Efficacy and safety of cryoablation for localized renal tumor as an alternative approach to partial nephrectomy.
Renal cryoablation displays a profile of high tolerance, including in a frail population. Cryoablation appears as a validated alternative treatment to surgery for renal tumors smaller than 4 cm. However, evidence is lacking for larger tumors, despite encouraging data for tumors up to 7 cm. This retrospective descriptive study of a population with a stage T1b renal tumor treated by cryoablation was conducted at the Nantes University Hospital between January 2009 and July 2021. Primary endpoint was 3-year rate of local recurrence. Secondary endpoints included technical efficacy, overall and cancer-specific survivals, and safety assessment. A total of 63 patients were analyzed. Three-year rate of local recurrence was 11.1%. Primary and secondary technical efficacies were achieved in 88.9% and 96.8% of patients, respectively, and 3-year overall and cancer-specific survival were 87.3% and 95.2%, respectively. Most patients (73%) experienced no complications, 13% of patients had minor (CIRSE grades 1 or 2) adverse effects, and 13% had severe but non-lethal (CIRSE grade 3) adverse effects. One patient died following cryoablation due to colic perforation. The most common AE (all grades) was hemorrhage (9.5%). This study showed a good efficacy and safety of cryoablation for renal tumors up to 7 cm (T1b). Our results were consistent with a rather sparse literature and contributed to guide future recommendations about cryoablation as an alternative to surgery for T1b renal tumors.


CSF monoamine levels in normal-weight bulimia: evidence for abnormal noradrenergic activity.
Normal-weight bulimic patients have disturbed appetite, mood, and neuroendocrine function and often respond to antidepressants. Since these findings suggest abnormalities in brain monoaminergic pathways, the authors measured CSF monoamine concentrations in 27 normal-weight bulimic patients and 14 volunteers. Bulimic patients had a significantly lower mean CSF norepinephrine concentration. Levels of CSF 5-HIAA, the major serotonin metabolite, and CSF HVA, the major dopamine metabolite, were normal, although more frequent binge-eating in bulimic subjects was associated with a significantly lower CSF HVA level. Whether trait- or state-related, monoaminergic disturbances are part of this disorder's neurobiological syndrome. The lower CSF norepinephrine concentration suggests bulimia is not simply a variant of affective disorders.


Base of skull chordoma. A correlative study of histologic and clinical features of 62 cases.
Chordomas are uncommon primary malignant tumors of bone that typically occur in the axial skeleton including the sacrum, vertebrae, and skull base. The base of skull tumors usually are not amenable to complete surgical resection, and most require postoperative radiotherapy. The natural history of skull base chordoma is typified by slow locally invasive tumor progression and eventual death, although few parameters are known that allow stratification of patients into prognostic groups. Sixty-two patients with skull base chordomas treated at the Massachusetts General Hospital by proton beam irradiation therapy with at least 2 years of follow-up information were reviewed in an attempt to identify clinical and pathologic parameters that predicted outcome. Female sex, tumor necrosis in preradiation treatment biopsy, and tumor volume in excess of 70 ml were each independent predictors of shortened overall survival after radiation therapy for skull base chordoma. Stratification of patients with skull base chordoma into poor and good outcome groups can be performed using the three parameters identified in our study. In addition, the striking difference in survival between the sexes suggests that further investigations of these tumors should include determination of their hormonal receptors status and consideration of hormonal manipulation in their management.


Mycobacterium ulcerans disease: experience with primary oral medical therapy in an Australian cohort.
Mycobacterium ulcerans (MU) is responsible for disfiguring skin lesions and is endemic on the Bellarine peninsula of southeastern Australia. Antibiotics have been shown to be highly effective in sterilizing lesions and preventing disease recurrences when used alone or in combination with surgery. Our practice has evolved to using primarily oral medical therapy. From a prospective cohort of MU patients managed at Barwon Health, we describe those treated with primary medical therapy defined as treatment of a M. ulcerans lesion with antimicrobials either alone or in conjunction with limited surgical debridement. From 1/10/2010 through 31/12/11, 43 patients were treated with exclusive medical therapy, of which 5 (12%) also underwent limited surgical debridement. The median patient age was 50.2 years, and 86% had WHO category 1 and 91% ulcerative lesions. Rifampicin was combined with ciprofloxacin in 30 (70%) and clarithromycin in 12 (28%) patients. The median duration of antibiotic therapy was 56 days, with 7 (16%) receiving less than 56 days. Medication side effects requiring cessation of one or more antibiotics occurred in 7 (16%) patients. Forty-two (98%) patients healed without recurrence within 12 months, and 1 patient (2%) experienced a relapse 4 months after completion of 8 weeks of antimicrobial therapy. Our experience demonstrates the efficacy and safety of primary oral medical management of MU infection with oral rifampicin-based regimens. Further research is required to determine the optimal and minimum durations of antibiotic therapy, and the most effective antibiotic dosages and formulations for young children.


Advances in the treatment of Hodgkin lymphoma: Current and future approaches.
Hodgkin lymphoma (HL) is a rare type of lymphoma with unique histologic, immunophenotypic, and clinical features. It represents approximately one-tenth of lymphomas diagnosed in the United States and consists of two subtypes: classical Hodgkin's lymphoma (cHL), which accounts for majority of HL cases, and nodular lymphocyte predominant Hodgkin lymphoma represent approximately 5% of Hodgkin lymphoma cases. From this point, we will be focusing on cHL in this review. In general, it is considered a highly curable disease with first-line chemotherapy with or without the addition of radiotherapy. However, there are patients with disease that relapses or fails to respond to frontline regimens and the standard treatment modality for chemo sensitive cHL is high dose chemotherapy followed by autologous hematopoietic stem cell transplant (AHSCT). In recent years, targeted immunotherapy has revolutionized the treatment of cHL while many novel agents are being explored in addition to chimeric antigen receptor (CAR) T-cell therapy which is also being investigated in clinical trials as a potential treatment option.


Blast injury.
Individuals with a blast injury are the victims most likely to be seen by any healthcare professional. An awareness of the potential injuries is important. Individual care should follow standards established for all trauma patients.


[Toxoplasmic pleuro-pericarditis associated with Hodgkin's disease].
Pericarditis caused by toxoplasma infection is exceptional: 16 cases only have been published since 1943. The authors report a case of Hodgkin's disease associated with, and revealed by, toxoplasmic pleuro-pericarditis, and they review the literature on this complication of toxoplasmosis. Since the infection can be cured and since pericarditis may become chronic and constrictive if untreated, toxoplasmosis should be envisaged and confirmed or infirmed by serological tests in all patients presenting with pericarditis of uncertain origin. Provided it has not reached the chronic stage, toxoplasmic pericarditis responds well to the conventional treatment with pyrimethamine and sulfonamides.


Plasma-treated water eliminates Streptococcus mutans in infected dentin model.
Non-mechanical procedures for removing caries-infected dentin are warranted in dentistry. We previously demonstrated the marked sterilization effect for direct irradiation of low-temperature plasma using dentin model infected with Streptococcus mutans. However it requires 180 s of intraoral plasma irradiation to eliminate bacteria. We alternatively investigated whether plasma-treated water (PTW), i.e., pure water exposed to plasma in an atmosphere, has a same bactericidal activity with the plasma irradiation. In the infected dentin model, the viable S. mutans counts recovered by bur at depth of 0.8-2.4 mm from the cavity floor were 104-106 CFU/round bur. After PTW application for only 10 s, the count was significantly decreased to below the detection limit (2.5 CFU/round bur) or 3.0±5.0 CFU/round bur. Since the bactericidal activity of PTW is rapidly deactivated at body temperature (37°C), PTW is likely to be biocompatible and holds significant potential for non-mechanical procedures for removing caries-infected dentin.


Correlation Between Central Corneal Thickness and Radial Peripapillary Capillary Density, in Patients With Ocular Hypertension.
Purpose To investigate any possible relationship between the central corneal thickness and the radial peripapillary capillary density detected by optical coherence tomography (OCT) angiography in eyes with ocular hypertension. Materials and methods In this observational study, 135 eyes were examined. OCT angiography of the optic disc (4.5 mm) and ultrasound corneal pachymetry were performed in all cases. Age, medical treatment for ocular hypertension, sex, and retinal nerve fiber layer thickness were evaluated. The main indices of blood flow were also examined. Spearman correlation coefficients were used to explore the association between two continuous variables. Results A directly proportional significance regarding the correlation between central corneal thickness and radial peripapillary network was indicated in eyes with ocular hypertension (p = .036). Conclusions Central corneal thickness and radial peripapillary capillary density constitute two essential screening parameters for patients with ocular hypertension.


Electrophysiological correlates of emotional meaning in context in relation to facets of schizotypal personality traits: A dimensional study.
The aim of this study was to investigate the neurocognitive processes mediating the processing of emotional information during the integration of contextual and social information in a schizotypal population. One hundred and thirty-one healthy participants were evaluated using the Schizotypal Personality Questionnaire and event-related potentials were recorded during a linguistic task in which participants read sentence pairs describing short social situations to themselves. The first sentence implicitly conveyed the positive or negative emotional state of a character. The second sentence was emotionally congruent or incongruent with the first sentence. Across our overall sample, our results revealed a greater N400 effect at right sites than left sites, whereas the late positive component effect was only observed at left sites. Concerning the correlation results, we observed a negative link between positive and global schizotypy and N400 modulation in response to congruent targets for positive context sentences. Results also showed a positive correlation between negative schizotypy and late positive component modulation in response to congruent targets for negative context sentences. These results suggest that the different facets of the schizotypal personality traits influenced the integration of emotional context at the level of both early and later-mobilized neurocognitive processes.


