Dopamine dependent setting of a circadian oscillator underlying the memory for time of day.
Animals learn and remember the time of day that significant conditions occur, and anticipate recurrence at 24-h intervals, even after only one exposure to the condition. On several place-conditioning tasks, animals show context avoidance or preference only near the time of day of the experience. The memory for time of day is registered by a circadian oscillator that is set at the time of the training. We show that manipulations of dopamine (DA) neurotransmission can set a time memory in place preference and avoidance tasks, indicating that time of day is part of the context that is learned. Single injections of the DA agonist, d-amphetamine sulfate given without further exposure to the conditioning apparatus, can reset the timing of anticipatory behavior evoked by previously acquired place-event associations. The data support a model for time memory in which DA signaling sets the phase of a circadian oscillator, which returns to the same state at regular 24-h intervals. The data also raise the possibility that some apparent impairments of memory formation or retention could reflect post-experience resetting of the optimal retrieval time rather than impairment of memory or retrieval per se.


Modified secondary lithium metal batteries with the polyaniline-carbon nanotube composite buffer layer.
A modified secondary lithium metal battery inserted with a polyaniline-carbon nanotube nanoporous composite buffer layer was fabricated. This unique and simple design of battery has the great potential to decrease the safety risk of the secondary Li metal battery in cycles of recharging processes and improve its cycle life in the future.


Bone Marrow Stromal Cell Intraspinal Transplants Fail to Improve Motor Outcomes in a Severe Model of Spinal Cord Injury.
Bone marrow stromal cells (BMSCs) have been reported to exert potential neuroprotective properties in models of neurotrauma, although precise mechanisms underlying their benefits are poorly understood. Despite this lack of knowledge, several clinical trials have been initiated using these cells. To determine whether local mechanisms mediate BMSC neuroprotective actions, we grafted allogeneic BMSCs to sites of severe, compressive spinal cord injury (SCI) in Sprague-Dawley rats. Cells were administered 48 h after the original injury. Additional animals received allogeneic MSCs that were genetically modified to secrete brain-derived neurotrophic factor (BDNF) to further determine whether a locally administered neurotrophic factor provides or extends neuroprotection. When assessed 2 months post-injury in a clinically relevant model of severe SCI, BMSC grafts with or without BDNF secretion failed to improve motor outcomes. Thus, allogeneic grafts of BMSCs do not appear to act through local mechanisms, and future clinical trials that acutely deliver BMSCs to actual sites of injury within days are unlikely to be beneficial. Additional studies should address whether systemic administration of BMSCs alter outcomes from neurotrauma.


Renal cold storage followed by transplantation impairs proteasome function and mitochondrial protein homeostasis.
Identifying pathways related to renal cold storage (CS) that lead to renal damage after transplantation (Tx) will help us design novel pathway-specific therapies to improve graft outcome. Our recent report showed that mitochondrial function was compromised after CS alone, and this was exacerbated when CS was combined with Tx (CS/Tx). The goal of this study was to determine whether the proteasome exacerbates mitochondrial dysfunction after CS/Tx. We exposed the kidneys of male Lewis rats (in vivo) and rat renal proximal tubular (NRK) cells (in vitro) to CS/Tx or rewarming (CS/RW), respectively. To compare CS-induced effects, in vivo kidney Tx without CS exposure (autotransplantation; ATx) was also used. Our study provides the first evidence that the chymotrypsin-like (ChT-L) peptidase activity of the proteasome declined only after CS/Tx or CS/RW, but not after CS or ATx. Interestingly, key mitochondrial proteins involved with respiration [succinate dehydrogenase complex, subunit A (SDHA), a complex II subunit, and ATP5B, an ATP synthase/complex V subunit] were detected in the detergent-insoluble fraction after CS/Tx or CS/RW, with compromised complex V activity. Pharmacological inhibition of ChT-L activity in NRK cells decreased the activity of mitochondrial complexes I, II, and V and also increased the levels of SDHA and ATP5B in the insoluble fraction. On the other hand, inhibiting mitochondrial respiration in NRK cells with antimycin A compromised ChT-L function and increased the amounts of SDHA and ATP5B in the insoluble fraction. Our results suggest that mitochondrial respiratory dysfunction during CS precedes compromised ChT-L function after CS/Tx and proteasome dysfunction further alters mitochondrial protein homeostasis and decreases respiration in the kidneys after CS/Tx. Therefore, therapeutics that preserve mitochondrial and proteasome function during CS may provide beneficial outcomes following transplantation.


Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease.
Several postmortem studies have shown iron accumulation in the substantia nigra of Parkinson's disease patients. Iron concentration can be estimated via MRI-R2∗ mapping. To assess the changes in R2∗ occurring in Parkinson's disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson's disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality. The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R2∗ values were measured in subcortical regions of interest (substantia nigra, red nucleus, striatum, globus pallidus externus and globus pallidus internus) contralateral (dominant side) and ipsilateral (non dominant side) to the most clinically affected hemibody. As the observed inter-subject R2∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R2∗ in the red nucleus as an intra-subject reference. R2∗ values significantly increased in Parkinson's disease patients when compared with controls; in the substantia nigra (SN) in the dominant side (D) and in the non dominant side (ND), respectively (PSN_D and PSN_ND < 0.0001). After stratification into four subgroups according to the disease duration, no significant R2∗ difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R2(ISQR)∗ values significantly increased in the substantia nigra (PSN_D and PSN_ND < 0.0001) when comparing all Parkinson's disease patients to controls. R2(ISQR)∗ values in the substantia nigra significantly increased with the disease duration (PSN_D = 0.01; PSN_ND = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, PSN_D = 0.02). Additionally, correlations between R2(ISQR)∗ and clinical features, mainly related to the severity of the disease, were found. Our results support the use of ISQR to reduce variations not directly related to Parkinson's disease, supporting the concept that ISQR strategy is useful for the evaluation of Parkinson's disease.


Pattern Of Leukaemia Patients Admitted In Ayub Teaching Hospital Abbottabad.
Any tissue of the body can give rise to cancer. However, those tissues which multiply rapidly are at high risk of developing cancer and haematopoietic system is one of them. Neoplasms of this system are known as leukaemia and lymphoma, according to the types of white cells involved. Study of cancer patterns in different societies, however can contribute a substantial knowledge about the aetiology of cancer. The present Study was designed and aimed to estimate the frequency of different types of leukaemia in patients admitted in Ayub Teaching hospital Abbottabad. Data from the patients admitted at oncology Department of Ayub Teaching Hospital Abbottabad from 2010 to 2015 was collected and analysed to calculate cumulative and year-wise frequency of leukaemia and its major types. Frequency distribution with reference to gender and age was also calculated. In our analysis about 16% patients had acute myelocytic leukaemia and 32% patients had acute lymphocytic leukaemia; while chronic myeloid leukaemia outnumbered chronic lymphocytic leukaemia (11% and 3%); Hodgkin lymphoma was seen in 18% cases while Non Hodgkin lymphoma (NHL) was present in 20% cases. Out of the total, 150 cases (75%) belonged to mountainous areas of Hazara, i.e., 40 cases belonged to Kohistan, another 40 cases were residents of Battagram, 45 cases belonged to hilly areas of Mansehra and 25 cases to Kaghan valley, while only 50 (25%) cases were from the plain areas of Abbottabad and Haripur districts, i.e., 20 and 30 cases respectively. Leukaemia is more common in hilly areas of Hazara, since majority of the cases belonged to well-known mountainous regions of Kohistan, Battagram, Kaghan or Mansehra and only few cases belonged to the plain areas of Abbottabad and Haripur districts.


Self-assembly of a mesoporous ZnS/mediating interface/CdS heterostructure with enhanced visible-light hydrogen-production activity and excellent stability.
We designed and successfully fabricated a ZnS/CdS 3D mesoporous heterostructure with a mediating Zn1-x Cd x S interface that serves as a charge carrier transport channel for the first time. The H2-production rate and the stability of the heterostructure involving two sulfides were dramatically and simultaneously improved by the careful modification of the interface state via a simple post-annealing method. The sample prepared with the optimal parameters exhibited an excellent H2-production rate of 106.5 mmol h-1 g-1 under visible light, which was 152 and 966 times higher than CdS prepared using ethylenediamine and deionized water as the solvent, respectively. This excellent H2-production rate corresponded to the highest value among the CdS-based photocatalysts. Moreover, this heterostructure showed excellent photocatalytic stability over 60 h.


[A double-blind, cross-over clinical trial of recombinant human G-CSF on neutropenia induced by chemotherapy for non-Hodgkin's lymphoma].
A double-blind, placebo-controlled, cross-over clinical trial of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was conducted in 46 patients receiving intensive chemotherapy for non-Hodgkin's lymphoma. Each patient received 2 cycles of CHOP therapy. rG-CSF (2 micrograms/kg/day) or its placebo was given subcutaneously to each patient for 14 days from 2 days after initiation of the chemotherapy, in a cross-over fashion. rG-CSF significantly increased the absolute neutrophil counts (ANC) at nadir, and reduced the number of days with ANC less than 1,000/mm3 and also the number of days for recovery to ANC greater than or equal to 2,000/mm3. Bone marrow examination showed a significant increase in the number of myeloid cells after rG-CSF treatment. 12 infective episodes were observed during placebo cycles, while 6 infective episodes were observed during rG-CSF cycles. No serious side effects were observed. We concluded that rG-CSF was effective in neutropenia induced by intensive chemotherapy for non-Hodgkin's lymphoma.


Strategies for data management engagement.
The research landscape is growing dramatically, and librarians are examining new roles, services, and types of collaborations to support data-intensive research. This column describes curricular enhancements at one School of Library and Information Science in the United States. Several key areas of data management in which health sciences librarians may wish to build or enhance their skills are outlined. Possible roles and opportunities for health sciences librarians to strategically engage in data management initiatives are also presented.


