"How Can We Talk about Patient-centered Care without Patients at the Table?" Lessons Learned from Patient Advisory Councils.
Patient advisory councils (PACs) are a strategy for primary care clinics to engage patients in practice improvement. However, there is scant research on how PACs function. This study aimed to understand how PACs are organized and identify common challenges and perceived benefits of high-functioning PACs. Key informants identified 8 primary care clinics in California with high-functioning PACs. Leaders from each of the 8 clinics nominated 1 clinic staff member and 1 PAC patient member to be interviewed. Semistructured, one-on-one interviews were conducted at each clinic site or by phone. Interviews were dual-coded using modified grounded theory. Common themes were identified that would be pertinent to the development of future best practices for running PACs. Common characteristics of high-functioning PACs included careful attention to participant recruitment, facilitation strategies guiding diverse personalities toward a common purpose, and assigning accountability for practice improvement projects. Interviewees identified a variety of positive outcomes that ranged from tangible improvements to the waiting area to a more patient-centered staff culture. PACs show potential for promoting patient-centered practice improvements in primary care. Lessons learned from high-functioning PACs can inform a common set of strategies to assist practices in creating and sustaining effective advisory councils.


Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: A systematic review.
The accurate identification of peripheral artery disease (PAD) in patients with diabetes and foot ulceration is important, in order to inform timely management and to plan intervention including revascularisation. A variety of non-invasive tests are available to diagnose PAD at the bedside, but there is no consensus as to the most useful test, or the accuracy of these bedside investigations when compared to reference imaging tests such as magnetic resonance angiography, computed tomography angiography, digital subtraction angiography or colour duplex ultrasound. Members of the International Working Group of the Diabetic Foot updated our previous systematic review, to include all eligible studies published between 1980 and 2018. Some 15 380 titles were screened, resulting in 15 eligible studies (comprising 1563 patients, of which >80% in each study had diabetes) that evaluated an index bedside test for PAD against a reference imaging test. The primary endpoints were positive likelihood ratio (PLR) and negative likelihood ratio (NLR). We found that the most commonly evaluated test parameter was ankle brachial index (ABI) <0.9, which may be useful to suggest the presence of PAD (PLR 6.5) but an ABI value between 0.9 and 1.3 does not rule out PAD (NLR 0.31). A toe brachial index >0.75 makes the diagnosis of PAD less likely (NLR 0.14-0.24), whereas pulse oximetry may be used to suggest the presence of PAD (if toe saturation < 2% lower than finger saturation; PLR 17.23-30) or render PAD less likely (NLR 0.2-0.27). We found that the presence of triphasic tibial waveforms has the best performance value for excluding a diagnosis of PAD (NLR 0.09-0.28), but was evaluated in only two studies. In addition, we found that beside clinical examination (including palpation of foot pulses) cannot reliably exclude PAD (NLR 0.75), as evaluated in one study. Overall, the quality of data is generally poor and there is insufficient evidence to recommend one bedside test over another. While there have been six additional publications in the last 4 years that met our inclusion criteria, more robust evidence is required to achieve consensus on the most useful non-invasive bedside test to diagnose PAD.


How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin.
Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAG interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3-7. Small angle x-ray scattering indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT·heparin complexes form β-sheet-rich heparin-covered fibrils. Solid-state NMR reveals that heparin does not alter the sCT fibrillary core around Lys(11) but makes changes to Val(8) on the exterior side of the β-strand, possibly through contacts to Lys(18) Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting with both monomeric and aggregated sCT.


Epitope Mapping of BmpA and BBK32 Borrelia burgdorferi Sensu Stricto Antigens for the Design of Chimeric Proteins with Potential Diagnostic Value.
Lyme disease is a tick-borne zoonosis caused by Gram-negative bacteria belonging to the Borrelia burgdorferi sensu lato (s.l.) group. In this study, IgM- and IgG-specific linear epitopes of two B. burgdorferi sensu stricto (s.s.) antigens BmpA and BBK32 were mapped using a polypeptide array. Subsequently, two chimeric proteins BmpA-BBK32-M and BmpA-BBK32-G were designed to validate the construction of chimeras using the identified epitopes for the detection of IgM and IgG, respectively, by ELISA. IgG-ELISA based on the BmpA-BBK32-G antigen showed 71% sensitivity and 95% specificity, whereas a slightly lower diagnostic utility was obtained for IgM-ELISA based on BmpA-BBK32-M, where the sensitivity was also 71% but the specificity decreased to 89%. The reactivity of chimeric proteins with nondedicated antibodies was much lower. These results suggest that the identified epitopes may be useful in the design of new forms of antigens to increase the effectiveness of Lyme disease serodiagnosis. It has also been proven that appropriate selection of epitopes enables the construction of chimeric proteins exhibiting reactivity with a specific antibody isotype.


Eucommia ulmoides Oliv. Bark. protects against hydrogen peroxide-induced neuronal cell death in SH-SY5Y cells.
Eucommia ulmoides Oliv. Bark. (EUE), has commonly been used to fortify the muscles and lungs, lower blood pressure, prevent miscarriage, improve the tone of liver and kidneys, and promote longevity the traditional tonic medicines of Korea, China, and Japan. In this study, we investigated that the neuroprotective activities and possible mechanisms of EUE aqueous extract in hydrogen peroxide (H(2)O(2))-induced neuronal cell death in human SH-SY5Y neuroblastoma cells. We examined the effects of EUE against H(2)O(2)-induced cytotoxicity, DNA condensation, the production of reactive oxygen species (ROS), loss of mitochondria membrane potential (MMP), the proteolysis of cleaved poly-ADP-ribose polymerase (PARP), and the expression of Bcl-2, Bcl-xL, cleaved caspase-3, and release of cytochrome c. Moreover, we attempted to determine whether EUE suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), and phosphoinositide 3-kinase (PI3K)/Akt. Pretreatment with EUE increased cell viability and inhibited cytotoxicity and DNA condensation. EUE also attenuated the increase in ROS production and MMP reduction. Western blot data revealed that EUE inhibited H(2)O(2)-induced up- or down-regulation of cleaved PARP, cleaved caspase-3, Bcl-2, and Bcl-xL. The EUE inhibited release of cytochrome c from mitochondria to the cytosol, and significantly attenuated H(2)O(2)-induced phosphorylation of JNK, p38 MAPK, ERK 1/2, and PI3K/Akt. The potent neuroprotective capacity of EUE, shown in these experiments, may potentially be applied in the prevention or treatment of neurodegenerative diseases such as Alzheimer's disease (AD).


A 67-Year-Old Male Patient With COVID-19 With Worsening Respiratory Function and Acute Kidney Failure.
A 67-year-old obese man (BMI 38.0) with type 2 diabetes mellitus (DM), chronic atrial fibrillation, and chronic lymphocytic leukemia stage II, stable for 8 years after chemotherapy, and a history of smoking presented to the ED with progressive dyspnea and fever due to SARS-CoV-2 infection. He was admitted to a general ward and treated with dexamethasone (6 mg IV once daily) and oxygen. On day 3 of hospital admission, he became progressively hypoxemic and was admitted to the ICU for invasive mechanical ventilation. Dexamethasone treatment was continued, and a single dose of tocilizumab (800 mg) was administered. On day 9 of ICU admission, voriconazole treatment was initiated after tracheal white plaques at bronchoscopy, suggestive of invasive Aspergillus tracheobronchitis, were noticed. However, his medical situation dramatically deteriorated.


Use of the trunk for reaching targets placed within and beyond the reach in adult hemiparesis.
Multijoint movements such as reaching are impaired after brain lesions involving sensorimotor areas and pathways. However, the mechanisms by which such lesions affect motor control are not fully understood. Direct effects of the lesion may be partly compensated by both the system's redundancy and its plasticity. Indeed stroke patients with limited arm movement can reach objects placed within the reach of the arm by using a compensatory strategy involving trunk recruitment. A similar strategy is observed in healthy individuals reaching for objects placed beyond the reach of the arm. Determining the control mechanism(s) governing this compensatory strategy in stroke patients was the goal of this study. Kinematics of reaching movements in hemiparetic and healthy participants to targets placed within and beyond the length of the arm were analysed. Targets were placed sagittally in front of the midline of the body. Two targets (targets 1 and 2) were within reaching distance defined as the length of the stretched arm from axilla to wrist crease. Two others were beyond arm's reach so that one required a forward trunk inclination (target 3) and the other required body raising to a semi-standing position (target 4). Healthy participants used minimal trunk displacement for reaches to targets 1 and 2. For reaches to targets 3 and 4, trunk displacement increased with target distance. Whenever the trunk was involved, there was a stereotyped sequential recruitment of the arm and trunk in that the trunk began moving simultaneously with or before the hand and stopped moving after the end of hand movement. This suggested that the control system predicts that the trunk movement will be needed to extend the reach and includes the trunk, in an anticipatory way, into the reach. In contrast, most hemiparetic participants recruited their trunk for reaches to all four targets, even those placed close to the body. Similar to healthy individuals, the sequence of hand and trunk recruitment was stereotyped, suggesting that temporal planning aspects of the motor program underlying movement coordination were relatively unaffected. In contrast to healthy participants, the contribution of the trunk movement to the endpoint displacement was substantially higher in the hemiparetic group and occurred earlier in the reach. It is suggested that the target distance at which the trunk is integrated into the movement to extend the reach of the arm is attained around the limit of arm extension and that this limit is reduced in hemiparetic individuals.


