Evaluation of the diagnostic performance of thyroid-stimulating immunoglobulin and thyrotropin receptor antibodies for Graves' disease.
To evaluate thyroid-stimulating immunoglobulin (TSI) and thyrotropin receptor antibodies (TRAb) diagnostic performance for Graves' disease (GD) and determine clinical cut-off value for diagnosing GD. Of 1369 retrospectively enrolled subjects, 1364 had a definitive diagnosis of untreated GD (GD-UT, n = 87); treated GD (GD-T, n = 206); autoimmune thyroid disease (AIT, n = 241); thyroid nodules (TN, n = 677); subacute thyroiditis (ST, n = 28); healthy subjects (HS, n = 125); other diseases with serological hyperthyroidism (n = 5) and were grouped into the following: UT-GD and control groups (AIT, TN, ST, and HS); and UT-GD and non-GD hyperthyroidism groups. Diagnostic performance of TSI and TRAb was evaluated using area under the curve (AUC) of receiver-operating characteristic (ROC) curve, and optimal clinical cut-off value was determined using maximization of Youden index. TRAb AUC and clinical cut-off value for diagnosing GD were 0.981 and 1.245 IU/L (sensitivity, 96.6%; specificity, 97.1%; positive predictive value [PPV], 71.8%; negative predictive value [NPV], 99.9%; positive likelihood ratio [PLR], 33.31; negative likelihood ratio [NLR, 0.035), respectively, for the GD-UT and control groups. Those for TSI were 0.992 and 0.467 IU/L (sensitivity 98.8%; specificity, 96.4%; PPV, 68.8%; NPV, 99.9%; PLR, 27.472; NLR, 0.011). Those for TRAb in GD-UT and non-GD hyperthyroidism groups were 0.923 and 1.78 IU/L (sensitivity, 92.0%; specificity, 89.1%; PPV, 93%; NPV, 87.5%; PLR, 8.44; NLR, 0.089), respectively. For TSI, these were 0.92 and 0.545 IU/L (sensitivity, 97.7%; specificity, 83.6%; PPV, 90.4%; NPV, 95.8%; PLR27.472, NLR, 0.011), respectively. TSI diagnostic performance for GD was excellent and had better sensitivity than TRAb.


Taurochenodeoxycholic acid mediates cAMP-PKA-CREB signaling pathway.
Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.


[Patient education for osteoarthritis].
Therapeutic education is part of the nonpharmacological management of osteoarthritis (OA) both at the medical and surgical phase. The aim of education at an early stage of OA is to change patients' lifestyle, especially the regular practice of physical activity and weight reduction. When a surgical option is considered, the aim of education is to hasten patient recovery, improve autonomy after surgery, facilitate the return home and reduce the rate of transfer to a rehabilitation unit. Like other nonpharmacological treatment, therapeutic education implementation seems insufficient for OA management. One way to improve therapeutic education in the management of OA could be to propose dedicated continuing medical education programs supported by specific economic sources for health care professionals.


Development of an outcome measure to document pain relief for home hospice patients: a collaboration between nursing education and practice.
In the spring of 1997, an Eastern Michigan University nursing educator, a master's nursing student, and a hospice clinical nursing director collaborated to develop a pain outcome instrument as a part of the student's clinical practicum. The instrument was designed to describe and measure pain control of home hospice patients in preparation for fall accreditation of a home hospice program by the Joint Commission on Accreditation of Healthcare Organizations. A chart audit of all on-call communications (n = 63 charts) by the educator and student supported the organization's need to improve patients' pain control. The collaborators reviewed the pain instrument literature, developed measurement instruments, and presented information to nurses at staff meetings for input and instrument revisions. A pilot study of the Home Hospice Patient Pain Assessment Instrument (HHPPAI) was conducted, the instrument was revised, and a second pilot was performed (n = 51 pain episodes). A description of those findings is presented. Further research needs to be conducted to examine instrument reliability and validity. The use of a pain outcome instrument, such as the HHPPAI, can improve patients' pain control and, therefore, promote their quality of life.


Exposures of aquatic organisms to the organophosphorus insecticide, chlorpyrifos resulting from use in the United States.
Concentrations of CPY in surface waters are an integral determinant of risk to aquatic organisms. CPY has been measured in surface waters of the U.S. in several environmental monitoring programs and these data were evaluated to characterize concentrations, in relation to major areas of use and changes to the label since 2001, particularly the removal of domestic uses. Frequencies of detection and 95th centile concentrations of CPY decreased more than fivefold between 1992 and 2010. Detections in 1992-2001 ranged from 10.2 to 53%, while 2002-2010 detections ranged from 7 to 11%. The 95th centile concentrations ranged from 0.007 to 0.056 j.lg L -I in 1992-2001 and 0.006-0.008 j.lg L -I in 2002-2010.The greatest frequency of detections occurred in samples from undeveloped and agricultural land-use classes. Samples from urban and mixed land-use classes had the smallest frequency of detections and 95th centile concentrations, consistent with the cessation of most homeowner uses in 2001. The active metabolite of CPY, CPYO, was not detected frequently or in large concentrations. In 10,375 analyses from several sampling programs conducted between 1999 and 2012, only 25 detections (0.24% of samples) of CPYO were reported and estimated concentrations were less than the LOQ.Although the monitoring data on CPY provide relevant insight in quantifying the range of concentrations in surface waters, few monitoring programs have sampled at a frequency sufficient to quantify the time-series pattern of exposure. Therefore,numerical simulations were used to characterize concentrations of CPY in water and sediment for three representative high exposure environments in the U.S. Thefate of CPY in the environment is dependent on a number of dissipation and degradation processes. In terms of surface waters, fate in soils is a major driver of the potential for runoff into surface waters and results from a number of dissipation studies in the laboratory were characterized. Aerobic degradation of CPY exhibits hi-phasic behavior in some soils; initial rates of degradation are greater than overal rates by factors of up to threefold. Along with fate in water, these data were considered in selecting parameters for the modeling concentrations in surface waters. An assessment of vulnerability to runoff was conducted to characterize the potential for CPY to be transported beyond a treated field in runoff water and eroded sediment across the conterminous U.S. A sensitivity analysis was performed on use practices of CPY to determine conditions that resulted in the highest potential runoff of CPY to aquatic systems to narrow the application practices and geographical areas of the country for selecting watersheds for detailed modeling. The selected focus-watersheds were Dry Creek in Georgia (production of pecans), Cedar Creekin Michigan (cherries), and Orestimba Creek in California (intensive agricultural uses). These watersheds provided realistic but reasonable worst-case predictions of concentrations of CPY in water and sediment.Estimated concentrations of CPY in water for the three watersheds were in general agreement with ambient monitoring data from 2002 to 20 I 0 in the datasets from US Geological Survey (USGS), California Department of Pesticide Regulation(CDPR), and Washington State Department of Ecology (WDOE). Maximum daily concentrations predicted for the watershed in California, Georgia, and Michigan were 3.2, 0.04 I, and 0.073 Jlg L -I, respectively, with the 28-d aerobic soil metabolism half-life and 4.5, 0.042, and 0. I 22 Jlg L - 1, respectively, with the 96-d soil halflife.These estimated values compared favorably with maximum concentrations measured in surface water, which ranged from 0.33 to 3.96 Jlg L -1• For sediments,the maximum daily concentrations predicted for the watersheds in California,Georgia, and Michigan were I 1.2, 0.077, and 0.058 Jlg kg-1, respectively, with the 28-d half-life and 22.8, 0.080, and 0.087 Jlg kg-1, respectively, with the 96-d soil half-life. CYP was detected in 12 samples (I 0%) out of 123 sample analyses that existed in the USGS, CDPR, and WDOE databases. The concentrations reported in these detections were from <2.0, up to 19 Jlg kg- 1, with the exception of one value reported at 58.6 Jlg kg- 1• Again, the modeled values compared favorably with these measured values. Duration and recovery intervals between toxicity threshold concentrations of 0.1 and 1.0 Jlg L - 1 were also computed. Based on modeling with the half-life of 28 d, no exceedance events were identified in the focus watersheds in Georgia or Michigan. Using the half-life of 96 d, only three events of 1-d duration only were identified in the Michigan focus-watershed. Frequency of exceedancc was greater in the California focus watershed, though the median duration was only I -d.


17q12-21 and asthma: interactions with early-life environmental exposures.
17q12-21 polymorphisms are associated with asthma presence and severity across different populations. To extensively investigate the genes in this region among Croatian schoolchildren in a case-control study, taking account of early-life environmental exposures. We included 423 children with asthma and 414 controls aged 5 to 18 years. Fifty-one haplotype tagging single-nucleotide polymorphisms (SNPs) were genotyped (GSDMA, GSDMB, ORMDL3, IKZF3, ZPBP2, and TOP2). Data on exposure to smoking and furry pet ownership were collected using a validated questionnaire. Information on severe asthma exacerbations with hospital admission were retrieved from hospital notes. All patients underwent spirometry. We found 2 SNPs (1 novel rs9635726 in IKZF3) to be associated with asthma. Among children with asthma, 4 SNPs (in ZPBP2, GSDMB, and GSDMA) were associated with hospital admissions and 8 SNPs with lung function. One SNP (rs9635726) remained significantly associated with a predicted forced expiratory volume in 1 second after false discovery rate correction. Nine markers across 5 genes showed interaction with early-life environmental tobacco smoke (ETS) exposure in relation to asthma and 2 with furry pet ownership. Among children with asthma, we observed significant interactions between early-life ETS exposure and 3 SNPs for lung function and among early-life ETS exposure, 3 SNPs (in ORMDL3 and GSDMA), and hospital admission with asthma exacerbation. Three SNPs (in ORMDL3) interacted with current furry pet ownership in relation to hospital admissions for asthma exacerbation. Our results indicate that several genes in the 17q12-21 region may be associated with asthma. This study confirms that environmental exposures may need to be included into the genetic association studies.


The prevalence of human papillomavirus in cervical lesions with koilocytosis and/or CIN I.
Thirty-one patients with koilocytosis and/or concomitant CIN I were analysed for the presence of HPV types 11, 16 and 18 by in situ hybridization and Southern blot analysis. The prevalence of HPV was 48% and 55%, respectively, when measured by the two methods and among the HPV positive, HPV 11 and 16 were present in 47% and 60%, respectively, whereas HPV 18 was not found.


