Strategic Litigation to Advance Public Health.
The HIV movement has relied on strategic litigation as an important tool to develop and enforce legal protections critical to health. This experience contains lessons on the potential of strategic litigation to advance public health more generally. Beyond impacting laws and policies, strategic litigation can change practice, breathing life into existing legal rules never implemented. While cases may target a particular law, policy, or practice, indirect impacts beyond a particular court decision on future cases, other branches of government, and the public record may be just as important. Each case is only one step towards change, and a judgment can be helpful in laying groundwork and in other contexts. Strategic litigation can also shape public discourse on issues relevant to health through development of the court's record, integration of expert testimony, and the use of media advocacy. It provides a means to harness the law's potential to construct reality and historical truth, creating an opening for the narratives of marginalized and affected communities. Strategic litigation and social movements can also have a reciprocal relationship, strengthening each other. Connection to a movement gives a case a political dimension, and social movements can assist in identifying issues, supporting clients, mobilizing communities, engaging media, and following up on the implementation of judgments. Strategic litigation, in turn, can galvanize social movements, creating events around which mobilization and media engagement can occur and facilitating coalition-building and the development of leadership.


Appearance of nuclear protease activity after embryonal carcinoma cells undergo differentiation.
Proteolytic systems are involved via multiple mechanisms in the regulation of gene expression, including tightly controlled metabolism of transcription factors. In this study, we demonstrate that differentiation of mouse embryonal carcinoma cells to parietal endoderm-like cells is accompanied by the appearance of nuclear protease activity. Interestingly, this nuclear-associated protease activity is not observed in the visceral endoderm-like cell line, PSA-5E, or in the differentiated cells derived from both mouse embryonic stem cells and the human embryonal carcinoma cell line NT2/D1. We also determined that this differentiation-associated nuclear protease activity causes proteolysis of a wide range of different transcription factors, including ATF-1, Sp1, NF-YA and B, and octamer-binding proteins Oct-1 and Oct-3. Based on the effects of specific inhibitors, the nuclear protease(s) can be classified as a cysteine protease; however, lack of inhibition by calpastatin and EGTA distinguishes this protease activity from the calpain family of proteases. Given the properties of the differentiation-associated nuclear protease(s), we discuss the possibility that this protease(s) plays a role in the metabolism of transcription factors during the differentiation of specific embryonic cells.


Anti-GITR antibodies--potential clinical applications for tumor immunotherapy.
Since the development of the first vaccines, modern medicine has been consistently aiming to improve the efficacy of immune responses. Traditionally, adjuvants have been used as non-specific immune modulators to enhance recognition and activation against a desired antigen. By providing 'danger' signals to the immune system, adjuvants activate innate immunity, which enhances the development of protective and therapeutic adaptive immune responses. The newest class of immune modulators bypasses the innate response and targets cells of the adaptive response directly. Targeted immunomodulatory therapy is focused primarily on the activation of costimulatory receptors (eg, 4-1BB, OX40 and GITR [glucocorticoid-induced TNF receptor-related gene]) or the blockade of co-inhibitory receptors (eg, CTLA-4, PD-1 and PD-L1) on T-cells during activation and/or effector responses. With promising clinical results obtained to date, immunomodulatory therapy is becoming an integral part of immunotherapeutic approaches. The modulation of GITR is listed as one of the top 25 most promising research areas by the NCI, and has demonstrated potential in both antitumor and vaccine settings. This review discusses the role of GITR as a potential target for immunomodulatory therapy, as well as the research involved in understanding the mechanisms of anti-GITR therapy and current progress in translation into the clinic.


The synthesis and characterization of four new uranium(IV) chlorophosphates: UCl₄(POCl₃), [U₂Cl₉][PCl₄], UCl₃(PO₂Cl₂), and U₂Cl₈(POCl₃).
The new uranium(IV) chlorophosphate compounds UCl4(POCl3) and [U2Cl9][PCl4] have been synthesized by the solid-state reactions of U, P2O5, and PCl5 at 648 K; the compounds UCl3(PO2Cl2) and U2Cl8(POCl3) have been synthesized at 648 K with the same reactants plus added S. Their structures are, respectively, chainlike, a simple salt, three-dimensional, and sheetlike. From ab initio calculations, U2Cl8(POCl3) and UCl3(PO2Cl2) are found to be ferromagnetic, whereas UCl4(POCl3) is found to be antiferromagnetic. U2Cl8(POCl3) is a strong metal, whereas UCl3(PO2Cl2) is a weaker metal. In contrast, UCl4(POCl3) has a finite band gap, with a value of 0.35 eV.


Calcineurin inhibitor-free immunosuppressive regimen in type 1 diabetes patients receiving islet transplantation: single-group phase 1/2 trial.
Our final objective is to develop an adoptive therapy with tolerogenic donor-specific type 1 T regulatory cells for patients with type 1 diabetes undergoing islet transplantation. The achievement of this objective depends on the availability of an immunosuppressive treatment compatible with the survival, function, and expansion of type 1 T regulatory cells. For this purpose, we designed a single-group, phase 1 to 2 trial with an immunosuppression protocol including: (i) rapamycin treatment before the first islet infusion (starting ≥ 30 days before transplantation); (ii) induction therapy with anti-thymocyte globulin (ATG) instead of anti-interleukin-2Ra monoclonal antibody (after the first islet infusion only); (iii) short-term treatment with steroids and interleukin-1Ra (right before and for 2 weeks after each infusion); rapamycin+mycophenolate mofetil treatment as maintenance therapy. The target enrollment was 10 patients. Ten of 15 patients who started the pretransplant rapamycin treatment completed it. Nine of 10 patients did not complete the induction therapy with ATG, and three of 10 required adaptation of maintenance immunosuppression caused by side effects. Four of 10 patients acquired insulin independence which can be maintained up to year 3 after last infusion. All six other patients have lost their graft, and the early graft loss was associated with lower dose of ATG during induction. This protocol resulted feasible, safe but less efficient in maintaining graft survival during the time than other T-cell depletion-based protocols. An adequate induction at the first infusion should be considered to improve the overall clinical outcome.


In vitro susceptibility of oral Candida albicans strains to different pH levels and calcium hydroxide saturated aqueous solution.
Candida albicans is present in the oral cavity and in the whole digestive tract of humans and other animals, being frequently related to endodontic treatment failure. The present study determined the incidence of C. albicans in the oral cavity and the susceptibility of isolates to different pH values and saturated calcium hydroxide aqueous solution at pH 12.5. Sixty-five patients attending the Endodontic Clinic at the Sagrado Coração University participated in the study. The collected samples were cultivated in selective media for C. albicans and the isolates were tested in terms of resistance to both alkaline pH and saturated aqueous solution of calcium hydroxide. In relation to time variables, yeast viability was assessed by the Sabouraud's agar culture and fluorescein diacetate and ethidium bromide fluorescent staining method. Results from the different pHs and experimental times, including those from different techniques measuring fungal viability, were compared using the chi-square and Fisher's exact tests (α=0.05). The yeasts became completely inviable after 48 h of contact with the calcium hydroxide solution. On the other hand, when exposed to the alkaline culture broth, the yeasts were found to be viable at pHs 9.5 and 10.5 for up to 7 days. In conclusion, C. albicans can only be completely inhibited by direct contact with saturated calcium hydroxide aqueous solution after 48 h of exposure.


Repeated local emergence of carbapenem-resistant Acinetobacter baumannii in a single hospital ward.
We recently reported a dramatic increase in the prevalence of carbapenem-resistant Acinetobacter baumannii infections in the intensive care unit (ICU) of a Vietnamese hospital. This upsurge was associated with a specific oxa23-positive clone that was identified by multilocus VNTR analysis. Here, we used whole-genome sequence analysis to dissect the emergence of carbapenem-resistant A. baumannii causing ventilator-associated pneumonia (VAP) in the ICU during 2009-2012. To provide historical context and distinguish microevolution from strain introduction, we compared these genomes with those of A. baumannii asymptomatic carriage and VAP isolates from this same ICU collected during 2003-2007. We identified diverse lineages co-circulating over many years. Carbapenem resistance was associated with the presence of oxa23, oxa40, oxa58 and ndm1 genes in multiple lineages. The majority of resistant isolates were oxa23-positive global clone GC2; fine-scale phylogenomic analysis revealed five distinct GC2 sublineages within the ICU that had evolved locally via independent chromosomal insertions of oxa23 transposons. The increase in infections caused by carbapenem-resistant A. baumannii was associated with transposon-mediated transmission of a carbapenemase gene, rather than clonal expansion or spread of a carbapenemase-harbouring plasmid. Additionally, we found evidence of homologous recombination creating diversity within the local GC2 population, including several events resulting in replacement of the capsule locus. We identified likely donors of the imported capsule locus sequences amongst the A. baumannii isolated on the same ward, suggesting that diversification was largely facilitated via reassortment and sharing of genetic material within the localized A. baumannii population.


Developing genomic resources in two Linum species via 454 pyrosequencing and genomic reduction.
Recent advances in next-generation DNA sequencing (NGS) have enhanced the development of genomic resources such as contigs or single-nucleotide polymorphisms (SNPs) for evolutionary studies of a nonmodel species with a complex and unsequenced genome. This study presents an application of a NGS technique in combination with genomic reduction and advanced bioinformatics tools to identify contigs and SNPs from multiple samples of two Linum species. A full Roche 454 GS FLX run of 16 diverse Linum samples representing cultivated flax (Linum usitatissimum L.) and its wild progenitor (Linum bienne Mill.) generated approximately 1.6 million sequence reads with a total length of 498 Mbp. Application of the computational pipeline de novo identification of alleles identified 713 contigs and 1067 SNPs. A blast search revealed alignments of all 713 contigs with 491 existing Linum scaffolds and gene annotations associated with 512 contigs. Sanger sequencing confirmed 95% of 79 selected contigs and 94% of 272 SNPs and identified 211 new SNPs and 19 new indels. The scored 454 SNP data were highly imbalanced for assayed samples. These findings not only are useful for evolutionary studies of Linum species but also help to illustrate the utility of NGS technologies in SNP discovery for nonmodel organisms.


