Lifespan changes in working memory in fragile X premutation males.
Fragile X syndrome is the world's most common hereditary cause of developmental delay in males and is now well characterized at the biological, brain and cognitive levels. The disorder is caused by the silencing of a single gene on the X chromosome, the FMR1 gene. The premutation (carrier) status, however, is less well documented but has an emerging literature that highlights a more subtle profile of executive cognitive deficiencies that mirror those reported in fully affected males. Rarely, however, has the issue of age-related declines in cognitive performance in premutation males been addressed. In the present study, we focus specifically on the cognitive domain of working memory and its subcomponents (verbal, spatial and central executive memory) and explore performance across a broad sample of premutation males aged 18-69 years matched on age and IQ to unaffected comparison males. We further tease apart the premutation status into those males with symptoms of the newly identified neurodegenerative disorder, the fragile X-associated tremor/ataxia syndrome (FXTAS) and those males currently symptom-free. Our findings indicate a specific vulnerability in premutation males on tasks that require simultaneous manipulation and storage of new information, so-called executive control of memory. Furthermore, this vulnerability appears to exist regardless of the presence of FXTAS symptoms. Males with FXTAS symptoms demonstrated a more general impairment encompassing phonological working memory in addition to central executive working memory. Among asymptomatic premutation males, we observed the novel finding of a relationship between increased CGG repeat size and impairment to central executive working memory.


Risk factors for coronary heart disease: a study in inner London.
A survey was carried out among 281 men and women aged between 30 and 64 years randomly selected from five general practices located in the inner London borough of Tower Hamlets, to determine the prevalence of risk factors for coronary heart disease. Smoking and obesity were both more pronounced in Tower Hamlets than in comparable national studies: 51% of men and 44% of women were smokers and 57% of these were smoking 20 or more cigarettes per day. A body mass index of 30 or more was present in 18% of men and 10% of women and a body mass index of 25 or more in 71% of men and 49% of women. Two or more risk factors for coronary heart disease (smoking and/or hypertension and/or raised cholesterol levels) were present in 25% of men and 22% of women. For every person known by their general practitioner to have established cardiovascular disease, there were an additional two people also at risk on the basis of multiple risk factors. In this inner city population the prevalence of cardiovascular risk, for women as well as men, has major resource and organizational implications for primary care. A strategy for change requires action based on graded multiple risks for both men and women.


Male nurses' views of gender in the nurse-family relationship in paediatric care.
(1) To learn how male nurses view and manage their relationships with families of hospitalized children, in contrast to how they view those established by female nurses. (2) To know if male nurses' relationships with families of hospitalized children are influenced by gender roles and stereotypes. Relationships are essential in care. Prevailing gender stereotypes suggest that males have more difficulties with relationships than with technical aspects of nursing. Descriptive qualitative research in a public tertiary hospital September-December 2015. Participants were male nurses who worked in maternal and child health. Purposive sampling, based on criteria of homogeneity-regularity and heterogeneity-diversity. Semi-structured interviews and content analysis. Twelve male nurses participated. Two key themes emerged. (1) Establishment of professional-family relationship. Male nurses denied that male and female nurses established relationships with families differently, attributing any differences to personality rather than gender. (2) Management of relationships. Male nurses claimed that they set more limits on their relationships with families than female nurses. Male nurses both disrupted and reproduced gendered stereotypes about relationships with families, revealing new models of masculinity. Male nurses reject the stereotype that nursing is a women's profession, but they interpret their relationships with families in terms of gender roles and stereotypes. These findings contribute to understandings of the influence of gender stereotypes in nursing. They support the work of professional associations and labour unions in Spain and other countries to combat gender stereotypes and gender differences in nursing.


Detection of enterovirus 68 in serum from pediatric patients with pneumonia and their clinical outcomes.
Enterovirus 68 (EV68) infection occasionally manifests with fatal outcomes. However, detection of EV68 in serum and its clinical outcomes are yet to be determined. In this study, we retrospectively tested stored serum samples collected from pediatric pneumonia patients whose nasopharyngeal specimens were positive for EV68. Of total 28 nasopharyngeal sample-positive patients, EV68 was detected in serum samples among 12 (43%) patients aged between 1 and 4 years. Our results suggest that EV68 can cause viremia by which the virus may exhibit systemic manifestations.


Systematic review of oncology nurse practitioner navigation metrics.
Nurse practitioners should become more active in patient navigation and its subcomponent, care coordination, because research has shown that these roles are influential in improving patient care at all levels of an organization. Well-defined process and outcome measures, as well as educational initiatives, are critical to these programs because they serve as the structure for program evaluation. This article aims to assess and define metrics that nurse practitioners in the oncology setting can use to evaluate navigation programs, which is essential for the evolution of research pertaining to the navigation field. The current article is a systematic review that describes oncology nurse practitioner navigation metrics using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) format for the systematic literature review process. These metrics are then compared to current standards of care. Seven studies met the criteria for this review. Research is emerging that shows benefit in using an oncology nurse practitioner navigator for ensuring timely care and patient and staff satisfaction. These metrics are in line with expert consensus recommendations. The need for more research identifying sound research tools that have been rigorously tested has been identified.


Stereotactic Radiosurgery for Cavernous Sinus Versus Noncavernous Sinus Dural Arteriovenous Fistulas: Outcomes and Outcome Predictors.
Dural arteriovenous fistulas (DAVFs) can be categorized based on location. To compare stereotactic radiosurgery (SRS) outcomes between cavernous sinus (CS) and non-CS DAVFs and to identify respective outcome predictors. This is a retrospective study of DAVFs treated with SRS between 1988 and 2016 at 10 institutions. Patients' variables, DAVF characters, and SRS parameters were included for analyses. Favorable clinical outcome was defined as angiography-confirmed obliteration without radiological radiation-induced changes (RIC) or post-SRS hemorrhage. Other outcomes were DAVFs obliteration and adverse events (including RIC, symptomatic RIC, and post-SRS hemorrhage). The overall study cohort comprised 131 patients, including 20 patients with CS DAVFs (15%) and 111 patients with non-CS DAVFs (85%). Rates of favorable clinical outcome were comparable between the 2 groups (45% vs 37%, P = .824). Obliteration rate after SRS was higher in the CS DAVFs group, even adjusted for baseline difference (OR = 4.189, P = .044). Predictors of favorable clinical outcome included higher maximum dose (P = .014) for CS DAVFs. Symptomatic improvement was associated with obliteration in non-CS DAVFs (P = .005), but symptoms improved regardless of whether obliteration was confirmed in CS DAVFs. Non-CS DAVFs patients with adverse events after SRS were more likely to be male (P = .020), multiple arterial feeding fistulas (P = .018), and lower maximum dose (P = .041). After SRS, CS DAVFs are more likely to obliterate than non-CS ones. Because these 2 groups have different total predictors for clinical and radiologic outcomes after SRS, they should be considered as different entities.


Spatial heterogeneity of plant-soil feedback affects root interactions and interspecific competition.
Plant-soil feedback is receiving increasing interest as a factor influencing plant competition and species coexistence in grasslands. However, we do not know how spatial distribution of plant-soil feedback affects plant below-ground interactions. We investigated the way in which spatial heterogeneity of soil biota affects competitive interactions in grassland plant species. We performed a pairwise competition experiment combined with heterogeneous distribution of soil biota using four grassland plant species and their soil biota. Patches were applied as quadrants of 'own' and 'foreign' soils from all plant species in all pairwise combinations. To evaluate interspecific root responses, species-specific root biomass was quantified using real-time PCR. All plant species suffered negative soil feedback, but strength was species-specific, reflected by a decrease in root growth in own compared with foreign soil. Reduction in root growth in own patches by the superior plant competitor provided opportunities for inferior competitors to increase root biomass in these patches. These patterns did not cascade into above-ground effects during our experiment. We show that root distributions can be determined by spatial heterogeneity of soil biota, affecting plant below-ground competitive interactions. Thus, spatial heterogeneity of soil biota may contribute to plant species coexistence in species-rich grasslands.


Enhancer responses to similarly distributed antagonistic gradients in development.
Formation of spatial gene expression patterns in development depends on transcriptional responses mediated by gene control regions, enhancers. Here, we explore possible responses of enhancers to overlapping gradients of antagonistic transcriptional regulators in the Drosophila embryo. Using quantitative models based on enhancer structure, we demonstrate how a pair of antagonistic transcription factor gradients with similar or even identical spatial distributions can lead to the formation of distinct gene expression domains along the embryo axes. The described mechanisms are sufficient to explain the formation of the anterior and the posterior knirps expression, the posterior hunchback expression domain, and the lateral stripes of rhomboid expression and of other ventral neurogenic ectodermal genes. The considered principles of interaction between antagonistic gradients at the enhancer level can also be applied to diverse developmental processes, such as domain specification in imaginal discs, or even eyespot pattern formation in the butterfly wing.


Effect of addition of commercial rosemary extracts on potent odorants in cooked beef.
Solid-phase microextraction-gas chromatography-olfactometry (SPME-GCO) and aroma extract dilution analysis (AEDA) were applied to measure the effects of the addition of two commercial rosemary extracts (RE) on the potent odorants in cooked beef extracts (BE). On the basis of the results of SPME-GCO and AEDA, the addition of RE imparted sweet and floral notes to BE as a result of the addition of esters and terpenes of RE. In addition, RE suppressed the formation of odorants derived via lipid oxidation and Maillard reactions. The most potent lipid oxidation volatiles consisted of 1-octen-3-one (mushroom-like), (E)-2,4-epoxy-(E)-2-decenal (metallic), and eight different aldehydes (fatty). The Maillard reaction volatiles, necessary for typical cooked beef flavor, included compounds with meaty [2-methyl-3-furanthiol, 2-methyl-3-(methylthio)furan, 2-methyl-3-(methyldithio)furan], roasty (2-furanmethanethiol), caramel-like [4-hydroxy-2,5-dimethyl-3(2H)-furanone], baked potato-like [3-(methylthio)propanal], and spicy [3-hydroxy-4,5-dimethyl-2(5H)-furanone] attributes. The suppressive effects of RE may be caused by the action of antioxidative substances in RE alone or in combination with the pH increase in BE induced by the matrix components of RE.


