BDNF and Netrin-1 repression by C/EBPβ in the gut triggers Parkinson's disease pathologies, associated with constipation and motor dysfunctions.
Chronic constipation is one of the most prominent prodromal symptoms in Parkinson's disease (PD), and Lewy bodies, enriched with aggregated α-Synuclein (α-Syn), propagation from the gut into the brain has been proposed to play a key role in PD etiopathogenesis. BDNF (Brain-derived neurotrophic factor) and Netrin-1 promote both neuronal survival and regulate the gut functions. We hypothesize that C/EBPβ represses BDNF and Netrin-1 in peripheral nervous system and central nervous system, contributing to GI tract and brain malfunctions in PD. To test the hypothesis, we performed the studies in both human PD gut tissues and BDNF or Netrin-1 gut conditional KO mice models. Lewy bodies with α-Syn aggregation and neuro-inflammation were measured in the colon and brain samples from PD patients and healthy controls and rotenone or vehicle-treated WT and CEBPβ (+/-) mice. We show that both BDNF and Netrin-1 are strongly decreased in the brain and the gut of PD patients, and conditional KO of these trophic factors in the gut elicits dopaminergic neuronal loss, constipation and motor dysfunctions. Interestingly, the inflammation and oxidative stress-induced transcription factor C/EBPβ acts as a robust repressor for both BDNF and Netrin-1 and suppresses the expression of trophic factors, and its levels inversely correlate with BDNF and Netrin-1 in PD patients. Our findings support that gut inflammation induces C/EBPβ activation that leads to both BDNF and Netrin-1 reduction and triggers PD non-motor and motor symptoms. Possibly, C/EBPβ-mediated biological events might be early diagnostic biomarkers for PD.


The effects of mannose on rat embryos grown in vitro.
Rat embryos have been cultured in vitro from 9.5 days of gestation for different times in serum containing mannose, and the embryos have been observed by scanning electron microscopy. Embryos cultured in 3 mg/ml (1.7 X 10(-2) M) or 6 mg/ml (3.3 X 10(-2) M) mannose for 48 h showed inhibition of the expansion of the yolk sac and were smaller than the control embryos. Mannose-treated embryos also showed delayed development according to morphological criteria, and a range of abnormalities including abnormalities of the neural tube. Embryos cultured in 6 mg/ml mannose for 24 h also showed significant inhibition of yolk-sac expansion and were smaller and less advanced than the control embryos. Abnormalities were seen, including a delay in the closure of the neural folds. Abnormalities were also observed in embryos cultured in mannose for 10 h; embryos at the neural groove stage showed irregularities in the neural groove. Mannose did not inhibit the re-elevation of neural folds which had been caused to collapse by exposure to medium containing low calcium. These results are compatible with the idea that mannose retards development and thereby perturbs the morphogenesis of the neural tube.


Detection of circulating tumour cells enables early recurrence prediction in hepatocellular carcinoma patients undergoing liver transplantation.
Liver transplantation (LTx) is one of the most effective treatments for hepatocellular carcinoma (HCC); however, tumour recurrence after LTx often leads to poor outcomes. This study investigated the value of circulating tumour cells (CTCs) as a predictor of recurrence following LTx in patients with HCC. This analysis included 193 patients with HCC who underwent LTx at our institute and accepted pre- and post-operative CTC detection; 38 were selected for serial CTC monitoring. The predictive value of CTCs for tumour recurrence in patients with HCC following LTx was evaluated. Single-cell whole genome sequencing was used to characterize CTCs. Overall, the CTC burden decreased after LTx (P < .05). Post-operative CTC count ≥ 1 per 5 mL peripheral blood was identified as a potential biomarker for predicting tumour recurrence after LTx, especially in patients with no detectable CTCs prior to LTx and negative tumour serological biomarkers. The predictive value of post-operative CTC count ≥ 1 per 5 mL blood was retained in patients who did not meet the Milan criteria, University of California San Francisco (UCSF) criteria, or Fudan criteria (all P < .05). Furthermore, post-operative serial CTC detection may be useful in post-surgical surveillance for HCC recurrence. CTCs may be a useful biomarker to evaluate recurrence risk following LTx in patients with HCC. Evaluation based on CTC detection may enhance the post-transplant management of HCC, and improve the therapeutic efficacy of LTx.


[The relationship between adenoids hypertrophy and secretory otitis media].
To investigate the relationship between immune status of adenoids and secretory otitis media (SOM). All the 76 cases of SOM were divided into 2 groups: recurrent group (46 cases) and control group (30 cases whose occurrence was less than 3 times). The manifestation of CD45RO, CD20, PCNA and BCL-2 in adenoids was detected with ultrasensitive (TM)S-P immunohistology. The expression of CD44Ro, CD20, PCNA and BCL-2 in recurrent group was significantly higher than that in control group (P < 0.05 or P < 0.01). In adenoid tissues of recurrent SOM patients, the activities of lymphocytes and cells in hypertrophic status increase, the adenoids enlarge and local immunity enhances. Therefore, adenoidectomy for SOM patients should be carried out as early as possible.


Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins.
Programmed cell death or apoptosis is central to many physiological processes and pathological conditions such as organogenesis, tissue homeostasis, cancer, and neurodegenerative diseases. Bcl-2 family proteins tightly control this cell death program by regulating the permeabilization of the mitochondrial outer membrane and, hence, the release of cytochrome c and other pro-apoptotic factors. Control of the formation of the mitochondrial apoptosis-induced channel, or MAC, is central to the regulation of apoptosis by Bcl-2 family proteins. MAC is detected early in apoptosis by patch clamping the mitochondrial outer membrane. The focus of this review is on the regulation of MAC activity by Bcl-2 family proteins. The role of MAC as the putative cytochrome c release channel during early apoptosis and insights concerning its molecular composition are also discussed.


Historical thinking and the shaping of nursing identity.
Nursing history was a core component of nurse training programs as early as 1907, when American Adelaide Nutting published her three-volume history. However, it had all but disappeared by the end of the 20th century, supplanted by other subjects. The University of Ottawa Nursing History Research Unit developed two online nursing history courses, in English and French, respectively, which proved popular and prompted substantial interest in the reintroduction of nursing history to our curriculum. This article presents findings of a study that examined the concept of "historical thinking"-what it is, how it develops, and what it contributes to practice-based professions-based on student postings in these courses. Analysis suggests that primary sources and critical appraisal skills are keys to the formation of historical thinking, and that these courses fostered a strong sense of professional identity among participants who often lamented lack of previous exposure to nursing history. Online nursing history courses can capitalize on e-learning technologies, and fit crowded curricula and student learning styles, while extending the reach of historians beyond traditional university walls.


Noninvasive detection of insulation break.
The electric current leak through an unsealed connector or insulation break can be a source of problems in cardiac pacing. This study describes a method of leak detection. The underdrive inhibition test--chest wall stimulation with external stimulator (ES)--was used for this purpose. Three cutaneous electrodes (CE) were applied: the first one above the indifferent electrode, the second one above the suspected leak location, and the third one above the active electrode. Two inhibition thresholds (IT) were measured: the first one connecting ES on first CE and second CE, and the second one connecting ES on first CE and third CE. The inhibition threshold is the value of ES output charge at which the inhibition of implanted pacemaker occurs. The relation between two ITs, not the absolute value, is significant for leak estimation. The former should be at least five times higher than the latter, if there is no current leak. During the two years of follow-up of 541 patients, 272 measurements were performed. In 52 cases the connector leak was found-both ITs were approximately equal. Twenty-seven cases were confirmed by surgery for EOL pacemaker replacement; the intrusion of body fluid was evident. Five operations were indicated because of the leak problem: two--muscle twitching, one--loss of capture, one-undersensing, and one--insulation break with lead fracture. The method, although approximate, is a reliable qualitative estimation of leak.


Inducible nitric oxide synthase mediates cytokine release: the time course in conscious and septic rats.
Nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1-beta (IL-1beta) are postulated to play a key pathophysiologic role during sepsis. In this study, we examined the time course of inducible NO synthase (iNOS) mRNA expression and the plasma TNF-alpha and IL-1beta in lipopolysaccharide (LPS)-treated conscious rats. The hemodynamic pattern in septic shock is more similar to clinical conditions without anesthesia. The data showed that a significant increase in iNOS mRNA levels was found in the spleen, lung, liver, with slight elevation in the heart and kidney at 3 h after LPS administration. However, iNOS mRNA levels were not elevated significantly in all tissues examined at 24 h. In the plasma, TNF-alpha and IL-1beta culminated within 1 h, and reduced gradually to baseline levels in a relatively short period (within 9 h). The results suggest that local NO production by activation of iNOS mRNA expression and cytokine release may contribute to LPS-induced organ dysfunction at various time points.


Isolation of bacterial plasmids by density gradient centrifugation in cesium trifluoroacetate (CsTFA) without the use of ethidium bromide.
Plasmids extracted from bacterial cells by alkaline extraction can easily be isolated from linear DNA by isopycnic centrifugation in CsTFA. This is a fast and simple method which circumvents the use of the intercalating dye, ethidium bromide, and consequently the problems associated with its removal. The buoyant densities for covalently closed circular DNA and linear DNA in CsTFA are 1.60 g/ml and 1.65 g/ml, respectively. The isolation is achieved regardless of plasmid size and can be accomplished at temperatures of between 4 and 30 degrees C. Plasmid DNA isolated in gradients of CsTFA are of a high purity and have been found to be intact when cleaved with restriction enzymes and ligated with T4 DNA ligase.


Intra-thoracic desmoid tumour in a patient with a previous aortocoronary bypass.
Intra-thoracic desmoid tumours with mediastinal invasion are very rare. Although rare they have to be taken into account in the differential diagnosis of a thoracic mass and therapeutic options have to be weighted since surgical treatment may require wide excision. A 48-year-old male diabetic, dyslipidaemic, former heavy smoker with psychiatric illness was operated by sternotomy for a triple aorto-coronary bypass 4 years before, presented with complains of recent onset such as constant and oppressive chest pain. At surgery a mass extending from the aortic arch into the entire anterior mediastinum and to most of the right pleural cavity was found. The mass was separated from sternal periosteum and vessels of aorto-coronary by pass were isolated starting from the aortic arch up to the pericardium. The histological examination revealed aggressive fibromatosis. Although technically demanding, radical surgical excision is actually the most indicated therapeutic approach for intra-thoracic desmoid tumours.