Merocyanine 540, a fluorescent probe sensitive to lipid packing.
Binding of the lipophilic probe merocyanine 540 to artificial bilayers was assessed by measuring the enhancement of fluorescence which results when dye enters the hydrophobic environment of the membrane. Titration of a constant amount of dye with increasing amounts of vesicles revealed that much more dye binds to multilamellar and 1000-A unilamellar vesicles which are in the fluid-phase state than to comparable vesicles which are in the gel-phase state. Incorporation of cholesterol into fluid-phase vesicles at levels of greater than 20 mol% reduced dye binding, whereas cholesterol had no effect at any concentration when incorporated into gel-phase vesicles. Sonicated 200--300-A unilamellar gel-phase vesicles, which because of their reduced radius of curvature resemble fluid-phase bilayers in their more widely spaced exterior leaflet lipids, bound more dye than 1000-A unilamellar gel-phase vesicles constructed from the same lipid. These results suggest that merocyanine 540 is able to sense the degree of lipid packing of bilayers and inserts preferentially into bilayers whose lipids are more widely spaced.


Identification and primary application of hybridomas cell secreting monoclonal antibodies against mink (Neovison vison) interferon-gamma.
Due to their susceptibility to several human viruses, the mink has been proposed as potential animal models for the study of human viral infections. However, there are no specific monoclonal antibody (mAbs) currently available for the detection of mink-specific interferon-gamma (miIFN-γ). The BALB/c mice were immunized intraperitoneally with purified recombinant miIFN-γ protein. The splenocytes were obtained and fused with murine myeloma cells. Five of 24 hybridoma clones were obtained to produce mAbs steadily with the strongest affinity to recombinant miIFN-γ protein. The isotype of the 31A, 31B and 31G were lgG 2b. The isotype of 44 and 46 were lgG 2a and 1. All five mAbs were κ light chains. Western blotting and indirect ELISA method showed that 5 mAbs were positive to miIFN-γ. Immunofluorescence showed that 2 mAbs (44 and 46) had a positive reaction to miIFN-γ. The hybridoma clone 46 had the highest sensitivity for the detection of miIFN-γ. Most importantly, our primary sandwich ELISA system (mAbs 46 and polyclonal antiserum) detected endogenous IFN-γ in mink lymphocytes infected with canine distemper virus (CDV). We have thus developed a novel mAbs could recognize miIFN-γ, and have demonstrated the first ELISA-based measurement of IFN-γ in lymphocyte of the mink.


Case-control study on association of peroxisome proliferator-activated receptor-δ and SNP-SNP interactions with essential hypertension in Chinese Han population.
The aim of this study was to investigate the association of peroxisome proliferator-activated receptor-δ (PPAR-δ) and additional SNP-SNP interaction with essential hypertension (EH) in Chinese Han population. A total of 1248 subjects (625 males, 623 females), including 620 EH patients and 628 normotension subjects, were included in the study. The mean age was 51.2 ± 15.1 years old. Logistic regression model was used to examine the association between four SNP and EH; odds ratio (OR) and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze SNP-SNP interaction. EH risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with TT (TC + CC versus TT, adjusted OR (95%CI) = 0.61 (0.49-0.78)). In addition, we also found a significant association between rs9794 and EH; EH risk was also significantly lower in carriers of G allele of the rs9794 polymorphism than those with CC (CG + GG versus CC, adjusted OR (95%CI) = 0.65 (0.53-0.83)). We also found a potential SNP-SNP interaction between rs2016520 and rs9794; subjects with TC or CC of rs2016520 and CG or GG of rs9794 genotype have the lowest EH risk, compared to subjects with TT of rs2016520 and CC of rs9794 genotype; OR (95%CI) was 0.32 (0.23-0.62) after covariate adjustment. Our results support an important association between rs2016520 and rs9794 minor allele of PPAR-δ and decreased risk of EH and additional interaction between rs2016520 and rs9794.


Association of neighbourhood social and physical attributes with depression in older adults in Hong Kong: a multilevel analysis.
Previous studies investigating the independent effects of neighbourhood-level factors on depression are rare within the Asian context, especially in the elderly population. Data for 29 099 older adults aged 65 years or above who have received health examinations at elderly health centres in Hong Kong in 2008-2011 were analysed. Using multilevel regression modelling, the cross-sectional associations of neighbourhood social attributes (neighbourhood poverty, ethnic minority, residential stability and elderly concentration) and physical (built) attributes (recreational services and walkability) with depression outcomes (depressive symptoms and depression) after adjusting for individual-level characteristics were investigated. Gender interaction effects were also examined. Neighbourhood poverty was associated with both depressive symptoms and depression in the elderly. Neighbourhood elderly concentration, recreational services and walkability were associated with fewer depressive symptoms. The association between neighbourhood poverty and elderly depressive symptoms was found in women only and not in men. Policies aimed at reducing neighbourhood poverty, increasing access to recreational services and enhancing walkability might be effective strategies to prevent depression in older adults in the urban settings.


Polarographic determinations of nimetrazepam in serum and whole blood.
In the elaborated polarograhic technique, serum has been shown the best biological material for the direct determination of nimetazepam.]


Employment of vasopressin receptor antagonists in management of hyponatraemia and volume overload in some clinical conditions.
Hyponatraemia, the most common electrolyte imbalance occurring in hospitalized subjects, is usually classified as hypovolaemic, euvolaemic or hypervolaemic. Hyponatraemia is a predictor of death among subjects with chronic heart failure and cirrhosis. The inappropriate secretion of the antidiuretic hormone (AVP) seems to be of pivotal importance in the decline of serum sodium concentration in these clinical conditions. The objective of this review was to summarize recent progress in management of hyponatraemia in SIADH, cirrhosis and heart failure. Literature searches were conducted on the topics of hyponatraemia and vasopressin receptor antagonists, using PubMed, pharmaceutical company websites and news reports. The information was evaluated for relevance and quality, critically assessed and summarized. The initial treatment of severe hyponatraemia is directed towards the prevention or management of neurological manifestations and consists of an intravenous infusion of hypertonic saline. Fluid restriction is indicated in oedematous states. Diuretics alone or in combination with other specific drugs remain the main strategy in the management of volume overload in heart failure. In resistant cases, ultrafiltration can lead to effective removal of isotonic fluid preventing new episodes of decompensation; however, aquapheresis is associated with increased costs and other limits. In several trials, the efficacy of vasopressin receptor antagonists in euvolaemic patients (inappropriate antidiuretic hormone secretion) or in hypervolaemic hyponatraemia (chronic heart failure, cirrhosis) has been evaluated. It was found that vaptans, which promote aquaresis, were superior to a placebo in raising and maintaining serum sodium concentrations in these subjects. Combined with conventional therapy, vasopressin receptor antagonists (AVP-R antagonists) are able to increase the excretion of electrolyte-free water and the sodium concentration. Further studies are needed to assess efficacious outcomes of aquaresis compared with aquapheresis and with conventional therapy.


Swine cysticercosis and associated risk factors in non-technified pig breeding in semi-arid region of Sergipe state, Brazil.
The aim of this study was to determine the frequency of Taenia solium anti-metacestode antibodies in slaughtered pigs in a semi-arid region of the "Alto Sertão" of Sergipe state, Brazil, and verify the risk factors associated with swine cysticercosis. For this, 230 samples of swine blood from two slaughterhouses were collected and analyzed by indirect ELISA. The pigs came from five non-technical properties in the semi-arid region of the Alto Sertão of Sergipe state. Searches for cysts in the skeletal muscles of the pigs were performed during slaughter. In addition, an epidemiological questionnaire was applied to the pigs' original properties to determine risk factors. Besides that, the official health services database was evaluated for confirmed cases of neurocysticercosis and taeniasis in humans in the last 5 years, living in the studied region. Seropositivity in pigs was 12.6%, with no significant difference between males and females. No cysts were found in the carcasses of the slaughtered pigs. A positive association was found for properties that discharge domestic sewage into the environment, in river or streams, increasing the risk of positivity by 5.72 times. When analyzing the database of official agencies, there were no records of cases of neurocysticercosis or taeniasis in the resident population in the last 5 years. However, there were frequent cases of idiopathic epilepsy. The results demonstrate that study area is endemic for swine cysticercosis and serves as a warning of the possibility of the occurrence of the taeniasis-cysticercosis complex.


Previous help sought by patients presenting to mental health services in Kumasi, Ghana.
There are four services providing mental health care to the people of Kumasi, Ghana. This study aimed to identify previous help sought by patients presenting to the services for an initial assessment. New patients presenting to each of the four services were asked about distance travelled, previous help sought and time since symptoms of illness started. Staff also recorded basic demographic details and clinical diagnoses. Of the 322 patients presenting to the four sites,only 6% had seen a traditional healer whereas 14% had seen a pastor before presentation. There was a greater delay in presenting to that service if the patient had seen a traditional healer or pastor. Many patients had previously used one of the other mental health units in Kumasi. It is possible that fewer patients with mental health problems present to traditional healers in modern, urban Africa compared to rural areas. More patients consult with pastors than traditional healers and liaison with these groups may improve mental health care. It is important to maintain liaison between the four services as patients presenting to one clinic may have presented previously to another local clinic.


Electronic monitoring of offenders: an ethical review.
This paper considers electronic monitoring (EM) a promising alternative to imprisonment as a criminal sanction for a series of criminal offenses. However, little has been said about EM from an ethical perspective. To evaluate EM from an ethical perspective, six initial ethical challenges are addressed and discussed. It is argued that since EM is developing as a technology and a punitive means, it is urgent to discuss its ethical implications and incorporate moral values into its design and development.


[Effect of sodium transport inhibitors on maximal glucose reabsorption and cardiotrast excretion by the kidneys].
Effects of intrarenal infusion of potassium cyanide and strophanthinum were studied in acute experiments on dogs. The decrease fractional of reabsorption of sodium to 80--82 per cent did not affect renal reabsorption of glucose and tubular excretion of cardiotrast. Combined infusion of strophanthinum and cyanide decreased the fractional sodium reabsorption to 65.6 per cent. During this period maximal reabsorption of glucose reduced but not so the tubular excretion of cardiotrast.


