Probiotic OMNi-BiOTiC® 10 AAD Reduces Cyclophosphamide-Induced Inflammation and Adipose Tissue Wasting in Mice.
Cancer therapy is often associated with severe side effects such as drug induced weight loss, also known as chemotherapy-induced cachexia. The aim of this study was to investigate the effects of a multispecies probiotic (OMNi-BiOTiC® 10 AAD) in a chemotherapy mouse model. A total of 24 male BALB/c mice were gavage-fed with the probiotic formulation or water, once a day for 3 weeks. In the third week, the mice received intraperitoneal cyclophosphamide. At euthanasia, the organs were dissected, and serum was sampled for cytokine analysis. Tight junction components, myosin light chain kinase, mucins, and apoptosis markers were detected in the ileum and colon using histological analyses and qRT-PCR. Lipolysis was analyzed by enzymatic activity assay, Western blotting analyses, and qRT-PCR in WAT. The fecal microbiome was measured with 16S-rRNA gene sequencing from stool samples, and fecal volatile organic compounds analysis was performed using gas chromatography/mass spectrometry. The probiotic-fed mice exhibited significantly less body weight loss and adipose tissue wasting associated with a reduced CGI58 mediated lipolysis. They showed significantly fewer pro-inflammatory cytokines and lower gut permeability compared to animals fed without the probiotic. The colons of the probiotic-fed animals showed lower inflammation scores and less goblet cell loss. qRT-PCR revealed no differences in regards to tight junction components, mucins, or apoptosis markers. No differences in microbiome alpha diversity, but differences in beta diversity, were observed between the treatment groups. Taxonomic analysis showed that the probiotic group had a lower relative abundance of Odoribacter and Ruminococcus-UCG014 and a higher abundance of Desulfovibrio. VOC analysis yielded no significant differences. The results of this study indicate that oral administration of the multispecies probiotic OMNi-BiOTiC® 10 AAD could mitigate cyclophosphamide-induced chemotherapy side effects.


Characterization of Sarcocystis falcatula isolates from the Argentinian opossum, Didelphis albiventris.
Two isolates of Sarcocystis falcatula were obtained from the lungs of budgerigars (Melopsittacus undulatus) fed sporocysts from two naturally-infected South American opossums (Didelphis albiventris). The two isolates were designated SF-1A and SF-2A. Both isolates induced fatal infections in budgerigars. Both isolates underwent schizogony in African green monkey kidney cells. The structure of schizonts in the lungs of budgerigars was more variable than that observed in cell culture. The two isolates were identified as S. falcatula by the two species-specific Hinf 1 restriction fragments dervied from digestion of a PCR amplification using primers JNB33/JNB54. Thus, the South American opossum, D. albiventris, is a definitive host for S. falcatula.


Comparison of different intraocular pressure measurement techniques in normal eyes and post small incision lenticule extraction.
The purpose of the study was to determine the accuracy of intraocular pressure (IOP) measurement after small incision lenticule extraction (SMILE) using Goldmann applanation tonometry (GAT) and ocular response analyzer (ORA). This is a prospective clinical study that was conducted on 30 eyes in the interval between February 2016 and September 2016. The age of the patients ranged between 19 and 40 years. The patients underwent SMILE surgery using the femto laser. IOP was measured preoperatively and 1 month postoperatively by both techniques, the GAT and the ORA. GAT recorded lower values than ORA values (IOPcc) preoperatively and postoperatively and the difference was statistically significant. Both GAT and ORA IOP measurements decreased after SMILE. There was no statistically significant correlation between the changes in the GAT and ORA readings and the postoperative corneal pachymetry or the lenticule thickness. Both corneal hysteresis and corneal resistance factor showed significant decline after the procedure, which correlated with the lenticule thickness. SMILE causes significant reduction in IOP measurement by ORA and GAT. Corneal biomechanics decreases following SMILE and this correlates with lenticule thickness.


Collective Migrations of Drosophila Embryonic Trunk and Caudal Mesoderm-Derived Muscle Precursor Cells.
Mesoderm migration in the Drosophila embryo is a highly conserved, complex process that is required for the formation of specialized tissues and organs, including the somatic and visceral musculature. In this FlyBook chapter, we will compare and contrast the specification and migration of cells originating from the trunk and caudal mesoderm. Both cell types engage in collective migrations that enable cells to achieve new positions within developing embryos and form distinct tissues. To start, we will discuss specification and early morphogenetic movements of the presumptive mesoderm, then focus on the coordinate movements of the two subtypes trunk mesoderm and caudal visceral mesoderm, ending with a comparison of these processes including general insights gained through study.


Plasma glucose concentration determines direct versus indirect liver glycogen synthesis.
In the present study hepatic glycogenesis by the direct versus indirect pathway was determined as a function of the glucose infusion rate. Glycogen synthesis was examined in catheterized conscious rats that had been fasted 48 h before receiving a 3-h infusion (iv) of glucose. Glucose, containing tracer quantities of [U-14C]- and [6-3H]glucose, was infused at rates ranging from 0 to 230 mumol X min-1 X kg-1. Plasma concentrations of glucose, lactate, and insulin were positively correlated with the glucose infusion rate. Despite large changes in plasma glucose, lactate, and insulin concentrations, the rate of hepatic glycogen deposition (0.46 +/- 0.03 mumol X min-1 X g-1) did not vary significantly between glucose infusion rates of 20 and 230 mumol X min-1 X kg-1. However, the percent contribution of the direct pathway to glycogen repletion gradually increased from 13 +/- 2 to 74 +/- 4% in the lowest to the highest glucose infusion rates, with prevailing plasma glucose concentrations from 9.4 +/- 0.5 to 21.5 +/- 2.1 mM. Endogenous glucose production was depressed (by up to 40%), but not abolished by the glucose infusions. Only a small fraction (7-14%) of the infused glucose load was incorporated into liver glycogen via the direct pathway irrespective of the glucose infusion rate. Our data indicate that the relative contribution of the direct and indirect pathways of hepatic glycogen synthesis are dependent on the glucose load or plasma glucose concentration and emphasize the predominance of the indirect pathway of glycogenesis at plasma glucose concentrations normally observed after feeding.


Deploying and using volunteer health practitioners in response to emergencies: proposed uniform state legislation provides liability protections and workers' compensation coverage.
To respond effectively to natural disasters and other public health emergencies, government resources must be augmented with the resources of volunteer organizations. Governmental actors are prepared to utilize volunteer health practitioners (VHPs) to meet patient surge capacity and provide essential public health services. However, difficult legal challenges arise regarding licensure, the scope of practice of volunteers, the relationship of volunteers to local healthcare delivery systems, disciplinary enforcement, the extent of exposure to civil liability, and how to provide compensation for volunteers injured or killed during disaster response activities. The Uniform Emergency Volunteer Health Practitioner Act (UEVHPA) seeks to address these problems and provide a better legal environment that facilitates VHPs efforts. This article discusses two important provisions of the UEVHPA, Section 11 which provides immunity against claims for negligence, under certain circumstances, for volunteers and organizations engaged in the deployment and use of volunteers, and Section 12 which provides workers' compensation benefits to VHPs when other sources of coverage are not available. Disaster relief organizations and healthcare provider organizations have consistently identified uncertainty and a lack of uniformity with respect to these issues as a major source of concern to volunteer practitioners and as a potential deterrent to their effective recruitment and utilization. Uniform state enactment of the UEVHPA would resolve many inconsistencies and gaps in the regulation and protection of VHPs across states.


Approach to therapy of diffuse large B-cell lymphoma in the elderly: the International Society of Geriatric Oncology (SIOG) expert position commentary.
Diffuse large B-cell lymphoma (DLBCL) is a treatable and potentially curable malignancy that is increasing in prevalence in the elderly. Until recently, older patients with this malignancy were under-represented on clinical treatment trials, so optimal therapeutic approaches for these patients were generally extrapolated from the treatment of younger patients with this disorder. Because of heightened toxicity concerns, older patients were sometimes given reduced dose therapy, potentially negatively impacting outcome. Geriatric considerations including functional status and comorbidities often were not accounted for in treatment decisions. Because of these issues as well as the lack of treatment guidelines for the elderly population, the International Society of Geriatric Oncology convened an expert panel to review DLBCL treatment in the elderly and develop consensus guidelines for therapeutic approaches in this patient population. The following treatment guidelines address initial DLBCL therapy, in both limited and advanced stage disease, as well as approaches to the relapsed and refractory patient.


Discovery of gorilla MHC-C expressing C1 ligand for KIR.
In comparison to humans and chimpanzees, gorillas show low diversity at MHC class I genes (Gogo), as reflected by an overall reduced level of allelic variation as well as the absence of a functionally important sequence motif that interacts with killer cell immunoglobulin-like receptors (KIR). Here, we use recently generated large-scale genomic sequence data for a reassessment of allelic diversity at Gogo-C, the gorilla orthologue of HLA-C. Through the combination of long-range amplifications and long-read sequencing technology, we obtained, among the 35 gorillas reanalyzed, three novel full-length genomic sequences including a coding region sequence that has not been previously described. The newly identified Gogo-C*03:01 allele has a divergent recombinant structure that sets it apart from other Gogo-C alleles. Domain-by-domain phylogenetic analysis shows that Gogo-C*03:01 has segments in common with Gogo-B*07, the additional B-like gene that is present on some gorilla MHC haplotypes. Identified in ~ 50% of the gorillas analyzed, the Gogo-C*03:01 allele exclusively encodes the C1 epitope among Gogo-C allotypes, indicating its important function in controlling natural killer cell (NK cell) responses via KIR. We further explored the hypothesis whether gorillas experienced a selective sweep which may have resulted in a general reduction of the gorilla MHC class I repertoire. Our results provide little support for a selective sweep but rather suggest that the overall low Gogo class I diversity can be best explained by drastic demographic changes gorillas experienced in the ancient and recent past.