A review of autophagy mechanism of statins in the potential therapy of Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegeneration csharacterized by amyloid-β (Aβ) deposition and abnormally phosphorylated Tau protein aggregation. Autophagy, as an important cellular metabolic activity, is closely related to the production, secretion and clearance of Aβ peptide and Tau phosphorylation level. Therefore, autophagy may become a potential target for AD treatment. A large number of molecules are involved in the mammalian target of rapamycin (mTOR)-dependent or mTOR-independent pathway of autophagy. More and more evidences show that statins can intervene autophagy by regulating the activity or expression level of autophagy-related proteins and genes. On the one hand, statins can induce autophagy through Sirtuin1 (SIRT1), P21, nuclear P53 and adenylate activated protein kinase (AMPK). On the other hand, statins inhibit the mevalonate metabolism pathway, thereby interfering with the prenylation of small GTPases, leading to autophagy dysfunction. Statins can also reduce the levels of LAMP2 and dynein, destroying autophagy. In this review, we focused on the role of autophagy in AD and the autophagy mechanism of statins in the potential treatment of AD.


Integrating Physician Practice Management Courses Into Health Administration Curricula.
In today's health care industry, physicians face considerable regulatory and social trends that compel them to modify their practices-and these changes will continue throughout their careers. Emerging reimbursement systems are increasingly tying payment to quality metrics. To appropriately obtain and report patient data to payors, physician practices should adopt electronic health records. Physician practices have the opportunity to complete a clinical care redesign that meets the requirements of health care reform's focus on value-based care. With the shift toward value, patients are taking an active participation in their health care and are moving away from being patients to becoming consumers who demand transparency in their health care and costs. Social media platforms allow physician practices to market to and interact with their patients. In addition to these reforms and social trends, physician practices face the challenge of caring for an aging US population. With these challenges and trends, physicians are increasingly relying on physician practice managers to take on administrative duties. By incorporating physician practice management into health care-related programs, not only will health care programs' curriculum remain relevant to current and future health care trends, demands, and challenges, but also the programs will provide students with the competencies necessary to succeed in the health care field.


[Indications for antidepressive agents in relation to diseases of the cardiovascular system].
Antidepressants, in particular tricyclic ones (TCA), and inhibitors of monoaminooxidase (IMAO) exert a number of undesirable cardiovascular effects. TCA and IMAO frequently cause postural hypotension (PH). IMAO administration is associated with the risk of hypertensive crisis. TCA raises the heart rate and can cause abnormalities in the conduction of the cardiac excitation. TCA are contraindicated after myocardial infarction and are the cause of death after overdosage. When PH is undesirable, in hypertension and cardiac insufficiency the following safe antidepressants are recommended: nortriptyline, mianserine, trazodone and viloxazine. In abnormalities of conduction of the cardiac excitation and after myocardial infarction only mianserine, trazodione and viloxazine are recommended. With regard to cardiovascular toxicity, antidepressants from the series of selective inhibitors of serotonin reabsorption are very promising: fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. The same applies also to the reversible IMAO type A moclobemide.


Impaired tissue homing by the Ikzf3N159S variant is mediated by interfering with Ikaros function.
AIOLOS, encoded by IKZF3, is a member of the IKZF family of proteins that plays an important role in regulating late B-cell differentiation. Human individuals heterozygous for the AIOLOS p.N160S variant displayed impaired humoral immune responses as well as impaired B and T cell development. We have previously reported that a mouse strain harboring an Ikzf3N159S allele that corresponds to human IKZF3N160S recapitulated immune-deficient phenotypes, such as impaired B cell development and loss of CD23 expression. In this study, we investigated the effect of the Ikzf3N159S variant and found that B1a cell development was impaired in Ikzf3N159S/N159S mice. In addition, CD62L expression was severely decreased in both B and T lymphocytes by the Ikzf3N159S mutation, in a dose-dependent manner. Mixed bone marrow chimera experiments have revealed that most immunodeficient phenotypes, including low CD62L expression, occur in intrinsic cells. Interestingly, while Ikzf3N159S/N159S lymphocytes were still present in the spleen, they were completely outcompeted by control cells in the lymph nodes, suggesting that the capacity for homing or retention in the lymph nodes was lost due to the Ikzf3N159S mutation. The homing assay confirmed severely decreased homing abilities to lymph nodes of Ikzf3N159S/N159S B and T lymphocytes but selective enrichment of CD62L expressing Ikzf3N159S/N159S lymphocytes in lymph nodes. This finding suggests that impaired CD62L expression is the major reason for the impaired homing capacity caused by the Ikzf3N159S mutation. Interestingly, an excess amount of Ikaros, but not Aiolos, restored CD62L expression in Ikzf3N159S/N159S B cells. Together with the loss of CD62L expression due to Ikaros deficiency, the AiolosN159S mutant protein likely interferes with Ikaros function through heterodimerization, at least in activating the Sell gene encoding CD62L expression. Thus, our results revealed that AiolosN159S causes some immunodeficient phenotypes via the pathogenesis referred to as the heterodimeric interference as observed for AiolosG158R variant.


Pharmacological and toxicological effects of chronic porcine growth hormone administration in dogs.
The purpose of this study was to evaluate the pharmacological and toxicological effects of exogenous GH administration in normal adult dogs. Because porcine GH (pGH) is structurally identical to canine GH, pGH was selected for a 14-wk study in dogs. Thirty-two dogs (< 2 yr) were randomized to 4 groups (4 dogs/sex/group); 1 group was treated with the vehicle and 3 groups received pGH at 0.025, 0.1, or 1.0 IU/kg/day subcutaneously. Daily clinical signs and weekly body weights were recorded. Hematology, serum biochemistry, urinalyses, electrocardiograms, and ophthalmoscopic examinations were done. Serum GH, insulin-like growth factor-1 (IGF-1), insulin, thyroxine (T4), triiodothyronine (T3), and cortisol levels were determined. Necropsies were performed, organs weighed, and tissues were fixed and processed for light microscopic examination. Porcine GH caused increased body weight gain (p < or = 0.05) through the mid dose; the mean weight gains at study termination in mid- and high-dose groups were 2.8 kg and 4.7 kg, respectively, compared to 0.4 kg and 0.8 kg in control and low-dose groups, respectively. Dose-related increased weights of liver, kidney, thyroid, pituitary gland, skeletal muscle, and adrenal gland were noted. In pGH-treated dogs, increased skin thickness seen grossly correlated histologically with increased dermal collagen. There was no gross or histomorphological evidence of edema. There were dose-related increased serum IGF-1 levels (approximately 2-10-fold; p < or = 0.05) that correlated with the elevated serum GH levels in pGH-treated dogs. Also, increased serum insulin levels (p < or = 0.05) through the mid dose were seen throughout the study. In high-dose dogs, the insulin levels remained elevated over 24 hr postdose. The serum glucose levels in fasted dogs remained within the control range and there was no chronic hyperglycemia based on glycosylated hemoglobin levels. Renal glomerular changes, significant polyuria with decreased urine specific gravity, and increased serum insulin levels suggested that the dogs had early insulin-resistant diabetes. There was minimal or no biologically significant effect of pGH on serum T3, T4, and cortisol levels in dogs. Other serum biochemical changes in pGH-treated dogs included decreased urea nitrogen and creatinine, and increased potassium, cholesterol, and triglycerides. Significant increases in serum calcium and phosphorous levels and alkaline phosphatase activity (bone isozyme) correlated with the histological changes in bone. In pGH-treated dogs, there was a dose-related normochromic, normocytic, nonregenerative anemia. The changes described above, except for the anemia, are related to either anabolic or catabolic effects of high doses of GH. Based on this study, it is concluded that the dog is a good model in which to evaluate the safety of GH secretagogues as well as compounds with GH-like activity.


Making health care safer: What is the contribution of health psychology?
While health care brings great benefits, all treatments, and many investigations, carry some risk. As patients, we should be told of the risks of specific treatments but we are also at risk from failings in the health care system itself. We suggest that, while there are many examples of individual health psychologists who have made important contributions, this has not yet translated into a broader disciplinary engagement. Health psychologists have devoted much more attention to patients and devoted much less attention to the potentially huge impact of studying and intervening with staff, clinical practice, and organizations. We believe that there are considerable opportunities for health psychology to engage more closely with patient safety and, more importantly, that this would be of great benefit to both patients and staff. Statement of contribution What is already known on this subject? While health care brings great benefits, all treatments, and many investigations, carry some risk. Patients are also at risk from failings in the health care system itself. Studies using review of medical records in many countries have found that between 8% and 12% of patients in hospital suffer an unintended harm due to health care. What does this study add? There are many examples of individual psychologists who have made important contributions, but this has not yet translated into a broader disciplinary engagement. There are considerable opportunities for health psychology to engage more closely with patient safety. These include health behaviour change, teamwork, communication after medical error, diagnosis and decision making, organisational culture, and improving compliance with rules and standards. Psychologists providing a clinical service to specialist services in any area could expand their remit from supporting patients to a more general support and engagement with safety and quality initiatives. Health psychologists have models to understand the behaviour of people, and recent developments in changing behaviour should be applicable to health professionals in addition to their patients.


Total Parenteral Nutrition Successfully Treating Black Esophagus Secondary to Hypovolemic Shock.
We present a patient who developed black esophagus secondary to hypovolemic shock and was placed on total parenteral nutrition for three weeks after hospital discharge. The area of interest is the multimodal approach used in treatment of this noncompliant patient. Even with a high mortality rate, this case illustrates a successful outcome of a patient who responded to appropriate immediate therapy resulting in complete resolution of the necrosis with no further development of complications.


