On the Concurrent Use of Self-System Therapy and Functional Magnetic Resonance Imaging-Guided Transcranial Magnetic Stimulation as Treatment for Depression.
Despite the growing use of repetitive transcranial magnetic stimulation (rTMS) as a treatment for unipolar depression, its typical effect sizes have been modest, and methodological and conceptual challenges remain regarding how to optimize its efficacy. Linking rTMS to a model of the neurocircuitry underlying depression and applying such a model to personalize the site of stimulation may improve the efficacy of rTMS. Recent developments in the psychology and neurobiology of self-regulation offer a conceptual framework for identifying mechanisms of action in rTMS for depression, as well as for developing guidelines for individualized rTMS treatment. We applied this framework to develop a multimodal treatment for depression by pairing self-system therapy (SST) with simultaneously administered rTMS delivered to an individually targeted region of dorsolateral prefrontal cortex identified via functional magnetic resonance imaging (fMRI). In this proof-of-concept study, we examined the acceptability, feasibility, and preliminary efficacy of combining individually fMRI-targeted rTMS with SST. Using the format of a cognitive paired associative stimulation paradigm, the treatment was administered to 5 adults with unipolar depression in an open-label trial. The rTMS/SST combination was well tolerated, feasible, and acceptable. Preliminary evidence of efficacy also was promising. We hypothesized that both treatment modalities were targeting the same neural circuitry through cognitive paired associative stimulation, and observed changes in task-based fMRI were consistent with our model. These neural changes were directly related to improvements in depression severity. The new combination treatment represents a promising exemplar for theory-based, individually targeted, multimodal intervention in mood disorders.


Glutathione reductase in leaves of cowpea: cloning of two cDNAs, expression and enzymatic activity under progressive drought stress, desiccation and abscisic acid treatment.
Reactive oxygen species are frequently produced when plants are exposed to abiotic stresses. Among the detoxication systems, two enzymes, ascorbate peroxidase and glutathione reductase (GR) play key roles. GR has also a central role in keeping the reduced glutathione pool during stress thus allowing the adjustments on the cellular redox reactions. The aim of this work was to study the variations in cytosolic and dual-targeted GR gene expression in the leaves of cowpea plants submitted to progressive drought, rapid desiccation and application of exogenous abscisic acid (ABA). Two cowpea (Vigna unguiculata) cultivars, one drought-resistant ('EPACE-1'), the other drought-sensitive ('1183') were submitted to progressive drought stress by withholding irrigation. Cut-off leaves were air-dried or treated with exogenous ABA. Two GR cDNAs, one cytosolic, the other dual-targeted to chloroplasts and mitochondria were isolated by PCR and cloned in plasmid vectors. Reverse-transcription PCR was used to study the variations in GR gene expression. Two new cDNAs encoding a putative dual-targeted and a cytosolic GR were cloned and sequenced from leaves of V. unguiculata. Drought stress induced an up-regulation of the expression of the cytosolic GR gene directly related to the intensity of the stress in both cultivars. The expression of dual-targeted GR was up-regulated by the drought treatment in the susceptible cultivar only. Under a fast desiccation, the '1183' cultivar responded later than the 'EPACE-1', although in 'EPACE-1' it was the cytosolic isoform which responded and in '1183' the dual-targeted one. Exogenous ABA enhanced significantly the activity and expression levels of GR in both cultivars after treatment for 24 h. These results demonstrate a noticeable activation in both cultivars of the antioxidant metabolism under a progressive water stress, which involves both GR genes in the case of the susceptible cultivar. Under a fast desiccation, the susceptible cultivar responded later than the resistant one, suggesting a weaker capacity of response versus the resistant one. Exogenous ABA probably acts on GR gene expression via a mediated signal transduction pathway.


Updated Italian cohort data continues to confirm lack of mesothelioma risk in pooled cohort of international cosmetic talc miners and millers.
To assess potential mesothelioma risk following inhalation of cosmetic talc, we updated previous iterations of a pooled cohort analysis, post-study statistical power analysis, and confidence interval function analysis for a pooled cohort of international cosmetic talc miners/millers given new Italian cohort data. Five cohorts of cosmetic talc miners/millers were pooled. Expected numbers of mesotheliomas for each cohort were reported by the original authors. We based our post-study statistical power analysis on an a priori one-sided significance level of 0.05, and exact Poisson and approximate distribution probabilities. To evaluate the confidence interval function for the observed pooled mesothelioma standardized mortality ratios (SMRs), we calculated the probability for the upper 100(1-2α)% confidence limit that equals various SMRs of interest. The pooled cohorts generated a total observation time of 135,524.38 person-years. Overall, 4.14 mesotheliomas were expected (mid-value estimate), though only one case of mesothelioma has been confirmed in the pooled cohort to date. We calculated 71% and 87% post-study power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. Our complimentary confidence interval function analysis demonstrated that the probability that the true mesothelioma SMR for the pooled cohort was at or above 2.0 or at or above 3.0 was 0.00235 and 0.00005, respectively. Based on the updated results of our various analyses, the current epidemiological evidence from cosmetic talc miner/miller cohort studies continues to not support the hypothesis that the inhalation of cosmetic talc is associated with an increased risk of mesothelioma.


[Effects and mechanism of action of antiestrogens in breast cancer].
Tamoxifen, a non-steroidal antioestrogen, is currently used to treat post-menopausal breast cancer. In oestrogen-sensitive breast cancer cell lines, tamoxifen and some of its metabolites display, for the induction of oestrogen-regulated proteins, a partial agonist/antagonist activity. They also inhibit totally the proliferation of these cells. Evidence is given, which suggests that the pharmacological properties of these antioestrogens are mediated by the oestrogen receptor. These antioestrogens interact with the oestrogen receptor but they appear to induce only a partial or altered activation of the receptor. This partial or altered activation and the competition with oestrogens for binding to the oestrogen receptor could explain the oestrogen agonist/antagonist properties of antioestrogens.


Theoretical analysis of singlet and triplet excited states of nickel porphyrins.
Local density and generalized gradient approximation time-dependent density functional methods have been used for calculation of the singlet and triplet excited states of nickel-porphine, Ni-tetraphenyloporphine, and Ni-octaethyloporphyrine. Special attention is paid to metal-ligand transitions and d-d transitions. It is shown that the lowest exited singlet states of the three compounds can be described as a transfer of an electron from the porphine ring to the d(x2-y2) orbital of the nickel atom. On the other hand, the lowest excited triplet state arises from promotion of an electron between two nickel d orbitals, an occupied d(z2) and an empty d(x2-y2). It is proposed that a rapid quenching of the excited singlet states is due to an ultrafast intersystem crossing between 1Eg)and 3Eg or 3B1g states.


Once-daily insulin glargine compared with twice-daily NPH insulin in patients with type 1 diabetes.
To present the findings in a randomized, parallel-group study, comparing once-daily insulin glargine with twice-daily NPH insulin in patients with type 1 diabetes previously treated with multiple daily injections of basal and regular insulin. Of 394 patients with type 1 diabetes treated for up to 28 weeks, 195 received insulin glargine and 199 received NPH insulin, in addition to preprandial regular insulin. Glycemic control and hypoglycemic episodes were assessed. A greater mean decrease in fasting blood glucose (FBG) was achieved at endpoint with insulin glargine than with NPH insulin (-21 mg/dL versus -10 mg/dL [-1.17 mmol/L versus -0.56 mmol/L]; P = 0.015), and a greater percentage of patients treated with insulin glargine reached the target FBG (32.6% versus 21.3%; P = 0.015). Similar percentages of patients in both treatment groups achieved glycosylated hemoglobin values of 7.0% or less at endpoint (insulin glargine, 35.8%; NPH insulin, 35.4%). After the 1-month titration phase, the percentage of patients who reported at least one symptomatic hypoglycemic event confirmed by a blood glucose value of less than 50 mg/dL (2.8 mmol/L) was significantly lower with insulin glargine than with NPH insulin (73.3% versus 81.7%; P = 0.021). Furthermore, the percentage of patients who reported at least one symptomatic hypoglycemic event confirmed by a blood glucose value of less than 36 mg/dL (2.0 mmol/L) was significantly lower with insulin glargine than with NPH insulin (36.6% versus 46.2%; P = 0.033). Once-daily insulin glargine was at least as effective as twice-daily NPH insulin in improving fasting glycemic control and resulted in fewer reported symptomatic hypoglycemic events.


The position of mitochondria and ER in relation to that of the secretory sites in chromaffin cells.
Knowledge of the distribution of mitochondria and endoplasmic reticulum (ER) in relation to the position of exocytotic sites is relevant to understanding the influence of these organelles in tuning Ca(2+) signals and secretion. Confocal images of probes tagged to mitochondria and the F-actin cytoskeleton revealed the existence of two populations of mitochondria, one that was cortical and one that was perinuclear. This mitochondrial distribution was also confirmed by using electron microscopy. In contrast, ER was sparse in the cortex and more abundant in deep cytoplasmic regions. The mitochondrial distribution might be due to organellar transport, which experiences increasing restrictions in the cell cortex. Further study of organelle distribution in relation to the position of SNARE microdomains and the granule fusion sites revealed that a third of the cortical mitochondria colocalized with exocytotic sites and another third located at a distance closer than two vesicle diameters. ER structures were also present in the vicinity of secretory sites but at a lower density. Therefore, mitochondria and ER have a spatial distribution that suggests a specialized role in modulation of exocytosis that fits with the role of cytosolic Ca(2+) microdomains described previously.


Single-stage bilateral total hip arthroplasty.
The number of single-stage bilateral total hip arthroplasties done each year is increasing. The risk of postoperative complications in medically stable patients is acceptable; complications are approximately 1.3 times more frequent than with unilateral total hip arthroplasty. Although there are no absolute indications for a single-stage bilateral total hip arthroplasty, the procedure is usually contraindicated in patients with such comorbidities as heart disease, pulmonary insufficiency, or diabetes, and it is absolutely contraindicated in patients with a documented patent ductus arteriosus or septal defect. The primary postoperative concern is that the cardiopulmonary insult associated with two surgical wounds and surgeries can lead to an increase in thromboembolic events. The cost for single-stage bilateral total arthroplasty is less than that for a two-stage bilateral total hip arthroplasty, with savings predominantly due to reduced length of acute hospital stay. However, the decision to undergo single-stage bilateral total hip arthroplasty is one that must be made in concert with the patient.