Mechanisms of cranial placode assembly.
Cranial placodes are transient ectodermal structures contributing to the paired sensory organs and ganglia of the vertebrate head. Placode progenitors are initially spread and intermixed within a continuous embryonic territory surrounding the anterior neural plate, the so-called pan-placodal region, which progressively breaks into distinct and compact placodal structures. The mechanisms driving the formation of these discrete placodes from the initial scattered distribution of their progenitors are poorly understood, and the implication of cell fate changes, local sorting out or massive cell movements is still a matter of debate. Here, we discuss different models that could account for placode assembly and review recent studies unraveling novel cellular and molecular aspects of this key event in the construction of the vertebrate head.


Reconfigurable Photonic Crystal Reversibly Exhibiting Single and Double Structural Colors.
Unlike absorption-based colors of dyes and pigments, reflection-based colors of photonic crystals, so called "structural colors", are responsive to external stimuli, but can remain unfaded for over ten million years, and therefore regarded as a next-generation coloring mechanism. However, it is a challenge to rationally design the spectra of structural colors, where one structure gives only one reflection peak defined by Bragg's law, unlike those of absorption-based colors. Here, we report a reconfigurable photonic crystal that exhibits single-peak and double-peak structural colors. This photonic crystal is composed of a colloidal nanosheet in water, which spontaneously adopts a layered structure with single periodicity (407 nm). After a temperature-gradient treatment, the photonic crystal segregates into two regions with shrunken (385 nm) and expanded (448 nm) periodicities, and thus exhibits double reflection peaks that are blue- and red-shifted from the original one, respectively. Notably, the transition between the single-peak and double-peak states is reversible.


Less is more? Antibiotic duration and outcomes in Fournier's gangrene.
Antibiotic management of Fournier's gangrene (FG) is without evidence-based guidelines and is based on expert opinion. The effect of duration of antibiotic therapy on outcomes in FG is unknown. A retrospective review was performed of FG patients from 2012 to 2015 at a single institution. Patients were managed by our institutional practice of complete primary wound closure as possible, with antibiotic duration according to physician judgment. Patients were stratified into multiple durations of antibiotic administration. Overall, 168 patients with FG were included. When examining multiple stratifications of antibiotic therapy of 7 days or less, 8 days to 10 days, 11 days to 14 days, or 15 days or more of antibiotics, there was no significant difference in mortality (p = 0.11), primary closure (p = 0.75), surgical site infection (SSI) (p = 0.52), or Clostridium difficile infection (p = 0.63). There were no cases of recurrent FG in any antibiotic stratification. Mortality was not increased (p = 1.00) and ability to achieve primary closure was not decreased (p = 0.08) with initial antibiotic therapy exclusive of cultured organisms. Shorter antibiotic courses for patients in whom source control is obtained and initial antibiotic selection exclusive of many resistant organisms were not associated with worse outcomes in FG. Therapeutic, level IV.


Incidence and implications of altered semen quality on family planning.
Alterations in the expression of the human genome, or interference with its products, can be induced in the male reproductive system by chemicals mimicking or antagonizing naturally occurring hormones. Opportunities exist for disruption at the hypothalamus, pituitary and testis levels. Recent concerns generated by the increased incidence of testicular cancer, congenital anomalies of the male genitalia and possible alterations in human semen quality have been linked to the environment. The report by Carlsen in 1992 [1] suggested that semen quality has deteriorated over the past six decades. More recent reports suggest that the decline may be globally non-uniform and regional in nature. The effects of any such declines upon overall pregnancy rates are generally unknown, although some studies have attempted to address them. A preliminary review of the impact of a small decrease in sperm concentrations suggests that a directly measurable reduction in fecundity does not occur, but that future problems could be anticipated. Decrements in semen quality will alter the epidemiological probabilities of pregnancy due to coitus on different cycle days and may thereby change the duration of the fertile time. Current understanding of the implications of altered semen quality on relative fertility is not sufficient to change our current teaching and practice of NFP.


Comparison of performances of two commercially available tests, a PCR assay and a ligase chain reaction test, in detection of urogenital Chlamydia trachomatis infection.
The diagnostic performance of a PCR test (Roche Cobas Amplicor CT/NG Test) and that of a ligase chain reaction (LCR) test (Abbott LCx Chlamydia trachomatis assay) were compared by using endocervical and urethral swab specimen culture as a reference test. First-void urine (FVU) and endocervical and urethral swab specimens were collected from 1,015 unselected patients attending a sexually transmitted disease clinic and a clinic for adolescents in Helsinki, Finland. Chlamydia trachomatis was cultured from samples from the endocervix or urethra. PCR was performed with fresh and frozen urine and the culture transport medium. LCR was performed with fresh and frozen urine and LCx swab transport medium. Diagnostic consistency and diagnostic accuracy were statistically tested. The test results were identical for 984 patients (97%). Discrepant results were observed for 31 patients. Overall, LCR and PCR showed excellent kappa coefficients of consistency for both swab and FVU specimens (0.93 and 0.95, respectively). Sixty-one patients (6%) were culture positive. Testing of FVU by LCR or PCR increased the overall positivity rates to 7.0 and 7.7%, respectively. While PCR of FVU detected the greatest number of C. trachomatis infections (sensitivity, 96.1%), for some PCR-positive FVU specimens the results could not be confirmed (specificity, 99.6%). PCR and LCR were more sensitive than culture (sensitivities, 92 and 93% versus 79% for culture) in the diagnosis of genital C. trachomatis infection. In conclusion, both tests can be recommended for use in the clinical laboratory and for the screening of asymptomatic C. trachomatis infections.


Verified hormone therapy improves episodic memory performance in healthy postmenopausal women.
Studies of hormone therapy (HT) and cognition have yielded conflicting results. The aim of this observational study was to examine the effect of estradiol, via serum verified HT (estradiol, estriol, progesterone) and endogenous estradiol, on 108 healthy postmenopausal women's cognitive performance. The results demonstrated that the 43 HT-users performed at a significantly higher level than non-users on episodic memory tasks and on a verbal fluency task, whereas HT-users and non-users did not differ on tasks assessing semantic memory and spatial visualization. In addition, there was a positive relationship between serum estradiol level and episodic memory performance, indicating that postmenopausal HT is associated with enhanced episodic memory and verbal fluency, independent of age and education. These observational results suggest that HT use may be sufficient to exert small, yet positive effects on female sensitive cognitive tasks. Hormone therapy compliance and formulation is discussed as confounding factors in previous research.


Multimedia electronic medical record systems.
A wide range of imaging technologies are becoming increasingly important to the practice of medicine. In addition, many medical specialties are highly visual, independent of their use of new imaging modalities. Because today's medical record contains text, images, and physiologic signals, it is inherently multimedia in nature. However, most electronic medical record systems handle only the textual portion of the patient record, resulting in a fragmentation of the database that physicians need to make timely, effective clinical decisions. Advances in database-, storage-, data-compression, and networking technologies will facilitate the development of multimedia electronic medical record systems for the 21st century. These systems will become widely used over the next decade, and in addition to enhancing patient care, will also present new opportunities for using clinical imaging data for biomedical research and education.


Machine Learning models for detection and assessment of progression in Alzheimer's disease based on blood and cerebrospinal fluid biomarkers.
Machine-learning techniques were applied to human blood plasma and cerebrospinal fluid (CSF) biomarker data related to cognitive decline in Alzheimer's Disease (AD) patients available via Alzheimer Disease Neuroimaging Initiative (ADNI) study. We observed the accuracy of AD diagnosis is greatest when protein biomarkers from cerebrospinal fluid are combined with plasma proteins using Support Vector Machines (SVM); this is not improved by adding age and sex. The area under the receiver operator characteristic (ROC) curve for our model of AD diagnosis based on a full (unbiased) set of plasma proteins was 0.94 in cross-validation and 0.82 on an external validation (test) set. Taking plasma in combination with CSF, the model reaches 0.98 area under the ROC curve on the test set. Accuracy of prediction of risk of mild cognitive impairment progressing to AD is the same for blood plasma biomarkers as for CSF and is not improved by combining them or adding age and sex as covariates.Clinical relevance- The identification of accurate and cost-effective biomarkers to screen for risk of developing AD and monitoring its progression is crucial for improved understanding of its causes and stratification of patients for treatments under development. This paper demonstrates the feasibility of AD detection and prognosis based on blood plasma biomarkers.


Anterior cervical discectomy, drainage and non-instrumented cortico-cancellous allograft fusion: a treatment option for ventral cervical spinal epidural abscess.
Ventral cervical spinal epidural abscess is a very rare clinical condition with a relatively high morbidity and mortality. Due to the paucity of reported cases there is heterogeneity and no clear "gold standard" in the treatment of these patients. The authors report four consecutive patients with ventral cervical spinal epidural abscess treated with anterior cervical discectomy, abscess drainage and original non-instrumented cortico-cancellous allograft spinal fusion. The authors retrospectively reviewed a series of four patients treated for ventral cervical epidural spinal abscess. All patients were treated with an urgent operation. Anterior cervical discectomy, abscess drainage, and non-instrumented cortico-cancellous allograft spinal fusion followed by cervical immobilization and systemic antibiotic treatment were utilized. The bone fusion occurred within a mean of 3.5 months of follow-up. No significant radiologic or clinical evidence of graft subsidence was noted after a minimum of 2.5 years follow-up. All patients resolved infection and were neurologically intact. No complications of treatment were noted. Urgent operative treatment with anterior cervical discectomy, abscess drainage and non-instrumented cortico-cancellous allograft spinal fusion, followed by immobilization and the appropriate systemic antibiotic treatment is an effective original modification for the treatment and resolution of ventral cervical epidural spinal abscess.


