Positive attitudes towards feline obesity are strongly associated with ownership of obese cats.
Overweight and obesity (O&O) is a risk factor for several health conditions and can result in a shorter lifespan for cats. The objectives of this study were to investigate (a) cat owners' attitudes towards feline O&O and their associations with O&O in their cats; and (b) the risk factors for feline O&O and underweight, particularly those involving owner practice. An online survey comprising questions related to cat owners' attitudes towards feline O&O, owner-reported body weight and body condition of their cat, and potential risk factors for feline O&O was conducted. Primarily targeting the Australian population, the survey attracted 1,390 valid responses. In response to ten attitude-related questions, more participants (percentage range among the ten questions: 39.1-76.6%) held a disapproving attitude towards feline O&O than a neutral (17.1-31.9%) or approving attitude (3.9-27.7%). A greater proportion of participants had a more disapproving attitude towards obesity than towards overweight. Cats belonging to owners with an approving attitude towards O&O were more likely to be overweight or obese than cats belonging to owners with a disapproving attitude towards O&O. The cats had particularly high odds of overweight or obesity if their owner agreed that 'being chubby says that the cat has a quality life' (OR: 3.75, 95% CI: 2.41-5.82) and 'being fat says that the cat has a quality life' (OR: 4.98, 95%CI: 2.79-8.91). This study revealed, for the first time, that begging for food was a risk factor for O&O in cats. Other important feline risk factors for O&O identified included being middle-aged, being mixed-breed, dry food as the major diet, the amount of feed not being quantified, and frequently spending time indoors. Being over 11 years, receiving no dry food and receiving measured amounts of feed were associated with an increased odds of underweight in cats. As specific attitudes often lead to certain behaviours, reducing approving attitudes towards feline O&O may potentially reduce the frequency of O&O and the risks of O&O-related disorders in cats.


Localized maxillary ridge augmentation with a block allograft for dental implant placement: case reports.
Autogenous block bone grafts have been highly successful in treating human periodontal defects, restoring esthetics, and developing adequate bone volume for dental implant placement. Limitations in available donor bone, the need for an added surgical procedure, and other potential complications have made the use of allogenic bone graft materials an important alternative. One patient described in this report presented with fractured root syndrome of the right maxillary incisor with severe resorption of the buccal plate. After atraumatic tooth extraction, a staged treatment approach involving localized ridge augmentation with an allogenic iliac bone block material and dental implant placement was used. The host bone completely incorporated the graft with only minor resorption, which enabled the implant to be placed. The allogenic bone block material used in this study was an effective alternative to harvesting and grafting autogenous bone for implant site development. The cases presented in this article clinically demonstrate the efficacy of using a block allograft in generating effective new bone fill for dental implant placement.


Conceptual Models of Social Determinants of Health: A Narrative Review.
There are several conflicting conceptual models to explain social determinants of health (SDH) as responsible for most health inequalities. This study aimed to present these models in historical perspective and provide main component of SDH models as an SES indicators. This was a narrative study using international databases to retrieve literature dealing with conceptual models of SDH. All publication in English language until Mar 2015 was included. The CASP and PRISMA were used to summarize the literature. Overall, 248 publications were retrieved and screened. After exclusion of irrelevant and duplicates, 94 citations were found to be relevant and 21 publications included in this review. In general, 21 models of SDH were found: some models presented before year 1995(n=4), some models presented between 1995 and 2005 (n=13) and some models presented after 2005 (n=4). However, we found three categories of indicators that contribute to SDH models and that were classic factors, fixed and demographic factors and proxy factors. Reduction of socioeconomic inequalities in health requires understanding of mechanisms and causal pathways; therefore, every country needs to design the specific model. As the available models are for developed countries, lack of a specific model for developing ones is tangible. As there is no gold standard related to SES indicators, therefore, it is proposed to use the various indicators based on life course approach, which leads to understanding and adopting effective policy interventions.


Trauma rehabilitation in a teaching hospital in Antananarivo, Madagascar: current provision and patients' perspectives.
Purpose: This study aims to describe the current provision of trauma rehabilitation in Antananarivo, Madagascar and explore the experiences and perspectives of users of this service in order to inform future research and service development.Material and methods: A qualitative study supplemented by a descriptive service review were applied in the central government hospital in Antananarivo. Registers in the rehabilitation department were analyzed for a 3 month period. Semi-structured interviews were conducted with a convenience sample of users of the rehabilitation service and were subject to thematic analysis.Results: One in six patients treated in the rehabilitation department has survived a traumatic injury, with limb injuries comprising the majority. Analysis of interviews with 10 adult patients, following traumatic injuries to the lower limbs (6), upper limbs (3) or polytrauma (1) generated seven broad themes: health seeking behavior, organization of services, clinical management, costs and financial impact, effect on function and role, psychological impact and societal attitudes.Conclusions: Financial constraints and impact on personal finances pervade the overall picture. The perspectives and experiences elucidated will inform future research into the development of context-specific models of care for people with trauma-related disabilities in Madagascar.Implications for rehabilitationPotentially treatable traumatic injury can have a profound effect on function and societal participation in Madagascar.Interventions to increase access to timely acute trauma care and rehabilitation are needed, and may include different models of financing and innovations to reduce materials costs and length of stay.A structured rehabilitation pathway must be integrated to the earliest stages of trauma care, including scrutinizing the use of prolonged immobilization.Consideration should be given to models of care which are financially and geographically accessible to the population.


Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Georgia, USA, February 1-July 13, 2020.
The serial interval and effective reproduction number for coronavirus disease (COVID-19) are heterogenous, varying by demographic characteristics, region, and period. During February 1-July 13, 2020, we identified 4,080 transmission pairs in Georgia, USA, by using contact tracing information from COVID-19 cases reported to the Georgia Department of Public Health. We examined how various transmission characteristics were affected by symptoms, demographics, and period (during shelter-in-place and after subsequent reopening) and estimated the time course of reproduction numbers for all 159 Georgia counties. Transmission varied by time and place but also by persons' sex and race. The mean serial interval decreased from 5.97 days in February-April to 4.40 days in June-July. Younger adults (20-50 years of age) were involved in most transmission events occurring during or after reopening. The shelter-in-place period was not long enough to prevent sustained virus transmission in densely populated urban areas connected by major transportation links.


Topographic analysis of flash visual evoked potentials in dogs.
Visual evoked potentials by flash stimulation (flash VEP) were analyzed in dogs using a topographic method. The flash VEP consisted of 3 positive (P1, P2 and P3) and 2 negative (N1 and N2) components by 150 msec after the flash stimuli. On the topographic mappings, a negative response area was observed in the frontal region of the scalp in the stimulated site followed by the shifting of the area to the contralateral frontal region and occipital region, during the first 100 msec. The negative response area in the frontal region in the stimulated site, contralateral frontal and temporal region, and occipital region were corresponded to N1, P2, and N2 on the flash VEP, respectively, according to their latencies. In the dogs with experimentally impaired the right lateral geniculate body, the latency of P2 was prolonged, and N2 and P3 were disappeared after the left eye stimulation. On the topographic mapping, only the early negative response area was detected on the stimulated site of the frontal region of the brain. Therefore, it is concluded that P1 and N1, P2, and N2 are referred to the retinal potentials, the potentials from the retina to the brainstem included the lateral geniculate body, and those from the brainstem to the visual cortex, respectively.


Receptor-mediated endocytosis of apamin by liver cells.
The binding and uptake of the bee venom toxin apamin, by guinea-pig and rat liver were studied. Guinea-pig liver plasma membranes contain inhibitable, high-affinity binding sites for [125I]monoiodoapamin: Kd = 12.6 +/- 0.8 pM (SE); Bmax = 4.2 +/- 0.2 fmol/mg protein. No binding sites for [125I]monoiodoapamin on rat liver plasma membranes were detected in agreement with the absence of a physiological response to the toxin by rat hepatocytes. [125I]Monoiodoapamin, injected into the portal vein of guinea-pigs, was recovered in an undegraded form in a liver endosome fraction. The uptake of [125I]monoiodoapamin by rat livers was less than 4% of that taken up by guinea-pig livers and there was little evidence of radiolabelled toxin appearing in isolated rat endocytic vesicles. Inhibitable, high-affinity binding sites for [125I]monoiodoapamin were also identified on isolated guinea-pig liver endosomal membranes; Kd = 10.6 +/- 3.3 pM; Bmax = 2.5 +/- 0.6 fmol/mg protein. No inhibitable apamin binding sites were detected on rat endosomal membranes. Plasma membranes and endosomal membranes isolated from guinea-pig liver showed a similar spectrum of polypeptides to that previously reported for plasma membranes and endosomal membranes isolated from rat liver. The enzymatic composition of guinea-pig endosomes was also similar to that previously reported for rat endosomes. The results indicate that apamin was internalised by receptor-mediated endocytosis by guinea-pig liver cells in an analogous manner to that already shown for a variety of endogenous ligands.


Effect of Kangshuanyihao Formula on the Inflammatory Reaction and SIRT1/TLR4/NF-κB Signaling Pathway in Endothelial Injury.
Endothelial injury plays an important role in atherosclerosis (AS). Kangshuanyihao formula uses therapeutic principles from Chinese medicine to supplement Qi, thereby promoting blood circulation, and remove blood stasis. The mechanism by which the formula inhibits endothelial injury was examined in a rat model of 1,25-dihydroxyvitamin D3 (VD3) intraperitoneal injection and high-fat-induced endothelial injury. Rats were randomly divided into the model, high-dose, middle-dose, low-dose, positive drug (rosuvastatin), and combination (positive drug + middle-dose) groups; 10 Sprague-Dawley rats served as the blank group. The aortic endothelium was stained with hematoxylin and eosin and the levels of blood lipids and inflammation markers (mRNA and protein) were measured. Endothelial injury, lipid levels, and inflammation were increased in the model. Kangshuanyihao formula reduced endothelial injury, improved lipid levels, and downregulated inflammation, as shown by significant reduction of the protein levels of SIRT1, TLR4, and NF-κB and mRNA levels of SIRT1, TLR4, NF-κB, IL-1β, IL-6, and IL-12. Thus, we conclude that Kangshuanyihao formula can inhibit the inflammatory reaction in the rat model of high-fat-induced endothelial injury after intraperitoneal injection of VD3. This mechanism may be attributed to regulating the SIRT1/TLR4/NF-κB signaling pathway.