Integrated miRNA and mRNA expression profiling of tension force-induced bone formation in periodontal ligament cells.
Tension force-induced bone formation is a complex biological process altered by various factors, for example miRNAs and gene regulatory network. However, we know little about critical gene regulators and their functional consequences on this complex process. The aim of this study was to determine the integrated relation between microRNA and mRNA expression in tension force-induced bone formation in periodontal ligament cells by a system biological approach. We identified 818 mRNAs and 32 miRNAs differentially expressed between cyclic tension force-stimulated human periodontal ligament cells and control cells by microarrays. By using miRNA/mRNA network analysis, protein-protein interactions network analysis, and hub analysis, we found that miR-195-5p, miR-424-5p, miR-1297, miR-3607-5p, miR-145-5p, miR-4328, and miR-224-5p were core microRNAs of tension force-induced bone formation. WDR33, HSPH1, ERBB3, RIF1, IKBKB, CREB1, FGF2, and PAG1 were identified as hubs of the PPI network, suggesting the biological significance in this process. The miRNA expression was further examined in human PDLC and animal samples by using quantitative real-time PCR. Thus, we proposed a model of tension force-induced bone formation which is co-regulated through integration of the miRNA and mRNA. This study illustrated the benefits of system biological approaches in the analysis of tension force-induced bone formation as a complex biological process. We used public information and our experimental data to do comprehensive analysis and revealed the coordination transcriptional control of miRNAs of tension force-induced bone formation.


The Neuroprotective Effects of Cannabis-Derived Phytocannabinoids and Resveratrol in Parkinson's Disease: A Systematic Literature Review of Pre-Clinical Studies.
Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson's disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed, and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.


Graphene-In2Se3 van der Waals Heterojunction Neuristor for Optical In-Memory Bimodal Operation.
Functional diversification at the single-device level has become essential for emerging optical neural network (ONN) development. Stable ferroelectricity harnessed with strong light sensitivity in α-In2Se3 holds great potential for developing ultrathin neuromorphic devices. Herein, we demonstrated an all-2D van der Waals heterostructure-based programmable synaptic field effect transistor (FET) utilizing a ferroelectric α-In2Se3 nanosheet and monolayer graphene. The devices exhibited reconfigurable, multilevel nonvolatile memory (NVM) states, which can be successively modulated by multiple dual-mode (optical and electrical) stimuli and thereby used to realize energy-efficient, heterosynaptic functionalities in a biorealistic fashion. Furthermore, under light illumination, the prototypical device can toggle between volatile (photodetector) and nonvolatile optical random-access memory (ORAM) logic operation, depending upon the ferroelectric-dipole induced band adjustment. Finally, plasticity modulation from short-term to prominent long-term characteristics over a wide dynamic range was demonstrated. The inherent operation mechanism owing to the switchable polarization-induced electronic band alignment and bidirectional barrier height modulation at the heterointerface was revealed by conjugated electronic transport and Kelvin-probe force microscopy (KPFM) measurements. Overall, robust (opto)electronic weight controllability for integrated in-sensor and in-memory logic processors and multibit ORAM systems was readily accomplished by the synergistic ferrophotonic heterostructure properties. Our presented results facilitate the technological implementation of versatile all-2D heterosynapses for next-generation perception, optoelectronic logic systems, and Internet-of-Things (IoT) entities.


Deinhibition of cardiac Na+-K+-ATPase after exposure to exogenous phospholipase A2.
After 2 h of exogenous phospholipase A2 (PLA2) exposure, membrane phospholipid decreased from 3.22 +/- 0.31 to 1.06 +/- 0.13 mumol/mg (33% of control). All classes of phospholipid, except sphingomyelin, were hydrolyzed, whereas total cholesterol content was unaffected. Increases in nonesterified fatty acids (NEFA) were reflected primarily in oleic (18:1), linoleic (18:2), and arachidonic (20:4). Na+-K+-adenosinetriphosphatase (ATPase) activity was inhibited to 29% of control by 2 h of PLA2 treatment, and this inhibition was reversed (albeit, not completely after 5 min of PLA2 treatment) by removal of the hydrolysis products with 0.1% bovine serum albumin (BSA). In contrast, the apparent binding capacity for [3H]ouabain was not affected by PLA2 treatment. Unmasking of latent [3H]ouabain binding by alamethicin was utilized to estimate changes in the proportion of sealed vesicles present before and after PLA2 treatment. PLA2 treatment resulted in a time-dependent loss of sealed vesicles that paralleled the time course of phospholipid hydrolysis and was not reversed by washing with BSA. These studies demonstrate that cardiac Na+-K+-ATPase activity is inhibited by accumulation of endogenously produced lysophospholipids and NEFA. In contrast, loss of vesicle integrity may result from both accumulation of endogenously produced hydrolysis products and membrane phospholipid depletion.


Ochratoxin A reduces NMDA receptor subunits 2A and 2B concentrations in rat hippocampus: partial protective effect of melatonin.
Ochratoxin A (OTA) is a mycotoxin produced by several fungi. Many foods can be contaminated by OTA, which is consequently found in the blood of humans and animals. It is known that OTA accumulates in the brain. The aim of this study was to investigate the effects of OTA on the brain. For this purpose, the effect of OTA on N-methyl-D-aspartate (NMDA) receptor subunits 2A (NR2A) and 2B (NR2B) in the hippocampus and the protective effect of melatonin were investigated. Three groups of eight rats were used: controls, OTA-treated rats (OTA dose 289 microg/kg per day) and OTA+melatonin-treated rats (melatonin dose 10 mg/kg per day). After four weeks of treatment, electrophoretic examinations were performed using SDS-polyacrylamide gel electrophoresis and Western blotting of hippocampal homogenates of the different groups. The concentrations of NR2A and NR2B in the OTA group were significantly lower than in the control group. The concentration of NR2B was significantly increased when melatonin was co-administered with OTA compared with OTA only. There was also a significant increase in NR2A levels when melatonin was co-administered with OTA. As a result, subchronic administration of OTA reduced hippocampal NMDA receptor subunits 2A and 2B concentrations in rats. It was thought that this alteration might affect cognitive functions because hippocampal NMDA receptors are involved in the memory and learning processes. Melatonin exhibited a partially protective effect on NR2A and NR2B against OTA.


Factors influencing the outcome of idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy.
Idiopathic sudden sensorineural hearing loss (ISSNHL) is an otologic emergency with an incidence of about 5-20 per 100,000 of the population per year. There is no universally accepted standard protocol for the treatment of patients with ISSNHL. Hyperbaric oxygen therapy (HBOT), was first reported to improve the outcome following acute inner ear disorders during the late 1960s by both French and German authors. The increase in perilymph oxygenation produced by HBOT provides logical basis for the use of this treatment modality in ISSNHL. We reviewed the records of 97 cases that received HBOT for SSNHL to identify the factors that may affect the treatment outcomes. The effects of age, gender, affected ear, status of the contralateral ear, symptoms associated with hearing loss, presence of a cardiovascular disease, dyslipidemia, history of diabetes mellitus, seasonal factor, smoking, degree of hearing loss, audiogram type, medical treatments provided prior to HBOT, onset time, and number of HBOT sessions were evaluated. The mean hearing gain in all cases after the HBOT was 29.5 dB. The gains were statistically significant in the following cases: early onset of HBOT (p = 0.016), higher number of HBOT sessions (p < 0.01), steroid usage (p = 0.009), low frequency-ascending and total audiogram configuration (p < 0.01) and profound hearing loss (p = 0.011). The success rate was significantly lower in cases with high frequency-descending audiogram configuration (p < 0.001). The most important factor affected the prognosis favorably was found as steroid therapy. This retrospective study and our clinical experience suggest that HBOT has beneficial effects when administered in the early phase of the disease together with steroids. HBOT is a safe practice when used properly by an experienced hyperbaric team. In the treatment of ISSNHL, 20 sessions of HBOT at 2.5 ATA can be tolerated well besides some minor side effects. HBOT should be considered for the cases especially with total or profound hearing loss.


Properties of the pH-sensitive site that controls the lambda max of Limulus metarhodopsin.
A pH-sensitive site controls the lambda max of Limulus metarhodopsin. The properties of this site were examined using intracellular recordings of the early receptor potential (ERP) as a pigment assay. ERPs recorded over a range of extracellular pHs indicate that the apparent pK of the site is in the range of 8.3-8.6. Several lines of evidence indicate that the site responds directly to changes in extracellular pH (pHo) rather than to changes in intracellular pH(pHi) that follow as a secondary result of changing pHo : (a) the effect of changing pHo was rapid (less than 60 s); (b) when pHo was raised, the simultaneous rise in pHi, as measured with phenol red, was relatively small; (c) raising pHi by intracellular injection of pH 10 glycine buffer did not affect the site; and (d) the effect of changing pH0 could not be blocked by increasing the intracellular pH buffering capacity. It is concluded that the pH-sensitive site on metarhodopsin is on the extracellular surface of the plasma membrane.


The risk of gastric cancer according to changes in smoking status among Korean men.
Smoking is a risk factor for gastric cancer. Studies have shown that the risk of gastric cancer can vary by smoking status and smoking amount at a single point in time. However, few data have been reported about the effect of changes in smoking status over time on the risk of gastric cancer. This study collected data from the National Health Insurance Corporation in Korea on 97,700 Korean men without gastric cancer who underwent health check-ups from 2002 to 2013. The smoking status (never smoked, quit smoking, and currently smoking) of study participants was assessed in 2003-2004 and 2009, and the results were categorized into 7 groups: never-never, never-quit, never-current, quit-quit, quit-current, current-quit, and current-current. Participants were followed until 2013 to identify incident gastric cancer. A multivariate Cox proportional hazard model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident gastric cancer according to changes in smoking status and smoking amount (pack-years). Compared with group 1 (never-never), participants currently smoking in 2009 (never-current, quit-current, and current-current) had higher HRs for gastric cancer (never-quit: 1.077; 95% CI, 0.887 to 1.306, never-current: 1.347; 95% CI, 0.983 to1.846, quit-quit: 1.086; 95% CI, 0.863 to 1.366, quit-current: 1.538; 95% CI, 1.042 to 2.269, current-quit: 1.339; 95% CI, 1.077 to 1.666, and current-current: 1.589; 95% CI, 1.355 to 1.864, respectively). The risk for gastric cancer was highest in heavy smokers, followed by moderate smokers. In all categories of smoking status, current smoking was associated with the highest risk of gastric cancer. Heavy smoking was associated with an increased risk of gastric cancer, even in former smokers.


Pulmonary embolism in a trauma patient with liver and orthopedic injuries.
We report the case of a 41-year-old man admitted for lower limb and liver trauma following a car accident. Surgical repair of a tibial fracture was performed under general anesthesia 5 days after admission while the liver injury was managed conservatively. At the time of tourniquet inflation, the patient presented a pulmonary embolism. Low-molecular-weight heparin administration had been delayed for 72 hours after admission due to the liver injury. Risk factors for bleeding and thromboembolism in trauma patients with liver injury are discussed.


