Evaluation, Treatment, and Outcomes of Meniscal Root Tears: A Critical Analysis Review.
Meniscal root tears or avulsions compromise the biomechanical function of the menisci to a greater extent than simple meniscal tears do. As such, if left untreated, root injuries render the menisci incapable of properly distributing axial load and resisting rotation and translation. The clinical diagnosis of meniscal root abnormalities may be difficult as the signs and symptoms typically associated with meniscal body injuries, such as mechanical locking and catching, may not be present in patients with root injury and there may not be a history of an acute traumatic event. Treating practitioners need to have a high suspicion for meniscal root abnormalities in patients presenting with joint line tenderness and pain with deep flexion activities. Magnetic resonance imaging (MRI) signs indicative of meniscal root abnormality include a radial tear of the meniscal root (on axial imaging), a vertical linear defect in the meniscal root (truncation sign on coronal imaging), meniscal extrusion >3 mm outside the peripheral margin of the joint (on coronal imaging), and increased signal within the meniscal root (ghost sign on sagittal sequences). Two main approaches for meniscal root repair have evolved. One approach involves the use of a transtibial pullout technique, and the other involves the use of a suture anchor repair. The goal of both approaches is to restore an anatomical attachment of the meniscal root to bone that is capable of converting axial weight-bearing loads into hoop stresses. In a recent systematic review of meniscal root repairs, healing (partial and complete) was reported to have occurred in 96% of cases, with all studies demonstrating improvements in terms of subjective and functional scores at a mean of 30.2 months postoperatively.


Interval Laparoscopic Transabdominal Cervical Cerclage (ILTACC) Using Needleless Mersilene Tape for Cervical Incompetence.
Interval Laparoscopic Transabdominal Cervical Cerclage (ILTACC) has become a procedure of choice for many laparoscopic surgeons in nonpregnant patients diagnosed with cervical incompetence (CI) due to the inherent advantages it offers. The study was conducted to describe the feasibility of performing a three-step approach of ILTACC using a needleless mersilene tape in patients diagnosed with CI. A case series of three patients diagnosed with CI who underwent ILTACC using needleless mersilene tape referred at a tertiary hospital for cerclage. Women diagnosed with CI who underwent ILTACC using a needleless mersilene tape were included in the study, and surgical outcomes were measured. Descriptive statistics were used to describe the demographic profile and surgical outcomes of the patients. Three patients with a mean age of 31 (standard deviation [SD] = 4.96) years with a gravidity of 2.67 (SD, 0.82) and parity of 0.33 (SD, 0.47) were selected. The cervical length was 1.98 (SD, 0.76) cm. The average operative time was 149 (SD, 43.87) minutes. All patients had minimal blood loss (≤ 60 ml) without intraoperative blood transfusion. The hospital stay was 1.33 (SD, 0.47) days with a median of 1 and a range of 1-2 days. No intraoperative or postoperative complications were noted. No cases were converted to laparotomy. The result of this article shows the safety and feasibility of ILTACC using needleless mersilene tape. However, it should be evaluated in more cases.


Phosphorylation of the cytoplasmic domain of Alzheimer's beta-amyloid precursor protein at Ser655 by a novel protein kinase.
The cytoplasmic domain of Alzheimer's beta-amyloid precursor protein (APP) can be phosphorylated at Thr654, Ser655, and Thr668 (APP695 isoform numbering). Previous studies demonstrated that Ser655 of APP was phosphorylated by protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMKII) in vitro and by unidentified protein kinase(s) in vivo. We report here the characterization of a novel protein kinase (designated APP kinase I) which phosphorylates Ser655 of APP. APP kinase I was partially purified over 7,000-fold from rat brain and identified as a approximately 43 kDa protein that is distinct from a number of known protein kinases, including PKC and extracellular signal-regulated kinases (ERKs). The identification of a novel protein kinase that phosphorylates Ser655 will hopefully contribute to our understanding of the metabolism and/or function of APP in the pathogenesis of Alzheimer's disease (AD).


Fetal heart rate pattern recognition by the method of auscultation.
The thesis that obstetric health care personnel can discriminate characteristics of baseline fetal heart rate (FHR) and FHR patterns by auscultation needs to be tested. For this study, audiotones of the FHR signals were recorded for eight representative FHR patterns. Each recording was for three minutes and included one uterine contraction. Physicians and nurses who use continuous electronic FHR monitoring on a regular basis listened to the eight recordings and attempted to identify the baseline rate, variability, and periodic patterns, and then matched their perceptions with the eight corresponding FHR tracings (not in order). Baseline FHR and FHR without periodic patterns were most frequently identified correctly. Late decelerations with and without good baseline variability were misdiagnosed 18.4 and 33% of the time, respectively. Although the FHR characteristics and periodic patterns were correctly identified most of the time, failure to recognize significant periodic patterns by as many as one-third of the participants is unacceptable in modern obstetrics.


UV-Induced unimolecular photochemistry of diketene isolated in cryogenic inert matrices.
Diketene (C(4)H(4)O(2)) monomers were isolated in cryogenic Ar (15 K) and Xe (30 K) matrices. The infrared (IR) spectra of the freshly deposited matrices show that diketene monomers exclusively adopt the 4-methylene-oxetan-2-one form. In situ photochemical transformations of diketene were induced by tunable UV laser light. Diketene was found to be photostable when exposed to near-UV irradiations (λ> 300 nm). Irradiations in the middle-UV domain showed different types of photochemical reactivity occurring upon irradiations with 280 > λ > 240 nm and λ = 225 nm. The photoproducts were characterized by IR spectroscopy supported by B3LYP/6-311++G(d,p) calculations. Upon irradiation in the 280 > λ > 225 nm range, diketene was found to decompose in two ways: (i) with production of two parent ketene molecules (O═C═CH(2)), and (ii) with production of cyclopropanone (CP) plus carbon monoxide. For irradiations in the 280 > λ > 240 nm range, diketene exhibited two additional reactions: (iii) decomposition to allene (H(2)C═C═CH(2)) and carbon dioxide, and (iv) isomerization into cyclobutane-1,3-dione (CB). Of the above photoproducts, CP and CB were consumed by the same UV irradiations that resulted in their generation. Positive spectroscopic identification of CP and CB turned out to be possible with near-UV irradiations: CP decomposes to ethylene and carbon monoxide upon irradiation with λ = 345 nm; CB decomposes exclusively to two parent ketene molecules, without isomerization back to diketene or decarbonylation, upon irradiation with λ = 330 nm. Natural bond orbital (NBO) analysis showed that the two lowest excited singlet states of diketene are almost degenerate in energy and correspond to π* orbitals of C═C and C═O moieties. The NBO calculations helped to establish that the third excited singlet state, in terms of energy, has σ*(3s) Rydberg character, in accord with the literature.


Courtship and agonistic sounds by the cichlid fish Pseudotropheus zebra.
Courtship and agonistic interactions in an African cichlid species present a richer diversity of acoustic stimuli than previously reported. Male cichlids, including those from the genus Pseudotropheus (P.), produce low frequency short pulsed sounds during courtship. Sounds emitted by P. zebra males in the early stages of courtship (during quiver) were found to be significantly longer and with a higher number of pulses than sounds produced in later stages. During agonistic intrasexual quiver displays, males produced significantly longer sounds with more pulses than females. Also, male sounds had a shorter duration and pulse period in courtship than in male-male interactions. Taken together, these results show that the acoustic repertoire of this species is larger than what was previously known and emphasize the importance of further research exploiting the role of acoustic stimuli in intra- and interspecific communication in African cichlids.


Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery.
The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy.


Clinical nurse specialist practice: addressing populations with HIV/AIDS.
Clinical nurse specialists (CNSs) in public health and human immunodeficiency virus/acquired immune deficiency syndrome are needed to eliminate healthcare disparities, especially with African American women, ages 25-44. This population of women accounts for 64% of acquired immunodeficiency syndrome cases reported among women, and most of these women need nursing care in community settings. Epidemiologic data and nursing research findings demonstrate an urgent need for nurses with advanced practice competencies in human immunodeficiency virus/acquired immune deficiency syndrome. The competencies identified by the National Association of Clinical Nurses Specialists in 3 spheres of influence-direct care, nursing personnel, and organizations/networks-are used to describe clinical nurse specialist competencies as they relate to this population. Leininger's Sunrise Model serves as a framework to help this population preserve, accommodate, and repattern behaviors for the prevention and treatment of human immunodeficiency virus/acquired immune deficiency syndrome.


A highly stable and versatile heterobifunctional fluoroalkylation reagent for preparation of fluorinated organic compounds.
A highly stable heterobifunctional fluoroalkylation reagent, 1-azido-2-chloro-1,1,2-trifluoro-2-iodoethane (ACTI) has been prepared in high yield for the first time by a new method. Moreover, the reactivity of both the azido group and the iodine atom of the reagent was systematically investigated and the results demonstrate that this compound is a very versatile and useful new fluoroalkylation reagent for preparation of fluorinated organic compounds.


Stability Limits and Defect Dynamics in Ag Nanoparticles Probed by Bragg Coherent Diffractive Imaging.
Dissolution is critical to nanomaterial stability, especially for partially dealloyed nanoparticle catalysts. Unfortunately, highly active catalysts are often not stable in their reactive environments, preventing widespread application. Thus, focusing on the structure-stability relationship at the nanoscale is crucial and will likely play an important role in meeting grand challenges. Recent advances in imaging capability have come from electron, X-ray, and other techniques but tend to be limited to specific sample environments and/or two-dimensional images. Here, we report investigations into the defect-stability relationship of silver nanoparticles to voltage-induced electrochemical dissolution imaged in situ in three-dimensional detail by Bragg coherent diffractive imaging. We first determine the average dissolution kinetics by stationary probe rotating disk electrode in combination with inductively coupled plasma mass spectrometry, which allows in situ measurement of Ag+ ion formation. We then observe the dissolution and redeposition processes in single nanocrystals, providing unique insight about the role of surface strain, defects, and their coupling to the dissolution chemistry. The methods developed and the knowledge gained go well beyond a "simple" silver electrochemistry and are applicable to all electrocatalytic reactions where functional links between activity and stability are controlled by structure and defect dynamics.


