoplacental unit.
Cytogenetic prenatal diagnosis on chorionic villi (CV) can be complicated by the detection of "chromosomal mosaicism." This is one of the main issues of first-trimester cytogenetic prenatal diagnosis as it can involve different types of chromosomal abnormalities, and the prediction of the fetal involvement is challenging because the detected abnormal mosaic cell line is not necessarily extended to fetal tissues. In addition, because the cell-free fetal DNA that is targeted by the new technologies for fetal aneuploidy risk assessment is mainly derived from the CV cells, the same challenges related to chromosomal mosaicism can be transferred into this new clinical field. This review illustrates the phenomenon of fetoplacental mosaicism, the management of prenatal diagnosis cases complicated by the detection of such a biological phenomenon, and the implications of its presence for the management of high-risk cfDNA testing results for fetal aneuploidies.


Human tools of the European tertiary? Artefacts, brains and minds in evolutionist reasoning, 1870-1920.
This essay explores evolutionary reasoning and notions of progress at the turn of the twentieth century by focusing on the various interpretations used to understand eoliths. These 'dawn' (Greek eos) 'stones' (Greek lithos) were contested objects and I focus on three geographic episodes in which they were used to support scientific, and sometimes socially inspired, accounts of human origins. Particular attention is paid to the work of Gabriel de Mortillet (1821-98), James Reid Moir (1879-1944) and Henry Fairfield Osborn (1857-1935).


The WES triad -- a specific sonographic sign of gallstones in the contracted gallbladder.
The "WES" triad -- that is, the demonstration of the gallbladder Wall, the Echo of the stone, and the acoustic Shadow -- permits the specific diagnosis of stones in a contracted gallbladder. This triad positively identifies the gallbladder and helps to differentiate the contracted gallbladder with stones from a loop of bowel containing gas.