Comparative study between fundus autofluorescence and red reflectance imaging of choroidal nevi using ultra-wide-field scanning laser ophthalmoscopy.
To explore the utility of fundus autofluorescence (FAF) and red reflectance (RR) imaging using ultra-wide-field scanning laser ophthalmoscope in choroidal nevi. Retrospective observational case study reviewing clinical data, color, FAF, and RR images of patients with choroidal nevi and comparing the findings. The ultra-wide-field scanning laser ophthalmoscope uses green laser 532 nm and red laser 633 nm that enabled FAF and RR imaging, respectively in separate channels. Superimposition of both images yielded a composite color image. The study included 46 eyes of 45 patients. Nevi were unilateral in 44 patients (98%). Forty-one nevi (89.1%) were located temporally between the macula and the equator. All nevi (100%) were deeply pigmented. The most frequent surface changes were lipofuscin pigments, zones of retinal pigment epithelium atrophy, and retinal pigment epithelium pigment clumps in 31 (67.3%), 18 (39.1%), and 8 eyes (17.3%), respectively. Color photographs were superior to FAF in detecting nevus boundaries and surface changes. Red reflectance correlated strongly with color images, although the nevus boundaries and surface changes were better delineated in RR mode. Red reflectance was superior to FAF in delineating the boundaries and surface changes of the nevus; clear visibility (3+) for RR versus no or poor visibility (0/1+) for FAF. Nevertheless, the areas of retinal pigment epithelium atrophy were better delineated in FAF mode; clear visibility (3+) for FAF versus poor visibility (1+) for FAF. Red reflectance imaging is more sensitive than conventional photography for follow-up of choroidal nevi. Fundus autofluorescence should be considered only as a complementary tool to RR imaging.


SARS-CoV-2 vaccines: Lights and shadows.
Vaccines to prevent acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicit an immune neutralizing response. Some concerns have been raised regarding the safety of SARS-CoV-2 vaccines, largely based on case-reports of serious thromboembolic events after vaccination. Some mechanisms have been suggested which might explain the adverse cardiovascular reactions to SARS-CoV-2 vaccines. Different vaccine platforms are currently available which include live attenuated vaccines, inactivated vaccines, recombinant protein vaccines, vector vaccines, DNA vaccines and RNA vaccines. Vaccines increase the endogenous synthesis of SARS-CoV-2 Spike proteins from a variety of cells. Once synthetized, the Spike proteins assembled in the cytoplasma migrate to the cell surface and protrude with a native-like conformation. These proteins are recognized by the immune system which rapidly develops an immune response. Such response appears to be quite vigorous in the presence of DNA vaccines which encode viral vectors, as well as in subjects who are immunized because of previous exposure to SARS-CoV-2. The resulting pathological features may resemble those of active coronavirus disease. The free-floating Spike proteins synthetized by cells targeted by vaccine and destroyed by the immune response circulate in the blood and systematically interact with angiotensin converting enzyme 2 (ACE2) receptors expressed by a variety of cells including platelets, thereby promoting ACE2 internalization and degradation. These reactions may ultimately lead to platelet aggregation, thrombosis and inflammation mediated by several mechanisms including platelet ACE2 receptors. Whereas Phase III vaccine trials generally excluded participants with previous immunization, vaccination of huge populations in the real life will inevitably include individuals with preexisting immunity. This might lead to excessively enhanced inflammatory and thrombotic reactions in occasional subjects. Further research is urgently needed in this area.


Impact of the learning curve in the use of a novel electronic chest drainage system after pulmonary lobectomy: a case-matched analysis on the duration of chest tube usage.
The objective of this investigation was to verify the impact of the learning curve involved after the introduction of a novel electronic chest drainage device on the duration of chest tube usage following pulmonary lobectomy. Propensity score case-matched analysis was used to compare the first consecutive 51 lobectomy patients managed with an electronic chest drainage (E) device with 51 controls managed with a traditional device (T). There was no difference in the characteristics of the two matched groups. Compared with patients managed with a traditional device, those with the electronic one had 1.9-day shorter duration of chest tube drainage (2.5 vs. 4.4 days; P<0.0001) and a 1.5-day shorter hospital stay (4.5 vs. 6 days; P=0.0003). Consequently, they had an average reduction in hospital costs of €751 (€1802 vs. €2553; P=0.0002). Compared with those in group T, patients in group E had a consistently shorter duration of chest tube use in relation to the very first patients treated. The learning curve sloped down for the first 40 patients before reaching a plateau, when the maximum benefit of using the electronic device was evident. Compared with traditional devices, the use of a novel electronic chest drainage system was beneficial from its initial application. The inherent learning curve was short and did not affect the efficiency of the system.


Engineering of Siloxanes for Stabilizing Silicon Anode Materials.
Silicon (Si) is considered the most promising anode material for the next generation of lithium-ion batteries (LIBs) because of its high theoretical specific capacity and abundant reserves. However, the volume expansion of silicon in the cycling process causes the destruction of the electrode structure and irreversible capacity loss. As a result, the commercial application of silicon materials is greatly hindered. In recent years, siloxane-based organosilicon materials have been widely used in silicon anode of LIBs because of their unique structure and physical and chemical properties, and have shown excellent electrochemical properties. The comprehensive achievement of siloxanes in silicon-based LIBs can be understood better through a systematic summary, which is necessary to guide the design of electrodes and achieve better electrochemical performance. This paper systematically introduces the unique advantages of siloxane materials in electrode, surface/interface modification, binder, and electrolyte. The challenges and future directions for siloxane materials are presented to enhance their performance and expand their application in silicon-based LIBs.


The surgeon as an endovascular interventionist. Why and how?
Catheter-based endovascular techniques have advanced significantly over the past three decades. It is only recently that surgeons have become more interested in these developments, and are now rapidly gaining in training and widening practice opportunities. Endovascular training and credentialing for the surgeon continue to be poorly-defined areas. Several pathways, albeit incomplete, are available for the incorporation of endoluminal/percutaneous skills into the surgical armamentarium. Ultimately, it can only be through established postgraduate residency and fellowship programs that the subspecialty of endovascular surgery can have a more universal applicability. The basic necessary catheter skills have been defined. Imaging requirements, both radiographic and endoscopic/ultrasonographic, are most significant and of great significance for the safe and successful performance of endoluminal vascular techniques. On balance, it is felt strongly that endoluminal catheter techniques are crucially important for the vascular surgeon of today and tomorrow.


The form of causation in health, disease and intervention: biopsychosocial dispositionalism, conserved quantity transfers and dualist mechanistic chains.
Causation is important when considering: how an organism maintains health; why disease arises in a healthy person; and, how one may intervene to change the course of a disease. This paper explores the form of causative relationships in health, disease and intervention, with particular regard to the pathological and biopsychosocial models. Consistent with the philosophical view of dispositionalism, we believe that objects are the fundamental relata of causation. By accepting the broad scope of the biopsychosocial model, we argue that psychological and social constructs be considered objects. We think that this 'biopsychosocial dispositionalism' offers the flexibility required to describe causation throughout health, disease and intervention pathways. When constructing mechanistic chains to describe causative pathways, we argue that an object will causally connect with others through actions; transfers of energy from one object to another, initiated by the manifestation of one or more dispositional property. Finally, our analysis of causative interactions utilises the concept that a common form of interaction exists between disease and intervention pathways. This common form will always be an object, but the mode of interaction will vary with each disease. We describe how intervention may act through objects being shared between converging mechanistic chains, or through the removal and/or insertion of objects in such chains. We believe that this analysis provides novel insight to the forms of causative transactions that can occur. In addition, we hope that the findings of this analysis represent the first step towards developing a framework for appraising the composition of mechanistic theories.


Outcomes of the Hemi-Hamatum Arthroplasty.
Background: Multi-fragmental intra-articular middle phalanx base fractures mostly occur in young adults during sports or work-related activities. If left untreated properly proximal interphalangeal joint (PIPJ) instability and pain persists, thus impairing the hand's function and the patient's quality of life. Joint surface reconstruction with hamate osteochondral graft can be used for multi-fragmental middle phalanx base reconstruction. Methods: A retrospective study was conducted. The technique was used for 17 patients. Follow-up was performed at least 6 months after the surgery. Patients were asked to fulfil multiple surveys: Disabilities of the Arm, Shoulder and Hand (DASH), Patient-Rated Wrist Evaluation (PRWE) and Modern Activity Subjective Survey 2007 (MASS07). Objective measurements included strength of the power and pinch grip, range of motions (ROM) in both proximal interphalangeal and distal interphalangeal (DIPJ) joints. All measurements were taken on both hands, on operated and contralateral fingers. Results: Out of 17 patients 5 were females and 12 males, mean age 40 (ranged 22-65 years) Eleven patients agreed to participate in the follow-up. All patients were right-handed, 8 patients had injured their right hand. The injuries' aetiologies were sports (n = 3), fighting (n = 2) and work-related (n = 4). Six patients were treated with immobilisation before the surgery, which was performed on average 45 days after the injury (ranged 1-184 days). Two patients developed arthrosis post-operatively and received synthetic joints. Mean DASH score was 6.9, PRWE score was 5.2 and mean MASS07 score was 6.8. Patients achieved on average 90% of power grip and 100% of pinch grip with their injured hand compared to their healthy hand. Average ROM in PIPJ was 82.2° and in DIPJ 68.9°. No patients experienced joint instability or chronic pain. Conclusions: Hemi-hamate arthroplasty provides satisfactory results in patients with both acute and chronic dislocated intra-articular middle phalanx base fractures.


The ADP ribosylation factor-nucleotide exchange factors Gea1p and Gea2p have overlapping, but not redundant functions in retrograde transport from the Golgi to the endoplasmic reticulum.
The activation of the small ras-like GTPase Arf1p requires the action of guanine nucleotide exchange factors. Four Arf1p guanine nucleotide exchange factors have been identified in yeast: Sec7p, Syt1p, Gea1p, and its homologue Gea2p. We identified GEA2 as a multicopy suppressor of a sec21-3 temperature-sensitive mutant. SEC21 encodes the gamma-subunit of coatomer, a heptameric protein complex that together with Arf1p forms the COPI coat. GEA1 and GEA2 have at least partially overlapping functions, because deletion of either gene results in no obvious phenotype, whereas the double null mutant is inviable. Conditional mutants defective in both GEA1 and GEA2 accumulate endoplasmic reticulum and Golgi membranes under restrictive conditions. The two genes do not serve completely overlapping functions because a Deltagea1 Deltaarf1 mutant is not more sickly than a Deltaarf1 strain, whereas Deltagea2 Deltaarf1 is inviable. Biochemical experiments revealed similar distributions and activities for the two proteins. Gea1p and Gea2p exist both in membrane-bound and in soluble forms. The membrane-bound forms, at least one of which, Gea2p, can be visualized on Golgi structures, are both required for vesicle budding and protein transport from the Golgi to the endoplasmic reticulum. In contrast, Sec7p, which is required for protein transport within the Golgi, is not required for retrograde protein trafficking.