Capuchin and rhesus monkeys but not humans show cognitive flexibility in an optional-switch task.
Learned rules help us accurately solve many problems, but by blindly following a strategy, we sometimes fail to find more efficient alternatives. Previous research found that humans are more susceptible to this "cognitive set" bias than other primates in a nonverbal computer task. We modified the task to test one hypothesis for this difference, that working memory influences the advantage of taking a shortcut. During training, 60 humans, 7 rhesus macaques, and 22 capuchin monkeys learned to select three icons in sequence. They then completed 96 baseline trials, in which only this learned rule could be used, and 96 probe trials, in which they could also immediately select the final icon. Rhesus and capuchin monkeys took this shortcut significantly more often than humans. Humans used the shortcut more in this new, easier task than in previous work, but started using it significantly later than the monkeys. Some participants of each species also used an intermediate strategy; they began the learned rule but switched to the shortcut after selecting the first item in the sequence. We suggest that these species differences arise from differences in rule encoding and in the relative efficiency of exploiting a familiar strategy versus exploring alternatives.


The comprehensive alcohol expectancy questionnaire: confirmatory factor analysis, scale refinement, and further validation.
The Comprehensive Alcohol Expectancy Questionnaire (CAEQ; Demmel & Hagen, 2003a, 2003b) is a self-report measure designed to assess an individual's alcohol expectancies. In this study, we examined the CAEQ in a student sample (N= 932) and in a clinical sample of alcohol-dependent inpatients (N= 744). The Five-factor structure was confirmed by means of confirmatory factor analysis. Convergent validity of the revised CAEQ was supported by showing significant relationships to quantity and frequency of drinking. The results of this study suggest that the revised CAEQ appears to be a psychometrically sound tool for the assessment of alcohol expectancies among both students and alcohol-dependent inpatients.


Upregulation of CYP2S1 by oxaliplatin is associated with p53 status in colorectal cancer cell lines.
Oxaliplatin displays a wide spectrum of antitumor activities and is widely used in the treatment of metastatic colorectal cancer (CRC). However, tumor responses to this agent are variable, and the underlying mechanisms are poorly understood. In the present study, oxaliplatin was found to strongly inhibit the growth of HCT116 cells harboring wild-type p53 but to only weakly inhibit SW480 cells, HT29 cells or p53-/- HCT116 cells, which all lack p53 expression. Administration of oxaliplatin significantly induced p53 accumulation and enhanced expression of CYP2S1 in HCT116 cells with wild-type p53. CYP2S1 knockdown conferred a cell survival advantage after oxaliplatin treatment to cells harboring wild-type p53 in vitro and in vivo. Interestingly, enzyme immunoassays, TOPFlash/FOPFlash reporter activity assays and western blotting analysis demonstrated oxaliplatin-mediated downregulation of PGE2 and Wnt/β-catenin signaling in a manner dependent on p53. Moreover, oxaliplatin treatment of mice with subcutaneous tumor xenografts drastically reduced the volume of wild-type p53 HCT116 tumors but had no effect on isogenic p53-/- HCT116 tumors. These results suggest that oxaliplatin exerts its inhibitory effects in human CRC cells via upregulation of CYP2S1 expression in a p53-dependent manner.


SBROME: a scalable optimization and module matching framework for automated biosystems design.
The development of a scalable framework for biodesign automation is a formidable challenge given the expected increase in part availability and the ever-growing complexity of synthetic circuits. To allow for (a) the use of previously constructed and characterized circuits or modules and (b) the implementation of designs that can scale up to hundreds of nodes, we here propose a divide-and-conquer Synthetic Biology Reusable Optimization Methodology (SBROME). An abstract user-defined circuit is first transformed and matched against a module database that incorporates circuits that have previously been experimentally characterized. Then the resulting circuit is decomposed to subcircuits that are populated with the set of parts that best approximate the desired function. Finally, all subcircuits are subsequently characterized and deposited back to the module database for future reuse. We successfully applied SBROME toward two alternative designs of a modular 3-input multiplexer that utilize pre-existing logic gates and characterized biological parts.


Up-regulation of survivin by AKT and hypoxia-inducible factor 1α contributes to cisplatin resistance in gastric cancer.
This study investigated the contribution of survivin and its upstream regulators, AKT and hypoxia-inducible factor 1α (HIF-1α), to the resistance of gastric cancer cells to cisplatin (CDDP). We found that over-expression of survivin increased the resistance of SGC7901 and BGC823 gastric cancer cells to CDDP. Its over-expression abrogated CDDP-induced inhibition of cell proliferation and CDDP-induced cell apoptosis. In contrast, down-regulation of survivin expression using small hairpin RNA (shRNA) vectors and the small-molecule inhibitor YM155, or inhibition of survivin function using a recombinant cell-permeable dominant-negative survivin protein (dNSur9), promoted CDDP-induced apoptosis. CDDP-resistant sub-lines generated from the parental SGC7901 and BGC823 cells by exposure to increasing concentrations of CDDP expressed higher levels of HIF-1α and survivin in response to hypoxia, and higher levels of phosphorylated AKT (pAKT). Specific inhibition of AKT reduced the expression of HIF-1α and survivin, whereas specific inhibition or depletion of HIF-1α reduced survivin expression but had no effect on the expression of phosphorylated AKT. The expression levels of survivin affected the therapeutic efficacy of CDDP in treating gastric tumors in mice. Specific inhibition of survivin, AKT and HIF-1α enhanced the sensitivity of CDDP-resistant cells to CDDP. Specific inhibition of survivin, AKT and HIF-1α synergized with CDDP to suppress the growth of gastric tumors that had been engineered to overexpress survivin. In summary, the results provide evidence that up-regulation of survivin by AKT and HIF-1α contributes to CDDP resistance, indicating that inhibition of these pathways may be a potential strategy for overcoming CDDP resistance in the treatment of gastric cancer.


Upregulation of the anti-apoptotic protein Bcl-2 may be an early event in neurodegeneration: studies on Parkinson's and incidental Lewy body disease.
Apoptosis and oxidative stress have been suggested to be involved in Parkinson's disease (PD). However, whether this is a cause or consequence of neurodegeneration is unknown. Incidental Lewy Body disease (ILBD) appears to be a presymptomatic form of Parkinson's disease where individuals are neurologically normal, but after post-mortem examination pathology similar to Parkinson's disease is present. Thus, ILBD can be used to examine the early stages of the pathological process in PD. We investigated the levels of Bcl-2, an anti-apoptotic protein known to decrease cell death induced by several mechanisms, including oxidative stress. Our data show that Bcl-2 is significantly raised in the basal ganglia regions of PD patients as compared to age-matched controls. A similar trend is also found in ILBD. We propose that Bcl-2 increases in some brain regions as an early event and that these brain regions are under a stress for perhaps many years before any symptomatic changes occur.


Prescribing for pregnancy: inflammatory bowel disease.
Inflammatory bowel diseases commonly present in young adulthood and it is estimated that up to one in 200 pregnant women have IBD. Key factors for successful pregnancy outcome are disease remission at the time of conception and optimal disease control during pregnancy, with active disease increasing the risk of adverse effects for both mother and baby. This article forms part of a series on prescribing for pregnancy and discusses the impact of IBD on pregnancy and the influence pregnancy may have on IBD. It highlights the importance of prepregnancy care and collaborative working between obstetric and gastroenterology specialties as well as focusing on prescribing before, during and after pregnancy, exploring treatment options for IBD which are evolving rapidly as new immunosuppressive agents emerge.


ORL1 and opioid receptor preferences of nociceptin and dynorphin A analogues with Dmp substituted for N-terminal aromatic residues.
Nociceptin (NOC) and dynorphin A (DYN) analogues containing 2',6'-dimethylphenylalanine (Dmp) in place of Phe or Tyr in position 1 and/or 4 were synthesized and their metabolic stability and receptor-binding properties were investigated. [Dmp1]NOC(1-13)-NH2 (1) possessed high ORL1 receptor affinity comparable to that of the parent peptide with substantially improved affinities for kappa-, mu-, and delta-opioid receptors. However, Dmp4 substitution of NOC peptide (2) reduced ORL1 receptor affinity. [Dmp1]DYN(1-13)-NH2 (4) and its Dmp4 analogue (5) possessed a 3-fold greater kappa-opioid receptor affinity and improved kappa-receptor selectivity compared to the parent peptide. Analogue 4 however exhibited an unexpectedly low in vitro bioactivity (GPI assay), suggesting, the phenolic hydroxyl group at the N-terminal residue in DYN peptide is extremely important for activation of the kappa-opioid receptor. Analogue 5 possessed an improved kappa-opioid receptor selectivity with an IC50 ratio of 1(kappa)/509(mu)/211598(delta); thus, this peptide may serve as a highly selective kappa-receptor agonist for pharmacological study. Dmp1 substitution in both the NOC and DYN peptides improved metabolic stability toward these peptides, while Dmp4 substitution provided no additional metabolic stability.


23 years of managing diabetic ketoacidosis at Auckland Hospital
To examine the length of stay and need for intensive care of people admitted with diabetic ketoacidosis (DKA) to a single centre between 1988 and 2011. Patients aged ≥15 years admitted for the first time with DKA (plasma glucose ≥ 10mmol/L and a bicarbonate concentration ≤15mmol/L and a pH <7.35, and raised plasma or urine ketones or anion gap) to Auckland City Hospital from 1988-2011 were identified retrospectively. The patients were divided into four cohorts (1988-1996; 1997-2001; 2002-2006; 2007-2011). Over this time period there was no significant change to the insulin infusion protocol. There were 576 admissions with DKA in 388 people over the 23 years. The mean age of the patients and glucose concentration at presentation to hospital fell significantly over time. The admission pH and bicarbonate concentration was higher in more recent cohorts. The length of stay and need for intensive care admission fell significantly over time, but the number of patients subsequently readmitted with DKA remained high. In-hospital mortality remained low. DKA remains an important reason for admission to this hospital, but the severity of DKA at presentation has reduced over time. The need for intensive care admission and length of stay has fallen dramatically.