Feasibility of vibro-acoustography with a quasi-2D ultrasound array transducer for detection and localizing of permanent prostate brachytherapy seeds: a pilot ex vivo study.
Effective permanent prostate brachytherapy (PPB) requires precise placement of radioactive seeds in and around the prostate. The impetus for this research is to examine a new ultrasound-based imaging modality, vibro-acoustography (VA), which may serve to provide a high rate of PPB seed detection while also effecting enhanced prostate imaging. The authors investigate the ability of VA, implemented on a clinical ultrasound (US) scanner and equipped with a quasi-2D (Q2D) array US transducer, to detect and localize PPB seeds in excised prostate specimens. Nonradioactive brachytherapy seeds were implanted into four excised cadaver prostates. A clinical US scanner equipped with a Q2D array US transducer was customized to acquire both US and C-scan VA images at various depths. The VA images were then used to detect and localize the implanted seeds in prostate tissue. To validate the VA results, computed tomography (CT) images of the same tissue samples were obtained to serve as the reference by which to evaluate the performance of VA in PPB seed detection. The results indicate that VA is capable of accurately identifying the presence and distribution of PPB seeds with a high imaging contrast. Moreover, a large ratio of the PPB seeds implanted into prostate tissue samples could be detected through acquired VA images. Using CT-based seed identification as the standard, VA was capable of detecting 74%-92% of the implanted seeds. Additionally, the angular independency of VA in detecting PPB seeds was demonstrated through a well-controlled phantom experiment. Q2DVA detected a substantial portion of the seeds by using a 2D array US transducer in excised prostate tissue specimens. While VA has inherent advantages associated with conventional US imaging, it has the additional advantage of permitting detection of PPB seeds independent of their orientation. These results suggest the potential of VA as a method for PPB imaging that ultimately may allow US-based real-time intraoperative dosimetry.


Overexpression of the dual specificity phosphatase, Cdc25C, confers sensitivity on tumor cells to doxorubicin-induced cell death.
Cdc25C is a dual-specificity phosphatase that is involved in induction of mitosis by removal of the inhibitory phosphates from cyclin-dependent kinase 1/cyclin B. In this study, adenovirus-mediated overexpression of Cdc25C sensitizes U2OS tumor cells to doxorubicin-induced apoptosis. U2OS cells that stably overexpress Cdc25C are also sensitized to doxorubicin-induced cell death. These cells show reduced phosphorylation of cyclin-dependent kinase 1 on Tyr15 and impaired up-regulation of p21 in response to treatment with doxorubicin. In contrast to doxorubicin, overexpression of Cdc25C does not confer sensitivity to apoptosis on treatment with 5-fluorouracil or hydroxyurea. This sensitization of tumor cells to doxorubicin-induced cell death by overexpression of Cdc25C is not p53 dependent. Intriguingly, nontransformed MCF10A cells are not sensitized to doxorubicin treatment by overexpression of Cdc25C nor does the lack of Cdc25C affect cell cycle progression or the G2 arrest caused by doxorubicin. These results support the idea that a combination of overexpressing Cdc25C with treatment with conventional genotoxic agents should be given serious considerations as a novel therapeutic strategy.


Layered Double Hydroxides-Based Mixed Metal Oxides: Development of Novel Structured Sorbents for CO2 Capture Applications.
Layered double hydroxide (LDHs)-based mixed metal oxides (MMOs) are widely studied as the medium to high temperature (200-400 °C) CO2 capture sorbents. However, most of the studies are carried out using the powdered samples. To upgrade these sorbents for industrial-scale CO2 capture, it is important to move away from the powdered form and develop structured sorbents. Moreover, the CO2 capture properties of these sorbents need to be improved in terms of capture capacity and cycling stability. Here we are utilizing a modified amide hydrolysis method to improve the CO2 capture capacities of LDHs-based MMOs. Subsequently, aqueous exfoliation coupled with the freeze-drying technique was utilized to develop LDHs-based novel MMOs. Exfoliated LDH nano sheets were pelletized (2 mm) to circumvent the challenges associated with powder samples when used in industrial-scale applications. The obtained pellets have an average crushing load of 11.1 N and 4.3 MPa of compressive strength, which indicate their good mechanical stability. The MMOs pellets showed a narrow distribution of pores (8-10 nm) with very good surface area (264 m2/g) and pore volume (1.27 cm3/g). They also had much improved CO2 capture capacities at ambient pressure and both low (2.17 mmol/g, 30 °C) and medium temperature (1.43 mmol/g, 200 °C), as compared to previously reported pristine MMOs powder samples. The pelletized structured sorbents also outperformed commercial LDH-based pellets by several fold.


Low-dose BCG instillations in the treatment of stage T1 grade 3 bladder tumours: recurrence, progression and success.
The aim of this retrospective study was to evaluate the effects and results of low-dose bacillus Calmette-Guérin (BCG) therapy on a selective high-risk population of stage T1, grade 3 (G3) bladder tumours. Recurrence and progression were also analysed. Thirty-five consecutive patients presenting with T1 G3 tumours were treated with intravesical BCG. All patients underwent complete transurethral tumour resection. A course of BCG 75 mg Pasteur strain was begun 4 weeks after the first resection of the diagnosed tumour and continued for a 6-week period. At the end of treatment, a complete urological evaluation was routinely carried out: urine cytology test, cystoscopy with bladder biopsies randomly performed, and any recurrences were resected. In cases of abnormal cytology and/or recurrence an additional course of BCG was initiated, followed by the same tests. Follow-up examination and cystoscopy or fibroscopy were conducted every 3 months for 1 year, semiannually and annually thereafter. Median follow-up was 45 months (range 10-120); 7 patients (20%) did not respond to BCG instillations. Of these patients, 5 underwent cystectomy and in 2 patients the bladder was left in place in spite of recurrence because of age (+80 years). Twenty-eight patients (80%) responded positively, 24 after one single course of BCG, and 4 patients after two courses. During follow-up, recurrence was observed in 8 cases: stage T1 G3 in 4 patients, T1 CIS (carcinoma in situ) in 2 patients, Ta G2 and Ta G1 in 2 patients. Three of these patients were treated by cystectomy and the remaining patients with transurethral resection alone or combined with additional courses of BCG. Overall, 25 patients (71%) were considered free of tumour occurrence after low-dose BCG therapy. Ten patients underwent cystectomy (29%) or remained in occurrence and 2 patients died of the disease. These results can be closely compared to the results of other trials conducted on stage T1 G3 and BCG treatment, using a different dosage and BCG protocol therapy. BCG is an effective prophylactic and therapeutic agent for T1 G3 carcinoma of the bladder responders. The identification of these responders before beginning instillations still remains a challenge.


Non-volatile conductive gels made from deep eutectic solvents and oxidised cellulose nanofibrils.
Ionogels offer huge potential for a number of applications including wearable electronics and soft sensors. However, their synthesis has been limited and often relies on non-renewable or non-biocompatible components. Here we present a novel two-component ionogel made using just deep eutectic solvents (DESs) and cellulose. DESs offer a non-volatile alternative to hydrogels with highly tuneable properties including conductivity and solvation of compounds with widely varying hydrophobicity. DESs can be easily made from cheap, biodegradable and biocompatible components. This research presents the characterisation of a series of soft conductive gels made from deep eutectic solvents (DESs), specifically choline chloride-urea and choline chloride-glycerol, with the sole addition of TEMPO-oxidised cellulose nanofibrils (OCNF). A more liquid-like rather than gel-like conductive material could be made by using the DES betaine-glycerol. OCNF are prepared from sustainable sources, and are non-toxic, and mild on the skin, forming gels without the need for surfactants or other gelling agents. These DES-OCNF gels are shear thinning with conductivities up to 1.7 mS cm-1 at ∼26 °C. Given the thousands of possible DESs, this system offers unmatched tunability and customisation for properties such as viscosity, conductivity, and yield behaviour.


Concentrations of seven iodothyronine metabolites in brain regions and the liver of the adult rat.
The concentrations of the iodothyronine metabolites T(4), T(3), 3,5-diiodothyronine (3,5-T(2)), 3,3'-diiodothyronine (3,3'-T(2)), reverse T(3) (rT(3)), 3,3'-T(2) sulfate (3,3'T(2)S), and T(3) sulfate (T(3)S) were measured in 12 regions of the brain, the pituitary gland, and liver in adult male rats. Quantification of iodothyronine was performed by RIA following a newly developed method of purification and separation by HPLC. 3,5-T(2), 3,3'-T(2), rT(3) and T(2)S were detectable in the low femtomolar range (20-200 fmol/g) in most areas of the rat brain. T(3)S was detectable only in the hypothalamus. The concentrations of T(3) and T(4) were approximately 20- to 60-fold higher, ranging between 1 and 6 pmol/g. There was a significant negative correlation between the activities of inner-ring deiodinase and T(3) concentrations across brain areas. In the liver, 3,5-T(2), rT(3), and T(3)S were measurable in the low femtomolar range, whereas 3,3'-T(2) and 3,3'T(2)S were not detectable. 3,5-T(2) and 3,3'-T(2) were not detectable in mitochondrial fractions of the brain regions. Tissue concentrations of 3,5-T(2) exhibited a circadian variation closely parallel to those of T(3) in the brain regions and liver. T(3) was not a substrate for outer-ring deiodination under different experimental conditions; thus, it remains unclear which substrate(s) and enzyme(s) are involved in the production of 3,5-T(2). These results indicate that five iodothyronine metabolites other than T(3) and T(4) are detectable in the low femtomolar range in the rat brain and/or liver. The physiological implications of this finding are discussed.


