Physician's Perceptions of Telemedicine in HIV Care Provision: A Cross-Sectional Web-Based Survey.
Telemedicine, or electronic interactive health care consultation, offers a variety of benefits to both patients and primary care clinicians. However, little is known about the opinions of physicians using these modalities. The aim of this study was to examine physician perceptions, including challenges, risks, and benefits of the use of telemedicine in human immunodeficiency virus (HIV) patient care. A Web-based, self-administered, anonymous, cross-sectional survey was sent to physicians known to be providing medical care to patients living with HIV in Ontario, Canada. Descriptive statistics and frequencies were used to examine physician perceptions and characteristics of participants. Among the 51 invited participants, 48 (94%) completed the survey. Sixty-two percent (29/47) of respondents reported that they used some form of telemedicine to care for HIV patients in their practice. Of the respondents who identified as having used telemedicine in their practice, telephone (86%, 25/29), email (69%, 20/29), and teleconsultation (24%, 7/29) were listed as frequent modalities used. A significant number of physicians (83%, 38/46) agreed that an obstacle to adopting telemedicine is their perception that this modality does not allow for a comprehensive assessment of their patients' health. In addition, 65% (28/43) of physicians agreed that patients may not feel adequately connected to them as a provider if they used telemedicine. However, 85% (39/46) of respondents believed that telemedicine could improve access and timeliness to care along with increasing the number of times physicians can interact with their patients. From the perceptions of physicians, telemedicine shows promise in the care of patients living with HIV. More than half of the respondents are already using telemedicine modalities. Whereas many physicians are concerned about their ability to fully assess the health of a patient via telemedicine, most physicians do see a need for it-to reduce patient travel times, reduce exposure to stigma, and improve efficiency and timely access to care. Challenges and risks such as technological gaps, confidentiality, and medicolegal concerns must be addressed for physicians to feel more comfortable using telemedicine.


3D material cytometry (3DMaC): a very high-replicate, high-throughput analytical method using microfabricated, shape-specific, cell-material niches.
Studying cell behavior within 3D material niches is key to understanding cell biology in health and diseases, and developing biomaterials for regenerative medicine applications. Current approaches to studying these cell-material niches have low throughput and can only analyze a few replicates per experiment resulting in reduced measurement assurance and analytical power. Here, we report 3D material cytometry (3DMaC), a novel high-throughput method based on microfabricated, shape-specific 3D cell-material niches and imaging cytometry. 3DMaC achieves rapid and highly multiplexed analyses of very high replicate numbers ("n" of 104-106) of 3D biomaterial constructs. 3DMaC overcomes current limitations of low "n", low-throughput, and "noisy" assays, to provide rapid and simultaneous analyses of potentially hundreds of parameters in 3D biomaterial cultures. The method is demonstrated here for a set of 85 000 events containing twelve distinct cell-biomaterial micro-niches along with robust, customized computational methods for high-throughput analytics with potentially unprecedented statistical power.


Platelet glycoprotein IIb/IIIa inhibitor therapy in non-ST segment elevation acute coronary syndromes.
Platelet glycoprotein (GP) IIb/IIIa inhibitors prevent fibrinogen binding and platelet aggregation. They decrease ischemic complications associated with non-ST segment elevation acute coronary syndromes and percutaneous coronary intervention. Meta-analyses of 6 randomized trials of parenteral GP IIb/IIIa inhibitors in patients with acute coronary syndromes suggest a significant reduction in death and myocardial infarction in high risk patients. These include patients undergoing early percutaneous coronary intervention or those with high TIMI risk score, elevated troponin values, or diabetes mellitus. Despite guideline recommendations supporting therapy for these indications, only a minority of appropriate candidates are being treated. The risk of major bleeding is small; thrombocytopenia can result from abciximab therapy. Optimal dosing strategies continue to evolve.


Predictors of COVID-19 Severity in Elderly Patients Infected by Omicron in China, 18 December 2022-5 February 2023.
To analyze the clinical characteristics and prognosis of patients hospitalized with non-severe, severe pneumonia and death in Omicron COVID-19. We collected clinical data from 118 patients with COVID-19 in China from 18 December, 2022 and 5 February, 2023. According to the outcome, the patients were divided into non-severe group, severe group and death group. Subsequently, we statistically analyzed the general condition, clinical manifestations, laboratory parameters, NLR, MLR, PLR and HALP of these groups. We also retrospectively analyzed the possible factors affecting the prognostic regression of patients with COVID-19. A total of 118 COVID-19 patients were enrolled in this study, including 64 non-severe patients, 38 severe patients and 16 death patients. Compared with the non-severe group, T lymphocytes, B lymphocytes, Th1, Th2, Th17, Treg cells, IgA, IgG, IgM in the severe and death groups decreased more significantly (P<0.05). The levels of myocardial markers, ALT, AST, BUN, Cr, D-dimer, fibrinogen, NLR, MLR and PLR in the severe and death groups were significantly higher than those in the non-severe group (P<0.05). The level of HALP was significantly lower than that of non-severe group (P<0.05). MLR is not only an independent risk factor for the transition from non-severe to severe disease, but also an independent risk factor for predicting the possibility of death in COVID-19 patients. The analysis of COVID-19 patients in China showed that severe patients were older, more likely to have related complications, lower lymphocyte count, liver and kidney function disorder, glucose and lipid metabolism disorders, myocardial injury, and abnormal coagulation function, suggesting the need for early anticoagulant therapy. In addition, NLR, MLR, PLR and HALP can be used as biomarkers to evaluate the severity and prognosis of COVID-19 patients.


Investigation of the Influence of Roughness and Dental Implant Design on Primary Stability via Analysis of Insertion Torque and Implant Stability Quotient: An In Vitro Study.
In the placement of dental implants, the primary fixation between the dental implant and the bone is of great importance and corresponds to compressive mechanical fixation that aims to prevent micromovement of the implant. The aim of this research was to determine the role of roughness and the type of dental implant (tissue-level or bone-level) in implant stability, measured using resonance frequency analysis (RFA) and insertion torque (IT). We analyzed 234 titanium dental implants, placed in fresh calf ribs, at the half-tissue level and half-bone level. The implant surface was subjected to grit-blasting treatments with alumina particles of 120, 300, and 600 μm at a projection pressure of 2.5 bar, resulting in three types of roughness. Roughness was determined via optical interferometry. The wettability of the surfaces was also determined. Implant stability was measured using a high-precision torquemeter to obtain IT, and RFA was used to determine the implant stability quotient (ISQ). The results show that rough surfaces with Sa values of 0.5 to 4 μm do not affect the primary stability. However, the type of implant is important; bone-level implants obtained the highest primary stability values. A good correlation between the primary stability values obtained via IT and ISQ was demonstrated. New in vivo studies are necessary to know whether these results can be maintained in the long term.


Phase transitions and critical behavior in human bimanual coordination.
Conditions that give rise to phase shifts among the limbs when an animal changes gait are poorly understood. Often a "switch mechanism" is invoked that has a neural basis which remains speculative. Abrupt phase transitions also occur between the two hands in humans when movement-cycling frequency is continuously increased. The asymmetrical out-of-phase mode shifts suddenly to a symmetrical in-phase mode involving simultaneous activation of homologous muscle groups. The boundary between the two coordinative states is indexed by a dimensionless critical number, which remains constant regardless of whether the hands move freely or are subject to resistive loading. Coordinated shifts appear to arise because of continuous scaling influences that render the existing mode unstable. Then, at a critical point, bifurcation occurs and a new stable (and perhaps energetically more efficient) mode emerges.


Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.
Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future.


Stat proteins as intracellular regulators of resistance to myocardial injury in the context of cardiac remodeling and targeting for therapy.
The roles of STAT (signal transducers and activators of transcription) proteins are widely discussed in relation to other agents like IFN-γ that are involved in cardiovascular diseases. STAT3 protects cardiomyocytes during endotoxic shock and ischemia and prolongs survival of these cells by activation of antiapoptotic genes like Bcl-2 and c-Fos. Moreover, IL-6 dependent expression of STAT3 is probably responsible for hypertrophy of cardiomyocytes. On the contrary, STAT1 mediates cell death by induction of caspase-1. STAT6 probably enhances cellular damage in myocardial infraction, which is significantly reduced in mice with the knockout STAT6 gene. Considering these facts, we attempted to review in this paper the role of STAT proteins in myocardial remodeling, highlighting STAT3 as a potent mediator of cardioprotection. Our review also aims to acquaint a broad audience of internal medicine practitioners with the STAT3-related molecular mechanisms that underlie the therapeutic properties of such widely administered drugs as angiotensin II type 1 (AT1) receptor antagonists and HMG-CoA reductase inhibitors, such as losartan and lovastatin.


Contribution of the CD5+ B cell to D-proximal VH family expression early in ontogeny.
In this study, the contribution of the CD5+ B cell to the preferential expression of VH 7183 and Q52 observed early in development was determined. CD5+ and CD5- B cells from BALB/c mice were isolated by fluorescence-activated cell sorter and the expression of particular VH gene families was determined directly by in situ hybridization. The results indicate that CD5+ B cells obtained from both adult and neonatal animals express Q52 at increased levels compared with CD5- B cells. Preferential expression of VH 7183 was observed only in the neonatal CD5- B cell subset. Thus, the increased expression of VH 7183 early in development is caused by the CD5- subset whereas increased Q52 expression is caused by the CD5+ subset. These results indicate that the fetal/neonatal conventional B cell is distinct from conventional adult B cells in terms of Ig gene repertoire expression.


Heterogeneous dynamics of ionic liquids: A four-point time correlation function approach.
Many ionic liquids show behavior similar to that of glassy systems, e.g., large and long-lasted deviations from Gaussian dynamics and clustering of "mobile" and "immobile" groups of ions. Herein a time-dependent four-point density correlation function-typically used to characterize glassy systems-is implemented for the ionic liquids, choline acetate, and 1-butyl-3-methylimidazolium acetate. Dynamic correlation beyond the first ionic solvation shell on the time scale of nanoseconds is found in the ionic liquids, revealing the cooperative nature of ion motions. The traditional solvent, acetonitrile, on the other hand, shows a much shorter length-scale that decays after a few picoseconds.


