Solar UV doses of adult Americans and vitamin D(3) production.
Sunlight contains UV radiation that affects human health in both detrimental (skin cancers) and beneficial (vitamin D(3)) ways. An evaluation of the vitamin D status of adult Americans (22-40, 41-59, 60+ yr) show many have deficient or insufficient serum levels of 25-hydroxyvitamin D, indicating they are not getting enough from dietary sources or sunlight. Those findings are in conflict with calculated values from the American Academy of Dermatology who insist people make "ample" vitamin D(3) (≥1,000 IU/day) from their "casual," or everyday, outdoor UV exposures even if they use sunscreens with sun protection factor 15. We investigated this situation using the everyday outdoor UV doses of indoor-working adult Americans (∼7,000) in the north (45°N) and south (35°N) to calculate how much vitamin D(3) they produce each season with and without vacationing. Only during the summer can skin type II Caucasian adults (21-59 yr) meet their minimum (600 IU/day) vitamin D(3) needs from everyday exposures, but only if they do not wear professional clothes or sunscreens (except beach vacations). To do vitamin D(3) calculations properly, we used action spectrum and geometric conversion factors, not previously incorporated into other calculations. Most adult Americans do not go outside enough to meet their minimum or optimum (≥1,200 IU/day) vitamin D(3) needs all year. The darker skin types (III-VI) and the oldest people (>59 yr) are at the highest risk for not making enough vitamin D(3) during the year from everyday outdoor exposures even with a 2-3 week summer vacation.


Incidence and disease burden of herpes zoster in the population aged ≥50 years in China: Data from an integrated health care network.
Herpes zoster (HZ) mainly affects elderly and immunocompromised individuals and is characterized by a painful vesicular rash. Data on the epidemiology of HZ, particularly in unvaccinated individuals aged ≥50 years, are still limited in China. Thus, this study aimed to evaluate the epidemiological features, disease burden, and associated risk factors of HZ in the population aged ≥50 years in China. We evaluated HZ patients who were aged ≥50 years between January 1, 2015 and December 31, 2017 in the electronic health record database of Yinzhou district. HZ and its complications were identified using ICD-10 codes. In addition, post-herpetic neuralgia (PHN) as a complication of HZ was defined as pain occurring or persisting 90 days after rash onset. The disease burden was estimated according to the duration of hospitalization, frequency of visits, pharmacological treatment cost, and examination cost. Cox proportional hazards regression was used to investigate the associated risk factors for HZ. The overall incidence of HZ was 6.64 per 1000 person-years. Of the 4,313 initial episodes from 2015 to 2017, there were 99 recurrent cases. In total, 7.26% and 3.94% of the HZ patients had PHN and other complications, respectively. The average frequency of outpatient visits was significantly lower in patients with initial disease than that in patients with recurrence (3.6 vs. 6.7 per patient). The mean duration of hospital stay was longer in the recurrent episode than that in the initial episode (24.0 vs. 21.6 days). The inpatient and outpatient cost per new-onset HZ was approximately ¥8116.9 and ¥560.2 per patient, respectively. Age; female sex; suburban residency; and presence of immunocompromised disease, hypertension, or diabetes were significantly associated with the development of HZ. The incidence and recurrence rates of HZ showed different trends with increasing age. The presence of HZ-related complications increased the direct medical costs. Our findings help provide a basis for developing appropriate strategies for HZ prevention and control.


CSF tap test - Obsolete or appropriate test for predicting shunt responsiveness? A systemic review.
There is no accurate test for diagnosing normal pressure hydrocephalus or for screening for patients who will benefit from shunt surgery. Additional tests, such as cerebrospinal fluid tap test (CSF-TT), are often used in practice to provide further predictive value in detecting suitable patients for shunting. We performed a systematic review of the literature to evaluate the CSF-TT's effect on the outcome of main symptoms and on validity parameters in screening patients suitable for shunting. In February 2015 we searched electronic databases from their inception to the current date, using the following key words: normal pressure hydrocephalus, idiopathic normotensive hydrocephalus, shunt operation, CSF tap test, predictive value, validity. The search retrieved 8 articles explicitly addressing the topic. There was a very high positive predictive value of CSF-TT: 92% (range from 73% to 100%) but a low negative predictive value: 37% (18%-50%). Also, the CSF-TT has high specificity: 75% (33%-100%) but average sensitivity: 58% (26%-87%). The overall accuracy of the test was 62% (45%-83%). This systematic review did not provide unambiguous validity of the CSF-TT in the screening of patients for shunting. The validity of the CSF-TT is good for patient inclusion for shunting due to the fact that the positive response to the test is very reliable. Unfortunately, the negative response to the test does not reliably make these patients ineligible for shunting. Further studies are needed to improve and standardize the methodology in order to optimize the detection power of the test.


The strategy of Myxococcus xanthus for group cooperative behavior.
New evidence has been presented from our laboratory that the gliding bacterium, Myxococcus xanthus, does not home by chemotaxis toward a nutrient source. Our experiments, those of others, and the theory presented here combine to suggest a model, called the 'Pied Piper' model. It hypothesizes a gene that has a high mutation rate forward and back (say something in excess 10(-4) mutations per cell generation) which leads to switching between two motility states. Occasionally rare organisms become genetically, but reversibly, changed so that they move unidirectionally instead of mostly forward and back as do the bulk of the cells. When such a 'leader' cell arises, it continues to move in its original orientation, and causes a cohort of cells to move together away from the bulk of the cells. That is, in the less common mutational state it counteracts the usual tendency to just move forward and backward achieving little net movement. The assumption of a genetic element that mutates in a reversible way is suggested by numerous cases of reversible switches now known in a wide range of bacteria serving a variety of functions. A second aspect of the model is that mechanisms exist that cause cells to move in the same direction as their nearby neighbors. This process results in a regular spacing of bands of cells to form mounds in the absence of a leader. The action of C-factor, a factor-secreted by the cells which has been largely studied in the laboratory of Dale Kaiser, and extracellular fibrils, (rod-shaped protein and carbohydrate bodies) largely studied in the laboratory of Martin Dworkin, may be key elements in coordinating (or linking) the movements of neighboring cells. Based on the assumption of the absence of chemotaxis, computer simulations of pattern formation for gliding bacterial swarms and flares are consistent with observed behaviors and thus are additional evidence that chemotactic motility of the type exhibited by Escherichia coli, is not necessary for the group movements of M. xanthus. Some tests for this model are suggested.


Regulating the biodegradation of petroleum hydrocarbons with different carbon chain structures by composting systems.
Composting can decrease petroleum hydrocarbons in petroleum contaminated soils, however the microbial degradation mechanisms and regulating method for biodegradation of petroleum hydrocarbons with different carbon chain structures in the composting system have not yet been investigated. This study analyzed variations of total petroleum hydrocarbon concentrations with C ≤ 16 and C > 16, Random Forest model was applied to identify the key microorganisms for degrading the petroleum hydrocarbon components with specific structure in biomass-amended composting. Regulating method for biodegradation of petroleum hydrocarbons with different carbon chain structures was proposed by constructing the influence paths of "environmental factors-key microorganisms- total petroleum hydrocarbons". The results showed that composting improved the degradation rate of C ≤ 16 fraction and C > 16 fraction of petroleum hydrocarbons by 67.88 % and 61.87 %, respectively. Analysis of the microbial results showed that the degrading bacteria of the C ≤ 16 fraction had degradation advantages in the heating phase of the compost, while the C > 16 fraction degraded better in the cooling phase. Moreover, microorganisms that specifically degraded C > 16 fractions were significantly associated with total nitrogen and nitrate nitrogen. The biodegradation of C ≤ 16 fraction was regulated by organic matter, moisture content, and temperature. The composting system modified by biogas slurry was effective in removing of petroleum hydrocarbons with different carbon chain structures in soil by regulating the metabolic potential of the 46 key microorganisms. This study given their expected importance to achieve the purpose of treating waste with waste and contributing to soil utilization as well as pollution remediation.


Progressive changes in somatosensory cortical maps in 6-week-old kittens cord-transected at T12.
Maps of primary somatosensory cortex were obtained using multiunit recordings immediately, and 3, 6, 9 and 12 weeks following cord-transection (T12) performed on 6-week-old kittens. Results suggest that cortex responds to the injury in two stages: (1) after 3 weeks, all deprived cortex can be excited by the remaining afferent input with little somatotopic organization: and (2) by 12 weeks, the area of drivable cortex has decreased, but somatotopic organization is present within this region.


Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae testing susceptible to cefepime by reference methods.
β-Lactam susceptibility of 499 Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae, determined by reference broth microdilution, demonstrated that 14.4% of isolates were categorized as cefepime susceptible according to current CLSI breakpoints. Ceftazidime- and meropenem-susceptible isolates were also observed (2.6 and 3.0%, respectively). Cefepime-susceptible KPC-producing isolates may confuse laboratory staff and clinicians in their therapeutic choices.


Quorum sensing and the anaerobic regulator (ANR) control polyhydroxyalkanoate (PHA) production in Pseudomonas chlororaphis PA23.
Pseudomonas chlororaphis PA23 is a biocontrol agent that, in addition to producing antifungal compounds, synthesizes polyhydroxyalkanoate (PHA) polymers as a carbon and energy sink. Quorum sensing (QS) and the anaerobic regulator (ANR) are required for PA23-mediated fungal suppression; however, the role of these regulators in PHA production is unknown. Strains lacking either QS or ANR accumulated less PHA polymers when propagated on Ramsay's minimal medium (RMM) with glucose or octanoate as the carbon source. In the acyl-homoserine lactone (AHL)-deficient background, all six of the genes in the pha locus (phaC1, phaC2, phaZ, phaD, phaF, phaI) showed reduced expression in RMM glucose, and all except phaC2 were repressed in RMM octanoate. Although changes in gene activity were observed in the anr mutant, they were less pronounced. Analysis of the promoter regions for QS- and ANR-binding consensus sequences revealed putative phzboxes upstream of phaZ and phaI, but no anr boxes were identified. Our findings indicate that altered pha gene expression likely contributes to the lower PHA accumulation in the QS- and ANR-deficient strains, which may be in part indirectly mediated. This study is the first to show that mcl-PHA production is under QS and ANR control.