Dual processing theory and experts' reasoning: exploring thinking on national multiple-choice questions.
An ongoing debate exists in the medical education literature regarding the potential benefits of pattern recognition (non-analytic reasoning), actively comparing and contrasting diagnostic options (analytic reasoning) or using a combination approach. Studies have not, however, explicitly explored faculty's thought processes while tackling clinical problems through the lens of dual process theory to inform this debate. Further, these thought processes have not been studied in relation to the difficulty of the task or other potential mediating influences such as personal factors and fatigue, which could also be influenced by personal factors such as sleep deprivation. We therefore sought to determine which reasoning process(es) were used with answering clinically oriented multiple-choice questions (MCQs) and if these processes differed based on the dual process theory characteristics: accuracy, reading time and answering time as well as psychometrically determined item difficulty and sleep deprivation. We performed a think-aloud procedure to explore faculty's thought processes while taking these MCQs, coding think-aloud data based on reasoning process (analytic, nonanalytic, guessing or combination of processes) as well as word count, number of stated concepts, reading time, answering time, and accuracy. We also included questions regarding amount of work in the recent past. We then conducted statistical analyses to examine the associations between these measures such as correlations between frequencies of reasoning processes and item accuracy and difficulty. We also observed the total frequencies of different reasoning processes in the situations of getting answers correctly and incorrectly. Regardless of whether the questions were classified as 'hard' or 'easy', non-analytical reasoning led to the correct answer more often than to an incorrect answer. Significant correlations were found between self-reported recent number of hours worked with think-aloud word count and number of concepts used in the reasoning but not item accuracy. When all MCQs were included, 19 % of the variance of correctness could be explained by the frequency of expression of these three think-aloud processes (analytic, nonanalytic, or combined). We found evidence to support the notion that the difficulty of an item in a test is not a systematic feature of the item itself but is always a result of the interaction between the item and the candidate. Use of analytic reasoning did not appear to improve accuracy. Our data suggest that individuals do not apply either System 1 or System 2 but instead fall along a continuum with some individuals falling at one end of the spectrum.


Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer.
On 12 December 2014, the U.S. Food and Drug Administration (FDA) approved ramucirumab for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Areas covered: This review discusses the best treatment strategy for ramucirumab, a vascular endothelial growth factor receptor-2 inhibitor for patients with advanced NSCLC. Expert opinion: The addition of ramucirumab to docetaxel in the treatment of patients with metastatic NSCLC who have progressed on or after platinum-based chemotherapy confers a 1.4-month improvement in overall survival, with an acceptable toxicity profile. The potential impact of the approval of the programmed death receptor-1 (PD-1)-blocking antibody nivolumab or pembrolizumab on the use of ramucirumab plus docetaxel in advanced NSCLC patient population is uncertain in clinical practice. In order to improve overall outcomes for patients with advanced NSCLC, both ramucirumab plus docetaxel and the PD-1-blocking antibody should be used in any treatment line.


Evolving "faces" of the next generations of pediatric patients.
Bureau of the Census projections for the next decades indicated dramatic increases in the numbers of minority children in our population and actual decreases in the numbers of non-Hispanic white children. A summary of these projections is provided.


Green tea polyphenols ameliorate ethanol-induced spatial learning and memory impairments by enhancing hippocampus NMDAR1 expression and CREB activity in rats.
The current research probed into the effects of green tea polyphenols (GTPs) on ethanol-induced spatial learning and memory impairments and inquired the potential molecular mechanism in rats. Thirty 8-week-old male Sprague-Dawley rats were randomly divided into three groups. The control group (control, n=10), ethanol group (ethanol, n=10), and GTPs intervention group (GTP, n=10) received gavage administration of saline, ethanol, and ethanol-GTP solution, respectively, for 8 weeks. Morris water maze was applied to assess the spatial learning and memory function of rats in each group at the last week of treatment. There was no dramatic change in body weight of rats in the different groups. Compared with rats in the control group, 8-week ethanol gavaged rats showed increased escape latency period and decreased time in the target quadrant. Moreover, 8-week ethanol gavage decreased the density of pyramidal layer neurons, expression of NMDAR1, and CREB phosphorylation in the hippocampus region. In contrast, GTP intervention decreased escape latency period and increased the time in the target quadrant, the density of pyramidal layer neurons, expression of NMDAR1, and CREB phosphorylation in the hippocampus region. The current findings indicated that GTP intervention can improve ethanol-induced spatial learning and memory impairments in rats after ethanol withdrawal, which is related to the upregulated density of pyramidal layer neurons, expression of NMDAR1, and CREB phosphorylation in the hippocampus region.


Cooling techniques for targeted temperature management post-cardiac arrest.
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.


Factors related to the physical capacity of upper and lower limbs in quilombola elderly people.
This paper aimed to assess the factors related to the physical capacity of upper and lower limbs in quilombola older adults. This is a cross-sectional, analytic study performed with elderly residents in the quilombola community Caiana dos Crioulos, Alagoa Grande, Paraíba, Brazil. The researched dependent variables were the physical capacity of upper and lower limbs. It was performed the Spearman correlation and multiple and linear simple regression (95% CI; p<0.05). This work was performed per Resolution 466/2012 from National Health Council. Forty-three older adults were assessed. The bivariate analyses showed a positive correlation between handgrip strength (HGS) and physical activity (PA), between HGS and arm muscle circumference (AMC), and an inverse correlation between Short Physical Performance Battery (SPPB) and age. The multiple-model for HGS was significantly correlated with age, AMC, and years of study (R2=0.374; p<0.05). Regarding the SPPB, it showed a significant correlation with age (R2=0.2524; p=0.001). Therefore, the muscle mass reserve, years of study, and age were factors related to the physical capacity among quilombola older adults. The strict compliance of these aspects and the early intervention can preserve physical capacity and ensure the productive inclusion and economic autonomy so much sought in the communities' social agenda.


Lipid biomarkers of glioma cell growth arrest and cell death detected by 1 H magic angle spinning MRS.
Biomarkers of early response to treatment have the potential to improve cancer therapy by allowing treatment to be tailored to the individual. Alterations in lipids detected by in vivo MRS have been suggested as noninvasive biomarkers of cell stress and early indicators of cell death. An improved understanding of the relationship between MRS lipids and cell stress in vitro would aid in the translation of this technique into clinical use. Rat BT4C glioma cells were treated with 50 µ m cis-dichlorodiammineplatinum II (cisplatin), a commonly used chemotherapeutic agent, and harvested at several time points up to 72 h. High-resolution magic angle spinning (1) H MRS of cells was then performed on a 600-MHz NMR spectrometer. The metabolites were quantified using a time domain fitting method, TARQUIN. Increases were detected in saturated and polyunsaturated fatty acid resonances early during the exposure to cisplatin. The fatty acid CH(2) /CH(3) ratio was unaltered by treatment after allowing for contributions of macromolecules. Polyunsaturated fatty acids increased on treatment, with the group -CH=CH-CH(2) -CH=CH- accounting for all the unsaturated fatty acid signals. Transmission electron microscopy, in addition to Nile red and 4',6-diamino-2-phenylindole co-staining, revealed that the lipid increase was associated with cytoplasmic neutral lipid droplets. Small numbers of apoptotic and necrotic cells were detected by trypan blue, annexin V-fluorescein isothiocyanate-labelled flow cytometry and DNA laddering after up to 48 h of cisplatin exposure. Propidium iodide flow cytometry revealed that cells accumulated in the G1 stage of the cell growth cycle. In conclusion, an increase in the size of the lipid droplets is detected in morphologically viable cells during cisplatin exposure. (1) H MRS can detect lipid alterations during cell cycle arrest and progression of cell death, and has the potential to provide a noninvasive biomarker of treatment efficacy in vivo.


Employment services for persons with serious mental illness in northeastern Ontario: the case for partnerships.
To better understand why employment success is low, a case study was conducted to examine the influence of place on access to employment for persons with serious mental illness (SMI) residing in two northeastern Ontario communities (Rebeiro, in progress). Community-based participatory research methods were used to engage persons who experience SMI, decision-makers and providers in the research. Forty-six interviews were conducted, complemented by primary and secondary quantitative data sources. While most consumers consider employment to be a key element of their recovery, employment rates for persons with SMI remain limited in northeastern Ontario, Canada. The findings of this case study reveal the importance of collaborative partnerships to fostering better employment outcomes in northeastern Ontario. The challenges of collaboration due to rural and northern tensions, as well as various jurisdictional and funding tensions existing at the level of community support the case for partnerships in the provision of employment services in northern and rural places.


Complement factor C5a mediates renal ischemia-reperfusion injury independent from neutrophils.
The complement system has been shown to mediate renal ischemia-reperfusion (I/R) injury. However, the contribution of complement factor C5a to I/R injury, in particular in the kidney, remains to be established. In this study, we investigated the impact of blocking the C5aR pathway on the inflammatory response and on the renal function in a murine model of I/R injury. First, we analyzed C5aR expression in kidneys of healthy mice. Intriguingly, we found expression on mesangial, as well as on tubular epithelial, cells. After I/R injury, C5aR expression was up-regulated in tubular epithelial cells. In addition, mRNA levels of CXC chemokines and TNF-alpha increased significantly and kidneys were heavily infiltrated by neutrophils. Blocking the C5aR pathway by a specific C5a receptor antagonist (C5aRA) abrogated up-regulation of CXC chemokines but not of TNF-alpha and reduced neutrophil infiltration by >50%. Moreover, application of the C5aRA significantly reduced loss of renal function. This improvement of function was independent of the presence of neutrophils because neutrophil depletion by mAb NIMP-R14 did not affect the protective effect of C5aRA treatment. Furthermore, blocking of the C5aR pathway had no influence on renal apoptosis. These data provide evidence that C5a is crucially involved in the pathogenesis of renal I/R injury by modulation of neutrophil-dependent as well as neutrophil-independent pathways, which include the regulation of CXC chemokines but not TNF-alpha or apoptotic pathways.


[Emergency due to allergy: the therapy--adrenaline for physicians and patients].
Emergency due to allergy may proceed within minutes to life-threatening respiratory and circulatory problems. Therefore, after diagnosis prompt and correct therapy might be vital. Because of its effect on alpha-, beta1-, and beta2-receptors, adrenaline is the treatment of choice in emergency due to allergy. For fear of cardiovascular side effects, often adrenaline is withheld even in case of anaphylaxis. If given properly such as an intramuscular injection the danger of undesirable side effects, however, is small. After a systemic, allergic reaction each patient needs to be equipped with rescue medications. If an adrenaline-containing device is prescribed--nowadays with EpiPen and the metered-dose inhaler Primatene Mist 2 systems are available--, the patient must get a correct instruction in its use. In case of a severe allergic reaction, antihistamines and corticosteroids are given in second line. Following any systemic allergy, an allergological work-up should be required. Only through exact diagnosis and profound patient's education, recurrences can be avoided, and in some cases, specific immunotherapy is indicated.