Atomic force microscopy investigation of the dependence of cellular elastic moduli on glutaraldehyde fixation.
Summary The atomic force microscope (AFM) has provided nanoscale analyses of surfaces of cells that exhibit strong adhesive and cell spreading properties. However, it is frequently reported that prior fixation is required for reliable imaging of cells with lower adhesive properties. In the present study, the AFM is used to assess the effects of fixation by glutaraldehyde on the elastic modulus of a human rhabdomyosarcoma transfectant cell line RDX2C2. Our results show a sharp increase in the elastic modulus for even mild fixation (0.5% glutaraldehyde for 60 s), accompanied by a dramatic improvement in imaging reproducibility. An even larger increase is seen in NIH-3T3 mouse fibroblasts, although in that case fixation is not typically necessary for successful imaging. In addition, our results suggest that treatment with glutaraldehyde restricts the content of the resulting images to features nearer to the cell surface.


Effect of seat belt pretensioners on human abdomen and thorax: Biomechanical response and risk of injuries.
A better coupling of the occupant to the car seat in the early phase of a frontal or far side impacts using pretensioner systems may reduce the likelihood of the submarining effect or increases the likelihood of seat belt engaging the shoulder, respectively. However, the high belt forces may also increase the risk of upper body injuries to the vehicle occupant (especially in abdominal region). It was hypothesized that human body characteristics, such as body mass index (BMI) influence the biomechanical response and injury outcome to the abdominal regions during static pretensioning deployment tests. Four postmortem human specimens (PMHS), in a BMI range from 15.6 to 31.2, were positioned in production seats in a normal passenger position and were restrained using a standard three-point belt system. The pretension forces in the belts were generated at two points (retractor and right anchorage) or at all three locations (retractor, left anchorage, and right anchorage). An optical motion capture system and acceleration cubes mounted to the lumbar spine were used to measure the abdomen deformation during testing. The normalized deflections of the thorax recorded at the level of fourth rib were under 10% (noninjury level). Two different patterns were observed in the time histories of abdominal penetration rate in the four PMHSs associated with lower and higher BMI. Abdominal injuries (spleen lacerations) were observed only in the two PMHS with highest BMI. Based on data from this study and similar data from the literature, belt velocity and FmaxCmax were shown to be the best injury predictors for injury risk analysis for Abbreviated Injury Scale 2+ and for Abbreviated Injury Scale 3+ injuries, respectively.


Antithrombotic therapy and cancer.
To assess the current evidence from recent clinical trials investigating antithrombotic agents for the prophylaxis and treatment of venous thromboembolism in cancer patients and for the effects of these agents on cancer progression. A growing body of evidence supports the preventive use of antithrombotic strategies in subgroups of cancer patients. Moreover, in the long-term management of deep venous thrombosis in cancer patients, low-molecular-weight heparin seems to represent a valid alternative to vitamin K antagonists. Finally, several studies have claimed a direct anticancer activity and a positive impact on prognosis of some antithrombotic agents, eg, aspirin and low-molecular-weight heparin. Although recent evidence suggests low-molecular-weight heparin as a possible option in the management and prevention of venous thromboembolism in cancer patients, more evidence from large randomized, prospective, controlled trials is needed to determine the exact the magnitude of the risk-benefit ratio associated with its use. The promising results on the effects of antithrombotic agents in the prognosis of cancer patients deserve further evaluation to estimate the potential and the feasibility of this approach.


Comparison of two external fixator systems for fracture reduction during minimally invasive plate osteosynthesis in simulated antebrachial fractures.
To compare the Minimally Invasive Reduction Instrumentation System (MIRIS) to a two-ring circular fixator construct (CFC) for indirect reduction during minimally invasive plate osteosynthesis. Cadaveric antebrachial fracture model. Ten skeletally mature dog cadavers. Simulated bilateral antebrachial fractures were reduced and stabilized with the MIRIS on one limb, and a CFC on the contralateral limb, prior to placing a 10 hole Locking Compression Plate. Time to satisfactory reduction and implant placement were compared. Difficulty of fracture reduction and plate application was subjectively scored (1 to 5) for each procedure. Prefracture and postoperative orthogonal antebrachial radiographs were compared to assess restoration of radial length and angulation in sagittal and frontal planes. A paired t test (P ≤ .05) was used to compare parameters between the two reduction techniques. Reduction was faster (P = .0191) and plate application was subjectively easier (P = .047) when using the MIRIS compared to the CFC. There were no differences in subjective difficulty of reduction or plate application time between techniques. Mean postoperative radial length was reduced by approximately 4-mm, and procurvatum were decreased by approximately 7° compared to prefracture measurements, regardless of reduction technique. The MIRIS allowed for faster fracture reduction, and simplified plate placement compared to a temporary application of a CFC in our simulated antebrachial fracture model.


The assessment of protective behavioral strategies: comparing the absolute frequency and contingent frequency response scales.
The purpose of the present studies was to examine the effects of response scale on the observed relationships between protective behavioral strategies (PBS) measures and alcohol-related outcomes. We reasoned that an "absolute frequency" scale (stem: "how many times …"; response scale: 0 times to 11+ times) conflates the frequency of using PBS with the frequency of consuming alcohol; thus, we hypothesized that the use of an absolute frequency response scale would result in positive relationships between types of PBS and alcohol-related outcomes. Alternatively, a "contingent frequency" scale (stem: "When drinking … how often …"; response scale: never to always) does not conflate frequency of alcohol use with use of PBS; therefore, we hypothesized that use of a contingent frequency scale would result in negative relationships between use of PBS and alcohol-related outcomes. Two published measures of PBS were used across studies: the Protective Behavioral Strategies Survey (PBSS) and the Strategy Questionnaire (SQ). Across three studies, we demonstrate that when measured using a contingent frequency response scale, PBS measures relate negatively to alcohol-related outcomes in a theoretically consistent manner; however, when PBS measures were measured on an absolute frequency response scale, they were nonsignificantly or positively related to alcohol-related outcomes. We discuss the implications of these findings for the assessment of PBS.


The Role of Improved Motion-Sensitized Driven Equilibrium Blood Suppression and Fat Saturation on T2 Relaxation Time, Using GraSE Sequence in Cardiac Magnetic Resonance Imaging.
T2 mapping is a valuable technique in cardiac MR imaging that offers insights into the microstructural characteristics of myocardial tissue. However, it was shown that myocardial T2 relaxation times (T2 ) measured vary significantly depending on sequence, sequence parameters, and field strength. To assess T2 variability and image quality in cardiac T2 maps using four variants of the gradient-spin echo (GraSE) sequence, having different methods of blood signal suppression (double inversion recovery (DIR) and improved motion-sensitized driven equilibrium (iMSDE) and with and without the addition of fat saturation (FS). Prospective. 48 healthy volunteers (46.7 +/- 21.5 years, 24 male) with no cardiac history. GraSE sequence with DIR (GraSEDIR ), with iMSDE (GraSEiMSDE ) and FS (GraSEDIR -FS) and with both iMSDE and FS (GraSEiMSDE -FS) at 1.5T. Global T2 from three short axis myocardial slices. and image quality assessments using a 5-point Lickert scale (1, (non-diagnostic) to 5, (excellent)) were conducted to evaluate the impact of DB and FS techniques on myocardial T2 measurements and image quality. Paired t-tests or non-parametric equivalents for comparisons between sequences. The Bland-Altmann plots and Pearson rank correlation analyses, as appropriate. A P value <0.05 was considered statistically significant. The mean global T2 values for GraSEDIR , GraSEDIR -FS, GraSEiMSDE , and GraSEiMSDE -FS, were 52.84 ± 5.72 msec, 54.98 ± 3.59 msec, 53.9 ± 4.05 msec, and 55.14 ± 4.28 msec, respectively, with no significant differences (P = 0.092). High image quality scores (>4 out of 5) were obtained for all sequence variants with no significant differences between them (P = 0.11). All GraSE sequence variants exhibited approximately the same results and variations in the DB technique and addition of FS did not have significant impact on myocardial T2 values. 2 TECHNICAL EFFICACY: Stage 1.


Structural characterization of a novel monotreme-specific protein with antimicrobial activity from the milk of the platypus.
Monotreme lactation protein (MLP) is a recently identified protein with antimicrobial activity. It is present in the milk of monotremes and is unique to this lineage. To characterize MLP and to gain insight into the potential role of this protein in the evolution of lactation, the crystal structure of duck-billed platypus (Ornithorhynchus anatinus) MLP was determined at 1.82 Å resolution. This is the first structure to be reported for this novel, mammalian antibacterial protein. MLP was expressed as a FLAG epitope-tagged protein in mammalian cells and crystallized readily, with at least three space groups being observed (P1, C2 and P21). A 1.82 Å resolution native data set was collected from a crystal in space group P1, with unit-cell parameters a = 51.2, b = 59.7, c = 63.1 Å, α = 80.15, β = 82.98, γ = 89.27°. The structure was solved by SAD phasing using a protein crystal derivatized with mercury in space group C2, with unit-cell parameters a = 92.7, b = 73.2, c = 56.5 Å, β = 90.28°. MLP comprises a monomer of 12 helices and two short β-strands, with much of the N-terminus composed of loop regions. The crystal structure of MLP reveals no three-dimensional similarity to any known structures and reveals a heretofore unseen fold, supporting the idea that monotremes may be a rich source for the identification of novel proteins. It is hypothesized that MLP in monotreme milk has evolved to specifically support the unusual lactation strategy of this lineage and may have played a central role in the evolution of these mammals.


