Incidence, significance, and pharmacological responses of catheter-induced mechanical trauma in patients receiving radiofrequency ablation for supraventricular tachycardia.
Catheter-induced mechanical trauma is unfavorable during electrophysiological study. However, its incidence, significance, and pharmacological responses in patients receiving radiofrequency ablation for supraventricular tachycardia have not been investigated. A prospective study was performed in 666 consecutive patients with documented, symptomatic supraventricular tachycardia. All had been referred for electrophysiological study and radiofrequency ablation. Catheter-induced mechanical trauma was defined by either disappearance of or change in preexcitation pattern induced by the electrode catheters or noninducibility of tachycardia after the electrode catheter-induced termination of tachycardia, confirmed by electrophysiological study. Adenosine, isoproterenol, and atropine were serially administered 1 hour after the mechanical trauma to study pharmacological response. "Rescue" radiofrequency ablation was defined as delivery of radiofrequency energy just at the presumed ablation site immediately after the mechanical trauma. Of the 666 patients, 254 had atrioventricular (AV) nodal reentrant tachycardia, 367 patients had accessory pathways, 30 patients had atrial tachycardia, and 15 had atrial flutter. Catheter-induced mechanical trauma occurred in 17 patients (2.6%): 4 patients had AV nodal reentrant tachycardia, 9 had accessory pathways, and 4 had atrial tachycardia. Five patients had such episodes during the placement of electrode catheters and 12, during mapping and ablation procedures. Of the 4 patients with AV nodal reentrant tachycardia, 3 had mechanical trauma on the retrograde fast pathway and 1, on the antegrade slow pathway. In the 9 patients with accessory pathways, those pathways were located in the left free wall in 4 patients, right free wall in 1, right posteroseptum in 1, and right anteroseptum in 3. Atrial tachycardia was more easily traumatized than AV nodal reentrant tachycardia (P < .01) and than accessory pathways (P < .01). The clinical courses of mechanical trauma were variable: 1 patient had spontaneous recovery within 1 week, 5 patients had recurrence of tachycardia within 3 months, and the rest have been free of tachycardia from 3 to 35 months. The recurrence rate was higher in patients with mechanical trauma than in those without (33.3% versus 3.5%, P < .0001) despite rescue radiofrequency ablation given in 7 patients. Pharmacological agents were generally unable to revive the traumatized tissues, and recurrence was unpredictable. Catheter-induced mechanical trauma was not common in patients receiving radiofrequency ablation for supraventricular tachycardia. Their clinical courses were variable, and pharmacological manipulation offered little assistance. More than half of the patients had long-term cures. However, the recurrence rate was, on the whole, significantly high despite rescue radiofrequency ablation. There is a need for great caution in the placement of electrode catheters in every patient during electrophysiological study and radiofrequency ablation.


A survey of the effectiveness of the assessment of the welfare of the child in UK in-vitro fertilization units.
Seventy-one clinics in the UK offering in-vitro fertilization (IVF) treatment were surveyed for their protocols on the assessment of the welfare of the children produced. A total of 44 (62%) responded. Of these, five (12%) did not have operational protocols, seven (16%) declined to provide their protocols, and 32 (73%) provided information used in the survey. The information was in the form of a protocol for only 16 (50%) of these clinics. The remaining clinics submitted as their 'protocols' letters to general practitioners, patient information, patient questionnaires and/or a copy of their policy on the assessment of child welfare. From the submitted material, it was possible to determine that 94% of clinics seek information on aspects of child welfare assessment, 78% have a procedure for making further enquiries where there is any cause for concern, 44 % include counselling opportunities explicitly in protocols, 30-38% of clinics see a full medical and social history from each prospective parent as part of the child welfare assessment, 16% include explicit consideration of the impact of multiple births on the welfare of the child, and 3% include consideration of the issue of disclosure of the mode of conception of the child on its welfare. Most clinics did not have clearly defined procedures on how to reach a decision on whether or not to treat. Eight clinics (25%) made explicit in their protocols any exclusion criteria. It is concluded that clinics are not currently producing completely effective protocols. Two possible reasons for this are considered: lack of technical knowledge about what constitutes an effective protocol, and lack of clear policy development and propagation underlying protocols within clinics. Possible approaches to improving the situation are considered.


Nosocomial Pathogens: An In-Depth Analysis of the Vectorial Potential of Cockroaches.
Nosocomial or healthcare-associated infections are regarded as the most frequent adverse event that threatens patients' safety and has serious economic and social consequences. Cockroach infestation is common in many hospitals, especially in the developing world. Common nosocomial pathogens isolated from cockroaches include Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. Cockroaches also harbor epidemiologically significant antibiotic-resistant organisms, such as carbapenem-resistant Enterobacteriaceae, which complicate nosocomial infections. Therefore, cockroaches constitute an important vector for nosocomial pathogens, and there should be zero tolerance for their presence in healthcare facilities. This paper aims to elucidate the possible role of cockroaches in nosocomial infections by reviewing the relevant research publications.


Highly sensitive detection of sodium in aqueous solutions using laser-induced breakdown spectroscopy with liquid sheet jets.
Laser-induced breakdown spectroscopy (LIBS) combined with liquid jets was applied to the detection of trace sodium (Na) in aqueous solutions. The sensitivities of two types of liquid jets were compared: a liquid cylindrical jet with a diameter of 500 µm and a liquid sheet jet with a thickness of 20 µm. Compared with the cylindrical jet, the liquid sheet jet effectively reduced the splash from the laser-irradiated surface and produced long-lived luminous plasma. The limit of detection (LOD) of Na was determined to be 0.57 µg/L for the sheet jet and 10.5 µg/L for the cylindrical jet. The LOD obtained for the sheet jet was comparable to those obtained for commercially available inductively coupled plasma emission spectrometers.


Inhibition of nitrification in soil by metal diethyldithiocarbamates.
Nitrification acts as a key process in determining fertilizer use efficiency by crops as well as nitrogen losses from soils. Metal dithiocarbamates in addition to their pesticidal properties can also inhibit biological oxidation of ammonium(nitrification) in soil. Metal [M = V(III), Cr(III), Mn(II), Fe(III), Ni(II), Cu(II), Zn(II) and Co(II)] diethyldithiocarbamates (DEDTC) were synthesized by the reaction of sodium diethyldithiocarbamate with metal chloride in dichloromethane/water mixture. These metal diethyldithiocarbamates were screened for their ability to inhibit nitrification at different concentrations( 10 microg/g soil, 50 microg/g soil and 100 microg/g soil). With increasing concentration of the complex, capacity to retard nitrification increased but the extent of increase varied for different metals. At 100 microg/g soil, different complexes showed nitrification inhibition from 22.36% to 46.45% . Among the diethyldithiocarbamates tested, Zn(DEDTC)2 proved to be the most effective nitrification inhibitor at 100 microg/g soil. Manganese, iron and chromium diethyldithiocarbamates also proved to be effective nitrification inhibitors than the others at 100 microg/g soil. The order of percent nitrification inhibition in soil by metal diethyldithiocarbamates was: Zn(II) > Mn(II) > Fe(III) > Cr(III) > V(III) > Co(II) > Ni(II) > Cu(II).


G protein-coupled receptor 30 ligand G-1 increases aryl hydrocarbon receptor signalling by inhibition of tubulin assembly and cell cycle arrest in human MCF-7 cells.
Regulatory crosstalk between the aryl hydrocarbon receptor (AHR) and oestrogen receptor α (ERα) is well established. Apart from the nuclear receptors ERα and ERβ, oestrogen signalling further involves an unrelated G protein-coupled receptor termed GPR30. In order to investigate potential regulatory crosstalk, this study investigated the influence of G-1 as one of the few GPR30-specific ligands on the AHR regulon in MCF-7 cells. As a well-characterised model system, these human mammary carcinoma cells co-express all three receptors (AHR, ERα and GPR30) and are thus ideally suited to study corresponding regulatory pathway interactions on transcript level. Indeed, treatment with micromolar concentrations of the GPR30-specific agonist G-1 resulted in up-regulation of AHR as well as the transcripts for cytochromes P450 1A1 and 1B1, two well-known targets of the AHR regulon. While this was partly attributable to G-1-mediated inhibition of tubulin assembly and subsequent cell cycle arrest in the G2/M phase, the effects nevertheless required functional AHR. However, G-1-induced up-regulation of CYP 1A1 was not mediated by GPR30, as G15 antagonist treatment as well as a knockdown of GPR30 and AHR failed to inhibit this effect.


Licorice strips enhance predator-mediated biological control in China's cotton crop.
Habitat management such as field- or farm-level diversification can conserve arthropod natural enemies, enhance biological pest control and lower (or suspend) insecticide use in agricultural crops. These approaches however have been underexploited to manage the aphid Aphis gossypii in cotton cropping systems of Xinjiang, China. In this study, we investigated whether the presence of licorice (Glycyrrhiza uralensis) at the field edge benefits generalist predator abundance and aphid biological control in local cotton crops. Field trials during 2020 and 2021 showed that licorice strips enhanced the in-field abundance of generalist predators (primarily ladybeetles) 2.2-4.3 fold during early season, i.e. initial growth before A. gossypii peak infestation pressure. During peak outbreak conditions in July, treatment fields with licorice strips experienced a respective 17.5-61.2% lowered aphid density and 12.3-14.6-fold higher predator-to-aphid abundance ratio (PAR) than control fields. In late season (aphid decline phase) of either year, cotton fields with licorice strips also attained a respective 4.7-9.9 fold higher PAR. Exclusion cage assays quantitatively assessed predator-mediated A. gossypii biological control and the relative contribution of licorice strips. The biocontrol services index (BSI) was 2.8 times (2020) and 1.4 times (2021) higher at 5 m distances from the licorice strip as compared to control fields. Licorice strips in the immediate vicinity of cotton fields benefit generalist arthropod predators and improve aphid biological control throughout the cotton cropping season. These findings help to integrate habitat management within integrated pest management (IPM) frameworks in the biggest cotton production region of China. © 2022 Society of Chemical Industry.