New tricks for old dogmas: optogenetic and designer receptor insights for Parkinson's disease.
Optogenetics and novel designer receptors have revolutionized the way neuroscientists can interrogate neural circuits. These new tools are being rapidly applied to many facets of neuroscience including the study of Parkinson's disease circuitry and therapies. This review highlights how optogenetics and designer receptors can be applied in the study of Parkinsonian dysfunction to understand the mechanisms behind motor and non-motor symptoms. We discuss how these tools have recently advanced our understanding of basal ganglia function and outline how they can be applied in future to refine existing treatments and generate novel therapeutic strategies for Parkinson's disease. This article is part of a Special Issue entitled Optogenetics (7th BRES).


Functional brain maturation and sleep organisation in neonates with congenital heart disease.
Neonates with Congenital Heart Disease (CHD) have structural delays in brain development. To evaluate whether functional brain maturation and sleep-wake physiology is also disturbed, the Functional Brain Age (FBA) and sleep organisation on EEG during the neonatal period is investigated. We compared 15 neonates with CHD who underwent multichannel EEG with healthy term newborns of the same postmenstrual age, including subgroup analysis for d-Transposition of the Great Arteries (d-TGA) (n = 8). To estimate FBA, a prediction tool using quantitative EEG features as input, was applied. Second, the EEG was automatically classified into the 4 neonatal sleep stages. Neonates with CHD underwent neurodevelopmental testing using the Bayley Scale of Infant Development-III at 24 months. Preoperatively, the FBA was delayed in CHD infants and more so in d-TGA infants. The FBA was positively correlated with motor scores. Sleep organisation was significantly altered in neonates with CHD. The duration of the sleep cycle and the proportion of Active Sleep Stage 1 was decreased, again more marked in the d-TGA infants. Neonates with d-TGA spent less time in High Voltage Slow Wave Sleep and more in Tracé Alternant compared to healthy terms. Both FBA and sleep organisation normalised postoperatively. The duration of High Voltage Slow Wave Sleep remained positively correlated with motor scores in d-TGA infants. Altered early brain function and sleep is present in neonates with CHD. These results are intruiging, as inefficient neonatal sleep has been linked with adverse long-term outcome. Identifying how these rapid alterations in brain function are mitigated through improvements in cerebral oxygenation, surgery, drugs and nutrition may have relevance for clinical practice and outcome.


Lethal nephrotoxicity and hematologic toxicity of cis-diamminedichloroplatinum ameliorated by optimal circadian timing and hydration.
Three hundred and forty-one female F344 (Fischer) rats were kept in light for 8 hr alternating with darkness for 16 hr; some were observed for survival for 21 days, while others were killed for blood sampling 4.5 days after a single intraperitoneal (i.p.) injection of 11 mg/kg cis-diamminedichloroplatinum (cis-DDP). cis-DDP was administered with or without concomitant i.p. saline load at one of six equispaced circadian stages. This high dose of cis-DDP resulted in marked lethal and renal toxicity, but in a moderate bone marrow suppression. Blood urea nitrogen (BUN), circulating total white blood cell counts (WBC) and survival times revealed statistically significant circadian rhythms of drug toxicity (P less than 0.03). Optimal tolerance for cis-DDP gauged by these three variables resulted from drug administration in the second half of the dark span. Renal tolerance for cis-DDP guaged by BUN was improved two-fold by appropriate drug timing. This benefit from drug timing alone was further improved two-fold if hydration and cis-DDP were given at the optimal circadian stage. Hydration-induced ameloriation of cis-DDP nephrotoxicity requires time qualification of both hydration and cis-DDP.


Awareness of the Importance of and Adherence to Patients' Rights Among Physicians and Nurses in Oman: An analytical cross-sectional study across different levels of healthcare.
This study aimed to determine the extent to which physicians and nurses in Oman were aware of the importance of and adhere to patients' rights and whether this differed according to role, nationality, position and institutional healthcare level. This analytical cross-sectional study was carried out between December 2015 and March 2016 at various governmental healthcare institutions in Oman. A self-administered questionnaire was distributed to 1,385 practitioners at all healthcare levels. A total of 1,213 healthcare practitioners (response rate: 87.58%) completed the survey, of which 685 (56.47%) were nurses and 528 (43.53%) were physicians. Overall, awareness of the importance of patients' rights was high (91.51%), although adherence to these rights in practice was low (63.81%). The right of the patient to be informed was considered least important and was least adhered to (81.2% and 56.39%). Nationality, role and institutional level were significantly associated with awareness (P = 0.002, 0.024 and 0.034, respectively). Non-Omani staff were significantly more likely than Omani staff to be aware of (odds ratio [OR] = 1.696; P = 0.032) and adhere to (OR = 2.769; P <0.001) patient rights. Furthermore, tertiary care staff were twice as likely as primary care staff to perceive the importance of patient rights (OR = 2.076; P = 0.019). While physicians were more likely than nurses to be aware of the importance of patient rights, this difference was not significant (OR = 1.516; P = 0.126). These findings may help inform measures to enhance awareness of and adherence to patients' rights in Oman.


[Is efalizumab a safe treatment for a chronic disease?].
Psoriasis is a chronic disease that has a very negative impact on the quality of life of those suffering it. Therefore, treatments that make it possible to satisfactorily control the disease in the long term and maintain a good safety profile are needed. Efalizumab fulfills both requirements. In this article, the potential risks involved in treatment with efalizumab, specifically the acute flu-like syndrome, alterations in laboratory data (leukocytosis, lymphocytosis, thrombocytopenia, hemolytic anemia, elevation of alkaline phosphatase and hepatic biochemistry), infections, neoplasms, skin disorders related with psoriasis (localized papular rash, generalized inflammatory rash, changes in the morphology of psoriasis, rebound phenomenon), joint manifestations, acute inflammatory polyradiculoneuropathy and hypersensitivity reactions are reviewed. The contraindications, presence of antiefalizumab antibodies, their drug interactions, use of vaccines and relationship with pregnancy and breast-feeding are also discussed. An adequate selection of the patient, detailed information to the patient on the benefits and risks and correct knowledge of the potential adverse effects by the clinician are essential requirements for satisfactory use of efalizumab in long-term continued therapy.


Phosphoinositide sensitivity of ion channels, a functional perspective.
Phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] are required for the activity of many different ion channels. This chapter will highlight various aspects of this paradigm, by discussing current knowledge on four different ion channel families: inwardly rectifying K(+) (Kir) channels, KCNQ voltage gated K(+) channels, voltage gated Ca(2+) (VGCC) channels and Transient Receptor Potential (TRP) channels. Our main focus is to discuss functional aspects of this regulation, i.e. how changes in the concentration of PtdIns(4,5)P(2) in the plasma membrane upon phospholipase C activation may modulate the activity of ion channels, and what are the major determinants of this regulation. We also discuss how channels act as coincidence detectors sensing phosphoinositide levels and other signalling molecules. We also briefly discuss the available methods to study phosphoinositide regulation of ion channels, and structural aspects of interaction of ion channel proteins with these phospholipids. Finally, in several cases the effect of PtdIns(4,5)P(2) is more complex than a simple dependence of ion channel activity on the lipid, and we will discuss some these complexities.


Dead-end hollow-fiber ultrafiltration for concentration and enumeration of Escherichia coli and broad-host-range plasmid DNA from wastewater.
Broad-host-range plasmids can facilitate dissemination of antibiotic resistance determinants among diverse bacterial populations. We evaluated hollow-fiber ultrafiltration for increases in detection efficiency of broad-host-range plasmids and Escherichia coli DNA in wastewater. Ultrafiltration followed by PCR showed limited increases in DNA detection and quantification in effluent compared with membrane filtration alone.


Statewide data on surgical ablation for atrial fibrillation: The data provide a path forward.
Atrial fibrillation (AF), if left untreated, is associated with increased intermediate and long-term morbidity/mortality. Surgical treatment for AF is lacking standardization in patient selection and lesion set, despite clear support from multi-society guidelines. The aim of this study was to analyze a statewide cardiac surgery registry to establish whether or not there is an association between center volume and type of index procedure with performance of surgical ablation (SA) for AF, the lesion set chosen, and ablation technology used. Adult, first-time, nonemergency patients with preoperative AF between 2014 and 2022 excluding standalone SA procedures from a statewide registry of Society of Thoracic Surgeons data were included (N = 4320). AF treatment variability by hospital volume (ordered from smallest to largest) and surgery type were examined with χ2 analyses. Hospital-level Spearman correlations compared hospital volume with proportion of AF patients treated with SA. Overall, 37% of patients with AF were ablated at the time of surgery (63% of mitral procedures, 26% of non-mitrals) and 15% had left atrial appendage management only. There was a significant temporal trend of increasing performance of SA for AF over time (Cochran-Armitage = 27.8; P < .001). Hospital cardiac surgery volume did not correlate with the proportion of AF patients treated with SA (rs = 0.19; P = .603) with a rate of SA below the state average for academic centers. Of cases with SA (n = 1582), only 43% had a biatrial lesion set. Procedures that involved mitral surgery were more likely to include a biatrial lesion set (χ2 = 392.3; P < .001) for both paroxysmal and persistent AF. Similarly, ablation technology use was variable by type of concomitant operation (χ2 = 219.0; P < .001) such that radiofrequency energy was more likely to be used in non-mitral procedures. These results indicate an increase in adoption of SA for AF over time. No association between greater hospital volume or academic status and performance of SA for AF was established. Similar to national data, the type of index procedure remains the most consistent factor in the decision to perform SA with a disconnect between AF pathophysiology and decision making on the type of SA performed. This analysis demonstrates a gap between evidence-based guidelines and real-world practice, highlighting an opportunity to confer the benefits of concomitant SA to more patients.


