Fear about adverse effect on fertility is a major cause of COVID-19 vaccine hesitancy in the United States.
Although COVID-19 vaccine access has increased nationwide, vaccination rates have been slow-moving, with many studies showing significant vaccine hesitancy in the U.S. We conducted an online survey using Amazon Mechanical Turk (MTurk) to identify reasons for vaccine hesitancy among unvaccinated adults between June 30 and July 1, 2021. We found that 58% of unvaccinated respondents were worried about unknown long-term adverse effects. Of these, 41% believed that the COVID-19 vaccines can negatively impact reproductive health and or fertility, and 38% were unsure of the effects on fertility. Our study demonstrates that fear regarding COVID-19 vaccine adverse effects and belief that they can negatively impact fertility is a major cause of vaccine hesitancy in the United States. We identified that urban residents, married individuals, those born outside the U.S., those with health insurance, and people with higher education and income greater than $100,000 felt that the vaccine would affect fertility more than their counterparts did. Finally, we found that 48% of unvaccinated respondents cited 'more information and research conducted on the COVID-19 vaccines' as the action that would most encourage vaccine uptake.


Relation between reduced electrophoretic mobility of human lymphocytes and the inhibition of spreading of human monocytes caused by the same anti-human lymphocyte globulin.
Slowing of electrophoretic mobility of human peripheral blood lymphocytes after adding anti-human lymphocyte globulin (AHLG) in vitro correlated with indices of the monocyte spreading inhibition obtained by the same AHLG. Consequently, electrophoretic results may be associated with the prolongation of skin allograft survival in primates - the best and the only practical in vivo test for determination of the immunosuppressive potency of AHLG. If so, the simple electrophoretic test could be used in combination with other in vitro tests, preferably for monitoring of the AHLG production.


Ring-Stacking Water Clusters: Morphology and Stabilities.
The structures and interaction energies of water clusters with ring stacking motifs are studied by using ab initio calculations. The structures of the water clusters are constructed by stacking either single rings or multi-rings of tetramer, pentamer, and hexamer. We found that, in the single-ring-stacking motif, the most stable isomers exhibit an alternative clockwise-anticlockwise stacking pattern. We also show that four-layer single-ring-stacking isomers are not energetically favorable in comparison with those of two-layer multi-ring-stacking isomers. The relative stability of the isomers is also analyzed in terms of H-bond strength and elastic distortions of the water molecules.


Size separation of sodium dodecyl sulfate-proteins by capillary electrophoresis in dilute and ultra-dilute dextran solutions.
SDS capillary gel electrophoresis is a widely used in the biopharma and the biomedical fields for rapid size separation of proteins. However, very limited information is available on the use of dilute and ultra-dilute sieving matrices for SDS-protein analysis. Here, background electrolytes (BGEs) containing 1%-0% dextran were used in borate-based BGE to separate a protein sizing ladder (PSL) ≤225 kDa and the intact and subunit forms of a therapeutic monoclonal antibody (mAb). The separation performance for the PSL and mAb components differed significantly with decreasing dextran concentration. Ferguson and reptation plots were used to elucidate the separation mechanism. Highly diluted dextran solutions resulted in linear Ferguson plots for both solute types (cf. Ogston theory) in spite of this model assumes a rigid pore structure, thus cannot describe the separation mechanism in ultra-dilute polymer solutions with no reticulations. The saddle differences between the resolution of the PSL and the intact/subunit mAb forms in ultra-dilute dextran-borate matrices suggested the importance of shape selectivity, manifested by the adequate separation of the SDS covered intact as well as light and heavy chain subunits of the therapeutic mAb even at zero dextran concentration.


Assessment of the pharmaceutical quality of marketed enteric coated pantoprazole sodium sesquihydrate products.
Pantoprazole sodium sesquihydrate (PSS) is a proton pump inhibitor, used in acid-related disorders, like peptic ulcer and gastroesophageal reflux. Increasing the number of pantoprazole containing products in the market, raises questions of its efficacy and generic substitution. The pharmaceutical quality of 6 generic PSS enteric coated tablets in 2 local markets was assessed relative to the innovator product (pantozol®). Uniformity of dosage unit, disintegration and in vitro drug release were determined using United States pharmacopeia for delayed release tablets. The similarity factor (f2) was assessed using the FDA recommended approach (f2 similarity factor). The content uniformity of the innovator product was 98.39% of the labeled claim with RSD value of 1.08%, while the content of generic products ranged from 96.98% to 98.80% with RSD values of 1.24-2.19%. All the products showed no disintegration, cracks or swelling in 0.1 N HCl, except product 1, which showed complete disintegration after 20 min. However, the disintegration of all the products in phosphate buffer met USP requirements. Dissolution of tablets in 0.1 N HCl showed no drug release after 2 h except product 1 in which one tablet showed a drug release more than 10% at acid stage level A1. In addition, three tablets of this product showed dissolution of 45%, 48% and 69% at acid stage level A2. The similarity factor f2 of the products was between 71 and 74 indicating the similarity in dissolution profiles of all the products in accordance to FDA requirements, except product 1 in which f2 value was 18.67.


Integration of life cycle assessment and system dynamics modeling for environmental scenario analysis: A systematic review.
System dynamics (SD) is widely recognized as a tool for simulating spatial and temporal dynamics in life cycle assessment (LCA) studies of the product system. However, there is no agreement on how SD and LCA could be applied effectively together in a consistent way. To address this gap, this research conducted a systematic literature review, analyzing 54 scientific articles published worldwide between 2010 and 2023, to explore the joint application of LCA with SD. The study aimed to answer three research questions: (1) What can be considered an integration of LCA and SD? (2) How can SD and LCA be effectively integrated? and (3)What are the advantages and constraints of this integration? The results highlighted the popularity of LCA and SD as impact assessment tools for sustainable design, each with its own strengths and limitations. Two primary integration types were identified when LCA was jointly applied with SD: (1) inclusion of the life cycle inventory and characterization factors in an SD model, and (2) inclusion of SD model results in an LCA. In the second type of integration, SD models the components of the technical system, and its outcomes served as input for scenario analysis, providing temporal and potentially spatial inventory data for the LCA model. The integrated approach offers a comprehensive understanding of product sustainability, aids decision-making, and enhances stakeholder engagement. The study also identifies knowledge gaps in the joint application of SD and LCA for environmental scenario analysis, suggesting the incorporation of optimization tools and strategy guidance for policy makers.


Immunoperoxidase labeling of the anterograde tracer fluoro-ruby (tetramethylrhodamine-dextran amine conjugate).
Fluoro-Ruby (tetramethylrhodamine-dextran amine conjugate) has been shown recently to be an effective anterograde tracer readily visible in brain sections with fluorescence microscopy. We show in this study that further microscopic analysis of Fluoro-Ruby-labeled elements is feasible with a conventional immunoperoxidase reaction using an antiserum raised against tetramethylrhodamine.


Vision and hearing loss associated with lifetime drug use: NHANES 2013-2018.
One in four American adults has a disability. Individuals with disabilities are more likely to have mental health issues and use substances and are less likely to attend substance use rehabilitation compared to individuals without disabilities. However, most research about substance use and substance use rehabilitation does not focus specifically on sensory disabilities. The purpose was to test the association between vision and/or hearing loss, lifetime drug use, and lifetime drug rehabilitation. Data files from National Health and Nutrition Examination Survey cycles (2013-2014, 2015-2016, 2017-2018) were combined. Ordinal logistic regression was used to test the association between vision and hearing loss and lifetime drug use and binary logistic regression to test the association with lifetime rehabilitation among those who had used drugs, adjusting for multiple testing and the complex survey design. There was a significant association between vision and hearing loss status and lifetime drug use (p = .018), but not with lifetime rehabilitation (p = .972). Post-hoc comparisons were not statistically significant. However, individuals with vision loss only and hearing loss only had 36% and 37% greater odds, respectively, of drug use than those without a disability, and those with both vision and hearing loss had 18% greater odds of drug use than those with either alone. Persons with disability were more likely to have used drugs but were not more likely to have gone to drug rehabilitation.


Elimination of total coliforms and Escherichia coli from water by means of filtration with natural clays and silica sand in developing countries.
This research presents the results of a pilot system used for water treatment to be supplied to single-family or small housing nucleus at rural sector. The pilot system is constituted by an up-flow aerated filter with ceramic carrier, followed by a second down-flow filter of silica sand. The pilot plant was installed in a rural sector of the province of Loja, Ecuador, with the main purpose of monitoring the reduction in bacteria in the water for human consumption. Two natural clays from the area were tested. They were transformed into sphere-type ceramics, and then, they were placed in the pilot filters. These both natural clays are inorganic materials with high content of aluminosilicate clay minerals with favourable characteristics to achieve greater efficiency for the reduction in bacteria. The acclimatization time of 60 days allowed to achieve optimum treatment efficiency performance until 90 days of operation. The physicochemical parameters, namely temperature, pH, dissolved oxygen and total dissolved solids, were monitored throughout the experiments. Regarding microbiological parameters, up to 99% of total coliforms removal was reached for the clay called CF-CC and 79% for the other, called CF-CV. In addition, 100% of total coliforms and Escherichia Coli removal was reached for both clay systems. Social and economic viability of the proposed treatment is also analysed in the manuscript.


Total-Body PET/Computed Tomography Highlights in Clinical Practice: Experiences from Zhongshan Hospital, Fudan University.
"The initial experience of using total-body PET/computed tomography (CT) (uExplorer) in Zhongshan Hospital, Fudan University, is described. Compared with conventional PET/CT, total-body PET/CT imaging provides more comprehensive information for evaluation of disease. Using fludeoxyglucose F 18, regular-dose (3.7 MBq/kg), low-dose (1.85 MBq/kg), or extra low-dose (0.37 MBq/kg) scanning, as well as high-quality imaging, protocols were used in clinical practice according to the situation. Dynamic studies were also used to assess tumor biological characteristics or for radiotracer angiography."


[Reasons for consultation and healthcare strategies analyzed from a neighborhood dermatological assistance device. Qualitative research: Skin problems. Qualitative research.
identify consultation reasons, experiences with seeking dermatological assistance and skin care strategies within neighbours from an urban deprived settlement in Buenos Aires province, Argentina. This setting lies onto a sanitary landfill with a high index of environmental contamination. a dermatological health care team from the main local hospital designed a dermatological assistance device (DAD), in cooperation with social leaders and institutions of the neighborhood. The DADs included walks around the neighborhood for attending those who could not get a consultation. The experiences were evaluated through a qualitative research strategy, developed from the theoretical framework of Sociocultural Epidemiology. Those who attended the DADs were interviewed. Ethnographic field notes were also recorded. Multiple accessibility barriers to the public health care system were identified and self care practices were also recognized. The most frequent consultations to the DADs were for "pimples", "stains'' and "lumps" on exposed areas of the skin. These lesions generated discomfort or pain, or even affected the interviewees aesthetically or emotionally. Most of them were associated to extremely dry skin and a high sun exposure, in connection with the lack of shade in the neighbourhood. An initiative to plant trees was promoted in order to prevent sun radiation-induced dermatoses. the reflective immersion of the dermatology team in the realm of the neighborhood daily life enabled the development of attention strategies grounded on the perceived needs of the population.