Crosstalk of protein kinase C ε with Smad2/3 promotes tumor cell proliferation in prostate cancer cells by enhancing aerobic glycolysis.
Protein kinase C ε (PKCε) has emerged as an oncogenic protein kinase and plays important roles in cancer cell survival, proliferation, and invasion. It is, however, still unknown whether PKCε affects cell proliferation via glucose metabolism in cancer cells. Here we report a novel function of PKCε that provides growth advantages for cancer cells by enhancing tumor cells glycolysis. We found that either PKCε or Smad2/3 promoted aerobic glycolysis, expression of the glycolytic genes encoding HIF-1α, HKII, PFKP and MCT4, and tumor cell proliferation, while overexpression of PKCε or Smad3 enhanced aerobic glycolysis and cell proliferation in a protein kinase D- or TGF-β-independent manner in PC-3M and DU145 prostate cancer cells. The effects of PKCε silencing were reversed by ectopic expression of Smad3. PKCε or Smad3 ectopic expression-induced increase in cell growth was antagonized by inhibition of lactate transportation. Furthermore, interaction of endogenous PKCε with Smad2/3 was primarily responsible for phosphorylation of Ser213 in the Samd3 linker region, and resulted in Smad3 binding to the promoter of the glycolytic genes, thereby promoting cell proliferation. Forced expression of mutant Smad3 (S213A) attenuated PKCε-stimulated protein overexpression of the glycolytic genes. Thus, our results demonstrate a novel PKCε function that promotes cell growth in prostate cancer cells by increasing aerobic glycolysis through crosstalk between PKCε and Smad2/3.


Metabolomic identification of pregnancy-specific biomarkers in blood plasma of BOS TAURUS beef cattle after transfer of in vitro produced embryos.
Blood biomarkers may help to predict pregnancy in recipients of in vitro produced (IVP) embryos. Using 1H nuclear magnetic resonance, we quantified 36 metabolites in the blood plasma of recipients (90% heifers, healthy, 1.95 years on average at the time of 1st embryo transfer -ET-) collected at Day-0 (estrus) and Day-7 (before ET time). First, IVP embryos were transferred to Asturiana de los Valles recipients as fresh (F) (N = 26) and vitrified/warmed (V/W) (N = 48) (discovery groups). Only at estrus, we discovered 4, 11, and 5 (F-ET), and 2, 2, and 4 (V/W-ET) metabolites that predicted pregnancy on Day-40, Day-62 and calving time, respectively (ROC-AUC > 0.700; P < .05). Thereafter, validation was performed in independent samples (N = 67 F and N = 63 V/W) of three cattle breeds by an index of overall classification accuracy (OCA>0.650, P < .05). The numbers of candidate biomarkers validated were 2, 9 and 1 (F-ET) and 2, 2, and 3 (V/W-ET) on Day 40, Day-62 and calving time. Relevant metabolites were validated at the three (2-Oxoglutaric acid (F-ET), and 2-Hydroxybutyric acid and Dimethylamine (V/W-ET)) and two pregnancy endpoints (Ketoleucine (F-ET); Day-40 and Day-62) analysed. Fatty acid degradation and oxidative metabolism were enriched in pregnant recipients. The candidate biomarkers identified can improve embryo-recipient selection. SIGNIFICANCE: We identified, for the first time, reliable pregnancy and birth candidate metabolite biomarkers for fresh and vitrified IVP embryos in blood of beef cattle recipients. Our findings can help to improve embryo-recipient selection, which is usually carried out in a way that females that will not become pregnant are not well differentiated.


Changes in intracellular cyclic AMP levels of human peripheral blood lymphocytes in bronchial asthma.
Peripheral blood lymphocytes of asthmatic patients in the acute stage manifest low basal levels of cyclic AMP. These levels were higher in the lymphocytes of patients in remission than in controls. Trypsin treatment of the lymphocytes increased cyclic AMP content to almost the same additional activation site of the receptor in theophylline- and catecholamines-treated patients.


Intravenous levetiracetam for epileptic seizure emergencies in older people.
Clinical experience with intravenous levetiracetam (LEV IV) is still very limited, especially in elderly subjects. The primary objective of this retrospective observational study was to describe the efficacy and tolerability of LEV IV in older patients presenting with epileptic seizure emergencies. Medical records of 14 older people treated with LEV IV were analysed retrospectively. All patients suffered from series of complex partial seizures or convulsive or non-convulsive status epilepticus needing emergent intravenous (IV) antiepileptic drug (AED) treatment. Nine patients were taking AED therapy when LEV IV was administered. Mean age was 73.9 years (range 61-97). Mean dosage was 1,643 mg/day (range 500-4,000). Seizure control could be achieved in 11/14 patients (78.6%). No significant adverse events were noted besides sedation. LEV IV was effective and well tolerated in these critically ill older patients. LEV IV seems to be a reasonable practical alternative in multimorbid older patients who need IV treatment with an AED.


Extended interval aminoglycoside dosing: from concept to clinic.
Extended-interval aminoglycoside dosing (EIAD), while a relatively recent concept in mainstream clinical practice, actually has its roots in the mid 1970s. Early trial and error approaches of manipulating the dosage regimen to avoid toxicity and improve efficacy have helped to characterize the pharmacodynamic properties of these drugs. The increasing successful use of EIAD and improved understanding of pharmacodynamics has helped this dosing regimen gain acceptance into routine clinical practice. A 1998 United States survey demonstrated that approximately 75% of hospitals have adopted EIAD into routine patient care. However, controversy still exists regarding some aspects of infrequent aminoglycoside administration, such as length of the drug-free interval and patient exclusion criteria. After more than 50 years of experience with the aminoglycosides we continue to learn how to most appropriately use these drugs.


Impact of Multiple En Face Image Averaging on Quantitative Assessment from Optical Coherence Tomography Angiography Images.
To investigate the impact of multiple en face image averaging on quantitative measurements of the retinal microvasculature using optical coherence tomography angiography (OCTA). Prospective, observational, cross-sectional case series. Twenty-one healthy individuals with normal eyes. Macular OCTA images were acquired from all participants using the Zeiss Cirrus 5000 with Angioplex OCTA software (Carl Zeiss Meditec, Dublin, CA). Nine OCTA cube scans per eye were obtained and 9 superficial retinal layer (SRL) and deep retinal layer (DRL) en face OCTA image slabs were averaged individually after registration. Quantitative parameters from the retinal microvasculature were measured on binarized and skeletonized OCTA images and compared with single OCTA images without averaging. Vessel density (VD), vessel length density (VLD), vessel diameter index (VDI), and fractal dimension (FD). Participants with artifact or poor image quality were excluded, leaving 18 eyes for the analysis. After averaging, qualitatively there was apparent reduction in background noise, and fragmented vessels in the images before averaging became continuous with smoother walls and showed sharper contrast in both the SRL and DRL. Binarized and skeletonized derivates of these averaged images also showed fewer line fragments and dots in nonvascular areas and more continuous vessel images than those of images without averaging. In both SRL and DRL, VD (P = 0.0010 and P = 0.0003, respectively), VLD (P < 0.0001 for both), and FD (P < 0.0001 for both) significantly decreased and VDI significantly increased after averaging (P < 0.0001 for both). Averaging of multiple en face OCTA images improves image quality and also significantly impacts quantitative measurements. Reducing noise that could be misinterpreted as flow and annealing discontinuous vessel segments seem to be major mechanisms by which averaging may be of benefit.


Results of reconstruction of the anterior cruciate ligament with the tendons of semitendinosus and gracilis in acute capsulo-ligamentous lesions of the knee.
This report presents the mid-term results of 55 cases of anterior cruciate ligament (ACL) lesions surgically treated in "acute phase" using intra-articular transfer of the semitendinosus and gracilis tendons, performed at the First Orthopedic Clinic of "La Sapienza" University in Rome since 1979. The follow-up is based on clinical (point system comprising subjective and objective criteria), instrumental (KT-1000 arthrometer), and radiographic (comparative AP view radiographic exam of the knees under load) data. On the basis of the results obtained, ACL reconstruction with the semitendinosus and gracilis tendons in the treatment of acute lesions can provide the patient with a good possibility of complete functional recovery of the knee.


The influence of socioeconomic status on the hemoglobin level and anthropometry of sickle cell anemia patients in steady state at the Lagos University Teaching Hospital.
Sickle cell anemia (SCA) has multisystemic manifestations and is associated with severe morbidity and high mortality. It commonly affects growth leading to wasting and stunting. This study aimed to determine the influence of socioeconomic status on the nutritional status using anthropometric measurements and steady-state hemoglobin, of children with homozygous SCA, aged 1 year to 10 years in steady state at the Lagos University Teaching Hospital. This is a cross-sectional study involving 100 children with SCA and 100 age-, sex-, and social class-matched controls that fulfilled the inclusion criteria. Social class was assessed using educational attainment and occupation of parents. Hemoglobin concentration was determined using the oxy-hemoglobin method. This study demonstrated a significantly lower mean weight and weight-for-height in the SCA patients than those of controls (P < 0.001). By contrast, this study did not demonstrate any statistical significant difference in the mean height and mean body mass index of SCA patients and controls (P = 0.06) and (P = 0.12), respectively. The mean weight, height, and body mass indices of the subjects and controls were consistently below those of the NCHS standards. The magnitude of the difference from the NCHS standard was also more pronounced in the subjects, increased with advancing age and affected male subjects more than females. Progressive declines in the anthropometric attainment and hemoglobin concentration were observed from social class 1 to 4; this was statistically significant in controls (P = 0.00) but not in subjects (P > 0.1). However, SCA patients had significantly lower values than controls in each of the social classes. Poor socioeconomic status has an adverse effect on the nutritional status and hemoglobin of SCA patients.


Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer.
ISG15 plays a crucial role in the innate immune response and has been well-studied due to its antiviral activity and regulation of signal transduction, apoptosis, and autophagy. ISG15 is a ubiquitin-like protein that is activated by an E1 enzyme (Uba7) and transferred to a cognate E2 enzyme (UBE2L6) to form a UBE2L6-ISG15 intermediate that functions with E3 ligases that catalyze conjugation of ISG15 to target proteins. Despite its biological importance, the molecular basis by which Uba7 catalyzes ISG15 activation and transfer to UBE2L6 is unknown as there is no available structure of Uba7. Here, we present cryo-EM structures of human Uba7 in complex with UBE2L6, ISG15 adenylate, and ISG15 thioester intermediate that are poised for catalysis of Uba7-UBE2L6-ISG15 thioester transfer. Our structures reveal a unique overall architecture of the complex compared to structures from the ubiquitin conjugation pathway, particularly with respect to the location of ISG15 thioester intermediate. Our structures also illuminate the molecular basis for Uba7 activities and for its exquisite specificity for ISG15 and UBE2L6. Altogether, our structural, biochemical, and human cell-based data provide significant insights into the functions of Uba7, UBE2L6, and ISG15 in cells.