The quality of YouTube videos on endoscopic third ventriculostomy and endoscopic third ventriculostomy with choroid plexus cauterization procedures available to families of patients with pediatric hydrocephalus.
YouTube has become an important information source for pediatric neurosurgical patients and their families. The goal of this study was to determine whether the informative quality of videos of endoscopic third ventriculostomy (ETV) and endoscopic third ventriculostomy with choroid plexus cauterization (ETV + CPC) is associated with metrics of popularity. This cross-sectional study used comprehensive search terms to identify videos pertaining to ETV and ETV + CPC presented on the first 3 pages of search results on YouTube. Two pediatric neurosurgeons, 1 neurosurgery resident, and 2 patient families independently reviewed the selected videos. Videos were assessed for overall informational quality by using a validated 5-point Global Quality Score (GQS) and compared to online metrics of popularity and engagement such as views, likes, likes/views ratio, comments/views ratio, and likes/dislikes ratio. Weighted kappa scores were used to measure agreement between video reviewers. A total of 58 videos (47 on ETV, 7 on ETV + CPC, 4 on both) of 120 videos assessed met the inclusion criteria. Video styles included "technical" (62%), "lecture" (24%), "patient testimonial" (4%), and "other" (10%). In terms of GQS, substantial agreement was seen between surgeons (kappa 0.67 [95% CI 0.55, 0.80]) and excellent agreement was found between each surgeon and the neurosurgical resident (0.77 [95% CI 0.66, 0.88] and 0.89 [95% CI 0.82, 0.97]). Only fair to moderate agreement was seen between professionals and patient families, with weighted kappa scores ranging from 0.07 to 0.56. Academic lectures were more likely to be rated good or excellent (64% vs 0%, p < 0.001) versus surgical procedure and testimonial video types. There were significant associations between a better GQS and more likes (p = 0.01), views (p = 0.02), and the likes/dislikes ratio (p = 0.016). The likes/views ratio (p = 0.31) and comments/views ratio (p = 0.35) were not associated with GQS. The number of likes (p = 0.02), views (p = 0.03), and the likes/dislikes ratio (p = 0.015) were significantly associated with video style (highest for lecture-style videos). Medical professionals tended to agree when assessing the overall quality of YouTube videos, but this agreement was not as strongly seen when compared to parental ratings. The online metrics of likes, views, and likes/dislikes ratio appear to predict quality. Neurosurgeons seeking to increase their online footprint via YouTube would be well advised to focus more on the academic lecture style because these were universally better rated.


Kinetic analysis of cloning patterns by human marrow cells in leukemia.
In leukemia and preleukemic disorders the progeny of a single cell proliferate and ultimately come to occupy the hemopoietic system. In the process normal stem cells are suppressed and in time may become extinct. This implies that neoplastic clones have a biological advantage. In this paper evidence is presented that the cloning of granulocytic colony forming cells in the clonal hemopathies is influenced by cell products that regulate cloning of normal colony forming cells. We have attempted to develop an approach to the study of clone-clone interactions in order to determine at what level(s) the battle between clones is fought. Future studies on relative responsiveness might help in understanding the mechanisms by which normal hemopoiesis is suppressed during the evolution of leukemia and re-established during remission induction.


Dabigatran Treatment of Acute Noncardioembolic Ischemic Stroke.
Background and Purpose- Patients with transient ischemic attack (TIA) and minor ischemic stroke are at risk for early recurrent cerebral ischemia. Anticoagulants are associated with reduced recurrence but also increased hemorrhagic transformation (HT). The safety of the novel oral anticoagulant dabigatran in acute stroke has not been evaluated. Methods- DATAS II (Dabigatran Treatment of Acute Stroke II) was a phase II prospective, randomized open label, blinded end point trial. Patients with noncardioembolic stroke/transient ischemic attack (National Institutes of Health Stroke Scale score, ≤9; infarct volume, ≤25 mL) were randomized to dabigatran or aspirin. Magnetic resonance imaging was performed before randomization and repeated at day 30. Imaging end points were ascertained centrally by readers blinded to treatment. The primary end point was symptomatic HT within 37 days of randomization. Results- A total of 305 patients, mean age 66.59±13.21 years, were randomized to dabigatran or aspirin a mean of 42.00±17.31 hours after symptom onset. The qualifying event was a transient ischemic attack in 21%, and ischemic stroke in 79% of patients. Median National Institutes of Health Stroke Scale (interquartile range) was 1 (0-2), and mean infarct volume 3.2±6.5 mL. No symptomatic HT occurred. Asymptomatic petechial HT developed in 11/142 (7.8%) of dabigatran-assigned patients and 5/142 (3.5%) of aspirin-assigned patients (relative risk, 2.301 [95% CI, 0.778-6.802]). Baseline infarct volume predicted incident HT (odds ratio, 1.07 [95% CI, 1.03-1.12]; P=0.0026). Incident covert infarcts on day 30 imaging occurred in 9/142 (6.3%) of dabigatran-assigned and 14/142 (9.8%) of aspirin-assigned patients (relative risk, 0.62 [95% CI, 0.26, 1.48]). Conclusions- Dabigatran was associated with a risk of HT similar to aspirin in acute minor noncardioembolic ischemic stroke/transient ischemic attack. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02295826.


Systemic lupus erythematosus in three ethnic groups. VI: Factors associated with fatigue within 5 years of criteria diagnosis. LUMINA Study Group. LUpus in MInority populations: NAture vs Nurture.
To determine the frequency, degree and associated features of fatigue among Hispanic (H), African American (AA) and Caucasian (C) patients with recent onset (< or = 5 yr) systemic lupus erythematosus (SLE) at their baseline evaluation. H (n = 69), AA (n = 83) and C (n = 71) patients from the LUMINA (LUpus in MInority populations: NAture vs Nurture) cohort were studied. Fatigue [Fatigue Severity Scale (FSS)] was defined as present if FSS score > or = 3.0. Variables from functional, clinical, sociodemographic, health behaviors, behavioral and psychological and immunogenetics domains were ascertained at study entry. Associations were examined using regression models. Eighty-six percent (85.7%) of patients reported having fatigue (82.6% H; 85.5% AA; 88.7% C); median FSS score, 5.3. Factors from the psychological and clinical domains were primarily associated with FSS; immunogenetic (HLA Class II phenotypes) features were not. Increased fatigue was strongly associated with decreasing function, both physical and mental. Variables associated with significantly greater degree of fatigue at baseline in the multivariable stepwise model in order of decreasing additional partial R2 explained included: abnormal illness-related behaviors, older age, higher self-reported pain, greater degree of helplessness, greater disease activity, Caucasian race, and lacking health insurance (model R2 = 37%). Fatigue is one of the most prevalent clinical manifestations of SLE across all ethnic groups. The perception of fatigue severity in SLE may be multifactorial in origin, including psychosocial factors and disease activity. If these prove causal, knowledge of their contribution may suggest therapeutic and/or behavioral interventions, which could ameliorate this pervasive and often incapacitating symptom of SLE.


Human papillomaviruses in women with a history of abnormal Papanicolaou smears and in their male partners.
Human papillomavirus infection of the genital tract was identified by the filter in situ hybridization test. Exfoliated cervical cells were tested separately for the prevalence of human papillomavirus 6/11 and 16/18. Human papillomavirus deoxyribonucleic acid (DNA) was identified in 70 and 92% of specimens of U.S. and West German women, respectively, who showed concurrent cytologic and colposcopic abnormalities, and in 50 and 54% of women, respectively, who showed neither cytologic nor colposcopic abnormalities at the time of examination. In the cytologic categories of condyloma, mild to moderate dysplasia (cervical intraepithelial neoplasia I/II), and severe dysplasia-carcinoma in situ (cervical intraepithelial neoplasia III), the overall DNA detection rate of human papillomavirus 6/11 and 16/18 varied between 75 and 83%; but human papillomavirus 16/18 was recovered relatively more frequently from the more severe lesions. Forty-eight West German women were monitored cytologically over a period of three to 24 months; progression to carcinoma in situ (cervical intraepithelial neoplasia III) was correlated with initial isolation of human papillomavirus 16/18. The vagina and vestibule were found to be frequent sites of human papillomavirus infection with the same virus type as in the cervix. In an investigation of male partners of 40 human papillomavirus-positive women, human papillomavirus was identified in exfoliated cells from 26; in 19 instances, the males harbored the same human papillomavirus types as their female partners.


Transmembrane serine protease 2 Polymorphisms and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Type 2 Infection: A German Case-Control Study.
The transmembrane serine protease 2 (TMPRSS2) is the major host protease that enables entry of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) into host cells by spike (S) protein priming. Single nucleotide polymorphisms (SNPs) in the gene TMPRSS2 have been associated with susceptibility to and severity of H1N1 or H1N9 influenza A virus infections. Functional variants may influence SARS-CoV-2 infection risk and severity of Coronavirus disease 2019 (COVID-19) as well. Therefore, we analyzed the role of SNPs in the gene TMPRSS2 in a German case-control study. We performed genotyping of the SNPs rs2070788, rs383510, and rs12329760 in the gene TMPRSS2 in 239 SARS-CoV-2-positive and 253 SARS-CoV-2-negative patients. We analyzed the association of the SNPs with susceptibility to SARS-CoV-2 infection and severity of COVID-19. SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding their demographics. The CC genotype of TMPRSS2 rs383510 was associated with a 1.73-fold increased SARS-CoV-2 infection risk, but was not correlated to severity of COVID-19. Neither TMPRSS2 rs2070788 nor rs12329760 polymorphisms were related to SARS-CoV-2 infection risk or severity of COVID-19. In a multivariable analysis (MVA), the rs383510 CC genotype remained an independent predictor for a 2-fold increased SARS-CoV-2 infection risk. In summary, our report appears to be the first showing that the intron variant rs383510 in the gene TMPRSS2 is associated with an increased risk to SARS-CoV-2 infection in a German cohort.