Successful commercialisation of locally fabricated bioceramics for clinical applications.
This paper chronicled the development of a locally produced bone graft substitute based on calcium phosphate bioceramics called "GranuMaS--from concepts to clinics, and finally to its successful commercialization all within 5-year duration. It was a Prioritized Research (PR) collaborative project of 5 institutions namely SIRIM, ANM, USM, UKM and IIUM, funded by MOSTI to the amount of approximately RM2.5 millions under RM8. This paper also highlighted the requirements needed in terms of technical expertise/manpower, facilities and infrastructure, and government/institutional supports, as well as the challenge faced in developing and commercializing such product.


Functional vessel density in the first month of life in preterm neonates.
Changes in microcirculation have been recognized as central to many disease processes. The aim of this study was to evaluate factors, which influence the microcirculation of the skin during the first month of life in premature infants. Red blood cell (RBC) velocity, vessel diameter, and functional small vessel density (FSVD) were measured daily for the first 30 d on the upper arm in preterm infants with gestational age <30 wk. Orthogonal polarization spectral (OPS) images were analyzed off-line with the Capi- Scope-Image program. In 25 infants, FSVD decreased significantly from week 1 (mean +/- SD 236 +/- 33 cm/cm2) to week 4 (207 +/- 30 cm/cm2) and correlated directly with Hb levels and incubator temperature. Vessel diameters and RBC velocity did not change significantly, nor did clinical parameters such as blood pressure, heart rate or body temperature. Microvascular parameters were not dependent on gestational or postnatal age. The microcirculation of the skin might be an easily accessible window to obtain better understanding of circulatory changes in the postnatal period. Our data are essential as basis for further studies in this field. Hb levels and possible incubator temperatures have a substantial influence on functional small vessel density and therefore need to be taken in account.


Metabolic signatures of T-cells and macrophages in rheumatoid arthritis.
In most autoimmune diseases, a decade-long defect in self-tolerance eventually leads to clinically relevant, tissue-destructive inflammatory disease. The pathogenic potential of chronic persistent immune responses during the pre-clinical and clinical phase is ultimately linked to the bioenergetic fitness of innate and adaptive immune cells. Chronic immune cell stimulation, high cellular turn-over, structural damage to the host tissue and maladaptive wound healing, all require a reliable supply of nutrients, oxygen, and biosynthetic precursors. Here, we use the model system of rheumatoid arthritis (RA) to discuss immunometabolism from the vantage point of T-cells and macrophages that encounter fundamentally different metabolic stress scenarios in the RA host. We outline the general principle that both insufficient nutrient supply, as well as nutrient excess generate cellular stress responses and guide immune function. ATPlow, NADPHhigh, ROSlow T-cells hyperproliferate and are forced into premature senescence. ATPhigh, ROShigh macrophages dimerize the glycolytic enzyme pyruvate kinase to amplify STAT3-dependent inflammatory effector functions. A corollary of this model is that simple nutraceutical interventions will be insufficient to re-educate the immune system in RA. Instead, interference with cell-type-exclusive and differentiation-stage-dependent metabolic setpoints will be needed to reprogram arthritogenic pathways.


Bilateral arterial occlusions masking retinitis in a HIV-positive male.
We report an interesting case of 36-year-old HIV-positive male with uveitis, cilioretinal artery occlusion in OD, and superotemporal branch retinal artery occlusion in OS. Hypercoagulability, cardiovascular, and rheumatologic workups were unremarkable. Aqueous taps were negative for toxoplasma, viruses, and MTb by multiplex polymerase chain reaction. Patches of retinitis were seen on clearing of retinal edema. Serology was positive for toxoplasma and rickettsia. Management included doxycycline, azithromycin, bactrim DS, and oral steroids. Vision improvement to 6/60 and 6/24 in OD and OS refer to the right eye and left eye, respectively, were noted at 4-month follow-up. Infections should be considered in arterial occlusions associated with inflammation in HIV-positive individuals.


Mechanism of Histone H3K4me3 Recognition by the Plant Homeodomain of Inhibitor of Growth 3.
Aberrant access to genetic information disrupts cellular homeostasis and can lead to cancer development. One molecular mechanism that regulates access to genetic information includes recognition of histone modifications, which is carried out by protein modules that interact with chromatin and serve as landing pads for enzymatic activities that regulate gene expression. The ING3 tumor suppressor protein contains a plant homeodomain (PHD) that reads the epigenetic code via recognition of histone H3 tri-methylated at lysine 4 (H3K4me3), and this domain is lost or mutated in various human cancers. However, the molecular mechanisms targeting ING3 to histones and the role of this interaction in the cell remain elusive. Thus, we employed biochemical and structural biology approaches to investigate the interaction of the ING3 PHD finger (ING3PHD) with the active transcription mark H3K4me3. Our results demonstrate that association of the ING3PHD with H3K4me3 is in the sub-micromolar range (KD ranging between 0.63 and 0.93 μm) and is about 200-fold stronger than with the unmodified histone H3. NMR and computational studies revealed an aromatic cage composed of Tyr-362, Ser-369, and Trp-385 that accommodate the tri-methylated side chain of H3K4. Mutational analysis confirmed the critical importance of Tyr-362 and Trp-385 in mediating the ING3PHD-H3K4me3 interaction. Finally, the biological relevance of ING3PHD-H3K4me3 binding was demonstrated by the failure of ING3PHD mutant proteins to enhance ING3-mediated DNA damage-dependent cell death. Together, our results reveal the molecular mechanism of H3K4me3 selection by the ING3PHD and suggest that this interaction is important for mediating ING3 tumor suppressive activities.


An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzyme Q Biosynthesis.
The biosynthesis of coenzyme Q presents a paradigm for how cells surmount hydrophobic barriers in lipid biology. In eukaryotes, CoQ precursors-among nature's most hydrophobic molecules-must somehow be presented to a series of enzymes peripherally associated with the mitochondrial inner membrane. Here, we reveal that this process relies on custom lipid-binding properties of COQ9. We show that COQ9 repurposes the bacterial TetR fold to bind aromatic isoprenes with high specificity, including CoQ intermediates that likely reside entirely within the bilayer. We reveal a process by which COQ9 associates with cardiolipin-rich membranes and warps the membrane surface to access this cargo. Finally, we identify a molecular interface between COQ9 and the hydroxylase COQ7, motivating a model whereby COQ9 presents intermediates directly to CoQ enzymes. Overall, our results provide a mechanism for how a lipid-binding protein might access, select, and deliver specific cargo from a membrane to promote biosynthesis.


Destigmatizing public health concerns and supply of COVID-19 vaccines.
The end of the global pandemic caused by COVID-19 and a future without masks and restrictions are promising with the discovery of a vaccine. Still, there is much worry about the vaccine itself. Fears about what is inside the vaccine, how quickly it was created and plans for distribution are major concerns. This article aims to address these concerns to relieve vaccine hesitancy. Methods for distribution within the United States as well as different strategies to ensure proper and equitable allocation of COVID-19 vaccine worldwide is also described.


High cost of illness in fibromyalgia patients in Iran, irrespective of disease severity: A prospective cost study.
This study aimed to estimate the economic burden of fibromyalgia (FM) in 6 months, using a cost-diary, and to evaluate its relationship with the disease severity. This is a prospective cost-of-illness study on 62 participants with an FM diagnosis within a 6 month period. Patients completed the questionnaires, including FIQR (Revised Fibromyalgia Impact Questionnaire) and SF-12 (12-item short-form survey). The cost-diary method was used to track the cost of the disease. The participants received six cost-diary booklets during the study period to report their FM-related costs, hours, and days of productivity loss. The final costs are reported in US dollars. Most of the participants were women (90.3%) with a mean (±SD) age of 40.80 (±5.50) years and a mean (±SD) FIQR score of 54.38 (±14.13). Moreover, 45.2% of patients fulfilled all six booklets, whereas 24.2% returned only one booklet. The participants showed a mean (±SD) direct healthcare, non-healthcare, and indirect cost of $ 2817.08 (±$ 1860.04), $ 1497.98(±$ 1358.21), and $ 1449.05(±$ 3637.41) per patient for 6 months, respectively. Fibromyalgia is associated with high health-related and non-health-related costs in our country, irrespective of its severity. This study warrants urgent consideration in managing the disease burden on both patients and society.


A systematic review of pharmacologic treatment efficacy for depression in older patients with cancer.
Older adults ≥65 years of age represent the majority of new cancer diagnoses and are vulnerable to developing depression-like symptoms. Evaluation and management of depression in older cancer patients is underappreciated despite its high prevalence and impact on health-related quality of life. Although antidepressants are the primary pharmacologics used to treat depressive-like symptoms, the efficacy and overall benefit(s) are not well-characterized in older adult patients with cancer. The objective of this investigation was to review what is known about the efficacy of pharmacologic treatment for older adults with depression and cancer. PubMed (Medline) and EMBASE (Elsevier) databases were analyzed for relevant literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 1,919 unique studies were identified for title and abstract screening. Forty-eight publications were retrieved for full review. None of the identified studies evaluated the potential for benefit after pharmacological treatment among older adults with cancer and depression. Twenty-seven publications met all study criteria except for an analysis focused on older patients. We discovered a universal absence of literature with a relevance to pharmacologic antidepressant treatment effects in older adult patients with cancer. This included a lack of evaluation in patients with brain tumors who have an unusually high predilection for developing depression. Our findings suggest that new research is critically needed for understanding optimal clinical management strategies in older adults with cancer and depression who are treated with antidepressants.


Total Synthesis and Antibacterial Investigation of Plusbacin A3.
The total synthesis of plusbacin A3 (1) has been accomplished using a solvent-dependent diastereodivergent Joullié-Ugi three-component reaction (JU-3CR) as a key step. Two trans-3-hydroxy-l-proline residues were constructed by combining the JU-3CR with a convertible isocyanide strategy. Subsequent peptide coupling and macrolactamization afforded plusbacin A3. Investigating the antibacterial activity of 1 compared with that of its dideoxy analogue revealed that the threo-β-hydroxyaspartic acid residues are essential for antibacterial activity. Notably, there is a low potential for the development of resistance in S. aureus against plusbacin A3.