Separation of peptides on mixed mode of reversed-phase and ion-exchange capillary electrochromatography with a monolithic column.
The mixed mode of reversed phase (RP) and strong cation-exchange (SCX) capillary electrochromatography (CEC) based on a monolithic capillary column has been developed. The capillary monolithic column was prepared by in situ copolymerization of 2-(sulfooxy)ethyl methacrylate (SEMA) and ethylene dimethacrylate (EDMA) in the presence of porogens. The sulfate group provided by the monomer SEMA on the monolithic bed is used for the generation of the electroosmotic flow (EOF) from the anode to the cathode, but at the same time serves as a SCX stationary phase. A mixed-mode (RP/SCX) mechanism for separation of peptides was observed in the monolithic column, comprising hydrophobic and electrostatic interaction as well as electrophoretic migration at a low pH value of mobile phase. A column efficiency of more than 280,000 plates/m for the unretained compound has been obtained on the prepared monoliths. The relative standard deviations observed for t(0) and retention factors of peptides were about 0.32% and less than 0.71% for ten consecutive runs, respectively. Effects of mobile phase compositions on the EOF of the monolithic column and on the separation of peptides were investigated. The selectivity on separation of peptides in the monolithic capillary column could be easily manipulated by varying the mobile phase composition.


Significance of conservative asparagine residues in the thermal hysteresis activity of carrot antifreeze protein.
The approximately 24-amino-acid leucine-rich tandem repeat motif (PXXXXXLXXLXXLXLSXNXLXGXI) of carrot antifreeze protein comprises most of the processed protein and should contribute at least partly to the ice-binding site. Structural predictions using publicly available online sources indicated that the theoretical three-dimensional model of this plant protein includes a 10-loop beta-helix containing the approximately 24-amino-acid tandem repeat. This theoretical model indicated that conservative asparagine residues create putative ice-binding sites with surface complementarity to the 1010 prism plane of ice. We used site-specific mutagenesis to test the importance of these residues, and observed a distinct loss of thermal hysteresis activity when conservative asparagines were replaced with valine or glutamine, whereas a large increase in thermal hysteresis was observed when phenylalanine or threonine residues were replaced with asparagine, putatively resulting in the formation of an ice-binding site. These results confirmed that the ice-binding site of carrot antifreeze protein consists of conservative asparagine residues in each beta-loop. We also found that its thermal hysteresis activity is directly correlated with the length of its asparagine-rich binding site, and hence with the size of its ice-binding face.


Unravelling Vaccine Scepticism in South Tyrol, Italy: A Qualitative Analysis of Personal, Relational, and Structural Factors Influencing Vaccination Decisions.
Low vaccine uptake in South Tyrol, particularly for non-coronavirus and SARS-CoV-2 vaccines, poses a significant public health challenge in the northernmost province of Italy. This qualitative study conducted in-depth interviews with a purposive sample of vaccine-sceptical parents to examine the factors that contribute to their vaccination decisions. The ten participants' children had varied vaccination statuses, ranging from unvaccinated to partially vaccinated or vaccinated as late as possible. Only one adult participant received the SARS-CoV-2 vaccine. Using Grounded Theory analysis, the emergent meta-category of 'self-relatedness' was identified, highlighting the importance of individual experiences and the social context. The study found that participants' social circles consisted of individuals with similar vaccination attitudes, often characterized by a shared affinity for nature. Although they accepted individuals with different views, they remained uninfluenced. Participants perceived healthcare professionals as one-sided and uncritical, expressing distrust toward state orders. They believed that parents should be responsible for their children's well-being rather than the state. Distrust in the state and healthcare system, exacerbated by the SARS-CoV-2 pandemic, was rooted in negative experiences. In contrast, the participants had positive experiences with natural healing, homeopathy, and trusting the natural course of events. They perceived themselves as tolerant, non-radical, curious, health-conscious, yet critical and questioning. Participants resisted coercion, fear-mongering, and state sanctions and sought alternatives to mandatory vaccination. To address the complex social and behavioural factors underlying vaccination refusal, this study suggests that vaccination advocates, policymakers, and information providers should engage in appreciative, personal, and well-founded information exchanges with vaccine-hesitant individuals. Broad and comprehensible information dissemination, flexibility, and freedom of decision are essential for increasing informed decision making. Further research is required to better understand the epistemic basis of vaccine hesitancy.


Atmospheric contamination in the city of Valencia: relation to noise and climate.
A qualitative and quantitative study is made of the polycyclic aromatic hydrocarbons (PAH), nitrogen oxide, and sulfur dioxide in the atmosphere of the city of Valencia for the period 1988-1989; an analysis is made of their concentrations during the year in terms of season and noise levels. Eleven sampling points in the city were used to determine PAH composition by reverse-phase, high-resolution liquid chromatography with fluorimetric detection, employing an acetonitrile-water gradient; nitrogen oxides and sulfur dioxide were determined by the Valencia city government. Environmental noise levels were determined using a BK 2221 integrated precision sonometer, and temperature values were obtained from the city Meteorological Institute. Daily PAH values varied between 0.1769 and 2.0916 micrograms/m3, whereas the figures for nitrogen oxide were between 91.5 and 100.67 micrograms/m3 during 1982-1989 (only one value, 58.01 micrograms/m3, is available for 1988-1989, corresponding to the Mercadona sampling point), and between 17.33 and 129.36 micrograms/m3 for sulfur dioxide for a total of 9 sampling points; the highest concentrations were recorded in the winter and spring months, the association between PAH and temperature being statistically significant (p less than or equal to .05). The relation to noise was also significant (p less than or equal to .005), Fluoranthene was the predominant PAH in all samples analyzed.


Interactions among COX-2, GPIIIa and P2Y1 variants are associated with aspirin responsiveness and adverse events in patients with ischemic stroke.
The effect of gene variants and their interactions on response to aspirin and clinical adverse outcomes after an acute ischemic stroke (IS) is not fully understood. The aim of this study was to investigate the association of aspirin-relevant gene variants and their interactions with clinical adverse outcomes in IS patients taking aspirin. A total of 14 variants from six genes encoding COX enzymes (COX-1, COX-2), platelet membrane receptors (TXAS1, P2Y1, P2Y12) and glycoprotein receptor (GPIIIa) were examined in 850 acute IS patients. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients were followed up for 1 year after admission. Primary outcome was a composite of recurrent ischemic stroke (RIS), myocardial infarction (MI) and death. The primary outcome occurred in 112 (13.5%) patients (81 RIS, 16 MI and 15 deaths). There were no significant differences in the frequencies of the genotypes of the 14 variants between the patients with and without primary outcome using single-locus analytical approach. However, there was significant gene-gene interaction among rs20417, rs1371097 and rs2317676. The high-risk interactive genotypes of rs20417, rs1371097 and rs2317676 were independently associated with primary adverse outcome of RIS, MI, and death after acute IS. The three-loci interactions are associated with sensitivity of IS patients to aspirin and aspirin-induced adverse clinical events. The combinatorial analysis used in this study may be helpful to elucidate complex genetic risk of aspirin resistance (AR). The study described here is registered at http://www.chictr.org/ (unique identifier: ChiCTR-OCH-14004724).


Effects of drug and exercise intervention on functional capacity and quality of life in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.
Patients with heart failure with preserved ejection fraction (HFpEF) are often elderly and their primary chronic symptom is severe exercise intolerance that results in a reduced quality of life (QOL).Thus, improvement of exercise capacity and QOL presents an important clinical outcome in HFpEF patients. Although the effects of interventions such as cardiovascular drugs and exercise training on exercise capacity and QOL in HFpEF patients have been examined in a number of clinical trials, the results are inconsistent due in part to limited power with small sample sizes. We aimed to conduct a meta-analysis of the randomized controlled trial (RCT)s on the effect of drug or exercise intervention on exercise capacity and QOL in HFpEF patients. The search of electronic databases identified five RCTs on exercise (245 patients) and eight RCTs on cardiovascular drugs (1080 patients). The pooled analysis showed that exercise training improved peak exercise oxygen uptake (VO2) (weighted mean difference (WMD) 2.283, 95% confidence interval (CI)) (1.318-3.248) ml/min/kg), six-minute walk distance (6MWD) (30.275 m (4.315-56.234)), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) total score (8.974 points (3.321-14.627)) compared with usual care. In contrast, drug intervention did not improve peak VO2 (WMD (95% CI), -0.393 (-1.005-0.220) ml/min/kg), 6MWD (-9.463 (-21.455-2.530) m), or MLHFQ total score (1.042 (-0.982-3.066) point) compared with placebo or no treatment. Our meta-analysis indicates that exercise training may be a therapeutic option to improve functional capacity and QOL in HFpEF patients.


Evaluation of spatial and seasonal radioactivity dose fluctuations in a Wierzchowska Górna limestone cave.
Measurements of the dose rate changes were carried out in order to assess seasonal and spatial radioactivity variations in the largest limestone cave of the Polish Jura Wierzchowska Górna. Thermoluminescence detectors, which were annealed, calibrated and protected against humidity were used. Measurements were repeated four times in 13 locations to observe possible changes. The external dose rate was in the range of 0.004-0.106 mGy/quarter. The results were influenced by the detector locations - lower doses were estimated closer to the cave entrance and the highest doses were in the so-called 'primitive man room'. Doses measured in four periods were statistically significantly different. The external dose level as well as seasonal and spatial dose changes measured in the cave were low. In other caves where external doses are higher, seasonal and spatial dose changes may have a stronger impact on radiological hazard.


Goblet-like cells in atrophic vaginal smears and their histologic correlation. Possible confusion with endocervical cells.
The occurrence and origin of goblet-like cells seen between clusters of parabasal cells in atrophic vaginal smears were investigated. The goblet-like cells were cytologically identified in the vaginal smears from 23 (19.2%) of 120 patients whose smears showed an atrophic pattern, but without any inflammatory, dysplastic or malignant changes. Histologically, these cells were found in sections from 6 (18.8%) of 32 elderly women with atrophic vaginal epithelium. The goblet-like cells were situated among the squamous cells of the upper layer of the atrophic squamous epithelium from the vagina to the portio. These goblet-like cells in atrophic smears were initially misinterpreted as endocervical cells, which are regarded as a marker of smear adequacy in the cytologic screening for cancer of the uterine cervix. The correct interpretation of these goblet-like cells in smears from postmenopausal and elderly women is thus obviously important in assessing the adequacy of the sample for the detection of abnormal cells.