Epidemiology of human immunodeficiency virus testing among patients with tuberculosis in North Carolina.
Human immunodeficiency virus (HIV) testing is recommended for all patients with tuberculosis (TB). Surveillance data for all reported cases of TB in North Carolina from 1993 to 1999 were examined to assess HIV testing practices. Of 3,680 TB patients, 3,119 (85%) had HIV testing data reported. Of these, 604 (19%) were not offered HIV testing, 465 (18%) refused testing, 379 (15%) were HIV seropositive, 29 (0.8%) were tested but results were not reported, and 1 (0.03%) had an indeterminate result. Older patients were significantly less likely to be offered HIV testing and more likely to refuse testing. Males and African Americans were more likely to be offered and to accept testing. At least 34% of TB patients in North Carolina from 1993 to 1999 did not receive HIV testing. Patients in higher-risk groups were more likely to be tested, but even within the highest-risk groups, testing was not universal. Health care providers should offer HIV testing to all individuals with TB.


Axillo-axillary bypass for in-stent restenosis in Takayasu arteritis.
We report a patient with Takayasu arteritis (TA) who initially received stent placement (SP) following percutaneous transluminal balloon angioplasty for stenotic lesion of the left subclavian artery and subsequently had recurrent in-stent restenosis three times. Every time restenosis occurred, percutaneous transluminal rotational arterectomy (RA) was performed. After all, the patient underwent axillo-axillary bypass and has remained asymptomatic for 10 months after the surgery. We suggest that surgical treatment is beneficial for in-stent restenosis in patient with Takayasu arteritis.


Assessing the impact of organ-specific lesion dynamics on survival in patients with recurrent urothelial carcinoma treated with atezolizumab or chemotherapy.
Tumor dynamics typically rely on the sum of the longest diameters (SLD) of target lesions, and ignore heterogeneity in individual lesion dynamics located in different organs. Here we evaluated the benefit of analyzing lesion dynamics in different organs to predict survival in 900 patients with metastatic urothelial carcinoma treated with atezolizumab or chemotherapy (IMvigor211 trial). Lesion dynamics varied largely across organs, with lymph nodes and lung lesions showing on average a better response to both treatments than those located in the liver and locoregionally. A benefit of atezolizumab was observed on lung and liver lesion dynamics that was attributed to a longer duration of treatment effect as compared to chemotherapy (P value = 0.043 and 0.001, respectively). The impact of lesion dynamics on survival, assessed by a joint model, varied greatly across organs, irrespective of treatment. Liver and locoregional lesion dynamics had a large impact on survival, with an increase of 10 mm of the lesion size increasing the instantaneous risk of death by 12% and 10%, respectively. In comparison, lymph nodes and lung lesions had a lower impact, with a 10-mm increase in the lesion size increasing the instantaneous risk of death by 7% and 5%, respectively. Using our model, we could anticipate the benefit of atezolizumab over chemotherapy as early as 6 months before the end of the study, which is 3 months earlier than a similar model only relying on SLD. We showed the interest of organ-level tumor follow-up to better understand and anticipate the treatment effect on survival.


Towards a circular economy: valorization of banana peels by developing bio-composites thermal insulators.
The building construction materials are responsible for a large amount of energy and natural resource consumption. In light of the current challenges of resource scarcity and global climate change, the circular economy (CE) is a promising strategy to mitigate pressure on the environment, improve supplying of raw materials, and increase new market and employment opportunities. Developing eco-friendly thermal insulation materials based on agro-waste is a new waste management trend to achieve the sustainability of the resource and energy consumption in the construction sectors. In this work, banana-polystyrene composites were prepared by mixing the banana peels powder (BP) with polystyrene (PS) in different weight ratios (90:10, 80:20, 70:30, and 60:40). The physical and thermal properties such as thermal conductivity, electrical conductivity, Fourier Transform Infrared (FTIR), crystallographic structures of the fibers, X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC) were carried out on BP and BP-PS1 that were prepared with ten wt.% and 20 wt.% of polystyrene powder (BP-PS2). The bio-composites results showed low thermal conductivity ranging from 0.028 to 0.030 W/m.K. The BP-PS2 exhibited a lower thermal conductivity of 0.027 W/m.K, while the pure peel powder demonstrated notable thermal stability, indicated by a total weight loss of 66.4% and a high crystallinity value of 56.1%. Furthermore, the thermal analysis (TGA) and X-Ray Diffraction (XRD) demonstrated that the pure banana peel has the highest thermal stability and crystallinity. These findings indicate that using banana peel-polystyrene composites represents an innovative solution for thermal insulation in buildings as an alternative to conventional materials to reduce energy and resource consumption.


The prevalence and factors associated with mental disorders in a community setting in central Uganda.
Mental disorders are known to predict poverty, morbidity and mortality. In resource limited settings, low levels of mental health literacy (MHL) and high mental illness stigma (MIS) have been sighted as possible factors that may impede access to mental health care. However, little has been done to examine the association between mental disorders and these factors (MHL and MIS) in sub-Saharan Africa. We assessed for the prevalence of major depressive disorders (MDD), substance use disorders (SUD), post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), documented MHL and MIS among 814 participants from 24 villages in central Uganda. We conducted regression analyses to examine the association between the prevalence of mental disorders, demographic factors as well as MIS and MHL. Over two thirds of the participants 581 (70%) were female. The mean age of the participants was 38 years (SD± 13.5). The prevalence of mental disorders ranged from 6.8-32%. Participants who were older were less likely to screen positive for GAD (OR 0.98; 0.96-0.99), female gender was protective against SUD (OR 0.46; 0.3-0.68) and those with MDD had lower education level (OR 0.23; 0.1-0.53). The mean MIS score was 11.3 (SD± 5.4) with a range of 6-30 and the mean MHL score was 21.7 (SD ±3.0) with a range of 10-30. MIS was negatively associated with GAD [β = -1.211 (-2.382 to -0.040)]. There no statistically significant association between MHL and a mental disorder. There was a high prevalence of mental disorders in the community that we studied. Adequate resources should be allocated to address this burden.


A new computational model for protein folding based on atomic solvation.
A new model for calculating the solvation energy of proteins is developed and tested for its ability to identify the native conformation as the global energy minimum among a group of thousands of computationally generated compact non-native conformations for a series of globular proteins. In the model (called the WZS model), solvation preferences for a set of 17 chemically derived molecular fragments of the 20 amino acids are learned by a training algorithm based on maximizing the solvation energy difference between native and non-native conformations for a training set of proteins. The performance of the WZS model confirms the success of this learning approach; the WZS model misrecognizes (as more stable than native) only 7 of 8,200 non-native structures. Possible applications of this model to the prediction of protein structure from sequence are discussed.


Antimetastatic action of orally administered lysozyme in mice bearing Lewis lung carcinoma.
The pharmacological activity of orally administered lysozyme, for the control of the growth of solid tumor metastases, was examined in mice bearing Lewis lung carcinoma. Groups of at least 10 tumor-bearing mice, fed daily for three consecutive weeks from subcutaneous tumor implantation with lysozyme, prepared from hen egg-white, had a pronounced reduction of the weight of their metastatic tumor to 25-50 per cent of controls within a wide range of doses (25-200 mg/kg/day). The antimetastatic effect was not related to the length of the treatment schedule employed; a short course of 7 days, given on days 1-7 after tumor implantation, proved equally active. The inhibition of the formation of lung metastases, in mice treated with lysozyme prior to tumor inoculation, lasts for at least 2 weeks after discontinuation of treatment, indicating that the antimetastatic activity observed is not associated with cytotoxic activity of the lysozyme, and is probably mediated by the elicitation of host responses. The examination of the therapeutic potential of the antimetastatic action of lysozyme supplied through the usual diet indicates that this treatment synergizes with the antitumor effects of cisplatin, given to mice after surgical removal of the primary tumor, causing a statistically significant prolongation of the survival time of the animals as compared with chemotherapy alone.


Novel approach for extraction of grape skin antioxidants by accelerated solvent extraction: Box-Behnken design optimization.
Grape skin can be considered as an excellent and inexpensive source of polyphenol antioxidant compounds. A high-efficiency accelerated solvent extraction (ASE) method was developed for antioxidant polyphenols from grape skin. A three-factors three-level Box-Behnken design by response surface methodology was employed for optimization of extraction parameters in terms of total phenolic content, total anthocyanins content and antioxidant activity. The optimized condition was ethanol concentration of 48.80%, temperature of 50.79 °C and extraction time of 14.82 min. Under these conditions, the highest yields of polyphenol, the total phenolic content (15.24 mg GAE/g), total anthocyanins content (346.68 mg CGE/100 g) in grape skin, were obtained with significant antioxidant properties by DPPH, ABTS and FRAP assays. Moreover, the extracts from various grape skins by ASE, possessed ten main antioxidant polyphenols with the highest concentration of p-hydroxybenzoic acid and malvidin-3-O-glucoside. Compared with conventional solvent extraction, ASE extracted more amounts of polyphenols, exhibited more extraction level with shorter time and higher reproducibility.


Studies on kynurenine in human cerebrospinal fluid: lowered levels in epilepsy.
Kynurenine, tryptophan and 5-hydroxyindoleacetic acid were measured in human lumbar and cisternal cerebrospinal fluid (CSF) taken during pneumoencephalography. The results do not support the hypothesis that any substantial part of the CSF kynurenine is of central origin. However, the results suggest that CSF kynurenine is reduced in some epileptic subjects and this seems to be due to the disease rather than anticonvulsants. This finding is of interest in view of the reported convulsant effect of kynurenine in experimental animals.


