Noise limitations in solid state photodetectors.
The first part of this paper deals with general concepts of noise and response in photodetectors. The noise in photodetectors is of a fivefold nature: (i) noise produced by the blackbody photon field, J(b); (ii) noise produced by the ambient photon field J(a); (iii) noise associated with the signal J(s); (iv) spontaneous noise characteristic for the device and not associated with J(a); (v) noise associated with the circuitry or amplifiers. Concepts for the characterization of the noise are-the noise equivalent powers P'(eq.)lambda[lambda,f,Deltaf,A], P'(eq).lambda[lambda,f,Deltaf, A], P'(eq).T[T,f,Deltaf,A], and P(eg).T[T,f,Deltaf,A]; the photon limited noise equivalent powers P(eq).lambda[lambda,f,Deltaf,A], P(eg).T[T,f,Deltaf,A]; various detectivities Dlambda*[lambda,f], D(T)*[T,f]; the photon limited detectivities D(T)*{T(s), Omega(s)}, D(lambda)*{T(e), Omega(s)}, D(lambda)*{T(e), Omega(e)}, and Dlambda; dagger giving the ultimate limit attainable with a detector in radiative equilibrium; the noise figure F and the signal-to-noise ratio sigma/N. The merits and limitations of photon limited behavior are discussed and the theoretical detectivitis are calculated for various circumstances. If, in the absence of a signal, the noise stems mainly from the circuitry (class B), a characterization by P(eq) or D is largely arbitrary. Such is the case for photoemissive detectors and photoconductive insulators in the absence of bias light. In the event that the device operates and produces the main noise in the absence of a signal (class A), concepts like P(eq), D, F, are meaningful (semiconductors, p-n junctions, bolometers, PEM cells, etc.). Special attention has been given to introducing a consistent notation. In the second part of this paper we discuss two topics: some aspects of the photodetective conversion processes and the fluctuations of the photon field. The photodetective processes in emission diodes, junction diodes, photovoltaic cells, and avalanche diodes are simple. The noise is mainly of (amplified) shot noise nature. In photoconductors and PEM cells we must consider the collective carrier processes (unless the electrodes are blocking as in etectors in the thirties). Such processes do not fit too well a gain mechanism as has often been suggested as is testified by ambipolar sweep out and by the non-Poisson nature of generation-recombination (g-r) and transport fluctuations. The noise in a blackbody field is stated and the effect of imperfect absorbers is considered, involving stimulated emission. The commonly applied variance theorem leads to a degrading of the Boson factor. The noise of nonthermal photon fields is discussed following Mandel-Wolf, Alkemade, and Enns. In a nonthermal equilibrium state the effects of coherence and wave-interaction noise are manifest in the detector-output noise. In the final part the detectivity is derived for various devices. We first consider briefly photoemission devices, junction photodiodes, both in short-circuited and photovoltaic operation, and avalanche diodes. Avalanche multiplication decreases the detectivity by a factor G((1/2)), where G is the gain. A new derivation of Mclntyre's fomula-including the effect of a non-Poissonian Boson field is presented. The remainder is devoted to photoconductive detectors. Four classes are distinguished: intrinsic, minority trapping models (like PbS), two center models (like CdS), extrinsic semiconductors (like Ge: Au). The main theoretical results are stated and illustrative experimental results are discussed. Some remarks are made on hot electron photoconductivity and Landau level transitions in magnetically tuned InSb detectors.


[Brain function before and after sleep deprivation in patients with primary generalized epileptic seizures].
A clinical analysis covers 11 patients with primary-generalized spastic epilepsy aged 15-43 (9 males and 2 females). Sleep deprivation showed EEG-recorded extreme stress of the brain activating structures necessitating corresponding vascular response. Rheography records cerebral hemodynamics and provides control of vascular drugs effect in relevant patients.


Unraveling the Anomalous Grain Size Dependence of Cavitation.
Experimental studies have identified an anomalous grain size dependence associated with the critical tensile pressure that a metal may sustain before catastrophic failure by cavitation processes. Here we derive the first quantitative theory (and its associated closed-form solution) capable of explaining this phenomena. The theory agrees well with experimental measurements and atomistic calculations over a very wide range of conditions. Utilizing this theory, we are able to map out three distinct regimes in which the critical tensile pressure for cavitation failure (i) increases with decreasing grain size in accordance with conventional wisdom, (ii) nonintuitively decreases with decreasing grain size, and (iii) is independent of grain size. The theory also predicts microscopic signatures of the cavitation process which agree with available data.


Transmural DC electrograms after coronary artery occlusion and latex embolization in pigs.
Changes in epicardial and endocardial direct current (DC) electrograms and ventricular arrhythmias observed during 60 min of left anterior descending coronary artery (LAD) occlusion in nine anesthetized pigs were compared with those observed in eight other pigs after embolization of the LAD with latex, a procedure able to block collateral blood flow to the ischemic area. After LAD occlusion 1) T-Q segment depression and S-T segment elevation showed a faster rate of development, and monophasic potentials occurred earlier in the endocardium than in the epicardium; 2) T-Q segment depression was greater at the center than at the periphery of the ischemic area during the first 20-30 min, and later it become greater at the periphery than at the center; and 3) a period of transient recovery in the local activation beginning after 8-15 min and lasting for 10-20 min occurred in all cases, commonly associated with T-wave alternans. LAD embolization with latex induced greater T-Q and S-T segment changes in the epicardium than in the endocardium, increased the incidence of ventricular fibrillation, and failed to impede the appearance of the period of transient electrical recovery. Thus, within an acutely ischemic area in the in situ pig heart, there are inhomogeneities in the magnitude and time course of the electrical changes, which are not prevented by procedures able to block collateral blood flow to the ischemic area. Ventricular fibrillation was also not prevented by such a procedure.


An exploration of patient satisfaction with and experience of a sexual abuse survivors clinic.
The scale and extent of sexual violence perpetrated in the United Kingdom is being increasingly acknowledged. Support after the initial disclosure is often sought in NHS sexual health clinics. The purpose of this service evaluation was to explore patient satisfaction and experience amongst sexual health clinic attendees who disclosed sexual violence and were subsequently managed in a specialist sexual abuse survivors clinic. Semi-structured interviews were conducted with ten service users and interview transcripts were analysed using interpretative phenomenological analysis (IPA) to assess users' experiences within the clinic. Participants were all female (aged 18-54 years) and had experienced sexual violence between 2 weeks and 15 years prior to interview, and the majority self-identified as White British (6/10). IPA analysis revealed three distinct overarching themes which were important to this group of patients when evaluating their care: delivery of care in the context of judgement and stigma, aspects of care identified as healing or harmful to recovery, and the importance of the processes of providing care. Understanding the experiences of sexual violence survivors in healthcare settings can optimise the provision of patient-oriented care and support. This includes ensuring the service user is in control of the consultation, the risks of re-traumatisation are minimised, and individuals receive relevant and accurate information but in a manageable volume and format.


Mutism: review, differential diagnosis, and report of 22 cases.
Mutism is a common manifestation of both psychiatric and neurologic illness. Psychiatric disturbances associated with mutism include schizophrenia, affective disorders, conversion reactions, dissociative states, and dementias. Neurologic disorders producing mutism involve the basal ganglia, frontal lobes, or limbic system structures. In psychiatric and neurologic conditions, mutism is often associated with other signs of catatonia. The authors review the literature on mutism, including psychiatric, neurologic, toxic-metabolic, and drug-induced causes. Methods to discriminate among the many causes of mutism in the clinical setting are discussed, and 22 new cases of mutism are reported to emphasize the wide differential diagnosis.


Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature.
The prevalence of TP53 mutations greatly varies between tumor types; in multiple myeloma (MM) they were rarely detected at presentation, while increased frequency was reported with disease progression. Using next-generation sequencing, we analyzed TP53 exons 4-9 in a large representative cohort comprising patients with MM at diagnosis and more aggressive forms of plasma cell (PC) dyscrasia, identifying mutations in 4/129 (3%) MM, 6/24 (25%) primary PC leukemia, and 2/10 (20%) secondary PC leukemia cases. A similar increase in prevalence associated with disease aggressiveness (5%, 29.2% and 44%, respectively) was observed for TP53 deletion. Interestingly, in five patients mutations were not concomitant with TP53 deletion. Furthermore, longitudinal analysis revealed the acquisition of TP53 mutations in three of nineteen cases analyzed at relapse. Identified variants were mostly missense mutations concentrated in the DNA binding domain, only partly reflecting the pattern globally observed in human cancers. Our data confirm that TP53 mutations are rare in MM at presentation and rather represent a marker of progression, similarly to del(17p); however, their occurrence even in absence of deletions supports the importance of their assessment in patients with PC dyscrasia, in terms of both risk stratification and therapeutic implications.


Functionally Distinct Neuronal Ensembles within the Memory Engram.
Memories are believed to be encoded by sparse ensembles of neurons in the brain. However, it remains unclear whether there is functional heterogeneity within individual memory engrams, i.e., if separate neuronal subpopulations encode distinct aspects of the memory and drive memory expression differently. Here, we show that contextual fear memory engrams in the mouse dentate gyrus contain functionally distinct neuronal ensembles, genetically defined by the Fos- or Npas4-dependent transcriptional pathways. The Fos-dependent ensemble promotes memory generalization and receives enhanced excitatory synaptic inputs from the medial entorhinal cortex, which we find itself also mediates generalization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitory drive from local cholecystokinin-expressing interneurons, the activity of which is required for discrimination. Our study provides causal evidence for functional heterogeneity within the memory engram and reveals synaptic and circuit mechanisms used by each ensemble to regulate the memory discrimination-generalization balance.


