Population code, noise correlations, and memory.
Changes in the correlated activity in the population code can increase neural discrimination by facilitating noise suppression. In this issue, Jeanne et al. (2013) observe learning-dependent changes in high-level avian auditory cortical neurons after a song discrimination task.


Lighting and Nurses at Medical-Surgical Units: Impact of Lighting Conditions on Nurses' Performance and Satisfaction.
This study investigates the perception of nurses about their lighting environment at medical-surgical hospital units in order to understand areas of improvement for lighting at these units. The bulk of the research about nurses and lighting is focused on nighttime nursing, exploring the disruptions of nurses' circadian rhythm and maintaining alertness. The understanding of nurses' perception about lighting and its impact on nurses' task performance and patient examination remains imprecise. This study used an online survey to ask a set of questions about lighting in medical-surgical units at five key locations including centralized nurse stations, decentralized nurse stations (DCNS), patient bedsides, patient bathrooms, and corridors from 393 survey participants. It then explored the survey findings in more depth through conducting focus groups with eight volunteer nurses. Lighting conditions at patient besides and DCNSs were significantly less desirable for nurses compared to other locations. A significant relationship between nurses' access to lighting controls (switches and dimmers) and satisfaction about the lighting environment was found. No significant relationship was observed between the individual characteristics of nurses (such as age, years of experience, etc.) and findings of this study. Thoughtful design of the lighting environment can improve nurses' satisfaction and perception about their working environment.


Long-term administration of prazosin improves bladder storage function: results from a study in spontaneously hypertensive rats.
To investigate the effects of long-term administration of the α(1) -adrenoceptor antagonist prazosin on afferent inputs from the lower urinary tract (LUT). Twenty female spontaneously hypertensive rats (SHR) were randomized to receive a 4-week course of prazosin (0.12 mg/kg per day) or vehicle; 10 female Wistar-Kyoto (WKY) rats were given vehicle. Prazosin or vehicle was administered via an osmotic pump. The effect of prazosin on urodynamic parameters was determined by continuous cystometry in conscious animals. After cystometry, rats were killed and c-fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. The bladder contraction interval was significantly shorter in untreated SHR compared with WKY rats (2.36 ± 0 vs 4.27 ± 0.12 min, respectively; P < 0.05) and cystometric capacity was decreased significantly in SHR compared with WKY rats. L6 spinal cord c-Fos expression was also significantly greater in SHR than WKY rats. The administration of prazosin significantly increased the micturition interval (4.07 ± 0.58 min; P < 0.05) and bladder capacity, but it did not affect micturition pressure. In SHR, the number of c-Fos-positive neurons was significantly lower following the administration of prazosin compared with vehicle. Increased afferent input from the LUT may induce an increase in urinary frequency in SHR. Furthermore, long-term administration of prazosin can exert inhibitory effects on afferent pathways from the LUT during the storage phase. Reductions of afferent input can result in increased bladder capacity and increased micturition interval.


The impact of the Covid-19 pandemic on the stage of endometrial cancer at diagnosis.
Endometrial cancer generally presents at an early stage affording a high rate of surgical cure. Early in the Covid-19 pandemic it was suggested that treatment of tumors with favorable pathologic features might safely be delayed. We hypothesized that disruption to health care services during the pandemic would impact the stage at presentation for these patients. Here we compare the stage at presentation of Endometrial Cancer in the months immediately preceding the pandemic to the stage at presentation during the pandemic. Charts of patients presenting with Endometrial Cancer between January 1, 2018 and April 30, 2022 were reviewed. March 1, 2020 separated the "pre-pandemic" era from the "pandemic" era. Data was collected regarding patient age, body mass index (BMI), tumor stage, histology, grade, size, and depth of invasion. 322 of 374 (86.09%) of surgically staged patients presented with FIGO stage I disease "pre-pandemic" compared to 263 of 329 (71.73%) of surgically staged patients in the "pandemic" cohort (p =.029). 2.08% pre-pandemic compared to 5.48% during the pandemic presented with FIGO stage IV (p =.015). We found a significant difference in the stage at presentation in endometrial cancer patients, a statistic which may be attributed to the disruption of healthcare services caused by the Covid-19 pandemic.


Wide-range and area-selective threshold voltage tunability in ultrathin indium oxide transistors.
The scaling of transistors with thinner channel thicknesses has led to a surge in research on two-dimensional (2D) and quasi-2D semiconductors. However, modulating the threshold voltage (VT) in ultrathin transistors is challenging, as traditional doping methods are not readily applicable. In this work, we introduce a optical-thermal method, combining ultraviolet (UV) illumination and oxygen annealing, to achieve broad-range VT tunability in ultrathin In2O3. This method can achieve both positive and negative VT tuning and is reversible. The modulation of sheet carrier density, which corresponds to VT shift, is comparable to that obtained using other doping and capacitive charging techniques in other ultrathin transistors, including 2D semiconductors. With the controllability of VT, we successfully demonstrate the realization of depletion-load inverter and multi-state logic devices, as well as wafer-scale VT modulation via an automated laser system, showcasing its potential for low-power circuit design and non-von Neumann computing applications.


Contribution of Musa paradisiaca in the inhibition of α-amylase, α-glucosidase and Angiotensin-I converting enzyme in streptozotocin induced rats.
Unripe plantain based-diets are part of folklore remedy for the management of diabetes in tropical Africa; however, with the dearth of information on the rationale behind this practice; this study therefore, sought to investigate the antihyperglycemic effect of traditional unripe plantain products (Amala and Booli) in high fat fed/low dose streptozotocin-induced diabetic rats and to provide a possible rationale for their antidiabetic properties. Diabetes was induced experimentally by high fat fed/low dose streptozotocin-diabetic rats (25mg/kg body wt.) and the diabetic rats were fed diets supplemented with 20-40% Amala and Booli for 14 days. The effect of the diets on the blood glucose level, pancreatic α-amylase, intestinal α-glucosidase and Angiotensin-I converting enzyme (ACE) activities and plasma antioxidant status as well as amylose/amylopectin content of the unripe plantain products were determined. A marked increase in the blood glucose, α-amylase, α-glucosidase and ACE activities with a corresponding decrease in plasma antioxidant status was recorded in diabetic rats. However, these indices were significantly (P < 0.05) reversed after unripe plantain product supplemented diet treatments for 14 days. Also, the amylose/amylopectin ratio of the products is 1:3. This study revealed that unripe plantain products exert antihyperglycemic effects which could be attributed to the inhibition of α-amylase and α-glucosidase activities by their constituent phytochemicals as well as their amylose/amylopectin contents in the diabetic rats, hence, providing the possible rationale behind their antidiabetic properties.


Tonsillar surface swab bacterial culture results differ from those of the tonsillar core in recurrent tonsillitis.
We aimed to determine whether there was a difference between core and surface bacteriology of Finnish adults with recurrent or chronic tonsillitis to understand whether a surface swab is worthwhile and which bacteria are involved. Case series. Uninflamed tonsillar surface swabs and core biopsies were taken prior to and during surgery, respectively, in 103 patients aged 16 to 66 years undergoing tonsillectomy for recurrent or chronic tonsillitis. The McNemar test was used to determine differences between the surface and core in the most prevalent bacterial species. Twenty-seven bacterial species were isolated in addition to normal flora and were more commonly found in the core (1.11 surface and 4.75 core bacteria isolated per patient). Viridans group streptococci were the most commonly detected bacteria, found in 88% of the patients, mainly in the core. The bacteria in general were mainly isolated from the core. Of the 10 most prevalent bacteria, only group C β-hemolytic streptococci showed no difference between detection from core and surface swabs. Other bacteria found mainly in the core include Prevotella melaninogenica, Staphylococcus aureus, and fusobacteria. There is discord between the surface and core bacteria. A different population of bacteria exists in the core, especially anaerobic bacteria, suggesting that a core sample may be useful in evaluating recurrent and chronic tonsillitis. 4 Laryngoscope, 2019.


Immunization against bovine herpesvirus-1 infection. Preliminary tests in calves with a DNA vaccine.
A bovine herpesvirus-1 (BHV-1) vaccine expressing glycoprotein D, the form with the transmembrane anchor removed, was evaluated for inducing immunity in calves. The plasmid encoding gD of BHV-1 was injected three times to nine calves, using three animals for each of the following routes: intramuscularly (i.m.), intradermally (i.d.), or intranasally (i.n.). Three additional calves were given the plasmid vector only and served as unvaccinated controls. When calves were subjected to challenge infection with BHV-1, all vaccinated calves as well as the controls developed a typical severe form of infectious bovine rhinotracheitis. However, compared to the controls, the vaccinated calves showed earlier clearance of challenge virus. Moreover, the calves given the vaccine i.m. developed neutralizing antibody to BHV-1 between 21 and 42 days following the first injection of vaccine, whereas in calves vaccinated either i.d. or i.n., as well as the controls, antibody first appeared in their sera 14 days post-challenge infection.


Influence of MMP-8 promoter polymorphism in early osseointegrated implant failure.
Dental implants consist in the treatment of choice to replace tooth loss. The knowledge that implant loss tends to cluster in subsets of individuals may indicate that host immuneinflammatory response is influenced by genetic factors. In fact, genetic polymorphisms influence the osseointegration process. The objective of this study was investigate the possible relationship between C-799T polymorphism in matrix metalloproteinase 8 (MMP-8) gene and early implant failure in nonsmoker patients. Subjects were divided into two groups: control group (100 patients with one or more healthy implants) and test group (80 patients that had suffered one or more early implant failures). Genomic DNA from oral mucosa was amplified by PCR and analyzed by restriction endonucleases. The significance of the differences in observed frequencies of polymorphisms was assessed by Chi-square. Statistical analysis shows that in the MMP-8 gene, the T allele in 76.25% in the test group and the T/T genotype, 63.75% in the same group, may predispose to early loss of implants osseointegrated. These results suggest that polymorphism in the promoter region of MMP-8 gene is associated with early implant failure. This polymorphism can be a genetic marker to risk of implant loss. The determination of this genetic pattern in osseointegration would enable the identification of individuals at higher risk to loss implant. Thus, genetic markers will be identified, contributing to an appropriate preoperative selection and preparation of strategies for prevention and therapy individualized to modulate the genetic markers and increase the success rate of treatments.