Cultural values and performance appraisal: assessing the effects of rater self-construal on performance ratings.
Much of the prior research investigating the influence of cultural values on performance ratings has focused either on conducting cross-national comparisons among raters or using cultural level individualism/collectivism scales to measure the effects of cultural values on performance ratings. Recent research has shown that there is considerable within country variation in cultural values, i.e. people in one country can be more individualistic or collectivistic in nature. Taking the latter perspective, the present study used Markus and Kitayama's (1991) conceptualization of independent and interdependent self-construals as measures of individual variations in cultural values to investigate within culture variations in performance ratings. Results suggest that rater self-construal has a significant influence on overall performance evaluations; specifically, raters with a highly interdependent self-construal tend to show a preference for interdependent ratees, whereas raters high on independent self-construal do not show a preference for specific type of ratees when making overall performance evaluations. Although rater self-construal significantly influenced overall performance evaluations, no such effects were observed for specific dimension ratings. Implications of these results for performance appraisal research and practice are discussed.


[Are there alternatives to emergency admissions?].
Emergency admissions account for an increasing number of admissions to hospitals, especially to medical departments. Several hospitals in Norway are planning alternatives to emergency admissions, e.g. emergency outpatient departments and observation units. We registered emergency admissions to internal medicine and surgical, orthopaedic and gynaecological departments to St. Olavs University Hospital during one week in June 2003. Using questionnaires we received the admitting and the treating doctors' evaluation of the reason for admissions and also of the possibilities for alternatives as emergency care, nursing homes, observations units or treatment by general practitioners. 202 out of 262 admissions were included the study. Recently oncoming illness was the most important reason. For the whole group, only 10% of the admissions were caused by social issues, but social issues were often the main cause for admissions for older patients. Only 12% of the patients were admitted by their own general practitioner. An observation unit was the mostly recommended alternative to admission, but there were disagreements between primary care and hospital doctors as to which patients would be suitable. The study suggests that it is difficult to identify patients at the time of admission who could be treated without regular admission.


[The influence of age and sex on the results of otosclerosis surgery].
The influence of age and sex on auditory improvement after stapes surgery was investigated retrospectively on 127 otosclerotic ears (99 subjects) that were followed up for 6 months postoperatively. The prostheses used were the Shuknecht-type Teflon wire piston (87 ears), the House-type wire loop (29 ears), and the Cawthone-type Teflon piston (11 ears). While closure of the air-bone gap after surgery was good at 2 kHz, it was poor at 8 kHz and frequencies lower than 1 kHz, and especially poor at 250 Hz. At all frequencies, both air and bone thresholds were significantly improved by the surgery, but the greatest improvements in air and bone thresholds resulted from the use of Teflon wire pistons. Ears receiving Teflon wire prostheses were divided into 5 age groups: under 20 years, 20-29, 30-39, 40-49, and 50 or above. Both air and bone thresholds at higher frequencies before surgery worsened with increasing age. However, there were no significant differences among age groups in the postsurgical improvement of either air or bone thresholds. Similarly, no gender-related differences in either air or bone thresholds were recognized postsurgically. The authors speculate that light cases of otosclerosis are common among Japanese patients, while severe cases are rare even among the elderly.


[Changes in head circumference and ventricular system size after neuro-endoscopic third ventriculostomy in children].
The aim of the study was to compare changes in the head circumference ventricular system size after neuroendoscopic third ventriculostomy with those following shunt implantation in children suffering from chronic hydrocephalus. The data were analysed to establish criteria of success of neuroendoscopic procedures. In the years 1999-2001 neuroendoscopic third ventriculostomy was performed in 59 children at the Neurosurgery Department of the Research Institute of Polish Mothers' Memorial Hospital. However, the sample analysed in the paper consists of 29 children (16 boys, 13 girls aged from 18 days to 18 years, mean age 7.03, SD = 7.11 years) with chronic hydrocephalus successfully treated with neuroendoscopic procedures. The control group consists of 59 children (31 boys, 28 girls) selected out of 80 patients who underwent primary shunt implantation at the same Neurosurgical Department in the years 1992-1994. The control children (aged from 2 weeks to 9 months, mean age 2 months, SD = 1.92 months) did not need shunt revision during the clinical observation period. The ventricular system size was assessed in terms of the Frontal Index, while postoperative changes in the system size were expressed by the ratio of the Final Frontal Index to the Baseline Frontal Index. If the ventricular system size remained the same, the ratio was 1; if its size decreased after surgery, the ratio was less than 1, while any increases in the system size were reflected by a ratio over 1. Moreover, the head circumference (HC) was measured before and after surgery only in infants and neonates with non-communicating hydrocephalus. HC was expressed in centiles using the centile chart developed by Kurniewicz-Witczakowa for various age and sex groups of Polish children. The analysis included also post-surgery changes in HC over the observation period, in terms of the difference between the baseline HC value and HC measurements in relation to the observation period duration. A positive sign of this index evidenced a decrease in the rate of HC enlargement, while a negative sign--an increased rate of HC growth. The mean HC at the end of the observation period was 72.96 centile in the neuroendoscopy group and 52.36 centile in children after shunt implantation. The reduction of head circumference following neuroendoscopic procedures was significantly smaller than that after shunt implantation, as the average decrease in HC after neuroendoscopy was only 0.4 centile as compared to about 18 centiles after shunt implantation. In the neuroendoscopy group a relationship was found between HC and age: in newborns HC was significantly smaller than that in infants (20.25 and 82.55 centiles, respectively). An analysis of HC changes (in centiles) in relation to the time since the surgery in all the children aged under 1 year, successfully treated with neuroendoscopic procedures, indicated no tendency to a steady increase in the rate of HC enlargement, even though in many cases the HC after surgery was larger than that prior to the surgery. As regards changes in the ventricular system size, the average ratio of Final to Baseline Frontal Index was 0.9 in the neuroendoscopy group and 0.5 in the group after shunt implantation. The ventricular system turned out to be significantly larger in infants after neuroendoscopy than in other age groups (the mean Frontal Index values were 0.65 vs. 0.53, respectively). No tendency to constant enlargement of the ventricular system size after neuroendoscopy was found. In children with non-communicating hydrocephalus due to Chiarii II malformation a mild enlargement of the ventricular system was seen after successful neuroscopy (the ratio of the Final to Baseline Frontal Index amounted to 1.3). The rate of head circumference (HC) enlargement in infants after succeeded neuroendoscopic procedures did not continually increase during the postoperative period, although their HC expressed in centiles could be higher than that before surgery. The average reduction of the ventricular system size was much smaller after neuroendoscopic ventriculostomy than than after shunt implantations. In children with Chiarii II malformation and in infants the ventricle system size may be somewhat increased in comparison to pre-operative levels. However, no tendency to a steady enlargement with time was found either in the HC or in the ventricle system size.


[Comparison of sonographic and roentgenologic findings in the paranasal sinuses in children].
Sonography of maxillary sinuses was performed in 362 asymptomatic children with chronic airway diseases, using a 7.5 MHz sector scanner. Pathologic findings were detected in 78 (21.5%) children. Occipito-frontal radiographs of the sinuses were performed in 40 (11%) randomly chosen children and the findings were later compared with those of sonography. An overall agreement in terms of "normal-abnormal" findings was present in 94% of the 80 sinuses examined. In sinuses judged as "normal" or "abnormal" in either of the methods, findings were corresponding as "normal" in 40 of 45 (89%) and as "abnormal" in 35 of 40 (87%) sinuses. A differentiated assessment of pathologic findings showed an agreement in only 19 of 40 (48%) sinuses. Thus, an overall agreement of differentiated findings was present in 59 of 80 (74%) sinuses. Sonography was superior to radiography especially in differentiating the sinus content in secretion, swelling of the mucosa, polyps, cysts and air. In conclusion, sonography offers an accurate screening method for assessment of paranasal sinuses in children.


Long-term hypervitaminosis D-induced hypercalcaemia treated with glucocorticoids and bisphosphonates.
Hypercalcaemia is a common diagnosis with the majority of cases resulting from hyperparathyroidism or malignancy. We report a rare case of persistent symptomatic hypervitaminosis D-induced hypercalcaemia in an individual taking 50 000 IU of vitamin D supplement daily for several months following a diagnosis of vitamin D deficiency. His hypercalcaemia was initially treated with calcitonin and intravenous fluids, but due to recurrent symptomatic hypercalcaemia after discharge, additional treatment with glucocorticoids and bisphosphonates was warranted during his second admission. The pathophysiology of hypercalcaemia from vitamin D intoxication results from the long-term effects of vitamin D storage in adipose tissue. In the present case, we discuss this pathophysiology and treatment approaches in the context of increasing awareness of and testing for vitamin D deficiency, and growing access to over-the-counter supplements.


IgG4-Related Sclerosing Cholangitis Involving the Intrahepatic Bile Ducts Diagnosed with Liver Biopsy.
IgG4-related disease is characterized by lymphoplasmacytic inflammation and fibrosis, often leading to mass-forming lesions in different organs. When IgG4-related disease affects the bile ducts, it is called IgG4-related sclerosing cholangitis. A 74-year-old male complained of dysphagia and abdominal pain. Endoscopic retrograde cholangiography and magnetic resonance cholangiography revealed bile duct changes suspicious of a bile duct carcinoma or cholangitis. Liver biopsy showed storiform fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, and a portal-based inflammatory nodule with expansion of a portal tract. Hot spots revealed 339 IgG4-positive cells per high power field (HPF) and an IgG4/IgG ratio of 72%. Eight months earlier, an inguinal lymph node had been removed, showing expanded interfollicular zones and increased plasma cells. Hot spots revealed 593 IgG4-positive cells and an IgG4/IgG ratio of 92%. The serum IgG4 of the patient was elevated nearly 10 times upper limit of normal. The diagnosis of IgG4-related sclerosing cholangitis associated with IgG4-related lymphadenopathy was made. There was good response to treatment with prednisolone and azathioprine. The differentiation of IgG4-related sclerosing cholangitis from primary sclerosing cholangitis and bile duct carcinoma is often difficult. Liver biopsy only rarely contributes to this setting, but we describe and report in detail a case where liver biopsy showed a portal-based inflammatory nodule with the characteristic features of this disease.


