Surgical outcomes of open cholecystectomy in the laparoscopic era.
Although laparoscopic cholecystectomy has become the standard of care for symptomatic cholelithiasis and cholecystitis, 10% to 30% of cholecystectomies are still performed in open fashion. Because the total number of cholecystectomies is increasing with time, the average patient undergoing open cholecystectomy in the laparoscopic era is older and has more comorbidities. The records of 1629 consecutive patients who underwent cholecystectomy from July 1997 to September 2006 were evaluated. Analysis of variance, chi-square test, logistic regression, and linear regression were used to compare the following outcomes: length of procedure, length of stay, readmission (within 15 days and within 31 days), reoperation, and complication. Major complications (death, bile duct injury, bile leak, or bleeding requiring reoperation or transfusion) occurred more frequently in laparoscopic cholecystectomy patients who were coverted to open procedure (5.9%) than in those who underwent open cholecystectomy (4.4%). Mortality rates were 2.9%, 1.5%, and 0% for open, converted, and laparoscopic cholecystectomy, respectively. Older patients, male patients, and patients with previous upper abdominal surgery are at higher risk for mortality. They should be considered for open cholecystectomy given their increased likelihood of major complications when laparoscopic cholecystectomy is converted to open surgery.


Anesthesia for intraoperative radiation therapy in children.
Intraoperative radiation therapy (IORT) is a relatively new mode of cancer treatment which is being used with increasing frequency. IORT presents several challenges to the anesthesiologist, including patients who are debilitated from their disease or chemotherapy, operations involving major tumor resections, intraoperative interdepartmental transport of patients, and remote monitoring of patients during electron beam therapy. This report discusses the anesthetic management of ten children undergoing IORT. With adequate preparation and interdepartmental communication, complications can be avoided during these challenging cases.


P21(WAF1/CIP1) may be a tumor suppressor after all.
The cyclin-dependent kinase inhibitor p21WAF1/CIP1 was originally considered to be a tumor-suppressor because it was identified as a key mediator of p53-dependent cell cycle arrest. However, it has been suggested that p21 may also act as an oncogene because it often inhibits apoptosis. For example, deletion of p21 from p53-deficient mice resulted in longer survival and in a significantly reduced number of thymic lymphomas that was explained by higher apoptotic rates in these mice. However, recently it has been shown that a p53 mutant that had lost its ability to induce apoptosis, but retained its ability to induce p21 and cell cycle arrest, was able to suppress lymphomagenesis in different cancer models. Tumor suppression by this p53 mutant was modulated by p21, which induced senescence and preserved chromosomal stability. These data suggest that the ability of p21 to induce cell-cycle arrest may lead to tumor suppression in some types of cancer.


[Using ultracision-harmonic scalpel as major instrument for tonsillectomy via nasal endoscope (a report of 31 cases)].
To investigate the feasibility of applying ultracision-harmonic scalpel in tonsillectomy. Thirty-one cases treated with tonsillectomy which applied with nasal endoscope and ultracision-harmonic scalpel (ultrasonic scalpel group) and 31 cases treated with routine operation (routine group) respectively. The operating time and blood loss during operation and the degree of pain and the region of inflammation humidity as well as hospitalization days were observed. All indexes in ultrasonic scalpel group were lower than that in the routine group, including operating time and blood loss during operation, and they were obviously difference in statistics (P < 0.01). The application of ultracision-harmonic scalpel in tonsillectomy was safe, efficient and feasible, and would have a nice application prospect during ear-nose-throat operation.


New assistive technologies in dementia and mild cognitive impairment care: A PubMed review.
Dementia is characterized by global cognitive dysfunction, which can cause difficulties in performing Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs), leaving people with dementia (PwD) who do not have the proper support extremely vulnerable. Dementia management should involve preventative methods, including during the stage of mild cognitive impairment (MCI). Lay-caregivers are found to have poorer health in all three domains of the biopsychosocial model, as a result of the burden of care. New assistive technologies (ATs) have been designed to help care for PwD. ATs aim to be more affordable and widely available than human workers, achieving greater health equity and quality of life for all. To identify relevant articles, a literature search using PubMed was undertaken by one independent reviewer: S.L.C. The keywords of "dementia", "technology", and "management" were used, with no date of publication limitations, which revealed 571 results. 44 articles were included in this review. Articles regarding new technologies to diagnose dementia or MCI were not included. ATs aim to help facilitate aging-in-place, reduce medical costs, and rates of caregiver burnout, by helping maintain patient functioning. Legal issues in the form of workplace safety laws, data privacy laws and regulations, and health care ethics are major barriers to implementation that need to be resolved. The hope is that artificial intelligence (AI) systems may be able to advance what they are able to perceive and help uncover new knowledge and management options for dementia and MCI.