Impacts of Flow Rate and Pulsed Electric Field Current Mode on Protein Fouling Formation during Bipolar Membrane Electroacidification of Skim Milk.
Fouling is one of the major problems in electrodialysis. The aim of the present work was to investigate the effect of five different solution flow rates (corresponding to Reynolds numbers of 162, 242, 323, 404 and 485) combined with the use of pulsed electric field (PEF) current mode on protein fouling of bipolar membrane (BPM) during electrodialysis with bipolar membranes (EDBM) of skim milk. The application of PEF prevented the fouling formation by proteins on the cationic interface of the BPM almost completely, regardless of the flow rate or Reynolds number. Indeed, under PEF mode of current the weight of protein fouling was negligible in comparison with CC current mode (0.07 ± 0.08 mg/cm2 versus 5.56 ± 2.40 mg/cm2). When a continuous current (CC) mode was applied, Reynolds number equals or higher than 323 corresponded to a minimal value of protein fouling of BPM. This positive effect of both increasing the flow rate and using PEF is due to the facts that during pauses, the solution flow flushes the accumulated protein from the membrane while in the same time there is a decrease in concentration polarization (CP) and consequently decrease in H+ generation at the cationic interface of the BPM, minimizing fouling formation and accumulation.


Relationship between mercury in kidney, blood, and urine in environmentally exposed individuals, and implications for biomonitoring.
Individuals without occupational exposure are exposed to mercury (Hg) from diet and dental amalgam. The kidney is a critical organ, but there is limited information regarding the relationship between Hg in kidney (K-Hg), urine (U-Hg), blood (B-Hg), and plasma (P-Hg). The aim was to determine the relationship between K-Hg, U-Hg, B-Hg, and P-Hg among environmentally exposed individuals, estimate the biological half-time of K-Hg, and provide information useful for biomonitoring of Hg. Kidney cortex biopsies and urine and blood samples were collected from 109 living kidney donors. Total Hg concentrations were determined and the relationships between K-Hg, U-Hg, P-Hg, and B-Hg were investigated in regression models. The half-time of K-Hg was estimated from the elimination constant. There were strong associations between K-Hg and all measures of U-Hg and P-Hg (rp=0.65-0.84, p<0.001), while the association with B-Hg was weaker (rp=0.29, p=0.002). Mean ratios between K-Hg (in μg/g) and U-Hg/24h (in μg) and B-Hg (in μg/L) were 0.22 and 0.19 respectively. Estimates of the biological half-time varied between 30 and 92days, with significantly slower elimination in women. Adjusting overnight urine samples for dilution using urinary creatinine resulted in less bias in relation to K-Hg or U-Hg/24h, compared with other adjustment techniques. The relationship between K-Hg and U-Hg is approximately linear. K-Hg can be estimated using U-Hg and gender. Women have longer half-time of Hg in kidney compared to men. Adjusting overnight urine samples for creatinine concentration resulted in less bias.


Ameliorating effects of curcumin-loaded superparamagnetic iron oxide nanoparticles (SPIONs) on the mouse testis exposed to the transient hyperthermia: A molecular and stereological study.
Testicular hyperthermia can have negative effects on male fertility. Despite reported therapeutic benefits of curcumin, several factors often limit its application such as low water solubility and instable structure. Curcumin-loaded superparamagnetic iron oxide nanoparticles (SPIONs) were designed to solve its limitation of use. In the present study, we evaluated the effect of curcumin-loaded SPIONs on transient testicular hyperthermia in mouse. A total of 18 adult male NMRI mice were divided into three groups (n = 6): I. Controls (Cont), II. Scrotal hyperthermia (Hyp), III. Scrotal hyperthermia + curcumin-loaded iron particles (240 μL) (Hyp + Cur). After seventy days, the animals were sacrificed and used for further molecular and stereological evaluations. Sperm count, motility and viability significantly decreased in group hyp as compared to cont group. Furthermore, Sperm DNA fragmentation and cell apoptosis in testes increased remarkably in group hyp, compared with group cont. Stereological study showed a reduction in number of spermatogenic and Leydig cells, as well as reduced weight and volume of testes in hyp group. Degenerative appearance of testes exposed to hyperthermia was also observed. In addition, higher mRNA expression of inflammatory cytokines (IL1-α, IL6, and TNF-α) was detected in group hyp compared to cont group. However, curcumin-loaded SPIONs alleviated all of the pathologic changes in the Hyp + Cur group compared to the hyp group. Here, we used nanoparticle form of curcumin in testicular hyperthermia model and showed its ameliorating effects on testes damages caused by heat stress, which can be an appropriate method to overcome the problems that limit curcumin application in cases with increased intra testicular temperature.


Multi-Source and Multi-Representation Adaptation for Cross-Domain Electroencephalography Emotion Recognition.
Due to the non-invasiveness and high precision of electroencephalography (EEG), the combination of EEG and artificial intelligence (AI) is often used for emotion recognition. However, the internal differences in EEG data have become an obstacle to classification accuracy. To solve this problem, considering labeled data from similar nature but different domains, domain adaptation usually provides an attractive option. Most of the existing researches aggregate the EEG data from different subjects and sessions as a source domain, which ignores the assumption that the source has a certain marginal distribution. Moreover, existing methods often only align the representation distributions extracted from a single structure, and may only contain partial information. Therefore, we propose the multi-source and multi-representation adaptation (MSMRA) for cross-domain EEG emotion recognition, which divides the EEG data from different subjects and sessions into multiple domains and aligns the distribution of multiple representations extracted from a hybrid structure. Two datasets, i.e., SEED and SEED IV, are used to validate the proposed method in cross-session and cross-subject transfer scenarios, experimental results demonstrate the superior performance of our model to state-of-the-art models in most settings.


Increased Surgical Site Subcutaneous Fat Thickness Is Associated with Infection after Posterior Cervical Fusion.
Background: Previous literature has associated increased body mass index (BMI) with risk of surgical site infection (SSI) after posterior cervical fusion (PCF) surgery. However, few studies have examined the association between local adiposity and risk of SSI, re-admission, and re-operation after PCF. Local adiposity is easily measured on pre-operative magnetic resonance imaging (MRI) and may act as a more accurate predictor compared with BMI. Patients and Methods: Subjects undergoing PCF from 2013-2018 at a single institution were identified retrospectively. Posterior cervical subcutaneous fat thickness, paraspinal muscle thickness, and lamina-to-skin distance measurements were obtained from computed tomography (CT) or MRI scans. Subjects with active infection, malignancy, or revision procedures were excluded. Results: Two hundred five patients were included with 20 developing SSIs. Subjects with SSIs had a longer fusion construct (4.90 vs. 3.71 levels; p = 0.001), higher Elixhauser comorbidity index (ECI; 2.05 vs. 1.34; p = 0.045), had a history of diabetes mellitus (30% vs. 10.8%; p = 0.026), higher subcutaneous fat thickness (30.5 vs. 23.6 mm; p = 0.013), and higher lamina-to-skin distance (66.4 vs. 57.9 mm; p = 0.027). Subcutaneous fat thickness (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.10]; p = 0.026) and lamina-to-skin distance (OR, 1.05; 95% CI, 1.01-1.09]; p = 0.014) were associated with SSI in multivariable analysis. A subcutaneous fat thickness cutoff value of 23.2 mm had 90% sensitivity and 54.1% specificity for prediction of SSI. There was no association need for re-admission or re-operation. Conclusions: Increased posterior cervical fat may increase the risk of SSI after PCF. Pre-operative advanced imaging may be a valuable tool for assisting with patient counseling, optimization, and risk stratification.


First-trimester screening for Down syndrome using nuchal translucency measurement with free beta-hCG and PAPP-A between 10 and 13 weeks of pregnancy--the combined test.
In a population of 1467 women attending the 'G. Gaslini' Institute for antenatal care, we evaluated first-trimester risk screening for Down syndrome using the 'combined test' based on ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG, and maternal age. No clinical action was taken on these results. The gestational age, determined by scan measurement of crown rump length, ranged from 10 weeks to 13 weeks 6 days. The median maternal age was 31 years 8 months. There were 13 Down syndrome pregnancies. The risk of having an affected pregnancy was estimated from a multivariate Gaussian distribution, using commercially available software. With a risk cut-off of 1 in 350, 11 affected pregnancies were detected (detection rate 85 per cent, 95 per cent confidence interval: 56-100 per cent) with a 3.3 per cent false-positive rate. The odds of being affected given a positive result were 1 in 30. Further data are needed to determine, with greater statistical reliability, the relative performance of the combined test with current second-trimester screening.


Human immunodeficiency virus seropositivity in adolescents with syphilis.
The purpose of this study was to assess the relationship between syphilis and human immunodeficiency virus (HIV) infection among inner-city, minority group adolescents. From August 1989 through June 1990, serum from all positive serologic tests for syphilis, obtained from patients attending a comprehensive adolescent health center in an acquired immunodeficiency syndrome epicenter and its two school-based clinics, were frozen without patient identifiers and were subsequently screened for HIV by enzyme-linked immunosorbent assay with confirmatory Western blot for positives. In addition, a retrospective chart review was performed for all patients with a positive serologic test for syphilis during the study period. Of the 59 specimens with a positive syphilis serologic test, 9 (15.3%) were HIV seropositive. Of the patients with syphilis, 57.4% were black and 42.6% were Hispanic; 16.4% were male (mean age 18.1) and 83.6% were female (mean age 17.8). Only 1 subject (female) was an injection drug user; 4 of the male subjects self-identified as having had sex with other males. Of the subjects, 27.8% had primary, 19.7% had secondary, and 52.5% had latent syphilis at the time of diagnosis. A prior or concurrent sexually transmitted disease was present in 90% of the males and 80% of the females; gonorrhea was the most prevalent sexually transmitted disease in the males (89%) and chlamydia was most prevalent in the females (35%). A history of chancroid and/or herpes was present in 16.4% of the subjects. It is concluded that the diagnosis of syphilis in an adolescent is a risk factor for HIV infection. All sexually active adolescents should be routinely screened for syphilis, regardless of sexual practices. Those with syphilis should be specifically counseled about their increased risk for HIV infection and the importance of consistent condom use, and they should be referred for formal HIV pretest counseling.