[Influence of salivary gland hormone on the number of leukocytes and level of calcium in the blood of experimental rabbits].
The authors examined the influence of single venous doses of hormone from the saliva glands on the calcium level and leucocytes in the blood of nonnarcotized experimental rabbits. They investigated the effect in the following doses: 20, 10.5 and 1 mg/kg of body weight. The indicated two indices were examined 2, 4, 6 and 10 hours after the injection of the preparation. The venous administration of all exa mined doses of the hormone from the saliva glands caused statistically significant lowering of leucocytes on the second hour and respective increase on the sixth and tenth hour since the onset of the experiment. The hormone of the saliva glands lowered the amount of calcium ions in blood, but the difference was not always statistically significant in various doses and time intervals.


Gracilis Myocutaneous Flap: Adding to the Armamentarium of Complex Sacrococcygeal Defect Reconstruction.
Background With increasing radicality of rectal cancer surgeries, the postoperative defects are becoming more complex. This demands an ideal reconstructive option with minimal morbidity to the patient. Although vertical rectus abdominis myocutaneous (VRAM) flap is the commonly used flap, gracilis myocutaneous flap is increasingly being performed to avoid morbidity associated with VRAM flap. Results We share our experience about two of our patients treated for rectal malignancy with pelvic exenteration who were reconstructed immediately with pedicled gracilis myocutaneous flap. Both the patients had an uneventful postoperative recovery period and were discharged on postoperative day 10. During follow-up period both patients had a healthy flap with no evidence of recurrence. No perineal hernias or gross dehiscence of skin closure occurred. Conclusion Gracilis myocutaneous flap has its own place with unique advantages adding to the armamentarium of reconstructive options for complex perineal defects, thereby avoiding the morbidity associated with VRAM flap. It stands as a reliable alternative in patients where VRAM cannot be used.


Poststroke epilepsy: occurrence, predictors and treatment.
Although a well-known clinical phenomenon, there still remain some questions regarding the definitions, pathophysiology and epidemiology of early and late poststroke seizures and of poststroke epilepsy. Poststroke seizures and epilepsy constitute important complications in patients surviving a stroke. Several studies of the prevalence and possible predictors of poststroke seizures and epilepsy have been undertaken during the past few decades. Unfortunately, these studies have not consistently used the established definitions. There are only few studies concerning treatment of poststroke epilepsy in the elderly, especially regarding the effect of the newer antiepileptic drugs. The aim of this article is to give an overview of the latest studies of poststroke seizures, with special emphasis on poststroke epilepsy, by presenting data on occurrence, predictors and treatment. The results from the recent studies on both poststroke seizures (early and late) and poststroke epilepsy are quite consistent. Poststroke epilepsy appears to occur in 2-4% of patients. The most convincing predictors of late poststroke seizures and epilepsy and treatment options are discussed in this review.


Laparoscopic revision of gastric pacing wires.
Currently, electrical stimulation is utilized to treat morbid obesity, gastroparesis, and diaphragmatic paralysis. Although this technology is in its infancy, numerous case reports and small series appear throughout the literature. Furthermore, electrical stimulation is not relegated to only academic centers and tertiary referral centers. As these technologies continue to evolve and alter the treatment of several different pathophysiologic processes, the general surgeon needs to understand the technical aspects of these devices and their potential complications. This paper presents the management of a gastroparetic patient with chronic abdominal pain following the successful placement of gastric pacing wires. A 45-year-old female with idiopathic gastroparesis underwent laparoscopic placement of gastric pacing wires without complications. Four months postoperatively, she presented with chronic left upper quadrant abdominal pain. Her nausea and vomiting had dissipated and she was tolerating a regular diet. Abdominal and pelvic computed tomography (CT) was normal except for the presence of a generator and pacing wires. Ultimately, she required a diagnostic laparoscopy and an upper endoscopy. The upper endoscopy was normal. The diagnostic laparoscopy showed a wide adhesive band from the seromuscular tunnel of the pacing wires to the abdominal wall in the left upper quadrant. The band was lysed and an omental patch was sutured over the insertion site of the wires. On postoperative day 1, the patient was pain-free and discharged home on a regular diet. This case presents an unusual complication of electrical pacing wires. This patient experienced somatic pain due to an adhesive band from her pacing wires to the abdominal wall. Based on the findings of this case, an omental patch was placed on top of the seromuscular electrode tunnel in order to prevent adhesions and potentially persistent abdominal wall pain.


Multiple effect of social influence on cooperation in interdependent network games.
The social influence exists widely in the human society, where individual decision-making process (from congressional election to electronic commerce) may be affected by the attitude and behavior of others belonging to different social networks. Here, we couple the snowdrift (SD) game and the prisoner's dilemma (PD) game on two interdependent networks, where strategies in both games are associated by social influence to mimick the majority rule. More accurately, individuals' strategies updating refers to social learning (based on payoff difference) and above-mentioned social influence (related with environment of interdependent group), which is controlled by social influence strength s. Setting s = 0 decouples the networks and returns the traditional network game; while its increase involves the interactions between networks. By means of numerous Monte Carlo simulations, we find that such a mechanism brings multiple influence to the evolution of cooperation. Small s leads to unequal cooperation level in both games, because social learning is still the main updating rule for most players. Though intermediate and large s guarantees the synchronized evolution of strategy pairs, cooperation finally dies out and reaches a completely dominance in both cases. Interestingly, these observations are attributed to the expansion of cooperation clusters. Our work may provide a new understanding to the emergence of cooperation in intercorrelated social systems.


[Delayed diagnosis of neurocysticercosis: two case reports].
Neurocysticercosis is the most frequently encountered cerebral parasitic infection worldwide. It is due to infection of the central nervous system by Taenia solium larval form. According to the location of the cysts, parenchymal and extra-parenchymal forms may be identified, with different clinical expressions. We report two cases of neurocysticercosis, one with typical parenchymal involvement and the second with extra-parenchymal involvement revealed by increased intra-cranial pressure. In both cases, the diagnosis was established over 10 years after the onset of symptoms. Neurocysticercosis is very frequent in non-Islamic developing countries, and its incidence is increasing in industrialized nations in relation to tourism and immigration from highly endemic areas. Symptoms usually appear several years after infection and this accounts for the frequent delays before the diagnosis is established.


Cooperative dimerization of fibroblast growth factor 1 (FGF1) upon a single heparin saccharide may drive the formation of 2:2:1 FGF1.FGFR2c.heparin ternary complexes.
The related glycosaminoglycans heparin and heparan sulfate are essential for the activity of the fibroblast growth factor (FGF) family as they form an integral part of the signaling complex at the cell surface. Using size-exclusion chromatography we have studied the capacities of a variety of heparin oligosaccharides to bind FGF1 and FGFR2c both separately and together in ternary complexes. In the absence of heparin, FGF1 had no detectable affinity for FGFR2c. However, 2:2:1 complexes formed spontaneously in solution between FGF1, FGFR2c, and heparin octasaccharide (dp8). The dp8 sample was the shortest chain length that bound FGFR2c, that dimerized FGF1, and that promoted a strong mitogenic response to FGF1 through FGFR2c. Heparin hexasaccharide and various selectively desulfated heparin dp12s failed to bind FGFR2c and could only interact with FGF1 monomerically. These saccharides formed 1:1:1 complexes with FGF1 and FGFR2c, which had no tendency to self-associate, suggesting that binding of two FGF1 molecules to the same saccharide chain is a prerequisite for subsequent FGFR2c dimerization. We found that FGF1 dimerization upon heparin was favored over monomeric interactions even when a large excess of saccharide was present. A cooperative mechanism of FGF1 dimerization could explain how 2:2:1 signaling complexes form at the cell surface, an environment rich in heparan sulfate.


Effect Of Medical Waste Management Trainings On Behavior Change Among Doctors Versus Nurses And Paramedical Staff In Pakistan.
Healthcare waste management is a neglected issue in hospitals of developing countries due to poor practices among health staff. This study was aimed to determine the differences in knowledge, attitude and practices of physicians versus nursing and paramedical staff about standard health care waste management (HCWM). This quasi-experimental study was conducted among healthcare workers of the two tertiary care hospitals in Rawalpindi. A total of 138 hospital workers in intervention and 137 in control hospital were given training on HCWM. Subjects were followed up at one year and after 18 months of the intervention. We found that nursing and paramedical staff was more knowledgeable and compliant with the HCWM standards, knowledge and practices as compared to physicians. A higher proportion of nursing and paramedical staff was able to retain more of high level of knowledge but more of the doctors had achieved and retained positive attitudes towards HCWM standards after the training. More of nursing and paramedical staff also had good HCWM practices; both at first as well as second follow up. As nursing and paramedical staff was more knowledgeable and practiced optimum standards they needed to be rewarded adequately and given further regular trainings to help them maintain their knowledge and best practices about HCWM. As HCWM and patient safety standards keep on changing regularly, the hospital workers especially doctors need to be focused to comply with the standard practices in hospitals.


[Alveolar rhabdomyosarcoma of the parotid gland].
Alveolar rhabdomyosarcoma of salivary glands is a rare malignant neoplasm, presenting a striated muscular differentiation. It is typically observed in children, adolescents, and young adults but can sometimes be diagnosed in older people. We report the case of a 57 year-old man presenting with a primary alveolar rhabdomyosarcoma of the parotid gland. The patient was treated by surgery and radiotherapy. According to literature data, alveolar rhabdomyosarcoma of the parotid gland is exceptionally described after 40 years of age. In that case it has the worst prognosis and its lethality is due mainly to its very early metastasis.