Love and loss. Conversations with parents of babies with spinal bifida managed without surgery, 1971-1981.
Looking back over the span of years surveyed, it appears that a sad experience, even many years ago, commonly leaves residual pain. This can be modified by sympathetic support enabling parents and baby to interact, although such interaction is not without painful as well as pleasurable effects. Coming to terms with loss may take longer than was previously thought. This study highlights the need for bereavement care, which aims to leave families with positive rather than negative feelings. Perhaps, for mental health, the eventual feelings about past happenings are more important than the happenings themselves, although we have also shown that a greater insight into the needs of parents at the time modified their long-term feelings for the good, some even indicating that they had been enriched by the whole experience. The interviews suggested that parents who were involved with their baby's care were more able to accept the reality of their loss and to adjust to the experience of pain and grief than was possible for those who had been kept apart from their children. This supports conclusions by other grief counsellors (e.g. Warden 1983).


Power and Area Efficient Cascaded Effectless GDI Approximate Adder for Accelerating Multimedia Applications Using Deep Learning Model.
Approximate computing is an upsurging technique to accelerate the process through less computational effort while keeping admissible accuracy of error-tolerant applications such as multimedia and deep learning. Inheritance properties of the deep learning process aid the designer to abridge the circuitry and also to increase the computation speed at the cost of the accuracy of results. High computational complexity and low-power requirement of portable devices in the dark silicon era sought suitable alternate for Complementary Metal Oxide Semiconductor (CMOS) technology. Gate Diffusion Input (GDI) logic is one of the prompting alternatives to CMOS logic to reduce transistors and low-power design. In this work, a novel energy and area efficient 1-bit GDI-based full swing Energy and Area efficient Full Adder (EAFA) with minimum error distance is proposed. The proposed architecture was constructed to mitigate the cascaded effect problem in GDI-based circuits. It is proved by extending the proposed 1-bit GDI-based adder for different 16-bit Energy and Area Efficient High-Speed Error-Tolerant Adders (EAHSETA) segmented as accurate and inaccurate adder circuits. The proposed adder's design metrics in terms of delay, area, and power dissipation are verified through simulation using the Cadence tool. The proposed logic is deployed to accelerate the convolution process in the Low-Weight Digit Detector neural network for real-time handwritten digit classification application as a case study in the Intel Cyclone IV Field Programmable Gate Array (FPGA). The results confirm that our proposed EAHSETA occupies fewer logic elements and improves operation speed with the speed-up factor of 1.29 than other similar techniques while producing 95% of classification accuracy.


Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1.
Mst1 is a ubiquitously expressed serine-threonine kinase, homologous to the budding yeast Ste20, whose physiological regulation and cellular function are unknown. In this paper we show that Mst1 is specifically cleaved by a caspase 3-like activity during apoptosis induced by either cross-linking CD95/Fas or by staurosporine treatment. CD95/Fas-induced cleavage of Mst1 was blocked by the cysteine protease inhibitor ZVAD-fmk, the more selective caspase inhibitor DEVD-CHO and by the viral serpin CrmA. Caspase-mediated cleavage of Mst1 removes the C-terminal regulatory domain and correlates with an increase in Mst1 activity in vivo, consistent with caspase-mediated cleavage activating Mst1. Overexpression of either wild-type Mst1 or a truncated mutant induces morphological changes characteristic of apoptosis. Furthermore, exogenously expressed Mst1 is cleaved, indicating that Mst1 can activate caspases that result in its cleavage. Kinase-dead Mst1 did not induce morphological alterations and was not cleaved upon overexpression, indicating that Mst1 must be catalytically active in order to mediate these effects. Mst1 activates MKK6, p38 MAPK, MKK7 and SAPK in co-transfection assays, suggesting that Mst1 may activate these pathways. Our findings suggest the existence of a positive feedback loop involving Mst1, and possibly the SAPK and p38 MAPK pathways, which serves to amplify the apoptotic response.


Chiropractic Management of Neck Pain Complicated by Symptomatic Vertebral Artery Stenosis and Dizziness.
BACKGROUND Vertebrobasilar insufficiency (VBI) is most often caused by vertebrobasilar atherosclerosis, often presenting with dizziness and occasionally neck pain. Little research or guidelines regarding management of neck pain in affected patients exists. CASE REPORT A 62-year-old male hypertensive smoker presented to a chiropractor with a 13-year history of insidious-onset neck pain, dizziness, and occipital headache with a Dizziness Handicap Inventory (DHI) of 52%. The patient had known VBI, caused by bilateral vertebral artery plaques, and cervical spondylosis, and was treated with multiple cardiovascular medications. The chiropractor referred patient to a neurosurgeon, who cleared him to receive manual therapies provided manual-thrust cervical spinal manipulative therapy (SMT) was not performed. The chiropractor administered thoracic SMT and cervicothoracic soft tissue manipulation. The neck pain and dizziness mostly resolved by 1 month. At 1-year follow-up, DHI was 0%; at 2 years it was 8%. A literature search revealed 4 cases in which a chiropractor used manual therapies for a patient with VBI. Including the present case, all patients had neck pain, 60% had dizziness, and all were treated with SMT either avoiding manual cervical manipulation altogether or modifying it to avoid or limit cervical rotation, yielding positive outcomes. CONCLUSIONS The present and previous cases provide limited evidence that some carefully considered chiropractic manual therapies can afford patients with VBI relief from concurrent neck pain and possibly dizziness. Given the paucity of research, cervical SMT cannot be recommended in such patients. These findings do not apply to vertebral artery dissection, for which SMT is an absolute contraindication.


Higher Serum Brain-Derived Neurotrophic Factor Levels Are Associated With a Lower Risk of Cognitive Decline: A 2-Year Follow Up Study in Community-Dwelling Older Adults.
To assess the relationship of serum brain-derived neurotrophic factor (BDNF) levels with the subsequent short-term decline in cognitive functioning in community-dwelling older adults. Two-year prospective, observational study. The study included 405 adults aged 65-84 years, initially free of a dementia diagnosis who were living in Tokyo, Japan. Participants underwent health assessments at baseline (2011) and follow-up (2013). Serum BDNF levels and scores from the Montreal Cognitive Assessment-Japanese version (MoCA-J) were systematically measured. Logistic regression was used to estimate the odds of cognitive decline between baseline and follow-up assessments in the full MoCA-J scale (operationally defined as a decrease of two or more points), as well as in MoCA-J subscales (decline of one or more points in a specific subscale), as a function of serum BDNF level, adjusting for baseline demographics, prevalent chronic diseases, and baseline cognitive scores. Among individuals who performed worse on the full MoCA-J at baseline (i.e., scores in the bottom quartile [≤21], which is consistent with a mild cognitive impairment status), but not among those who performed better (top 3 quartiles), those with highest baseline serum BDNF levels (top quartile) had lower odds of subsequent decline in the full MoCA-J scale than those with lowest (bottom quartile); i.e., odds ratio (OR): 0.10 (95% confidence interval [CI]: 0.02-0.62; p = 0.013). Regarding MoCA-J subscales, adjusted odds of decline in the executive function subscale, but not in the other five subscales, were substantially low among those with highest baseline serum BDNF levels (top quartile), as compared to those with the lowest (bottom quartile), i.e., OR: 0.27 (95% CI:0.13-0.60; p < 0.001). Higher serum BDNF levels were associated with a lower risk of decline in cognitive function in a sample of community-dwelling older Japanese adults. Risk varied across cognitive subdomains and according to baseline cognition. This warrants further research to evaluate the added-value of serum BDNF in health promotion initiatives directed toward cognitive decline prevention in community-dwelling older adults.


Frailty and risk of complications in head and neck oncologic surgery. Systematic review and dose-response meta-analysis.
There is emerging evidence that frail individuals present a decreased physiological reserve, decreased ability to maintain homeostasis, and increased vulnerability to stressors. The concept of frailty has become increasingly recognized as a valuable measure in oncological surgical patients, including those with head and neck cancer. Preoperative screening for frailty may provide an individualized risk assessment that can be used by an interdisciplinary team for preoperative counseling and to improve outcomes. The aim of this meta-analysis was to evaluate the relationship between frailty and the risk of major postoperative complications in frail individuals submitted to head and neck oncologic surgery. PubMed, SCOPUS, Web of Science, Google Scholar and OpenThesis were systematically searched to identify studies that evaluated the risk of major postoperative complications in frail individuals undergoing head and neck oncologic surgery. The search was performed on August 31, 2020, without language or date restrictions. Two independent investigators screened the searched studies based on each paper's title and abstract. Relevant studies were read in full and selected according to the eligibility criteria. Frailty was assessed by modified Frailty Index (mFI-11) and major postoperative complications were measured by the Clavien-Dindo classification. We performed a categorical and dose-response meta-analysis using a random-effects model to evaluate the association between frailty and the risk of major postoperative complications in patients submitted to head and neck oncologic surgery. The results of the meta-analysis were expressed as relative risk (RR) and 95% confidence interval (95% CI). The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Four studies (9,947 patients) were included in this systematic review and meta-analysis. Frail patients presented an increased risk of life-threatening complications requiring intensive care unit (ICU) admission (RR = 4.67; 95% CI 1.54-14.10) and 30-day mortality (RR = 8.10; 95% CI 2.30-28.57) compared to non-frail patients. We found evidence of dose-response trend between mFI-11 and major postoperative complications. Higher frailty scores are associated with a significant increase in ICU-level complications and 30-day mortality after head and neck oncologic surgery.