Molecular magnetic resonance imaging with targeted contrast agents.
Magnetic resonance imaging (MRI) produces high-resolution three-dimensional maps delineating morphological features of the specimen. Differential contrast in soft tissues depends on endogenous differences in water content, relaxation times, and/or diffusion characteristics of the tissue of interest. The specificity of MRI can be further increased by exogenous contrast agents (CA) such as gadolinium chelates, which have been successfully used for imaging of hemodynamic parameters including blood perfusion and vascular permeability. Development of targeted MR CA directed to specific molecular entities could dramatically expand the range of MR applications by combining the noninvasiveness and high spatial resolution of MRI with specific localization of molecular targets. However, due to the intrinsically low sensitivity of MRI (in comparison with nuclear imaging), high local concentrations of the CA at the target site are required to generate detectable MR contrast. To meet these requirements, the MR targeted CA should recognize targeted cells with high affinity and specificity. They should also be characterized by high relaxivity, which for a wide variety of CA depends on the number of contrast-generating groups per single molecule of the agent. We will review different designs and applications of targeted MR CA and will discuss feasibility of these approaches for in vivo MRI.


Identification and care of substance-dependent neonates.
Identification and care of substance-dependent neonates requires a holistic, family-centered approach to care, starting in the prenatal period and continuing long after the infant is born. Interventions useful in working with families of substance-dependent neonates include psychological support, substance abuse treatment, and physiologic support in the form of nonpharmacologic and pharmacologic therapies. The nurse can play a powerful role in determining the fate of each family. Early recognition of the problem and appropriate, decisive intervention is necessary if the long-term outcomes of substance dependence are to be improved.


Type-IV Pilus deformation can explain retraction behavior.
Polymeric filament like type IV Pilus (TFP) can transfer forces in excess of 100 pN during their retraction before stalling, powering surface translocation(twitching). Single TFP level experiments have shown remarkable nonlinearity in the retraction behavior influenced by the external load as well as levels of PilT molecular motor protein. This includes reversal of motion near stall forces when the concentration of the PilT protein is loweblack significantly. In order to explain this behavior, we analyze the coupling of TFP elasticity and interfacial behavior with PilT kinetics. We model retraction as reaction controlled and elongation as transport controlled process. The reaction rates vary with TFP deformation which is modeled as a compound elastic body consisting of multiple helical strands under axial load. Elongation is controlled by monomer transport which suffer entrapment due to excess PilT in the cell periplasm. Our analysis shows excellent agreement with a host of experimental observations and we present a possible biophysical relevance of model parameters through a mechano-chemical stall force map.


Isolevuglandins Scavenger Ameliorates Myocardial Ischemic Injury by Suppressing Oxidative Stress, Apoptosis, and Inflammation.
Augmented levels of reactive isolevuglandins (IsoLGs) are responsible for cardiovascular diseases. The role of IsoLGs in myocardial infarction (MI) remains elusive. Here we explored the effect of IsoLGs scavenger 2-hydroxybenzylamine (2-HOBA) in post-infarction cardiac repair. We observed that infarcted cardiac tissues expressed high IsoLGs in mice. Following MI injury, 2-HOBA treated mice displayed decreased infarction area and improved heart function compared with the saline-treated group. Moreover, 2-HOBA effectively attenuated MI-induced cardiac remodeling, oxidative stress, apoptosis, and inflammation. 4-hydroxybenzylamine (4-HOBA), a less reactive isomer of 2-HOBA, barely antagonized the MI-induced injury. These findings suggest that IsoLGs elimination may be helpful in MI therapy.


Hibernating myocardium--mechanisms and clinical implications.
Hibernating myocardium is defined as persistently impaired myocardial and left ventricular function at rest resulting from reduced myocardial blood flow. It is postulated that despite the reduced coronary blood flow, metabolic activity is sufficient to prevent tissue necrosis. Recovery of the hibernating myocardium has clearly been shown to occur with the establishment of successful revascularization either by coronary bypass surgery or by percutaneous transluminal coronary angioplasty. The differentiation of viable, hibernating myocardium from non-viable myocardium in patients with coronary artery disease and left ventricular dysfunction is a key issue in the current era of myocardial revascularization.


Factors associated with calcific aortic valve degeneration in the elderly.
This study aimed at identifying factors influencing aortic valve calcification in old age. Echocardiographic and Doppler characteristics of the aortic valve were compared with possible clinical and biochemical predictors in 501 people aged 75-86 years and in 76 aged 55-71. Slight calcification was seen in 222 people (40%) and severe calcification in 72 (13%); 21 people had moderate or severe aortic stenosis. Age (P = 0.000) and serum parathyroid hormone (P = 0.015) were higher and body mass index lower (P = 0.002) in the presence of aortic valve calcification. In multivariate analysis, age (P = 0.000), hypertension (P = 0.005) and body mass index (P = 0.005) were independent predictors of aortic valve calcification, and age (P = 0.022) and serum ionized calcium (P = 0.037) of valve stenosis. The odds ratio (95% confidence interval) for valve calcification was 1.89 (1.42-2.50) for a 10-year increase in age, 1.74 (1.19-2.55) in the presence of hypertension, and 1.39 (1.10-1.76) for a 5 kg.m-2 decrease in body mass index. Sex, smoking, diabetes, serum lipids and insulin were unrelated to valvular calcification. These data suggest that leanness and a history of hypertension increase the likelihood of senile aortic valve calcification. Calcium metabolism may also be of significance. The mechanisms of these associations deserve further study.


Metabolic characterization of triple negative breast cancer.
The aims of this study were to characterize the metabolite profiles of triple negative breast cancer (TNBC) and to investigate the metabolite profiles associated with human epidermal growth factor receptor-2/neu (HER-2) overexpression using ex vivo high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). Metabolic alterations caused by the different estrogen receptor (ER), progesterone receptor (PgR) and HER-2 receptor statuses were also examined. To investigate the metabolic differences between two distinct receptor groups, TNBC tumors were compared to tumors with ER(pos)/PgR(pos)/HER-2(pos) status which for the sake of simplicity is called triple positive breast cancer (TPBC). The study included 75 breast cancer patients without known distant metastases. HR MAS MRS was performed for identification and quantification of the metabolite content in the tumors. Multivariate partial least squares discriminant analysis (PLS-DA) modeling and relative metabolite quantification were used to analyze the MR data. Choline levels were found to be higher in TNBC compared to TPBC tumors, possibly related to cell proliferation and oncogenic signaling. In addition, TNBC tumors contain a lower level of Glutamine and a higher level of Glutamate compared to TPBC tumors, which indicate an increase in glutaminolysis metabolism. The development of glutamine dependent cell growth or "Glutamine addiction" has been suggested as a new therapeutic target in cancer. Our results show that the metabolite profiles associated with HER-2 overexpression may affect the metabolic characterization of TNBC. High Glycine levels were found in HER-2(pos) tumors, which support Glycine as potential marker for tumor aggressiveness. Metabolic alterations caused by the individual and combined receptors involved in breast cancer progression can provide a better understanding of the biochemical changes underlying the different breast cancer subtypes. Studies are needed to validate the potential of metabolic markers as targets for personalized treatment of breast cancer subtypes.


Cell surface protein receptors in oral streptococci.
Streptococci have a vast repertoire of adherence properties which include binding to human tissue components, epithelial cells and to other bacterial cells. These interactions are determined by the expression of cell-surface receptors some of which are species-specific. In the oral streptococci, two families of surface protein receptors with highly conserved amino acid sequences have been identified. The antigen I/II family of polypeptides are wall-associated high molecular mass proteins (158-166 kDa) with several binding functions that may be attributed to different domains of the receptor molecules. The LraI family of polypeptides are surface-associated lipoproteins (32-33 kDa) involved in adherence of streptococci to salivary glycoprotein pellicle and to oral Actinomyces. A region of amino acid sequence similarity is evident amongst members of the two protein families in Streptococcus gordonii. Ligand-binding specificities of these receptor polypeptides may account for species-specific adherence and site-directed colonization of streptococci within the human oral cavity.


Optimization of microfluidic biosensor efficiency by means of fluid flow engineering.
Binding reaction kinetics of analyte-ligand at the level of a sensitive membrane into a microchannel of a biosensor has been limited by the formation of the boundary diffusion layer. Therefore, the response time increases and affects the overall performance of a biosensor. In the present work, we develop an approach to engineer fluid streams into a complex configuration in order to improve the binding efficiency. We investigate numerically the flow deformations around a parallelepiped with square cross-section inside the microfluidic channel and exploit these deformations to simulate the analyte transport to the sensitive membrane and enhance both association and dissociation processes. The effect of several parameters on the binding reaction is provided such as: the obstacle location from the inlet of the microchannel, the average flow velocity, and the inlet analyte concentration. The optimal position of the obstacle is determined. An appropriate choice of the inlet flow velocity and inlet analyte concentration may reduce significantly the response time.


[Arterial hypertension and renal vascular disease: nephroangiosclerosis].
Nephroangiosclerosis and nephrosclerosis are terms used to define the renal disease induced by essential hypertension. The predominant histologic changes occur in the preglomerular microvasculature. Epidemiological data about the risk of hypertensive patients from developing renal failure offer conflicting results. Nevertheless, renal vascular disease, including nephroangiosclerosis and/or ischemic nephropathy, appears to be an important cause of end-stage renal disease. Presumably, nephrosclerosis is the renal expression of systemic atherosclerosis: male sex, age > 55-60 years, black race, high serum cholesterol and/or uric acid levels, and coronary heart disease, peripheral artery disease, and/or cerebrovascular disease are common associations with the renal alteration. Treatment strategy should include an intensive blood pressure control, probably below 130/80 mmHg, together with antiplatelet and lipid-lowering agents when necessary. Although specific studies are lacking, ACE inhibitors and angiotensin II antagonists may offer additional benefits in slowing the renal disease progression.


The silence of Socrates.
This paper emphasizes the humanistic and phenomenologic approach to the mind (soul, self) and contrasts it to the "era of the brain" that is so idealized by psychiatry today. It describes the debate between those who expect science to explain everything sooner or later and those who believe there are certain essential aspects of the world, such as the qualia of consciousness, that cannot be reduced to material factors. Plato's dialogue Timaeus is taken as the historically first example of this debate. The connection between it and what has been labeled "neuroism" in contemporary psychiatry is established and the relevance of this debate to the practice of psychoanalysis and dynamic psychiatry is discussed. Finally the wider consequences of the scientific or materialistic approach to the world as forecast already by Nietzsche are indicated.