Development of an Obstetric Hemorrhage Response Intervention: The Postpartum Hemorrhage Cart and Medication Kit.
Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity in the United States, and timely treatment is imperative. Delay in treatment of PPH can lead to significant blood loss and increased morbidity and mortality. Supplies and medications essential for treating PPH are typically not located in close proximity to the hemorrhaging patient, leading to inefficiency and delay in timely response to hemorrhage. An in situ hemorrhage simulation was created dictating the collection of a prespecified list of supplies commonly used in response to PPH on labor and delivery (L&D). Baseline data were collected, then Lean Six Sigma tools were used to construct a process map, including recording times and cumulative distance traveled for collection of each item. The simulation was repeated after development, creation, and deployment of each intervention. For the first intervention, a PPH cart was created containing the supplies most used in response to PPH. Second, a PPH medication kit was created consisting of a refrigerated box containing all medications typically administered during a PPH. The average time to collect a prespecified list of supplies and medications in response to a PPH scenario was 11 minutes 5 seconds (standard deviation [SD] = 3 minutes 33 seconds), with an average cumulative distance traveled of 4,092 feet. Following Intervention 1, the time decreased to 4 minutes 0 seconds, with 918 feet traveled (only one trial performed). Intervention 2 further reduced the average time and cumulative distance to 2 minutes 14 seconds (SD = 16 seconds) and 462 feet, respectively. This represents a 79.8% reduction in time and an 88.7% reduction in distance from baseline to postintervention. A PPH cart and medication kit can significantly reduce the amount of time and distance traveled to obtain materials necessary to treat hemorrhage, thus optimizing a team's ability to efficiently treat PPH.


Infectious episodes lead to the oxidative stress response after lung transplantation.
Reactive oxygen species function as key metabolites that can impair biological processes. In lung transplantation, severe oxidative stress is expected when ischemia/reperfusion injury, acute allograft rejection, and various infections occur. Two clinical cases in which serial measurements of the oxidative stress response (levels of diacron-reactive oxygen metabolites) were taken during hospitalization using a Free Radical Elective Evaluator are reported. In the first case, a 30-year-old man underwent right single lung transplantation for juvenile pulmonary emphysema. Immunosuppression was maintained using tacrolimus, mycophenolate mofetil, and steroid. The oxidative stress response fluctuated significantly (p<0.01) during the infections caused by bronchial stenosis compared to the stable condition. No acute rejection was seen during hospitalization. In the second case, a 44-year-old woman underwent right single lung transplantation for lymphangioleiomyomatosis. Immunosuppression was maintained by the same regimen as in case 1. The patient's postoperative course was uneventful, and there was no allograft rejection or infection. The oxidative stress response remained at the non-stress level. The oxidative stress response was measured by the levels of diacron-reactive oxygen metabolites in lung transplantation. High oxidative stress responses were seen during exposure to infections. This might become a non-invasive marker of complications after transplantation.


Mn-doped ZnSe d-dots-based α-methylacyl-CoA racemase probe for human prostate cancer cell imaging.
In this paper, we report the successful use of non-cadmium-based Mn-doped ZnSe d-dots (Mn/ZnSe) as highly efficient and nontoxic optical probes for human prostate cancer cells imaging. Mn/ZnSe d-dots are directly prepared in aqueous solution. The α-methylacyl-CoA racemase (AMACR) is overexpressed in prostate cancers; the presence of antibodies specific for AMACR is more sensitive and specific than serum prostate specific antigen levels in distinguishing patients with prostate cancers. Mn/ZnSe d-dots were linked to anti-AMACR to form Mn/ZnSe d-dots-anti-AMACR bioconjugates for the direct prostate cancer cell imaging. 3-(4,5-Dimethylthiazol-2-yl)-2 and 5-diphenyl tetrazolium bromide assay demonstrated that Mn/ZnSe d-dots exhibited favorable cytocompatibility to LNCaP cells with high concentration (1 mM) and long-time incubation (24 h). Furthermore, cellular imaging results demonstrated that Mn/ZnSe d-dots were remarkably efficacious for high-specificity cell imaging. The antibody-mediated delivery of the bioconjugates was further confirmed by the observation of no fluorescence signals in vitro targeting in nonprostate-cancer-based cell lines which are negative for AMACR. Mn/ZnSe d-dots as non-cadmium-based safe and efficient optical imaging nanoprobes could therefore be used for targeting imaging and treatment of cancers in the early stage.


Anticoagulants in frail patients. Seven situations at risk.
In the case of venous thromboembolic disease (VTE), physicians are facing more and more difficulties in managing VTE and their treatment in frail patients. These patients could present several risk situations such as: chronic kidney disease (CKD), underweight or malnourished, falls, cognitive impairment, multi-medicated patients, cancer and pregnancy. Guidelines typically recommend anticoagulation. There are multiple challenges in the safe use of anticoagulation in frail patients, including bleeding risk, monitoring and adherence, and polypharmacy. The objective of this review is to explore these at-risk situations and to suggest adequate anticoagulation therapy, when possible, in each of these complex situations.


Exploratory analysis of local extreme-temperature attributable mortality in an urban city of Madrid.
to assess the Heat (HW) and Cold Waves (CW) risks on health in the urban municipality of Getafe. time series analysis between 01/01/1999-31/10/2013. daily mortality due to natural causes - (ICD-10): A99-R99-. the maximum (Tmax) and minimum (Tmin) daily temperature. The mortality-temperature relationship was analysed to determine the thresholds of HW (Thresholdheat) and CW (Thresholdcold). Using Poisson GLM (link = log), the Relative Risk (RR), Attributable Risk (AR) and Attributable Mortality (AM) were determined for each degree of the Tmax exceeding the Thresholdheat (Theat) and for each degree of Tmin under the Thresholdcold (Tcold). Finally, socioeconomic variables were analysed descriptively. Thresholdheat was 36 °C while Thresholdcold was 0 °C. The RRs associated with Theat, i.e. 1.08 (1.03 1.14), are akin to those obtained for Tcold, i.e. 1.05 (1.03 1.08). There were 202 HW and 430 CW episodes. The AM to HW totalled 61 (25, 96) deaths, while that attributable to CW reached 146 (82,211) deaths. The vulnerability in Getafe seems to be lower than in surrounding similar urban and rural cities. The singular urban development of the municipality may have granted it an advantage over surrounding municipalities regarding temperature extremes.


Glycogen synthase kinase-3β inhibits tubular regeneration in acute kidney injury by a FoxM1-dependent mechanism.
Acute kidney injury (AKI) is characterized by injury to the tubular epithelium that leads to the sudden loss of renal function. Proper tubular regeneration is essential to prevent progression to chronic kidney disease. In this study, we examined the role of FoxM1, a forkhead box family member transcription factor in tubular repair after AKI. Renal FoxM1 expression increased after renal ischemia/reperfusion (I/R)-induced AKI in mouse kidneys. Treatment with thiostrepton, a FoxM1 inhibitor, reduced FoxM1 regulated pro-proliferative factors and cell proliferation in vitro, and tubular regeneration in mouse kidneys after AKI. Glycogen synthase kinase-3 (GSK3) was found to be an upstream regulator of FoxM1 because GSK3 inhibition or renal tubular GSK3β gene deletion significantly increased FoxM1 expression, and improved tubular repair and renal function. GSK3 inactivation increased β-catenin, Cyclin D1, and c-Myc, and reduced cell cycle inhibitors p21 and p27. Importantly, thiostrepton treatment abolished the improved tubular repair in GSK3β knockout mice following AKI. These results demonstrate that FoxM1 is important for renal tubular regeneration following AKI and that GSK3β suppresses tubular repair by inhibiting FoxM1.


Analysis of the accuracy of a dynamic navigation system in endodontic microsurgery: A prospective case series study.
To evaluate the accuracy of a dynamic navigation system (DNS) for guided osteotomy and root-end resection during endodontic microsurgery (EMS) and assess its prognosis. Nine patients who met inclusion criteria underwent DNS-guided EMS. Osteotomy and root-end resection were performed with assistance of DNS (DHC-ENDO1, DCARER Medical Technology, Suzhou, China). The preoperative virtually planned path and postoperative cone-beam computed tomography images were superimposed using DNS software. Accuracy was assessed based on deviations in the platform, apex, and angle of the osteotomy, as well as in the length and angle of the root-end resection. Follow-up evaluations were performed after at least a year postoperatively. Among the nine patients (11 teeth with 12 roots), the mean platform, apex, and angular deviation of the osteotomy were 1.05 mm, 1.2 mm, and 6.24°, respectively. The mean length and angle deviation of the root-end resection were 0.46 mm and 4.9°, respectively. Significant differences were observed according to tooth position. The platform and apex deviated significantly less in the posterior than in the anterior teeth (p < .05). No significant differences were observed according to arch type, side, and depth of the surgical path (p > .05). Eight patients were evaluated after at least a year postoperatively; clinical and radiographic evaluation revealed a 90% success rate (9/10 teeth). This study demonstrated high accuracy of DNS in EMS. Furthermore, DNS-guided EMS had a success rate similar to that of freehand EMS over a short-term follow-up. Further study with a larger sample size is necessary. The present novel DNS technology is a viable method for guided osteotomy and root-end resection in EMS. ChiCTR2100042312.


The states of water in tryptophan grafted hydroxypropyl methylcellulose hydrogels and their effect on the adsorption of methylene blue and rhodamine B.
Tryptophan (Trp) decorated hydroxypropyl methylcellulose (HPMC) cryogels were prepared by a one-step reaction with citric acid. The increase of Trp content in the 3D network from 0 to 2.18 wt% increased the apparent density from 0.0267 g.cm-3 to 0.0381 g.cm-3 and the compression modulus from 94 kPa to 201 kPa, due to hydrophobic interactions between Trp molecules. The increase of Trp content in HPMC-Trp hydrogels increased the amount of non-freezing water, estimated from differential scanning calorimetry, and the amount of freezing water, which was determined by time-domain nuclear magnetic resonance. The adsorption capacity of methylene blue (MB) and rhodamine B (RB) on HPMC-Trp hydrogels increased with Trp content and the amount of freezing water. HPMC-Trp hydrogels could be recycled 6 times keeping the original adsorptive capacity. The diffusional constants of MB and RB tended to increase with Trp content. RB adsorbed on HPMC-Trp hydrogels presented a bathochromic shift of fluorescence.