Stimulated Emission Depletion (STED) Imaging of Clathrin-Mediated Endocytosis in Living Cells.
The recent development of probes and labeling strategies for multicolor super-resolution imaging in living cells allows cell biologists to follow cellular processes with unprecedented details. Here we describe how to image endocytic events at the plasma membrane of living cells using commercial (Leica, Abberior Instruments) or custom built STED microscopes.


SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin.
Trichloroethylene (TCE) is an occupational and environmental chemical that can cause severe hepatotoxicity. While our previous studies showed that the phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis, the molecular mechanisms remain elusive. Using quantitative phosphoproteomic analysis, we report here that nucleolin is a SET-regulated phosphoprotein in human liver HL-7702 cells. Functional analysis suggested that SET promoted dephosphorylation of nucleolin, decreased its binding to its transcriptional activator, c-myc, and upregulated nucleolin expression in TCE-treated cells. Importantly, TCE-induced hepatocyte apoptosis was significantly attenuated when nucleolin was downregulated with specific siRNAs. These findings indicate that TCE may induce hepatocyte apoptosis via SET-mediated dephosphorylation and overexpression of nucleolin.


Covalent binding of oxidative biotransformation intermediates is associated with halothane hepatotoxicity in guinea pigs.
In vivo covalent binding of halothane biotransformation-reactive intermediates to hepatic protein and lipid was examined in association with the subsequent development of hepatic necrosis in the guinea pig. Oxidative halothane biotransformation was inhibited by the use of deuterated halothane, whereas reductive metabolism was enhanced by low inspired oxygen concentrations. Male outbred Hartley guinea pigs (n = 8) were exposed to either 1% (v/v) halothane or deuterated halothane--with a fractional inspired O2 concentration (FIO2) of 0.40 or 0.10--for 4 h. Livers removed from half of the animals immediately after anesthesia were evaluated for organic fluorine bound to protein and lipid. The remaining animals were evaluated for a hepatotoxic response up to 96 h after exposure. Only guinea pigs that received 1% halothane at an FIO2 of 0.40 had centrilobular necrosis develop with significantly increased plasma alanine aminotransferase activities. All other treatment conditions significantly reduced oxidative halothane biotransformation, as indicated by decreased plasma trifluoroacetic acid concentrations. These reductions were associated with a significant decrease in organic fluorine bound to hepatic proteins. An FIO2 of 0.10 during halothane anesthesia significantly enhanced reductive biotransformation, as indicated by plasma fluoride ion concentrations. This was associated with a significant increase in organic fluoride bound to hepatic lipids. Centrilobular necrosis did not develop under these conditions. Thus, covalent binding to subcellular proteins by the trifluoroacetyl acid chloride intermediate generated by oxidative halothane biotransformation is implicated as a mechanism of centrilobular necrosis in guinea pigs. Binding to lipids by reductive pathway generated free radicals does not appear to be involved in production of the lesion.


Alexithymia, depression and serum lipids in suicide attempters.
Over the last decade several studies have discussed the association between serum cholesterol, depressive disorders and suicide. A specific psychological variable related to affect is alexithymia. Alexithymia has been linked to depression and suicidal behaviour. Concerning lipid levels there are several studies that suggest changes in serum lipid composition maybe related to depression and suicidal behaviour. In this study we examined the possible relationship between alexithymia, depression and serum lipids in suicide attempters. We studied 50 non-violent suicide attempters (drug overdosers) with a mean age of 35.0 (±12.2) years. Alexithymia was measured using the Shalling-Sifneos Personality Scale Revised (SSPS-R) and depression using the Montgomery-Asberg Depression Rating Scale (MADRS). Serum lipids concentrations were determined by enzymatic method within 24h of hospital admission. For the statistical evaluation Spearman's rank correlation coefficients were used. The mean serum lipid levels were: total serum cholesterol (TC) 175.2 (±29.6) mg/dL, highdensity lipoprotein cholesterol (H-DLC) 47.08 (±13.1) mg/dL, low density lipoprotein cholesterol (L-DLC) 109.5 (±23.5) mg/dL and the mean serum triglycerides (TR) level was 89.4 (±39.1) mg/dL. The mean scores on the questionnaires were: SSPS-R 10.3 (±3.7), MADRS 33.5 (±5.9). There were significant correlations between: (a) SSPS-R score and MADRS score (r=0.439, p<0.001), (b) SSPS-R score and TR level (r=0.323, p<0.05). There were no significant correlations between MADRS score and any of the lipid fractions measured. To our knowledge, only few studies have examined the association between alexithymia and clinical-psychopathological parameters in suicide attempters. There are no previous studies comparing serum lipid profile with alexithymia in suicide attempters. This is the first study to compare at the same time serum lipids, alexithymia and depression in suicide attempters. The results suggest that although there was a strong relationship between alexithymia and depression in suicide attempters only alexithymia was correlated to Serum triglyceride levels.


Analysis of human herpesvirus 6 glycoproteins recognized by monoclonal antibody OHV1.
A virus-specific glycoprotein (gp) from human herpes-virus 6 (HHV-6) was studied using the anti-HHV-6 monoclonal antibody OHV1. Immunoprecipitation with extracts from infected cells revealed that the antibody recognized four glycosylated proteins (gps) with Mrs of 106K, 102K, 65K and 63K under reducing conditions. However, only two gps, of 106K (gp106) and 102K, were detected under non-reducing conditions. Pulse-chase experiments revealed that gp65 and gp63 were cleavage products of gp106 and gp102. When infected cells were treated with tunicamycin, none of these gps was detected. With endo-beta-N-acetylglucosaminidase H (endo H) and endo-beta-N-acetylglucosaminidase F (endo F) treatment, gp106 and gp102 disappeared. Moreover, gp65 and gp63 were not affected by endo H treatment but were sensitive to endo F treatment. These data suggest that sugar residues of gp106 and gp102 are high-mannose type N-linked oligosaccharides, whereas those of gp65 and gp63 are complex type N-linked oligosaccharides.


Effect of acute stress on oesophageal motility in patients with gastro-oesophageal reflux disease.
Sixty four per cent of people with heartburn believe that it is exacerbated by stress. An alteration in oesophageal motility is one possible mechanism for this apparent change with stress. This study aimed to assess the effect of acute stressors on oesophageal motility in patients with gastro-oesophageal reflux disease (GORD). Sixty patients were studied. Twenty had oesophagitis, 20 had increased oesophageal acid exposure on pH monitoring but no endoscopic oesophagitis, and 20 had neither oesophagitis nor abnormal oesophageal acid exposure. Oesophageal motility was studied in these patients during psychological stress (Stroop test) and physical stress (cold pressor test). Blood pressure (BP) and heart rate increased in response to both stressors (mean systolic BP increased by > 10 mm Hg, diastolic BP by > 4 mm Hg and heart rate by > 3 beats per minute (p < 0.00001). The amplitude, duration, and velocity of propagation of oesophageal peristaltic contractions were not altered by the stressors. The percentage of simultaneous waves increased in patients with oesophagitis during the cold pressor test (median increase in these patients was 6% (p < 0.05)). This effect was not noted in the patients without oesophagitis. Acute stressors did not induce significant changes in oesophageal motility in patients with GORD but no oesophagitis. For these patients, dysmotility is not likely to be a cause of oesophageal symptoms which are exacerbated by stress. There was, however, a significant increase in simultaneous waves during cold pressor stress in patients with oesophagitis.


Treating vulvar cancer in the new millennium: are patients receiving optimal care?
The purpose of our study is to describe patterns of care of invasive vulvar carcinoma in the province of Ontario, Canada. Our ultimate goal is to improve vulvar cancer care by understanding variations in care and their impact on outcome. In this pilot study, we specifically evaluate the use of groin node dissection (GND). The provincial cancer registry was used to identify incident cases of vulvar carcinoma diagnosed between 1994 and 2003. These cases were linked to physician billings claims and hospital discharge records to identify treatment given in the first year after diagnosis. The cohort included 978 women with vulvar carcinoma. 85% had at least one surgical procedure. 62% of these had a GND. GND was more likely in those who were treated by a gynecologic oncologist or who had less co-morbid illness. Approximately 25% received radiotherapy. The rate of GND appears to be low. As proper management of the groins is critical for most patients with vulvar cancer, this observation raises concerns about the quality of treatment received by patients with vulvar carcinoma. Further investigation is required to verify the observations made in this hypothesis generating study.


Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change.
Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data.


Static Memory Deduplication for Performance Optimization in Cloud Computing.
In a cloud computing environment, the number of virtual machines (VMs) on a single physical server and the number of applications running on each VM are continuously growing. This has led to an enormous increase in the demand of memory capacity and subsequent increase in the energy consumption in the cloud. Lack of enough memory has become a major bottleneck for scalability and performance of virtualization interfaces in cloud computing. To address this problem, memory deduplication techniques which reduce memory demand through page sharing are being adopted. However, such techniques suffer from overheads in terms of number of online comparisons required for the memory deduplication. In this paper, we propose a static memory deduplication (SMD) technique which can reduce memory capacity requirement and provide performance optimization in cloud computing. The main innovation of SMD is that the process of page detection is performed offline, thus potentially reducing the performance cost, especially in terms of response time. In SMD, page comparisons are restricted to the code segment, which has the highest shared content. Our experimental results show that SMD efficiently reduces memory capacity requirement and improves performance. We demonstrate that, compared to other approaches, the cost in terms of the response time is negligible.