Study of Helicobacter hepaticus in gallbladders with cholelithiasis and its sensitivity pattern.
Cholelithiasis is one of the most common digestive surgical disorders. The natural history of gallstone development is unknown. Bacteria are found in high concentration in bile and stone. It is difficult to ascertain whether bacterial infection of the bile arose before stone formation or vice versa. Prospective study was carried out in 30 cholecystectomy specimens of patients with cholelithiasis collected from 15th January 2005 to 24th July 2005 in Department of Pathology, Kathmandu Medical College Teaching Hospital. The samples were collected in a sterile vial containing 0.5% saline. A small piece of gallbladder was taken in Blood agar and Chocolate agar media for micro anaerobic culture at 370 degrees Celsius. The growth of the organism was observed after 48 hours of incubation. Gram stain and various biochemical tests were performed for the confirmation of Helicobacter hepaticus and its sensitivity pattern was studied. Histologically Helicobacter hepaticus was demonstrated in formalin fixed tissue sections using Warthin Starry Silver stain. A total of 76.66% cases showed growth positivity. Nitrofurantoin was found to be the most sensitive drug (95.7%) for Helicobacter hepaticus followed by Ciprofloxacin (91.3%), Cephalaxin (91.3%), Certriaxone (91.3%),Ofloxacin (82.6%), Amikacin (65.2%) and Norfloxacin (60.9%). Helicobacter hepaticus was least sensitive to Amoxycillin (57%). From this study, it is quite apparent that Helicobacter hepaticus infection is commonly associated (76.66%) with cholelithiasis. If the patients are treated with the sensitive antibiotics regularly and the infection, that is the number one cause for the precipitation of bile leading to the formation of gallstones, can be controlled, the incidence of cholelithiasis can be reduced so that the health care expenditure related to gallbladder disease can be reduced markedly.


Polymorphism of MnSOD (Val16Ala) gene in pregnancies with blighted ovum: A case-control study.
Blighted ovum is one of the most common reasons for abortion during the first three months of pregnancy. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme in the human immune system. The gene is located on 6q25 chromosome and acts on mitochondrial matrix. In the case of mutation or inactivity of this enzyme, mitochondrial and nuclear DNA will severely be destructed. The most common polymorphism of its gene is Val16Ala. The aim was to investigate a possible mutation in pregnant women who had abortion during the first trimester of pregnancy due to blighted ovum. In this case-control study, 34 women were entered as the case and control groups, respectively. Genome DNA was extracted from saliva samples and its genotype was determined using Tetra-primer amplification refractory mutation system polymerase chain reaction technique. In the case group, 16 (48%) cases had Val/Val genotype, 17 (50%) were heterozygote and had Val/Ala genotype, and 1 (2%) had Ala/Ala genotype. Among controls, 7 (22%) items had Val/Val genotype, 6 (17%) had Val/Ala genotype, and 21 (61%) had Ala/Ala genotype. The frequency of TT, CT, and CC genotypes was 48%, 50%, and 2% in case group and 22%, 17%, and 61% in control group, respectively. Statistical analysis revealed a significant relationship between Val16Ala polymorphism of MnSOD gene and blighted ovum (p= 0.0003). It has concluded that a significant relationship exists between Val16Ala polymorphism of MnSOD gene and blighted ovum.


Persistent T1 hypointensity as an MRI marker for treatment efficacy in multiple sclerosis.
MRI is often used as primary outcome measure in phase II clinical trials in multiple sclerosis (MS). Since persistent T1 hypointense lesions are a surrogate parameter for axonal damage and demyelination, they may serve as a marker for monitoring the efficacy of neuroprotective drugs. At present, a power analysis using black hole (BH) evolution as primary outcome measure has not been performed. To assess the feasibility of using BH evolution on serial brain MR images as primary outcome measure in proof of concept studies in MS. MRI-data obtained from 169 active RRMS patients were analysed for BH evolution by determining the cumulative number of contrast enhancing lesions (CEL) evolving into a persistent black hole (PBH) after 3 months. With a parametric simulation procedure, based on a statistical distribution fitting the data, sample sizes were calculated. 21.2% of the total number of CELs observed during the study period evolved into a PBH. Ring enhancing lesions evolved most frequently into a PBH (59.4%), followed by lesions larger than 10 mm (57.4%) and periventricular CELs (30.6%). The simulation procedure, based on the statistical negative binomial (NB) model resulted in a sample sizes between 200 subjects and 30 subjects per arm, for treatment effects ranging from 50% to 90% reduction of the number of CELs evolving into a PBH, respectively. To perform a MRI monitored phase II clinical trial with a feasible sample size, using the evolution of CELs into PBHs as primary outcome parameter, a potent drug is required to obtain sufficient power.


The chop gene contains an element for the positive regulation of the mitochondrial unfolded protein response.
We have previously reported on the discovery of a mitochondrial specific unfolded protein response (mtUPR) in mammalian cells, in which the accumulation of unfolded protein within the mitochondrial matrix results in the transcriptional activation of nuclear genes encoding mitochondrial stress proteins such as chaperonin 60, chaperonin 10, mtDnaJ, and ClpP, but not those encoding stress proteins of the endoplasmic reticulum (ER) or the cytosol. Analysis of the chaperonin 60/10 bidirectional promoter showed that the CHOP element was required for the mtUPR and that the transcription of the chop gene is activated by mtUPR. In order to investigate the role of CHOP in the mtUPR, we carried out a deletion analysis of the chop promoter. This revealed that the transcriptional activation of the chop gene by mtUPR is through an AP-1 (activator protein-1) element. This site lies alongside an ERSE element through which chop transcription is activated in response to the ER stress response (erUPR). Thus CHOP can be induced separately in response to 2 different stress response pathways. We also discuss the potential signal pathway between mitochondria and the nucleus for the mtUPR.


How do you implement value-based care methodologies in dentistry with existing dental organizational paradigms?
The U.S. healthcare sector is a paradox - achieving comparatively poor population health outcomes despite outspending the world - and the current paradigm is a dichotomy - pursuing value definition consisting of quality, outcome, and cost, but failing to act in aligned and informed manner. In 2018, U.S. dental spending was $136 billion, accounting for 3.7 percent of total healthcare spending, a relatively nominal amount when considering oral diseases are among the most prevalent and have serious health and economic burdens, greatly reducing quality of life for those affected. Consistent and growing evidence shows that primary care-oriented systems achieve better health outcomes, more health equity, and lower costs; however, to date, there is little means to structuralize the role of oral health and quantify the value provided. To understand the reasons behind the abstract nature of value-based care requires an in-depth understanding of the drivers impeding the transition to a value based oral health system of care. One large clinically integrated network will provide detail of their experience.


Epidural analgesia in hepatic resection.
Randomized trials show equivocal benefit of epidural analgesia (EA) for patients undergoing abdominal operations. Partial hepatectomy is often performed using low central venous pressure anesthesia to reduce intraoperative blood loss. We examined effects of pain management strategy on blood pressure, transfusion, and complications in patients undergoing hepatic resection with either EA or IV analgesia (IVA). Data on patients undergoing hepatectomy from 2001 to 2004 at Emory University Hospital were analyzed according to route of perioperative pain management. Patient and treatment factors were analyzed for associations with transfusion and morbidity. From 2001 through 2004, 367 patients underwent elective partial hepatectomy at Emory University Hospital. EA patients were more likely to be older, men, and with malignancy. There were no differences between the groups in extent of resection, operative time, blood loss, or starting hematocrit level. The EA group had lower mean arterial pressure in recovery (86.6+/-14.0 mmHg versus 94.5+/-13.2 mmHg, p < 0.001) and were more likely to be transfused with packed red cells during the hospital course (44.5% versus 27.9%, p < 0.001). On multivariate analysis, age greater than 65 years, American Society of Anesthesiologists grade>2, starting hematocrit<38%, operative time>300 minutes, blood loss>1 L, and use of EA were associated with increased numbers of patients receiving packed red blood cells. Complications and length of stay were similar for both groups. Epidural analgesia was independently associated with increased risk of packed red blood cell transfusion after hepatectomy. EA did not appear to minimize complications or shorten hospital stay. Caution should be exercised when considering EA use in hepatic resection.


Optofluidic micro-sensors for the determination of liquid concentrations.
We present a novel optofluidic device for non-invasive and label-free determination of liquid concentrations. A microfluidic channel filled with the sample solution is hit by laser light in an angle close to the critical angle for total internal reflection. Due to the intentionally defined divergence of the incident beam, parts of the rays will experience total internal reflection while another part will be transmitted. Both reflected and transmitted light signals are recorded and the ratio of these signals is used for sample characterization. The stability compared to single signal analyses is significantly improved, resulting in a resolution of approximately 40 mmol L(-1). The typical working range of the device under investigation is between a few tens of mmol L(-1) and 5 mol L(-1) making it useful for applications in the food industry, for example to determine the amount of phosphates in liquid products.


Myopic shift and its mechanism in nephropathia epidemica or Puumala virus infection.
Nephropathia epidemica (NE) is a zoonose caused by Puumala virus. NE belongs to the group of haemorrhagic fevers with renal syndrome. Transient myopia has been described in the acute phase of the disease. This prospective study presents the changes of refraction and the results of ophthalmic A scan measurements of patients who were managed at Savonlinna Central Hospital for NE during an epidemic in the winter of 1992-3. This involved 37 patients and 74 eyes. The incidence of transient myopia was 8.1% and that of myopic shift 40.5%. A scan ultrasound measurements were performed in patients in the acute phase and after total recovery of their general illness. Statistical analysis revealed that there were significant differences in anterior chamber depth and lens thickness between the acute and control phases of the disease and between the patients who had myopic shift compared with those who did not have a significant myopic change in refraction. Based on these results it seems that the reason for transient myopic shift of NE is mainly a combination of two factors: forward movement of the anterior diaphragm and thickening of the crystalline lens. The term myopic shift should be used rather than transient myopia because it better describes the overall refractive change in NE.


Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.
There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for <14 days at Palmetto Health Hospitals in Columbia, SC, from 1 January 2010 through 31 December 2013 and discharged on oral antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, <75%). Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine treatment failure. Among the 362 patients, high, moderate and low bioavailability oral antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines.


