Toward the development of true "off-the-shelf" synthetic T-cell immunotherapy.
Recent outstanding clinical results produced by engineered T cells, including chimeric antigen receptors, have already facilitated further research that broadens their applicability. One such direction is to explore new T cell sources for allogeneic "off-the-shelf" adoptive immunotherapy. Human pluripotent stem cells could serve as an alternative cell source for this purpose due to their unique features of infinite propagation ability and pluripotency. Here, we describe the current state of engineered T cell transfer with the focus on cell manufacturing processes and the potentials and challenges of induced pluripotent stem cell-derived T cells as a starting material to construct off-the-shelf T-cell banks.


Differences in clinical experiences based on gender of third-year medical students in a required family medicine preceptorship.
To investigate whether the gender of a student or preceptor affects the students' level of experience with clinical skills in a preceptorship. A total of 451 third-year medical students completed a required family medicine preceptorship during three academic years (1997-2000) at one medical school. Students recorded their highest levels of experience with 57 clinical skills at the completion of the preceptorship using a five-point scale. Mean levels of experience were compared according to student and preceptor gender and by student-preceptor gender dyads. For the majority of clinical skills, levels of experience did not differ according to gender of the student or preceptor. However, women students received more experience with seven of 12 female-specific skills and men students received more experience with two of three male-specific skills. Women preceptors provided more experience with seven of 12 female-specific skills, as well as with depression and anxiety; men preceptors provided more experience with procedures. For the vast majority of gender-specific skills, the highest levels of student experience were received by pairs of students and preceptors of the same gender who were seeing patients of their same gender; the lowest levels of experience occurred in student-preceptor pairs of the same gender seeing patients of the opposite gender. There was no evidence for student-preceptor interactions. The gender of a student and that of the preceptor affect the level of experience the student receives with a number of gender-specific skills and procedures. Ways should be found to minimize these differences in training.


Multi-omics analysis reveals molecular mechanisms of shoot adaption to salt stress in Tibetan wild barley.
Tibetan wild barley (Hordeum spontaneum L.) has been confirmed to contain elite accessions in tolerance to abiotic stresses, including salinity. However, molecular mechanisms underlying genotypic difference of salt tolerance in wild barley are unknown. In this study, two Tibetan wild barley accessions (XZ26 and XZ169), differing greatly in salt tolerance, were used to determine changes of ionomic, metabolomic and proteomic profiles in the shoots exposed to salt stress at seedling stage. Compared with XZ169, XZ26 showed better shoot growth and less Na accumulation after 7 days treatments. Salt stress caused significant reduction in concentrations of sucrose and metabolites involved in glycolysis pathway in XZ169, and elevated level of tricarboxylic acid (TCA) cycle, as reflected by up-accumulation of citric acid, aconitic acid and succinic acid, especially under high salinity, but not in XZ26. Correspondingly, proteomic analysis further proved the findings from the metabolomic study. XZ26 maintained a lower Na concentration in the shoots and developed superior shoot adaptive strategies to salt stress. The current result provides possible utilization of Tibetan wild barley in developing barley cultivars for salt tolerance.


Hitching a Ride: Examining the Ability of a Specialist Baculovirus to Translocate through Its Insect Host's Food Plant.
Plant vascular systems can translocate the entomopathogen Bacillus thuringiensis from the soil into plant tissues. However, whether other soil dwelling entomopathogens utilize plant vascular tissue for movement has not yet been fully explored. We used Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) to evaluate whether baculoviruses, a common entomopathogen and bioinsecticide, can be transported through the plant vascular pathways of Zea mays. We found that our treatments did not allow a sufficient virus translocation into the plant to induce a lethal infection in insects, which was confirmed by a molecular analysis. While other entomopathogens translocate, baculoviruses may not be one of them.


Oxidized LDL modulates apoptosis of regulatory T cells in patients with ESRD.
Increased levels of oxidized low-density lipoproteins (oxLDL) contribute to the increased risk for atherosclerosis, which persists even after adjusting for traditional risk factors, among patients with ESRD. Regulatory T cells (CD4+/CD25+ Tregs), which down-regulate T cell responses to foreign and self-antigens, are protective in murine atherogenesis, but whether similar immunoregulation occurs in humans with ESRD is unknown. Because cellular defense systems against oxLDL involve proteolytic degradation, the authors investigated the role of oxLDL on proteasome activity of CD4+/CD25+ Tregs in patients with ESRD. CD4+/CD25+ Tregs isolated from uremic patients' peripheral blood, especially that of chronically hemodialyzed patients, failed to suppress cell proliferation, exhibited cell-cycle arrest, and entered apoptosis by altering proteasome activity. Treating CD4+/CD25+ Tregs with oxLDL or uremic serum ex vivo decreased the number and suppressive capacity of CD4+/CD25+ Tregs. In vitro, oxLDL promoted the accumulation of p27Kip1, the cyclin-dependent kinase inhibitor responsible for G1 cell cycle arrest, and increased apoptosis in a time- and concentration-dependent manner. In summary, proteasome inhibition by oxLDL leads to cell cycle arrest and apoptosis, dramatically affecting the number and suppressive capacity of CD4+/CD25+ Tregs in chronically hemodialyzed patients. This response may contribute to the immune dysfunction, microinflammation, and atherogenesis observed in patients with ESRD.


New Treatments for Spinal Nerve Root Avulsion Injury.
Further progress in the treatment of the longitudinal spinal cord injury has been made. In an inverted translational study, it has been demonstrated that return of sensory function can be achieved by bypassing the avulsed dorsal root ganglion neurons. Dendritic growth from spinal cord sensory neurons could replace dorsal root ganglion axons and re-establish a reflex arch. Another research avenue has led to the development of adjuvant therapy for regeneration following dorsal root to spinal cord implantation in root avulsion injury. A small, lipophilic molecule that can be given orally acts on the retinoic acid receptor system as an agonist. Upregulation of dorsal root ganglion regenerative ability and organization of glia reaction to injury were demonstrated in treated animals. The dual effect of this substance may open new avenues for the treatment of root avulsion and spinal cord injuries.


[Surface enhanced Raman scattering spectra of phytic acid in the sol silver oxide].
Surface enhanced Raman scattering spectra of phytic acid were recorded in the sol oxide silver. Based on ab-initio/ STO-3 quantum calculations results, assignments to the vibrational modes of phytic acid were carried out. On the basis of the mechanism of SERS, the adsorption modes were suggested that phytic acid chemically adsorbed on the oxide silver surface through four phosphate bonds.


Social determinants for infant mortality in the Nordic countries, 1980-2001.
Social equity in health is an important goal of public health policies in the Nordic countries. Infant mortality is often used as an indicator of the health of societies, and has decreased substantially in the Nordic welfare states over the past 20 years. To identify social patterns in infant mortality in this context the authors set out to review the existing epidemiological literature on associations between social indicators and infant mortality in Denmark, Finland, Norway, and Sweden during the period 1980-2000. Nordic epidemiological studies in the databases ISI Web of Science, PubMed, and OVID, published between 1980 and 2000 focusing on social indicators of infant, neonatal, and postneonatal mortality, were identified. The selected keywords on social indicators were: education, income, occupation, social factors, socioeconomic status, social position, and social class. Social inequality in infant mortality was reported from Denmark, Finland, Norway, and Sweden, and it was found that these increased during the study period. Post-neonatal mortality showed a stronger association with social indicators than neonatal mortality. Some studies showed that neonatal mortality was associated with social indicators in a non-linear fashion, with high rates of mortality in both the lowest and highest social strata. The pattern differed, however, between countries with Finland and Sweden showing consistently less social inequalities than Denmark and Norway. While the increased inequality shown in most studies was an increase in relative risk, a single study from Denmark demonstrated an absolute increase in infant mortality among children born to less educated women. Social inequalities in infant mortality are observed in all four countries, irrespective of social indicators used in the studies. It is, however, difficult to draw inferences from the comparisons between countries, since different measures of social position and different inclusion criteria are used in the studies. Nordic collaborative analyses of social gradients in infant death are needed, taking advantage of the population-covering registers in longitudinal designs, to explore the mechanisms behind the social patterns in infant mortality.


Treatment of inoperable elderly head and neck cancer patients.
Elderly head and neck cancer (HNC) patients are very rarely enrolled in clinical trials, and even more so in dedicated trials in curative or palliative setting. As a result, no standards of treatment exist for this population and thus, adaptation of standard treatments is commonly used. The choice between a monotherapy and a platinum-cetuximab combination is based on the performance status, which is not suitable and/or sufficient to evaluate the patient ability to receive a systemic treatment combined or not with radiotherapy. The evaluation of functional age using geriatric assessment is recommended. However, access to comprehensive geriatric assessment is limited in many centers, and the choice of the type of treatment is often not based on objective and reproducible criteria. As a result, fragile elderly HNC patients may be overtreated with a risk of increased toxicity and fit patients proposed for suboptimal treatment with a risk of failure of tumor control. It is therefore crucial to develop and evaluate customized treatments by enrolling elderly HNC patients in dedicated therapeutics trials, such as the ELAN (Elderly Head and Neck Cancer) studies or new approaches involving promising immunotherapies. To administer the most suitable therapy, a simple and reproducible geriatric assessment could efficiently guide practitioners.


Hip dysplasia with bilateral ischiatic nerve entrapment in a dog.
Dysfunction of both ischiatic nerves was detected in a 5-year-old spayed Labrador Retriever with radiographic evidence of severe bilateral hip dysplasia. Marked hyperflexion of the hip and stifle was evident when the dog walked. Results of electromyography confirmed the ischiatic nerve involvement. At staged operations, both ischiatic nerves were found to be compressed between the sacrotuberous ligament and proliferative tissue around the hip. One year after surgery, electromyographic and physical findings were essentially normal.


Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics.
Post-transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus-based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium-glucose-linked transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1-RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1-RAs that have not brought forth major concerns, likely indicating that GLP1-RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.