Capabilities of direct sample introduction--comprehensive two-dimensional gas chromatography--time-of-flight mass spectrometry to analyze organic chemicals of interest in fish oils.
Most analytical methods for persistent organic pollutants (POPs) focus on individual groups of targeted analytes. Therefore, analysis of multiple classes of POPs typically entails several sample preparations, fractionations, and injections, whereas other chemicals of possible interest are neglected or lost. To analyze a wider scope of organic contaminants in fish oil, we developed an approach to combine the analysis of targeted and untargeted chemicals using an automated direct sample introduction (DSI) and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC x GC/ ToF-MS). DSI-GC x GC/ToF-MS is a powerful tool that attains high quality separations to achieve high selectivity while still providing a wide analytical scope with minimal sample preparation, especially in conjunction with DSr's high tolerance to dirty extracts. Gel permeation chromatography (GPC) was used for initial separation of lipids from POPs and other GC-amenable organic compounds from dietary cod liver oil. For comparison purposes, additional cleanup of the GPC extracts was done by silica adsorption and acidification, which helped provide clues in the identification of untargeted compounds, but in routine analysis, only GPC is needed for this analytical approach. The approach allowed simultaneous identification of known-POPs in the fish liver oils, and further permitted presumptive identifications of multiple groups of halogenated natural products (HNPs) and other organic chemicals of interest through comparisons of the mass spectra from analyses with those from mass spectral libraries and/or reports in the literature (approximately 60 PCB congeners and 76 compounds in total). Subsequent confirmations were made by reanalysis and comparison of chromatographic retention times and mass spectra with contemporaneously analyzed reference standards. Otherwise, ion fragmentation patterns of unknown compounds were assessed for tentative identifications. Some of the HNPs in the fish oils were detected and identified for the first time. Our study demonstrates that the wide monitoring scope provided by the DSI-GC x GC/ToF-MS method after GPC provides many logistical and performance advantages over the conventional use of several different methods designed for individual classes of targeted analytes after extensive sample preparation.


Caregiver Experiences of Care Coordination for Recently Discharged Patients: A Qualitative Metasynthesis.
Caregivers of patients often provide key support for patients after hospitalization. This qualitative metasynthesis describes caregiver perspectives about care coordination for patients discharged from the hospital. A literature search of Ovid Medline and CINAHL completed on May 23, 2018, identified 1,546 studies. Twelve articles were included in the final metasynthesis. Caregiver perspectives about care coordination were compiled into overall themes. A subanalysis of studies in which patients were discharged with home health services was completed. Five main themes emerged related to caregiver perspectives on care coordination after hospitalization: (a) Suboptimal access to clinicians after discharge, (b) Feeling disregarded by clinicians, (c) Need for information and training at discharge, (d) Overwhelming responsibilities to manage appointments and medications, and (e) Need for emotional support.Findings from this metasynthesis suggest the need for clinicians to engage with caregivers to provide support, training, and communication after hospital discharge.


Rose Bengal- and Riboflavin-Mediated Photodynamic Therapy to Inhibit Methicillin-Resistant Staphylococcus aureus Keratitis Isolates.
To evaluate the in vitro efficacy of rose bengal- and riboflavin-mediated photodynamic therapy for inhibition of methicillin-resistant Staphylococcus aureus (MRSA) isolates. Experimental study. Two different multidrug-resistant, clinical MRSA isolates were grown on nutrient agar, prepared in suspension, and adjusted to concentrations of 1.5 × 10(4) colony-forming units per milliliter. Bacterial suspensions were mixed with rose bengal, riboflavin, or water according to experimental group. Tested in triplicate, groups included: Group I, MRSA control; Group II, MRSA with 0.1% rose bengal; Group III, MRSA with 0.03% rose bengal; and Group IV, MRSA with 0.1% riboflavin. All experimental groups were exposed to 3 lighting conditions: dark, ambient room light for 30 minutes, and 5.4 J/cm(2) with either green light-emitting diode (LED) or ultraviolet-A (UV-A) irradiation. Plates were photographed at 72 hours and custom software measured bacterial growth inhibition. Complete growth inhibition of both MRSA strains was demonstrated (1) for both rose bengal concentrations under ambient and green LED irradiation, and (2) for the 0.1% rose bengal in the dark. The 0.03% rose bengal in dark conditions showed complete inhibition of strain 2 but incomplete inhibition of strain 1. Riboflavin showed almost complete inhibition with UV-A irradiation but demonstrated minimal inhibition for both strains in dark and ambient light conditions. Rose bengal- and riboflavin-mediated photodynamic therapy demonstrated complete growth inhibition in vitro of 2 multidrug-resistant MRSA strains. Rose bengal was also effective in dark and ambient conditions. These results may have implications for in vivo therapy.


Egocentric boundary vector tuning of the retrosplenial cortex.
The retrosplenial cortex is reciprocally connected with multiple structures implicated in spatial cognition, and damage to the region itself produces numerous spatial impairments. Here, we sought to characterize spatial correlates of neurons within the region during free exploration in two-dimensional environments. We report that a large percentage of retrosplenial cortex neurons have spatial receptive fields that are active when environmental boundaries are positioned at a specific orientation and distance relative to the animal itself. We demonstrate that this vector-based location signal is encoded in egocentric coordinates, is localized to the dysgranular retrosplenial subregion, is independent of self-motion, and is context invariant. Further, we identify a subpopulation of neurons with this response property that are synchronized with the hippocampal theta oscillation. Accordingly, the current work identifies a robust egocentric spatial code in retrosplenial cortex that can facilitate spatial coordinate system transformations and support the anchoring, generation, and utilization of allocentric representations.


Lowering the threshold for the diagnosis of gestational diabetes.
Our purpose was to determine whether lowering the diagnostic threshold for gestational diabetes mellitus on 3-hour 100 gm oral glucose tolerance testing will select a population at risk for adverse perinatal outcome. In this retrospective study 434 patients with an abnormal 50 gm glucose screen result (> or = 140 mg/dl) underwent a standardized 3-hour oral glucose tolerance test. The results were stratified according to maternal weight and the criteria recommended by Sacks or Carpenter. Birth weight and rate of macrosomia were the primary perinatal outcome variables analyzed. Analysis of the data set stratified according to the Sacks criteria revealed results very similar to the Carpenter criteria data set. Patients who would have been newly diagnosed with gestational diabetes mellitus only if the lowered criteria were used (group 2) were older and heavier. No other variable comparisons achieved statistical significance. When the same patients were stratified according to prepregnancy weight, overweight patients were older, gained less weight during the third trimester, underwent cesarean section more often, and had higher cumulative maternal morbidity. Regression analysis showed that the degree of hyperglycemia did not predict macrosomia or influence birth weight, but prepregnant maternal body mass index was associated with macrosomia. Fetal macrosomia is influenced by maternal prepregnant body mass index. Lowering the glucose tolerance test threshold would result in overdiagnosis of gestational diabetes mellitus without improving perinatal outcome.


Melanocytes and iris color. Light microscopic findings.
To systematically evaluate morphologic differences in iris stroma that contribute to clinically perceptible differences in iris color, using immunohistochemical identification of stromal melanocytes and fluorescence microscopy. Paraffin-embedded sections from 51 human irides were stained with S100a and fluorescein isothiocyanate. Cells were counted and scored as melanocytes or other. Melanocyte number, proportion, and density were determined for light-colored (blue), medium-colored (hazel) and dark-colored (brown) irides and compared. No statistically significant difference was observed for mean total cellularity or mean melanocyte number among the three color groups. Mean total stromal cell count was 1177 +/- 259 (mean +/- SEM), and mean melanocyte number was 778 +/- 196 per 5-micrometer section. In human irides, 65.9% of the iris stroma is composed of melanocytes. Melanocyte density (number of cells per square millimeter) is not related to iris color. The number of melanocytes, the proportion of melanocytes, and iris stromal cellularity are not major contributors to iris color.


dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo.
The first step in the differentiation of the Drosophila mesoderm is the activation of two regulatory genes, twist (twi) and snail (sna), in ventral regions of early embryos. sna is a transcriptional repressor that is uniformly expressed throughout the presumptive mesoderm. Its sharp lateral limits help to establish the boundary between the mesoderm and neuroectoderm. Genetic studies suggest that sna is a target of the dorsal (dl) morphogen, and this interaction provides a model for determining how a morphogen gradient establishes a sharp, on/off threshold response. We present evidence that dl and twi directly activate sna expression. Site-directed mutagenesis of dl- and twi-binding sites within defined regions of the sna promoter suggest that the two proteins (containing the Rel and helix-loop-helix domains, respectively) function multiplicatively to ensure strong, uniform expression of sna, particularly in ventral-lateral regions where there are diminishing amounts of dl. These results are consistent with the possibility that the sharp sna borders are formed by multiplying the shallow dl gradient and the steeper twi gradient.


[Surgical treatment of volar wrist ganglia].
We evaluated surgery-related issues concerning the excision of volar wrist ganglia in the light of data obtained from our patients. The study included 40 patients (10 males, 30 females; mean age 32.5 years; range 18 to 65 years) who underwent surgery for volar ganglia. All the patients had unilateral involvement. All operations were performed under axillary brachial plexus regional anesthesia in the microsurgery operating room. The mean follow-up period was 2.5 years (range 1 to 5 years). The ganglia originated from the radioscaphoid joint capsule in 18 patients (45%), scaphotrapezial joint capsule in 16 patients (40%), and from the flexor carpi radialis tendon in two patients (5%). The ganglia were attached to the radial artery in 26 patients (65%), in two patients (5%) the radial artery completely merged into the lesion. The pedicles could not be dissected in four patients (10%), all of whom developed recurrences. Complications included recurrences in nine patients (22%), injury to the median palmar cutaneous nerve in four patients (10%), injury to the radial artery in two patients (5%) and wrist stiffness in five patients (12.5%). No significant correlation was found between complications and experience of the operating surgeons. Considering possible dissections and interventions for complication-associated repairs, and potential recurrences, surgical removal of volar ganglia should be performed under appropriate circumstances, especially in a formal operating room.