Malignant Lesions Mimicking Endodontic Pathoses Lesion: A Systematic Review.
Malignant nonendodontic periapical lesions represent a rare diagnosis, in which few case have been reported about this condition. Due to the low occurrence and little exploration of this subject, serious errors of diagnosis are observed in the oral medicine services. In this sense, the purpose of the present review was to integrate the information on the record published on malignant lesions that mimic endodontic pathoses into a comprehensive analysis of their clinical, radiologic, and histopathologic features. An online search was made in March 2020 in the following databases: Pubmed, Web of Science, and Scopus. Eligibility criteria included publications having enough clinical, radiologic, and histopathologic information to confirm the diagnosis. Data were assessed descriptively. Forty-nine publications from 16 countries comprising 60 cases were included. There is a nearly equal occurrence rate between males and females (male/female ratio is 49.15%/50.84%) with a mean age of 46.56 years. The lesions were more prevalent in the posterior mandibles (40.69%), and, radiographically, they were unilocular radiolucent. Histopathologic analysis showed metastasis (26.67%) as the most prevalent lesion followed by salivary gland malignant disease (25%). The present systematic review revealed several histologic types of malignant periapical lesions that could be mimicking endodontic pathoses. Because these lesions usually do not show clinical or radiologic features of malignant alteration, clinicians should consider these hypotheses in their routine.


3D printing combined with biopredictive dissolution and PBPK/PD modeling optimization and personalization of pharmacotherapy: Are we there yet?
Precision medicine requires selecting the appropriate dosage regimen for a patient using the right drug, at the right time. Model-Informed Precision Dosing (MIPD) is a concept suggesting utilization of model-based prediction methods for optimizing the treatment benefit-harm balance, based on individual characteristics of the patient, disease, treatment method, and other factors. Here, we discuss a theoretical workflow comprising several elements, beginning from the physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models, through 3D printed tablets with the model proposed dose, information range and flow, and the patient themselves. We also describe each of these elements, and the connection between them, highlighting challenges and potential obstacles.


Vasopeptidase inhibitor ilepatril (AVE7688) prevents obesity- and diabetes-induced neuropathy in C57Bl/6J mice.
Previously we demonstrated that inhibition of neutral endopeptidase (NEP), a protease that degrades vaso- and neuro-active peptides, and angiotensin converting enzyme (ACE) with a vasopeptidase inhibitor improves vascular and neural function in diabetic rat models. The purpose of this study was to determine whether inhibition of NEP and ACE or deletion of NEP provides protection from nerve impairment caused by diabetes or diet induced obesity (DIO). To determine the role of NEP and ACE inhibition in neuropathy related to insulin-deficient diabetes or DIO we used C57Bl/6J mice treated with AVE7688, a vasopeptidase inhibitor, or NEP deficient (-/-) mice. Mice at 12 weeks of age were fed a high fat diet for 12 weeks or were diabetic for duration of 12 weeks following a single injection of high dose streptozotocin. Both a prevention and intervention protocol was used for AVE7688 treatment. Glucose utilization was impaired in DIO C57Bl/6J and NEP -/- mice. However, treating DIO C57Bl/6J or NEP -/- mice with AVE7688 improved glucose tolerance. Thermal hypoalgesia and nerve conduction slowing were present in both streptozotocin-diabetic and DIO C57Bl/6J mice but not in AVE7688 treated C57Bl/6J mice or NEP -/- mice exposed to either streptozotocin-induced diabetes or a high fat diet. Intraepidermal nerve fiber (IENF) profiles were decreased in the hindpaw of C57Bl/6J diabetic or DIO mice and this improved when the mice were treated with AVE7688. IENF profiles were not decreased in diabetic or DIO NEP (-/-) mice. These studies suggest that NEP plays a role in regulating nerve function in insulin-deficient diabetes and DIO.


Informed Consent: Does Anyone Really Understand What Is Contained In The Medical Record?
Despite efforts to provide standard definitions of terms such as "medical record", "computer-based patient record", "electronic medical record" and "electronic health record", the terms are still used interchangeably. Initiatives like data and information governance, research biorepositories, and learning health systems require availability and reuse of data, as well as common understandings of the scope for specific purposes. Lacking widely shared definitions, utilization of the afore-mentioned terms in research informed consent documents calls to question whether all participants in the research process - patients, information technology and regulatory staff, and the investigative team - fully understand what data and information they are asking to obtain and agreeing to share. This descriptive study explored the terminology used in research informed consent documents when describing patient data and information, asking the question "Does the use of the term "medical record" in the context of a research informed consent document accurately represent the scope of the data involved?" Informed consent document templates found on 17 Institutional Review Board (IRB) websites with Clinical and Translational Science Awards (CTSA) were searched for terms that appeared to be describing the data resources to be accessed. The National Library of Medicine's (NLM) Terminology Services was searched for definitions provided by key standards groups that deposit terminologies with the NLM. The results suggest research consent documents are using outdated terms to describe patient information, health care terminology systems need to consider the context of research for use cases, and that there is significant work to be done to assure the HIPAA Omnibus Rule is applied to contemporary activities such as biorepositories and learning health systems. "Medical record", a term used extensively in research informed consent documents, is ambiguous and does not serve us well in the context of contemporary information management and governance.


Contribution of various host factors to resistance to experimentally induced bacterial endotoxemia in calves.
The reactions of 15 calves to IV administered bacterial lipopolysaccharide was investigated and was correlated with the capacity of 2 host defense mechanisms. The calves had a wide range of changes in clinical response, total WBC count, plasma lactate dehydrogenase (LD) activity, reaction to intradermally inoculated lipid A, and rectal temperature response. The early rectal temperature response of an individual calf was correlated with plasma LD activity, indicating a relationship between cell damage and fever. The concentration of antibody against lipid A at the time of lipopolysaccharide inoculation was negatively correlated with the rectal temperature changes recorded during endotoxemia, suggesting a protective ability of antibody. The capacity of a plasma inhibitor of lipopolysaccharide-mediated clotting of limulus amebocyte lysate was correlated with increases in plasma LD activity. Therefore, antibody to lipid A probably is involved in protection of cattle during endotoxemia, but the plasma lipopolysaccharide inhibitor actually may potentiate lipopolysaccharide toxicity.


A new murine osteoblastic cell line immortalized with the SV40 large T antigen.
The murine preosteoblastic cell line, MC3T3-E1, is widely used to study bone formation and differentiation in vitro. However, this cell line is unstable in culture. The current study was designed to establish a stable osteoblastic cell line. A mammalian expression vector carrying the SV 40 large T antigen was introduced into a primary culture of cells isolated from the calvaria of newborn mice. Among isolated cell lines, the MN16 cell line was selected for further characterization. The MN16 cell line was cultured for 28 days, and compared with the MC3T3-E1 cell line with or without induction. The expression of bone-related genes was examined using the real-time RT-PCR technique. Alizarin red and von Kossa staining were used to detect mineralization of nodules in the cultures. The cell line showed the characteristics of osteoblastic cells in term of gene expression patterns of various molecular markers and calcium deposition in the cell layer after induction. Furthermore, the MN16 cells showed strong adhesion to the basic domain of collagen, a result that is specific for bone-derived cells. The MN16 cell line was found to be stably differentiated into bone formation cells in vitro and should be useful for studying bone biology.


Sleep in an At Risk Adolescent Group: A Qualitative Exploration of the Perspectives, Experiences and Needs of Youth Who Have Been Excluded From Mainstream Education.
The sleep needs, experiences and viewpoints were explored for UK adolescents who have been excluded from mainstream education. Qualitative data was gathered through interviews with 9 participants, aged 11-15 years, who also completed questionnaires. The participants had symptoms of inadequate sleep, poor sleep hygiene behaviours and were not getting the recommended amount of sleep on school nights. Participants described sleep patterns involving often staying up late and having different sleep timing on weekends than weekdays and having difficulties with their sleep. Use of technology and the relevance of family were identified as important and associated with facilitating and hindering factors for sleep. Participants communicated that they lack control over aspects of their sleep and their lives. The experiences and views of the participants can inform professionals' understanding of how to collaborate with adolescents to improve their sleep and highlight that continued development of sleep education programmes is timely.


Self-Participation Experiences among Well-Adapted Hemodialysis Patients.
A successful self-participation experience empowers patients to adapt to living with hemodialysis. However, few studies regarding the subjective experiences of such patient participation have been conducted. This study's purpose was to describe hemodialysis patients' perspectives on integrating hemodialysis into a new life regarding self-participation experience. A qualitative study using the grounded theory method was applied. Thirty-two well-adaptive hemodialysis Taiwanese patients attended in-depth interviews. "Integrating hemodialysis into a new life journey" was identified as the core category guiding the entire self-participation experience of hemodialysis patients. The three antecedent themes were "Sense of worthlessness", "Life is still worth living", and "Friendly and joyful atmosphere of the hemodialysis room". Once the patients went through the three antecedent themes, they gradually began making efforts to participate more fully in their hemodialysis. Within this participation experience, the hemodialysis patients exhibited these four interactive themes: "Overcoming one's predicament", "Integrating self-care skills into my life", "Resuming previous roles and tasks", and "Adapting to independent living". Finally, most adaptive patients master the hemodialysis life. Encouraging patients to discover that their life is worth living and providing a friendly and joyful atmosphere in hemodialysis units are the keys to facilitating patients' self-participation more fully.