Initiation of Liver Transplant in Nepal: A Milestone.
The incidence of chronic liver disease is increasing in the Nepalese population. Liver transplantation (LT) is the best option for patients with end-stage liver disease (ESLD). Nepal's first liver transplant was performed in 2016 in an international collaborative effort at Shahid Dharmabhakta National Transplant Centre (SDNTC), Bhaktapur, Nepal. We aim to report details of the first five patients who had undergone liver transplantation in SDNTC before the beginning of the COVID-19 outbreak in the history of transplantation in Nepal. A descriptive analysis of the clinical data of five adult recipients of liver transplantation at SDNTC was done. We described the patient's demographics, length of stay, and survival of all the first five patients who had undergone four living donor liver transplantations and one brain-dead donor liver transplantation in SDNTC before the beginning of the COVID-19 outbreak. Recipients were between 36 and 63 years old. The recipients of the four live donor liver transplants (LDLT) and one brain-dead donor liver transplant (DDLT) had alcoholic liver disease and cryptogenic liver disease, leading to end-stage liver disease. The model for end-stage liver disease (MELD) scores ranged from 23 to 34. Out of five, four recipients and four donors are doing well and relishing the prospect of a normal life, while the recipient of a brain-dead donor liver transplant passed away due to postoperative primary graft failure. Despite the small number of liver transplants that have been done, the success of these has created confidence in a sustainable liver transplantation program in Nepal.


Challenges and Advances in Nanotoxicology.
This Special Issue of Nanomaterials examines the potential for engineered nanomaterials to negatively impact biological systems and highlights some advances in evaluating key areas of their hazard potential. Nanomaterial science is evolving rapidly with the generation of more complex nanostructures with exciting potential applications. Keeping modern toxicology abreast of this innovation to the point that it guides a safer nanotechnology presents an equally exciting and eminently worthwhile challenge. [...].


Localisation of P2Y1 and P2Y4 receptors in dorsal root, nodose and trigeminal ganglia of the rat.
The presence and distribution of P2Y (nucleotide) receptor subtypes in rat sensory neurons has been investigated. RT-PCR showed that P2Y(1), P2Y(2), P2Y(4) and P2Y(6) receptor mRNA is expressed in sensory ganglia [dorsal root ganglion (DRG), nodose ganglion (NG) and trigeminal ganglion (TG)]. The regional and cellular distribution of P2Y(1) and P2Y(4) receptor proteins in these ganglia was investigated using immunohistochemistry. P2Y(1) polyclonal antibodies stained over 80% of the sensory neurons, particularly the small-diameter (neurofilament-negative) neurons. The P2Y(4) receptor antibody stained more medium- and large- (neurofilament-positive) diameter neurons than small-diameter neurons. P2Y(1) and P2Y(4) receptor immunoreactivity (P2Y(1)-IR and P2Y(4)-IR) was often coexpressed with P2X(3) receptor immunoreactivity (P2X(3)-IR) in subpopulations of neurons. Double immunohistochemistry showed that 73-84% of P2X(3) receptor-positive neurons also stained for the P2Y(1) receptor in DRG, TG and NG while only 25-35% also stained for the P2Y(4) receptor. Subpopulations of P2Y(1)-IR neurons were coexpressed with NF200, CGRP and IB(4); most P2Y(4)-IR neurons were coexpressed with NF200, while only a few neurons were coexpressed with CGRP (10-20%) or with IB(4) (1-2%). The results suggest that P2Y as well as P2X receptor subtypes contribute to purinergic signalling in sensory ganglia.


Flow coupling between active and passive fluids across water-oil interfaces.
Active fluid droplets surrounded by oil can spontaneously develop circulatory flows. However, the dynamics of the surrounding oil and their influence on the active fluid remain poorly understood. To investigate interactions between the active fluid and the passive oil across their interface, kinesin-driven microtubule-based active fluid droplets were immersed in oil and compressed into a cylinder-like shape. The droplet geometry supported intradroplet circulatory flows, but the circulation was suppressed when the thickness of the oil layer surrounding the droplet decreased. Experiments with tracers and network structure analyses and continuum models based on the dynamics of self-elongating rods demonstrated that the flow transition resulted from flow coupling across the interface between active fluid and oil, with a millimeter-scale coupling length. In addition, two novel millifluidic devices were developed that could trigger and suppress intradroplet circulatory flows in real time: one by changing the thickness of the surrounding oil layer and the other by locally deforming the droplet. This work highlights the role of interfacial dynamics in the active fluid droplet system and shows that circulatory flows within droplets can be affected by millimeter-scale flow coupling across the interface between the active fluid and the oil.


Prosthodontic management of a patient with neurological disorders after resection of an acoustic neurinoma: a clinical report.
This clinical report describes the treatment of an edentulous patient who had undergone resection of an acoustic neurinoma and subsequently developed neurological problems. A replacement maxillary denture combined with a mandibular denture placed in the neutral zone was selected as the treatment of choice. A simple procedure for recording the neutral zone is presented.


Detection of twin reversed arterial perfusion sequence at the time of first-trimester screening: the added value of 3-dimensional volume and color Doppler sonography.
Twin reversed arterial perfusion (TRAP) sequence, also known as acardiac malformation, is a rare complication unique to monozygotic multiple gestations. It occurs in approximately 1 per 35,000 pregnancies and in 0.3% of all monozygotic twin gestations. The malformation is characterized by the lack of a well-defined cardiac structure in one twin (acardiac), which acts as a parasite that is hemodynamically dependent on the normal (pump) twin. The malformation in the acardiac twin is always incompatible with survival regardless of its extent, whereas the prognosis of the pump twin may vary considerably. Common complications that affect the prognosis of the pump twin include complications of prematurity secondary to preterm delivery and polyhydramnios as well as congestive heart failure due to the expended cardiac demand. Without prompt detection, follow-up, and treatment, mortality rates for pump twins have been noted to be as high as 50% to 70%. Early sonographic diagnosis, appropriate follow-up, and intervention via cord occlusion when indicated are the mainstays of prenatal care in cases of TRAP sequence and have been associated with substantial improvements in survival. We report a case that emphasizes the added value of 3-dimensional (3D) and color Doppler techniques for both diagnosis of TRAP sequence and detection of poor prognostic features in the first or early second trimester.


Comparative Evaluation of Two Remineralizing Agents on Artificial Carious Lesion Using DIAGNOdent.
The current in vitro study was conducted to assess the remineralization potential of CPP-ACP and a customized dentifrice (tricalcium-phosphate) on artificial carious lesions using DIAGNOdent. Fifty-one extracted premolars that satisfied the inclusion criteria were painted using acid-resistant nail varnish. A window of 4 × 4 mm was exposed on the center of the buccal surface of each tooth. After 20 minutes of drying, the baseline reading of enamel specimens was assessed using DIAGNOdent. The teeth were then immersed in a bath of demineralizing solution. An incubation period of 96 hours at 37°C resulted in artificial caries-like lesions on the specimen. Readings of the specimen within the window after demineralization were recorded using DIAGNOdent for all the samples. The specimens were divided into three groups randomly [group I-casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), group II-customized dentifrice, group III-artificial saliva]. Samples were subjected to the daily treatment regimen for a period of 30 days. The samples were evaluated for remineralization by laser fluorescent device (DIAGNOdent) on the 15th and 30th day, respectively. The statistical analysis was done using the Friedman test, Kruskal-Wallis test, Wilcoxon sign rank test, and Mann-Whitney test. The results showed that both CPP-ACP and customized dentifrice showed almost similar remineralization potential but CPP-ACP showed significant remineralization (p < 0.001). The DIAGNOdent observation conclusively proves that CPP-ACP and customized dentifrice remineralizes the demineralized tooth samples in vitro with CPP-ACP showing significant remineralization. Arjun DS, Bhat SS, Hegde SK, et al. Comparative Evaluation of Two Remineralizing Agents on Artificial Carious Lesion Using DIAGNOdent. Int J Clin Pediatr Dent 2021;14(2):192-195.


Changes in physical fitness profile in female basketball players during the competitive season including explosive type strength training.
Ten female basketball players served as subjects in order to examine changes in a physical fitness profile during a 22-week official competitive season. Specific explosive type strength training (1-2 sessions per week) was utilized throughout the season. The present findings showed that the entire competitive season led to no systematic changes in the maximum oxygen uptake (from 48.0 +/- 6.6 to 47.0 +/- 6.0 ml.kg-1.min-1), in anthropometric characteristics or in maximal isometric force of the leg extensor muscles (from 2567 +/- 490 to 2622 +/- 747 N). However, significant (p < 0.05) increases occurred during the season both in the average power output during the first 15 s work in an anaerobic jumping test and in the maximal vertical jumping heights in the squat jump (from 21.7 +/- 2.3 to 24.2 +/- 2.4 cm) and in the counter movement jump (from 24.9 +/- 2.6 to 26.3 +/- 2.9 cm). A considerable change occurred also in the shape of the isometric force-time curve of the leg extensor muscles so that the times to produce submaximal force level shortened (p < 0.05). The individual changes during the competitive season both in the power output and in the times of rapid force production correlated negatively (p < 0.05) with the individual initial values recorded before the season. The present findings suggest that the prolonged competitive season in the present female basketball players seemingly placed sufficient demands on the athletes in energy production through aerobic processes to maintain their level of VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)


Recombinant human erythropoietin use in intensive care.
To review the literature concerning the role of recombinant human erythropoietin (rHuEPO) in reducing the need for transfusion in critically ill patients. Articles were obtained through searches of the MEDLINE database (from 1990 to June 2001) using the key words erythropoietin, epoetin alfa, anemia, reticulocytes, hemoglobin, critical care, intensive care, critical illness, and blood transfusion. Additional references were found in the bibliographies of the articles cited. The Cochrane library was also consulted. Controlled, prospective, and randomized studies on the use of rHuEPO in critically ill adults were selected. Anemia is a common complication in patients requiring intensive care. It is caused, in part, by abnormally low concentrations of endogenous erythropoietin and is mainly seen in patients with sepsis and multiple organ dysfunction syndrome, in whom inflammation mediator concentrations are often elevated. High doses of rHuEPO produce a rapid response in these patients, despite elevated cytokine concentrations. There have been 3 studies on rHuEPO administration in intensive care and 1 trial in acutely burned patients. Only 2 of these studies looked at the impact of rHuEPO administration on the need for transfusion. Few randomized, controlled trials explore the role of rHuEPO in critical care. Only 1 was a large, randomized clinical trial, but it presents many limitations. Future outcome and safety studies comparing rHuEPO with placebo must include clinical endpoints such as end-organ morbidity, mortality, transfusion criteria, and pharmacoeconomic analysis. rHuEPO appears to provide an erythropoietic response. Optimal dosage and the real impact of rHuEPO on the need for transfusion in intensive care remain to be determined. Currently, based on the evidence available from the literature, rHuEPO cannot be recommended to reduce the need for red blood cell transfusions in anemic, critically ill patients.