Evaluation of effects of histochrome and mexidol on structural and functional characteristics of the brain in senescence-accelerated OXYS rats by magnetic resonance imaging.
The effects of histochrome and mexidol on the morphology and function of the brain and behavior were studied in senescence-accelerated OXYS and Wistar rats. MRI showed that signs of neurodegenerative changes were present in OXYS rats at the age of 3 months and were pronounced at the age of 12 months. Histochrome (1 mg/kg, 5 days) more effectively than mexidol (4 mg/kg, 7 days) reduced anxiety and increased exploratory activity of 1-year-old OXYS rats. Both drugs improved the morphology and function of the brain. Their effects consisting in correction of diffuse changes in the white matter and reduction of edema were comparable; in addition, histochrome reduced the intensity of demyelinization processes.


Near-infrared spectroscopy to detect absence of cerebrovascular autoregulation in preterm infants.
Our aim was to explore clinical parameters that might predict the absence of cerebrovascular autoregulation (CAR) assessed by a negative relationship between mean arterial blood pressure (MABP) and fractional tissue oxygen extraction (FTOE) as measured by near-infared spectroscopy (NIRS) in preterm infants. We included preterm infants (gestational age (GA) <32 weeks). Within 72 h after birth, we recorded the infants' NIRS parameters and MABP for a 24-h period. Fractional tissue oxygen extraction (FTOE) was calculated. For each infant we calculated Spearman rank (rho) correlations. A statistically significant negative correlation between MABP and FTOE indicated the absent CAR. We related the absent CAR to clinical parameters. Ten (40%) out of 25 infants (median GA 29.1 weeks, range 25.4-31.7, birth weight 1245 g, 560-1780) had a statistically significant negative correlation between MABP and FTOE (rho -0.432 to -0.156), suggesting the absence of CAR. None of the clinical variables predicted the absence of CAR. We were unable to predict the absence of CAR in terms of clinical variables. Nevertheless, we found a statistically significant negative correlation between MABP and FTOE using NIRS, suggesting the absence of CAR in almost half of the preterm infants studied. NIRS could be a helpful tool to assess the presence or absence of CAR.


Danazol concentrations in human ovarian follicular fluid and their relationship to simultaneous serum concentrations.
Danazol concentrations in follicular fluid and serum were studied in eight women scheduled for laparoscopy because of suspected endometriosis. In order to obtain some variation in follicular maturity, danazol administration was started 2 to 7 days before the expected day of ovulation. A total of nine doses were given, i.e., 200 mg four times daily for 2 days; the last 200-mg dose was given 3 hours before the laparoscopy during which the follicular fluid from the dominant follicle was aspirated. Peripheral venous blood samples were drawn before, during, and after laparoscopy. Danazol concentrations were assayed by means of a high-performance liquid chromatography method. At the time of follicular aspiration, the mean concentration of danazol was estimated at 96 ng/ml in serum and at 71 ng/ml in follicular fluid, i.e., an average of 73% of the simultaneous serum concentration. The data suggest that even short-term therapy with danazol is likely to produce intrafollicular drug concentrations that have a direct inhibitory effect on follicular steroidogenesis.


Changes in 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D during pregnancy.
Serum concentrations of 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured in a cross-sectional study of 94 normal pregnant women at various stages of gestation in order to assess the hormonal regulation of calcium homeostasis during gestation. The 40 week gestational period was divided into four 10 weeks quarters. 25OHD concentration were significantly below control levels (32.2 +/- 3.1 (S.E.) ng/ml) by the second quarter of pregnancy and were even lower at term. Serum levels of 24,25(OH)2D did not decrease until the fourth quarter, when the mean concentration (0.8 +/- 0.1 ng/ml) was approximately one half the control values (1.5 +/- 0.3, p less than 0.025). These data suggest that the metabolic pathways of vitamin D are altered during gestation, perhaps in response to increasing mother-to-fetus transport of calcium. There is decreased 24-hydroxylation and, in view of the lowered 25OHD levels, possibly increased production of 1,25-hydroxyvitamin D (1,25(OH)2D).


[Ischemic colitis as a cause of intestinal bleeding after marathon running].
A 33-year-old long-distance runner had three episodes of bloody diarrhoea, all occurring after competitive marathon runs. Colonoscopy revealed a small lesion in the caecum histologically compatible with ischaemia of the mucosa. The discussion centres on the pathophysiology of impaired intestinal blood supply during excessive effort and the frequency of gastrointestinal symptoms and occult blood loss due to jogging.


Evaluation of scleral and corneal thickness in keratoconus patients.
To determine whether the scleral stroma is affected as much as the corneal stroma in keratoconus. University Eye Clinic, Bern, Switzerland. Comparative case-control study. Eyes with keratoconus (keratoconus group) and eyes of age-, sex-, and axial length-matched controls (control group) were analyzed. Corneal videokeratometry and pachymetry were performed using a Scheimpflug tomographer (Pentacam). For measurements of the peripheral cornea and the anterior sclera, a spectral-domain anterior segment optical coherence tomography device (Spectralis) was used. The study group comprised 51 eyes and the control group, 50 eyes. The mean central corneal thickness in the keratoconus group was statistically significantly lower than in the control group (447.8 μm ± 57.8 [SD] versus 550.5 ± 35.5 μm) (P < .0001). No significant difference in the mean anterior scleral thickness was found between the keratoconus group and the control group (479.1 ± 43.7 μm versus 474.2 ± 43.0 μm) (P =.57). Although corneal thinning was observed in keratoconus patients, the anterior scleral stroma thickness in these patients seemed to be similar to that in healthy control eyes.


Binding of the soybean Bowman-Birk proteinase inhibitor and of its chymotrypsin and trypsin inhibiting fragments to bovine alpha-chymotrypsin and bovine beta-trypsin. A thermodynamic study.
The effect of pH and temperature on the apparent association equilibrium constant (Ka) for the binding of the soybean Bowman-Birk proteinase inhibitor (BBI) and of its chymotrypsin and trypsin inhibiting fragments (F-C(p), F-T(p) and F-T(t), respectively) to bovine alpha-chymotrypsin (alpha-chymotrypsin) and bovine beta-trypsin (beta-trypsin) has been investigated. On the basis of Ka values, the proteinase inhibitor affinity can be arranged as follows: alpha-chymotrypsin: BBI approximately beta-trypsin:BBI approximately beta-trypsin:F-T(t) approximately beta-trypsin:F-T(p) much greater than alpha-chymotrypsin:F-C(p). F-C(p), F-T(p) and F-T(t) do not inhibit beta-trypsin and alpha-chymotrypsin action, respectively. On lowering the pH from 9.5 to 4.5, values of Ka for BBI, F-C(p), F-T(p) and/or F-T(t) binding to alpha-chymotrypsin and beta-trypsin decrease, thus reflecting the acid-pK shift of the invariant His57 catalytic residue from 7.0, in the free enzymes, to 5.2, in the proteinase:inhibitor complexes. Considering the known molecular models, the observed binding behaviour of BBI, F-C(p), F-T(p) and F-T(t) was related to the inferred stereochemistry of the proteinase:inhibitor contact regions.


SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.
Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0·5 μg mL(-1) recombinant human SLURP-1 protein. Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.


Gender Difference in Relationship between Health-Related Quality of Life and Work Status.
This study investigated the association of employment status with health-related quality of life in adult Koreans, as well as the gender difference in the relationship, using a large, nationally representative sample. Using data from the Korea Health Panel survey, we examined the relationship between quality of life measured by EQ-5D and work status among Korean adults. We also tested whether and how the relationship between quality of life and work status differed by gender. Quality of life among working adults was better than among non-working adults. The gap between the two groups was larger among male than female participants. Further, the gender differential effect was larger in the 41-60-year-old age group than in the 18-40-year-old and 61-or-older groups. Being employed has a positive relation to quality of life among adults. Work status plays a more important role in quality of life for men than for women, especially for the working elderly men than working elderly women.


Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors or methotrexate: A multicenter research network study.
Data on the impact of biologics and immunomodulators on coronavirus disease 2019 (COVID-19)-related outcomes remain scarce. We sought to determine whether patients taking tumor necrosis factor inhibitors (TNFis) or methotrexate are at increased risk of COVID-19-related outcomes. In this large comparative cohort study, real-time searches and analyses were performed on adult patients who were diagnosed with COVID-19 and were treated with TNFis or methotrexate compared with those who were not treated. The likelihood of hospitalization and mortality were compared between groups with and without propensity score matching for confounding factors. More than 53 million (53,511,836) unique patient records were analyzed, of which 32,076 (0.06%) had a COVID-19-related diagnosis documented starting after January 20, 2020. Two hundred fourteen patients with COVID-19 were identified with recent TNFi or methotrexate exposure compared with 31,862 patients with COVID-19 without TNFi or methotrexate exposure. After propensity matching, the likelihood of hospitalization and mortality were not significantly different between the treatment and nontreatment groups (risk ratio = 0.91 [95% confidence interval, 0.68-1.22], P = .5260 and risk ratio = 0.87 [95% confidence interval, 0.42-1.78], P = .6958, respectively). All TNFis may not behave similarly. Our study suggests that patients with recent TNFi or methotrexate exposure do not have increased hospitalization or mortality compared with patients with COVID-19 without recent TNFi or methotrexate exposure.


PROPERTIES AND FUNCTIONS OF THE NOVEL TYPE I INTERFERON EPSILON.
Interferon epsilon (IFNε) is a type I IFN with unusual patterns of expression and therefore, function. It is constitutively expressed by reproductive tract epithelium and regulated by hormones during estrus cycle, reproduction, and menopause and by exogenous hormones. The IFNe protein is encoded by a gene in the type I IFN locus, binds to IFNAR1 and 2 which are required for signaling via the JAK STAT pathway. Its affinity for binding receptors and transducing signals is less potent than IFNα or β subtypes in vitro. Nevertheless, in vivo experiments indicate its efficacy in regulating mucosal immune responses and protecting from bacterial and viral infections. These studies demonstrate a different mechanism of action to type I IFNs. In this organ system with dynamic fluxes in cellularity, requirement to tolerate an implanted fetus, and be protected from disease, there is co-option of a special IFN from a family of effective immunoregulators, with unique controls and modified potency to make it a safe and effective constitutive reproductive tract cytokine.