Phase II metabolism in human skin: skin explants show full coverage for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation.
Although skin is the largest organ of the human body, cutaneous drug metabolism is often overlooked, and existing experimental models are insufficiently validated. This proof-of-concept study investigated phase II biotransformation of 11 test substrates in fresh full-thickness human skin explants, a model containing all skin cell types. Results show that skin explants have significant capacity for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation. Novel skin metabolites were identified, including acyl glucuronides of indomethacin and diclofenac, glucuronides of 17β-estradiol, N-acetylprocainamide, and methoxy derivatives of 4-nitrocatechol and 2,3-dihydroxynaphthalene. Measured activities for 10 μM substrate incubations spanned a 1000-fold: from the highest 4.758 pmol·mg skin(-1)·h(-1) for p-toluidine N-acetylation to the lowest 0.006 pmol·mg skin(-1)·h(-1) for 17β-estradiol 17-glucuronidation. Interindividual variability was 1.4- to 13.0-fold, the highest being 4-methylumbelliferone and diclofenac glucuronidation. Reaction rates were generally linear up to 4 hours, although 24-hour incubations enabled detection of metabolites in trace amounts. All reactions were unaffected by the inclusion of cosubstrates, and freezing of the fresh skin led to loss of glucuronidation activity. The predicted whole-skin intrinsic metabolic clearances were significantly lower compared with corresponding whole-liver intrinsic clearances, suggesting a relatively limited contribution of the skin to the body's total systemic phase II enzyme-mediated metabolic clearance. Nevertheless, the fresh full-thickness skin explants represent a suitable model to study cutaneous phase II metabolism not only in drug elimination but also in toxicity, as formation of acyl glucuronides and sulfate conjugates could play a role in skin adverse reactions.


The formation and properties of wheat flour doughs.
Among the cereal flours, only wheat flour will form a viscoelastic dough when mixed with water. The viscoelasticity appears to be because the gluten proteins are water compatible and thus will swell and interact. The gluten protein's large molecular size and low charge density appear to allow them to interact by both hydrogen and hydrophobic bonds. Wheat flour doughs are also unique in their ability to retain gas. This property appears to result from a slow rate of gas diffusion in the dough. The third major unique property of wheat flour doughs is their ability to set in the oven during baking, and thereby to produce a rigid loaf of bread. Although not clearly understood, this appears to be a heat-induced crosslinking of the gluten proteins.


Plant Functional Traits Are the Mediators in Regulating Effects of Abiotic Site Conditions on Aboveground Carbon Stock-Evidence From a 30 ha Tropical Forest Plot.
Understanding the relative contribution of abiotic and biotic factors to the formation of ecosystem functioning across scales is vital to evaluate ecosystem services. Here, we elucidate the effects of abiotic site conditions (i.e., soil and topographic properties) and plant functional traits on variations of stand aboveground carbon (AGC) stock in an old-growth tropical montane rain forest. The response-effect framework in functional ecology is adopted in examining how plant functional traits respond to environmental changes and affect ecosystem functioning. We measured specific leaf area and wood density of 270 woody plant species and estimated stand AGC stocks in a 30-ha forest plot. The relationships among environmental factors (ENVIRONMENT), community-weighted means of functional traits (TRAITS) and stand AGC stocks across nested spatial scales were disentangled by structural equation modeling. The results showed that the stands composed of 'acquisitive' species (high specific leaf area and low wood density) had low AGC, whereas stands composed of 'conservative' species (low specific leaf area and high wood density) had high AGC. TRAITS responded to ENVIRONMENT and affected AGC directly. ENVIRONMENT had an indirect effect on AGC through its direct effect on TRAITS. TRAITS were more important than ENVIRONMENT in driving variations of AGC. The effects of TRAITS on AGC increased, while the effects of ENVIRONMENT on AGC decreased with the increase of spatial scales in the tropical montane rain forest. Our study suggests that plant functional traits are the mediators in regulating effects of abiotic site conditions on ecosystem functions.


[Solubilization of mitochondria-bound rat skeletal muscle hexokinase isoenzyme II by glucose-6-phosphate].
Solubilization of bound to outer mitochondrial membrane hexokinase isoenzyme II by glucose-6-phosphate (G-6-P) has been studied. Dissociation of the enzyme-membrane complex was analyzed in both active (in the presence of reaction substrates) and inactive states. The magnitude of the complex dissociation constants was determined under G-6-P action in the presence and absence Mg.ATP. Besides, some kinetic parameters of hexokinase isoenzyme II in its free and bound forms were estimated. It is suggested that the mechanism of dissociation of the hexokinase-membrane complex by G-6-P is coupled with the kinetic mechanism of the reaction catalyzed by hexokinase isoenzyme II.


Non-homogeneous combination of two porous genomes induces complex body shape trajectories in cyprinid hybrids.
Hybridization is a common phenomenon in fish and is considered to be a major source of diversification. Deciphering the remoulding of genomic regions and phenotypes in zones where hybrid specimens occur is of particular interest to elucidate the emergence of evolutionary novelties. This approach is particularly challenging because the first step of hybridization seems to be the most important stage in the emergence of hybrid lineages. However, the signal can be significantly altered after only a few generations. We studied 41 microsatellites and partial cytochrome b gene sequences in 970 specimens belonging to two fish species (Chondrostoma nasus and Parachondrostoma toxostoma) in allopatric/parapatric zones, hybrids between them in a natural sympatric zone: the Ardèche basin. We showed that the genomic architecture in hybrids presented pattern heterogeneity of selection for the different loci. Indeed, the upstream part of the river (Rosières and Labeaume) presented an overdominant fitness of heterozygotes (12.20%) corresponding to a genomic compatibility, and underselection was observed for 4.88%-7.32% of the loci tested indicating a genomic incompatibility. Moreover the upstream station (Rosières) presented a positive selection of invasive C. nasus homozygotes (17.07% to 21.95%) indicating that hybridization may increase the fitness of admixed individuals.We showed that hybrid morphology (body shape based on 21 landmarks) correlated with genomic dilution indicating a species fingerprint. However, we demonstrated that the hybrid morphology was not a linear modification between the two parental species but a trade-off between several correlated traits. Hybrid specimens present a mosaic of genomic combination, showing regions with genomic compatibility and others with genomic incompatibility between the two species. Positive selection (invasive advantage ranging from 9.76% to 21.95% of the loci) was evidenced in the upstream part of the Ardèche indicating that environmental selection makes a substantial contribution. Although the presence of a dam is known to impose heterogeneous hybrid zones between these two species, we demonstrated in this study that a natural environment can also generate a hybrid zone with a large number (and diversity) of hybrids. The combination of the two genomes in the hybrids results in complex ontogenetic trajectories (with different morphological traits evolving at different rates) that correspond to novel developmental pathways.


Progranulin: an emerging target for FTLD therapies.
Frontotemporal lobar degeneration (FTLD), a neurodegenerative disease primarily affecting the frontal and temporal lobes, is one of the most common types of dementia. While the majority of FTLD cases are sporadic, approximately 10-40% of patients have an inherited form of FTLD. Mutations in the progranulin gene (GRN) have recently been identified as a major cause of FTLD with ubiquitin positive inclusions (FTLD-U). Because over 70 disease-linked GRN mutations cause abnormal deficiencies in the production of PGRN, a protein that plays a crucial role in embryogenesis, cell growth and survival, wound repair and inflammation, researchers now aim to design therapies that would increase PGRN levels in affected individuals, thereby alleviating the symptoms associated with disease. Several compounds and genetic factors, as well as PGRN receptors, have recently been identified because of their ability to regulate PGRN levels. Strict quality control measures are needed given that extreme PGRN levels at either end of the spectrum - too low or too high - can lead to neurodegeneration or cancer, respectively. The aim of this review is to highlight what is known regarding PGRN biology; to improve understanding of the mechanisms involved in regulating PGRN levels and highlight studies that are laying the groundwork for the development of effective therapeutic modulators of PGRN. This article is part of a Special Issue entitled RNA-Binding Proteins.


[Contrast enhanced MR-angiography (CE-MRA): do contrast media with higher T1 relaxation improve imaging of carotid stenoses?].
CE-MRA is a powerful tool for the non-invasive evaluation of carotid artery occlusive disease. However, due to certain drawbacks, it has not completely replaced DSA. The purpose of this study was to evaluate if Gd-BOPTA, a contrast agent with high T1 relaxivity, can increase the diagnostic accuracy of CE-MRA. The CE-MRA examinations of 54 consecutive patients were evaluated by two experienced radiologists, independently. The examinations of 27 patients were contrasted either with 20 ml Gd-BOPTA or with 20 ml Gd-DTPA. The reviewers were blinded to the contrast agent chosen and to the ultrasound results. They rated the overall image quality and the degree of the ICA stenoses. For the estimation of the degree of the ICA stenoses there was a high interrater validity. In comparison to the ultrasound findings, 6 of 50 high-degree stenoses were underestimated as moderate stenoses. In one of seven sonographically occluded vessels, MRA revealed residual patency in the vessel lumen. It was not possible to identify the contrast agent that was taken for a study. Subjective estimation of the image quality (arterial contrast of the ICA, contrast of the other vessels, and general impression) did not significantly change with the contrast agent employed. The diagnostic accuracy of CE-MRA for the evaluation of internal carotid artery stenoses is not improved by Gd-BOPTA if identical volumina of contrast media are applied. The potential of this contrast agent can be the reduction of the amount of contrast without loss of diagnostic information. Further studies are necessary.