Post-traumatic cysts and cyst-like lesions of bone.
We describe two patients with cyst-like lesions of bone that developed at sites of healed or healing fractures. One case showed histological features of a unicameral bone cyst, which, to the best of our knowledge, is a previously unreported finding in a post-traumatic cyst. It is suggested that there are two principal clinical and radiological types of post-traumatic cyst, of which each of our cases represents an example: (1) asymptomatic transient cortical lesions, found only in children, and (2) more central expanding lesions, found in a wider age group and associated with pain, swelling, and pathological fractures.


[Ambulatory indirect long-term blood pressure measurement in primary and secondary hypertension].
Ambulatory 24 hour blood pressure measurements were performed in 21 patients with various forms of secondary hypertension and were compared with the blood pressure profile of a matched group of patients with primary hypertension. Patients with renovascular (n = 8) and renoparechymal hypertension (n = 8), and with primary hyperaldosteronism (n = 4) showed no significant fall in systolic blood pressure during the sleeping period (00-03 a.m.) and in systolic and diastolic blood pressure in the early morning (06 a.m.) as compared with essential hypertensives. However, in a single case of hypertension due to coarctation of the aorta the 24 hour blood pressure profile is not different from essential hypertension. Thus, ambulatory 24 hour blood pressure recording is a good method for screening secondary forms of hypertension.


Preoperative diagnosis of malignant transformation arising from mature cystic teratoma of the ovary.
Mature cystic teratoma of the ovary (MCT) is the most common ovarian cystic disease in young women. Although it is a rare occurrence, some cases develop malignant transformation (MT), which results in serious consequences. However, MT is currently diagnosed only by postoperative pathology in most cases. We have conducted a retrospective study in an attempt to seek the factor to diagnose MT from MCT prior to surgery. Eighty-one patients with MCT and 39 patients with MT were entered in this study. Patient's age, tumor size, serum CEA levels, and serum SCC levels were tested by the Mann-Whiteney U test. Sensitivity and specificity were calculated, and the most suitable point was searched from the receiver operating characteristic (ROC) curve. A significant difference was recognized in both patient's age and serum SCC level (P < 0.0001). For a patient less than 40 years old, the sensitivity to MT was 95%, and then the specificity to MT was 63%. When the standard value of the SCC level of the serum was established as 2.5 ng/ml, the sensitivity to MT was 80% and the specificity to MT was 94%. We apply two criteria at the same time (serum SCC levels less than 2.5 ng/ml and patient's age less than 40 years old). The sensitivity for MT was 77% and specificity was 96%. The combination of the two criteria which are patient's age (under 40 years old) and serum SCC level (under 2.5 ng/ml) was considered a suitable marker for differential diagnosis between MCT and MT. Further the possibility for MT is quite low when the patient is 39 years old or younger and the serum SCC level is under 2.5 ng/ml. When any patient satisfies this condition, laparoscopic surgery will be able to be planned safely.


Mitochondria-mediated apoptosis and endoplasmic reticulum stress are involved in the toxicity induced by copper in the porcine spleen.
Copper (Cu) is one of the common heavy metal pollutants in the environment, and its toxic mechanisms have been extensively studied. However, the immunotoxicity induced by Cu remains rarely reported, and the effects of Cu on endoplasmic reticulum stress and mitochondria-mediated apoptosis have been little studied in the spleen. In this study, pigs were fed with different contents of Cu (10, 125, and 250 mg/kg Cu) for 80 days to establish a toxicity model. The results showed the Cu exposure triggered endoplasmic reticulum stress in the spleen, as evidenced by increased mRNA and protein levels of GRP94, GRP78, CHOP, XBP1, ATF6, and JNK; the positive rate of GRP78 increased by immunofluorescence analysis. Additionally, mitochondrial fission and fusion homeostasis were disrupted, the expression levels of mitochondrial dynamics-related genes Mfn1, Mfn2, and OPA1 decreased, DRP1 increased, and the positive rate of Mfn1 decreased by immunofluorescence analysis. Furthermore, Cu exposure could induce apoptosis, as demonstrated by the increased expression level of related proteins and genes Bak, Bax, Caspase-3, P53, and Cytc. In conclusion, these results suggest chronic Cu exposure can lead to endoplasmic reticulum stress and imbalance in mitochondrial dynamics and induced apoptosis of pig spleen, and these results provided new insights into the underlying mechanism of Cu exposure caused splenic toxicity, which has public health implications where humans and animals are exposed to copper contamination.


Evaluation of Endo Perio Lesions Using Cone Beam Computed Tomography (CBCT) - A Cross Sectional Study.
An accurate assessment of the disease extent and lesion size is needed for appropriate therapy decisions of endodontic-periodontic (endo-perio) lesions. CBCT imaging with less radiation and high spatial resolution can provide a comprehensive evaluation of endo-perio lesions. A total of 71 teeth with endo-perio lesions were assessed using CBCT. Periodontal bone defects were studied for bone loss pattern (horizontal/vertical) along with bone loss levels on mesial and distal sides in association with furcation involvement. The periapical lesions were studied for their prevalence and extent based on CBCT PAI Score. Horizontal and vertical bone loss were detected in 54 teeth (76.1%) and 17 teeth (23.95%), respectively. Mean crestal bone loss levels on mesial and distal aspects were 4.80 ± 3.21 mm and 5.74 ± 3.91 mm, respectively. The mean height, width, and depth of furcation defects were 3.19 ± 2.99 mm, 1.94 ± 0.98 mm, and 4.44 ± 1.92 mm, respectively. Periapical lesions were recorded in 55 teeth (77.5%). A CBCT PAI score of 5 was scored in 35 teeth with a mean lesion diameter of 11.3 ± 2.83 mm, while 16 teeth had healthy periapical tissues (scores of 0 and 1). CBCT is a valuable diagnostic tool that can help assess endo-perio lesions by providing morphometric measurements of periodontal bone defects and the extent of associated periapical lesions.


Isolation and developmental expression of the ecdysteroid-induced GHR3 gene of the wax moth Galleria mellonella.
Three degenerate primers were designed to match the most conserved regions within the DNA-binding domains of several selected members of the steroid hormone receptor family. Use of these primers in the polymerase chain reaction with cDNA from Galleria mellonella prepupae detected a 177 bp fragment that had 87% identity to the Manduca sexta gene MHR3 and 75% to the Drosophila melanogaster DHR3 gene, and therefore was named "GHR3". Screening of a Galleria penultimate instar cDNA library with this fragment yielded a cDNA clone that contained a 557 codon open reading frame, predicting a 62.3 kDa protein. The deduced amino acid sequence of GHR3 showed 92% overall identity with the MHR3 protein and 97 and 70% identity with DHR3 in the putative DNA- and ligand-binding domains, respectively. Hybridization of whole body RNA revealed high GHR3 mRNA levels during both the larval and pupal molts, coincident with the molt-inducing ecdysteroid pulses, and low or undetectable levels during the first half of the last instar. During the larval-pupal transformation, no GHR3 mRNA was found at the beginning of the stemmatal pigment retraction at the onset of the ecdysteroid rise; maximal levels were observed 4 h later, coincident with the peak ecdysteroid titer (over 2.3 micrograms 20E equivalents/ml hemolymph). Two mRNAs (4.6 and 3.6 kb) were detected when the ecdysteroid titer was high. Injection of 2 micrograms/gm 20E into isolated final instar larval abdomens induced the appearance of the 4.6 kb mRNA within 1.5 h; the mRNA level then reached maximum by 3 h and declined by 6 h. No 3.6 kb mRNA was detectable during that time. A 10-fold lower 20E dose caused only trace induction by 3 h.


Daily hemodialysis: why the renewed interest?
There has been an increasing interest in new hemodialysis regimens aiming to address issues of inadequate dialysis, poor quality of life, and poor outcomes. This article reviews the current state of short daily and nocturnal hemodialysis and outlines the advantages of daily over conventional hemodialysis reviews. Furthermore, it attempts to compare these two dialysis regimens.