Hepatic cytochrome P450 activity and pollutant concentrations in paradise shelducks and southern black-backed gulls in the South Island of New Zealand.
Cytochrome P450 (CYP) enzymes catalyse the oxidative metabolism of various xenobiotics including environmental pollutants. We investigated liver microsomal CYP marker activities in 60 paradise shelducks (Tadorna variegata; herbivore) and 77 southern black-backed gulls (Larus dominicanus; omnivore) collected at three sites with putatively different levels of pollution in the South Island of New Zealand. Ethoxyresorufin O-deethylase (EROD) activity was high in birds at an urban landfill site compared to those at a relatively pristine and an agricultural site. Analysis of p-nitrophenol hydroxylase and erythromycin demethylase activities indicated the presence of two additional CYP isoforms in shelducks but no additional form in gulls. Total polychlorinated biphenyl (PCB) concentrations (ranges: shelducks, 0.073-6.2; gulls, 8.2-330 ng/g wet weight) were high in landfill samples suggesting a link to EROD induction and, in landfill shelducks, EROD was independently associated with Hg and Pb concentration. PCB congener-specific assessments indicated the metabolism of at least two congeners (#28 and #74) is induced in shelducks. DDE concentrations (ranges: shelducks, 0.85-320; gulls, 44-4800 ng/g) were high in birds at the landfill and agricultural sites. Body weight tended to be lower in landfill birds, but whether this reflects the greater energetic demands of pollutant detoxification remains to be investigated.


A simultaneous oral and intramuscular prime/sublingual boost with a DNA/Modified Vaccinia Ankara viral vector-based vaccine induces simian immunodeficiency virus-specific systemic and mucosal immune responses in juvenile rhesus macaques.
A pediatric vaccine to prevent breast milk transmission of human immunodeficiency virus (HIV) may generate greater immune responses at viral entry sites if given by an oral route. We compared immune responses induced in juvenile macaques by prime/boosting with simian immunodeficiency virus (SIV)-expressing DNA/modified vaccinia Ankara virus (MVA) by the intramuscular route (IM), the oral (O)/tonsillar routes (T), the O/sublingual (SL) routes, and O+IM/SL routes. O/T or O/SL immunization generated SIV-specific T cells in mucosal tissues but failed to induce SIV-specific IgA in saliva or stool or IgG in plasma. IM/IM or O+IM/SL generated humoral and cellular responses to SIV. IM/IM generated greater frequencies of TFH in spleen, but O+IM/SL animals had higher avidity plasma IgG and more often demonstrated mucosal IgA responses. These results suggest that codelivery of HIV DNA/MVA vaccines by the oral and IM routes might be optimal for generating both systemic and mucosal antibodies.


Temporal changes in health-related lifestyle during the COVID-19 epidemic in Finland - a series of cross-sectional surveys.
Public health recommendations and governmental restrictions during the COVID-19 epidemic have affect everyday life. This study aimed to examine temporal changes in health-related lifestyle and the accumulation of positive and negative changes in the key lifestyle factors (vegetable consumption, leisure-time physical activity, sleeping, alcohol consumption, smoking) in the same individuals among Finnish adults during the epidemic. This study was based on a series of cross-sectional surveys conducted between April 2020 and June 2021 to investigate antibody levels for the new coronavirus in the population. In each survey, a random sample of adults (18 to 69 years) from five university hospital regions were invited. A total of 5655 (response rate 32%) responded to the questionnaire including questions on lifestyle changes during epidemic. On average one-sixth of respondents (17%) reported at least two negative changes in the key lifestyle factors during the study period. An increase in snacking and sleep problems and decrease in leisure-time physical activity and active commuting to work were the most common of individual negative changes. The proportion of negative changes in physical activity increased as the epidemic drags on. In contrast, on average every seventh of the respondents (14%) reported at least two positive lifestyle changes in the key lifestyle factors. The most common individual positive changes were increased consumption of fruit, berries and vegetables and decreased consumption of alcohol. More negative changes were reported on average, when both negative and positive changes in the key lifestyle factors were summed. The most negative changes were reported in the late 2020. The results of the present study suggest that the lifestyle changes during the COVID-19 epidemic have been diverse being on average more commonly unfavorable than favorable for health. The deteriorated epidemic situation in the late 2020 and, on the other hand, prolonged epidemic predisposed to negative lifestyle changes. Further studies are important to examine whether these changes are maintained over time and to identify the factors that contribute to changes and their accumulation in the same individuals. Health promotion actions are needed to prevent the long-term effects of the epidemic on health and welfare.


Blocking prostanoid receptors switches on multiple immune responses and cascades of inflammatory signaling against larval stages in snail fever.
Schistosomiasis, also known as snail fever or bilharziasis, is a worm infection caused by trematode called schistosomes that affects humans and animals worldwide. Schistosomiasis endemically exists in developing countries. Inflammatory responses elicited in the early phase of infection represent the rate limiting step for parasite migration and pathogenesis and could be a valuable target for therapeutic interventions. Prostaglandin E2 (PGE2) and interleukin (IL)-10 were found to be differentially affected in case of immune-modulation studies and cytokine analysis of hosts infected with either normal or radiation-attenuated parasite (RA) which switches off the development of an effective immune response against the migrating parasite in the early phase of schistosomiasis. Normal parasites induce predominantly a T helper 2 (Th2)-type cytokine response (IL-4 and IL-5) which is essential for parasite survival; here, we discuss in detail the downstream effects and cascades of inflammatory signaling of PGE2 and IL10 induced by normal parasites and the effect of blocking PGE2 receptors. We suggest that by selectively constraining the production of PGE2 during vaccination or therapy of susceptible persons or infected patients of schistosomiasis, this would boost IL-12 and reduce IL-10 production leading to a polarization toward the anti-worm Thl cytokine synthesis (IL-2 and Interferon (IFN)-γ).


Selected plant triterpenoids and their amide derivatives in cancer treatment: A review.
Medicinal plants have been used to treat different diseases throughout the human history namely in traditional medicine. Most of the plants mentioned in this review article belong among them, including those that are widely spread in the nature, counted frequently to be food and nutrition plants and producing pharmacologically important secondary metabolites. Triterpenoids represent an important group of plant secondary metabolites displaying emerging pharmacological importance. This review article sheds light on four selected triterpenoids, oleanolic, ursolic, betulinic and platanic acid, and on their amide derivatives as important natural or semisynthetic agents in cancer treatment, and, in part, in pathogenic microbe treatment. A literature search was made in the Web of Science for the given key words covering the required area of secondary plant metabolites and their amide derivatives. The most recently published findings on the biological activity of the selected triterpenoids, and on the structures and biological activity of their relevant amide derivatives have been summarized therein. Mainly anti-cancer effects, and, in part, antimicrobial and other effects of the four selected triterpenoids and their amide derivatives have also been reviewed. A comparison of the effects of the parent plant products and those of their amide derivatives has been made.


Combining cell-based therapies and neural prostheses to promote neural survival.
Cochlear implants provide partial restoration of hearing for profoundly deaf patients by electrically stimulating spiral ganglion neurons (SGNs); however, these neurons gradually degenerate following the onset of deafness. Although the exogenous application of neurotrophins (NTs) can prevent SGN loss, current techniques to administer NTs for long periods of time have limited clinical applicability. We have used encapsulated choroid plexus cells (NTCells; Living Cell Technologies, Auckland, New Zealand) to provide NTs in a clinically viable manner that can be combined with a cochlear implant. Neonatal cats were deafened and unilaterally implanted with NTCells and a cochlear implant. Animals received chronic electrical stimulation (ES) alone, NTs alone, or combined NTs and ES (ES + NT) for a period of as much as 8 months. The opposite ear served as a deafened unimplanted control. Chronic ES alone did not result in increased survival of SGNs or their peripheral processes. NT treatment alone resulted in greater SGN survival restricted to the upper basal cochlear region and an increased density of SGN peripheral processes. Importantly, chronic ES in combination with NTs provided significant SGN survival throughout a wider extent of the cochlea, in addition to an increased peripheral process density. Re-sprouting peripheral processes were observed in the scala media and scala tympani, raising the possibility of direct contact between peripheral processes and a cochlear implant electrode array. We conclude that cell-based therapy is clinically viable and effective in promoting SGN survival for extended durations of cochlear implant use. These findings have important implications for the safe delivery of therapeutic drugs to the cochlea.


Micafungin in combination with voriconazole in Aspergillus species: a pharmacodynamic approach for detection of combined antifungal activity in vitro.
Preclinical and clinical evidence indicate that echinocandin-triazole combinations provide enhanced killing versus triazoles alone against some Aspergillus isolates, however, in vitro test results designed to detect this combined effect are difficult to interpret. We used a straightforward pharmacodynamic approach based on a microdilution format and a colorimetric analysis to harmonize growth end points. We detected a fourfold decrease in the EC90 of voriconazole when tested in combination with micafungin (4 mg/L) against isolates of Aspergillus fumigatus and Aspergillus terreus, but not against an isolate of Aspergillus flavus. Echinocandin-enhanced voriconazole activity was confirmed in A. fumigatus and A. terreus but not A. flavus by fluorescent morbidity staining and fluorescence microscopic analysis of damaged hyphae. A microdilution-based pharmacodynamic method for testing antifungal combinations provides a less ambiguous description of the combined effects of antifungals against moulds and could be useful in reference laboratories that routinely evaluate the activity of antifungal combinations in vitro and in vivo.


Rearrangement of nuclear calmodulin during proliferative liver cell activation.
Calmodulin increases about three-fold in rat liver nuclei after partial hepatectomy. The increase is maximal after 24 hours, when DNA synthesis is also maximal. During the same time re-distribution of calmodulin within the nuclear structure takes place, leading to its association with the nuclear matrix. Incubation of normal rat liver nuclei with Ca2+ induces association of calmodulin with the matrix, indicating that the re-distribution of calmodulin during the replicative period is related to the increase in nuclear Ca2+. The nuclear matrix contains several calmodulin binding proteins of which one, having Mr of 130 kDa, has been identified as myosin light chain kinase (MLCK). Three acceptor proteins, having Mr of 120, 65, and 60 kDa decrease 24 hours after partial hepatectomy, MLCK and a protein of Mr 150 kDa instead increase.