Polymorphisms of SPINK1 N34S and CFTR in patients with sporadic and familial pancreatic cancer.
Long standing chronic pancreatitis is a risk factor for developing pancreatic cancer. Inheritance of polymorphisms in SPINK1 and CFTR are associated with an increased risk of developing pancreatitis. The aim of this study was to determine if patients who carry polymorphisms in SPINK1 and CFTR are at increased risk of developing pancreatic cancer through the development of chronic pancreatitis. DNA from patients with histologically-confirmed surgically-treated chronic pancreatitis, familial and sporadic pancreatic adenocarcinoma and controls were analyzed for the N34S polymorphism of SPINK1 and the two commonest polymorphisms of the CFTR gene, the DF508 mutation and the 5T polymorphism. These polymorphisms were determined using restriction fragment length polymorphism, PCR and cycle sequencing methods. The SPINK1 N34S polymorphism was detected in 5 of 172 (2.9%) patients with chronic pancreatitis, in 4 of 200 (2.0%) patients with sporadic pancreatic adenocarcinoma, in 0 of 36 (0%) of patients with familial pancreatic cancer and in 3 of 177 (1.7%) controls of chronic cholecystitis. The CFTR 5T polymorphism was identified in 31 of 334 (9.3%) patients of sporadic pancreatic cancer, in 5 of 43 (11.6%) patients with familial pancreatic cancer and in 10 of 112 (8.9%) controls with colorectal cancer. The CFTR DF508 mutation was recognized in 6 of the 240 (2.5%) patients with pancreatic adenocarcinoma, a prevalence similar to that of control populations. We conclude that the N34S polymorphism of SPINK1 and the 5T and DF508 CFTR polymorphisms do not predispose to the development of pancreatic adenocarcinoma. Furthermore, the N34S polymorphism is rarely found in patients with severe idiopathic chronic pancreatitis.


Apply innovative technologies to explore cancer genome.
Molecular genetic alterations characterize the development of human cancer. Recent advances in molecular genetic technology and the success of the human genome project have empowered investigators with new tools in dissecting the cancer genome for discovery of new cancer-associated genes. The purpose of this review is to highlight the emerging molecular genetic methodologies and summarize their principles, applications, and potential technical challenges. The critical issue in sample preparation and a strategy that combines different molecular techniques to facilitate the identification of novel cancer-associated genes will be discussed. Digital karyotyping and array-based techniques including array comparative genomic hybridization and representational oligonucleotide microarray analysis have been recently developed to study the genomic landscape in human cancer. These innovations provide tools to quantitatively measure DNA copy number changes in cancer and to map those changes directly onto the human genome. Digital karyotyping is based on counting the sequence tags that are distributed in the human genome and thus, it provides a digital readout to precisely outline the amplified and deleted chromosomal regions. Array-based technologies, on the other hand, compare the content of cancer and reference genomes followed by localizing the amplified or deleted signals in chromosomal regions using an array hybridization technique. In addition, a high-throughput mutational analysis platform has been available for a large-scale mutational analysis by using an automated capillary sequencing device and sophisticated bioinformatic tools. A number of examples have demonstrated the promise of these new molecular genetic approaches in identifying several potential new oncogenes and tumor suppressors. As compared with conventional cytogenetics methods, digital karyotyping, array comparative genomic hybridization, and representational oligonucleotide microarray analysis provide an unprecedented mapping resolution that allows a precise localization of the amplified and deleted chromosomal regions. These technologies can be combined with gene expression profiling and high-throughput mutational analysis to facilitate the search for new cancer-associated genes. It is expected that applying these new technologies will lead to discovery of a host of novel oncogenes and tumor suppressors, which will have a significant impact in our understanding of tumorigenesis and in the clinical management of cancer patients.


Differential effect of cis-platinum (cis-diamminedichloroplatinum) on regulation of liver and kidney haem and haemoprotein metabolism. Possible involvement of gamma-glutamyl-cycle enzymes.
The treatment of rats with cis-platinum (cis-diamminedichloroplatinum) for 1, 3 or 7 days elicited vastly different responses in the liver and the kidney in activities of enzymes of haem-metabolism pathway and gamma-glutamyl-cycle enzymes. The differences resided in the magnitude, direction and the time course of responses. In general, the liver was by far less severely affected, and when a response was elicited, it displayed an earlier onset (1-3 days), with a return to normal at 7 days. In the kidney, however, the effects were notable after 3 days of treatment, and became more pronounced at 7 days. Specifically, the activity of 5-aminolaevulinic acid (ALA) synthetase and contents of cytochrome P-450 and the microsomal haem were decreased in the liver. In contrast, in the kidney, cytochrome P-450 and haem concentrations were significantly increased, with no change in ALA synthetase activity. The increase in the kidney haem content appeared to reflect an increased formation of haem, as suggested by the elevated activity of ferrochelatase and the concomitant decrease in tissue porphyrin levels. In the kidney, a time-dependent and pronounced inhibition of activities of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione production, and gamma-glutamyl transpeptidase, the first enzyme in glutathione breakdown, were observed. The enzyme activities, 7 days after treatment, were only 40 and 60% of the control values respectively. In contrast, these enzyme activities were not affected in the liver. Complexing cis-platinum with cysteine considerably intensified the entire spectrum of effects of cis-platinum in the kidney. Notably, cytochrome P-450 concentration and haem oxygenase activity were increased to about 3.5 and 6 times the control values, respectively. gamma-Glutamylcysteine synthetase activity was decreased to less than 20% of the control. It is suggested that the differential effectiveness of cis-platinum in the liver and the kidney in alternating haem metabolism is related to the vast differences which exist between these organs in the activities of gamma-glutamyl-cycle enzymes. It is further suggested that this may promote the formation in the kidney, but not in the liver, of a cis-platinum-cysteine complex that is more stable, and thus biologically more effective, than the parent compound.


The dissection profile and mechanism of tissue-selective dissection of the piezo actuator-driven pulsed water jet as a surgical instrument: laboratory investigation using Swine liver.
The water jet technique dissects tissue while sparing cord-like structures such as blood vessels. The mechanism of such tissue-selective dissection has been unknown. The novel piezo actuator-driven pulsed water jet (ADPJ) system can achieve dissection with remarkably reduced water consumption compared to the conventional water jet; however, the system's characteristics and dissection capabilities on any organ have not been clarified. The purposes of this study were to characterize the physical properties of the novel ADPJ system, evaluate the dissection ability in swine organs, and reveal the mechanism of tissue-selective dissection. The pulsed water jet system comprised a pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle. The peak pressure of the pulsed water jet was measured through a sensing hole using a pressure sensor. The pulsed water jet technique was applied on swine liver in order to dissect tissue on a moving table using one-way linear ejection at a constant speed. The dissection depth was measured with light microscopy and evaluated histologically. The physical properties of swine liver were evaluated by breaking strength tests using tabletop universal testing instruments. The liver parenchyma was also cut with three currently available surgical devices to compare the histological findings. The peak pressure of the pulsed water jet positively correlated with the input voltage (R(2) = 0.9982, p < 0.0001), and this was reflected in the dissection depth. The dissection depth negatively correlated with the breaking strength of the liver parenchyma (R(2) = 0.6694, p < 0.0001). The average breaking strengths of the liver parenchyma, hepatic veins, and Glisson's sheaths were 1.41 ± 0.45, 8.66 ± 1.70, and 29.6 ± 11.0 MPa, respectively. The breaking strength of the liver parenchyma was significantly lower than that of the hepatic veins and Glisson's sheaths. Histological staining confirmed that the liver parenchyma was selectively dissected, preserving the hepatic veins and Glisson's sheaths in contrast to what is commonly observed with electrocautery or ultrasonic instruments. The dissection depth of liver tissue is well controlled by input voltage and is influenced by the moving velocity and the physical properties of the organ. We showed that the device can be used to assure liver resection with tissue selectivity due to tissue-specific physical properties. Although this study uses an excised organ, further in vivo studies are necessary. The present work demonstrates that this device may function as an alternative tool for surgery due to its good controllability of the dissection depth and ability of tissue selectivity.


Adaptation in a plant-hummingbird association.
Sexual dimorphism in bill morphology and body size of the Caribbean purple-throated carib hummingbird is associated with a reversal in floral dimorphism of its Heliconia food plants. This hummingbird is the sole pollinator of H. caribaea and H. bihai, with flowers of the former corresponding to the short, straight bills of males, the larger sex, and flowers of the latter corresponding to the long, curved bills of females. On St. Lucia, H. bihai compensates for the rarity of H. caribaea by evolving a second color morph with flowers that match the bills of males, whereas on Dominica, H. caribaea evolves a second color morph with flowers that match the bills of females. The nectar rewards of all Heliconia morphs are consistent with each sex's choice of the morph that corresponds to its bill morphology and energy requirements, supporting the hypothesis that feeding preferences have driven their coadaptation.


Community pharmacy-based intervention to improve self-monitoring of blood glucose in type 2 diabetic patients.
Self-monitoring of blood glucose (SMBG) is clearly correlated with increased life expectancy and quality of life in type 2 diabetic patients. The objective of our study was to record and assess the errors patients make in preparing, performing, and processing self-monitoring of blood glucose (SMBG). Furthermore, the study aimed to determine to what extent a single standardized SMBG instruction session in a community pharmacy might reduce the number of patients making errors or the number of errors per patient. Between May and October 2005, SMBG of 462 randomly selected patients with type 2 diabetes was monitored in 32 pharmacies specialized in diabetes care. The patients performed blood glucose self-tests using their own blood glucose meters. Self-testing was monitored using a standardized documentation sheet on which any error made during the performance of the test was recorded. If necessary, patients were instructed in the accurate operation of their meter and the use of the necessary equipment. Additionally, patients obtained written instructions. Six weeks later, assessment of the quality of patient's SMBG was repeated. During the first observation, 383 patients (83%) made at least one mistake performing SMBG. By the time of the second observation, this frequency had fallen to 189 (41%) (p<0.001). The average number of mistakes fell from 3.1 to 0.8 per patient. Mistakes that may potentially have led to inaccurate readings were initially recorded for 283 (61%) and at study end for 110 (24%) patients (p<0.001). It is important to periodically instruct type 2 diabetic patients in the proper SMBG technique in order to ensure accurate measurements. In this study it was shown that community pharmacies specialized in diabetes care can provide this service effectively.