Laminin-411 and -511 Modulate the Proliferation, Adhesion, and Morphology of Gastric Cancer Cells.
Laminins (Ln), a type of extracellular matrix glycoprotein, are key regulators of cellular behavior. Recent work revealed that in various tumor cell lines, laminin isoforms influence specific responses, such as cell anchorage, survival, proliferation, migration, organization, and specialization. The contribution of laminin isoforms to the function of gastric cancer cells, however, remain unclear. Here, we revealed that in gastric cancer, laminin isoforms Ln411, Ln421, Ln511, and Ln521 promote cellular proliferation; Ln511 and Ln521 increase cell cytoplasmic volume; Ln511 hampers invadopodia formation in some cells, Ln511 enables prompt adhesion of cells to plates, and Ln411 and Ln511 do not alter the gastric cancer stem cell markers CD44 and Lgr5. These results indicate that Ln411 and Ln511 dynamically modulate the proliferation, adhesion, and morphology of gastric cancer cells in different ways that are independent of stem cell properties. In particular, Ln511 showed a high affinity for gastric cancer cells. Our observations broaden the possible options for controlling cancer cell progression and metastasis by modulating laminin-integrin interactions.


Boronate-Modified Interdigitated Electrode Array for Selective Impedance-Based Sensing of Glycated Hemoglobin.
An impedance-based label-free affinity sensor was developed for the recognition of glycated hemoglobin (HbA1c). Interdigitated gold microelectrode arrays (IDAs) were first modified with a self-assembled monolayer of cysteamine followed by cross-linking with glutaraldehyde and subsequent binding of 3-aminophenylboronic acid (APBA), which selectively binds HbA1c via cis-diol interactions. Impedance sensing was demonstrated to be highly responsive to the clinically relevant HbA1c levels (0.1%-8.36%) with a detection and quantitation limit of 0.024% (3σ/slope) and 0.08% (10σ/slope), respectively. The specificity of the assay was evaluated with nonglycated hemoglobin (HbAo), showing that the impedance response remained unchanged over the concentration range of 10 to 20 g dL-1 HbAo. This demonstrated that the sensor system could be used to specifically distinguish HbA1c from HbAo. Moreover, the binding of HbA1c to the APBA-modified electrodes was reversible, providing a reusable sensing interface as well as showing a stable response after 4 weeks (96% of the initial response). When assaying normal (4.10%) and diabetic (8.36%) HbA1c levels (10 assays per day during a three-day period including a regeneration step after each assay), the overall assay reproducibility, expressed as relative standard error of the mean (n = 30), was 1.1%. The performance of the sensor system was also compared with a commercial method (n = 15) using patient-derived blood samples. A good agreement (Bland-Altman bias plot) and correlation (Passing-Bablok regression analysis) was demonstrated between the boronate-based affinity sensor and the standard method.


[Measuring cerebral vasoregulation--the possible clinical implications].
Cerebral vessels can keep cerebral perfusion more or less constant. This process is called cerebral vasoregulation and can be measured using different neuromonitoring techniques, which will be discussed in this overview. Cerebral perfusion deficits after brain damage caused by a cerebrovascular accident (CVA), subarachnoid haemorrhage (SAH) or severe traumatic skull and brain injury (TSBI) can be detected early and better understood by using these techniques. In current clinical guidelines on the treatment of CVA, SAB and TSBI, impaired cerebral vasoregulation is often assumed. However, there is a need to measure cerebral vasoregulation status at the individual level, with follow-up over time. Some vasoregulation techniques inform the clinician about subtle local regulation disorders ('snapshot' assessment). Other techniques are suitable for the global long-term monitoring of vasoregulation ('monitoring' assessment) where the results could serve as feedback for treatment interventions. Appropriate use of the techniques in daily clinical practice requires standardisation of the methods available for the monitoring of cerebral vasoregulation. Presently, use is mostly restricted to the research setting.


Biodiversity sampling using a global acoustic approach: contrasting sites with microendemics in New Caledonia.
New Caledonia is a Pacific island with a unique biodiversity showing an extreme microendemism. Many species distributions observed on this island are extremely restricted, localized to mountains or rivers making biodiversity evaluation and conservation a difficult task. A rapid biodiversity assessment method based on acoustics was recently proposed. This method could help to document the unique spatial structure observed in New Caledonia. Here, this method was applied in an attempt to reveal differences among three mountain sites (Mandjélia, Koghis and Aoupinié) with similar ecological features and species richness level, but with high beta diversity according to different microendemic assemblages. In each site, several local acoustic communities were sampled with audio recorders. An automatic acoustic sampling was run on these three sites for a period of 82 successive days. Acoustic properties of animal communities were analysed without any species identification. A frequency spectral complexity index (NP) was used as an estimate of the level of acoustic activity and a frequency spectral dissimilarity index (Df ) assessed acoustic differences between pairs of recordings. As expected, the index NP did not reveal significant differences in the acoustic activity level between the three sites. However, the acoustic variability estimated by the index Df , could first be explained by changes in the acoustic communities along the 24-hour cycle and second by acoustic dissimilarities between the three sites. The results support the hypothesis that global acoustic analyses can detect acoustic differences between sites with similar species richness and similar ecological context, but with different species assemblages. This study also demonstrates that global acoustic methods applied at broad spatial and temporal scales could help to assess local biodiversity in the challenging context of microendemism. The method could be deployed over large areas, and could help to compare different sites and determine conservation priorities.


[Medical expenses for diabetes care in Japan: Analysis of inter-prefecture differences].
Objectives Medical expenses for diabetes differ between Japan's 47 prefectures. The medical care expenditure regulation plan aims to reduce regional differences in outpatient medical costs through prevention of severe diabetes, promotion of specific health checkups and specific health guidance, promotion of generic drugs, and proper use of medicines. To achieve this goal, we need to conduct an in-depth analysis of inter-prefecture differences in diabetes care expenses. This study analyzed regional differences in prescription fees for dipeptidyl peptidase-4 (DPP-4) inhibitors and the use of generic sulfonylureas (SUs), glinides, biguanides, α-glucosidase inhibitors (α-GIs), and thiazoline derivatives, using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Furthermore, we analyzed regional differences in consultancy fees for dialysis prevention.Methods We analyzed the 2nd NDB Open Data Japan website of the Ministry of Health, Labor, and Welfare. Pearson's correlation coefficient (r) was used to evaluate the relationship between the medical costs of diabetes and each factor. The correlation coefficient was analyzed with Student's t-test, and a P-value<0.05 was considered statistically significant.Results Regarding oral hypoglycemic drugs, prefectures with a large number of DPP-4 inhibitors tended to have higher medical costs of diabetes (r=0.40, P=0.0048). Furthermore, such expenses tended to be low in prefectures where the use of generic SU drugs was high (r=-0.43, P=0.0023).Conclusions In conclusion, the results revealed regional differences in the use of DPP-4 inhibitors and generic SU drugs, which may contribute to the regional differences in medical expenses for diabetes. This study suggests that NDB open data are useful for policy making to reduce regional differences in outpatient medical costs of diabetes.


Improving Gerontological Survey Participation With Mixed-Mode Response Options, Multiple Contacts, and Noncontingent Incentives.
Surveys are a prominent tool in gerontological research but are hindered by low response rates. This study examined methods to improve response rate among social workers, an understudied cohort in survey methodology literature. In this brief report, we analyzed factors that influence response rate using mixed-mode survey design (mail vs. online response) and randomized monetary ($10 gift card) and in-kind (continuing education coupon) noncontingent incentives with three reminder postcards among social workers (N = 307). Response rate was 34.1% with more surveys returned via mail than online. Participants who received a gift card responded at a higher rate (46.33%) than those who received continuing education coupons (28.0%). The results add to the literature of survey methodology to improve response rates among social workers and support noncontingent gift cards and mixed-mode survey return procedures as best practices for reducing bias and improving the quality of gerontological research.


Impact of carotid endarterectomy upon cognitive functioning. A systematic review of the literature.
The extent to which carotid endarterectomy (CEA) influences cognitive functioning has been the subject of a number of studies often with conflicting conclusions. This paper systematically reviews the literature in an attempt to clarify this issue. Although the majority of studies (16/28) reported an improvement in cognition after surgery, a substantial minority (12/28) found no change. Studies before 1984 tended to report an improvement, while later studies tended to report no change in cognition. Cognitive improvement was also more likely the longer the time interval between CEA and assessment. The studies were found to differ on many methodological factors, e.g. sample size, type of patient and control group, severity and side of carotid stenosis, the range of cognitive tests and timing of postoperative assessment. Given the conflicting findings, and the methodological issues, it is not possible to draw a clear conclusion regarding the impact of carotid endarterectomy upon cognition. Future research which pays attention to these methodological factors is needed in order to adequately resolve the current debate.


Discrimination between target and non-target interactions on the viral surface by merging fluorescence emission into Rayleigh scattering.
Direct and quantitative determination of antibodies or cellular receptors dynamically binding to the surface of viral particles is the key issue for predicting the efficacy of therapeutic materials or host susceptibility to a new emerging pathogen. However, targeted visualization of infectious viruses is still highly challenging owing to their nanoscopic sizes and uncontrollable nonspecific interactions with loading molecules responsible for false signals. Here we present a multimodal single-molecule and single-particle (SMSP) visualization capable of simultaneously yet independently tracking Rayleigh scattering and fluorescence that, respectively, are generated from viruses (approximately 100 nm) and labeled interacting molecules. By analyzing real-time trajectories of fluorescent antibodies against a virus surface protein with reference to single virus-derived Rayleigh scattering, we determined heterogeneous binding stoichiometry of virus-antibody couplings irrespective of the nonspecific binder population. Therefore, our multimodal (or multi-level) SMSP assay visually identifies and selectively quantifies specific interactions between them with single binding event accuracy. As a 'specific-binding quantifier' to assess variable host susceptibility to a virus, it was further applied for distinguishing ratiometric bindings and spontaneous dissociation kinetics of synthesized isomeric receptors to influenza virus. The present framework could offer a solid analytical foundation for the development of a direct-acting antiviral agent inhibiting an integral viral enveloped protein and for nanobiological investigation for dissecting spatiotemporal nanoparticle-molecule interactions, which have been scarcely explored compared to those among plasmonic nanoparticles or among molecules only.