Intracranial region of the vertebral artery: morphometric study in the context of clinical usefulness.
The aim of this study was to analyse the morphometry of the intracranial segment of the vertebral artery in the context of clinical usefulness. The results were compared with published data available in full-text archived medical journals. More than 100 digital subtraction angiography (DSA) and 3-dimensional (3D) angio-computed tomography (CT) examinations were used to measure the following parameters: the whole and partial length of V4 in characteristic anatomical points, the diameter in three places (on the level of foramen magnum, in point of exit to the posterior inferior cerebellar artery, and in the vertebro-basilar junction), the angle of connection to the vertebral arteries, and all anatomical variations including fenestration, duplication, dolichoectasia or absent artery. The left V4 section was predominant over the right artery, which is manifested by length, width, cases of ectasia and fewer cases of hypoplasia. The incidences of V4 ectasia were identified more often than those documented in the accessible literature, and they were found in the natural location of formation of saccular aneurysms. The presented knowledge of anatomical variation and abnormali-ties of vertebral circulation can improve the accuracy and "safety" of the surgical procedures in this region, help to determine the range of surgical approach and avoid associated complications. The radiological examinations using 3D CT, DSA reveal unlimited observation of anatomical structures in contrast to studies based on cadavers, and can complement the morphometry in anatomical preparations.


Phenoxybenzamine reduces bladder outlet obstruction in benign prostatic hyperplasia. A urodynamic investigation.
Nine patients with bladder outlet obstruction attributable to benign prostatic hyperplasia were treated with 15 mg of phenoxybenzamine daily. Spontaneous urinary flow, water cystometry, simultaneous pressure-flow-EMG, and the urethral closure pressure profile were measured before and at the end of 4 weeks of treatment with phenoxybenzamine. A significant reduction in residual urine volume and a significant increase in the first sensation and bladder capacity were found. All voiding pressure parameters were significantly reduced and flow rates significantly increased. Urethral closure pressure decreased significantly.


Head-to-Head Comparison of Chest X-Ray/Head and Neck MRI, Chest CT/Head and Neck MRI, and 18F-FDG PET/CT for Detection of Distant Metastases and Synchronous Cancer in Oral, Pharyngeal, and Laryngeal Cancer.
The purpose of this study was to determine the detection rate of distant metastasis and synchronous cancer, comparing clinically used imaging strategies based on chest x-ray + head and neck MRI (CXR/MRI) and chest CT + head and neck MRI (CHCT/MRI) with 18F-FDG PET/CT upfront in the diagnostic workup of patients with oral, pharyngeal, or laryngeal cancer. Methods: This was a prospective cohort study based on paired data. Consecutive patients with histologically verified primary head and squamous cell carcinoma at Odense University Hospital from September 2013 to March 2016 were considered for the study. Included patients underwent CXR/MRI and CHCT/MRI as well as PET/CT on the same day and before biopsy. Scans were read masked by separate teams of experienced nuclear physicians or radiologists. The true detection rate of distant metastasis and synchronous cancer was assessed for CXR/MRI, CHCT/MRI, and PET/CT. Results: A total of 307 patients were included. CXR/MRI correctly detected 3 (1%) patients with distant metastasis, CHCT/MRI detected 11 (4%) patients, and PET/CT detected 18 (6%) patients. The absolute differences of 5% and 2%, respectively, were statistically significant in favor of PET/CT. Also, PET/CT correctly detected 25 (8%) synchronous cancers, which was significantly more than CXR/MRI (3 patients, 1%) and CHCT/MRI (6 patients, 2%). The true detection rate of distant metastasis or synchronous cancer with PET/CT was 13% (40 patients), which was significantly higher than 2% (6 patients) for CXR/MRI and 6% (17 patients) for CHCT/MRI. Conclusion: A clinical imaging strategy based on PET/CT demonstrated a significantly higher detection rate of distant metastasis or synchronous cancer than strategies in current clinical imaging guidelines, of which European ones primarily recommend CXR/MRI, whereas U.S. guidelines preferably point to CHCT/MRI in patients with head and neck squamous cell carcinoma.


Hidden two-qubit dynamics of a four-level Josephson circuit.
Multi-level control of quantum coherence exponentially reduces communication and computation resources required for a variety of applications of quantum information science. However, it also introduces complex dynamics to be understood and controlled. These dynamics can be simplified and made intuitive by employing group theory to visualize certain four-level dynamics in a 'Bell frame' comprising an effective pair of uncoupled two-level qubits. We demonstrate control of a Josephson phase qudit with a single multi-tone excitation, achieving successive population inversions between the first and third levels and highlighting constraints imposed by the two-qubit representation. Furthermore, the finite anharmonicity of our system results in a rich dynamical evolution, where the two Bell-frame qubits undergo entangling-disentangling oscillations in time, explained by a Cartan gate decomposition representation. The Bell frame constitutes a promising tool for control of multi-level quantum systems, providing an intuitive clarity to complex dynamics.


Sleep and mental health: the moderating role of perceived adolescent-parent attachment.
The present study investigated whether the effects of sleep duration and quality on adolescent adjustment were moderated by perceived attachment to mothers and fathers. The study used a cross-sectional design. Participants were recruited from small town and semirural communities in Alabama. Participants were 106 adolescents (mean age=13.61 years, SD=.73; 55% girls; 28% African American, 72% European American) and their parents. Sleep duration (minutes) and sleep quality (efficiency, number of long wake episodes) were derived using actigraphy, and subjective sleep/wake problems were derived with adolescent reports. Adolescents also reported on perceived attachment to mothers and fathers, internalizing symptoms, and self-esteem. Mothers and fathers reported on externalizing behaviors. Path model analyses indicated that perceived attachment to parents moderated relations between adolescents' sleep quality and their adjustment. For externalizing symptoms and self-esteem, adolescents at greatest risk for maladjustment were those who reported poor quality sleep (ie, more sleep/wake problems, lower sleep efficiency) coupled with less secure attachment to parents. Conversely, adolescents who experienced better actigraphy-based sleep quality (ie, higher sleep efficiency, fewer long wake episodes) in conjunction with more secure attachment to parents experienced the lowest levels of anxiety symptoms. Less secure attachment was associated with high levels of anxiety symptoms independent of sleep quality. Similar patterns of associations emerged for attachment to mothers and fathers. Findings highlight the importance of examining the conjoint influence of sleep and adolescent-parent relationships toward explication of adolescent's mental health.


Effect of the Spatial Configuration of Donors on the Photovoltaic Performance of Double D-π-A Organic Dyes.
Three double D-π-A sensitizers (A1, A3, and A5) containing different donors (triphenylamine, methoxy-modified triphenylamine, and cyclic thiourea-functionalized triphenylamine) are synthesized to investigate the role of different donors in dye-sensitized solar cells (DSSCs). Detailed investigations of the sensitizers reveal that the spatial characteristics of donor units have a considerable impact on the light-harvesting, electrochemistry, and photovoltaic properties. Benefiting from the strong shielding ability of alkyl chains in the donor to its branch chains as observed in density functional theory (DFT), the open-circuit voltage (VOC = 712.0 mV) of A5-based DSSC is higher than those of A1 and A3 by 90 and 78 mV, respectively. Therefore, the A5-based DSSC delivers a good efficiency of 8.54%, relying on its effective suppression of interfacial recombination. The results indicate that the judiciously tailored donor unit is an effective approach to optimize dye configurations to further improve power conversion efficiencies.


Cannabinoid receptor 1 inhibition improves the intestinal microcirculation in experimental endotoxemia.
Impairment of the intestinal microcirculation in endotoxemia may cause a deterioration of the mucosal barrier function thus releasing intraluminal bacteria and their toxins into the systemic circulation. In clinical sepsis this mechanism may influence disease severity and outcome. The aim of the study was to investigate the impact of cannabinoid receptor 1 (CB1R) modulation within the intestinal microcirculation with regard to leukocyte activation and capillary perfusion, and on intestinal histology in experimental endotoxemia in rats. Endotoxemia was induced by intravenous lipopolysaccharide (LPS) administration. We studied 5 groups of animals: controls (CON), LPS, LPS + CB1R agonist (ACEA, 2.5 mg/kg), LPS + CB1R antagonist (AM281, 2 mg/kg) and LPS + CB1R agonist (ACEA, 2.5 mg/kg) + CB1R antagonist (AM281, 2 mg/kg). Intestinal intravital microscopy (IVM) was performed two hours following LPS/placebo administration. Intestinal leukocyte adhesion in submucosal venules and functional capillary density (FCD) of the intestinal wall was quantified using IVM. Histological changes were assessed using a standardized injury score. After two hours of endotoxemia, we observed a significant increase of leukocyte adhesion in intestinal submucosal venules. Administration of the CB1R antagonist in endotoxemic animals significantly reduced the number of adhering leukocytes (p < 0.05). The CB1R agonist did not further increase leukocyte adhesion. FCD was significantly improved by the CB1R antagonist (p < 0.05). Administration of the CB1R agonist, ACEA, reversed the beneficial effect of the CB1R antagonist, AM281. CB1R inhibition significantly improved intestinal microcirculation by reducing leukocyte adhesion and increasing FCD in acute endotoxemia in rats. The data supports the involvement of the CB1R signaling in leukocyte activation during sepsis. Drugs targeting the CB1R may have therapeutic potential in systemic inflammation, such as sepsis.