Crosstalk between the heme oxygenase system, aldosterone, and phospholipase C in hypertension.
Aldosterone is a mineral corticoid hormone that is produced in response to angiotensin-II, and like angiotensin-II, stimulates inflammation, oxidative stress, and fibrosis by activating nuclear factor-kappaB and activating protein-1. Recent evidence, however, indicates that aldosterone stimulates phospholipase C and activates nuclear factor-kappaB and activating protein-1. Although the heme oxygenase system is cytoprotective, its effects on aldosterone-phospholipase C signaling in deoxycorticosterone acetate (DOCA-salt) hypertension, a model of aldosteronism, and spontaneously hypertensive rat, a genetic model of human essential hypertension, have not been fully characterized. In the present study, the heme oxygenase inducer, hemin, was given to spontaneously hypertensive and deoxycorticosterone acetate hypertensive rats, and the effects on blood pressure, aldosterone, nuclear factor-kappaB, activating protein-1, phospholipase C, and inositol 1,4,5-triphosphate were examined. Hemin therapy restored physiological blood pressure to spontaneously hypertensive rats (209.9 +/- 0.9 to 127.3 +/- 0.85 mmHg, n = 10, P < 0.01) and to deoxycorticosterone acetate salt hypertensive rats (195.7 +/- 1.8 vs.132.5 +/- 2.1 mmHg; P < 0.01, n = 10), but had no effect on age-matched normotensive Wistar-Kyoto or Sprague-Dawley strains. The antihypertensive effect was accompanied by enhanced heme oxygenase activity, upregulated cyclic guanosine monophosphate-protein kinase G signaling, increased superoxide dismutase activity, and the potentiation of total antioxidant capacity, whereas aldosterone, activating protein-1, and nuclear factor-kappaB were reduced. Furthermore, hemin suppressed phospholipase C activity, attenuated inositol 1,4,5-triphosphate, and reduced resting intracellular calcium in the aorta. Collectively, our results suggest that the concomitant depletion of aldosterone, phospholipase C-inositol 1,4,5-triphosphate activity, resting intracellular calcium and the corresponding decline of inflammatory, and oxidative insults may account for the antihypertensive effects of hemin in deoxycorticosterone acetate hypertension and spontaneously hypertensive rats.


Schizophrenia: the cellular biology of a functional psychosis.
Structural abnormalities are found in the brains of schizophrenics. They affect preferentially, but not exclusively, medial temporal lobe structures (parahippocampal gyrus, hippocampus and amygdala), and can be found in all sub-types of schizophrenia. The structures of the medial temporal lobe are believed to have a crucial role in the integration and processing of the output from association cortex. It is probable that all schizophrenics have abnormalities in the medial temporal lobe that differ in degree but not in kind. Dysfunction of this system could result in the clinical symptoms that form the core of the schizophrenia syndrome. The changes in brain structure are not the result of neurodegenerative processes or destructive lesions but suggest a disturbance in the normal pattern of brain development.


Proteasuria in nephrotic syndrome-quantification and proteomic profiling.
Nephrotic syndrome is characterized by urinary excretion of plasma proteases or proteasuria. There is a lack of data on the quantity, activity status and identity of these aberrantly filtered proteases. We established a fluorescence-based substrate assay to quantify protease activity in urine samples from healthy and nephrotic humans and mice. Protease class activity was determined after addition of specific inhibitors. Individual proteases were identified by tandem mass spectrometry (MS/MS). In spot urine samples from 10 patients with acute nephrotic syndrome of various etiology, urinary protease activity was significantly increased compared to that of healthy persons (753 ± 178 vs. 244 ± 65 relative units, p < 0.05). The corresponding proteases were highly sensitive to inhibition by the serine protease inhibitors AEBSF (reduction by 85 ± 6% and 72 ± 8%, respectively) and aprotinin (83 ± 9% vs. 25 ± 6%, p < 0.05). MS/MS of all urinary proteins or after AEBSF purification showed that most of them were active serine proteases from the coagulation and complement cascade. These findings were recapitulated in mice, pointing to a similar pathophysiology. In conclusion, nephrotic syndrome leads to increased urinary excretion of active plasma proteases which can be termed proteasuria. Serine proteases account for the vast majority of urinary protease activity in health and nephrotic syndrome. SIGNIFICANCE STATEMENT: In this study, we found that nephrotic urine samples of humans and mice have a significantly increased protease activity compared to healthy urine samples, using a universal pentapeptide substrate library. This was driven by increased excretion of aprotinin-sensitive serine proteases. With tandem mass spectrometry, we provide a comprehensive and systematic overview of all urinary proteases or the "urine proteasome". We identified renally expressed proteases in health and addition of proteases from the coagulation and complement cascade in the nephrotic state. These results set the basis to study the role of urinary proteases at both health and nephrotic syndrome to find diagnostic markers of renal disease as well as possible therapeutic targets.


Nurse staffing studies: no need to reinvent the wheel.
The authors estimate that hospitals spend $15,000,000 yearly on nurse staffing studies. Unfortunately, much of this annual investment is used to reinvent the wheel. Therefore, this article recommends standardizing the terminology and some of the basic principles for patient classification (the basis of nurse staffing systems) so that directors of nursing can better assess their organizations and make meaningful comparisons with other institutions. This article is adapted from a presentation at the annual meeting of the Hospital Management Systems Society, Tucson, Arizona, February 15, 1979.


Trends in temporomandibular joint surgery: economic implications and complications.
A 5-year retrospective study of 103 patient records was undertaken. It analyzed the trend toward outpatient surgical management of patients requiring temporomandibular joint arthroplasties and determined the relative economic value and complication rate associated with this trend. Complication rates were not significantly different during the 5-year study interval, and comparative costs to the patient showed a 26% reduction for the 5-year interval.


A sustainable single-component "Silk nacre".
Synthetic composite materials constructed by hybridizing multiple components are typically unsustainable due to inadequate recyclability and incomplete degradation. In contrast, biological materials like silk and bamboo assemble pure polymeric components into sophisticated multiscale architectures, achieving both excellent performance and full degradability. Learning from these natural examples of bio-based "single-component" composites will stimulate the development of sustainable materials. Here, we report a single-component "Silk nacre," where nacre's typical "brick-and-mortar" structure has been replicated with silk fibroin only and by a facile procedure combining bidirectional freezing, water vapor annealing, and densification. The biomimetic design endows the Silk nacre with mechanical properties superior to those of homogeneous silk material, as well as to many frequently used polymers. In addition, the Silk nacre shows controllable plasticity and complete biodegradability, representing an alternative substitute to conventional composite materials.


Mandibular fibular graft reconstruction with CAD/CAM technology: A clinical report and literature review.
This clinical report describes the treatment of a partially dentate patient who presented with dental implants placed in a reconstructed fibula graft in the mandible. A complete mouth rehabilitation with a maxillary complete denture and a mandibular implant-supported fixed complete denture was fabricated with computer-aided design and computer-aided machining technology.


Rostral ventromedial medulla and the control of cutaneous vasoconstrictor activity following i.c.v. prostaglandin E(1).
Neurones within the rostral ventromedial medulla project to the intermediolateral cell column of the spinal cord where they may influence sympathetic preganglionic neuronal activity controlling cutaneous vascular beds. Here we assess whether such neurones contribute to cutaneous sympathetic vasoconstrictor activity in a fever-like state induced by i.c.v. injection of E-series prostaglandin. In urethane-anaesthetised rats, we recorded population sympathetic activity to the tail (an index of vasoconstrictor discharge regulating cutaneous thermoregulatory circulations). A survey of the effects of GABA microinjections (200 mM; 60-80 nl; 111 sites in 57 rats) demonstrated that those into the rostral ventromedial medulla (in the region of raphe pallidus and magnus; approximately bregma -10 to -12 mm) markedly decreased (51%-100%) population sympathetic cutaneous vasoconstrictor activity during "normothermic control." In contrast, injections at sites dorsal and lateral to this region tended to produce either a smaller decrease or have no effect. In heat-clamp (nine animals: body temperature 40-41 degrees C) cutaneous vasoconstrictor activity was decreased by 83+/-5%. I.c.v. prostaglandin E(1) (100 ng and above) restored activity to, or above, control levels in these animals and where body temperature was maintained at control levels (12 animals: body temperature 35.5-36.5 degrees C). The depressant action of GABA was sustained in both conditions. GABA did not significantly influence concurrently recorded splanchnic nerve activity and heart rate in any condition although both were increased following i.c.v. prostaglandin E(1) (500 ng). This study is the first to demonstrate that inhibition of neuronal activity within the rostral ventromedial medulla decreases sympathetic cutaneous vasoconstrictor activity during normothermic control and following i.c.v. prostaglandin E(1) (both with and without heat-clamp). Therefore, sympathetic premotor neurones in this area contribute to vasoconstrictor drive in these conditions. In contrast, we were unable to demonstrate that the same area had a substantial involvement in the control of splanchnic nerve activity or heart rate, even when these were enhanced following i.c.v. prostaglandin E(1).


Effect of neonatal seizure burden and etiology on the long-term outcome: data from a randomized, controlled trial.
Neonatal seizures are common, but the impact of neonatal seizures on long-term neurologic outcome remains unclear. We addressed this question by analyzing data from an early-phase controlled trial of bumetanide to treat neonatal seizures. Neonatal seizure burden was calculated from continuous video-EEG data. Neurologic outcome was determined by standardized developmental tests and post-neonatal seizure recurrence. Of 111 enrolled neonates, 43 were randomized to treatment or control groups. There were no differences in neurologic outcome between treatment and control groups. A subgroup analysis was performed for 84 neonates with acute perinatal brain injury (57 HIE, 18 stroke, 9 ICH), most of whom (70%) had neonatal seizures. There was a significant negative correlation between seizure burden and developmental scores (p<0.01). Associations between seizure burden and developmental scores were stronger in HIE and stroke groups compared with ICH (p<0.05). Bumetanide showed no long-term beneficial or adverse effects, as expected based on treatment duration versus duration of neonatal seizures. For neonates with perinatal brain injury, higher neonatal seizure burden correlated significantly with worse developmental outcome, particularly for ischemic versus hemorrhagic brain injury. These data highlight the need for further investigation of the long-term effects of both neonatal seizure severity and etiology.


Comparison of epidemiologic methods for active surveillance of vaccine safety.
We performed a simulation study to compare four study designs [(matched-cohort, vaccinated-only (risk-interval) cohort, case-control, and self-controlled case-series (SCCS)] in the context of vaccine safety active surveillance. For each combination of various incidence levels (3, 30, 300 per 10(5) person-years) and relative risks (RR 1.5-18), 100 case sets were infused into the cohort, matching 10(5) vaccinated to 10(5) unvaccinated on age and gender. The matched-cohort was converted into weekly accumulated data intervals with the other three study design samples drawn from each. Analyses were with appropriate regression models. The signal detection time was the first week where the log likelihood ratio (LLR) exceeded the upper boundary from the MaxSPRT sequential analysis method. Empirical type I (false positive) and type II (power) error rates and risk estimate bias were also calculated. The matched-cohort design exhibited the shortest detection time, lowest false positive rate and highest empirical power followed by the risk-interval cohort, SCCS, and case-control. In most monitoring weeks, the risk estimate bias was smallest for the cohort, followed by the risk-interval, SCCS and case-control designs. The cohort study design performed the best in the sequential analysis of active surveillance for vaccine safety. The risk-interval cohort and SCCS designs offer reasonable and efficient alternatives, especially if selection bias is a concern. Future research should address seasonality or age effects.