Beyond Macromolecules: Extracellular Vesicles as Regulators of Inflammatory Diseases.
Inflammation is the defense mechanism of the immune system against harmful stimuli such as pathogens, toxic compounds, damaged cells, radiation, etc., and is characterized by tissue redness, swelling, heat generation, pain, and loss of tissue functions. Inflammation is essential in the recruitment of immune cells at the site of infection, which not only aids in the elimination of the cause, but also initiates the healing process. However, prolonged inflammation often brings about several chronic inflammatory disorders; hence, a balance between the pro- and anti-inflammatory responses is essential in order to eliminate the cause while producing the least damage to the host. A growing body of evidence indicates that extracellular vesicles (EVs) play a major role in cell-cell communication via the transfer of bioactive molecules in the form of proteins, lipids, DNA, RNAs, miRNAs, etc., between the cells. The present review provides a brief classification of the EVs followed by a detailed description of how EVs contribute to the pathogenesis of various inflammation-associated diseases and their implications as a therapeutic measure. The latter part of the review also highlights how EVs act as a bridging entity in blood coagulation disorders and associated inflammation. The findings illustrated in the present review may open a new therapeutic window to target EV-associated inflammatory responses, thereby minimizing the negative outcomes.


Mesial temporal lobe morphology in intractable pediatric epilepsy: so-called hippocampal malrotation, associated findings, and relevance to presurgical assessment.
OBJECTIVE Diagnostic criteria for hippocampal malrotation (HIMAL) on brain MRI typically include a rounded hippocampus, vertical collateral sulcus, and architectural blurring. Relationship to epileptogenesis remains speculative, and usefulness for surgical guidance is unknown. The study was performed to determine the prevalence of hippocampal rotational anomalies in a cohort of pediatric patients with intractable epilepsy undergoing evaluation for surgery and to determine the significance of this finding in the context of surgical planning. METHODS Forty-eight surgically treated children with intractable epilepsy were compared with matched healthy subjects; reviewers were blinded to surgical side. Each temporal lobe was evaluated for rounded hippocampus, blurring, vertical collateral sulcus, wide choroidal fissure, enlarged temporal horn, low fornix, hippocampal signal, and findings of hippocampal sclerosis. A mesial temporal lobe (MTL) score was calculated by summing the number of features, and the collateral sulcus angle (CSA) was measured in each temporal lobe. Surgical side, pathological diagnosis, and imaging findings elsewhere in the brain were tabulated. Presence of HIMAL, associated imaging features, and MTL score were compared between sides, between epilepsy and control groups, in relationship to side of surgery, and in relationship to postoperative outcome. RESULTS Only 3 epilepsy patients (6.2%) and no controls exhibited all 3 features of HIMAL (p = 0.12). Eight of 48 (16.7%) epilepsy versus 2 of 48 (4.6%) control subjects had both a rounded hippocampus and vertical collateral sulcus (suggesting HIMAL) (p = 0.045). In control and epilepsy subjects, most findings were more prevalent on the left, and the left CSA was more vertical (p < 0.0001). Epilepsy subjects had higher MTL scores (z = -2.95, p = 0.002) and more acute CSAs (p = 0.04) than controls. Only lateralizing raw MTL score had a significant association with surgical side (p = 0.03, OR 7.33); however, this was not significant when hippocampal sclerosis cases were excluded. HIMAL findings were more prevalent and MTL scores were higher in patients with resections involving the temporal lobes. On group analysis, HIMAL findings did not predict eventual surgical side and did not predict outcome, although the numbers are small. In 4 patients the abnormally rotated hippocampus was resected and showed hippocampal sclerosis and/or dysplastic changes on histopathology. All of these patients had a good outcome after surgery. CONCLUSIONS While increased in prevalence in children with intractable epilepsy, imaging findings of HIMAL did not have preoperative lateralizing utility in this group. Findings of HIMAL (including round hippocampus, architectural blurring, and vertical collateral sulcus) did not predict outcome after surgery, although the small number of patients with these findings limits evaluation. In the small number of patients in which the malrotated hippocampus was removed, outcome was good. Further research is needed to continue to define this association in children with intractable epilepsy, focusing on a temporal lobe cohort.


Contributions of developmental studies in the dogfish Scyliorhinus canicula to the brain anatomy of elasmobranchs: insights on the basal ganglia.
The basic anatomy of the elasmobranch brain has been previously established after studying the organization of the different subdivisions in the adult brain. However, despite the relatively abundant immunohistochemical and hodologic studies performed in different species of sharks and skates, the organization of some brain subdivisions remains unclear. The present study focuses on some brain regions in which subdivisions established on the basis of anatomical data in adults remain controversial, such as the subpallium, mainly the striatal subdivision. Taking advantage of the great potential of the lesser spotted dogfish, Scyliorhinus canicula, as a model for developmental studies, we have characterized the subpallium throughout development and postembryonic stages by analyzing the distribution of immunomarkers for GABA, catecholamines, and neuropeptides, such as substance P. Moreover, we have analyzed the expression pattern of regulatory genes involved in the regionalization of the telencephalon, such as Dlx2, Nkx2.1, and Shh, and followed their derivatives throughout development in relation to the distribution of such neurochemical markers. For further characterization, we have also analyzed the patterns of innervation of the subpallium after applying tract-tracing techniques. Our observations may shed light on postulate equivalences of regions and nuclei among elasmobranchs and support homologies with other vertebrates.


Situational panic attacks. Behavioral, physiologic, and biochemical characterization.
To investigate the pathophysiology of nonpharmacologically induced panic attacks, 18 drug-free agoraphobic patients and 13 matched healthy subjects underwent structured exposure to phobic situations. Heart rate, blood pressure, and plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG), cortisol, growth hormone, and prolactin levels were measured before, during, and after exposure. Fifteen patients experienced situational panic attacks during exposure. Panicking patients displayed significantly greater increases in heart rate but not blood pressure or plasma free MHPG or cortisol in comparison with the healthy subjects. Growth hormone and prolactin responses tended to be smaller in the patients. If brain noradrenergic hyperactivity occurs during situational panic attacks, it may be too brief or too restricted in regional localization to affect MHPG levels in plasma. Chronically recurrent attacks may cause an adaptation of neuroendocrine mechanisms activated by anxiety or stress.


[Bilateral ageusia caused by right thalamic infarction].
A 58-year-old man noticed left hemiparesis at 01:00 pm on a particular day in March 2006. Because his symptoms developed gradually, he was referred to the emergency room of our hospital at 05:00 pm and was admitted with the diagnosis of cerebral infarction. While he presented slight left hemiparesis involving the face, impairment of sensation was not apparent. Diffusion-weighted magnetic resonance imaging of the head showed a high-intensity area in the ventromedial area in the right thalamus. The patient was treated with anticoagulant and edaravone, and his symptoms resolved on hospital day 3. When he began eating, he noticed that he was unable to distinguish tastes. On day 5, we performed taste examination using a commercial kit. The taste sensation on both sides of his tongue was severely affected, while the touch sensations in the mouth and olfaction were preserved. His symptoms improved spontaneously and resolved on hospital day 15. This is the second case report of bilateral ageusia caused by right thalamic infarction. Our study indicates the importance of the right thalamus in taste sensation involving both sides of the tongue.


Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis.
Jiawei Taohe Chengqi Tang (JTCD) is a modified formulation of Traditional Chinese Medicine (TCM) known as Taohe Chengqi Decoction, which has been described in the ancient TCM literature "Treatise on Febrile Diseases". As a formula that can activate blood circulation and eliminate blood stasis and regulate Yin and Yang in traditional Chinese medicine applications, JTCD has been reported to be effective in the treatment of chronic liver disease and hepatic fibrosis (HF). The current study aimed to evaluate the effectiveness of JTCD in modulating hepatic macrophages by regulating the Notch signal pathway, and to further investigate the mechanisms underlying macrophage reprogramming that leads to HF. Molecular assays were performed using in vitro cultures of human mononuclear THP-1 cells and human-derived hepatic stellate cells LX-2. CCl4-induced mice were utilized as an in vivo model to simulate HF. Our results demonstrated that JTCD exhibited dual effects by inhibiting hepatic stellate cell (HSCs) activation and modulating the polarisation of macrophages towards the M2 phenotype while decreasing the M1 phenotype. Network pharmacological analyses and molecular docking studies revealed that the Notch signal pathway was significantly enriched and played a crucial role in the therapeutic response of JTCD against HF. Moreover, through the establishment of a co-culture model, we validated that JTCD inhibited the Notch signal pathway in macrophages, leading to alterations in macrophage reprogramming, subsequent inhibition of HSC activation, and ultimately exerting anti-HF effects. In conclusion, our findings provide solid evidence for JTCD in treating HF, as it suppresses the Notch signal pathway in macrophages, regulates macrophage reprogramming, and inhibits HSC activation.


TLR6-driven lipid droplets in Mycobacterium leprae-infected Schwann cells: immunoinflammatory platforms associated with bacterial persistence.
The mechanisms responsible for nerve injury in leprosy need further elucidation. We recently demonstrated that the foamy phenotype of Mycobacterium leprae-infected Schwann cells (SCs) observed in nerves of multibacillary patients results from the capacity of M. leprae to induce and recruit lipid droplets (LDs; also known as lipid bodies) to bacterial-containing phagosomes. In this study, we analyzed the parameters that govern LD biogenesis by M. leprae in SCs and how this contributes to the innate immune response elicited by M. leprae. Our observations indicated that LD formation requires the uptake of live bacteria and depends on host cell cytoskeleton rearrangement and vesicular trafficking. TLR6 deletion, but not TLR2, completely abolished the induction of LDs by M. leprae, as well as inhibited the bacterial uptake in SCs. M. leprae-induced LD biogenesis correlated with increased PGE(2) and IL-10 secretion, as well as reduced IL-12 and NO production in M. leprae-infected SCs. Analysis of nerves from lepromatous leprosy patients showed colocalization of M. leprae, LDs, and cyclooxygenase-2 in SCs, indicating that LDs are sites for PGE(2) synthesis in vivo. LD biogenesis Inhibition by the fatty acid synthase inhibitor C-75 abolished the effect of M. leprae on SC production of immunoinflammatory mediators and enhanced the mycobacterial-killing ability of SCs. Altogether, our data indicated a critical role for TLR6-dependent signaling in M. leprae-SC interactions, favoring phagocytosis and subsequent signaling for induction of LD biogenesis in infected cells. Moreover, our observations reinforced the role of LDs favoring mycobacterial survival and persistence in the nerve. These findings give further support to a critical role for LDs in M. leprae pathogenesis in the nerve.