Analysis of codon usage bias of mitochondrial genome in Bombyx mori and its relation to evolution.
Synonymous codon usage bias (SCUB) is an inevitable phenomenon in organismic taxa, generally referring to differences in the occurrence frequency of codons across different species or within the genome of the same species. SCUB happens in various degrees under pressure from nature selection, mutation bias and other factors in different ways. It also attaches great significance to gene expression and species evolution, however, a systematic investigation towards the codon usage in Bombyx mori (B. mori) has not been reported yet. Moreover, it is still indistinct about the reasons contributing to the bias or the relationship between the bias and the evolution of B. mori. The comparison of the codon usage pattern between the genomic DNA (gDNA) and the mitochondrial DNA (mtDNA) from B. mori suggests that mtDNA has a higher level of codon bias. Furthermore, the correspondence analysis suggests that natural selection, such as gene length, gene function and translational selection, dominates the codon preference of mtDNA, while the composition constraints for mutation bias only plays a minor role. Additionally, the clustering results of the silkworm superfamily suggest a lack of explicitness in the relationship between the codon usage of mitogenome and species evolution. Among the complicated influence factors leading to codon bias, natural selection is found to play a major role in shaping the high bias in the mtDNA of B. mori from our current data. Although the cluster analysis reveals that codon bias correlates little with the species evolution, furthermore, a detailed analysis of codon usage of mitogenome provides better insight into the evolutionary relationships in Lepidoptera. However, more new methods and data are needed to investigate the relationship between the mtDNA bias and evolution.


Impact of the anatomical location and the number of metastatic lymph nodes on gastric cancer patient´s survival.
The most serious problem in surgical treatment of gastric cancer includes the area of resection and the extent of lymphadenectomy. The extent of gastric resection is determined by the extent of tumor affection. The aim of radical surgical intervention is to achieve microscopically clear resection line, since R0 resection is the main criterion for the patient´s prognosis. Curative surgical resection for gastric cancer includes the lymph nodes dissection. In the treatment of gastric cancer, there are two views on the importance of lymphadenectomy. The Far East considers that operation improves the survival and the Europe considers that surgery is not curative, but it determines the staging and prognosis. There is also a difference in staging systems. The one from East is importance based on the anatomical location of affected lymph nodes, the second from Europe is based on the number of positive lymph nodes. This work is a retrospective observational study. In the study cohort, comparing the survival of patients according to different classification systems, depending on the N-stage of disease, 119 patients with gastric adenocarcinoma in clinical stage I to III, i.e. without metastasis, who underwent a radical surgical resection with D2 lymphadenectomy, were enrolled. For the evaluation of the survival versus the time after operation, we used Kaplan‒Meier method. To evaluate the correlation between the survival rate and the explanatory variables, Cox regression and Kendall correlation coefficient were used. The median survival, according to different classification systems, depending on the N-stage of the disease, was significantly correlated with the survival for the 6th and 7th editions of TNM classification system for the Japanese classification system, for N-ratio classification system).The new finding was differentiation of patients in groups N1 vs N2 under the 6th TNM classification (HR=0.910249), also a little differentiation in groups N1 vs N2 according to the classification of N-ratio (HR=0.8750926) and equally a poor differentiation in the survival in groups N2 vs N3 according to the 7th TNM classification (HR=0.881797).The strongest correlation reached the Japanese classification system, but not significantly different from the 6th TNM classification system. In the 7th edition of TNM classification system, we then found the weakest correlation with the survival time, but not significantly different from the previous two. Our retrospective study confirmed the strongest correlation between the patient´s prognosis and the anatomic localization of the affected lymph nodes. This correlation was not statistically significant compared to the correlation between patient´s prognosis and the number of positive lymph nodes. It leads us to the conclusion that both classification systems are comparable and the difference is statistically insignificant (Tab. 4, Fig. 8, Ref. 16).


Positioning-Group-Enabled Biocatalytic Oxidative Dearomatization.
Biocatalysts have the potential to perform reactions with exceptional selectivity and high catalytic efficiency while utilizing safe and sustainable reagents. Despite these positive attributes, the utility of a biocatalyst can be limited by the breadth of substrates that can be accommodated in the active site in a reactive pose. Proven strategies exist for optimizing the performance of a biocatalyst toward unnatural substrates, including protein engineering; however, these methods can be time intensive and require specialized equipment that renders these approaches inaccessible to synthetic chemists. Strategies accessible to chemists for the expansion of a natural enzyme's substrate scope, while maintaining high levels of site- and stereoselectivity, remain elusive. Here, we employ a computationally guided substrate engineering strategy to expand the synthetic utility of a flavin-dependent monooxygenase. Specifically, experimental observations and computational modeling led to the identification of a critical interaction between the substrate and protein which is responsible for orienting the substrate in a pose productive for catalysis. The fundamental hypothesis for this positioning group strategy is supported by binding and kinetic assays as well as computational studies with a panel of compounds. Further, incorporation of this positioning group into substrates through a cleavable ester linkage transformed compounds not oxidized by the biocatalyst SorbC into substrates efficiently oxidatively dearomatized by the wild-type enzyme with the highest levels of site- and stereoselectivity known for this transformation.


Erectsterates A and B, a pair of novel highly degraded steroid derivatives from the South China Sea soft coral Sinularia erecta.
Two novel steroidal derivatives, erectsterates A (1) and B (2), a pair of epimers at C-10, were isolated from the South China Sea soft coral Sinularia erecta. Their structures were established by extensive spectroscopic analysis and deduction from biosynthesis route. Compounds 1 and 2 are rare steroids with a highly degradation in ring B and an ester linkage between A and C/D rings, similar with the known compounds chaxines B (3) and D from an edible mushroom Agrocybe chaxingu. To the best of our knowledge, this is the first report of such kind of steroid from soft coral. And a different biosynthetic route from the reported approach of chaxines was proposed in this paper. Interestingly, the ring C of 1 and 2 was formally oxidized by Baeyer-Villiger reaction to provide an unprecedented seven-membered lactone moiety in ring C of steroid. The in vitro anti-proliferative activities of 2 were evaluated against A549, HT-29, SNU-398 and Capan-1 cell lines. The results indicated that it showed weak cytotoxicity against the tested four cell lines.


Characterisation of Aronia powders obtained by different drying processes.
Nowadays, food industry is facing challenges connected with the preservation of the highest possible quality of fruit products obtained after processing. Attention has been drawn to Aronia fruits due to numerous health promoting properties of their products. However, processing of Aronia, like other berries, leads to difficulties that stem from the preparation process, as well as changes in the composition of bioactive compounds. Consequently, in this study, Aronia commercial juice was subjected to different drying techniques: spray drying, freeze drying and vacuum drying with the temperature range of 40-80 °C. All powders obtained had a high content of total polyphenols. Powders gained by spray drying had the highest values which corresponded to a high content of total flavonoids, total monomeric anthocyanins, cyaniding-3-glucoside and total proanthocyanidins. Analysis of the results exhibited a correlation between selected bioactive compounds and their antioxidant capacity. In conclusion, drying techniques have an impact on selected quality parameters, and different drying techniques cause changes in the content of bioactives analysed. Spray drying can be recommended for preservation of bioactives in Aronia products. Powder quality depends mainly on the process applied and parameters chosen. Therefore, Aronia powders production should be adapted to the requirements and design of the final product.


Noise characterization and compensation for a charge-coupled-device-based pyrometer.
The pyrometer based on the charge coupled device (CCD) is a cost-effective and widely used system for temperature measurement in various industrial fields. However, due to the inter-element sensitivity deviations of the CCD-array detector and the influence of various types of noise, the digital signal output of the CCD sensor itself is not completely equal to the ideal value as expected. In this work, based on a classical calibration method, the inter-element sensitivity deviations, dark current, shot noise, and readout-quantization noise for a CCD-based pyrometer are characterized, and the influence of these noises on the temperature measurement accuracy is evaluated quantitatively. Furthermore, the non-uniformity correction coefficient for each pixel is obtained by a simple segment correction method to reduce the inter-element sensitivity deviations, and meanwhile, the Kalman filter is introduced to remove the temperature fluctuations caused by these noises. Experimental results show that mean value of the spatial standard deviation of temperature measurement results in the total measurement range (800-1200 °C) is only 2.2 °C after non-uniformity correction, and the temperature fluctuations can be reduced from 26.6 to 1.98 °C based on the Kalman filter.


Mitochondrial Functioning ≠ General Intelligence.
Geary puts forward an appealing argument for the consideration of mitochondrial functioning as a candidate for a formative g Geary (2019); it is also an ambitious argument [...].


Group interactions in SFINCSS-99: lessons for improving behavioral support programs.
Human factors can significantly influence successful mission completion of prolonged space missions such as ISS expeditions or future Mars missions. This paper describes group dynamics and group interactions during SFINCSS-99, a very unique international long-term confinement study in a space mission analog environment. Many interpersonal or inter-group conflicts occurred, and these caused the early retirement of a Japanese subject. This paper cites examples of these conflicts, and analyzes their causes with our results. The international cooperation to extract lessons learned, which could be used to refine behavioral support programs for the ISS or similar international studies, is also introduced.


Angiotensin I converting enzyme activity in portal vein studied in normotensive rats and in models of primary and secondary hypertension.
The effects of angiotensin I (AT I), angiotensin II (AT II) and the activity of AT I converting enzyme (ACE) were investigated in isolated portal veins of normotensive rats (WKR and NCR) and of rats with primary (SHR) and secondary (one clip 2 kidney renal; RHR) hypertension. Based on ED50 values, the tissue sensitivity to AT II was slightly less in the portal veins of RHR than SHR, while the sensitivity of smooth muscle in NCR and WKR was similar to that of SHR. Angiotensin I induced contractions were inhibited by saralasin and by captopril, indicating presence of functionally active converting enzyme in the this vascular tissue. The local concentration of AT II formed from AT I, was evaluated based on AT II dose response curves and AT I response magnitude. The AT II formation was essentially similar in SHR, WKR and NCR and slightly enhanced in RHR. Inhibition of AT II formation with captopril and/or blockade of AT II receptors with saralasin failed to alter the spontaneous myogenic activity of the portal vein. Captopril reduced smooth muscle activity only in concentration several orders of magnitude greater than that needed to inhibit ACE. The concentration of captopril needed to inhibit AT I responses was similar in all strains of rats. It is concluded that AT II is rapidly formed in the portal vein due to local conversion of AT I. In the RHR portal vein the extent of AT I conversion is increased and the tissue sensitivity to AT II is decreased possibly due to mechanisms involved in the development of renovascular hypertension.