Induction chemotherapy in patients with resectable laryngeal cancer: A meta-analysis.
Head and neck squamous cell carcinoma (SCC) ranks 6th among the most frequently diagnosed carcinomas globally. Laryngeal carcinoma is quite common, and 95% of the cases are SCCs. Since the introduction of larynx-preserving surgery, induction chemotherapy (IC) has played a substantial role. The aim of IC is to shrink or downstage primary laryngeal carcinomas, increasing the chances of complete surgical removal, particularly in cases with advanced but potentially resectable lesions. The aim of the present study was to investigate the value of IC in patients with resectable laryngeal cancer. A meta-analysis was performed of randomized controlled trials (1985-2017) investigating the effect of IC on survival, disease control, larynx-preserving surgery and disease-free survival. Engauge-Digitizer software was used to construct Kaplan-Meier curves and RevMan software was used for the analysis of the data. A total of 12 trials (4,320 patients) were included. There was no significant difference in local recurrence or locoregional control between patients receiving and those not receiving IC (P>0.05). However, the experimental group (IC) exhibited a lower propensity for distant metastasis by 11.7% (95% confidence interval: 10.3-13.3%, P=0.02) compared with the control group (no IC). Among patients with laryngeal cancer, larynx preservation was possible in those who responded well to IC, without a significant decrease in survival compared with radical surgery (P<0.05). Taking into consideration these findings, IC confers an advantage in terms of lowering the risk of distant metastasis in patients with resectable laryngeal carcinoma, and enables laryngeal preservation in responders. Moreover, IC increases the overall survival rate in patients with locally advanced but resectable LC.


[Optodan: a new-generation laser semiconductor physiotherapeutic device].
The design of a new-generation semiconductor laser with automated operate is described (wavelength 0.85 to 0.95 mm, power up to 4 W, frequency 0.1 to 3 kHz) and potentialities of its use for laser physio- and reflex therapy of stomatological and general somatic diseases after the authors (patented and certified) methods outlined, including computer-aided laser systems for the differential diagnosis and treatment.


Parthenolide induces apoptosis via TNFRSF10B and PMAIP1 pathways in human lung cancer cells.
Parthenolide (PTL) is a sesquiterpene lactone which can induce apoptosis in cancer cells and eradicate cancer stem cells such as leukemia stem cells, prostate tumor-initiating cells and so on. However, the mechanism remains largely unclear. Lung cancer cells were treated with parthenolide and the cell lysates were prepared to detect the given proteins by Western Blot analysis, and the cell survival was assayed by SRB and MTT assay. Cell cycle was evaluated by DNA flow cytometry analysis. TNFRSF10B, PMAIP1, ATF4 and DDIT3 genes were knocked down by siRNA technique. Apoptosis was evaluated by using Annexin V-FITC/PI staining and flow cytometry analysis. Parthenolide (PTL) induces apoptosis and cell cycle arrest in human lung cancer cells. Moreover, PTL treatment in NSCLC cells increases expression of TNFRSF10B/DR5 and PMAIP1/NOXA. Silencing of TNFRSF10B or PMAIP1 or overexpression of CFLAR /c-FLIP (long form) could protect cells from PTL-induced apoptosis. Furthermore, PTL could increase the levels of endoplasmic reticulum stress hallmarks such as ERN1, HSPA5, p-EIF2A, ATF4 and DDIT3. Knockdown of ATF4 and DDIT3 abrogated PTL-induced apoptosis, which suggested that PTL induced apoptosis in NSCLC cells through activation of endoplasmic reticulum stress pathway. More importantly, we found that ATF4, DDIT3, TNFRSF10B and PMAIP1 were up-regulated more intensively, while CFLAR and MCL1 were down-regulated more dramatically by PTL in A549/shCDH1 cells than that in control cells, suggesting that PTL preferred to kill cancer stem cell-like cells by activating more intensive ER stress response in cancer stem cell-like cells. We showed that parthenolide not only triggered extrinsic apoptosis by up-regulating TNFRSF10B and down-regulating CFLAR, but also induced intrinsic apoptosis through increasing the expression of PMAIP1 and decreasing the level of MCL1 in NSCLC cells. In addition, parthenolide triggered stronger ER stress response in cancer stem cell-like cells which leads to its preference in apoptotic induction. In summary, PTL induces apoptosis in NSCLC cells by activating endoplasmic reticulum stress response.


How smartphone usage correlates with social anxiety and loneliness.
Early detection of social anxiety and loneliness might be useful to prevent substantial impairment in personal relationships. Understanding the way people use smartphones can be beneficial for implementing an early detection of social anxiety and loneliness. This paper examines different types of smartphone usage and their relationships with people with different individual levels of social anxiety or loneliness. A total of 127 Android smartphone volunteers participated in this study, all of which have agreed to install an application (MobileSens) on their smartphones, which can record user's smartphone usage behaviors and upload the data into the server. They were instructed to complete an online survey, including the Interaction Anxiousness Scale (IAS) and the University of California Los Angeles Loneliness Scale (UCLA-LS). We then separated participants into three groups (high, middle and low) based on their scores of IAS and UCLA-LS, respectively. Finally, we acquired digital records of smartphone usage from MobileSens and examined the differences in 105 types of smartphone usage behaviors between high-score and low-score group of IAS/UCLA-LS. Individuals with different scores on social anxiety or loneliness might use smartphones in different ways. For social anxiety, compared with users in low-score group, users in high-score group had less number of phone calls (incoming and outgoing) (Mann-Whitney U = 282.50∼409.00, p < 0.05), sent and received less number of text messages in the afternoon (Mann-Whitney U = 391.50∼411.50, p < 0.05), used health & fitness apps more frequently (Mann-Whitney U = 493.00, p < 0.05) and used camera apps less frequently (Mann-Whitney U = 472.00, p < 0.05). For loneliness, users in low-score group, users in high-score group had less number of phone calls (incoming and outgoing) (Mann-Whitney U = 305.00∼407.50, p < 0.05) and used following apps more frequently: health & fitness (Mann-Whitney U = 510.00, p < 0.05), system (Mann-Whitney U = 314.00, p < 0.01), phone beautify (Mann-Whitney U = 385.00, p < 0.05), web browser (Mann-Whitney U = 416.00, p < 0.05) and social media (RenRen) (Mann-Whitney >U = 388.50, p < 0.01). The results show that individuals with social anxiety or loneliness receive less incoming calls and use healthy applications more frequently, but they do not show differences in outgoing-call-related features. Individuals with higher levels of social anxiety also receive less SMSs and use camera apps less frequently, while lonely individuals tend to use system, beautify, browser and social media (RenRen) apps more frequently. This paper finds that there exists certain correlation among smartphone usage and social anxiety and loneliness. The result may be useful to improve social interaction for those who lack social interaction in daily lives and may be insightful for recognizing individual levels of social anxiety and loneliness through smartphone usage behaviors.


Adaptation of the Evidence-Based Practices Attitude Scale in Spanish child welfare professionals.
Implementation of evidence-based practices (EBPs) into real-world settings represents an organizational change that may be limited or facilitated by provider attitudes towards the adoption of new interventions and practices. The objective of the present study was to analyze psychometric properties of the Evidence Based Practices Attitude Scale (EBPAS) Spanish version in Child Welfare professionals. The EBPAS 50-item version was administered to a sample of professionals (N = 240) providing services to children/adolescents and their families in Child Welfare Services from three Spanish regions. Most of the dimensions measured by the EBPAS (50 items) were confirmed in the Spanish version administrated to Child Welfare professionals. Internal consistency reliabilities were fair to excellent. Provider attitudes varied by professional discipline and organizational context. The EBPAS Spanish version is an adequate instrument to be used as a measure of attitudes toward implementation of evidence-based practices.


Selective activation of Th1- and Th2-like cells in vivo--response to human collagen IV.
Mice immunized with human collagen IV develop either antibody responses or T-cell proliferative responses as a function of the MHC genotype of the immunized mice. CD4+ T cells, similar to Th1 and Th2 cells, participate in these two types of responses, with CD4+ T-cell proliferative responses associating with IL-2 and IFN gamma release, and antibody production associating with CD4+ T-cell IL-4 and IL-5 release. Thus it would appear that the same antigen can induce responses consistent with either cell-mediated or humoral immunity depending on MHC class II genotype. In attempting to understand how MHC genotype controls the class of immunity observed several models are discussed. It was proposed, based on results obtained upon priming with human collagen IV, that the activation of Th1 and Th2 responses may be regulated at several levels (presentation by different APCs, presentation of different densities of the T-cell receptor ligand and presentation of different T-cell epitopes). With the identification of the peptide recognized by the CD4+ T cells, it was clear that the inability to induce Th1 responses in H-2b and the inability to induce Th2 responses in H-2s could not be accounted for by the failure to generate an immunodominant peptide during processing or the failure of the peptides to bind to the MHC class II molecules. Furthermore, the difference in the type of response generated could not be explained by the use of different peptides of the human collagen IV molecule in the two mouse strains, as a single peptide will induce both types of CD4+ T-cell response. However, it cannot be ruled out that the a2 peptide-class II interaction forms different T-cell ligands in the two strains either because the two class II MHC molecules are different or that the peptide is processed and reveals a different antigenic activity (Fox et al. 1988). Perhaps the most important finding from the peptide studies is that the lack of proliferative response in H-2b mice is not absolute, but can be overcome either by priming with high doses of the a2 peptide or by increasing the amount of peptide needed to elicit a recall response. It seems reasonable to speculate that changes in the dose required for priming Th1 or Th2 responses may reflect differences in the activation requirements of the two types of cells with Th1 cells requiring a high ligand density and Th2 cells a low ligand density.(ABSTRACT TRUNCATED AT 400 WORDS)


Model system-bath Hamiltonian and nonadiabatic rate constants for proton-coupled electron transfer at electrode-solution interfaces.
An extension of the Anderson-Newns-Schmickler model for electrochemical proton-coupled electron transfer (PCET) is presented. This model describes reactions in which electron transfer between a solute complex in solution and an electrode is coupled to proton transfer within the solute complex. The model Hamiltonian is derived in a basis of electron-proton vibronic states defined within a double adiabatic approximation for the electrons, transferring proton, and bath modes. The interaction term responsible for electronic transitions between the solute complex and the electrode depends on the proton donor-acceptor vibrational mode within the solute complex. This model Hamiltonian is used to derive the anodic and cathodic rate constants for nonadiabatic electrochemical PCET. The derivation is based on the master equations for the reduced density matrix of the electron-proton subsystem, which includes the electrons of the solute complex and the electrode, as well as the transferring proton. The rate constant expressions differ from analogous expressions for electrochemical electron transfer because of the summation over electron-proton vibronic states and the dependence of the couplings on the proton donor-acceptor vibrational motion. These differences lead to additional contributions to the total reorganization energy, an additional exponential temperature-dependent prefactor, and a temperature-dependent term in the effective activation energy that has different signs for the anodic and cathodic processes. This model can be generalized to describe both nonadiabatic and adiabatic electrochemical PCET reactions and provides the framework for the inclusion of additional effects, such as the breaking and forming of other chemical bonds.