Temporal changes in bias of body mass index scores based on self-reported height and weight.
To investigate temporal changes in the bias associated with self-reported (as opposed to measured) body mass index (BMI) and explore the relationship of such bias to changing social attitudes towards obesity. Using data from the National Health and Nutrition Examination Survey covering two time periods, 1988-1994 and 2005-2008, discrepancy scores between self-reported vs measured BMI were generated. Changes in the sensitivity of BMI categories based on self-reports were examined for six weight groups, both for the US adult population as a whole and major demographic groups. Linear regression models were used to examine temporal changes in average bias, as well as attitudes about weight within each weight category and by demographic group. Between 2005-2008 and 1988-1994, the bias towards underestimation of a person's BMI based on interview responses has declined among obese individuals, a trend evident in virtually all demographic subgroups explored. Conversely, most demographic groups showed little change in the extent of bias among underweight and normal-weight individuals. Although the 2005-2008 survey respondents underestimated their measured BMI more than the 1988-1994 respondents, this shift can be entirely explained by the increased prevalence of obesity in more recent years. In fact, obese individuals in 2005-2008 were less likely to overreport their height and underreport their weight than their counterparts in the 1988-1994. Evidence from responses to questions about ideal weight and desire to lose weight point in the direction of a shift in social attitudes, which may make it easier to 'admit' to greater weight in surveys. Over the past 20 years, the bias in self-reported height and weight has declined leading to more accurate BMI categorizations based on self-report. This change is likely to affect efforts to find correction factors to adjust BMI scores based on self-reported height and weight.


Enhancement of chain amplification in photoreactions of N-methoxypyridinium salts with alcohols.
Recently we reported a chain-amplified photochemical reaction, initiated by electron transfer from an excited sensitizer to N-methoxypyridinium salts, which leads to N-O bond cleavage (26). Hydrogen atom abstraction by the methoxy radical from an alcohol yields an alpha-hydroxy radical, which reduces another N-methoxypyridinium molecule and propagates the chain. We now report that the chain amplification can be significantly enhanced in the presence of water. Detailed kinetic studies of the reaction of 4-cyano-N-methoxypyridinium salt (CMP) with benzhydrol (BH) showed that the rate constant for reduction of CMP by the diphenyl ketyl radical (1.1 x 10(6) M(-1) s(-1)) increases by more than an order of magnitude in the presence of water. This increase in the rate constant is the result of coupling of the electron transfer to a proton transfer from the ketyl radical to water, which decreases the endothermicity of the reaction. Unfortunately, this increase in the rate constant for one of the two propagation steps is accompanied by a larger increase in the rate constant(s) of the competing termination reaction(s) of the ketyl radical. The observed enhancement in chain amplification is the result of a significant increase in the ratio of propagation to termination rate constants of the reactions of the methoxy radical. The main chain-terminating reactions of the methoxy radical are deuterium abstraction from the solvent, CD(3)CN, and reaction with the sensitizer, thioxanthone. The effect of increase in the ratios of the propagation rate constant of the methoxy radical (hydrogen abstraction from BH) to those of both termination reactions is larger than the unfavorable effect of water on the reactions of the ketyl radical. The increase in chain amplification depends on the concentration of the reactants; at 0.037 M of both reactants, the quantum yield increases form approximately 16 to approximately 45 in the presence of <1% water. The reaction of 4-phenyl-N-methoxypyridinium (PMP) with 4-methoxybenzyl alcohol does not proceed via chain amplification because of large endothermicity for electron transfer from the alpha-hydroxy radical to the pyridinium salt. However, chain amplification could be induced, simply by addition of water, where at approximately 10% water content, a quantum yield of approximately 5 was obtained. Water-induced, proton-coupled electron transfer increases the rate constant for reduction of PMP from a negligible level to becoming the dominant path.