Transcription of PRDM1, the master regulator for plasma cell differentiation, depends on an SP1/SP3/EGR-1 GC-box.
The positive regulatory domain containing 1, encoded by the PRDM1 gene, is a transcriptional repressor considered as a master regulator that is required and sufficient for plasma cell differentiation. In the present study we have performed sequence analysis of the upstream region of the human PRDM1 gene to detect the minimal promoter region necessary for PRDM1 gene transcription. This region comprises the region upstream of the initiation site, as well as the first exon. Collectively, deletion and mutation analysis in conjunction with luciferase reporter assays, EMSA and supershift assays identified a phylogenetically conserved GC-box as an essential element for PRDM1 expression. This GC-box element matches to a binding site for multiple transcription factors such as SP1 and SP3 isoforms as well as early growth response 1. Chromatin immunoprecipitation assays confirmed the in vivo binding capability of these factors to the human PRDM1 promoter. These studies together characterize for the first time the basal activity of the human PRDM1 promoter, through which several factors, including SP1, SP3 and early growth response 1, modulate its expression through a conserved GC-box.


Ethylene and not embolism is required for wound-induced tylose development in stems of grapevines.
The pruning of actively growing grapevines (Vitis vinifera) resulted in xylem vessel embolisms and a stimulation of tylose formation in the vessels below the pruning wound. Pruning was also followed by a 10-fold increase in the concentration of ethylene at the cut surface. When the pruning cut was made under water and maintained in water, embolisms were prevented, but there was no reduction in the formation of tyloses or the accumulation of ethylene. Treatment of the stems with inhibitors of ethylene biosynthesis (aminoethoxyvinylglycine) and/or action (silver thiosulfate) delayed and greatly reduced the formation of tyloses in xylem tissue and the size and number of those that formed in individual vessels. Our data are consistent with the hypotheses that wound ethylene production is the cause of tylose formation and that embolisms in vessels are not directly required for wound-induced tylosis in pruned grapevines. The possible role of ethylene in the formation of tyloses in response to other stresses and during development, maturation, and senescence is discussed.


Hybrid Dielectric Films of Inkjet-Printable Core-Shell Nanoparticles.
A new type of hybrid core-shell nanoparticle dielectric that is suitable for inkjet printing is introduced. Gold cores (dcore ≈ 4.5 nm diameter) are covalently grafted with thiol-terminated polystyrene (Mn = 11000 Da and Mn = 5000 Da) and used as inks to spin-coat and inkjet-print dielectric films. The dielectric layers have metal volume fractions of 5 to 21 vol% with either random or face-centered-cubic structures depending on the polymer length and grafting density. Films with 21 vol% metal have dielectric constants of 50@1 Hz. Structural and electrical characterization using transmission electron microscopy, small-angle X-ray scattering, and impedance spectroscopy indicates that classical random capacitor-resistor network models partially describe this hybrid material but fail at high metal fractions, where the covalently attached shell prevents percolation and ensures high dielectric constants without the risk of dielectric breakdown. A comparison of disordered to ordered films indicates that the network structure affects dielectric properties less than the metal content. The applicability of the new dielectric material is demonstrated by formulating inkjet inks and printing devices. An inkjet-printed capacitor with an area of 0.79 mm2 and a 17 nm thick dielectric had a capacitance of 2.2 ± 0.1 n F @ 1 k H z .


Hemozoin differentially regulates proinflammatory cytokine production in human immunodeficiency virus-seropositive and -seronegative women with placental malaria.
Pregnant women are at an increased risk for malarial infection. Plasmodium falciparum accumulates in the placenta and is associated with dysregulated immune function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in the placenta and may modulate local immune function. In this study, the impact of hemozoin on cytokine production by intervillous blood mononuclear cells from malaria-infected placentas was investigated. There was a dose-dependent, suppressive effect of hemozoin on production of gamma interferon (IFN-gamma), with less of an effect on tumor necrosis factor alpha (TNF-alpha) and interleukin-10, in human immunodeficiency virus-seronegative (HIV(-)) women. In contrast, IFN-gamma and TNF-alpha production tended to increase in HIV-seropositive women with increasing hemozoin levels. Production patterns of cytokines, especially IFN-gamma in HIV(-) women, followed different trends as a function of parasite density and hemozoin level. The findings suggest that the influences of hemozoin accumulation and high-density parasitemia on placental cytokine production are not equivalent and may involve different mechanisms, all of which may operate differently in the context of HIV infection. Cytokine production dysregulated by accumulation of hemozoin or high-density parasitemia may induce pathology and impair protective immunity in HIV-infected and -uninfected women.


Effect of Sm + Er and Heat Treatment on As-Cast Microstructure and Mechanical Properties of 7055 Aluminum Alloy.
The 7055 aluminum alloy is an ultra-high strength aluminum alloy, which is widely used in the aerospace field and new energy automobile manufacturing industry. As it retains high strength, its plastic deformation ability needs to be improved, which limits its application in plastic processing. In this study, the cast grains of the 7055 aluminum alloy were refined by adding Sm + Er, and the proper heat treatment procedure was utilized to further precipitate the rare earth phase in order to increase the alloy's strength and toughness. The grain size, microstructure and phase were characterized by optical microscopes (OMs), scanning electron microscopy-energy spectrum (SEM-EDS) and a XRD diffractometer (XRD). The macroscopic hardness, yield strength and tensile strength of alloy materials were measured by a hardness meter and universal electronic tensile machine. The results showed that the as-cast sample and the heat treatment sample all contained Al10Cu7Sm2 and Al8Cu4Er rare earth phases. But, after heat treatment, the volume percentage of the rare earth phase dramatically increased and the dispersion was more unified. When 0.3 wt.%Sm and 0.1 wt.%Er were added, the grain size could be refined to 53 μm. With the increase in the total content of rare earth elements, the refining effect first increased and then decreased. Under 410 °C solid solution for 2 h + 150 °C and aging for 12 h, the macroscopic hardness, yield strength, tensile strength and elongation of 0.3 wt.%Sm + 0.1 wt.%Er + 7055 as-cast samples were 155.8 HV, 620.5 MPa, 658.1 MPa and 11.90%, respectively. After the addition of Sm and Er elements and heat treatment, the grain refinement effect of 7055 aluminum alloy was obvious and the plastic property was greatly improved under the premise of maintaining its high-strength advantage.


Combination treatment with secukinumab and dimethyl fumarate in a patient with psoriasis and recent diagnosis of multiple sclerosis.
The therapeutic approach to patients with psoriasis and concomitant multiple sclerosis is challenging. We report the clinical case of a 44-year-old man affected by psoriasis and psoriatic arthritis treated with secukinumab for 2 years, who received also dimethyl fumarate because of a recent diagnosis of relapsing remitting multiple sclerosis. Moreover, a mini-review of the available literature regarding the use of secukinumab in patients with psoriasis or ankylosing spondylitis and coexisting central nervous system demyelinating diseases was performed. To the best of our knowledge, this is the first case of successfully combining secukinumab and dimethyl fumarate for the treatment of two different immune mediated inflammatory diseases with good response and safety outcomes. Our case emphasizes the potential efficacy of this combination therapy, which may represent an effective synergistic strategy to manage such challenging patients.


Challenges in Taking Sexual History: A Qualitative Study of Indian Postgraduate Psychiatry Trainees.
In India, psychiatrist is an important point of helpseeking for sexual complaints. A detailed sexual history can go a long way in understanding sexual difficulties. In this background, there is inadequate information on the difficulties that psychiatry postgraduate trainees experience while taking a sexual history as part of a routine mental health evaluation. The aim was to study the difficulties experienced by postgraduate psychiatry trainees while taking sexual history as a part of routine mental health evaluation. This study was conducted in an Indian medical college general hospital psychiatry setting. This is a qualitative study using focus group discussions and in-depth interviews with postgraduate psychiatry trainees. Content analysis was used to identify direct and latent themes. Thematic saturation was achieved with 17 participants. Major themes of difficulties that emerged included trainee-related factors such as gender and sociocultural background of the trainee; patient-related factors such as age, gender, and sexual orientation; setting-related factors; and language-related difficulties. Specific and regular training in taking a sexual history is essential in addressing the difficulties faced by postgraduate psychiatry trainees in India.


Improved neural microcirculation and regeneration after peripheral nerve decompression in DPN rats.
Recently, neural microcirculation and regeneration were regarded as critical factors in diabetic peripheral neuropathy (DPN) improvement. In the present study, we explored the cytological and molecular mechanisms how peripheral nerve decompression impaired nerve injury. Forty-five male SD rats were established as the DPN model. HE staining was used to observe the morphology and distribution of microvessels. Transmission electron microscopy was applied to observe the morphology and distribution of Schwann cells. Immunohistochemical staining was performed to measure nerve growth factor (NGF), tyrosine kinase receptor A (TrkA) and growth-associated protein 43 (GAP-43) in the distal sciatic nerve. Distribution of microvessels and Schwann cells decreased in the DPN group (p < 0.05). NGF, TrkA and GAP-43 also decreased significantly in the DPN group (p < 0.05). NGF, TrkA, GAP-43 and distribution of microvessels and Schwann cells increased in the decompressed group (p < 0.05). In DPN rats, after nerves are compressed, microcirculation disturbance and hypoxia ischemia will happen, which cause decreased expression of NGF, TrkA and GAP-43. Finally, the self-healing function of compressed nerves is impacted. Conversely, nerve decompression can improve neural microcirculation and regeneration and change the former pathological process.


[Simultaneous separation of creatine kinase and lactate dehydrogenase isoenzymes using an electrophoresis method].
A specific and sensitive rapid method for simultaneous electrophoretic separation of the blood serum creatine kinase (CK) and lactate dehydrogenase (LDH) isoenzymes is described, fit for rapid diagnosis. A common electrophoresis scheme was used for the separation of both enzymes on the same cellulose acetate plate. Then the isoenzymes were separately detected by their enzymic activities. To detect the enzymic activities at the sites of isoenzymes' localization, the samples were incubated with substrate gel. Optimal conditions for the detection of CK and LDH activities were defined. To illustrate the diagnostic value of the method, the blood serum CK and LDH isoenzymic activities were measured in the patients with acute myocardial infarction and in those operated on for aortocoronary shunting.