Crystal structure of Aspergillus fumigatus AroH, an aromatic amino acid aminotransferase.
Aspergillus fumigatus is a saprophytic ubiquitous fungus whose spores can trigger reactions such as allergic bronchopulmonary aspergillosis or the fatal invasive pulmonary aspergillosis. To survive in the lungs, the fungus must adapt to a hypoxic and nutritionally restrictive environment, exploiting the limited availability of aromatic amino acids (AAAs) in the best possible way, as mammals do not synthesize them. A key enzyme for AAAs catabolism in A. fumigatus is AroH, a pyridoxal 5'-phosphate-dependent aromatic aminotransferase. AroH was recently shown to display a broad substrate specificity, accepting L-kynurenine and α-aminoadipate as amino donors besides AAAs. Given its pivotal role in the adaptability of the fungus to nutrient conditions, AroH represents a potential target for the development of innovative therapies against A. fumigatus-related diseases. We have solved the crystal structure of Af-AroH at 2.4 Å resolution and gained new insight into the dynamics of the enzyme's active site, which appears to be crucial for the design of inhibitors. The conformational plasticity of the active site pocket is probably linked to the wide substrate specificity of AroH.


Costimulation blockade in pig artery patch xenotransplantation - a simple model to monitor the adaptive immune response in nonhuman primates.
CD154 blockade-based immunosuppression successfully prevents both humoral and cellular adaptive immune responses in baboons receiving α1,3-galactosyltransferase gene-knockout (GTKO) pig organs. Using a GTKO pig artery transplantation model in baboons, we evaluated the efficacy of CD28/B7 costimulatory pathway blockade in comparison with CD154 blockade. Baboons received artery patch grafts from GTKO pigs, with no (Group1), anti-CD154mAb-based (Group2), or CTLA4-Ig-based (Group3) immunosuppressive therapy. Anti-pig IgM and IgG antibody and cellular responses were monitored. Xenografts were immunohistologically evaluated for antibody and complement deposition, and cellular infiltration. Group1 baboons developed increased IgM and IgG antibody and cellular responses against GTKO antigens. In Group2, anti-CD154mAb alone prevented the development of both IgM and IgG antibody and cellular responses,but not cellular infiltration of the graft. In the single baboon that received anti-thymocyte globulin (ATG) + mycophenolate mofetil (MMF) + anti-CD154mAb, cellular infiltration of the graft was not seen. In Group3, CTLA4-Ig with ATG + MMF inhibited the cellular proliferative response to pig antigens but did not prevent the IgG response or cellular infiltration. (i) Artery patch transplantation is a simple model to monitor the adaptive immune response to xenografts; (ii) anti-CD154mAb prevents sensitization but not cellular infiltration (but, without anticoagulation, may result in early thrombosis of a pig xenograft); (iii) although in only one baboon, the addition of ATG and MMF prevents cellular infiltration and (iv) replacement of anti-CD154mAb by CTLA4-Ig (at the doses used), even in combination with ATG and MMF, prevents the cellular proliferative response to GTKO pig antigens but is insufficient to prevent the development of anti-pig antibodies.


Aid effectiveness and women's empowerment: practices of governance in the funding of international development.
Although the empowerment of women is a prominent goal in international development, feminist development professionals, activists, and scholars remain deeply dissatisfied with the limited extent to which women's empowerment is actually achieved. Their experiences and analyses raise questions about the connections and disjunctions between discourse, institutional practices, and everyday life. A major effort to reform development aid guided by the Paris Declaration on Aid Effectiveness raises new questions about the place of gender in development practice. Drawing on recently conducted research on women and development in Kyrgyzstan and using a range of institutional texts, we interrogate how development professionals and activists engage with the aid effectiveness discourse. Our analytic approach, institutional ethnography, shares with work on governmentality an empirical focus on practices undertaken by diversely situated people and how these practices constitute a particular field of action. Institutional ethnography directs analytic attention to the operation of texts as local and translocal coordinators of people's everyday activities. The product of this coordinated work is what we call, in this case, the development institution. For those concerned about women and development, we see the usefulness of making visible how global governance is accomplished in both enactments of and resistance to institutional practices, but in ways that do not necessarily benefit women.


Differences in predictors for gait speed and gait endurance in Parkinson's disease.
Both gait speed and gait endurance directly impact independence and community engagement for individuals with Parkinson's disease (PD). However, factors accounting for variability in gait speed and gait endurance performance are unclear. The purpose of this study was to investigate whether key factors associated with gait speed in individuals with PD also predicted gait endurance. Community dwelling ambulatory individuals with PD were recruited for a single session. Key measures included 10 Meter Walk Test (10MWT) and 6 Minute Walk Test (6MWT) and key factors: age, disease severity [Movement Disorders Society United Parkinson's Disease Rating Scale (motor scale only) (MDS-UPDRS motor)], plantar flexor strength [Calf Raise Senior (CRS)], fatigue [Fatigue Severity Scale (FSS)], cognition [Montreal Cognitive Assessment (MoCA)], and balance [Four Square Step Test (FSST)]. Multiple linear regression analyses were conducted to determine clinical relationships. Seventy-two individuals with PD (mean (standard deviation) (age = 70.83 (7.91) years; 50 males; MDS-UPDRS motor = 30.67 (13.50)) completed all assessments. The model predicting gait speed was significant, F(6, 65) = 15.143, p <.001, accounting for 54 % of the variance. Of the predictor variables age, MDS-UPDRS motor, CRS, MoCA and FSST scores were significant predictors. The model predicting gait endurance was significant, F(6, 65) = 15.608, p <.001, accounting for 55 % of the variance. Of the predictor variables, age, MDS-UPDRS motor scale, and CRS scores were significant predictors. Gait speed and gait endurance are similarly influenced by age, motor impairment, and plantarflexion strength. However, cognition and balance were predictors only of gait speed, which may suggest unique task differences exist between gait speed and gait endurance.


Research on Detection of Ultra-Low Concentration Anthrax Protective Antigen Using Graphene Field-Effect Transistor Biosensor.
Protective antigen (PA) is an important biomarker for the early diagnosis of anthrax, and the accurate detection of protective antigen under extremely low concentration conditions has always been a hot topic in the biomedical field. To complete the diagnosis of anthrax in a timely manner, it is necessary to detect PA at extremely low concentrations, as the amount of PA produced in the early stage of anthrax invasion is relatively small. Graphene field-effect transistor (Gr-FET) biosensors are a new type of material for preparing biosensors, with the advantages of a short detection time and ultra-low detection limit. The effect of different concentrations of diluents on the affinity of PA monoclonal antibodies was determined via an ELISA experiment. Combined with the Debye equation, 0.01 × PBS solution was finally selected as the diluent for the experiment. Then, a PA monoclonal antibody was selected as the bio-recognition element to construct a Gr-FET device based on CVD-grown graphene, which was used to detect the concentration of PA while recording the response time, linear range, detection limit, and other parameters. The experimental results showed that the biosensor could quickly detect PA, with a linear range of 10 fg/mL to 100 pg/mL and a detection limit of 10 fg/mL. In addition, the biosensor showed excellent specificity and repeatability. By constructing a Gr-FET device based on CVD-grown graphene and selecting a PA monoclonal antibody as the bio-recognition element, a highly sensitive, specific, and repeatable Gr-FET biosensor was successfully prepared for detecting extremely low concentrations of anthrax protective antigen (PA). This biosensor is expected to have a wide range of applications in clinical medicine and biological safety monitoring.


Thoracic manifestations of AIDS.
Of 67 hospitalized AIDS patients, 39 had pulmonary pathology. More than half of these patients died of pulmonary disease. Pneumocystis carinii, cytomegalovirus, Cryptococcus neoformans and Mycobacterium avium-intracellulare were the most common pulmonary pathogens, and Kaposi's sarcoma was the most common neoplasm. Infections and neoplasms frequently coexist in the thorax of an AIDS patient. The chest radiograph may be normal in an AIDS patient with active Pneumocystis pneumonia.


[Factors associated with psychological distress among military police in Rio de Janeiro, Brazil].
This study investigates factors associated with psychological distress among military police (n = 1,120) in Rio de Janeiro, Brazil. The article describes their social, economic, and demographic characteristics, quality of life, mental health, and work conditions. Measurement of psychological distress used the Self-Reported Questionnaire. Analysis of associations used logistic regression, considering factors associated with psychological distress. The results indicate an association between psychological distress and factors such as ability to react to difficult situations, dissatisfaction with life, health problems (especially digestive, nervous, and musculoskeletal symptoms), and adverse work conditions such as excessive workload, constant stress, and victimization. The article concludes by highlighting the need for health promotion interventions for the military police, focusing especially on their mental health.


Incorporation of phosphate group modulates bone cell attachment and differentiation on oligo(polyethylene glycol) fumarate hydrogel.
In this work, we have investigated the development of a synthetic hydrogel that contains a negatively charged phosphate group for use as a substrate for bone cell attachment and differentiation in culture. The photoreactive, phosphate-containing molecule, bis(2-(methacryloyloxy)ethyl)phosphate (BP), was incorporated into oligo(polyethylene glycol) fumarate hydrogel and the mechanical, rheological and thermal properties of the resulting hydrogels were characterized. Our results showed changes in hydrogel compression and storage moduli with incorporation of BP. The modification also resulted in decreased crystallinity as recorded by differential scanning calorimetry. Our data revealed that incorporation of BP improved attachment and differentiation of human fetal osteoblast (hFOB) cells in a dose-dependent manner. A change in surface chemistry and mineralization of the phosphate-containing surfaces verified by scanning electron microscopy and energy dispersive X-ray analysis was found to be important for hFOB cell attachment and differentiation. We also demonstrated that phosphate-containing hydrogels support attachment and differentiation of primary bone marrow stromal cells. These findings suggest that BP-modified hydrogels are capable of sustaining attachment and differentiation of both bone marrow stromal cells and osteoblasts that are critical for bone regeneration.