Complications and Impact on Quality of Life of Vertical Rectus Abdominis Myocutaneous Flaps for Reconstruction in Pelvic Exenteration Surgery.
Pelvic exenteration for malignancy sometimes necessitates flap reconstruction. This study's aim was to investigate flap-related morbidity. A prospective database was reviewed from 2003 to 2016. All medical charts, correspondence, and outpatient follow-up records up to May 2017 were reviewed. This study was conducted at a tertiary referral unit. Patients who underwent pelvic exenteration surgery were selected. Reconstruction was performed with a vertical rectus abdominis myocutaneous flap. Primary outcome was flap-related complications (short or long term >3 months). Secondary outcomes were hospital stay, readmission, mortality, and quality of life (Short Form-36, Functional Assessment of Cancer Therapy for patients with colorectal cancer). Of 519 patients undergoing pelvic exenteration surgery, 87 (17%) underwent flap reconstruction. Median follow-up was 20 months (interquartile range, 8-39 months). Median age was 60 years (interquartile range, 51-66). Flap-related complications were found in 59 patients (68%), with minor recipient-site complications diagnosed in 33 patients (38%). In the short term, 15 patients experienced major recipient-site complications (17%), including flap separation (n = 7) and partial (n = 3) or complete necrosis (n = 4). Flap removal was required in 1 patient. Obesity was the single independent risk factor for short-term flap-related complications (p = 0.02). Hospital admission was significantly longer in patients with short-term major flap complications (median 65 days, p < 0.001) compared with patients without or with minor complications. There was no 90-day mortality. Patients who required flap reconstruction reported lower baseline quality-of-life scores than patients without flap reconstruction, but both recovered over time. In the long term, minor flap-related complications occurred in 12 patients, and 11 patients had major donor-site complications. Fourteen patients developed major recipient-site complications (16%), including sacral collections, enterocutaneous fistulas, perineal ulcer, or hernia. This was a retrospective analysis of prospectively collected data. Vertical rectus abdominis myocutaneous flaps in pelvic exenteration surgery have a high incidence of morbidity that has significant impact on hospital stay and a temporary impact on quality of life. Flap reconstruction should be used selectively in pelvic exenteration surgery. See Video Abstract at http://links.lww.com/DCR/B274. COMPLICACIONES E IMPACTO EN LA CALIDAD DE VIDA DE LOS COLGAJOS MIOCUTÁNEOS DE MUSCULO RECTO DEL ABDOMEN EN CASOS DE RECONSTRUCCIÓN DE EXENTERACIÓN PÉLVICA: La exenteración pélvica (EP) para malignidad a veces requiere reconstrucción con colgajos musculares.El propósito del presente estudio fue investigar la morbilidad relacionada con los colagajos musculares.Revisión de una base de datos prospectiva de 2003-2016. Se evaluaron todas las historias clínicas, la correspondencia y los registros de seguimiento de pacientes ambulatorios hasta mayo de 2017.Unidad de referencia terciaria.Todos aquellas personas con cirugía de exenteración pélvica.Reconstrucción con colgajo miocutáneo de musculo recto vertical del abdomen.El resultado primario fueron las complicaciones relacionadas con el colgajo (a corto o largo plazo >3 meses). Los resultados secundarios fueron la estadía hospitalaria, la readmisión, la mortalidad y la calidad de vida (QOL; SF-36, FACT-C).De 519 pacientes sometidos a EP, 87 (17%) se sometieron a reconstrucción con colgajos miocutáneos. La mediana de seguimiento fue de 20 meses (RIC 8-39 meses). La mediana de edad fue de 60 años (IQR 51-66). Se encontraron complicaciones relacionadas con el colgajo en 59 pacientes (68%), con complicaciones menores en el sitio del receptor diagnosticadas en 33 pacientes (38%). A corto plazo, quince pacientes sufrieron complicaciones mayores en el sitio del receptor (17%), incluida la separación del colgajo (n = 7), necrosis parcial (n = 3) o necrosis completa (n = 4). Se requirió la extracción del colgajo en un paciente. La obesidad fue el único factor de riesgo independiente para complicaciones relacionadas con el colgajo a corto plazo (p = 0.02). El ingreso hospitalario fue significativamente mayor en pacientes con complicaciones de colgajos mayores a corto plazo (mediana 65 días p <0.001) en comparación con pacientes sin complicaciones menores o con complicaciones menores. No hubo mortalidad a los 90 días. Los pacientes que requirieron reconstrucción con colgajo informaron puntajes de calidad de vida basales más bajos que los pacientes sin reconstrucción con colgajo, pero ambos se recuperaron con el tiempo. A largo plazo, ocurrieron complicaciones menores relacionadas con el colgajo en 12 pacientes y 11 pacientes tuvieron complicaciones mayores en el sitio donante. Catorce pacientes desarrollaron complicaciones mayores en el sitio del receptor (16%), incluidas colecciones sacras, fístulas enterocutáneas, úlceras perineales o herniación.Análisis retrospectivo de datos recolectados prospectivamente.Los colgajos miocutáneos del musculo recto vertical del abdomen en casos de cirugía de exenteración pélvica tienen una alta incidencia de morbilidad conllevando a un impacto significativo en la estadía hospitalaria y un impacto temporal en la calidad de vida. Las reconstrucciones con colgajos deben aplicarse muy selectivamente en la cirugía de exenteración pélvica. Consulte Video Resumen en http://links.lww.com/DCR/B274.


Efficacy and safety of atropine in myopic children: A meta-analysis of randomized controlled trials.
To evaluate the safety and efficacy of atropine for childhood myopia and further explore the optimal concentration of atropine, so as to provide more reference for clinical application. PubMed, Embase, Cochrane Library and ClinicalTrials.gov were comprehensively searched for randomized controlled trials (RCTs) up to October 14, 2021. The efficacy outcomes were progression of spherical equivalent (SE) and axial length (AL). The safety outcomes included accommodation amplitude, pupil size and adverse effects. The meta-analysis was performed using Review Manager 5.3. Eighteen RCTs involving 3002 eyes were included. The results showed that at 6-36 months of treatment, atropine was effective in slowing the progression of myopia in children. At 12 months, the WMD of SE and AL of low-dose atropine was 0.25 diopters (D) and 0.1 millimeter (mm), moderate-dose atropine was 0.44 D and 0.16mm, high-dose atropine was 1.21 D and 0.82mm, respectively, compared with the control group. Similarly, at 24 months, low-dose atropine was 0.22 D and 0.14mm, moderate-dose atropine was 0.60 D, high-dose atropine was 0.66 D and 0.24mm, respectively. Interestingly, we also found that there was no significant difference in the effects of low-dose atropine on accommodation amplitude and photopic pupil size compared with the control group, and the rate of photophobia, allergy, blurred vision and other side effects was similar between the low-dose atropine group and the control group. In addition, atropine appears to be more effective in myopic children in China than in other countries. Atropine in various concentrations can effectively slow myopia progression in children, and its effect is dose-dependent, while low-dose atropine (0.01% atropine) appears to be safer.


Psychopharmacology in Primary Care Settings.
Psychopharmacology requires clinicians to stay current on the latest guidelines and to use dynamic treatment strategies. Psychiatric conditions are prevalent in the primary care population. Choice of treatment with psychopharmacology should be based on controlling the patient's predominant symptoms while taking into consideration patient age, treatment compliance, patient past response to treatments, dosing frequency, patient preference, medication side effects, potential medication interactions, drug precautions/warnings, and cost. Response to therapy, as well as side effects, needs to be evaluated at regular intervals. The goal is to minimize symptoms and return patients to their maximal level of functioning.


Suppression of experimental allergic encephalomyelitis by MBP-coupled lymphoid cells and by MBP-liposomes: a comparison.
In previous experiments, we showed that administration of myelin basic protein (MBP) inserted into phosphatidyl-serine liposomes, to susceptible animals suppressed the clinical manifestations of both acute and chronic-relapsing EAE. In this report we compare the effectiveness of treatment with MBP-liposomes and with MBP-coupled syngeneic spleen cells in EAE protection. Lewis rats treated with 150 micrograms MBP-liposomes or with 160 micrograms (35 x 10(6] MBP-coupled spleen cells, given 7 days before and 7 days after encephalitogenic challenge were equally protected against clinical EAE, when compared to untreated controls. In addition to clinical protection, in vitro proliferative responses of lymphocytes from treated rats were significantly reduced, but delayed hypersensitivity (DTH) reactions remained unaffected. Proliferation of lymphocytes from MBP-sensitized donors was inhibited by the addition of spleen cells but not of lymph node cells from treated donors. The inhibitory effect was observed with spleen cells regardless of whether the donors were treated or not, was antigen nonspecific, and localized in a radio-resistant, adherent cell population. Adoptive transfers of spleen cells from treated donors, after a 48-hr in vitro incubation with concanavalin A, showed that the cells from donors treated with MBP-coupled spleen cells, but not with MBP-liposomes, suppressed the disease in recipients, following challenge with MBP-complete Freund's adjuvant (CFA). These results suggest that two distinct mechanisms operate in the protection by MBP-coupled cells and MBP-liposomes, respectively.


Synthesis and in vitro cytotoxicity of 3-substituted-1,8-diazaanthraquinones produced by Lewis-acid catalyzed hetero Diels-Alder reaction.
A hetero Diels-Alder reaction of quinoline-5,8-dione with 1-(N,N-dimethylamino)-3-methyl-1-aza-1,3-butadiene proceeded to give 3-methyl-1,8-diazaanthraquinone (100% regioselectivity) in the presence of Lewis-acid catalyst (ZnCl2 or ZnBr2). Subsequent functionalizations of the benzylic methyl group resulted in the 1,8-diazaanthraquinone analogues as potential antitumor agents. The most active compound, 8, exhibited in vitro cytotoxic activity comparable to that of doxorubicin.


Modulation of visual event-related potentials by spatial and non-spatial visual selective attention.
Event-related potentials (ERPs) were recorded in two experiments involving selective visual processing. In Experiment 1, subjects attended to light flashes emanating from one visual field, in order to detect occasional slightly deviant "targets", while ignoring equiprobable stimuli from the opposite field. ERPs elicited by stimuli in an attended field were characterised by larger posteriorly distributed P120 and N170 components, and a larger anteriorly distributed N145 component. In addition, these ERPs were, in comparison to those elicited by unattended stimuli, more negative-going in the latency region of approx. 200-400 msec. This late effect had a marked fronto-central distribution. In Experiment 2 subjects attended to either horizontal or vertical bars, displayed equiprobably in the same spatial location. No enhancement of early components was observed as a function of attention but, as in Experiment 1, a late, sustained, fronto-centrally distributed negative shift was observed in ERPs elicited by "attended" compared to "unattended" stimuli. It was concluded that the enhancement of P120 (P1) observed in Experiment 1 reflects the engagement of attentional mechanisms specific to the selection of stimuli on the basis of spatial cues. The later sustained negative shift seen in both experiments was considered to reflect a feature of within-channel processing common to both spatial and non-spatial selective tasks.


Ethnic and sex disparities in colorectal neoplasia among Hispanic patients undergoing screening colonoscopy.
Colorectal cancer (CRC) has a high prevalence among the US Hispanic population. In Puerto Rico, CRC is the third leading cause of cancer death in men and the second in women. There are limited published data on the prevalence of colorectal neoplasia (CRN) among the US Hispanic population. We determined the prevalence of CRN (colorectal adenomas and cancer) among asymptomatic, Hispanic subjects who were screened in Puerto Rico and evaluated risk factors associated with CRN. We performed a retrospective review of the medical, endoscopic, and pathology records of individuals who underwent first-time screening colonoscopies at an ambulatory gastroenterology practice from January 1, 2008, to December 1, 2009. The prevalence of CRN (overall and advanced), documented by colonoscopy and pathology reports, was calculated for the complete cohort and by sex. Of the 745 Hispanic individuals who underwent screening colonoscopies during the study period, the prevalence for overall CRN was 25.1% and for advanced CRN (≥ 1 cm and/or with advanced histology) was 4.0%. The prevalence of CRN was higher for men than women (32.0% vs 20.6%; P = .001; odds ratio, 1.92; 95% confidence interval, 1.4-2.6). CRN was more frequently located in the proximal colon (67.7% proximal vs 32.3% distal). A family history of CRC was associated with advanced CRN (odds ratio, 2.73; 95% confidence interval, 1.10-6.79). CRN was more common among Hispanic men than women and increased with age. CRNs among Hispanic individuals were predominantly located in the proximal colon. These findings indicate that there are ethnic and sex disparities in patterns of CRN that might be related to genomic admixture and have important implications for screening algorithms for Hispanic individuals.