α-Chaconine Facilitates Chondrocyte Pyroptosis and Nerve Ingrowth to Aggravate Osteoarthritis Progression by Activating NF-κB Signaling.
With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that α-Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure. To determine whether α-Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between α-Chaconine and OA progression. We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 μM α-Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1β, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence. We found that α-Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, α-Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that α-Chaconine stimulated NF-κB signaling by promoting I-κB α phosphorylation and p65 nuclear translocation. Collectively, our findings raise the possibility that α-Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.


Interferometrical single-molecule localization based on dynamic PSF engineering.
We present a method for interferometric single-molecule localization based on dynamic point spread function (PSF) engineering. By using two galvo mirrors, a hexagonal PSF is constructed and the fluorescent signal under different illumination patterns could be acquired simultaneously. This method was evaluated using simulation, fluorescent nanosphere imaging, and single-molecule imaging. The study indicates a twofold improvement in localization precision while maintaining the same photon budget. This strategy, we believe, is a cost-effective way to increase the resolution of single-molecule localization microscopy.


On the role and fate of LPS-dephosphorylating activity in the rat liver.
Gut-derived lipopolysaccharide (LPS) plays a role in the pathogenesis of liver diseases like fibrosis. The enzyme alkaline phosphatase (AP) is present in, among others, the intestinal wall and liver and has been previously shown to dephosphorylate LPS. Therefore, we investigated the effect of LPS on hepatic AP expression and the effect of AP on LPS-induced hepatocyte responses. LPS-dephosphorylating activity was expressed at the hepatocyte canalicular membrane in normal and fibrotic animals. In addition to this, fibrotic animals also displayed high LPS-dephosphorylating activity around bile ducts. The enzyme was shown to dephosphorylate LPS from several bacterial species. LPS itself rapidly enhanced the intrahepatic mRNA levels for this enzyme within 2 h by a factor of seven. Furthermore, in vitro and in vivo studies showed that exogenous intestinal AP quickly bound to the asialoglycoprotein receptor on hepatocytes. This intestinal isoform significantly attenuated LPS-induced hepatic tumor necrosis factor-alpha and nitric oxide (nitrite and nitrate) responses in vitro. The enzyme also reduced LPS-induced hepatic glycogenolysis in vivo. This study shows that LPS enhances AP expression in hepatocytes and that intestinal AP is rapidly taken up by these same cells, leading to an attenuation of LPS-induced responses in vivo. Gut-derived LPS-dephosphorylating activity or enzyme upregulation within hepatocytes by LPS may therefore be a protective mechanism within the liver.


Regulation of water-soluble glucan synthesis by the Streptococcus mutans dexA gene effects biofilm aggregation and cariogenic pathogenicity.
The cariogenic pathogen Streptococcus mutans effectively utilizes dietary sucrose for the synthesis of exopolysaccharides (EPS), which act as a scaffold for its biofilm and thus contribute to its cariogenic pathogenicity. Dextranase (Dex), which is a type of glucanase, participates in the degradation of water-soluble glucan (WSG); however, the structural features of the EPS regulated by the dexAgene have received limited attention. Our recent studies reported novel protocols to fractionate and analyzed the structural characteristics of glucans from S mutans biofilms. In this study, we identify the role of the S mutans dexAgene in dextran-dependent aggregation in biofilm formation. Our results show that deletion of dexA (SmudexA) results in increased transcription of EPS synthesis-related genes, including gtfB, gtfD, and ftf. Interestingly, we reveal that inactivating the dexA gene may lead to elevated WSG synthesis in S mutans , which results in dysregulated cariogenicity in vivo. Furthermore, structural analysis provides new insights regarding the lack of mannose monosaccharides, especially in the WSG synthesis of the SmudexA mutants. The biofilm phenotypes that are associated with the reduced glucose monosaccharide composition in both WSG and water-insoluble glucan shift the dental biofilm to reduce the cariogenic incidence of the SmudexA mutants. Taken together, these data reveal that EPS synthesis fine-tuning by the dexA gene results in a densely packed EPS matrix that may impede the glucose metabolism of WSG, thereby leading to the lack of an energy source for the bacteria. These results highlight dexA targeting as a potentially effective tool in dental caries management.


Causes and Prevention of Early-Onset Colorectal Cancer.
Sporadic colorectal cancer (CRC) has historically been considered a disease of the elderly. However, early-onset colorectal cancer (eoCRC) incidence and prevalence have steadily increased over the last few decades, highlighting the critical need for a comprehensive understanding of its causes and prevention. This research examines the numerous factors contributing to the increasing incidence of eoCRC. These factors include a combination of genetic predispositions and environmental effects. We also investigate the impact of modifiable lifestyle factors like obesity, physical inactivity, and an unhealthy diet on eoCRC risk. Understanding these factors is critical in developing future diagnostic, prognostic, disease monitoring, and therapy planning strategies in managing eoCRC and will help optimize guidelines for CRC screening.


[Visualization of EIM simulation data on real cardiac model].
Although 3D heart and torso model with realistic geometry are the basis of simulation computation in LFX Virtual Cardiac Model, the simulation results are mostly output in 2D format. Voxel mapping method is presented to solve this problem and extend the function of LFX Virtual Cardiac Model. Excitation Isochrone Map (EIM), one of the most important simulation results, was mapped from cardiac model with realistic geometry to real Visible Man cardiac model, then the EIM simulation data before and after mapping were visualized in the 4DView which is a real-time 3D medical image visualization platform. With this method, the output format of EIM simulation data of LFX Virtual Cardiac Model was extended from 2D to 4D (time is the 4th dimension) and from cardiac model with realistic geometry to real cardiac model. According to the EIM simulation data visualization results before and after mapping, the LFX virtual cardiac model shows its characteristics with more realistic and effective simulation.


Dewetting of ultrathin solid films.
Ultrathin crytalline solid films are found to dewet with a faceted rim. In the case of heterogeneous dewetting initiated from a linear trench or from periodically arranged holes, the dewetted area expands either with a faceted multilayer rim or in a layer-by-layer fashion. In the case of homogeneous dewetting, holes are accompanied with multilayer rims and the uncoverage increases as a power law of time. Results of kinetic Monte Carlo simulations are elucidated within the frame of nucleation theory and surface diffusion limited dynamics.


[Transvaginal contrast hysterosonography. A new diagnostic procedure for the differentiation of intrauterine and myometrial findings].
In 30 patients with sterility problems, menstrual irregularities, and/or suspected tumor the uterine wall was evaluated by transvaginal hystero-contrast-sonography (CoSy). These findings were compared with those of hysterosalpingography (HSG) or chromo-laparoscopy which were done during the same anesthesia. In 6 patients there was no coincidence, and additional information of relevance could be achieved by the other procedure. One case of submucous and an other of intramural fibroid were exactly differentiated by the transvaginal CoSy. This was not possible by the HSG. In addition two large intramural fibroids were exactly localized by CoSy, where as this couldn't be demonstrated endoscopically. Two uteri arcuati have not been seen by CoSy, but were recognized by HSG. So we recommend the transvaginal CoSy of the uterus as a pretherapeutic procedure for the differentiation and localization of intracavital and myometrial findings. At least at moment it seems to be that the image of light uterine malformations could be better demonstrated by conventional diagnostic methods.


Basic fibroblast growth factor expression in isolated small human ovarian follicles.
Basic fibroblast growth factor (bFGF) is involved in cell proliferation, differentiation, and angiogenesis. It has long been known that bFGF acts as a powerful mitogen for various mammalian granulosa cells in culture. To investigate the possible involvement of bFGF expression in follicle initiation and growth in vivo, we performed nested RT-PCR on ovarian cortical biopsies and quantitative PCR on human follicle populations isolated by laser capture microdissection. Using morphological criteria, follicles were characterized as putative non-growing, primary, or small secondary. RNA was extracted from samples, reverse-transcribed, and relative gene expression levels determined with TaqMan real-time PCR, using 18S rRNA as the endogenous control. Results confirmed bFGF expression in human adult ovarian cortex, and in the isolated follicles a down-regulation of bFGF mRNA was evident as small follicles develop. This study demonstrates a possible relationship between bFGF mRNA expression and follicle development.


Dumbbell-shaped paraganglioma of the cervical spine in a child.
Paragangliomas are tumors arising from extra-adrenal paraganglia and account for 0.3% of all neoplasms. The carotid body and temporal bone are the most frequent sites of paraganglioma, though it has been reported to occur in almost every part of the body. Spinal paragangliomas are uncommon and mainly take the form of intradural compression of the cauda equina or thoracic cord. Extradural paragangliomas are still rare; only few cases involving the dorsolumbar spine have been reported. We are reporting an interesting case of a dumbbell-shaped primary extradural paraganglioma of the cervical spine in an 8-year-old boy that presented with progressively increasing spastic quadriparesis.


[Psychiatry and genetics: A bond to face uncertainty].
This article complements a previous one, in which theoretical concepts about etiologic categories, suspicion criteria and timely referral to the specialist were explained. This time we will focus on genetic counselling (GC), describing this process and its characteristics, in particular we will emphasize on psychiatry genetic counseling (PGC). PGC has particular characteristics considering the fact that there are still no tools (genetic testing) for diagnosis and that most mental pathologies are multifactorial inheritance disorders. This is complex, since it results from the interaction of genetics and environmental circumstances. Uncertainty is a given due to the number of factors involved in its appearance and, despite great strides, these should be further investigated. PGC seems to be a useful tool for both patients and families for better adapting to the disease and to cope with consequences derived from it. In conclusion, we consider of great importance to create an enabling collaborative workspace between psychiatrists and clinical geneticists in order to provide patients and their families a comprehensive approach to their problems.