Comment on "Water harvesting from air with metal-organic frameworks powered by natural sunlight".
Kim et al (Reports, 28 April 2017, p. 430) presented results for the solar-driven harvesting of water from air via metal-organic frameworks as a prodigious potential advance toward remedying global water shortages. Basic thermodynamics and a survey of multiple off-the-shelf technologies show that their approach is vastly inferior in efficiency (and thereby in feasibility) to available alternatives.


[PERIPHERALLY INSERTED CENTRAL VENOUS CATHETER THROUGH DRUM SYSTEM].
It described a one lumen central venous catheter peripherally inserted drum system whose insertion into the vein is performed through a plastic splittable cannula by braunula technique. The braunula technique is particularly important in certain urgent or emergency situations, where speed and aseptic conditions of which the procedure is performed represent a further improvement over other insertion techniques. The catheter mantains the advantages, in terms of easy placement, that all devices equipped with a drum system have but at the same time eliminates the complications presented by other similar catheters whose insertion to the venous circulation used to be performed through a needle. These catheters allow quick, simple and safe access to the central venous circulation and reduce risks associated with the procedure, improving patient safety.


Chlorine dioxide against bacteria and yeasts from the alcoholic fermentation.
The ethanol production in Brazil is carried out by fed-batch or continuous process with cell recycle, in such way that bacterial contaminants are also recycled and may be troublesome due to the substrate competition. Addition of sulphuric acid when inoculum cells are washed can control the bacterial growth or alternatively biocides are used. This work aimed to verify the effect of chlorine dioxide, a well-known biocide for bacterial decontamination of water and equipments, against contaminant bacteria (Bacillus subtilis, Lactobacillus plantarum, Lactobacillus fermentum and Leuconostoc mesenteroides) from alcoholic fermentation, through the method of minimum inhibitory concentration (MIC), as well as its effect on the industrial yeast inoculum. Lower MIC was found for B. subtilis (10 ppm) and Leuconostoc mesenteroides (50 ppm) than for Lactobacillus fermentum (75 ppm) and Lactobacillus plantarum (125 ppm). Additionally, these concentrations of chlorine dioxide had similar effects on bacteria as 3 ppm of Kamoran® (recommended dosage for fermentation tanks), exception for B. subtilis, which could not be controlled at this Kamoran® dosage. The growth of industrial yeasts was affected when the concentration of chlorine dioxide was higher than 50 ppm, but the effect was slightly dependent on the type of yeast strain. Smooth yeast colonies (dispersed cells) seemed to be more sensitive than wrinkled yeast colonies (clustered cells/pseudohyphal growth), both isolated from an alcohol-producing unit during the 2006/2007 sugar cane harvest. The main advantage in the usage of chlorine dioxide that it can replace antibiotics, avoiding the selection of resistant populations of microorganisms.


Opioid therapy in non-cancer chronic pain patients: Trends and efficacy in different types of pain, patients age and gender.
In both developing and developed countries, chronic pain remains a real issue and a true disease that affects up to 42% of the population in some areas. Opioids are widely used for the management of chronic pain with variations in prescribing practices, indications and observed efficacy. to analyze trends in opioids prescribing and patient response in chronic non-cancer pain conditions. Retrospective study of 1500 casenotes of patients suffering variable non-cancer chronic pain conditions. Detailed review of those cases who were managed using opioids. Statistical analysis using "SOFA" software set. The prevalence of opioids prescribing in patients suffering this condition was thus around 35% (n=526). Women older than 50 years were more likely than men to have a chronic pain condition and to be given opioid therapy for 1 year or more. Opioid efficacy on neuropathic and mixed types of pain was found to be significant with relatively low rate of drop-out and limited side-effects that are not life threatening. Overall, patients stopped or changed their opioid medication due to inefficacy in only 12.7% of cases. The simple fact of having pain is itself a source of self-reported disability regardless of the actual physiological or pathological mechanism. Policy makers should be aware of the huge impact of chronic pain disease and of its serious effects on social and economical well-being. In developing countries, chronic pain could represent a real challenge for all parties. Multimodal management, including opioids, appears crucial for the approach of this disease.


Impaired pericyte recruitment and abnormal retinal angiogenesis as a result of angiopoietin-2 overexpression.
Angiopoietin-2 (Ang2) is among the relevant growth factors induced by hypoxia and plays an important role in the initiation of retinal neovascularizations. Ang2 is also involved in incipient diabetic retinopathy, as it may cause pericyte loss. To investigate the impact of Ang2 on developmental and hypoxia-induced angiogenesis, we used a transgenic mouse line overexpressing human Ang2 in the mouse retina. Transgenic mice displayed a reduced coverage of capillaries with pericytes (-14%; p < 0.01) and a 46% increase of vascular density of the capillary network at postnatal day 10 compared to wild type mice. In the model of oxygen-induced retinopathy (OIR), Ang2 overexpression resulted in enhanced preretinal (+103%) and intraretinal neovascularization (+29%). Newly formed intraretinal vessels in OIR were also pericyte-deficient (-26%; p < 0.01). The total expression of Ang2 in transgenic mice was seven-fold, compared with wild type controls. Ang2 modulated expression of genes encoding VEGF (+65%) and Ang1 (+79%) in transgenic animals. These data suggest that Ang2 is involved in pericyte recruitment, and modulates intraretinal, and preretinal vessel formation in the eye under physiological and pathological conditions.


Genetic Pathways and Functional Subnetworks for the Complex Nature of Bipolar Disorder in Genome-Wide Association Study.
Bipolar disorder is a complex psychiatric trait that is also recognized as a high substantial heritability from a worldwide distribution. The success in identifying susceptibility loci for bipolar disorder (BPD) has been limited due to its complex genetic architecture. Growing evidence from association studies including genome-wide association (GWA) studies points to the need of improved analytic strategies to pinpoint the missing heritability for BPD. More importantly, many studies indicate that BPD has a strong association with dementia. We conducted advanced pathway analytics strategies to investigate synergistic effects of multilocus within biologically functional pathways, and further demonstrated functional effects among proteins in subnetworks to examine mechanisms underlying the complex nature of bipolarity using a GWA dataset for BPD. We allowed bipolar susceptible loci to play a role that takes larger weights in pathway-based analytic approaches. Having significantly informative genes identified from enriched pathways, we further built function-specific subnetworks of protein interactions using MetaCore. The gene-wise scores (i.e., minimum p-value) were corrected for the gene-length, and the results were corrected for multiple tests using Benjamini and Hochberg's method. We found 87 enriched pathways that are significant for BPD; of which 36 pathways were reported. Most of them are involved with several metabolic processes, neural systems, immune system, molecular transport, cellular communication, and signal transduction. Three significant and function-related subnetworks with multiple hotspots were reported to link with several Gene Ontology processes for BPD. Our comprehensive pathway-network frameworks demonstrated that the use of prior knowledge is promising to facilitate our understanding between complex psychiatric disorders (e.g., BPD) and dementia for the access to the connection and clinical implications, along with the development and progression of dementia.


Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone.
Meniscal tears in the avascular zone have a poor self-healing potential, however partial meniscectomy predisposes the knee for early osteoarthritis. Tissue engineering with mesenchymal stem cells and a hyaluronan collagen based scaffold is a promising approach to repair meniscal tears in the avascular zone. 4 mm longitudinal meniscal tears in the avascular zone of lateral menisci of New Zealand White Rabbits were performed. The defect was left empty, sutured with a 5-0 suture or filled with a hyaluronan/collagen composite matrix without cells, with platelet rich plasma or with autologous mesenchymal stem cells. Matrices with stem cells were in part precultured in chondrogenic medium for 14 days prior to the implantation. Menisci were harvested at 6 and 12 weeks. The developed repair tissue was analyzed macroscopically, histologically and biomechanically. Untreated defects, defects treated with suture alone, with cell-free or with platelet rich plasma seeded implants showed a muted fibrous healing response. The implantation of stem cell-matrix constructs initiated fibrocartilage-like repair tissue, with better integration and biomechanical properties in the precultured stem cell-matrix group. A hyaluronan-collagen based composite scaffold seeded with mesenchymal stem cells is more effective in the repair avascular meniscal tear with stable meniscus-like tissue and to restore the native meniscus.


Humibacter ginsengiterrae sp. nov., and Humibacter ginsengisoli sp. nov., isolated from soil of a ginseng field.
Two novel Gram-staining-positive bacteria, designated DCY60T and DCY90T, were isolated from soil of a ginseng field in the Republic of Korea. 16S rRNA gene sequence comparisons showed the two novel strains were closely related to members of the genus Humibacter with greatest similarity to Humibacter antri KCTC 33009T (98.8 and 98.4% for DCY60T and DCY90T, respectively). The predominant menaquinones present were MK-11 and MK-12. The major fatty acids were anteiso-C17 : 0 and summed feature 8 containing C18 : 1ω7c and/or C18 : 1ω6c. The DNA G+C contents of strains DCY60T and DCY90T were 62.8 and 66.8 mol%, respectively. The peptidoglycan of both strains contained the amino acids ornithine, 2,4-diaminobutyric acid, alanine, glutamic acid and glycine. The cell-wall sugars of strain DCY60T comprised glucose, galactose, rhamnose and xylose, while strain DCY90T contained glucose, galactose, rhamnose and ribose. The major polar lipids of both strains were phosphatidylglycerol, an unidentified glycolipid, and an unknown phospholipid. On the basis of the phenotypic analysis strains DCY60T and DCY90T represent novel species of the genus Humibacter, for which names Humibacter ginsengiterrae sp. nov. (type strain DCY60T = KCTC 33520T = JCM 30079T) and Humibacter ginsengisoli sp. nov. (type strain DCY90T = KCTC 33521T = JCM 30080T) are proposed.