Low Ouabain Doses and AMP-Activated Protein Kinase as Factors Supporting Electrogenesis in Skeletal Muscle.
Many motor disorders are associated with depolarization of the membrane of skeletal muscle fibers due to the impaired functioning of Na,K-ATPase. Here, we studied the role of ouabain (specific Na,K-ATPase ligand) and AMP-activated protein kinase (key regulator of muscle metabolism) in the maintenance of muscle electrogenesis; the levels of these endogenous factors are directly related to the motor activity. After 4-day intraperitoneal administration of ouabain (1 µg/kg daily), a hyperpolarization of sarcolemma was registered in isolated rat diaphragm muscles due to an increase in the electrogenic activity of Na,K-ATPase. In acute experiments, addition of nanomolar ouabain concentrations to the bathing solution resulted in the muscle membrane hyperpolarization within 15 min. The effect of ouabain reversed to membrane depolarization with the increase in the external potassium concentration. It is possible that Na,K-ATPase activation by ouabain may be regulated by such factors as specific subcellular location, interaction with molecular partners, and changes in the ionic balance. Preventive administration of the AMP-activated protein kinase activator AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside; 400 mg/kg body weight daily for 7 days) in chronic experiments resulted in the stabilization of the endplate structure and abolishment of depolarization of the rat soleus muscle membrane caused by the motor activity cessation. The obtained data can be useful for creating approaches for correction of muscle dysfunction, especially at the early stages, prior to the development of muscle atrophy.


Novel cross-linked polymers having pH-responsive amino acid residues for the removal of Cu2+ from aqueous solution at low concentrations.
Two novel cross-linked anionic polyelectrolytes (CAPE) I and II containing pH-responsive amino acid residues have been synthesized via cycloco- and ter-polymerization of a monomer having diallylammonioethanoate motif (90mol%) and a cross-linker 1,1,4,4-tetraallylpiperazinium dichloride (10mol%) in the absence and presence of SO2 (100mol%), respectively. The experimental data for the adsorption of Cu(2+) on the CAPES fitted Lagergren second-order kinetic model thereby indicating the chemical nature of the adsorption process. The fitness order of Freundlich>Langmuir>Temkin for the isotherm models for CAPE I showed the favorability of adsorption on a heterogeneous surface, whereas for CAPE II the fitness order of Langmuir>Freundlich>Temkin certified the favorability toward monolayer adsorption. The adsorption process was spontaneous and endothermic in nature with negative and positive values for ΔG and ΔH, respectively. For the sorbents CAPE I and CAPE II, the efficiency of Cu(2+) removal at an initial metal concentration of 200ppb was found to be 77.5 and 99.4%, respectively. Desorption efficiencies were found to be 88 and 93% for CAPE I and CAPE II, respectively. Treatment of real wastewater samples spiked with Cu(2+) ions showed the excellent ability of the resins to adsorb metal ions.


5 S RNA-protein complex is involved in ribosomal subunit association.
The immobilized tRNA-50 S ribosomal subunit protein (TP50) complex binds the smaller ribosomal subunit. We constructed tRNA . TP50 . 5 S [32P] RNA and tRNA . TP50 . t [32P] RNA complexes and investigated the accessibility of the 32P-labelled tRNAs to ribonuclease T1. It was found that in this complex both 5 S RNA and tRNA are attacked by T1 RNase. In sharp contrast, the addition of 30 S subunit protects 5 S RNA as well as tRNA from degradation. We suggest that 5 S RNA-TP50 complex is exposed to the ribosomal interface and is involved in subunit interaction.


Epithelial damage beyond the tip of the endotracheal tube.
The effects of ventilator rate and inspired humidity on the large airway epithelium of newborn lambs have been studied using scanning electron microscopy. Significant deciliation, denudation and necrosis occurred at both high and conventional rates if the inspired gas had low humidity. The damage observed was mild in the high humidity groups.


Overexpression of Ipe protein from the coliphage mEp021 induces pleiotropic effects involving haemolysis by HlyE-containing vesicles and cell death.
Lysogenic Escherichia coli K-12 harbouring the prophage mEp021 displays haemolytic activity. From a genomic library of mEp021, we identified an open reading frame (ORF 4) that was responsible for the haemolytic activity. However, the ORF 4 sequence contains four initiation codons in the same frame: ORF 4.1-ORF 4.4, coding for 83-a.a., 82-a.a., 77-a.a. and 72-a.a. products, respectively. The expression of the cloned ORF 4.3, or inducer of pleiotropic effects (ipe), reproduced the haemolytic phenotype in a native strain carrying the gene hlyE(+), but not in the mutant hlyE(-) strain. The overexpression of Ipe induced several pleiotropic effects, such as the inhibition of cell growth and the deregulation of cell division, which resulted in a mixture of normal and desiccated-like cells: normal-filamentous, desiccated-like-filamentous bacilli, minicells etc. Other effects included abnormalities of the cell membrane, the production of vesicles containing HlyE, and finally, cell death. These events were analysed at the molecular level by microarray assays. The global transcription profile of E. coli K-12 strain MC4100, which expressed Ipe after 4 h, revealed differential expression of various genes, most of which were related either to cell membrane and murein biosynthesis or to cell division. The up-regulation of some of these transcripts was confirmed by qRT-PCR. Additional research is needed to determine whether these effects are directly related to Ipe activity or are consequences of the cellular responses to putative structural damage induced by Ipe.


Selective destruction of abnormal proteins by ubiquitin-mediated protein quality control degradation.
Misfolded proteins are continuously produced in the cell and present an escalating detriment to cellular physiology if not managed effectively. As such, all organisms have evolved mechanisms to address misfolded proteins. One primary way eukaryotic cells handle the complication of misfolded proteins is by destroying them through the ubiquitin-proteasome system. To do this, eukaryotes possess specialized ubiquitin-protein ligases that have the capacity to recognize misfolded proteins over normally folded proteins. The strategies used by these Protein Quality Control (PQC) ligases to target the wide variety of misfolded proteins in the cell will likely be different than those used by ubiquitin-protein ligases that function in regulated degradation to target normally folded proteins. In this review, we highlight what is known about how misfolded proteins are recognized by PQC ubiquitin-protein ligases.


Biological decomposition efficiency in different woodland soils.
The decomposition (meaning disappearance) of different leaf types and artificial leaves made from cellulose hydrate foil was studied in three forests - an alluvial forest (Ulmetum), a beech forest on limestone soil (Melico-Fagetum), and a spruce forest in soil overlying limestone bedrock.Fine, medium, and coarse mesh litter bags of special design were used to investigate the roles of abiotic factors, microorganisms, and meso- and macrofauna in effecting decomposition in the three habitats. Additionally, the experimental design was carefully arranged so as to provide information about the effects on decomposition processes of the duration of exposure and the date or moment of exposure. 1. Exposure of litter samples oor 12 months showed: a) Litter enclosed in fine mesh bags decomposed to some 40-44% of the initial amount placed in each of the three forests. Most of this decomposition can be attributed to abiotic factors and microoganisms. b) Litter placed in medium mesh litter bags reduced by ca. 60% in alluvial forest, ca. 50% in beech forest and ca. 44% in spruce forest. c) Litter enclosed in coarse mesh litter bags was reduced by 71% of the initial weights exposed in alluvial and beech forests; in the spruce forest decomposition was no greater than observed with fine and medium mesh litter bags. Clearly, in spruce forest the macrofauna has little or no part to play in effecting decomposition. 2. Sequential month by month exposure of hazel leaves and cellulose hydrate foil in coarse mesh litter bags in all three forests showed that one month of exposure led to only slight material losses, they did occur smallest between March and May, and largest between June and October/November. 3. Coarse mesh litter bags containing either hazel or artificial leaves of cellulose hydrate foil were exposed to natural decomposition processes in December 1977 and subsampled monthly over a period of one year, this series constituted the From-sequence of experiments. Each of the From-sequence samples removed was immediately replaced by a fresh litter bag which was left in place until December 1978, this series constituted the To-sequence of experiments. The results arising from the designated From- and To-sequences showed: a) During the course of one year hazel leaves decomposed completely in alluvial forest, almost completely in beech forest but to only 50% of the initial value in spruce forest. b) Duration of exposure and not the date of exposure is the major controlling influence on decomposition in alluvial forest, a characteristic reflected in the mirror-image courses of the From- and To-sequences curves with respect to the abscissa or time axis. Conversely the date of exposure and not the duration of exposure is the major controlling influence on decomposition in the spruce forest, a characteristic reflected in the mirror-image courses of the From-and To-sequences with respect to the ordinate or axis of percentage decomposition. c) Leaf powder amendment increased the decomposition rate of the hazel and cellulose hydrate leaves in the spruce forest but had no significant effect on their decomposition rate in alluvial and beech forests. It is concluded from this, and other evidence, that litter amendment by leaf fragments of phytophage frass in sites of low biological decomposition activity (eg. spruce) enhances decomposition processes. d) The time course of hazel leaf decomposition in both alluvial and beech forest is sigmoidal. Three s-phases are distinguished and correspond to the activity of microflora/microfauna, mesofauna/macrofauna, and then microflora/microfauna again. In general, the sigmoidal pattern of the curve can be considered valid for all decomposition processes occurring in terrestrial situations. It is contended that no decomposition (=disappearance) curve actually follows an e-type exponential function. A logarithmic linear regression can be constructed from the sigmoid curve data and although this facilitates inter-system comparisons it does not clearly express the dynamics of decomposition. 4. The course of the curve constructed from information about the standard deviations of means derived from the From- and To-sequence data does reflect the dynamics of litter decomposition. The three s-phases can be recognised and by comparing the actual From-sequence deviation curve with a mirror inversion representation of the To-sequence curve it is possible to determine whether decomposition is primarily controlled by the duration of exposure or the date of exposure. As is the case for hazel leaf decomposition in beech forest intermediate conditions can be readily recognised.