The effect of inulin as a fat substitute on the physicochemical and sensory properties of chicken sausages.
Due to its high thermal resistance and compatibility with the sausage emulsion system, the long-chain inulin can be used as a fat substitute in the formulation of this product. This study was conducted to investigate the effect of inulin on the physicochemical, textural, and sensory properties of chicken sausages. The study included treatments of 25%, 50%, 75%, and 100% substitution. After preparing the samples, their physicochemical, textural, calorimetric, and sensory properties were evaluated. The treatment of 100% substitution of inulin had the maximum amount of sugar (29.90%), moisture (72.63%), protein (51.34), ash (6.95%), and salt (4.02%) (dry basis). The fat content was decreased with the increased levels of inulin substitution (p < .05). The increased amount of inulin reduced hardness, cohesiveness, gumminess, and stringiness, but increased springiness and chewiness up to the 25% substitution of inulin. The highest color difference and hue angle were related to 100% substitution treatment. The sensory evaluation of the samples showed that with the increase in the amount of inulin, the mean scores of the factors including color, appearance, and texture were increased, but the mean scores of smell and mouthfeel were decreased. Overall, the substitution of the entire fat existing in the formulation of the sausage with inulin led to the best physicochemical, textural, colorimetric, and sensory results. The use of inulin could be recommended as a fat substitute in the formulation of chicken sausages.


The educational homogamy gap between married and cohabiting couples in Latin America.
The explosive expansion of non-marital cohabitation in Latin America since the 1970s has led to the narrowing of the gap in educational homogamy between married and cohabiting couples (what we call "homogamy gap") as shown by our analysis of 29 census samples encompassing eight countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico and Panama (N = 2,295,160 young couples). Most research on the homogamy gap is limited to a single decade and a small group of developed countries (the United States, Canada, and Europe). We take a historical and cross-national perspective and expand the research to a range of developing countries, where since early colonial times traditional forms of cohabitation among the poor, uneducated sectors of society have coexisted with marriage, although to widely varying degrees from country to country. In recent decades, cohabitation is emerging in all sectors of society. We find that among married couples educational homogamy continues to be higher than for those who cohabit, but in recent decades the difference has narrowed substantially in all countries. We argue that assortative mating between cohabiting and married couples tend to be similar when the contexts in which they are formed are also increasingly similar.


Recurrent primary thunderclap headache and benign CNS angiopathy: spectra of the same disorder?
To investigate the clinical pictures of patients with recurrent thunderclap headaches of unknown etiology and to field-test two relevant International Classification of Headache Disorders, 2nd edition (ICHD-II) criteria, i.e., primary thunderclap headache (Code 4.6) and benign (or reversible) angiopathy of the CNS (Code 6.7.3). We prospectively recruited patients presenting with idiopathic recurrent thunderclap headaches from a hospital-based headache clinic. Detailed histories, neurologic examinations, and MRIs and magnetic resonance angiographies (MRAs) were performed in all patients to exclude secondary causes. Patients with cerebral vasoconstriction received serial MRA follow-up. Fifty-six consecutive patients (51 female/5 male, mean age 49.6 +/- 9.8 [range 22 to 76] years) were enrolled. Segmental vasoconstriction (or benign CNS angiopathy) was found in 22 patients (39%). Thunderclap headache recurred in all patients with a median frequency of 0.7 times per day for a median period of 14 days (range 6 to 86 days). The median duration for each single attack was 3 hours. Most patients (84%) reported at least one trigger. Nimodipine effectively aborted further attacks in 83% of the treated patients. Headache attacks subsided within 3 months. Four patients (7%) developed ischemic complications. Patients with and without vasoconstriction based on MRA images were similar regarding demographics and headache profile. Except for the duration criterion, our patients generally mapped well into the proposed ICHD-II criteria. This study suggests that the two diagnostic entities proposed by the ICHD-II may present different spectra of the same disorder. The distinct headache profile may help physicians quickly recognize this disabling headache disorder with risk of stroke and provide timely treatment.


Re-ingestion of Plasmodium berghei sporozoites after delivery into the host by mosquitoes.
Malaria-infected mosquitoes feeding on a mammalian host inject sporozoites into the skin to induce a malaria infection. The numbers of sporozoites ultimately able to reach the liver may be important determinants of the characteristics of the ensuing blood infection. Because feeding mosquitoes not only inject sporozoites into the host but concomitantly ingest blood to obtain their bloodmeal, some sporozoites are re-ingested by the feeding mosquito. We studied transmission of fluorescent Plasmodium berghei sporozoites injected into mice by Anopheles stephensi mosquitoes and found that the numbers of sporozoites re-ingested by mosquitoes are comparable to numbers previously reported to be delivered directly into mice. Thus, re-ingestion of sporozoites likely plays a significant role in transmission dynamics of malaria by mosquitoes, and may account for the failure of some sporozoite-infected mosquitoes to induce a blood infection.


How to make a cardiomyocyte.
During development, cardiogenesis is orchestrated by a family of heart progenitors that build distinct regions of the heart. Each region contains diverse cell types that assemble to form the complex structures of the individual cardiac compartments. Cardiomyocytes are the main cell type found in the heart and ensure contraction of the chambers and efficient blood flow throughout the body. Injury to the cardiac muscle often leads to heart failure due to the loss of a large number of cardiomyocytes and its limited intrinsic capacity to regenerate the damaged tissue, making it one of the leading causes of morbidity and mortality worldwide. In this Primer we discuss how insights into the molecular and cellular framework underlying cardiac development can be used to guide the in vitro specification of cardiomyocytes, whether by directed differentiation of pluripotent stem cells or via direct lineage conversion. Additional strategies to generate cardiomyocytes in situ, such as reactivation of endogenous cardiac progenitors and induction of cardiomyocyte proliferation, will also be discussed.


2-substituted thioadenine nucleoside and nucleotide analogues: synthesis and receptor subtype binding affinities (1).
The design, synthesis, and receptor subtype binding affinities of several 2-substituted thioadenosine nucleoside and nucleotide analogues are described. Alkylation of 2-thioadenosine (1) with iodopentenylboronic acid followed by iododeboronation gave 2-((E)-1-iodo-1-penten-5-yl) thioadenosine (9). Compound 1 on treatment with 4-nitrobenzyl bromide and propargyl bromide furnished compounds 3 and 5, respectively. The 5'-monophosphate analogues of compounds 3, 5, 7, and 9 were prepared similarly using 2-thioadenosine 5'-monophosphate (2). Treatment of 1 with bromoethylamine hydrobromide provided 2-[(aminoethyl)thio]adenosine (11) which on coupling with N-succinimidyl 3-(4-hydroxyphenyl)propionate gave 2-[[[3-(4-hydroxyphenyl)propionamido]ethyl]thio]adenosine (12). Iodination of 12 gave 2-[[[3-(4-hydroxy-3-iodophenyl)propionamido]ethyl]thio]adenosine (13). Compounds 3-13 were evaluated for their affinities toward A1 and A2 adenosine receptors in rat brain cortex and striatum, respectively using [3H]DPCPX and [3H]CGS21680 as ligands. The nucleotide analogues 4, 6, 8, and 10 inhibited binding of [3H]DPCPX by 10-20% and of [3H]CGS21680 by 40-50% at a concentration of 100 microM suggesting weak affinity toward adenosine receptors. The nucleoside analogues 3, 5, 7, 9, 12, and 13 inhibited the A2 receptor binding of [3H]CGS21680 with Ki values of 1.2-3.67 microM, while A1 receptor binding of [3H]DPCPX was inhibited with Ki values 10-17 microM. The A1/A2 ratios suggest 4-8-fold A2 receptor selectivity.


A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing.
Monoclonal antibodies (mAb) are commonly manufactured by either discontinuous operations like fed-batch (FB) or continuous processes such as steady-state perfusion. Both process types comprise opposing advantages and disadvantages in areas such as plant utilization, feasible cell densities, media consumption and process monitoring effort. In this study, we show feasibility of a promising novel hybrid process strategy that combines beneficial attributes of both process formats. In detail, our strategy comprises a short duration FB, followed by a fast media exchange and cell density readjustment, marking the start of the next FB cycle. Utilizing a small-scale screening tool, we were able to identify beneficial process parameters, including FB interval duration and reinoculation cell density, that allow for multiple cycles of the outlined process in a reproducible manner. In addition, we could demonstrate scalability of the process to a 5L benchtop system, using a fluidized-bed centrifuge as scalable media exchange system. The novel process showed increased productivity (+217%) as well as longer cultivation duration, in comparison to a standard FB with a significantly lower media consumption per produced product (-50%) and a decreased need for process monitoring, in comparison to a perfusion cultivation. Further, the process revealed constant glycosylation pattern in comparison to the perfusion cultivation and has strong potential for further scale-up, due to the use of fully scalable cultivation and media exchange platforms. In summary, we have developed a novel hybrid process strategy that tackles the key challenges of current biomanufacturing of either low productivity or high media consumption, representing a new and innovative approach for future process intensification efforts.


Hunger mediates apex predator's risk avoidance response in wildland-urban interface.
Conflicts between large mammalian predators and humans present a challenge to conservation efforts, as these events drive human attitudes and policies concerning predator species. Unfortunately, generalities portrayed in many empirical carnivore landscape selection studies do not provide an explanation for a predator's occasional use of residential development preceding a carnivore-human conflict event. In some cases, predators may perceive residential development as a risk-reward trade-off. We examine whether state-dependent mortality risk-sensitive foraging can explain an apex carnivore's (Puma concolor) occasional utilization of residential areas. We assess whether puma balance the risk and rewards in a system characterized by a gradient of housing densities ranging from wildland to suburban. Puma GPS location data, characterized as hunting and feeding locations, were used to assess landscape variables governing hunting success and hunting site selection. Hunting site selection behaviour was then analysed conditional on indicators of hunger state. Residential development provided a high energetic reward to puma based on increases in prey availability and hunting success rates associated with increased housing density. Despite a higher energetic reward, hunting site selection analysis indicated that pumas generally avoided residential development, a landscape type attributed with higher puma mortality risk. However, when a puma experienced periods of extended hunger, risk avoidance behaviour towards housing waned. This study demonstrates that an apex carnivore faces a trade-off between acquiring energetic rewards and avoiding risks associated with human housing. Periods of hunger can help explain an apex predator's occasional use of developed landscapes and thus the rare conflicts in the wildland-urban interface. Apex carnivore movement behaviours in relation to human conflicts are best understood as a three-player community-level interaction incorporating wild prey distribution.