A radiobiological probe for simultaneous NMR spectroscopy and 192Ir gamma irradiation of Saccharomyces cerevisiae.
A novel nuclear magnetic resonance (NMR) spectroscopy probe was designed and constructed for the study of transient metabolic changes in cellular systems during exposure to ionizing radiation. The probe incorporated a bioreactor, a radiation source, and a radiofrequency detection circuit tunable between 100 and 300 MHz for in vivo NMR spectroscopy of 23Na, 13C, and 31P at 11.7 Tesla. The bioreactor system allowed perfusion, oxygenation, and temperature control of cultured cells during irradiation and while performing simultaneous spectroscopic experiments. The concentric design of the bioreactor allowed for the insertion of a 192Ir gamma ray source (E(gamma) = 370 keV) to allow irradiation of the bioreactor system during the acquisition of NMR spectra. Initial results of 31P spectra obtained during simultaneous gamma irradiation of Saccharomyces cerevisiae at approximately 8 Gy/hr show rapid decreases in adenosine triphosphate (ATP) and polyphosphate at the onset of irradiation followed by a slow recovery of polyphosphate.


Multimodal imaging of focal choroidal excavation and macular choroidal cavitation associated to choroidal neovascularization.
Purpose: To report multimodal imaging features of an unusual case of multiple focal choroidal excavations (FCE) associated to macular intrachoroidal cavitations (ICC) and choroidal neovascularization (CNV) in a non-myopic patient with normal choroidal thickness. Methods: Observational case report. Results: A 69-year-old non-myopic male patient with history of macular CNV of unknown etiology in the right eye (RE), initially treated with Bevacizumab intravitreal injections with significant improvement of visual acuity. He presented with acute vision loss in the same eye related to recurrent CNV exudation. Multimodal imaging of the RE confirmed the diagnosis of active type 2 CNV, associated to multiple FCE. Besides, it highlighted incidental unusual macular ICC in the same eye. Choroidal thickness was within normal limits (217 μm). Conclusion: Focal choroidal excavations and intrachoroidal cavitations can be observed in emmetropic patients in the absence of pachychoroid disease. In presence of CNV of unknown etiology, complete multimodal imaging can be of a great help to better define choroidal anomalies, allowing structural and vascular correlations between different lesions. Key words: Focal choroidal excavation; Choroidal cavitation; Multimodal imaging.


Cbl signaling networks in the regulation of cell function.
Cbl proteins control multiple cellular processes by acting as ubiquitin ligases and multifunctional adaptor molecules. They are involved in the control of cell proliferation, differentiation and cell morphology, as well as in pathologies such as autoimmune diseases, inflammation and cancer. Here we review recent advances in understanding the role of Cbl and the importance of a growing repertoire of Cbl-interacting proteins in the regulation of signaling pathways triggered by growth factors, antigens, cell adhesion, cytokines and hormones. We also address key issues of the nature of proteins that bind Cbl in particular cells, where they are located, and how they are altered or traffic within cells upon stimulation. It is becoming obvious that temporal and spatial changes in Cbl signaling networks are essential for the control of physiological processes in a variety of cells and organs and that their deregulation can result in the development of human diseases.


Royal Brisbane Hospital--no lifting 1998.
In August of 1997 the Royal Brisbane Hospital commenced working towards the implementation of a no-lift policy in line with the Queensland Nurses' Union No Lifting by the Year 2000 policy. This is a report on that implementation.


Vertical versus Lateral Two-Dimensional Heterostructures: On the Topic of Atomically Abrupt p/n-Junctions.
The key appeal of two-dimensional (2D) materials such as graphene, transition metal dichalcogenides (TMDs), or phosphorene for electronic applications certainly lies in their atomically thin nature that offers opportunities for devices beyond conventional transistors. It is also this property that makes them naturally suited for a type of integration that is not possible with any three-dimensional (3D) material, that is, forming heterostructures by stacking dissimilar 2D materials together. Recently, a number of research groups have reported on the formation of atomically sharp p/n-junctions in various 2D heterostructures that show strong diode-type rectification. In this article, we will show that truly vertical heterostructures do exhibit much smaller rectification ratios and that the reported results on atomically sharp p/n-junctions can be readily understood within the framework of the gate and drain voltage response of Schottky barriers that are involved in the lateral transport.


Chemical signal interactions of the bark beetle with fungal symbionts, and host/non-host trees.
The symbiosis between the bark beetle (Ips subelongatus) and its fungal symbiont (Endoconidiophora fujiensis) poses a serious threat to larch forests. However, the signaling pathways between these symbiotic partners and their host/non-host trees are not fully understood. Inoculation of the host larch (Larix principis-rupprechtii) with two strains of E. fujiensis induced a rapid and long-term release of monoterpenes. Although the fungi had a level of tolerance to these compounds, many monoterpenes inhibited fungal growth in culture. Moreover, monoterpenes with stronger inhibitory effects on fungal growth exhibited weaker synergistic effects on the attraction of I. subelongatus to aggregation pheromone. Surprisingly, individual isomers of aggregation pheromone components promoted fungal symbiont growth in a culture medium. Non-host volatiles (NHVs) were tested and shown to completely inhibit the growth of fungal symbionts in culture but had no effects on beetle responses to aggregation pheromone, with the exception of (Z)-3-hexen-1-ol. These results reveal convergence and mutualism patterns in the evolution of I. subelongatus and E. fujiensis with respect to host tree volatiles but not in response to NHVs. Ultimately, we put forward a hypothesis that host plants are ecological and evolutionary determinants of bark beetle-fungus symbioses in terms of their complex signaling interactions.


Charnley low-friction arthroplasty in teenage patients: the ultimate challenge.
Increasing follow-up identifies the outcome in younger patients who have undergone total hip replacement (THR) and reveals the true potential for survival of the prosthesis. We identified 28 patients (39 THRs) who had undergone cemented Charnley low friction arthroplasty between 1969 and 2001. Their mean age at operation was 17.9 years (12 to 19) and the maximum follow-up was 34 years. Two patients (4 THRs) were lost to follow-up, 13 (16 THRs) were revised at a mean period of 19.1 years (8 to 34) and 13 (19 THRs) continue to attend regular follow-up at a mean of 12.6 years (2.3 to 29). In this surviving group one acetabular component was radiologically loose and all femoral components were secure. In all the patients the diameter of the femoral head was 22.225 mm with Charnley femoral components used in 29 hips and C-stem femoral components in ten. In young patients who require THR the acetabular bone stock is generally a limiting factor for the size of the component. Excellent long-term results can be obtained with a cemented polyethylene acetabular component and a femoral head of small diameter.


Quantitative aspects of the excretion of radioactive and microbiologically active material in urine after parenteral hydroxocobalamin.
The radioactive material in urine after parenteral radioactive hydroxocobalamin is composed of radioactive cyanocobalamin, radioactive hydroxocobalamin, and a radioactive anionic complex. Studies in vitro suggest that these materials have a similar microbiological activity. Comparison of the amounts of radioactive and microbiologically active material in urine after parenteral radioactive hydroxocobalamin show a significant correlation both in the first and second 24 hours after injection showing that the amount of radioactivity is an acceptable measure of the loss of cobalamin in urine. The slope of the regression lines obtained from cobalamin-deficient and normal subjects implies that there is no equilibration of injected radioactive hydroxocobalamin and body stores: this may be due to the absence of hydroxocobalamin from tissues or to the fact that tissue hydroxocobalamin is bound and incapable of equilibration.


Characteristics of dermal invasion in experimental cutaneous candidiasis of leucopenic mice.
The course of experimental cutaneous Candida albicans infections produced in mice made leucopenic by the administration of cyclophosphamide was compared to that in untreated animals. In the latter, neutrophils characteristically infiltrated the area of infection and the organisms were virtually always confined to the epidermis. However, even though many fewer foci of infection were associated with neutrophils in the cyclophosphamide-treated animals, a majority of these foci were also unable to penetrate past the epidermis. Although Candida yeast proliferated relatively poorly when cultured in homogenates of skin lacking the epidermis, Candida pseudohyphae could invade into the dermis if inoculated skin was isolated from normal animals and cultured in vitro, or if the epidermis was removed by gentle scraping prior to inoculation with Candida yeast onto the remaining skin of leucopenic animals. Therefore, in the absence of neutrophil contact and killing of Candida pseudohyphae in the epidermis, other cutaneous defense mechanisms appear to be capable of preventing invasion of a majority of the organisms into the dermis. These findings may help to explain why deep Candida infections are rare in patients who have extensive superficial candidiasis.


Plasma leptin, but not adiponectin, is associated with cognitive impairment in older adults.
Leptin and adiponectin are adipose-tissue derived hormones primarily involved in glucose, lipid, and energy metabolism, inflammation, and atherosclerosis. Both adipokines may cross the blood-brain barrier but evidence on their roles in cognitive impairment is limited and conflicting. Here, we determined associations of plasma adipokine concentration with cognitive impairment in older adults. Cross-sectional analysis of baseline data from 669 participants aged ≥65 years of the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study were recruited 2014-2017 at study sites in Berlin, Germany and Utrecht, the Netherlands. Cognitive impairment was defined as the lowest tertile of a cognitive summary score derived from six neuropsychological tests. After adjustment for age, sex, fasting, BMI, diabetes, hypertension, cerebrovascular disease, and coronary heart disease, higher leptin concentrations and a higher leptin/adiponectin ratio (LAR) were associated with a higher odds of cognitive impairment (OR per 1 SD higher leptin concentration, 1.33; 95 % CI 1.05, 1.69; p = 0.02; OR per 1 SD higher LAR, 1.26; 95 % CI 1.01, 1.57; p = 0.04). Sensitivity analyses determined that these findings were driven by the non-obese group (BMI < 30 kg/m2), whereas leptin and LAR were not associated with cognitive impairment in the obese group (BMI ≥ 30 kg/m2). Soluble leptin receptor, leptin/soluble leptin receptor ratio, total adiponectin and high-molecular weight adiponectin concentrations were each not associated with impairment. With leptin as a known promoter of atherosclerosis and inflammation, our findings point to a pathogenic role of leptin in age-related cognitive impairment that may be limited to non-obese individuals and warrants further investigation.


Functional efficacy of tendon repair processes.
Despite various attempts to repair and replace injured tendon, an understanding of the repair processes and a systematic approach to achieving functional efficacy remain elusive. In this review the epidemiology of tendon injury and repair is first examined. Using a traditional paradigm for repair assessment, the biology and biomechanics of normal tendon, natural healing, and repair are then explored. New treatment strategies such as functional tissue engineering are discussed, including a functional approach to treatment that involves the development of in vivo functional design parameters to judge the acceptability of a repair outcome. The paper concludes with future directions.