The permeability of the capsule of autonomic ganglia to horseradish peroxidase.
Horseradish peroxidase (HRP) was applied to the capsules of various autonomic ganglia in vivo. The capsules of the inferior mesenteric ganglion and superior cervical ganglion of guinea-pigs and the inferior mesenteric ganglion of mice were readily penetrated by the enzyme. The capsule of the mouse superior cervical ganglion was apparently impermeable to HRP, while that of the guinea-pig lumbar sympathetic trunk was intermediate in permeability, being most readily penetrated by HRP around the blood vessels entering or leaving the ganglia. The results of retrograde transport experiments from the guinea-pig inferior mesenteric ganglion to spinal ganglia are considered in the light of the ready permeability of its capsule.


Dairy consumption is inversely associated with the prevalence of the metabolic syndrome in Tehranian adults.
Although previous studies showed some benefits from dairy consumption with respect to obesity and insulin resistance syndrome, epidemiologic data on the association between dairy intakes and metabolic syndrome are sparse. The objective was to evaluate the relation between dairy consumption and metabolic syndrome in Tehranian adults. Dairy consumption and features of metabolic syndrome were assessed in a population-based cross-sectional study of 827 subjects (357 men and 470 women) aged 18-74 y. Metabolic syndrome was defined according to guidelines of the Adult Treatment Panel III. Multivariate logistic regression adjusted for lifestyle and nutritional confounders was used in 4 models. Mean (+/-SD) consumption of milk, yogurt, and cheese was 0.7 +/- 0.2, 1.06 +/- 0.6, and 0.9 +/- 0.3 servings/d, respectively. Subjects in the highest quartile of dairy consumption had lower odds of having enlarged waist circumference [odds ratio (OR) by quartile: 1, 0.89, 0.74, 0.63; P for trend < 0.001], hypertension (OR by quartile: 1, 0.88, 0.79, 0.71; P for trend < 0.02), and metabolic syndrome (OR by quartile: 1, 0.83, 0.74, 0.69; P for trend < 0.02). The values of ORs became weaker after further adjustment for calcium intake. Dairy consumption is inversely associated with the risk of having metabolic syndrome. It seems that this relation is somewhat attributed to calcium.


Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study.
Patients with locally advanced gastric cancer (cT3, cT4, N+, M0) have a dismal prognosis, despite complete resection. The objective of this study was to evaluate the toxicity and efficacy of neoadjuvant chemotherapy using the PLF (cisplatin/leucovorin [folinic acid]/5-fluorouracil [FU]) regimen in these patients. Primary endpoints of the study were the toxicity and the response to chemotherapy. Secondary endpoints were the rate of complete resection, survival, and first site of failure. Forty-nine patients with adenocarcinoma of the stomach were enrolled. Staging was based on abdominal computed tomography (CT) scans, endosonography, and laparoscopy. The intention was to administer two cycles (each containing six courses) of preoperative chemotherapy, consisting of cisplatin 50 mg/m(2), high-dose folinic acid (HD-FA) 500 mg/m(2), and HD 5-FU (HD-5-FU) 2000 mg/m(2) (PLF). Following chemotherapy all patients were referred to surgery. To be evaluable for response, survival, and first site of failure, the patient had to receive at least one cycle of chemotherapy. Toxicity observed was low, with grade 3 toxicity in fewer than 5% of the patients and two events of grade 4 toxicity (diarrhea and pulmonary embolism). Forty-two of the patients (86%) received at least one cycle of chemotherapy. The clinical response rate in these patients was 26% (11/42 patients). In 76% of the patients (32/42), a complete resection was possible. The median duration of follow-up for the surviving patients was 58 months (range, 38 to 80+ months). The median survival time for the 42 patients assessable for response was 25.4 months (range, 6 to 80+ months). After complete resection, median survival time was 32 months (range, 7.6 to 80+ months). The median survival time for clinically responding patients has not yet been determined, but 5-year survival is 90%. Twenty of the 32 completely resected patients (62.5%) had recurrences. First site of failure was peritoneal dissemination in 10 patients; locoregional and distant recurrences were rare. Neoadjuvant chemotherapy with PLF in patients with locally advanced gastric cancer has low toxicity and reasonable efficacy, allowing administration on an outpatient basis. Clinically responding patients have an excellent outcome after complete resection. The development of peritoneal dissemination even after neoadjuvant chemotherapy and complete resection remains an unsolved problem in patients with nonintestinal type tumors.


The effects of electroconvulsive therapy and antidepressant drugs on monoamine receptors in rodent brain--similarities and differences.
Repeated administration to rodents of electroconvulsive shock (ECS) produces changes in brain monoamine biochemistry and function, several of which are also seen after repeated administration of antidepressant drugs. Both repeated ECS and antidepressant drug administration decrease cortical beta-adrenoceptor density and attenuate the alpha 2-adrenoceptor-mediated sedation response to clonidine injection. Neither procedure alters phenylephrine-induced locomotor activity in mice, a measure of alpha 1-adrenoceptor function. Most antidepressant drugs decrease type 2 5-hydroxytryptamine (5-HT2) receptor density in frontal cortex and 5-HT2 receptor-mediated head-twitch behaviour in mice. In contrast, repeated ECS increases both 5-HT2 receptor density and the head-twitch response, making it difficult to propose any simple hypothesis linking changes in this receptor with antidepressant activity. The putative agonist for the 5-HT1A receptor 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) produces a hypothermic response in mice, apparently by acting as an agonist at presynaptic 5-HT1 receptors. Repeated administration of antidepressant drugs and lithium markedly attenuates this hypothermic response. Repeated ECS also attenuates this response, the attenuation lasting for at least 20 days after the last ECS. Repeated ECS, but not antidepressant drug administration, markedly enhances dopamine-mediated behaviour. While the similarities in action between ECS and antidepressant drugs may help explain the therapeutic action of electroconvulsive treatment, the differences may provide clues to the efficacy of this treatment in drug-resistant depressive illness.


Reduced local diffusion homogeneity as a biomarker for temporal lobe epilepsy.
In the present study, we adopted a novel method-local diffusion homogeneity (LDH)-to characterize the structure feature in mesial temporal lobe epilepsy (MTLE). Diffusion-weighted images were acquired from 11 left MTLE patients, 16 right MTLE patients, and 20 healthy controls from May 2014 to January 2015. Local diffusion homogeneity was compared among patient groups and controls by 2 sample t test. The discriminative value of LDH abnormalities was examined by receiver operating characteristic (ROC) curve analysis. Correlations with disease duration and onset age in both patient groups were assessed using Pearson's coefficient. Both patient groups exhibited lower LDH in the anterior corpus callosum (P < 0.05, corrected), and this regional anomaly exhibited excellent classification performance in left MTLE patients (sensitivity = 82%, specificity = 100%), right MTLE patients (sensitivity = 81%, specificity = 90%), and the entire patient cohort (sensitivity = 82%, specificity = 95%). In summary, left and right MTLE patients show common pathological changes in the anterior corpus callosum. This regional LDH abnormality is a potential quantitative biomarker for MTLE.


Telehealth Use and Access to Care for Underserved Populations Before and During the COVID-19 Pandemic.
While several studies have documented the rapid growth in telehealth visits during the pandemic, none have examined its relationship with greater overall access to care among vulnerable populations. We use Association of American Medical Colleges' Consumer Survey data to examine the relationship between access to care and telehealth use before and during the pandemic. The proportion of survey respondents who were always able to get medical care when needed was slightly lower in 2020 compared with prior years while telehealth use rose dramatically. Disparities in telehealth use for Medicaid beneficiaries and rural respondents disappeared during the pandemic, but remained for lower-income populations. Before the pandemic, telehealth use was associated with greater access, but not during the pandemic-when it appears to have become a substitute for in-person. After the pandemic, telehealth could once again be an opportunity to supplement access to care, if telehealth policies enacted during the pandemic are made permanent.


Literature on methadone maintenance clinics.
The literature on the impact of methadone maintenance clinics is presented and it is pointed out that only a very tentative evaluation can be made. The authors themselves, however, are opposed to these clinics based on the balance of the evidence available.


[Statistical analysis of mediator release from the cyto-neural junction of the posterior canal of the labyrinth isolated from the frog].
The transmitter release mechanism was investigated at the cyto-neural junction of the frog labyrinth posterior canal. Low frequency (less than 100/s) non overlapping EPSPs were intracellularly recorded both at rest and during inhibitory mechanical stimulation of the canal (2-8 deg/s2). Recordings were obtained: in control solution; in the presence of increased external Ca2+ (9 mM); in Ca-free EGTA (5 mM) solution and during electrical activation at 50 Hz of the posterior canal inhibitory efferent system. Individual synaptic potentials were digitized and their peak amplitudes, their time integrals as well as the time intervals between them were evaluated. The time intervals proved to be exponentially distributed, suggesting a random EPSP occurrence. The analytical reconstruction of the EPSP waveform indicated that a gamma- function fitted reasonably well both the single and averaged events. As regards the averaged event, despite the scatter in the values of the gamma-function exponential factor (range 1.1-2.2), in the EPSP time-to-peak (0.6-1.2 ms) and peak amplitude (0.9-2.7 mV) displayed by the units, no significant differences were observed in the same fibre between control and test conditions. Moreover, the event peak amplitude distribution represented by cumulative plots or amplitude histograms was fitted by a lognormal function. The distributions obtained for the same unit in control solution proved to be not significantly different from those successively obtained under test conditions. The unimodal and continuous EPSP distributions, together with the unvarying characteristics of the single events, strongly suggest that the observed potentials are true mEPSPs due to the release of single quanta of transmitter.(ABSTRACT TRUNCATED AT 250 WORDS)


Prescription Stimulant Misuse Among Nursing Students: A Systematic Review.
Nonmedical prescription stimulants are used to reduce symptoms of inattention, impulsivity, and hyperactivity in children and adults with attention-deficit hyperactivity/disorder. They are Schedule II controlled substances because of their high potential for dependence, and individuals who misuse them without a valid prescription are subject to criminal charges. Stimulant medications are also associated with common side effects (e.g., insomnia) as well as more serious but less common side effects (e.g., arrhythmias). Despite the potential health and legal consequences, misuse of prescription stimulants has become a public health crisis on college campuses in the United States. Neurocognitive enhancement is the primary reason that college students report misusing prescription stimulants, despite no enhancement of cognitive functioning when taken by healthy adults. Nursing students may be at risk for misuse because of their high levels of academic and clinical demands and because many start misusing in nursing school. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the databases PubMed, Science Direct, EBSCOhost, and Academic OneFile were systematically searched to investigate the (a) percentage of prescription stimulant misuse studies that have included nursing students, (b) prevalence of prescription stimulant misuse among nursing students, (c) motivations for prescription stimulant misuse among nursing students, and (d) demographic factors associated with increased use among nursing students. Results revealed that of the 197 studies conducted within the past decade (2010-2021), only 1.02% (two) included nursing students. Future studies must investigate the prevalence and nature of prescription stimulant misuse among nursing students.