Detection, characterization, and molecular typing of human Mycoplasma spp. from major hospitals in Cairo, Egypt.
Mycoplasmas are fastidious slow growing organisms lacking a cell wall and mostly isolated from the mucosal surfaces of the respiratory and genitourinary tracts. There is a dearth of information regarding clinical Mycoplasma spp. isolates among Egyptian patients. A total of 170 samples were collected from patients and apparently healthy personnel in local public hospitals in Cairo, Egypt. Isolation of Mycoplasma spp. was carried out using appropriate culture media and further identification was carried out by biochemical tests followed by serotyping using specific antisera. Confirmation was done by PCR for detection of different Mycoplasma spp. using genus-specific primers targeting 16S ribosomal RNA gene. Characterization of the antibiotic resistance and sensitivity pattern against different antimicrobials was carried out using disc diffusion test. The results indicated the presence of six Mycoplasma spp. in 22.94% of the samples. Mycoplasmas were detected more frequently in throat swabs than sputum. Mycoplasma pneumoniae was highly sensitive to macrolides and quinolones but less sensitive to aminoglycosides and tetracyclines. Molecular techniques were found to be of more rapid, highly sensitive, able to detect nonviable organisms, and cost effective. These results shed light on difficulties of Mycoplasma detection and the superiority of molecular techniques over culture.


Adult-Attention Deficit Hyperactive Disorder Symptoms Seem Not to Influence the Outcome of an Enhanced Agonist Opioid Treatment: A 30-Year Follow-Up.
The role of opioids and opioid medications in ADHD symptoms is still largely understudied. We tested the hypothesis that, in Heroin Use Disorder (HUD), when patients are treated with Agonist Opioid medications (AOT), treatment outcome is associated with the presence of Adult Attention-Deficit/Hyperactive Disorder (A-ADHD) symptomatology. A retrospective cohort study of 130 HUD patients in Castelfranco Veneto, Italy, covering 30 years, was divided into two groups according to the Adult ADHD Self-Report Scale (ASRS) score and compared them using demographic, clinical and pharmacological factors. Survival in treatment was studied by utilizing the available data for leaving treatment and relapsing into addictive behavior and for mortality during treatment as poor primary outcomes. Thirty-five HUD subjects (26.9%) were unlikely to have A-ADHD symptomatology, and 95 (73.1%) were likely to have it. Only current age and co-substance use at treatment entry differed significantly between groups. Censored patients were 29 (82.9%) for HUD patients and 70 (73.9%) for A-ADHD/HUD patients (Mantel-Cox test = 0.66 p = 0.415). There were no significant linear trends indicative of a poorer outcome with the presence of A-ADHD after adjustment for demographic, clinical and pharmacological factors. Conclusions: ADHD symptomatology does not seem to exert any influence on the retention in AOT of HUD patients.


Death Anxiety and Loneliness among Older Adults: Role of Parental Self-Efficacy.
Death anxiety and loneliness are major issues for older people. The present study aimed to broaden the understanding of factors that are linked with increased loneliness in old age by examining the association between death anxiety and loneliness, and the role of an unexplored variable among older adults, namely, parental self-efficacy. A convenience sample of 362 Israeli parents over the age of 65 was recruited through means of social media. Participants completed self-reported questionnaires, which included background characteristics, death anxiety, parental self-efficacy, and loneliness measures. The findings showed that death anxiety was positively associated with loneliness among older adults. The findings also confirmed that parental self-efficacy moderated this association in this population. We concluded that the combination of death anxiety and low parental self-efficacy identified a group of older adults that are at higher risk of developing increased loneliness levels. Mental health professionals should consider intergenerational relationships as a fundamental component of older adults' daily lives, focusing on parental self-efficacy in old age, as this appears to be a resilience resource.


An individually based lifestyle intervention for workers at risk for cardiovascular disease: a process evaluation.
Evaluate counselors' adherence to an intervention protocol, counselors' competence, and the associations between three process indicators and body weight at follow-up in a 6-month individually based lifestyle intervention for construction workers. Process evaluation with qualitative and quantitative data. Occupational health service. A total of 408 male construction workers with an elevated risk of cardiovascular disease received the intervention, and 27 occupational health professionals delivered the intervention. Seven counseling sessions, the first during which four prescribed items had to be discussed. Motivational interviewing (MI) was used as a counseling technique. The number of sessions and the items discussed were registered by the counselors. Adherence to MI was determined by expert scoring of transcripts of random segments of 19 counseling sessions. Counselors' competence was rated by participants and counselors separately. Associations between three process indicators and body weight at follow-up were determined by linear and logistic regression analyses. Two-thirds of all participants attended five or more sessions, and 38.5% attended all seven sessions. In 90.2% of all cases, the counselor discussed all obligatory items in the first session. MI adherence was reached in one audiotaped fragment. Most (86.3%) of all participants agreed with the counselor being competent. Neither counselors' competence nor number of sessions or items discussed was significantly associated with body weight loss. Performing five sessions and discussing four prescribed items was feasible for the counselors, whereas performing MI was not. Still, participants were positive about the counselors' competence and willing to attend the intervention sessions. Investigators are encouraged to report the evaluation of their intervention process to improve future lifestyle interventions in research or in practice.


Effects of a single methylprednisolone dose on a facilitatory response of mammalian motor nerve.
Long-term glucocorticoid dosing directly enhances a facilitatory function of cat soleus motor nerve terminals. Posttetanic potentiation (PTP) of soleus contraction is a manifestation of this prejunctional facilitation. The present study demonstrates that the same enhancement of facilitation is produced with a single large intravenous dose methylprednisolone. The single dosing method, however, showed an initial suppression of facilitation that neared recovery in four hours. Thereafter, the characteristic augmentation of prejunctional facilitation emerged, peaking in 24 hours. Return to control required four days. Knowledge of this time course enabled centrally disconnected motor nerve endings to be identified as the site of both phases of the steroid action. Since the neuromuscular facilitation studied is equivalent to that triggered by neostigmine-like drugs, the results infer that the antimyasthenic effect of glucocorticoids may involve a direct action on motor nerve endings.


Spread of an OmpK36-modified ST15 Klebsiella pneumoniae variant during an outbreak involving multiple carbapenem-resistant Enterobacteriaceae species and clones.
We aim to characterise multiple ertapenem-resistant (ERT-R, n = 15) Enterobacteriaceae isolates identified as presumptive carbapenemase producers in a Portuguese hospital in a short period of time (March-July 2010). Antibiotic susceptibility patterns, β-lactamases, genetic relatedness [pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST)], plasmid content and major enterobacterial porins were investigated. Ertapenem resistance was associated with deficiencies in major porins and, in some cases, extended-spectrum β-lactamase (ESBL) or AmpC β-lactamase production among outbreak and non-outbreak clones. Most isolates (n = 8) corresponded to two ERT-R Klebsiella pneumoniae ST15 PFGE-types: (i) a sporadic variant (Kp-A-ERT, n = 1) presenting a premature stop codon in ompK36 and (ii) an epidemic variant (Kp-B-ERT, n = 7) exhibiting a new OmpK36 porin variant, which differed additionally in plasmid and antibiotic susceptibility profiles. ST14 (n = 1) and ST45 (n = 1) K. pneumoniae, ST131 (n = 1) and ST354 (n = 1) Escherichia coli, Enterobacter asburiae (n = 1), Enterobacter cloacae (n = 1) and Enterobacter aerogenes (n = 1) ERT-R clones were also sporadically detected. Porin changes in these isolates included non-sense mutations [ompK35, ompK36, ompF; minimum inhibitory concentration (MIC) = 4-32 mg/l], IS-mediated porin disruptions (ompK36, ompC; MIC = 12->32 mg/l) or alterations in the L3 loop (ompK36; MIC = 4-16 mg/l). We describe, for the first time in Portugal, the simultaneous emergence of multiple ERT-R Enterobacteriaceae species and clones in a short period of time. Moreover, our results support that a CTX-M-15-producing ST15 K. pneumoniae with an OmpK36-modified porin might successfully spread in the nosocomial setting.


Lesion correlates of conversational speech production deficits.
We assess brain areas involved in speech production using a recently developed lesion-symptom mapping method (voxel-based lesion-symptom mapping, VLSM) with 50 aphasic patients with left-hemisphere lesions. Conversational speech was collected through a standardized biographical interview, and used to determine mean length of utterance in morphemes (MLU), type token ratio (TTR) and overall tokens spoken for each patient. These metrics are used as indicators of grammatical complexity, semantic variation, and amount of speech, respectively. VLSM analysis revealed that damage to the anterior insula was predictive of low scores on MLU and tokens, consistent with prior findings of the role of this region in speech production [Dronkers, N. F. (1996). A new brain region for coordinating speech articulation. Nature, 384(6605), 159-161]. Additionally, the inferior frontal gyrus, sensorimotor and anterior temporal areas were also associated with lower scores on both of these measures. Overall, token and MLU maps were highly similar, suggesting an overlap between grammatical language networks and overall fluency. TTR maps also shared some portions of this network, but damage to posterior temporal regions also reduced scores on this measure. These results represent the first voxel-based lesion analysis of speech production performance in aphasic patients.