FoxM1 regulates mammary luminal cell fate.
Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.


Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury.
Recent evidence has suggested that long non-coding RNAs (lncRNAs) may play a significant role in the pathogenesis of several neurological diseases, including spinal cord injury (SCI). However, little is known about the role of lncRNAs in SCI. The aim of the present study was to evaluate the potential functions of lncRNAs in SCI and to identify the underlying mechanisms of action. We firstly analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly-expressed lncRNAs which might be involved in the pathogenesis of SCI. The long non-coding RNA X-inactive specific transcript (XIST) was found to be one of the most significantly upregulated lncRNAs in the GEO dataset analysis, and is associated with apoptosis. We, therefore, selected this as a candidate lncRNA and investigated its function. We found that knockdown of lncRNA-XIST by Lv-shRNA had a prominent protective effect on SCI recovery by suppressing apoptosis through reactivation of the PI3K/AKT signaling pathway in rat spinal cord tissue. In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway. These results suggested that lncRNA-XIST knockdown may play an important role in limiting neuronal apoptosis in rats following SCI, and that the observed protective effects of lncRNA-XIST knockdown might have been mediated by its regulation on the phosphorylation of AKT by competitively binding miR-494. These findings have revealed, for the first time, the importance of the XIST/miR-494/PTEN/AKT signaling axis in the pathogenesis of SCI and suggest that lncRNA-XIST may be a promising molecular target for SCI therapy.


Long-term shoulder function after type I and II acromioclavicular joint disruption.
Acromioclavicular joint separations are very common lesions, with the majority falling into Rockwood classification type I and II. It is generally agreed that conservative treatment of these injuries leads to good functional results, although there are some studies that suggest these injuries are associated with a high incidence of persistent symptoms. Type I and II acromioclavicular joint disruption significantly impairs long-term shoulder function. Case series; Level of evidence, 4. The shoulder function of 23 patients who were treated for type I or II acromioclavicular joint disruption was evaluated at a mean of 10.2 years after injury. The objective and subjective measures of the injured shoulder were assessed using Constant, University of California-Los Angeles Shoulder Scale, and Simple Shoulder Test scores and were compared with results of the uninjured shoulder. At an average follow-up of 10.2 years, 12 of 23 patients (52%) reported at least occasional acromioclavicular joint symptoms. The average Constant score for the injured shoulder was 70.5 and 86.8 for the uninjured shoulder (P < .001). The average University of California-Los Angeles Shoulder Scale score for the injured shoulder was 24.1 and 29.2 for the uninjured shoulder (P < .001). The average Simple Shoulder Test value for the injured shoulder was 9.7 and 10.9 for the uninjured shoulder (P < .002). The extent of acromioclavicular joint disruption and acromioclavicular joint width did not have any statistically significant influence on the shoulder functional scores. Type I and II acromioclavicular joint disruptions impair long-term shoulder function in about half of patients 10 years after injury.


Ochratoxin A in food and feed: occurrence, legislation and mode of action.
Ochratoxins, of which ochratoxin A (OA) is the most prevalent, are secondary fungal metabolites of some toxigenic species of Aspergillus and Penicillium. OA has been shown to be nephrotoxic, hepatotoxic, teratogenic, carcinogenic and immunosuppressive. The natural occurrence of OA in food and feed stuffs is widespread, especially in temperate areas such as Canada, Denmark, Germany, Sweden and the United Kingdom, and detectable amounts were even found in randomly collected human milk samples in Germany, Sweden and Italy. Of greatest concern in humans is its implicated role in an irreversible and fatal kidney disease referred to as Balkan Endemic Nephropathy. The mean dietary intake for humans in the European Union was found to be in the range of 1 to 2 ng/kg bw/day. Compared with the Provisional Tolerable Daily Intake (PTDI) proposed by the WHO of 16 ng OA/kg bw/day for humans, the average OA intake in Europe seems to be rather low. The main contributor to the OA intake in humans are cereals and cereal products, other possible contributors are coffee, beer, pork, products containing pig blood/plasma, pulses and spices. Only very few countries have regulations for OA in food and feed products. Based on the current literature, the mechanisms involved in the toxicity of OA indicate three major effects: (1) inhibition of mitochondrial respiration correlated with a depletion of ATP; (2) inhibition of tRNA-synthetase accompanied by a reduced protein synthesis; and (3) enhanced lipid peroxidation. Generation of free radicals and lipid peroxidation as an important mode of action of OA in vitro and in vivo is discussed in detail, as well as counteracting effects of dietary antioxidants.


"Why not bathe the baby today?": A qualitative study of thermal care beliefs and practices in four African sites.
Recommendations for care in the first week of a newborn's life include thermal care practices such as drying and wrapping, skin to skin contact, immediate breastfeeding and delayed bathing. This paper examines beliefs and practices related to neonatal thermal care in three African countries. Data were collected in the same way in each site and included 16-20 narrative interviews with recent mothers, eight observations of neonatal bathing, and in-depth interviews with 12-16 mothers, 9-12 grandmothers, eight health workers and 0-12 birth attendants in each site. We found similarities across sites in relation to understanding the importance of warmth, a lack of opportunities for skin to skin care, beliefs about the importance of several baths per day and beliefs that the Vernix caseosa was related to poor maternal behaviours. There was variation between sites in beliefs and practices around wrapping and drying after delivery, and the timing of the first bath with recent behavior change in some sites. There was near universal early bathing of babies in both Nigerian sites. This was linked to a deep-rooted belief about body odour. When asked about keeping the baby warm, respondents across the sites rarely mentioned recommended thermal care practices, suggesting that these are not perceived as salient. More effort is needed to promote appropriate thermal care practices both in facilities and at home. Programmers should be aware that changing deep rooted practices, such as early bathing in Nigeria, may take time and should utilize the current beliefs in the importance of neonatal warmth to facilitate behaviour change.


Environmental context determines the limiting demographic processes for plant recruitment across a species' elevational range.
Plant recruitment is a multi-stage process determining population dynamics and species distributions. Still, we have limited understanding of how the successive demographic processes depend on the environmental context across species' distributional ranges. We conducted a large-scale transplant experiment to study recruitment of Pinus cembra over six years. We quantified the effects of environmental conditions on four demographic processes and identified the most limiting across and beyond the pines' elevational range over several years. Realized transition probabilities of the demographic processes varied substantially across the species' distributional range. Seed deposition decreased from the lower to the upper elevational range margin by 90%, but this reduction was offset by increased seed germination and seedling survival. Dispersal limitation at the upper range margin potentially stems from unsuitable seed caching conditions for the animal seed disperser, whereas increased seed germination might result from enemy escape from fungal pathogens and favourable abiotic conditions at the upper range margin. Our multi-year experiment demonstrates that environmental context is decisive for the local relevance of particular demographic processes. We conclude that experimental studies identifying the limiting demographic processes controlling species distributions are key for projecting future range dynamics of plants.


Clostridium tertium Bacteremia in a Non-neutropenic Patient with Liver Cirrhosis.
Clostridium tertium bacteremia is a rare condition that predominantly occurs in neutropenic patients. Clostridium tertium bacteremia, although extremely rare in non-neutropenic patients, represents the second-most common cause of bacteremia among Clostridium species. Infection with this bacteria can present variably and is usually managed with broad-spectrum antibiotics.


Extended-release naltrexone for treatment of alcohol dependence in primary care.
The feasibility of using extended-release injectable naltrexone (XR-NTX) to treat alcohol dependence in routine primary care settings is unknown. An open-label, observational cohort study evaluated 3-month treatment retention, patient satisfaction, and alcohol use among alcohol-dependent patients in two urban public hospital medical clinics. Adults seeking treatment were offered monthly medical management (MM) and three XR-NTX injections (380 mg, intramuscular). Physician-delivered MM emphasized alcohol abstinence, medication effects, and accessing mutual help and counseling resources. Seventy-two alcohol-dependent patients were enrolled; 90% (65 of 72) of eligible subjects received the first XR-NTX injection; 75% (49 of 65) initiating treatment received the second XR-NTX injection; 62% (40 of 65), the third. Among the 56% (n = 40) receiving three injections, median drinks per day decreased from 4.1 (95% confidence interval = 2.9-6) at baseline to 0.5 (0-1.7) during Month 3. Extended-release naltrexone delivered in a primary care MM model appears a feasible and acceptable treatment for alcohol dependence.


Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells.
The expression of the alpha 6 beta 4 and alpha 6 beta 1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits alpha 6, beta 4, and beta 1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immuno-electron microscopy. The identity of these cells as LC was further established by coincident staining for alpha 6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-alpha (TNF alpha), the predominant cytokine in mast cell granules, also induced LC to express alpha 6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNF alpha antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce alpha 6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNF alpha in the regulation of the integrins alpha 6 beta 4 and alpha 6 beta 1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.


Age-related Changes with the Trabecular Bone of Ward's Triangle and Neck-shaft Angle in the Proximal Femur: A Radiographic Study.
The Ward triangle is an important area used clinically to diagnose and assess osteoporosis and its fracture risk in the proximal femur. The main objective of this study was to investigate the rules of development and maturation of the trabeculae of Ward's triangle to provide a basis for the prevention and treatment proximal femur fracture. From January 2018 to December 2019, individuals from 4 months to 19 years old who underwent hip growth and development assessments at the Third Hospital of Hebei Medical University were selected retrospectively. The outpatient electronic medical record system was used to collect information such as age, gender, imaging images, and clinical diagnosis. The development score and maturity characteristics of the trabecular bone were analyzed using hip radiograph data. Correlation analysis was performed to identify the relationship among age, neck-shaft angle and development and maturity score of the trabecular bone. A total of 941 patients were enrolled in this study, including 539 males and 402 females. Primary compression trabeculae were all present at 1 year of age and matured at 7 years of age and older; primary tension trabeculae were all present at 4 years of age and matured at 18 years of age. Secondary compression trabeculae were present at 4 years of age and matured at 18 years of age. In addition, the neck-shaft angle progressively decreases from 4 months to 14 years of age but barely changes between 15 and 19 years of age. In short, the development and maturation of the trabeculae in the ward' triangle followed a specific temporal pattern that was related to the neck-shaft angle. Therefore, these findings can help us understand structure and mechanical characteristics of proximal femoral trabeculae, and improve our understanding of the mechanism and treatment of proximal femoral fractures.