Sensorimotor modulation of mood and depression: in search of an optimal mode of stimulation.
Depression involves a dysfunction in an affective fronto-limbic circuitry including the prefrontal cortices, several limbic structures including the cingulate cortex, the amygdala, and the hippocampus as well as the basal ganglia. A major emphasis of research on the etiology and treatment of mood disorders has been to assess the impact of centrally generated (top-down) processes impacting the affective fronto-limbic circuitry. The present review shows that peripheral (bottom-up) unipolar stimulation via the visual and the auditory modalities as well as by physical exercise modulates mood and depressive symptoms in humans and animals and activates the same central affective neurocircuitry involved in depression. It is proposed that the amygdala serves as a gateway by articulating the mood regulatory sensorimotor stimulation with the central affective circuitry by emotionally labeling and mediating the storage of such emotional events in long-term memory. Since both amelioration and aggravation of mood is shown to be possible by unipolar stimulation, the review suggests that a psychophysical assessment of mood modulation by multimodal stimulation may uncover mood ameliorative synergisms and serve as adjunctive treatment for depression. Thus, the integrative review not only emphasizes the relevance of investigating the optimal levels of mood regulatory sensorimotor stimulation, but also provides a conceptual springboard for related future research.


Lateral and anterior-posterior mandibular position discrimination by normal subjects.
This study examined and compared lateral and anterior-posterior (A-P) mandibular position discrimination for a group of twenty normal subjects (mean age = 26 years). A specially designed and constructed sliding scale required subjects to position their mandible precisely in the horizontal plane and to try to discriminate differences in the control of their mandibular position. The results revealed that subjects are more sensitive in detecting changes in the lateral positioning of their mandible than in the A-P positions. Subjects' difference limen (DL) values (threshold of discrimination between two positions) in detecting changes in mandibular position to the right of centre was 1.59 mm, and to left of centre was 1.41 mm. Subjects' DL values obtained with the mandible forward, and back of, the reference position were 1.39 and 2.61 mm respectively.


Manganese oxide nanomaterials boost cancer immunotherapy.
Immunotherapy, a strategy that leverages the host immune function to fight against cancer, plays an increasingly important role in clinical tumor therapy. In spite of the great success achieved in not only clinical treatment but also basic research, cancer immunotherapy still faces many huge challenges. Manganese oxide nanomaterials (MONs), as ideal tumor microenvironment (TME)-responsive biomaterials, are able to dramatically elicit anti-tumor immune responses in multiple ways, indicating great prospects for immunotherapy. In this review, on the basis of different mechanisms to boost immunotherapy, major highlighted topics are presented, covering adjusting an immunosuppressive TME by generating O2 (like O2-sensitized photodynamic therapy (PDT), programmed cell death ligand-1 (PD-L1) expression downregulation, reprogramming tumor-associated macrophages (TAMs), and restraining tumor angiogenesis and lactic acid exhaustion), inducing immunogenic cell death (ICD), photothermal therapy (PTT) induction, activating the stimulator of interferon gene (STING) pathway and immunoadjuvants for nanovaccines. We hope that this review will provide holistic understanding about MONs and their application in cancer immunotherapy, and thus pave the way to the translation from bench to bedside in the future.


Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease: implications for physicians.
The appearance of bovine spongiform encephalopathy (BSE) followed by new spongiform encephalopathies and variant Creutzfeldt-Jakob disease (CJD) in the United Kingdom indicates that these diseases may be linked. To give an understanding of this risk, the authors review the literature on the pathogenesis of CJD and BSE and the current findings on how these diseases are transmitted. They also discuss the implications for Canada's food and blood supply and outline previously published recommendations for disease prevention.


Improved visualization of folded collagen alpha-chains by ultra-rapid freezing.
Transmission electron microscopy techniques are commonly employed to examine the folded polymer structure of collagen polypeptides. These techniques include deposition of a sample by spraying, slow freeze-fixation, air drying and vacuum drying the specimen at room temperature, and using additives such as glycerol in the collagen preparation. Here we report preliminary observations of type I collagen alpha-chains, folded in water, at a concentration of 35 micrograms ml-1 and 10 micrograms ml-1, visualized by an ultra-rapid, freeze-fixation technique designed to minimize structural deformation caused by spraying, additives and poor freeze-fixation. The technique also allows the use of submicrolitre sample volumes of known concentrations with negligible loss and shearing, while at the same time providing excellent contrast to the collagen polymer for electron microscopy. This technique can be employed to study the structure of a wide range of macromolecules (proteins and carbohydrates).


Decreased expression of antioxidant enzymes is associated with aggressive features in ependymomas.
The purpose of this study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in 67 ependymal tumors. We included into the analysis antioxidant enzymes (AOEs) and related proteins, such as, manganese superoxide dismutase (MnSOD), gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), thioredoxin (Trx) and thioredoxin reductase (TrxR). Their expression was studied in 46 primary (10 grade I, 30 grade II and 6 grade III) and 21 recurrent (3 grade I, 12 grade II and 6 grade III) tumors. Immunoreactivity for MnSOD was found in 87%, GLCL-C in 74%, GLCL-R in 89%, Trx in 72%, TrxR in 54%, of primary tumors. Lower GLCL-C and GLCL-R expression was associated with higher tumor grade (P = 0.047 and 0.049, respectively). MnSOD, GLCL-C and TrxR expressions were significantly higher in tumors located in the spinal cord compared to those in the brain (P = 0.044, 0.046 and 0.004, respectively). In the primary tumors Trx-positivity was found to correlate significantly with patient survival. In univariate survival analysis patients whose tumors did not express Trx had shorter survival (P = 0.045) and there was even more significant association (P = 0.011) when only adults were included in the analysis (in the total material median follow-up time of Trx-positive tumors was 9.7 years and of Trx-negative 5.4 years). The results indicate that AOEs have several biological functions in ependymal tumors. Trx had important prognostic value: all adults with Trx-positive tumors were alive at follow-up (median 7.8 years).


Epicardium: interstitial Cajal-like cells (ICLC) highlighted by immunofluorescence.
During the last few years, there is an increasing interest in the role of the epicardium in cardiac development, myocardial remodelling or repair and regeneration. Several types of cells were described in the subepicardial loose connective tissue, beneath the epicardial mesothe-lium. We showed previously (repeatedly) the existence of interstitial Cajal-like cells (ICLCs) in human and mammalian myocardium, either in atria or in ventricles. Here, we describe ICLCs in adult mice epicardium and primary culture as well as in situ using frozen sections. The identification of ICLCs was based on phase contrast microscopy and immunophenotyping. We found cells with characteristic morphologic aspects: spindle-shaped, triangular or polygonal cell body and typical very long (tens to hundreds micrometres) and very thin cyto-plasmic processes, with a distinctive 'beads-on-a-string' appearance. The dilations contain mitochondria, as demonstrated by MitoTracker Green FM labelling of living cells. Epicardial ICLCs were found positive for c-kit/CD117 and/or CD34. However, we also observed ICLCs positive for c-kit and vimentin. In conclusion, ICLCs represent a distinct cell type in the subendocardium, presumably comprising at least two subpopulations: (i) c-kit/CD34-positive and (ii) only c-kit-positive. ICLCs might be essential as progenitor (or promoter) cells for developing cardiomyocyte lineages in normal and/or injured heart.


Optimization of the Fermentation Media and Parameters for the Bio-control Potential of Trichoderma longibrachiatum T6 Against Nematodes.
The cereal cyst nematode Heterodera avenae is one of the important soil-borne pathogens of cereal crops and causes high yield losses worldwide. Trichoderma spp. formulations are applied as commercial bio-control agents against soil-borne plant pathogens such as H. avenae. However, the relationship between Trichoderma longibrachiatum fermentation parameters and its bio-control potential against H. avenae has not been exclusively established. In the present study, the effect of 10 different fermentation media and conditions on the nematicidal activity of T. longibrachiatum T6 (T6) was evaluated with a single-factor method and a Plackett-Burman design, and the interaction between different fermentation parameters was investigated by a Box-Behnken design. The variables for enhancing the nematicidal activity of T6 culture filtrates were explored and optimized using response surface methodology (RSM). The Minor Medium (MM) plus wheat bran-2 medium was found to be the most effective fermentation medium for T6 culture filtrates against the second stage juveniles (J2s) of H. avenae. The maximum mortality of the J2s was obtained using the T6 culture filtrates under the following fermentation conditions: initial pH 6, 28°C culture temperature, 180 rpm rotating speed, 60 ml of fermentation media, 7 days of incubation time, and 1 ml of inoculation volumes. Among these parameters, the initial pH, inoculation volume, and incubation day were identified as the most significant parameters and critical independent variables for enhancing the nematicidal activity of the T6 culture filtrates. After further optimizations based on statistical predictions, the highest nematicidal activity (92.42%) was obtained with the T6 culture filtrates fermented under an initial pH of 6.06, an inoculation volume of 1.62 ml, and an incubation time of 7.15 days. The nematicidal activity was increased approximately by as high as 1.07% compared with that before optimization. Bio-control efficacy of T6 culture filtrates was 83.88% at the 70th day after wheat seeds sowing in greenhouse experiments. The results from the validation experiments agreed with the model predictions. Our study has improved the bio-control potential of Trichoderma spp. against the plant-parasitic nematodes H. avenae and provided a cost-efficient bio-resource in the future development of novel bio-control agents.


Child sexual abuse revisited by the U.S. Supreme Court.
In deciding a landmark child sexual abuse case, the U.S. Supreme Court broke new ground in addressing the unique needs and qualities of child witnesses. The Court unanimously decided that the spontaneous statement of an abused child, made outside of a courtroom and while receiving medical treatment because of molestation, is trustworthy and may be allowed as evidence at trial. The Court curtailed the right of a defendant to go face to face against the child accuser, considering that a victimized child's statement, made while he or she is emotionally injured, has substantial value that cannot be duplicated simply by testifying later in court.