The Impact of Transition Readiness and Stress on Patient-Centered Outcomes in Young Adults With Inflammatory Bowel Disease.
Young adults, 18-35 years of age, account for nearly half of all inflammatory bowel disease emergency department visits annually, costing millions of healthcare dollars and signifying undue pain and suffering. To mitigate this sequela, the study aimed to characterize the relationships between transition readiness (self-management ability), stress, and patient-centered outcomes. Outcomes were defined as disease activity and inflammatory bowel disease-related healthcare utilization (emergency department visits and inpatient hospitalization). This was a descriptive, correlational design via online survey of young adults with inflammatory bowel disease. Participants (n = 284) utilized an estimated 2.77 million healthcare dollars in 12 months. Transition readiness decreased the odds of having consistently active disease and healthcare utilization, with adjusted odds ratio ranging from 6.4 to 10.9 (p < .05). Higher stress levels increased the odds of having consistently active disease and healthcare utilization, with adjusted odds ratio ranging from 9.5 to 10.5 (p < .0001). Twenty-five percent (24.7%) of the variation in transition readiness was explained by changes in stress (p < .0001). Transition readiness and stress impacted all patient-centered outcomes. Stress negatively impacted transition readiness. These results are powerful reminders for healthcare providers to assess and treat stress and support transition readiness in young adults with inflammatory bowel disease. The potential to decrease pain, suffering, and healthcare cost is enormous.


Prognostic factors in second-line targeted therapy for metastatic clear-cell renal cell carcinoma after progression on an anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor.
About 40% of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients receive a second-line targeted therapy after failure of anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKI). Efficacy of second-line therapy is usually limited and prognostic and predictive factors at the start of second-line therapy are lacking. To identify the subgroup of patients that will benefit from such treatment remains a challenge. We performed a multi-institutional, retrospective study of patients who received a second-line therapy after progression on an anti-VEGFR-TKI. Univariate and multivariate analyses were performed in order to identify prognostic factors for progressive disease (PD) as best response, progression-free survival (PFS) and overall survival (OS) on second-line therapy. For the whole cohort of 108 patients, mOS from the start of second-line therapy was 8.9 months while mPFS on second-line therapy was 2.8 months. A total of 49/105 (47%) patients had PD, 50/105 (48%) stable disease (SD) and 6/105 (6%) a partial response (PR). On multivariate analysis, the following markers were associated with improved outcome on second-line therapy: a PFS on first-line therapy ≥12 months (HR for PFS: 1.961; p = 0.008) (HR for OS: 1.724; p = 0.037) and Fuhrman grade 1-2 tumors (HR for OS: 2.198; p = 0.007). Markers associated with poorer outcome on second-line therapy were: elevated serum lactate dehydrogenase (LDH) levels (HR for PFS: 0.511; p = 0.04) (HR for OS: 0.392; p = 0.017), low albumin (HR for OS: 0.392; p = 0.01) and elevated corrected calcium levels (HR for OS: 0.416; p = 0.01). The impact on OS of the Memorial Sloan Kettering Cancer Centre (MSKCC) and International Renal Cell Carcinoma Database Consortium (IMDC) prognostic scores as calculated at start of second-line therapy was validated in our patient series. Duration of first-line PFS, Fuhrman grade, serum LDH levels, albumin levels, corrected calcium levels and the MSKCC and IMDC scores calculated at start of second-line therapy are prognostic factors for m-ccRCC patients treated with second-line targeted therapy.


High-altitude illness: updates in prevention, identification, and treatment.
High-altitude illness is a continuum of syndromes that includes the potential for death. Understanding how to prevent altitude illness and how to treat it if it occurs is fundamental to trip planning and is an important role of medical advisors to travelers. Gradual ascent, along with pharmacotherapy where indicated, are the mainstays of prevention. Travelers with certain chronic medical conditions may require additional pretravel counseling and preparation. Diagnostic recognition of the differing manifestations of high-altitude illness as well as recommendations on appropriate therapeutic options are discussed in detail.


Decontamination Methods for Reuse of Filtering Facepiece Respirators.
The novel coronavirus disease 2019 (COVID-19) has proven to be highly infectious, putting health care professionals around the world at increased risk. Furthermore, there are widespread shortages of necessary personal protective equipment (PPE) for these individuals. Filtering facepiece respirators, such as the N95 respirator, intended for single use, can be reused in times of need. We explore the evidence for decontamination or sterilization of N95 respirators for health care systems seeking to conserve PPE while maintaining the health of their workforce. The filtration properties and fit of N95 respirators must be preserved to function adequately over multiple uses. Studies have shown that chemical sterilization using soap and water, alcohols, and bleach render the respirator nonfunctional. Decontamination with microwave heat and high dry heat also result in degradation of respirator material. UV light, steam, low-dry heat, and commercial sterilization methods with ethylene oxide or vaporized hydrogen peroxide appear to be viable options for successful decontamination. Furthermore, since the surface viability of the novel coronavirus is presumed to be 72 hours, rotating N95 respirator use and allowing time decontamination of the respirators is also a reasonable option. We describe a protocol and best practice recommendations for redoffing decontaminated N95 and rotating N95 respirator use. COVID-19 presents a high risk for health care professionals, particularly otolaryngologists, owing to the nature of viral transmission, including possible airborne transmission and high viral load in the upper respiratory tract. Proper PPE is effective when used correctly, but in times of scarce resources, institutions may turn to alternative methods of preserving and reusing filtering facepiece respirators. Based on studies conducted on the decontamination of N95 respirators after prior outbreaks, there are several options for institutions to consider for both immediate and large-scale implementation.


Young children's beliefs about self-disclosure of performance failure and success.
Self-disclosure of performance information involves the balancing of instrumental, learning benefits (e.g., obtaining help) against social costs (e.g., diminished reputation). Little is known about young children's beliefs about performance self-disclosure. The present research investigates preschool- and early school-age children's expectations of self-disclosure in different contexts. In two experiments, 3- to 7-year-old children (total N = 252) heard vignettes about characters who succeeded or failed at solving a puzzle. Both experiments showed that children across all ages reasoned that people are more likely to self-disclose positive than negative performances, and Experiment 2 showed that children across all ages reasoned that people are more likely to self-disclose both positive and negative performances in a supportive than an unsupportive peer environment. Additionally, both experiments revealed changes with age - Younger children were less likely to expect people to withhold their performance information (of both failures and successes) than older children. These findings point to the preschool ages as a crucial beginning to children's developing recognition of people's reluctance to share performance information.


Comparison of multiple doses of cyclosporine A on germ cell apoptosis and epididymal sperm parameters after testicular ischemia/reperfusion in rats.
Testicular torsion/detorsion (T/D) is an inflammatory problem in men genital system with infertility effects. Cyclosporine A (CsA) as an immunosuppressant medication, exerts anti-inflammatory properties in tissue injuries. We sought to compare the efficacy of 3 doses of CsA on oxidative stress, apoptosis and epididymal sperm quality after ipsilateral testicular T/D. 96 mature male rats were divided into six groups 16 each in: Control group (Group1), Sham operated (Group2), In rest groups, the right testis was twisted 720° in a clockwise direction for 1 h; T/D + 0.1% dimethylsulfoxide) DMSO((Group3), and in groups 4-6; CsA were administered 1, 5, and 10 mg/kg, intravenously (iv) 30 and 90 min after torsion, respectively. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities decreased in compared with control group 4 h after detorsion (p < .001). In six rats of each group 24 h after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by determining mean of seminiferous tubules diameters (MSTD) and TUNEL assay. Moreover, 30 days after T/D, sperm concentration and motility were examined in rest of animals. Pre- and post-reperfusion CsA diminished MDA and caspase-3levels and normalized antioxidant enzymes activities. Germ cell apoptosis was significantly reduced, as well as, MSTD and long-term sperm insults were improved. Inhibition of mitochondrial permeability transition pore opening is suggested mechanism for cell protection against testicular T/D insults.


The course of age-related macular degeneration following bilateral cataract surgery.
Progression of age-related macular degeneration (AMD) following cataract surgery has been described. The aim of this study was to investigate whether an uneventful postoperative maculopathic course in one eye (the first eye) may predict a similar prognosis for the fellow eye (the second eye). Thirty-three patients with bilateral, similar, early AMD (defined by the presence of drusen and/or pigmentary abnormalities on fundal examinations and by the absence of late leakage as documented by fluorescein angiography) who had undergone unilateral cataract surgery, had had a stable postoperative maculopathic course following the first operation, and were scheduled for cataract surgery in the second eye were prospectively observed for at least 1 year after the second operation. The course of maculopathy of the second eye was compared with that of the first eye during the follow-up period of the second eye. A total of 9 of the second eyes (27.2%) showed progression to wet AMD. Of these, 1 patient (3%) had progression in both eyes and 8 patients (24.2%) had progression in the second eye only. The conditions of 2 of the first operated on eyes (6.1%) deteriorated (P < .05). Hypertension (P < .05), soft drusen (P < .01), and Nd:YAG laser capsulotomy (P < .05) were risk factors for development of wet AMD. In this study, 24.2% of the patients with early AMD who underwent bilateral cataract surgery and had an uneventful maculopathic course in the first eye had wet AMD in the second eye. Thus, patients with early AMD and soft drusen undergoing bilateral cataract surgery should be monitored for early detection of progression of maculopathy. Further prospective studies are needed to determine the course of maculopathy following cataract surgery.