Association of neck circumference and hypertension among adults in a rural community Thailand: A cross-sectional study.
Hypertension (HT) is a major non-communicable disease worldwide and a growing global public health problem. Although several studies have investigated the independent associations of neck circumference (NC) and hypertension, no such studies have been conducted among the Thai population. This study aims to identify risk factors associated with hypertension, which may be used to predict HT among asymptomatic adults residing in a remote rural community in central Thailand. 1,084 adults were included in this community-based cross-sectional study by a population-based total survey. The participants were included those who had been living in 6 villages in the rural community in the central area of Thailand. Anthropometric information, NC, body composition indexes such as waist circumference and blood pressure were measured. Logistic regression models were fitted to calculate the multi-variable adjusted prevalence and the association of NC with HT. The prevalence of HT among adults in the rural community was 27.7% (95% CI: 25.0-30.3). Of the 300 adults with HT, 164 participants (54.7%) were found within the unawareness HT category. We found that associated factors with HT were included larger neck circumference both continuous and categorical (≥ 37.5 in male, ≥ 32.5 in female), pre-existing diabetes mellitus, male, and higher body mass index. Almost one-third of participants in the remote rural areas presented hypertension. NC was associated with HT independent from other risk factors. NC is a simple and useful anthropometric index to identify HT in rural Thai adults.


ECAP analysis in cochlear implant patients as a function of patient's age and electrode-design.
Electric compound action potentials (ECAPs) provide information about the nerve's and device's function in and after cochlear implantation. In general, lower ECAP values are expected to generate better results. Aim was an analysis of ECAPs in the course of time as a function of the patient's age and electrode design. Between 2008 and 2013, 168 patients of eight defined age groups were included into the investigation. NRTs were measured intraoperatively, after 6 and after 12months. The intraoperative mean value of ECAP was 174.14CL (current level) and decreased after 6months to 156.38CL. Highest ECAPs were achieved intraoperatively in the clusters "younger than 18months" (181.04CL) and "older than 80 years" (190.45CL). CI 422 showed apparently higher ECAP thresholds (182.69) during surgery than CI 24 RE (171.47) and CI 512 (170.64). ECAPs are a well-established method to get information about the CI's and nerve's function during and after surgery. After initial higher values NRTs decrease after 6months and remain stable in the following controls. Very young and older patients tend to have higher thresholds than middle-aged groups. Perimodiolar electrodes are significantly attached to lower values because there is a closer nerve-electrode interaction.


Differential developmental process of respective behavioral states in human fetuses.
The presence of behavioral states has been recognized in human fetuses. However, developmental process of fetal behavioral states remains to be clarified. In thirty-one normal pregnant women between 20 and 41 weeks' gestation, fetal movements were examined by using multiple ultrasonic machines. The entire period was divided into eye movement (EM), no eye movement (NEM), and unclassified periods according to the mode of appearance of rapid eye movements. We investigated changes in the ratio of EM and NEM periods and the incidence of various fetal movements in these periods. The ratio of EM periods increased stepwise between 20 and 32 weeks. The difference in the incidence of "startle" and jaw movements between EM and NEM periods was found at 24-27 and 32-35 weeks, respectively. We found a significant decrease in the incidence of total body movements exclusively in NEM periods at 36-39 weeks and a significant increase in the incidence of "rolling" in EM periods at 40-41 weeks. Eye opening was ultrasonographically recognized, providing evidence for awake state in the human fetus. This study revealed the characteristic appearance of fetal movements as related to the presence or absence of EM during the second half of pregnancy, and thereby pointed to differential development process of behavioral states of human fetuses.


Nesprin 1α2 is essential for mouse postnatal viability and nuclear positioning in skeletal muscle.
The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin. However, previous studies have yet to identify which isoform is responsible. To elucidate this, we generated a series of nesprin 1 mutant mice. We showed that the actin-binding domains of nesprin 1 were dispensable, whereas nesprin 1α2, which lacks actin-binding domains, was crucial for postnatal viability, nuclear positioning, and skeletal muscle function. Furthermore, we revealed that kinesin 1 was displaced in fibers of nesprin 1α2-knockout mice, suggesting that this interaction may play an important role in positioning of myonuclei and functional skeletal muscle.


Cesarean delivery: background, trends, and epidemiology.
To examine trends in cesarean delivery for the overall population and for women with "no indicated risk" for cesarean section, and to summarize the available literature on "maternal request" cesarean deliveries. Nearly 3 in 10 births were delivered by cesarean section in 2004 (29.1%), the highest rate ever reported in the United States. The overall rate has increased by over 40% since 1996, reflecting two concurrent trends: an increase in the primary rate (14.6% to 20.6%), and a steep decline in the rate of vaginal birth after cesarean (28.3% to 9.2%). There has been a clear increase in primary cesarean delivery without a medical or obstetrical indication, and studies using hospital discharge data or birth certificate data estimate the rate of primary cesarean deliveries with no reported medical or obstetrical indication to be between 3% and 7% of all deliveries to women who had not had a previous cesarean delivery. However, these studies contain no direct information on whether these cesareans were the result of maternal request or because of physician recommendation. There was little data to support the contention that the rise in the cesarean rate was the result of maternal request. There are no systematic data available on cesarean delivery by "maternal request." However, the rate of primary cesarean delivery is increasing rapidly for women of all ages, races, and medical conditions, as well as for births at all gestational ages. Since a first cesarean section virtually guarantees that subsequent pregnancies will be cesarean deliveries (the repeat cesarean delivery rate is now almost 91%), research is needed on physician practice patterns, maternal attitudes, clinical outcomes for mother and infant (harms, benefits), and clinical and nonclinical factors (institutional, legal, economic) that affect the decision to have a cesarean delivery.


Synthesis and spectral characterization of EuPO4 and LaPO4:Eu nanorods.
Monoclinic monazite-type EuPO4 and LaPO4:Eu nanorods were synthesized by a microemulsion-assisted solvothermal method. Their morphologies, structures, and fluorescent properties were characterized by SEM, XRD, and photoluminescence (PL) modern analytic means, respectively. The aspect ratios of EuPO4 and LaPO4:Eu nanorods have a decreasing tendency with increasing carbon chain length of assisted surfactants. When the assisted surfactant was n-butyl alcohol, the EuPO4 exhibited nanorod morphology with diameters from 20 to 30 nm and lengths from 100 to 150 nm. When the assisted surfactant was n-pentanol, the EuPO4 nanorods had lengths between 200 and 300 nm and a diameter range similar to that of the n-butyl alcohol nanorods. When the assisted surfactant was n-hexanol and n-octyl alcohol, only elliptical EuPO4 products were obtained. The LaPO4:Eu nanorods synthesized in the presence of different assisted-surfactants exhibited elliptical morphologies with diameters of 40-60 nm and lengths of 70-110 nm. The LaPO4:Eu and EuPO4 nanorods showed a orange prominent emission peak from magnetic-dipole transition 5D0 --> F1 (593 nm) of Eu3+ ions whose sites in the EuPO4 and LaPO4:Eu nanorods have C1 symmetry. Compared with bulk LaPO4:Eu, the fine structure of the Eu-O charge transfer band has very small red shift resulting from the slight increase of the length of Eu-O bond due to nanoscale size effect.


Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson's disease.
Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson's disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients. A prospective study involving idiopathic PD patients on levodopa therapy. 13C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa 'onset' time and ON-duration were recorded. Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement. H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa. ClinicalTrials.gov NCT02112812.


The genetics of the persistent infection and demyelinating disease caused by Theiler's virus.
Theiler's virus causes a persistent and demyelinating infection of the central nervous system of the mouse, which is one of the best animal models to study multiple sclerosis. This review focuses on the mechanism of persistence. The virus infects neurons for a few weeks and then shifts to white matter, where it persists in glial cells and macrophages. Oligodendrocytes are crucial host cells, as shown by the resistance to persistent infection of mice bearing myelin mutations. Two viral proteins, L and L*, contribute to persistence by interfering with host defenses. L, a small zinc-finger protein, restricts the production of interferon. L*, a unique example of a picornaviral protein translated from an overlapping open reading frame, facilitates the infection of macrophages. Susceptibility to persistent infection, which varies among inbred mouse strains, is multigenic. H2 class I genes have a major effect on susceptibility. Among several non-H2 susceptibility loci, Tmevp3 appears to regulate the expression of important cytokines.


Case report: a balance training program using the Nintendo Wii Fit to reduce fall risk in an older adult with bilateral peripheral neuropathy.
A recent systematic review supported the use of strength and balance training for older adults at risk for falls, and provided preliminary evidence for those with peripheral neuropathy (PN). However, the role of gaming systems in fall risk reduction was not explored. The purpose of this case report was to describe the use of the Nintendo® Wii™ Fit gaming system to train standing balance in a community-dwelling older adult with PN and a history of recurrent near falls. A 76-year-old patient with bilateral PN participated in 1 h of Nintendo® Wii™ Fit balance training, two times a week for 6 weeks. Examination was conducted using a Computerized Dynamic Posturography system (i.e. Sensory Organization Test (SOT), Limits of Stability (LOS), Adaptation Test (ADT) and Motor Control Test (MCT) and clinical testing with the Berg Balance Scale (BBS), Timed Up and Go (TUG), Activities-specific Balance Confidence (ABC) scale and 30-s Chair Stand. Following training, sensory integration scores on the SOT were unchanged. Maximum excursion abilities improved by a range of 37-86% on the LOS test. MCT scores improved for amplitude with forward translations and ADT scores improved for downward platform rotations. Clinical scores improved on the BBS (28/56-34/56), ABC (57.5-70.6%) and TUG (14.9-10.9 s) which indicated reduced fall risk. Balance training with a gaming system showed promise as a feasible, objective and enjoyable method to improve physical performance and reduce fall risk in an individual with PN.