Urinary schistosomiasis in school aged children of two rural endemic communities in Edo State, Nigeria.
Urinary schistosomiasis is endemic in many rural communities of Nigeria and school aged children are mostly affected. A cross-sectional study was carried out to assess the prevalence and intensity of urinary schistosomiasis infection among 251 school aged children in two communities of Ovia South West LGA of Edo State, Nigeria, as well as their knowledge on the control/elimination measures. Urine samples were collected and examined by microscopy using filtration technique. In addition, a questionnaire survey was conducted among school-aged children and health care providers, probing their knowledge, attitude and practices on on-going control activities. The prevalence of urinary schistosomiasis among the school-aged children was 65.3%. The prevalence was generally higher among females (68.8%) and children in the age groups 10-14 (69.9%). The intensity of infection ranged from 1 to 5044 (mean=449.8) eggs/10ml of urine with a higher proportion having heavy infections (76.8%, P<0.05). Water contact was attested by 123 (49.0%) of the children; of these 123, 74 (60.1%) were infected. The children's knowledge on urinary schistosomiasis was deficient. The high prevalences reported in these communities require integrated approach to control which essentially should incorporate the provision of safe water supply and sanitary facilities, and health education in addition to the annual mass praziquantel distribution, to reduce transmission.


Assessment of endoscopic aspiration cytology and endoscopic retrograde cholangio-pancreatography in patients with cancer of the hepato-biliary tract. Part II.
Aspiration cytology and ERCP were evaluated in 66 patients with cancer of the hepato-biliary tract. Cytology was diagnostic in 100% of ampullary cancer, 83% of cancer of extrahepatic bile duct, 0% of cancer of intrahepatic bile duct, 25% of cancer of gall bladder and 0% of cancer of liver. ERCP was diagnostic in 65% of ampullary cancer, 90% of cancer of extrahepatic bile duct, 100% of cancer of intrahepatic bile duct, 25% of cancer of gall bladder and 25% of cancer of liver. Endoscopic findings was diagnostic in 77% of cancer of ampullary region. By combining these approaches, a diagnostic result was obtained in 100% of ampullary cancer, 96.5% of cancer of extrahepatic bile duct, 100% of cancer of intrahepatic bile duct, 50% of cancer of gall bladder and 25% of cancer of liver. It is concluded that the combined diagnostic approach has enhanced the diagnostic accuracy of malignant lesions of the hepato-biliary tract and that it has not yet led to an improvement in resectability and mortality.


Influence of Lactic Acid on Cell Cycle Progressions in Lactobacillus bulgaricus During Batch Culture.
Lactic acid has been proved to inhibit the proliferation of lactic acid bacteria in the fermentation process. To shed light on the cell cycle alterations in acidic conditions, the cell division of Lactobacillus bulgaricus sp1.1 in batch culture was analyzed directly by implementing of the intracellular fluorescent tracking assay in different pH adjusted by lactic acid. Cell proliferation and cell division were investigated to be negatively controlled by the decrease of pH, and pH 4.1 was the critical condition of downregulating cell division but retains cell culturability. The cell area and cell length in pH 4.1 were examined by using fluorescent labeling, and they reduced to about 29.18-34.89% and 32.67-40% of cells cultured in the unacidified medium, respectively. The DNA replication initiation was undergoing prompted by the low extent of DNA condensation and higher expression of the dnaA gene in this critical pH. The results indicated that the cell cycle progressions of Lactobacillus bulgaricus sp1.1 in acidic conditions were arrested at intracellular biomass accumulation and cell division stage. These findings provide fundamental insight into cell cycle control of the acidic environment in Lactobacillus bulgaricus sp1.1.


miR-1271 inhibits migration, invasion and epithelial-mesenchymal transition by targeting ZEB1 and TWIST1 in pancreatic cancer cells.
Pancreatic cancer (PC) remains one of the most lethal types of cancer in adults. The purpose of this study was to determine the role of miR-1271 in regulation of epithelial mesenchymal transition (EMT) and metastasis of pancreatic cancer cells. miR-1271 was identified to be significantly down-regulated in PC tissues by miRNA array. Also, an increase of EMT-regulators ZEB1 and TWIST1 expression level is accompanied by a decrease of miR-1271. We showed that expression of miR-1271 was significantly down-regulated in PC tissues as compared with that in normal tissues. In addition, our results showed that miR-1271 expression levels were decreased while ZEB1 and TWIST1 expression levels were increased in detected PC cell lines. Moreover, ectopic expression of miR-1271 suppressed and antagomiR-1271 promoted proliferation, migration, and invasion in SW1990 and PANC-1 cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-1271 inhibited expression of ZEB1 and TWIST1, which are master regulators of tumor metastasis. Our study first indicates that miR-1271 functions as a suppressor in regulating of pancreatic cancer EMT by targeting ZEB1 and TWIST1, and it promise as a therapeutic target and prognostic marker for metastatic pancreatic cancer.


Lipid effects of smoking.
Cigarette smoking is believed to cause harmful cardiovascular and atherogenic effects resulting from changes in lipid metabolism. Intravenous nicotine and smoking raise plasma free fatty acid (FFA) levels through enhanced lipolysis resulting from sympathoadrenal stimulation. The study reported here investigated FFA-stimulated myocardial oxygen consumption (MVO2) in intact dogs. It was found that about half of the nicotine-induced rise in MVO2 resulted from metabolic stimulation by high concentrations of FFA, and the remainder was a result of enhanced mechanical activity of the heart directly produced by nicotine. In intact dogs, the increase in myocardial oxygen requirement resulting from excess myocardial FFA uptake also increased the severity of myocardial ischemic injury after acute coronary occlusion. Human studies with men who had smoked for more than 10 years showed that smokers had lower plasma high-density lipoprotein cholesterol fractions 2 and 3. High-density lipoprotein fraction 2 is reported to be antiatherogenic. Thus smoking appears to have at least two lipid effects that may promote coronary heart disease and atherosclerosis: increased plasma FFA and decreased plasma high-density lipoprotein cholesterol fraction 2.


ConTemplate Suggests Possible Alternative Conformations for a Query Protein of Known Structure.
Protein function involves conformational changes, but often, for a given protein, only some of these conformations are known. The missing conformations could be predicted using the wealth of data in the PDB. Most PDB proteins have multiple structures, and proteins sharing one similar conformation often share others as well. The ConTemplate web server (http://bental.tau.ac.il/contemplate) exploits these observations to suggest conformations for a query protein with at least one known conformation (or model thereof). We demonstrate ConTemplate on a ribose-binding protein that undergoes significant conformational changes upon substrate binding. Querying ConTemplate with the ligand-free (or bound) structure of the protein produces the ligand-bound (or free) conformation with a root-mean-square deviation of 1.7 Å (or 2.2 Å); the models are derived from conformations of other sugar-binding proteins, sharing approximately 30% sequence identity with the query. The calculation also suggests intermediate conformations and a pathway between the bound and free conformations.


Extreme sensitivity of enveloped viruses, including herpes simplex, to long-chain unsaturated monoglycerides and alcohols.
Unsaturated monoglycerides and alcohols of chain lengths of 16 or 18 carbons were found to be extremely potent inactivators of two enveloped viruses, herpes simplex virus type 2 and bacteriophage phi6. The lipid-containing bacteriophage PM2 was also inactivated by some of these amphiphilic molecules. Treatment of herpes simplex virus type 2 with these compounds at concentrations as low as 0.2 muM reduced virus survival to 50% in 30 min, making these agents the most potent inactivators of herpes simplex viruses discovered that are not cytotoxic to mammalian cells. Detailed characterizations of the effects of unsaturated monoglycerides and alcohols on bacteriophages phi6 and PM2 showed that the inactivated phi6 virion remained nearly intact but that PM2 was almost completely disrupted by the inactivating treatment. Some of the compounds inactivate the viruses even at low temperature (0 degrees C). Excess amounts of diglycerides and phospholipids interfere with the inactivating abilities of some of the unsaturated monoglycerides and alcohols against phi6 and PM2. Our findings suggest that the unsaturated monoglycerides and some of the unsaturated alcohols should be further studied as potential antiviral agents, particularly for application to herpesvirus-infected areas of the skin and accessible epithelium.


Asymptomatic haematuria and proteinuria: renal pathology and clinical outcome in 54 children.
In a mass screening programme, 54 children with haematuria and proteinuria were detected and evaluated by clinical findings and renal histology. IgA glomerulonephritis (GN) occurred in 29 patients, diffuse mesangial proliferative GN (DPGN) in 16, membranous GN (MGN) in 4, membranoproliferative GN (MPGN) in 3, and focal segmental glomerular sclerosis (FSGS) was seen in 2. Of the 35 children with proteinuria less than or equal to 1 g/m2 per day, 21 with IgA GN and 14 with DPGN had only mild to moderate glomerular changes. None of these children had developed renal impairment after a mean period of 6.5 years (range 5-10 years). On the other hand, 8 children with IgA GN, 2 with DPGN, 4 with MGN, 3 with MPGN, and 2 with FSGS had proteinuria that exceeded 1 g/m2 per day. The biopsy specimens from these children showed moderate to severe glomerular changes, and 7 of these children had hypertension or renal impairment during the period of evaluation. This study suggests that a poor outcome correlates with the level of proteinuria and the severity of renal pathology in children with haematuria and proteinuria.


Analysis of the structure of magnetic fields that induced inhibition of stimulated neurite outgrowth.
The important experiments showing nonlinear amplitude dependences of the neurite outgrowth in pheochromocytoma nerve cells due to ELF magnetic field exposure had been carried out in a nonuniform ac magnetic field. The nonuniformity entailed larger than expected variances in magnetic field magnitudes associated with specific levels of biological effects, thereby evoking a question about validity of the interpretations formulated for the case of a uniform field. In this work, we calculate the relative value of nonuniformity and deviations in ac magnetic field. It is shown that these factors do not affect the main conclusion in the original papers about the form of the amplitude dependence of the observed biological effect.