N-Acetylcysteine ameliorates the late phase of liver ischaemia/reperfusion injury in the rabbit with hepatic steatosis.
Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury and, therefore, the aim of the present study was to evaluate the in vivo effect of NAC (N-acetylcysteine) on hepatic function in the early and initial late phase of warm liver I/R injury in steatotic rabbits. Twelve New Zealand White rabbits were fed a high-cholesterol (2%) diet. The control group (n=6) underwent lobar liver ischaemia for 1 h, followed by 6 h of reperfusion. In the treated group receiving NAC (n=6), an intravenous infusion of NAC was administered prior to and during the 6 h reperfusion period. Systemic and hepatic haemodynamics were monitored continuously. ALT (alanine aminotransferase) activity and bile production were measured. NMR spectroscopy was used to analyse bile composition. Oxidation of DHR (dihydrorhodamine) to RH (rhodamine) was used as a marker of production of reactive oxygen and nitrogen species. Moderate centrilobular hepatic steatosis was demonstrated by histology. The results showed that NAC administration significantly improved portal flow, hepatic microcirculation, bile composition and bile flow after 5 h of reperfusion. NAC administration was also associated with less hepatocellular injury, as indicated by ALT serum activity, and decreased the oxidation of DHR to RH. In conclusion, NAC administration decreased the extent of I/R injury in the steatotic liver, particularly during the late phase of reperfusion.


Prostate specific antigen detection in patient sera by fluorescence-free BioCD protein array.
Fluorescence-free biosensor arrays for protein detection directly measure the protein surface density, and do not require a fluorophore or enzyme label, and provide quantitative and consistent signals. However, few fluorescence-free biosensor protein arrays have demonstrated successful application in high-background samples, such as serum, due to non-specific binding. We tested the BioCD as a fluorescence-free biosensor based on optical interferometry, and used it to detect prostate specific antigen (PSA, a biomarker of prostate cancer) in patient sera in a 96-well anti-PSA microarray. We have attained a 4 ng/ml detection limit in serum and have measured PSA concentrations in patient sera. The measured concentrations correlated well with enzyme-linked immunosorbent assay (ELISA) results. The measurement of PSA concentrations in high-level protein backgrounds suggests that the BioCD has a potential for clinical applications by removing the restriction of fluorescence-free biosensors from high-background applications.


Exploring circulating micro-RNA in the neoadjuvant treatment of breast cancer.
Breast cancer is the most frequently diagnosed malignancy amongst females worldwide. In recent years the management of this disease has transformed considerably, including the administration of chemotherapy in the neoadjuvant setting. Aside from increasing rates of breast conserving surgery and enabling surgery via tumour burden reduction, use of chemotherapy in the neoadjuvant setting allows monitoring of in vivo tumour response to chemotherapeutics. Currently, there is no effective means of identifying chemotherapeutic responders from non-responders. Whilst some patients achieve complete pathological response (pCR) to chemotherapy, a good prognostic index, a proportion of patients derive little or no benefit, being exposed to the deleterious effects of systemic treatment without any knowledge of whether they will receive benefit. The identification of predictive and prognostic biomarkers could confer multiple benefits in this setting, specifically the individualization of breast cancer management and more effective administration of chemotherapeutics. In addition, biomarkers could potentially expedite the identification of novel chemotherapeutic agents or increase their efficacy. Micro-RNAs (miRNAs) are small non-coding RNA molecules. With their tissue-specific expression, correlation with clinicopathological prognostic indices and known dysregulation in breast cancer, miRNAs have quickly become an important avenue in the search for novel breast cancer biomarkers. We provide a brief history of breast cancer chemotherapeutics and explore the emerging field of circulating (blood-borne) miRNAs as breast cancer biomarkers for the neoadjuvant treatment of breast cancer. Established molecular markers of breast cancer are outlined, while the potential role of circulating miRNAs as chemotherapeutic response predictors, prognosticators or potential therapeutic targets is discussed.


10α-Hy-droxy-13-{[4-(4-meth-oxy-phen-yl)piperazin-1-yl]meth-yl}-4,9-dimethyl-3,8,15-trioxatetra-cyclo-[10.3.0.0.0]penta-decan-14-one.
The title compound, C(26)H(36)N(2)O(6), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo-[220.127.116.11(2,4)]tetra-dec-7-en-13-one), which was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The mol-ecule is built up from fused five- and ten-membered rings with two additional ep-oxy ring systems and a meth-oxy-phenyl-piperazine group as a substituent. The ten-membered ring adopts an approximate chair-chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring shows an envelope conformation with the C atom closest to the hy-droxy group forming the flap. The mol-ecular conformation is determined by an O-H⋯N hydrogen bond between the hy-droxy group and a piperazine N atom. The crystal structure is built up by weak C-H⋯O inter-actions.


Scales and dermal skeletal histology of an early bony fish Psarolepis romeri and their bearing on the evolution of rhombic scales and hard tissues.
Recent discoveries of early bony fishes from the Silurian and earliest Devonian of South China (e.g. Psarolepis, Achoania, Meemannia, Styloichthys and Guiyu) have been crucial in understanding the origin and early diversification of the osteichthyans (bony fishes and tetrapods). All these early fishes, except Guiyu, have their dermal skeletal surface punctured by relatively large pore openings. However, among these early fishes little is known about scale morphology and dermal skeletal histology. Here we report new data about the scales and dermal skeletal histology of Psarolepis romeri, a taxon with important implications for studying the phylogeny of early gnathostomes and early osteichthyans. Seven subtypes of rhombic scales with similar histological composition and surface sculpture are referred to Psarolepis romeri. They are generally thick and show a faint antero-dorsal process and a broad peg-and-socket structure. In contrast to previously reported rhombic scales of osteichthyans, these scales bear a neck between crown and base as in acanthodian scales. Histologically, the crown is composed of several generations of odontodes and an irregular canal system connecting cylindrical pore cavities. Younger odontodes are deposited on older ones both superpositionally and areally. The bony tissues forming the keel of the scale are shown to be lamellar bone with plywood-like structure, whereas the other parts of the base are composed of pseudo-lamellar bone with parallel collagen fibers. The unique tissue combination in the keel (i.e., extrinsic Sharpey's fibers orthogonal to the intrinsic orthogonal sets of collagen fibers) has rarely been reported in the keel of other rhombic scales. The new data provide insights into the early evolution of rhombic (ganoid and cosmoid) scales in osteichthyans, and add to our knowledge of hard tissues of early vertebrates.


Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings?
Vitamin D deficiency is widespread in the world including the vulnerable group of pregnant women. Vitamin D deficiency during pregnancy is hypothesized to contribute to the cause of autism. Further, it is hypothesized that vitamin D supplementation during pregnancy and early childhood will reduce the recurrence rate of autism in newborn siblings. To investigate the hypothesis an open label prospective study was performed prescribing vitamin D during pregnancy to mothers of children with autism at a dose of 5000IU/day. The newborn siblings were at high risk for the recurrence of autism. The newborn infants were also prescribed vitamin D, 1000IU/day to their third birthday. The newborn siblings were followed for three years and during that time, were assessed for autism on two separate occasions: at 18months and 36months of age. The results were compared to the reported recurrence rates in siblings of autistic children in the literature. The final outcome was 1 out of 19 (5%) developed autism in contrast to the recurrence rate of approximately 20% in the literature. We did not have a control group, nor was there blinding. The results are promising, however, this is a preliminary study with very small numbers and was uncontrolled. Further study with larger numbers is indicated. The ethics of prescribing a low dosage of vitamin D such as 400IU D3/day to a control group of mothers in comparison to a large dose such as 5000IU D3/day are problematic in our opinion.


On Students' Willingness to Use Online Learning: A Privacy Calculus Theory Approach.
Online learning platforms frequently collect and store learners' data to personalize content and improve learning analytics, but this also increases the likelihood of privacy breaches which may reduce learners' willingness to use online learning. This study aims to examine how perceptions of benefits, privacy, risk, and trust affect students' willingness to use online learning. We used the Privacy Calculus Theory as a theoretical framework for this study. To test the model, we surveyed 203 undergraduate students who used online learning. The results of the AMOS analysis revealed that students' risk perception has a significant negative effect on their willingness to use online learning, while their benefit perception and trust perception have positive effects. Furthermore, the study found that improved trust can reduce perceived risk and improve willingness to use online learning. Interestingly, privacy perception is not a significant predictor of students' willingness to use online learning, although it is a high concern factor. Discussion and conclusion are discussed at the end.


Minimally invasive adrenalectomy for pheochromocytoma during pregnancy.
Pheochromocytoma during pregnancy is a very rare condition; fewer than 200 cases have been reported in the literature. We present the case of a 24-year-old pregnant woman found to have a pheochromocytoma during investigation of abdominal pain. This is the second reported case of laparoscopic adrenalectomy for pheochromocytoma detected during pregnancy. After appropriate radiologic investigation and medical management, a laparoscopic left adrenalectomy was performed at the beginning of the second trimester. There were no complications, and she was delivered of a healthy baby at term. We review the management of pheochromocytoma in pregnant patients and discuss the role of laparoscopy.


Spatially Annotated Single Cell Sequencing for Unraveling Intratumor Heterogeneity.
Intratumor heterogeneity is a major obstacle to effective cancer treatment. Current methods to study intratumor heterogeneity using single-cell RNA sequencing (scRNA-seq) lack information on the spatial organization of cells. While state-of-the art spatial transcriptomics methods capture the spatial distribution, they either lack single cell resolution or have relatively low transcript counts. Here, we introduce spatially annotated single cell sequencing, based on the previously developed functional single cell sequencing (FUNseq) technique, to spatially profile tumor cells with deep scRNA-seq and single cell resolution. Using our approach, we profiled cells located at different distances from the center of a 2D epithelial cell mass. By profiling the cell patch in concentric bands of varying width, we showed that cells at the outermost edge of the patch responded strongest to their local microenvironment, behaved most invasively, and activated the process of epithelial-to-mesenchymal transition (EMT) to migrate to low-confluence areas. We inferred cell-cell communication networks and demonstrated that cells in the outermost ∼10 cell wide band, which we termed the invasive edge, induced similar phenotypic plasticity in neighboring regions. Applying FUNseq to spatially annotate and profile tumor cells enables deep characterization of tumor subpopulations, thereby unraveling the mechanistic basis for intratumor heterogeneity.