Inequalities in the uptake of human papillomavirus vaccination: a systematic review and meta-analysis.
The human papillomavirus (HPV) vaccine offers an opportunity to reduce health inequalities associated with cervical cancer provided the vaccine is delivered equitably at population level. Method We reviewed evidence of inequalities in HPV vaccine uptake in young women after undertaking a comprehensive search of databases from inception to March 2012. Studies that compared HPV vaccination initiation and/or completion by at least one ethnicity or socioeconomic-related variable in adolescent young women were included. There were no language restrictions. Data were extracted by two reviewers and pooled in a meta-analysis using a random-effects model; sub-analyses and meta-regression were undertaken to investigate sources of heterogeneity. In all, 29 publications related to 27 studies were included in the review. Black young women were less likely to initiate HPV vaccination compared with White young women (combined OR: 0.89, 95% CI: 0.82-0.97). In the USA, young women without healthcare insurance were less likely to initiate (combined OR: 0.56, 95% CI: 0.40-0.78). There was no strong evidence that lower family income (combined OR: 1.16, 95% CI: 1.00-1.34) or lower parental education (combined OR 1.06, 95% CI: 0.92-1.22) influenced HPV vaccination initiation. We found strong evidence for differences in HPV vaccination initiation by ethnicity and healthcare coverage, but did not find a strong association with parental education or family income variables. The majority of studies originated from the USA. Population-based studies reporting both initiation and completion of the HPV vaccination programme are required to establish patterns of uptake in different healthcare contexts.


MRI technique for the snapshot imaging of quantitative velocity maps using RARE.
A quantitative PGSE-RARE pulse sequence was developed and successfully applied to the in situ dissolution of two pharmaceutical formulations dissolving over a range of timescales. The new technique was chosen over other existing fast velocity imaging techniques because it is T(2) weighted, not T(2)(∗) weighted, and is, therefore, robust for imaging time-varying interfaces and flow in magnetically heterogeneous systems. The complex signal was preserved intact by separating odd and even echoes to obtain two phase maps which are then averaged in post-processing. Initially, the validity of the technique was shown when imaging laminar flow in a pipe. Subsequently, the dissolution of two drugs was followed in situ, where the technique enables the imaging and quantification of changes in the form of the tablet and the flow field surrounding it at high spatial and temporal resolution. First, the complete 3D velocity field around an eroding salicylic acid tablet was acquired at a resolution of 98×49 μm(2), within 20 min, and monitored over ∼13 h. The tablet was observed to experience a heterogeneous flow field and, hence a heterogeneous shear field, which resulted in the non-symmetric erosion of the tablet. Second, the dissolution of a fast dissolving immediate release tablet was followed using one-shot 2D velocity images acquired every 5.2 s at a resolution of 390×390 μm(2). The quantitative nature of the technique and fast acquisition times provided invaluable information on the dissolution behaviour of this tablet, which had not been attainable previously with conventional quantitative MRI techniques.


Hydrangea-like architectures composed of Zr-based metal-organic framework nanosheets with enhanced iodine capture.
Zirconium-based metal-organic framework nanosheet assembled hydrangea-like architectures were reported and an enhanced iodine capture capacity was achieved.


Salivary heme proteins distinguish Rhodnius prolixus from Rhodnius robustus (Hemiptera: Reduviidae: Triatominae).
Rhodnius prolixus interpopulation variability was studied based on a new approach using salivary heme proteins (nitrophorins) electrophoresis in starch gel. We compared salivary proteins profiles of R. prolixus from three different laboratory colonies from Honduras, Venezuela, Brazil and Rhodnius robustus from Venezuela, constructing a UPGMA. The Honduran and Venezuelan populations could not be distinguished from each other, but the Brazilian population was well separated from the others. The high similarity between Honduran and Venezuelan specimens lends support to current theories that the Central American populations of R. prolixus may have been introduced from a Venezuelan origin. The low polymorphism shown by the Honduran specimens is in agreement with a possible founder effect. This new approach also distinguished R. prolixus populations from R. robustus, species with extreme phenotypical similarity.


Preliminary results of a new small-bore percutaneous pleural catheter used for treatment of malignant pleural effusions in ECOG PS 3-4 patients.
In cancer patients with malignant pleural effusions(MPEs),the commonest procedure to treat them with palliative intention is talc pleurodesis (TP) which can be obtained with talc slurry (TS) using small-bore catheters(SBC)or with thoracoscopic poudrage. SBC use is therefore rapidly increasing. The aim of this paper is to present our preliminary TP results using a new percutaneous chest drainage system(UNICO®, Redax, Mirandola Modena, Italy). In the period 1st March-20th of July 2011,seven consecutive ECOG PS 3-4 patients(4 females, mean age 73.2 ± 12.1 years),unfit for thoracoscopic talc poudrage, were enrolled in our study. All patients received many thoracentesis before the placement of a chest drainage(median thoracentesis number:4.42 ± 1.13).UNICO® was bedside placed in all cases and TS was administered through the drainage when the overall fluid amount didn't exceed 150-200 ml/24 h and the lung was correctly re-expanded at the chest X-ray control. There were no clinical complications following the placement of the drainage: its placement was easy, safe and well-tolerated by all patients. The median chest tube stay, before TS, was 7.2 ± 2.7 days while the median chest tube stay after TS was 1.5 ± 0.7 days. A satisfactory radiological lung expansion was achieved in all cases; PL effectiveness and dyspnea relief were complete in 6 and 4 cases, respectively. No patients required any further thoracentesis. TS through UNICO® is safe and efficient. The drainage was well-tolerated by all patients, even in case of its long-term stay. We may conclude that bedside TS through this new small-bore percutaneous drainage should be proposed as a viable clinical solution for MPEs in ECOG PS 3-4 patients, unfit for a thoracoscopic procedure. Moreover, with this device, we believe that TS might be an accessible procedure for pulmonologists and oncologists too.


The 2016 VGTC Virtual Reality: Best Dissertation Award.
The 2016 IEEE VGTC Virtual Reality Best Dissertation Award goes to Ravish Mehra, a 2014 graduate from the University of North Carolina at Chapel Hill, for his dissertation entitled: "Efficient Techniques for Wave-Based Sound Propagation in Interactive Applications".


Australia antigen 'ad' and 'ay' subtypes. Purification and partial characterization.
The two commonly-found Australia antigen subtypes have been purified by simple inexpensive, reproducible, physico-chemical methods involving ammonium sulfate precipitation, peptic digestion, calcium phosphate gel fractionation and molecular sieving on Sepharose 4B. The overall recovery of the two subtypes varied between 50 and 60% of the total antigen content on the starting serum. The purified antigens were found homogeneous by discontinuous gel electrophoresis, analytical ultracentrifugation, and isopycnic banding ultracentrifugation. No contaminating serum proteins could be detected by immunoelectrophoresis. The two purified antigen subtypes have similar Stokes radii and buoyant densities. The sedimentation coefficients for the 'ad' and 'ay' subtypes were found to be 33.0 and 40.1 times 10- minus 13 sec, respectively.


Olfactory mechanisms in the control of maternal aggression, appetite, and fearfulness: effects of lesions to olfactory receptors, mediodorsal thalamic nucleus, and insular prefrontal cortex.
During lactation the female rat is hyperphagic, aggressive toward adult conspecifics, and less fearful than usual. In the first experiment the importance of olfactory receptors was investigated by surgically removing the olfactory epithelium of the nasal cavity. Mother rats subjected to this treatment consumed significantly less food and weighed less than sham-operated females. Moreover, experimental subjects displayed a dramatic decrease in maternal aggression. Fear behavior (sound-elicited freezing), on the other hand, was not affected by the lesions. The mediodorsal thalamic nucleus and the prefrontal insular cortex form part of the central olfactory system. The second experiment assessed the involvement of this olfactory-related thalamocortical system and the behavioral profile of mother rats. It was found that whereas the thalamic and cortical lesions left food intake and fear behavior unaffected, they significantly decreased the frequency with which the mother would attack an intruder male placed into her home cage. The sense of smell appears, according to the present experiments, to play a crucial role in maternal aggression.


Key regulatory elements of a strong constitutive promoter, P GCW14, from Pichia pastoris.
The promoter of the Pichia pastoris gene GCW14 is strong and constitutive when glycerol is the available carbon source. To identify the cis-acting elements of this promoter (P GCW14), we constructed expression plasmids where the enhanced green fluorescent protein gene was fused to a series of mutants of P GCW14. We identified one negative (-114 to -94) and three positive regulatory regions (-426 to -152, -134 to -114, -94 to -77). The TATA box of P GCW14 was located at -48. One negative and four positive regulatory sites were identified combining error-prone PCR and directed mutation. The mutated promoter, M+20, with an increased promoter activity, was then used to express the gene for lipase B from Candida antarctica.


A weighting approach for judging the effect of patient strata on high-dimensional risk prediction signatures.
High-dimensional molecular measurements, e.g. gene expression data, can be linked to clinical time-to-event endpoints by Cox regression models and regularized estimation approaches, such as componentwise boosting, and can incorporate a large number of covariates as well as provide variable selection. If there is heterogeneity due to known patient subgroups, a stratified Cox model allows for separate baseline hazards in each subgroup. Variable selection will still depend on the relative stratum sizes in the data, which might be a convenience sample and not representative for future applications. Such effects need to be systematically investigated and could even help to more reliably identify components of risk prediction signatures. Correspondingly, we propose a weighted regression approach based on componentwise likelihood-based boosting which is implemented in the R package CoxBoost (https://github.com/binderh/CoxBoost). This approach focuses on building a risk prediction signature for a specific stratum by down-weighting the observations from the other strata using a range of weights. Stability of selection for specific covariates as a function of the weights is investigated by resampling inclusion frequencies, and two types of corresponding visualizations are suggested. This is illustrated for two applications with methylation and gene expression measurements from cancer patients. The proposed approach is meant to point out components of risk prediction signatures that are specific to the stratum of interest and components that are also important to other strata. Performance is mostly improved by incorporating down-weighted information from the other strata. This suggests more general usefulness for risk prediction signature development in data with heterogeneity due to known subgroups.