[Expression of gene and content of adiponectin in fatty tissue in patients with ischemic heart disease].
The purpose of the study was to investigate the features of expression and adiponectin content in the adipocyte culture of subcutaneous, epicardial, and perivascular adipose tissue and the effect of various doses of rosuvastatin on these processes. 29 patients with coronary artery disease were examined. Adipocytes were isolated from the samples of SAT, EAT and PVAT which were taken during coronary artery bypass surgery, followed by cultivation in the presence of rosuvastatin and evaluation of gene expression and adiponectin concentration. Adipocytes SAT, EAT and PVAT differed in the level of adiponectin secretion and expression of its gene. On day 1 of cultivation the expression of the adiponectin gene in the EAT was 2.3 times lower than in the PVAT. On day 2 of cultivation the expression of the adiponectin gene was reduced both in the EAT and the PVAT as compared to the SAT. When rosuvastatin was added at a concentration of 1 mmol/L, adiponectin gene expression in PVAT was higher than when rosuvastatin was added at a concentration of 5 mmol/L, in the adipocyte culture of SAT effect was opposite. Thus, the adipocytes of EZhT and, to a greater extent, PAS, can be a therapeutic target for statins in the case of the pathological activation of adipose tissue.


Mortality in Mild Cognitive Impairment: A Longitudinal Study in Memory Clinics.
Patients with mild cognitive impairment (MCI) are at greater risk of mortality than the general population. Comparatively little research has examined predictors of mortality in MCI and no research has examined whether time-varying variables, such as change in cognition and function, predict survival. To identify predictors of mortality in patients with MCI. 185 patients with MCI were recruited from nine memory clinics around Australia. Patients completed measures of cognition, function, and neuropsychiatric symptoms over three years. Mortality data were obtained from state registries eight years after baseline. 55 (30%) patients died within this period. Older age, lower cognitive and functional ability at baseline, and greater decline in functional ability over six months predicted mortality. Easily measurable clinical data predict mortality in patients with MCI. Longitudinal assessment over time can provide additional information about patients' risk.


TNF superfamily control of tissue remodeling and fibrosis.
Fibrosis is the result of extracellular matrix protein deposition and remains a leading cause of death in USA. Despite major advances in recent years, there remains an unmet need to develop therapeutic options that can effectively degrade or reverse fibrosis. The tumor necrosis super family (TNFSF) members, previously studied for their roles in inflammation and cell death, now represent attractive therapeutic targets for fibrotic diseases. In this review, we will summarize select TNFSF and their involvement in fibrosis of the lungs, the heart, the skin, the gastrointestinal tract, the kidney, and the liver. We will emphasize their direct activity on epithelial cells, fibroblasts, and smooth muscle cells. We will further report on major clinical trials targeting these ligands. Whether in isolation or in combination with other anti-TNFSF member or treatment, targeting this superfamily remains key to improve efficacy and selectivity of currently available therapies for fibrosis.


CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Effects in an SKG Arthritis Model.
Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-γ, and IL-6 and increased level of immunoregulatory IL-10.


Plasma profiles of adrenocorticotropic hormone, cortisol, alpha-melanocyte-stimulating hormone, and growth hormone in dogs with pituitary-dependent hyperadrenocorticism before and after hypophysectomy.
The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte-stimulating hormone (alpha-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery. The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and alpha-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and alpha-MSH, the AUC for alpha-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of alpha-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy. The results of this study demonstrate that ACTH, cortisol, alpha-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.


Monitoring for vowels in isolation and in a consonantal context.
The identifiability of isolated vowels (/V/) was compared to that of vowels in consonantal context (/pVp/) when subjects performed a monitoring task. On successive blocks of trials in a test series, the subjects listened for instances of one or another of nine monophthongal vowels (Formula: see text) and identified each test item as being an instance or not. On average, resulting false alarm errors occurred significantly less often in the /pVp/ condition, consistent with the previous finding that vowel perception may be aided by consonantal context. This beneficial effect of context was found to be restricted to the class of open vowels, however, with perception of the close vowels being somewhat hindered by context. The error data for misses also showed an interaction between context and vowel height. Various accounts of the interaction are considered.


The single radial immunodiffusion assay highlights small antigenic differences among influenza virus hemagglutinins.
The results of single radial immunodiffusion assays of influenza virus hemagglutinin were found to be greatly altered by small antigenic differences between test and reference strains. When such differences were present, the precise specificity of the antiserum used had a critical effect on the measured hemagglutinin antigen content obtained.


Analysis of large 16S rRNA Illumina data sets: Impact of singleton read filtering on microbial community description.
Next-generation sequencing technologies give access to large sets of data, which are extremely useful in the study of microbial diversity based on 16S rRNA gene. However, the production of such large data sets is not only marred by technical biases and sequencing noise but also increases computation time and disc space use. To improve the accuracy of OTU predictions and overcome both computations, storage and noise issues, recent studies and tools suggested removing all single reads and low abundant OTUs, considering them as noise. Although the effect of applying an OTU abundance threshold on α- and β-diversity has been well documented, the consequences of removing single reads have been poorly studied. Here, we test the effect of singleton read filtering (SRF) on microbial community composition using in silico simulated data sets as well as sequencing data from synthetic and real communities displaying different levels of diversity and abundance profiles. Scalability to large data sets is also assessed using a complete MiSeq run. We show that SRF drastically reduces the chimera content and computational time, enabling the analysis of a complete MiSeq run in just a few minutes. Moreover, SRF accurately determines the actual community diversity: the differences in α- and β-community diversity obtained with SRF and standard procedures are much smaller than the intrinsic variability of technical and biological replicates.


Impact of Phrenic Nerve Palsy and Need for Diaphragm Plication Following Surgery for Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collaterals.
Injury to the phrenic nerves may occur during surgery for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA-VSD and MAPCAs). These patients may develop respiratory failure and require diaphragm plication. The purpose of this study was to evaluate the impact of phrenic nerve palsy on recovery following surgery for PA-VSD and MAPCAs. Between 2007 and 2016, approximately 500 patients underwent surgery for PA-VSD and MAPCAs at our institution. Twenty-four patients (4.8%) subsequently had evidence of new phrenic nerve palsy. Sixteen patients were undergoing their first surgical procedure, whereas 8 were undergoing reoperations. All 24 patients underwent diaphragm plication. A cohort of matched controls was identified based on identical diagnosis and procedures but did not sustain a phrenic nerve palsy. Eighteen of the 24 patients (75%) had clinical improvement following diaphragm plication as evidenced by the ability to undergo successful extubation (5 ± 2 days), transition out of the intensive care unit (32 ± 16 days), and discharge from the hospital (42 ± 19 days). In contrast, there were 6 patients (25%) who did not demonstrate a temporal improvement following diaphragm plication, as evidenced by intervals of 61 ± 38, 106 ± 45, and 108 ± 46 days, respectively (P < 0.05 for all 3 comparisons). The 6 patients who failed to improve following diaphragm plication had a significantly greater number of comorbidities compared to the 18 patients who demonstrated improvement (2.2 vs 0.6 per patient, P < 0.05). When compared with the control group, patients who improved following diaphragm plication spent an additional 22 days and patients who failed to improve an additional 90 days in the hospital. The data demonstrate a bifurcation of clinical outcome in patients undergoing diaphragm plication following surgery for PA-VSD and MAPCAs. This bifurcation appears to be linked to the presence or absence of other comorbidities.


Neutrophils in antiviral immunity: inhibition of virus replication by a mediator produced by bovine neutrophils.
Neutrophils collected from bovine mammary glands were placed in culture with virus-infected cell preparations that had been inactivated by ultraviolet light. Upon culture with infectious bovine rhinotracheitis (IBR) virus-infected Georgia bovine kidney cells, a material was released from the neutrophils that, like interferon, inhibited the replication of vesicular stomatitis virus and IBR virus. Cell-free IBR virus was a less effective inducer of the inhibitor produced by neutrophils. Other herpesviruses (including herpes simplex type 1), as well as equine rhinopneumonitis virus and pseudorabies virus, caused release of the inhibitor, but most other viruses tested, including Newcastle disease virus, a good inducer of type 1 interferon, failed to stimulate the production of inhibitor by polymorphonuclear neutrophils. Preliminary characterization studies revealed differences between the inhibitor produced by the polymorphonuclear neutrophils and type 1 and type II bovine interferons. The possible role of such an inhibitor in the recovery from herpesvirus infection is briefly discussed.


Strengthening Effects of Zn Addition on an Ultrahigh Ductility Mg-Gd-Zr Magnesium Alloy.
A newly developed Mg-2Gd-0.5Zr-xZn (x = 0.5, 1.0, 2.0, 3.0 wt %) alloy system exhibits significant strengthening by doping with Zn. In order to understand the strengthening mechanism, the microstructure, texture evolution, and mechanical properties of ultrahigh ductility Mg-2Gd-0.5Zr alloys with a Zn addition were systematically investigated. The addition of Zn results in the formation of Mg-Gd-Zn intermetallic compounds along grain boundaries, which encourages grain refinement during hot extrusion via the particle stimulated nucleation (PSN) mechanism. Furthermore, during texture sharpening the pole changes from <20 2 ¯ 1> to <01 1 ¯ 0>, which also occurred in the extruded alloys with Zn addition, which is unfavorable for the basal slip and tensile twinning. Mg-2Gd-0.5Zr-3Zn shows well-balanced strength and ductility with a tensile yield strength (YS) and ultimate tensile strength (UTS) of 285 and 314 MPa, accompanied by a high tensile elongation of 24%. They are superior to those of commercial AZ31. The enhanced strength is attributed to grain refinement, precipitation strengthening, and texture sharpening induced by alloying with Zn. The research result is also of great value to the development of low rare-earth, high strength, and high room temperature ductility magnesium alloy.