Cross-Resistance of UV- or Chlorine Dioxide-Resistant Echovirus 11 to Other Disinfectants.
The emergence of waterborne viruses with resistance to disinfection has been demonstrated in the laboratory and in the environment. Yet, the implications of such resistance for virus control remain obscure. In this study we investigate if viruses with resistance to a given disinfection method exhibit cross-resistance to other disinfectants. Chlorine dioxide (ClO2)- or UV-resistant populations of echovirus 11 were exposed to five inactivating treatments (free chlorine, ClO2, UV radiation, sunlight, and heat), and the extent of cross-resistance was determined. The ClO2-resistant population exhibited cross-resistance to free chlorine, but to none of the other inactivating treatments tested. We furthermore demonstrated that ClO2 and free chlorine act by a similar mechanism, in that they mainly inhibit the binding of echovirus 11 to its host cell. As such, viruses with host binding mechanisms that can withstand ClO2 treatment were also better able to withstand oxidation by free chlorine. Conversely, the UV-resistant population was not significantly cross-resistant to any other disinfection treatment. Overall, our results indicate that viruses with resistance to multiple disinfectants exist, but that they can be controlled by inactivating methods that operate by a distinctly different mechanism. We therefore suggest to utilize two disinfection barriers that act by different mechanisms in order to control disinfection-resistant viruses.


Using the proximal perforator-based anterolateral thigh flap from the same donor site to salvage the reconstruction after failure of the distal perforator-based anterolateral thigh flap.
We presented a patient who experienced the anterolateral thigh (ALT) flap failure but the reconstruction was successfully salvaged by harvesting a second ALT flap from the same donor site 2 days after the first reconstruction. A 47-year-old man received cancer ablation for right mouth floor squamous cell carcinoma. The resultant defect was planned to be reconstructed with the ALT flap. During the flap dissection, we identified three proximal cutaneous perforators originating from the transverse branch of the lateral circumflex femoral artery (t-LCFA) and two distal cutaneous perforators originating from the descending branch (d-LCFA). We harvested a skin flap based on the distal two perforators and divided the d-LCFA just distal to the bifurcation of the d-LCFA and the t-LCFA. Unfortunately, the ALT flap showed venous congestion on postoperative day 2 and eventually failed. We harvested a second ALT flap from the same donor site based on the previously preserved perforators. The recovery course was smooth thereafter. We believe that the harvest of a second ALT flap from the same donor site may be an option, to avoid other donor site violation, in some patients who experienced the first flap loss. © 2014 Wiley Periodicals, Inc. Microsurgery 34:409-412, 2014.


Endorsement of psychotic-like experiences and problematic cannabis use associated with worse executive functioning performance in undergraduates.
Emerging adults who endorse more positive psychotic-like experiences (PLEs; bizarre experiences, delusional ideations) may experience greater cannabis-related impairments in executive function. Negative and depressive PLEs are also associated with cannabis use, however, less is known about their relation to executive functioning. Here, we hypothesize that high positive PLEs and cannabis use are associated with worse performance on computerized versions of the Iowa Gambling Task (IGT) and the Card Sorting Task (CST); exploratory analyses are conducted with negative and depressive PLEs. We recruited university students (N = 543) who completed an online study consisting of self-report measures of problematic cannabis use (Cannabis Use Disorder Identification Test; CUDIT-R) and PLEs (Community Assessment of Psychotic Experiences; CAPE). Of these, n=270 completed the CST and n=251 completed the IGT. Problematic cannabis use and high endorsement of positive PLEs related to significantly worse performance on the IGT and greater perseverative errors on the CST. In addition, people who endorsed high levels of positive PLEs were also significantly more likely to complete the IGT with less money relative to those who endorsed fewer PLEs, regardless of cannabis use. Further analyses based on negative PLEs revealed a similar pattern for perseverative errors on the CST; depressive PLEs were not related to task performance. Findings highlight that problematic cannabis use and more frequent and distressing positive PLEs are associated with poorer executive functioning. Thus, executive functioning may have implications for intervention among those high on both attributes, who are at high risk of onset of psychosis.


Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus. The DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland. Medicines Monitoring Unit.
Intensive insulin treatment effectively delays the onset and slows the progression of microvascular complications in insulin-dependent diabetes mellitus (IDDM). Variable adherence to insulin treatment is thought to contribute to poor glycaemic control, diabetic ketoacidosis, and brittle diabetes in adolescents and young adults with IDDM. We assessed the association between the prescribed insulin dose and the amount dispensed from all community pharmacies with the Diabetes Audit and Research in Tayside Scotland (DARTS) database. We studied 89 patients, mean age 16 (SD 7) years, diabetes duration 8 (4) years, and glycosylated haemoglobin (HbA1c) 8.4 (1.9)%, who attended a teaching hospital paediatric or young-adult diabetes clinic in 1993 and 1994. The medically recommended insulin dose and cumulative volume of insulin prescriptions supplied were used to calculate the days of maximum possible insulin coverage per annum, expressed as the adherence index. Associations between glycaemic control (HbA1c), episodes of diabetic ketoacidosis, and all hospital admissions for acute complications and the adherence index were modelled. Insulin was prescribed at 48 (19) IU/day and mean insulin collected from pharmacies was 58 (25) IU/day, 25 (28%) of the 89 patients obtained less insulin than their prescribed dose (mean deficit 115 (68; range 9-246] insulin days/annum). There was a significant inverse association between HbA1c and the adherence index (R2 = 0.39; p < 0.001). In the top quartile (HbA1c > 10%), 14 (64%) of individuals had an adherence index suggestive of a missed dose of insulin (mean deficit 55 insulin days/annum). There were 36 admissions for complications related to diabetes. The adherence index was inversely related to hospital admissions for diabetic ketoacidosis (p < 0.001) and all hospital admissions related to acute diabetes complications (p = 0.008). The deterioration in glycaemic control observed in patients aged 10-20 years was associated with a significant reduction (p = 0.01) in the adherence index. We found direct evidence of poor compliance with insulin therapy in young patients with IDDM. We suggest that poor adherence to insulin treatment is the major factor that contributes to long-term poor glycaemic control and diabetic ketoacidosis in this age group.


Special Issue "Machine Learning Methods for Biomedical Data Analysis".
Machine learning is an effective method for developing automatic algorithms for analysing sophisticated biomedical data [...].


The influence of gamete co-incubation length on the in vitro fertility and sex ratio of bovine bulls with different penetration speed.
The objectives of this work were to evaluate whether the sperm penetration speed is correlated to the in vitro fertility and whether adapting the gamete co-incubation length to the kinetics of the bull improves in vitro fertility and affects the sex ratio. In vitro matured oocytes were co-incubated with spermatozoa from four different bulls (A-D). At various post-insemination (p.i.) times (4, 8, 12, 16 and 20 h), samples of oocytes were fixed and stained with DAPI for nuclei examination, while the remaining ones were transferred into culture to evaluate embryo development. The blastocysts produced were sexed by PCR. Two bulls (A and B) had faster kinetics than the others (C and D), as shown by the higher penetration rates recorded at 4 h p.i. (43%, 30%, 11% and 6%, respectively for bulls A, B, C and D; p<0.01). The differences in the kinetics among bulls did not reflect their in vitro fertility. The incidence of polyspermy was higher for faster penetrating bulls (36%, 24%, 16% and 4%, respectively for bulls A, B, C and D; p<0.01) and at longer co-incubation times (0%, 16%, 19%, 30% and 34%, respectively at 4, 8, 12, 16 and 20 h p.i.; p<0.01). The fertilizing ability of individual bulls may be improved by adapting the co-incubation length to their penetration speed. A sperm-oocyte co-incubation length of 8 h ensured the greatest blastocyst yields for the two faster penetrating bulls. On the contrary, 16 h co-incubation was required to increase (p<0.01) cleavage rate of the two slower bulls. Bulls with a faster kinetics did not alter the embryo sex ratio towards males. The female/male (F/M) ratios recorded were 2.1, 1.4, 1.2, 1.3 and 1.6, respectively at 4, 8, 12, 16 and 20 h p.i.


Dual covalent functionalization of single-walled carbon nanotubes for effective targeted cancer therapy.
Chemotherapy is a mainstay strategy in the management of cancer. Regrettably, current chemotherapeutic agents are cytotoxic not only to cancer cells but also to healthy cells, resulting in dose-limiting serious side effects. Therefore, many researchers are eager to develop new drug delivery systems that may help to decrease the side effects and the target delivery of chemotherapy to cancer cells. One of the epochal drug delivery systems in this field is based on carbon nanotubes technology. The aim of this work is the dual covalent functionalization of single-walled carbon nanotubes (SWCNTs) with doxorubicin (DOX) connected with acid-labile linkage and mannose (Man) as a targeting agent. The characterization of the developed nano-drug by transmission electron microscopy showed good dispersibility of the functionalized SWCNTs with diameters (6-10) nm. Moreover, the percentage of functionalization was determined by thermogravimetric analysis showing 25% of functionalization in the case of SWNCTs-NHN-DOX (7) and 51% for SWCNTs-Man-NHN-DOX (11). The in vitro release profile of Dox from SWNCTs-NHN-DOX (7) showed 45% of the loaded drug was released over 18 h at pH 7.4 and almost complete release at pH 6.4 at 37 °C. However, the in vitro release profile of Dox from SWCNTs-Man-NHN-DOX (11) showed 75% of the loaded drug was released over 5 h at pH 6.4 at 37 °C. The cytotoxic effect of the compounds was studied on liver cancer cells (HepG2) at different concentrations and different pH conditions and was compared with DOX alone. The cytotoxicity of compounds SWCNTs-NHN-DOX (7) and SWCNTs-Man-NHN-DOX (11) was enhanced at pH 6.5, where the cell viability in both test compounds was significantly reduced by almost 50% compared to the cell viability at pH 7.4 for the same test compound Moreover, the pre-incubation of cells with different concentrations of mannose reduced the cytotoxicity of compound (11) by more than 50%, suggesting that the entry of this complex could be at least in part facilitated by mannose receptors, which imparts this complex a kind of selectivity for cancer cells that overexpress this type of receptors.


[Tuberculosis epidemiology in Catalonia: 1982-1989].
The epidemiological indicators of tuberculosis in Catalonia and their trends since 1982 were evaluated. It was shown that the reported morbidity rate has increased because of an increased number of reports, but it probably is still lower than the real one. The epidemiological value of the parameters of tuberculous infection was also shown, particularly the yearly infection rate (YIR), or probability of an individual to be infected. In spite of the multiple interferences that these indexes may have undergone during the past BCG vaccination campaign, their reduction is very important, the yearly reduction of YIR being estimated in 11%.