High expression of survivin in sacral chordoma.
Chordoma is a rare and invasive malignant tumor which primarily relies on surgical treatments. Anticipation of its recurrence and patient survival longevity has been a critical issue of the treatments. This retrospective study examined the survivin expression of sacral chordoma in 30 patients undergoing surgery in our hospital from January 2000 to July 2010, and compared it with chordoma recurrence. Survivin expression was 70 % positive in 30 patients. The positive expression of survivin with recurrence was significantly higher than that without recurrence (p = 0.017) and was inversely related to the continuous disease-free survival time (p < 0.001). Survivin expression was associated with recurrence. The correlation suggested that the survivin expression could be used as an independent predictor of recurrence and could be a potential bio-target gene of angiogenesis in sacral chordoma.


Phylogeography in the northern Andes: complex history and cryptic diversity in a cloud forest frog, Pristimantis w-nigrum (Craugastoridae).
We investigated the pattern of genetic and morphological variation and the timing of diversification in a Neotropical direct developing frog, Pristimantis w-nigrum (Craugastoridae) to gain insight into the historical biogeography of the northern Andes. Phylogenetic inference and analyses of genetic differentiation at mitochondrial and nuclear markers reveal eight mitochondrial clades that display concordant and highly structured nuclear genetic variation along both eastern and western slopes of the Ecuadorian Andes. These eight phylogroups are deeply divergent and show little evidence of change in effective size over substantial periods of time. Consistent with other phylogenetic studies of vertebrates in the Andes, the timing of genetic divergence among lineages coincides with sequential bouts of Andean orogenesis during the late Miocene and early Pliocene. Morphometric analyses recover little morphological variation among populations in spite of considerable genetic divergence. The deep genetic differentiation among populations of P. w-nigrum suggests that this species harbors unrecognized diversity and may represent a complex of cryptic species. These results illuminate the evolutionary processes that generate diversity in tropical montane biomes and underscore the fact that cryptic diversity may be an important component of Neotropical montane biodiversity.


Phospholipid cofactor solubilization inhibits formation of native prions.
Cofactor molecules are required to generate infectious mammalian prions in vitro. Mouse and hamster prions appear to have different cofactor preferences: Whereas both mouse and hamster prions can use phosphatidylethanolamine (PE) as a prion cofactor, only hamster prions can also use single-stranded RNA as an alternative cofactor. Here, we investigated the effect of detergent solubilization on rodent prion formation in vitro. We discovered that detergents that can solubilize PE (n-octylglucoside, n-octylgalactoside, and CHAPS) inhibit mouse prion formation in serial protein misfolding cyclic amplification (sPMCA) reactions using bank vole brain homogenate substrate, whereas detergents that are unable to solubilize PE (Triton X-100 and IPEGAL) have no effect. For all three PE-solubilizing detergents, inhibition of RML mouse prion formation was only observed above the critical micellar concentration (CMC). Two other mouse prion strains, Me7 and 301C, were also inhibited by the three PE-solubilizing detergents but not by Triton X-100 or IPEGAL. In contrast, none of the detergents inhibited hamster prion formation in parallel sPMCA reactions using the same bank vole brain homogenate substrate. In reconstituted sPMCA reactions using purified substrates, n-octylglucoside inhibited hamster prion formation when immunopurified bank vole PrPC substrate was supplemented with brain phospholipid but not with RNA. Interestingly, phospholipid cofactor solubilization had no effect in sPMCA reactions using bacterially expressed recombinant PrP substrate, indicating that the inhibitory effect of solubilization requires PrPC post-translational modifications. Overall, these in vitro results show that the ability of PE to facilitate the formation of native but not recombinant prions requires phospholipid bilayer integrity, suggesting that membrane structure may play an important role in prion formation in vivo.


The effects of short-term exposure to air pollution on mortality in Baotou, China, during 2015-2019.
Air pollution was considered one of the main causes linked to increased morbidity and mortality around the world. This study aimed to estimate the effect of air pollutants on daily death in Baotou city of Inner Mongolia. Daily deaths data were provided by Baotou Centers for Disease Control and Prevention for the years 2015-2019 (Baotou CDC). The air pollutants, PM2.5, PM10, NO2, SO2, CO and maximum 8-h average concentrations of O3, came from the eight environmental monitoring stations in Baotou city. Time-series plots were used to exploit the trend of air pollutants at calendar time. Generalized additive model was used to estimate the effect of air pollutants on daily death. Restricted cubic spline was employed to investigate non-line relationships between air pollutants and daily death. After adjusting the meteorological factors, non-accidental daily deaths were related to PM2.5 (ER = 0.074%) and PM10 (ER = 0.023%), respectively. In stratified analysis, population aged over 65 years and females were more sensitive to air pollutants exposure and warm season might make people more susceptible to air pollutants compared with cold season. PM2.5 and PM10 increase the risk of non-accidental and cardiovascular daily death, but not respiratory daily death.


Pediatric ptosis as a sign of treatable autonomic dysfunction.
To report the ophthalmic findings in young patients with dopamine β-hydroxylase deficiency and to assess them in the context of other reports in an attempt to discern if ophthalmic criteria may assist in early detection of this debilitating, yet treatable, disorder. Prospective, observational case series. An ophthalmic examination, including measuring intraocular and systemic blood pressures while supine, sitting, and standing, and eyelid function and pupillary function testing, was completed on 3 young patients with recently documented dopamine β-hydroxylase deficiency at a single institution. Mean arterial blood pressures were 90.1 ± 18.5 mm Hg supine, 79.1 ± 25.7 mm Hg sitting, and 45.8 ± 11.6 mm Hg standing (P = .021). Mean intraocular pressures in these patients were 15.8 ± 1.0 mm Hg supine, 15.0 ± 3.6 mm Hg sitting, and 7.7 ± 2.3 mm Hg standing (P = .03). Mean palpebral fissure, levator function, and margin reflex distance were 8.2 ± 1.0 mm, 16.0 ± 0 mm, and 2.8 ± 0.6 mm, respectively. Measurable miosis was present in only 1 patient, and pupillary supersensitivity to 2.5% phenylephrine was not observed. The ophthalmologic findings of the patients in this case series documented mild ptosis and striking orthostatic reductions in intraocular pressure and mean arterial blood pressure, as might be expected with a lack of intrinsic sympathetic function. Orthostatic intraocular pressure and mean arterial blood pressure may be a helpful early screening tool for autonomic dysfunction in children undergoing a ptosis evaluation.


Reconstituted high-density lipoproteins acutely reduce soluble brain Aβ levels in symptomatic APP/PS1 mice.
Many lines of evidence suggest a protective role for high-density lipoprotein (HDL) and its major apolipoprotein (apo)A-I in Alzheimer's Disease (AD). HDL/apoA-I particles are produced by the liver and intestine and, in addition to removing excess cholesterol from the body, are increasingly recognized to have vasoprotective functions. Here we tested the ability of reconstituted HDL (rHDL) consisting of human apoA-I reconstituted with soy phosphatidylcholine for its ability to lower amyloid beta (Aβ) levels in symptomatic APP/PS1 mice, a well-characterized preclinical model of amyloidosis. Animals were treated intravenously either with four weekly doses (chronic study) or a single dose of 60mg/kg of rHDL (acute study). The major finding of our acute study is that soluble brain Aβ40 and Aβ42 levels were significantly reduced within 24h of a single dose of rHDL. By contrast, no changes were observed in our chronic study with respect to soluble or deposited Aβ levels in animals assessed 7days after the final weekly dose of rHDL, suggesting that beneficial effects diminish as rHDL is cleared from the body. Further, rHDL-treated animals showed no change in amyloid burden, cerebrospinal fluid (CSF) Aβ levels, neuroinflammation, or endothelial activation in the chronic study, suggesting that the pathology-modifying effects of rHDL may indeed be acute and may be specific to the soluble Aβ pool. That systemic administration of rHDL can acutely modify brain Aβ levels provides support for further investigation of the therapeutic potential of apoA-I-based agents for AD. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.


[Vector analysis of the repolarization phase in the exercise-ecg with Frank leads (author's transl)].
The bioelectrical activity of the heart during repolarization is analysed with Frank leads in a spatial vector model. After physical work most of the test persons showed an amplification of the repolarization vector. It is discussed whether the amplification of the T-vector after physical work should be interpreted as an indication of subendocardial ischemia.


Considerations in the analysis and treatment of dietary effects on behavior: a case study.
Scientific and public interest in the effects of diet of behavior disorders has recently increased. This paper argues that (1) the experimental analysis of behavior offers an effective scientific methodology for assessing the effects of dietary substances on behavior problems, and that (2) such analysis permits behavioral consequences to be considered as an alternative treatment to dietary control. A case study of a 9-year-old retarded boy with autistic behaviors is presented. Suspected dietary substances were demonstrated to be effective influences on the child's behavior, whereas a simple behavior modification program improved his problem behaviors. Also discussed are issues and problems which arise in research on dietary effects on behavior and in selection of effective and ethical treatments.


Retrieval of an intra-cardiac embolised very long wire via transhepatic access from a war victim child.
We present the case report of a war victim child with severe burn scars, orthopnoea, and dyspnoea due to diffuse pulmonary thromboembolism. During ICU stay, a central venous catheter's 45-mm wire embolised into the heart. The embolised wire was successfully removed via transhepatic access through the creation of an artificial simple snare.


Nutritional deficiencies in morbidly obese patients: a new form of malnutrition? Part A: vitamins.
It is a common belief that clinical vitamin or mineral deficiencies are rare in Western countries because of the low cost and unlimited diversity of food supply. However, many people consume food that is either unhealthy or of poor nutritional value that lacks proteins, vitamins, minerals, and fiber. In this, article we reviewed the literature and highlighted the vitamin deficiencies in obese patients before bariatric surgery. Deficiency of dietary minerals is described in the accompanying manuscript. The prevalence of vitamin deficiencies in the morbidly obese population prior to bariatric surgery is higher and more significant than previously believed.