Destabilization of junctional ACh receptors by a reinnervating frog motor nerve.
The distribution of ACh receptors (AChRs) in neuromuscular junctions of the frog cutaneous pectoris muscle has been investigated at various times after denervation, as the motor nerve regenerates to reinnervate the junctions. Original extent of synaptic gutter is judged by the distribution of ACh esterase, which is compared with the staining pattern of rhodamine-labelled alpha-bungarotoxin. It is found that within 8-10 days after the beginning of reinnervation, many junctions show loss of AChR from large stretches of original gutter, in contrast to other regions, which still have a high density of receptors. This loss of receptor does not happen if the muscle remains denervated. It is suggested that the innervated portions of the junctions retain AChR, while the receptors in uninnervated portions are destabilized and rapidly lost. These findings indicate a powerful role for the nerve in eliminating both extrajunctional receptors and junctional receptors that are not stabilized by the direct action of an overlying nerve. One can imagine that a similar removal of AChR or other important synaptic molecules from gutters that are innervated later or by a terminal of lower efficacy might account for the competitive elimination of certain inputs and retention of others during development of reinnervation.


[The "aging" of the male genital system: erection].
Between 1/2/89 and 31/1/92 we have studied 300 old patients (the average patient age was 72 years). We used scores of sexual functionality to study the accordances between voluntary and spontaneous erection, the characteristics of the erection per age, the frequency of intercourse per age, the sexual preferences in males and females. Also the partner's extrangement has been valued. These factors together with the socio-economic conditions, in the same body causes represent an important obstacle in the sexuality of the old man.


L1-like non-LTR retrotransposons in the yeast Candida albicans.
Non-LTR retrotransposons (also known as LINEs) have had a major influence on the structure of many eukaryote genomes. They are abundant in many multicellular eukaryotes, including mammals, but appear to be absent from the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. This absence has, to date, precluded the development of a yeast model system for the study of non-LTR retrotransposons. In this report we describe several families of non-LTR retrotransposons from the yeast Candida albicans. These elements, which we call Zorro elements, are all members of the L1 clade of non-LTR retrotransposons. Some are intact, transcriptionally active and have transposed recently. This finding should allow the development of a yeast model system.


[Study on hemodynamic changes and cardiac troponin I level in pig model of acute experimental pulmonary embolism].
To evaluate the hemodynamic effects and cardiac troponin I (cTn I), creatine kinase-MB (CK-MB), myoglobin (Mb) releasing kinetics of acute experimental pulmonary embolism of pigs. Sixteen juvenile pigs, of either gender and weighing 30 to 40 kg were studied, 8 in the embolism group and 8 in the control group. The 8 embolism animals received 0.1 g/kg polystyrene beads (diameter range 0.65 to 0.67 mm) suspended in 0.9% saline by venous injection. Pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), pulmonary capillary wedged pressure (PCWP), cardiac output (CO), blood gases and serum cTn I, CK-MB, and Mb were measured before and immediately, 30 min, 1 hour, 2 hour, and 3 hour after acute pulmonary embolism. PAP was increased to 2 - 3 fold of the baseline and the control level immediately, and then decreased to the baseline level in 2 to 3 hours. Serum cTn I and Mb increased significantly after embolism and remained at a higher level through the 3 hour experimental procedure. The CK-MB was not changed after acute pulmonary embolism. Acute pulmonary embolism caused lung gas exchange abnormality and acute pulmonary hypertension. The hemodynamic effects of acute pulmonary embolism include injury to the myocardial cells and releasing of cTn I and Mb to blood stream. cTn I can be detected in the early phase of acute pulmonary embolism, and maybe a useful marker in diagnosis and management of acute pulmonary embolism.


Photochemical charge separation within aromatic hydrazines and the effect of excited-state intervalence in dihydrazines.
Photolysis into the longest wavelength absorption band of 2-tert-butyl-2,3-diazabicyclo[2.2.2]oct-3-yl hydrazine (Hy) substituted naphthalenes causes aryl group reduction electron transfer to give (+)Hy-Ar(-). Electrooptical absorption measurements characterize the charge separation properties from these bands. Emission studies demonstrate that the separation between absorption and emission maxima for symmetrically disubstituted compounds is smaller than that for monosubstituted compounds, which is attributed to excited-state intervalence. The excited-state diabatic surfaces may be described as a Hy(+)-NA(- )-Hy(0), Hy(0)-NA(-)-Hy(+) pair, for which electronic interaction produces a double minimum that qualitatively resembles that in the ground state of the disubstituted intervalence radical cations.


Inference of Gene Flow in the Process of Speciation: An Efficient Maximum-Likelihood Method for the Isolation-with-Initial-Migration Model.
The isolation-with-migration (IM) model is commonly used to make inferences about gene flow during speciation, using polymorphism data. However, it has been reported that the parameter estimates obtained by fitting the IM model are very sensitive to the model's assumptions-including the assumption of constant gene flow until the present. This article is concerned with the isolation-with-initial-migration (IIM) model, which drops precisely this assumption. In the IIM model, one ancestral population divides into two descendant subpopulations, between which there is an initial period of gene flow and a subsequent period of isolation. We derive a very fast method of fitting an extended version of the IIM model, which also allows for asymmetric gene flow and unequal population sizes. This is a maximum-likelihood method, applicable to data on the number of segregating sites between pairs of DNA sequences from a large number of independent loci. In addition to obtaining parameter estimates, our method can also be used, by means of likelihood-ratio tests, to distinguish between alternative models representing the following divergence scenarios: (a) divergence with potentially asymmetric gene flow until the present, (b) divergence with potentially asymmetric gene flow until some point in the past and in isolation since then, and (c) divergence in complete isolation. We illustrate the procedure on pairs of Drosophila sequences from ∼30,000 loci. The computing time needed to fit the most complex version of the model to this data set is only a couple of minutes. The R code to fit the IIM model can be found in the supplementary files of this article.


Conformational and solvation studies via computer simulation of the novel large scale diastereoselectively synthesized phosphinic MMP inhibitor RXP03 diluted in selected solvents.
Structure-activity relationship studies, regarding the influence of side chains of phosphinic pseudotripeptidic inhibitors on matrix metalloproteinases (MMPs), provided potent and selective inhibitors for this family of structurally and functionally related proteases. Among them, phosphinic pseudopeptide CbzPhepsi[P(O)(OH)CH(2)] phenylpropyl TrpNH(2), known as RXP03, has been extensively used for in vivo and in vitro studies so far. The large quantities of RXP03 required for in vivo studies, as well as the necessity for diastereoisomeric purity, motivated us to further explore and develop an efficient synthetic methodology, which allows separation of the four diastereoisomers of RXP03 based on the astonishing observed differences in solubility of the four isomers in various solvents. This fact prompted us to examine theoretically the conformational differences of these four isomers via computer simulations in the solvents used experimentally. Given the fact that the four examined diastereoisomeric forms of the phosphinic peptides exhibit different behavior in terms of potency and selectivity profiles toward zinc-metalloproteases, this theoretical study provides valuable information on the conformation of phosphinic inhibitors and therefore improves the design and synthesis of active structures. The differences in solubility of RXP03 diastereoisomers in the used solvents were examined in terms of intra- and intermolecular structure. It is found that the different solubility of the RRS and RSS diastereoisomers in EtOH is a result of the different number of hydrogen bonds formed by each isomer with EtOH molecules. In the case of SRS and SSS in Et(2)O, their different solubility might be attributed to the different intramolecular hydrogen bonds formed on these diastereoisomers.


Coupling of human delta-opioid receptor to retinal rod transducin in Chinese hamster ovary cells.
Reverse transcription-polymerase chain reaction was used to identify the pertussis toxin (Ptx)-sensitive G protein alpha-subunit pool in Chinese hamster ovary (CHO) and mouse fibroblast (B82) cells. We detected the presence of mRNA for G(ialpha2), G(ialpha3), and G(oalpha) in both cell lines. G(ialpha1) and G(alphaz) mRNAs were not detected. We also found a homolog of the retinal rod transducin (G(talpha1)) in CHO, and the mouse cone transducin (G(talpha2)) in B82 cells. The presence of the transducin alpha-subunit proteins in CHO and B82 cells was confirmed by immunoprecipitation with specific antibodies. To test the interaction of heterologously expressed receptors with transducin in CHO cells, a Ptx-insensitive (C347S) rod transducin mutant was transfected into a CHO cell line stably expressing the human delta-opioid receptor (hDOR/CHO). (+)-4-[(alphaR)-alpha-((2S,2R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide, a selective delta-opioid receptor agonist, stimulated guanosine-5'-O-(3-[(35)S]thio)triphosphate binding by 293 +/- 36% after Ptx pretreatment in the mutant cell line with an EC(50) value of 54 +/- 32 nM, showing that transducin can functionally couple to the human delta-opioid receptors in these cells.


Surface ligation-based resonance light scattering analysis of methylated genomic DNA on a microarray platform.
DNA methylation is a crucial epigenetic modification and is closely related to tumorigenesis. Herein, a surface ligation-based high throughput method combined with bisulfite treatment is developed for analysis of methylated genomic DNA. In this method, a DNA microarray is employed as a reaction platform, and resonance light scattering (RLS) of nanoparticles is used as the detection principle. The specificity stems from allele-specific ligation of Taq DNA ligase, which is further enhanced by improving the fidelity of Taq DNA ligase in a heterogeneous reaction. Two amplification techniques, rolling circle amplification (RCA) and silver enhancement, are employed after the ligation reaction and a gold nanoparticle (GNP) labeling procedure is used to amplify the signal. As little as 0.01% methylated DNA (i.e. 2 pmol L(-1)) can be distinguished from the cocktail of methylated and unmethylated DNA by the proposed method. More importantly, this method shows good accuracy and sensitivity in profiling the methylation level of genomic DNA of three selected colonic cancer cell lines. This strategy provides a high throughput alternative with reasonable sensitivity and resolution for cancer study and diagnosis.