Paratracheal placement of orotracheal tube: a complication when aborting percutaneous tracheotomy.
Percutaneous dilatational tracheotomies (PT) are commonly performed in the ICU. The procedure carries the risk of complications, among them severe events as loss of airway or pneumothorax. In this case report we describe complications related to a PT procedure in the ICU. The procedure was performed with a single dilator kit, and by visual guidance of a bronchoscope. Because of difficulties with the insertion of the tracheal cannula, the procedure was aborted, and the endotracheal tube (ET) reinserted. After placement of the ET, subcutaneous emphysema emerged. Upon digital exploration in the tracheotomy incision the tube was found to exit from the trachea, the tube-tip being situated para-tracheally. The tube position was corrected using a finger in the incision, and the patient could again be ventilated. Poor visual conditions may occur during PT because of bleeding. Importantly, there is a risk for the ET to exit an incision in the trachea when reintubating during a PT procedure, or after decannulation. This can be prevented using digital occlusion of the tracheal opening.


[Clinical assessment of toxics deleterious to fertility].
This paper reviews the main toxics which are deleterious to fertility. Toxics are identified through in vitro, animal and clinical studies. The practitioner tries to assess whether a couple consulting for infertility has been exposed to such toxics. Some toxics are voluntarily taken: this is the case for tobacco, alcohol and other, maybe illegal, recreative drugs. Tobacco is the most frequently observed. The assessment of tobacco consumption and the implementation of weaning procedures have been studied in numerous papers: psychological, pharmacological and even immunotherapy-based approaches have been proposed. Alcohol abuse is even more difficult to assess: the border between acceptable convivial and excessive consumption is not clear-cut, except during pregnancy where there should be no alcohol consumption. This also holds for "recreative" drugs. It is usual clinical practice to register the medicine taken; some of these may be toxic for fertility. There is an ongoing work for listing these toxic drugs. Occupational life may also lead to exposure to toxics or be deleterious for fertility by imposing body constraints.


Rapid Flame Synthesis of Atomically Thin MoO3 down to Monolayer Thickness for Effective Hole Doping of WSe2.
Two-dimensional (2D) molybdenum trioxide (MoO3) with mono- or few-layer thickness can potentially advance many applications, ranging from optoelectronics, catalysis, sensors, and batteries to electrochromic devices. Such ultrathin MoO3 sheets can also be integrated with other 2D materials (e.g., as dopants) to realize new or improved electronic devices. However, there is lack of a rapid and scalable method to controllably grow mono- or few-layer MoO3. Here, we report the first demonstration of using a rapid (<2 min) flame synthesis method to deposit mono- and few-layer MoO3 sheets (several microns in lateral dimension) on a wide variety of layered materials, including mica, MoS2, graphene, and WSe2, based on van der Waals epitaxy. The flame-grown ultrathin MoO3 sheet functions as an efficient hole doping layer for WSe2, enabling WSe2 to reach the lowest sheet and contact resistance reported to date among all the p-type 2D materials (∼6.5 kΩ/□ and ∼0.8 kΩ·μm, respectively). These results demonstrate that flame synthesis is a rapid and scalable pathway to growing atomically thin 2D metal oxides, opening up new opportunities for advancing 2D electronics.


Seven-year itch: a perplexing case of lichen planus-lupus erythematosus overlap syndrome.
Lichen planus-lupus erythematosus overlap syndrome is a rare disorder characterized by clinical and histopathological features of both lichen planus (LP) and lupus erythematosus (LE). Cutaneous lesions commonly affect the distal arms, legs, face, and trunk and these plaques are often large, scaly, painful, and atrophic, often exhibiting hypopigmentation or a red to blue-violet color. We report a case of LP-LE overlap syndrome diagnosed in a man previously believed to have atypical lichen planus who presented with an exacerbation of exuberant pruritic erythematous scaly plaques. The patient had six separate skin biopsies all of which displayed features of LP. Because the clinical symptoms did not correlate to the histopathological picture, a seventh skin biopsy with direct immunofluorescence (DIF) was performed and immunologic markers measured. The DIF demonstrated early lupus bands; serologic testing exhibited elevated ANA and anti-SSA. These findings established the diagnosis of LP-LE overlap syndrome. The patient was started on hydroxychloroquine with short-term trials of oral prednisone during disease flares, which took place in the first three months of treatment.


Preferential transfer of endogenous ovarian steroid hormones to the uterus during both the follicular and luteal phases.
Ovarian steroids are thought to be released into the systemic circulation and reach the uterus via the uterine arteries. However, results of experimental and clinical studies suggest the existence of local transfer of steroids from the ovary to the uterus. This study aimed to verify the existence of preferential distribution of ovarian steroids to the uterus in the two phases of the menstrual cycle. We performed parallel measurements of serum levels of estradiol and progesterone in the systemic circulation (arterial and venous) and in the uterine vessels in two groups of cycling women; one group were in the follicular phase (six women) and the other group were in the luteal phase (10 women) of the menstrual cycle. Both in the follicular phase and in the luteal phase groups, mean estradiol levels in the uterine blood were significantly higher than in both sides of the systemic circulation (F = 7.30, df = 15, P < 0.006; and F = 4.70, df = 27, P < 0.02). Similar results were obtained in the luteal phase group for progesterone (F = 9.38, df = 27, P < 0.0001). Both estradiol and progesterone levels in arterial and venous systemic blood were similar. The results of this study demonstrate that ovarian steroid levels are significantly higher in the uterine vessels than in both sides of the systemic blood circulation, and strongly suggest the existence in the female pelvis of mechanisms of local distribution of ovarian hormones.


The polymorphism of type 1 collagen (COL1A1) gene does not correlate with an increased risk of foot ulcers in patients with diabetes mellitus.
Diabetic foot syndrome (DFS) is a multifactorial debilitating complication of diabetes mellitus (DM). The identification of markers for predicting the risk of developing DFS could help and direct the efforts in the prevention to the highest risk patients. Type I collagen α1 (COL1A1) is the main component of type I collagen, the most abundant structural protein of the extracellular matrix of subcutaneous tissue. COL1A1 polymorphism has been previously investigated with regard to many clinical conditions affecting the bone or the skin. In this prospective study, we have assessed COL1A1 polymorphism in patients without and with DFS. 202 DM patients without and 103 patients with DFS have been recruited. COL1A1 polymorphism, due to a mutation affecting the zinc-finger transcription factor specific protein, has been investigated. The most relevant clinical data (HbA1c, vascular risk factors, insulin treatment) have been collected and analyzed. No statistically significant difference in the distribution of the 3 genotypes constituting COL1A1 polymorphism between patients without and with DFS has been observed. Almost all DFS patients had at least one vascular risk factor, with a high rate of arterial hypertension and dyslipidemia. A multifaceted set of factors is involved in the development of DFS and only a combination of them may lead to such occurrence. In our DM patient population, COL1A1 polymorphism does not correlate with the occurrence of DFS, which appears to depend mostly on the presence of vascular risk factors. However, the impact of genetic factors affecting other components of the subcutaneous tissue cannot be excluded.


Altered brain activation during cognitive control in patients with moderate to severe traumatic brain injury.
Persistent deficits in cognitive control have been documented following traumatic brain injury (TBI) but are inconsistently related to the presence and location of focal lesions. Functional magnetic resonance imaging (fMRI) was used to examine brain activation during a cognitive control task in patients with moderate to severe TBI or orthopedic injury (OI). Fourteen TBI patients and 10 OI patients underwent fMRI at 3 months postinjury using a stimulus-response compatibility task in which response accuracy and reaction time were measured. Performance between the groups was equated by individually adjusting the amount of training. Groups did not differ in age, gender, or education. Brain activation during stimulus-response incompatibility was greater in TBI patients than in OI patients within the cingulate, medial frontal, middle frontal, and superior frontal gyri. However, the positive regression of activation with response accuracy during stimulus-response incompatibility indicated a stronger relationship for OI patients than the TBI group within the anterior cingulate gyrus, medial frontal, and parietal regions, as well as deep brain structures (eg, brainstem). The number of focal lesions within either the whole brain or within prefrontal areas was not related to brain activation, but there was a relationship between activation and TBI severity. These findings suggest that neural networks mediating cognitive control are altered after moderate to severe TBI, possibly as a result of diffuse axonal injury, and that the typical relationship of brain activation to performance is disrupted.


Halobetasol Propionate Lotion, 0.05% Provides Superior Hydration Compared to Halobetasol Propionate Cream, 0.05% in a Double-Blinded Study of Occlusivity and Hydration.
This study measured skin hydration and occlusivity of two test products [halobetasol propionate lotion, 0.05% (HBP Lotion) and Ultravate® (halobetasol propionate) cream, 0.05% (HBP Cream)] at 2, 4, and 6 hours after application to skin test sites previously challenged by dry shaving, which was performed to compromise the integrity of the stratum corneum barrier. Trans-epidermal water loss (TEWL), an indicator of skin barrier function, was measured using cyberDERM, inc. RG-1 evaporimeter. Skin hydration was evaluated using IBS SkiCon-200 conductance meter. Test products were applied bilaterally on dry-shaved sites on the volar forearm sites, according to a randomization scheme, with two test sites untreated to serve as "dry-shaved" controls. TEWL and conductance were measured at 2, 4, and 6 hours post-treatment. HBP Lotion displayed a significant increase in skin hydration at 2, 4, and 6 hours post-treatment compared to the baseline values and dry-shaved controls (each, P less than 0.001). However, HBP Cream produced statistically significant increased skin hydration only after 6 hours (P less than 0.05). HBP Lotion was significantly more effective than HBP Cream in increasing skin hydration at 2 and 4 hours post-treatment (each, P less than 0.001), and had a directional advantage (not statistically significant) at 6 hours. Neither test product had a significant occlusive effect as measured by TEWL at 2, 4, and 6 hours post-application. Both formulations of HBP (Lotion and Cream) contributed to skin moisturization, as measured by skin conductance. HBP Lotion produced a significantly more rapid onset and higher level of moisturization at 2 and 4 hours post-application compared to HBP Cream. The TEWL results indicate that neither HBP Lotion nor HBP Cream provided any significant occlusivity to the skin.
J Drugs Dermatol. 2017;16(2):140-144.
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Tunable exciton-polaritons emerging from WS2 monolayer excitons in a photonic lattice at room temperature.
Engineering non-linear hybrid light-matter states in tailored lattices is a central research strategy for the simulation of complex Hamiltonians. Excitons in atomically thin crystals are an ideal active medium for such purposes, since they couple strongly with light and bear the potential to harness giant non-linearities and interactions while presenting a simple sample-processing and room temperature operability. We demonstrate lattice polaritons, based on an open, high-quality optical cavity, with an imprinted photonic lattice strongly coupled to excitons in a WS2 monolayer. We experimentally observe the emergence of the canonical band-structure of particles in a one-dimensional lattice at room temperature, and demonstrate frequency reconfigurability over a spectral window exceeding 85 meV, as well as the systematic variation of the nearest-neighbour coupling, reflected by a tunability in the bandwidth of the p-band polaritons by 7 meV. The technology presented in this work is a critical demonstration towards reconfigurable photonic emulators operated with non-linear photonic fluids, offering a simple experimental implementation and working at ambient conditions.