Developing an Automated Registry (Autoregistry) of Spine Surgery Using Natural Language Processing and Health System Scale Databases.
Clinical registries are critical for modern surgery and underpin outcomes research, device monitoring, and trial development. However, existing approaches to registry construction are labor-intensive, costly, and prone to manual error. Natural language processing techniques combined with electronic health record (EHR) data sets can theoretically automate the construction and maintenance of registries. Our aim was to automate the generation of a spine surgery registry at an academic medical center using regular expression (regex) classifiers developed by neurosurgeons to combine domain expertise with interpretable algorithms. We used a Hadoop data lake consisting of all the information generated by an academic medical center. Using this database and structured query language queries, we retrieved every operative note written in the department of neurosurgery since our transition to EHR. Notes were parsed using regex classifiers and compared with a random subset of 100 manually reviewed notes. A total of 31 502 operative cases were downloaded and processed using regex classifiers. The codebase required 5 days of development, 3 weeks of validation, and less than 1 hour for the software to generate the autoregistry. Regex classifiers had an average accuracy of 98.86% at identifying both spinal procedures and the relevant vertebral levels, and it correctly identified the entire list of defined surgical procedures in 89% of patients. We were able to identify patients who required additional operations within 30 days to monitor outcomes and quality metrics. This study demonstrates the feasibility of automatically generating a spine registry using the EHR and an interpretable, customizable natural language processing algorithm which may reduce pitfalls associated with manual registry development and facilitate rapid clinical research.


The PCDD/F and PBDD/F pollution in the ambient atmosphere of Shanghai, China.
Rapid economic growth in the last two decades in Shanghai has had a great adverse influence on its air quality. Therefore, the atmospheric pollutants of Shanghai have received much concern. In this study, concentrations of 2,3,7,8-substituted PCDD/Fs and PBDD/Fs congeners were measured in the ambient air of four districts in Shanghai. The mean atmospheric concentrations (TEQs) of total 2,3,7,8-PCDD/Fs and 2,3,7,8-PBDD/Fs were 8031 fg m(-3) (497.1 fg I-TEQ m(-3)) and 1358 fg m(-3) (304.1 fg I-TEQ m(-3)) for Jiading District, 5308 fg m(-3) (289.0 fg I-TEQ m(-3)) and 709 fg m(-3) (146.9 fg I-TEQ m(-3)) for Zhabei District, 4014 fg m(-3) (144.4 fg I-TEQ m(-3)) and 1239 fg m(-3) (256.9 fg I-TEQ m(-3)) for Pudong District, 3348 fg m(-3) (143.2 fg I-TEQ m(-3)) and 699 fg m(-3) (148.4 fg I-TEQ m(-3)) for Huangpu District, respectively. Our results showed that almost all the PCDD/Fs and PBDD/Fs congeners were partitioned into the particulate phase except the lower chlorinated or brominated ones. The logarithm of the gas/particle partitioning coefficient K(p) has good linear correlation with that of the sub-cooled vapor pressure p(L). Concentrations of PCDD/Fs and PBDD/Fs were both positively correlated to elemental carbon in all districts except Pudong District, suggesting elemental carbon could be a good indicator for dioxins' air pollution. It is intensively suggested that more detailed and deeper studies about PBDD/Fs should be carried out due to their relatively high atmospheric concentrations in Shanghai.


Duodenum inversum: a report and review of the literature.
Duodenum inversum is a rare congenital malformation defined by a duodenum which travels superiorly and then posteriorly prior to crossing the midline above the pancreas. It is often confused with other, more common, anomalies of intestinal rotation. We present a case of duodenum inversum diagnosed incidentally in a one-month old infant with Trisomy 21 during evaluation for reflux disease. Due to an inability to definitively rule out malrotation, the diagnosis was confirmed with a diagnostic laparoscopy. We discuss available literature concerning this rare anatomic anomaly as well as provide recommendations for diagnosis and treatment.


Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex.
T-brain gene-2 (Tbr2) is specifically expressed in the intermediate (basal) progenitor cells (IPCs) of the developing cerebral cortex; however, its function in this biological context has so far been overlooked due to the early lethality of Tbr2 mutant embryos. Conditional ablation of Tbr2 in the developing forebrain resulted in the loss of IPCs and their differentiated progeny in mutant cortex. Intriguingly, early loss of IPCs led to a decrease in cortical surface expansion and thickness with a neuronal reduction observed in all cortical layers. These findings suggest that IPC progeny contribute to the correct morphogenesis of each cortical layer. Our observations were confirmed by tracing Tbr2+ IPC cell fate using Tbr2::GFP transgenic mice. Finally, we demonstrated that misexpression of Tbr2 is sufficient to induce IPC identity in ventricular radial glial cells (RGCs). Together, these findings identify Tbr2 as a critical factor for the specification of IPCs during corticogenesis.


Effect on radioactivity concentration estimation of radon progenies with NaI(Tl) pulse height distribution from considering geometric structure around detector and infiltration of radionuclides.
The surface radioactivity concentrations of the radon progenies, (214)Pb and (214)Bi, were estimated from NaI(Tl) pulse height distributions during rain. The improvement in estimation errors caused by considering geometric structures around measuring points and infiltration of radionuclides was discussed. The surface radioactivity concentrations were determined by comparing the count rates at the full-energy peak ranges between observation and calculation with the electron-photon transport code EGS5. It was shown that the concentrations can be underestimated by about 30 % unless the obstacles around the detector or infiltration of radionuclides are considered in gamma ray transfer calculations at measuring points, where there are many tall obstacles, or the ground is covered with unpaved areas.


Spontaneous spermagglutination in ejaculates from men with head-to-head or tail-to-tail spermagglutinating antibodies in serum.
Weak or sometimes up to moderate spermagglutination was encountered in ejaculates from a group of men without spermagglutinating antibodies in serum. A similar pattern of spermagglutination was seen in ejaculates from men with head-to head (H-H) spermagglutinating antibodies in serum, even when a high titer (greater than or equal to 1:64) of antibodies was present. In contrast, men with high titers of tail-to-tail (T-T) sperm agglutinating antibodies in serum showed very marked or complete spermagglutination in the ejaculates. The agglutination in ejaculates from men with low titers (less than or equal to 1:32) of T-T spermagglutinating antibodies in serum was much less conspicuous and equaled that in ejaculates from men without such antibodies. This indicates that only a high titer of T-T spermagglutinating antibodies is associated with marked or complete spermagglutination in ejaculates.


Pathologic Complete Response in Rectal Cancer: Can We Detect It? Lessons Learned From a Proposed Randomized Trial of Watch-and-Wait Treatment of Rectal Cancer.
Chemoradiotherapy has the potential to downsize and downstage tumors before surgery, decrease locoregional recurrence, and induce a complete sterilization of tumor cells for middle and low locally advanced rectal cancer. A watch-and-wait tactic has been proposed for patients with clinical complete response. The purpose of this study was to verify our ability to identify complete clinical response in patients with rectal cancer based on clinical and radiologic criteria. This was a prospective study. The study was conducted at a single institution, in the setting of a watch-and-wait randomized trial. Consecutive patients with stage T3 to T4N0M0 or T(any)N+M0 cancer located within 10 cm from anal verge or T2N0 within 7 cm from anal verge were included in the study. Patients were staged and restaged 8 weeks after completion of chemoradiation (5-fluorouracil, 5040 cGy) by digital examination, colonoscopy, pelvic MRI, and thorax and abdominal CT scans. Clinical and radiologic judgments of tumor response were compared with pathologic response of patients treated by total mesorectal excision or clinical follow-up of patients selected for nonoperative treatment. A total of 118 patients were treated. Six patients were considered clinic complete responders (2 randomly assigned for surgery (1 ypT0N0 and 1 ypT2N0) and 4 patients randomly assigned for observation (3 sustained clinic complete response and 1 had tumor regrowth)). The 112 clinic incomplete responders underwent total mesorectal excision, and 18 revealed pathologic complete response. These 18 patients were not considered complete responders at restaging because they presented at least 1 of the following conditions: mucosal ulceration and/or deformity and/or substenosis of rectal lumen at digital rectal examination and colonoscopy (n = 16), ymrT1 to T4 (n = 16), ymrN+ (n = 2), involvement of circumferential resection margin on MRI (n = 3), extramural vascular invasion on MRI (n = 4), MRI tumor response grade 2 to 4 (n = 15), and pelvic side wall lymph node involvement on MRI (n = 1). Sensitivity for identification of ypT0N0 or sustained clinic complete response was 18.2%. This study has a short follow-up and small sample size. Radiologists who reviewed the restaging examination were not blinded to the pretreatment stage. Only 1 radiologist read the images of each patient. Evaluation of clinic complete response according to current adopted criteria has low sensitivity because pathologic complete response more frequently presented as clinic incomplete response (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A221).


Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes.
Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label 'amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene)-1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides.


Is epsilon-aminocaproic acid as effective as aprotinin in reducing bleeding with cardiac surgery?: a meta-analysis.
Although aprotinin is known to be effective in reducing postoperative hemorrhage after cardiac surgery, epsilon-aminocaproic acid, an alternative antifibrinolytic, is considerably less expensive. Because the results of 3 small randomized clinical trials comparing these 2 agents directly were inconclusive, we performed a meta-analysis to compare the relative effectiveness and adverse-effect profile of these 2 agents against placebo. Data from 52 randomized clinical trials published between 1985 and 1998 involving the use of epsilon-aminocaproic acid (n=9) or aprotinin (n=46) in patients undergoing cardiac surgery were abstracted. Our primary outcomes were total blood loss, red blood cell transfusion rates and amounts, reexploration, stroke, myocardial infarction, and mortality. The meta-analysis revealed substantial reductions in total blood loss with epsilon-aminocaproic acid and low-dose aprotinin (each with a 35% reduction versus placebo, P<0.001) and high-dose aprotinin (53% reduction, P<0.001). There were identical reductions in total postoperative transfusions with epsilon-aminocaproic acid (61% reduction versus placebo, P<0. 010) and high-dose aprotinin (62% reduction, P<0.001). The proportion of patients transfused was similarly reduced with epsilon-aminocaproic acid (OR, 0.32; 95% CI, 0.15 to 0.69) and high-dose aprotinin (OR, 0.28; 0.22 to 0.37). Although both drugs reduced rates of reexploration to similar degrees, this effect was statistically significant only with high-dose aprotinin (OR, 0.39; 0. 24 to 0.61). epsilon-Aminocaproic acid and aprotinin had no effect on risks of postoperative myocardial infarction or overall mortality. Because the 2 antifibrinolytic agents appear to have similar efficacies, the considerably less-expensive epsilon-aminocaproic acid may be preferred over aprotinin for reducing hemorrhage with cardiac surgery.