In Their Own Words: Caregiver and Patient Perspectives on Stressors, Resources, and Recommendations in Craniofacial Microsomia Care.
This study describes stressors, resources, and recommendations related to craniofacial microsomia (CFM) care from the perspective of caregivers of children with CFM and adults with CFM to inform improved quality of healthcare delivery. A mixed method design was used with fixed-response and open-ended questions from an online survey in English. The survey included demographics, CFM phenotypic information, and items about CFM-related experiences across settings. Themes were identified by qualitative analysis of responses to open-ended questions. Respondents (n = 51) included caregivers (n = 42; 90% mothers) and adults with CFM (n = 9; 78% female), who had a mean age of 45 ± 6 years. Most children were male (71%) with an average age of 7 ± 4 years. Respondents were primarily white (80%), non-Hispanic (89%), from the United States (82%), had a college degree (80%), and had private health insurance (80%). Reflecting the high rate of microtia (84%) in the sample, themes centered on the impact of hearing difficulties across settings with related language concerns. Negative social experiences were frequently described and school needs outlined. Multiple medical stressors were identified and corresponding suggestions included: providers need to be better informed about CFM, treatment coordination among specialists, and preference for a family-centered approach with reassurance, empathy, and clear communication. Advice offered to others with CFM included positive coping strategies. Overall, caregivers' and patients' responses reflected the complexity of CFM treatment. Incorporating these perspectives into routine CFM care has the potential to reduce family distress while improving their healthcare.


Use of MMV as a Single Worst-Case Model Virus in Viral Filter Validation Studies.
Typical platform processes for biopharmaceutical products derived from animal cell lines include a parvovirus filtration unit operation to provide viral safety assurance of the drug product. The industry has adopted this platform unit operation and gained a wider understanding of its performance attributes, leading to the possibility of streamlined approaches to virus clearance validation. Here, the concept of virus validation on a parvovirus-grade filter with a single worst-case model virus is presented. Several lines of evidence, including published literature and Amgen's own data, support the use of a parvovirus, such as mouse minute virus (MMV), as a worst-case model virus to assess virus removal by parvovirus filters. The evidence presented includes a discussion of the design and manufacture of virus filters with a size exclusion mechanism for removal. Next, the characteristics of different model viruses are compared and a risk assessment on the selection of the relevant model viruses for clearance studies is presented. Finally, a comprehensive summary of literature and Amgen data is provided, comparing the clearance of larger viruses against MMV. Together, this analysis provides a strong scientific rationale for the use of a single, worst-case model virus for assessing virus removal by parvovirus filters, which will ultimately allow for more efficient and streamlined viral clearance study designs. Demonstrating the virus clearance capability of a purification process is an important aspect of biopharmaceutical process development. A key component of the viral safety of the process is the inclusion of a parvovirus-grade filter as an effective and robust virus removal step. Traditional methodologies for viral clearance studies have been based on a conservative, data-intensive approach, but recent trends in the field of virus clearance and process development show evolution towards streamlined and more efficient study designs that are based on understanding the mechanism of viral clearance by downstream unit operations. The publication of scientific datasets and awareness of the underlying mechanisms involved with these unit operations have fueled this trend. Here, the concept of virus validation on a parvovirus-grade filter using a parvovirus as single, worst-case model virus is presented. Multiple lines of evidence are provided to support this proposal, including a review of published literature and Amgen historical data. The adoption of this approach provides benefits in terms of cost savings for executing viral clearance studies, but it also simplifies the necessary dataset and focuses on only supplying value-added information to demonstrate the viral safety of the process.


[Letter: Effect of a reversible increase in plasma membrane permeability of plant root cells during deplasmolysis].
The studied effect of a reversible increase of permeability of plasmic membranes of plant root cells does not depend on chemical nature of plasmolys-inducing agents. This effect is conditioned by the process of deplasmolysis itself. It is suggested that the process of reversible depolimerization of the protein component similar to F-action and located in the membrane polar regions.


The Role of Engagement in Teleneurorehabilitation: A Systematic Review.
The growing understanding of the importance of involving patients with neurological diseases in their healthcare routine either for at-home management of their chronic conditions or after the hospitalization period has opened the research for new rehabilitation strategies to enhance patient engagement in neurorehabilitation. In addition, the use of new digital technologies in the neurorehabilitation field enables the implementation of telerehabilitation systems such as virtual reality interventions, video games, web-based interventions, mobile applications, web-based or telephonic telecoach programs, in order to facilitate the relationship between clinicians and patients, and to motivate and activate patients to continue with the rehabilitation process at home. Here we present a systematic review that aims at reviewing the effectiveness of different engagement strategies and the different engagement assessments while using telerehabilitation systems in patients with neurological disorders. We used PICO's format to define the question of the review, and the systematic review protocol was designed following the Preferred Reported Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Bibliographical data was collected by using the following bibliographic databases: PubMed, EMBASE, Scopus, and Web of Science. Eighteen studies were included in this systematic review for full-text analyses. Overall, the reviewed studies using engagement strategies through telerehabilitation systems in patients with neurological disorders were mainly focused on patient self-management and self-awareness, patient motivation, and patient adherence subcomponents of engagement, that are involved in by the behavioral, cognitive, and emotional dimensions of engagement. Conclusion: The studies commented throughout this systematic review pave the way for the design of new telerehabilitation protocols, not only focusing on measuring quantitative or qualitative measures but measuring both of them through a mixed model intervention design (1). The future clinical studies with a mixed model design will provide more abundant data regarding the role of engagement in telerehabilitation, leading to a possibly greater understanding of its underlying components.


Immunomodulatory Effects of Lycium barbarum Polysaccharide Extract and Its Uptake Behaviors at the Cellular Level.
Lycium barbarum L. is a widely used functional food and medicinal herb in Asian countries. L. barbarium polysaccharides (LBP) are considered as one of the major medicinal components of L. barbarium fruit and exhibits a wide range of biological activities. Here, we investigated the immunomodulatory effects of LBP and its uptake behaviors at the cellular level. LBP was prepared by water extraction and ethanol precipitation, and divided into two fractions based on the molecular weight distribution by ultrafiltration (LBP > 10 kDa and LBP < 10 kDa). The physicochemical properties of LBP and LBP fractions were well characterized. The LBP > 10 kDa fraction greatly enhanced the viability of macrophages RAW264.7 cells and induced cell polarization, but had weak effects to other tested tumor cell lines and normal cell line. This fraction could regulate the production of NO, TNF-α, IL-6 and ROS in RAW264.7 cells, suggesting both pro-inflammatory and anti-inflammatory effects. The dye-labeled LBP could be internalized into all tested cell lines and accumulated in lysosomes. The internalization of LBP in RAW264.7 cells is mainly through the clathrin-mediated endocytosis pathway. The Caco-2 intestinal transport experiment demonstrated that the dye labeled LBP could be transported through the Caco-2 cell monolayer (mimic intestinal epithelium) through clathrin-mediated endocytosis. These results demonstrate the immunomodulatory effects of LBP and its effective uptake by macrophages and intestine.


Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours.
The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-alpha) making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis.


Ischemic heart disease in the elderly: the role of coronary angioplasty and coronary artery bypass grafting.
Management of ischemic heart disease in the elderly is complex. Invasive therapies such as percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) are associated with significant morbidity and mortality. The short-term advantage of PTCA is that its associated noncardiac morbidity and mortality are less than that of CABG, particularly in the incidence of stroke. Unfortunately, PTCA revascularization is less complete and less durable than CABG revascularization. The advantages of CABG are that cardiac revascularization is more complete, the result is more durable, and long-term results are improved over those of PTCA. Conversely, the initial morbidity and mortality are higher for CABG and are adversely affected by factors such as recent myocardial infarction, lung disease, and renal failure. We provide an overview of the results and outcomes of PTCA and CABG in the elderly, as well as suggestions for management.


The benefits of early jejunal hyperalimentation in the head-injured patient.
To determine the efficacy of early jejunal hyperalimentation as nutritional support in the head-injured patient, 32 head-injured patients with Glasgow Coma Scale scores less than 10 were studied for the first 7 days after injury. The experimental (E) group had nasojejunal feeding tubes placed fluoroscopically. Within 36 hours of injury, they received nutritional support equal to their measured resting energy expenditure. The control (C) group was fed gastrically when bowel sounds returned. There were no significant differences (P greater than 0.05) in age, Glasgow Coma Scale score, type of neurological injury, or associated injuries between the two groups. The mean resting energy expenditure, serum albumin, glucose, lymphocyte count, body weight, and total nitrogen loss were nearly identical for both groups. With the jejunal feedings, daily caloric (E = 2102 kcal versus C = 1100 kcal) and nitrogen intake (E = 11.1 g versus C = 5.6 g) and daily nitrogen balance (E = -4.3 g versus C = -11.8 g) improved. The incidence of bacterial infections (E = 3 versus C = 14) and days of intensive care unit hospitalization (E = 6 versus C = 10) were significantly reduced (P less than .05). Head-injured patients will tolerate early jejunal hyperalimentation despite the presence of a clinically silent abdomen, and the cost and complications of total parenteral nutrition are avoided. The increased caloric and nitrogen intake and improved nitrogen retention markedly reduced infections and days of stay in the intensive care unit.


Directly monitoring the growth of gold nanoparticle seeds into gold nanorods.
This paper describes the use of atomic force microscopy to directly image surface-attached 3-5 nm diameter gold nanoparticle seeds before and after seed-mediated growth into gold nanorods (Au NRs) and other shapes (spheres, triangles, and hexagons). Results show that Au NRs form from seeds growing in either one or two directions. A direct correlation exists between seed diameter and NR diameter; small diameter seeds form small diameter NRs. However, correlation between seed diameter and nanostructure shape or NR length is less evident. We describe our results in terms of growth mechanisms proposed in the literature and discuss possible reasons for the large size dispersity observed for surface-grown Au NRs. A better understanding of Au NR and other metal and semiconductor one-dimensional (1D) growth processes is necessary to improve synthesis, tailor their properties, and utilize 1D nanostructures for useful technological applications.