Schema benefit vs. proactive interference: Contradicting behavioral outcomes and coexisting neural patterns.
Prior knowledge can either assist or hinder the ability to learn new information. These contradicting behavioral outcomes, referred to as schema benefit and proactive interference respectively, have been studied separately. Here we examined whether the known neural correlates of each process coexist, and how they are influenced by attentional loading and aging. To this end we used an fMRI task that affected both processes simultaneously by presenting pairs of related short movies in succession. The first movie of each pair provided context for the second movie, which could evoke schema benefit and/or proactive interference. Inclusion of an easy or hard secondary task performed during encoding of the movies, as well as testing both younger (22-35y) and older (65-79y) adults, allowed examining the effect of attentional load and older age on the neural patterns associated with context. Analyses focused on three predefined regions and examined how their inter-subject correlation (inter-SC) and functional connectivity (FC) with the hippocampi changed between the first and second movie. The results in the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) matched and expanded previous findings: higher inter-SC and lower FC were observed during the second compared to the first movie; yet the differentiation between the first and second movies in these regions was attenuated under high attentional load, pointing to dependency on attentional resources. Instead, at high load there was a significant context effect in the FC of the left ventrolateral prefrontal cortex (vlPFC), and greater FC in the second movie was related to greater proactive interference. Further, older adults showed context effect in the PCC and vlPFC. Intriguingly, older adults with inter-SC mPFC patterns similar to younger adults exhibited schema benefit in our task, while those with inter-SC PCC patterns similar to younger adults showed proactive interference in an independent task. The brain-behavior relationships corroborate the functional significance of these regions and indicate that the mPFC mainly contributes to schema benefit, while the left vlPFC and PCC contribute to proactive interference. Importantly, our findings show that the functions of the regions are retained throughout the lifespan and may predict the predominant behavioral outcome.


In search of a perennial philosophy for behavioral health integration in primary care.
The "perennial philosophy," a concept religious scholars have studied for centuries, represents a search for the values, themes, and constructs that transcend individual religions. Can we who develop and disseminate behavioral health integration in primary care step back from individual models to identify our perennial philosophy? If so, what are the components? What does the evidence tell us? What do we need to learn? Four case examples are presented which represent many patients seen by both of us-a family therapist and a family physician-over our combined 55 years of collaborative practice within integrated primary care settings. Can these patients be cared for in a primary care setting? Our experience provides a simple answer-yes. However, providing care for this range of patients requires variability in team configurations, frequency of visits, lengths of relationships, and interventional strategies. Is there a perennial philosophy of how to design and implement the integration of behavioral health in primary care? We think there should be. we highlight a recent publication from the Eugene S. Farley, Jr. Health Policy Center, entitled "Core Competencies For Behavioral Health Providers Working In Primary Care." The authors purposefully transcend models in delineating eight core competencies. Embedded within these competencies are common or perennial factors. These factors may guide our field going forward, helping us avoid "religious" divisions, seek to understand diverse designs, and embrace integration of models to meet the needs of the populations and teams we serve. (PsycINFO Database Record


A Retrospective Trail Investigating Temozolomide Neoadjuvant Chemotherapy Combined with Radiotherapy in Low-Grade Pituitary Tumors.
To study and analyze the clinical application of temozolomide (TMZ) combined with radiotherapy in the treatment of low-grade pituitary tumors. A retrospective trail was conducted among 67 patients with low-grade pituitary tumors who were treated in our hospital from March 2018 to June 2020. According to different treatment methods, they were assigned into a combined group (37 cases, temozolomide capsules and radiotherapy) and a control group (30 cases, radiotherapy). The changes of serum prolactin (PRL), insulin-like growth factor-1 (IGF-1), GH levels, thyroid-stimulating hormone (TSH), serum free thyroxine (FT4), and adrenocorticotropic hormone (ACTH) were compared. The chi-square test reports a significantly higher total effective rate in the combined group vs. control group (91.89% vs. 70.00%). Significant reductions in serum levels of PRL, IGF-1, and GH were observed in both groups after treatment, whereas the combined group treated with radiotherapy and TMZ resulted in significantly lower levels compared with the control group (p < 0.05). After treatment, TSH decreased, and FT4 and ACTH increased in both groups, and the treatment with radiotherapy and TMZ in the combined group led to a significantly greater amplitude of variation (p < 0.05). The combination of temozolomide and radiotherapy might be a promising technique for the treatment of pituitary tumors, thereby meriting promotion.


[Mathematical classification of root canal curvature of human teeth].
Endodontic research requires a mathematically based classification method of root canal forms. The aim of this study was to give a mathematical description of root canal forms using differential geometrical pattern analysis and computer graphics. The measurements of 433 extracted human roots were carried out on isometric radiographs taken from clinical view. Seven points of root canal axis of the same radiographs were approximated using fourth degree polynomial functions describing the imaginary axis of canals. The Schneider's angle of each root was also measured for grouping the samples according to this parameter. The classification of root canal form on the basis of Schneider's angle differs from the classification of geometrical pattern analysis. This type of classification of root canals is suitable for standardizing test specimens, including natural human teeth used for testing root forms: I (straight), J (apically curved), C (continuously curved) or S (multicurved).


Singapore National Medical Image Resource Centre (SN.MIRC): a world wide web resource for radiology education.
Radiology education is heavily dependent on visual images, and case-based teaching files comprising medical images can be an important tool for teaching diagnostic radiology. Currently, hardcopy film is being rapidly replaced by digital radiological images in teaching hospitals, and an electronic teaching file (ETF) library would be desirable. Furthermore, a repository of ETFs deployed on the World Wide Web has the potential for e-learning applications to benefit a larger community of learners. In this paper, we describe a Singapore National Medical Image Resource Centre (SN.MIRC) that can serve as a World Wide Web resource for teaching diagnostic radiology. On SN.MIRC, ETFs can be created using a variety of mechanisms including file upload and online form-filling, and users can search for cases using the Medical Image Resource Center (MIRC) query schema developed by the Radiological Society of North America (RSNA). The system can be improved with future enhancements, including multimedia interactive teaching files and distance learning for continuing professional development. However, significant challenges exist when exploring the potential of using the World Wide Web for radiology education.


Stabilized hole-selective layer for high-performance inverted p-i-n perovskite solar cells.
P-i-n geometry perovskite solar cells (PSCs) offer simplified fabrication, greater amenability to charge extraction layers, and low-temperature processing over n-i-p counterparts. Self-assembled monolayers (SAMs) can enhance the performance of p-i-n PSCs but ultrathin SAMs can be thermally unstable. We report a thermally robust hole-selective layer comprised of nickel oxide (NiOx) nanoparticle film with a surface-anchored (4-(3,11-dimethoxy-7H-dibenzo[c,g]carbazol-7-yl)butyl)phosphonic acid (MeO-4PADBC) SAM that can improve and stabilize the NiOx/perovskite interface. The energetic alignment and favorable contact and binding between NiOx/MeO-4PADBC and perovskite reduced the voltage deficit of PSCs with various perovskite compositions and led to strong interface toughening effects under thermal stress. The resulting 1.53-electron-volt devices achieved 25.6% certified power conversion efficiency and maintained >90% of their initial efficiency after continuously operating at 65 degrees Celsius for 1200 hours under 1-sun illumination.


Clinical significance of miR-195 in hepatocellular carcinoma and its biological function in tumor progression.
Hepatocellular carcinoma (HCC) is one of the most lethal cancer types all over the world. Chronic viral hepatitis B and hepatitis C are risk factors that are associated with the development of HCC. The aim of this study is to identify the diagnostic role of serum miR-195 in HCC. The expression levels of miR-195 were detected in 120 HCC patients, 64 hepatitis only patients, and 118 healthy control as well as 4 HCC cell lines, by using quantitative real-time PCR. The association of miR-195 with clinicopathological parameters of patients was analyzed with the chi-squared test. The receiver operating characteristic (ROC) curve was adopted to estimate the potential diagnostic value of miR-195. The cell experiments were carried out to verify the functional role of miR-195. The expression of miR-195 was downregulated in HCC cells and serum of patients compared to the controls (all P<0.05). The miR-195 expression was associated with lymph node metastasis and TNM stage. The ROC curve analysis showed that miR-195 may be a noninvasive diagnostic marker for patients. By using miR-195 mimic or inhibitor, cell proliferation, migration, and invasion were inhibited by miR-195 overexpression but promoted by reduced expression of miR-195. The downregulation of miR-195 may serve as a novel diagnostic biomarker for differentiating HCC patients, healthy individuals, and hepatitis patients, and may involve in the tumor progression of HCC.


Enantioselective direct vinylogous aldol-cyclization cascade reaction between β,γ-unsaturated amides and o-quinones.
1,2-Diketones are employed, for the first time, as electrophiles in the vinylogous aldol reaction. With 5 mol% of chiral tertiary amine-thiourea , a direct vinylogous aldol-cyclization cascade reaction between β,γ-unsaturated amides and o-quinones has been achieved to produce spirocyclic dihydropyranones in 76-99% yield and 82-95% ee.