Epidemiology, Diagnosis and Therapeutic Approaches of Cryptorchidism at the Panzi General Hospital, DR Congo: A 5-year Retrospective Study.
Cryptorchidism is a common congenital malformation characterized by unilateral or bilateral undescended testis in the scrotum. It is a common disease in pediatric urology although the prevalence is yet to be determined in the East DR Congo. The aim of this study was to describe the prevalence, clinical and therapeutic features of cryptorchidism at the Panzi General Hospital. Medical records of patients who underwent pediatric surgery between January 2011 and December 2016 were reviewed. The prevalence of cryptorchidism, associated malformations, sociodemographic features of patients and therapeutic protocols were examined. Collected data were analyzed using SPSS software. A total of 5066 children were received during the study period in the service, of which 76 suffered from cryptorchidism giving a prevalence of 1.50% and an annual incidence of 12.70. Unilateral cases were found in 53(69.74%) patients among which 66.04% and 33.96% had unilateral right and left cryptorchidism respectively. Cryptorchidism was associated with other malformations in 71.1% of patients. The age of patients ranged from 0 to 15 years and 78.9% were older than two years. Surgery was the only therapeutic approach and fixation of cryptorchid testis in dartos through inguinal incision was the preferred therapeutic used method. This study indicates that cryptorchidism is a relatively common and neglected disease in the Est-DR Congo, due to late consultation. Therefore, the local population and pediatricians should be sensitized on scrotal palpation techniques in order to shorten the consultation delay and prevent testis damages.


Outcome of patients with pregnancy during or after breast cancer: a review of the recent literature.
An increasing number of young women are delaying childbearing; hence, more are diagnosed with breast cancer (bca) before having a family. No clear recommendations are currently available for counselling such a population on the safety of carrying a pregnancy during bca or becoming pregnant after treatment for bca. Using a Web-based search of PubMed we reviewed the recent literature about bca and pregnancy. Our objective was to report outcomes for patients diagnosed with bca during pregnancy, comparing them with outcomes for non-pregnant women, and to evaluate prognosis in women diagnosed with and treated for bca who subsequently became pregnant. "Pregnancy and bca" should be divided into two entities. Pregnancy-associated bca tends to be more aggressive and advanced in stage at diagnosis than bca in control groups; hence, it has a poorer prognosis. With respect to pregnancy after bca, there is, despite the bias in reported studies and meta-analyses, no clear evidence for a different or worse disease outcome in bca patients who become pregnant after treatment compared with those who do not. Pregnancy-associated bca should be treated as aggressively as and according to the standards applicable in nonpregnant women; pregnancy after bca does not jeopardize outcome. The guidelines addressing risks connected to pregnancy and bca lack a high level of evidence for better counselling young women about pregnancy considerations and preventing unnecessary abortions. Ideally, evidence from large prospective randomized trials would set better guidelines, and yet the complexity of such studies limits their feasibility.


Knowledge and Perceptions of Child Protection and Mandatory Reporting: A Survey of Nurses in Hong Kong.
In the absence of a mandatory reporting (MR) structure, it is unclear how nurses perceive or exercise their role in child protection. This study examined knowledge and perceptions of child protection and MR among nurses working in Hong Kong. This cross-sectional web-based survey used the Child Abuse Report Intention Scale to measure nurses' child protection knowledge and attitudes, and their perceived norms, control, and intention to report suspected maltreatment. Nurses also indicated if they support MR and to provide an explanation for their preference. Quantitative data were described and analyzed using bivariate and regression analyses. Open-ended responses were analyzed using directed content analysis. A convenient sample of 91 nurses working in Hong Kong completed the survey. The majority (86%) were female with a mean of 9.5 years of nursing experience; their mean knowledge score was 6.64 out of 13 (range 2-10). Compared with other maltreatment types, sexual abuse was perceived to be most severe and most likely to be reported. Perceived severity and attitudes toward child maltreatment was significantly associated with nurses' intention to report. Over half (58%) supported MR; those against MR expressed concerns about lack of support from management. Although nurses working in Hong Kong still hold polarized views about MR, findings point to the importance of creating a supportive reporting culture, and designing training programs that focus on changing perceptions about child protection in order to improve their tendency to report.


[Effect of phenyl derivative of gamma-aminobutyric acid phenybut on autorhythmic contractile activity of the portal vein].
The phenyl derivative of the GABA phenybute exerts a direct regulating effect upon phasic and tonic components of the v.cava autorhythmical contractile activity in Wistar rats in media with an altered calcium contents, whereas no such effect occurred in hyper-potassium solution or against the background of verapamil blockade of the potential-dependent calcium channels.


Patients' perspective and usability of innovation technology in a new rehabilitation pathway: An exploratory study in patients with multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system, which causes sensori-motor and cognitive disabilities, as well as neuropsychiatric abnormalities. Technological innovations could offer a valuable way to improve neurorehabilitation outcomes. Aim of the study is to assess the feasibility and usability of new rehabilitation technologies as perceived by patients suffering from MS. MS inpatients attending the Robotic and Behavioral Neurorehabilitation Service of the IRCCS Centro Neurolesi Bonino Pulejo (Messina, Italy) from February 2017 to April 2019, were enrolled in this exploratory study. The patients were submitted to a personalized rehabilitation treatment using robotics (such as Lokomat, Geosystem, Ekso, Armeo) and virtual reality (i.e. BTS-Nirvana, CAREN, VRRS), following a dedicated innovative pathway. All patients completed the study. Significant pre-post-treatment differences were found in the perception of patients' quality of life, regarding both physical and mental items (p<0,001), as well as in the achievement of the therapeutic goal. Finally, we observed that patients declared a high usability of the robotic devices, and that rehabilitation with the new devices was well tolerated. our results support the idea that neurorehabilitation using innovation technologies can be useful for the commitment and motivation during the rehabilitation process, with possible positive effects on the functional and psychological outcomes of patients with MS.


Assessing outcomes in advanced practice nursing practice: the use of quality indicators and evidence-based practice.
Advanced practice nurses (APNs) impact both patient care and healthcare systems on a daily basis. Tracking and documenting the outcomes of APN practice have become essential, due partly to the emphasis on outcomes that has become a component of the majority of healthcare initiatives. This article outlines important aspects related to assessing outcomes and discusses the use of quality indicators to demonstrate outcomes of APN practice. Examples from clinical practice are provided in order to demonstrate that assessing the outcomes of APN practice can be incorporated into daily practice as part of ongoing initiatives. In delineating the outcomes of APN care, the value of APNs can be formally acknowledged.


Associative learning increases adult neurogenesis during a critical period.
Learning increases the number of immature neurons that survive and mature in the adult hippocampus. One-week-old cells are more likely to survive in response to learning than cells in animals that are exposed to training but do not learn. Because neurogenesis is an ongoing and overlapping process, it is possible that learning differentially affects new cells as a function of their maturity. To address this issue, we examined the effects of associative learning on the survival of cells at different stages of development. Training did not alter the number of cells that were produced during the training experience. Cells that were 1-2 weeks of age at the time of training survived after learning but cells that were younger or older did not. In contrast, cells that were produced during training were less likely to survive than cells in untrained animals. Additionally, the number of cells that were generated after learning in trained animals was not different from the number in untrained animals. Finally, survival was not increased if the memory was expressed when the cells were about 1-week-old. Together, these results indicate that new neurons are rescued from death by initial acquisition, not the expression or reacquisition, of an associative memory and only during a critical period. Overall, these results suggest the presence of a feedback system, which controls how many new neurons become incorporated into the adult brain in response to learning.


Effect of vaccination on serum concentrations of total and antigen-specific immunoglobulin E in dogs.
To determine the effect of vaccination on serum concentrations of total and antigen-specific IgE in dogs. 20 female Beagles. Groups of 5 dogs each were vaccinated repeatedly between 8 weeks and 4 years of age with a multivalent and rabies vaccine, a multivalent vaccine only, or a rabies vaccine only. A fourth group of 5 dogs served as unvaccinated controls. Serum concentrations of total immunoglobulins and antigen-specific IgE were determined following vaccination. -The multivalent vaccine had little effect on serum total IgE concentrations. The concentration of IgE increased slightly following vaccination for rabies at 16 weeks and 1 year of age and increased greatly after vaccination at 2 and 3 years of age in most dogs, with a distinct variation between individual dogs. Vaccination had no effect on serum concentrations of IgA, IgG, and IgM as measured at 2 and 3 years of age. The rabies vaccine contained aluminum adjuvant in contrast to the multivalent vaccine. An increase of IgE that was reactive with vaccine antigens, including bovine serum albumin and bovine fibronectin, was detected in some of the dogs vaccinated for rabies. There was no significant correlation between serum concentrations of total IgE and antigen-specific IgE following vaccination. Serum total IgE concentration rapidly returned to preimmunization concentrations in most dogs, but high concentrations of antigen-specific IgE persisted. Vaccination of dogs for rabies increases serum concentrations of total IgE and induces IgE specific for vaccine antigens, including tissue culture residues. Vaccination history should be considered in the interpretation of serum total IgE concentrations.


Neural correlates of auditory-cognitive processing in older adult cochlear implant recipients.
With the growing number of older adults receiving cochlear implants (CI), there is general agreement that substantial benefits can be gained. Nonetheless, variability in speech perception performance is high, and the relative contribution and interactions among peripheral, central-auditory, and cognitive factors are not fully understood. The goal of the present study was to compare auditory-cognitive processing in older-adult CI recipients with that of older normal-hearing (NH) listeners by means of behavioral and electrophysiologic manifestations of a high-load cognitive task. Auditory event-related potentials (AERPs) were recorded from 9 older postlingually deafened adults with CI (age at CI >60) and 10 age-matched listeners with NH, while performing an auditory Stroop task. Participants were required to classify the speaker's gender (male/female) that produced the words 'mother' or 'father' while ignoring the irrelevant congruent or incongruent word meaning. Older CI and NH listeners exhibited comparable reaction time, performance accuracy, and initial sensory-perceptual processing (i.e. N1 potential). Nonetheless, older CI recipients showed substantially prolonged and less efficient perceptual processing (i.e. P3 potential). Congruency effects manifested in longer reaction time (i.e. Stroop effect), execution time, and P3 latency to incongruent versus congruent stimuli in both groups in a similar fashion; however, markedly prolonged P3 and shortened execution time were evident in older CI recipients. Collectively, older adults (CI and NH) employed a combined perceptual and postperceptual conflict processing strategy; nonetheless, the relative allotment of perceptual resources was substantially enhanced to maintain adequate performance in CI recipients. In sum, the recording of AERPs together with the simultaneously obtained behavioral measures during a Stroop task exposed a differential time course of auditory-cognitive processing in older CI recipients that was not manifested in the behavioral end products of processing. These data may have implications regarding clinical evaluation and rehabilitation procedures that should be tailored specifically for this unique group of patients.