Structure refinement of fly ash in connection with its reactivity in geopolymerization.
It's an oversimplification to evaluate the reactivity of fly ash in geopolymerization using bulk elemental ratios like Si/Al. In this study, quantitative XRD by means of Rietveld refinement was employed to proportionate the mineral and glass phases of five fly ashes. The chemical environment of Si and Al in the fly ashes was investigated by 29Si and 27Al MAS NMR spectra. By counting the contributions of Al phase from mullite, the proportion of different coordination states of Al in the glass phase was speculated. The results reveal that the coordination number of Al is directly associated with the amount of alkali cations present in the glass phase for the most fly ashes, whereby higher the alkali content, the more four fold coordinated Al species are present in the system. Five and six fold coordinated Al as well as highly polymerized silicate species are also present in the glass structure of the fly ash. All these results point to an inherent inhomogeneous glass structure in fly ash. Despite that, a reactivity index derived from the NBO/T ratio (Non-Bridging Oxygen per Tetrahedral network former, e.g. SiO44-, AlO45-) modelled in a simplified glass setup, correlates well with the reaction heat of the geopolymers.


Intralingual naloxone injection for narcotic-induced respiratory depression.
Narcotic-induced respiratory depression in a 25-year-old man was completely reversed with the administration of intralingual naloxone. Use of this route has been advocated when the IV route is unobtainable. No specific case report or case data have been published regarding this route.


Chromatographic separation of germanium and arsenic for the production of high purity (77)As.
A simple column chromatographic method was developed to isolate (77)As (94±6% (EtOH/HCl); 74±11 (MeOH)) from germanium for potential use in radioimmunotherapy. The separation of arsenic from germanium was based on their relative affinities for different chromatographic materials in aqueous and organic environments. Using an organic or mixed mobile phase, germanium was selectively retained on a silica gel column as germanate, while arsenic was eluted from the column as arsenate. Subsequently, enriched (76)Ge (98±2) was recovered for reuse by elution with aqueous solution (neutral to basic). Greater than 98% radiolabeling yield of a (77)As-trithiol was observed from methanol separated [(77)As]arsenate [17].


Risk factors of foot and mouth disease in an endemic area on low vaccination rate in Xayaboury province of Lao People's Democratic Republic (Lao PDR).
In Xayaboury province, located in the northern region of Lao PDR, the foot and mouth disease (FMD) vaccination campaign just began in 2009. Up until now, a small number of farms have been vaccinated. When FMD outbreaks occur, it is interesting to determine the risk factors of FMD, especially in the area where vaccination rates are low. The questionnaire survey, using a case-control design at the household level, was carried out. From 59 villages with a total number of 434 households, 181 households who experienced FMD were assigned as case households, 146 households without FMD occurrence inside the outbreak villages as inside control households, and 107 households without FMD occurrence outside the outbreak villages as outside control households. Household owners were interviewed. The logistic regression model was used to identify the relationship between FMD occurrence (dependent variable) and the collected data (independent variables), including the social status of livestock owners, FMD prevention strategies, and farm locations. A non-parametric test was performed to determine the association of FMD and network parameters of animal movements among villages. In general, results show that a limited number of holders did vaccinate animals before the outbreaks (13.8-17.8%). The results indicated that livestock owners who had known information about FMD before the outbreaks had been less severely affected by the FMD outbreak than the owners who had not known information about FMD (P < 0.01, OR 0.16, 95% CI 0.09-0.29). Before the outbreaks, higher FMD risk was observed in owners who sold the livestock through animal traders (P < 0.01, OR 4.76, 95% CI 1.68-13.50). Spatial data show that households in the community closer to the main roads had higher FMD risk (P < 0.01, OR 4.76, 95% CI 1.68-13.50). In addition, the network parameters including in-degree, out-degree, and betweenness indicated that the villages with high movements of livestock were at high risk of FMD (P < 0.05). The present study emphasized the importance of the government units to distribute the information about FMD to all livestock farmers in Xayaboury. Disease awareness and prevention strategy should be prioritized in areas close to high density communities and in the trading of livestock.


Perioperative and long-term outcomes of Ross versus mechanical aortic valve replacement.
The ideal aortic valve replacement strategy in young- and middle-aged adults remains up for debate. Clinical practice guidelines recommend mechanical prostheses for most patients less than 50 years of age undergoing aortic valve replacement. However, risks of major hemorrhage and thromboembolism associated with long-term anticoagulation may make the pulmonary autograft technique, or Ross procedure, a preferred approach in select patients. Data were retrospectively collected for patients 18-50 years of age who underwent either the Ross procedure or mechanical aortic valve replacement (mAVR) between January 2000 and December 2016 at a single institution. Propensity score matching was performed and yielded 32 well-matched pairs from a total of 216 eligible patients. Demographic and preoperative characteristics were similar between the two groups. Median follow-up was 7.3 and 6.9 years for Ross and mAVR, respectively. There were no early mortalities in either group and no statistically significant differences were observed with respect to perioperative outcomes or complications. Major hemorrhage and stroke events were significantly more frequent in the mAVR population (p < .01). Overall survival (p = .93), freedom from reintervention and valve dysfunction free survival (p = .91) were equivalent. In this mid-term propensity score-matched analysis, the Ross procedure offers similar perioperative outcomes, freedom from reintervention or valve dysfunction as well as overall survival compared to traditional mAVR but without the morbidity associated with long-term anticoagulation. At specialized centers with sufficient expertize, the Ross procedure should be strongly considered in select patients requiring aortic valve replacement.


Effects of fasting, feeding and exercise on plasma acylcarnitines among subjects with CPT2D, VLCADD and LCHADD/TFPD.
The plasma acylcarnitine profile is frequently used as a biochemical assessment for follow-up in diagnosed patients with fatty acid oxidation disorders (FAODs). Disease specific acylcarnitine species are elevated during metabolic decompensation but there is clinical and biochemical heterogeneity among patients and limited data on the utility of an acylcarnitine profile for routine clinical monitoring. We evaluated plasma acylcarnitine profiles from 30 diagnosed patients with long-chain FAODs (carnitine palmitoyltransferase-2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), and long-chain 3-hydroxy acyl-CoA dehydrogenase or mitochondrial trifunctional protein (LCHAD/TFP) deficiencies) collected after an overnight fast, after feeding a controlled low-fat diet, and before and after moderate exercise. Our purpose was to describe the variability in this biomarker and how various physiologic states effect the acylcarnitine concentrations in circulation. Disease specific acylcarnitine species were higher after an overnight fast and decreased by approximately 60% two hours after a controlled breakfast meal. Moderate-intensity exercise increased the acylcarnitine species but it varied by diagnosis. When analyzed for a genotype/phenotype correlation, the presence of the common LCHADD mutation (c.1528G > C) was associated with higher levels of 3-hydroxyacylcarnitines than in patients with other mutations. We found that feeding consistently suppressed and that moderate intensity exercise increased disease specific acylcarnitine species, but the response to exercise was highly variable across subjects and diagnoses. The clinical utility of routine plasma acylcarnitine analysis for outpatient treatment monitoring remains questionable; however, if acylcarnitine profiles are measured in the clinical setting, standardized procedures are required for sample collection to be of value.


Using visual displays to communicate risk of cancer to women from diverse race/ethnic backgrounds.
This study evaluated how well women from diverse race/ethnic groups were able to take a quantitative cancer risk statistic verbally provided to them and report it in a visual format. Cross-sectional survey was administered in English, Spanish or Chinese, to women aged 50-80 (n=1160), recruited from primary care practices. The survey contained breast, colorectal or cervical cancer questions regarding screening and prevention. Women were told cancer-specific lifetime risk then shown a visual display of risk and asked to indicate the specific lifetime risk. Correct indication of risk was the main outcome. Correct responses on icon arrays were 46% for breast, 55% for colon, and 44% for cervical; only 25% correctly responded to a magnifying glass graphic. Compared to Whites, African American and Latina women were significantly less likely to use the icon arrays correctly. Higher education and higher numeracy were associated with correct responses. Lower education was associated with lower numeracy. Race/ethnic differences were associated with women's ability to take a quantitative cancer risk statistic verbally provided to them and report it in a visual format. Systematically considering the complexity of intersecting factors such as race/ethnicity, educational level, poverty, and numeracy in most health communications is needed.


Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms.
Major depressive disorder (MDD) and bipolar disorder (BPD) have significant genetic predisposition. The P2RX7 gene (coding for P2X7 purinergic receptor) has been suggested as a susceptibility gene for both MDD and BPD. In the current study the genetic effects of rs2230912 (Gln460Arg) and rs1653625 (located in the 3' untranslated region of the P2RX7 gene) were explored in mood disorders. Genotype frequencies were established in 315 patients (195 with MDD and 120 with BPD diagnosis) and in 373 controls. Depression severity was assessed by the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) and by the self-report Hospital Anxiety and Depression Scale (HADS). In the case-control analysis we did not find any significant differences between genotype frequencies of either BPD or MDD cases and controls. However, BPD patients carrying at least one rs2230912G-allele scored higher on both MADRS and HADS-depression scale (nominal p-value was 0.028 and 0.003, respectively). The rs1653625AA genotype was also associated with higher depression scores in the BPD group (nominal p-value of MADRS: 0.019, HADS-depression: 0.017). After correction for multiple testing, the association between rs2230912 and HADS-depression score remained significant in the BPD group (p<0.006); this genetic effect explained 9% of the variance (partial η(2)=0.09). In the MDD group we did not find any significant genetic effect. The relatively small number of BPD patients warrants for a replication study. Our genetic association study supports the association between P2RX7 gene and severity of depressive symptoms in BPD patients.


The structure and function of Na+ channels.
The past year has seen major advances in our understanding of voltage-gated ion channels through a powerful combination of patch-clamp and molecular biological techniques. These approaches have identified regions (in some cases single amino acid residues) that are essential for voltage-dependent activation and inactivation, lining of the pore, and regulation of channel function.


Chemical detection of leukocytes in urine by means of a new multiple test strip.
The performance of the leukocyte test area of the new multiple urine test strip, Multistix-10-SG, was evaluated in both field trials and model experiments. The detection limit was found to be adequate for routine purposes. Unspecific reactions are rare and generally indicated by the results of the other test areas.


Global physiological understanding and metabolic engineering of microorganisms based on omics studies.
Through metabolic engineering, scientists seek to modify the metabolic pathways of living organisms to facilitate optimized, efficient production of target biomolecules. During the past decade, we have seen notable improvements in biotechnology, many of which have been based on metabolically engineered microorganisms. Recent developments in the fields of functional genomics, transcriptomics, proteomics, and metabolomics have changed metabolic engineering strategies from the local pathway level to the whole system level. This article focuses on recent advances in the field of metabolic engineering, which have been powered by the combined approaches of the various "omics" that allow us to understand the microbial metabolism at a global scale and to develop more effectively redesigned metabolic pathways for the enhanced production of target bioproducts.