Evolving views of disability and public health: the roles of advocacy and public health.
Promoting health, quality of life, and participation of persons with disabilities is a relatively recent development in public health. Its brief history reflects three distinct public health perspectives toward disability-a traditional approach that focuses on preventing disability, a contemporary approach that regards disability as a minority group experiencing disparities relative to people without disabilities, and an emerging perspective where disability status is considered one of multiple determinants of health. The field of disability and health has been influenced by the interaction of disability advocacy with the public health process of surveillance, epidemiology research, and intervention. Advocacy draws on political and legal arguments to press for action on issues such as health care access, control of services, and choice of residence. Public health uses surveillance to document magnitude of problems; epidemiology to identify specific groups, develop measures, and apply rigorous research methods; and intervention to improve health behaviors and health outcomes. The field of disability and public health, however, has lagged in addressing the role of environmental factors in the disabling process, in moving to societal participation as an outcome, and in implementing population scale interventions.


Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients.
This study is aimed at identifying discrete severity classes among adults with hypermobile Ehlers-Danlos syndrome (hEDS)/hypermobility spectrum disorders (HSD). Subjects were selected according to the old and new nomenclatures and all completed a set of questionnaires exploring pain, fatigue, dysautonomic symptoms, coordination and attention/concentration deficits and quality of life in general. Data were investigated by hierarchical clustering on principal components. Cluster comparisons were then performed by using the two-sample unpaired t test and the standardized mean difference was reported as a measure of effect size. Conditional classification tree analysis and multivariable logistic regression were carried out in order to identify the profiles that were at higher risk to belong to the more severe cluster. Weighted linear combination was used to identify a numerical score measuring this risk. A total of 105 patients were selected and distributed in two distinct severity groups. These groups were statistically separated on the basis of 47 of 59 items/characteristics. One group featured the worse values of most questionnaire items (complex/severe cluster) and the other was dominated by the better values (simplex/milder cluster). Only three items were able to stratify patients according to their risk to belong to the complex cluster. A severity score was then constructed on these three items. Adults with hEDS/HSD can be separated in two severity classes, which do not mirror either the old or new criteria for hEDS. The identified severity score could allow a bi-dimensional approach to adults with hEDS/HSD for optimal management planning.


Novel indolene-spiro-hydroxytetronimides as potential antineoplastic and antiviral agents.
In a continuing search for new antineoplastic and antiviral agents, the preparation of some substituted indol-2(3H)-one-3-spiro-2'-3',4'-dihydroxy-5'-imino-2',5'-dihydrofurans was designed. The synthesis was achieved by reacting isatin, 1-alkyl- or 1-aralkylisatin derivative with glyoxal sodium bisulfite and potassium cyanide. However, when 1-substituted aminomethyl derivatives of isatin or of 5-bromoisatin were used in this reaction, the indolone-spiro-hydroxytetronimide unsubstituted at position 1 was, unexpectedly, the only product isolated. Two compounds were tested against P-388 lymphocytic leukemia in mice and were inactive.


Design of an Ultrasound Transceiver ASIC with a Switching-Artifact Reduction Technique for 3D Carotid Artery Imaging.
This paper presents an ultrasound transceiver application-specific integrated circuit (ASIC) directly integrated with an array of 12 × 80 piezoelectric transducer elements to enable next-generation ultrasound probes for 3D carotid artery imaging. The ASIC, implemented in a 0.18 µm high-voltage Bipolar-CMOS-DMOS (HV BCD) process, adopted a programmable switch matrix that allowed selected transducer elements in each row to be connected to a transmit and receive channel of an imaging system. This made the probe operate like an electronically translatable linear array, allowing large-aperture matrix arrays to be interfaced with a manageable number of system channels. This paper presents a second-generation ASIC that employed an improved switch design to minimize clock feedthrough and charge-injection effects of high-voltage metal-oxide-semiconductor field-effect transistors (HV MOSFETs), which in the first-generation ASIC caused parasitic transmissions and associated imaging artifacts. The proposed switch controller, implemented with cascaded non-overlapping clock generators, generated control signals with improved timing to mitigate the effects of these non-idealities. Both simulation results and electrical measurements showed a 20 dB reduction of the switching artifacts. In addition, an acoustic pulse-echo measurement successfully demonstrated a 20 dB reduction of imaging artifacts.


Wnt-5a ligand modulates mitochondrial fission-fusion in rat hippocampal neurons.
The Wnt signaling pathway plays an important role in developmental processes, including embryonic patterning, cell specification, and cell polarity. Wnt components participate in the development of the central nervous system, and growing evidence indicates that this pathway also regulates the function of the adult nervous system. In this study, we report that Wnt-5a, a noncanonical Wnt ligand, is a potent activator of mitochondrial dynamics and induces acute fission and fusion events in the mitochondria of rat hippocampal neurons. The effect of Wnt-5a was inhibited in the presence of sFRP, a Wnt scavenger. Similarly, the canonical Wnt-3a ligand had no effect on mitochondrial fission-fusion events, suggesting that this effect is specific for Wnt-5a alone. We also show that the Wnt-5a effects on mitochondrial dynamics occur with an increase in both intracellular and mitochondrial calcium (Ca(2+)), which was correlated with an increased phosphorylation of Drp1(Ser-616) and a decrease of Ser-637 phosphorylation, both indicators of mitochondrial dynamics. Electron microscope analysis of hippocampal tissues in the CA1 region showed an increase in the number of mitochondria present in the postsynaptic region, and this finding correlated with a change in mitochondrial morphology. We conclude that Wnt-5a/Ca(2+) signaling regulates the mitochondrial fission-fusion process in hippocampal neurons, a feature that might help to further understand the role of Wnt-related pathologies, including neurodegenerative diseases associated with mitochondrial dysfunction, and represents a potentially important link between impaired metabolic function and degenerative disorders.


The effects of taxation on the individual consumption of sugar-sweetened beverages.
To assess the impact of taxation on the consumption of sugar-sweetened beverages (SSBs) most economic studies using household data consider the average consumer. Individual consumption is, however, very heterogeneous. In this paper, we propose a three-step methodology to evaluate the impact of SSB taxation on individual consumption. First, we use a disaggregation method to recover individual consumption from observed household consumption. Second, we estimate the demand for different categories of households. Finally, we simulate the impact of a tax policy on individual consumption. We find a high level of heterogeneity in consumption. Adults, both men and women, consume a greater quantity of SSBs than children. More importantly, for any given age category, the average consumption of SSBs increases with body mass index (BMI). Among heavy consumers of SSBs, obese and overweight people are over-represented. In France, a €0.20/l tax on SSBs might decrease sugar intake by more than 2 kg per year on average and by more than 5 kg, roughly 3 teaspoons/day, for 5% of the adult population. Moreover, overweight and obese men and women, who correspond to 41% of the adult population, represent 56% of the last five percentiles of the distribution of the variation in sugar intake. This is a key result because the objective of taxation is to decrease the consumption of individuals who are more at risk, that is those who are overweight and obese. We also show that classical method of the assessment of tax policies based on per-capita consumption underestimate the effect of the tax for obese adults by 9%. Finally, we estimate that a €0.20/l tax on SSBs might avoid about 640 deaths (about 1.6% of the considered diseases) as a consequence of the decrease in SSB consumption.


The feasibility and acceptability of a task-shifted intervention for perinatal depression among women living with HIV in Malawi: a qualitative analysis.
Perinatal depression (PND) is prevalent and negatively impacts HIV care among women living with HIV (WLHIV), yet PND remains under-identified in Malawian WLHIV. Accordingly, this formative study explored perceptions of the feasibility and acceptability of an integrated, task-shifted approach to PND screening and treatment in maternity clinics. We completed consecutive PND screenings of HIV+ women attending pre- or post-natal appointments at 5 clinics in Lilongwe district, Malawi. We conducted in-depth interviews with the first 4-5 women presenting with PND per site (n = 24 total) from July to August 2018. PND classification was based on a score ≥ 10 on the Edinburgh Postnatal Depression Scale (EPDS). We conducted 10 additional in-depth interviews with HIV and mental health providers at the 5 clinics. Most participants endorsed the feasibility of integrated PND screening, as they believed that PND had potential for significant morbidity. Among providers, identified barriers to screening were negative staff attitudes toward additional work, inadequate staffing numbers and time constraints. Suggested solutions to barriers were health worker training, supervision, and a brief screening tool. Patient-centered counselling strategies were favored over medication by WLHIV as the acceptable treatment of choice, with providers supporting the role of medication to be restricted to severe depression. Providers identified nurses as the most suitable health workers to deliver task-shifted interventions and emphasized further training as a requirement to ensure successful task shifting. Improving PND in a simple, task-shifted intervention is essential for supporting mental health among women with PND and HIV. Our results suggest that an effective PND intervention for this population should include a brief, streamlined PND screening questionnaire and individualized counselling for those who have PND, with supplemental support groups and depression medication readily available. These study results support the development of a PND intervention to address the gap in treatment of PND and HIV among WLHIV in Malawi.


Early Archean origin of heterodimeric Photosystem I.
When and how oxygenic photosynthesis originated remains controversial. Wide uncertainties exist for the earliest detection of biogenic oxygen in the geochemical record or the origin of water oxidation in ancestral lineages of the phylum Cyanobacteria. A unique trait of oxygenic photosynthesis is that the process uses a Type I reaction centre with a heterodimeric core, also known as Photosystem I, made of two distinct but homologous subunits, PsaA and PsaB. In contrast, all other known Type I reaction centres in anoxygenic phototrophs have a homodimeric core. A compelling hypothesis for the evolution of a heterodimeric Type I reaction centre is that the gene duplication that allowed the divergence of PsaA and PsaB was an adaptation to incorporate photoprotective mechanisms against the formation of reactive oxygen species, therefore occurring after the origin of water oxidation to oxygen. Here I show, using sequence comparisons and Bayesian relaxed molecular clocks that this gene duplication event may have occurred in the early Archean more than 3.4 billion years ago, long before the most recent common ancestor of crown group Cyanobacteria and the Great Oxidation Event. If the origin of water oxidation predated this gene duplication event, then that would place primordial forms of oxygenic photosynthesis at a very early stage in the evolutionary history of life.