Preliminary behavioral assessment of cagemates living with conspecifics submitted to chronic restraint stress in mice.
The capacity of rodents to recognize and respond to emotional signs from a conspecific is a valuable adaptive behavior, which provides essential skills for species survival. However, repeated exposure to aversive situations may elicit maladaptive behavioral responses in subjects that experience noxious episodes and their colony members. Previous findings by our group demonstrated that living with a subject in neuropathic pain induces anxiogenic-like behaviors and hypernociception in mice. Whereas chronic pain may be considered a stressful stimulus, we extended our findings on stress-induced emotional transfer. For this purpose, we investigated whether cohabitation with a partner subjected to chronic restraint stress was able to promote alterations in anxiety-like behaviors, pain sensibility and defensive responses. Male Swiss mice were housed in pairs for 14days and then separated into control, stress, and cagemate groups. The stress group was subjected to 14days of restraint stress (1h/day) in the presence of the cagemates, while the pair-housed control group was left undisturbed. A day after last stress session control, stress, and cagemate groups were evaluated using elevated plus maze test, writhing test, and rat exposure test. Results demonstrated that chronic stress attenuated weight gain in the stress group. Moreover, cohabitation with mice subjected to chronic restraint stress induced anxiogenic-like behaviors, pain hypernociception, and alterations in defensive responses in both cagemate and stress groups. These preliminary findings suggest that chronic exposure to aversive stimulus may induce behavioral alterations even in observers.


How cell migration helps immune sentinels.
The immune system relies on the migratory capacity of its cellular components, which must be mobile in order to defend the host from invading micro-organisms or malignant cells. This applies in particular to immune sentinels from the myeloid lineage, i.e. macrophages and dendritic cells. Cell migration is already at work during mammalian early development, when myeloid cell precursors migrate from the yolk sac, an extra embryonic structure, to colonize tissues and form the pool of tissue-resident macrophages. Later, this is accompanied by a migration wave of precursors and monocytes from the bone marrow to secondary lymphoid organs and the peripheral tissues. They differentiate into DCs and monocyte-derived macrophages. During adult life, cell migration endows immune cells with the ability to patrol their environment as well as to circulate between peripheral tissues and lymphoid organs. Hence migration of immune cells is key to building an efficient defense system for an organism. In this review, we will describe how cell migratory capacity regulates the various stages in the life of myeloid cells from development to tissue patrolling, and migration to lymph nodes. We will focus on the role of the actin cytoskeletal machinery and its regulators, and how it contributes to the establishment and function of the immune system.


Virus interference between H7N2 low pathogenic avian influenza virus and lentogenic Newcastle disease virus in experimental co-infections in chickens and turkeys.
Low pathogenicity avian influenza virus (LPAIV) and lentogenic Newcastle disease virus (lNDV) are commonly reported causes of respiratory disease in poultry worldwide with similar clinical and pathobiological presentation. Co-infections do occur but are not easily detected, and the impact of co-infections on pathobiology is unknown. In this study chickens and turkeys were infected with a lNDV vaccine strain (LaSota) and a H7N2 LPAIV (A/turkey/VA/SEP-67/2002) simultaneously or sequentially three days apart. No clinical signs were observed in chickens co-infected with the lNDV and LPAIV or in chickens infected with the viruses individually. However, the pattern of virus shed was different with co-infected chickens, which excreted lower titers of lNDV and LPAIV at 2 and 3 days post inoculation (dpi) and higher titers at subsequent time points. All turkeys inoculated with the LPAIV, whether or not they were exposed to lNDV, presented mild clinical signs. Co-infection effects were more pronounced in turkeys than in chickens with reduction in the number of birds shedding virus and in virus titers, especially when LPAIV was followed by lNDV. In conclusion, co-infection of chickens or turkeys with lNDV and LPAIV affected the replication dynamics of these viruses but did not affect clinical signs. The effect on virus replication was different depending on the species and on the time of infection. These results suggest that infection with a heterologous virus may result in temporary competition for cell receptors or competent cells for replication, most likely interferon-mediated, which decreases with time.


The dexamethasone suppression test in children and adolescents with major depressive disorder: a review.
The authors review the available studies on the use of the dexamethasone suppression test (DST) in children and adolescents with psychiatric disorders. For the purposes of analysis, the authors divided the studies according to the two age groups. Pooled sensitivity, specificity, and positive predictive power were calculated for each age group per diagnostic category. DST nonsuppression among subjects with major depressive disorder (MDD) in the children's group was 69.6%, with a specificity of 69.7%, whereas for adolescent subjects, DST sensitivity was 41.3%, and specificity was 79.3%. The positive predictive power of an abnormal DST result in helping diagnose MDD in the children's group was 69.7%, whereas for the adolescent group, the positive predictive power was 66.6%. The authors conclude that the evidence cannot support the routine clinical use of the DST in children and in adolescents, but there may be a research role for the DST in these patient populations.


Experiences of newly qualified midwives during their transition to practice: a systematic review of qualitative research.
To summarize and evaluate the experiences and expectations of newly qualified midwives (NQMs) during their transition from school to clinical practice. One of the main objectives was to provide references for the development of midwifery professional teaching and provide a basis for hospital administrators and instructors of midwifery to develop guidelines and strategies. A systemic review of qualitative research using meta-aggregation was conducted. We collected studies from 12 databases between inception and February 2023. All qualitative studies published in English and Chinese that reported on the experiences of NQMs during their transition to practice were included. Two independent reviewers assessed the study quality and the credibility of study findings by using the JBI Qualitative Assessment and Review Instrument. The process of searching followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. A total of 14 studies were included, and 84 findings were extracted. The results were grouped into 8 new categories and synthesized into 3 main themes: multi-dimensional challenges, physical and emotional responses, and demands and expectations. The included studies were identified to be of good quality and the results of the methodological quality appraisal were all B grade or higher. The transition period is a critical career development for NQMs. However, they faced various stress during the period, which had a negative impact on their physical and mental health. Therefore, it's important to deeply understand their challenges and needs. And effective management strategies should be implemented, such as in-depth cooperation between hospitals and schools, improvement of the clinical transition support system, enhancement of continuing education, and standardization of the management system. This may be beneficial to improve the quality of clinical midwifery and maintain the stability and sustainable development of the midwifery team.


PREVALENCE OF CLEFT LIP AND PALATE IN GEORGIA.
Cleft lip and palate take significant place in congenital malformations. We aimed to study epidemiological peculiarities of these pathologies in Georgia for 2006-2015. We compared magnitude of its distribution with the data from 1981-1990. Prevalence of cleft lip and palate in Georgia in 2006-2015 was 0.95±0.04 per 1000 live births, while in 1981-1990- it was 1.05, i.e. in contrast to 1980's frequency of these pathological conditions decreased to some extent. Distribution of cleft lip and palate varies across the country regions. The most intensive spread has been observed in Mtskheta-Mtianeti region, where prevalence composed 2.28/1000. In the rest of the regions frequency of these pathologies is significantly lower. For instance, in Kakheti the rate is equal to 1,87/1000, in Kvemo Kartli - 1.56/1000, in Shida Kartli - 1.55/1000. In the rest of the regions prevalence rate is lower than the country average. It should be noted that in Tbilisi the rate is as low as 0.80/1000. The lowest level has been reported in Guria - 0.56/1000. Currently cleft lip with palate is the most frequently occurring anomaly in Georgia accounting for 39.8% of all congenital malformations. Cleft lip alone ranks the second - 36.1%, followed by cleft palate (24.1%). These pathologies are more frequent in boys than in girls. 60.3% of the cases are reported in males, in contrast to girls - 39.7% (p<0.01). Usually, cleft palate is the most common among girls, but in our case, it had higher prevalence among boys, 53.6% vs. 46,4%. Thus cleft lip and palate distribution in Georgia is characterized by epidemiological peculiarities, which should be considered in implementation of preventive measures.


The mRNA and miRNA transcriptomic landscape of Panax ginseng under the high ambient temperature.
Ginseng is a popular traditional herbal medicine in north-eastern Asia. It has been used for human health for over thousands of years. With the rise in global temperature, the production of Korean ginseng (Panax ginseng C.A.Meyer) in Korea have migrated from mid to northern parts of the Korean peninsula to escape from the various higher temperature related stresses. Under the high ambient temperature, vegetative growth was accelerated, which resulted in early flowering. This precocious phase change led to yield loss. Despite of its importance as a traditional medicine, biological mechanisms of ginseng has not been well studied and even the genome sequence of ginseng is yet to be determined due to its complex genome structure. Thus, it is challenging to investigate the molecular biology mechanisms at the transcript level. To investigate how ginseng responds to the high ambient temperature environment, we performed high throughput RNA sequencing and implemented a bioinformatics pipeline for the integrated analysis of small-RNA and mRNA-seq data without a reference genome. By performing reverse transcriptase (RT) PCR and sanger sequencing of transcripts that were assembled using our pipeline, we validated that their sequences were expressed in our samples. Furthermore, to investigate the interaction between genes and non-coding small RNAs and their regulation status under the high ambient temperature, we identified potential gene regulatory miRNAs. As a result, 100,672 contigs with significant expression level were identified and 6 known, 214 conserved and 60 potential novel miRNAs were predicted to be expressed under the high ambient temperature. Collectively, we have found that development, flowering and temperature responsive genes were induced under high ambient temperature, whereas photosynthesis related genes were repressed. Functional miRNAs were down-regulated under the high ambient temperature. Among them are miR156 and miR396 that target flowering (SPL6/9) and growth regulating genes (GRF) respectively.


Antiribosomal P protein antibodies in different populations of patients with systemic lupus erythematosus.
We report a significantly increased prevalence of antiribosomal P protein antibodies in Malaysian Chinese patients (38%) with SLE compared to white Caucasian (13%) and Afro-Caribbean (20%) patients. The increased prevalence was not due to a generalized increase in autoantibody production because anti-dsDNA and anti-SSA antibodies were present in comparable frequencies in the three ethnic groups while anti-Sm and anti-SSB antibodies were rarely found in the Malaysian Chinese patients.