[Ovarian metastases in breast carcinoma].
The effect on prognosis of the presence of ovarian metastases was studied in patients oophorectomized in treatment of progressive breast cancer. At laparotomy, 28% (n = 42) were found to have ovarian metastases. This high percentage indicates that cases studied were in a relatively progressed state. In the cases with ovarian metastases, the clinical course of the disease was no different to those histologically free from metastases. It appears therefore that the presence of secondary ovarian metastases at oophorectomy is of no therapeutic or prognostic significance. The time interval between oophorectomy and mastectomy, however, apparently does have a bearing on the progress of the disease.


Two new virtual reality tasks for the assessment of spatial orientation Preliminary results of tolerability, sense of presence and usability.
Spatial orientation is a cognitive domain frequently impaired in Alzheimer's Disease and can be one of its earliest symptoms. This paper describes the results of tolerability, sense of presence and usability of two immersive virtual reality tasks for the assessment of spatial orientation, using VR headset in adults. 31 healthy adults recruited from university and the local community performed two experimental immersive virtual reality tasks of spatial orientation: the SOIVET-Maze for the assessment of allocentric to egocentric spatial abilities and the SOIVET-Route for the assessment of spatial memory and landmark recognition. Participants completed questionnaires about sense of presence, cybersickness symptoms, technology use profile and motion sickness history. Usability measures were assessed by spontaneous feedback from participants. All participants were able to understand the task instructions and how to interact with the system. Both tasks seemed to induce a strong sense of presence, as assessed by the Witmer and Singer Presence Questionnaires (M=128 and 143 for SOIVET-Maze and SOIVET-Route, respectively). The SOIVET-Route had a small numeric advantage over the SOIVET-Maze tolerability scores assessed by the Cybersickness Questionnaire (M=4.19, SD=5.576 and M=3.52, SD=6.418 for SOIVET-Maze and SOIVET-Route respectively). Also, there were no drop-outs on the SOIVET-Route due to tolerability issues, unlike the SOIVET-Maze, which had two drop-outs. However, this difference was not statistically significant (Z= -.901, p= 0.368, Wilcoxon signed-rank test).


Low expression of microRNA-21 inhibits trophoblast cell infiltration through targeting PTEN.
We investigate whether microRNA-21 could increase the infiltration ability of trophoblast cells via regulating PTEN expression, thus participating in the occurrence and development of preeclampsia. MicroRNA-21 expression in the placenta tissues of preeclampsia women and normal pregnant women was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The effects of microRNA-21 on cell proliferation and infiltration were examined by cell counting kit-8 (CCK-8) and transwell assay, respectively. The dual-luciferase reporter gene assay was used to determine the binding relationship between microRNA-21 and PTEN. Western blot was performed to detect PTEN and microRNA-21 in trophoblasts. QRT-PCR results showed that the microRNA-21 expression was significantly lower in the placenta of the preeclampsia women than those of normal pregnant women. Overexpression of microRNA-21 in HTR-8/SVneo cells had no effect on cell proliferation, but enhanced cell infiltration ability. Inhibition of microRNA-21 in trophoblasts showed the opposite effects. The results of luciferase activity assay and Western blot showed that microRNA-21 could target PTEN and downregulate its expression. Overexpression of PTEN in HTR-8/SVneo cells partially reversed the enhanced invasive ability induced by microRNA-21 overexpression. Low expression of microRNA-21 attenuated cell infiltration of trophoblasts via direct regulating PTEN expression.


Inflammatory cell distribution within and along asthmatic airways.
Asthmatic airways are infiltrated with inflammatory cells that release mediators and cytokines into the microenvironment. In this study, we evaluated the distribution of CD45-positive leukocytes and eosinophils in lung tissue from five patients who died with severe asthma compared with five patients with cystic fibrosis. For morphometric analysis, the airway wall was partitioned into an "inner" area (between basement membrane and smooth muscle) and an "outer" area (between smooth muscle and alveolar attachments). Large airways (with a perimeter greater than 3.0 mm) from patients with asthma or cystic fibrosis had a greater density of CD45-positive cells (p < 0.05) and eosinophils (p < 0.001) in the inner airway region compared with the same airway region in small airways. Furthermore, in small airways, asthmatic lungs showed a greater density of CD45-positive cells (p < 0.01) and eosinophils (p < 0.01) in the outer compared with the inner airway wall region. These observations indicate that there are regional variations in inflammatory cell distribution within the airway wall in patients with asthma that are not observed in airways from patients with cystic fibrosis. We speculate that this inflammatory cell density in peripheral airways in severe asthma may relate to the peripheral airway obstruction characteristic of this condition.


[Body niacin status in experimental diabetes mellitus; effect of protein level in the ration].
Administration of a high-protein diet providing 7-7.8 g of tryptophan per kg of the ration to rats with streptozotocin and alloxan diabetes mellitus resulted in development of a trend to increased liver content of nicotinamide coenzymes and in increased 1-methylnicotinamide excretion with the urine in both groups of animals, this reflecting increased niacin synthesis from tryptophan. Sugar-reducing effect of high-dose nicotinamide was not potentiated by increase of protein share in the ration. These results permitted the authors to suggest that intensification of endogenous niacin synthesis from tryptophan contained in the ration may be one of the mechanisms of a protective effect of high-protein diets in diabetes.


Erosion of Digital Professionalism During Medical Students' Core Clinical Clerkships.
The increased use of social media, cloud computing, and mobile devices has led to the emergence of guidelines and novel teaching efforts to guide students toward the appropriate use of technology. Despite this, violations of professional conduct are common. We sought to explore professional behaviors specific to appropriate use of technology by looking at changes in third-year medical students' attitudes and behaviors at the beginning and conclusion of their clinical clerkships. After formal teaching about digital professionalism, we administered a survey to medical students that described 35 technology-related behaviors and queried students about professionalism of the behavior (on a 5-point Likert scale), observation of others engaging in the behavior (yes or no), as well as personal participation in the behavior (yes or no). Students were resurveyed at the end of the academic year. Over the year, perceptions of what is considered acceptable behavior regarding privacy, data security, communications, and social media boundaries changed, despite formal teaching sessions to reinforce professional behavior. Furthermore, medical students who observed unprofessional behaviors were more likely to participate in such behaviors. Although technology is a useful tool to enhance teaching and learning, our results reflect an erosion of professionalism related to information security that occurred despite medical school and hospital-based teaching sessions to promote digital professionalism. True alteration of trainee behavior will require a cultural shift that includes continual education, better role models, and frequent reminders for faculty, house staff, students, and staff.


Protein Quality Control Activation and Microtubule Remodeling in Hypertrophic Cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder. It is mainly caused by mutations in genes encoding sarcomere proteins. Mutant forms of these highly abundant proteins likely stress the protein quality control (PQC) system of cardiomyocytes. The PQC system, together with a functional microtubule network, maintains proteostasis. We compared left ventricular (LV) tissue of nine donors (controls) with 38 sarcomere mutation-positive (HCMSMP) and 14 sarcomere mutation-negative (HCMSMN) patients to define HCM and mutation-specific changes in PQC. Mutations in HCMSMP result in poison polypeptides or reduced protein levels (haploinsufficiency, HI). The main findings were 1) several key PQC players were more abundant in HCM compared to controls, 2) after correction for sex and age, stabilizing heat shock protein (HSP)B1, and refolding, HSPD1 and HSPA2 were increased in HCMSMP compared to controls, 3) α-tubulin and acetylated α-tubulin levels were higher in HCM compared to controls, especially in HCMHI, 4) myosin-binding protein-C (cMyBP-C) levels were inversely correlated with α-tubulin, and 5) α-tubulin levels correlated with acetylated α-tubulin and HSPs. Overall, carrying a mutation affects PQC and α-tubulin acetylation. The haploinsufficiency of cMyBP-C may trigger HSPs and α-tubulin acetylation. Our study indicates that proliferation of the microtubular network may represent a novel pathomechanism in cMyBP-C haploinsufficiency-mediated HCM.


[Estrogen and progesterone receptors in esophageal carcinoma cells].
Distribution of estrogen and progesterone receptors (ER and PR) was studied in esophageal tissue (48 patients with esophageal carcinoma, 20 normal subjects and 12 fetuses) and Eca 109 cell line using enzyme-linking affinity immunohistochemistry method. In the meantime, plasma estradiol and progesterone levels were determined in 8 patients with esophageal carcinoma using radioimmunoassay method. The results showed that the positive rates of ER and PR in esophageal carcinoma were 43.75% (21/48) and 39.58% (19/48). Both ER and PR were positive in Eca 109 cell line whereas they were negative in the control groups. Sex and grade of cancer were the factors influencing the positive rates of ER and PR. It is indicated that carcinogenesis of esophageal carcinoma might be related to sex hormone metabolism. The measurement of ER and PR may be useful in clinical practice.


Institute of Medical Ethics Guidelines for confirmation of appointment, promotion and recognition of UK bioethics and medical ethics researchers.
This document is designed to give guidance on assessing researchers in bioethics/medical ethics. It is intended to assist members of selection, confirmation and promotion committees, who are required to assess those conducting bioethics research when they are not from a similar disciplinary background. It does not attempt to give guidance on the quality of bioethics research, as this is a matter for peer assessment. Rather it aims to give an indication of the type, scope and amount of research that is the expected in this field. It does not cover the assessment of other activities such as teaching, policy work, clinical ethics consultation and so on, but these will be mentioned for additional context. Although it mentions the UK's Research Excellence Framework (REF), it is not intended to be a detailed analysis of the place of bioethics in the REF.


Biological factors contributing to failures of osseointegrated oral implants. (II). Etiopathogenesis.
The aim of the present review is to evaluate the English language literature regarding factors associated with the loss of oral implants. An evidence-based format in conjunction, when possible, with a meta-analytic approach is used. The review identifies the following factors to be associated with biological failures of oral implants: medical status of the patient, smoking, bone quality, bone grafting, irradiation therapy, parafunctions, operator experience, degree of surgical trauma, bacterial contamination, lack of preoperative antibiotics, immediate loading, nonsubmerged procedure, number of implants supporting a prosthesis, implant surface characteristics and design. Excessive surgical trauma together with an impaired healing ability, premature loading and infection are likely to be the most common causes of early implant losses. Whereas progressive chronic marginal infection (peri-implantitis) and overload in conjunction with the host characteristics are the major etiological agents causing late failures. Furthermore, it appears that implant surface properties (roughness and type of coating) may influence the failure pattern. Various surface properties may therefore be indicated for different anatomical and host conditions. Finally, the histopathology of implant losses is described and discussed in relation to the clinical findings.