Assessment of the double contrast barium meal: method and application.
A method of assessing and comparing double contrast barium meals has been devised. The use of the linear analogue scale has been found to be a consistent method of recording and measuring radiological impression of mucosal coating and gaseous distension. By this means the effectiveness of various currently available barium and gas preparations has been assessed in 125 patients. Appreciable differences in mucosal coating achieved by different barium preparations were detected. Satisfactory gaseous distension of the stomach and duodenum was produced in the majority of patients by all of the methods tested, and the following measurements are suggested as an index of good distension: gastric fundus 10 cm, gastric midbody 7 cm, duodenal loop 4 cm. The relationships between mucosal coating, gaseous distension and areae gastricae have been shown to be tenuous. It is suggested that the methods we have used are very suitable for repetition in other centres for the comparison of any of the many barium and gas-producing agents which continue to come on to the market.


Nosocomial enterococcal infections: association with use of third-generation cephalosporin antibiotics.
Enterococcal infections consistently account for approximately 10% of all nosocomial infections reported to the Centers for Disease Control. There is concern that an increase in nosocomial enterococcal infection is due to the increased severity of inpatient illnesses and to the widespread use of broad-spectrum beta-lactam antibiotics. Nosocomial enterococcal infections were analyzed at our medium-sized community hospital over a time period spanning 9 years. A significant increase in the infection rate was detected during the latter half of 1986. This increase was due primarily to a disproportionate rise in the incidence of the urinary tract as a site of infection. There were no associated clusters of infection, no predilection for certain patient care areas, and no preceding change in the hospital infection control policies and procedures. Total hospital use of cephalosporins remained stable during the period of increased enterococcal infections, but use of third-generation cephalosporins almost doubled in 1986 compared with the 4 preceding years. Selective pressure of third-generation cephalosporin use appeared to be a factor in the increased incidence of nosocomial enterococcal urinary tract infection.


Bullatenone, 1,3-dione and sesquiterpene chemotypes of Lophomyrtus species.
The only known natural source of the volatile bioactive compounds bullatenone 1 and 4-methyl-1-phenylpentane-1,3-dione 2 is the New Zealand endemic shrub Lophomyrtus bullata (Myrtaceae). GC and NMR analyses of essential oils and solvent extracts of L. bullata, L. obcordata and the hybrid L. "ralphii" showed several chemotypes, which did not correlate with species. Levels of 1 and 2 varied from dominant to low/undetectable and the most common chemotype was rich in allo-aromadendrene and other sesquiterpenes. The rare natural product E-4-methyl-1-phenyl-1-penten-3-one 4 was detected for the first time in this genus. The non-volatile cytotoxic compound bullataketal 5 co-occurred with bullatenone 1. An essential oil from the relatively rare bullatenone 1 chemotype showed antifungal activity against Candida albicans and Cladosporium resinae, and an oil from the 4-methyl-1-phenylpentane-1,3-dione 2 chemotype showed antibacterial activity against Bacillus subtilis.


Driver's views and behaviors about safety in China--what do they NOT know about driving?
Driving safety has become an extremely severe problem in China due to rapid motorization. Unless more effective measures are taken, the fatality risk and the total fatalities due to road traffic accidents are expected to continue to increase. Therefore, focus group discussions were conducted to explore driver attitudes and safe driver characteristics. The results were then compared with a similar study conducted with US drivers. Although similarities were found, differences were of more importance. The Chinese drivers concentrate more on driving skills and capabilities, whereas the US drivers concentrate more on practical safe driving guidelines. Then direct field observations were conducted for the Chinese drivers to empirically investigate the issues discovered. The use of safety belts, running lights, headlights, and turn signals were observed to investigate the drivers' behaviors. Results show that the safety belt use ratio is about 64%, running light use is nearly zero during rainy and snowy weather, headlights use after sunset is substantially delayed, and only about 40% of drivers use turn signals to indicate their intention to change lanes. These findings indicate that the authorities need to take appropriate countermeasures to change the views of the Chinese drivers regarding driving safety and their unsafe driving behaviors. Improvement of training content and methods as well as police enforcement would be recommended.


Validity and Reliability of Farsi Version of Youth Sport Environment Questionnaire.
The Youth Sport Environment Questionnaire (YSEQ) had been developed from Group Environment Questionnaire, a well-known measure of team cohesion. The aim of this study was to adapt and examine the reliability and validity of the Farsi version of the YSEQ. This version was completed by 455 athletes aged 13-17 years. Results of confirmatory factor analysis indicated that two-factor solution showed a good fit to the data. The results also revealed that the Farsi YSEQ showed high internal consistency, test-retest reliability, and good concurrent validity. This study indicated that the Farsi version of the YSEQ is a valid and reliable measure to assess team cohesion in sport setting.


A facile synthesis of alpha,alpha'-(EE)-bis(benzylidene)-cycloalkanones and their antitubercular evaluations.
An economical and facile synthesis of alpha,alpha'-(EE)-bis(benzylidene)-cycloalkanones was achieved by the reaction of cycloalkanones with different aromatic aldehydes using ethanolic KOH in good yields. Few of the selected compounds were reduced with NaBH(4) to the respective alpha,alpha'-(EE)-bis(benzylidene)-cycloalkanols. All these compounds and our earlier synthesized cyclohexyl phenyl methanols were evaluated for their antitubercular, antifungal and antibacterial activities. Several compounds displayed moderate antitubercular activity with MIC=12.5-1.56 microg/mL. However, none of the compounds displayed any significant antifungal activity.


Does the Centers for Disease Control and Prevention's Recommendation of Opt-Out HIV Screening Impact the Effect of Stigma on HIV Test Acceptance?
HIV/AIDS-related stigma is a key factor impeding patient utilization of HIV testing services. To destigmatize HIV testing, the Centers for Disease Control and Prevention recommended an 'opt-out' screening strategy aimed at all patients in all clinical settings, regardless of HIV risk. This study assessed whether opt-out screening as compared to opt-in screening was associated with increased uptake of HIV testing among patients with HIV/AIDS-related stigma concerns. This study included 374 patients attending two Los Angeles ambulatory care clinics. Stigma items were grouped into three constructs: Blame/isolation, abandonment, and contagion. Individuals endorsing the blame/isolation subscale (AOR = 0.52; 95 % CI 0.29-0.92; p\0.05) and abandonment subscale (AOR = 0.27; 95 % CI 0.13-0.59; p\0.01) were significantly less likely to accept an HIV test. Additionally, the opt-out model did not counter the negative effects of stigma on HIV test acceptance. These findings indicate that stigma remains a barrier to HIV testing, regardless of the opt-out screening approach.


Facile encapsulation of nano zero-valent iron with calcium carbonate: synthesis, characterization and application for iron remediation.
In this study, CaCO3 was used as a modifier for nano zero-valent iron (nZVI) surface to prevent rapid aggregation and effectively utilized for iron remediation from aqueous solution. Surface chemistry and morphology of CaCO3 encapsulated nZVI (CaCO3-nZVI) before and after treatment of contaminant iron solution were characterized by scanning electron microscopy-energy dispersive X-ray (SEM-EDX), X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The mechanisms of surface modification as well as iron remediation were well depicted with the help of these characterisation tools. Iron removal efficacy of 96.4% was achieved with 0.25 g/L adsorbent dose for an influent iron of 0.5 mg/L at pH 10 after a 3 h treatment process. When the influent concentration was increased to 10 mg/L, the removal capacity decreased to 92.1%. The study demonstrates that CaCO3 and nZVI in the encapsulated nanoparticle have a significant synergistic effect. The pseudo-second- order reaction kinetics and Freundlich isotherm model correctly portrayed the experimental data for iron removal by CaCO3-nZVI. The CaCO3-nZVI is a viable option for iron removal from various aqueous media due to its facile preparation, high iron removal capability, and reusability.


Photogenerated Intrinsic Free Carriers in Small-molecule Organic Semiconductors Visualized by Ultrafast Spectroscopy.
Confirmation of direct photogeneration of intrinsic delocalized free carriers in small-molecule organic semiconductors has been a long-sought but unsolved issue, which is of fundamental significance to its application in photo-electric devices. Although the excitonic description of photoexcitation in these materials has been widely accepted, this concept is challenged by recently reported phenomena. Here we report observation of direct delocalized free carrier generation upon interband photoexcitation in highly crystalline zinc phthalocyanine films prepared by the weak epitaxy growth method using ultrafast spectroscopy. Transient absorption spectra spanning the visible to mid-infrared region revealed the existence of short-lived free electrons and holes with a diffusion length estimated to cross at least 11 molecules along the π-π stacking direction that subsequently localize to form charge transfer excitons. The interband transition was evidenced by ultraviolet-visible absorption, photoluminescence and electroluminescence spectroscopy. Our results suggest that delocalized free carriers photogeneration can also be achieved in organic semiconductors when the molecules are packed properly.


Preparation and physicochemical characterization of films prepared with salmon skin gelatin extracted by a trypsin-aided process.
The recovery of gelatins from Atlantic salmon (Salmo salar) skin for film formation and characterization was studied. Fish skins pre-treated with trypsin (250 U/g) produced the highest hydroxyproline content (7.41 ± 0.49 mg hydroxyproline/g treated skin) and yield (53.05 ± 4.38%) of gelatin, as compared to the use of saline solution. Pre-treatment with a lower concentration of trypsin (1 U/g) at a shorter pre-treatment time successfully reduced the degradation of gelatin with co-production of high molecular weight α-chains. Gelatin was further extracted by a trypsin-aided process for film formation and characterization. Films with increasing protein concentration (from 1 to 5%, w/v) exhibited higher thickness, tensile strength, and elongation at break (EAB), but a marked decrease in EAB for films with 6 and 7% (w/v). Films with 5% proteins showed higher thickness, lower tensile strength and higher EAB with increasing concentrations of glycerol (from 10 to 50% of proteins, w/w). All films exhibited high water uptake, decrease in light transmission and an increase in opacity as the protein and glycerol contents increased. Electrophoretic studies showed that the increase in the mechanical properties of the films was correlated with the increase in protein concentration, owing to the increased content of high molecular weight chain fractions. Furthermore, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) revealed the interaction between the proteins and glycerol for all films. This study demonstrated the viability of the trypsin supplementation process to obtain salmon skin gelatin for film formation.