[The review of questionnaires and scales evaluating patients with amyotrophic lateral sclerosis].
In patients with amyotrophic lateral sclerosis (ALS), it is advisable to provide multidisciplinary care, due to rapid progression and specific disease symptoms, in order to maintain the best quality of life for the patient and their family. Abroad, questionnaires and scales are used to assess the patient´s health condition, to determine disease progression, followed by the provision of personalized care. The aim of this review article is to describe and analyze the scales used in evaluating ALS patients in both functional and psychosocial areas. Having searched in electronic databases, 14 scales for patients with ALS or motor neuron disease were found, and 4 scales for patients with chronic diseases, which are appropriate and used also in patients with ALS. The ALSFRS scale (The Amyotrophic Lateral Sclerosis Functional Rating Scale) is most often used for assessment of functional status. All areas of care are best covered in the ALSSQOL-R (Amyotrophic Lateral Sclerosis Specific Quality of life) questionnaire, designed for assessment of quality of life. The use of both scales is recommended in clinical practice and research.


Mechanism of killing of pneumococci by lysozyme.
Lysozyme is abundant in respiratory secretions and may play a role in lung host defenses. Mechanisms by which lysozyme killed Streptococcus pneumoniae, an important respiratory pathogen, were studied. Lysozyme caused optical clearing of pneumococcal suspensions and released fragments containing [3H]choline from their cell walls. Electron micrographs revealed wide-spread cell wall destruction and bacteriolysis. Breakdown of the cell wall appeared to be mediated mostly by the major pneumococcal autolysin, N-acetylmuramoyl-L-alanine amidase, because it was blocked by phosphorylcholine, a specific inhibitor of amidase, or by substitution of ethanolamine for choline in the cell wall. Blockade of amidase did not greatly increase survival of lysozyme-treated pneumococci on blood agar. Pneumococci in which amidase was blocked appeared intact immediately after treatment with lysozyme, but when they were reincubated at 37 degrees C in fresh culture medium they swelled and lysed. Thus, widespread triggering of the major pneumococcal autolysin is not essential for the bactericidal effect of lysozyme.


Analyzing the sensory characteristics and taste-sensor ions of MSG substitutes.
This study analyzed the sensory attributes of MSG substitutes to determine whether they exerted synergistic or inhibition effects on taste, and the correlation between sensory attributes (which are subjective measures) and the results of electronic-tongue analysis (which are objective measures). Descriptive and electronic-tongue analyses were conducted with 10 MSG substitutes comprising combinations of 3 commercial products, and with MSG. In the descriptive analysis, the sensory characteristics of MSG substitutes were evaluated using 16 attributes; and in the electronic-tongue analysis, the taste-sensor ions of MSG substitutes were evaluated using 10 taste-sensor types. Principal components analysis was applied separately to the sensory evaluation data and the electronic-tongue data to summarize the structure of each data set. Partial least-squares regression was used to assess the relationship between the sensory evaluation data and the electronic-tongue data. The MSG substitutes show different sensory attributes when they are used alone or in mixtures, suggesting the presence of synergistic or inhibitory effects between them. Therefore, when replacing MSG, the characteristics of each possible substitute should be determined in relation to the particular food system.


Aesthetic treatment considerations for the eyebrows and periorbital complex.
The periorbital complex is a critical cosmetic unit. Treatments for this region range from topical prescriptions to enhance the brow hair to topical cosmeceuticals that improve the tone and texture of the skin. Lasers, radiofrequency, botulinum toxins, fillers, and a host of other treatments are used to treat the periorbital region. Judicious use of these treatments, alone or in combination, can greatly alter the appearance of the region. However, adverse events may also be associated with these treatments, and the clinician and patients need to consider both the risks and the benefits of treatment prior to embarking upon a regimen.


Dehydrophenylalanine zippers: strong helix-helix clamping through a network of weak interactions.
A decapeptide Boc-L-Ala-(Delta Delta Phe)(4)-L-Ala-(Delta Delta Phe)3-Gly-OMe (Peptide I) was synthesized to study the preferred screw sense of consecutive alpha,beta-dehydrophenylalanine (Delta Delta Phe) residues. Crystallographic and CD studies suggest that, despite the presence of two L-Ala residues in the sequence, the decapeptide does not have a preferred screw sense. The peptide crystallizes with two conformers per asymmetric unit, one of them a slightly distorted right-handed 3(10)-helix (X) and the other a left-handed 3(10)-helix (Y) with X and Y being antiparallel to each other. An unanticipated and interesting observation is that in the solid state, the two shape-complement molecules self-assemble and interact with an extensive network of C-H...O hydrogen bonds and pi-pi interactions, directed laterally to the helix axis with amazing regularity. Here, we present an atomic resolution picture of the weak interaction mediated mutual recognition of two secondary structural elements and its possible implication in understanding the specific folding of the hydrophobic core of globular proteins and exploitation in future work on de novo design.


PD-L1 Expressing Recurrent Clear Cell Carcinoma of the Vulva with Durable Partial Response to Pembrolizumab: A Case Report.
The optimal treatment and molecular landscape of recurrent clear cell carcinoma of the vulva (VCCC) are unknown. No reported data exist regarding the efficacy of anti-programmed death 1 (PD-1) immune checkpoint inhibition in VCCC. We report on a patient with chemotherapy-refractory recurrent VCCC, who was found to have high tumor programmed death-ligand 1 (PD-L1) combined positive score (CPS), and subsequently experienced a durable partial response (PR), after treatment with off-label fifth-line pembrolizumab. A forty-year-old Filipino woman presented to our center with recurrent VCCC that had progressed on multiple prior lines of cytotoxic chemotherapy. She had a large 25 cm fungating left groin tumor causing marked lower limb lymphedema, pain and limited mobility. PD-L1 CPS by immunohistochemistry was 45. She was treated with off-label pembrolizumab monotherapy and had a dramatic clinical, biochemical and radiological partial response. The progression-free survival of this patient's VCCC after treatment with pembrolizumab, defined as the time from initiation of pembrolizumab until disease progression (by Response Evaluation Criteria in Solid Tumors (version 1.1)), was 8 months. While receiving pembrolizumab, she was diagnosed with concurrent secondary myelodysplastic syndrome with excess blasts (MDS-EB), thought to be related to her prior exposure to multiple lines of cytotoxic chemotherapy. This eventually progressed to acute myeloid leukemia (AML), leading to her demise. Overall survival from time of initiation of pembrolizumab till death was 16 months. Pembrolizumab was active in this patient with chemotherapy-refractory VCCC which harbored high PD-L1 CPS. Further studies to determine the role of immune check-point blockade in the treatment of VCCC are warranted.


Trauma-Responsive Scaffold Synchronizing Oncolysis Immunization and Inflammation Alleviation for Post-Operative Suppression of Cancer Metastasis.
Tumor surgery can create an inflammatory trauma to aggravate residual tumor "seed" to colonize pre-metastatic niches (PMNs) "soil" at secondary sites, thereby promoting post-operative metastasis. However, two-pronged strategies for post-surgical elimination of asynchronous "seeds" and "soil" at different regions are currently lacking. Here, we have designed a hydrogel that can be injected into a resection cavity, where it immediately forms a scaffold and gradually degrades responding to enriched reactive oxygen species at adjacent trauma for local delivery and on-demand release of autologous cancer cells succumbing to oncolysis (ACCO) and anti-inflammatory agent. The autologous cell source self-provides a whole array of tumor-associated antigens, and the oncolysis orchestration of a subcellular cascade confers a self-adjuvanting property, together guaranteeing high immunogenicity of the ACCO vaccine that enables specific antitumor immunization. In parallel, inflammation alleviation exerted bidirectional functions to reshape the local immune landscape and resuscitate ACCO, leading to the eradication of residual tumor "seeds" while simultaneously intercepting the "seed-soil" crosstalk to normalize distant lung leading to regression of pre-existing PMN "soil". As a result, regional and metastatic recurrence were completely thwarted. Together, this framework synchronizing oncolysis immunization and inflammation alleviation provides an effective option for post-operative suppression of metastasis.


Using an Algorithm to Assess Vaccination Among Patients Who Attended a Pharmacy Student-Driven Statewide Free Health Screening.
National vaccination rates remain below goals. Given the geographic availability of community pharmacies, pharmacists are uniquely positioned to provide immunizations. However, many pharmacists may not be proactively recommending vaccinations to patients. The objective of this project was to assess recommendation acceptance rates among patients who attended a pharmacy student-driven statewide free health screening. A brief algorithm addressing 4 routine adult vaccinations was created for use by student pharmacists to initiate conversations regarding potentially indicated vaccines with patients. This algorithm was employed at statewide screenings in 2014 and 2015 with expert users available for further discussion. Follow-up to determine recommendation acceptance and identify barriers to immunization occurred 3 to 12 months after screening. The primary end point of change in immunization recommendation acceptance rates between 2014 and 2015 was analyzed using a chi-square test; secondary objectives included changes in consent rates and thematic analysis of reported barriers. A total of 1016 patients were screened. Of these, 403 (39.7%) patients gave consent for student pharmacists to follow-up on vaccine recommendations. The overall recommendation acceptance rate was 27%, with approximately 46% of patients accepting at least 1 recommendation. Acceptance rates significantly decreased in the second year (36.5% vs 23.5%, P < .001), while consent for follow-up significantly increased (20% vs 64%, P < .001). Commonly reported barriers to immunization included resistance to vaccines, forgetfulness, and cost. This algorithm provided a method for novice users to initiate conversations with patients about immunizations and may allow novices to act as pharmacist extenders to improve immunization rates.