Cholesterol-Dependent Cytolysins: Membrane and Protein Structural Requirements for Pore Formation.
The cholesterol-dependent cytolysins (CDCs) are a family of bacterial protein toxins specifically targeting eukaryotic cells through the absolute requirement for high concentrations of cholesterol in the target cells' lipid membrane. The soluble monomeric protein secreted by the bacteria oligomerizes on the surface of the target cell, and the complex formed then undergoes a concerted structural transition that results in the creation of a multimeric protein pore. Recognition of the cholesterol-rich membrane by CDCs is a surprisingly subtle process that takes place at the interface between the membrane and surrounding aqueous environment. The structure and composition of the lipid membrane modulates the efficiency with which the protein can identify cholesterol and alters the concentration of sterol required for membrane binding. Some of the details of the interplay between protein and membrane remain to be resolved, and in this review we present a current perspective on CDC pore formation, with particular focus on the role of the lipid bilayer and cholesterol accessibility.


Suspected dimethoate toxicity in cattle.
Dimethoate, an organophosphorus insecticide, was the suspected cause of toxicosis in a group of young cattle grazing on pasture that had been sprayed 6 weeks before the onset of clinical signs. Affected animals had primarily nicotinic signs, such as muscle twitching, stiffness, weakness and paralysis, though muscarinic signs, such as diarrhea, salivation and pollakiuria, were also observed. Whole blood acetylcholinesterase activity was depressed in 3 animals. The atypical clinical syndrome and poor response to treatment with atropine and other anticholinergics may have been due to coexistent hypomagnesemia.


[Characteristics of shrimp allergy from childhood to adulthood in Japan].
We examined profiles and clinical symptoms of shrimp allergy patients and investigated the correlation of shrimp-specific IgE to crustaceans-specific IgE, mollusks-specific IgE and shellfish-specific IgE. In addition, symptoms when eating crustaceans other than shrimp, mollusks and shellfish were examined, because they shared tropomyosin as a major allergen. We examined 99 definitive shrimp allergy cases with questionnaire. Their onset started during either childhood or young adulthood. Symptoms appeared within an hour after ingestion of shrimp in 87.9% cases. The most common symptoms were skin symptoms, followed by oral allergic syndrome (OAS) like symptoms, respiratory symptoms. Anaphylaxis were observed in 61 cases including 2 anaphylactic shock cases. Among 99 shrimp allergy cases, 44 cases (64.7%) showed positive reaction to crabs out of 68 cases experiencing crab ingestion. Only 11 cases (17.5%) reacted against squid out of 63 cases with the experience in squid ingestion. Crab-specific IgE (C.I. 0.954, p < 0.001) and squid-specific IgE (C.I. 0.582, p > 0.001) were strongly correlated with shrimp-specific IgE. We conclude that a lot of cases with shrimp allergy react to crabs clinically, and which seem to be different from the reaction against mollusk and shellfish intake in spite of sharing tropomyosin as a major allergen among them.


Depolarization-induced calcium responses in sympathetic neurons: relative contributions from Ca2+ entry, extrusion, ER/mitochondrial Ca2+ uptake and release, and Ca2+ buffering.
Many models have been developed to account for stimulus-evoked [Ca(2+)] responses, but few address how responses elicited in specific cell types are defined by the Ca(2+) transport and buffering systems that operate in the same cells. In this study, we extend previous modeling studies by linking the time course of stimulus-evoked [Ca(2+)] responses to the underlying Ca(2+) transport and buffering systems. Depolarization-evoked [Ca(2+)](i) responses were studied in sympathetic neurons under voltage clamp, asking how response kinetics are defined by the Ca(2+) handling systems expressed in these cells. We investigated five cases of increasing complexity, comparing observed and calculated responses deduced from measured Ca(2+) handling properties. In Case 1, [Ca(2+)](i) responses were elicited by small Ca(2+) currents while Ca(2+) transport by internal stores was inhibited, leaving plasma membrane Ca(2+) extrusion intact. In Case 2, responses to the same stimuli were measured while mitochondrial Ca(2+) uptake was active. In Case 3, responses were elicited as in Case 2 but with larger Ca(2+) currents that produce larger and faster [Ca(2+)](i) elevations. Case 4 included the mitochondrial Na/Ca exchanger. Finally, Case 5 included ER Ca(2+) uptake and release pathways. We found that [Ca(2+)](i) responses elicited by weak stimuli (Cases 1 and 2) could be quantitatively reconstructed using a spatially uniform model incorporating the measured properties of Ca(2+) entry, removal, and buffering. Responses to strong depolarization (Case 3) could not be described by this model, but were consistent with a diffusion model incorporating the same Ca(2+) transport and buffering descriptions, as long as endogenous buffers have low mobility, leading to steep radial [Ca(2+)](i) gradients and spatially nonuniform Ca(2+) loading by mitochondria. When extended to include mitochondrial Ca(2+) release (Case 4) and ER Ca(2+) transport (Case 5), the diffusion model could also account for previous measurements of stimulus-evoked changes in total mitochondrial and ER Ca concentration.


The apoptotic effect and associated signalling of HSP90 inhibitor 17-DMAG in hepatocellular carcinoma cells.
Primary liver cancer is one of the highly malignant tumours. The traditional surgery, chemotherapy and radiation therapy only established 6% of 5-year survival rate in HCC (hepatocellular carcinoma). Therefore there is an urgent need to develop new therapeutic strategies. HSP90 (heat shock protein 90) is one of the important molecular chaperones and was identified with high expression in the primary liver cancer. In this study, we evaluated the therapeutic effect of specific HSP90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxy geldanamycin) in HCC cells. The time and concentration effects of 17-DMAG were investigated in HCC cells. Cell proliferation was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and cell counting. Apoptosis was detected by flow cytometry with staining of Annexin V-FITC/PI (propidium iodide). The protein levels of survivin, cyclin D1, p53 and NF-κB (nuclear factor κB) were measured by Western blotting. 17-DMAG inhibited the proliferation of HCC cells in a time- and concentration-dependent manner. Treatment with 400 nmol/l 17-DMAG for 48 h significantly induced early-stage apoptosis (22.4%). Conversely, it induced less late-stage apoptosis (3.03%). The 5 mg/l of cisplatin induced significantly less early-stage apoptosis (6.5%), but similar proportion of late-stage apoptosis (4.89%) compared with 17-DMAG. Inhibition of HSP90 activity by 400 nmol/l 17-DMAG decreased protein levels of survivin, cyclin D1 and NF-κB protein levels, whereas increased p53 protein level. HSP90 plays a key role in HCC cell growth and survival through regulation of survivin, cyclin D1, p53 and nucleus NF-κB protein levels and the specific HSP90 inhibitor 17-DMAG can play a therapeutic role in HCC treatment.


Examining the Relationship Between Self-Reported Drinking and In-Laboratory Drinking and Craving: Is There Concordance?
In-laboratory drinking sessions that allow direct assessment of drinking and craving are an emerging method for testing novel pharmacotherapy compounds and behavioral interventions for alcohol use disorders. Despite wide implementation, limited evidence supports the concordance between drinking in the laboratory and in a natural setting. This study examined the relationship between self-reports of drinking prior to and drinking and craving during an alcohol drinking paradigm (ADP). Participants were adult heavy drinkers (N = 64) who participated in a pharmacotherapy study. Participants completed self-report alcohol assessments and a baseline ADP session prior to any medication administration. Alcohol craving was assessed during priming and ad lib ADP phases. Outcomes were the associations of total drinks consumed in-laboratory and summary drinking measures for the 30 days prior to the ADP and reports of maximum drinks (past year and lifetime). Additional outcomes were the association of self-reported drinking and alcohol craving during the ADP and the concordance between self-report and ADP World Health Organization (WHO) drinking classifications. Number of drinking days, average drinks per drinking occasion, and lifetime and past-year maximum drinks were all related to drinking in the laboratory. Heavy drinking days were not related to drinking in the laboratory but were associated with ADP craving. Alcohol craving was also associated with other measures of self-reported drinking. There was also a significant association between WHO drinking risk classification and in-laboratory drinking. The observed relationships between self-reported drinking and drinking in-laboratory across drinking indices suggest that in-laboratory alcohol consumption may reflect participants' real-world alcohol consumption, supporting the value of laboratory-based drinking paradigms. The demonstrated relationship with self-reported drinking and ADP alcohol craving further supports the value of such paradigms to model key drinking predictors. These results provide support for the validity of laboratory-based paradigms to accurately reflect participants' recent drinking levels.


Entropy Generation Minimization Analysis of Active Magnetic Regenerators.
A performance assessment of active magnetocaloric regenerators using entropy generation minimization is presented. The model consists of the Brinkman-Forchheimer equation to describe the fluid flow and coupled energy equations for the fluid and solid phases. Entropy generation contributions due to axial heat conduction, fluid friction and interstitial heat transfer are considered. Based on the velocity and temperature profiles, local rates of entropy generation per unit volume were integrated to give the cycle-average entropy generation in the regenerator, which is the objective function of the optimization procedure. The solid matrix is a bed of gadolinium spherical particles and the working fluid is water. Performance evaluation criteria of fixed cross-section (face) area (FA) and variable geometry (VG) are incorporated into the optimization procedure to identify the most appropriate parameters and operating conditions under fixed constraints of specified temperature span and cooling capacity.


Uric acid and divergent thinking: a possible relationship.
An exploratory investigation of the relationship between serum uric acid levels in male university students and their scores on tests of convergent and divergent thinking was carried out. The data suggested that uric acid levels are lower in highly divergent thinkers than in less divergent. This led to the speculation that uric acid may be an important biochemical precursor of intellectual functioning. If it does affect intellectual functioning, this may result from the action of uric acid as an endogenous cortical stimulant, or possibly from its action as a facilitator of learning.


Sterno-costo-clavicular hyperostosis. A case report with a review of the literature.
The clinical and radiologic findings in a case of sterno-costo-clavicular hyperostosis are reported and compared with the findings in the 23 Caucasian and about 300 Japanese cases reported in the literature. The main complaints are pain in the upper anterior chest wall and sometimes limited mobility of the shoulders. Radiologically, the clavicles, the sternum and the first ribs are grossly enlarged with complete fusion between them. As reported in previous cases, our patient had conspicuous congestion of the external jugular veins, but no other signs of compression in the thoracic inlet. There was asymptomatic compression of both subclavian veins, but none of the previously reported skin manifestations and no complaints from other parts of the locomotive system. The patient was HLA-B27 negative.