The role of histamine in the cardiovascular system.
This article reviews briefly the role of histamine through its H1 and H2 receptors on the cardiovascular system and its action on calcium and catecholamines. The analogy between the adrenergic and the histaminergic systems is well demonstrated and there is evidence that histamine participates in myocardial damage and arrythmias, but the question of its exact role in the early stages of cardiovascular diseases, such as myocardial ischaemia and atherosclerosis, requires further study.


Molecular analysis of infant acute leukemia.
Infant acute leukemia, known to have a poor outcome with conventional therapy, usually has a molecular rearrangement at chromosome band 11q23. The 11q23 translocation partner is typically at 4q21 in infant ALL, but other 11q23 translocation partners occur in infant ALL and AML. The MLL gene at 11q23, and the AF4 gene at 4q21, have been extensively studied to identify heterogeneity of structural rearrangement and prognostic indicators, to look for clues as to etiology, and to improve therapy.


FISH analysis of pachytene chromosome and DNA fiber of telomere sequence in rice (Oryza sativa L. indica).
Telomere sequences were analyzed by using pachytene chromosome and extended DNA fiber FISH in rice (Oryza, sativa ssp. indica cv. -Guangluai No.4). Pachytene FISH results showed that most of chromosome ends possess the telomere tandem repeats, but the signals on different chromosomes were not the same in intensity. Fiber FISH results indicated that the longest string of beads was 6.55 microm, while the shortest one was 1.82 microm long,which were equal to 16.44 and 4.56 kb correspondingly based on a stretching factor of 2.51 kb/microm. The average value of signal length was 3.62 +/- 1.32 microm, i.e. 9.09 +/- 3.31 kb. It could be estimated that the longest and the shortest as well as the average value were equal to 2,349,651 and 1298 +/- 473 of copy number respectively.


8-Hydroxydeoxyguanosine levels in white blood cell DNA and ex vivo oxidation resistance of plasma in smokers.
Oxidative DNA damage in peripheral white blood cell of smokers were estimated in accordance with the levels of 8-Hydroxydeoxyguanosine (8-OHdG) in nuclear DNA and the antioxidant status of these smokers' plasma was investigated in terms of the ex vivo oxidation resistance of plasma. In a survey of 12 smokers (4 women) aged 22 to 48, the mean level of 8-OHdG was 3.79+/-0.65 residue/10(6) dG (mean +/- S.D.) with a range from 2.83 to 4.62 residue/10(6) dG. These measurements showed approximately 1.6-fold inter-individual variations of 8-OHdG level in smokers. A higher level of 8-OHdG was found for smokers whose ex vivo plasma oxidation resistance was weak. Significant association is seen between oxidized bases in white blood cells and plasma oxidation resistance, whereas signs of any association with plasma concentration of alpha-tocopherol, ascorbic acid, bilirubin, and uric acid are weak and sporadic. These findings indicate that apparent heterogeneity exists among smokers in some sort of resistance to the oxidative effects of smoking.


Risk Factors of Discharged Against Medical Advice among Adolescents Self-inflicted Injury and Attempted Suicide in the Korean Emergency Department.
Suicide is a leading cause of death among Korean adolescents. Many suicide attempting adolescents often are discharged against medical advice in the emergency department. The aim of the present study was to determine the risk factors for discharge against medical advice (DAMA) after self-inflicted injury or attempted suicide in the emergency department. We extracted data on adolescents (10-19 yr old) from the national emergency department information system; we used data from 2007 and 2011. A total of 6,394 adolescents visited EDs after self-inflicted injury or attempted suicide. Among these patients, the median age was 17 yr (Interquatile range, 15-18 yr), 83.2% were between 15-19 yr of age, and 63.3% were female. Poisoning was the most common method of attempted suicide, while hanging and fall were the most common methods of fatality. The rate of DAMA from the ED was 22.8%. Independent risk factors for DAMA included female gender (odds ratio [OR], 1.49), older age adolescents (OR, 1.96), residence in a metropolitan/large city area (OR, 1.49), and discharge at night (OR, 1.38). These risk factors should be considered in establishing management and counseling plans for patients discharged against medical advice by community services and EDs.


Leading towards the future: implementing nursing leadership principles at the front line.
Federal and provincial professional bodies of nursing and healthcare are examining the role of nursing leadership and its relation in creating and sustaining quality work environments for nursing. Using the findings and recommendations of the Canadian Nursing Advisory Report Committee (2002) as a catalyst, nurse leaders from Children's and Women's Health Centre of British Columbia (C&W) have collaborated to develop principles of nursing leadership to be used as a resource in determining roles and functions of front-line nurse leaders throughout the organization. In this paper, the process of creating those nursing leadership principles is described with a focus on the unit-based operational leader. Suggestions are made on how to evaluate the effectiveness of principle-based nursing leadership as implemented at C&W and its utility to the unit-based operational leader.


[Ketamine and neuroprotection. Clinical outlook].
As the mechanism of action of ketamine, particularly its non-competitive antagonism at the N-methyl-D-aspartate receptor (NMDA), has become better understood, the use of the drug as a neuroprotective agent has received increasing interest. Although the potential prometabolic effects of ketamine might be counterproductive to neuroprotection, the increase in intracranial pressure it has repeatedly been reported to produce does not appear to be relevant clinically under certain conditions, e.g. in patients with normocapnia and a stable blood pressure. Also, the drug has been shown to be anticonvulsant in clinically applied doses rather than epileptogenic, as was previously assumed. These insights have opened up entirely new perspectives for the use of ketamine as a neuroprotective agent. But as both in vitro and in vivo studies are inconclusive, the benefits of the drug are still controversial. In addition, the potential neurotoxicity attributed to extremely high ketamine doses is poorly understood. Consequently, well controlled animal experiments and studies in humans would be necessary to establish the role of ketamine and its more potent enantiomer S-(+)-ketamine in combination with other neuroprotective measures and to shed light on its true neuroprotective potential and its possible neuroregenerative effects.


Analytical determination of bioactive compounds as an indication of fruit quality.
The aim of this investigation was to determine the bioactive compounds in kiwifruit as an indication of quality after extraction using methanol and ethyl acetate. Using FTIR and three-dimensional fluorescence spectroscopy and electrospray ionization/MS, the contents of polyphenols, flavonoids, flavanols, and tannins, and the level of the antioxidant activity by 2, 2-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) diammonium salt, 1, 1-diphenyl-2-picrylhydrazyl, ferric-reducing/ antioxidant power, and cupric reducing antioxidant capacity assays were determined and compared. It was found that the methanol extracts of kiwifruit showed significantly higher amounts of bioactive acetate extracts. The cultivar Bidan, in comparison compounds and antioxidant activities than the ethyl with the classic Hayward, showed significantly higher bioactivity. For the first time, Bidan organic kiwifruit was analyzed for its antioxidant activities and compared with the widely consumed Hayward organic based on its bioactive compounds and fluorescence properties. Relatively high content of bioactive compounds and positive antioxidant and antiproliferative properties of kiwifruit determined by the advanced analytical methods justify its use as a source of valuable antioxidants. The methods used are applicable for bioactivity determination, in general, for any food products.


Directionality of individual cone photoreceptors in the parafoveal region.
The pointing direction of cone photoreceptors can be inferred from the Stiles-Crawford Effect of the First Kind (SCE-I) measurement. Healthy retinas have tightly packed cones with a SCE-I function peak either centered in the pupil or with a slight nasal bias. Various retinal pathologies can change the profile of the SCE-I function implying that the arrangement or the light capturing properties of the cone photoreceptors are affected. Measuring the SCE-I may reveal early signs of photoreceptor change before actual cell apoptosis occurs. In vivo retinal imaging with adaptive optics (AO) was used to measure the pointing direction of individual cones at eight retinal locations in four control human subjects. Retinal images were acquired by translating an aperture in the light delivery arm through 19 different locations across a subject's entrance pupil. Angular tuning properties of individual cones were calculated by fitting a Gaussian to the reflected intensity profile of each cone projected onto the pupil. Results were compared to those from an accepted psychophysical SCE-I measurement technique. The maximal difference in cone directionality of an ensemble of cones, ρ¯, between the major and minor axes of the Gaussian fit was 0.05 versus 0.29mm(-2) in one subject. All four subjects were found to have a mean nasal bias of 0.81mm with a standard deviation of ±0.30mm in the peak position at all retinal locations with mean ρ¯ value decreasing by 23% with increasing retinal eccentricity. Results show that cones in the parafoveal region converge towards the center of the pupillary aperture, confirming the anterior pointing alignment hypothesis.


Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis.
Many of oncogenes and tumor suppressor genes have been found to exert variable and even opposing roles in different kinds of tumors or at different stages of cancer development. Here we showed that tumorigenic potential of mouse embryonic carcinoma P19 cells cultured in adherent plates (attached-P19-cells) was suppressed by a chemotherapeutic agent, 5-aza-2'-deoxycytidine (ZdCyd), whereas the higher pro-tumorigenicity of P19 cells growing in suspension (detached-P19-cells) was generated by the ZdCyd treatment. Surprisingly, p53 activity was highly up-regulated by ZdCyd in both growing conditions. By our developed computational approaches, we revealed that there was a significant enrichment of apoptotic pathways in the ZdCyd-induced p53-dominant gene-regulatory network in attached P19 cells, whereas the pro-survival genes were significantly enriched in the ZdCyd-induced p53 network in detached P19 cells. The protein-protein interaction network of the ZdCyd-treated detached P19 cells was significantly different from that of ZdCyd-treated attached P19 cells. On the other hand, inhibition of p53 expression by siRNA suppressed the ZdCyd-induced tumorigenesis of detached P19 cells, suggesting that the ZdCyd-activated p53 plays oncogenic function in detached P19 cells. Taken together, these results indicate a context-dependent role for the ZdCyd-activated p53-dominant network in tumorigenesis.


Ultrasound guidance versus anatomical landmark approach for femoral artery access in coronary angiography: A randomized controlled trial and a meta-analysis.
The objective was to assess the effect of ultrasound (US)-guidance compared to the anatomical landmark (AL) approach in patients requiring femoral artery (FA) access for coronary angiography/percutaneous coronary interventions (PCI). US-guidance has been proposed as a strategy to optimize FA access, potentially leading to decreased vascular complications. Patients requiring FA access for coronary angiography/PCI were randomized to the US-guided or AL approaches. The primary endpoint was a composite of immediate procedural vascular outcomes, and access-site outcomes at day one. Results were subsequently pooled in a study-level meta-analysis of randomized trials comparing US-guided FA access to another strategy. A total of 129 patients were randomized (64 US-guided group; 65 AL group). The primary endpoint occurred in 30 patients (47%) with US, and in 39 patients (62%) with AL (P = 0.09). Four additional studies met the inclusion criteria and were included in the meta-analysis (1553 patients). Following data pooling, bleeding events (OR = 0.41; 95%CI 0.20-0.83; P = 0.01), venipunctures (OR = 0.18; 95%CI: 0.11-0.29; P < 0.0001), and multiple puncture attempts (OR = 0.24; 95%CI: 0.19-0.31; P < 0.0001) were significantly improved with US-guidance, but not successful common FA cannulation (OR = 0.84; 95%CI: 0.60-1.17; P = 0.29). Our study did not show significant benefits for the use of US to guide arterial femoral access compared to the anatomical landmark approach, but pooled analysis of five randomized trials showed decreased rates of bleeding events and venipunctures, and improved first-pass success. The clinical impact of these findings is uncertain, and do not warrant a systematic use of US-guidance in this clinical setting.


A pediatric overview of the spectrum of developmental disabilities.
The developmental disabilities are specific diagnoses on a spectrum of chronic neurologic handicaps. Complete diagnosis and habilitation planning demands awareness of the underlying continuum of cerebral dysfunction common to all the disabilities. Careful attention to this continuum can result in the recognition of critically important associated deficits. Developmental dissociation is a useful developmental phenomenon in the early diagnosis of a particular disability. Developmental deviancy is an aid in early detection of milder disabilities or associated deficits. Professionals familiar with the entire spectrum are necessary to provide optimal care for developmentally disabled children.


Evaluation of the antifungal activity of individual and combined monoterpenes against Rhizopus stolonifer and Absidia coerulea.
The development of natural plant extracts and essential oils will help to decrease the negative effects of synthetic chemicals. In the present study, the antifungal activity of individual and combined monoterpenes against Rhizopus stolonifer and Absidia coerulea was evaluated. The results from antifungal tests showed that eugenol, carvacrol, and isoeugenol, among all the tested compounds, exhibited strong antifungal activity against the two tested fungi. Furthermore, carvacrol exhibited the most toxic effects against R. stolonifer and A. coerulea, and the IC50 values of carvacrol for the two fungi were 44.94 μg/ml and 50.83 μg/ml, respectively. The compounds (±)-menthol, b-citronellol, geraniol, 3,7-dimethyl-1-octanol, citral, and cuminaldehyde had only strong antifungal activity against R. stolonifer. In addition, the value of the synergistic co-efficient (SR) of a combination of isoeugenol and eugenol (1:1) showed an additive effect against R. stolonifer. The combination of isoeugenol and cuminaldehyde (1:1) showed an antagonistic effect against A. coerulea. Our results indicated that carvacrol and isoeugenol had potential antifungal effects against the two tested fungi and could be utilized in novel biological fungicide development.


Quantum effects in the evolution of vortices in the electromagnetic field.
We analyze the influence of electron-positron pairs creation on the motion of vortex lines in electromagnetic field. In our approach the electric and magnetic fields satisfy nonlinear equations derived from the Euler-Heisenberg effective Lagrangian. We show that these nonlinearities may change the evolution of vortices.


Co-localization of the alpha-subunit of BK-channels and c-PLA2 in GH3 cells.
Large conductance, calcium-activated potassium channels (maxi K- or BK-channels) can be regulated by arachidonic acid produced by c-Phospholipase A2 (c-PLA2). Since in every excised patch from GH3 cells where there was BK-channel activity, treatment with either a stimulator or inhibitor of c-PLA2 resulted in a corresponding increase or decrease in BK-channel activity, we hypothesized that there must be a close association between BK-channel proteins and c-PLA2 in the cell membrane. To test this hypothesis, we first determined whether the two proteins would co-immunoprecipitate. We then used confocal imaging of fluorescently tagged proteins to determine where in the cells BK-channel proteins and c-PLA2 co-localize. The alpha-subunit of the BK-channel was strongly co-immunoprecipitated by c-PLA2 antibodies, suggesting that most of the BK channel alpha-subunits are associated with c-PLA2. This interaction was not affected by pharmacologically inhibiting c-PLA2 suggesting that the association does not require functionally active c-PLA2. Following dual immunohistochemical labeling and confocal microscopy, image analysis revealed that in the cytosol there was some co-localization, but most of the c-PLA2 was separate from BK-channel proteins. On the other hand, the c-PLA2 and BK-channel proteins at the plasma membrane were strongly co-localized. Immunoprecipitation experiments conducted with plasma membrane proteins support these findings. We conclude that c-PLA2 is likely physically associated with BK-channel proteins at the cell surface.


Sexual Aggression Victimization and Perpetration Among Female and Male University Students in Poland.
This study examined the prevalence of victimization and perpetration of sexual aggression since age 15 in a convenience sample of 565 Polish university students (356 females). The prevalence of sexual aggression was investigated for both males and females from the perspectives of both victims and perpetrators in relation to three coercive strategies, three different victim-perpetrator relationships, and four types of sexual acts. We also examined the extent to which alcohol was consumed in the context of sexually aggressive incidents. The overall self-reported victimization rate was 34.3% for females and 28.4% for males. The overall perpetration rate was 11.7% for males and 6.5% for females. The gender difference was significant only for perpetration. Prevalence rates of both victimization and perpetration were higher for people known to each other than for strangers. In the majority of victimization and perpetration incidents, alcohol was consumed by one or both parties involved. The findings are discussed in relation to the international evidence and the need for tailored risk prevention and reduction programs.


[The efficacy of sorafenib to prevent relapse in patients with FLT3-ITD mutation positive acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].
To study the efficacy of sorafenib to prevent relapse in patients with FLT3-ITD mutation positive acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 7 cases with FLT3-ITD positive AML have received allo-HSCT in our department from May 2013 to January 2015. Six cases were administrated with sorafenib after hematopoietic reconstruction. Another patient relapsed on day 192 past allo-HSCT, then she started to use sorafenib after remission of re-induction regimens. Five patients survived. The median progression free survival was 280(126-366)day. This study suggests that sorafenib might prevent relapse past allo-HSCT and improve survival in patients with FLT3-ITD positive AML.


Virtual Reality Meditation for Fatigue in Persons With Rheumatoid Arthritis: Mixed Methods Pilot Study.
Effective symptom management is crucial to enhancing the quality of life for individuals with chronic diseases. Health care has changed markedly over the past decade as immersive, stand-alone, and wearable technologies including virtual reality have become available. One chronic pain population that could benefit from such an intervention is individuals with rheumatoid arthritis (RA). Recent pharmacologic advances in the management of RA have led to a decrease in inflammatory symptoms (eg, chronic pain) or even disease remission, yet up to 70% of patients with RA still suffer from fatigue. While VR-delivered behavior, meditation, and biofeedback programs show promise for pain and anxiety management, there is little information on the use of virtual reality meditation (VRM) for fatigue management among individuals with RA. This study aims to (1) examine the feasibility of implementing a study protocol that uses VRM, (2) determine the acceptability of using VRM for fatigue management in an outpatient population, and (3) identify barriers and contextual factors that might impact VRM use for fatigue management in outpatients with RA. We used a convergent, mixed methods design and enrolled adults aged 18 years or older with a clinical diagnosis of RA. Patient-Reported Outcome Measure Information System (PROMIS) measures of fatigue, depression, anxiety, pain behavior, and physical function were assessed alongside the brief mood introspection scale at baseline and weekly for 4 weeks. VRM use across the 4-week study period was automatically stored on headsets and later extracted for analysis. Semistructured interview questions focused on feedback regarding the participant's experience with RA, previous experience of fatigue, strategies participants use for fatigue management, and the participant's experience using VRM and recommendations for future use. A total of 13 participants completed this study. Most participants completed all study surveys and measures (11/13, 84% and 13/13, 100%, respectively) and were active participants in interviews at the beginning and end of the program. Participants used VRM an average of 8.9 (SD 8.5) times over the course of the 4-week program. Most participants enjoyed VRM, found it relaxing, or recommended its use (12/13, 92%), but 8 (62%) noted barriers and conceptual factors that impacted VRM use. On average, participants saw decreases in PROMIS fatigue (-6.4, SD 5.1), depression (-5.6, SD 5.7), anxiety (-4.5, SD 6), and pain behavior (-3.9, SD 5.3), and improvements in PROMIS physical function (1.5, SD 2.7) and Brief Mood Introspection Scale mood (5.3, SD 6.7) over the course of this 4-week study. While this study's implementation was feasible, VRM's acceptability as an adjunctive modality for symptom management in RA is contingent on effectively overcoming barriers to use and thoughtfully addressing the contextual factors of those with RA to ensure successful intervention deployment. ClinicalTrials.gov NCT04804462; https://classic.clinicaltrials.gov/ct2/show/NCT04804462.