Assessment of interrater and intrarater reliability in the evaluation of metered dose inhaler technique.
To determine if a training session using videotaped metered dose inhaler (MDI) performances can result in high interrater and intrarater reliability of five evaluators assessing MDI technique. Five evaluators (three pharmacists, two pulmonary fellows) were trained to evaluate MDI technique during a 2-h training session. The training session consisted of verbal instruction and practical experience in evaluating MDI technique using video-taped MDI performances of six nonstudy subjects. After the training session, the evaluators independently observed the same videotaped MDI demonstrations of 14 subjects on two occasions separated by a 7- to 10-day interval. Interrater and intrarater reliability was determined for individual steps by calculating percent agreement and intraclass correlation (ICC) coefficient. Interrater. The interrater reliability for individual steps ranged from 29 to 86 percent (ICC coefficient = 0.13 to 0.81). Steps in which evaluators were in agreement for less than 9 of the 14 subjects were shaking the inhaler before inhalation, exhaling, continuing to inhale slowly, and adequate breath hold. Intrarater: The overall percent agreement by step ranged from 74 to 97 percent. Exhaling to functional residual volume (76 percent) and continuing to inhale slowly and deeply (74 percent) had the lowest overall agreement between the first and second observation day. The consistency of evaluating a step between the two observation days varied considerably depending on the step and evaluator. High interrater and intrarater reliability in MDI evaluation is difficult to obtain. Clinicians and researchers involved in MDI evaluation and education should be trained to achieve consistency. A single training session using videotaped MDI demonstrations was not adequate in achieving consistency among evaluators. To improve accuracy of research results, researchers should include at least two evaluators to assess MDI technique or take other measures to show and report reliability.


Fitness to practise in pharmacy: a study of impairment in professional practice.
To explore the opinions and knowledge of Australian pharmacists about impairment in the profession, and their awareness of new legislation regarding impairment and mandatory reporting. Pharmacy practice in Australia. Pharmacists' opinions and knowledge were explored using a purposively designed, de-identified survey distributed by an intermediate mailing house to randomly selected pharmacists registered with the Pharmacy Board. Descriptive statistics and thematic analyses were conducted on the data. KEY OUTCOME MEASURES: This being an explorative study, we analysed various items using standard statistical methods and qualitative thematic analysis for responses to open-ended questions. Responses from 370 registered pharmacists were obtained. Of these, nearly 60% were not confident in their knowledge of legislation relating to impairment. The vast majority stated they would consider reporting an impaired colleague in principle, but only after consulting the colleague. Older pharmacists demonstrated increased awareness of new legislation; this was accompanied however, by a marked decrease in confidence regarding knowledge about impairment. Thematic analysis of the qualitative data revealed four main themes: (1) perception of impairment and support systems available (2) stigma related to implications of impairment and whistle-blowing (3) factors affecting reporting of impairment and (4) management of impairment. Australian pharmacists in this study recognised the importance of the issue of impairment, but appeared to lack confidence and/or awareness of legislative requirements regarding impairment in the profession. There is a need for educative programs and accessible, profession-specific rehabilitative programs to be instigated for management of impairment in the profession of pharmacy in Australia.


BreastIdea Volume Estimator: A New Tool for Breast Volume Estimation-Presentation and Validation for Women.
Breast volume assessment is crucial in a breast surgeon's clinical practice. The aim of this study was to present and validate a new Web application, BreastIdea Volume Estimator, a module for breast estimation of the already validated BreastIdea application. Forty breasts in 20 women were scanned using a three-dimensional scanner. They were then photographed in nonstandardized conditions, and volume estimations were calculated using BreastIdea Volume Estimator. Accuracy in addition to relative and absolute reliability of BreastIdea Volume Estimator measurements were investigated. In addition, breast volume differences were analyzed. Breast volume estimation using BreastIdea Volume Estimator yielded satisfactory accuracy and presented precision of the level of clinical measures. The mean absolute difference for both observers was 4.33 ± 3.79 cc and 6.78 ± 4.66 cc, which correspond to 1.87 ± 1.89 percent and 2.75 ± 2.05 percent errors of measurement. Similar relations were found for measurements of breast volume differences. BreastIdea Volume Estimator is a clinically oriented, reliable tool for breast volume evaluation. It provides results of appropriate accuracy regardless of chest abnormality and photograph standardization.


Endorectal pull-through with conservation of the rectal mucosa: experimental study.
The present experimental work was designed to study an abdominoanal pull-through technique, with conservation of rectal mucosa. Continence was evaluated from clinical, radiologic, and histopathologic standpoints. The animals defecated normally. A good retention of barium was seen in the radiologic enema. On the reexploration of the animals, we found a distal dehiscence with elevation of the intussuscepted stump towards the rectum in all. A reepithelization process of serosa of the intussuscepted segment was noted.


Integrative analysis of gene expression in response to low-dose ionizing radiation in a human skin model.
The advance in medical imaging and utilization has raised the concern about exposure to low-dose ionizing radiation (LDIR). Cellular and molecular responses to high-dose ionizing radiation have been characterized, but in the range of low dose, these responses are poorly understood. Here, we investigate the gene expression in response to LDIR (10 cGy) in the EpiDermFT human skin model. We identified 3299 differentially expressed genes (DEGs) in response to LDIR. Among these DEGs, we noted several well-characterized long noncoding RNAs. Gene Ontology and KEGG pathway analysis were performed to detect altered molecular response. GO and KEGG pathway results showed that genes corresponding to "regulation of cell proliferation" were enriched. Gene set enrichment analysis showed that KRAS signaling pathway was enriched in response to LDIR and transcription targets of NF-κB were also enriched when exposed to LDIR.


Hoffa fracture of the femoral condyle: Injury mechanism, classification, diagnosis, and treatment.
Hoffa fractures are coronal-plane fractures of the femoral condyle, which are rarer than sagittal-plane condylar fractures. This study aimed to systematically review the clinical knowledge base of Hoffa fractures to facilitate the diagnosis and management of such injuries. We searched Medline, Embase, Cochrane Library, Google Scholar, China National Knowledge Infrastructure, and China Biology Medicine disc, using the terms "Hoffa fracture" and "coronal fracture of femoral condyle." One hundred five articles on Hoffa fractures were reviewed, and the clinical knowledge base was summarized. High-energy trauma is a common cause of a Hoffa fracture, although low-energy trauma and iatrogenic injury can also lead to these fractures. Commonly used classifications include the Letenneur classification, a computed tomography (CT) classification, the AO classification, and modified AO classification. Radiography can reveal fracture lines. If radiographic findings are negative in questionable cases, CT and magnetic resonance imaging (MRI) should be performed. Nondisplaced fractures can be managed conservatively; however, they involve a high risk of redisplacement. Open reduction and internal fixation are preferred. For young patients with good compliance, simple medial or lateral condylar fractures can be treated via a medial or lateral parapatellar approach. After fracture exposure, headless compression screws can be inserted perpendicularly to the fracture line from posterior to anterior. For bicondylar fractures, a median parapatellar incision can be used. For complex fractures in patients with osteoporosis or a high body mass index, cannulated screws with antigliding plate fixation should be used. Here, we summarized the injury mechanism, diagnosis, classification, and treatment options of Hoffa fractures.


Interaction of heavy metals and biocide/herbicide from stormwater runoff of buildings with dissolved organic matter.
Stormwater runoff from roofs and façades can be contaminated by heavy metals and biocides/herbicides. High efficiency on-site treatment methods are now urgently needed to safeguard the ecosystem. The basis for developing such treatment facilities is an in-depth understanding of their interactions with dissolved organic matter (DOM), as this affects their migration in the environment. Hence, the interactions between copper (Cu), zinc (Zn), benzyl-dimethyl-tetradecylammonium chloride dihydrate (BAC), mecoprop-P (MCPP) and DOM at pH 5 to 9 were investigated separately in this study. The evaluation of the interaction processes was achieved by applying excitation emission matrix and parallel factor analysis (EEM-PARAFAC) to titration samples; obtained data were fitted by two different models. Mechanisms involved in BAC/MCPP-DOM interactions were revealed by Fourier-transform infrared spectroscopy (FTIR) and two-dimensional correlation spectrum (2D-COS) analysis. Results showed that the applied DOM was composed of the two different fluorescent components C1 and C2. More interaction with C1 than with C2 was observed for both Cu/Zn and BAC/MCPP. Increasing the pH enhanced the interactions between Cu/Zn and DOM. At pH 5 with a maximum quencher addition, the remaining fluorescence of CuC1 and ZnC1 were 15.7% and 87.1%, respectively. Corresponding data at pH 9 decreased to 3% and 69.5%. Contrarily, interactions between BAC/MCPP and DOM were impaired by high pH conditions. The increase of pH from 5 to 9 with maximum BAC and MCPP added raised the remaining fluorescence of BAC-C1 and MCPP-C1 by 15.9% and 21.3% separately. The fitting outcomes from the Ryan-Weber equation (Cu/Zn titration) and the Stern-Volmer equation (BAC/MCPP titration) corresponded well with the titration studies. FTIR coupled with 2D-COS analysis revealed that mechanisms involved in BAC/MCPP titration include hydrogen bonding, π-π interaction, and electrostatic effect. The order of mechanisms taking effect during the interaction with DOM is affected by the molecular structure of BAC and MCPP.


Prevalence of modifiable cardiovascular risk factors among undergraduate students in Kano Nigeria: A need for action.
Early adulthood is a period characterised by many lifestyle choices that could predispose an individual to cardiovascular disease (CVD) later in life. However, data on CVD risk factors among young adults in sub-Saharan Africa are lacking. We aim to determine the prevalence of modifiable CVD risk factors among undergraduates in Kano, Nigeria. One hundred and fifty undergraduate students were recruited for this descriptive cross-sectional study. Blood pressure, weight, waist circumference, hip circumference, and height were measured using standard protocols. The body mass index was calculated as weight (kg) divided by height in square metre. Serum total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) were determined via an enzymatic method. Low-density lipoprotein cholesterol (LDL-c) was calculated using the Friedewald equation. The mean age of the participants was 23.12 ± 2.97 (17-31) years. Notably, 90% of the participants had at least one CVD risk factor and 65% had at least one abnormal lipid parameter. The prevalence of elevated systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, LDL-c, and reduced HDL-c were 7.33%, 50%, 0.67%, 7.33%, 0.67%, and 58.67%, respectively. Moreover, the prevalence of general and truncal obesity were 0.67% and 4%, respectively, while the prevalence of metabolic syndrome and diabetes were 4% and 0%, respectively. There is high prevalence of modifiable CVD risk factors among undergraduates in Kano, Nigeria. Thus, appropriate policies for screening, early detection, and treatment of these risk factors should be developed.