Clinical Outcomes with GLP-1 Receptor Agonists in Patients with Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, there remains uncertainty about the efficiency of GLP-1 RAs in patients with heart failure (HF). Randomized placebo-controlled trials (RCTs) that reported the effect of GLP-1 RAs on prognosis in patients with HF were identified by searching databases. The primary outcome was defined as MACE. Trail Sequential Analysis (TSA) was used to evaluate the reality and authenticity. Nine RCTs involving 8920 patients with HF were included. GLP-1 RAs significantly reduced the risk of MACE compared with placebo (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.77-0.98) in HF coexisting with T2DM. The benefit was not observed in all-cause death (HR 0.99, 95% CI 0.84-1.15), hospitalization for heart failure (HR 1.04, 95% CI 0.89-1.22), cardiovascular death (HR 0.95, 95% CI 0.79-1.16), myocardial infarction (HR 0.88, 95% CI 0.71-1.08), stroke (HR 1.03, 95% CI 0.75-1.43) and death or hospitalization for HF (HR 1.07, 95% CI 0.78-1.46). GLP-1 RAs did not improve the change in LVEF (mean difference [MD]): - 0.86, p = 0.12, left-ventricular end-diastolic volume (LVEDV) (MD: 3.54, p = 0.11), left-ventricular end-systolic volume (LVESV) (MD: 2.78, p = 0.07) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD: - 140.36, p = 0.08). However, GLP-1 RAs significantly increased the change in the 6-min walk test (MWT) distance (MD: 19.74, p = 0.002). In the subgroup analyses, human GLP-1 RAs, but not nonhuman GLP-1 RAs, reduced the risk of MACE in patients with HF (p interaction = 0.11). Grading of Recommendations Assessment, Development and Evaluation (GRADE) showed moderate certainty for MACE, all-cause death and hospitalization for HF. Trail Sequential Analysis revealed that there may be a high possibility of false positive results for MACE. Compared with placebo, GLP-1 RAs may reduce the risk of MACE in patients with HF coexisting with T2DM, with a more significant efficiency of human GLP-1 RAs. More RCTs are needed to assess the cardiovascular benefits of GLP-1 RAs in HF, regardless of T2DM. The protocol for this meta-analysis is registered on PROSPERO [CRD42022357886].


Tumor suppressive miR-509-5p contributes to cell migration, proliferation and antiapoptosis in renal cell carcinoma.
The aim of this study was to determine the expression and function of miR-509-5p in renal cell carcinoma (RCC). In this research, we have conducted quantitative real-time polymerase chain reaction (qRT-PCR) assay to determine the expression level of miR-509-5p in tissues and plasma from renal cell carcinoma patients. We preformed in vitro migration scratch assay, flow cytometry analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine the exact function of miR-509-5p. We evaluated the expression level of miR-509-5p in RCC tissues and paired adjacent normal tissues from 42 patients and found that miR-509-5p expression in 42 RCC specimens was significantly down-regulated compared to that in adjacent normal tissue. Furthermore, the level of miR-509-5p in RCC patients' plasma was significantly lower than that in control plasma. In addition, the overexpression of miR-509-5p suppressed the proliferation of RCC cell (786-0), induced cell apoptosis and inhibited cell migration in vitro. In this study, we have shown that miR-509-5p played an important role in RCC by inhibiting cell proliferation and migration and by promoting cell apoptosis. In addition, miR-509-5p expression was significantly lower in RCC patient plasma compared to that in normal individuals.


ZnO nanoparticles induce apoptosis in human dermal fibroblasts via p53 and p38 pathways.
The production of engineered nanoparticles is growing rapidly as the field of nanotechnology continues to expand. Zinc oxide nanoparticles (ZnO NPs) are used in various applications, including catalysis, electronics, biosensors, medicine, paints, sunscreens and cosmetics, thus it is important to understand the biological effects and risks of ZnO NPs. This study was designed to investigate the apoptosis induction by ZnO NPs via mitogen-activated protein kinase p38 and cell cycle checkpoint protein p53 pathways in human dermal fibroblasts. MTT-based cell viability assay showed a significant decrease in cell survivorship after ZnO NP exposure, and phase contrast images revealed that ZnO NP treated cells had lower density and a rounded morphology. Apoptosis induction was confirmed by the annexin V assay and Western blot analysis showed the up-regulation of p53 and phospho-p38 proteins. Furthermore, in ZnO NP exposed cells, p53 protein was phosphorylated at Ser33 and Ser46 sites known to be phosphorylated by p38. Our results suggest that ZnO NPs have the potential to induce apoptosis in human dermal fibroblasts via p53-p38 pathways.


Transcriptional changes of Pacific oyster Crassostrea gigas reveal essential role of calcium signal pathway in response to CO2-driven acidification.
There is increasing evidence that ocean acidification (OA) has a significant impact on marine organisms. However, the ability of most marine organisms to acclimate to OA and the underlying mechanisms are still not well understood. In the present study, whole transcriptome analysis was performed to compare the impacts of short- (7 days, named as short group) and long- (60 days, named as long group) term CO2 exposure (pH 7.50) on Pacific oyster Crassostrea gigas. The responses of C. gigas to short- and long-term CO2 exposure shared common mechanisms in metabolism, membrane-associated transportation and binding processes. Long-term CO2 exposure induced significant expression of genes involved in DNA or RNA binding, indicating the activated transcription after long-term CO2 exposure. Oysters in the short-term group underwent significant intracellular calcium variation and oxidative stress. In contrast, the intracellular calcium, ROS level in hemocytes and H2O2 in serum recovered to normal levels after long-term CO2 exposure, suggesting the compensation of physiological status and mutual interplay between calcium and oxidative level. The compensation was supported by the up-regulation of a series of calcium binding proteins (CBPs) and calmodulins (CaMs) related signal pathway. The results provided valuable information to understand the molecular mechanism underlying the responses of Pacific oyster to the acidified ocean and might have implications for predicting the possible effects of global climate changes on oyster aquaculture.


Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ERα/ERβ balance in female mice.
Aging is among the major causes for the lack of cardiovascular protection by estrogen (E2) during postmenopause. Our study aims to determine the mechanisms whereby aging changes E2 effects on nitric oxide (NO) production in a mouse model of accelerated senescence (SAM). Although we found no differences on NO production in females SAM prone (SAMP, aged) compared to SAM resistant (SAMR, young), by either DAF-2 fluorescence or plasmatic nitrite/nitrate (NO2/NO3), in both cases, E2 treatment increased NO production in SAMR but had no effect in SAMP. Those results are in agreement with changes of eNOS protein and gene expression. E2 up-regulated eNOS expression in SAMR but not in SAMP. E2 is also known to increase NO by decreasing its catabolism by superoxide anion (O(2)(-)). Interestingly, E2 treatment decreased O(2)(-) production in young females, while increased O(2)(-) in aged ones. Furthermore, we observed that aging changed expression ratio of estrogen receptors (ERβ/ERα) and levels of DNA methylation. Increased ratio ERβ/ERα in aged females is associated to a lack of estrogen modulation of NO production and with a reversal in its antioxidant effect to a pro-oxidant profile. Together, our data suggest that aging has detrimental effects on E2-mediated benefits on NO bioavailability, partially by affecting the ability of E2 to induce up regulation of eNOS and decrease of O(2)(-). These modifications may be associated to aging-mediated modifications on global DNA methylation status, but not to a specific methylation at 5'flanking region of ERα gene.


Blood volume measurement using cardiovascular magnetic resonance and ferumoxytol: preclinical validation.
The hallmark of heart failure is increased blood volume. Quantitative blood volume measures are not conveniently available and are not tested in heart failure management. We assess ferumoxytol, a marketed parenteral iron supplement having a long intravascular half-life, to measure the blood volume with cardiovascular magnetic resonance (CMR). Swine were administered 0.7 mg/kg ferumoxytol and blood pool T1 was measured repeatedly for an hour to characterize contrast agent extraction and subsequent effect on Vblood estimates. We compared CMR blood volume with a standard carbon monoxide rebreathing method. We then evaluated three abbreviated acquisition protocols for bias and precision. Mean plasma volume estimated by ferumoxytol was 61.9 ± 4.3 ml/kg. After adjustment for hematocrit the resultant mean blood volume was 88.1 ± 9.4 ml/kg, which agreed with carbon monoxide measures (91.1 ± 18.9 ml/kg). Repeated measurements yielded a coefficient of variation of 6.9%, and Bland-Altman repeatability coefficient of 14%. The blood volume estimates with abbreviated protocols yielded small biases (mean differences between 0.01-0.06 L) and strong correlations (r2 between 0.97-0.99) to the reference values indicating clinical feasibility. In this swine model, ferumoxytol CMR accurately measures plasma volume, and with correction for hematocrit, blood volume. Abbreviated protocols can be added to diagnostic CMR examination for heart failure within 8 min.


Noninvasive Optical Monitoring of Bladder Filling to Capacity Using a Wireless Near Infrared Spectroscopy Device.
Lack of bladder fullness sensation is an issue that arises in different neurogenic conditions and in addition to influencing patients' quality of life, can result in serious kidney damage. We describe a wireless wearable sensor for detecting bladder fullness using near infrared spectroscopy (NIRS). The sensor has been tested in vitro and in vivo to verify its feasibility and is shown to be capable of detecting changes in bladder content noninvasively.


A Case Report of Kidney After Heart Transplant in Patient With Fabry Disease.
Fabry disease is an X-linked inherited lysosomal storage disorder caused by a mutation in the gene encoding the enzyme α-galactosidase A. It is characterized by the accumulation of globotriaosylceramide in different tissues, resulting in a wide range of clinical presentations. Fabry cardiomyopathy and Fabry nephropathy are the disease's 2 most important life-threatening manifestations and can contribute to higher morbidity and mortality. Heart and kidney transplants can play a major role in patients with Fabry disease who develop end organ damage. We report a case of a successful heart transplant in a male patient with Fabry disease at the age of 62, followed by a kidney transplant later at the age of 69. He has had an uneventful post-transplant course and has been tolerating maintenance immunosuppression and enzyme replacement therapy with recombinant human α-galactosidase A.


[Diagnosis of intraabdominal abscesses by the ultrasound echo technique (author's transl)].
The diagnosis of abdominal abscesses with diagnostic methods generally used up to the present has not proved to be accurate and reliable. The authors give an account of their experience with a new ultrasound echo technique. By employing this technique, abdominal abscesses and effusions can be visualized with accuracy and their size can also be measured. From the examinations performed in 21 patients, 20 gave an accurate diagnosis and there was only one case presenting a false positive result. The authors emphasize the accuracy of this method and its non-invasive character as well.