Generation of restriction map of Enterococcus faecalis OG1 and investigation of growth requirements and regions encoding biosynthetic function.
A defined synthetic medium was used to determine the amino acid requirements of Enterococcus faecalis OG1 and to demonstrate the absence of a requirement for exogenous purines or pyrimidines. Genomic libraries prepared from strain OG1 were transduced into Escherichia coli auxotrophic mutants, and cloned DNAs which complemented pyrC, pyrD, purF, purL, and guaAB mutations were identified. These and other cloned DNAs with known functions were localized on a restriction map of OG1 which was generated with SfiI (5 fragments), AscI (9 fragments), and NotI (15 fragments); the size of the OG1 chromosome was revised from a previous estimate of approximately 2,750 kb to 2,825 kb. The synthetic medium and the restriction map should be useful for studying enterococcal metabolic functions and the relationships between chromosomally encoded genes.


[Impact of the practice of "Extended Focused Assessment with Sonography for Trauma" (e-FAST) on clinical decision in the emergency department].
We aimed to show the sensitivity of Extended Focused Assessment with Sonography for Trauma (e-FAST) for detection of pneumothorax, hemothorax and intraabdominal injury. We also investigated the relationship between e-FAST and need for invasive treatment. This study included patients who experienced multiple trauma. The emergency physician, who had no clinical information about the patient, performed e-FAST. Findings on a supine chest X-ray and invasive interventions were recorded. The results of abdomen and thorax computed tomography (CT) were reviewed (the size of the pneumothorax was scored). Compared with CT, the sensitivities of e-FAST for intraabdominal injury and hemothorax were 54.5% and 71%, respectively. The patients with hemothorax and intraabdominal injuries were not identified with e-FAST, didn't need for invasive intervention. Pneumothorax diagnosis was established in 27 patients with e-FAST (sensitivity 81.8%) from among 33 (30.8%) pneumothorax patients. According to the grading on CT, pneumothoraces less than 1 cm in width and not exceeding the midcoronal line in length were not identified. e-FAST was positive for all patients performed with tube thoracostomy. e-FAST can be used with high sensitivity for determination of pneumothorax requiring invasive procedure. It has low sensitivity in the diagnosis of intraabdominal injury and hemothorax; however, e-FAST can predict the need for invasive procedures.


Sensitized excited free-radical processes as read-write tools: impact on non-linear lithographic processes.
A prefluorescent radical probe in which a 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) unit is sensitized with visible light via energy transfer from a tethered coumarin dye has been synthesized. The excited TEMPO moiety undergoes hydrogen abstraction from a polymer with concomitant functionalization of the polymeric matrix; this writing process can be reversed thermally. The fluorescent probes can be bleached under high intensity illumination, making these new materials suitable for dual-tone lithography with potential applications in sub-diffraction lithographic imaging.


[Preparation and hemostatic evaluation of chitosan composite hemostatic membrane].
To improve the flexibility and hemostatic properties of chitosan (CS)/carboxymethyl chitosan (CMCS) hemostatic membrane by using glycerol and etamsylate to modify CS/CMCS hemostatic membrane. To investigate the mechanical properties and hemostatic capability of modified CS/CMCS hemostatic membrane. The 2% CS solution, 2% CMCS solution, 10%, 15%, 20%, 25%, 30% glycerol with or without 0.5% etamsylate were used to prepare CS/CMCS hemostatic membrane with or without etamsylate by solution casting according to ratio of 16 : 4 : 5. The tensile properties were evaluated by tensile test according to GB 13022-1991. Twenty venous incisions and five arterial incisions hemorrhage of 1 cm x 1 cm in rabbit ears were treated by CS/CMCS hemostatic membrane modified by 15% (group A) and 25% (group B) of glycerol, and a combination of them and 0.5% etamsylate (groups C and D). The bleeding time and blood loss were recorded. The pH of yellow CS/ CMCS hemostatic membrane with thickness of 30-50 microm was 3-4. The incorporation glycerol into CS/CMCS hemostatic membrane resulted in decreasing in tensile strength (7.6%-60.2%) and modulus (97%-99%). However, elongation at break and water content increased 5.7-11.6 times and 13%-125% markedly. CS/CMCS hemostatic membrane adhered to wound rapidly, absorbed water from blood and became curly. The bleeding time and blood loss of venous incisions were (70 +/- 3) seconds and (117.2 +/- 10.8) mg, (120 +/- 10) seconds and (121.2 +/- 8.3) mg, (52 +/- 4) seconds and (98.8 +/- 5.5) mg, and (63 +/- 3) seconds and (90.3 +/- 7.1) mg in groups A, B, C, and D, respectively; showing significant differences (P < 0.05) between groups A, B and groups C, D. The bleeding time and blood loss of arterial incision were (123 +/- 10) seconds and (453.3 +/- 30.0) mg in group C. CS/CMCS hemostatic membrane modified by glycerol and etamsylate can improve the flexibility, and shorten the bleeding time.


Populus species from diverse habitats maintain high night-time conductance under drought.
We investigated the interspecific variability in nocturnal whole-plant stomatal conductance under well-watered and drought conditions in seedlings of four species of Populus from habitats characterized by abundant water supply (mesic and riparian) or from drier upland sites. The study was carried out to determine whether (i) nocturnal conductance varies across different species of Populus according to their natural habitat, (ii) nocturnal conductance is affected by water stress similarly to daytime conductance based on species habitat and (iii) differences in conductance among species could be explained partly by differences in stomatal traits. We measured whole-plant transpiration and conductance (G) of greenhouse-grown seedlings using an automated high-resolution gravimetric technique. No relationship was found between habitat preference and daytime G (GD), but night-time G (GN) was on average 1.5 times higher in riparian and mesic species (P. deltoides Bartr. ex Marsh. and P. trichocarpa Torr. & Gray) than in those from drier environments (P. tremuloides Michx. and P. × petrowskyana Schr.). GN was not significantly reduced under drought in riparian species. Upland species restricted GN significantly in response to drought, but it was still at least one order of magnitude greater that the cuticular conductance until leaf death was imminent. Under both well-watered and drought conditions, GN declined with increasing vapour pressure deficit (D). Also, a small increase in GN towards the end of the night period was observed in P. deltoides and P. × petrowskyana, suggesting the involvement of endogenous regulation. The anatomical analyses indicated a positive correlation between G and variable stomatal pore index among species and revealed that stomata are not likely to be leaky but instead seem capable of complete occlusion, which raises the question of the possible physiological role of the significant GN observed under drought. Further comparisons among closely related species that occupy ecologically diverse habitats may provide a better understanding of the genetic versus environmental regulations of nocturnal water loss.


Colloidal particles interacting with a polymer brush: a self-consistent field theory.
The interaction of colloidal particles with a planar polymer brush immersed in a solvent of variable thermodynamic quality is studied by a numerical self-consistent field method combined with analytical mean-field theory. The effect of embedded particle on the distribution of polymer density in the brush is analyzed and the particle insertion free energy profiles are calculated for variable size and shape of the particles and sets of polymer-particle and polymer-solvent interaction parameters. In particular, both cases of repulsive and attractive interactions between particles and brush-forming chains are considered. It is demonstrated that for large particles the insertion free energy is dominated by repulsive (osmotic) contribution and is approximately proportional to the particle volume in accordance with earlier theoretical predictions [Halperin et al., Macromolecules, 2011, 44, 3622]. For the particles of smaller size or/and large shape asymmetry the adsorption or depletion of a polymer from the particle surface essentially contributes to the insertion free energy balance. As a result, depending on the set of polymer-solvent and polymer-particle interaction parameters and brush grafting density the insertion free energy profile may exhibit complex patterns, i.e., from a pure repulsive effective potential barrier to an attractive well. The results of our study allow for predicting equilibrium partitioning and controlling diffusive transport of (bio)nanocolloids across (bio)polymer brushes of arbitrary geometry including polymer-modified membranes or nanopores.


Obesity-related increase in whole blood viscosity includes different profiles according to fat localization.
In a precedent study we observed that overall adiposity evaluated with the body mass index (BMI) was correlated with plasma viscosity and red blood cells (RBC) aggregation while abdominal obesity as assessed with the waist to hip ratio (WHR) was correlated with hematocrit. We investigated this issue in 129 women (age 15-65 years, BMI: 15 to 44 kg/m(2), WHR: 0.65 to 1.13, fatness: 12-58%) who were divided into fatness groups: 17 underweight women (BMI <18.5), 75 normal weigh (BMI 18.5-24.9), 11 overweight (BMI 25-29.9), and 26 obese (BMI >30) divided according to WHR into 13 lower body and 13 upper body obese women. Whole blood viscosity significantly increases across obesity classes, and is higher in upper body than in lower body obesity (2.84 ± 0.08 vs 3.29 ± 0.09 mPa.s, p < 0.05). The correlations between whole blood viscosity and BMI (r = 0.383 p < 0.01) and WHR (r = 0.364 p < 0.01) are found again. The former is explained by correlations of BMI with plasma viscosity (r = 0.303 p < 0.01) and red cell rigidity (r = 0.356 p < 0.01) and the latter is only explained by a correlation between WHR and hematocrit (r = 0.524 p < 0.01). BMI is also correlated with RBC aggregation parameters. Actually, when total fatness is evaluated with the percentage of fat (%fat) given by bioimpedance analysis (BIA), the picture is slightly different, since %fat is correlated with whole blood viscosity and RBC aggregation parameters but not with hematocrit, plasma viscosity and red cell rigidity. Fat free mass is also correlated with whole blood viscosity (r = 0.227 p < 0.02) due to a correlation with hematocrit (r = 0.483 p < 0.01) but neither RBC rheology nor plasma viscosity. This study shows that fatness by its own is associated with increased red cell aggregation, that abdominal fat increases blood viscosity due to a rise in hematocrit, and that overall body size as assessed with the BMI is associated with increased plasma viscosity and red cell rigidity.