Magnetoencephalography in clinical practice.
Magnetoencephalography (MEG) is a neurophysiological technique that measures the magnetic fields associated with neuronal activity in the brain. It is closely related but distinct from its counterpart electroencephalography (EEG). The first MEG was recorded more than 50 years ago and has technologically evolved over this time. It is now well established in clinical practice particularly in the field of epilepsy surgery and functional brain mapping. However, underutilization and misunderstanding of the clinical applications of MEG is a challenge to more widespread use of this technology. A fundamental understanding of the neurophysiology and physics of MEG is discussed in this article as well as practical issues related to implementation, analysis, and clinical applications. The future of MEG and some potential clinical applications are briefly reviewed.


Naphthalenesulfonamides as calmodulin antagonists and protein kinase inhibitors.
N-(6-Aminoethyl)-5-chloro-1-naphthalenesulfonamide (A-3), which is a shorter alkyl chain derivative of the calmodulin (CaM) antagonist, W-7, was found to inhibit smooth muscle myosin light chain kinase (MLC-kinase) through a mechanism different from that related to W-7. Both the holoenzyme and the catalytic fragment, which is active without CaM, were susceptible to A-3 with a similar concentration dependency, thereby indicating that the inhibitory effect is due to the direct interaction of the compound with the enzyme molecule and not with the enzyme activator. Naphthalenesulfonamides are both CaM antagonists and direct inhibitors of MLC-kinase, and these actions depend on the length of the alkyl chain (C2-C6). Although the potencies in inhibiting CaM functions increased, the direct effects on MLC-kinase decreased with extension of the carbon chain of the derivatives. Kinetic studies indicated that A-3 inhibited MLC-kinase competitively with respect to ATP and that the Ki value was 7.4 microM. A-3 was also a competitive inhibitor of cAMP-dependent protein kinase, cGMP-dependent protein kinase, protein kinase C, casein kinase I, and casein kinase II, with respect to ATP. The Ki values of naphthalenesulfonamides for these enzymes also increased with extension of the carbon chain of the derivatives. These results suggest that naphthalenesulfonamides inhibit protein phosphorylation not only by inhibition of the enzyme-activating process but also by inhibition of the catalytic process. The mode of interaction between the derivatives and protein kinases differs from the interaction between the derivatives and CaM.


Suppression of a cold-sensitive mutation in ribosomal protein S5 reveals a role for RimJ in ribosome biogenesis.
A specific mutation of Escherichia coli ribosomal protein S5, in which glycine is changed to aspartate at position 28 [S5(G28D)], results in cold sensitivity and defects in ribosome biogenesis and translational fidelity. In an attempt to understand the roles of S5 in these essential cellular functions, we selected extragenic suppressors and identified rimJ as a high-copy suppressor of the cold-sensitive phenotype associated with the S5(G28D) mutation. Our studies indicate that RimJ overexpression suppresses the growth defects, anomalous ribosome profiles and mRNA misreading exhibited by the S5(G28D) mutant strain. Although previously characterized as the N-acetyltransferase of S5, our data indicate that RimJ, when devoid of acetyltransferase activity, can suppress S5(G28D) defects thus indicating that the suppression activity of RimJ is not dependent on its acetyltransferase activity. Additionally, RimJ appears to associate with pre-30S subunits indicating that it acts on the ribonucleoprotein particle. These findings suggest that RimJ has evolved dual functionality; it functions in r-protein acetylation and as a ribosome assembly factor in E. coli.


[Diagnosis and treatment of diaphragm traumatic ruptures].
29 patients with traumatic ruptures of left cupola of the diaphragm were studied. Pain, dispnoe, tachycardia more intensive after a meal due to repletion and dislocation of the stomach into pleural cavity and its pressure on the organs of the mediastinum were the main symptoms of the disease. The diagnosis of traumatic rupture of the diaphragm was made on the base of clinical and roentgenological examination. In the acute period of trauma the diagnosis is difficult, especially in combined trauma. In 92.3% of cases the stomach and the bowel move into the pleural cavity, which may simulate pneumothorax or relaxation of the diaphragm. Contrast examination of the gastro-intestinal tract and pleural puncture help in differential diagnosis. All the cases of traumatic ruptures of the diaphragm should be subjected to surgical treatment. Urgent operation is indicated in continuing bleeding, incarceration of organs, acute cardiopulmonary insufficiency due to the collapse of the lung and dislocation of mediastinal organs of into contralateral position. Thoracotomy in VII intercostal space is considered as a valid approach. There were 2 (6.9%) lethal outcomes after 29 operations. Long-term results are quite favourable.


Associated factors of white matter hyperintensity volume: a machine-learning approach.
To identify the most important parameters associated with cerebral white matter hyperintensities (WMH), in consideration of potential collinearity, we used a data-driven machine-learning approach. We analysed two independent cohorts (KORA and SHIP). WMH volumes were derived from cMRI-images (FLAIR). 90 (KORA) and 34 (SHIP) potential determinants of WMH including measures of diabetes, blood-pressure, medication-intake, sociodemographics, life-style factors, somatic/depressive-symptoms and sleep were collected. Elastic net regression was used to identify relevant predictor covariates associated with WMH volume. The ten most frequently selected variables in KORA were subsequently examined for robustness in SHIP. The final KORA sample consisted of 370 participants (58% male; age 55.7 ± 9.1 years), the SHIP sample comprised 854 participants (38% male; age 53.9 ± 9.3 years). The most often selected and highly replicable parameters associated with WMH volume were in descending order age, hypertension, components of the social environment (i.e. widowed, living alone) and prediabetes. A systematic machine-learning based analysis of two independent, population-based cohorts showed, that besides age and hypertension, prediabetes and components of the social environment might play important roles in the development of WMH. Our results enable personal risk assessment for the development of WMH and inform prevention strategies tailored to the individual patient.


[Construction and expression of anti-human AFP ScFv gene in BL-21 (DE3) E. coli].
To construct anti-human AFP single chain fragment variable (ScFv) gene, transform it into BL-21 (DE3) E. coli for expression, and identify its bioactivity. VH and VL genes of anti-human AFP monoclonal antibody were cloned by RT-PCR from hybridoma. The ScFv gene was spliced by sequence overlap extending (SOE) PCR, and then it was ligated into pGEM-T vector to be identified by endonuclease digestion, PCR and sequencing. ScFv gene was cloned into pET32 (a+) vector and transformed into BL-21 (DE3) E. coli. The positive clones were screened out by IPTG induction, and the ScFv antibody was purified to be identified by SDS-PAGE and competitive inhibition ELISA test. The VH DNA consisted of 339 bases, coming from the mouse IgG gamma chain. The VL DNA consisted of 312 bases, coming from the mouse IgG kappa chain. The VH and VL genes were spliced by 45 bases coding a (G4S)3 flexible linker. The ScFv gene consisted of 696 bases. The ScFv antibody expressed by BL-21 (DE3) fused with TrxA tag protein and formed inclusions. The relative molecular mass of TrxA-ScFv fusion protein is about 40 x 10(3) and that of ScFv is about 24 x 10(3). The ScFv antibody has excellent activity tested by competitive inhibition ELISA, the TrxA-ScFv could inhibit about 41% of the McAb to bind antigen and ScFv could inhibit about 53%. We have successfully constructed an anti-human AFP ScFv gene with 696 bases; it can express in BL-21 with high activity.


Exploring the runtime of an evolutionary algorithm for the multi-objective shortest path problem.
We present a natural vector-valued fitness function f for the multi-objective shortest path problem, which is a fundamental multi-objective combinatorial optimization problem known to be NP-hard. Thereafter, we conduct a rigorous runtime analysis of a simple evolutionary algorithm (EA) optimizing f. Interestingly, this simple general algorithm is a fully polynomial-time randomized approximation scheme (FPRAS) for the problem under consideration, which exemplifies how EAs are able to find good approximate solutions for hard problems. Furthermore, we present lower bounds for the worst-case optimization time.


[Stability analysis of on-board calibration system of spatially modulated imaging Fourier transform spectrometer].
Spatially modulated imaging Fourier transform spectrometer (SMIFTS) was an instrument that depended on interference, and after calibration, the reconstruction spectrum can quantificationally reflect the diffuse reflection of target under sunshine. On-board calibration of SMIFTS confirmed the change of SMIFTS according to relative spectrum calibration, inspected long-time attenuation of SMIFTS optical system, and corrected export data of SMIFTS. According to the requirement of remote sensor application, it must stay in vacuum environment for a long time. As a radiant standard, the stability of lamp-house in long time is the most important characteristic of on-board calibration system. By calculation and experimentation, analyses of on-board calibration of SMIFTS, and testing spaceflight environment characteristic of on-board calibration, the difficulty in the key parts of on-board calibration of SMIFTS such as lamp-house, spectrum filter and integrating sphere was solved. According to the radiation-time stability testing for lamp-house and optics, particle-radiation testing, environmental-mechanics testing and hot vacuum examination, good result was obtained. By whole-aperture and part-field comparative wavelength calibration, the spectrum curve and before-launch interferogram were obtained. After comparison with reconstruction spectrum under different condition, the stability and credibility of SMIFTS on-board calibration system was proved.


Prediction of volume responsiveness in critically ill patients with spontaneous breathing activity.
Predicting volume responsiveness in patients with spontaneous breathing activity is a difficult challenge in the emergency room as well as in the intensive care unit because heart-lung interactions indices cannot be reliably used as they can be in mechanically ventilated patients fully adapted to their ventilator. The aim of this review is to summarize the different tools that have been proposed to predict the hemodynamic response to fluid infusion in the presence of spontaneous breathing activity. Clinical studies recently demonstrated that neither indicators of cardiac preload (filling pressures and end-diastolic ventricular dimensions) nor arterial pulse pressure respiratory variation was an accurate predictor of volume responsiveness in patients with spontaneous breathing activity with or without mechanical support. In contrast, performing a passive leg-raising test has been proved as valuable for this purpose. The passive leg-raising test is the only method that has been repeatedly shown to be reliable for predicting volume responsiveness in patients who experience spontaneous breathing. The appropriate utilization of this test requires a real-time assessment of its effects on systemic blood flow.