Relationship of distraction rate with inferior alveolar nerve degeneration-regeneration shift.
Distraction osteogenesis is an important technique for the treatment of maxillofacial abnormities and defects. However, distraction osteogenesis may cause the injury of the inferior alveolar nerve. The relationship between distraction rate and nerve degeneration-regeneration shift remains poorly understood. In this study, 24 rabbits were randomly divided into four groups. To establish the rabbit mandibular distraction osteogenesis model, the mandibles of rabbits in distraction osteogenesis groups were subjected to continuous osteogenesis distraction at a rate of 1.0, 1.5 and 2.0 mm/d, respectively, by controlling rounds of screwing each day in the distractors. In the sham group, mandible osteotomy was performed without distraction. Pin-prick test with a 10 g blunt pin on the labium, histological and histomorphometric analyses with methylene blue staining, Bodian's silver staining, transmission electron microscopy and myelinated fiber density of inferior alveolar nerve cross-sections were performed to assess inferior alveolar nerve conditions. At 28 days after model establishment, in the pin-prick test, the inferior alveolar nerve showed no response in the labium to a pin pricks in the 2 mm/d group, indicating a severe dysfunction. Histological and histomorphometric analyses indicated that the inferior alveolar nerve suffered more degeneration and injuries at a high distraction rate (2 mm/d). Importantly, the nerve regeneration, indicated by newborn Schwann cells and axons, was more abundant in 1.0 and 1.5 mm/d groups than in 2.0 mm/d group. We concluded that the distraction rate was strongly associated with the inferior alveolar nerve function, and the distraction rates of 1.0 and 1.5 mm/d had regenerative effects on the inferior alveolar nerve. This study provides an experimental basis for the relationship between distraction rate and nerve degeneration-regeneration shift during distraction osteogenesis, and may facilitate reducing nerve complications during distraction osteogenesis.


Club cell secretory protein and lung function in children with cystic fibrosis.
Club cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF). We used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment. Circulating levels of CC16 and an inflammatory score (generated from CRP, SAA, calprotectin, G-CSF) were compared between participants with the lowest and highest FEV1 levels in adolescence (LLF and HLF groups, respectively; N = 130-per-group). Single nucleotide variants (SNVs) in the SCGB1A1, EHF-APIP loci were tested for association with circulating CC16 and with decline of FEV1 and FEV1/FVC% predicted levels between ages 7-16 using mixed models. Compared with the HLF group, the LLF group had lower levels of CC16 (geometric means: 8.2 vs 6.5 ng/ml, respectively; p = 0.0002) and higher levels of the normalized inflammatory score (-0.21 vs 0.21, p = 0.0007). Participants in the lowest CC16 and highest inflammation tertile had the highest odds for having LLF (p<0.0001 for comparison with participants in the highest CC16 and lowest inflammation tertile). Among seven SNVs associated with circulating CC16, the top SNV rs3741240 was associated with decline of FEV1/FVC and, marginally, FEV1 (p = 0.003 and 0.025, respectively; N = 611 participants, 20,801 lung function observations). Serum CC16 deficits are strongly associated with severity of CF lung disease and their effects are additive with systemic inflammation. The rs3741240 A allele is associated with low circulating CC16 and, possibly, accelerated lung function decline in CF.


Semistochastic Heat-Bath Configuration Interaction Method: Selected Configuration Interaction with Semistochastic Perturbation Theory.
We extend the recently proposed heat-bath configuration interaction (HCI) method [Holmes, Tubman, Umrigar, J. Chem. Theory Comput. 2016, 12, 3674], by introducing a semistochastic algorithm for performing multireference Epstein-Nesbet perturbation theory, in order to completely eliminate the severe memory bottleneck of the original method. The proposed algorithm has several attractive features. First, there is no sign problem that plagues several quantum Monte Carlo methods. Second, instead of using Metropolis-Hastings sampling, we use the Alias method to directly sample determinants from the reference wave function, thus avoiding correlations between consecutive samples. Third, in addition to removing the memory bottleneck, semistochastic HCI (SHCI) is faster than the deterministic variant for many systems if a stochastic error of 0.1 mHa is acceptable. Fourth, within the SHCI algorithm one can trade memory for a modest increase in computer time. Fifth, the perturbative calculation is embarrassingly parallel. The SHCI algorithm extends the range of applicability of the original algorithm, allowing us to calculate the correlation energy of very large active spaces. We demonstrate this by performing calculations on several first row dimers including F2 with an active space of (14e, 108o), Mn-Salen cluster with an active space of (28e, 22o), and Cr2 dimer with up to a quadruple-ζ basis set with an active space of (12e, 190o). For these systems we were able to obtain better than 1 mHa accuracy with a wall time of merely 55 s, 37 s, and 56 min on 1, 1, and 4 nodes, respectively.


Astrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity.
To determine how astrocytic leptin signaling regulates the physiological response of mice to diet-induced obesity (DIO), we performed metabolic analyses and hypothalamic leptin signaling assays on astrocytic leptin-receptor knockout (ALKO) mice in which astrocytes lack functional leptin receptor (ObR) signaling. ALKO mice and wild-type (WT) littermate controls were studied at different stages of DIO with measurement of body wt, percent fat, metabolic activity, and biochemical parameters. When fed regular chow, the ALKO mice had similar body wt, percent fat, food intake, heat dissipation, respiratory exchange ratio, and activity as their WT littermates. There was no change in blood concentrations of triglyceride, soluble leptin receptor (sObR), mRNA for leptin and uncoupling protein 1 (UCP1) in adipose tissue, and insulin sensitivity. Unexpectedly, in response to a high-fat diet the ALKO mice had attenuated hyperleptinemia and sObR, a lower level of leptin mRNA in subcutaneous fat, and a paradoxical increase in UCP1 mRNA. Thus, ALKO mice did not show the worsening of obesity that occurs with normal WT mice and the neuronal ObR mutation that results in morbid obesity. The findings are consistent with a competing, counterregulatory model between neuronal and astrocytic leptin signaling.


The impact of obesity on the male reproductive axis.
Obesity, defined as a body mass index (BMI) >30 kg/m2, has seen an important increase in prevalence in the last decades, not only in Europe and the United States, but also in developing countries. It is an established risk factor for numerous pathologic conditions like diabetes mellitus, cardiovascular diseases and cancer, but has also been linked to male hypogonadism. Several studies showed a negative impact of excessive BMI on testosterone levels, sexual function and sperm parameters. Possible mechanisms beyond this phenomenon are reduced hypothalamic and pituitary secretory function, excess estrogen production and reduced circulating sex-hormone binding globulin (SHBG). Peptides produced by the adipocyte may also trigger modifications of the reproductive function. Independently of the method used, non-surgical approach or bariatric techniques, weight reduction and a return to a normal BMI have been associated with improvement in the sexual function and levels of sexual hormones in obese males, showing that obesity related hypogonadism is preventable. Sexual and reproductive health might represent additional motivational factors for men in order to maintain a healthy life-style.


Transcription factor CASZ1 increases an oncogenic transcriptional process in tumorigenesis and progression of glioma cells.
As a transcription factor, the role of CASZ1 in different entities is inconsistent. Glioma is one of the leading causes of cancer death worldwide. Its prognostic relevance and biological functions in glioma remain obscure. We focused on the role, mechanism, and prognostic value of CASZ1 in glioma cells. Herein, CASZ1 was identified as a novel potential oncogene in glioma tissues from GEO and TCGA datasets. CASZ1 was highly expressed in glioma tissues, predicting poor prognosis in glioma patients. Knockdown of CASZ1 inhibited proliferation and invasion in vitro, whereas upregulation of CASZ1 presented opposite results. Overexpression of CASZ1 increased transcriptional process of target gene p75NTR. CASZ1 was the potential transcriptional regulators for p75NTR. In addition, the p75NTR expression is essential for CASZ1 to exert its function as an oncogene. Our findings indicate that highly expressed CASZ1 in glioma cells acts as a pro-oncogene factor in gliomas via regulating transcriptional process of target gene p75NTR, which was identified as an unfavorable prognostic marker in patients with gliomas. CASZ1 is expected to become a novel target for the treatment of gliomas.


Occult glucose intolerance: incidence in a general population.
A survey of two-hour postprandial glycemic responses to an oral dose of 100 gm of glucose was conducted in 456 appparently healthy adult members of a small Southern California community. Serum glucose levels of 32 per cent of the men and 36 per cent of the women exceeded 140 mg per 100 ml at the two-hour sampling period. In both sexes, there was a tendency for hyperglycemia to become more conspicuous with age. Under the age of 50, a much higher percentage of women than men had seemingly excessive serum glucose values. These findings may suggest a need for modifying criteria currently used for interpreting glycemic responses to oral glucose challenges.


Effect of glecaprevir/pibrentasvir on weight-adjusted tacrolimus trough/dose ratios in heart and kidney transplant recipients.
The pharmacokinetic implications of direct-acting antiviral (DAA) use on tacrolimus posttransplant are unknown. This study sought to investigate the effects of glecaprevir/pibrentasvir (G/P), a CYP3A4 substrate and inhibitor, on weight-adjusted tacrolimus (FK) trough/dose ratio (T/D) following heart or kidney transplantation. This was a single-center, retrospective analysis of hepatitis C virus (HCV) viremic donors to HCV negative heart or kidney transplant recipients who received 12 weeks of G/P therapy. Weight-adjusted T/D was assessed while patients were at steady-state before, during, and after G/P treatment. Forty-one HCV negative recipients (three heart, 38 kidney) were evaluated. The weight-adjusted T/D significantly increased during G/P treatment (119.31, IQR 88-173.8) compared to before G/P treatment (67.4, IQR 53.4-115.9) (p < 0.01), but decreased after completion of treatment (90.1, IQR 52.9-122.7) (p < 0.01). There was no difference in weight-adjusted T/D before and after G/P treatment (p = 0.42). Four patients experienced acute rejection. Initiation of G/P in heart or kidney transplant recipients induces a reversible change in tacrolimus metabolism. A 33%-50% tacrolimus dose reduction may be considered at the time of G/P initiation. Regardless of tacrolimus dose adjustment, tacrolimus trough levels should be monitored 3 days after initiation of G/P. No clear relationship between HCV viremic organ transplantation and rejection risk was found. Larger studies are warranted to validate these findings.