From Production to Consumption: A Coupled Human-Environmental Nitrogen Flow Analysis in China.
Anthropogenic inputs of reactive nitrogen (Nr) provide sufficient food, energy, and industrial products to meet human demands; however, only a fraction of Nr is consumed as food and nonfood goods, and the rest is lost to the environment and negatively affects ecosystems. High-resolution studies of nitrogen flows are invaluable to increase nitrogen use efficiencies and reduce environmental emissions. In this study, a comprehensive substance flow analysis of nitrogen for China in 2014 is presented. Based on the conceptual framework, which highlights the key roles of human drivers, the analysis of the synthetic ammonia supply and demand balance shows that 75% of ammonia is used for agricultural purposes. Moreover, the life cycle analysis of food nitrogen shows that human food consumption accounts for approximately 7% of the total Nr inputs. A quantitative analysis of pollutant emissions shows that industrial and crop production are the main sources of atmospheric emissions, while livestock farming and crop production are the main sources of water emissions. Finally, we investigate four scenarios (efficiency improvement, high recycling rate, nitrogen oxide emission reduction, and a combined scenario) and provide relevant policy recommendations (large farm size, standardized agricultural production model, flue gas denitration, etc.) for improving nitrogen management practices.


Survival of rat sciatic nerve segments preserved in storage solutions ex vivo assessed by novel electrophysiological and morphological criteria.
Most organ or tissue allografts with viable cells are stored in solutions ex vivo for hours to several days. Most allografts then require rapid host revascularization upon transplantation to maintain donor-cell functions (e.g., cardiac muscle contractions, hepatic secretions). In contrast, peripheral nerve allografts stored ex vivo do not require revascularization to act as scaffolds to guide outgrowth by host axons at 1-2 mm/d, likely aided by viable donor Schwann cells. Using current storage solutions and protocols, axons in all these donor organ/tissue/nerve transplants are expected to rapidly become non-viable due to Wallerian degeneration within days. Therefore, ex vivo storage solutions have not been assessed for preserving normal axonal functions, i.e., conducting action potentials or maintaining myelin sheaths. We hypothesized that most or all organ storage solutions would maintain axonal viability. We examined several common organ/tissue storage solutions (University of Wisconsin Cold Storage Solution, Normosol-R, Normal Saline, and Lactated Ringers) for axonal viability in rat sciatic nerves ex vivo as assessed by maintaining: (1) conduction of artificially-induced compound action potentials; and (2) axonal and myelin morphology in a novel assay method. The ten different storage solution conditions for peripheral nerves with viable axons (PNVAs) differed in their solution composition, osmolarity (250-318 mOsm), temperature (4°C vs. 25°C), and presence of calcium. Compound action potentials and axonal morphology in PNVAs were best maintained for up to 9 days ex vivo in calcium-free hypotonic diluted (250 mOsm) Normosol-R (dNR) at 4°C. Surprisingly, compound action potentials were maintained for only 1-2 days in UW and NS at 4°C, a much shorter duration than PNVAs maintained in 4°C dNR (9 days) or even in 25°C dNR (5 days). Viable axons in peripheral nerve allografts are critical for successful polyethylene glycol (PEG)-fusion of viable proximal and distal ends of host axons with viable donor axons to repair segmental-loss peripheral nerve injuries. PEG-fusion repair using PNVAs prevents Wallerian degeneration of many axons within and distal to the graft and results in excellent recovery of sensory/motor functions and voluntary behaviors within weeks. Such PEG-fused PNVAs, unlike all other types of conventional donor transplants, are immune-tolerated without tissue matching or immune suppression. Preserving axonal viability in stored PNVAs would enable the establishment of PNVA tissue banks to address the current shortage of transplantable nerve grafts and the use of stored PEG-fused PNVAs to repair segmental-loss peripheral nerve injuries. Furthermore, PNVA storage solutions may enable the optimization of ex vivo storage solutions to maintain axons in other types of organ/tissue transplants.


Early Maternal Thyroid Function During Gestation Is Associated With Fetal Growth, Particularly in Male Newborns.
Intrauterine growth patterns are influenced by maternal thyroid function during gestation and by fetal sex. It is unknown, however, whether the relationships between maternal thyrotropin (TSH) and free thyroxine (fT4) levels in early pregnancy and fetal growth outcomes are modified by fetal sex. Data were obtained from a community-based cohort study of pregnant women living in Amsterdam (Amsterdam Born Children and Their Development study). TSH and fT4 levels were determined during the first prenatal screening at median 13 weeks (interquartile range, 12 to 14). Women with live-born singletons and no overt thyroid dysfunction were included (N = 3988). Associations between these maternal hormones and birth weight, small for gestational age (SGA), and large for gestational age (LGA) were analyzed separately for each sex. After adjustments, 1 pmol/L increase in maternal fT4 levels was associated with a reduction in birth weight of 33.7 g (P < 0.001) in male newborns and 16.1 g (P < 0.05) in female newborns. Increased maternal fT4 was not associated with increased odds for SGA, but was associated with a decreased odds for LGA in boys [per 1 pmol/L; odds ratio (OR), 0.79; 95% confidence interval (CI), 0.69 to 0.90]. Maternal subclinical hypothyroidism in early pregnancy (TSH > 2.5 mU/L, 7.3%) was associated with increased odds for LGA in male newborns (OR, 1.95; 95% CI, 1.22 to 3.11). Maternal fT4 in early pregnancy was observed to be inversely associated with birth weight, with a stronger relationship in males. Male infants also had increased odds for LGA in mothers with subclinical hypothyroidism. Sexual dimorphism appears to be present in the relationship between maternal thyroid metabolism and fetal intrauterine growth, with stronger associations in male infants.


Negotiating public-health intellectual property licensing agreements to increase access to health technologies: an insider's story.
Public health voluntary licensing of intellectual property has successfully been applied to increase access to medicines in certain disease areas, producing health benefits and economic savings, particularly in low-income and middle-income countries. There is however limited understanding of the intricacies of the approach, the modalities by which it works in practice, its levers and the trade-offs made. Such knowledge may be critical in deciding what role licensing should have in pandemic preparedness and equitable access to health technologies more broadly. This paper examines the case for licensing, the considerations for balancing public health needs, the challenges of negotiations, and the processes for validating proposed agreements. No access mechanism is perfect, but evidence suggests that public-health licensing has an important role to play, although it remains underused. Understanding some of the realities, strengths, limitations and complexities of applying the model may help calibrate expectations and develop incentives to expand its applications.


Fewer Bonuses, More Penalties At Skilled Nursing Facilities Serving Vulnerable Populations.
The first round of incentives and penalties under the Medicare Skilled Nursing Facility Value-Based Purchasing Program were distributed October 1, 2018. Our results show that facilities serving vulnerable groups were less likely to receive bonus payments and more likely to be penalized.


Lenalidomide modulates IL-8 and anti-prostate antibody levels in men with biochemically recurrent prostate cancer.
We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25 mg of lenalidomide in a randomized phase 2 trial, and determined whether those changes correlated with disease progression. Cytokine levels were compared for each patient at baseline and after 6 months of treatment with lenalidomide. Regression models for correlated data were used to assess associations of cytokine levels with lenalidomide treatment effect. Estimates were obtained using generalized estimating equations. Changes in circulating anti-prostate antibodies were evaluated using a high-throughput immunoblot technique. Treatment with lenalidomide was associated with global changes in immunoreactivity to a number of prostate-associated antigens, as well as with changes in circulating levels of the T(H) 2 cytokines IL-4, IL-5, IL-10, and IL-13. Disease progression in treated patients was associated with an increase in circulating IL-8 levels, while IL-8 levels decreased significantly in non-progressors. Lenalidomide demonstrates immunomodulatory properties in patients with biochemically recurrent prostate cancer. The induction of novel anti-prostate antibodies is a potential mechanism for lenalidomide response. Changes in serum IL-8 levels may serve as a potential biomarker in treated patients. These hypotheses require formal testing in future prospective trials.


[Relationship between event-related potentials and brain injury].
Event-related potentials (ERPs) develop promptly as one kind of special evoked potentials. And it is one of the most effective methods to investigate human's cognition function in these years. P300 is the component of ERPs which is widely and maturately researched and has intimate relation with attention, memory and other high psychological activity. The evaluation of recognition change after brain injury is the focus of the research. With the development of relatively research, it is deemed that this technique has wide application perspective in many aspects such as forensic clinical medicine and forensic psychiatry.


A cross-sectional study: serum CCL3/MIP-1α levels may reflect lumbar intervertebral disk degeneration in Han Chinese people.
The macrophage inflammatory protein-1α (MIP-1α), also named chemokine cytokine ligand 3 (CCL3), has been detected in nucleus pulposus and increased following cytokine stimulation. The current study was performed to explore the relationship between serum CCL3/MIP-1α levels with lumbar intervertebral disk degeneration (IDD). A total of 132 disk degeneration patients confirmed by magnetic resonance imaging and 126 healthy controls were enrolled in the current study. Radiological evaluation of the IDD was conducted using a 3.0-T magnetic resonance imaging scanner for entire lumbar vertebra region. Degeneration of intervertebral disk was assessed by Schneiderman criteria. Serum CCL3/MIP-1α levels were investigated using a sandwich enzyme-linked immunosorbent assay. The Visual Analog Scale scores and Oswestry Disability Index index were recorded for clinical severity. Elevated concentrations of CCL3 in serum were found in IDD patients compared with asymptomatic volunteers. The case group included 49 IDD patients with grade 1, 42 with grade 2, and 41 with grade 3. Grade 3 and 2 had significantly higher CCL3 concentrations in serum compared with those with grade 1. The serum CCL3 levels were positively related to the degree of disk degeneration. In addition, the serum CCL3 levels also demonstrated a significant correlation with the clinical severity determined by Visual Analog Scale scores and Oswestry Disability Index index. Serum CCL3 may serve as a biomarker of IDD.