Bioinformatics-based discovery of the urinary BBOX1 mRNA as a potential biomarker of diabetic kidney disease.
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the world. Emerging evidence has shown that urinary mRNAs may serve as early diagnostic and prognostic biomarkers of DKD. In this article, we aimed to first establish a novel bioinformatics-based methodology for analyzing the "urinary kidney-specific mRNAs" and verify their potential clinical utility in DKD. To select candidate mRNAs, a total of 127 Affymetrix microarray datasets of diabetic kidney tissues and other tissues from humans were compiled and analyzed using an integrative bioinformatics approach. Then, the urinary expression of candidate mRNAs in stage 1 study (n = 82) was verified, and the one with best performance moved on to stage 2 study (n = 80) for validation. To avoid potential detection bias, a one-step Taqman PCR assay was developed for quantification of the interested mRNA in stage 2 study. Lastly, the in situ expression of the selected mRNA was further confirmed using fluorescent in situ hybridization (FISH) assay and bioinformatics analysis. Our bioinformatics analysis identified sixteen mRNAs as candidates, of which urinary BBOX1 (uBBOX1) levels were significantly upregulated in the urine of patients with DKD. The expression of uBBOX1 was also increased in normoalbuminuric diabetes subjects, while remained unchanged in patients with urinary tract infection or bladder cancer. Besides, uBBOX1 levels correlated with glycemic control, albuminuria and urinary tubular injury marker levels. Similar results were obtained in stage 2 study. FISH assay further demonstrated that BBOX1 mRNA was predominantly located in renal tubular epithelial cells, while its expression in podocytes and urothelium was weak. Further bioinformatics analysis also suggested that tubular BBOX1 mRNA expression was quite stable in various types of kidney diseases. Our study provided a novel methodology to identify and analyze urinary kidney-specific mRNAs. uBBOX1 might serve as a promising biomarker of DKD. The performance of the selected urinary mRNAs in monitoring disease progression needs further validation.


Relationship among health-related quality of life, depression and awareness of home care services in elderly patients.
The present descriptive study was carried out to determine the relationship between health-related quality of life, depression and awareness of home care services among elderly patients. Patients aged 65 years or older staying at the surgery and internal medicine clinics were included in the study. The "Patient Introduction Form," "Short Form-36 Quality of Life Questionnaire" and "Geriatric Depression Scale" were utilized in the collection of data. In the present study, it was determined that only approximately half of elderly patients (54.9%) knew the concept of home care, most of them had not previously received home care and requested home care related to medical care. The mean scores were lower in some areas of the quality of life questionnaire in some factors that could influence home care awareness. These factors were determined as: female sex, history of falling, chronic illness, functionally, moderately or severely dependent, no previous receipt of home care and wishing to receive home care. The home care requirement of elderly patients can be influenced by many physiological, psychological and social factors that can affect their quality of life. Thus, it is of utmost importance that medical professionals evaluate the quality of life of elderly individuals and its influencing factors. Geriatr Gerontol Int 2016; 16: 1211-1219.


Decision tree distinguish affective disorder diagnosis from psychotic disorder diagnosis with clinical and lab factors.
Affective symptoms usually occur at the same time of psychotic symptoms. An effective predictive method would help the differential diagnosis at an early stage of the mental disorder. The purpose of the study was to establish a predictive model by using laboratory indexes and clinical factors to improve the diagnostic accuracy. Subjects were patients diagnosed with psychiatric disorders with affective and/or psychotic symptoms. Two patient samples were collected in the study (n = 309) With three classification methods (logistic regression, decision tree, and discriminant analysis), we established the models and verified the models. Seven predictors were found to be significant to distinguish the affective disorder diagnosis from the psychotic disorder diagnosis in all three methods, the 7 factors were Activities of daily living, direct bilirubin, apolipoproteinA1, lactic dehydrogenase, creatinine, monocyte count and interleukin-8. The decision tree outperformed the other 2 methods in area under the receiver operating characteristic curve, and also had the highest percentage of correctly classification. We established a predictive model that included activities of daily living, biochemical, and immune indicators. In addition, the model established by the decision tree method had the highest predictive power, which provided a reliable basis for future clinical work. Our work would help make diagnosis more accurate at an early stage of the disorder.


Studies on the specificity of phosphorylase kinase using peptide substrates.
The action of phosphorylase kinase on synthetic peptides is reported. These peptides are variants of the amino acid sequence. Ser-Asp-Gln-Glu-Lys-Arg-Lys-Gln-Ile-Ser-Val-Arg-Gly-Leu, found in the natural substrate, phosphorylase b. The effects of size, the cluster of basic groups at the NH2-terminal side, the phosphorylatable seryl residue, the hydrophobic groups surrounding serine, and the arginyl function at the COOH-terminal side were tested and analyzed by evaluation of the kinetic parameters, Km and Vmax. The first 6 residues were found to be nonessential, but substitution of residues in the sequence. Lys-Gln-Ile-Ser-Val-Arg, had a large effect on phosphorylation. A comparison was made between the action of nonactivated and activated phosphorylase kinase on selected peptides and phosphorylase b. Various forms of phosphorylase b were tested as substrates for cyclic AMP-dependent protein kinase in the presence of effectors and salts. Although phosphorylase would not serve as a substrate for protein kinase, the aforementioned synthetic peptide of the phosphorylase b sequence would do so, indicating that the primary sequence surrounding the phosphorylatable serine did not block phosphorylation, which suggests that higher order structural features prohibit the phosphorylation.


Acetylcholinesterase sensor based on screen-printed carbon electrode modified with prussian blue.
Acetylcholinesterase (ChE) sensor based on Prussian blue (PB) modified electrode was developed and tested for the detection of organophosphorus and carbamic pesticides. The signal of the sensor was generated in PB mediated oxidation of thiocholine recorded at +200 mv in DC mode. ChE from electric eel was immobilized by cross-linking with glutaraldehyde in the presence of bovine serum albumin (BSA) on the surface of screen-printed carbon electrode covered with PB and Nafion. The content of the surface layer (specific enzyme activity, Nafion and BSA amounts) was optimized to establish high and reliable response toward the substrate and ChE inhibitors. The ChE/PB sensor makes it possible to detect Aldicarb, Paraoxon and Parathion-Methyl with limits of detection 30, 10 and 5 ppb, respectively (incubation 10 min). The feasibility of practical application of the ChE/PB sensor developed for the monitoring of degradation of the pesticides in wine fermentation was shown. To diminish matrix interferences, the electrolysis of the grape juice with Al anode and evaporation of ethanol were suggested, however the procedures decrease the sensitivity of pesticide detection and stability of the sample tested.


Reversible changes in the accumulation and activities of tyrosine hydroxylase and dopamine-beta-hydroxylase in neurons of nucleus locus coeruleus during the retrograde reaction.
To examine the biochemical events associated with the retrograde reaction in central noradrenergic neurons, changes in the activities of several enzymes subserving the metabolism of catecholamines, including tyrosine hydroxylase (TH),dopamine-beta-hydroxylase (DBH), DOPA decarboxylase (DDC), and monoamine oxidase (MAO), were measured in the nucleus locus coeruleus of rat brain following transection of the ascending axons from neurons in this nucleus by electrolytic lesions of the posterolateral hypothalamus. Such lesions produced a triphasic response in the activities of TH and DBH consisting of: (a) an increase to approximately 150 percent of control during the first 48 h followed by (b) a reduction reaching 60 percent of control by day 14, and (c) a full recovery of activity by day 21-28. In contrast, the activities of DDC and MAO, enzymes non-specific for catecholamine neurons, were unchanged. Immunochemical titration with specific antibodies to TH and DBH demonstrated that the fall in enzyme activity was entirely attributable to reduced accumulation of specific enzyme protein and not inhibition of pre-existing enzyme molecules. There was no reduction in the number of neurons in the nucleus locus coeruleus as a consequence of the lesion. We conclude that a reduction in the accumulation of specific enzymes subserving transmitter biosynthesis characterizes a reversible retrograde reaction of central noradrenergic neurons. The coincidence of the time course of reduced enzyme accumulation with regenerative sprouting from damaged noradrenergic axons and also the absence of classical signs of chromatolysis in locus coeruleus neurons following comparable lesions suggest that, first, during the retrograde reaction there may be a reordering of priorities governing accumulation of specific proteins favoring accumulation of those required for reconstitution of cellular processes by sprouting at the expense of proteins utilized in the synthesis of neurotransmitters, and second, some intrinsic neurons of the CNS may undergo reversible biochemical changes of a retrograde reaction in the absence of the classical morphological appearance of chromatolysis.


A comparison of the cost of outpatient care delivered by Aam Aadmi Mohalla Clinics compared to other public and private facilities in Delhi, India.
Aam Admi Mohalla Clinics (AAMCs) were introduced in Delhi in 2015 as neighbourhood clinics to strengthen the delivery of primary care. To inform the policies on government investments for outpatient care, this study estimated the cost of outpatient care per visit in Delhi for 2019-20 for AAMCs and compared it with urban primary health centres (UPHCs), public hospitals, private clinics and private hospitals. Facility costs for AAMCs and UPHCs were also estimated. Using the data from a national health survey, government annual budgets and reports, a modified top-down methodology was adopted to measure the true cost of public facilities, taking into account both government expenditure and out-of-pocket expenditure (OOPE). Inflation-adjusted OOPE was used to measure the cost of private facilities. The cost per visit at a private clinic at ₹1146 (US$16) was more than 3-times higher than that at a UPHC (₹325/US$5) and 8-times higher than that at AAMCs (₹143/US$2.0). These costs were ₹1099 (US$15) and ₹1818 (US$25) at public and private hospitals respectively. The annual economic cost per facility of a UPHC at ₹ 9 280 000/$130 000 is ∼4-times that at AAMC (₹2 474 000/$35 000). Unit costs are found to be lower at AAMCs. Utilization for outpatient care has shifted in favour of public primary care facilities. Higher investment in public primary care facilities with expanded services for prevention and promotion, upscaled infrastructure and a gate-keeping mechanism can strengthen the delivery of primary care and promote universal health care at a lower cost.