The effect and mode of action of zinc pyrithione on cell growth. I. In vitro studies.
The effects of zinc pyrithione (ZnPTO) were studied in a series of in vitro tests to determine whether its mode of action is primarily cytostatic or cytotoxic. Sodium pyrithione (NaPTO) was also studied, to check that pyrithione was the active moiety, and the known cytostatic chemical hydroxyurea was included for comparison. ZnPTO had a reversible inhibitory effect on the growth of BHK 21 cells at 0.1 microgram/ml, but had a rapid, irreversible inhibitory effect at 1 microgram/ml associated with cell rounding and detachment. NaPTO produced a similar effect but hydroxyurea produced an essentially reversible inhibition even at a dose well above that producing complete inhibition. ZnPTO and NaPTO both caused contraction, rounding and blebbing of BHK 21 cells in perfusion-chamber tests, at higher levels (1 and 10 micrograms/ml) than required for growth inhibition, but only 10 micrograms ZnPTO/ml caused lactate dehydrogenase (LDH) release. Hydroxyurea had no effects in these tests. ZnPTO and NaPTO also reduced the survival of Chinese hamster V79 cells sharply over a narrow dose range (0.01-0.03 microgram/ml), but the effect of hydroxyurea was not as sharp and occurred at much higher doses. All three showed elements of cytostasis and cytotoxicity as demonstrated by analysis of the relationship between survival and colony area. Of the three, only ZnPTO (at greater than or equal to 5 micrograms/ml) caused significant LDH release from the cells, though both ZnPTO and NaPTO (at 0.1-1 microgram/ml) inhibited cell growth as indicated by total LDH values. In studies with rat peritoneal mast cells, ZnPTO and NaPTO (at 10 ng/ml) both suppressed histamine release induced by 48/80 or Ca ionophore A23187, though neither caused histamine release directly. The combined results of these tests show that ZnPTO is primarily cytotoxic, rather than cytostatic.


Sternal resection and reconstruction for primary malignant tumors.
Primary malignant sternal tumors (PMST) are locally aggressive and their optimal surgical management still continues to evolve. From 1986 to 2002, 38 patients (25 females/13 males) underwent radical resection of PMST. This series included 33 sarcomas, 17 of which had been radiation-induced, 3 hematologic tumors, and 2 carcinomas. Seventeen were high-grade tumors. Nine patients had received preoperative chemotherapy. Twelve patients required extensive skin excision. Eight total, seven subtotal, and 23 partial sternectomies were performed. Resection was extended to the anterior chest-wall in 4 patients, lung in 4, brachiocephalic vein in 3, superior vena cava in 2, and pericardium in 1. In 36 patients, chest wall stability was obtained by Marlex (n = 21) or Vicryl (n = 2) mesh and polytetrafluoroethylene patch (n = 13), with methylmethacrylate reinforcement in 12 patients. Soft tissue coverage was done by the pectoralis major muscles with skin advancement in 25 patients, a myocutaneous flap in 11, a breast transposition in 1, and a skin flap in 1. Omentoplasty was performed in 3 patients. One patient died from pneumonia. Two patients needed a tracheostomy after total sternectomy. No flap-related complication was observed. Four local septic complications required removal of the composite prosthesis with reoperations. Local recurrence occurred in 9 patients, 7 patients having a repeat resection. Metastases developed in eight. The 5-year overall and disease-free survival was 66% and 53%, respectively. The histologic grade of sarcomas was a survival predictor (high grade versus others p = 0.035). Wide resection of PMST is necessary to minimize local recurrence. Large sternal defects are safely reconstructed with a musculocutaneous flap. We suggest that the use of methylmethacrylate should be limited to reconstruction after total sternectomy.


Characterization of bioconversion of fumarate to succinate by alginate immobilized Enterococcus faecalis RKY1.
In this study, the immobilization characteristics of Enterococcus faecalis RKY1 for succinate production were examined. At first, three natural polymers--agar, kappa-carrageenan, and sodium alginate--were tried as immobilizing matrices. Among these, sodium alginate was selected as the best gel for immobilization of E. faecalis RKY1. Efficient conditions for immobilization were established to be with a 2% (w/v) sodium alginate solution and 2-mm-diameter bead. The bioconversion characteristics of the immobilized cells at various pH values and temperatures were examined and compared with those of free cells. The optimum pH and temperature of the immobilized cells were the same as for free cells, 7.0 and 38 degrees C respectively, but the conversion ratio was higher by immobilization for all the other pH and temperature conditions tested. When the seed volume of the immobilized cells was adjusted to 10% (v/v), 30 g/L of fumarate was completely converted to succinate (0.973 g/g conversion ratio) after 12 h. In addition, the immobilized cells maintained a conversion ratio of >0.95 g/g during 4 wk of storage at 4 degrees C in a 2% (w/v) CaCl2 solution. In repetitive bioconversion experiments, the activity of the immobilized cells decreased linearly according to the number of times of reuse.


Extracellular matrix in synovium development, homeostasis and arthritis disease.
Extracellular matrix (ECM) is a three-dimensional network entity composed of extracellular macromolecules. ECM in synovium not only supports the structural integrity of synovium, but also plays a crucial role in regulating homeostasis and damage repair response in synovium. Obvious disorders in the composition, behavior and function of synovial ECM will lead to the occurrence and development of arthritis diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and psoriatic arthritis (PsA). Based on the importance of synovial ECM, targeted regulation of the composition and structure of ECM is considered to be an effective measure for the treatment of arthritis disease. This paper reviews the current research status of synovial ECM biology, discusses the role and mechanism of synovial ECM in physiological status and arthritis disease, and summarizes the current strategies for targeting synovial ECM to provide information for the pathogenesis, diagnosis and treatment of arthritis disease.


Therapeutic experience with the new dopamine agonist CU 32-085 in advanced Parkinson's disease.
Twenty patients with advanced progressing Parkinson's disease have been treated with the 8-alpha-ergoline CU 32-085 in combination therapy for 3 months. With a mean daily dose of 12.65 mg, CU 32-085 together with levodopa plus a decarboxylase inhibitor produced a significant reduction in akinesia, rigor and tremor. Adverse reactions were rare and mild; in one case the drug was discontinued because of dyskinetic movements. Many of the pre-existing side effects were reduced or eliminated, particularly the involuntary movements and the levodopa response swings. The compound was considered useful in the treatment of advanced, progressing Parkinson's disease.


Vitamin D Status in Pediatric and Young Adult Cystic Fibrosis Patients. Are the New Recommendations Effective?
In recent years, guidelines for vitamin D supplementation have been updated and prophylactic recommended doses have been increased in patients with cystic fibrosis (CF). To evaluate safety and efficacy of these new recommendations. Two cohorts of pancreatic insufficient CF patients were compared before (cohort 1: 179 patients) and after (cohort 2: 71 patients) American CF Foundation and European CF Society recommendations were published. Cohort 2 patients received higher Vitamin D doses: 1509 (1306-1711 95% CI) vs 1084 (983-1184 95% CI) IU/Day (p < 0.001), had higher 25 OH vitamin D levels: 30.6 (27.9-33.26 95% CI) vs. 27.4 (25.9-28.8 95% CI) ng/mL (p = 0.028), and had a lower prevalence of insufficient vitamin D levels (<30 ng/mL): 48% vs 65% (p = 0.011). Adjusted by confounding factors, patients in cohort 1 had a higher risk of vitamin D insufficiency: OR 2.23 (1.09-4.57 95% CI) (p = 0.028). After the implementation of new guidelines, CF patients received higher doses of vitamin D and a risk of vitamin D insufficiency decreased. Despite this, almost a third of CF patients still do not reach sufficient serum calcidiol levels.


Establishment and characterization of a new human bladder cancer cell line showing features of squamous and glandular differentiation.
Tumour-cell heterogeneity has been studied in a continuous cell line, UCRU-BL-17CL, established from a xenografted human primary bladder carcinoma. The cell line, grown in vitro for more than 30 generations, reflects the pathology of both the xenograft from which it was derived and the original human tumour. It comprises mainly adenocarcinoma cells which secrete mucin in vitro, as well as squamous and transitional carcinoma cells. Features of both adenocarcinomatous and squamous differentiation have been observed within the same cell. The line expresses ABH blood group isoantigens, binds to peanut lectin and reacts with monoclonal antibodies (MAbs) raised against keratin and against normal and malignant epithelial cells. It also reacts with MAbs against ras p21 proteins and the epidermal growth factor receptor (EGFR). It shows high levels of lactic acid dehydrogenase isozyme 5, consistent with a high-grade tumour, forms colonies in methylcellulose and is tumorigenic in nude mice. The karyotype (human) shows many marker chromosomes, consistent with expression of EGF receptors and ras p21 proteins, and an 11:13 translocation. DNA content, as studied by flow cytometry, reveals a shift from tetraploid to near triploid. This line may provide a useful model for studies of the histogenesis of bladder cancer and the relationship between transitional-cell carcinoma and the other histological subtypes of this disease.


Resection of an intracardiac metastasis from malignant teratoma of the testis.
Nonseminomatous germ cell testicular neoplasm is a disease cured primarily by platinum-based combination chemotherapy. Operation is reserved for those patients who continue to harbor residual masses after chemotherapy. Locoregional lymph nodes and lungs are common sites for residual deposits. Intracardiac metastases are very rare. We report a case of successful resection of bilateral lung and single intracardiac secondary deposits from a malignant teratoma, treated by orchidectomy 6 years previously.


Evaluation of stool GeneXpert MTB/RIF for the diagnosis of pulmonary tuberculosis among presumptive patients in Tanzania.
Diagnosis of pulmonary tuberculosis remains grim, especially in resource-limited settings. Low quality of sputum, particularly among seriously ill, HIV/AIDS, and pediatric patients might result in missing the diagnosis. This study evaluated the performance of GeneXpert MTB/RIF for the detection of pulmonary tuberculosis on stool specimens as an alternative to respiratory specimens. A cross-sectional study design was used to evaluate the performance of GeneXpert MTB/RIF to detect TB in stool specimens from presumptive TB patients. Sputum culture on Lowenstein-Jensen media was used as the gold standard. Recruitment of patients into the study was conducted in 12 selected health facilities in Tanzania. Two sputa and a stool specimen were collected from each study participant. Both sputa and stool samples were tested at their respective study sites of collection using GeneXpert, and their respective portions shipped to the Central Tuberculosis Reference Laboratory for testing by stool GeneXpert and sputum culture in the LJ media. Statistical analysis was performed using STATA software version 14.1. A total of 590 presumptive tuberculosis patients were enrolled in this study. Their median age was 35 years (IQR = 21-47 years). More than half (57.5%, n = 339) of the study participants, were males. Children aged below 15 years constituted 17.6% (n = 104) of the study participants. A total of 75 tuberculosis cases were detected by sputum culture. The sensitivity and specificity of Stool GeneXpert conducted at CTRL was 84% (95% CI: 81.0-87.0%), and 93.4% (CI: 98.5-99.9%) respectively. The overall sensitivity and specificity of stool GeneXpert at the peripheral laboratories was 63.0% (95% CI: 47.8-76.1) and 76.7% (95% CI: 72.1-81.4), respectively. Findings from this study suggest that stool is a potential alternative to respiratory specimen for use in routine diagnosis of tuberculosis, especially when obtaining a respiratory specimen is challenging.