Visual assessment of foot type and relationship of foot type to lower extremity injury.
The purpose of this study was 1) to establish the interrater reliability of classifying foot type by visual appraisal and 2) to determine any relationship between foot type and subsequent knee pain or ankle sprains. Seventy-seven athletes were evaluated by three trained physical therapists to determine interrater reliability of a visual appraisal to identify foot type. Feet were classified according to operational definitions, and specific criteria had to be met for the foot to be classified as supinated, pronated, or neutral. Questionnaires concerning knee pain were completed at the beginning of the season, and incidence of ankle sprain was followed throughout the football and cross country seasons for 55 athletes. The Kappa value for interrater reliability for visually assessing foot type was .72. There was a significant relationship between foot type and knee pain (X2 = 4.45, N = 55, df = 2, p < .05). There was no relationship between foot type and incidence of ankle sprain. These results indicate that 1) physical therapists trained in the procedure can reliably use visual appraisal to classify foot type, and 2) athletes with excessively pronated or supinated foot types may be more susceptible to knee pain than athletes with neutral foot types. J Orthop Sports Phys Ther 1991;14(2):70-74.


A novel system of human submandibular/sublingual saliva collection.
The assessment of submandibular/sublingual (sm/sl) saliva is a procedure of increasing significance. However, the collection of these fluids by traditional techniques is difficult and therefore often neglected. To collect sm/sl saliva, we have assembled a novel, universal system consisting of four parts-collecting tubing, a buffering chamber, a storing tube, and a suction device. Submandibular/sublingual saliva samples were collected from ten healthy and ten xerostomic individuals. The system showed intra-examiner reproducibility of 0.92 for healthy and 0.89 for xerostomic subjects, and inter-examiner reproducibility of 0.93 for normal subjects and 0.80 for xerostomic individuals. The flow rates obtained by the present collecting set-up were similar to those measured by all known previous methods that were published during the last 40 years. The system was also efficient, in that more than 90% of the fluid that entered the system was eventually collected in the storing tube for analysis. The system appears to collect relatively pure sm/sl fluids, since contamination of the collected sample by a stimulant solution swabbed repeatedly over the tongue during saliva collection was minimal. The system is reliable, safe, practical, and comfortable for the patient.


Ca-induced K transport in human red blood cell ghosts containing arsenazo III. Transmembrane interactions of Na, K, and Ca and the relationship to the functioning Na-K pump.
Increasing free intracellular Ca (Cai) from less than 0.1 microM to 10 microM by means of A23187 activated Ca-stimulated K transport and inhibited the Na-K pump in resealed human red cell ghosts. These ghosts contained 2 mM ATP, which was maintained by a regenerating system, and arsenazo III to measure Cai. Ca-stimulated K transport was activated 50% at 2-3 microM free Cai and the Na-K pump was inhibited 50% by 5-10 microM free Cai. Free Cai from 1 to 8 microM stimulated K efflux before it inhibited the Na-K pump, dissociating the effect of Ca on the two systems. 3 microM trifluoperazine inhibited Ca-stimulated K efflux and 0.5 mM quinidine reduced Na-K pumping by 50%. In other studies, incubating fresh intact cells in solutions containing Ca and 0.5 microM A23187 caused the cells to lose K heterogeneously. Under the same conditions, increasing A23187 to 10 microM initiated a homogeneous loss of K. In ATP-deficient ghosts containing Cai equilibrated with A23187, K transport was activated at the same free Cai as in the ghosts containing 2 mM ATP. Neither Cao nor the presence of an inward Ca gradient altered the effect of free Cai on the permeability to K. In these ghosts, transmembrane interactions of Na and K influenced the rate of Ca-stimulated K efflux independent of Na- and K-induced changes in free Cai or sensitivity to Cai. At constant free Cai, increasing Ko from 0.1 to 3 mM stimulated K efflux, whereas further increasing Ko inhibited it. Increasing Nai at constant Ki and free Cai markedly decreased the rate of efflux at 2 mM Ko, but had no effect when Ko was greater than or equal to 20 mM. These transmembrane interactions indicate that the mechanism underlying Ca-stimulated K transport is mediated. Since these interactions from either side of the membrane are independent of free Cai, activation of the transport mechanism by Cai must be at a site that is independent of those responsible for the interaction of Na and K. In the presence of A23187, this activating site is half-maximally stimulated by approximately 2 microM free Ca and is not influenced by the concentration of ATP. The partial inhibition of Ca-stimulated K efflux by trifluoperazine in ghosts containing ATP suggests that calmodulin could be involved in the activation of K transport by Cai.(ABSTRACT TRUNCATED AT 400 WORDS)


Emended description of the genus Pantoea, description of four species from human clinical samples, Pantoea septica sp. nov., Pantoea eucrina sp. nov., Pantoea brenneri sp. nov. and Pantoea conspicua sp. nov., and transfer of Pectobacterium cypripedii (Hori 1911) Brenner et al. 1973 emend. Hauben et al. 1998 to the genus as Pantoea cypripedii comb. nov.
Bacterial strains belonging to DNA hybridization groups (HG) II, IV and V, in the Erwinia herbicola-Enterobacter agglomerans complex, of Brenner et al. [Int J Syst Bacteriol 34 (1984), 45-55] were suggested previously to belong to the genus Pantoea, but have never been formally described and classified. Additionally, it has been shown in several studies that Pectobacterium cypripedii is more closely related to species of Pantoea than to those of Pectobacterium. In this study, the phylogenetic positions of Brenner's DNA HG II, IV and V and Pectobacterium cypripedii were re-examined by both 16S rRNA gene sequencing and multilocus sequence analyses (MLSA) based on the gyrB, rpoB, atpD and infB genes. The analyses revealed that DNA HG II, IV and V and Pectobacterium cypripedii form five separate branches within the genus Pantoea (strains from HG V were split into two branches). DNA-DNA hybridization data further confirmed that DNA HG II, IV and V constitute four separate species. Pectobacterium cypripedii was shown to be a close phylogenetic relative of Pantoea dispersa and DNA HG IV by both 16S rRNA gene sequence and MLSA analyses. Biochemical analyses performed on strains from DNA HG II, IV and V and Pectobacterium cypripedii confirmed their taxonomic position within the genus Pantoea and revealed phenotypic characteristics that allow the differentiation of these species from each other and from their closest phylogenetic neighbours. It is proposed to emend the description of the genus Pantoea and to describe Pantoea septica sp. nov. for DNA HG II (type strain LMG 5345(T) =BD 874(T) =CDC 3123-70(T)), Pantoea eucrina sp. nov. for DNA HG IV (type strain LMG 2781(T) =BD 872(T) =CDC 1741-71(T) =LMG 5346(T)), Pantoea brenneri sp. nov. for strains of DNA HG V excluding LMG 24534 (type strain LMG 5343(T) =BD 873(T) =CDC 3482-71(T)) and Pantoea conspicua sp. nov. for the remaining strain of DNA HG V (type strain LMG 24534(T) =BD 805(T) =CDC 3527-71(T)) and to transfer Pectobacterium cypripedii to the genus as Pantoea cypripedii comb. nov. (type strain LMG 2657(T) =ATCC 29267(T) =DSM 3873(T) =LMG 2655(T)).


Lactobacillus rhamnosus probiotic treatment modulates gut and liver inflammatory pathways in a hepatocellular carcinoma murine model. A preliminary study.
Hepatocellular carcinoma (HCC) is a growing global concern with an increasing incidence rate. The intestinal microbiota has been identified as a potential culprit in modulating the effects of antitumoral drugs. We aimed to assess the impact of adding Lactobacillus rhamnosus probiotic to regorafenib in mice with HCC. Cirrhosis and HCCs were induced in 56 male Swiss mice via diethylnitrosamine injection and carbon tetrachloride administration. Mice were divided into four groups: treated with vehicle (VC), regorafenib (Rego), L. rhamnosus probiotic, and a combination of regorafenib and probiotic (Rego-Pro). After 3 weeks of treatment, liver and intestinal fragments were collected for analysis. Regorafenib elevated gut permeability, an effect mitigated by probiotic intervention, which exhibited a notable correlation with reduced inflammation (p < 0.01). iNOS levels were also reduced by adding the probiotic with respect to the mice treated with regorafenib only (p < 0.001). Notably, regorafenib substantially increased IL-6, TNF-a and TLR4 in intestinal fragments (p < 0.01). The administration of the probiotic effectively restored IL-6 to its initial levels (p < 0.001). Reducing systemic and intestinal inflammation by administering L. rhamnosus probiotic may alleviate tumoral resistance and systemic adverse effects.


Alleviation of gut inflammation by Cdx2/Pxr pathway in a mouse model of chemical colitis.
Pregnane X Receptor (PXR), a master regulator of drug metabolism and inflammation, is abundantly expressed in the gastrointestinal tract. Baicalein and its O-glucuronide baicalin are potent anti-inflammatory and anti-cancer herbal flavonoids that undergo a complex cycle of interconversion in the liver and gut. We sought to investigate the role these flavonoids play in inhibiting gut inflammation by an axis involving PXR and other potential factors. The consequences of PXR regulation and activation by the herbal flavonoids, baicalein and baicalin were evaluated in vitro in human colon carcinoma cells and in vivo using wild-type, Pxr-null, and humanized (hPXR) PXR mice. Baicalein, but not its glucuronidated metabolite baicalin, activates PXR in a Cdx2-dependent manner in vitro, in human colon carcinoma LS174T cells, and in the murine colon in vivo. While both flavonoids abrogate dextran sodium sulfate (DSS)-mediated colon inflammation in vivo, oral delivery of a potent bacterial β-glucuronidase inhibitor eliminates baicalin's effect on gastrointestinal inflammation by preventing the microbial conversion of baicalin to baicalien. Finally, reduction of gastrointestinal inflammation requires the binding of Cdx2 to a specific proximal site on the PXR promoter. Pharmacological targeting of intestinal PXR using natural metabolically labile ligands could serve as effective and potent therapeutics for gut inflammation that avert systemic drug interactions.


Effects of anandamide on potassium channels in rat ventricular myocytes: a suppression of I(to) and augmentation of K(ATP) channels.
Anandamide is an endocannabinoid that has antiarrhythmic effects through inhibition of L-type Ca(2+) channels in cardiomyocytes. In this study, we investigated the electrophysiological effects of anandamide on K(+) channels in rat ventricular myocytes. Whole cell patch-clamp technique was used to record K(+) currents, including transient outward potassium current (I(to)), steady-state outward potassium current (I(ss)), inward rectifier potassium current (I(K1)), and ATP-sensitive potassium current (I(KATP)) in isolated rat cardiac ventricular myocytes. Anandamide decreased I(to) while increasing I(KATP) in a concentration-dependent manner but had no effect on I(ss) and I(K1) in isolated ventricular myocytes. Furthermore, anandamide shifted steady-state inactivation curve of I(to) to the left and shifted the recovery curve of I(to) to the right. However, neither cannabinoid 1 (CB(1)) receptor antagonist AM251 nor CB(2) receptor antagonist AM630 eliminated the inhibitory effect of anandamide on I(to). In addition, blockade of CB(2) receptors, but not CB(1) receptors, eliminated the augmentation effect of anandamide on I(KATP). These data suggest that anandamide suppresses I(to) through a non-CB(1) and non-CB(2) receptor-mediated pathway while augmenting I(KATP) through CB(2) receptors in ventricular myocytes.