Public health impact of mass sporting and cultural events in a rising COVID-19 prevalence in England.
A subset of events within the UK Government Events Research Programme (ERP), developed to examine the risk of transmission of COVID-19 from attendance at events, was examined to explore the public health impact of holding mass sporting events. We used contact tracing data routinely collected through telephone interviews and online questionnaires, to describe the potential public health impact of the large sporting and cultural events on potential transmission and incidence of COVID-19. Data from the EURO 2020 matches hosted at Wembley identified very high numbers of individuals who tested positive for COVID-19 and were traced through NHS Test & Trace. This included both individuals who were potentially infectious (3036) and those who acquired their infection during the time of the Final (6376). This is in contrast with the All England Lawn Tennis Championships at Wimbledon, where there were similar number of spectators and venue capacity but there were lower total numbers of potentially infectious cases (299) and potentially acquired cases (582). While the infections associated with the EURO 2020 event may be attributed to a set of socio-cultural circumstances which are unlikely to be replicated for the forthcoming sporting season, other aspects may be important to consider including mitigations for spectators to consider such as face coverings when travelling to and from events, minimising crowding in poorly ventilated indoor spaces such as bars and pubs where people may congregate to watch events, and reducing the risk of aerosol exposure through requesting that individuals avoid shouting and chanting in large groups in enclosed spaces.


Inhibitory effects of levetiracetam on absence seizures in a novel absence-like epilepsy animal model, Groggy rat.
Levetiracetam (LEV) is known to inhibit convulsive seizures and is clinically used for treating both partial and generalized seizures. The study was performed to determine whether LEV possesses an inhibitory effect on absence seizures in a novel genetic animal model of absence epilepsy, Groggy (GRY) rats. Single injections of LEV at doses ranging from 20 to 160 mg/kg i.p. markedly inhibited absence seizures in GRY rats. The anti-absence action of LEV was potent and the cumulative duration of spike and wave discharges (SWD) in GRY rats was almost completely suppressed even at 20 mg/kg (i.p.). When the time-course of the inhibitory action of LEV (80 mg/kg i.p.) was examined up to 24 h after the treatment, the appearance of SWD was suppressed for over 6 h after injection of LEV in contrast to the action of sodium valproate (200 mg/kg i.p.) which had a very short effect (< 2 h). The maximum level of blood concentration of LEV was attained within 2 h after administration, and the drug disappeared from the blood in 24 h with T(¹/₂) of 2.7 h. These results revealed that LEV displays potent and relatively long-lasting inhibitory effects on absence seizures in GRY rats.


Proton pump inhibitor indications in a Brazilian tertiary hospital.
OBJECTIVES To evaluate the frequency of prescription of proton pump inhibitors (PPIs) and their indications in patients hospitalized at the Hospital de Clínicas of the Federal University of Uberlândia (HC-UFU). METHODS This is a quantitative cross-sectional observational study that analyzes data obtained from patient records on prescriptions of PPIs for patients hospitalized at the HC-UFU and from a questionnaire applied to assistant physicians on the indications of the drug in each case and evaluates the indication based on literature data. RESULTS On a pre-determined day, of a total of 462 inpatients, there was a prescription of PPI for 183 (39.3%), with a higher frequency (73.5%) in the Intensive Care Unit (ICU), followed by the infirmaries and the Emergency Room. The assistant physician was located in 116 cases, and the main motivation referred to prescription was prophylaxis of digestive hemorrhage (77%). However, after reviewing medical records, it was noticed that in 50.8% of the cases, the prescription was not supported by the literature. CONCLUSION The frequency of PPI prescriptions for inpatients in the HC-UFU is among the lowest described in the literature, but there are still unnecessary prescriptions. Instruction and awareness of the assisting team can minimize these numbers.


Evolvement of French advanced practice nurses.
The purpose of this review is to chronicle the development of the advanced practice nurse (APN) in France and compare international APN indictors of quality care with French studies. A review of the literature was performed by accessing the MEDLINE, Science Direct, and Cochrane Databases for studies of quality of care by APNs during 1965-2012. The author's participation on a national task force in collaboration with the French Ministry of Health provided additional information. After applying limits of this search, 36 studies fulfilled inclusion and exclusion criteria. In both the French and international APN nursing literature, the most frequently described quality of care measures were level of patient satisfaction and other patient outcomes (clinical and laboratory measures) according to evidence-based guidelines. In three French studies (nephrology, neuro-oncology, and urology settings), nurses performed direct patient care and were legally permitted to take on some limited responsibilities usually held by French physicians, including clinical examinations, diagnosing, and prescribing. Creation of the APN role in France can respond to public health challenges including the rising incidence of chronic diseases and an impending physician shortage. Future APN research should focus on rigorous, innovative design development including collaborative care models.


Examination of bilayer lipid membranes for 'pin-hole' character.
BLM prepared on electrode substrates by supporting or tethering were tested for 'pin-hole' character, comparing data from cyclic voltammetry (CV), surface plasmon resonance (SPR) and rotating disc electrodes (RDE). 1-hexadecylamine tethered BLMs on SAM modified gold electrodes were compared with BLMs assembled on modified polyHEMA or sol-gel layers. BLM formation followed by SPR showed that the initial phase of the assembly was complete in 5-20 minutes and produced layers of thickness >5 nm, compared with the expected final BLM thickness of approximately 3 nm. The CVs of the K(3)[Fe(CN)(6)] couple were significantly suppressed irrespective of the method of BLM assembly, without major differences emerging for the different methods. However, data from the RDE distinguished the 'pin-hole' character of the different preparations. The data were consistent with incomplete initial (<1 h, SPR estimated BLM thickness >5 nm) vesicle fusion leaving 'pin-holes' of approximately 2 microm (HDA-11-mercaptoundecanoic acid (MUA) tethered BLM) to approximately 3 microm (tetraethylorthosilicate sol-gel supported BLM) followed by a slow maturation (>15 h; impedance spectroscopy estimated thickness approximately 3 nm) and lateral spreading and fusion, resulting in loss of 'pin-hole' character (<1 microm). The BLM could be used in conjunction with potentiometric measurement to observe the incorporation of nystatin into the BLM and the rate of incorporation adjusted according to original permeability of the BLM. The 'pin-hole-free' BLM construction with lowest permeability (TEOS supported, 4 x 10(-10) cm s(-1) compared with HDA-MUA, 3 x 10(-9) cm s(-1)) gave a potentiometric signal independent of bulk ion-concentration across 5 decades change in concentration. Formed on an ion-selective electrode, nystatin incorporation could be followed as a change in potential, over >2 h, whereas the TEOS supported BLM with permeability 1 x 10(-9) cm s(-1) shows nystatin incorporation within 1 h. In this instance, addition of ConA reduced the potential to the same value as prior to nystatin incorporation, consistent with nystatin channel closure.


High-grade chondrosarcoma of the larynx: treatment and management.
We present a case of an 88-year-old man with high-grade chondrosarcoma of the larynx. The patient presents with a history worsening dysphonia and dyspnoea treated with antibiotic and corticosteroid therapy as it was a bronchopneumonia. Thanks to fibrolaryngoscopy, radiological imaging and final biopsy with immunohistochemistry, we have done differential diagnosis with the others sarcomas of the larynx. The histological diagnosis and the correct grading are essential for treatment and management of the pathology. The best treatment is primary surgical resection with negative margins. Chemoradiotherapy may provide some benefit if there are margin positive resections or with palliative intent. In our case, we performed only surgery treatment and a close follow-up at 1-3-6 months and after every 6 months. After 18 months from surgery, there are no signs of recurrence of disease.


Fibre-optical microendoscopy.
Microendoscopy has been an essential tool in exploring micro/nano mechanisms in vivo due to high-quality imaging performance, compact size and flexible movement. The investigations into optical fibres, micro-scanners and miniature lens have boosted efficiencies of remote light delivery to sample site and signal collection. Given the light interaction with materials in the fluorescence imaging regime, this paper reviews two classes of compact microendoscopy based on a single fibre: linear optical microendoscopy and nonlinear optical microendoscopy. Due to the fact that fluorescence occurs only in the focal volume, nonlinear optical microendoscopy can provide stronger optical sectioning ability than linear optical microendoscopy, and is a good candidate for deep tissue imaging. Moreover, one-photon excited fluorescence microendoscopy as the linear optical microendoscopy suffers from severe photobleaching owing to the linear dependence of photobleaching rate on excitation laser power. On the contrary, nonlinear optical microendoscopy, including two-photon excited fluorescence microendoscopy and second harmonic generation microendoscopy, has the capability to minimize or avoid the photobleaching effect at a high excitation power and generate high image contrast. The combination of various nonlinear signals gained by the nonlinear optical microendoscopy provides a comprehensive insight into biophenomena in internal organs. Fibre-optical microendoscopy overcomes physical limitations of traditional microscopy and opens up a new path to achieve early cancer diagnosis and microsurgery in a minimally invasive and localized manner.


Dentigerous cyst containing multiple impacted teeth: a rare case report.
The dentigerous cyst is a developmental odontogenic cyst, which apparently develops by accumulation of fluid between reduced enamel epithelium and the tooth crown of an unerupted tooth. It is one of the most prevalent types of odontogenic cysts associated with erupted, developing, or impacted tooth, particularly the mandibular third molars, the other teeth that are commonly affected are maxillary canines. The present case report is unique as it enclosed three permanent maxillary teeth: the central incisor, lateral incisor, and canine that had to be extracted during surgical enucleation of the cyst.