Investigation of the uterine cavity in recurrent aborters.
To prospectively compare the diagnostic ability of both HSG and diagnostic hysteroscopy in recurrent aborters, an HSG followed by a diagnostic hysteroscopy was performed in 106 patients during an investigation into recurrent abortions. The uterine cavity findings on HSG and at hysteroscopy were compared. Among the 60 abnormal HSG patients, intrauterine pathology was demonstrated in 37 (34.9%). Among the 46 normal HSG patients, a normal uterine cavity was found in 33 (31.3%). The sensitivity of the HSG in revealing intrauterine abnormalities was therefore 79% and its specificity 60%. In 23 pathologic HSG, no abnormalities were seen by hysteroscopy. In 13 cases, hysteroscopy demonstrated mild intrauterine findings overlooked by HSG. The false-positive rate was 38% and the false-negative rate was 28%. Hysterosalpingography showed a high false-positive rate, especially in the intrauterine adhesions group. In view of the low specificity and high false-positive and false-negative rates, we believe that hysteroscopic evaluation of the uterine cavity is superior to HSG in recurrent abortions.


Corticotropin-releasing hormone stimulation test before and after transsphenoidal selective microadenomectomy in 30 patients with Cushing's disease.
Thirty patients with ACTH-dependent Cushing's disease were tested with CRH before and 7-10 days and 3-6 months after selective transsphenoidal adenomectomy. In 28 of 30 patients an adenoma was found, and in 22 (79%) clinical and endocrinological remission occurred. Preoperatively, the majority of the patients had basal and CRH-stimulated plasma ACTH levels that were markedly increased compared to those in normal subjects. On the basis of the CRH stimulation test and low dose (2 mg) dexamethasone suppression test results 7-10 days after surgery, these 30 patients were divided into 4 groups. Groups I, II, and III were patients in remission, as defined by undetectable, subnormal, or normal basal plasma ACTH and cortisol levels in addition to sufficient suppression of cortisol (less than 2 micrograms/dL) during the low dose (2 mg) dexamethasone suppression test. Patients in group IV were not in remission. In group I (n = 6), CRH failed to raise undetectable basal ACTH levels in the early postoperative period; however, 3-6 months later plasma ACTH did increase in response to CRH. In group II (n = 11), undetectable or low basal ACTH levels increased after CRH, and the increase was similar to that in normal individuals. In group III (n = 5), basal ACTH levels were normal, and the response to CRH was exaggerated, but all patients responded normally to the dexamethasone suppression test. The CRH-induced ACTH increase in group III was significantly greater (P less than 0.003) than that in normal subjects, but was similar to that in patients not in remission in group IV (n = 6). Three to 6 months later, the ACTH response to CRH in group III was normal. In summary, the CRH test 7-10 days after surgery in patients with Cushing's disease indicated remission when there was no CRH-induced ACTH response or the response was normal (groups I and II). The test failed to predict remission in patients with an exaggerated CRH-induced ACTH response (groups III and IV). However, with regard to group II, the CRH-induced ACTH increase 1 week after selective adenomectomy indirectly supports the concept of CRH deficiency during hypercorticism and thus, in these patients as well as in group I, a pituitary origin of the disease.


The mammalian ribonucleotide reductase R2 component cooperates with a variety of oncogenes in mechanisms of cellular transformation.
Ribonucleotide reductase, which is composed of the two protein components R1 and R2, is a highly regulated enzyme activity that is essential for DNA synthesis and repair. Recent studies have shown that elevated expression of the rate-limiting R2 component increases Raf-1 protein activation and mitogen-activated protein kinase activity and acts as a novel malignancy determinant in cooperation with H-ras and rac-1. We show that R2 cooperation in cellular transformation extends to a variety of oncogenes with different functions and cellular locations. Anchorage-independent growth of cells transformed with v-fms, v-src, A-raf, v-fes, c-myc, and ornithine decarboxylase was markedly enhanced when the R2 component of ribonucleotide reductase was overexpressed. In addition, we observed that elevated R2 expression conferred on c-myc-transformed NIH 3T3 cells an increased tumorigenic potential in immunoincompetent mice. Taken together, these observations demonstrate that the R2 protein is not only a rate-limiting component for ribonucleotide reduction but that it is also capable of acting in cooperation with a variety of oncogenes to determine transformation and tumorigenic potential.


Theoretical study of the He-HF+ complex. I. The two asymptotically degenerate ground state potential energy surfaces.
Two three-dimensional potential energy surfaces (PESs) are reported for the cationic complex He-HF+; they are degenerate for linear geometries of the complex and correlate with the doubly degenerate X2Pi ground state of the HF+monomer. The PESs are computed from the interaction energies of the neutral dimer and the ionization potentials of the He-HF complex and the HF molecule. Ionization potentials are obtained from the outer valence Green's function (OVGF) method, while the energies of the neutral species are computed by means of the single and double coupled-cluster method with perturbative triples [CCSD(T)]. For comparison, interaction energies of the ionic complex were computed also by the use of the partially spin-restricted variant of the CCSD(T) method. After asymptotic scaling of the OVGF results, good agreement is found between the two methods. A single global minimum is found in the PES, for the linear He-HF+ geometry. The well depth and equilibrium separation are 2.240 A and 1631.3 cm(-1), respectively, at an HF+ bond length r=1.0012 A, in rather good agreement with results of Schmelz and Rosmus [Chem. Phys. Lett. 220, 117 (1994)]. The well depth depends much more strongly on the internuclear H-F separation than in the neutral He-HF complex and the global minimum in a full three-dimensional PES occurs at r=1.0273 A.


Isolation of two polyketide synthase gene fragments from the uncultured microbial symbiont of the marine bryozoan Bugula neritina.
"Candidatus Endobugula sertula," the uncultured microbial symbiont of the bryozoan Bugula neritina, produces ecologically and biomedically important polyketide metabolites called bryostatins. We isolated two gene fragments from B. neritina larvae that have high levels of similarity to polyketide synthase genes. These gene fragments are clearly associated with the symbiont and not with the host.


An examination of pre- and postsynaptic alpha-adrenoceptors in the autoperfused rabbit hindlimb.
Pre- and postsynaptic alpha-adrenoceptors in autoperfused rabbit hindlimbs were examined employing the yohimbine diastereomers rauwolscine and corynanthine, as well as other drugs with varying selectivities for alpha 1-and alpha 2-adrenoceptors. Vasoconstrictor responses were elicited by sympathetic nerve stimulation and by intraarterial injection of agonists. The alpha 2-selective antagonist rauwolscine (10(-7) and 10(-6) M) reduced responses to injected noradrenaline (mixed alpha 1- and alpha 2-agonist) but not to injected phenylephrine (alpha 1-selective agonist); rauwolscine (10(-6) M) actually enhanced nerve-mediated responses. Corynanthine (alpha 1-selective antagonist) was about equipotent against agonist- and nerve-mediated responses. In another series of experiments, rauwolscine (10(-6) M) strongly antagonized the response to xylazine (alpha 2-selective agonist), antagonized the responses to alpha-methylnoradrenaline and noradrenaline (mixed agonists) less strongly, and did not affect the response to phenylephrine, Conversely, prazosin (alpha 1-selective antagonist, 10(-8) M) strongly antagonized phenylephrine, antagonized noradrenaline and alpha-methylnoradrenaline less strongly, and did not antagonize xylazine. Potentiation of neuroeffector responses by rauwolscine demonstrates the operation of an endogenous autoinhibition of noradrenaline release mediated by presynaptic alpha 2-adrenoceptors. However, in comparison with previous in vitro results on rabbit pulmonary artery, the potentiation was small due to the presence of postsynaptic alpha 2-adrenoceptors.


Invasive lobular carcinoma stable for 4.5 years in a postmenopausal woman user of hormone therapy for 25 years.
We present a case of a 72-year-old woman referred to the breast disorder service due to abnormalities on mammography and breast ultrasound. The patient reported using different hormone therapy (HT) formulations during 25 years and had stopped taking HT for 4 years. Physical examination showed no alterations in the breasts or axilla. Mammography from 2012 detected asymmetry at the 3 o'clock position in the anterior right breast. Ultrasound revealed an irregular, hypoechoic mass with indistinct margins, and posterior acoustic shadowing. A retrospective analysis of mammographies from 2007, 2009 and 2010 showed that a very subtle asymmetry had existed since 2007. Follow-up imaging demonstrated no change in asymmetry during 4.5 years. The patient underwent breast-conserving therapy and sentinel lymph node biopsy. Histopathologic examination demonstrated classic invasive lobular carcinoma. There were no sentinel node metastases. The patient received radiotherapy and endrocrine therapy. This case demonstrates that breast cancer may remain stable and not grow for many years. This aspect should be kept in mind by all professionals dealing with women's healthcare, in particular HT users who may develop breast cancer with a less aggressive behavior. Any suspicious finding on mammography, despite being unchanged for a number of years, must be investigated.


Genome Sequence of Arthrobacter sp. Phage Scuttle.
Arthrobacter phage Scuttle was isolated by enrichment from a dry soil sample (collected in Upper Darby, Pennsylvania) on host Arthrobacter sp. ATCC 21022. The genome of this phage is 43,729 bp long, has a GC content of 61.1%, and has 61 annotated protein-coding genes.


Development and Evaluation of a Novel Set of EST-SSR Markers Based on Transcriptome Sequences of Black Locust (Robinia pseudoacacia L.).
Black locust (Robinia pseudoacacia L. of the family Fabaceae) is an ecologically and economically important deciduous tree. However, few genomic resources are available for this forest species, and few effective expressed sequence tag-derived simple sequence repeat (EST-SSR) markers have been developed to date. In this study, paired-end sequencing was used to sequence transcriptomes of R. pseudoacacia by the Illumina HiSeq TM2000 platform, and EST-SSR loci were identified by de novo assembly. Furthermore, a total of 1697 primer pairs were successfully designed, from which 286 primers met the selection screening criteria; 94 pairs were randomly selected and tested for validation using polymerase chain reaction amplification. Forty-five primers were verified as polymorphic, with clear bands. The polymorphism information content values were 0.033-0.765, the number of alleles per locus ranged from 2 to 10, and the observed and expected heterozygosities were 0.000-0.931 and 0.035-0.810, respectively, indicating a high level of informativeness. Subsequently, 45 polymorphic EST-SSR loci were tested for amplification efficiency, using the verified primers, in an additional nine species of Leguminosae, 23 loci were amplified in more than three species, of which two loci were amplified successfully in all species. These EST-SSR markers provide a valuable tool for investigating the genetic diversity and population structure of R. pseudoacacia, constructing a DNA fingerprint database, performing quantitative trait locus mapping, and preserving genetic information.