Polarization controlled directional propagation of Bloch surface wave.
Bloch surface waves (BSWs) are recently developing alternative to surface plasmon polaritons (SPPs). Due to dramatically enhanced propagation distance and strong field confinement these surface states can be successfully used in on-chip all-optical integrated devices of increased complexity. In this work we propose a highly miniaturized grating based BSW coupler which is gathering launching and directional switching functionalities in a single element. This device allows to control with polarization the propagation direction of Bloch surface waves at subwavelength scale, thus impacting a large panel of domains such as optical circuitry, function design, quantum optics, etc.


Triple-combination rilpivirine, emtricitabine, and tenofovir (Complera™/Eviplera™) in the treatment of HIV infection.
The combination rilpivirine (RPV)/emtricitabine (FTC)/tenofovir (TDF) is a once-daily, single-tablet regimen (STR) containing one nonnucleoside reverse-transcriptase inhibitor associated with two nucleos(t)ide reverse transcriptase inhibitors. It is approved by regulatory agencies (eg, US Food and Drug Association, European Medicines Agency) in all countries in which it is manufactured, except Switzerland, as first-line highly active antiretroviral therapy (HAART) for the treatment of naïve patients with HIV infection and a viral load HIV-RNA level of ≤100,000 copies/mL. Two large trials (ECHO and THRIVE) comparing RPV with efavirenz, along with different background regimens, led to approval of the drug, while a more recent trial (STaR) explored the use of STR. RPV showed noninferiority to efavirenz in all the studies, including superiority as an STR in patients with HIV-RNA ≤100,000 copies/mL in the STaR study. A positive CD4 cell response was observed in all the studies, both in the RPV and efavirenz groups. The incidence of virologic failures was higher for RPV, but was mostly referred to patients with HIV-RNA >100,000 copies/mL. There were fewer adverse events (AEs) with the RPV-based regimens versus efavirenz-based regimens, with a lower discontinuation rate because of AEs, especially psychiatric-neurological AEs, and a significantly lower rate of blood-lipid abnormalities. In the SPIRIT study (a switch study), significantly greater improvements from baseline in serum total cholesterol, low-density lipoprotein cholesterol, and trygliceride were demonstrated in patients switching to RPV/FTC/TDF from a ritonavir-boosted protease inhibitor (PI/r)-based regimen, than in those who continued treatment with a PI/r regimen. RPV's better tolerability, associated with its once-daily STR formulation, is key to improving patients' adherence and quality of life, which are among the most important factors affecting the therapeutic efficacy of an antiretroviral regimen. In summary, RPV/FTC/TDF STR is a valuable treatment option for the majority of antiretroviral-naïve HIV-infected patients. Furthermore, the use of this STR in the therapeutic switch, like in the SPIRIT study, can result in another valuable option by which to reduce AEs and improve patients' quality of life.


Influence of betamethasone on the development of mechanical properties in the fetal rhesus monkey lung.
Previous investigations of the effect of glucocorticoids on fetal lung development have suggested that changes in lung structural properties may be of greater functional significance than changes in lung surfactant. In this study we examined the mechanism of the glucocorticoid-induced change in lung structure and compared it with the changes that occur during normal development. Rhesus monkeys (Macaca Mulatta) were treated with betamethasone prior to 133 days gestational age and then delivered by cesarian section either at 133 days or near term at 160 days. Our results show that normal fetal lung development over the last month of gestation occurs with a 45% increase in lung dry weight and a 56% increase in the maximal air volume per gram lung (Vmax/g). The immediate effect of the steroid was to cause a similar percentage increase in Vmax/g but no increase in lung weight. In fact, there were significant decreases in lung weight at both 133 and 160 days in the treated animals. In addition, we found no significant changes in the mean alveolar size either with normal development or with the steroid treatment. We thus conclude that in the rhesus monkey, the lung maturation process involves both an increase in lung mass and an increase in the number of alveoli per gram of that mass. The betamethasone treatment results in accelerated recruitment of alveoli coupled with impaired growth of lung tissue.


Long range detection of line-array multi-pulsed coding lidar by combining the Accumulation coherence and Subpixel-energy detection method.
This paper presents a multi-pulsed line-array push broom lidar, the pixel array scale reaches Geiger mode detectors in time-of-flight (TOF) depth imaging: by using time and space correlation between array elements of array avalanche photo detector (APD), light coding technology and a diode pumped solid-state laser with 10kHz repetition rate and 5µJ per pulses. Two signal enhancement methods, accumulation-coherence and high accuracy energy detection were combined improves the decode effect and realizes further long detection range. Experimental results and theory analysis indicating that the retrieval and denoising results of both simulated and real signals demonstrate that our method is practical and effective; what's more, the increasing scale of array sensor and the code bits can further improve system performance.


N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials.
Objective. To review the benefits and harms of N-acetylcysteine (NAC) in women with polycystic ovary syndrome (PCOS). Method. Literature search was conducted using the bibliographic databases, MEDLINE (Ovid), CINAHL, EMBASE, Scopus, PsyInfo, and PROQUEST (from inception to September 2013) for the studies on women with PCOS receiving NAC. Results. Eight studies with a total of 910 women with PCOS were randomized to NAC or other treatments/placebo. There were high risk of selection, performance, and attrition bias in two studies and high risk of reporting bias in four studies. Women with NAC had higher odds of having a live birth, getting pregnant, and ovulation as compared to placebo. However, women with NAC were less likely to have pregnancy or ovulation as compared to metformin. There was no significant difference in rates of the miscarriage, menstrual regulation, acne, hirsutism, and adverse events, or change in body mass index, testosterone, and insulin levels with NAC as compared to placebo. Conclusions. NAC showed significant improvement in pregnancy and ovulation rate as compared to placebo. The findings need further confirmation in well-designed randomized controlled trials to examine clinical outcomes such as live birth rate in longer follow-up periods. Systematic review registration number is CRD42012001902.


Psychoeducation as an active ingredient for interventions for perinatal depression and anxiety in youth: a mixed-method systematic literature review and lived experience synthesis.
Psychoeducation is a common element in psychological interventions for youth depression and anxiety, but evidence about its use with youth perinatally is limited. This review aims to understand outcomes and mechanisms of psychoeducation for the indicated prevention and treatment of perinatal depression and anxiety in youth. For this review, we synthesised published quantitative and qualitative evidence. Seven databases (ASSIA, Medline, PubMed, PsycINFO, PsycArticles, Scopus and Web of Science) were searched for studies published before 10 August 2021. We also had consultations with a youth advisory group (N = 12). In total, 20 studies met the inclusion criteria. Seven quantitative studies examined multicomponent interventions that included psychoeducation, and one study evaluated psychoeducation as a standalone intervention for postnatal depression. Multicomponent interventions showed significant effects on postnatal depression in two out of six studies, as well as being effective at reducing prenatal anxiety in one study. Standalone psychoeducation for postnatal depression was also effective in one study. Evidence from 12 qualitative studies, corroborated by commentaries from the youth advisory group, suggested that psychoeducation could increase knowledge about symptoms, generate awareness of relevant services and enhance coping. Psychoeducation may be an important foundational ingredient of interventions for perinatal depression and, potentially, anxiety in adolescents and young adults through stimulating help-seeking and self-care.


Cross-talk between chromatin acetylation and SUMOylation of tripartite motif-containing protein 24 (TRIM24) impacts cell adhesion.
Proteins with domains that recognize and bind post-translational modifications (PTMs) of histones are collectively termed epigenetic readers. Numerous interactions between specific reader protein domains and histone PTMs and their regulatory outcomes have been reported, but little is known about how reader proteins may in turn be modulated by these interactions. Tripartite motif-containing protein 24 (TRIM24) is a histone reader aberrantly expressed in multiple cancers. Here, our investigation revealed functional cross-talk between histone acetylation and TRIM24 SUMOylation. Binding of TRIM24 to chromatin via its tandem PHD-bromodomain, which recognizes unmethylated lysine 4 and acetylated lysine 23 of histone H3 (H3K4me0/K23ac), led to TRIM24 SUMOylation at lysine residues 723 and 741. Inactivation of the bromodomain, either by mutation or with a small-molecule inhibitor, IACS-9571, abolished TRIM24 SUMOylation. Conversely, inhibition of histone deacetylation markedly increased TRIM24's interaction with chromatin and its SUMOylation. Of note, gene expression profiling of MCF7 cells expressing WT versus SUMO-deficient TRIM24 identified cell adhesion as the major pathway regulated by the cross-talk between chromatin acetylation and TRIM24 SUMOylation. In conclusion, our findings establish a new link between histone H3 acetylation and SUMOylation of the reader protein TRIM24, a functional connection that may bear on TRIM24's oncogenic function and may inform future studies of PTM cross-talk between histones and epigenetic regulators.


Near-Infrared Spectroscopy Evaluations for the Differentiation of Carbapenem-Resistant from Susceptible Enterobacteriaceae Strains.
Antimicrobial Resistance (AMR) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) is a global threat. Accurate identification of these bacterial species with associated AMR is critical for their management. While highly accurate methods to detect CRE are available, they are costly, timely and require expert skills, making their application infeasible in low-resource settings. Here, we investigated the potential of Near-Infrared Spectroscopy (NIRS) for a range of applications: (i) the detection and differentiation of isolates of two pathogenic Enterobacteriaceae species, Klebsiella pneumoniae and Escherichia coli, and (ii) the differentiation of carbapenem resistant and susceptible K. pneumoniae. NIRS has successfully differentiated between K. pneumoniae and E. coli isolates with a predictive accuracy of 89.04% (95% CI; 88.7-89.4%). K. pneumoniae isolates harbouring carbapenem-resistance determinants were differentiated from susceptible K. pneumoniae strains with an accuracy of 85% (95% CI; 84.2-86.1%). To our knowledge, this is the largest proof of concept demonstration for the utility and feasibility of NIRS to rapidly differentiate between K. pneumoniae and E. coli as well as carbapenem-resistant K. pneumoniae from susceptible strains.