Deformed optic chiasm and colloid cyst in a patient with visual disturbances.
Colloid cysts of the third ventricle are rare intracranial lesions which comprise 0.5 to 1% of all intracranial tumors. We describe a patient with a third ventricle colloid cyst who presented with non specific visual deterioration.


Low-Profile Induced-Voltage Distance Ranger for Smart Contact Lenses.
In this paper, we present a novel, low-profile, scleral-coil based, distance ranging system which is suitable for smart, accommodating contact lenses. We measure the induced emf between a set of four thin semi-circular coils patterned on flexible Kapton substrates that conform to the eyes' sclera. This induced emf is a function of eye gaze angles. The system then determines the distance from the eyes to the desired object via the triangulation of these eye gaze angles Results: Experiments on eyeball simulated tissue gels indicate an accurate prediction of object distance in the 0.1-15 D range with a 0.15 D RMS error and object direction in the -15 to 15-degree arc with 0.4-degree RMS error, respectively. The energy required was determined to be as low as 20 μJ per range reading. Experimental data shows that our proposed new method of eye-tracking and distance ranging system can accurately predict eye-gaze angles and object-distance, whilst using only 20 μJ per range reading. The high-accuracy, low-profile and reduced energy requirements of the proposed eye-tracking technique, make it suitable for applications in the vast field of adaptive optics such as smart contact lenses and other low-power vision corrective applications.


Functional movements of putative jaw muscle insertions.
The craniomandibular muscles control jaw position and forces at the teeth and temporomandibular joints, but little is known regarding their biomechanical behaviour during dynamic function. The objective of this study was to determine how jaw muscle insertions alter position during different jaw movements in living subjects. Computer 3D reconstruction of MR images and jaw-tracking were combined to permit the examination of movement with six degrees of freedom. Maximum mandibular opening, protrusive and laterotrusive positions were recorded in four subjects, and the translation and rotation of the putative insertions of masseter, temporal, medial, and lateral pterygoid muscles were measured. The sizes and shapes of regional attachments varied markedly among subjects, and their displacement patterns were different in specific muscles. For instance, when the jaw closed to the dental intercuspal position from maximum gape, the region near the superior insertion site of the masseter moved backward and upward, whereas the region near the inferior insertion site displaced mainly forward. In three subjects, the jaw's rotational center during this act was approximately 26-34 mm below the mandibular condyles. Since the movements of each muscle part differ according to variations in the size and shape of insertion areas, individual musculoskeletal form, and patterns of jaw motion during function, the prediction of motion-related muscle mechanics in any one subject is unlikely to be possible without direct measurement of the motion of visualized muscle parts. The present study shows that this information can be obtained.


Effect of task complexity on motor and cognitive preparatory brain activities.
In the present study, we investigated scalp-recorded activities of motor and cognitive preparation preceding stimulus presentation in relatively simple and complex visual motor discriminative response tasks (DRTs). Targets and non-targets were presented (with equal probability) in both tasks, and the complexity of the task depended on the discrimination and categorization processing load, which was based on the number of stimuli used (two stimuli in the simple- and four in the complex-DRT, respectively). We recorded event-related potentials (ERPs) in 16 participants in simple-DRT and 16 participants in complex-DRT. At the behavioral level, the performance was faster and more accurate in simple-DRT. Two pre-stimulus ERPs were considered: the central Bereitschaftspotential (BP) and the prefrontal negativity (pN). Both components showed earlier onset and larger amplitude in the complex-DRT. Overall, the simple-DRT required less motor and cognitive preparation in premotor and prefrontal areas compared to the complex-DRT. Present findings also suggest that the pN component was not reported in previous studies, likely because most ERP literature focusing on pre-stimulus ERP used simple-DRTs, and with such a task the pN amplitude is small and can easily go undetected.


X-ray beam angulation can compromise 2-dimensional diagnosis of interradicular space for mini-implants.
The aim of this research was to evaluate the influence of x-ray projection geometry on interradicular space of the posterior maxillary arch. Cone-beam computed tomography (CBCT) scans of 32 patients (16.85 ± 4.93 years) who met the selection criteria were enrolled. One hundred ninety-two interradicular sites of the posterior maxillary arch were evaluated. Before measurements, each side of the maxillary arch was orientated in all 3 planes of space to obtain CBCT synthesized periapical radiographs with 0° projection geometry (orthogonal x-ray beam-orthogonal X-ray angulation [OX]). Standardized CBCT axial rotations (10°, 20°, -10°, and -20°) were used to simulate periapical radiographs taken with mesial and distal angulation of the x-ray beam (mesial x-ray angulation [MX] and distal x-ray angulation [DX]). Interradicular space widths were measured on OX, MX, and DX CBCT synthesized periapical radiographs. Measurements were performed parallel to the occlusal plane at 3 mm and 6 mm apical to the midpoint of the alveolar crest. Interradicular distances were statistically compared (P <0.05). Interradicular distances measured on MX and DX CBCT synthesized periapical radiographs were significantly smaller than those measured on OX. Interradicular distance was significantly correlated with the horizontal angulation of the x-ray beam. X-ray projection angle was the most influential variable on interradicular distance. About 30% reduction in interradicular space was observed for every 10° of deviation from orthogonal x-ray. Two-dimensional radiographs obtained away from the 0° projection geometry can reduce the actual interradicular space for mini-implants, inducing misdiagnosis.


Multilocus sequence typing of pathogenic Mycoplasma mycoides subsp. capri reveals the predominance of a novel clonal complex among isolates from goats in India.
Mycoplasma mycoides subsp. capri (Mmc) typically causes pneumonia, mastitis, arthritis, keratitis and septicaemia in goats. Mortality associated with Mmc in goat flocks is lower compared to Mycoplasma capricolum subsp. capripneumoniae-associated respiratory infections. Case fatality rates associated with Mmc ranged from 9.8 to 26.8% among several states in India. Molecular epidemiology approaches aimed at genotyping help to identify the diversity of isolates involved in a disease. Ten clinical pathogenic Mmc isolates were analysed by multilocus sequence typing (MLST) for studying genotypic relationships with 50 isolates available from public databases. The MLST analysis indicates high genetic diversity among Mmc isolates. From a total number of 60 isolates, 43 six sequence types (STs) were recognized comprising of six STs from India and 37 STs from other geographical regions. MLST profiles of isolates revealed none of the STs observed in Indian isolates were shared with global isolates. Some of the STs representing Indian isolates (four STs) were clustered into a novel clonal complex 1 (CC1). Maintenance of genetically related STs forming CCs among the goat population in India for longer periods indicates disease causing potentiality of these isolates. Based on various recombination analysis, weak clonal relationship among Mmc isolates were identified. The present study has enlightened further steps in disease investigations and to design future control measures by employing prevalent genotypes as vaccine candidates against Mmc infections.


A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer.
The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. Tumour sections were stained for HER2, CD34, and MIB-1. HER2 scores were based on staining intensity, 3+ being considered HER2+. Angiogenesis was scored by the Chalkley method. MIB-1 was evaluated using systematic random sampling. PAI-1 was measured by ELISA. TP53 mutations were evaluated by DGGE analysis and DNA sequencing. Ninety one patients (22%) were HER2 positive. TP53 was mutated in 101 cases (25%). Median PAI-1, Chalkley and MIB-1 was 0.72 ng/mg protein (range, 0-90 ng/mg protein), 5.00 (range, 2.67-12.00) and 15% (range, 1-83%). MIB-1 was correlated with HER2+, Chalkley counts, TP53 mutations (all p <0.0001), and PAI-1 (p =0.002). In univariate analyses with DSS as endpoint, HER2+ (p <0.0001), mutated TP53 (p <0.0001), high Chalkley (p =0.008), MIB-1 (p =0.002), tumour size (p =0.008), grade (p <0.0001), negative estrogen receptor (p =0.0001), and lymph node status (p <0.0001) were prognostic markers. Among node-negative patients, HER2+ (p =0.0002), mutated TP53 (p =0.001), high PAI-1 levels (p =0.02), and grade (p =0.03) indicated poor DSS. In node-positive patients, HER2+ (p =0.0002), mutated TP53 (p <0.0001), MIB-1 (p =0.01), Chalkley scores (p =0.007), negative estrogen receptor (p <0.0001) and grade (p =0.001) indicated poor prognosis. In multivariate analysis, metastatic nodes (1-3 positive: RR 1.56 95% CI 1.02-2.38; >3 positive: RR 3.70 95% CI 2.54-5.38), HER2+ (RR 1.91, 95% CI 1.35-2.70), mutated TP53 (RR 1.70, 95% CI 1.21-2.38), PAI-1 (RR 1.04, 95% CI 1.01-1.07) and grade 3 (RR 1.96, 95% CI 1.83-3.22) were independent markers of poor outcome. Compared to PAI-1 protein levels, Chalkley counts and MIB-1, HER2+ and mutations of TP53 were the strongest independent markers of poor prognosis irrespective of nodal status.


Stokes meta-hologram toward optical cryptography.
Optical cryptography manifests itself a powerful platform for information security, which involves encrypting secret images into visual patterns. Recently, encryption schemes demonstrated on metasurface platform have revolutionized optical cryptography, as the versatile design concept allows for unrestrained creativity. Despite rapid progresses, most efforts focus on the functionalities of cryptography rather than addressing performance issues, such as deep security, information capacity, and reconstruction quality. Here, we develop an optical encryption scheme by integrating visual cryptography with metasurface-assisted pattern masking, referred to as Stokes meta-hologram. Based on spatially structured polarization pattern masking, Stokes meta-hologram allows multichannel vectorial encryption to mask multiple secret images into unrecognizable visual patterns, and retrieve them following Stokes vector analysis. Further, an asymmetric encryption scheme based on Stokes vector rotation transformation is proposed to settle the inherent problem of the need to share the key in symmetric encryption. Our results show that Stokes meta-hologram can achieve optical cryptography with effectively improved security, and thereby paves a promising pathway toward optical and quantum security, optical communications, and anticounterfeiting.