Characteristics of Organellar Genomes and Nuclear Internal Transcribed Spacers in the Tertiary Relict Genus Dipelta and Their Phylogenomic Implications.
Dipelta (Caprifoliaceae) is a Tertiary relict genus endemic to China, comprising three species with horticultural and medicinal values. For the lack of genomic information, interspecific relationships and divergence times in the genus remain unresolved. In the present study, we assembled and characterized the complete plastomes, the partial mitogenomes, and nuclear internal transcribed spacer (ITS) fragments from genome skimming datasets of 14 Dipelta individuals. The plastomes were conserved in genomic structure, gene order, and gene content, but with highly variable repeat sequences. Three genes (rpl23, ycf1, ycf2) were examined with positive selection, and nine divergent hotpot regions (psbL, accD, rpl23, ycf2, ycf3, rbcL-accD, trnI-CAU-ycf2, ndhH-rps15, and rps18 intron) were potentially valuable for DNA barcodes. Contrasted to the variability in plastome sequences, mitogenomes contained 12 protein-coding genes with limited indels and nucleotide substitutions, and no gene was found under positive selection. Genes in organellar genomes tended to have a similar pattern of codon usage bias, with a preference of A/U ending codons. Phylogenetic trees constructed with plastomes, mitogenomes, and ITS sequences consistently supported that Dipelta was monophyletic, and Dipelta elegans was sister to the other two taxa. Interspecific divergences were estimated at about 33-37 Ma in the Eocene/Oligocene boundary, suggesting the paleo-endemism of the extant species as "living fossils" of the East Asian Flora. Our study well-exhibited that genome skimming could provide valuable genomic information to elucidate the evolutionary history of the complex group in a cost-efficient way.


[Molecular and cellular bases of intestinal epithelial cell invasion by Shigella flexneri].
A key step in the pathogenesis of shigellosis is the capacity of the causative bacteria, shigellae, to invade colonic and rectal epithelial cells in humans. This invasive process encompasses several steps: entry into epithelial cells by induction of a macropinocytic event caused by secreted Ipa proteins. the bacterium then escapes from the vacuole and reaches the cytoplasmic compartment in which it divides rapidly and becomes motile via the expression of a surface protein, IcsA, whose polar localization achieves directed polymerization of actin filaments that push the bacterial body forward. Bacteria then engage the inner face of the cellular membrane in the junctional area and form protrusions allowing their passage into the adjacent cell. Lysis of the double membrane eventually allows access to the cytoplasmic compartment of the adjacent cell, thus providing the bacterium with a very efficient mechanism of epithelial colonization.


Pediatric and adolescent sledding-related injuries treated in US emergency departments in 1997-2007.
The objectives were to examine comprehensively the patterns and to estimate the rates of sledding-related injuries among children and adolescents treated in US emergency departments between 1997 and 2007. Through the use of the National Electronic Injury Surveillance System database, cases of sledding-related injuries were selected by using diagnosis codes for sleds. Sample weights were used to calculate national estimates. US Census Bureau data were used to calculate injury rates per 100,000 individuals<or=19 years of age. Computation of odds ratios with 95% confidence intervals was performed. From 1997 through 2007 an estimated 229 023 patients<or=19 years of age were treated for sledding-related injuries in US emergency departments, with an average of 20,820 cases per year. Children 10 to 14 years of age sustained 42.5% of sledding-related injuries, and boys represented 59.8% of all cases. The most frequent injury diagnoses were fractures (26.3%), followed by contusions and abrasions (25.0%). The head was the most commonly injured body part (34.1%), and injuries to the head were twice as likely to occur during collisions as through other mechanisms. Traumatic brain injuries were more likely to occur with snow tubes than with other sled types. A total of 4.1% of all cases required hospitalization. More research on the prevention of sledding-related injuries is warranted, particularly regarding the impact of helmets in reducing injury rates. The use of sledding products that may reduce visibility (such as snow tubes) should be discouraged.


Galvanizing medical students in the administration of influenza vaccines: the Stanford Flu Crew.
Many national organizations call for medical students to receive more public health education in medical school. Nonetheless, limited evidence exists about successful servicelearning programs that administer preventive health services in nonclinical settings. The Flu Crew program, started in 2001 at the Stanford University School of Medicine, provides preclinical medical students with opportunities to administer influenza immunizations in the local community. Medical students consider Flu Crew to be an important part of their medical education that cannot be learned in the classroom. Through delivering vaccines to where people live, eat, work, and pray, Flu Crew teaches medical students about patient care, preventive medicine, and population health needs. Additionally, Flu Crew allows students to work with several partners in the community in order to understand how various stakeholders improve the delivery of population health services. Flu Crew teaches students how to address common vaccination myths and provides insights into implementing public health interventions. This article describes the Stanford Flu Crew curriculum, outlines the planning needed to organize immunization events, shares findings from medical students' attitudes about population health, highlights the program's outcomes, and summarizes the lessons learned. This article suggests that Flu Crew is an example of one viable service-learning modality that supports influenza vaccinations in nonclinical settings while simultaneously benefiting future clinicians.


Multimerin-1 and cancer: a review.
Multimerin-1 (MMRN1) is a platelet protein with a role in haemostasis and coagulation. It is also present in endothelial cells (ECs) and the extracellular matrix (ECM), where it may be involved in cell adhesion, but its molecular functions and protein-protein interactions in these cellular locations have not been studied in detail yet. In recent years, MMRN1 has been identified as a differentially expressed gene (DEG) in various cancers and it has been proposed as a possible cancer biomarker. Some evidence suggest that MMRN1 expression is regulated by methylation, protein interactions, and non-coding RNAs (ncRNAs) in different cancers. This raises the questions if a functional role of MMRN1 is being targeted during cancer development, and if MMRN1's differential expression pattern correlates with cancer progression. As a result, it is timely to review the current state of what is known about MMRN1 to help inform future research into MMRN1's molecular mechanisms in cancer.


Is depression severity the sole cause of psychotic symptoms during an episode of unipolar major depression? A study both between and within subjects.
Despite the common clinical assumption that psychosis is an indicator of severity in depression, it is not known what determines the presence of psychotic features in major depression. Our aim was to answer the question: Is depression severity the sole cause of psychotic symptoms during an episode of unipolar major depression? In a sample of 585 patients from the UK, meeting criteria for both DSM-IV and ICD-10 major recurrent depression, we assessed measures of severity of depression and the presence of psychotic features, both within and between subjects. Within patients, psychotic episodes tended to be more severe than non-psychotic episodes. However, between patients there was wide variation in severity in both those that did, and did not, experience psychotic episodes. We used retrospective interview information together with case note data. Our cases may not be typical of usual case loads because they were selected to avoid family history of bipolar illness or schizophrenia. Individuals with a predisposition to psychotic features tend to display such features during more severe episodes of depression. However, patients with no history of psychosis may experience non-psychotic depressive episodes of equal or greater severity, in terms of depressive symptomatology, compared to patients with psychotic depression. Thus, there is individual variation in susceptibility to psychosis during mood episodes and severity is not the sole determinant.


Drosophila as a developmental paradigm of regressive brain evolution: proof of principle in the visual system.
Evolutionary developmental biology focuses heavily on the constructive evolution of body plan components, but there are many instances such as parasitism, cave adaptation, or postembryonic growth rate optimization where evolutionary regression is of adaptive value. This is particularly true in the nervous system because of its massive energy costs. However, comparatively little effort has thus far been made to understand the evolutionary developmental trajectories of adaptive nervous system reduction. This review focuses on the organization and evolution of the Drosophila larval brain, which represents an exceptional example of miniaturization, most dramatically in the visual system. It is specifically discussed how the dependency of outer optic lobe development on retinal innervation can be assumed to have facilitated a first evolutionary phase of larval visual system reduction. Afferent input-contingent development of neu- ral compartments very likely plays a widespread role in adaptive brain evolution. Understanding the complete deconstruction of the larval optic neuropiles in Drosophila awaits expanded comparative analysis but has the promise to inform about further developmental trajectories and mechanisms underlying regressive evolution of the brain.


[The epidemiology and cost of AIDS in France].
Throughout the world the AIDS epidemic continues and even seems to accelerate in regions previously thought to be untouched. The number of cases has increased by 60% in one year. With its 15,000 seropositive persons and 35,000 cases of declared AIDS, France is the most affected of all European countries. Sexual contamination remains predominant with a relative increase of heterosexual transmissions. However, particularly in the South, transmission is prevalent in intra-venous drug addicts. In all cases worldwide it is the socially deprived, marginal and fragile populations which are the most vulnerable. Various previsions are possible in France, depending on the prophylactic measures applied. In any event, the number of seropositive subjects should be levelling out at the end of this decade, and the prevalence of the disease should stabilized at between 15,000 to 20,000 patients. At present, the cost of AIDS exceeds 5.5 billion francs.


Chlorpyrifos and lambda cyhalothrin-induced oxidative stress in human erythrocytes.
Pesticides are one of the most potentially harmful chemicals introduced into the environment, and their adverse impacts on non-target organisms can be significant. The present study was conducted to shed light on effects of locally used insecticides chlorpyrifos (CPF) and lambda cyhalothrin (LCT) on oxidative stress biomarkers in human erythrocytes. The activity of catalase (CAT), superoxide dismutase (SOD), and protein contents as well as the levels of malondialdehyde (MDA) and osmotic fragility (OF) were measured in human erythrocytes exposed to CPF at concentrations of 0, 100, 500, 1000, and 2000 ppm and LCT at concentrations of 0, 100, 300, 600, and 800 ppm for 1 h and 3 h at 37°C. MDA levels and OF of erythrocytes were significantly higher in erythrocytes incubated with CPF and LCT at increasing concentrations of both insecticides and increased incubation time. However, erythrocyte CAT and SOD activities were decreased at all concentrations of CPF and LCT tested. Protein oxidation products were decreased at lower doses of CPF (100 and 500 ppm); at higher doses (1000 and 2000 ppm), total protein content was increased compared with control. In contrast LCT was associated with decreased in protein contents at all the concentrations. These results clearly demonstrated that CPF and LCT can induce oxidative stress in human erythrocytes ( in vitro).


Strong hyaluronan expression in the full-thickness rat articular cartilage repair tissue.
Articular cartilage lesions have a poor capacity to regenerate. In full-depth articular cartilage defects, the repair process involves an ingrowth of mesenchymal cells from the bone marrow to the injured area, and these cells attempt to restore the lesion with cartilage-like repair tissue. In this study, we investigated histologically the distribution of hyaluronan in the rat repair tissue in relation to other glycosaminoglycans. Full-depth lesions were drilled to the weight-bearing region of rat medical femoral condyle. The rats were divided into two groups: intermittent active motion (IAM) and running training (RT) groups. In the RT group, programmed exercise was started 1 week after surgery, while the rats in the IAM group could move freely in their cages. The lesions were investigated 4 and 8 weeks after the surgery. Semiquantitative histological grading showed no significant differences in the repair between the groups. In normal articular cartilage, hyaluronan was stained mainly around chondrocytes. During repair, strong hyaluronan staining was observed in loose mesenchymal tissue, while in the repair area undergoing endochondral ossification, hyaluronan was intensively stained mainly around the hypertrophic chondrocytes. Remarkably strong staining for hyaluronan was noticed in areas of apparent mesenchymal progenitor cell invasion, the areas being simultaneously devoid of staining for keratan sulphate. In conclusion, hyaluronan is strongly expressed in the early cartilage repair tissue, and its staining intensity and distribution shows very sensitively abnormal articular cartilage structure.