Improving Hypoxia Adaption Causes Distinct Effects on Growth and Bioactive Compounds Synthesis in an Entomopathogenic Fungus Cordyceps militaris.
Cordyceps militaris is an entomopathogenic fungus producing a variety of bioactive compounds. To meet the huge demand for medicinal and edible products, industrialized fermentation of mycelia and cultivation of stromata have been widely developed in China. The content of bioactive metabolites of C. militaris, such as cordycepin, is higher when cultivated on silkworm pupae than on rice or in broth. However, compared with other cultivation methods, C. militaris grows more slowly and accumulates less biomass. The hypoxic environment in pupa hemocoel is one of environmental factor which is not existed in other cultivation methods. It is suggested that hypoxia plays an important role on the growth and the synthesis of bioactive compounds in C. militaris. Here, we demonstrated that the distinct effects on the growth and synthesis of bioactive compounds employing different strategies of improving hypoxia adaption. The introduction of Vitreoscilla hemoglobin enhanced growth, biomass accumulation, and crude polysaccharides content of C. militaris. However, cordycepin production was decreased to 9-15% of the control group. Meanwhile, the yield of adenosine was increased significantly. Nonetheless, when the predicted bHLH transcription factor of sterol regulatory element binding proteins (SREBPs) was overexpressed in C. militaris to improve the hypoxia adaption of fungal cells, cordycepin content was significantly increased more than two-fold. These findings reveal the role of SREBPs on growth and bioactive compounds synthesis. And it also provides a scientific basis for rationally engineering strains and optimization strategies of air supply in cultivation and fermentation.


Ten key research issues for integrated and sustainable wastewater reuse in the Middle East.
Wastewater management is not limited to the technology used to collect and treat wastewater. It begins with the early planning phase of building a society and includes considerations of how that society will grow. Therefore, history, culture, religion, and socioeconomy are important components to include in any relevant and integrated studies of wastewater management and reuse. Engineering, health, chemistry, biology, food production, cultural heritage, and the needs of people of all ages should be considered together when making management decisions regarding issues so intimately tied with humanity as water and sanitation. Other escalating challenges such as poverty, food, and water scarcity, migration and instability, flooding and catastrophes, diseases and mortality, etc. should also be considered as part of wastewater management and reuse planning. Emerging contaminants could be associated with the urbanization, modernization, and industrialization of several countries. Several arid countries have developed water security strategies where wastewater reuse is a major component. The existing wastewater treatment technologies in these countries are, in most cases, unable to remove such contaminants which may affect irrigation waters, industrial products, groundwater, etc. People would have to accept that the food on their tables could be irrigated with treated wastewater that they generated a few months ago, even if very advanced technologies were used to treat it. The purpose of this review is to highlight multidisciplinary areas of research on wastewater and to propose applicable and affordable mechanisms by which we may consider wastewater as a legitimate resource.


The family, family therapy, and borderline personality disorder.
The authors review recent controlled studies on the interrelationship of the family and its members with borderline disorder and propose a new model for understanding and managing this relationship. The focus of the model is on psychopathology, evaluation, and treatment of patient and family as they influence each other. In the authors' view this illness originates in cerebral dysfunction, in the patient in combination with impaired relationships among family members. When the family is available, we believe that the treatment of choice is a multimodal approach involving family psychoeducation and family systems or dynamic intervention where possible, in combination with medications, individual psychotherapy, or both.


Post-traumatic stress disorder following childbirth.
Childbirth experience could be complicated and even traumatic. This study explored the possible risk factors for post-traumatic stress disorder following childbirth (PTSD-FC) in mothers and partners. Through a cross-sectional online survey biographical, medical, psychological, obstetrical and trauma history data were collected. The PTSD-FC, postnatal depression, social support, and perceived mother-infant bond in 916 mothers and 64 partners were measured through self-reported psychometric assessments. Our findings highlight the possible impact of several risk factors such as emergency childbirth, past traumatic experiences and distressing events during childbirth on PTSD-FC. The difficulties in mother-infant bond and the postpartum depression were highly associated with the total score of PTSD-FC symptoms for mothers. While for partners, post-partum depression was highly associated with the total score of PTSD-FC. Our study demonstrated significant links between psychological, traumatic and birth-related risk factors as well as the perceived social support and the possible PTSD following childbirth in mothers and partners. Given that, a specific attention to PTSD-FC and psychological distress following childbirth should be given to mothers and their partners following childbirth.


[Parathyroid adenoma: surgical strategy].
The purpose of this study is to reach a better understanding in the handling of parathyroid adenomas, and to emphasize the importance of pre-operatory explorations in order to establish the best surgical approach and its cost. We are using a retrospective study of 51 patients that underwent surgery in our department between the years 1997 and 2002, for the treatment of primary hyperparathyroidism. Every patient received to a pre-operatory exploration in order to localize the parathyroid tumors, including cervical echography in 51 of the cases, and a sestamibi scintigraphy in 49 of the cases. Two surgical procedures were performed: unilateral approach, and bi-lateral approach. The implementation of a systematic pre-surgical checkup allowed for unilateral surgery in 76% of the patients (39 out of 51), from which 31% (12 out of 39) under local anesthesia. The accuracy of the pre-operatory explorations in order to localize the parathyroidian tumors in regard to HPTP, allows for precise surgery via unilateral approach under local anesthesia. The benefits are significant with shorter procedure time, shorter patient hospitalization, and lower risks for complications. The pre-operatory explorations also decrease the total cost of the procedure and are a critical tool for the surgeon.


The tricyclic antidepressant amitriptyline is cytotoxic to HTB114 human leiomyosarcoma and induces p75(NTR)-dependent apoptosis.
Nerve growth factor (NGF) receptors, TrKA and p75(NTR), are being investigated in cancer therapy. Our previous data show that, in HTB114 uterine leiomyosarcoma cells, p75(NTR)-dependent apoptosis is inducible by cytotoxic drugs and can suppress nerve growth factor-dependent growth. Although amitriptyline can kill cancer cells and bind TrKA/B, its effects on p75-dependent apoptosis are unknown. The aim of this paper was to evaluate the antineoplastic potential of amitriptyline, and the role of p75(NTR)-dependent apoptosis in the chemoresistant uterine HTB114 leiomyosarcoma. Using proliferation assays and fluorescence-activated cell sorting analysis, we found that amitriptyline caused a marked reduction in HTB114 cell viability, associated with the parallel upregulation of p75(NTR) expression. This converted the TrKA⁺-proliferating cells into TrKA⁺/p75(NTR⁺), leading to downregulation of TrKA-prosurvival signaling (AKT) and activation of p75(NTR)-dependent apoptosis (through caspase-3). Overall, we provide novel evidence that HTB114 uterine leiomyosarcoma cells are highly sensitive to amitriptyline, supporting the role of p75(NTR)-dependent apoptosis as a novel cytotoxic mechanism of this drug and of p75(NTR) as an inducible stress receptor and a novel target in clinical oncology.


Autoimmune Axonal Neuropathies.
This article reviews autoimmune axonal neuropathies, their characteristic clinical features, disease and antibody associations, appropriate ancillary testing, treatment, and prognosis. In 2021, the American College of Rheumatology and the Vasculitis Foundation released new summary guidelines for the treatment of antineutrophil cytoplasmic autoantibody-associated vasculitides. In addition, novel autoantibodies have been recently identified; they are often paraneoplastic and associated with axonal neuropathies. Recognition of autoimmune axonal neuropathies is important because of the potential for effective treatment to either reverse deficits or slow the progression of disease. It is necessary to properly assess for associations with other systemic disorders (eg, systemic vasculitis, connective tissue disease, neoplasm) so that adequate treatment for both neurologic and non-neurologic aspects of the disease can be initiated.


Essential Role of T cells in the postexposure prophylaxis of rabies in mice.
Athymic nude mice injected intramuscularly with a street stain of rabies virus were not protected against rabies by postexposure administration of beta-propiolactone-inactivated rabies vaccine. In contrast, their normal littermates were completely protected from death by the same vaccination regimens. Nude mice did not produce IgG antibody as a result of the vaccine during the test period of 15 days, whereas normal littermates produced IgG antibody from day 5 after vaccination. However, passive immunization with antirabies hyperimmune mouse ascites showed that antibody was completely ineffective in protecting either nude mice or their normal littermates against rabies when given later than 2 days after infection. No significant difference in the induction of circulating interferon by the vaccination was noted in these mice. Passive transfer of immune spleen cells to nude mice immediately after infection resulted in 30 to 37.5% protection of the mice. Passively transferred spleen cells did not produce detectable amounts of neutralizing antibody in the recipient mice except on day 2 after the transfer, when a low level of antibody was detected. These observations demonstrate the essential role of T cells in the postexposure prophylaxis of rabies in mice. The mechanisms of the failure of postexposure vaccination in nude mice are discussed.


Lead-Free α-La₂WO₆ Ferroelectric Thin Films.
(001)-Epitaxial La2WO6 (LWO) thin films are grown by pulsed laser deposition on (001)-oriented SrTiO3 (STO) substrates. The α-phase (high-temperature phase in bulk) is successfully stabilized with an orthorhombic structure (a = 16.585(1) Å, b = 5.717(2) Å, c = 8.865(5) Å). X-ray-diffraction pole-figure measurements suggest that crystallographic relationships between the film and substrate are [100]LWO ∥ [110]STO, [010]LWO ∥ [11̅0]STO and [001]LWO ∥ [001]STO. From optical properties, investigated by spectroscopic ellipsometry, we extract a refractive-index value around 2 (at 500 nm) along with the presence of two absorption bands situated, respectively at 3.07 and 6.32 eV. Ferroelectricity is evidenced as well on macroscale (standard polarization measurements) as on nanoscale, calling for experiments based on piezo-response force-microscopy, and confirmed with in situ scanning-and-tunneling measurements performed with a transmission electron microscope. This work highlights the ferroelectric behavior, at room temperature, in high-temperature LWO phase when stabilized in thin film and opens the way to new functional oxide thin films dedicated to advanced electronic devices.