Critical evaluation of oncology clinical practice guidelines.
Significant concerns exist regarding the content and reliability of oncology clinical practice guidelines (CPGs). The Institute of Medicine (IOM) report "Clinical Practice Guidelines We Can Trust" established standards for developing trustworthy CPGs. By using these standards as a benchmark, we sought to evaluate recent oncology guidelines. CPGs and consensus statements addressing the screening, evaluation, or management of the four leading causes of cancer-related mortality in the United States (lung, breast, prostate, and colorectal cancers) published between January 2005 and December 2010 were identified. A standardized scoring system based on the eight IOM standards was used to critically evaluate the methodology, content, and disclosure policies of CPGs. All CPGs were given two scores; points were awarded for eight standards and 20 subcriteria. No CPG fully met all the IOM standards. The average overall scores were 2.75 of 8 possible standards and 8.24 of 20 possible subcriteria. Less than half the CPGs were based on a systematic review. Only half the CPG panels addressed conflicts of interest. Most did not comply with standards for inclusion of patient and public involvement in the development or review process, nor did they specify their process for updating. CPGs were most consistent with IOM standards for transparency, articulation of recommendations, and use of external review. The vast majority of oncology CPGs fail to meet the IOM standards for trustworthy guidelines. On the basis of these results, there is still much to be done to make guidelines as methodologically sound and evidence-based as possible.


The effect of tourniquets on muscle enzymes during foot and ankle surgery.
The use of lower extremity tourniquets for procedures of the foot and ankle is considered routine in podiatric surgery, yet, lower extremity tourniquets are not benign. Recent publications in the orthopedic and podiatric literature report incidents of rhabdomyolysis with associated myoglobinurea as a consequence of prolonged tourniquet use. An unselected series of 40 patients undergoing a variety of surgical procedures on the foot and ankle with tourniquet control were studied. Preoperative and postoperative laboratory values were used to evaluate the effect of tourniquets on muscle enzymes during podiatric surgery.


Effects of work hour reduction on residents' lives: a systematic review.
The Accreditation Council for Graduate Medical Education implemented mandatory work hour limitations in July 2003, partly out of concern for residents' well-being in the setting of sleep deprivation. These limitations are likely to also have an impact on other aspects of the lives of residents. To summarize the literature regarding the effect of interventions to reduce resident work hours on residents' education and quality of life. We searched the English-language literature about resident work hours from 1966 through April 2005 using MEDLINE, EMBASE, and Current Contents, supplemented with hand-search of additional journals, reference list review, and review of abstracts from national meetings. Studies were included that assessed a system change designed to counteract the effects of resident work hours, fatigue, or sleep deprivation; included an outcome directly related to residents; and were conducted in the United States. For each included study, 2 investigators independently abstracted data related to study quality, subjects, interventions, and findings using a standard data abstraction form. Fifty-four articles met inclusion criteria. The interventions used to decrease resident work hours varied but included night and day float teams, extra cross-coverage, and physician extenders. Outcomes included measures of resident education (operative experience, test scores, satisfaction) and quality of residents' lives (amount of sleep, well-being). Interventions to reduce resident work hours resulted in mixed effects on both operative experience and on perceived educational quality but generally improved residents' quality of life. Many studies had major limitations in their design or conduct. Past interventions suggest that residents' quality of life may improve with work hour limitations, but interpretation of the outcomes of these studies is hampered by suboptimal study design and the use of nonvalidated instruments. The long-term impact of reducing resident work hours on education remains unknown. Current and future interventions should be evaluated with more rigorous methods and should investigate links between residents' quality of life and quality of patient care.


Perceptual measurement of articulatory goodness in young children: Relationships with age, speech sound acquisition, and intelligibility.
Speech language pathologists regularly use perceptual methods in clinical practice to assess children's speech. In this study, we examined relationships between measures of speech intelligibility, clinical articulation test results, age, and perceptual ratings of articulatory goodness for children. We also examined the extent to which established measures of intelligibility and clinical articulation test results predicted articulatory goodness ratings, and whether goodness ratings were influenced by intelligibility. A sample of 164 (30-47 months) typically developing children provided speech samples and completed a standardised articulation test. Single word intelligibility scores and ratings of articulatory goodness were gathered from 328 naïve listeners; scores on a standardised articulation test were obtained from each child. Bivariate Pearson correlation, linear regression, and linear mixed effects modelling were used for analysis. Results showed that articulatory goodness ratings had the highest correlation with intelligibility, followed by age, followed by articulation score. Age and clinical articulation scores were both significant predictors of goodness ratings, but articulation scores made only a small contribution to prediction. Articulatory goodness ratings were substantially lower for unintelligible words compared to intelligible words, but articulatory goodness scores increased with age at the same rate for unintelligible and intelligible words. Perceptual ratings of articulatory goodness are sensitive to developmental changes in speech production (regardless of intelligibility) and yield a different kind of information than clinical articulation scores from standardised measures.


β-Connectin studies by small-angle x-ray scattering and single-molecule force spectroscopy by atomic force microscopy.
The three-dimensional structure and the mechanical properties of a β-connectin fragment from human cardiac muscle, belonging to the I band, from I(27) to I(34), were investigated by small-angle x-ray scattering (SAXS) and single-molecule force spectroscopy (SMFS). This molecule presents an entropic elasticity behavior, associated to globular domain unfolding, that has been widely studied in the last 10 years. In addition, atomic force microscopy based SMFS experiments suggest that this molecule has an additional elastic regime, for low forces, probably associated to tertiary structure remodeling. From a structural point of view, this behavior is a mark of the fact that the eight domains in the I(27)-I(34) fragment are not independent and they organize in solution, assuming a well-defined three-dimensional structure. This hypothesis has been confirmed by SAXS scattering, both on a diluted and a concentrated sample. Two different models were used to fit the SAXS curves: one assuming a globular shape and one corresponding to an elongated conformation, both coupled with a Coulomb repulsion potential to take into account the protein-protein interaction. Due to the predominance of the structure factor, the effective shape of the protein in solution could not be clearly disclosed. By performing SMFS by atomic force microscopy, mechanical unfolding properties were investigated. Typical sawtooth profiles were obtained and the rupture force of each unfolding domain was estimated. By fitting a wormlike chain model to each peak of the sawtooth profile, the entropic elasticity of octamer was described.


Beta-casomorphin-7 prevents epithelial-mesenchymal transdifferentiation of NRK-52E cells at high glucose level: Involvement of AngII-TGF-β1 pathway.
Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, β-casomorphin-7 may exert anti-fibrotic activities in diabetic rats. However, the role of β-casomorphin-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, this study was designed to investigate the protective effect of β-casomorphin-7 on epithelial-mesenchymal transition (EMT) of NRK-52E cells treated under hyperglycemic condition and to explore the possible mechanism. NRK-52E cells were cultured in high glucose (30 mM) for 3 days. Different concentrations of β-casomorphin-7, naloxone (antagonist of opioid receptor) and losartan (antagonist of angiotensin II type I receptor) were added in the culture. Expression of α-smooth muscle actin (α-SMA), E-cadherin, vimentin and cytokeratin19 mRNA were determined by real-time PCR. Protein levels of E-cadherin and α-SMA were analyzed by Western blotting. The concentrations of angiotensin (Ang) II and transforming growth factor β1 (TGF-β1) in the culture medium were determined. High glucose-induced up-regulation of vimentin mRNA and α-SMA mRNA and protein were significantly inhibited by β-casomorphin-7. On the contrary, high glucose-induced down-regulation of cytokeratin19 mRNA and E-cad mRNA and protein was significantly reversed by β-casomorphin-7. β-casomorphin-7 significantly alleviate high glucose induced increase of AngII and TGF-β1 in the culture. Moreover, losartan significantly attenuated the expression of TGF-β1 and EMT of NRK-52E cells treated under hyperglycemic condition. But naloxone did not affect the EMT of NRK-52E cells treated by high glucose and β-casomorphin-7. We demonstrate that β-casomorphin-7 has the potential to inhibit high glucose-induced renal proximal tubular EMT partly by modulating AngII-TGF-β1 pathway, but not by opioid receptor.


[The hospitalization experience explained by the child himself].
This study, was accomplished with 20 school-age children hospitalized in pediatric units. The goals were: how children expressed their perception of the illness and the hospitalization; what sources were available to obtain knowledge about their experience of illness and hospitalization and what were their interest and concerns.


Intratympanic corticosteroids for sudden idiopathic sensorineural hearing loss.
To determine whether instillation of intratympanic steroids is effective in the treatment of sudden idiopathic sensorineural hearing loss. A retrospective chart review of all patients who underwent intratympanic steroid treatment (methylprednisolone and/or dexamethasone) between 1996 and 2002 at a tertiary care university otology clinic. Thirty-three patients were identified, of which 26 met inclusion criteria for having an idiopathic hearing loss. Pretreatment and posttreatment pure-tone audiograms and speech discrimination scores were compared. Overall, there was a 27.2 +/- 5.7 dB improvement in the pure-tone thresholds and a 25.4 +/- 6.2% improvement in speech discrimination scores. Those treated within 10 days of onset had a statistically significant better outcome than those treated after 10 days. No adverse reactions or complications were reported. Instillation of intratympanic steroids represents a safe and potentially effective treatment of sudden idiopathic sensorineural hearing loss.


First-in-human prediction of chronic pain state using intracranial neural biomarkers.
Chronic pain syndromes are often refractory to treatment and cause substantial suffering and disability. Pain severity is often measured through subjective report, while objective biomarkers that may guide diagnosis and treatment are lacking. Also, which brain activity underlies chronic pain on clinically relevant timescales, or how this relates to acute pain, remains unclear. Here four individuals with refractory neuropathic pain were implanted with chronic intracranial electrodes in the anterior cingulate cortex and orbitofrontal cortex (OFC). Participants reported pain metrics coincident with ambulatory, direct neural recordings obtained multiple times daily over months. We successfully predicted intraindividual chronic pain severity scores from neural activity with high sensitivity using machine learning methods. Chronic pain decoding relied on sustained power changes from the OFC, which tended to differ from transient patterns of activity associated with acute, evoked pain states during a task. Thus, intracranial OFC signals can be used to predict spontaneous, chronic pain state in patients.