Microscopic hematuria in pregnancy: relevance to pregnancy outcome.
The significance of dipstick or microscopic hematuria in pregnancy is uncertain, with some studies suggesting this is associated with a greater risk for preeclampsia. We sought to determine the prevalence and clinical significance of microscopic hematuria during pregnancy. This was a prospective case-control study in the antenatal Clinic of St George Hospital, Kogarah, Australia, a teaching hospital without tertiary referral antenatal care, with approximately 2,600 deliveries per year. One thousand pregnant women attending for routine antenatal care were invited to have a routine urinalysis performed and be referred to a nephrology clinic for further investigation if dipstick microscopic hematuria was detected on more than 1 occasion before 32 weeks' gestation. Main outcome measures were the prevalence of dipstick hematuria, prevalence of hematuria confirmed by urine microscopy, and the development of preeclampsia or gestational hypertension or delivery of a small-for-gestational-age baby. One hundred seventy-eight of 902 women (20%) who entered the study had dipstick hematuria on at least 2 occasions in pregnancy; 66 of 126 women (53%) who had hematuria before 32 weeks attended the nephrology clinic, where microscopic hematuria was confirmed in 40 women (61%). Renal imaging results were normal in all except 1 woman, and all women had a serum creatinine level of 0.90 mg/dL or less (< or =80 micromol/L). The development of preeclampsia or gestational hypertension or delivery of a small-for-gestational-age baby were similar in women with and without dipstick hematuria. Microscopic hematuria persisted in half (15 women) of those who attended for follow-up after 3 months postpartum. Dipstick hematuria is very common during pregnancy, but rarely signifies a disorder likely to impact on the pregnancy outcome. Postpartum follow-up is recommended to detect women who have persistent hematuria and presumed underlying mild glomerulonephritis.


Hip Adductor Intramuscular Nerve Distribution Pattern of Children: A Guide for BTX-A Treatment to Muscle Spasticity in Cerebral Palsy.
To investigate the intramuscular nerve distribution pattern in the hip adductors of children and to precisely locate the injection site for botulinum toxin type A (BTX-A) as a treatment for hip adductor spasticity in children with cerebral palsy. Modified Sihler's whole mount nerve staining technique was employed to observe the distribution of intramuscular nerves in hip adductors of children and to further locate zones where terminal nerves are concentrated. The terminal nerves of the adductor longus appeared in a longitudinal distribution band parallel to the line between the upper 1/3 point of the lateral boundary and the center of the medial boundary. In adductor brevis, the terminal nerves showed a sheet-like distribution with a nerve dense area located in the middle of the muscle belly that extends from the upper-inner region to the lower-outer region. Gracilis showed a dense area of terminal nerves in the middle of the muscle belly, closer to the posterior boundary. In adductor magnus, the dense area of terminal nerves showed a sheet-like distribution in the middle and lower region of the muscle belly. The dense area of terminal nerves in the pectineus was located in the middle of the muscle belly. This study is the first to systematically investigate the intramuscular nerve distribution pattern in the hip adductors. The results indicated that the best targets for BTX-A injection, when treating spasticity, are the dense regions of terminal nerves described above.


Expression of the tobacco Tnt1 retrotransposon promoter in heterologous species.
The expression of the tobacco (Nicotiana tabacum) retrotransposon Tnt1 has previously been shown to be strongly regulated and driven from the 5' long terminal repeat (LTR). We report here that the Tnt1 LTR can promote activity of the beta-glucuronidase (GUS) reporter gene in two heterologous species of the Brassicaceae family, namely rapeseed (Brassica napus) and Arabidopsis thaliana. The translational LTR-GUS fusion was active in transient expression studies performed with tobacco and rapeseed protoplasts, indicating that the LTR sequences are recognized in heterologous species. Our results also showed that Tnt1 LTR-promoted GUS expression in transgenic Arabidopsis is strongly regulated, and that, in contrast to tobacco, hormonal activation plays a significant role in the expression of the Tnt1 LTR in Arabidopsis. LTR sequences were shown to be more effective than the CaMV 35S enhancer region in transient expression studies performed with tobacco or rapeseed protoplasts, and substitution of the LTR sequences upstream from the major transcriptional start with the CaMV 35S enhancer region gave high levels of expression in transgenic tobacco and Arabidopsis leaves, suggesting that a Tnt1 element with similar substitutions in its 5' LTR might be suited for gene-tagging experiments in heterologous species.


Systemic sarcoidosis with significant granulomatous swelling of the pharyngeal tonsil.
A pharyngeal tonsil biopsy specimen from a 27-year-old male revealed epithelioid cell granulomas with noncaseating necrosis. Systemic enlargement of the lymph nodes was present. Plain chest radiographic and computed tomography (CT) images showed ground-glass attenuation in the lungs and bilateral hilar lymphadenopathy. Biopsy of inguinal region nodes confirmed the diagnosis of systemic sarcoidosis. Detailed examination of the nasopharynx should be performed in any case presenting with systemic sarcoidosis because the specimen is readily removable and the pathologic findings of the local lesion may support the diagnosis.


Hypoxia-like effect of cobalt chromium alloy micro particles on fibroblasts in vitro.
Periprosthetic osteolysis leading to asceptic loosening remains the primary cause of failure of joint replacement. Although many inflammatory cell types have been implicated, the exact pathomechanisms of asceptic loosening have not been delineated. In the present study we have adopted a proteomic approach to elucidate the initial signals that are expressed to particulate material, using an in vitro cell culture system. Human lung fibroblasts MRC-5 were cultured with Cobalt Chromium (CoCr ASTM F-75, 1-7 µm) particles. Cells were harvested after 72 h incubation and total cellular proteins extracted for downstream analysis via 2D Gel Electrophoresis and tandem mass spectrometry using MALDI-TOF-TOF-MS. Thirteen protein spots showed greater than twofold increase, following 72 h incubation of fibroblast with CoCr particles. Four of these proteins were identified by tandem mass spectrometry. These were Annexin II, Pyruvate kinase, Triose phosphate isomerase, and N-myc downstream regulated gene 1 protein. Cobalt is a hypoxia mimicking agent and N-myc downstream regulated gene 1 protein, Triose phosphate isomerase, Pyruvate kinase, and Annexin II are important hypoxia regulated gene products that are found to be over expressed in cellular oxidative stress response. Our data indicates that exposure of fibroblast to CoCr alloy induces the transition of these cells into a hypoxia like state and oxidative stress even in normoxic culture conditions. The study reflects the possibility of the presence of a hypoxic environment in the periprosthetic tissue surrounding metallic implants.


Measurement of the new anticoagulants.
New oral anticoagulants are given at fixed daily doses without laboratory dose adjustment for prevention of venous thromboembolism following elective total knee- and hip replacement, for treatment and prevention of recurrent events of acute venous thromboembolism, and for prevention of embolic events in atrial fibrillation. However, it may be necessary to determine the anticoagulant effect of new oral anticoagulants in special patient populations such as in elderly, for renal impairment, before operation, bleeding or thrombotic episodes and to monitor self-compliance. Oral factor Xa and oral thrombin inhibitors influence dose dependently global and specific coagulation assays. Standardization of assays is currently undertaken. Determination of the new oral anticoagulants in serum samples would facilitate blood sampling and analysis from samples taken and stored for creatinine or other biochemical parameters. Point of care methods from plasma or urine for the new oral anticoagulants would improve patient care. First data demonstrate the feasibility of such assays in urine.


Landing response of Aedes (Stegomyia) polynesiensis mosquitoes to coloured targets.
Aedes polynesiensis Marks (Diptera: Culicidae) is the primary vector of lymphatic filariasis (LF) in the island countries and territories of the South Pacific. In the development of a novel control tool, the response of Ae. polynesiensis to six different colours (three solid fabrics, two patterned fabrics and a plastic tarp) was measured using a digital photographic system. Adult mosquitoes were placed into an environmental chamber and allowed to choose between a white target and one of six experimental targets. Mosquito landing frequency and landing duration were calculated. Adult female Ae. polynesiensis preferred all of the experimental targets to the white control target. Mosquito landing frequency was highest for the solid targets (black, navy blue and red) followed in turn by the two colour pattern targets and the polyethylene target. Mosquito landing duration was greater for experimental targets when compared with white control targets. Mosquito landing frequencies did not change over time during the course of the assay. The response of male Ae. polynesiensis was also measured when exposed to a 100% cotton black target. Male mosquitoes preferred the black target to the white control target, although at levels lower than that observed in female mosquitoes. The results suggest that future investigations evaluating the visual responses of Ae. polynesiensis mosquitoes are warranted, with a special emphasis on semi-field and field-based experiments.


IgE in experiemental schistosomiasis. I. Serum IgE levels after infection by Schistosoma mansoni in various strains of rats.
Serum IgE levels were measured by radioimmunoassay in four strains of rats, before and after infection by Schistosoma mansoni. Differences were observed in basal IgE levels, depending on the strain considered. Serum IgE rose 10--20 days after infection and the maximum level, between days 30 and 50, ranged from 14 to 60 times the basal level. One of the most characteristic features of IgE production in rat schistosomiasis was the persistence of high IgE levels for a long time after rejection of the worms.


The use of untreated bednets and malaria infection, morbidity and immunity.
The effect of bednet use was investigated, without undertaking a specific intervention, in four cross-sectional community-based surveys in 10 villages of a highly endemic area of Papua New Guinea. Over half (55%) of the villagers interviewed reported that they had used a bednet on the previous night. In general and after adjustment for age, village and housing characteristics, bednet users, particularly children, had lower parasite prevalences and spleen rates and less enlarged spleens than non-users. However, users were similar to non-users in terms of fever reported for the previous week, axillary temperature, parasite density and haemoglobin level. The prevalence of antibody to the ring erythrocyte surface antigen and the major merozoite surface antigen 2 was lower in users than non-users. The association with malariometric indices and immune responses remained significant when bednet users were compared with non-users in houses without bednets. Thus, untreated bednets do not reduce malaria transmission sufficiently to decrease morbidity. They might paradoxically increase the risk of clinical malaria by lowering the development of humoral immunity.