CAGS and ACS Evidence Based Reviews in Surgery. 34: effects of ß-blockers in patients undergoing noncardiac surgery.
Do ß-blockers have an effect on the 30-day risk of major cardiovascular events in patients with or at risk of atherosclerotic disease undergoing noncardiac surgery? Randomized controlled trial. Multicentre trial in 190 hospitals in 23 countries. In total, 8351 patients with or at risk of atherosclerotic disease undergoing noncardiac surgery. Patients were randomly assigned by a computerized 24-hour phone service to receive extended-release metoprolol succinate 200 mg (n = 4174) or placebo (n = 4177). Treatment was started 2-4 hours before surgery and continued for 30 days. Cardiovascular death, nonfatal myocardial infarction (MI) and nonfatal cardiac arrest. Of those randomized, 8331 (99.8%) patients completed the 30-day follow-up. Fewer patients in the metoprolol group than in the placebo group had an MI (176 [4.2%] v. 239 [5.7%] patients; hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.60-0.089, p = 0.0017). However, there were more deaths in the metoprolol group than in the placebo group (129 [3.1%] v. 97 [2.3%] patients; HR 1.33, 95% CI 1.03-1.74, p = 0.0317). More patients in the metoprolol group than in the placebo group had a stroke (41 [1.0%] v. 19 [0.5%] patients; HR 2.17, 95% CI 1.26-3.74, p = 0.0053). A perioperative ß-blocker regimen results in fewer MIs but is associated with an increased risk of stroke and perioperative death in patients with or at risk for atherosclerotic disease undergoing noncardiac surgery. Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol use.


[The genetic control of cell growth and development in yeast Saccharomyces cerevisiae. Disturbed sporulation in diploids with decreased activity of the Ras/cAMP signal transduction pathway].
Seven haploid strains (four with the MAT alpha mating type and three with the MATa mating type) were selected from the Peterhof genetic collection of yeast. Previous phenotypic analysis assigned six of these strains to a physiological group of strains with a lower activity of the Ras/cAMP signal transduction pathway. The haploids were crossed, and the resulting 12 diploids showed higher glycogen accumulation, tolerance to heat shock and nitrogen starvation, and sporulation in complete media. Ten of the diploids expressed the hypersporulation phenotype (higher sporulation efficiency). The phenotypic characters of these ten diploids suggested a reduced activity of the Ras/cAMP pathway. All 12 diploids were tested for sporulation and production of two groups of asci (those with one or two spores and those with three or four spores) as dependent on culture conditions (21, 30, or 34 degrees C; standard sporulation medium or a complete medium containing potassium acetate or glycerol in place of glucose). Sporulation proved to depend on temperature and medium composition. The results are collated with the data on yeast phenotypes associated with a lower activity of the Ras/cAMP signal transduction pathway.


The influence of maternal triglyceride levels on infant birth weight in Peruvian women with pre-eclampsia.
Hypertriglyceridemia is an important pathophysiological feature of pre-eclampsia, a complication associated with retarded fetal growth. We studied the relation between third-trimester maternal triglyceride levels and infant birth weight in 113 pre-eclamptic and 150 normotensive women. Plasma triglyceride concentrations were determined using enzymatic methods. The relative risk of infant low birth weight (LBW, < 2500 g) was determined using logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). Approximately 12% of normotensive and 32% of pre-eclamptic mothers delivered LBW infants. After adjusting for maternal age, parity, pre-pregnancy adiposity and gestational age at delivery, pre-eclamptics were 2.3 times more likely to deliver a LBW infant as compared with normotensive mothers (95% CI 1.1-5.0). There was no association between plasma triglyceride level and infant birth weight. Pearson correlation coefficients for birth weight and triglyceride were r = 0.10 (p = 0.24) and r = 0.06 (p = 0.49) for normotensive and pre-eclamptic women, respectively. The OR for LBW associated with high triglyceride level (> or = 233 mg/dl) was 0.8 (95% CI 0.2-3.1) and 0.9 (95% CI 0.4-2.0) for the two groups. Triglyceride levels did not modify the pre-eclampsia and LBW association. Compared to normotensive women with low triglyceride level (< 233 mg/dl), the ORs for LBW were 1.2 (95% CI 0.4-4.0), 3.6 (95% CI 1.0-12.5) and 2.8 (95% CI 1.0-8.0) for normotensive and high triglyceride, pre-eclamptic and low triglyceride, and pre-eclamptic and high triglyceride mothers, respectively. Hypertriglyceridemia in late pregnancy, considered a maternal adaptation to maintain stable fuel distribution to the fetus, was not related to birth weight.


Stimulating effects of bovine small intestine mucosal factors on rat hepatocyte development.
A mass of pure adult rat parenchymal hepatocytes, obtained by a newly devised isolation technique, developed into organized micro-liverlike layered multicellular colonies in long-term primary cultures grown in the presence of bovine small intestine mucosal factors (SIMFs). These factors stimulated proliferation, aggregation, and orderly arrangement of the hepatocytes, and differentiation into partially functional micro-livers in vitro. SIMFs derived from other mammalian species affected rat hepatocytes in the same manner. Studies of the effects of mammalian SIMFs on hepatocytes may provide new insights into the kinetics and mechanisms of liver regeneration.


Matrix proteins of human hair as a tool for identification of individuals.
A rapid, simple, reproducible and relatively inexpensive electrophoretic technique for displaying the structural proteins of hair is described. Hairs from a large number of individuals were examined and a number of distinct differences are presented. The possibility of using these individual differences as a means of individual identification is discussed.


A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.
We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: -0.37 ± 0.15 mmol/min, mean ± SE, p < 0.01; Rd-high: LFD: 0.11 ± 0.37 vs. HFD: -0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p < 0.01) with a trend on the HFD (r = 0.60, p = 0.07), whereas there was no association with intra-abdominal fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = -0.77; p < 0.01; HFD: r = -0.71; p = 0.02). A diet very high in fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. CLINICALTRIALS. NCT00930371.


Antioxidant activity of L-carnosine, a natural histidine-containing dipeptide in crystalline lens.
Lipid peroxidation was shown to be an initiatory cause of cataract development in some cases. It has been established that injection into the vitreous body of the rabbit eye of a suspension of liposomes prepared from phospholipids containing lipid peroxidation products induces the development of posterior subcapsular cataract. Such modelling of cataract is based on a type of clouding of the crystalline lens similar to that observed in cataract resulting from diffusion of toxic lipid peroxidation products from the retina to the lens through the vitreous body on degeneration of the photoreceptors. Saturated liposomes (prepared from dipalmitoylphosphatidylcholine) did not cause clouding of the lens, which demonstrated the peroxide mechanism of the genesis of this form of cataract. Clouding of the lens was accompanied by accumulation of fluorescing lipid peroxidation products in the vitreous body, aqueous humor and the lens and also by a fall in the concentration of reduced glutathione in the lens. The ability of L-carnosine (beta-alanyl-L-histidine) to interact directly with lipid peroxidation products suggested its anticataract properties. The effect of L-carnosine on inhibiting or reversing the formation of cataract induced by the administration of lipid peroxidation products was discovered. This phenomenon appeared to be related with normalization of the peroxide metabolism parameters in the crystalline lens. In view of the data, an aqueous solution of L-carnosine is physiologically acceptable in effective nonsurgical treatment of cataracts.


In Situ Encapsulated Moiré Perovskite for Stable Photodetectors with Ultrahigh Polarization Sensitivity.
Nanostructures provide a simple, effective, and low-cost route to enhance the light-trapping capability of optoelectronic devices. In recent years, nano-optical structures have been widely used in perovskite optoelectronic devices to greatly enhance the device performance. However, the inherent instability of perovskite materials hinders the practical application of these nanostructured optoelectronic devices. Here, in situ encapsulated moiré lattice perovskite photodetectors (PDs) by two nanograting-structured soft templates with relative rotation angles is fabricated. The confinement growth of the two nanograting templates leads to crystal growth with moiré lattice structure, which improves the light-harvesting ability of the perovskite crystal, thereby improving the device performance. The PD exhibits responsivity to 1026.5 A W-1 . The Moiré lattice-perovskite-based PD maintained 95% of the initial performance after 223 days. After being continuously sprayed with water moist for 180 min, the performance is maintained at 95.7% of its initial level. The nanograting structure endows the device with high polarization sensitivity of Imax /Imin as high as 9.1.


Application of statistical parametric mapping for comparison of scapular kinematics and EMG.
Scapular kinematics and EMG are frequently measured as a functional assessment of the shoulder. Previous studies have compared interval averaging for these time series data, but it is not clear whether this method exactly captures the dynamics of scapular kinematics and muscle activity. Statistical parametric mapping (SPM) can be used to compare time series data. The purpose of this study was to investigate whether there is a difference between the results of SPM and interval averaging (every 10° or 30°) in comparing scapular kinematics, EMG, and EMG ratio. Scapular kinematics and EMG of the upper trapezius (UT), middle trapezius (MT), and lower trapezius (LT) and serratus anterior (SA) were measured in 21 healthy males. Tasks included arm raising and lowering with or without load, and we compared scapular kinematics, EMG, and EMG ratio in the loaded and unloaded conditions. Results suggest disagreement between SPM and interval averaging. Characteristic results are that for scapular kinematics during lowering SPM showed a decrease in upward rotation in only the regions 113-65° and 42-30°, while interval averaging showed a decrease in all range. For EMG during lowering, SPM results were not significantly different in SA over 50-48 and 45-30°, while interval averaging suggested increased activity in all ranges. For EMG ratio during raising, SPM showed no significant difference, while interval averaging showed a decrease in UT/LT during the latter period. These results indicate that SPM provides better resolution regarding effect regions than interval averaging, and suggest that SPM may improve shoulder function assessment accuracy.


Melanopsin-dependent phototransduction is impaired in delayed sleep-wake phase disorder and sighted non-24-hour sleep-wake rhythm disorder.
The circadian system must perform daily adjustments to align sleep-wake and other physiologic rhythms with the environmental light-dark cycle: This is mediated primarily through melanopsin containing intrinsically photosensitive retinal ganglion cells. Individuals with delayed sleep-wake phase disorder (DSWPD) exhibit a delay in sleep-wake timing relative to the average population, while those with sighted non-24-hour sleep-wake rhythm disorder (N24SWD) exhibit progressive delays. An inability to maintain appropriate entrainment is a characteristic of both disorders. In this study, we test the hypothesis that individuals with DSWPD exhibit alteration in melanopsin-dependent retinal photo-transduction as measured with the postillumination pupil response (PIPR). Twenty-one control and 29 participants with DSWPD were recruited from the community and clinic. Of the 29 DSWPD participants, 17 reported a history of N24SWD. A pupillometer was used to measure the PIPR in response to a bright 30-second blue or red-light stimulus. The PIPR was calculated as the difference in average pupil diameter at baseline and 10-40 seconds after light stimulus offset. The PIPR was significantly reduced in the DSWPD group when compared with the control group (1.26 ± 1.11 mm vs 2.05 ± 1.04 mm, p < 0.05, t-test). The PIPR was significantly reduced in the sighted N24SWD subgroup when compared with individuals with the history of only DSWPD (0.88 ± 0.58 mm vs 1.82 ± 1.44 mm, p < 0.05, analysis of variance [ANOVA]) or controls (0.88 ± 0.58 mm vs 2.05 ± 1.04 mm, p < 0.01, ANOVA). These results indicate that reduced melanopsin-dependent retinal photo-transduction may be a novel mechanism involved in the development of DSWPD and sighted N24SWD.