A female infant with duplication of chromosome 2q33 to 2q37.3.
We report a 13-month-old female child with a de-novo inverted duplication of chromosome 2q extending from 2q33 to 2q37.3. She had microcephaly and craniofacial dysmorphism compatible with previously reported cases with overlapping duplications of chromosome 2q. Although a facial phenotype for pure partial trisomy 2q3 has been described, some controversy still exists regarding possible band specificity for the facial findings. We consider this child provides further evidence for a recognizable facial appearance associated with duplication of chromosome band 2q33 to 2q37.3. Other clinical features found with duplication for chromosome 2q3 have been variable and we provide a summary of the findings in previously reported cases.


Violence against nurses by patients and visitors in the emergency department: An integrative review.
This integrative review explored violence against emergency nurses by patients/visitors, examining its nature, contributing factors and consequences. Integrative review. Articles were obtained from PubMed, CINAHL, EMBASE, Web of Science and PsycInfo databases, up until December 2021. 26 articles were reviewed, evaluating study quality with the Crowe Critical Appraisal Tool and synthesizing conclusions through theme development and coding. This review delves into the issue of violence perpetrated against emergency nurses by patients and visitors. It elucidates three overarching themes: the nature of violence, the contributing factors and the consequences of such acts. The findings inform healthcare policy for the development of prevention approaches while identifying research gaps and emphasizing the need for alternative study designs and methodologies. This review has implications for nursing practice, policymaking and research, emphasizing the need for stakeholder engagement and tailored interventions for at-risk emergency nurses. This project was an integrative review of the literature therefore no patient or public contribution was necessary. Violence by patients and visitors in healthcare settings, especially in emergency departments, has garnered considerable attention. This review specifically examines violence-targeting emergency department nurses from patients and visitors, assessing its characteristics, contributing factors and consequences. The findings will guide stakeholder engagement in developing interventions to support vulnerable emergency nurses.


Studies in pericardial function. I. Cardiovascular effects of assisted ventilation, thoracotomy and pericardiectomy in the anesthetized dog.
In anesthetized dogs, initially breathing spontaneously, the effects of intermittent positive pressure ventilation (IPPV), thoractomy and pericardiectomy on cardiac function, pericardial-ventricular relationships and cardiopulmonary volumes were evaluated. After IPPV stroke volume and work decreased. After thoracotomy there was no further change in cardiac output or work. Pericardiectomy superimposed at this point had no clear-cut effect. End-diastolic transmural pressures (ventricular minus pericardial) and cardiopulmonary volumes were not altered at any stage of the study. In the ventilated open-chest dog the effects of IPPV are greater than those of thoracotomy, and the extent of the effects is related to the level of IPPV. With moderate IPPV and adequate ventilation, the systemic hypotension, marked decreases in cardiac output and reduction of heart volumes reported by previous investigators can be avoided. The removal of the pericardium does not appear to have any deleterious effect in the normal dog.


[Preoperative factors for the development of acute kidney injury after cardiac surgery: prospective study].
To evaluate the clinical characteristics and co-morbidities associated with development of Acute kidney injury (AKI) after cardiac surgery in patients of a predominantly tertiary care university hospital. One hundred and fifty cardiac surgery patients were prospectively studied at the Botucatu School of Medicine University Hospital - UNESP, using a protocol which started 48h before and finished 48h after surgery. AKI was defined as a 30% increase in baseline serum creatinine. Were expressed as mean +/- standard deviation or median, with a significance level of 5%. Results: There was a slight male predominance (57%); mean age of the studied population was 56+/-14 years. Sixty-five per cent of patients underwent myocardial revascularization. AKI was diagnosed in 34% of cases. Multivariate analysis showed that age over 60 years and peripheral vascular disease were significantly associated with AKI development. AKI was a common complication in cardiac surgery patients at this hospital. AKI was associated with age over 60 years and presence of peripheral vascular disease.


Fairness for Transgender People in Sport.
Increasingly visible participation by transgender people in athletic competition has resulted in efforts to include transgender women in the women's categories while addressing possible advantage they might have from exposure to typically male levels of testosterone. There does not seem to be any reason to expect advantage for transgender people prior to puberty of or for transgender people whose gender-affirming treatment begins at the onset of puberty. To date, the only established driver of athletic advantage in men over women is testosterone. Further, the existing literature suggests that treatment to lower testosterone may be sufficient to erase that advantage in at least some athletic activities. Whether other aspects of puberty are advantages or disadvantages in certain sports remains to be established. There is need for more research on the topic. In addition, there is a need to prioritize the need to motivate people to participate in sport for better health.


Flexible a-Si:H Solar Cells with Spontaneously Formed Parabolic Nanostructures on a Hexagonal-Pyramid Reflector.
Flexible amorphous silicon (a-Si:H) solar cells with high photoconversion efficiency (PCE) are demonstrated by embedding hexagonal pyramid nanostructures below a Ag/indium tin oxide (ITO) reflector. The nanostructures constructed by nanoimprint lithography using soft materials allow the top ITO electrode to spontaneously form parabolic nanostructures. Nanoimprint lithography using soft materials is simple, and is conducted at low temperature. The resulting structure has excellent durability under repeated bending, and thus, flexible nanostructures are successfully constructed on flexible a-Si:H solar cells on plastic film. The nanoimprinted pyramid back reflector provides a high angular light scattering with haze reflectance >98% throughout the visible spectrum. The spontaneously formed parabolic nanostructure on the top surface of the a-Si:H solar cells both reduces reflection and scatters incident light into the absorber layer, thereby elongating the optical path length. As a result, the nanopatterned a-Si:H solar cells, fabricated on polyethersulfone (PES) film, exhibit excellent mechanical flexibility and PCE increased by 48% compared with devices on a flat substrate.


Th0 cells in the thymus: the question of T-helper lineages.
Although peripheral naive cells only secrete IL-2 upon primary stimulation, their presumptive immediate precursors, HSAlow CD4+8- thymocytes, can produce a large amount of the set of lymphokines usually associated with preactivated or memory CD4+ lymphocytes: IL-4, IL-5, IL-10 and gamma-IFN. This phenotype can be attributed to true virgin thymocytes and not only to recirculating lymphocytes, because it is found in newborn thymuses and in fetal thymic organ culture. This mature stage of CD4+8- thymocytes is itself preceded by an immature stage (HSAhigh) where only IL-2 and small amounts of gamma-IFN can be elicited by the combination of calcium ionophore and phorbol ester, but not by TCR cross-linking. CD8+4- thymocytes pass through a similar immature HSAhigh stage, where their pattern of lymphokine secretion is not yet differentiated from that of CD4+8- HSA high thymocytes. The subsets acquire their specific profiles at the HSAlow stage. We propose that recent thymic CD4+8- emigrant cells include a significant proportion of Th0 type cells, and that their role is critical to prime the immune system for IL-4 production, as well as to explain the longstanding observations of synergy between helper cell subpopulations in the periphery.


Autoantibodies to tumor-associated antigens as diagnostic biomarkers in hepatocellular carcinoma and other solid tumors.
Liver cancer, especially hepatocellular carcinoma (HCC), is one of the most common tumors worldwide. The majority of people with HCC will die within 1 year of its detection. The high case-fatality rate can, in part, be attributed to a lack of diagnostic methods that enable the early detection of liver cancer. Hence, there is a need for further understanding of tumor biology and host response mechanisms so that new diagnostic and therapeutic tools can be developed. There has been a growing interest in using serum anti-tumor-associated antigen (TAA) antibodies as serological cancer biomarkers. This interest stems from the notion that these anti-TAA antibodies are 'sensors' or 'reporters' of molecular events associated with tumorigenesis. The persistence and stability of autoantibodies in the serum of cancer patients is an advantage over other potential markers, including the TAAs themselves, some of which are released by tumors but rapidly degrade or are cleared after circulating in the serum for a limited time. Furthermore, the widespread availability of methods and reagents to detect serum autoantibodies facilitates their characterization in cancer patients and assay development. The hypothesis is that 'customized' TAA arrays constitute promising and powerful tools for enhancing the serological anti-TAA antibody detection of cancer. The present review will focus on the recent advances in our studies primarily associated with the idea and possibility that autoantibodies to TAAs can be used as biomarkers in immunodiagnosis of HCC and other solid tumors.


Considerations for double-hand replantation in a resource-constrained healthcare facility.
Bilateral-hand amputation is extremely rare and double-hand replantation is even rarer. Only one case of successful double replantation at arm level has been reported from India. We present a case of double-hand replantation at proximal palmar level in a young adult executed in a small nursing home. The patient presented 5 h after injury with limbs preserved well in ice. There were difficulties in executing such an unusual case in a small nursing home set-up. The patient is performing his activities of daily living and basic functions independently. We share our experience of this double-hand replantation with special emphasis on problems encountered.


Admissions to substance use treatment facilities for cannabis use disorder, 2000-2017: Does legalization matter?
A growing number of US states have legalized marijuana use in the past decade. We examined if marijuana legalization is associated with increased marijuana-related admissions to substance use treatment facilities between 2000 and 2017. Data from the Treatment Episode Data Set-Admissions were used to examine the relationship between marijuana-related admissions among adults aged ≥18 by year and legalization status (i.e., fully legalized, medical use only [partially legalized], and illegal) (N = 35,457,854). Using interaction analyses, we further examined whether certain patient characteristics were associated with residence in states that legalized marijuana use as compared to those in which marijuana remained illegal. Overall, the proportion of marijuana-related admissions in states with legalization decreased by 2.3% from 31.7% in 2000-2005 to 29.4% in 2012-2017 (odds ratio [OR], 0.90; 95% confidence intervals [CI], 0.89-0.90) with little difference from states where marijuana use remained illegal, in which marijuana use as any reason for admissions decreased by 0.3% from 39.8% in 2000-2005 to 39.5% in 2012-2017 (OR, 0.99; 95% CI, 0.98-0.99). We did not find any striking patient characteristics (e.g., referral by the police) associated with admissions in states that legalized compared to those that had not. While earlier studies suggested that marijuana legalization is associated with increased levels of use, emergency department visits, and traffic fatalities, our findings suggest that marijuana legalization did not increase marijuana-related treatment use in the United States. This is the first study to examine the association of marijuana legalization with marijuana-related treatment use.