Development and evaluation of an intravascular link nurse network to sustain improvements in practice.
Link nurses have been used to support many areas of specialist nursing practice since the 1980s. They add value as they provide a practical and timely way of sharing information and knowledge and raising awareness with the wider multidisciplinary team. One strategy to improve standards and sustain improvements in the care of vascular access devices was to develop an intravascular link nurse network: 'Finding the missing link'. The link nurses are supported to attend quarterly masterclasses underpinned by the current evidence base. The masterclasses provide forums and workshops for learning, sharing initiatives, processes, progress and feedback. Results from the 2018/2019 sessions evaluation showed that 80% of the link nurses scored the workshops as excellent, 14% good, less than 1% fair and poor, and 4% did not provide an answer. Overall, 87% of link nurses were extremely likely to recommend the programme, 13% were likely to recommend it, and 93% found it helpful in their personal and professional growth. The network with supporting masterclasses has proven to be an effective strategy within the Trust.


Objective Visual Analog Scale for Biopsy Diagnosis of Helicobacter pylori Infection in Clinical Practice.
Historic and current pathology society guidelines recommend using visual gestalt to identify substantial inflammatory cell infiltrate in Helicobacter pylori gastritis, but these scales were subjectively designed. This study aims to objectively investigate the density of inflammation that justifies additional workup for H. pylori infection. We retrospectively identified 2 patient cohorts who had undergone endoscopy with gastric biopsies; 1 with H. pylori infection (n=66), confirmed with a positive stool antigen test and/or Campylobacter-like organism test, and 1 without infection (n=81). Antral and body biopsies were selected from each case, if available, and stained with MUM-1 to highlight mucosal plasma cells. Digital analysis was performed to calculate the number of plasma cells/mm2, termed the "inflammatory score" (IS). Patients with H. pylori infection had an average of 1289 plasma cells/mm2 in the antrum and 835 plasma cells/mm2 in the body, compared with 346 plasma cells/mm2 in the antrum and 178 plasma cells/mm2 in the body in patients without infection. IS cut-off values for a positive infection were 714 plasma cells/mm2 in the antrum and 316 plasma cells/mm2 in the body, with high sensitivities and specificities in both the antrum (92%, 92%) and body (85%, 84%), respectively. A visual analog scale was created to provide a histologic correlate of the observed IS ranges and cut-offs. This practical and objective scale is associated with a high sensitivity and specificity for diagnosing H. pylori infection and justifies moving away from upfront universal H. pylori testing in routine clinical practice.


Scrapie: concept of a virus-induced amyloidosis of the brain.
After an intraperitoneal infection disease-specific incorporation of [3H]leucine into protein and [3H]uridine into RNA in the brain precede clinical scrapie in hamsters. Onset of both incorporations are the earliest measurable events in the disease. Infectivity and subsequent clinical symptoms appear only after this biochemical activity has ceased. The disease-specific [3H]protein co-purifies with scrapie-associated fibrils (SAF) and infectivity during differential centrifugation and buffer extraction. SDS-PAGE shows that the [3H]protein is not SAF protein but a protein with an apparently higher mol. wt. The [3H]RNA is metabolically stable and separates from SAF and the main portion of infectivity in the last step of the purification. The appearance of SAF-protein is a late event and correlates with severe clinical symptoms. SAF seems to be derived from a brain protein turning over slowly. Our data are consistent with early pre-clinical virus replication. In this case treatment aimed at suppressing virus replication in the clinical phase of the human Creutzfeldt-Jakob disease is unlikely to produce any beneficial effect.


[Excitability of motor cortex with transcranial magnetic double stimulation in the intact man].
To evaluate the excitability of central motor tract, we studied a transcranial magnetic double stimulation with short conditioning-test (C-T) interval of 1-10ms in eight normal volunteers. In addition, H-reflex of the forearm muscle was used to study the effect of the magnetic cortical conditioning stimulus on alpha-motoneuron, and the test response evoked by electrical cortical stimulation was also used to examine the effect of the magnetic cortical conditioning stimulus. The subthreshold conditioning and suprathreshold test stimuli were applied, and compound muscle responses were recorded in the relaxed abductor pollicis brevis muscle. There was a decrease of the test response size by the conditioning stimulus at C-T interval of 1-5ms. This attenuation was probably caused by intracortical inhibition. Because the identical magnetic cortical conditioning stimulus produced increase in H-reflex size. Moreover, the test response evoked by electrical cortical stimulus was not suppressed by the magnetic cortical conditioning stimulus; whereas, response evoked by the magnetic cortical test stimulus was suppressed at C-T intervals of 2ms. With the technique of transcranial magnetic double stimulation, therefore, it is possible to evaluate the inhibitory function in the motor cortex. The technique may be of use for pathophysiology, diagnosis and estimation of treatment in the diseases.


Clinical and histologic features of chronic hepatitis C virus infection after blood transfusion in Japanese children.
To characterize the clinical and histologic features of chronic hepatitis C virus (HCV) infection after blood transfusion in Japanese children. We studied 231 children with a history of blood product transfusion. Patients were divided into two groups: 116 patients with a history of malignant disease (group 1), 115 patients who had undergone open heart surgery (group 2). We examined changes in serum alanine aminotransferase (ALT) activity and HCV markers, and patients' clinical course. Moreover, in 38 patients in whom the time of HCV infection could be defined, we examined liver histology. The proportions of patients in each group who were anti-HCV-positive were 35 out of 116 (30%) and 20 out of 115 (17%), respectively. Of the anti-HCV-positive patients, the proportions of HCV RNA-positive patients in each group were 30 out of 35 (86%) and 12 out of 20 (60%), respectively. Levels of ALT activity in patients with HCV infection varied widely for several years after blood transfusion; thereafter ALT activity fell to <100 IU/L in 2 groups. Serum ALT activity in patients who were HCV RNA-negative became normal. With regard to liver histology, there were no differences in the grade of necroinflammation or stage of fibrosis in patients with different durations of infection or when patients were analyzed according to the presence or absence of malignant disease. Patients mostly had grade 2-4 inflammation and stage 1-2 fibrosis. Thus, chronic hepatitis C was a morphologically mild disease in most children in this study. Sixty percent to 80% of children with HCV infection in this study developed chronic hepatitis C. However, examination of liver histology findings in children with chronic hepatitis C showed only mild changes.


The effects of early environment on the development of functional laterality in Morris maze performance.
The current study examined the contribution of early postnatal experience to the functional lateralisation of spatial ability in the male rat. Litters were handled (H) or non-handled (NH) during the first 20 days of life, and three males from each litter were tested in the Morris water maze in adulthood. Two subjects from each litter were monocularly tested, one with the right eye patched and the other with the left eye patched. A third subject in each litter was tested with both eyes open. Handling interacted with Eye Patch for time and distance measures. Performance of Right- and Left-Patched rats was equivalent for the NH group, but the H subjects tested with the Right Patch outperformed H subjects with the Left Patch. These results confirm studies that found spatial navigation performance to be lateralised to the right hemisphere in male rats. The data indicate that functional asymmetry of spatial navigation behaviour in the adult male rat is sensitive to environmental influences during early development.


[Loeffler syndrome and Mycoplasma pneumonitis. A case report].
We describe a clinical case of Loeffler syndrome occurred in a famale aged 13 years. This syndrome is characterized by fleeting pulmonary infiltrates and blood eosinophilia until 70%. Patients usually are only mildly ill or asymptomatic and recovery occurs from few days to some months. Principle causes are: a) mycetes as Aspergillus; b) helmints as Toxocara, Ancylostoma, Trichinella, Ascaris, Strongyloides, Schistosoma; c) chemical agents such as penicillin, para-aminosalycilic acid, hydralazine, nitrofurantoine, chlorpropamide. This girl came to our observation in good general conditions with murmur reduction on the thorax left side, marked peripheral eosinophilia (E 55% of 6100 white blood cell), right pulmonary infiltrate on RX and CT scan. One month before she had fever, treated with amoxycillin and clavulanic acid. Mantoux, Prick tests for main inhalant allergenes, ACE, repeated stools and seric investigations for parasites, mycetes and organisms, were negative except for IgM anti-Myco-plasma antibodies. Broncholavage showed marked eosinophilia. Smear didn't show any blast. The girl recovered in about 40 days (E 4.1% of 8500 WBC, RX negative). Our hypotesis is a causative role of amoxycillin in inducing the syndrome, even if this is a rare event, with an overlapping of a Mycoplasma infection.


Nutrition in Asthma.
An emerging body of evidence suggests that diet plays an important role in both the development and management of asthma. The relationship between dietary intake and asthma risk has been explored in epidemiological studies, though intervention trials examining the effects of nutrient intake and dietary patterns on asthma management are scarce. Evidence for diets high in fruits and vegetables, antioxidants, omega-3 fatty acids and soluble fiber such as the Mediterranean diet is conflicting. However, some studies suggest that these diets may reduce the risk of asthma, particularly in young children, and could have positive effects on disease management. In contrast, a Westernized dietary pattern, high in saturated fatty acids, refined grains, and sugars may promote an inflammatory environment resulting in the onset of disease and worsening of asthma outcomes. This review will summarize the state of the evidence for the impact of whole dietary patterns, as well as individual nutrients, on the prevalence and management of asthma.


Mechanisms of desensitization to a PDE inhibitor (milrinone) in conscious dogs with heart failure.
The goal of this study was to determine the extent to which the effects of milrinone were desensitized in heart failure (HF) and to determine the mechanisms, i.e., whether these effects could be ascribed to changes in cAMP or phosphodiesterase (PDE) activity in HF. Accordingly, we examined the effects of milrinone in seven conscious dogs before and after HF was induced by rapid ventricular pacing at 240 beats/min. The dogs were chronically instrumented for measurements of left ventricular (LV) pressure and first derivative of LV pressure (dP/dt), arterial pressure, LV internal diameter, and wall thickness. Milrinone (10 micrograms . kg-1. min-1 iv) increased LV dP/dt by 1,854 +/- 157 from 2,701 +/- 105 mmHg/s (P < 0.05) before HF. After HF the increase in LV dP/dt in response to milrinone was attenuated significantly (P < 0.05); it increased by 615 +/- 67 from 1,550 +/- 107 mmHg/s, indicating marked desensitization. In the presence of ganglionic blockade the increases in LV dP/dt (+445 +/- 65 mmHg/s) in response to milrinone were markedly less (P < 0.01), and milrinone increased LV dP/dt even less in HF (+240 +/- 65 mmHg/s). cAMP and PDE activity were measured in endocardial and epicardial layers in normal and failing myocardium. cAMP was decreased significantly (P < 0.05) in LV endocardium (-26%) but not significantly in LV epicardium (-14%). PDE activity was also decreased significantly (P < 0.05) in LV endocardium (-18%) but not in LV epicardium (-4%). Thus significant desensitization to milrinone was observed in conscious dogs with HF. The major effect was autonomically mediated. The biochemical mechanism appears to be due in part to the modest reductions in PDE activity in failing myocardium, which, in turn, may be a compensatory mechanism to maintain cAMP levels in HF. Reductions in cAMP and PDE levels were restricted to the subendocardium, suggesting that the increased wall stress and reduced coronary reserve play a role in mediating these changes.