Histological study on the postnatal development and sequence of eruption of the mandibular cheek-teeth of rabbits (Oryctolagus cuniculus).
The postnatal development and sequence of eruption of mandibular cheek teeth of rabbits were studied by histological methods. Hemi-mandibles were dissected and sectioned in longitudinal sections of 7 mu and stained with hematoxylin-eosin and Masson's trichrome. The presence of two mandibular deciduous molars which are replaced by corresponding premolars and of three mandibular permanent monofisary molars was confirmed. Eruption of deciduous molars of the mandible begins at 4 days after birth and of the mandibular permanent molars at 9 days, while that of mandibular premolars occurs at 23 days, replacing the mandibular deciduous molars which have exfoliated. At 32 days all the mandibular permanent cheek-teeth are erupted. At birth the mandibular deciduous molars are completely developed and at 4 days their root resorption is initiated. At the first day P3 is in the bell stage and the P4 has begun dentinogenesis. In M1 and M2 amelogenesis is observed.


Present and future challenges of induced pluripotent stem cells.
Growing old is our destiny. However, the mature differentiated cells making up our body can be rejuvenated to an embryo-like fate called pluripotency which is an ability to differentiate into all cell types by enforced expression of defined transcription factors. The discovery of this induced pluripotent stem cell (iPSC) technology has opened up unprecedented opportunities in regenerative medicine, disease modelling and drug discovery. In this review, we introduce the applications and future perspectives of human iPSCs and we also show how iPSC technology has evolved along the way.


Delayed neuromonitoring alarm after scoliosis correction in Lenke type 4 adolescent idiopathic scoliosis.
A 12-year-old girl underwent surgery for Lenke type 4 adolescent idiopathic scoliosis. After scoliosis correction, the transcranial motor-evoked potential (Tc-MEP) showed no alarm. However, the Tc-MEP amplitude had declined ~10 min after correction, with a normal blood pressure (BP) and body temperature and without any technical monitoring errors. Therefore, we suspected indirect spinal cord ischaemia because of the delayed true-positive Tc-MEP alarm. All the strong corrections made loss of Tc-MEP and all the correction releases made recovers of waveform. Finally, a weak correction was performed, and the Tc-MEP amplitude was recovered. Because transient spinal cord ischaemia due to correction of triple curves may cause a delayed monitoring alarm, the monitoring team should frequently check Tc-MEP after these manoeuvres. This patient had no neurological deficits and was considered to be a rescue case.


T-wave loop area from a pre-implant 12-lead ECG is associated with appropriate ICD shocks.
In implantable cardioverter-defibrillator (ICD) patients, predictors of ICD shocks and mortality are needed to improve patient selection. Electrocardiographic (ECG) markers are simple to obtain and have been demonstrated to predict mortality. We aimed to assess the association of T-wave loop area and circularity with ICD shocks. The study investigated patients with ICDs implanted between 1998 and 2010 for whom digital 12-lead ECGs (Schiller CS200 ECG-Network) of sufficient quality were obtained within 1 month prior to the implantation. T-wave loop area and circularity were calculated. Follow-up data of appropriate shocks were obtained during ICD clinic visits that included reviews of device stored electrograms. A total of 605 patients (82% males) were included; 68% had ischemic cardiomyopathy and 72% were treated for primary prevention. Over 3.8±1.4 years of follow-up, 114 patients (19%) experienced appropriate shock(s). Those with smaller T-wave loop area received fewer shocks (TLA, hazard ratio, HR, per increase of 1 technical unit, 0.71; [95% confidence interval, 0.53-0.94]; P = 0.02) and those with larger T-wave loop circularity (TLC) representing rounder T wave loop received more shocks (HR per 1% TLC increase 2.96; [0.85-10.36]; P = 0.09). When the quartile containing the largest TLA and TLC values, respectively, were compared to the remaining cases, TLA remained significantly associated with fewer and TLC with more frequent shocks also after multivariate adjustment for clinical variables (HR, 0.59 [0.35-0.99], P = 0.044; and 1.64 [1.08-2.49], P = 0.021, respectively). The size and shape of the T-wave loop calculated from pre-implantation 12-lead ECGs are associated with appropriate ICD shocks.


Oligomeric interfaces under the lens: gemini.
The assembly of subunits in protein oligomers is an important topic to study as a vast number of proteins exists as stable or transient oligomer and because it is a mechanism used by some protein oligomers for killing cells (e.g., perforin from the human immune system, pore-forming toxins from bacteria, phage, amoeba, protein misfolding diseases, etc.). Only a few of the amino acids that constitute a protein oligomer seem to regulate the capacity of the protein to assemble (to form interfaces), and some of these amino acids are localized at the interfaces that link the different chains. The identification of the residues of these interfaces is rather difficult. We have developed a series of programs, under the common name of Gemini, that can select the subset of the residues that is involved in the interfaces of a protein oligomer of known atomic structure, and generate a 2D interaction network (or graph) of the subset. The graphs generated for several oligomers demonstrate the accuracy of the selection of subsets that are involved in the geometrical and the chemical properties of interfaces. The results of the Gemini programs are in good agreement with those of similar programs with an advantage that Gemini programs can perform the residue selection much more rapidly. Moreover, Gemini programs can also perform on a single protein oligomer without the need of comparison partners. The graphs are extremely useful for comparative studies that would help in addressing questions not only on the sequence specificity of protein interfaces but also on the mechanism of the assembly of unrelated protein oligomers.


Dynamic single crystals: kinematic analysis of photoinduced crystal jumping (the photosalient effect).
Crystals on the move: If they are subjected to a strong light stimulus, crystals of the cobalt coordination compound [Co(NH3)5(NO2)]Cl(NO3) undergo sudden jumps and leap over distances 10(2)-10(5) times their own size to release the strain that accumulates in their interior. The first quantitative kinematic analysis of this phenomenon is reported. The observed effect could be employed for actuation on the macroscopic scale.


Accidental hijab pin ingestion in Muslim women: an emerging endoscopic emergency?
Ingested foreign body is an infrequent indication for emergency endoscopy in the adult gastroenterology practice. We describe the clinical features and endoscopic management of the first four cases of accidental ingestion of hijab pins by Muslim women in our unit, all presenting within a 12-month period. The pins were all successfully retrieved without any complications. In this report, we review published guidelines and the current literature, as well as discussing the approach (conservative vs proactive endoscopic retrieval) and timing of endoscopic treatment. The Muslim community may need to be alerted to the potential health hazard of hijab pins.


Importance of receptor flexibility in binding of cyclam compounds to the chemokine receptor CXCR4.
We have elucidated the binding sites of four moncyclam and one bicyclam antagonist AMD3100, in the human chemokine receptor CXCR4. Using the predicted structural models of CXCR4, we have further predicted the binding sites of these cyclam compounds. We used the computational method LITiCon to map the differences in receptor structure stabilized by the mono and bicyclam compounds. Accounting for the receptor flexibility lead to a single binding mode for the cyclam compounds, that has not been possible previously using a single receptor structural model and fixed receptor docking algorithms. There are several notable differences in the receptor conformations stabilized by monocyclam antagonist compared to a bicylam antagonist. The loading of the Cu(2+) ions in the cyclam compounds, shrinks the size of the cyclam rings and the residue D262(6.58) plays an important role in bonding to the copper ion in the monocylam compounds while residue E288(7.39) is important for the bicyclam compound.


Mediterranean diet and erectile dysfunction: a current perspective.
In this current perspective we analyzed the role of Mediterranean diet (MedDiet) in sexual function and particularly in erectile dysfunction (ED), according to the latest scientific evidence. We conducted a systematic search of relevant full-length papers identified during the time period from 1 January 2010 to the present. Published studies showed that adherence to a MedDiet contributes to preventing ED through an improved lipid and glucose metabolism, increased antioxidant defenses, and increased arginine levels which could raise nitric oxide activity. Our findings suggest that the encouragement of a healthy lifestyle, such as MedDiet promotion, could be an attractive dietary approach to prevent ED and preserve sexual function.


Possible contribution of brain angiotensin III to ingestive behaviors in baboons.
Recent experiments with specific aminopeptidase inhibitors in rats have strengthened earlier proposals that ANG III may be an important regulatory peptide in the brain. Central mechanisms regulating blood pressure, ingestive behaviors, and vasopressin release could be involved. Arguments in favor of a role for ANG III depend, in part, on the efficacy of ANG III as an agonist. These first studies in primates tested whether ANG III stimulates ingestive behaviors in baboons. Intracerebroventricular (ICV) infusions of ANG III were as potent as ANG II in stimulating water drinking and intake of NaCl solution. On the basis of this criterion and consistent with findings in rats, ANG III could be a main effector peptide in the regulation of ingestive behaviors in a primate.


Plant growth-promoting trait of rhizobacteria isolated from soil contaminated with petroleum and heavy metals.
Three hundred and seventy-four rhizobacteria were isolated from the rhizosphere soil (RS) or rhizoplane (RP) of Echinochloa crus-galli, Carex leiorhyncha, Commelina communis, Persicaria lapathifolia, Carex kobomugi, and Equisetum arvense, grown in contaminated soil with petroleum and heavy metals. The isolates were screened for plant growth-promoting potential (PGPP), including indole acetic acid (IAA) productivity, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, and siderophore(s) synthesis ability. IAA production was detected in 86 isolates (23.0%), ACC deaminase activity in 168 isolates (44.9%), and siderophore(s) synthesis in 213 isolates (57.0%). Among the rhizobateria showing PGPP, 162 rhizobacteria had multiple traits showing more than two types of PGPP. The PGPP-having rhizobateria were more abundant in the RP (82%) samples than the RS (75%). There was a negative correlation (-0.656, p < 0.05) between the IAA-producers and the ACC deaminase producers. Clustering analysis by principal component analysis showed that RP was the most important factor influencing ecological distribution and physiological characterization of PGPP-possesing rhizobateria.