Noise pollution in metalwork and woodwork industries in the Kingdom of Saudi Arabia.
This study was conducted in metalwork and woodwork industries in Jeddah Industrial Estate. The purpose of this study was to assess the magnitude of industrial noise exposure and to propose remedial actions. Noise was measured at different times of a day in 28 randomly selected factories and workshops. Results indicated that noise levels varied according to the type and size of a factory, and the type and number of machines used. Mean noise levels in metalwork factories were higher than those in woodwork factories. The highest noise levels were observed while manufacturing cans and forming steel reinforcement for concrete, where noise levels exceed 90 dB(A). All mean noise levels in all studied metalwork factories and in 50% of studied woodwork industries were higher than the standard level of 85 dB(A).


Technological advancements in bio-recognition using liquid crystals: Techniques, applications, and performance.
The application of liquid crystal (LC) materials has undergone a modern-day renaissance from its classical use in electronics industry as display devices to new-fangled techniques for optically detecting biological and chemical analytes. This review article deals with the emergence of LC materials as invaluable material for their use as label-free sensing elements in the development of optical, electro-optical and electrochemical biosensors. The property of LC molecules to change their orientation on perturbation by any external stimuli or on interaction with bioanalytes or chemical species has been utilized by many researches for the fabrication of high sensitive LC-biosensors. In this review article we categorized LC-biosensor based on biomolecular reaction mechanism viz. enzymatic, nucleotides and immunoreaction in conjunction with operating principle at different LC interface namely LC-solid, LC-aqueous and LC-droplets. Based on bimolecular reaction mechanism, the application of LC has been delineated with recent progress made in designing of LC-interface for the detection of bio and chemical analytes of proteins, virus, bacteria, clinically relevant compounds, heavy metal ions and environmental pollutants. The review briefly describes the experimental set-ups, sensitivity, specificity, limit of detection and linear range of various viable and conspicuous LC-based biosensor platforms with associated advantages and disadvantages therein.


Differential determination of perceived stress in medical students and high-school graduates due to private and training-related stressors.
Numerous studies from diverse contexts have confirmed high stress levels and stress-associated health impairment in medical students. This study aimed to explore the differential association of perceived stress with private and training-related stressors in medical students according to their stage of medical education. Participants were high-school graduates who plan to study medicine and students in their first, third, sixth, or ninth semester of medical school or in practical medical training. The self-administered questionnaire included items addressing demographic information, the Perceived Stress Questionnaire, and items addressing potential private and training-related stressors. Results confirmed a substantial burden of perceived stress in students at different stages of their medical education. In particular, 10-28% of students in their third or ninth semesters of medical school showed the highest values for perceived stress. Training-related stressors were most strongly associated with perceived stress, although specific stressors that determined perceived stress varied across different stages of students' medical education. High-school graduates highly interested in pursuing medical education showed specific stressors similar to those of medical students in their third, sixth, or ninth semesters of medical school, as well as stress structures with heights of general stress rates similar to those of medical students at the beginning of practical medical training. High-school graduates offer new, interesting information about students' fears and needs before they begin medical school. Medical students and high-school graduates need open, comprehensive information about possible stressors at the outset of and during medical education. Programmes geared toward improving resilience behaviour and teaching new, functional coping strategies are recommended.


Frequency effect of 0.35-1.0 Hz horizontal translational oscillation on motion sickness and the somatogravic illusion.
Low frequency translational oscillation can provoke motion sickness in land vehicles, ships and aircraft. Nauseogenicity should decrease towards the higher frequencies. Some 12 subjects were exposed to horizontal sinusoidal motion (3.6 m.s-2 peak) at four different frequencies 0.35, 0.50, 0.70, and 1.00 Hz, at 1-week intervals, latin square order. Subjects were seated in the upright position; motion was through the head-body X-axis. Motion was stopped (motion endpoint) at moderate nausea or after 30 min. The proportion of subjects experiencing moderate nausea decreased towards the higher frequency: 9/12 at 0.35 Hz, 3/12 at 0.50 Hz, 0/12 at 0.70 Hz, and 2/12 at 1.00 Hz. The mean time to motion endpoint increased significantly (p < 0.001) towards the higher frequency: 17.4 min 0.35 Hz; 26.0 min 0.50 Hz; 30 min 0.70 Hz; 28.3 min 1.00 Hz. Differences between frequencies were significant (0.001 < p < 0.05) except for 0.70 Hz to 1.00 Hz. At all frequencies tested, horizontal stimuli were more nauseogenic than predicted by mathematical models based on the frequency and intensity of vertical oscillation. Somatogravic illusion (SGI) was reported by 9/12 subjects (mean illusory tilt angles 15.6 degrees forward, 14.1 degrees back). SGI tended to diminish at the higher frequencies, but there was no relationship between SGI and motion sickness. These results confirm previous findings (9), and furthermore indicate that horizontal X-axis translational oscillation has greatly reduced nauseogenic potential at frequencies greater than 0.5 Hz. A mathematical model is proposed to predict motion sickness intensity and incidence due to this stimulus, which may also be applicable to equivalent Y-axis motion.


How are women living with HIV in France coping with their perceived side effects of antiretroviral therapy? Results from the EVE study.
Side effects of antiretroviral therapy (ART) can have a negative impact on health-related quality of life threatening long-term retention in HIV care and adherence to ART. The aim of the French community-based survey EVE was to document personal experiences with side effects, the related physician-patient communication, and solutions found to deal with them. Cross-sectional study of women between September 2013 to September 2014. An anonymous online questionnaire included the HIV Symptom Distress Module, which explores 20 symptoms. In all, 301 women on ART participated in the study (median age: 49 years; median duration of ART: 14 years). They reported having experienced a median of 12 symptoms (Q1-Q3: 9-15) during the previous 12 months. Overall, 56% of them reported having found at least a partial solution to dealing with their symptoms. Women reporting financial difficulties were twice less likely to have found solutions to coping with their side effects (AOR: 0.5; 95% CI: 0.3-0.8). Feeling supported by the health-care provider (AOR: 2.1; 95% CI: 1.1-3.9) and being in contact with HIV/AIDS organisations (AOR: 1.9; 95% CI: 1.2-3.2) were positively associated with coping. Seventeen percent reported having modified their ART regimen to improve tolerance, with only 2 in 3 informing their physician afterwards. Reporting financial difficulties and living with more bothersome symptoms increased the risk of ART regimen modification without health-care provider consultation. The EVE study has called attention to the large number of side effects experienced by WLWHIV, only half of whom have found self-care strategies to manage their symptoms. Modification of ART regimen by the women themselves was not uncommon.


Social manipulation of sperm competition intensity reduces seminal fluid gene expression.
A considerable body of evidence supports the prediction that males should increase their expenditure on the ejaculate in response to sperm competition risk. The prediction that they should reduce their expenditure with increasing sperm competition intensity is less well supported. Moreover, most studies have documented plasticity in sperm numbers. Here we show that male crickets Teleogryllus oceanicus exhibit reduced seminal fluid gene expression and accessory gland mass in response to elevated sperm competition intensity. Together with previous research, our findings suggest that strategic adjustments in seminal fluid composition contribute to competitive fertilization success in this species.


GATA binding protein 5-mediated transcriptional activation of transmembrane protein 100 suppresses cell proliferation, migration and epithelial-to-mesenchymal transition in prostate cancer DU145 cells.
It has been reported that transmembrane protein 100 (TMEM100) acts as a tumor regulator in several types of cancers. However, whether the expression of TMEM100 is associated with the development and prognosis of prostate cancer (PCa) remains elusive. Therefore, the present study aimed to uncover the role of GATA binding protein 5 (GATA5)-mediated activation of TMEM100 in the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of PCa cells. The expressions of TMEM100 and GATA5 in PCa patients were analyzed by the GEPIA database. The binding site of GATA5 and TMEM100 promoter was predicted by the JASPAR database. Expressions of TMEM100 and GATA5 in PCa cells were detected by qRT-PCR and Western blot analysis. Cell Counting Kit 8 and colony formation assays were performed to measure cell proliferation. In addition, cell migration, invasion and the expression of EMT-associated proteins were evaluated using wound healing, transwell assay and Western blotting assays, respectively. The bioinformatics analysis revealed that TMEM100 was downregulated in PCa and was associated with overall survival of PCa. In addition, TMEM10 overexpression attenuated cell proliferation, migration, invasion and EMT in PCa cells. The interaction between TMEM100 and GATA5 was verified using dual luciferase reporter and chromatin immunoprecipitation assays. Furthermore, the results showed that GATA5 was downregulated and GATA5 silencing reversed the inhibitory effects of TMEM10 on PCa cells. Overall, the current study suggested that the GATA5-mediated transcriptional activation of TMEM100 could affect the behavior of PCa cells and was associated with poor prognosis in PCa.


Stereotactic body radiation therapy for stage I non-small-cell lung cancer: a historical overview of clinical studies.
Because of difficulties with stabilization, breathing motion and dosimetry, stereotactic body radiotherapy for lung cancer has only been practiced for the past 15 years. However, a large amount of case data has rapidly been accumulated in recent years. Stereotactic body radiotherapy for Stage I non-small-cell lung cancer has been actively investigated in inoperable patients since around 1995, and a number of clinical trials have been undertaken. Early studies from 2001 presented a 3-year local control rate of 94% and a 3-year overall survival rate of 66% for patients receiving 50-60 Gy in 10 fractions. Another study in 2005, using 48 Gy in four fractions, presented a 3-year local control rate of 98% and 3-year overall survival rates of 83% for Stage IA patients and 72% for Stage IB patients. A multi-institutional study showed favorable local control and survival rates in a group receiving a biologically effective dose of 100 Gy. A dose-escalation study in the USA suggested a maximum tolerated dose of 60 Gy in three fractions. A Phase II clinical trial (RTOG0236) followed, with a reported 3-year local control rate of 98% and a 3-year overall survival rate of 56% for patients who received 60 Gy in three fractions. A Japanese Phase II clinical trial (JCOG0403) investigated a dose of 48 Gy in four fractions among 165 Stage IA patients, showing a 3-year survival rate of 76% and a 3-year locally progression-free survival rate of 69% for the operable group. An overview of past clinical trials in stereotactic body radiotherapy for Stage I non-small-cell lung cancer and current issues is presented and discussed.