Vesicular nucleotide transport: a brief history and the vesicular nucleotide transporter as a target for drug development.
Neurons and neuroendocrine cells store nucleotides in vesicles and release them upon stimulation, leading to intercellular purinergic signaling. The molecular machinery responsible for the vesicular storage of nucleotides was a long standing enigma, however, recently the transporter involving in the process was identified. This article summarizes the history of vesicular storage of nucleotides and the identification of the vesicular nucleotide transporter (VNUT) responsible for the process. The significance of VNUT as a drug target to control purinergic chemical transmission is also discussed.


Hepatitis C antiviral treatment outcomes are comparable between clinical trial participants and recipients of standard-of-care therapy: an analysis of trial effect.
Trial effect refers to the impact of clinical trial participation on treatment outcomes. Little literature exists evaluating the magnitude and direction of trial effect in hepatitis C virus (HCV). A single-center, retrospective study on HCV antiviral therapy recipients was conducted. Sustained virologic response (SVR), virologic response at treatment weeks 4 and 12, dose interruptions, and adverse events were compared between clinical trial participants and standard-of-care antiviral recipients between September 2000 and November 2011. A total of 449 patients were evaluated (trial: 89, nontrial: 360). Patients were matched for age (trial: 47 years, nontrial: 45 years), sex (male: trial, 74%; nontrial, 72%), and ethnicity (white: trial, 87%; nontrial, 78%). The groups differed in the incidence of genotype 1 infection (trial: 83%, nontrial 53%; P<0.001), liver biopsy rates (trial: 98%, nontrial: 66%; P<0.001), and history of psychiatric illness (trial: 30%, nontrial: 53%; P<0.001). On intent-to-treat analysis, SVR rates were found to be similar (trial: 51%, nontrial: 54%; P=0.86), even when stratified for genotype (G1: trial, 47%; nontrial, 47%; P=0.78). Interferon dose reductions (trial: 18%, nontrial: 6%; P<0.01) were more likely in trial patients, whereas treatment discontinuation because of side effects (trial: 8%, nontrial: 18%; P<0.02) was less likely in them. No differences in safety issues were identified. Overall, a trial effect resulting in improved or diminished SVR rates was not identified. Other potential positive and negative variables should be focused upon for HCV patients deliberating between clinical trial participation and receiving standard-of-care treatment.


Should intakes with beneficial actions, often requiring supplementation, be considered for RDAs?
The conceptual framework upon which the Recommended Dietary Allowance (RDA) was derived is being replaced by a new, less population-based and more individualistic view of nutrition that relates to health more broadly than merely the prevention of overt nutrient deficiency disease. As this has occurred, problems have become apparent concerning the RDA, which constitutes the key linkage between nutrition understanding and dietary guidance, calling for its redefinition. Any reconstruction of the RDA must be based on the paradigm for nutrition that has, in fact, been adopted; this will require, where evidence warrants, the incorporation into the new construct of intakes with beneficial actions without regard for whether this may require supplementation in the context of contemporary diets.


Suppression of monocyte function and differential regulation of IL-1 and IL-1ra by IL-4 contribute to resolution of experimental arthritis.
IL-4 has diverse effects on hematopoietic cells, including the ability to suppress certain mononuclear cell functions. To evaluate the effect of IL-4 on the evolution of acute and chronic arthritis, murine recombinant IL-4 was administered systemically to animals receiving an arthropathic dose of group A streptococcal cell wall fragments. Daily treatment with IL-4 had a minimal effect on the acute phase, but significantly suppressed the chronic, destructive phase. By 4 wk after initiation of disease, the articular index of IL-4-treated animals was reduced > 60% (articular index = 4 +/- 0.9) compared with the untreated rats (11.5 +/- 0.48, p < 0.001). A substantial decrease in the influx of inflammatory cells and virtual elimination of pannus and erosions occurred after IL-4 therapy. Associated with the reduced accumulation of mononuclear leukocytes was a decrease in their proinflammatory functions including cytokine production and reactive oxygen intermediate metabolism. These observations are consistent with the selective effects of IL-4 on phagocytic cell function demonstrated in vitro. Furthermore, IL-4 induced gene expression for IL-1ra, a protein that antagonizes the action of IL-1 by binding to the IL-1 receptor without agonist activity. Through an expanding spectrum of effects on monocyte-macrophage phenotypic and functional parameters, IL-4 is emerging as an important inhibitor of cell-mediated immune responses and pathogenic processes.


[Is there a future for Fallopian tube insemination in women?].
In unselected patients, the pregnancy rate after intrauterine insemination (i.u.i.) seldom goes beyond 10-15% per cycle. An insufficient number of spermatozoa at the fertilization site has been hypothesized for a long time to explain the low efficacy of this technique. Thus, the introduction of a larger number of male gametes into the female tubes has been thought of to give better results since the late eighties. First, a direct tubal catheterisation has been proposed for injection of spermatozoa, either by laparoscopy or transvaginally under ultrasound guidance or by tactile sensation. However, these procedures have been abandoned because of some severe traumatic and infectious complications. Alternatively, a spermatozoa suspension of several millilitres can be injected under pressure into the uterine cavity while sealing the cervical os, by various systems. This technique called Fallopian sperm perfusion (FSP) has yielded some interesting results, particularly in unexplained infertility. Nevertheless, the superiority of FSP over i.u.i. still remains controversial. This review describes the current knowledge about intratubal insemination and its potential role in the management of human infertility.


Novel coronavirus 19 (COVID-19) associated sinus node dysfunction: a case series.
Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. To date, there have not been reports of sinus node dysfunction (SND) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of COVID-19 patients who experience de novo SND. We present two cases of new-onset SND in patients recently diagnosed with COVID-19. Patient 1 is a 70-year-old female with no major past medical history who was intubated for acute hypoxic respiratory failure secondary to COVID-19 pneumonia and developed new-onset sinus bradycardia without a compensatory increase in heart rate in response to relative hypotension. Patient 2 is an 81-year-old male with a past medical history of an ascending aortic aneurysm, hypertension, and obstructive sleep apnoea who required intubation for COVID-19-induced acute hypoxic respiratory failure and exhibited new-onset sinus bradycardia followed by numerous episodes of haemodynamically significant accelerated idioventricular rhythm. Two weeks following the onset of SND, both patients remain in sinus bradycardia. COVID-19-associated SND has not previously been described. The potential mechanisms for SND in patients with COVID-19 include myocardial inflammation or direct viral infiltration. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and haemodynamic instability.


Effects of twelve-month strength training subsequent to twelve-month stretching exercise in treatment of chronic neck pain.
Previously, in a randomized study, we showed that women with chronic neck pain were able to perform intensive training for neck and shoulder muscles and that the increase in strength was accompanied by a reduction in pain and disability. The changes were significantly greater in the training groups compared with controls. The aim of the present study was to evaluate whether the controls would achieve similar results. Thus, 59 women in the control group initiated high-intensity strength training. Maximal isometric neck strength increased by 44% in both flexion and rotation and 27% in extension at the 2-year follow-up. Statistically and also clinically significant decreases in neck pain and disability indices occurred. Stretching and aerobic exercising during the first follow-up year produced only minor changes in both subjective and functional measures. Adding progressive strength training for the second year led to a significant improvement in neck strength and also to a considerable decrease in the pain and disability scores. Thus, to achieve effective rehabilitation in cases of chronic neck pain, a combination of strength training and stretching exercises are recommended.


Quantitative Detection of Disseminated Melanoma Cells by Trp-1 Transcript Analysis Reveals Stochastic Distribution of Pulmonary Metastases.
A better understanding of the process of melanoma metastasis is required to underpin the development of novel therapies that will improve patient outcomes. The use of appropriate animal models is indispensable for investigating the mechanisms of melanoma metastasis. However, reliable and practicable quantification of metastases in experimental mice remains a challenge, particularly if the metastatic burden is low. Here, we describe a qRT-PCR-based protocol that employs the melanocytic marker Trp-1 for the sensitive quantification of melanoma metastases in the murine lung. Using this protocol, we were able to detect the presence of as few as 100 disseminated melanoma cells in lung tissue. This allowed us to quantify metastatic burden in a spontaneous syngeneic B16-F10 metastasis model, even in the absence of visible metastases, as well as in the autochthonous Tg(Grm1)/Cyld-/- melanoma model. Importantly, we also observed an uneven distribution of disseminated melanoma cells amongst the five lobes of the murine lung, which varied considerably from animal to animal. Together, our findings demonstrate that the qRT-PCR-based detection of Trp-1 allows the quantification of low pulmonary metastatic burden in both transplantable and autochthonous murine melanoma models, and show that the analysis of lung metastasis in such models needs to take into account the stochastic distribution of metastatic lesions amongst the lung lobes.


The importance of an endotoxin-free environment during the production of nanoparticles used in medical applications.
We investigated the effect of spherical gold nanoparticles on immature dendritic cells (DCs). Conventionally produced nanoparticles had a maturating effect on the DCs--a result of lipopolysaccharide (LPS) contamination. By modification of the production process, low-LPS particles were obtained, which had practically no effect on phenotypic maturation or cytokine production of the DCs. Our findings emphasize the importance of high purity in the production of nanoparticles, since possible contaminants may interfere with the assessment of biological/medical effects. They also highlight that nanoparticles can function as carriers of immune modulating contaminants.