Does acupuncture have a positive effect on school success in children?
To evaluate school success in pediatric patients undergoing acupuncture treatment for various indications. The grades achieved during both school terms by children undergoing acupuncture treatment for various indications at the pediatric outpatient clinic of Ulus State Hospital were analyzed. Exam grades in mathematics, social studies, and Turkish was compared between the first and the second terms. Forty children were included in the study, with 22 male and 18 female, and their average age was 11.1 years. These patients were undergoing acupuncture treatment for attention deficit-hyperactivity disorder (ADHD), enuresis nocturna, migraine, obesity, atopic dermatitis, alopecia areata, and Tourette's syndrome. Treatments were done at the beginning of the second term. Four of the 25 patients with ADHD had borderline intelligence quotients. The report cards of all 40 patients were examined, and their grades in the first and the second school term were compared. There was a statistically significant increase in the grades obtained in mathematics, social studies, and Turkish (P < 0.005) by the students from the first to the second school term. When 4 ADHD patients with borderline deficiency in intelligence were excluded, and the grades among the 21 patients with ADHD were compared for both terms, there was also a statistically significant increase in mathematics, social studies, and Turkish grades (P < 0.05). Acupuncture contributed to the academic success of the children who underwent acupuncture treatment for their primary symptoms.


Low health literacy: a barrier to effective patient care.
Health literacy is defined in the U.S. Department of Health and Human Services initiative Healthy People 2010 as "the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions." It is estimated that 48.8 million Americans are functionally illiterate, making health literacy a major obstacle for providing health care. Although communicating with physicians is a small component of the tasks that are incorporated in a definition of health literacy, it remains the most important aspect of this concept contributing to personal health. Primary care clinics within the Sioux Falls area were provided with both English and Spanish patient education brochures on communicating with physicians. A survey was then distributed to determine how low health literacy was affecting physician practices and what they were doing to remove the obstacles that health literacy presented. Physicians were asked to evaluate the multiple skills and competencies required by patients to access health care services and resources they use to assist patients. A total of 77 surveys were distributed. Twenty-two (28.6 percent) were returned. Of the physicians who returned the survey, the majority (77 percent) thought that low health literacy is a moderate obstacle in their practices. Several physicians stated that their offices had at least one method in place to assist those with low health literacy, but none of them were using a formal test of health literacy. Only six physicians could name a community resource to assist patients with low health literacy. Low health literacy is an unavoidable barrier to effective patient care for physicians across the country. If the full spectrum definition of health literacy is understood by physicians and carefully considered in the context of their own practices, it is likely they would come to the realization that health literacy is a greater obstacle to providing health care than they previously considered. In order to communicate more effectively and better serve our patients, we need to resist stereotyping patients when estimating (e.g., over estimating or under estimating) their health literacy. We also need to identify educational resources and methods of communication that will ease the burden of health illiteracy. With nearly half of patients having low health literacy nationwide, it is essential to understand health literacy and acknowledge this problem in all of our practices.


Prevention of Postoperative Complications by Prepectoral versus Subpectoral Breast Reconstruction: A Systematic Review and Meta-Analysis.
Implant-based breast reconstruction has evolved over time. However, the effects of prepectoral breast reconstruction (PBR) compared with those of subpectoral breast reconstruction (SBR) have not been clearly defined. Therefore, this study aimed to compare the occurrence of surgical complications between PBR and SBR to determine the procedure that is effective and relatively safe. The PubMed, Cochrane Library, and EMBASE databases were searched for studies published until April of 2021 comparing PBR and SBR following mastectomy. Two authors independently assessed the risk of bias. General information on the studies and surgical outcomes were extracted. Among 857 studies, 34 and 29 were included in the systematic review and meta-analysis, respectively. Subgroup analysis was performed to clearly compare the results of patients who underwent postmastectomy radiation therapy. Pooled results showed that prevention of capsular contracture (OR, 0.57; 95% CI, 0.41 to 0.79) and infection control (OR, 0.73; 95% CI, 0.58 to 0.92) were better with PBR than with SBR. Rates of hematoma, implant loss, seroma, skin-flap necrosis, and wound dehiscence were not significantly different between PBR and SBR. PBR considerably improved postoperative pain, BREAST-Q score, and upper arm function compared with SBR. Among postmastectomy radiation therapy patients, the incidence rates of capsular contracture were significantly lower in the PBR group than in the SBR group (OR, 0.14; 95% CI, 0.05 to 0.35). The results showed that PBR had fewer postoperative complications than SBR. The authors' meta-analysis suggests that PBR could be used as an alternative technique for breast reconstruction in appropriate patients.


[Systemic changes of the immune system in patients with Alzheimer's dementia].
The etiology of Alzheimer's disease (AD) is still unknown. Recent investigations have shown that immune and inflammatory mechanisms could be of importance in the pathophysiology of AD. In this study 10 different immune parameters were measured to further investigate immunological changes in AD. In 30 randomized patients with AD (20 females and ten males aged 74.5 +/- 6.5 years) as well as 13 controls aged 70.7 +/- 8.4 years, mostly relatives of the patients, all free of acute infection, serum concentrations of IgA, IgG, IgM, C3, C4, circulating immune complexes, sCD23, cardiolipin and the soluble cytokine receptors interleukin 2-receptor (sIL2-R) and tumor necrosis factor-receptor (sTNF-R) were measured. Diagnosis of AD was made according to NINCDS/ ADRDA criteria. The degree of dementia was determined by Mini-Mental-State-Examination (MMSE). Compared to the control group, patients with AD had significantly increased IgA (369,3 +/- 160,9 mg/dl vs 253.5 +/- 101.8 mg/dl [P = 0.02]), sCD23 [207.4 +/- 217.7 I. U./ml vs 80.6 +/- 35.5 I. U./ml [P = 0.004]), sIL2-R (829.6 +/- 742.1 I. U./ml vs 299.7 +/- 168.5 I. U./ml [P = 0.001]) and sTNF-R (4.6 +/- 2.0 I. U./ml vs 2.9 +/- 1.1 I. U./ml [P = 0.001]) levels. A negative correlation was seen between MMSE and sTNF-R (r = -0.34; P < 0.05). These findings indicate a chronic state of immune activation in AD and support the hypothesis of immune mediated mechanisms as part of the pathogenesis of AD. Prospective studies of the effect of anti-inflammatory drugs on the progression of AD will be needed.


Breastmilk, breastfeeding, and transmission of viruses to the neonate.
The benefits of breast milk have been well delineated, and breastfeeding should be encouraged whenever possible. However, the potential transmission of HIV-1, HTLV-1, and possibly HTLV-II warrant the recommendation that women in industrialized countries who are infected with these viruses not breastfeed their infants. These recommendations reflect what is currently known about the risks of viral transmission through breastfeeding; ongoing and future studies may provide additional data, enabling a better definition of the precise risks and factors associated with the transmission of viruses through breastfeeding.


Functional outcomes after total claviculectomy as a salvage procedure. A series of six cases.
Total claviculectomy has been used for the treatment of tumor, infection, nonunion, and vascular compromise. Given its limited indications, few reports on the outcome after claviculectomy exist. The purpose of the present study was to evaluate the function of the shoulder, with use of a modern scoring system, after total claviculectomy. A retrospective review of the records of six patients who had undergone unilateral claviculectomy was performed after an average duration of follow-up of 5.7 years. The indication for surgery had been an infection at the site of a clavicular nonunion for three patients, nonunion with subclavian vein compression for two, and pain after a failed medial clavicular excision for one. The preoperative and postoperative evaluations included testing of the range of motion, strength, and stability as well as determination of the American Shoulder and Elbow Surgeons score on the basis of a functional questionnaire. Range of motion was improved slightly or unchanged following claviculectomy. The mean American Shoulder and Elbow Surgeons score improved from 18 (range, 5 to 35) preoperatively to 88 (range, 75 to 95) postoperatively. The mean pain level (with 0 indicating no pain and 10 indicating the worst pain) decreased from 9.5 preoperatively to 1.5 postoperatively. Postoperatively, strength testing showed improvement from grade 4- (of 5) to 5 in all planes tested except extension (in which it remained at grade 4). Patient satisfaction was high, with a mean of 9.0 on a 10-point scale. There were five complications, including one subclavian vein laceration requiring vascular repair, two deep infections, and two superficial infections. Despite a high complication rate, the functional outcomes following claviculectomy were good in this group of six patients. Total claviculectomy may be a useful salvage procedure for clinical situations in which the restoration of normal clavicular osseous anatomy is impossible. Patients can expect acceptable pain relief and few or no deficits in activities of daily living. Therapeutic Level IV.


Use of pharmacokinetic/pharmacodynamic systems analyses to inform dose selection of tedizolid phosphate.
In the Staphylococcus aureus neutropenic murine thigh-infection model, the ratio of the free area under the 24-hour concentration-time curve to the minimum inhibitory concentration (fAUC/MIC) was found to be the pharmacodynamic index most closely linked to bacterial effect, with a ratio of approximately 50 producing a static effect. Further work was undertaken in neutropenic versus non-neutropenic animals. The presence of granulocytes increased the activity of tedizolid considerably, 25-fold on average, and maximal effect was achieved at an exposure equivalent to approximately 200 mg tedizolid phosphate per day in humans (dosing regimen used in phase 2 and 3 clinical trials). The fAUC/MIC was also found to be the pharmacodynamically linked variable in the S. aureus neutropenic murine pneumonia model; the fAUC/MIC ratio required for a static effect was approximately 20. Pharmacokinetic (PK) data demonstrate that tedizolid penetrates well into the epithelial lining fluid (ELF) of the lung. Data from the pneumonia infection model and ELF penetration PK study support exploring its use in pneumonia.