Plasmonic nanorod arrays of a two-segment dimer and a coaxial cable with 1 nm gap for large field confinement and enhancement.
Seeking plasmonic nanostructures with large field confinement and enhancement is significant for photonic and electronic nanodevices with high sensitivity, reproducibility, and tunability. Here, we report the synthesis of plasmonic arrays composed of two-segment dimer nanorods and coaxial cable nanorods with ∼1 nm gap insulated by a self-assembled Raman molecule monolayer. The gap-induced plasmon coupling generates an intense field in the gap region of the dimer junction and the cable interlayer. As a result, the longitudinal plasmon resonance of nanorod arrays with high tunability is obviously enhanced. Most interestingly, the field enhancement of dimer nanorod arrays can be tuned by the length ratio L1/L2 of the two segments, and the maximal enhancement appears at L1/L2 = 1. In that case, the two-photon luminescence (TPL) of dimer nanorod arrays and the Raman intensity in the dimer junction is enhanced by 27 and 30 times, respectively, under resonant excitation. In the same way, the Raman intensity in the gap region is enhanced 16 times for the coaxial cable nanorod arrays. The plasmonic nanorod arrays synthesized by the facile method, having tunable plasmon properties and large field enhancement, indicate an attractive pathway to the photonic nanodevices.


Determining hematological, biochemical and immunological reference values in healthy adults with high-risk for HIV acquisition in Mozambique.
In many African countries, laboratory reference values are not established for the local healthy adult population. In Mozambique, reference values are known for young adults (18-24yo) but not yet established for a wider age range. Our study aimed to establish hematological, biochemical and immunological reference values for vaccine trials in Mozambican healthy adults with high-risk for HIV acquisition. A longitudinal cohort and site development study in Mozambique between November 2013 and 2014 enrolled 505 participants between 18 to 35 years old. Samples from these healthy participants, were analyzed to determine reference values. All volunteers included in the analysis were clinically healthy and human immunodeficiency virus (HIV), hepatitis B and C virus, and syphilis negative. Median and reference ranges were calculated for the hematological, biochemical and immunological parameters. Ranges were compared with other African countries, the USA and the US National Institute of Health (NIH) Division of AIDS (DAIDS) toxicity tables. A total of 505 participant samples were analyzed. Of these, 419 participants were HIV, hepatitis B and C virus and syphilis negative including 203 (48.5%) females and 216 (51.5%) males, with a mean age of 21 years. In the hematological parameters, we found significant differences between sex for erythrocytes, hemoglobin, hematocrit, MCV, MCH and MCHC as well as white blood cells, neutrophils and platelets: males had higher values than females. There were also significant differences in CD4+T cell values, 803 cells/μL in men versus 926 cells/μL in women. In biochemical parameters, men presented higher values than women for the metabolic, enzymatic and renal parameters: total and direct bilirubin, ALT and creatinine. This study has established reference values for healthy adults with high-risk for HIV acquisition in Mozambique. These data are helpful in the context of future clinical research and patient care and treatment for the general adult population in the Mozambique and underline the importance of region-specific clinical reference ranges.


Cutaneous IgA-associated vasculitis induced by alcohol.
A patient with elevated levels of serum IgA developed purpuric lesions histologically resembling Henoch-Schönlein purpura brought on by consuming alcohol. Alcohol challenge with 5 units of alcohol reproduced the lesions, with a rapid rise of circulating CD4+ and CD8+ T cells followed by a fall of serum IgA and C3 concentration. The skin lesions and serum abnormalities resolved spontaneously within 6 weeks of the alcohol challenge.


Functional analysis of a breast cancer-associated mutation in the intracellular domain of the metalloprotease ADAM12.
A recently identified breast cancer-associated mutation in the metalloprotease ADAM12 alters a potential dileucine trafficking signal, which could affect protein processing and cellular localization. ADAM12 belongs to the group of A Disintegrin And Metalloproteases (ADAMs), which are typically membrane-associated proteins involved in ectodomain shedding, cell-adhesion, and signaling. ADAM12 as well as several members of the ADAM family are over-expressed in various cancers, correlating with disease stage. Three breast cancer-associated somatic mutations were previously identified in ADAM12, and two of these, one in the metalloprotease domain and another in the disintegrin domain, were investigated and found to result in protein misfolding, retention in the secretory pathway, and failure of zymogen maturation. The third mutation, p.L792F in the ADAM12 cytoplasmic tail, was not investigated, but is potentially significant given its location within a di-leucine motif, which is recognized as a potential cellular trafficking signal. The present study was motivated both by the potential relevance of this documented mutation to cancer, as well as for determining the role of the di-leucine motif in ADAM12 trafficking. Expression of ADAM12 p.L792F in mammalian cells demonstrated quantitatively similar expression levels and zymogen maturation as wild-type (WT) ADAM12, as well as comparable cellular localizations. A cell surface biotinylation assay demonstrated that cell surface levels of ADAM12 WT and ADAM12 p.L792F were similar and that internalization of the mutant occurred at the same rate and extent as for ADAM12 WT. Moreover, functional analysis revealed no differences in cell proliferation or ectodomain shedding of epidermal growth factor (EGF), a known ADAM12 substrate between WT and mutant ADAM12. These data suggest that the ADAM12 p.L792F mutation is unlikely to be a driver (cancer causing)-mutation in breast cancer.


Spatial variation of the rain-snow temperature threshold across the Northern Hemisphere.
Despite the importance of precipitation phase to global hydroclimate simulations, many land surface models use spatially uniform air temperature thresholds to partition rain and snow. Here we show, through the analysis of a 29-year observational dataset (n = 17.8 million), that the air temperature at which rain and snow fall in equal frequency varies significantly across the Northern Hemisphere, averaging 1.0 °C and ranging from -0.4 to 2.4 °C for 95% of the stations. Continental climates generally exhibit the warmest rain-snow thresholds and maritime the coolest. Simulations show precipitation phase methods incorporating humidity perform better than air temperature-only methods, particularly at relative humidity values below saturation and air temperatures between 0.6 and 3.4 °C. We also present the first continuous Northern Hemisphere map of rain-snow thresholds, underlining the spatial variability of precipitation phase partitioning. These results suggest precipitation phase could be better predicted using humidity and air temperature in large-scale land surface model runs.


[Fertility preservation in testicular cancer patients].
Germ cell tumors of the testicle account for 1% of all tumors. Testicular cancer (TC) is the most common malignancy in men aged 15-35 years. Patients with TC have an excellent survival rate but often have not yet attempted to father children, and fertility is one of the main concerns of survivors, therefore it is important to preserve it. The most commonly used method is sperm banking. Retrospective analysis of the Hungarian data showed that in case of testicular cancer spermatogenesis is more impaired in the more advanced disease. No correlation was found among the histological types and the proportion of azoo- and oligozoospermia. The parameters of testicular cancer and non-Hodgkin lymphoma patients were worse compared to the normal population. Sperm cryopreservation prior to initiating life-saving cancer treatment offers men the best chance to father children and should be offered to all men with testicular cancer before chemotherapy, since cytostatic therapy may lead to infertility.


Ordered arrays of ZnO nanorods grown on periodically polarity-inverted surfaces.
Periodically polarity inverted (PPI) ZnO templates were fabricated using molecular beam epitaxy by employing MgO buffer layers. The polarity of ZnO film was controlled by the transformation of crystal structure from hexagonal to rocksalt due to the thickness of the MgO buffer layers. The polarity of ZnO in the PPI template was confirmed by AFM and PRM measurement. Higher growth rate and lower current value under positive supplied voltage in the region of Zn-polar were measured with comparing to that of O-polar. Holographic lithographic technique was employed for the realization of submicron pattern of periodical inverted polar ZnO over large area. After reaction using a carbothermal reduction, spatially well-separated ZnO nanorods with pitch of submicron were only observed in the Zn-polar regions. The possible reason for the difference of surface characteristics was considered as being due to the configuration of dangling bonds according to polarity.


Pathway of Actin Folding Directed by the Eukaryotic Chaperonin TRiC.
The hetero-oligomeric chaperonin of eukarya, TRiC, is required to fold the cytoskeletal protein actin. The simpler bacterial chaperonin system, GroEL/GroES, is unable to mediate actin folding. Here, we use spectroscopic and structural techniques to determine how TRiC promotes the conformational progression of actin to the native state. We find that actin fails to fold spontaneously even in the absence of aggregation but populates a kinetically trapped, conformationally dynamic state. Binding of this frustrated intermediate to TRiC specifies an extended topology of actin with native-like secondary structure. In contrast, GroEL stabilizes bound actin in an unfolded state. ATP binding to TRiC effects an asymmetric conformational change in the chaperonin ring. This step induces the partial release of actin, priming it for folding upon complete release into the chaperonin cavity, mediated by ATP hydrolysis. Our results reveal how the unique features of TRiC direct the folding pathway of an obligate eukaryotic substrate.


Sister Mary Joseph's Nodule: Where Umbilicus Holds the Truth!
An umbilical metastasis from an internal visceral malignancy is defined as Sister Mary Joseph's nodule (SMJN), and, although a rare finding, it is a very poor prognostic indicator. We describe an interesting case of metastatic colon cancer with SMJN, emphasizing the significance of this classic finding. A 64-year-old female with a history of stage IV colon cancer with palliative right hemicolectomy and left hepatectomy presented to the hospital with nausea and abdominal discomfort. A computed tomography (CT) scan of the abdomen was performed, which showed small bowel obstruction secondary to metastatic tumor mass compressing the duodenum. She refused to undergo any chemotherapy or endoscopic intervention and was eventually discharged on hospice care. During the hospital stay an umbilical ulcerative lesion was also noted, which was violaceous, measuring 4.5 x 4 cm in size, firm in consistency with irregular borders, and tender to touch. Therefore, further history was obtained from the patient about it. Several months ago, she had developed localized swelling around the umbilicus, which gradually enlarged and ulcerated later. She eventually underwent the biopsy of that umbilical lesion, which confirmed it as SMJN with metastasis from the colonic primary. However, the patient refrained from the surgical intervention of the umbilical lesion. SMJN presents as a palpable periumbilical metastatic mass with diameter usually not exceeding 5 cm in size. It can be variable in color from violaceous to reddish brown. Once discovered, such lesions should be worked up with biopsy and imaging studies such as CT scan of the abdomen, as the nodule may be indicative of underlying malignancy or cancer recurrence. Its presence indicates a poor prognosis, with average survival time after diagnosis of SMJN of 10 months.