Bidirectional and mutually beneficial interactions between human mesenchymal stem cells and osteoarthritic chondrocytes in micromass co-cultures.
Mesenchymal stem cell (MSC)-based therapy presents a promising approach for treating osteoarthritis (OA). However, the molecular interactions between MSCs and OA chondrocytes (OACs) are not known. This study aims to investigate the bidirectional interactions between human MSCs (hMSCs) and human OACs (hOACs) in a 3D co-culture system. hMSC-collagen microspheres were cultured in hOAC-conditioned medium or co-cultured with hOAC-collagen microspheres. Growth characteristics, glycosaminoglycan (GAG) production, gene expression of major OA-associated chondrogenic markers, including SOX9, COL2A1, ACAN and MMP13, were investigated in both cell types. Both the conditioned medium and the co-culture induced MSC chondrogenesis with enhanced GAG production, SOX9 gene and protein expression, and gene expression of ACAN and COL2A1. Meanwhile, the co-culture also induced hOACs to partially resume the lost chondrogenic phenotype as shown by reduced proliferation, enhanced GAG production when hMSCs were chondrogenically predifferentiated, and reduced MMP13 gene expression. This work suggests that 3D co-culture of hMSCs and hOACs is mutually beneficial to each other, suggesting the potential therapeutic effect of delivering hMSC in scaffolds directly to OA defects.


Validation of a Spectral Method for Quantitative Measurement of Color in Protein Drug Solutions.
A quantitative spectral method has been developed to precisely measure the color of protein solutions. In this method, a spectrophotometer is utilized for capturing the visible absorption spectrum of a protein solution, which can then be converted to color values (L*a*b*) that represent human perception of color in a quantitative three-dimensional space. These quantitative values (L*a*b*) allow for calculating the best match of a sample's color to a European Pharmacopoeia reference color solution. In order to qualify this instrument and assay for use in clinical quality control, a technical assessment was conducted to evaluate the assay suitability and precision. Setting acceptance criteria for this study required development and implementation of a unique statistical method for assessing precision in 3-dimensional space. Different instruments, cuvettes, protein solutions, and analysts were compared in this study. The instrument accuracy, repeatability, and assay precision were determined. The instrument and assay are found suitable for use in assessing color of drug substances and drug products and is comparable to the current European Pharmacopoeia visual assessment method. In the biotechnology industry, a visual assessment is the most commonly used method for color characterization, batch release, and stability testing of liquid protein drug solutions. Using this method, an analyst visually determines the color of the sample by choosing the closest match to a standard color series. This visual method can be subjective because it requires an analyst to make a judgment of the best match of color of the sample to the standard color series, and it does not capture data on hue and chroma that would allow for improved product characterization and the ability to detect subtle differences between samples. To overcome these challenges, we developed a quantitative spectral method for color determination that greatly reduces the variability in measuring color and allows for a more precise understanding of color differences. In this study, we established a statistical method for assessing precision in 3-dimensional space and demonstrated that the quantitative spectral method is comparable with respect to precision and accuracy to the current European Pharmacopoeia visual assessment method.


The 20-kD human growth hormone reduces body fat by increasing lipolysis and decreasing lipoprotein lipase activity.
The aim of this study was to estimate the lipolytic activity of the human growth hormone variant, 20-kD human growth hormone (20K-hGH). Obese KV-A(y) mice were given daily subcutaneous injections of 20K-hGH (0.25, 0.5, 1.0 mg/kg), 22K-hGH (0.25 mg/kg) or saline as a control for 2 weeks. Body composition (fat, water and protein), lipolysis and lipoprotein lipase (LPL) activity were measured 24 h after the final injection. Both growth hormone isoforms significantly reduced relative fat pad and whole body lipids. In addition, 20K-hGH produced an inhibition of LPL activity in adipose tissue and stimulated lipolysis in adipocytes. These data strongly suggest that inhibition of LPL activity in adipose tissue and stimulation of lipolysis in adipocytes by 20K-hGH treatment reduce adipose tissue mass, resulting in body fat reduction.


The serotonin 2B receptor is required in neonatal microglia to limit neuroinflammation and sickness behavior in adulthood.
Severe peripheral infections induce an adaptive sickness behavior and an innate immune reaction in various organs including the brain. On the long term, persistent alteration of microglia, the brain innate immune cells, is associated with an increased risk of psychiatric disorders. It is thus critical to identify genes and mechanisms controlling the intensity and duration of the neuroinflammation induced by peripheral immune challenges. We tested the hypothesis that the 5-HT2B receptor, the main serotonin receptor expressed by microglia, might represent a valuable candidate. First, we observed that Htr2b-/- mice, knock-out for the 5-HT2B receptor gene, developed, when exposed to a peripheral lipopolysaccharide (LPS) challenge, a stronger weight loss compared to wild-type mice; in addition, comparison of inflammatory markers in brain, 4 and 24 hr after LPS injection, showed that Htr2b deficiency leads to a prolonged neuroinflammation. Second, to assess the specific contribution of the microglial 5-HT2B receptor, we investigated the response to LPS of conditional knock-out mice invalidated for Htr2b in microglia only. We found that deletion of Htr2b in microglia since birth is sufficient to cause enhanced weight loss and increased neuroinflammatory response upon LPS injection at adult stage. In contrast, mice deleted for microglial Htr2b in adulthood responded normally to LPS, revealing a neonatal developmental effect. These results highlight the role of microglia in the response to a peripheral immune challenge and suggest the existence of a developmental, neonatal period, during which instruction of microglia through 5-HT2B receptors is necessary to prevent microglia overreactivity in adulthood.


Akt regulates skeletal development through GSK3, mTOR, and FoxOs.
Although Akt plays key roles in various cellular processes, the functions of Akt and Akt downstream signaling pathways in the cellular processes of skeletal development remain to be clarified. By analyzing transgenic embryos that expressed constitutively active Akt (myrAkt) or dominant-negative Akt in chondrocytes, we found that Akt positively regulated the four processes of chondrocyte maturation, chondrocyte proliferation, cartilage matrix production, and cell growth in skeletal development. As phosphorylation of GSK3beta, S6K, and FoxO3a was enhanced in the growth plates of myrAkt transgenic mice, we examined the Akt downstream signaling pathways by organ culture. The Akt-mTOR pathway was responsible for positive regulation of the four cellular processes. The Akt-FoxO pathway enhanced chondrocyte proliferation but inhibited chondrocyte maturation and cartilage matrix production, while the Akt-GSK3 pathway negatively regulated three of the cellular processes in limb skeletons but not in vertebrae due to less GSK3 expression in vertebrae. These findings indicate that Akt positively regulates the cellular processes of skeletal growth and endochondral ossification, that the Akt-mTOR, Akt-FoxO, and Akt-GSK3 pathways positively or negatively regulate the cellular processes, and that Akt exerts its function in skeletal development by tuning the three pathways in a manner dependent on the skeletal part.


Update on carotid endarterectomy.
Progress in therapeutic decision-making for patients with carotid artery disease has come from evaluations made by several major randomized clinical trials. For patients who are symptomatic and have arteriographically proven stenoses of 70% or more, endarterectomy is clearly established as the treatment of choice. Symptomatic patients with stenoses of less than 70% remain the subject of ongoing study. Asymptomatic patients are at low risk of stroke save for those with the highest (80% to 90%) degrees of stenosis, and even for these subjects the annual stroke rate is close to the operative risk. Four trials have been reported but the practicing physician is still without clear guidelines. The appropriateness of endarterectomy remains unsettled for any group of patients with narrowing of the carotid artery in the absence of symptoms. The decision to apply endarterectomy to symptomatic and to asymptomatic patients must attend to not only the prognostic importance of the degree of stenosis, but also to the vascular risk profile of the individual patient.


Geriatric nutritional risk index was associated with in-hospital mortality among cardiac intensive care unit patients.
Identifying risk factors associated with cardiac intensive care unit (CICU) patients' prognosis can help clinicians intervene earlier and thus improve their prognosis. The correlation between the geriatric nutrition risk index (GNRI), which reflects nutritional status, and in-hospital mortality among CICU patients has yet to be established. The present study retrospectively enrolled 4,698 CICU patients. Based on the nutritional status, the participants were categorized into four groups. The primary endpoint was in-hospital mortality. The length of hospital stay and length of CICU stay were the secondary endpoints. To explore the correlation between nutritional status and in-hospital mortality, a logistic regression analysis was conducted. The nonlinear associations of GNRI with in-hospital mortality were evaluated using restricted cubic spline (RCS). Furthermore, subgroup analyses were conducted to evaluate the effect of the GNRI on in-hospital mortality across different subgroups, with calculation of the p for interaction. A higher risk of malnutrition was significantly linked to an increased incidence of in-hospital mortality (High risk vs. No risk: 26.2% vs. 4.6%, p < 0.001), as well as a longer length of hospital stay (High risk vs. No risk: 15.7, 9.1-25.1 vs. 8.9, 6.9-12.9, p < 0.001) and CICU stay (High risk vs. No risk: 6.4, 3.8-11.9 vs. 3.2, 2.3-5.1, p < 0.001). An elevated GNRI was significantly associated with an increased risk of in-hospital mortality even after controlling for pertinent confounding factors (High risk vs. No risk: OR, 95% CI: 2.37, 1.67-3.37, p < 0.001, p for trend <0.001). Additionally, the RCS model showed a linear relationship between GNRI and in-hospital mortality, with the risk of in-hospital mortality significantly decreasing as GNRI increased (non-linear p = 0.596). Furthermore, in the subgroups of hypertension, ventricular arrhythmias, cardiac arrest, shock, and chronic kidney disease, there was a significant interaction between nutritional status and in-hospital mortality. Among CICU patients, a low GNRI was a significant predictor of in-hospital mortality. Furthermore, patients with a higher risk of malnutrition, as indicated by low GNRI values, experienced significantly longer hospital and CICU stays.