Neural Stem Cell Dysfunction in Human Brain Disorders.
Neural stem cells (NSCs) give rise to the entire nervous system. Animal models suggest that defects in NSC proliferation and differentiation contribute to several brain disorders (e.g., microcephaly, macrocephaly, autism, schizophrenia, and Huntington's disease). However, animal models of such diseases do not fully recapitulate all disease-related phenotypes because of substantial differences in brain development between rodents and humans. Therefore, additional human-based evidence is required to understand the mechanisms that are involved in the development of neurological diseases that result from human NSC (hNSC) dysfunction. Human-induced pluripotent stem cells provide a new model to investigate the contribution of hNSCs to various neurological pathologies. In this chapter, we review the role of hNSCs in both neurodevelopment- and neurodegeneration-related human brain pathologies, with an emphasis on recent evidence that has been obtained using embryonic stem cell- or induced pluripotent stem cell-derived hNSCs and progenitors.


Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma.
To investigate changes in the tumor microenvironment (TME) during lung cancer progression, we interrogate tumors from two chest computed tomography (CT)-defined groups. Pure non-solid (pNS) CT density nodules contain preinvasive/minimally invasive cancers, and solid density nodules contain invasive cancers. Profiling data reveal a dynamic interaction between the tumor and its TME throughout progression. Alterations in genes regulating the extracellular matrix and genes regulating fibroblasts are central at the preinvasive state. T cell-mediated immune suppression is initiated in preinvasive nodules and sustained with rising intensity through progression to invasive tumors. Reduced T cell infiltration of the cancer cell nests is more frequently associated with preinvasive cancers, possibly until tumor evolution leads to a durable, viable invasive phenotype accompanied by more varied and robust immune suppression. Upregulation of immune checkpoints occurs only in the invasive nodules. Throughout progression, an effector immune response is present but is effectively thwarted by the immune-suppressive elements.


Sarcopenic obesity: a new challenge in the clinical practice.
Sarcopenic obesity has been associated with greater disability, morbidity and mortality. However, at present, there are few studies regarding the role of sarcopenia in the evolution of the comorbidities associated with obesity in individuals less than 65 years of age. The pathogenesis is multifactorial and uncompletely ilucidated, but it seems that inflammatory mediators and insulin resistance play an important role. Although there is no clear consensus on its definition and diagnostic methods, there is a growing interest in finding biomarkers useful for the detection and monitoring. Regarding the treatment, a multimodal approach is recomended, based on dietary recommendations, exercise and eventually bariatric surgery.


Two mink parvoviruses use different cellular receptors for entry into CRFK cells.
Mink enteritis virus (MEV) and Aleutian mink disease parvovirus (ADV) are two mink parvoviruses that replicate permissively in Crandell feline kidney (CRFK) cells. We have used this cell model to examine if these two mink parvoviruses use the same cellular receptor. Whereas the cellular receptor for MEV is expected to be the transferrin receptor (TfR), the cellular receptor for ADV has not been clearly identified. We used short hairpin RNAs (shRNAs) produced from plasmids to trigger RNA interference (RNAi), specifically and effectively reducing TfR expression in CRFK cells. TfR expression was reduced to levels undetectable by immunofluorescence in the majority of cells. In viral infection assays, we show that TfR expression was necessary for MEV infection but was not required for ADV infection. Thus, our results demonstrate that TfR is the cellular receptor for MEV, but not the cellular receptor for ADV. The use of two different receptors by MEV and ADV to infect the same cell line is yet another difference between these two parvoviruses that may contribute to their unique pathogenesis in mink.


Endoscopic transcortical expanded transforaminal transvenous transchoroidal approach to third ventricle lesion resection using an endoport.
To investigate the clinical experience and application value of endoscopic resection of lesions in and around the third ventricle using a transcortical expanded transforaminal transvenous transchoroidal approach with an endoport. Clinical data and follow-up results of seven patients who underwent the removal of lesions in the third ventricle and its adjacent area with an endoport-guided endoscopic system from January 2018 to December 2020 in the Department of Neurosurgery, Zhongshan Hospital Affiliated to Fudan University, were analyzed retrospectively. Two other patients from the Affiliated Pediatric Hospital of Fudan University and the Affiliated Hospital of Guizhou Medical University, respectively, were included in the analysis. A total of nine cases of third ventricle tumors were included in the study, including six women and three men, with an average age of 37.8 years (4-84 years old) and a follow-up time of 6-44 months. These nine tumor cases included two pilocytic astrocytomas, one diffuse midline glioma (H3 K27-altered), two craniopharyngiomas, two choroid plexus (CP) papillomas, one germinoma, and one pineal parenchymal tumor of intermediate differentiation. Total resection was completed in eight cases, with one near-total resection. There were no complications related to the surgical approach, such as epilepsy, aphasia, or hemiplegia. The endoscope transcortical expanded transforaminal transvenous transchoroidal approach using an endoport can safely and effectively remove third ventricle lesions. This approach can reach a wide area, from the anterior to the posterior third ventricle.


Measurement of diffuse ventricular fibrosis with myocardial T1 in patients with atrial fibrillation.
Atrial fibrillation (AF) is associated with cardiac fibrosis, which can now be measured noninvasively using T1-mapping with cardiac magnetic resonance imaging (CMRI). This study aimed to assess the impact of AF on ventricular T1 at the time of CMRI. Subjects with AF scheduled for AF ablation underwent CMRI with standard electrocardiography gating and breath-hold protocols on a 1.5 T scanner with post-contrast ventricular T1 recorded from 6 regions of interest at the mid-ventricle. Baseline demographic, clinical, and imaging characteristics were examined using univariate and multivariable linear regression modeling for an association with myocardial T1. One hundred fifty-seven patients were studied (32% women; median age, 61 years [interquartile range {IQR}, 55-67], 50% persistent AF [episodes>7 days or requiring electrical or pharmacologic cardioversion], 30% in AF at the time of the CMRI). The median global T1 was 404 ms (IQR, 381-428). AF at the time of CMRI was associated with a 4.4% shorter T1 (p=0.000) compared to sinus rhythm when adjusted for age, sex, persistent AF, body mass index, congestive heart failure, and renal dysfunction (estimated glomerular filtration rate<60). A post-hoc multivariate model adjusted for heart rate suggested that heart rate elevation (p=0.009) contributes to the reduction in T1 observed in patients with AF at the time of CMRI. No association between ventricular T1 and AF recurrence after ablation was demonstrated. AF at the time of CMRI was associated with lower post-contrast ventricular T1 compared with sinus rhythm. This effect was at least partly due to elevated heart rate. T1 was not associated with the recurrence of AF after ablation.


Willingness to Pay for Teledermoscopy Services at a University Health Center.
The study objective was to investigate the willingness to pay (WTP) for teledermoscopy services among students at a university health center. The hypothesis was that WTP for teledermoscopy among students would exceed the costs for traditional consultation. Between November 2013 and May 2014, students at a university health center were surveyed for their perceptions of teledermoscopy. One set of responses was collected from students visiting the health center for any reason (anonymous sample). An additional set of responses was collected from students visiting for dermatologic lesions (in-person sample). A contingent valuation method with a maximum likelihood estimation procedure was used to estimate the WTP distribution. A total of 214 surveys were collected for the anonymous sample and 41 responses for the in-person sample. The mean (standard deviation [SD]) WTP for the anonymous sample was $55.27 ($39.11; 95% confidence interval [CI]: $49.99-$60.55). The mean (SD) WTP for the in-person sample was $52.37 ($26.56; 95% CI: $43.99-$60.75). Median WTP for the 2 samples was similar: $48.84 and $48.01. We conclude that students would be willing to pay for teledermoscopy services that would provide the potential for significant system cost savings. This may be especially true in college health or similar settings where dermatology services may not be available.


The Construct, Convergent and Divergent Validity, and Reliability of Three Optimism Scales among North American University Students.
The primary objective of this study is to compare the construct, convergent and divergent validity and the reliability of three optimism scales. The study relied on a nonprobability sample of 100 social work students at Western Michigan University in the United States (Seventy-nine percent of the sample were female, and 21% were male). The sample's mean age was 26.35 years, SD = 7.70. Sixty-nine percent (69%) of the respondents self-identified as White, and 31% self-identified as African American, Hispanic/Latino, multiethnic, Native American or Asian American. The study used confirmatory factor and multiple regression analyses (CFA and MRA). The findings show that the Life Orientation Test-Revised (LOT-R) and the Personal Optimism Scale (POS) were supported by three indicators of goodness of fit, while the Brief Interactive Optimism Scale-Garcia (BIOS-G) was supported by eight. The LOT-R showed no acceptable internal consistency indicators, but the POS and the BIOS-G showed several good internal consistency indicators. Correlations of all of these scales with the Physical Well-being Scale-Garcia (PWS-G) ranged from r (100) = .303, p = .002 to r (100) = .439, p = .000. The three scales had divergent validity because their scores did not differ by gender (LOT-R: t(100) = -.885, p = .383; POS: t(100) = -.263, p = .794; BIOS-G: t(100) = -.840, p = .407). The findings suggest the advisability of recommending the BIOS-G, which is short and easy to use and understand.