ABCA1 Deficiency: A Rare Cause of Premature Coronary Artery Disease.
ATP-binding cassette transporter A1 (ABCA1) deficiency results in very low high-density lipoprotein cholesterol levels. Complete ABCA1 deficiency, or Tangier disease, is characterized by premature atherosclerotic cardiovascular disease, yellow-orange tonsils, hepatosplenomegaly, peripheral neuropathy, and corneal opacification. Early recognition of this condition can lead to regular monitoring for atherosclerotic cardiovascular symptoms and treatment of major modifiable risk factors. (Level of Difficulty: Beginner.).


Comparison of the moss Pleurozium schreberi with needles and bark of Pinus sylvestris as biomonitors of pollution by industry in Stalowa Wola (southeast Poland).
Concentrations of heavy metals were determined in the terrestrial bryophyte Pleurozium schreberi and in samples of bark and current and previous year needles of Pinus sylvestris collected along transects around the Stalowa Wola industry center (southeast Poland) and compared with material of the same species from a control site. The suitability of bark and pine needles for use in monitoring of serious heavy metal pollution was investigated. In the examined area current and previous year pine needles can be considered suitable biomonitors for atmospheric pollution for Cu and Zn and bark for only Cu. Bioaccumulation abilities of Cd and Cu in P. schreberi and P. sylvestris current and previous year needles were similar. Current and previous year needles were better accumulators of Mn, Ni, and Zn compared to the moss P. schreberi. Bark was a better accumulator of Cd, Cu, and Ni and an inferior accumulator of Mn compared to P. schreberi in the examined area.


Cocaine self-administration in rats: hold-down procedures.
For decades, researchers have used animal self-administration models to examine the effects drugs of abuse have on physiology and behavior. Sophisticated self-administration procedures have been developed to model many different aspects of drug addiction. The hold-down procedure provides animals with control over the amount of each injection. Holding the lever down turns the syringe pump on and subsequently releasing the lever turns the pump off. In this way, animals can hold the lever down for any duration of time thereby self-administering any dose on a continuous spectrum. This procedure eliminates some of the ambiguity in translating results from effects only observed at one unit dose and allows examination of which dose the animal "prefers" at different times.


Inhibition of cardiac sympathetic neurotransmission by adenosine.
Experiments were performed to study the effect of adenosine on sympathetic neurotransmission to the myocardium. Adenosine administration to pentobarbital-anesthetized dogs resulted in decrease in blood pressure and significant impairment of cardioacceleration produced by stimulation of cardiac sympathetic nerves. The positive chronotropic effect of intravenous norepinephrine was not affected by adenosine. The blood pressure lowering as well as the inhibitory effect of adenosine on cardiac sympathetic nerve function could be significantly antagonized by theophylline. These results provide in vivo evidence in support of the hypothesis that adenosine caused inhibition of sympathetic neurotransmission via an action on purinergic receptors located on sympathetic nerve terminals.


Plasma from cirrhotic patients induces inotropic changes on cultured rat heart cells.
Cultured monolayers of newborn rat heart cells were perfused with plasma from patients with alcoholic liver cirrhosis. The results showed that cirrhotic plasma, when compared to control plasma, depressed contractility of beating cardiac cells. The in-vitro deleterious effects of plasma from cirrhotic subjects on cell cultures were neither related to hemodynamic parameters nor to the levels of plasmatic catecholamines. This study suggests the presence in the plasma of patients with alcoholic liver cirrhosis, of humoral factor(s) which cause depressive effects on rat heart cells in culture.


Structural analysis of the extension peptides on matrix forms of type V collagen in fetal calf bone and skin.
The structure of the extension peptides retained on the tissue form of type V collagen molecules was determined. Type V collagen alpha chains containing extension peptides were extracted from fetal calf skin and bone by 4 M guanidine-HCl and 0.5 M acetic acid, respectively. Collagens present in both extracts were fractionated by sodium chloride precipitation. The collagen alpha(V) chains were then resolved by reverse-phase high performance liquid chromatography. The N-terminal extension peptides were characterized by direct sequence analysis after deblocking with pyroglutamate amino-peptidase and analysis of the products of digestion by bacterial collagenase, chymotrypsin, V8 protease and endoproteinase Lys-C. The results showed that the retained extension peptides on type V collagen molecules in the extracellular matrix of skin and bone were amino-propeptides and that the alpha 2(V) chain retains an intact amino-propeptide while the alpha 1(V) chain appears to be partially processed. The extended alpha 1(V) chain isolated from fetal calf bone gave an identical amino-terminal sequence to that of the alpha 1(V) chain isolated from fetal calf skin, suggesting that a specific enzyme may be involved in processing the alpha 1(V) amino-propeptide.


Squamous cell carcinoma of the oral cavity in young patients: a matched-pair analysis.
There is an increased incidence of oral squamous cell carcinoma (SCC) in young patients. However, the literature concerning prognosis for young patients with oral SCC is conflicting. The aim of this study was to compare the survival rates of patients under 45 years of age and diagnosed with SCC of the oral cavity with those of patients older than 45 years. A retrospective review of 28 patients under 45 years of age with SCC of the oral cavity was performed. We matched each of these patients by sex, tumor site, and overall stage with two patients older than 45 years. Overall survival, disease-free survival, disease-specific survival, rates of local, regional and distant metastasis were determined for both populations. Survival analysis was performed using Cox proportional hazard models. Stage and treatment modality were similar in the two groups. There were significant differences in overall survival (P=0.024) and disease-specific survival (P=0.03) favoring young patients. Locoregional recurrence and distant metastasis were higher in the older patients. Furthermore, matched survival analysis demonstrated a difference in overall survival rate [risk ratio (RR) 2.457; P=0.033] and disease-specific survival [RR 2.475; P=0.048]. Young patients with SCC of the oral cavity developed fewer locoregional recurrences and distant metastasis. The overall survival and disease-specific survival rates were better in the young patient population.


Hindi Adaptation and Psychometric Validation of the Affiliate Stigma Scale.
The Affiliate Stigma Scale (ASS) is a widely used tool to measure affiliate stigma in the caregivers of individuals with various types of mental illnesses. However, the Hindi adaptation of this scale with evident psychometric properties is not available. This study aimed to adapt the ASS in the Hindi language and, further, to validate it in the Indian setting. Translation and back-translation methods were used to translate the original items of the ASS to the Hindi language. After completion of translations and linguistic adaptation process, the Hindi translated version of the ASS, WHO Quality of Life-BREF (WHOQOL-BREF), General Health Questionnaire-12 (GHQ-12), and Hospital Anxiety and Depression Scale (HADS) were administered to 140 caregivers of persons with mental illness. Purposive sampling method was adopted. The age range of the participants was 17-60 years. Psychometric properties, as well as the factor structures of the scale, were evaluated. The Hindi version of the ASS has adequate internal consistencies (r = 0.87-0.93) and test-retest reliability (r = 0.78, P < 0.001). The concurrent validity of this scale was also high, as the correlation coefficients among the Hindi version of the ASS, WHOQOL-BREF, GHQ-12, and HADS were ranging from 0.23 to 0.35. The exploratory factor analysis revealed three underlying factors, namely, cognition, affect, and behavior. The Hindi version of the ASS is a reliable and valid psychometric tool to measure affiliate stigma in caregivers of patients with mental illness.


Update on the PennPET Explorer: A Whole-body Imager with Scalable Axial Field-of-View.
Following successful performance testing and human imaging of a prototype PennPET Explorer, the scanner has been expanded to a current axial field of view of 1.12 m. Initial studies on this instrument have demonstrated encouraging results for total-body positron emission tomography imaging. Planned studies will test the capabilities of the PennPET Explorer further and inform the design of further human imaging protocols.


Optimal duration of dual antiplatelet therapy after coronary stent implantation.
Dual antiplatelet pharmacotherapy reduces ischemic events at the cost of excess bleeding in patients who underwent coronary stenting. The currently recommended treatment period is based on trials held some 20 years ago and not relevant to current clinical practice. In recent years, numerous clinical trials have tried to answer the question of what is the optimal duration of therapy to maximize clinical benefit. These trials showed 2 seemingly conflicting answers-on one hand, shorter treatment duration seems to be safer in reducing bleeding while not increasing ischemic events, and on the other hand, longer duration is superior in terms of preventing ischemic events albeit at the cost of increased bleeding rates. In this review, we summarize the evidence favoring each approach, highlight the limitations of the various pivotal clinical trials in this field, review future directions of research and changes in practice that may influence the duration of antiplatelet therapy, and attempt to propose a personalized approach to achieve maximal benefit for the individual patient.


[Choice of the optimal variant of plastic surgery in head and neck tumors].
Indications for planning primary and delayed operations for head and neck tumors have been evolved on the basis of our 15-year experience with 667 reconstructive surgeries (550 patients) 425 of which (77%) were conducted in one stage.


Neurotensin in the human brain.
The localization of neurotensin-immunoreactive sites in the adult human brain was investigated by the indirect immunoperoxidase method of Sternberger [Sternberger (1979) Immunocytochemistry. Wiley, New York]. Our results demonstrate a widespread, albeit uneven occurrence of neurotensin-immunoreactive cells and processes throughout the central nervous system. Immunoreactive cells are prominent in the medial hypothalamus and in various regions of the limbic system, including the amygdaloid body, septal area, bed nucleus of the stria terminalis and piriform cortex. A few cells were also found in the dorsal synencephalon, superior colliculus, periaqueductal grey and spinal trigeminal nucleus. The distribution of immunoreactive fibres corresponds well with that reported for rodents. Areas with the highest concentration of neurotensin-immunoreactive processes included all the areas where immunoreactive neurons were found and, in addition, periventricular thalamic nuclei, the sublenticular region, lateral parts of the brainstem reticular formation and the vagus-solitarius complex. Comparison mapping studies of melanin-containing neurons on sections treated with neurotensin antiserum revealed an anatomical relation between almost all the catecholaminergic cell clusters with peptide-containing fibres.