Role of the LysR-type transcriptional regulator PecT and DNA supercoiling in the thermoregulation of pel genes, the major virulence factors in Dickeya dadantii.
Bacteria are colonizers of various environments and host organisms, and they are often subjected to drastic temperature variations. Dickeya dadantii is a pathogen infecting a wide range of plant species. Soft rot, the visible symptom, is mainly due to the production of pectate lyases (Pels) that destroy plant cell walls. The production of Pels is controlled by a complex regulation system that responds to various stimuli, such as the presence of pectin, growth phase and temperature. Despite numerous regulatory studies, the thermoregulation mechanism of Pel production remains unexplained. Here, we show that PecT, a previously identified repressor, modulates pel gene expression in a temperature-dependent manner, and we demonstrate that PecT binding on pel promoters increases concomitantly with temperature. High temperatures relax the DNA in D. dadantii, and remarkably, artificial relaxation of DNA at low temperatures increases PecT binding to DNA. Deletion of pecT augmented the capacity of D. dadantii to initiate soft-rot symptoms at high temperatures. These results reveal that DNA topology and PecT act in concert to fine-tune D. dadantii virulence in response to temperature. This novel combination between DNA topology and a conventional transcriptional regulator extends our understanding of the thermoregulation mechanisms involved in bacterial virulence.


Does Internet voting make elections less social? Group voting patterns in Estonian e-voting log files (2013-2015).
Remote Internet voting places the control and secrecy of the immediate voting environment on the shoulder of the individual voter but it also turns voting into yet another on-line activity thus endangering the well-known social nature of voting and possibly reducing the crucial sense of civic duty that is important for a healthy democracy. There is however a complete lack of evidence to what degree this actually materializes once electronic voting is introduced. This paper uses individual level log data on Internet voting in Estonian elections between 2013-2015 to inspect if Internet voting retains the social nature of the voting act. We do so by examining if Internet voting in groups takes place and what implications it has for voting speed. We find strong evidence of e-voting in pairs. Same aged male-female pairs seem to be voting in close proximity to each other, consistent with spouses or partners voting together. Also, female-female and female-male pairs with large age differences seem to be voting together, consistent with a parent voting with an adult aged offspring. With regards to voting speed we see the second vote in a vote pair being considerably faster than the first vote, again indicating a shared voting act. We end with a discussion of how the onset of electronic voting does not make elections less social, but does make vote secrecy more a choice rather than a requirement.


Cryopreservation of Galanthus elwesii Hook. apical meristems by droplet vitrification.
The aim of this study was to develop an efficient cryopreservation protocol for the geophyte giant snowdrop (Galanthus elwesii Hook.) that guarantees a high rate of survival and plant regeneration after cryopreservation. The excised apical meristems were obtained from cultures of in vitro grown bulb scales. Using a vitrification procedure and optimizing the duration of the exposure to the loading solution (LS), meristem post-rewarm survival rates higher than 90 percent were achieved. Also regrowth percentages were very high, ranging from 87 to 91 percent. After optimizing the time of exposure to the plant vitrification solution (PVS2), the survival rate was between 83 and 97 percent. During post-rewarm regeneration, good growth recovery was as high as 76 percent; however, hyperhydration and callusing were also observed. The results demonstrate that cryopreservation of Galanthus elwesii germplasm seems to be feasible.


Preoperative Assessment of Patients Undergoing Elective Gastrointestinal Surgery: Does Body Mass Index Matter?
At Queen Elizabeth Hospital Birmingham (QEHB), no specific protocol to stratify patients by body mass index (BMI) exists. This study sought to evaluate outcomes following gastrointestinal surgery. Patients undergoing gastrointestinal surgery attending preassessment screening clinic (PAS) from August to September 2016 at the QEHB were identified. Primary outcome was postoperative complications. Secondary outcomes were major complications and 30-day readmission rates. Of 368 patients preassessed, 31% (116/368) were overweight and 35% (130/368) were obese. Median age was 57 (range: 17-93). There was no difference of BMI between the low risk and high risk clinics. Patients in high risk clinic had significantly higher rates of comorbidities, major surgical grades, and malignancy as the indication for surgery. Overall complication rates were 14% (52/368), with 3% (10/368) having major complications (Clavien-Dindo Grades III-IV). Whilst BMI was associated with comorbidity (p = 0.03) and ASA grade (p < 0.001), it was not associated with worse outcomes. Patients attending high risk clinic had significantly higher rates of complications. Surgery grade was found to be an independent risk factor of complication rates. Use of BMI as an independent factor for preassessment level is not justified from our cohort.


Adult malaria mortality during 2019 at Bo Government Hospital, Sierra Leone.
It is uncertain whether malaria is an important cause of death among adults in endemic areas. We performed a chart review of adults admitted to Bo Government Hospital during 2019. Of 893 admissions, 149 (59% female, mean age 58.5 years) had a laboratory diagnosis of malaria and 22 (14.8%) died. Mortality was significantly higher among patients with severe malaria compared with those who had non-severe malaria (6/20 [30%] versus 16/129 [12.4%], p=0.031). Our results suggest that malaria is a common cause of death in hospitalized Sierra Leonian adults.


A prospective study of the association between living in a rural environment during childhood and risk of psoriasis.
Psoriasis is one of the most common immune-mediated inflammatory diseases (IMIDs). Living in a rural environment during childhood is associated with a decreased risk of certain IMIDs, like asthma, in adulthood. However, its role in other IMIDs, such as psoriasis is still unclear. To evaluate the relationships between different factors related to the environment during childhood and the risk of psoriasis in adulthood we conducted a study in E3N, a French prospective cohort composed of 98 995 women. During the 1990-2018 follow-up of 72 154 study participants, we identified 1 967 incident cases of psoriasis from self-reports in self-administered structured questionnaires. During the 2004-2018 follow-up of 67 917 study participants, 188 moderate-to-severe cases of psoriasis were identified through self-reports and from data from a drug reimbursement database. We fitted Cox proportional hazards regression models with age as the time scale from which we estimated hazard ratios adjusted for putative confounders (aHRs). We found inverse associations with risk of psoriasis for rural birthplace [aHR: 0.89 (95%CI: 0.79-0.96)] and for having farming parents [aHR: 0.84 (95%CI: 0.72-0.97)]. For moderate-to-severe psoriasis we found a nominally similar inverse association with rural birthplace but not with having farming parents. Our results suggest that an exposure to a rural environment during childhood may be associated with a reduced risk of psoriasis. These findings may help to improve our understanding of the pathogenesis of psoriasis.


[Development policies of health and nursing human resources].
The sanitary movement brought about, in the educational setting, demands for health training focused on primary care, considering the inconsistency between professional practice and population health needs. This is a documental research with the objective to identify human resources development policies in National and Health Human Resources Conferences, in the period from 1986 to 2005. Results show that the debate concerning nursing education is presented in the following categories: legal landmarks in nursing education; curricular dimension of health education; perspectives of teaching-learning methods; and health human resources training. This course of debate shows the current path that different education instances should trail.


Active-site coating for molecular discrimination in heterogeneous catalysis.
A coherent layer of zeolite A has been applied to a SiO2-supported Pt-Fe oxidation catalyst, using total surface charge-reversal. The zeolite has tracked the metals into the pore structure of the support, covering the active sites. The zeolite channel size is large enough to allow access of CO and O2 to the active sites, and to allow CO2 to emerge, but it excludes larger molecules. The presence of the zeolite membrane transforms the supported Pt-Fe into a highly specific catalyst, which can discriminate between CO and butane, even after the macroscopic catalyst particles are crushed.


High-Risk Fall Rehabilitation With Modified Otago Exercises and Medicinal Nano Gel Phonophoresis for Symptomatic Relief in Osteoarthritis of Knee.
Proprioception is a major affection faced by individuals who undergo lower limb injuries. Especially in the elderly population, this places a major role in increasing the risk of fall. We are reporting a case of an elderly female having severe pain in her lower limb and difficulties in performing activities of daily living. Post clinical assessment, a functional diagnosis of osteoarthritic knee was made. The patient was managed with proprioception exercises (Otago exercises) and phonophoresis. These exercises were also beneficial in improving the apprehension of patient towards daily activities, walking, stair climbing, and fall risk. The technique of phonophoresis helped in alleviation of pain when given with a beneficial adjunct, like a medicinal gel.


Determination of iron in blood serum using flow injection with luminol chemiluminescence detection.
A simple and rapid fl ow injection method is reported for the determination of iron in blood serum after acid digestion with HNO3 and HClO4, based on luminol CL detection in the absence of added oxidant. The detection limit (3 s) was 1.0 nmol/L with a sample throughput of 120/h. The calibration graph was linear over the range 0.001-1.0 micromol/L (r2 = 0.9974), with relative standard deviations (RSD) (n = 4) in the range 3.2-5%. The effect of interfering cations (Ca(II), Mg(II), Cu(II), Cd(II), Pb(II), Mn(II), Zn(II), Ni(II), Co(II) and Fe(III)) and anions (Cl-, SO4(2-), HCO3-, NO3-, NO2-) were studied using a luminol CL system for Fe(II) determination. The method was applied to normal blood serum and the results (1.32 +/- 0.08-1.74 +/- 0.05 mg/L) were compared with those from a spectrophotometric reference method (1.34 +/- 0.06-1.80 +/- 0.10 mg/L), which agree fairly well with the overall reference range in blood.


Evaluating coagulation disorders in the use of bevacizumab for metastatic colorectal cancer by thrombelastography.
The aim of this study was to evaluate coagulation disorders in patients with metastatic colorectal cancer treated with bevacizumab by using rotation thrombelastogram (ROTEM(®)) and correlate ROTEM(®) parameters with routine coagulation tests. A total of 18 colorectal cancer patients who received bevacizumab combined with chemotherapy were included. There was no statistically significant difference between results of platelet count, prothrombin time (PT) and activated partial thromboplastin time (APTT), fibrinogen, and D-Dimer obtained at baseline and on day 1 of chemotherapy cycles 4, 8, and 12. CFT value was significantly increased on day 1 of cycle 12 compared with baseline value by both INTEM and EXTEM assays while CT and MCF showed no significant difference. Correlation analysis revealed significant correlation between laboratory parameters and ROTEM(®) parameters. Platelet count showed a positive correlation with MCF in INTEM (r = 0.627) and EXTEM (r = 0.699) assays while showed a negative correlation with CFT in EXTEM (r = -603). There was a significant negative correlation between fibrinogen levels and CFT in INTEM (r = -0.617) and EXTEM (r = -0.512). Our data demonstrated the value of TEG over conventional coagulation tests in evaluating antiangiogenesis agents-induced coagulation disorders.