Synthesis and biological activity of 5-{4-[2-(methyl-p-substituted phenylamino)ethoxy]benzyl}thiazolidine-2,4-diones.
Thiazolidinedione derivatives are potential antidiabetic drugs that bind and activate peroxisome proliferator activated receptor gamma (PPARgamma), which is a member of the nuclear hormone receptor superfamily and enhances insulin sensitivity. In an effort to develop a novel and effective thiazolidindione derivative, 5-{4-[2-(methyl-p-substituted phenylamino) ethoxy] benzyl} thiazolidine-2,4-diones 7 have been prepared by Mitsunobu reaction of the hydrophobic segment, methyl-p-substituted phenylaminoethanol 4 with hydroxybenzylthiazolidinedione 5 and their ability to activate PPARgamma and inhibit LPS-induced NO production were evaluated.


Acceptance and Adherence to Continuous Positive Airway Pressure Therapy in patients with Obstructive Sleep Apnea (OSA) in a Southeast Asian privately funded healthcare system.
There is limited data on long term Continuous Positive Airway Pressure (CPAP) adherence in Southeast Asian countries. This is a prospective study on CPAP adherence among Obstructive sleep apnea (OSA) patients in a Southeast Asian privately funded healthcare system. Patients with moderate-severe OSA who had been initiated on CPAP at least one year previously were contacted for a scripted telephone interview to assess compliance and factors associated with CPAP adherence. Of 135 consecutive patients diagnosed to have moderate to severe OSA, 78 (57.8%) were initiated on CPAP treatment while 57 (42.2%) rejected CPAP upfront. 41 (52.6%) who initiated CPAP remained adherent at one year. OSA severity (AHI, ODI) and symptomatic improvement after CPAP were associated with better adherence. Presence of machine related side effects was associated with lower adherence. Inconvenience, cost and poor disease perception were reported as major barriers to uptake of CPAP therapy. In this Southeast Asian privately funded healthcare system, almost half of all patients with significant OSA rejected CPAP treatment upfront, but adherence among those who started CPAP is comparable to other reports. Challenges with CPAP acceptance as well as CPAP adherence need to be addressed to improve outcomes.


Conversion and optimization of telehealth in obstetric care during the COVID-19 pandemic.
When New York City became the international epicenter of the COVID-19 pandemic, telehealth at Columbia University Irving Medical Center was expanded in the inpatient and outpatient settings. The goals of telehealth during the pandemic were to maintain patient access to care while reducing the risk for COVID-19 exposure for patients and staff. Recommendations are made on how telehealth can be implemented and utilized to accomplish these goals. In the outpatient setting, virtual prenatal care visits and consultations can replace most in-person visits. When visitor restrictions are in effect telehealth can be used to engage support persons in the delivery room. Telehealth innovations can be leveraged to greatly improve care for COVID-19 mothers and their infants during the COVID-19 pandemic and beyond.


Lactobacillus fermentum promotes adipose tissue oxidative phosphorylation to protect against diet-induced obesity.
The gut microbiota has pivotal roles in metabolic homeostasis and modulation of the intestinal environment. Notably, the administration of Lactobacillus spp. ameliorates diet-induced obesity in humans and mice. However, the mechanisms through which Lactobacillus spp. control host metabolic homeostasis remain unclear. Accordingly, in this study, we evaluated the physiological roles of Lactobacillus fermentum in controlling metabolic homeostasis in diet-induced obesity. Our results demonstrated that L. fermentum-potentiated oxidative phosphorylation in adipose tissue, resulting in increased energy expenditure to protect against diet-induced obesity. Indeed, oral administration of L. fermentum LM1016 markedly ameliorated glucose clearance and fatty liver in high-fat diet-fed mice. Moreover, administration of L. fermentum LM1016 markedly decreased inflammation and increased oxidative phosphorylation in gonadal white adipose tissue, as demonstrated by transcriptome analysis. Finally, metabolome analysis showed that metabolites derived from L. fermentum LM1016-attenuated adipocyte differentiation and inflammation in 3T3-L1 preadipocytes. These pronounced metabolic improvements suggested that the application of L. fermentum LM1016 could have clinical applications for the treatment of metabolic syndromes, such as diet-induced obesity.


Direct-to-consumer marketing of psychological treatments for anxiety disorders.
Progress disseminating and implementing evidence-based psychological treatments (EBPTs) for the anxiety disorders has been gradual. To date, the dominant approach for promoting the uptake of EBPTs in clinical settings has been to target the education and training of mental health providers, with many consumers remaining unaware of the potential benefits of EBPTs for anxiety disorders. Direct-to-consumer (DTC) marketing may be a promising vehicle for increasing EBPT utilization rates in the treatment of anxiety disorders. This paper provides an overview of the rationale and important considerations for applying DTC efforts to promote evidence-based care in the treatment of anxiety disorders, and reviews current DTC efforts in this area, including resources on the Internet and other media and in-person events. We conclude with recommendations for future efforts in the DTC marketing of EBPTs for the anxiety disorders, including the need for increased funding and grassroots efforts to inform consumers about anxiety disorders and their most effective treatments.


Antisense Oligonucleotide Therapeutic Approach for Suppression of Ataxin-1 Expression: A Safety Assessment.
Spinocerebellar ataxia type 1 (SCA1) is a lethal, autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in the ATAXIN-1 (ATXN1) protein. Preclinical studies demonstrate the therapeutic efficacy of approaches that target and reduce Atxn1 expression in a non-allele-specific manner. However, studies using Atxn1-/- mice raise cautionary notes that therapeutic reductions of ATXN1 might lead to undesirable effects such as reduction in the activity of the tumor suppressor Capicua (CIC), activation of the protease β-secretase 1 (BACE1) and subsequent increased amyloidogenic cleavage of the amyloid precursor protein (APP), or a reduction in hippocampal neuronal precursor cells that would impact hippocampal function. Here, we tested whether an antisense oligonucleotide (ASO)-mediated reduction of Atxn1 produced unwanted effects involving BACE1, CIC activity, or reduction in hippocampal neuronal precursor cells. Notably, no effects on BACE1, CIC tumor suppressor function, or number of hippocampal neuronal precursor cells were found in mice subjected to a chronic in vivo ASO-mediated reduction of Atxn1. These data provide further support for targeted reductions of ATXN1 as a therapeutic approach for SCA1.


Feeding by whiteflies suppresses downstream jasmonic acid signaling by eliciting salicylic acid signaling.
Phloem-feeding whiteflies in the species complex Bemisia tabaci cause extensive crop damage worldwide. One of the reasons for their "success" is their ability to suppress the effectual jasmonic acid (JA) defenses of the host plant. However, little is understood about the mechanisms underlying whitefly suppression of JA-regulated defenses. Here, we showed that the expression of salicylic acid (SA)-responsive genes (EDS1 and PR1) in Arabidopsis thaliana was significantly enhanced during feeding by whitefly nymphs. Whereas upstream JA-responsive genes (LOX2 and OPR3) also were induced, the downstream JA-responsive gene (VSP1) was repressed, i.e., whiteflies only suppressed downstream JA signaling. Gene-expression analyses with various Arabidopsis mutants, including NahG, npr-1, ein2-1, and dde2-2, revealed that SA signaling plays a key role in the suppression of downstream JA defenses by whitefly feeding. Assays confirmed that SA activation enhanced whitefly performance by suppressing downstream JA defenses.


Hepatic and muscular effects of different dietary fat content in VLCAD deficient mice.
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common long-chain fatty acid oxidation defect presenting with heterogeneous clinical phenotypes. Dietary fat plays a crucial role in disease pathogenesis and fat restriction is a common treatment measure. We here investigate the hepatic and muscular effects of a fat-enriched and a fat-restricted diet. VLCAD knock-out (KO) and wild-type (WT) mice are subjected to a fat-rich (10.6%), a fat-reduced (2.6%) or a regular mouse diet (5.1%) for 5 weeks. Analyses are performed at rest and after one hour exercise on a treadmill. Acylcarnitines in muscle as well as lipid and glycogen content in muscle and liver are quantified. Expression of genes involved in lipogenesis is measured by Real-Time-PCR. At rest, VLCAD KO mice develop no clinical phenotype with all three diets, but importantly VLCAD KO mice cannot perform one hour exercise as compared to WT, this is especially apparent in mice with a fat-reduced diet. Moreover, changes in dietary fat content induce a significant increase in muscular long-chain acylcarnitines and hepatic lipid content in VLCAD KO mice after exercise. A fat-reduced diet up-regulates hepatic lipogenesis at rest. At the same time, muscular glycogen is significantly lower than in WT. We here demonstrate that a fat-reduced and carbohydrate-enriched diet does not prevent the myopathic phenotype in VLCAD KO mice. An increase in dietary fat is safe at rest with respect to the muscle but results in a significant muscular acylcarnitine increase after exercise.


Learning promotion of physiotherapy in neurological diseases: Design and application of a virtual reality-based game.
The virtual reality-based (VR) game can be considered as a new approach to education and to enhance the skills of health-care students. The purposes of this research were to design a VR game and to apply it to teach physiotherapy in neurological diseases. In this study, at first, a VR game was designed for upper limb rehabilitation in brain-injured patients based on the literature and the opinions of physiotherapy experts and game designers. Then, the designed game was used for teaching physiotherapy in neurological diseases. Thereafter, the opinions of 31 undergraduate students about the teaching session were evaluated by two anonymous questionnaires. Data analysis was performed using descriptive statistics through SPSS (version 19). The VR game developed under expert supervision. The evaluation showed that the median score for students' perception of learning was 3.11. The median scores of questions related to the "facilitating level of virtual reality" and "student satisfaction" were 8.66 and 9, respectively. The analysis of students' responses to open-ended questions highlighted the therapeutic aspect of the game compared to its educational aspect. Application of VR games in education can enhance the students' perception of learning. Furthermore, it can provide a better understanding of physiotherapy in patients with neurological diseases as well as the satisfaction of students. However, the survey indicated that the good results of this teaching method are due to the use of VR for guiding the patient's movements.