Patterns of sulfur isotope fractionation during microbial sulfate reduction.
Studies of microbial sulfate reduction have suggested that the magnitude of sulfur isotope fractionation varies with sulfate concentration. Small apparent sulfur isotope fractionations preserved in Archean rocks have been interpreted as suggesting Archean sulfate concentrations of <200 μm, while larger fractionations thereafter have been interpreted to require higher concentrations. In this work, we demonstrate that fractionation imposed by sulfate reduction can be a function of concentration over a millimolar range, but that nature of this relationship depends on the organism studied. Two sulfate-reducing bacteria grown in continuous culture with sulfate concentrations ranging from 0.1 to 6 mm showed markedly different relationships between sulfate concentration and isotope fractionation. Desulfovibrio vulgaris str. Hildenborough showed a large and relatively constant isotope fractionation ((34) εSO 4-H2S ≅ 25‰), while fractionation by Desulfovibrio alaskensis G20 strongly correlated with sulfate concentration over the same range. Both data sets can be modeled as Michaelis-Menten (MM)-type relationships but with very different MM constants, suggesting that the fractionations imposed by these organisms are highly dependent on strain-specific factors. These data reveal complexity in the sulfate concentration-fractionation relationship. Fractionation during MSR relates to sulfate concentration but also to strain-specific physiological parameters such as the affinity for sulfate and electron donors. Previous studies have suggested that the sulfate concentration-fractionation relationship is best described with a MM fit. We present a simple model in which the MM fit with sulfate concentration and hyperbolic fit with growth rate emerge from simple physiological assumptions. As both environmental and biological factors influence the fractionation recorded in geological samples, understanding their relationship is critical to interpreting the sulfur isotope record. As the uptake machinery for both sulfate and electrons has been subject to selective pressure over Earth history, its evolution may complicate efforts to uniquely reconstruct ambient sulfate concentrations from a single sulfur isotopic composition.


Improving the outcome of paediatric orthopaedic trauma: an audit of inpatient management in Southampton.
The patterns, management and outcome of non-fatal orthopaedic injury in childhood was audited over a 1 year period in Southampton. A computer-based audit (1 September 1993 to 31 August 1994) was conducted of all children aged under 15 years who were admitted to the orthopaedic unit after accidental injury. Management was audited by studying the primary conservative and operative treatment methods employed. Treatment outcome was evaluated in terms of need for secondary operative treatment, salvage internal fixation, length of hospital stay and unplanned readmission. In all, 398 children, representing 50/10,000 of the local paediatric population, were admitted with a traumatic injury. There was a significant (P < 0.001, Kolmogorov-Smirnov) seasonal variation in admission rate. There were 87.3% admissions required for fractures, 8.5% after soft tissue injury and 2.2% after joint injury. The following areas were identified where management and outcome could be improved: 1 A 12.1% readmission rate (47/346) in children with fractures owing to a 16% incidence of loss of position after closed reduction of distal radial, forearm shaft and distal humeral fractures. 2 In all, 24% of internal fixation procedures were performed as 'salvage' after failure of conservative treatment, entailing either reoperation during the initial admission or a further unplanned readmission. 3 A prolonged inpatient stay for patients with femoral fractures owing to a wide variation in treatment method. The outcome of non-fatal orthopaedic injury can be improved through the selective use of primary internal fixation of distal radial and humeral fractures and the close adherence to a management algorithm in femoral fractures. There may be a role for more specialised supervision of primary treatment of these particular fractures.


A computational fluid dynamics model for drug delivery in a nasal cavity with inferior turbinate hypertrophy.
Intranasal medications are commonly used in treating nasal diseases. However, technical details of the correct usage of these medications for nasal cavity with obstruction are unclear. A three-dimensional model of nasal cavity was constructed from MRI scans of a healthy human subject. Nasal cavities corresponding to healthy, moderate, and severe nasal obstruction (NO) were simulated by enlarging the inferior turbinate geometrically, which was documented by approximately one-third reduction of the minimum cross-sectional area for the moderate and two-thirds for the severe obstruction. The discrete phase model based on steady-state computational fluid dynamics was used to study the gas-particle flow. The results were presented with drug particle (from 7 x 10⁻⁵ to 10⁻⁷ m) deposition distribution along the lateral walls inside these three nasal cavities, and comparisons of the particle ratio escaping from the cavity were also presented and discussed. Nasal patency is an essential condition that had the most impact on particle deposition of the factors studied; the particle percentage escaping the nasal cavity decreased to less than a half and one-tenth for the moderately and severely blocked noses. Decreasing of flow rate and particle diameter increased the escaping ratio; however, zero escaping percentage was detected with the absence of air flow and the effect was less noticeable when the particle diameter was very small (<10⁻⁶ m). The existence of inspiratory flow and head tilt angle helped to improve the particle escaping ratio for the healthy nose; however, such changes were not significant for the moderately and severely blocked noses. When using an intranasal medication, it is advisable to have a moderate inspiratory air-flow rate and small size particles to improve particle escaping ratio. Various head positions suggested by clinicians do not seem to improve the drug escaping ratio significantly for the nasal cavities with inferior turbinate hypertrophy.


Sex differences in depression after widowhood. Do men suffer more?
This study focuses on sex differences in depression of the widowed. Previous research showed different results in sex differences and in depression after bereavement. We assessed the effects of widowhood on depressive symptoms for men and women and examined whether environmental strain like social support, finances and housekeeping concerns explain these effects. Data were used from a large community-based study of older people in three regions of the Netherlands. Our study sample consists of 2626 widowed and married subjects in the age group of 55-85 years. Depression was measured using the CES-D scale; the various strains were obtained by structured interviews. Multiple linear regression, performed for men and women separately, were used. The results show that widowhood is associated with higher levels of depressive symptoms and that this association is stronger for men than for women. The effect of widowhood is mediated by different types of environmental strain for men and women. However, a strong direct main effect of widowhood on depression remains. The difference in depression rates between men and women is most evident among those widowed for a longer period of time. It appears that, over time, women adapt to widowhood more successfully than men. From a clinical point of view this is important, as it suggests that men who remain alone after losing their partner are at a higher risk of developing symptoms of chronic depression.


Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs.
The early-weaned pig develops intestinal atrophy and provides a readily accessible animal model for determining the role of dietary supplementation of glutamine (Gln, a major fuel for enterocytes) in preventing intestinal damage. Three experiments were conducted to determine the stability of dietary Gln in the acidic part of the gastrointestinal tract using pigs surgically fitted with a T-cannula in mid-duodenum (Exp. 1), and the effects of dietary Gln supplementation on the villus height and lamina propria depth of duodenum and jejunum (Exp. 2) as well as growth performance (Exp. 3) of pigs weaned at 21 d of age. Postweaning pigs were fed for 14 d corn- and soybean meal-based diets supplemented with 0.0, 0.2, 0.6 or 1.0% free L-Gln. Dietary Gln was not subject to measurable acid hydrolysis in the stomach and upper part of duodenum and was substantially available for the small intestine for metabolic utilization. Glutamine supplementation (1.0%) prevented jejunal atrophy (as indicated by villus height) during the first week postweaning and increased the gain:feed ratio (an indicator of growth performance) by 25% during the second week postweaning. Glutamine supplementation (1.0%) increased plasma concentrations of aspartate, glutamate and alanine and reduced the extent to which plasma taurine concentration fell in postweaning pigs. These results provide an experimental basis for enteral use of Gln in swine production and clinical nutrition to prevent intestinal epithelial damage.


[The differentiation between identity crisis and identity diffusion and its impact on treatment].
The differentiation between an identity crisis, a transient phenomenon that usually results (after resolution) in a well-integrated identity with flexible and adaptive functioning, and an identity diffusion that is viewed as a basis for subsequent personality pathology, has a major impact on the selection of a treatment method. A new treatment method (Adolescent Identity Treatment, AIT), a modification of Transference Focused Psychotherapy, was developed to treat adolescents with identity diffusion in order to improve their relationships with friends, parents, and teachers and to help them acquire positive self-esteem, clarify life goals and establish a stable identity. In a case study we describe the basic approaches of AIT in assessment and treatment.


Smoking Status and Functional Outcomes in Young Stroke.
Objective: Stroke in young adults is uncommon, and the etiologies and risk factors of stroke in young adults differ from those in older populations. Smoker's paradox is an unexpected favorable outcome, and age difference is used to explain the association between smoking and the favorable functional outcome. This study aimed to investigate the existence of this phenomenon in young stroke patients. Methods: We analyzed a total of 9,087 young stroke cases registered in the nationwide stroke registry system of Taiwan between 2006 and 2016. Smoking criteria included having a current history of smoking more than one cigarette per day for more than 6 months. After matching for sex and age, a Cox model was used to compare mortality and function outcomes between smokers and non-smokers. Results: Compared with the non-smoker group, smoking was associated with older age, higher comorbidities, and higher alcohol consumption. Patients who report smoking with National Institutes of Health Stroke Scale scores of 11-15 had a worse functional outcome (adjusted odds ratio, 0.81; 95% confidence interval, 0.76 - 0.87). Conclusion: Smokers had a higher risk of unfavorable functional outcomes at 3 months after stroke, and therefore, we continue to strongly advocate the importance of smoking cessation.