Routine chest roentgenography in pregnancy.
In an effort to determine if routine prenatal chest roentgenograms were of practical value, the records of 12,109 consecutive deliveries at the Mayo Clinic were reviewed retrospectively. The roentgenograms were obtained during the first or second prenatal visit and additionally when warranted by notable symptoms or physical findings in subsequent prenatal visits. Forty-eight patients had appreciable roentgenographic abnormalities. The findings of the general medical examination (which was routinely done at the first prenatal visit) were reviewed to determine if the chest abnormalities would have been suspected from the results of physical examination alone. In every case, a positive history or abnormal physical finding would have suggested the presence of the major abnormality or of the need for roentgenography to be performed.


Improving osteoporosis management in patients with fractures.
A history of fracture is an independent risk factor for future fractures, but patients who have sustained a fracture are rarely evaluated for osteoporosis (OP). The objective of this study was to determine if a simple intervention in a general orthopedic clinic would lead to more fracture patients receiving evaluation and treatment for OP. Patients with a history of fracture visiting a weekly orthopedic clinic during a 6-month intervention period were educated about OP, and a bone mineral density (BMD) test was offered. The number of BMD tests performed and other OP-specific actions taken as a result of the intervention were compared with a 6-month pre-intervention period. The prevalence of OP in those who underwent BMD testing was examined. In the pre-intervention period, only 12.7% (16 of 126) had a BMD test as compared with 62.5% of the 136 intervention-period subjects (odds ratio [OR] 11.5, 95% confidence interval [CI] 6.1, 21.4). Based on BMD test results, 11.9% of the pre-intervention patients, and 41.9% of the intervention patients received OP-specific recommendations (OR 5.3, 95% CI 2.8, 10.1). The intervention led to more patients being treated for low bone mass (9.5% vs 23.5%); OR 2.9, 95% CI 1.4, 5.9. Low bone mass was common among all types of fracture patients: 20% had osteoporosis and 41%, osteopenia. BMD testing in patients with fractures should identify those at risk for future fractures, leading to appropriate treatment.


The lorisiform wrist joint and the evolution of "brachiating" adaptations in the hominoidea.
In lorisines (Loris, Nycticebus, Perodicticus, Arctocebus), the tip of the ulna is reduced to the dimensions of a styloid process, a new and more proximal ulnar head is developed, and the pisiform is displaced distally away from its primitive contact with the ulna. In some Nycticebus, intra-articular tissues separate the ulna from the triquetrum. These traits are not seen in other quadrupedal primates, but they are characteristic of extant hominoids. Among hominoids, these features have been interpreted as adaptations to arm-swinging locomotion. Since hominoid-like features of the wrist joint are found in lorisines, but not in New World monkeys that practice arm-swinging locomotion, these features may have been evolved in both lorisines and large hominoids to enhance wrist mobility for cautious arboreal locomotion involving little or no leaping. Most of the other morphological traits characteristic of modern hominoids can be explained as adaptations to cautious quadrupedalism as well as to brachiation, and may have developed for different reasons in different lineages descended from an unspecialized cautious quadruped resembling Alouatta.


Development and validation of a clinical prediction model for 90-day venous thromboembolism risk following total hip and total knee arthroplasty: a multinational study.
The risk of venous thromboembolism (VTE) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) is 1.0% to 1.5%, despite uniform thromboprophylaxis. To develop and validate a prediction model for 90-day VTE risk. A multinational cohort study was performed. For model development, records were used from the Oxford Royal College of General Practitioners Research and Surveillance Centre linked to Hospital Episode Statistics and Office of National Statistics UK routine data. For external validation, data were used from the Danish Hip and Knee Arthroplasty Registry, the National Patient Registry, and the National Prescription Registry. Binary multivariable logistic regression techniques were used for development. In the UK data set, 64 032 THA/TKA procedures were performed and 1.4% developed VTE. The prediction model consisted of age, body mass index, sex, cystitis within 1 year before surgery, history of phlebitis, history of VTE, presence of varicose veins, presence of asthma, history of transient ischemic attack, history of myocardial infarction, presence of hypertension and THA or TKA. The area under the curve of the model was 0.65 (95% CI, 0.63-0.67). Furthermore, 36 169 procedures were performed in the Danish cohort, of whom 1.0% developed VTE. Here, the area under the curve was 0.64 (95% CI, 0.61-0.67). The calibration slope was 0.92 in the validation study and 1.00 in the development study. This clinical prediction model for 90-day VTE risk following THA and TKA performed well in both development and validation data. This model can be used to estimate an individual's risk for VTE following THA/TKA.


Using Photovoice to examine adolescents' experiences receiving mental health services in the United States.
In the U.S., fewer than half of children and adolescents who report mental disorders receive care and the needs of those who receive care have yet to be explored. There is a scarcity of studies examining the needs of adolescents with mental conditions and at risk for suicide. Learning directly from the adolescents can fill in this gap by providing insight that clinicians and researchers lack about adolescents' experience. This study uses Photovoice, a Community-Based Participatory Research method that involves focus groups and the use of cameras by participants to visually capture their reality and express their ideas through photographs. By using Photovoice, this study aims to provide an opportunity for adolescents to voice their own perspectives and for researchers and clinicians to gain an understanding of adolescents' life experience away from the treatment setting, as well as their experience as consumers of mental health services. Four participants, including two 15 year olds and two 17 year olds, were recruited from a mental health clinic in New York City. Parental consent and adolescent assent were collected per Institutional Review Board requirements. Thematic analysis was used to identify and report response patterns. Four themes emerged: (i) sense of self, (ii) family, (iii) suicidal ideation and (iv) treatment. Findings suggest that Photovoice is valued by adolescents and leads to critical thinking, self-reflection, discovering strengths and social support. Adolescents reported feeling empowered, which is the ultimate goal of Photovoice. Photovoice presents a powerful opportunity to be used as therapeutic strategy with adolescents that demands further research.


More than just a pretty face. The relationship between infant's temperament, food acceptance, and mothers' perceptions of their enjoyment of food.
The goal of the present study was to determine whether mothers' assessment of their infants' temperament is associated with objective measures of the infant's acceptance patterns and their judgments of the infants' liking of a green vegetable. To this end, infants (N=92) were video-recorded as their mothers fed them green beans. From these videos, we determined the frequency of facial distaste expressions made during the first 2 min of the feeding. Other measures included intake, maternal ratings of infants' enjoyment of this vegetable, and temperament. Infants who scored high on the approach dimension of the temperament questionnaire were less likely to express facial expressions of distaste, consumed more food, and were perceived by their mothers as enjoying the food more. Mediation analyses revealed that ratings of enjoyment were not directly related to the child's approach temperament, but rather the relationship between mothers' ratings and temperament was mediated by the amount of time infants spent eating the vegetable. Regression analyses suggested that in addition to the length of time children ate, mothers' ratings of their infants' enjoyment was predicted by the number of squints that the infant expressed during the meal. These findings suggest that although certain aspects of children's temperament are related to their food acceptance, mothers attend to facial expressions and time spent eating independently of these temperamental characteristics when judging their infant's enjoyment of a food. Understanding how mothers use this information to decide which foods to feed their infants is an important area for future research.


Effect of different types of electrolyzed water on drying characteristics and quality of Spondias dulcis in oven drying.
Due to its less adverse impact on the environment as well as human health, electrolyzed water, a non-thermal method, has been recognized to be a promising alternative as a new disinfectant for the food industry, which does not change odor, texture, and flavor of foods. Spondias dulcis fruit is rich in bioactive compounds, vitamins and minerals, which are known to have many beneficial effects on health. Fresh S. dulcis has a short shelf life and drying is an option to preserve the fruit. In this study, the effects of electrolyzed water treatment on the quality characteristics of dried S. dulcis were investigated. Slices of fruit treated with four different electrolyzed waters (Anolyte NaCl, Catholyte NaCl, Anolyte Na2CO3, and Catholyte Na2CO3) were dried in a conventional oven at 70 °C. Color, Browning index, antioxidant characteristics, texture profile, rehydration capacity, pH, and Fourier transform infrared spectroscopy analyzes of dried S. dulcis were performed. The samples treated with electrolyzed water prior to drying showed higher antioxidant activity (59.46 ± 0.09), total phenolic content (287.00 ± 1.76), and rehydration capacity (4.52 ± 0.05) compared to the control samples. The findings of the current study showed that electrolyzed water treatment could prevent the browning of dried S. dulcis fruits and preserve bioactive compounds as well as chemical properties.


Characterization of yeast translation initiation factor 1A and cloning of its essential gene.
Translation initiation factor eIF1A is required in vitro for maximal rates of protein synthesis in mammalian systems. It functions primarily by dissociating ribosomes and stabilizing 40 S preinitiation complexes. To better elucidate its precise role in promoting the translation initiation process, the yeast form of eIF1A has been identified in Saccharomyces cerevisiae and purified to homogeneity on the basis of its cross-reaction with antibodies prepared against mammalian eIF1A. The apparent mass of yeast eIF1A (22 kDa) resembles that of the mammalian homolog (20 kDa), and the yeast factor is active in stimulating methionyl-puromycin synthesis in an assay composed of mammalian components. The gene encoding yeast eIF1A, named TIF11, was cloned and shown to be single copy. TIF11 encodes a protein comprising 153 amino acids (17.4 kDa); the deduced amino acid sequence exhibits 65% identity with the sequence of human eIF1A. Both human and yeast eIF1A contain clusters of positive residues at the N terminus and negative residues at the C terminus. Deletion/disruption of TIF11 demonstrates that eIF1A is essential for cell growth. Expression of human eIF1A cDNA rescues the growth defect of TIF11-disrupted cells, indicating that the structure/function of yeast and mammalian eIF1A is highly conserved.