Effect of barometric pressure on single-breath carbon monoxide diffusing capacity.
Single-breath diffusing capacity for carbon monoxide (DLCO) quantifies gas transfer in the lungs. DLCO measurement is affected by barometric pressure (Pb) and alveolar partial pressure of oxygen (PAO2). The current equations for adjusting DLCO for Pb and PAO2 may not be accurate given advances in test performance and technology. We quantify changes in DLCO with alterations in Pb in normal and COPD subjects, determine the accuracy of the current Pb and PAO2 adjustment equations and develop updated adjustment equations. We measured DLCO in 13 normal and 10 COPD subjects at 1330 m altitude and in a hypobaric/hyperbaric chamber at altitudes of sea-level and 2500 m; six normal subjects were tested at 3600 m. We determined if there were significant differences in DLCO between altitudes. We developed an equation for adjusting DLCO for changes in Pb from sea-level. We compared this equation with the existing Pb adjustment equation in normal and COPD subjects. We determined the accuracy of the current PAO2 adjustment equation and developed a new PAO2 adjustment equation. DLCO significantly increased with decreasing Pb. We developed a Pb adjustment equation that adjusts DLCO measured at altitudes between 1330 m and 3600 m to sea-level values. This Pb adjustment equation yields DLCO results that are not significantly different than the currently recommended equation. We developed a more accurate PAO2 adjustment equation. DLCO measurement is significantly affected by altitude. We developed equations that accurately adjust DLCO for changes in Pb and PAO2 in normal and COPD subjects.


A comprehensive karyotypic analysis on a newly established sarcomatoid hepatocellular carcinoma cell line SH-J1 by comparative genomic hybridization and chromosome painting.
We first established a sarcomatoid hepatocellular carcinoma cell line, designated as SH-J1, and applied comparative genomic hybridization and fluorescence in situ hybridization (FISH) with chromosome painting probes for the characterization of the chromosomal rearrangements. In the SH-J1 cell line, the pleomorphic spindle cells were arranged in bundles of interlacing patterns and were positive in immunohistochemical staining with hepatocyte-related markers. By G-banding and FISH, the chromosomal gains were detected at 6p and 17, whereas losses were observed at 3p21-pter, 3q27-qter, 4, 6q, 13pter-q11, 16, 18, 19p13, and Y.


Metabolic activation and toxicity of a DDT-metabolite, 3-methylsulphonyl-DDE, in the adrenal zona fasciculata in mice.
Whole-body autoradiography of 14C-labelled 3-methylsulphonyl-DDE (3-MeSO2-DDE) in female C57BL mice revealed a heavy accumulation in the adrenal cortex. Fairly high radioactivity appeared in the nasal mucosa and fat, while the labelling of the liver was intermediate. The adrenal radioactivity remained largely unextracted in tissue-sections treated with organic solvents. In the liver and intestinal contents the radioactivity was partly extracted, whereas in all other tissues almost completely extracted. According to light microscopic autoradiography, the tissue-bound adrenal radioactivity was confined to the zona fasciculata, leaving the other adrenal zones devoid of bound material. Incubation of 3-MeSO2-DDE with adrenal tissue (300 X g supernatant) revealed a dose- and time-dependent covalent binding to protein and formation of water-soluble metabolites. The cytochrome P-450 inhibitors metyrapone and carbon monoxide inhibited both covalent binding and polar metabolite formation. Addition of reduced glutathione decreased binding, while polar metabolite formation was increased. Histopathological examination of adrenals from 3-MeSO2-DDE-treated mice revealed extensive vacuolation and necrosis of the zona fasciculata 1-12 days after single doses down to 25 mg/kg. Degenerative changes were observed at 12.5 mg/kg. In contrast to 3-MeSO2-DDE, 14C-labelled 3,3'-bis(methylsulphonyl)-DDE was not accumulated in the adrenal cortex. 3-MeSO2-DDE is thus a persistent environmental pollutant with a unique ability to produce acute toxicity subsequent to metabolic activation in a mammalian tissue.


Dietary acid load in children with chronic kidney disease: its association with nutritional status and health-related quality of life.
This study aimed to determine the dietary acid load of children with chronic kidney disease (CKD) and to evaluate the relationship between dietary acid load, nutritional status, and health-related quality of life (HRQOL). A total of 67 children aged 3-18 years with a diagnosis of CKD stages II-V were included in the study. Anthropometric measurements (body weight, height, mid-upper arm circumference, waist, and neck circumference) and 3-day food consumption records were taken to evaluate the nutritional status. The net endogenous acid production (NEAP) score was calculated to determine the dietary acid load. "Pediatric Inventory of Quality of Life (PedsQL)" was used to assess the participants' HRQOL. The mean NEAP was 59.2 ± 18.96 mEq/day. Stunted and malnourished children had significantly higher NEAP than those who were not (p < 0.05). There were no significant differences in terms of HRQOL scores according to NEAP groups. The multivariate logistic regression analysis showed that waist circumference (OR: 0.890, 95% CI: 0.794-0.997), serum albumin (OR: 0.252, 95% CI: 0.068-0.929), and glomerular filtration rate (GFR) (OR: 0.985, 95% CI: 0.970-1.000) were negatively associated with high NEAP. This study shows that a diet shifted in an acidic direction in children with CKD and a higher dietary acid load are associated with lower serum albumin, GFR, and waist circumference, but not HRQOL. These results suggest that dietary acid load might affect nutritional status and CKD progression in children with CKD. Future studies with larger samples are needed to confirm these results and to understand underlying mechanisms. A higher resolution version of the Graphical abstract is available as Supplementary information.


A fully-automatic semi-supervised deep learning model for difficult airway assessment.
Difficult airway conditions represent a substantial challenge for clinicians. Predicting such conditions is essential for subsequent treatment planning, but the reported diagnostic accuracies are still quite low. To overcome these challenges, we developed a rapid, non-invasive, cost-effective, and highly-accurate deep-learning approach to identify difficult airway conditions through photographic image analysis. For each of 1000 patients scheduled for elective surgery under general anesthesia, images were captured from 9 specific and different viewpoints. The collected image set was divided into training and testing subsets in the ratio of 8:2. We used a semi-supervised deep-learning method to train and test an AI model for difficult airway prediction. We trained our semi-supervised deep-learning model using only 30% of the labeled training samples (with the remaining 70% used without labels). We evaluated the model performance using metrics of accuracy, sensitivity, specificity, F1-score, and the area under the ROC curve (AUC). The numerical values of these four metrics were found to be 90.00%, 89.58%, 90.13%, 81.13%, and 0.9435, respectively. For a fully-supervised learning scheme (with 100% of the labeled training samples used for model training), the corresponding values were 90.50%, 91.67%, 90.13%, 82.25%, and 0.9457, respectively. When three professional anesthesiologists conducted comprehensive evaluation, the corresponding results were 91.00%, 91.67%, 90.79%, 83.26%, and 0.9497, respectively. It can be seen that the semi-supervised deep learning model trained by us with only 30% labeled samples can achieve a comparable effect with the fully supervised learning model, but the sample labeling cost is smaller. Our method can achieve a good balance between performance and cost. At the same time, the results of the semi-supervised model trained with only 30% labeled samples were very close to the performance of human experts. To the best of our knowledge, our study is the first one to apply a semi-supervised deep-learning method in order to identify the difficulties of both mask ventilation and intubation. Our AI-based image analysis system can be used as an effective tool to identify patients with difficult airway conditions. ChiCTR2100049879 (URL: http://www.chictr.org.cn).


Lamellar bodies are markers of cholinergic neurons in ferret nucleus basalis.
Lamellar bodies are composed of stacks of closely-packed, ribosome-free cisterns which are in continuity with the rough endoplasmic reticulum. In the ferret nucleus basalis stained for choline acetyltransferase it was shown, by correlating light with electron microscopy, that only the cholinergic cells there possess lamellar bodies. The significance of lamellar bodies in the cholinergic neurons of the nucleus basalis is not known, but these structures may reflect a peculiar aspect of the functioning of the cholinergic cells which will need to be investigated further.


The use of virtual patients in medical school curricula.
The demonstration of patient-based cases using automated technology [virtual patients (VPs)] has been available to health science educators for a number of decades. Despite the promise of VPs as an easily accessible and moldable platform, their widespread acceptance and integration into medical curricula have been slow. Here, the authors review the technological underpinnings of VPs, summarize the literature regarding the use and limitations of VPs in the healthcare curriculum, describe novel possible applications of the technology, and propose possible directions for future work.


Naturalistic outcome of case formulation-driven cognitive-behavior therapy for anxious depressed outpatients.
This article describes a case formulation-driven approach to the treatment of anxious depressed outpatients and presents naturalistic outcome data evaluating its effectiveness. Fifty-eight patients who received case formulation-driven cognitive-behavior therapy (CBT) in a private practice setting were studied. All received individual CBT guided by a case formulation and weekly outcome monitoring; in addition, 40 patients received adjunct therapies, including pharmacotherapy, which were added as indicated by the case formulation and the results of weekly outcome monitoring. Patients treated with case formulation-driven CBT showed statistically and clinically significant changes in anxiety and depression that were generally comparable to those reported in published randomized controlled trials of empirically supported therapies (ESTs) for single mood and anxiety disorders. Findings support the proposal that anxious depressed patients who have multiple comorbidities and require multiple therapies can benefit from empirically supported treatments guided by a case formulation and weekly outcome monitoring.


Biological applications of copper-containing materials.
Copper is an indispensable trace metal element in the human body, which is mainly absorbed in the stomach and small intestine and excreted into the bile. Copper is an important component and catalytic agent of many enzymes and proteins in the body, so it can influence human health through multiple mechanisms. Based on the biological functions and benefits of copper, an increasing number of researchers in the field of biomaterials have focused on developing novel copper-containing biomaterials, which exhibit unique properties in protecting the cardiovascular system, promoting bone fracture healing, and exerting antibacterial effects. Copper can also be used in promoting incisional wounds healing, killing cancer cells, Positron Emission Tomography (PET) imaging, radioimmunological tracing and radiotherapy of cancer. In the present review, the biological functions of copper in the human body are presented, along with an overview of recent progress in our understanding of the biological applications and development of copper-containing materials. Furthermore, this review also provides the prospective on the challenges of those novel biomaterials for future clinical applications.


The impact of single versus repeated exposure of mice to Toxocara canis.
Infection with T. canis can alter dramatically the brain and behavior of the host. Previous results suggest that if the mammalian host is exposed either simultaneously to lead, or has a history of prior exposure to that toxic substance, the magnitude of the behavioral reaction to T. canis may be modified or even reduced. The present data suggest that the magnitude of both the behavioral and tissue/immune reactions may be less if the organism has multiple, instead of a single exposure, to T. canis. Lead, and perhaps other environmental toxicants may alter neurotropic products of the parasite, the behavior of the parasite, and/or reactivity of the host in the presence of the parasite. Such considerations may help explain, in part, the relative rarity of reported toxocariasis in humans, despite the fact that serological indices suggest that exposure to T. canis may be as high as 7% of the world population.