FITNESS CONSEQUENCES OF VARIATION IN EGG SIZE AND FOOD ABUNDANCE IN BROOK TROUT SALVELINUS FONTINALIS.
Relationships between egg size and juvenile survival in brook trout, Salvelinus fontinalis, were determined experimentally at two levels of food abundance and then incorporated into a model that related maternal fitness to egg size and food supply. Egg volume was positively correlated with juvenile size at hatching and size at yolk sac resorption but had no significant effect on embryonic survival or development time. Juvenile survival was linearly related to egg size throughout the first 50 days of exogenous feeding at high and low food levels. The effects of egg size and food abundance on juvenile survival were not additive. Decreased food abundance significantly increased mortality among the smallest eggs but had a negligible effect on the largest eggs. Model simulations indicate that maternal fitness is a curvilinear function of egg size and that food supply influences both the height and the shape of the function. The fitness functions provide empirical support for the hypothesis that selection favors an increase in offspring size with reductions in resource abundance.


Acute respiratory failure in a rapidly enlarging benign cervical goitre.
Benign goitres have the potential to reach massive sizes if neglected, but most have a protracted course that may or may not present with compressive symptoms. We report the case of a 57-year-old man who presented with a rapidly enlarging nodular goitre resulting in acute respiratory failure. Endotracheal intubation and emergency total thyroidectomy were performed, revealing massive thyroid nodules with minimal intrathoracic extension and tracheal erosion. Despite a course and clinical findings suggestive of malignant disease, histopathology was consistent with a benign multinodular goitre. Several cases of benign goitres necessitating endotracheal intubation have been reported. Airway compromise was attributed to a significant intrathoracic component, or inciting events such as thyroid haemorrhage, pregnancy, radioiodine uptake or major surgery. Obstructive symptoms may not correlate well with objective measures of upper airway obstruction such as radiographs or flow volume loops.


Individualized Compared With Standard Postdischarge Oxycodone Prescribing After Cesarean Birth: A Randomized Controlled Trial.
To evaluate whether individualized postdischarge oxycodone prescribing guided by inpatient opioid use reduces the number of unused opioid tablets after cesarean birth. We conducted a randomized, controlled trial of women aged 18 years or older undergoing cesarean birth. Participants were randomized at discharge in a 1:1 ratio to a standard (30 tablets of 5 mg oxycodone) or an individualized oxycodone prescription (predicted based on each patient's inpatient opioid use). All women were contacted starting 14 days after cesarean birth to assess number of oxycodone tablets used and adequacy of pain control. The Tennessee Controlled Substance Monitoring Database was accessed to confirm dispensed opioids. The primary outcome was number of unused oxycodone tablets prescribed for pain control after cesarean birth. A total sample size of 160 women was necessary to detect a 30% difference in leftover tablets between groups with 80% power and α of 0.05. Between June 14, 2017, and August 26, 2017, we screened 323 women and randomized 172. Baseline characteristics and inpatient opioid use were similar between groups. Women in the individualized group were prescribed fewer tablets (14 [interquartile range 12-16] vs 30 [interquartile range 30-30], P<.001) and had 50% fewer unused tablets than women in the standard group (5 [interquartile range 1-8] vs 10 [interquartile range 0-22], P<.001). Overall, 13% (23/172) used no opioids after discharge and 26% (44/172) used all prescribed opioids. There were no differences between the standard and individualized groups in the proportion of women who used no opioids or all opioids and no difference in the proportion of dispensed opioids used (60% [interquartile range 23-100] vs 61% [29-89], P=.93). Women in the individualized group used only half the number of prescribed opioids as women in the standard group (8 [interquartile range 4-14] vs 15 [interquartile range 6-30], P<.001). Patient-reported pain outcomes did not differ significantly by group. Individualized opioid prescribing based on inpatient use reduces the number of unused oxycodone tablets compared with standard prescribing. ClinicalTrials.gov, NCT03168425.


Parental exposure to pesticides and poor clutch viability in American alligators.
In central Florida, alligators (Alligator mississippiensis) inhabiting lakes contaminated with organochlorine pesticides (OCPs) produce eggs that have high OCP concentrations and low clutch viability (proportion of eggs in a clutch that yield a live hatchling) compared to those from less contaminated lakes (reference lakes). However, a clear dose-response relationship has not been established between OCPs and poor clutch viability. In order to better elucidate a cause and effect relationship between OCP exposure and clutch viability, we conducted concurrent field and laboratory studies. Our field study reaffirmed that eggs of wild alligators from OCP-contaminated lakes and wetlands continue to have lower clutch viability and higher OCP burdens than eggs from reference lakes. Our field study also demonstrated that OCP egg burdens were strongly correlated with clutch viability for some of the OCP-contaminated sites, but not all. To better test causal relationships, a parental exposure study was conducted using captive adult alligators. Our laboratory study demonstrated that dietary exposure of captive alligators to an ecologically relevant OCP mixture caused alligators to produce eggs with higher OCP burdens and reduced clutch viability, as compared to the captive-control population. The experimentally induced egg burdens and clutch viability reductions were similar to those of wild alligators from OCP-contaminated sites. Our field and laboratory results suggest parental OCP exposure may be contributing to low clutch viability in wild alligators inhabiting OCP-contaminated habitats, raising some concern for endangered crocodilians living in OCP-contaminated habitats.


Rationale and Design of the EMPA-TROPISM Trial (ATRU-4): Are the "Cardiac Benefits" of Empagliflozin Independent of its Hypoglycemic Activity?
The SGLT2 inhibitor empagliflozin reduced cardiovascular mortality by 38% and heart failure (HF) hospitalizations by 35% in diabetic patients. We have recently demonstrated the efficacy of empagliflozin in ameliorating HF and improving cardiac function in a non-diabetic porcine model of HF mediated via a switch in myocardial metabolism that enhances cardiac energetics. Therefore, we hypothesized that the cardiac benefits of empagliflozin can also be extended to non-diabetic HF patients. The EMPA-TROPISM clinical trial is a randomized, double-blind, parallel group, placebo-controlled, trial comparing the efficacy of and safety of empagliflozin in non-diabetic HF patients. Eighty patients with stable HF for over 3 months, LVEF < 50%, and New York Heart Association functional class II to IV symptoms will be randomized to empagliflozin 10 mg for 6 months or placebo. All patients will undergo cardiac magnetic resonance (CMR), cardiopulmonary exercise test (CPET), 6-min walk test, and quality of life questionnaires. The primary outcome is the change in left ventricular end-diastolic volume measured by CMR. Secondary end-points include change in peak VO2 (CPET); change in LV mass, in LVEF, in myocardial mechanics (strains), in left atrium volumes, in RV function and volumes, in interstitial myocardial fibrosis, and in epicardial adipose tissue (CMR); change in the distance in the 6-min walk test; and changes in quality of life (Kansas Cardiomyopathy questionnaire [KCCQ-12] and the 36-Item Short Form Survey [SF-36]). Safety issues (e.g., hypoglycemia, urinary infections, ketoacidosis,…) will also be monitored. In summary, EMPA-TROPISM clinical trial will determine whether the SGLT2 inhibitor empagliflozin improves cardiac function and heart failure parameters in non-diabetic HF patients (EMPA-TROPISM [ATRU-4]: Are the "cardiac benefits" of Empagliflozin independent of its hypoglycemic activity; NCT 03485222).


Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels.
In the present study, we examined the molecular mechanism by which homocysteine causes neuronal cell apoptosis. We further investigated the mechanisms of melatonin's ability to reduce homocysteine-induced apoptosis. Consistent with its antioxidant properties, melatonin reduced homocysteine-induced lipid peroxidation and stimulated glutathione peroxidase enzyme activity in hippocampus of rats with hyperhomocysteinemia. Furthermore, melatonin treatment diminished cytochrome c release from mitochondria and reduced caspase 3 and caspase 9 activation induced by hyperhomocysteinemia. Chronic hyperhomocysteinemia also led to poly(ADP-ribose) polymerase cleavage and subsequently DNA fragmentation. Treatment with melatonin markedly inhibited poly(ADP-ribose) polymerase cleavage and reduced DNA damage. Hyperhomocysteinemia caused an elevation of pro-apoptotic Bax levels while reducing anti-apoptotic protein, Bcl-2, levels. Daily administration of melatonin up-regulated Bcl-2 and down-regulated Bax levels. We propose that, in addition to its antioxidant properties, melatonin has the ability to protect neuronal cells against apoptosis mediated homocysteine neurotoxicity by modulating apoptosis-regulatory proteins in the hippocampus of rats.


Analyzing the Causes and Frequency of Early Dental Implant Failure among Iranians: An Epidemiological Study.
The rate of early dental implant failure (DIF) has increased in recent years, though the risk factors associated with this primary failure remain unclear. This study aimed to determine the rate of early implant failure and identify contributing factors. It was conducted from March 2018 to 2020 in Mashhad, Iran. This observational study examined the records of 983 implants from the Implant Department of Mashhad Dental School. Variables considered included age, gender, systemic diseases, smoking habits, implant type and size, and surgery-related factors. Data were analyzed using Chi-square, Mann-Whitney U, and Fisher exact tests in SPSS V22, with a p-value of 0.05 or less considered statistically significant. Of the 983 implants, 42 (4.3%) experienced early failure. The study population consisted of 555 (56.5%) females and 428 (43.5%) males, with an average age of 49.34 ± 13.67 years. A significant correlation was found between surgical complications (e.g., fracture of implant fixtures and inferior alveolar nerve exposure) and implant loading time (Yes or No) with early DIF (p=0.05 and p < 0.01, respectively). However, no significant correlation was observed between early failure and factors such as age, gender, smoking habits, systemic diseases, implant dimensions, or manufacturer. Surgical complications and loading time may be the most critical factors contributing to early implant failure. Therefore, we suggest dentists pay attention to the mentioned factors in the surgical protocols and their relationship. Further prospective studies on risk factors that could affect early implant failure are needed.