Reliability of a quantitative rating scale for assessment of horses with distal tarsal osteoarthritis.
Various radiographic rating scales have been described for use in horses with distal tarsal osteoarthritis but little information is available on their reliability. The aim of this study was to develop a radiographic rating scale based on the results of an expert consultation process (the Delphi process), and to test the reliability of the radiographic rating scale. Seven radiographic features were identified as important indicators of distal tarsal osteoarthritis and these were then incorporated in the radiographic rating scale, which used a 100-mm-long visual analog scale. On two occasions nine equine veterinarians applied the radiographic rating scale, and a verbal descriptive rating scale, to three sets of tarsal radiographs, each comprising four standard radiographic views. Reliability was assessed using Bland-Altman plots and by calculating the 95% agreement limits. Analysis of variance (ANOVA) was used to identify significant interactions between the ratings of different assessors made from different views and at each assessment. Rating of distal tarsal osteoarthritis was different for the nine assessors. The most precise second ratings were between 16 mm higher and 18 mm lower than the first. Significant variables were "joint," "assessor," and "assessment" (univariable ANOVA); and "joint and assessor" and "assessor and assessment" (multivariable ANOVA). The radiographic rating scale developed for interpretation of distal tarsal osteoarthritis was less reliable than a verbal descriptive rating scale.


Role of adenosine in the sympathetic activation produced by isometric exercise in humans.
Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate increased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 96 +/- 25% (n = 6, P < 0.01) and MABP by 12 +/- 3 mmHg (P < 0.01). Adenosine produced forearm discomfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adenosine. Furthermore, adenosine receptor antagonism with intrabrachial theophylline (1 microgram/ml forearm per min) blocked the increase in MSNA (92 +/- 15% vs. 28 +/- 6%, n = 7, P < 0.01) and MABP (38 +/- 6 vs. 27 +/- 4 mmHg, P = 0.01) produced by isometric handgrip (30% of maximal voluntary contraction) in the infused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle afferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans.


Power estimation of multiple SNP association test of case-control study and application.
At the current stage, a large number of single nucleotide polymorphisms (SNPs) have been deployed in searching for genes underlying complex diseases. A powerful method is desirable for efficient analysis of SNP data. Recently, a novel method for multiple SNP association test using a combination of allelic association (AA) and Hardy-Weinberg disequilibrium (HWD) has been proposed. However, the power of this test has not been systematically examined. In this study, we conducted a simulation study to further evaluate the statistical power of the new procedure, as well as of the influence of the HWD on its performance. The simulation examined the scenarios of multiple disease SNPs among a candidate pool, assuming different parameters including allele frequencies and risk ratios, dominant, additive, and recessive genetic models, and the existence of gene-gene interactions and linkage disequilibrium (LD). We also evaluated the performance of this test in capturing real disease associated SNPs, when a significant global P value is detected. Our results suggest that this new procedure is more powerful than conventional single-point analyses with correction of multiple testing. However, inclusion of HWD reduces the power under most circumstances. We applied the novel association test procedure to a case-control study of preterm delivery (PTD), examining the effects of 96 candidate gene SNPs concurrently, and detected a global P value of 0.0250 by using Cochran-Armitage chi(2)s as "starting" statistics in the procedure. In the following single point analysis, SNPs on IL1RN, IL1R2, ESR1, Factor 5, and OPRM1 genes were identified as possible risk factors in PTD.


Associations between selected state laws and teenagers' drinking and driving behaviors.
We examined the associations between selected state-level graduated driving licensing (GDL) laws and use-and-lose laws (laws that allow for the suspension of a driver's license for underage alcohol violations including purchase, possession, or consumption) with individual-level alcohol-related traffic risk behaviors among high school youth. Logistic regression models with fixed effects for state were used to examine the associations between the selected state-level laws and drinking and driving behaviors youth aged 16 to 17 years (obtained from the Youth Risk Behavior Surveillance System (YRBSS); responses dichotomized as "0 times" or "1 or more times") over an extended period of time (1999 to 2009). A total of 11.7% of students reported having driven after drinking any alcohol and 28.2% reported riding in a car with a driver who had been drinking on 1 or more occasions in the past 30 days. Restrictive GDL laws and use-and-lose laws were associated with decreased driving after drinking any alcohol and riding in a car with a driver who had been drinking alcohol. Restrictive GDL and use-and-lose laws may help to bolster societal expectations and values about the hazards of drinking and driving behaviors and are therefore partly responsible for the decline in these alcohol-related traffic risk behaviors.


Expression of TGF beta 1/beta 3 during early chick embryo development.
We have used an antibody against a TGF beta peptide fragment to localize this growth factor in the early chick embryo from laying to the ten-somite stage of development. Western blotting showed that the antibody reacted with both mammalian TGF beta 1 and chicken TGF beta 3. By immunocytochemistry we find that at the earliest developmental stage (stage X of Eyal-Giladi and Kochav) immunoreactivity to this antibody is primarily located in the cells of the area opaca and marginal zone, as well as in the most peripheral edge cells of the blastoderm. The yolk is non-reactive, except in a highly localized region subjacent to the edge cells. This pattern persists at stage XII, and at both stages individual isolated cells in the epiblast and hypoblast are also reactive. By the time of gastrulation, reactivity in the epiblast is polarized to the ventral extremity of the cells, and again some isolated cells in this layer are intensely immunoreactive. At this stage also, the endoderm cells, particularly those underlying the primitive streak, are positive, as are the mesoderm cells lateral to the streak. At somite stages, the neuroepithelium is not reactive but the ectoderm lateral to it is strongly positive. At the caudal primitive streak levels of early somite embryos, the ectoderm and endoderm are immunoreactive while the mesoderm loses the reactivity it showed at the early gastrulation stages. The neuroepithelial cells later show reactivity at their apical poles, and, as at the earlier stages, individual cells show intense labelling. These results indicate that TGF beta 1 and/or TGF beta 3 immunoreactivity is developmentally regulated from very early stages of morphogenesis in the chick, and together with data from earlier functional studies, suggest that this factor has roles in embryonic axis formation and in blastoderm expansion.


Triggering atrial fibrillation after omalizumab injection in a patient with chronic spontaneous urticarial. A case report.
Omalizumab is recommended as a third-line treatment in the treatment of chronic spontaneous urticaria. During omalizumab use, which has high efficacy and safety, the side effects observed are usually moderate and temporary. Here we discuss the triggering of atrial fibrillation following omalizumab injection. A 72-year-old female patient was treated with omalizumab 300 mg/day due to chronic spontaneous urticaria resistant to conventional treatments. Atrial fibrillation developed 6 hours after the second injection of omalizumab in the patient who had atrial fibrillation and who had been monitored with antiarrhythmic treatment and sinus rhythm for 1 year. The treatment was discontinued because omalizumab was thought to trigger atrial fibrillation, as no other reason to explain the triggering of atrial fibrillation could be found. There is no data in the literature on the use of omalizumab in patients with atrial fibrillation. Different side effects of biological treatments can be observed. In particular, omalizumab should be used with caution in elderly patients and patients with arrhythmia.


Ocular and oculodermal melanocytosis associated with uveal melanoma.
Fifteen patients with ocular or oculodermal melanocytosis were found after reviewing 1210 cases of histologically proven uveal melanomas. The melanoma in each of these patients developed in the eye affected with ocular or oculodermal melanocytosis and not in the unaffected eye. In the one case of bilateral involvement with oculodermal melanocytosis, the patient developed the melanoma in the eye more affected with melanocytosis. In the only case of partial ocular melanocytosis, the melanoma developed in a sector of the eye affected with melanocytosis. A comparison of the prevalence of ocular or oculodermal melanocytosis in patients with uveal melanoma with the prevalence of ocular or oculodermal melanocytosis in the general population, implies that there is an increased incidence of uveal melanomas in patients with ocular or oculodermal melanocytosis.


Formation of the sleep-regulating mechanisms in vertebrates.
The paper presents new data concerning the mechanisms of regulation of sleep-like states in vertebrates. Somato-vegetative and behavioral correlates of primary sleep (fish, amphibians), intermediate sleep (reptiles), slow-wave and paradoxical sleep (birds) are described. The evolutionary more ancient hypothalamo-cortical and young thalamo-cortical levels of regulation of different forms of sleep are examined. Problems of existence of functional analogues of homoiotherms' sleep are discussed.


Deterministic synthesis of Cu9S5 flakes assisted by single-layer graphene arrays.
The employment of two-dimensional materials, as growth substrates or buffer layers, enables the epitaxial growth of layered materials with different crystalline symmetries with a preferential crystalline orientation and the synthesis of heterostructures with a large lattice constant mismatch. In this work, we employ single crystalline graphene to modify the sulfurization dynamics of copper foil for the deterministic synthesis of large-area Cu9S5 crystals. Molecular dynamics simulations using the Reax force-field are used to mimic the sulfurization process of a series of different atomistic systems specifically built to understand the role of graphene during the sulphur atom attack over the Cu(111) surface. Cu9S5 flakes show a flat morphology with an average lateral size of hundreds of micrometers. Cu9S5 presents a direct band-gap of 2.5 eV evaluated with light absorption and light emission spectroscopies. Electrical characterization shows that the Cu9S5 crystals present high p-type doping with a hole mobility of 2 cm2 V-1 s-1.