Transgenic disruption of endogenous glucocorticoid signaling in osteoblasts does not alter long-term K/BxN serum transfer-induced arthritis.
Disruption of glucocorticoid (GC) signaling in osteoblasts results in a marked attenuation of acute antibody-induced arthritis. The role of endogenous GCs in chronic inflammatory arthritis is however not fully understood. Here, we investigated the impact of endogenous GC signaling in osteoblasts on inflammation and bone integrity under chronic inflammatory arthritis by inactivating osteoblastic GC signaling in a long-term K/BxN serum transfer-induced induced arthritis (STIA) model. Intracellular GC signaling in osteoblasts was disrupted by transgenic (tg) overexpression of 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2). Inflammatory arthritis was induced in 5-week-old male tg mice and their wild type (WT) littermates by intraperitoneal (i.p.) injection of K/BxN serum while controls (CTRLs) received phosphate-buffered saline (PBS). In a first cohort, K/BxN STIA was allowed to abate until the endpoint of 42 days (STIA). To mimic rheumatic flares, a second cohort was additionally injected on days 14 and 28 with K/BxN serum (STIA boost). Arthritis severity was assessed daily by clinical scoring and ankle size measurements. Ankle joints were assessed histopathologically. Systemic effects of inflammation on long bone metabolism were analyzed in proximal tibiae by micro-computed tomography (μCT) and histomorphometry. Acute arthritis developed in both tg and WT mice (STIA and STIA boost) and peaked around day 8. While WT STIA and tg STIA mice showed a steady decline of inflammation until day 42, WT STIA boost and tg STIA boost mice exhibited an arthritic phenotype over a period of 42 days. Clinical arthritis severity did not differ significantly between WT and tg mice, neither in the STIA nor in the STIA boost cohorts. Correspondingly, histological indices of inflammation, cartilage damage, and bone erosion showed no significant difference between WT and tg mice on day 42. Histomorphometry revealed an increased bone turnover in tg CTRL and tg STIA boost compared to WT CTRL and WT STIA boost animals, respectively. In contrast to the previously reported modulating effects of endogenous GC signaling in osteoblasts during acute K/BxN STIA, this effect seems to perish during the chronic inflammatory and resolution phase. These findings indicate that endogenous GC signaling in osteoblasts may mainly be relevant during acute and subacute inflammatory processes.


Claudin-4 reconstituted in unilamellar vesicles is sufficient to form tight interfaces that partition membrane proteins.
Tight junctions have been hypothesized to act as molecular fences in the plasma membrane of epithelial cells, helping to form differentiated apical and basolateral domains. While this fence function is believed to arise from the interaction of four-pass transmembrane claudins, the complexity of tight junctions has made direct evidence of their role as a putative diffusion barrier difficult to obtain. Here, we address this challenge by reconstituting claudin-4 into giant unilamellar vesicles using microfluidic jetting. We find that reconstituted claudin-4 alone can form adhesive membrane interfaces without the accessory proteins that are present in vivo By controlling the molecular composition of the inner and outer leaflets of jetted vesicle membranes, we show that claudin-4-mediated interfaces can drive partitioning of extracellular membrane proteins with ectodomains as small as 5 nm but not of inner or outer leaflet lipids. Our findings indicate that homotypic interactions of claudins and their small size can contribute to the polarization of epithelial cells.


Rationale, study design and methodology of the LANDMARC trial: a 3-year, pan-India, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.
India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country. The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period. The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452).


A 2S albumin-homologous protein from passion fruit seeds inhibits the fungal growth and acidification of the medium by Fusarium oxysporum.
Antimicrobial proteins have been isolated from a wide range of plant species. More recently, it has become increasingly clear that these types of proteins play an important role in the protection of plants. In this study, we investigate the presence of defense-related proteins from passion fruit (Passiflora edulis f. flavicarpa) seeds. Initially, seed flour was extracted for 2h (at 4 degrees C) with phosphate buffer, pH 5.5. The precipitate obtained between 0 and 70% relative ammonium sulfate saturation was re-dissolved in distilled water and heated at 80 degrees C for 15 min. The resulting suspension was clarified by centrifugation and the supernatant (F/0-70) was extensively dialyzed. A Sephadex G-50 size exclusion column was employed for further separation of proteins. The fraction with antifungal activity was pooled and submitted to CM-Sepharose cation exchange. Two proteins, named Pf1 and Pf2, were eluted in 0.1 and 0.2M of salt, respectively, and submitted to reverse-phase chromatography in HPLC. This fraction inhibited the growth, in an in vitro assay, of the phytopathogenic fungi Fusarium oxysporum and colletotrichum lindemuthianum and the yeast Saccharomyces cerevisiae and strongly inhibited glucose-stimulated acidification of the medium by F. oxysporum in a dose-dependent manner. The molecular masses of these proteins, referred to now as Pf1-RP and Pf2-RP, were obtained by MALDI-TOF spectrometry and corresponded to 12,088 Da for Pf1-RP and 11,930 Da for Pf2-RP. These proteins were also subjected to automated N-terminal amino acid sequencing. Sequence comparisons for the heavy subunit of Pf2-RP showed the presence of a protein with a high degree of homology to storage 2S albumins.


Rh-catalyzed aerobic oxidative cyclization of anilines, alkynes, and CO.
Transition-metal-catalyzed oxidative C-H cyclization of anilines has been an attractive and powerful strategy for the efficient construction of N-heterocycles. However, primary and tertiary anilines are rarely employed in this strategy due to the relative instability with strong oxidants or the presence of three C-N bonds. We describe here a novel Rh-catalyzed C-H cyclization of a wide range of anilines with alkynes and CO, using an aerobic oxidative protocol. Particularly, the simple primary anilines and readily prepared tertiary anilines could be easily converted to quinolin-2(1H)-ones, which are high value-added, biologically significant N-heterocycles, via C-N bond cleavage.


Importance of the 'area under the curve' from serial NT-proBNP measurements during treatment with sacubitril/valsartan.
Serial assessment of natriuretic peptides is widely utilized in heart failure clinics. Uncertainty exists regarding the value of multiple natriuretic peptide measurements and how they might be best interpreted. Six hundred thirty-two patients with heart failure with reduced ejection fraction (<40%) and complete biomarker data were enrolled to receive sacubitril/valsartan. Patients underwent periodic study visits during 1-year follow-ups. Echocardiographic data and cardiac biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected during study visits. Patients were categorized into three groups based on tertiles of baseline NT-proBNP levels. The area under the curve (AUC) of NT-proBNP measurements across study visits was calculated. Compared with patients with higher AUC (and thus higher concentrations over a longer period of time), those with lower AUC were younger, had a lower prevalence of chronic kidney disease, prior coronary artery bypass graft, atrial fibrillation, and higher body-mass index. A significant interaction existed between baseline NT-proBNP and subsequent AUC for predicting LVEF change across visits (P-value < 0.001): among those with lower baseline NT-proBNP, similar improvements in left ventricular (LV) volumes LV ejection fraction, and LV mass index were observed across subsequent AUC (P-value > 0.1). However, among those with higher baseline NT-proBNP, those with lower subsequent AUC had a greater improvement in cardiac remodelling indices (P-value < 0.05). Serial NT-proBNP monitoring (integrating the totality of measurements as an AUC) during treatment with sacubitril/valsartan informs unique information regarding the future changes in cardiac remodelling indices, especially among those with higher NT-proBNP levels at baseline.


Auditory brainstem response findings in brainstem ischemia following selective occlusion of the anterior inferior cerebellar artery in the rat.
Auditory brainstem responses (ABRs) were measured ipsilaterally (n = 13) or contralaterally (n = 5) after inducing permanent right and left anterior inferior cerebellar artery (AICA) occlusion. Three types of wave patterns were classified when ABRs were recorded ipsilaterally. In type 1 (n = 4) all components disappeared; in type 2 (n = 2) all components disappeared transiently and then reappeared; and in type 3 (n = 7) only the latency difference between components I and IV increased. These findings indicate that all components reappeared in type 2 responses because cochlear blood flow was re-established quickly by collateral circulation, while type 3 changes reflected the relative sensitivity of the cochlea to ischemic damage when compared with the rest of the auditory pathways. When the ABRs were recorded contralaterally, characteristic findings included a delay in latency of component IV and a significant increase in inter-peak latency in components I-IV and IIb-IV.


Optimisation of diagnosis and treatment of heart failure in a primary care setting.
Heart failure (HF) is one of the leading causes of emergency department visits and hospital admissions in the USA. We identified a gap in the diagnosis and the use of guideline-directed medical therapy in patients with HF at the internal medicine clinic. To improve the diagnosis and treatment of HF, as well as to reduce emergency department visits and hospitalisation over 12 months in patients aged 40-75 years. The multidisciplinary quality improvement (QI) team performed a root cause analysis and identified barriers to optimal guideline-directed medical therapy. Rates of patients on guideline-directed medical therapy with systolic HF diagnosis, emergency department visits and hospital admissions were the outcome measures. The process measures included echocardiogram order and completion rates, and rates of accurate classification of HF from the baseline rate of less than 10%. We used the focus, analyse, develop, execute and evaluate (FADE) model with five improvement cycles. The major components of interventions included (1) leveraging health information technology; (2) optimising teamwork; and (3) providing education to patients, physicians and internal medicine clinic staff. Data were analysed using statistical process control and run charts. We observed a reduction in the total number of emergency department visits (160 vs 108), hospital admissions (117 vs 114) and observation visits (22 vs 16) comparing the 1-year preproject and 1-year postproject periods. An increase in the use of ACE inhibitors or angiotensin receptor blockers occurred from the baseline rate of 20%-37% during the second half of the project and was sustained at 71.4% (median) during 6 months of the postproject period. We achieved a sustainable increase in the accurate diagnosis of HF and achieved 80% diagnosis during the 6-month poststudy period.