Heterorhabditis bacteriophora: seasonal dynamics and distribution in a stand of sugar maple, Acer saccharum.
The seasonal dynamics of an indigenous entomopathogenic nematode, a new strain of Heterorhabditis bacteriophora, "Nittany strain," in a stand of sugar maple, Acer saccharum, were examined utilizing a Galleria mellonella bait method. Seasonal dynamics are described in relation to soil temperature; occurrence is related to distance from a tree bole. A correlation between soil temperature and the number of infected G. mellonella was observed. Soil temperature had a significant effect on the number of positive samples, i.e., soil samples containing infected G. mellonella, obtained. In addition, seasonality had a significant effect on whether positive samples were obtained on a given date. There was no significant difference in the abundance of positive samples among three distances from a tree bole, namely, at the base of the tree, 2 m from the bole, or at the dripline.


[Finite element stress analysis of stress distribution endodontic posts at shoulder].
The objective of the present resarch is the comparative stress distribution of various design for post-core at shoulder. The purpose of this study was to analyse the stress distribution and concentration in the dentin of paralled-sided and taped posts by different shoulder designs with finite elements stress analysis method. It was found that stress tended to concentrate under the core shoulder with vertical force. When the force applied from the linqual side. The stress concentrated at the buccal side. The 90 degrees shoulder angles exhibited more even stress distribution than sharp shoulder angles. The analysis revealed that sharp angle should be avoided as occlusal shoulder in clinical practice because this design are less resistant to forces applied on them and are susceptible to fractures in the dentin.


Genetic diversity among Campylobacter jejuni isolates from pets in Ireland.
Campylobacter jejuni isolates obtained from pets housed in shelters and in private households were subtyped by fla typing (using DdeI and HinfI restriction enzymes) and pulsed-field gel electrophoresis (PFGE) techniques. Composite fla cluster analysis on 78 C jejuni isolates was more discriminative than either single fla typing technique with 39.7 per cent single isolate patterns. PFGE on 52 C jejuni isolates revealed 53.8 per cent single isolate patterns and was the most discriminative method applied. A database of C jejuni subtyping profiles from pets in Ireland was assembled. The presence of genetic heterogeneity detected in the C jejuni subtypes suggests that pets can acquire the organisms from multiple potential sources. In addition, heterogeneity was detected in the C jejuni subtypes obtained by different culture methods within the same pet. There was a link between isolates from dogs in close contact in the same environment, confirming that this is a potential route of infection, and clusters were detected containing both cat and dog C jejuni isolates, suggesting possible interspecies transmission.


Diffusion of Gases through Plant Tissues : Entry of Acetylene into Legume Nodules.
I have measured acetylene diffusion through plant tissues including nodules from several species of legume-vetch, peas, soybeans, and Sesbania rostrata. The observed half-time for reequilibration of internal and external concentration is less than 1 minute for typical nodules. Inward diffusion of acetylene in air is rapid relative to the use of acetylene by nitrogenase so that diffusion of acetylene would not be a significant limiting factor for nitrogenase activity in air. However, under an atmosphere of Ar:O(2) where there is no N(2) reduction, the inward diffusion rate of acetylene into larger nodules could produce a measurable limitation of observed nitrogenase activity at low acetylene concentrations.


Evidence of Polaron Excitations in Low Temperature Raman Spectra of Oxalic Acid Dihydrate.
Low temperature Raman spectra of oxalic acid dihydrate (8-300 K) for both the polycrystalline and single crystal phase show strong variation with temperature in the interval from 1200 to 2000 cm(-1). Previous low temperature diffraction studies all confirmed the stability of the crystal P21/n phase with no indications of any phase transition, reporting the existence of a strong hydrogen bond between the oxalic acid and a water molecule. A new group of Raman bands in the 1200-1300 cm(-1) interval below 90 K is observed, caused by possible loss of the center of inversion. This in turn could originate either due to disorder in hydroxyl proton positions or due to proton transfer from carboxylic group to water molecule. The hypothesis of proton transfer is further supported by the emergence of new bands centered at 1600 and 1813 cm(-1), which can be explained with vibrations of H3O(+) ions. The broad band at 1600 cm(-1) looses intensity, while the band at 1813 cm(-1) gains intensity on cooling. The agreement between quantum calculations of vibrational spectra and experimentally observed Raman bands of hydronium ions in oxalic acid sesquihydrate crystal corroborates this hypothesis.


Effects of fasting and refeeding on some metabolic characteristics of rat brown adipose tissue.
To investigate the effects of fasting and refeeding on rat interscapular brown adipose tissue (BAT), we determined in vitro oxygen consumption, in vitro lipolysis, DNA content and composition of fatty acid (FA). Fasting decreased the weights of body and BAT, and the DNA content of BAT. Fasting reduced both basal oxygen consumption and basal lipolysis of BAT. Fasting also suppressed the noradrenaline- and glucagon-induced increases in both oxygen consumption and lipolysis of BAT. In both triglyceride and phospholipid FA of BAT the extent of unsaturation was increased by fasting. Refeeding restored all of these parameters to the control level. These observations indicate that fasting reduces both oxygen consumption and lipolysis of BAT, resulting in reduced thermogenesis, while fasting could stimulate BAT in certain phases of its function as observed in FA composition.


Kinetics of urinary furosemide elimination in infants.
Using a one-compartment model, the urinary elimination kinetics of a single intravenous 1 mg/kg dose of furosemide (F) was studied in 13 infants, 9 days to 12 months old (mean 3.7 +/- (SD) 3.48 months old), and 1, 23-month-old child, with bilateral multifocal pneumonia, recovering from respiratory and cardiac insufficiency accompanying pneumonia and/or other diseases. F elimination half-life was determined with the use of a noninvasive method based on the drug's urinary excretion data. The drug urinary elimination t1/2 in the infants ranged from 0.654 to 3.29 h. Cumulative excretion of F in the infants' urine was similar to the values in healthy adults. Since the furosemide urinary half-lives found in infants were similar to the data reported in older children and healthy adults it is suggested that immaturity of renal function during the 1st year of life, i.e. in older infants, has no evident on the elimination kinetics of a 1 mg/kg intravenous dose of F. Mean F urinary elimination t1/2 in infants with pneumonia and cardiac insufficiency was significantly longer compared with the Ft1/2 found in children with the pneumonia alone (2.15 vs. 1.01 h, respectively), suggesting slower elimination of the drug in these patients.


Acute, multiple-dose dermal and genetic toxicity of Nu-3: a novel antimicrobial agent.
Nu-3 [butyl-phosphate-5'-thymidine-3'-phosphate-butyl] is a modified nucleotide that has been shown to have antimicrobial activity against a range of bacteria including Pseudomonas aeruginosa. However, data on the toxicological profile of Nu-3 are still lacking. In the present study, the toxicity of Nu-3 was evaluated by the following studies: acute oral toxicity, dermal and mucous membrane irritation, multiple-dose toxicity and genotoxicity in vivo and vitro. The acute oral toxicity test in mice showed that Nu-3 had an LD(50) of 2001 mg/kg body weight. The irritation tests on rats revealed that Nu-3 was not irritant, with an irritation scoring of 0. The multiple-dose toxicity study in rats showed that Nu-3 did not cause significant changes in histology, selected serum chemistry, and hematological parameters compared to the controls. Rats administrated with multiple-doses of Nu-3 showed no visible toxic symptoms. Both in vitro and in vivo, Nu-3 exhibited no notable genetic toxicity. Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treating Pseudomonas aeruginosa infection.


Surgical treatment of the ankle and foot in patients with rheumatoid arthritis.
Rheumatoid arthritis can be as devastating for the joints of the foot and ankle as for other joints of the lower and upper extremities. Early conservative treatment often is provided by a primary care provider or rheumatologist. Drug and injection therapies are used with footwear modifications, activity restrictions, and orthoses. Surgery often is the last treatment modality available to the patient; it has the potential to relieve pain and improve function.


Evaluation of brief treatment of symptoms of psychological trauma among veterans residing in a homeless shelter by use of Accelerated Resolution Therapy.
Posttraumatic stress disorder (PTSD) is prevalent in both homeless and nonhomeless veterans. To examine unique characteristics of being homeless that may influence PTSD treatment completion and clinical success. Twenty-three veterans who were homeless and residing in a homeless shelter, along with 94 veterans from the community, were enrolled to receive one to five sessions of Accelerated Resolution Therapy (ART), an emerging trauma-focused therapy for symptoms of PTSD. Rates of treatment completion with ART and acute and 6-month change in symptoms of PTSD were compared in an observational (nonrandomized) manner by housing status. Compared to veterans recruited from the community, veterans residing in the homeless shelter were older and presented with more extensive psychopathology yet had less combat exposure while being more likely to have experienced sexual assault. Rates of treatment completion were 52.2% (12 of 23) among homeless veterans compared to 81.9% (77 of 94) among veterans from the community (p = .005). Among treatment completers, both groups received an average of four sessions of ART. Reduction of symptoms of PTSD was substantial and nonsignificantly greater among homeless veterans vs. those treated from the community (p = .14), as were comorbidity reductions in depression, anxiety, sleep quality, pain, and improved quality of life. Results at 6-month posttreatment follow-up were similar. Although limited by small sample size and a nonrandomized design, ART appears to be an effective, brief treatment for symptoms of PTSD among veterans residing in a homeless shelter. However, development of effective strategies to maximize treatment completion among homeless veterans is needed.