Value of blood-pool subtraction in cardiac indium-111-labeled platelet imaging.
Blood-pool subtraction has been proposed to enhance 111In-labeled platelet imaging of intracardiac thrombi. We tested the accuracy of labeled platelet imaging, with and without blood-pool subtraction, in ten subjects with cardiac thrombi of varying age, eight with endocarditis being treated with antimicrobial therapy and ten normal controls. Imaging was performed early after labeled platelet injection (24 hr or less) and late (48 hr or more). Blood-pool subtraction was carried out. All images were graded subjectively by four experienced, "blinded" readers. Detection accuracy was measured by the sensitivity at three fixed levels of specificity estimated from receiver operator characteristic curve analysis and tested by three-way analysis of variance. Detection accuracy was generally improved on delayed images. Blood-pool subtraction did not improve accuracy. Although blood-pool subtraction increased detection sensitivity, this was offset by decreased specificity. For this population studied, blood-pool subtraction did not improve subjective detection of abnormal platelet deposition by 111In platelet imaging.


Ceramides as possible nutraceutical compounds: characterization of the ceramides of the Moro blood orange ( Citrus sinensis ).
Ceramides are presented as nutraceutical compounds for protection of colon carcinoma and as important cosmetic preparation components, increasing absorption through the skin. Therefore, the ceramide (Cer) content of Moro blood oranges was determined by mass spectrometry. A total of 114 Cer species were identified: ∼160 mg in the peels and ∼140 mg in the pulp per kilogram of oranges, expressed as "milligram equivalents of d18:1,17:0 Cer". The predominant ceramides contained 4-hydroxy-8-sphingenine (t18:1(Δ8)) and 4-hydroxysphinganine (t18:0) as long-chain bases (LCBs) and fatty acids (FAs) with different structures. In the pulp, t18:1(Δ8)- and t18:0-containing Cer species comprised 50.5 and 33.5% of the total, respectively, 11.5 and 3.5% non-hydroxylated FAs, respectively, 32.0 and 21.0% α-hydroxylated FAs, respectively, and 7.0 and 9.0% α,β-hydroxylated FAs, respectively. In the peels, t18:1(Δ8)- and t18:0-containing species comprised 49.5 and 34.5% of the total, respectively, 16.0 and 1.5% non-hydroxylated FAs, respectively, 31.5 and 29.0% α-hydroxylated FAs, respectively, and 2.0 and 4.0% α,β-hydroxylated FAs, respectively.


'Nobody will put baby in the corner!': A qualitative evaluation of a physical activity intervention to improve mental health.
Physical activity is beneficial for mental health, but people with mental health issues are less likely to be physically active than the general population. Socially prescribed programmes of activity are rarely adhered to, with high levels of drop out, and the proportion of people who continue after programmes have finished is even smaller. Lasting change therefore needs a fundamental change in behaviour, so an intervention grounded in behaviour change theory may be more likely to succeed. The aim of this original study was to understand the facilitators and barriers to participation and adherence to a supportive, personalised, physical activity programme for patients with mental health conditions. The intervention entailed a 16-week programme of activity, tailored to individual capability, supported by a dedicated 'behaviour change' practitioner trained in motivational interviewing. Fourteen people who had completed the intervention were interviewed in three focus groups in 2018. Data were transcribed verbatim then analysed for barriers and facilitators using Framework Analysis and the Theoretical Domains Framework. Twenty-five overarching themes were identified, which mapped onto 11 domains from the framework. Ten themes were barriers and 15 facilitators. Barriers included stigma, negative self-beliefs and difficulty trusting others. The facilitators reframed these negative attributes. For example, participants described feeling confident as a function of achieving personalised goals and learning something new. The intervention changed the way participants thought and acted. This original intervention has succeeded where many have failed, as it changed the way these participants with mental health conditions thought about physical activity. By reframing it as personally achievable and physically beneficial, participants' attitudes and behaviour changed as well, making it more likely they would sustain physical activity in future. These unique findings are likely to translate internationally due to the simplicity of the intervention, and the potential to improve lives of the most vulnerable.


[Expansion of HIV counseling and testing strategies: technical challenges and ethical-political tensions].
Incentives to provide universal access to antiretroviral therapy in order to control the HIV/AIDS epidemic also encouraged the diversification of HIV testing strategies, as demonstrated by the simultaneous existence of Voluntary Counseling and Testing (VCT) and Provider-Initiated HIV Testing and Counseling (PITC). This paper analyzes the concepts, principles and implementation of the VCT and PITC models regarding counseling, confidentiality and informed consent in Brazil and other countries, based on a literature review of works in the Lilacs, Medline, Sociological Abstracts and Cochrane databases published between 2000 and 2013. According to the literature, PITC increases rates of testing in comparison with VCT, but reduces sexual and reproductive rights and the autonomy of users. These findings suggest technical challenges and ethical tensions between the paradigm of exceptionalism and the normalization of HIV testing. The necessity to reconcile increased access to HIV tests with the local capacity to offer comprehensive care for people living with HIV/AIDS is highlighted. It is recommended that interdisciplinary studies about the social effects of VCT and PITC be amplified.


Exploration of transformational and distributed leadership.
Throughout government policy in Scotland, a new emphasis has been placed on clinical leaders as a way to improve quality and restore the public's confidence in health care. This article reports on a study that explored the leadership styles of senior charge nurses and the effects these may have on clinical teams. Findings suggest that, where there is transformational leadership and sharing of leadership roles across teams, staff are more engaged and organisational goals are met. The findings also highlight the need for better communication between senior management and clinical teams to ensure sustainable, good services.


Site-specific recombinases for manipulation of the mouse genome.
Site-specific recombination systems are widespread and popular tools for all scientists interested in manipulating the mouse genome. In this chapter, we focus on the use of site-specific recombinases (SSR) to unravel the function of genes of the mouse. In the first part, we review the most commonly used SSR, Cre and Flp, as well as the newly developed systems such as Dre and PhiC31, and we present the inducible SSR systems. As experience has shown that these systems are not as straightforward as expected, particular attention is paid to facts and artefacts associated with their production and applications to study the mouse genome. In the next part of this chapter, we illustrate new applications of SSRs that allow engineering of the mouse genome with more and more precision, including the FLEX and the RMCE strategies. We conclude and suggest a workflow procedure that can be followed when using SSR to create your mouse model of interest. Together, these strategies and procedures provide the basis for a wide variety of studies that will ultimately lead to the analysis of the function of a gene at the cellular level in the mouse.


Neonatal Development in Prenatally Zika Virus-Exposed Infant Macaques with Dengue Immunity.
Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment.


Anti-human hepatocellular carcinoma effects of tumor necrosis factor-related apoptosis-inducing ligand in vitro & in vivo.
To investigate the effect of over-expression of Bcl-2 protein on Trail protein-induced apoptosis in human hepatoma cells, and the cytotoxicity of Trail protein on human hepatoma cells in vitro and in vivo. The Trail gene was cloned and expressed in E coli. The cytotoxicity of the recombinant Trail protein was assayed on human hepatoma cells in vitro and in vivo. The cell viability was assessed by trypan blue exclusion. The stable human hepatoma cells clone in which Bcl-2 protein over-expressed was established by transfecting eukaryotic expression plasmid pcDNA3-Bcl-2 into BEL-7404 human hepatoma cells, and was selected with G418 400 mg/L. The recombinant Trail protein actively killed human hepatoma cells tested in this study such as BEL-7404, BEL-7402, and SMMC-7721. Over-expression of Bcl-2 protein could inhibit apoptosis induced by Trail in BEL-7404 human hepatoma cells in vitro. It was obvious that the purified recombinant Trail protein could inhibit tumor formation of BEL-7404 human hepatoma cells in nude mice. The recombinant Trail protein could kill human hepatoma cells in vitro and in vivo. Over-expression of Bcl-2 protein could inhibit Trail-induced apoptosis in BEL-7404 human hepatoma cells. The results suggested that Trail might be a potential agent for the liver cancer therapy.


Topographic peculiarities of the submucous plexus in the human anorectum--consequences for histopathologic evaluation of rectal biopsies.
Chronic colorectal motility disorders are commonly encountered in the pediatric population. While most cases can be managed successfully by conservative therapy, a subgroup of patients suffers from severe constipation and requires further diagnostic procedures to identify the underlying pathologies, such as aganglionosis, hypoganglionosis or intestinal neuronal dysplasia (IND). The present study provides reference data about the quantitative distribution of nerve cells and ganglia within the submucosal plexus of the human anorectum from healthy subjects. Anorectal specimens (n = 15) obtained postmortem were divided into 6 segments beginning from the dentate line (S1 = 0-2 cm, S 2 = 2-4 cm, S3 = 4-6 cm, S4 = 6-8 cm, S5 = 8-10 cm, S6 = 10-12 cm). From each segment sections (6 microm thickness) were immunostained with a pan-neuronal marker (Protein Gene Product 9.5) to visualize the enteric nervous system. A morphometric analysis was carried out for each segment recording the number of ganglia and nerve cells of the submucous plexus. Neither ganglia nor nerve cells showed a uniform distribution pattern, but decreased continuously towards the anus. However, even the lowest segments (S1, S2) contained nerve cells and were not aganglionic. In the remaining segments ganglia with 7 or more nerve cells could be detected. The findings demonstrate segment-specific quantitative differences of the anorectal submucous plexus which should be taken into consideration for the histopathologic evaluation of rectal biopsies. Moreover, the data support the concept of a physiologic hypoganglionosis of the anal canal.