Clinical efficacy and security of glycyrrhizic acid preparation in the treatment of anti-SARS-CoV-2 drug-induced liver injury: a protocol of systematic review and meta-analysis.
COVID-19 is a highly infectious acute pneumonia. Glycyrrhizic acid preparation (GAP) has been found to have hepatoprotective and antiviral effects, but there is no supporting evidence on its efficacy and security for patients with COVID-19. The systematic review methods will be defined by Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This study will start on 1 July 2021 and end on 31 October 2021. A comprehensive electronic search will be conducted with the search of Web of Science, PubMed, Ovid web, China National Knowledge Infrastructure, Chinese Scientific and Journal Database, Wanfang Database and grey literature, and manual search will be conducted to search literature of randomised controlled trials, single-arm trials and retrospective studies about GAP in the treatment of anti-SARS-CoV-2 drug-induced liver injury from 1 December 2019 to 1 July 2021. There is no time limitations of publication and language will be restricted to Chinese and English. Retrieved studies will be independently screened by two researchers and relevant data will be extracted from studies. Interstudy heterogeneity will be assessed using the I2 statistic and explored through meta-regressions and subgroup analyses. Depending on data availability, we plan to conduct subgroup analyses by study population, geographical region and other selected clinical variables of interest. Quality assessment of the studies will be performed. Cochrane Handbook for Systematic Reviews of Interventions will be used to assess the risk of bias, and Grading of Recommendations Assessment, Development and Evaluation will be used to access the confidence in cumulative evidence. Ethical approval will not be required for no primary data of individual patients will be collected. The final report will be shared with the scientific community through publication in a peer-reviewed journal, as well as with key stakeholders, including patients, healthcare professionals and those working on COVID-19 research. CRD42021234647.


WNT signaling pathway gene polymorphisms and risk of hepatic fibrosis and inflammation in HCV-infected patients.
Chronic hepatitis C infection is the leading cause of hepatocellular carcinoma (HCC), a highly lethal malignancy with rapidly increasing prevalence in the United States. Little is known about genetic variations and HCC risk. This study aimed to determine if genetic variation in Wnt signaling pathway genes are associated with advanced hepatic fibrosis and inflammation risk in a hepatitis C virus (HCV) infected population. We performed a genetic association cross-sectional study evaluating single nucleotide polymorphisms (SNPs) in 58 candidate genes and risk of FibroSURE-Acti Test determined advanced fibrosis (F3/F4-F4 advanced cases vs. F0-F3 mild controls) and inflammation (A2/A3-A3 advanced cases vs. A0-A2 mild controls). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) employing multivariate logistic regression. Haplotypes were inferred by the HAPLO.STAT program, interactions were evaluated using multifactor dimensionality reduction (MDR) analysis. Among 425 chronically HCV-infected male veterans, 155 (37%) had advanced fibrosis and 180 (42%) had advanced inflammation. Of 3016 SNPs evaluated, eight were significantly associated with fibrosis risk (e.g., SFRP2 rs11937424: OR = 2.19, 95% CI 1.48-3.23, P = 0.00004), and seven were significantly associated with inflammation risk (e.g., SFRP1 rs16890282: OR = 2.15, 95% CI 1.39-3.16, P = 0.0004). MDR analysis identified overweight/obese, SOST rs1405952, SFRP2 rs11937424, and FZD4 rs11234870 as the best interaction model for predicting risk of fibrosis; whereas race/ethnicity, FZD1 rs1346665, and TBX3 rs1520177 as the best interaction model for predicting risk of inflammation. Polymorphisms in several genes involved in the Wnt signaling pathway were associated with hepatic fibrosis or inflammation risk in HCV-infected males. Additional studies in other multi-ethnic HCV cohorts are needed to validate our findings in males and to assess if similar associations exist in chronically HCV-infected females.


Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock, and bacterial pneumonia.
To determine and compare the respective concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble TNF receptors, nitrite/nitrate (NO2-/NO3-), and procalcitonin in the plasma of patients with septic shock, cardiogenic shock, and bacterial pneumonia without shock; and to assess the predictive value of these mediators in defining patients with septic shock. Cohort study, comparing normal volunteers (controls) and patients with septic shock, cardiogenic shock, and bacterial pneumonia. A collaborative study among an intensive care unit, an emergency room, and three research laboratories. Mediators were measured at various times in 15 patients with septic shock (during the shock phase and during the recovery phase), in seven patients with cardiogenic shock during the shock phase, and in seven patients with severe bacterial pneumonia on day 1 of admission. Blood samples were collected at various times during the course of the disease. TNF-alpha values were highest in the acute phase of septic shock (53 to 131 pg/mL during septic shock), while patients with bacterial pneumonia had intermediate concentrations (32 pg/mL). TNF-alpha concentrations were normal in patients with cardiogenic shock. IL-6 concentrations were highest in patients with acute septic shock (85 to 385 pg/mL). However, in contrast to TNF-alpha concentrations, IL-6 concentrations were normal in patients with bacterial pneumonia and increased in patients with cardiogenic shock (78 pg/mL). Soluble TNF receptors were increased in all three groups vs. controls, with the highest increase in patients with septic shock. NO2-/NO3- concentrations were highest (72 to 140 mM) in patients with septic shock, and were < 40 mM in the other groups of patients. Procalcitonin concentrations were only markedly increased in patients with septic shock (72 to 135 ng/mL, compared with approximately 1 ng/mL in the three other groups). The best predictive value for septic shock was found to be the measurements of NO2-/NO3- and procalcitonin concentrations. These observations showed that increase of proinflammatory cytokines was a consequence of inflammation, not of shock. In this study comparing various shock and infectious states, measurements of NO2-/NO3- concentration and procalcitonin concentration represented the most suitable tests for defining patients with septic shock.


Transforming growth factor-β1 contributes to oxaliplatin resistance in colorectal cancer via epithelial to mesenchymal transition.
Transforming growth factor-β1 (TGF-β1), secreted by main components of tumor microenvironment, is considered to be closely associated with cancer development and chemoresistance. The present study aimed to analyze the effects and mechanisms underlying TGF-β1-induced chemoresistance to oxaliplatin (LOH) in human colorectal cancer (CRC) cell lines. The cytotoxic effects of LOH subsequent to TGF-β1 treatment were assessed in three CRC cell lines by MTT assay. In addition, epithelial to mesenchymal transition (EMT), DNA damage and apoptosis assays were performed to evaluate the mechanisms of drug resistance in vitro. It was revealed that an exposure of CRC cells to TGF-β1 induced EMT. This was followed by a decrease in the levels of DNA damage and LOH-induced apoptotic cell death at certain TGF-β1 concentrations compared with untreated cells, which was responsible for LOH resistance. TGF-β1 leads to resistance to LOH in CRC cells, primarily through EMT. These data not only provide insight into the understanding of the chemoresistant mechanisms, but also may guide the clinical applications of reducing EMT to enhance the sensitivity to chemotherapy, by targeting TGF-β1.


New generations of dihydropyridines for treatment of hypertension.
Since the calcium channel blocker (CCB) has become one of the most prescribed agents for antihypertensive monotherapy in the world, this brief review will focus on the recent research and development of the dihydropyridine (DHP) CCB, addressing pharmacological mechanisms for the clinical efficacy of the third and fourth generations of the DHP CCBs, especially on their possible central mechanisms underlying lowering blood pressure.


Ethical Challenges in the Provision of Dialysis in Resource-Constrained Environments.
The number of patients requiring dialysis by 2030 is projected to double worldwide, with the largest increase expected in low- and middle-income countries (LMICs). Dialysis is seldom considered a high priority by health care funders, consequently, few LMICs develop policies regarding dialysis allocation. Dialysis facilities may exist, but access remains highly inequitable in LMICs. High out-of-pocket payments make dialysis unsustainable and plunge many families into poverty. Patients, families, and clinicians suffer significant emotional and moral distress from daily life-and-death decisions imposed by dialysis. The health system's obligation to provide financial risk protection is an important component of global and national strategies to achieve universal health coverage. An ethical imperative therefore exists to develop transparent dialysis priority-setting guidelines to facilitate public understanding and acceptance of the realistic limits within the health system, and facilitate fair allocation of scarce resources. In this article, we present ethical challenges faced by patients, families, clinicians, and policy makers where dialysis is not universally accessible and discuss the potential ethical consequences of various dialysis allocation strategies. Finally, we suggest an ethical framework for use in policy development for priority setting of dialysis care. The accountability for reasonableness framework is proposed as a procedurally fair decision-making, priority-setting process.


Intestinal immune response of feeder pigs to infection with transmissible gastroenteritis virus.
Five feeder pigs 4 to 6 months old were orally inoculated with transmissible gastroenteritis virus. Diagnosis of transmissible gastroenteritis was made on the basis of clinical signs and examination of intestinal mucosa by the fluorescent antibody technique. Immunoglobulins were extracted from intestinal fluid of infected feeder pigs. Virus-binding and neutralizing antibodies were detected in intestinal extracts between 7 and 56 days after infection. The concentration of binding antibodies reached a peak at 21 days after infection and was on the decline at the end of the experiment on the 56th postinfection day. In contrast, neutralizing intestinal antibody concentration was increasing on day 56. In both systems, the predominant immunoglobulin was of the IgA class. Examination of blood serums of the pigs by the plaque-reduction technique showed progressive antibody increases ranging in titer from 1:8 on day 7 to 1:256 on day 56 after infection. An analysis of the protein profiles from these serums showed a significant increase in the concentration of gamma-globulins and a decrease in the albumin fraction.


Nursing the patient receiving continuous positive airway pressure therapy.
The shortfalls of standard oxygen therapy and the increasing trend toward avoiding mechanical ventilation has led to greater use of Continuous Positive Airway Pressure (CPAP) therapy. What was once the domain of intensive care units has now become a common therapy in many acute clinical settings.