Isolation, Transfection, and Long-Term Culture of Adult Mouse and Rat Cardiomyocytes.
Ex vivo culture of the adult mammalian cardiomyocytes (CMs) presents the most relevant experimental system for the in vitro study of cardiac biology. Adult mammalian CMs are terminally differentiated cells with minimal proliferative capacity. The post-mitotic state of adult CMs not only restricts cardiomyocyte cell cycle progression but also limits the efficient culture of CMs. Moreover, the long-term culture of adult CMs is necessary for many studies, such as CM proliferation and analysis of gene expression. The mouse and the rat are the two most preferred laboratory animals to be used for cardiomyocyte isolation. While the long-term culture of rat CMs is possible, adult mouse CMs are susceptible to death and cannot be cultured more than five days under normal conditions. Therefore, there is a critical need to optimize the cell isolation and long-term culture protocol for adult murine CMs. With this modified protocol, it is possible to successfully isolate and culture both adult mouse and rat CMs for more than 20 days. Moreover, the siRNA transfection efficiency of isolated CM is significantly increased compared to previous reports. For adult mouse CM isolation, the Langendorff perfusion method is utilized with an optimal enzyme solution and sufficient time for complete extracellular matrix dissociation. In order to obtain pure ventricular CMs, both atria were dissected and discarded before proceeding with the disassociation and plating. Cells were dispersed on a laminin coated plate, which allowed for efficient and rapid attachment. CMs were allowed to settle for 4-6 h before siRNA transfection. Culture media was refreshed every 24 h for 20 days, and subsequently, CMs were fixed and stained for cardiac-specific markers such as Troponin and markers of cell cycle such as KI67.


Use of bright light to treat maladaptation to night shift work and circadian rhythm sleep disorders.
Night work is associated with increased sleepiness and disturbed sleep. Maladaptation of the circadian system, which is phase-adjusted to day time work and thus promotes sleepiness during its nadir at night and wakefulness (or disturbed sleep) during the day, contributes substantially to this problem. A major cause of suboptimal circadian phase adjustment among night workers is the exposure to morning light, which prevents the delay needed for optimal adjustment to night work. Several laboratory studies indicate that careful application of bright light may cause the circadian system to shift to any desired phase. Furthermore, studies of simulated night work demonstrate that night exposure to bright light can virtually eliminate circadian maladjustment among night workers. While the results are promising, there is still, however, an urgent need for longitudinal studies of bright light application in real-life settings.


Factors Contributing to Snorkel Drowning in Hawai'i.
Causes of the extraordinarily high and increasing incidence of snorkeler drownings in Hawai'i have remained unexplained for years. Defining the mechanisms and factors predisposing to drowning while snorkeling is needed to provide recommendations to substantially mitigate the incidence of this form of preventable death. The mechanisms of drowning are described and insight into the predisposing factors are explored in this study. Methods included measuring snorkel airway resistance characteristics, case reports from the State of Hawai'i Medical Examiner's office, and collating information by survey, principally from rescued survivors. This study identified 2 modes of drowning while snorkeling that need further investigation: accidental or inadvertent aspiration, and hypoxia resulting from acute negative pressure pulmonary edema. The incidence of drowning from mechanisms of hypoxia due to rapid onset pulmonary edema is an important focus of the study and a number of potentially significant predisposing factors are presented that need further investigation but provide bases that may become part of updated policies and practices for snorkelers to substantially lower the risk of death. This report is meant for both medical and public health information purposes.


Health promotion and the "ideology of choice".
Assessment and intervention in public health nursing are intricately linked to health promotion. Health promotional strategies in turn focus attention on life-style modifications. A broad base of research warns of the dangers of the "ideology of choice" that currently accompany such lifestyle-change attempts. The "ideology of choice" is inherent in pervasive views that individuals are "responsible for" and "choose" their disease. The rhetoric of individual responsibility pervades the discourse around both health promotion and health care reform. Without continual awareness of both the complex and multifaceted nature of such life-style "choices," and the balancing of a compassionate stance toward human frailty, health promotion attempts easily degenerate into a victim-blaming stance. Public health nurses need to be particularly aware of these dangers during this period when cost constraints are generating more pervasive "ideology of choice" rhetoric, targeting those with the scarcest resources and the most profound needs.


Nonlinear network model analysis of vibrational energy transfer and localisation in the Fenna-Matthews-Olson complex.
Collective protein modes are expected to be important for facilitating energy transfer in the Fenna-Matthews-Olson (FMO) complex of photosynthetic green sulphur bacteria, however to date little work has focussed on the microscopic details of these vibrations. The nonlinear network model (NNM) provides a computationally inexpensive approach to studying vibrational modes at the microscopic level in large protein structures, whilst incorporating anharmonicity in the inter-residue interactions which can influence protein dynamics. We apply the NNM to the entire trimeric FMO complex and find evidence for the existence of nonlinear discrete breather modes. These modes tend to transfer energy to the highly connected core pigments, potentially opening up alternative excitation energy transfer routes through their influence on pigment properties. Incorporating localised modes based on these discrete breathers in the optical spectra calculations for FMO using ab initio site energies and excitonic couplings can substantially improve their agreement with experimental results.


An intervention to improve the adequacy of referrals from primary care to a department of urology.
This study analyses the effect of two interventions implemented in order to improve adherence to the terms of a protocol for referring patients from primary care to a urology department. A telephone counselling line for professionals was implemented, and joint training sessions were held (twice, at six-month intervals). The terms "appropriate" and "inappropriate" were used to identify referrals complying with the locally developed protocol and those that did not, respectively. Referral appropriateness at baseline (T0) was compared with that six months after the first (T1) and second (T2) meeting. Linear trend analysis was used to test for trends in adequacy across the study. Appropriateness of 6,088 consecutive referrals was analysed. At T0, 58% of the referrals (2810/4841) were judged to be "appropriate". Adequacy improved significantly at T1 (70.6% vs. 58% at T0; chi2 < 0.001). At T2, 75.4% of the referrals met the terms of the protocol; the difference between results at T1 and T2 was not statistically significant (chi2 = 0.06). Overall (T0 vs. T2), a 17.4% improvement was confirmed (chi2 < 0.001). A trend toward more appropriate referrals was detected over time (Mantel-Haenszel test for linear trend, z = 9.62; p < 0.001). As the use of communication resources was anecdotal, mathematical analysis of its effect on adequacy could not be performed. Training activities are worthwhile for improving referral adequacy. Stable rates over time are possible. Using communication resources may be unnecessary if accessibility is guaranteed.


Cost-effectiveness analysis of family planning programs in rural Bangladesh: evidence from Matlab.
The Family Planning Health Services Project in Matlab is often seen as more expensive than similar activities carried out by the government of Bangladesh. At the same time, it as been observed that the project is much more effective. The alleged high cost of the project is said to make it difficult to replicate throughout the nation. Previously, the true costs of the project had not been documented. This study systemically examines the cost of the project and assesses its cost-effectiveness. An experimental design framework is used as a basis for understanding the cost-effectiveness of the project, although a sensitivity analysis lends further support to the relative efficiency of the approach undertaken in Matlab. Although in the aggregate, the Matlab Project is more expensive than the government's family planning program, it is also more effective, generating enough output to offset the extra costs of the intensified delivery system.


Safety and effectiveness of nusinersen, a treatment for spinal muscular atrophy, in 524 patients: results from an interim analysis of post-marketing surveillance in Japan.
Nusinersen is an antisense oligonucleotide approved for the treatment of spinal muscular atrophy (SMA). A post-marketing surveillance (PMS) has been ongoing (August 2017-August 2025) in all patients in Japan who were administered nusinersen intrathecally in real-world clinical settings. We report the interim analysis results for safety and effectiveness. This interim analysis was conducted using data collected from 524 patients whose case report forms were obtained at least once by May 30, 2022. Collected data included patient demographics and adverse events (AEs) for safety, and motor function assessments and Clinical Global Impressions of Improvement (CGI-I) for effectiveness. Of the 524 patients in the safety analysis set, 522 patients who were diagnosed with SMA were included in the effectiveness analysis (infantile-onset SMA [n = 153, 29.3%], later-onset SMA [n = 369, 70.7%]). The median duration of treatment was 785.0 (range 1-1549) days. AEs occurred in 35.9% of patients (49.0% in infantile-onset SMA and 30.6% in later-onset SMA). Nusinersen treatment significantly improved Hammersmith Infant Neurological Examination scores in patients with infantile-onset SMA and Hammersmith Functional Motor Scale-Expanded scores in patients with later-onset SMA for up to nearly 3 years. Based on CGI-I assessments, 98.5-100% of patients receiving nusinersen 'improved' or remain 'unchanged'. This interim analysis of the large-scale, all-case PMS in patients who were administered nusinersen in Japan supports the safety and effectiveness of nusinersen. The benefit-risk balance of nusinersen treatment remains favorable.


Respiratory synctial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern.
Vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) caused excessive disease in infants upon subsequent natural infection with RSV. Recent studies with BALB/c mice have suggested that T cells are important contributors to lung immunopathology during RSV infection. In this study, we investigated vaccine-induced enhanced disease by immunizing BALB/c mice with live RSV intranasally or with FI-RSV intramuscularly. The mice were challenged with RSV 6 weeks later, and the pulmonary inflammatory response was studied by analyzing cells obtained by bronchoalveolar lavage 4 and 8 days after challenge. FI-RSV-immunized mice had an increased number of total cells, granulocytes, eosinophils, and CD4+ cells but a decreased number of CD8+ cells. The immunized mice also had a marked increase in the expression of mRNA for the Th2-type cytokines interleukin-5 (IL-5) and IL-13 as well as some increase in the expression of IL-10 (a Th2-type cytokine) mRNA and some decrease in the expression of IL-12 (a Th1-type cytokine) mRNA. The clear difference in the pulmonary inflammatory response to RSV between FI-RSV- and live-RSV-immunized mice suggests that this model can be used to evaluate the disease-enhancing potential of candidate RSV vaccines and better understand enhanced disease.


Cloning of Human T and Natural Killer Cells
The discovery of the lymphokine interleukin 2 (IL-2), which induces growth of T cells, set the stage for establishing methods for in vitro cloning of human T cells. More recently, it has become clear that in addition to IL-2, other T-cell growth factors, such as IL-4 and IL-7, can be used for generation and expansion of T-cell clones. In the past it was shown that it is possible to grow T cells differing in function and phenotype. In vitro-expanded T-cell clones have been instrumental in studies on the antigen specificities and biological properties of these cells. Cloned lines of natural killer (NK) cells can also be established using IL-2, permitting detailed studies on the biology of these cells. Here we describe the methods we use to generate and to expand human T-cell and NK cell clones. We discuss the differences between IL-2 and IL-4 as growth factors to expand T-cell clones. In addition, we summarize some recent findings of studies using T- and NK cell clones.