Concatemer chain reaction: a Taq DNA polymerase-mediated mechanism for generating long tandemly repetitive DNA sequences.
The concatemer chain reaction (CCR) uses Taq DNA polymerase to synthesize double- or single-stranded DNA concatemers whose length and yield can be controlled by varying the number of thermal cycling steps. Although the reactions which occur in CCR are slower and more complex than in polymerase chain reaction (PCR), the practical application of the CCR technique is simple. The CCR technique is less expensive, faster, and easier than conventional methods for producing concatemers and gives greatly improved yields. The templates used in CCR may be: (i) double-stranded concatemer templates produced by ligation, (ii) double-stranded concatemers from previous CCRs, or (iii) single-stranded oligonucleotides consisting of one copy of the sense strand repeat and a complementary but overlapping repeat for the antisense strand. Different molar ratios and lengths (masses) of the two strands of the helix may be obtained. We have used both single-stranded and double-stranded concatemers as targets for RNA hybridization. Applications of this concatemer technology are discussed, including the use of concatemers as hybridization probes or targets in applications such as run-on transcription or analysis of repetitive DNA sequences.


Modulation of Notch signaling as a therapeutic approach for liver cancer.
Notch signaling is an evolutionarily conserved pathway crucial for the development and homeostasis of many organs including liver. Aberrant Notch signaling has been mechanistically linked to cancer development including liver cancer. The two principal types of liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). HCCs comprise over 80% of all liver cancers and are the 6(th) most common malignancy worldwide. Hepatocellular carcinoma is also a cancer with an extremely poor prognosis, being the 3(rd) commonest cause of cancer-related mortality. Accumulating evidence indicates that the role of Notch signaling in liver cancer is more complex than once thought and is dependent on the expression of specific Notch signaling components and the complex crosstalk with other signaling pathways. Currently there are a variety of gene therapy based approaches used to target Notch signaling in preclinical studies to successfully treat liver cancer including neutralizing antibodies, siRNA, shRNA and miRNA. The use of targeted anti-Notch therapy in the clinic to treat liver cancer will require considerable refinement of our current knowledge on the regulation of Notch signaling components and their effects in both normal and malignant liver cells in order to target specific Notch subunits which are critical to liver cancer tumorigenesis but not to the homeostasis of normal cells. Using this approach will reduce the major side effects, which are frequently seen in patients treated with GSIs to inhibit the entire Notch signaling pathway. Here our understanding of Notch signaling is reviewed, highlighting its function in liver cancer initiation, progress and opportunities for liver cancer therapies.


Exposure to PM2.5 and Lung Function Growth in Pre- and Early-Adolescent Schoolchildren: A Longitudinal Study Involving Repeated Lung Function Measurements in Japan.
Rationale: Epidemiological evidence indicates that ambient exposure to particulate matter ⩽2.5 μm in aerodynamic diameter (PM2.5) has adverse effects on lung function growth in children, but it is not actually clear whether exposure to low-level PM2.5 results in long-term decrements in lung function growth in pre- to early-adolescent schoolchildren. Objectives: To examine long-term effects of PM2.5 within the 4-year average concentration range of 10-19 μg/m3 on lung function growth with repeated measurements of lung function tests. Methods: Longitudinal analysis of 6,233 lung function measurements in 1,466 participants aged 8-12 years from 16 school communities in 10 cities around Japan, covering a broad area of the country to represent concentration ranges of PM2.5, was done with a multilevel linear regression model. Forced expiratory volume in 1 second, forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC were used as lung function indicators to examine the effects of 10-μg/m3 increases in the PM2.5 concentration on relative growth per each 10-cm increase in height. Results: The overall annual mean PM2.5 level was 13.5 μg/m3 (range, 10.4-19.0 μg/m3). We found no association between any of the lung function growth indicators and increases in PM2.5 levels in children of either sex, even after controlling for potential confounders. Analysis with two-pollutant models with O3 or NO2 did not change the null results. Conclusions: This nationwide longitudinal study suggests that concurrent, long-term exposure to PM2.5 at concentrations ranging from 10.4 to 19.0 μg/m3 has little effect on lung function growth in preadolescent boys or pre- to early-adolescent girls.


Affective language and humor appreciation after right hemisphere brain damage.
Many adults with right hemisphere brain damage exhibit difficulties in the comprehension and expression of emotional language and humor. Affective comprehension deficits range in severity and can be modulated by task and response demands as well as by the strength of emotional content. Expressive emotional language deficits, as characterized by reduced emotional intensity, are more pervasive than comprehension deficits. Deficits in humor appreciation generally affect the ability to integrate an incongruous element (e.g., a punch line) with the preceding context. Several co-occurring disorders (e.g., depression, cognitive and visuoperceptual deficits, and reduced auditory comprehension) may exacerbate problems with affective language and humor. Although some formal measures evaluate humor appreciation, none specifically addresses emotional language. While no hard data exist regarding efficacy of treatment for deficits in affective language or humor processing, several suggestions for such treatment are provided.


Evaluation of proteoglycan gene polymorphisms as risk factors in the genetic susceptibility to high myopia.
PURPOSE. To investigate the relationship between high myopia and single nucleotide polymorphisms (SNPs) in six proteoglycan genes: aggrecan (ACAN), fibromodulin (FMOD), decorin (DCN), lumican (LUM), keratocan (KERA), and epiphycan (EPYC). These genes were selected for study because they are involved in induced myopia in animals and/or are within the human MYP3 locus identified by linkage analysis of families with high myopia. METHODS. Two groups of Chinese subjects were studied: group 1 (300 cases and 300 controls) and group 2 (356 cases and 354 controls). Cases were high myopes with spherical equivalent (SE) ≤ -8.00 D, and controls had SE between +1.0 and -1.0 D. From these candidate genes, 60 tagging SNPs were selected. First, 12 DNA pools were each constructed from 50 samples of the same phenotype from group 1 subjects and were tested for association with the SNPs. Second, putatively positive SNPs were confirmed by individual genotyping of group 1 subjects. Finally, positive results were replicated in group 2 subjects. RESULTS. Of the 58 SNPs successfully screened by DNA pooling, 8 ACAN SNPs passed the threshold of P ≤ 0.10 (nested ANOVA) and were then genotyped in the individual samples. Haplotypes rs3784757 and rs1516794 showed significant association with high myopia. However, the positive result could not be replicated in the second subject group. CONCLUSIONS. These six proteoglycan genes were not associated with high myopia in these Chinese subjects and hence are unlikely to be important in the genetic predisposition to high myopia.


Surgical management of syndactyly in a dog.
This report describes the treatment of simple syndactyly in a Golden Retriever. The left forepaw lacked cutaneous separation between the digits and had confluent metacarpal and digital pads. After vigorous exercise, the dog had intermittent non-weight-bearing lameness involving the affected forepaw. The lameness may have resulted from stretching of the thin skin on the dorsum of the paw as the digits attempted to spread during weight bearing. Surgical separation of digits 3 and 4 was performed by creating an interdigital web space with dorsal and palmar skin flaps and by covering the exposed axial surfaces with full-thickness skin grafts. At 11 weeks after surgery, the lameness had improved and the dog's level of activity had increased.


Comorbidities associated with epilepsy and headaches.
Comorbidities are often associated with chronic neurological diseases, such as headache and epilepsy. To identify comorbidities associated with epilepsy and headaches, and to determine possible drug interactions. A standardized questionnaire with information about type of epilepsy/headache, medical history, and medication was administered to 80 adult subjects (40 with epilepsy and 40 with chronic headache). Patients with epilepsy had an average of two comorbidities and those with headache of three. For both groups, hypertension was the most prevalent. On average, patients with epilepsy were taking two antiepileptic medications and those with headache were taking only one prophylactic medication. Regarding concomitant medications, patients with epilepsy were in use, on average, of one drug and patients with headache of two. Patients with chronic neurological diseases, such as epilepsy and headaches, have a high number of comorbidities and they use many medications. This may contribute to poor adherence and interactions between different medications.


Gene transfer and vascular disease.
Major advances in molecular biology over the past decade have increased our understanding of how genes are expressed and regulated in mammalian cells in vivo. This knowledge has been translated to investigations of the molecular and cellular biology of the cardiovascular system. Gene transfer, the introduction of a recombinant gene into host somatic cells, has become a useful tool for studying gene structure and function. It can be used to identify regulatory sequences that control gene expression. Transfer of a gene into a new cellular environment provides a means to determine gene function. These methods also allow investigators to introduce new genes into intact animals, permitting the development of animal models of human disease and investigations of gene function in vivo. The field of gene transfer and vascular disease is emerging as a new approach for studying the pathophysiology of vascular disease and for developing potential new genetic treatments for these disorders. In this review, we discuss the methods for gene transfer, how these methods can be employed to investigate the pathophysiology of cardiovascular diseases, and the potential for the development of molecular genetic treatments for human vascular diseases. The focus will be on cardiovascular diseases, although the principles may be applied to other disorders. In summary, gene transfer represents a new approach to applying molecular biology to the study and treatment of human disease.


A Comparative Assessment of Human and Chimpanzee iPSC-derived Cardiomyocytes with Primary Heart Tissues.
Comparative genomic studies in primates have the potential to reveal the genetic and mechanistic basis for human specific traits. These studies may also help us better understand inter-species phenotypic differences that are clinically relevant. Unfortunately, the obvious limitation on sample collection and experimentation in humans and non-human apes severely restrict our ability to perform dynamic comparative studies in primates. Induced pluripotent stem cells (iPSCs), and their corresponding differentiated cells, may provide a suitable alternative system for dynamic comparative studies. Yet, to effectively use iPSCs and differentiated cells for comparative studies, one must characterize the extent to which these systems faithfully represent biological processes in primary tissues. To do so, we compared gene expression data from primary adult heart tissue and iPSC-derived cardiomyocytes from multiple human and chimpanzee individuals. We determined that gene expression in cultured cardiomyocytes from both human and chimpanzee is most similar to that of adult hearts compared to other adult tissues. Using a comparative framework, we found that 50% of gene regulatory differences between human and chimpanzee hearts are also observed between species in cultured cardiomyocytes; conversely, inter-species regulatory differences seen in cardiomyocytes are found significantly more often in hearts than in other primary tissues. Our work provides a detailed description of the utility and limitation of differentiated cardiomyocytes as a system for comparative functional genomic studies in primates.