Short-term potentiation of mEPSCs requires N-, P/Q- and L-type Ca2+ channels and mitochondria in the supraoptic nucleus.
The glutamatergic synapses of the supraoptic nucleus display a unique activity-dependent plasticity characterized by a barrage of tetrodotoxin-resistant miniature EPSCs (mEPSCs) persisting for 5-20 min, causing postsynaptic excitation. We investigated how this short-term synaptic potentiation (STP) induced by a brief high-frequency stimulation (HFS) of afferents was initiated and maintained without lingering presynaptic firing, using in vitro patch-clamp recording on rat brain slices. We found that following the immediate rise in mEPSC frequency, STP decayed with two-exponential functions indicative of two discrete phases. STP depends entirely on extracellular Ca(2+) which enters the presynaptic terminals through voltage-gated Ca(2+) channels but also, to a much lesser degree, through a pathway independent of these channels or reverse mode of the plasma membrane Na(+)-Ca(2+) exchanger. Initiation of STP is largely mediated by any of the N-, P/Q- or L-type channels, and only a simultaneous application of specific blockers for all these channels attenuates STP. Furthermore, the second phase of STP is curtailed by the inhibition of mitochondrial Ca(2+) uptake or mitochondrial Na(+)-Ca(2+) exchanger. mEPSCs amplitude is also potentiated by HFS which requires extracellular Ca(2+). In conclusion, induction of mEPSC-STP is redundantly mediated by presynaptic N-, P/Q- and L-type Ca(2+) channels while the second phase depends on mitochondrial Ca(2+) sequestration and release. Since glutamate influences unique firing patterns that optimize hormone release by supraoptic magnocellular neurons, a prolonged barrage of spontaneous excitatory transmission may aid in the induction of respective firing activities.


Alternative Lengthening of Telomeres and Mediated Telomere Synthesis.
Telomeres are DNA-protein complexes that protect eukaryotic chromosome ends from being erroneously repaired by the DNA damage repair system, and the length of telomeres indicates the replicative potential of the cell. Telomeres shorten during each division of the cell, resulting in telomeric damage and replicative senescence. Tumor cells tend to ensure cell proliferation potential and genomic stability by activating telomere maintenance mechanisms (TMMs) for telomere lengthening. The alternative lengthening of telomeres (ALT) pathway is the most frequently activated TMM in tumors of mesenchymal and neuroepithelial origin, and ALT also frequently occurs during experimental cellular immortalization of mesenchymal cells. ALT is a process that relies on homologous recombination (HR) to elongate telomeres. However, some processes in the ALT mechanism remain poorly understood. Here, we review the most recent understanding of ALT mechanisms and processes, which may help us to better understand how the ALT pathway is activated in cancer cells and determine the potential therapeutic targets in ALT pathway-stabilized tumors.


Total-body digital X-ray in trauma. An experience report on the first operational full body scanner in Europe and its possible role in ATLS.
When patients enter our emergency room with suspected multiple injuries, Statscan provides a full body anterior and lateral image for initial diagnosis, and then zooms in on specific smaller areas for a more detailed evaluation. In order to examine the possible role of Statscan in the management of multiply injured patients we implemented a modified ATLS((R)) algorithm, where X-ray of C-spine, chest and pelvis have been replaced by single-total a.p./lat. body radiograph. Between 15 October 2006 and 1 February 2007 143 trauma patients (mean ISS 15+/-14 (3-75)) were included. We compared the time in resuscitation room to 650 patients (mean ISS 14+/-14 (3-75)) which were treated between 1 January 2002 and 1 January 2004 according to conventional ATLS protocol. The total-body scanning time was 3.5 min (3-6 min) compared to 25.7 (8-48 min) for conventional X-rays, The total ER time was unchanged 28.7 min (13-58 min) compared to 29.1 min (15-65 min) using conventional plain radiography. In 116/143 patients additional CT scans were necessary. In 98/116 full body trauma CT scans were performed. In 18/116 patients selective CT scans were ordered based on Statscan findings. In 43/143 additional conventional X-rays had to be performed, mainly due to inadequate a.p. views of fractured bones. All radiographs were transmitted over the hospital network (Picture Archiving and Communication System, PACS) for immediate simultaneous viewing at different places. The rapid availability of images for interpretation because of their digital nature and the reduced need for repeat exposures because of faulty radiography are also felt to be strengths.


Chronic Pain and Mood Disorders Are Not Barriers to Symptom Improvement Under Collaborative Co-managed Care (C3).
Patients with comorbid chronic pain and mood disorders have more severe gastrointestinal disease and higher healthcare expenses than their peers. We sought to determine whether management under our innovative Collaborative Co-Managed Care (C3) general gastroenterology care model improved outcomes. Patient questionnaires completed by outpatients at our GI Motility Center were analyzed alongside demographic information to determine predictors of response to treatment based on adequate relief of gastrointestinal symptoms and improvement in quality of life. These comorbidities did not significantly impair response and may be associated with improved response under our model. The C3 general gastroenterology care model anchors on setting expectations and team-based communication and improves outcomes of, and access to, care.


Thirty-day mortality after hip fractures: has anything changed?
Bone density insufficiency is the main cause for significant musculoskeletal trauma in the elderly population following low-energy falls. Hip fractures, in particular, represent an important public health concern taking into account the complicated needs of the patients due to their medical comorbidities as well as their rehabilitation and social demands. The annual cost for the care of these patients is estimated at around 2 billion pounds (£) in the UK and is ever growing. An increased early and late mortality rate is also recognised in these injuries together with significant adversities for the patients. Lately, in order to improve the outcomes of this special cohort of patients, fast-track care pathways and government initiatives have been implemented. It appears that these measures have contributed in a steady year-by-year reduction of the 30-day mortality rates. Whether we have currently reached a plateau or whether an ongoing reduction in mortality rates will continue to be observed is yet to be seen.


1,2-Dioctanoyl-glycerol induces a discrete but transient translocation of protein kinase C as well as the inhibition of MCF-7 cell proliferation.
Exposure of MCF-7 human breast cancer cells to phorbol esters such as 12-0-tetradecanoylphorbol-13-acetate (TPA) results in a dose-dependent inhibition of cell proliferation. One of the earliest biochemical events induced by TPA is the translocation of protein kinase C from the cytosolic to the particulate compartment. We have investigated the effects of permeant diacylglycerol 1,2-dioctanoyl-glycerol (diC8) on both protein kinase C activity and MCF-7 cell proliferation. DiC8 induces a discrete but significant translocation of protein kinase C within the first minutes of MCF-7 cell treatment (26 +/- 6%, mean +/- SD of 5 different experiments, upon 5 min incubation in the presence of 43 micrograms/ml diC8). However, this effect is only transient as the enzymatic activity returns to the control value after 60 min. DiC8 mimics the effect of TPA on MCF-7 cell proliferation. The dose-response curves for both protein kinase C translocation and cell growth inhibition show that diC8 exerts its effects on both parameters in the same range of concentrations, despite some discrepancies at the lowest doses. We also report that long-term treatment of the cells with diC8 does not lead to the protein kinase C disappearance observed during prolonged exposure to TPA. All together, our results reinforce the hypothesis of a negative modulatory role of protein kinase C in MCF-7 cell proliferation and suggest that the enzyme translocation but not its down-regulation could be a pre-requisite in the biological cell response.


Systemic inflammatory responses following welding inhalation challenge test.
The aim of this study was to investigate inflammatory and respiratory responses to welding fume exposure in patients with suspected occupational asthma. Sixteen patients referred to the Finnish Institute of Occupational Health underwent mild steel (MS) and stainless steel (SS) welding challenge tests, due to suspicion of OA. Platelet count, leucocytes and their differential count, hemoglobin, sensitive CRP, lipids, glucose and fibrinogen were analyzed in addition to interleukin (IL)-1β, IL-6, IL-8, TNF-α, endothelin-1, and E-selectin in plasma samples. Peak expiratory flow (PEF), forced expiratory volume in 1 min (FEV1) and exhaled nitric oxide (NO) measurements were performed before and after the challenge test. Personal particle exposure was assessed using IOM and a mini sampler. Particle size distribution was measured by an Electric Low Pressure Impactor (ELPI). The number of leukocytes, neutrophils, and platelets increased significantly, and the hemoglobin level and number of erythrocytes decreased significantly after both the MS and SS exposure tests. Five of the patients were diagnosed with OA, and their maximum fall in FEV1 values was 0.70 l (±0.32) 4 h after SS exposure. MS welding generated an average inhalable particle mass concentration of 31.6, and SS welding of 40.2 mg/m3. The mean particle concentration measured inside the welding face shields by the mini sampler was 30.2 mg/m3 and 41.7 mg/m3, respectively. Exposure to MS and SS welding fume resulted in a mild systemic inflammatory response. The particle concentration from the breathing zones correlated with the measurements inside the welding face shields.


Different ancestor alleles: a reason for the bimodal fragment size distribution in the minisatellite D2S44 (YNH24).
Three conserved repeat order motifs found in the D2S44 (YNH24) minisatellite by minisatellite variant repeat mapping by PCR (MVR-PCR) might be the remnants of three different ancestor alleles. One of the motifs is found in the group of alleles around the 2.8 kbp fragment size and the two others in the group of alleles around the 4.1 kbp fragment size in the bimodal frequency distribution of HinfI fragments characteristic for the D2S44 minisatellite. The conserved repeat-order motifs were found at the 3'-end of the alleles, whilst the 5'-end was highly polymorphic. This is the first time a minisatellite is shown to have repeat-order motifs that are associated with fragment length. These results were obtained by MVR-PCR mapping of 49 alleles with primers specific for the core nucleotide sequence variation ...(G)5TGTT, ...(G)4TTGTT or ...(G)4TGTT.