Iron-Deficiency Anemia Results in Transcriptional and Metabolic Remodeling in the Heart Toward a Glycolytic Phenotype.
Iron deficiency is the most prevalent micronutrient disorder globally. When severe, iron deficiency leads to anemia, which can be deleterious to cardiac function. Given the central role of iron and oxygen in cardiac biology, multiple pathways are expected to be altered in iron-deficiency anemia, and identifying these requires an unbiased approach. To investigate these changes, gene expression and metabolism were studied in mice weaned onto an iron-deficient diet for 6 weeks. Whole-exome transcriptomics (RNAseq) identified over 1,500 differentially expressed genes (DEGs), of which 22% were upregulated and 78% were downregulated in the iron-deficient group, relative to control animals on an iron-adjusted diet. The major biological pathways affected were oxidative phosphorylation and pyruvate metabolism, as well as cardiac contraction and responses related to environmental stress. Cardiac metabolism was studied functionally using in vitro and in vivo methodologies. Spectrometric measurement of the activity of the four electron transport chain complexes in total cardiac lysates showed that the activities of Complexes I and IV were reduced in the hearts of iron-deficient animals. Pyruvate metabolism was assessed in vivo using hyperpolarized 13C magnetic resonance spectroscopy (MRS) of hyperpolarized pyruvate. Hearts from iron-deficient and anemic animals showed significantly decreased flux through pyruvate dehydrogenase and increased lactic acid production, consistent with tissue hypoxia and induction of genes coding for glycolytic enzymes and H+-monocarboxylate transport-4. Our results show that iron-deficiency anemia results in a metabolic remodeling toward a glycolytic, lactic acid-producing phenotype, a hallmark of hypoxia.


[Interactions between various transition elements in their effect on pepsin activity].
Kinetic experiments were made with pepsin in the presence of Cu2+ ions and additional Fe2+, Ni2+ or Zn3+ ions as sulphates. As a parameter of the pepsin activity the turnover-rate curves were determined with haemoglobin as a substrate. An important activation of the pepsin was obtained by Cu2+ additions of 5-10(-4) mole/1. When Cu2+ and Fe2+ ions were added to the reaction mixture at the same time, an additive effect of both metal cations was observed. A competitive effect of both metal cations was found in the combination of Cu2+/Ni2+ ions. Zn2+ addition did not influence the activation of pepsin caused by Cu2+ ions.


Identification of a positively charged platform in Staphylococcus aureus HtsA that is essential for ferric staphyloferrin A transport.
In response to iron starvation, Staphylococcus aureus secretes both staphyloferrin A and staphyloferrin B, which are high-affinity iron-chelating molecules. The structures of both HtsA and SirA, the ferric-staphyloferrin A [Fe(III)-SA] and ferric-staphyloferrin B [Fe(III)-SB] receptors, respectively, have recently been determined. The structure of HtsA identifies a novel form of ligand entrapment composed of many positively charged residues. Through ionic interactions, the binding pocket appears highly adapted for the binding of the highly anionic siderophore SA. However, biological validation of the importance of the nine SA-interacting residues (six arginines, one tyrosine, one histidine, and one lysine) has not been previously performed. Here, we mutated each of the Fe(III)-SA-interacting residues in HtsA and found that substitutions R104A, R126A, H209A, R306A, and R306K resulted in a reduction of binding affinity of HtsA for Fe(III)-SA. While mutation of almost all proposed ligand-interacting residues decreased the ability of S. aureus cells to transport (55)Fe(III)-SA, S. aureus expressing HtsA R104A, R126A, R306A, and R306K showed the greatest transport defects and were incapable of growth in iron-restricted growth media in a SA-dependent manner. These three residues cluster together and, relative to other residues in the binding pocket, move very little between the apo and closed holo structures. Their essentiality for receptor function, together with structural information, suggests that they form a positively charged platform that is required for initial contact with the terminal carboxyl groups of the two citrates in the Fe(III)-SA complex. This is a likely mechanism by which HtsA discerns iron-bound SA from iron-free SA.


Heterochromatin-mediated association of achiasmate homologs declines with age when cohesion is compromised.
Normally, meiotic crossovers in conjunction with sister-chromatid cohesion establish a physical connection between homologs that is required for their accurate segregation during the first meiotic division. However, in some organisms an alternative mechanism ensures the proper segregation of bivalents that fail to recombine. In Drosophila oocytes, accurate segregation of achiasmate homologs depends on pairing that is mediated by their centromere-proximal heterochromatin. Our previous work uncovered an unexpected link between sister-chromatid cohesion and the fidelity of achiasmate segregation when Drosophila oocytes are experimentally aged. Here we show that a weak mutation in the meiotic cohesion protein ORD coupled with a reduction in centromere-proximal heterochromatin causes achiasmate chromosomes to missegregate with increased frequency when oocytes undergo aging. If ORD activity is more severely disrupted, achiasmate chromosomes with the normal amount of pericentric heterochromatin exhibit increased nondisjunction when oocytes age. Significantly, even in the absence of aging, a weak ord allele reduces heterochromatin-mediated pairing of achiasmate chromosomes. Our data suggest that sister-chromatid cohesion proteins not only maintain the association of chiasmate homologs but also play a role in promoting the physical association of achiasmate homologs in Drosophila oocytes. In addition, our data support the model that deterioration of meiotic cohesion during the aging process compromises the segregation of achiasmate as well as chiasmate bivalents.


Neurological Manifestations of SARS-CoV-2: A Narrative Review.
Coronavirus disease 2019 (COVID-19) pandemic started as an outbreak in China and soon crossed borders to affect the populations in all countries of the world. During the initial course of the disease, COVID-19 was perceived as a pneumonia-like illness. However, recent findings of COVID-19 patients suggest that the virus has the potential to disseminate to different tissues and organs, and cause significant complications. Neurological symptoms are of great significance as these usually present in and complicate critical cases. Many case reports and case series have documented the findings of neurological complications in COVID-19 patients. From the existing data, the most frequent symptoms in these patients were broadly classified into the central nervous system (CNS), peripheral nervous system, and skeletal muscular symptoms. CNS symptoms include meningitis, encephalitis, cerebrovascular complications, peripheral nervous system symptoms include anosmia, ageusia, and skeletal muscular symptoms include myalgias. It is postulated that the cause may be direct CNS injury through blood and neuronal pathways or indirectly because of an immune-mediated response, hypoxia caused by decreased oxygen saturation, or by the binding of subacute respiratory syndrome-coronavirus-2 to the host angiotensin-converting enzyme-2 receptors. Striking radiologic findings in COVID-19 patients with neurological symptoms have also emerged. As subacute respiratory syndrome-coronavirus-2 may potentially have lethal implications on the nervous system, it is important that neurologists are better informed about the spectrum of clinical manifestations, radiologic findings, and likely mechanisms of injury. Understanding the symptoms and radiologic imaging allows clinicians to consider brain imaging in any patient with suspected COVID-19 and neurological symptoms.


Early results after laparoscopic sleeve gastrectomy in adolescents with morbid obesity.
Obesity has been identified as one of the most important public health concerns in both children and adolescents. Unfortunately, even the most comprehensive and aggressive multidisciplinary weight management programs have shown only modest weight loss results. There has been increasing enthusiasm for bariatric surgery for adolescent patients with morbid obesity. Because of the relatively high morbidity and mortality associated with gastric bypass surgery, we have begun to explore laparoscopic sleeve gastrectomy as an alternative. We hypothesized that it would be a safe and effective short-term strategy. We have prospectively collected data from all patients undergoing bariatric surgery at our institution since the inception of our adolescent weight loss surgery program in January 2010. Baseline data collected included age, gender, race/ethnicity, height, weight, body mass index, and comorbid conditions. Postoperative data collected included the type of operation, length of stay, operative morbidity, the need for reoperation, and percent excess weight loss and body mass index at 3-month intervals. Twenty-three patients have undergone laparoscopic sleeve gastrectomy at our institution since January 2010. Of these, 18 were female and 5 were male. The mean age was 17.3 ± 1.5 years of age. The mean preoperative weight was 149 ± 30 kg with a body mass index of 52 ± 9 kg/m(2). There were no intraoperative complications, and the only postoperative complication has been pancreatitis in 1 patient. The mean length of stay was 2.2 ± 1.1 days. The mean follow-up was 10.9 ± 7.4 months. The percent excess weight loss at 3 months, 6 months, and 1 year postoperatively was 32%, 38%, and 40%, respectively, in those who had reached these time points. Laparoscopic sleeve gastrectomy is a safe operation for adolescent patients with morbid obesity and represents an effective early treatment strategy with approximately 40% excess weight loss at 6 months and 1 year of follow-up. Because of the minimal morbidity associated with laparoscopic sleeve gastrectomy, it may be the optimal non-device surgical option for this select group of adolescent patients.


Simultaneous anterior-posterior approach to the thoracic and lumbar spine for the radical resection of tumors followed by reconstruction and stabilization.
Thoracic or lumbar spine malignant tumors involving both the anterior and posterior columns represent a complex surgical problem. The authors review the results of treating patients with these lesions in whom surgery was performed via a simultaneous anterior-posterior approach. The hospital records of 26 patients who underwent surgery via simultaneous combined approach for thoracic and lumbar spinal tumors at our institution from July 1994 to March 2000 were reviewed. Surgery was performed with the patients in the lateral decubitus position for the procedure. The technical details are reported. The mean survival determined by Kaplan-Meier analysis was 43.4 months for the 15 patients with primary malignant tumors and 22.5 months for the 11 patients with metastatic spinal disease. At 1 month after surgery, 23 (96%) of 24 patients who complained of pain preoperatively reported improvements (p < 0.001, Wilcoxon signed-rank test), and eight (62%) of 13 patients with preoperative neurological deficits were functionally improved (p = 0.01). There were nine major complications, five minor complications, and no deaths within 30 days of surgery. Two patients (8%) later underwent surgery for recurrent tumor. The simultaneous anterior-posterior approach is a safe and feasible alternative for the exposure tumors of the thoracic and lumbar spine that involve both the anterior and posterior columns. Advantages of the approach include direct visualization of adjacent neurovascular structures, the ability to achieve complete resection of lesions involving all three columns simultaneously (optimizing hemostasis), and the ability to perform excellent dorsal and ventral stabilization in one operative session.