Trends in the effect of COVID-19 on consultations for persons with clinical and subclinical eating disorders.
The coronavirus disease 2019 (COVID-19) pandemic has increased the risk of individuals developing eating disorders and has exacerbated existing eating disorders. This observational study investigated the impact of the COVID-19 pandemic on patients with clinical and subclinical eating disorders. This study was conducted over a period of four years: two years before and after the onset of the COVID-19 pandemic in Japan. We recorded the number and types of consultations provided by the Eating Disorder Treatment and Support Center coordinator. For subgroup analysis, data were classified by age, body mass index, and source of consultation, including patients, families, and personnel. The Seasonal Decomposition of Time Series by Loess was used for time series analysis. The total number of consultations increased after the start of the pandemic and peaked around the beginning of 2022, before subsequently falling despite the increase in the number of COVID-19 infections. A similar trend was observed in patients aged 10-29 years. The study period coincided with social isolation and school/college/university closures. The number of eating disorder consultations increased after the start of the pandemic. Although COVID-19 infections persisted, the pandemic's impact was transient.


The cell based dressing with living allogenic keratinocytes in the treatment of foot ulcers: a case study.
In this study, we aimed to investigate the efficacy of cell based dressing with living allogenic keratinocytes in diabetic foot patients. To address this issue, the cultured keratinocytes were attached to the microcarriers produced from polyethylene and silica. The microcarriers were then applied to the wounds at 3-day intervals. Forty patients with grade II and III diabetic foot ulcers were included into the study. The patients were randomised into two groups (n=20). The treatment and control groups received cell based dressing and microcarriers kept in culture medium overnight, respectively. The wound size was recorded at 3 days intervals. The wounds were also categorised by a specific scoring system considering the wound contraction, granulation tissue formation, epithelisation and discharge from the wounds. The high score indicates better condition. The mean reduction of the wound area was 92% in the treatment group and 32% in the control group at the end of the 30 days treatment (p<0.001). When considered the complete healing, the mean number of dressings was 9.2+/-3.2 in the treatment group whereas it was 16.5+/-2.3 in the control group (p<0.001). The initial mean score of the treatment and control groups were 2.5 and 2.35, respectively. At the end of the 30th day, the mean score of the treatment group was 17.15+/-2.7 and of control group was 9.05+/-3. Allogenic keratinocyte treatment delivered with microcarriers can make significant contributions to wound healing in diabetic foot patients.


Determination of the rheological behavior and thermophysical properties of malbec grape juice concentrates (Vitis vinifera).
The rheological behavior and thermophysical properties (density, specific heat, and thermal conductivity) were experimentally determined as function of temperature (1-66 °C) and solid soluble content (13.6-45.0°Brix) for Malbec grape juice aiming at designing the unit operations involved in beverage industries. Mathematical modeling was performed to provide valuable information about the rheological behavior and thermophysical properties of Malbec grape juice at different concentrations and temperatures. The Ostwald-de Waele model fitted the concentrates rheological behavior with high accuracy. The consistency coefficients were significantly reduced by the temperature increase, following an Arrhenius relationship with activation energy ranging from 11.02 kJ/mol (45.0 °Brix) to 11.54 kJ/mol (21.0 °Brix). In contrast, they were increased by the higher concentration levels, ranging from 0.2044 Pa.sn (13.6 °Brix, 6 °C) to 20.9451 Pa.sn (45.0 °Brix, 1 °C). The flow behavior index was not influenced by temperature; however, it was strictly related to the concentration, assuming shear-thinning behavior (0.96 < n < 0.54), regardless of the solid soluble contents. Density, specific heat, and thermal conductivity were significantly correlated with both the temperature and concentration parameters by second-order polynomial models. The obtained results can be suitable for the potential use of Malbec juice concentrate as a chaptalization agent in winemaking and grape juice production.


Utility of alpha-glutathione S-transferase assessment in chronic hepatitis C patients with near normal alanine aminotransferase levels.
To study whether determining alpha-glutathione S-transferase (alpha-GST) might improve the assessment of chronic hepatitis C (CHC) patients with near normal alanine aminotransferase levels (NNA). We studied 119 viraemic CHC patients. They were subdivided into two groups according to the pattern of alanine aminotransferase (ALT) alteration, i.e. consistently above (HA) or below (NNA) twice the upper normal value. In these patients we assessed alpha-GST and correlated its levels to clinical, histological, and virological findings, further evaluating whether alpha-GST might improve the assessment of CHC patients with NNA. alpha-GST showed a significant correlation with aminotransferases, though not with histological necroinflammatory activity and fibrosis or with hepatitis C virus RNA levels. Twenty-seven patients had NNA (23%), and within this subgroup of patients alpha-GST identified a subset of patients with a higher viral load. alpha-GST in CHC patients is related to hepatocellular necrosis parameters, but unrelated both to histology and to viraemia. However, in patients with NNA, alpha-GST identified a subgroup of patients with a higher viral load. In this subgroup of patients alpha-GST alteration likely represents the expression of a more severe damage. Because this injury is not detectable by the usual biochemical or histological work-up, we suggest that alpha-GST could a useful tool for monitoring liver damage over time.


Heart rate variability in patients with atrial septal defect and healthy children.
Heart rate variability (HRV) measures are altered in various cardiac and non-cardiac situations in children. The autonomic nervous system is assumed to have a role in the pathophysiology of atrial septal defect (ASD). In this study, we evaluated the autonomic system by measuring HRV in children with ASD. Twenty-eight patients with ASD and 32 healthy children (mean ages: 6.6±2.1 years and 6.4±2.2 years, respectively) were enrolled in the study. Twenty-four-hour ambulatory electrocardiographic recordings were obtained and the seven time-domain (SDNN, SDANN, rMSSD, SD, SDNN index, PNN50, and mean RR) and four frequency-domain (VLF, LF, HF, and LF/HF ratio) indices of HRV were analyzed. A significant decrease in calculated HRV variables was observed in children with ASD as compared to controls. The HRV alteration was found in both time-domain and frequency-domain parameters. Our results indicate that HRV is decreased in children with ASD, which implies parasympathetic withdrawal and sympathetic predominance.


Binding of insulin dimers to receptors.
A synthesis of current views of the nature of the self-association of insulin in solution, of the identity of the amino acid residues in the insulin molecule constituting the receptor binding site, and of characteristics of the apparent 'negative cooperativity' of the binding leads to the seemingly contradictory conclusions that only the monomeric form of the protein is available and capable of binding, yet that other species must bind as well. A solution that has been proposed is that an alternative binding site exists, one which is not involved in insulin dimerization. Here, these conclusions are re-examined in the light of the characteristics of a new model for the polymerization of insulin. Firstly, it is found that the idea that dimers and higher polymers of insulin can bind to receptors is plausible, even necessary, secondly, that the postulate of an alternative binding site on insulin molecules is not required, and finally, that the characteristics of the insulin-receptor interaction warrant further investigation specifically in terms of the ability of some insulins to polymerize in solution and their potential to cross-link receptors.


Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells.
The pancreatic hormone, glucagon, is known to regulate hepatic glucose production, but recent studies suggest that its regulation of hepatic amino metabolism is equally important. Here, we show that chronic glucagon receptor activation with a long-acting glucagon analog increases amino acid catabolism and ureagenesis and causes alpha cell hypoplasia in female mice. Conversely, chronic glucagon receptor inhibition with a glucagon receptor antibody decreases amino acid catabolism and ureagenesis and causes alpha cell hyperplasia and beta cell loss. These effects were associated with the transcriptional regulation of hepatic genes related to amino acid uptake and catabolism and by the non-transcriptional modulation of the rate-limiting ureagenesis enzyme, carbamoyl phosphate synthetase-1. Our results support the importance of glucagon receptor signaling for amino acid homeostasis and pancreatic islet integrity in mice and provide knowledge regarding the long-term consequences of chronic glucagon receptor agonism and antagonism.


Endothelial microparticles (EMP) for the assessment of endothelial function: an in vitro and in vivo study on possible interference of plasma lipids.
Circulating endothelial microparticles (EMP) reflect the condition of the endothelium and are of increasing interest in cardiovascular and inflammatory diseases. Recently, increased numbers of EMP following oral fat intake, possibly due to acute endothelial injury, have been reported. On the other hand, the direct interference of lipids with the detection of EMP has been suggested. This study aimed to investigate the effect of lipid-rich solutions, commonly administered in clinical practice, on the detection, both in vitro and in vivo, of EMP. For the in vitro assessment, several lipid-rich solutions were added to whole blood of healthy subjects (n = 8) and patients with coronary heart disease (n = 5). EMP (CD31+/CD42b-) were detected in platelet poor plasma by flow cytometry. For the in vivo study, healthy volunteers were evaluated on 3 different study-days: baseline evaluation, following lipid infusion and after a NaCl infusion. EMP quantification, lipid measurements and peripheral arterial tonometry were performed on each day. Both in vitro addition and in vivo administration of lipids significantly decreased EMP (from 198.6 to 53.0 and from 272.6 to 90.6/µl PPP, respectively, p = 0.001 and p = 0.012). The EMP number correlated inversely with the concentration of triglycerides, both in vitro and in vivo (r = -0.707 and -0.589, p<0.001 and p = 0.021, respectively). The validity of EMP as a marker of endothelial function is supported by their inverse relationship with the reactive hyperemia index (r = -0.758, p = 0.011). This inverse relation was confounded by the intravenous administration of lipids. The confounding effect of high circulating levels of lipids, commonly found in patients that receive intravenous lipid-based solutions, should be taken into account when flow cytometry is used to quantify EMP.


Environmental regulation of the function of circulating erythrocytes via changes in age distribution in teleost fish: Possible mechanisms and significance.
The blood of fish has a continuous age distribution of erythrocytes. The properties of young and old erythrocytes differ with young erythrocytes being functionally much more versatile than old erythrocytes, which have higher haemoglobin content. Factors which affect the formation and breakdown of erythrocytes are reviewed. Erythropoiesis in fish is largely similar to that in mammals. However, definitive erythrocytes are mainly formed in the anterior part of the kidney, and erythropoietin is secreted mainly from the heart. Senescence of erythrocytes in fish has not been studied in detail, and consecutively the factors causing aging of erythrocytes in man are discussed. A major factor causing aging of erythrocytes is oxidative stress, which is also a major effect of toxicants on fish erythrocytes. Consequently, apparent age distribution of circulating erythrocytes will be affected by environmental pollution. At present, it is completely unknown, if the changes in age distribution of erythrocytes play a role in pollutant responses or if the age distribution of erythrocytes is actively regulated during environmental adaptation.


Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation.
We used optimized DNA expression vectors to compare two gene delivery methodologies in rhesus macaques, namely direct DNA injection and in vivo adaptive constant-current electroporation via the intramuscular route. The use of in vivo electroporation increased levels of gene expression and immune responses. We used an optimized HIV gag expression plasmid to show the development of new cellular immune responses in SIV-infected animals controlling viremia. Furthermore, after vaccination with SIV expression plasmids the recall responses to the SIV antigens were very high, indicating that DNA is a strong boost in the presence of antiretroviral treatment in SIV-infected animals. There was substantial animal-to-animal variability in DNA expression, revealed by plasma measurements of IL-15 produced by co-injected IL-15 DNA. IL-15 expression levels correlated with peak immune responses. Electroporation led to an expansion of antigen-specific CD4+ and CD8+ T cells of both central and effector memory phenotype. These results indicate that improved gene delivery and expression by electroporation dramatically increases immunogenicity of DNA vaccines. Electroporation is thus an important method to improve the effectiveness of DNA vaccination.


Urolithin B loaded in cerium oxide nanoparticles enhances the anti-glioblastoma effects of free urolithin B in vitro.
Glioblastoma multiforme (GBM) is the most aggressive kind of malignant primary brain tumor in humans. Given the limitation of Conventional therapeutic strategy, the development of nanotechnology and natural product therapy seems to be an effective method enhancing the prognosis of GBM patients. In this research, cell viability, mRNA expressions of various apoptosis-related genes apoptosis, and generation of reactive oxygen species (ROS) in human U-87 malignant GBM cell line (U87) treated with Urolithin B (UB) and CeO2-UB. Unlike CeO2-NPs, both UB and CeO2-UB caused a dose-dependent decrease in the viability of U87 cells. The half-maximal inhibitory concentration values of UB and CeO2-UB were 315 and 250 μM after 24 h, respectively. Moreover, CeO2-UB exerted significantly higher effects on U87 viability, P53 expression, and ROS generation. Furthermore, UB and CeO2-UB increased the accumulation of U87 cells in the SUB-G1 population, decreased the expression of cyclin D1, and increased the Bax/Bcl2 ratio expression. Collectively, these data indicate that CeO2-UB exhibited more substantial anti-GBM effects than UB. Although further in vivo investigations are needed, these results proposed that CeO2-NPs could be utilized as a potential novel anti-GBM agent after further studies.


Production and effects of 7 alpha-hydroxytestosterone on testosterone and dihydrotestosterone metabolism in rat testis.
1. Testicular 7 alpha-hydroxylation of testerone was assayed in cell extracts of rats between 12 and 79 days of age. Maximal 7 alpha-hydroxylase activity was observed about 60 days, while insignificant activity was obtained prior to 42 days of age. 2. 7 alpha-Hydroxytestosterone, a major metabolite of testosterone in mature rat testis, inhibited 5 alpha-reduction of testosterone in cell extracts of mature but not of immature rat testis. 3. Maximal testicular activity of 3 beta-hydroxysteroid dehydrogenase using dihydrotestosterone as substrate was obtained in the presence of NAD, while maximal 3 alpha-hydroxysteroid dehydrogenase activity was observed with NADP. Both enzyme activites were reversible. 4. Sensitivity toward testosterone inhibition of 3-hydroxysteroid dehydrogenase varied greatly with stage of testis development being highest at 25-27 days of age. In contrast to testosterone, 7 alpha-hydroxytestosterone was an inhibitor of 3 alpha-hydroxysteroid dehydrogenase only. In the mature rat testis 7 alpha-hydroxytestosterone may be a naturally occurring inhibitor of dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol formation.


Correcting the limited view in optical-resolution photoacoustic microscopy.
Optical-resolution photoacoustic microscopy (OR-PAM) has proven useful for anatomical and functional imaging with high spatial resolutions. However, the coherent signal generation and the desired reflection-mode detection in OR-PAM can result in a limited detectability of features aligned with the acoustic axis (ie, vertical structures). Here, we investigated the limited-view phenomenon in OR-PAM by simulating the generation and propagation of the acoustic pressure waves and determined the key optical parameters affecting the visibility of vertical structures. Proof-of-concept numerical experiments were performed with different illumination angles, optical foci and numerical apertures (NA) of the objective lens. The results collectively show that an NA of 0.3 can readily improve the visibility of vertical structures in a typical reflection-mode OR-PAM system. This conclusion was confirmed by numerical simulations on the cortical blood vessels in a mouse brain and by experiments in a suture-cross phantom and in a mouse brain in vivo.


Microperfusion study of the kinetics of reabsorption of cycloleucine in early and late segments of the proximal convolution of the rat nephron.
The proximal tubular reabsorptive capacity for the non-metabolizable amino acid, cycloleucine, was studied in the rat nephron by stationary microperfusion. Tubular reabsorptive rates were greatest near the glomerulus and declined progressively along the convolution. A kinetic analysis of cycloleucine reabsorption in terms of luminal concentration revealed that this reduced transport rate was associated with an increase in the half-saturation constant of the kinetic curve, rather than a decrease in the maximum transport capacity. Since our previous findings with the metabolizable amino acid, -L-histidine, were identical we can conclude that this decline in reabsorption of neutral amino acids as a function of distance along the convolution is an intrinsic property of the transport system and is not related to tubule cell amino acid metabolism. The transport curves for cycloleucine absorption did not give a simple Michaelis-Menten relation but rather followed a course suggesting that more than one transport system might be involved.


Massive epistaxis due to pseudoaneurysm of the sphenopalatine artery: a rare post-operative complication of orthognathic surgery.
To introduce pseudoaneurysm of the sphenopalatine artery as the possible aetiology of acute massive epistaxis in patients with a history of orthognathic surgery accompanied by Le Fort I osteotomy. Case report and literature review. This paper reports a case of acute life-threatening epistaxis following Le Fort I osteotomy. Computed tomography and angiography showed a pseudoaneurysm of the sphenopalatine artery, which was successfully treated by endovascular embolisation. Although a pseudoaneurysm of the sphenopalatine artery following Le Fort I osteotomy is extremely rare, it should be considered as the possible aetiology of acute massive epistaxis in patients with a history of orthognathic surgery accompanied by Le Fort I osteotomy.


SDC4-rs1981429, ATM-rs228590 and biomarkers of breast cancer risk.
This is a correspondence on published article on SDC4-rs1981429, ATM-rs228590 and biomarkers of breast cancer risk. Confounding factors are discussed.


Bioaugmentation reconstructed nitrogen metabolism in full-scale simultaneous partial nitrification-denitrification, anammox and sulfur-dependent nitrite/nitrate reduction (SPAS).
To enhance nitrogen removal of fermentation pharmaceutical wastewater with high nitrogen load, a full-scale process based on simultaneous partial nitrification-denitrification/ anammox/ sulfur autotrophic denitrification (SPAS) was established via inoculating with bioaugmentation consortia in a modified two-stage AO. More than 93 % TN and 98 % NH4+-N removal were obtained at a rate of 0.8 kg-N/ m3/d in the first A/O stage, in which short-cut SND was involved with 96.05 % ESND when bioaugmented with SND, while S0-SAD could coordinate with anammox to exert further deep denitrification in the second A/O stage. KEGG analysis demonstrated that the SPAS process was synergism of HD, PN/PDN, SND, SAD and anammox metabolism, bioaugmentation could significantly up-regulate genes related to microbial metabolism (TCA cycle, Carbon metabolism, ABC transporters) and environmental adaptation (Two-component system, Quorum sensing) based on the FAPROTAX and Picrust2 functional prediction. This study provided a new perspective in engineering applications.


Hexadecameric self-assembled dendrimers built from 2'-deoxyguanosine derivatives.
Herein we describe the construction of hexadecameric self-assembled dendrimers (SADs) using a series of dendronized 8-(m-acetylphenyl)-2'-deoxyguanosine (mAG) subunits. The azido-substituted mAG subunits were covalently linked to alkynyl polyester dendrons using a copper-catalyzed 1,3-dipolar cycloaddition reaction. Discrete SADs are formed with high fidelity and thermal stability even with the increased steric hindrance offered by the dendrons.


The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study.
The primary objective was to determine the effect of statin-fibrate combination therapy on inflammatory biomarkers in patients with diabetes. Atherosclerosis is a long-term, chronic inflammatory disease that is exacerbated in patients with diabetes. Patients (n = 300) with type II diabetes, mixed dyslipidemia (2 or more of low-density lipoprotein > or =100 mg/dl, triglycerides > or =200 mg/dl, or high-density lipoprotein <40 mg/dl), and no history of coronary heart disease were randomly assigned to receive simvastatin 20 mg, fenofibrate 160 mg, or a combination of simvastatin 20 mg and fenofibrate 160 mg daily. At 12 weeks after randomization, we measured levels of high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)). At 12 weeks, median hsCRP was significantly reduced (-14.6%, p = 0.004) from baseline, but the effect did not differ between treatments. The effect was greatest among patients with baseline hsCRP levels >2.0 mg/l (fenofibrate = -18.9%, p = 0.002 vs. baseline; simvastatin = -24.8%, p < 0.0001; combination = -27.3%, p = 0.002). Likewise, median Lp-PLA(2) levels in the overall study population were significantly reduced (-16.8%, p < 0.0001), and the effect did not differ among treatments. This effect also was greatest among patients with increased baseline levels of Lp-PLA(2) greater than the median of 320.9 ng/ml (fenofibrate = -41.3%, p < 0.0001; simvastatin = -47.5%, p < 0.0001; combination = -46.8%, p < 0.0001). Simvastatin, fenofibrate, and combination therapy each lowered hsCRP and Lp-PLA(2). These anti-inflammatory effects were most pronounced among patients with increased baseline levels. Combination therapy was no more effective than either form of monotherapy. (The DIACOR Study; http://www.clinicaltrials.gov/ct/show/NCT00309712?order=1).