EEG Spectral Power: A Proposed Physiological Biomarker to Classify the Hypoxic-Ischemic Encephalopathy Severity in Real Time.
Mild hypoxic-ischemic encephalopathy (HIE) constitutes a large unstudied population with considerable debate on how to define and treat due to the dynamic evolution of the clinical signs of encephalopathy. We propose to address this gap with quantitative physiological biomarkers to aid in stratification of the disease severity. The objectives of this prospective cohort study were to measure the electroencephalographic (EEG) power as an objective biomarker of the evolution of the clinical encephalopathy in newborns with mild to severe HIE. EEG was collected in infants with HIE using four bipolar electrodes analyzed for the first three hours of the recording. Delta power (DP, 0.5 to 4 Hz) and total power (TP, 0.5 to 20 Hz) were compared between groups with different HIE severity using a univariate ordinal logistic regression model and receiver operating characteristic curves. A total of 44 term-born infants with mild to severe HIE were identified within six hours of birth. The DP and TP values were significantly higher for the mild group than for the moderate group for all bipolar electrodes. A one-unit increase in DP was associated with significantly lower odds of encephalopathy. DP best distinguished mild from higher encephalopathy grades by area under the curve. We conclude that DP and TP are sensitive real-time biomarkers for monitoring the dynamic evolution of the encephalopathy severity in the first day of life. The quantitative EEG power may lead to timely recognition of the worsening of the encephalopathy and guide future therapeutic interventions targeting mild HIE.


Implementation on a desktop computer of the real time feedback control loop of a scanning probe microscope.
A software package has been developed to implement the real time feedback control loop needed in scanning probe microscopy on a general purpose desktop computer of the current high-speed/multicore generation. The main features of the implementation of both the feedback loop and the control of the experiment on the same computer are discussed. The package can work with several general purpose data acquisition boards and can be extended in a modular way to further board models; timing performance has been tested with several hardware configurations and some applications common in scanning probe microscopy. The package is available under an Open Source license.


A Light-Weight Artificial Neural Network for Recognition of Activities of Daily Living.
Human activity recognition (HAR) is essential for the development of robots to assist humans in daily activities. HAR is required to be accurate, fast and suitable for low-cost wearable devices to ensure portable and safe assistance. Current computational methods can achieve accurate recognition results but tend to be computationally expensive, making them unsuitable for the development of wearable robots in terms of speed and processing power. This paper proposes a light-weight architecture for recognition of activities using five inertial measurement units and four goniometers attached to the lower limb. First, a systematic extraction of time-domain features from wearable sensor data is performed. Second, a small high-speed artificial neural network and line search method for cost function optimization are used for activity recognition. The proposed method is systematically validated using a large dataset composed of wearable sensor data from seven activities (sitting, standing, walking, stair ascent/descent, ramp ascent/descent) associated with eight healthy subjects. The accuracy and speed results are compared against methods commonly used for activity recognition including deep neural networks, convolutional neural networks, long short-term memory and convolutional-long short-term memory hybrid networks. The experiments demonstrate that the light-weight architecture can achieve a high recognition accuracy of 98.60%, 93.10% and 84.77% for seen data from seen subjects, unseen data from seen subjects and unseen data from unseen subjects, respectively, and an inference time of 85 μs. The results show that the proposed approach can perform accurate and fast activity recognition with a reduced computational complexity suitable for the development of portable assistive devices.


Association Between Migraine and Benign Paroxysmal Positional Vertigo Among Adults in South Korea.
Patients with migraine often experience various types of vertigo, and several studies have suggested an epidemiologic and physiologic association of migraine and vertigo with vestibule. However, few researchers have investigated the association between migraine and benign paroxysmal positional vertigo (BPPV). To determine the incidence of BPPV in individuals with migraine in a large national population-based sample. This cohort study obtained data from the Korean Health Insurance Review and Assessment Service covering the period January 1, 2002, through December 31, 2013. These data included personal information, health insurance claim codes, diagnostic codes, death records, socioeconomic data, and medical examination data for each individual in the database. A 1:4 matching method was used to select individuals for the migraine group (n = 40 682) and the control group (n = 162 728). Individuals who had a history of BPPV before the index date, for whom a match could not be identified, and who received a migraine diagnosis before age 20 years were excluded from the analysis. Data analysis was conducted from September 1, 2015, to December 31, 2017. The crude and adjusted (by age, sex, income, region of residence, and medical history [hypertension, diabetes, or dyslipidemia]) hazard ratios for migraine and BPPV were analyzed using the Cox proportional hazards regression model. Of the 40 682 individuals in the migraine group, 10 381 (25.5%) were male and 30 301 (74.5%) were female. Of the 162 728 controls, 41 524 (25.5%) were male and 121 204 (74.5%) were female. The incidence of BPPV was statistically significantly higher in the migraine group than in the control group (2431 [6.0%] vs 3677 [2.3%]). Migraine increased the risk of BPPV (adjusted hazard ratio, 2.54; 95% CI, 2.41-2.68). In a subgroup analysis, the incidence of BPPV in all age groups and in both men and women was statistically significantly higher in the migraine group than in the control group. The incidence of BPPV was the highest in men younger than 40 years (adjusted hazard ratio, 4.49; 95% CI, 3.05-6.62), and the HR decreased in both men and women as age increased. Migraine appeared to be statistically significantly associated with higher incidence of BPPV; future studies are needed to determine the association between BPPV and specific factors related to migraine.


Study protocol: responding to the needs of patients with IgA nephropathy, a social media approach.
IgA nephropathy is the most common cause of glomerulonephritis in the Western world and predominantly affects young adults. Demographically these patients are the biggest users of social media. With increasing numbers of patients turning to social media to seek information and support in dealing with their disease, analysis of social media streams is an attractive modern strategy for understanding and responding to unmet patient need. To identify unmet patient need in this population, a framework analysis will be undertaken of prospectively acquired social media posts from patients with IgA nephropathy, acquired from a range of different social media platforms. In collaboration with patients and members of the clinical multidisciplinary team, resources will be created to bridge gaps in patient knowledge and education identified through social media analysis and returned to patients via social media channels and bespoke websites. Analysis of the impact of these resources will be undertaken with further social media analysis, surveys and focus groups. Patients with chronic diseases are increasingly using social networking channels to connect with others with similar diseases and to search for information to help them understand their condition. This project is a 21st century digital solution to understanding patient need and developing resources in partnership with patients, and has wide applicability as a future model for understanding patient needs in a variety of conditions.


Multimodal MEMPRAGE, FLAIR, and [Formula: see text] Segmentation to Resolve Dura and Vessels from Cortical Gray Matter.
While widely in use in automated segmentation approaches for the detection of group differences or of changes associated with continuous predictors in gray matter volume, T1-weighted images are known to represent dura and cortical vessels with signal intensities similar to those of gray matter. By considering multiple signal sources at once, multimodal segmentation approaches may be able to resolve these different tissue classes and address this potential confound. We explored here the simultaneous use of FLAIR and apparent transverse relaxation rates (a signal related to [Formula: see text] relaxation maps and having similar contrast) with T1-weighted images. Relative to T1-weighted images alone, multimodal segmentation had marked positive effects on 1. the separation of gray matter from dura, 2. the exclusion of vessels from the gray matter compartment, and 3. the contrast with extracerebral connective tissue. While obtainable together with the T1-weighted images without increasing scanning times, apparent transverse relaxation rates were less effective than added FLAIR images in providing the above mentioned advantages. FLAIR images also improved the detection of cortical matter in areas prone to susceptibility artifacts in standard MPRAGE T1-weighted images, while the addition of transverse relaxation maps exacerbated the effect of these artifacts on segmentation. Our results confirm that standard MPRAGE segmentation may overestimate gray matter volume by wrongly assigning vessels and dura to this compartment and show that multimodal approaches may greatly improve the specificity of cortical segmentation. Since multimodal segmentation is easily implemented, these benefits are immediately available to studies focusing on translational applications of structural imaging.


Actin Cytoskeleton Polymerization and Focal Adhesion as Important Factors in the Pathomechanism and Potential Targets of Mucopolysaccharidosis Treatment.
The main approach used in the current therapy of mucopolysaccharidosis (MPS) is to reduce the levels of glycosaminoglycans (GAGs) in cells, the deposits considered to be the main cause of the disease. Previous studies have revealed significant differences in the expression of genes encoding proteins involved in many processes, like those related to actin filaments, in MPS cells. Since the regulation of actin filaments is essential for the intracellular transport of specific molecules, the process which may affect the course of MPSs, the aim of this study was to evaluate the changes that occur in the actin cytoskeleton and focal adhesion in cells derived from patients with this disease, as well as in the MPS I mouse model, and to assess whether they could be potential therapeutic targets for different MPS types. Western-blotting, flow cytometry and transcriptomic analyses were employed to address these issues. The levels of the key proteins involved in the studied processes, before and after specific treatment, were assessed. We have also analyzed transcripts whose levels were significantly altered in MPS cells. We identified genes whose expressions were changed in the majority of MPS types and those with particularly highly altered expression. For the first time, significant changes in the expression of genes involved in the actin cytoskeleton structure/functions were revealed which may be considered as an additional element in the pathogenesis of MPSs. Our results suggest the possibility of using the actin cytoskeleton as a potential target in therapeutic approaches for this disease.