Decree-Law No. 199/88, 31 May 1988.
This Decree-Law establishes criteria for the determination of final compensation for expropriation or nationalization of land or agricultural capital. The lack of legal definition of criteria for the determination of such final compensation was a gap in recent Portuguese legislation on land reform. Although the holdings of many landlords and farmers had been nationalized or expropriated after 11 March 1975, the compensation obtained prior to the enactment of this Decree-Law was provisional and reflected outdated values. This Decree-Law closes this gap by establishing the criteria for the determination of final compensation with adjusted value. Under it, any farmer whose land or capital has been nationalized or expropriated since March 1975 may apply for final compensation, from which shall be deducted the value of any provisional compensation previously obtained and any property previously devolved as a "right of reserve" pursuant to pertinent legislation (see Law No. 109/88 of 26 September 1988 and Decree No. 44/88 of 14 December 1988). The final compensation shall be determined by administrative procedure in which the Ministry of Agriculture, Fisheries, and Food; the Ministry of Finance; and the applicant are represented.


Real-Time Estimation of Population Exposure to PM2.5 Using Mobile- and Station-Based Big Data.
Extremely high fine particulate matter (PM2.5) concentration has been a topic of special concern in recent years because of its important and sensitive relation with health risks. However, many previous PM2.5 exposure assessments have practical limitations, due to the assumption that population distribution or air pollution levels are spatially stationary and temporally constant and people move within regions of generally the same air quality throughout a day or other time periods. To deal with this challenge, we propose a novel method to achieve the real-time estimation of population exposure to PM2.5 in China by integrating mobile-phone locating-request (MPL) big data and station-based PM2.5 observations. Nationwide experiments show that the proposed method can yield the estimation of population exposure to PM2.5 concentrations and cumulative inhaled PM2.5 masses with a 3-h updating frequency. Compared with the census-based method, it introduced the dynamics of population distribution into the exposure estimation, thereby providing an improved way to better assess the population exposure to PM2.5 at different temporal scales. Additionally, the proposed method and dataset can be easily extended to estimate other ambient pollutant exposures such as PM10, O₃, SO₂, and NO₂, and may hold potential utilities in supporting the environmental exposure assessment and related policy-driven environmental actions.


Misplaced Cochlear Implant Electrodes Outside the Cochlea: A Literature Review and Presentation of Radiological and Electrophysiological Findings.
It is possible to detect when misplacement and malposition of the cochlear implant (CI) electrode array has occurred intraoperatively through different investigations. We aim to explore the literature surrounding cochlear implant misplacements and share our personal experience with such cases to formulate a quick-reference guide that may be able to help cochlear implant teams detect misplacements early. Misplacement and malposition of a cochlear implant array can lead to poor hearing outcomes. Where misplacements go undetected during the primary surgery, patients may undergo further surgery to replace the implant array into the correct intracochlear position. Systematic literature review on cochlear implant misplacements and malpositions and a retrospective review of our program's cases in over 6,000 CI procedures. Twenty-nine cases of CI misplacements are reported in the English literature. Sixteen cases of cochlear implant misplacements are reported from our institution with a rate of 0.28%. A further 12 cases of intracochlear malpositions are presented. The electrophysiological (CI electrically evoked auditory brainstem response, transimpedance matrix) and radiological (X-ray and computed tomography scan) findings from our experience are displayed in a tabulated quick-reference guide to show the possible characteristics of misplaced and malpositioned cochlear implant electrode arrays. Both intraoperative electrophysiological and radiological tests can show when the array has been misplaced or if there is an intracochlear malposition, to prompt timely intra-operative reinsertion to yield better outcomes for patients.


LncRNAs Are Differentially Expressed between Wildtype and Cell Line Strains of African Trypanosomes.
Trypanosoma brucei is a parasitic protist that causes African sleeping sickness. The establishment of T. brucei cell lines has provided a significant advantage for the majority of T. brucei research. However, these cell lines were isolated and maintained in culture for decades, occasionally accumulating changes in gene expression. Since trypanosome strains have been maintained in culture for decades, it is possible that difference may have accumulated in fast-evolving non-coding RNAs between trypanosomes from the wild and those maintained extensively in cultures. To address this, we compared the lncRNA expression profile of trypanosomes maintained as cultured cell lines (CL) to those extracted from human patients, wildtype (WT). We identified lncRNAs from CL and WT from available transcriptomic data and demonstrate that CL and WT have unique sets of lncRNAs expressed. We further demonstrate that the unique and shared lncRNAs are differentially expressed between CL and WT parasites, and that these lncRNAs are more evenly up-regulated and down-regulated than protein-coding genes. We validated the expression of these lncRNAs using qPCR. Taken together, this study demonstrates that lncRNAs are differentially expressed between cell lines and wildtype T. brucei and provides evidence for potential evolution of lncRNAs, specifically in T. brucei maintained in culture.


Dissipation-Assisted Prethermalization in Long-Range Interacting Atomic Ensembles.
We theoretically characterize the semiclassical dynamics of an ensemble of atoms after a sudden quench across a driven-dissipative second-order phase transition. The atoms are driven by a laser and interact via conservative and dissipative long-range forces mediated by the photons of a single-mode cavity. These forces can cool the motion and, above a threshold value of the laser intensity, induce spatial ordering. We show that the relaxation dynamics following the quench exhibits a long prethermalizing behavior which is first dominated by coherent long-range forces and then by their interplay with dissipation. Remarkably, dissipation-assisted prethermalization is orders of magnitude longer than prethermalization due to the coherent dynamics. We show that it is associated with the creation of momentum-position correlations, which remain nonzero for even longer times than mean-field predicts. This implies that cavity cooling of an atomic ensemble into the self-organized phase can require longer time scales than the typical experimental duration. In general, these results demonstrate that noise and dissipation can substantially slow down the onset of thermalization in long-range interacting many-body systems.


[Fatal primary influenza virus pneumonia in a patient with secondary myelofibrosis during ruxolitinib therapy].
In recent years, fatal cases of primary influenza virus pneumonia have been rare. A 67-year-old woman with secondary myelofibrosis, who had been diagnosed with polycythemia vera 25 years prior, died of primary influenza virus pneumonia. She was immunocompromised due to the underlying disease and ruxolitinib therapy, but she was not vaccinated against influenza. She might have caught the flu from an infected family member. This case reminds us of the importance of infection control measures such as preventing familial infection during ruxolitinib therapy in severely immunocompromised patients.


The prevalence of colorectal adenomas in Maori and New Zealand Europeans parallels colorectal cancer rates.
New Zealand (NZ) has a high incidence of colorectal cancer (CRC). Maori have a documented incidence that is approximately half that found in NZ Europeans, possibly the result of under-reporting. To determine and compare the prevalence of colorectal adenomas in Maori and NZ European patients. Colonoscopy records from the Middlemore Colonoscopy Audit Database between 1 July 2001 and 31 December 2005 were reviewed. Studies performed for indications associated with an increased risk of colorectal polyps were excluded from the analysis. Patient demographics, including self-identified ethnicity, and number and location of colonic polyps were recorded. All polyp histology was reviewed. Data was analysed from 2842 colonoscopies--2523 were NZ Europeans (mean age 67 yrs) and 319 were Maori patients (mean age 60.6 yrs). To adjust for age, a comparison of data between 40 and 59 years was undertaken. In 643 (81.2%) NZ Europeans, polyps were identified in 213 (33.1%). In the 149 (18.8%) Maori patients, polyps were identified in 35 (23.5%) p=0.029. The comparative rates of adenomas in NZ Europeans and Maori were 16.7% and 8.7% respectively (p=0.019; 8% difference, CI=2.3-13.9%). The prevalence of colorectal adenomas in Maori is approximately half that found in NZ Europeans. This mirrors the reported difference in CRC incidence between these groups and lends support to this being a real finding and not a bias in the manner in which the data has been collected.


[Demonstration and characterization of CD 46, membrane cofactor protein, in gastric cancer tissue].
CD 46, membrane cofactor protein, is a membrane protein which shows different expression and phenotypes with the organ or cell in the same individual. Previously, we reported that gastric CD 46 was expressed strongly in the mucosal epithelium, mucosa and endothelial cells of vessels in the submucosal layer. Western blot analysis revealed that gastric CD 46 was expressed as one broad band with a molecular weight ranging from 60 kDa to 69 kDa, which was different from that of lymphocytes. In this study, we investigated the differences in expression and characterization of CD 46 in gastric cancer obtained by surgery as compared with non-cancerous mucosa. Expression of CD 46 was greater in gastric cancer than in non-cancerous mucosa. In some cases, the phenotypes of CD 46 in gastric cancer were different from those in the non-cancerous tissue.


Current trends in explosive detection techniques.
The detection of explosives and explosive-related compounds has become a heightened priority in recent years for homeland security and counter-terrorism applications. There has been a huge increase in research within this area-through both the development of new, innovative detection approaches and the improvement of existing techniques. Developments for miniaturisation, portability, field-ruggedisation and improvements in stand-off distances, selectivity and sensitivity have been necessary to develop and improve techniques. This review provides a consolidation of information relating to recent advances in explosive detection techniques without being limited to one specific research area or explosive type. The focus of this review will be towards advances in the last 5 years, with the reader being referred to earlier reviews where appropriate.


Metastasis of Renal Cell Carcinoma to Spinal Hemangioblastoma in a Patient with von Hippel-Lindau Disease: A Case Report.
von Hippel-Lindau (VHL) disease is characterized by neoplastic and cystic lesions, such as central nervous system (CNS) hemangioblastoma and clear cell renal cell carcinoma (RCC), arising in multiple organs. Here, we report a case of an RCC that metastasized to a spinal hemangioblastoma in a patient diagnosed with VHL disease. This is a unique case study because visceral neoplasms rarely metastasize to the CNS. The patient had undergone posterior fossa surgery for the removal of hemangioblastomas in the right cerebellar hemisphere as a child. He was diagnosed with RCC at the age of 20 years, and he underwent partial nephrectomy at the age of 35 years. The patient underwent surgical removal of a spinal tumor from Th8, which was also diagnosed as a hemangioblastoma at the age of 40. However, the residual spinal tumor rapidly regrew within 1.5 years. A second surgery was performed due to progressive leg motor weakness. The resected tumor from the second surgery had two distinct components between the tumor center and the margin. Immunohistochemistry of CD10, PAX 8, and inhibin A demonstrated the predominant region of the tumor was RCC. Pathological findings confirmed tumor-to-tumor metastasis of the RCC migrating into residual spinal hemangioblastoma. It can be challenging to distinguish hemangioblastoma from RCC in neuroimaging. We suggest that tumor-to-tumor metastasis should be considered as a differential diagnosis if benign tumors grow rapidly, even if the pathological diagnosis does not initially confirm malignancy. The biological mechanisms of RCC migrating into residual hemangioblastoma are discussed.