Immunocytochemical localization of vitamin D-dependent calcium-binding protein in renal tubules of rabbit, rat, and chick.
Vitamin D-dependent calcium-binding protein (CaBP) was localized in tissue sections of kidneys from rabbits, rats, and chicks using antiserum specific for chick intestinal CaBP. In rabbit kidney, CaBP was present in all cells of the distal convoluted tubule and most cells of the connecting tubule. Fewer, but still a majority, of the cells of cortical collecting ducts contained CaBP. The intensity of immunochemical staining and the number of stained cells decreased markedly in medullary collecting ducts, and only a few collecting duct cells contained CaBP at the junction of the inner and outer medulla. In the rat kidney, CaBP was present in all distal convoluted tubule cells, but the immunochemical staining was less intense than in the rabbit. The protein also was found in most connecting tubule cells of the rat; however, only a few collecting duct cells in the superficial corte of the rat contained CaBP. CaBP was essentially absent from mid- to deep-cortical collecting duct cells, while a very few collecting duct cells always contained CaBP at the junction of the inner and outer stripes of the outer medulla. In the chick, CaBP was present in distal convoluted tubule cells as the distal convoluted tubule coursed adjacent to the central vein. CaBP was absent from chick collecting duct cells. In all three species CaBP was not detected in the other portions of the nephron.


Use of dynamic MRI during swallowing to assess carotid artery invasion by neck metastasis.
The effectiveness of dynamic MRI in evaluating the relationship between metastatic lymph nodes and the carotid artery was investigated. Thirty-two patients with metastatic lymph nodes, possibly adherent to the carotid artery, were evaluated with dynamic MRI before surgery. Consecutive axial and oblique images were obtained during swallowing. The displacement rate of the target carotid artery to the contralateral carotid artery and the low-intensity stripe between the metastatic lymph nodes and the carotid artery wall were compared with the surgical findings. A displacement rate > 50% indicated resectable metastatic lymph nodes. Low-intensity stripe was present in 65% of patients and indicated no invasion; 82% of patients without low-intensity stripe had resectable metastatic lymph nodes. The others without low-intensity stripe required carotid artery resection due to malignant invasion. The accuracy rate, sensitivity, and specificity were 78%, 83%, and 100%, respectively. Dynamic MRI during swallowing is useful for assessing suspected carotid artery involvement in patients with metastatic lymph nodes to achieve maximal safe resection.


Selective inhibition of the growth of cancer cells by diterpenes selected with embryonic cells of Xenopus.
We used Xenopus embryo cells with a cell cycle of 20-30 min to detect inhibitory effects on cell proliferation. Inhibition of proliferation was observed when isolated embryonic cells were incubated for 16 h in a simple salt solution containing the well-known anticancer drugs 5-fluorouracil and adriamycin. In addition, three diterpene compounds isolated from the anticancer herbal medicine kansui: kansuinin B, 20-OD-ingenol Z, and 20-OD-ingenol E specifically inhibited the proliferation of isolated embryonic cells. The inhibitory compounds selected using the embryonic cells also inhibited proliferation of certain mammalian cell types.


A pilot observational study of a psychotherapy incorporating equines resiliency intervention for staff at a large medical center.
and purpose: Stress and burnout among healthcare workers are significant public health concerns. The primary aim of this pilot study was to conduct preliminary assessments of safety, feasibility, and participant satisfaction with a psychotherapy incorporating equines (PIE)-based resiliency intervention for healthcare workers. The overarching goal was to lay the groundwork for future, more rigorous investigations. Lastly, a very preliminary assessment of using the Acceptance and Action Questionnaire II (AAQII) to assess for changes in psychological flexibility (PF) associated with PIE was conducted. Thirty-seven staff members from a medical center participated in a 4-h PIE-based resiliency retreat. Pre- and post-intervention instruments were utilized to assess participants' self-perception of physical and psychological health (PROMIS Global Short Form) and enjoyment of (Physical Activity Enjoyment Scale) and satisfaction with (Client Satisfaction Questionnaire) the intervention, as well as changes in PF (AAQII). There were no adverse effects on participants, staff, or equines. Preliminary results suggested that the intervention was perceived as enjoyable by participants. However, the intervention was not fully utilized. Finally, there was a significant (p = 0.02) pre-to post-intervention change in AAQII scores. This study provides a foundation for future rigorous studies of PIE-based resiliency interventions for medical staff. Given the limitations of this pilot work, firm conclusions cannot be drawn regarding safety and feasibility. However, the preliminary results suggest that future studies of this intervention are warranted and that the AAQII may be a useful instrument to assess for possible changes in PF.


Interrelationship between differentiation and malignancy-associated properties in glioma.
The phenotypic expression of cells derived from human anaplastic astrocytomas, rat glioma, normal human adult and foetal brain tissue have been examined for differentiated and malignancy-associated properties. Glial fibrillary acidic protein (GFAP), high affinity glutamate and gamma-amino butyric acid (GABA) uptake and glutamine synthetase were used as indicators of astroglial differentiation. Plasminogen activator and tumour angiogenesis factor were the malignancy-associated markers. The normal adult brain-derived lines showed some differentiated astroglial features and expressed low levels of the malignancy-associated properties. The foetal cultures contained highly differentiated astroglia while the glioma lines showed considerable phenotypic heterogeneity from highly differentiated to undifferentiated. The least differentiated glioma cells exhibited the highest plasminogen activator activities. The density-dependent control of phenotypic expression was also investigated. High affinity GABA uptake, and GFAP in rat C6 glioma cultures, increased with increasing monolayer cell density, events probably mediated by an increase in the formation of cell-cell contacts at confluence. Plasminogen activator activity decreased with increasing cell density.


Inefficient nitrogen resorption in genets of the actinorhizal nitrogen fixing shrubComptonia peregrina: physiological ineptitude or evolutionary tradeoff?
Nutrient resorption was measured in an actinorhizal nitrogen-fixing shrub,Comptonia peregrina, for five years in the understory of a deciduous oak forest in Rhode Island, USA. Mean resorption of nitrogen was extremely inefficient (11%) compared to most deciduous species (50%+), yet resorption of phosphorus was efficient (53%) and comparable to other species. Of the seven additional nutrients studied, only copper (6%) and zinc (10%) were resorbed from senescing leaves. Resorption of nitrogen (5%-20%) and phosphorus (40%-71%) varied significantly among years. Copper was resorbed from leaves in three years and accreted into leaves in two years. Five-year resorption means differed among individual genets by as much as a factor of 2.5 for nitrogen, and 1.3 for phosphorus. Resorption of nitrogen, copper, and zinc were highly correlated, yet resorption of phosphorus remained autonomous from other nutrients. The ecophysiological tradeoffs inComptonia which have resulted in the cooccurence of actinorhizal nitrogen fixation, inefficient nitrogen resorption, and efficient phosphorus resorption suggest that plant nutrient status does have an impact on resorption efficiency and that the evolution of nutrient conservation strategies is nutrient-specific.


Internal Mammary Sentinel Lymph Nodes in Breast Cancer - Effects on Disease Prognosis and Therapeutic Protocols - A Case Report.
The main prognostic factor in early staged breast cancer is the axillary lymph node metastatic affection. Sentinel lymph node biopsy, as a staging modality, significantly decreases surgical morbidity. The status of internal mammary lymph nodes gains an increased predictive role in grading breast carcinomas and modulation of postoperative therapeutic protocols. If positive, almost always are associated with worse disease outcome. Nevertheless, the clinical significance of internal mammary lymph node micrometastases has not been up to date precisely defined. To present a case of female patient clinically diagnosed as T1, N0, M0 (clinical TNM) ductal breast carcinoma with scintigraphic detection of internal mammary and axillary sentinel lymph nodes. Dual method of scintigraphic sentinel lymph node detection using 99mTc-SENTI-SCINT and blue dye injection, intraoperative gamma probe detection, radioguided surgery and intraoperative ex tempore biopsy were used. We present a case of clinically T1, N0, M0 ductal breast cancer with scintigraphic detection of internal mammary and axillary sentinel lymph nodes. Intraoperative ex tempore biopsy revealed micrometastases in the internal mammary node and no metastatic involvement of the axillary sentinel lymph node. Detection of internal mammary lymph node metastases improves N (nodal) grading of breast cancer by selecting a high risk subgroup of patients that require adjuvant hormone therapy, chemotherapy and/or radiotherapy.


Implantation site in complete molar pregnancy: a study of immunologically competent cells with monoclonal antibodies.
The nature and intensity of inflammatory cellular infiltrate in the implantation sites of 10 complete molar pregnancies were evaluated by immunohistochemical staining of frozen tissue sections with monoclonal antibodies. As compared to the implantation site in normal pregnancy, there was an increase in the number of infiltrating inflammatory cells in the molar implantation site. Most of the inflammatory cells were T cells with predominance of T4+ (Leu-3a+) cells over T8+ cells. Inflammatory cells were not detected in the molar vesicles. The possible implications of these findings in molar pregnancy are discussed.


Effect of Oblique-Angle Sputtered ITO Electrode in MAPbI3 Perovskite Solar Cell Structures.
This investigation reports on the characteristics of MAPbI3 perovskite films on obliquely sputtered ITO/glass substrates that are fabricated with various sputtering times and sputtering angles. The grain size of a MAPbI3 perovskite film increases with the oblique sputtering angle of ITO thin films from 0° to 80°, indicating that the surface properties of the ITO affect the wettability of the PEDOT:PSS thin film and thereby dominates the number of perovskite nucleation sites. The optimal power conversion efficiency (Eff) is achieved 11.3% in a cell with an oblique ITO layer that was prepared using a sputtering angle of 30° for a sputtering time of 15 min.


Prolactin levels in nursing mothers.
Plasma prolactin (hPRL) concentration was measured in four nursing mothers during 24 hour periods. Blood was collected via indwelling catheters and sleep and nursing periods were recorded. Elevated hRPL levels and amenorrhea were seen for as long as 13 months post partum in mothers whose infants nursed frequently. One mother, whose infant nursed less frequently, menstruated and had lower prolactin levels but continued to lactate. Plasma hPRL rose after nursing periods in nine of 18 instances at two months post partum, but in only five of 27 instances at six months post partum. Nighttime release hPRL was higher (five of six) in nursing mothers, just as in normal subjects (five of seven). Therefore it was concluded that prolactin levels in nursing mothers may remain elevated for over one year post partum if frequent nursing continues. Lactation may continue in spite of normal hPRL levels. A consistent rise in hPRL is not seen with nursing episodes occurring after two months post partum. Nursing mothers, like normal women, tend to have higher nighttime release of hPRL.