Magnetic resonance imaging of retroperitoneal lymph node metastases of non-seminomatous germ cell tumours of the testis.
The value of Magnetic Resonance Imaging (MRI) in the diagnosis, staging and treatment evaluation of retroperitoneal lymph node metastases of non-seminomatous germ cell tumours of the testis (NSGCT) was prospectively studied in 41 consecutive patients before, during and after cisplatin-based chemotherapy. MRI is a non-invasive method, with results equivalent to laparotomy in determining the anatomical localization and size of retroperitoneal lymph node metastases of non-seminomatous germ cell tumours of the testis and residual mass after chemotherapy. Components responding differently can be observed with MRI within the retroperitoneal lymph node metastases on the basis of the tumour signal intensity or homogeneity in the T1- and T2-weighted images; MRI cannot warrant any conclusion about viability of the residual mass or other effects of chemotherapy.


Legalism, countertransference, and clinical moral perception.
This target article focuses on dynamics that arise in three typical ethically complex cases in which psychiatric consultations are requested by physicians: a dying patient refuses life-prolonging treatment, an uncooperative patient demands to be allowed to go outside and smoke, and an angry patient demands to be admitted to the hospital. The discussion canvasses what is at stake morally and clinically in each of these cases and explores clinician-patient interactions, dynamics in relationships between consulting physicians and consultant psychiatrists, patient transference, and physician countertransference. The article defines legalism and countertransference and argues that an ethically and clinically important consequence of these phenomena for patients is distortion of clinicians' perceptions of patients' decisions and vulnerabilities. The discussion also describes how legalism and countertransference adversely affect how clinicians treat their psychiatrist colleagues. Finally, the article suggests how the effects of legalism and countertransference can be mitigated.


Confusing confusability: on the problems of using psychophysical measures of letter confusability in neuropsychological research.
The effect of letter confusability on reading has received increasing attention over the last decade. Confusability scores for individual letters, derived from older psychophysical studies, have been used to calculate summed confusability scores for whole words, and effects of this variable on normal and alexic reading have been reported. On this basis, letter confusability is now increasingly controlled for in stimulus selection. In this commentary, we try to clarify what letter confusability scores represent and discuss several problems with the way this variable has been treated in neuropsychological research. We conclude that it is premature to control for this variable when selecting stimuli in studies of reading and alexia. Although letter confusability may play a role in (impaired) reading, it remains to be determined how this measure should be calculated, and what effect it may have on word and letter identification.


Manipulation of Valley Pseudospin by Selective Spin Injection in Chiral Two-Dimensional Perovskite/Monolayer Transition Metal Dichalcogenide Heterostructures.
Monolayer two-dimensional (2D) transition metal dichalcogenides (TMDs) have attracted great interest in spintronics and valleytronics due to the spin-valley locking effect. To efficiently control and manipulate the valley pseudospin is of paramount importance for valley-based electronics and optoelectronics. A variety of strategies have been developed to address the valley pseudospin including optical, electrical, and magnetic methods; nonetheless, they involve either below liquid-nitrogen temperature or an external magnetic field, which increases the cost and complexity of the devices. Here, we report a straightforward way to manipulate valley polarization in monolayer TMDs via selective spin injection in chiral 2D perovskite/monolayer TMD (e.g., MoS2 and WSe2) van der Waals heterostructures without requiring an external magnetic field or specially designed device structures. We show the dangling-bond-free vdW interface can allow an impressive average spin injection efficiency of 78% to produce persistent valley polarization in monolayer MoS2 (WSe2) over 10% from liquid-nitrogen temperature to above 200 K. We attribute the valley polarization of monolayer MoS2 (WSe2) to selective spin injection from chiral 2D perovskites, which can effectively introduce population imbalance between valleys in monolayer MoS2 (WSe2). Our findings provide an alternative strategy to manipulate the valley polarization in TMDs without requiring circularly polarized light excitation, below liquid-nitrogen temperature, or external magnetic field, and thus would promote the development of perovskite-based spintronic and valleytronic devices.


Relationship between 22Na distribution and cerebral blood flow in ischemic gerbil brain.
Sodium transport in the early postischemic period was studied using Mongolian gerbils with right common carotid artery ligation. [22Na]sodium chloride ([22Na]NaCl) was infused immediately after, 10 minutes before, and 4 hours before carotid ligation, and the 22Na distribution was measured in symptomatic animals by autoradiography 1 hour after ischemia. Regional cerebral blood flow was determined by [14C]iodoantipyrine autoradiography. The specific gravity of the brain was measured in symptomatic gerbils 1 and 2 hours after carotid ligation by a gradient column. There was a low uptake of 22Na in the ischemic core and a high uptake in the ischemic periphery when the tracer was given 10 minutes before or immediately after ischemia. In contrast, tracer given 4 hours before ischemia showed an increased radioactivity in both the ischemic core and periphery. It is suggested that increased sodium in the ischemic core is due to a decreased sodium clearance rate and increased sodium in the ischemic periphery is due to some active transport process.


Osteolysis in failed total knee arthroplasty: a comparison of mobile-bearing and fixed-bearing knees.
Osteolysis is an important complication associated with total knee arthroplasty. The purpose of this study was to compare the prevalence of osteolysis after failed total knee arthroplasty with a mobile-bearing prosthesis and after failed arthroplasty with a fixed-bearing prosthesis. Eighty revision total knee arthroplasties performed between 1995 and 1998 were included in this study. All had radiographic evidence of advanced polyethylene wear. The mobile-bearing group consisted of thirty-four knees with a Low Contact Stress implant, and the fixed-bearing group included forty-six knees. The average time (and standard deviation) from the primary operation to the revision was 102.8 +/- 26.5 months in the mobile-bearing group and 96.0 +/- 30.1 months in the fixed-bearing group. The prerevision radiographs and operative findings were reviewed. The prevalence of osteolysis was significantly higher in the mobile-bearing group (47%; sixteen of thirty-four knees) than in the fixed-bearing group (13%; six of forty-six knees) (p = 0.003). The distal part of the femur was involved in thirteen knees in the mobile-bearing group and in four knees in the fixed-bearing group. Seventeen knees had osteolysis in the posterior aspect of the femoral condyle, which was the most common site of osteolysis; however, twelve of them had no evidence of osteolysis on prerevision radiographs. The prevalence of osteolysis was higher in the knees with a mobile-bearing prosthesis than in those with a fixed-bearing prosthesis. The osteolysis was predominantly on the femoral side, adjacent to the posterior aspect of the condyle. Radiographic evaluation of osteolysis in the distal part of the femur may not be reliable and usually leads to an underestimation of the degree of osteolysis.


Localized Degradation of Neutrophil Extracellular Traps by Photoregulated Enzyme Delivery for Cancer Immunotherapy and Metastasis Suppression.
Extrusion of neutrophil extracellular traps (NETs), a fundamental host innate immune defense against pathogens, has recently been linked to cancer resistance to immunotherapy and distant metastasis. These findings highlight interesting areas of cancer-elicited inflammation and potential therapeutic strategies. Disrupting existing NETs with DNase I has been proved to enhance the therapeutic efficacy of tumor immunotherapy and attenuate metastatic spread. However, systemic biodistribution of DNase I raises safety issues, potentially impairing host defense against infection. Hence, tumor-specific delivery and metastatic niche-targeted effects are attractive options for localized degradation of NETs. We have engineered a nanoplatform with a plasmonic gold blackbody (AuPB) core with broad-spectrum photo activity and a mesoporous polydopamine (mPDA) shell for efficient loading and photoregulated release of DNase I. The on-demand released DNase I triggered by the second near-infrared (NIR-II) light irradiation breaks the "NET-mediated physical barrier", thereby increasing the contact of immune cytotoxic cells with tumor cells in living mice and sensitizing immune checkpoint therapy of primary colorectal cancer (CRC). Moreover, the deposition and light-controlled cargo release from systemically delivered AuPB@mPDA carriers in liver, the most frequent site of CRC metastasis, abolished NET-mediated capture of circulating tumor cells and hence metastatic seeding. Our findings indicate that the localized, light-regulated release of DNase I by photoactive carriers in the NIR-II window represent a translational route for immune-mediated tumor regression and metastasis inhibition.


Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?
Aluminium (Al) toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps) whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water. HD patients only treated with Reverse Osmosis(RO) treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies. 39 patients (34 anuric) were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration) and the total amount of Al ingested.No patients had unexplained EPO resistance or biochemical evidence of adynamic bone. Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R² = 0.07) and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.


Enhancing the Faraday rotation of monolayer black phosphorus by the optical Tamm state at the photonic crystal interface.
Black phosphorus (BP) is a two-dimensional material with a direct bandgap that exhibits in-plane anisotropy, high charge carrier mobility, and excellent optical properties. It also can demonstrate a strong magneto-optical response under an external magnetic field. In this paper, we present a theoretical study to enhance the Faraday rotation of the monolayer BP by the optical Tamm state at the interface between two photonic crystals. The optical Tamm state can increase the Faraday rotation angle significantly through the localization of the electromagnetic field with high transmittance. When the externally applied magnetic field is 5 T, the gain in the Faraday rotation angle can reach 37.37 dB with a transmittance greater than 65%. The Faraday rotation angle can be adjusted proportionally by the external magnetic field while retaining the high transmittance, and the operating frequency also remains unchanged. In addition, the Faraday rotation angle and operating frequency can be adjusted by changing the carrier density and photonic crystal parameters.