Management of incidental adrenal nodules: a survey of abdominal radiologists conducted by the Society of Abdominal Radiology Disease-Focused Panel on Adrenal Neoplasms.
Adrenal incidentalomas are common findings discovered at abdominal CT and MRI, yet the most appropriate management remains controversial and guidelines vary. The Society of Abdominal Radiology (SAR) Disease-Focused Panel on Adrenal Neoplasms sought to determine the practice patterns of abdominal radiologists regarding the interpretation and management of adrenal incidentalomas. An electronic survey consisting of eleven multiple choice questions about adrenal incidentalomas was developed and distributed to the email list of current and past SAR members. The response rate was 11.8% (423/3581) and most respondents were academic radiologists (80.6%). The 2017 American College of Radiology White Paper was the most used guideline, yet the management of indeterminate adrenal incidentalomas was highly variable with no single management option reaching a majority. Hormonal evaluation and endocrinology consultation was most often rarely or never recommended. The results of the survey indicate wide variability in the interpretation of imaging findings and management recommendations for incidental adrenal nodules among surveyed radiologists. Further standardization of adrenal incidentaloma guidelines and education of radiologists is needed.


Evaluation of bone formation using recombinant human bone morphogenetic proteins-7 in small maxillofacial bony defects.
Bone morphogenetic proteins (BMP) are multifunctional molecules of transforming growth factor-β superfamily that induces the differentiation of fibroblasts into osteoblasts to form bone. This study was undertaken to evaluate the effects of recombinant human BMP-7 (rhBMP-7) in bone healing of small maxillofacial bone defects and assess the serum levels of osteopontin (OPN) and receptor activator of nuclear factor kappa-B ligand (RANKL) biomarkers for bone remodeling. Twenty patients with small maxillofacial bony defects were enrolled in this study and randomly allocated to two groups; wherein after apicoectomy of the involved teeth, the control group had defect filled with collagen sponge only while the experimental group had rhBMP-7 impregnated collagen sponge placed in the defect. The clinical parameters showed no significant difference between the two groups (P > 0.05). The radiographic parameters showed a significantly slower rate of reduction in bone defect volume (P < 0.01) in control group than the experimental group when followed at 2, 4 and 24 postoperative weeks. RANKL and OPN serum levels showed no significant changes in pre- and post-operative stage. This study confirms that rhBMP-7 in collagen definitely accelerates bone healing in maxillofacial bone defects and minimizes postoperative complications. RANKL and OPN biomarkers in serum may not show bone remodeling, hence tissue samples may be used to assess their levels.


[Point on Consideration of Products for Negative Pressure Wound Therapy Design and Evaluation].
Negative pressure wound therapy has become an important technology in the global field of wound care, and the development of this technology is inseparable from the development and application of negative pressure wound care products. Based on the characteristics of the negative pressure wound therapy products, this paper discusses the key contents that should be considered in the design and evaluation of the negative pressure wound protection products from the aspects of physical and chemical properties, biocompatibility, intended use and risk warning information, in order to provide reference for the development and technical review of such products.


Significance and Management of Isolated Hepatitis B Core Antibody (Anti-HBc) in HIV and HCV: Strategies in the DAA Era.
The purpose of this review is to summarize the prevalence and clinical implications of the isolated anti-HBc serologic profile in HIV-infected individuals. We highlight the rare but important issue of HBV reactivation in the setting of HCV therapy and describe an approach to management. The isolated anti-HBc pattern, a profile that most often indicates past exposure to HBV with waning anti-HBs immunity, is found commonly in HIV-infected individuals, particularly those with HCV. Some large cohort studies demonstrate an association with advanced liver disease, while others do not. Conversely, meta-analyses have found an association between occult HBV infection (a component of the isolated anti-HBc pattern) and advanced liver disease and hepatocellular carcinoma in HIV-uninfected individuals. In HIV-uninfected individuals with anti-HBc positivity, HBV reactivation has been reported in patients receiving HCV therapy. This phenomenon is likely the result of disinhibition of HBV with HCV eradication. In HIV-infected patients, the long-term liver outcomes associated with the isolated anti-HBc pattern remain to be fully elucidated, supporting the need for large cohort studies with longitudinal follow-up. HBV reactivation during HCV DAA therapy has been well-described in HIV-uninfected cohorts and can inform algorithms for the screening and management of the isolated anti-HBc pattern in this population.


The Medial Orbitofrontal Cortex Regulates Sensitivity to Outcome Value.
An essential component of goal-directed decision-making is the ability to maintain flexible responding based on the value of a given reward, or "reinforcer." The medial orbitofrontal cortex (mOFC), a subregion of the ventromedial prefrontal cortex, is uniquely positioned to regulate this process. We trained mice to nose poke for food reinforcers and then stimulated this region using CaMKII-driven Gs-coupled designer receptors exclusively activated by designer drugs (DREADDs). In other mice, we silenced the neuroplasticity-associated neurotrophin brain-derived neurotrophic factor (BDNF). Activation of Gs-DREADDs increased behavioral sensitivity to reinforcer devaluation, whereas Bdnf knockdown blocked sensitivity. These changes were accompanied by modifications in breakpoint ratios in a progressive ratio task, and they were recapitulated in Bdnf(+/-)mice. Replacement of BDNF selectively in the mOFC in Bdnf(+/-)mice rescued behavioral deficiencies, as well as phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2). Thus, BDNF expression in the mOFC is both necessary and sufficient for the expression of typical effort allocation relative to an anticipated reinforcer. Additional experiments indicated that expression of the immediate-early gene c-fos was aberrantly elevated in the Bdnf(+/-)dorsal striatum, and BDNF replacement in the mOFC normalized expression. Also, systemic administration of an MAP kinase kinase inhibitor increased breakpoint ratios, whereas the addition of discrete cues bridging the response-outcome contingency rescued breakpoints in Bdnf(+/-)mice. We argue that BDNF-ERK1/2 in the mOFC is a key regulator of "online" goal-directed action selection. Goal-directed response selection often involves predicting the consequences of one's actions and the value of potential payoffs. Lesions or chemogenetic inactivation of the medial orbitofrontal cortex (mOFC) in rats induces failures in retrieving outcome identity memories (Bradfield et al., 2015), suggesting that the healthy mOFC serves to access outcome value information when it is not immediately observable and thereby guide goal-directed decision-making. Our findings suggest that the mOFC also bidirectionally regulates effort allocation for a given reward and that expression of the neurotrophin BDNF in the mOFC is both necessary and sufficient for mice to sustain stable representations of reinforcer value.


Solitary Osteochondroma Presenting as a Dumbbell Tumor Compressing the Cervical Spinal Cord.
We report a case of a solitary osteochondroma as a dumbbell tumor compressing the spinal cord and its surgical strategy. The patient is a 16-year-old female with longstanding posterior neck pain and left arm abduction weakness. She was examined by plain X-ray, three-dimensional-computed tomography, magnetic resonance imaging, and vertebral angiography. The analyses indicated a calcified extradural mass compressing the cord in the C3-4 portion extending into the neural and vertebral foramen with eroded vertebral body. The tumor was successfully excised using a modified combined anterior and posterior approach. Histopathologic study of the resected material confirmed the diagnosis. The postoperative assessment was followed by clinical and radiologically therapy for 5 years after surgery. Osteochondroma arises from enchondral bone but it rarely involves the spine, especially not as s dumbbell type. In this patient, the tumor may have arisen from the neural arch and extended into the extradural and extraforaminal space over a long period. We successfully removed the dumbbell tumor with a combined anterior oblique and posterior approach. However, further observation is essential because of the possibility of recurrence and sarcomatous change.


Bioconcentration and phytotoxicity of chromium in Eichhornia crassipes.
Physico-chemical parameter and metal concentration in effluents of two industries i.e. Tannery industry, Jajmau, Kanpur and Electroplating industry, Scooter India Limited (SIL), Lucknow were determined to assess the toxicity of chromium. Metal accumulation in Eichhomia crassipes growing in these contaminated sites were also determined. For laboratory toxicity testing the plants were exposed to nutrient solution containing Cr concentration ranging from 0.01-10 microg ml(-1) for 24-96 hr. Accumulation of chromium was observed to be dependent on its concentration and time of exposure and was greater in roots (789.3 mg g(-1) d.wt.) than in leaves (335.6 mg g(-1) d.wt.) after 96 hrat 10 microg ml(-1) concentration. Under field conditions the accumulation of Cr was 1258 and 733.3 in roots and 94 and 53 microg g(-1) d.wt. in leaves of E. crassipes growing in Jajmau, Kanpur tanning industry and SIL effluents, respectively. It was found that lower doses (0.01-0.1 microg ml(-1)) of chromium had stimulatory effect on various metabolic activities in plants including chlorophyll a, b and total chlorophyll, protein, nitrate reductase and mitotic index. Whereas higher doses of chromium had inhibitory effect. The carotenoid content and number of micronuclei was found directly proportional to the concentration of chromium and increased with increase in concentration of chromium to which plants were exposed. It may be concluded from the present study that E. crassipes is tolerant to the elevated Cr concentration as there is no inhibition of chlorophyll and carotenoid up to 0.1 microg ml(-1) at 24 and 48 hr exhibiting phytotoxicity at higher concentration. Therefore, E. crassipes may be used as bioassay for biomonitoring and control of Cr pollution in the environment.