Inducing effect of skeletal muscle extracts on the appearance of calbindin-immunoreactive dorsal root ganglion cells in culture.
Calbindin D-28k is a calcium-binding protein which is not expressed by dorsal root ganglion cells cultured from 6-day-old (E6) chick embryos. When soluble muscle extracts from embryos at E11, E18 or chickens 2 weeks after hatching were added immediately after seeding, dorsal root ganglia cells grown at E6 displayed neuronal subpopulations expressing calbindin immunoreactivity with time; the effect of muscle extract on the percentage of calbindin-immunoreactive dorsal root ganglia cells followed a dose-response curve. When muscle extract was added to cultures after a 3 day delay, the percentage of calbindin-expressing neurons was unchanged. The effect produced by muscle extract and, to a lesser degree, skin extract on the appearance of calbindin-positive neurons was not reproduced by brain or liver extracts while all four exerted a trophic action on cultured neurons. Hence it is assumed that muscle extract contains a factor which produces an inductive effect on the initiation of calbindin-expression by uncommitted subpopulations of sensory neurons rather than a trophic influence on the selective survival of covertly committed neuronal subpopulations. The fact that muscle extract promoted calbindin expression by dorsal root ganglia cells in neuron-enriched as well as in mixed dorsal root ganglion cell cultures indicates that the factor would act directly on sensory neurons rather than indirectly through mediation of non-neuronal cells. Since the active muscular factor was non-dialysable, heat-inactivated, trypsin-sensitive and retained by molecular filters with a cut-off of 30 K, this factor is probably a protein.


Cognitive behavioral therapy versus general health education for family caregivers of individuals with heart failure: a pilot randomized controlled trial.
While support from family caregivers is essential in the care of patients with heart failure (HF), caregiving places a considerable burden on family caregivers. We examined the preliminary effects of cognitive behavioral therapy (CBT) for caregivers of individuals with HF. In this pilot randomized controlled trial, patients with HF and their primary family caregivers (30 dyads) were randomized into CBT (n = 15) or general health education (GHE, n = 15) groups. Caregivers received 8 weekly individual sessions of either CBT (intervention) or GHE (attention control condition). Caregivers completed questionnaires at baseline, post-intervention, and 6 months. Saliva samples collected from caregivers at baseline and post-intervention were analyzed for salivary cortisol. The cortisol awakening response (CAR) and area under the curve (AUC) were calculated using log-transformed cortisol values. We analyzed data from 26 (14 receiving CBT and 12 receiving GHE) caregivers who received at least one session of CBT or GHE (modified intention-to treat) using linear mixed models. Each model included time, study group, and time-by-study group interaction as fixed effects. Patients were older (66.94 ± 14.01 years) than caregivers (55.09 ± 15.24 years), and 54% of patients and 54% of caregivers were female. Most caregivers (58%) were spouses. A total of 14 (93%) CBT and 12 (80%) GHE participants received at least 1 session (p = .60), and 11 (73%) CBT and 11 (73%) GHE participants completed all 8 sessions (p = 1.00). There were no significant between-group differences in change for salivary cortisol or psychological outcomes. However, the CBT group had significant within-group improvements in perceived stress (p = .011), stress symptoms (p = .017), depression (p = .002), and anxiety (p = .006) from baseline to post-intervention, while the control group had no significant within-group change in the outcomes except for anxiety (p = .03). The significant improvements observed in the CBT group lasted for 6 months. No adverse effects were observed. In this pilot trial, although between-group differences in change were not significant, CBT resulted in significant improvements in some psychological outcomes with no improvement in the control group. Our findings suggest the potential of the intervention to alleviate psychological distress in HF caregivers. Further examination in larger randomized trials is warranted. ClinicalTrials.gov Identifier: NCT01937936 (Registered on 10/09/2013).


Etiologies and outcomes of acute liver failure in Germany.
Acute liver failure (ALF) is a severe form of acute liver injury that can progress to multiple organ failure. We investigated causes and outcomes of ALF. Eleven university medical centers in Germany were asked to report patients with (primary) severe acute liver injury (sALI) (international normalized ratio [INR] >1.5 but no hepatic encephalopathy) and primary ALF (INR >1.5 with overt hepatic encephalopathy) treated from 2008 to 2009. Data were analyzed from 46 patients with sALI and 109 patients with ALF. The most frequent etiologies of primary ALF were non-acetaminophen drug-induced (32%), indeterminate (24%), and viral (21%); acetaminophen ingestion was the cause of ALF in only 9% of patients. The support of a ventilator was required by 44% of patients with ALF, vasopressors by 38%, and renal replacement by 36%. Seventy-nine patients with ALF (72%) survived until hospital discharge, 38 (35%) survived without emergency liver transplantation (ELT), and 51 received ELT (47%); 80% of patients who received ELT survived until discharge from the hospital. In Germany, drug toxicity, indeterminate etiology, and viral hepatitis appear to be the major causes of primary ALF, which has high mortality. Patients with ALF are at great risk of progressing to multiple organ failure, but 80% of patients who receive ELT survive until discharge from the hospital.


D-penicillamine-templated copper nanoparticles via ascorbic acid reduction as a mercury ion sensor.
Mercury ion is one of the most hazardous metal pollutants that can cause deleterious effects on human health and the environment even at low concentrations. It is necessary to develop new mercury detection methods with high sensitivity, specificity and rapidity. In this study, a novel and green strategy for synthesizing D-penicillamine-capped copper nanoparticles (DPA-CuNPs) was successfully established by a chemical reduction method, in which D-penicillamine and ascorbic acid were used as stabilizing agent and reducing agent, respectively. The as-prepared DPA-CuNPs showed strong red fluorescence and had a large Stoke's shift (270nm). Scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, fluorescence spectroscopy, and ultraviolet-visible spectrophotometry were utilized to elucidate the possible fluorescence mechanism, which could be aggregation-induced emission effect. Based on the phenomenon that trace mercury ion can disperse the aggregated DPA-CuNPs, resulting in great fluorescence quench of the system, a sensitive and selective assay for mercury ion in aqueous solution with the DPA-CuNPs was developed. Under optimum conditions, this assay can be applied to the quantification of Hg(2+) in the 1.0-30μM concentration range and the detection limit (3σ/slope) is 32nM. The method was successfully applied to determine Hg(2+) in real water samples.


Comprehensive and quantitative mapping of RNA-protein interactions across a transcribed eukaryotic genome.
RNA-binding proteins (RBPs) control the fate of nearly every transcript in a cell. However, no existing approach for studying these posttranscriptional gene regulators combines transcriptome-wide throughput and biophysical precision. Here, we describe an assay that accomplishes this. Using commonly available hardware, we built a customizable, open-source platform that leverages the inherent throughput of Illumina technology for direct biophysical measurements. We used the platform to quantitatively measure the binding affinity of the prototypical RBP Vts1 for every transcript in the Saccharomyces cerevisiae genome. The scale and precision of these measurements revealed many previously unknown features of this well-studied RBP. Our transcribed genome array (TGA) assayed both rare and abundant transcripts with equivalent proficiency, revealing hundreds of low-abundance targets missed by previous approaches. These targets regulated diverse biological processes including nutrient sensing and the DNA damage response, and implicated Vts1 in de novo gene "birth." TGA provided single-nucleotide resolution for each binding site and delineated a highly specific sequence and structure motif for Vts1 binding. Changes in transcript levels in vts1Δ cells established the regulatory function of these binding sites. The impact of Vts1 on transcript abundance was largely independent of where it bound within an mRNA, challenging prevailing assumptions about how this RBP drives RNA degradation. TGA thus enables a quantitative description of the relationship between variant RNA structures, affinity, and in vivo phenotype on a transcriptome-wide scale. We anticipate that TGA will provide similarly comprehensive and quantitative insights into the function of virtually any RBP.


All-trans to 13-cis retinal isomerization in light-adapted bacteriorhodopsin at acidic pH.
The flash photolysis kinetic spectra of the intermediate M(412) of bacteriorhodopsin were monitored during the process of acid titration. In the light-adapted state, the maximum peak amplitude of M(412) absorbance of bacteriorhodopsin decreased (pK(a)=3.40+/-0.05) as the pH decreased from 7.3 to 1.9. In the dark-adapted state, the maximum peak amplitude of M(412) absorbance of bacteriorhodopsin increased as the pH decreased from 6.9 to 4.1, and then decreased (pK(a)=2.85+/-0.05) as the pH dropped to 2.1. These different trends in the change in the maximum peak amplitude suggested that not only the transition of purple membrane to blue membrane had taken place in both light and dark-adapted states, but also the fraction of all-trans-bR had changed during the acid titration. The pH-dependent absorption changes at 640 nm of bacteriorhodopsin in both light- and dark-adapted states were also observed. The pK(a)-values of the purple-to-blue transition were 3.80+/-0.05 in light-adapted state and 3.40+/-0.05 in dark-adapted state, respectively. According to Balashov's method, the fraction of all-trans-bR was assayed as the pH decreased. All these results indicated that the purple-to-blue transition of light-adapted bacteriorhodopsin was accompanied by an all-trans to 13-cis retinal isomerization at acidic pH.


Metal-phenolic network coated cellulose foams for solar-driven clean water production.
Solar-driven water steam generation is a promising strategy for seawater desalination and wastewater purification. However, oil contaminants commonly exist in real water resources, which drives us to design and fabricate photothermal materials with high efficient water steam generation and outstanding anti-oil-fouling ability. Herein, we developed a metal-phenolic network-coated cellulose foam (Fe3+/TA@CF), which exhibits not only superb hydrophilicity and underwater lipophobicity, but also achieves high water evaporation rate of ∼1.3 kg m-2 h-1 even in oil-polluted seawater under one sun illumination. In addition, Fe3+/TA@CF is demonstrated to be both anti-oil-fouling and anti-salt-fouling, which benefits to long-term evaporation in practical utilizations. Metal ions and oil contaminants in the condensed water vapor are almost eliminated after purification. We believe that this low-cost, biodegradable Fe3+/TA@CF paves a way for rationally designing and fabricating high-performance evaporator for oil contaminated water purification.


Suppression of renin secretion in the rat kidney by a nonvascular alpha-adrenergic mechanism.
We studied the effect of alpha-adrenergic stimulation, using phenylephrine, on basal and isoproterenol-provoked renin secretion in the isolated perfused rat kidney. Infusion of phenylephrine increased renal perfusion pressure and prevented the response in renin secretion to isoproterenol. No suppression of basal secretion was observed. Renal vasoconstriction was abolished, and the response in renin secretion to isoproterenol was restored by alpha-adrenoceptor blockade with phenoxybenzamine. In contrast, when renal vasoconstriction was prevented by dihydralazine, suppression of renin release by phenylephrine still occurred. These observations support an inhibitory effect of a nonvascular alpha-adrenergic mechanism on renin release. We suggest that the alpha receptor mediating this effect is related directly to the juxtaglomerular cell.