S1P2-Gα12 Signaling Controls Astrocytic Glutamate Uptake and Mitochondrial Oxygen Consumption.
Glutamate is the principal excitatory neurotransmitter in the human brain. Following neurotransmission, astrocytes remove excess extracellular glutamate to prevent neurotoxicity. Glutamate neurotoxicity has been reported in multiple neurologic diseases including multiple sclerosis (MS), representing a shared neurodegenerative mechanism. A potential modulator of glutamate neurotoxicity is the bioactive lysophospholipid sphingosine 1-phosphate (S1P) that signals through five cognate G-protein-coupled receptors, S1P1-S1P5; however, a clear link between glutamate homeostasis and S1P signaling has not been established. Here, S1P receptor knock-out mice, primary astrocyte cultures, and receptor-selective chemical tools were used to examine the effects of S1P on glutamate uptake. S1P inhibited astrocytic glutamate uptake in a dose-dependent manner and increased mitochondrial oxygen consumption, primarily through S1P2 Primary cultures of wild-type mouse astrocytes expressed S1P1,2,3 transcripts, and selective deletion of S1P1 and/or S1P3 in cerebral cortical astrocytes, did not alter S1P-mediated, dose-dependent inhibition of glutamate uptake. Pharmacological antagonists, S1P2-null astrocytes, and Gα12 hemizygous-null astrocytes indicated that S1P2-Gα12-Rho/ROCK signaling was primarily responsible for the S1P-dependent inhibition of glutamate uptake. In addition, S1P exposure increased mitochondrial oxygen consumption rates (OCRs) in wild-type astrocytes and reduced OCRs in S1P2-null astrocytes, implicating receptor selective metabolic consequences of S1P-mediated glutamate uptake inhibition. Astrocytic S1P-S1P2 signaling increased extracellular glutamate, which could contribute to neurotoxicity. This effect was not observed with the FDA-approved S1P receptor modulators, siponimod and fingolimod. Development and use of S1P2-selective antagonists may provide a new approach to reduce glutamate neurotoxicity in neurologic diseases.


WHO's role in the development of nursing in the African region.
Over the past 20 years WHO has contributed tremendously to the development and progress of the nursing profession in Africa. Its biggest achievement has been in upgrading the varied and inconsistent nursing education and training programmes introduced prior to 1953 during the colonial period. Then there were no independent states. The British controlled most of eastern and southern Africa and some countries in the west, while the French ruled over most of the colonies in western Africa.


Luteal oestradiol for patients with serum oestradiol levels lower than expected per oocyte.
Although the efficiency of progesterone in providing luteal phase support has been established, the role of oestradiol supplementation during the luteal phase remains controversial. We evaluated pregnancy outcomes of patients who had a ratio of serum E2 levels on the hCG day to the number of oocytes retrieved (oestradiol/oocyte ratio - EOR) levels of <100 pg/ml by supporting them with additional oestradiol during the luteal phase. In total, 150 patients with an EOR < 100 pg/ml of oestradiol undergoing antagonist intracytoplasmic sperm injection (ICSI) cycles were randomly assigned into two groups to receive either oral oestradiol (4 mg/d) plus vaginal progesterone (90 mg, 2 × 1/day) (group 1) or vaginal progesterone (90 mg, 2 × 1/d) alone (group 2). Implantation rate following transfer of a single embryo did not differ between the two groups (group 1 = 33.3%; group 2 = 34.9%; p = 0.85). Similarly, both groups gave comparable clinical pregnancy rates per embryo transfer with 31.7% in group 1 compared with 28.6% in group 2 (p = 0.69). In conclusion the study suggests that the addition of 4 mg oral E2 to progesterone does not increase the probability of pregnancy.


Ondansetron buccal administration for paediatric use: A comparison between films and wafers.
The objective of this study was the development of different solid formulations, such as wafers and films, for buccal administration of ondansetron, a selective and potent antagonist of 5-hydroxytryptamine 3 receptors used in children for the treatment of nausea and vomiting. Wafers and films have been prepared drying an aqueous solution of pectin, hydroxypropyl methylcellulose, sodium hyaluronate, sodium carboxymethylcellulose, chitosan or gelatin, through lyophilization or oven. Formulations were characterized in terms of morphology, drug solid state and ability to hydrate, adhere to mucosa, release and favour the permeation of the drug through porcine esophageal epithelium, used as model of human buccal epithelium. The most promising formulations were tested for in vitro biocompatibility in human pulp fibroblasts. Films showed greater hydration and mucoadhesion abilities and allowed the release and the permeation of a greater amount of ondansetron with respect to wafers. Chitosan or hyaluronate provided films with the best mucoadhesion properties and good biocompatibility profile. Moreover, chitosan based film allowed to obtain the highest amount of permeated drug and could represent a novel child-appropriate dosage form able to combine the advantages of solid dosage form with the possibility to avoid the swallowing.


Impact of COVID-19 on the mental health of children and young people: an umbrella review.
Over the past 3 years, a multitude of studies have highlighted the impact of the COVID-19 pandemic on the mental health of children and young people (CYP). In this umbrella review, we synthesise global evidence on the impact of COVID-19 on the mental health of CYP from existing systematic reviews with and/or without meta-analysis. Adopting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we evaluated 349 citations and identified 24 eligible reviews with medium to high methodological quality to be reviewed narratively. Most of the reviews reported a high prevalence of anxiety disorders, depression, suicidal behaviour, eating disorders and other mental health problems. Most studies that used data at multiple time points indicate a significant increase in mental health problems in CYP, particularly in females and older adolescents. Multipronged psychosocial care services, policies and programmes are needed to alleviate the burden of mental health problems in CYP as a consequence of the COVID-19 pandemic and associated global health measures. CRD42021276312.


Dynamics and Vibrational Spectroscopy of Alcohols in Ionic Liquids: Methanol and Ethanol.
The structure, dynamics, and vibrational spectroscopy of dilute HOD, methanol, and ethanol in the 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [emim][NTf2], ionic liquid (IL) are investigated with molecular dynamics (MD) simulations. The structure of the ILs around the solutes is qualitatively similar, where the OD bond of the deuterated alcohols donates an interaction to an [NTf2] anion and the [emim] cations interact with the oxygen atom of the OD group. The slowest time scale for the reorientational dynamics of the OD bond varied considerably for HOD, methanol, and ethanol (27, 71, and 87 ps, respectively). In contrast, the slowest time scales for spectral diffusion of the OD vibrational frequency were 11 ps for each of the three solutes, which indicates that the dynamics of the IL is relatively unchanged by the presence of the alcohols at dilute concentration. The theoretical results for the reorientational and spectral diffusion dynamics compare favorably with prior two-dimensional infrared (2D IR) spectroscopic measurements.


Bone-targeting radiopharmaceuticals for the treatment of bone-metastatic castration-resistant prostate cancer: exploring the implications of new data.
Clinical features of patients with castration-resistant prostate cancer (CRPC) are characterized by a high incidence of bone metastases, which are associated with impairment of quality of life, pain, skeletal-related events (SREs), and a negative impact on prognosis. Advances in the understanding of cancer cell-bone stroma interactions and molecular mechanisms have recently permitted the development of new agents. We review the merits, applications, and limitations of emerging data sets on bone-metastatic CRPC with a focus on radium-223, an α-emitting radiopharmaceutical, and its use in therapy for this disease. References for this review were identified through searches of PubMed and Medline databases, and only papers published in English were considered. Related links in the databases were reviewed, along with relevant published guidelines, recently published abstracts from major medical meetings, and transcripts from a recent round table of clinical investigators. Prior to radium-223, available bone-targeted therapies demonstrated the ability to delay SREs and palliate bone pain in patients with metastatic CRPC but without evidence of improvement in overall survival (OS). In a randomized controlled phase III trial, radium-223 demonstrated the ability to improve OS and delay SREs in docetaxel-pretreated or docetaxel-unfit men with symptomatic bone-metastatic CRPC and was not associated with significantly more grade 3 or 4 adverse events than placebo. Radium-223 has a targeted effect on bone metastases in CRPC and has an important role in docetaxel-pretreated or docetaxel-unfit men with symptomatic bone-metastatic CRPC.


The link between non-suicidal self-injury (NSSI), body image and activity on social networking sites among female adolescents with an eating disorder.
The link between engagement in non-suicidal self-injury (NSSI)-related activities on SNS (e.g. viewing, commenting, sharing and uploading NSSI content) with body image and NSSI behaviour remains under researched in adolescents with EDs. The main aim of the current research was to examine associations between NSSI-related activities on SNS with body image and NSSI behaviour severity among female adolescents diagnosed with an ED. A total of 52 female adolescents (mean age = 15.35 years, SD = 1.49) diagnosed with an ED completed self-report questionnaires related to NSSI behaviour, SNS usage and body image. Participants were divided into two groups: low NSSI behaviour severity (from 0 to 10 NSSI behaviours; n = 28) and high NSSI behaviour severity (more than ten NSSI behaviours; n = 24). Within the high NSSI severity group, individuals that comment and share NSSI online content significantly reported higher negative body image. A hierarchical binary logistic regression showed that the frequency of NSSI online content on SNS emerged as significant predictor of NSSI behaviour severity within last year after controlling for body image and searching for ED content on SNS. Our findings suggest that not only searching for ED content, but also being daily engaged in NSSI online activities may increase the risk of NSSI behaviour severity in female adolescents with EDs.