Age-related variance in decisions under ambiguity is explained by changes in reasoning, executive functions, and decision-making under risk.
Previous literature has explained older individuals' disadvantageous decision-making under ambiguity in the Iowa Gambling Task (IGT) by reduced emotional warning signals preceding decisions. We argue that age-related reductions in IGT performance may also be explained by reductions in certain cognitive abilities (reasoning, executive functions). In 210 participants (18-86 years), we found that the age-related variance on IGT performance occurred only in the last 60 trials. The effect was mediated by cognitive abilities and their relation with decision-making performance under risk with explicit rules (Game of Dice Task). Thus, reductions in cognitive functions in older age may be associated with both a reduced ability to gain explicit insight into the rules of the ambiguous decision situation and with failure to choose the less risky options consequently after the rules have been understood explicitly. Previous literature may have underestimated the relevance of cognitive functions for age-related decline in decision-making performance under ambiguity.


Cell fate specification by even-skipped expression in the Drosophila nervous system is coupled to cell cycle progression.
The correct specification of defined neurons in the Drosophila central nervous system is dependent on even-skipped. During CNS development, even-skipped expression starts in the ganglion mother cell resulting from the first asymmetric division of neuroblast NB 1-1. This first division of NB 1-1 (and of the other early neuroblasts as well) is temporally controlled by the transcriptional regulation of string expression, which we have manipulated experimentally, even-skipped expression still occurs if the first neuroblast division is delayed, but not if the division is prohibited. Moreover, even-skipped expression is also dependent on progression through S phase which follows immediately after the first division. However, cytokinesis during the first NB division is not required for even-skipped expression as revealed by observations in pebble mutant embryos. Our results demonstrate therefore that even-skipped expression is coupled to cell cycle progression, presumably in order to prevent a premature activation of expression by a positive regulator which is produced already in the neuroblast during G2 and segregated asymmetrically into the ganglion mother cell during mitosis.


[An inadequate intake of manganese may favour insulin resistance in girls].
to study the relationship between an adequate manganese (Mn) intake and glucose, insulin levels and insulin resistance among healthy children from Madrid (Spain). 573 schoolchildren between 8 and 13 years old were studied. Energy and nutrients intake (especially Mn) was calculated with a "3-day diet record". Mn intake was compared to Adequate Intakes (AI) for this mineral. Weight and height were measured and body mass index (BMI) calculated. Fasting glucose and insulin were determined and the HOMA index was calculated to establish the presence of insulin resistance in children. Girls with and inadequate intake (below the 100% of the AI value) had higher insulin and HOMA values than girls with adequate AI values (equal or higher to 100% of AI). Having in mind confounding factors (energy, carbohydrates and lipids intake, BMI and age), a significant positive correlation was found between the contribution of Mn intake to AI and HOMA levels in girls. It seems important to ensure an adequate Mn intake in girls in order to prevent insulin resistance and diabetes type 2 in the future.


Obesity in pregnancy.
Overweight and obesity are common findings in women of reproductive age in the UK; as 32% of 35- to 64-year-old women are overweight and 21% obese. Obesity causes major changes in many features of maternal intermediary metabolism. Insulin resistance appears to be central to these changes and may also be involved in increased energy accumulation by the fetus. Maternal obesity is associated with many risks to the pregnancy, with increased risk of miscarriage (three-fold) and operative delivery (20.7 versus 33.8% in the obese and 47.4% in the morbidly obese group). Other risks to the mother include an increased risk of pre-eclampsia (3.9 versus 13.5% in the obese group) and thromboembolism (0.05 versus 0.12% in the obese group). There are risks to the fetus with increased perinatal mortality (1.4 per 1000 versus 5.7 per 1000 in the obese group) and macrosomia (>90th centile; 9 versus 17.5% in the obese group). Maternal obesity is associated with an increased risk of obesity in the long term. Obese woman should try to lose weight before pregnancy but probably not during pregnancy. There is no real evidence base for the management of maternal obesity but some practical suggestions are made.


Provisioning of game meat to rural communities as a benefit of sport hunting in Zambia.
Sport hunting has reportedly multiple benefits to economies and local communities; however, few of these benefits have been quantified. As part of their lease agreements with the Zambia Wildlife Authority, sport hunting operators in Zambia are required to provide annually to local communities free of charge i.e., provision a percentage of the meat obtained through sport hunting. We characterized provisioning of game meat to rural communities by the sport hunting industry in Zambia for three game management areas (GMAs) during 2004-2011. Rural communities located within GMAs where sport hunting occurred received on average > 6,000 kgs per GMA of fresh game meat annually from hunting operators. To assess hunting industry compliance, we also compared the amount of meat expected as per the lease agreements versus observed amounts of meat provisioned from three GMAs during 2007-2009. In seven of eight annual comparisons of these GMAs, provisioning of meat exceeded what was required in the lease agreements. Provisioning occurred throughout the hunting season and peaked during the end of the dry season (September-October) coincident with when rural Zambians are most likely to encounter food shortages. We extrapolated our results across all GMAs and estimated 129,771 kgs of fresh game meat provisioned annually by the sport hunting industry to rural communities in Zambia at an approximate value for the meat alone of >US$600,000 exclusive of distribution costs. During the hunting moratorium (2013-2014), this supply of meat has halted, likely adversely affecting rural communities previously reliant on this food source. Proposed alternatives to sport hunting should consider protein provisioning in addition to other benefits (e.g., employment, community pledges, anti-poaching funds) that rural Zambian communities receive from the sport hunting industry.


Spoken language of individuals with mild fluent aphasia under focused and divided-attention conditions.
The spoken language of individuals with mild aphasia and age-matched control subjects was studied under conditions of isolation, focused attention, and divided attention. A picture-description task was completed alone and in competition with a tone-discrimination task. Regardless of condition, individuals with aphasia performed more poorly on most morphosyntactic, lexical, and pragmatic measures of spoken language than control subjects. Increasing condition complexity resulted in little quantitative or qualitative change in the spoken language of the control group. In contrast, the individuals with aphasia showed dual-task interference; as they shifted from isolation to divided-attention conditions, they produced fewer syntactically complete and complex utterances, fewer words, and poorer word-finding accuracy. In pragmatic terms, their communication was considered less successful and less efficient. These results suggest that decrements of attentional capacity or its allocation may negatively affect the quantity and quality of the spoken language of individuals with mild aphasia.


Symmetric bilateral transposition flap: a very versatile option in facial dermatological surgery.
Repair following excision of large tumours of the face can be problematic; primary closure may not be achievable and grafting or secondary intention healing carry the risk of necrosis and lengthy healing times. Flaps are usually associated with earlier healing and better cosmetic results, as the skin used for closure is similar to the tissue requiring repair. However, large wound sizes and difficulty in finding a suitable donor area means flaps can be complicated to perform. The aim of this paper was to identify a comparatively quick and simple alternative to standard repair techniques for the closure of large wound defects in critical anatomical areas, when the only realistic alternative would be grafting, offering both good cosmetic results and minimal risk of complications. We have developed a flap, modified from the classic, single lobe transposition flap. Two similar lobes placed symmetrically and perpendicularly to two opposite sides of the surgical wound are incised with fulcra centred on two opposite corners. The flaps are then rotated by approximately 80-90º into position side by side, sutured to the borders of the surgical wound and finally together with a longitudinal suture. The principle behind this flap is the split of the covering surface into 2 small units, rather than using a large single lobe, which, for large wounds, would make closure of the single donor area by first intention impossible. The split of the donor area in 2 smaller subunits makes it easier to close the two donor areas and allows a larger amount of tissue to be harvested. We have developed a twinned symmetric transposition flap to close large wounds on the face when the only realistic alternative would have been the use of grafting. It offers minimal distortion, and is both quick and simple to perform. The use of tissue similar to the original defect ensures good cosmetic results. Healing times were usually very rapid and complications limited to a very few cases of end flap necrosis. This technique is not applicable where donor areas fall in anatomic spots where harvesting of the lobes is impossible, e.g. when the wound is too close to the hair line and transposition of the lobes would cause the transfer of hairy skin to an area where the presence of hair is not desirable.


The effect of antioxidant and whitening action on Plantago asiatica L. leaf ethanol extract for health care.
The Plantago asiatica L. is easy to cultivate and has been used as a folk remedy since ancient times because of various pharmacological actions such as anti-inflammation and antioxidation. It also contains a variety of flavonoids such as aucubin, which is thought to be excellent for whitening, antioxidant and anti-inflammatory action. We investigated the effect of P. asiatica L. leaf ethanol extracts containing various active ingredients on antioxidative, anti-inflammation and whitening action and investigated its potential as a health care material. P. asiatica L. has been widely used in folk remedies. The cell toxicity test using RAW264.7 cells showed a high cell survival rate of over 75%, thus demonstrating the safety of the sample. In order to study the antioxidant activity of P. asiatica L. leaf ethanol extracts, we studied a sample which showed radical scavenging activity in a dose-dependent manner. To observe the antioxidant activity at the cell level, RAW 264.7 cells were used and inhibition of ROS production was measured. The ROS production was suppressed in a dose-dependent manner and the scavenging activity was stronger than the sample's own radical scavenging ability. To observe the anti-inflammatory effect of P. asiatica L. leaf ethanol extracts, inhibition of NO generation was observed using LPS-induced RAW 264.7 cells. NO generation was inhibited in a dose-dependent manner and was strongly inhibited by 31% at 100 μg/mL. In vitro, L-DOPA and L-tyrosine were used to inhibit tyrosinase action in a dose-dependent manner. The concentration of melanin at 1, 10, and 100 μg/mL was suppressed in B16 F10 melanin cells supplemented with α-MSH in the cells, and the inhibition was suppressed to 29% at 100 μg/mL. In the B16 F10 melanin cell stimulated with MSH, the P. asiatica L. leaf ethanol extracts inhibited melanin formation in a dose-dependent manner. P. asiatica L. leaf ethanol extracts are expected to be developed as whitening cosmeceutical ingredients and as health care ingredients with antioxidant and anti-inflammatory properties.