Double dissociation of the behavioural effects of R(+) 7-OH-DPAT infusions in the central and basolateral amygdala nuclei upon Pavlovian and instrumental conditioned appetitive behaviours.
Dopaminergic cell bodies located within the ventral mesencephalon innervate the amygdaloid complex, a region critically involved in the attribution of affective significance to environmental stimuli. Recently, we have shown that post-session intra-amygdala administration of a D3 dopamine receptor agonist enhances selectively the acquisition of an appetitive conditioned response. In the present study, we have investigated the potential involvement of the central nucleus and the basolateral nuclei of the amygdala in mediating this effect. Thus, rats were trained to associate an arbitrary stimulus (CS+) with the availability of 10% sucrose reward. Post-session infusions of the D3 receptor-preferring agonist, R(+) 7-OH-DPAT, were made into either the central nucleus or basolateral nuclei. Acquisition of a conditioned approach response was enhanced by R(+) 7-OH-DPAT infusions within the central nucleus, but not within the basolateral nuclei. Drug infusions into either region failed to affect approach behaviour elicited by presentation of a control stimulus (CS-), explicitly unpaired with sucrose reward. The effects of pre-test infusions of R(+) 7-OH-DPAT on the instrumental properties of the stimuli were then determined. Rats were presented with two novel levers, depression of one lever resulted in presentation of the CS+, while presentation of the CS- was contingent upon depression of the other lever. Rates of response upon each lever as well as the ability of the conditioned stimuli subsequently to elicit conditioned approach behaviour were recorded. Data revealed a double dissociation of the effects of R(+) 7-OH-DPAT on the expression of the Pavlovian and instrumental properties of the reward-related stimulus. Thus, within the central nucleus R(+) 7-OH-DPAT dose-dependently attenuated expression of the conditioned approach response, but had no effect upon instrumental responding maintained by the conditioned reward. In contrast, within the basolateral nuclei, R(+) 7-OH-DPAT had no effect upon expression of conditioned approach behaviour, but abolished selectively the ability of the reward-associated stimulus to support the acquisition of a novel instrumental response. Hence, these data indicate that distinct regions of the amygdaloid complex process distinct aspects of conditioned appetitive behaviours.


Serum immune modulators during the first cycle of anti-PD-1 antibody therapy in non-small cell lung cancer: Perforin as a biomarker.
Currently used biomarkers for immunotherapy are inadequate because they are only based on tumor properties. In view of microenvironment changes by tumors, host immunity should be considered, which may result in identifying more accurate and easily detectable biomarkers for daily clinical practice. Here, we assessed serum immune-modulating factor levels for the response to anti-PD-1 antibodies during the first cycle in non-small cell lung cancer (NSCLC) patients. Serum was collected from patients with advanced NSCLC treated with nivolumab or pembrolizumab at several time points during the first cycle. We applied the enzyme-linked immunosorbent assays (ELISAs) and multiplex assays to measure the levels of immune modulators. A total of 40 patients treated with nivolumab and 26 patients treated with pembrolizumab were studied. By ELISA, serum perforin, but not granzyme B, was measured in all samples. By multiplex assay, 10 immune modulators, including granzyme B, were measured in some, but not all, samples. Serum baseline perforin levels were strongly associated with increased progression-free survival (PFS) and overall survival (OS) times. Sequential changes in perforin levels during the first cycle were weakly associated with the clinical outcome. Serum baseline perforin levels may be used to predict the prognosis of NSCLC patients treated with anti-PD-1 antibody therapy. To identify a useful predictive marker for anti-PD-1 antibody therapy, using blood samples might be helpful. Serum baseline perforin levels were closely associated with prognosis with anti-PD-1 antibody therapy in non-small cell lung cancer.


Definition of benign versus malignant ventricular arrhythmias: targets for treatment.
The most important characteristics of arrhythmias that determine the need for treatment are the prevalence and clinical significance of the ventricular arrhythmia. Ventricular arrhythmias occur more frequently with advancing age, severity of heart disease and ventricular hypertrophy. Malignant ventricular arrhythmias are of 3 forms: out-of-hospital ventricular fibrillation (VF), recurrent sustained ventricular tachycardia and torsades de pointes ventricular tachycardia in the long QT syndrome. Each condition has a high 1-year mortality rate. Potentially malignant ventricular arrhythmias are ventricular premature complexes (VPCs) of greater than 10 per hour 10 to 16 days after acute infarction and repetitive VPCs. The most malignant arrhythmias occur with severely depressed ventricular function, but VPCs alone have independent prognostic significance. Benign ventricular arrhythmias occur in patients without known heart disease and do not require treatment. The exact effect of frequent and complex VPC in these patients needs further definition.


Episodic odor memory: influences of handedness, sex, and side of nose.
It is not known whether, or to what degree, odor memory is influenced by lateralized brain processes. In this study, we administered a 12-item match-to-sample odor memory test separately to the left and right sides of the nose of 30 left- and 30 right-handed subjects of equivalent age, sex distribution, and overall general smell ability. For each test item, one of three delay intervals (10-, 30-, and 60-s) was interspersed between smelling the target stimulus and smelling the first of four response alternatives. Women, but not men, performed significantly better on the left than on the right side of the nose, conceivably reflecting greater reliance upon left-hemisphere semantic processes. Subjects who received the first test on the right side of the nose outperformed those who received the first test on the left side of the nose. As in previous work, an age-related decrement in odor memory test scores was present. These data contribute to the debate on the role of lateralized brain processes in episodic odor memory, and suggest that performance on a standardized match-to-sample odor memory task is influenced by a number of interacting factors.


Right ventricular infarction: larger enzyme release with posterior than with anterior involvement.
To evaluate whether the right ventricle releases significant amount of cardiac enzymes during myocardial infarction, a clinicopathologic study of 50 patients with 60 infarcts was performed. Myocardial infarct size was determined at autopsy and compared with the corresponding peak serum lactate dehydrogenase and aspartate aminotransferase. Anterior and posterior infarcts had similar anatomic size, peak enzyme values, and coefficients of correlation (r = 0.86-0.88 versus r = 0.82-0.84 for lactate dehydrogenase). However, by disregarding the right ventricular infarct component considering the left ventricular infarction only, the coefficient of correlation between infarct size and peak serum lactate dehydrogenase decreased from r = 0.84 to r = 0.59 (P = 0.09), in 14 posterior infarcts while no change was observed in 24 anterior infarcts (r = 0.88). This indicates, that a considerable amount of enzymes released during posterior infarction originated from the right ventricle which was not the case for anterior infarction.


Racial/ethnic differences in the associations between obesity measures and severity of sleep-disordered breathing: the Multi-Ethnic Study of Atherosclerosis.
The objective of this study was to evaluate associations between obesity measures and sleep-disordered breathing severity among White, Black, Hispanic, and Chinese Americans. The method used in this study was a community-based cross-sectional study of 2053 racially/ethnically diverse adults in the Multi-Ethnic Study of Atherosclerosis. Anthropometry and polysomnography were used to measure obesity and apnea-hypopnea index (AHI). Linear regression models were fitted to investigate associations of body mass index (BMI) and waist circumference with AHI (log transformed) with adjustment for sociodemographics, lifestyle factors, and comorbidities. The mean participant age was 68.4 (range: 54-93) years; 53.6% of participants were women. The median AHI was 9.1 events/h. There were significant associations of BMI and waist circumference with AHI in the overall cohort and within each racial/ethnic group. A significant interaction was observed between race/ethnicity and BMI (Pinteraction = 0.017). Models predicted that for each unit increase in BMI (kg/m2), the mean AHI increased by 19.7% for Chinese, 11.6% for Whites and Blacks, and 10.5% for Hispanics. Similarly, incremental changes in waist circumference were associated with larger increases in AHI among Chinese than among other groups. Associations of BMI and waist circumference with AHI were stronger among Chinese than among other racial/ethnic groups. These findings highlight a potential emergence of elevated sleep-disordered breathing prevalence occurring in association with increasing obesity in Asian populations.


[Is the T-scan system a relevant diagnostic method for occlusal control?].
The T-Scan system has recently been introduced to the market as a computer-aided device for direct monitoring and documentation of individual occlusal patterns. To receive first assessments of diagnostic relevance of this method, sensitivity and planar resolution capacities of the T-Scan system was tested in an in-vitro study, that showed a lack in the resolution capacity and an excessive variation in sensor sensitivity. Therefore the clinical use of the system is very limited.


Results of plastic repair of a fragment of the deferent duct by autovenous prosthesis.
Plastic repair of a part of the deferent duct by a segment of autovein in a chronic experiment results in the formation of internal spermatogranuloma, which starts forming at the site of the epididymal anastomosis from days 5-7 and is completely formed by days 17-20 postoperation. These changes determine the negative outcome of the operation: obturation of the deferent duct. In addition, the pathological process (fibrous degeneration of autovenous prosthesis) progresses 30 days after the intervention.


Drying kinetics and attributes of fructus aurantii processed by hot air thin-layer drying at different temperatures.
The primary objectives of this study were to evaluate the drying kinetics of Fructus Aurantii (FA), and to investigate how hot air drying at various temperatures affected the surface texture and sensory quality of the volatile fragrance components. The results were best simulated by the Overhults model, and use of scanning electron microscopy (SEM) and Heracles Neo ultra-fast gas phase electronic nose technology allowed for detection of changes in surface roughness and aromatic odors. The limonene content varied from 74.1% to 84.2% depending on the drying temperature, which ranged from 35°C to 75 °C. Furthermore, principal component analysis (PCA) revealed that the aromatic compound profile underwent considerable changes during the drying process. Overall, the present findings demonstrate that hot air thin-layer drying at 55 °C can significantly enhance the final quality of FA while preserving the taste properties and providing optimum medicinal and culinary characteristics.


Calcium oxalate precipitation in urine following T.U.R. with glycine as irrigation fluid.
Precipitation of calcium oxalate was studied in a group of ten patients who underwent transurethral prostatectomy with glycine irrigation. Post operatively all patients showed hyperoxaluria; 60% with oxaluria higher than 10 times the critical concentration of calcium oxalate in urine. Other factors, known to favour crystallogenesis were modified during the same period: low urinary output, relative hypercalciuria and uraturia and hypomagnesuria. Thus, conditions for intraluminal precipitation of calcium oxalate were present post operatively. We suggest the use of a xanthine oxidase inhibitor to prevent hyperoxaluria.


Trade-offs between sexual and asexual reproduction in the genus Mimulus.
Six estimates of resource allocation to sexual reproduction (nectar concentration, nectar volume, sugar production, pollinator visitation rates, fruit-set, and seed production) and a single estimate of resource allocation to asexual reproduction (the rate of rooted-branch production) were examined for five species of Mimulus. There were significant interspecific differences for all paramaters. With the exception of nectar concentration, there was 1) a consistent positive correlation among the parameters measuring allocation to sexual reproduction, and 2) a significant negative correlation between parameters measuring allocation to sexual reproduction and the rate of rooted-branch production (asexual reproduction). The results indicate that Mimulus species which produce the highest volumes of nectar 1) receive the most pollinator visits, 2) have the highest fruit-set, 3) produce the most seeds, and 4) produce the fewest rooted branches.