Elevation of neutrophil carcinoembryonic antigen-related cell adhesion molecule 1 associated with multiple inflammatory mediators was related to different clinical stages in ischemic stroke patients.
We aimed to analyze the level of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in neutrophils of ischemic stroke (IS) patients at different stages, together with its roles in neutrophils. Sixty-seven patients were classified into acute phase group (n = 19), subacute phase group (n = 28), and stable phase group (n = 20), and 20 healthy individuals who had received physical examination at the same time period as healthy control. We then analyzed the expression level of CEACAM1 and cell viability in CEACAM1 positive and CEACAM1 negative neutrophils by flow cytometry and the content of plasma CEACAM1, neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinases-9 (MMP-9) was measured using enzyme-linked immunosorbent assay (ELISA), while that of interleukin-10 (IL-10) and tumor necrosis factor (TNF) was determined using a Human Enhanced Sensitivity Flex set. Compared with healthy control, the percentage of CEACAM1 positive neutrophils in IS patients showed a significant increase, and a significant increase was also noticed in the content of plasma CEACAM1 at the subacute stage. Reduction in cell viability was observed in CEACAM1 positive neutrophils compared with CEACAM1 negative counterparts. There was a positive correlation between CEACAM1 expression rate in neutrophils and plasma CEACAM1 and IL-10 content in the subacute group. Compared with acute group and healthy control group, there was an instinct increase in the level of plasma MMP-9 and NGAL in subacute group. Our data showed that there was a rapid increase of CEACAM1 in neutrophils at the acute stage of IS. We speculated that CEACAM1 may serve as an inhibitory regulator involving in the progression of IS.


The anthraquinone drug rhein potently interferes with organic anion transporter-mediated renal elimination.
Rhein, a major metabolite of the prodrug diacerein and a major component of the medicinal herb Rheum sp., is used for its beneficial effects in a variety of clinical applications including the treatment of osteoarthritis and diabetic nephropathy. The physicochemical properties of rhein are consistent with those of known organic anion transporter (OAT) substrates and inhibitors. Therefore, the inhibitory effect of rhein on human (h) OAT1, hOAT3, hOAT4, and murine (m) Oat1 and mOat3 was examined in heterologous cell lines stably expressing each transporter in isolation. Rhein was shown to potently inhibit hOAT1 and hOAT3, with IC50 estimates in the low nanomolar range (IC50=77.1±5.5 nM and 8.4±2.5 nM, respectively), while poor affinity was observed for hOAT4 (IC50>100 μM). Marked species differences were observed with hOAT1 and hOAT3 exhibiting 3- and 28-fold higher affinity for rhein as compared to their murine orthologs. The estimated drug-drug interaction (DDI) indices (>>0.1) indicated a very strong potential for clinically relevant, rhein perpetrated DDIs mediated by inhibition of hOAT1 (DDI index=5.0; 83% inhibition) and/or hOAT3 (DDI index=46; 98% inhibition) transport activity. These results suggested that rhein, from herbal medicines and/or prodrug conversion, may significantly impact the dosing, efficacy and toxicity (i.e., pharmacokinetics and pharmacodynamics) of co-administered hOAT1 and/or hOAT3 drug substrates.


Epstein-Barr virus-associated epithelial and mesenchymal neoplasms.
Epstein-Barr virus (EBV) is a ubiquitous human pathogen that usually maintains a harmonious relationship with its host. Rarely, this host-virus balance is perturbed, causing a diverse group of malignancies in both immunocompetent and immunosuppressed patients. In addition to its role in hematologic malignancies (Burkitt lymphoma, subsets of Hodgkin and T-cell lymphomas, posttransplant lymphomas), EBV has been implicated in both epithelial (undifferentiated nasopharyngeal carcinoma, a subset of gastric adenocarcinomas) and mesenchymal (EBV-associated smooth muscle tumor, inflammatory pseudotumor-like follicular dendritic cell tumor) neoplasms. This review will focus on EBV-associated epithelial and mesenchymal neoplasms.


Very low birthweight infants receive less enteral feeding than what is prescribed.
Feeding a very low birthweight (VLBW, <1500 g) infant is challenging. Our aims were to study how prescribed enteral feeding is implemented in VLBW infants and to identify factors associating with slow enteral feeding progression. Our retrospective cohort included 516 VLBW infants born before 32 weeks of gestation during 2005-2013 and admitted to Children's Hospital, Helsinki, Finland, for at least the two first weeks of life. Nutritional data were collected from birth until the age of 14-28 days, depending on the length of stay. We found that enteral feeding progressed slower than recommended and implementation differed from the prescriptions, especially during the parenteral nutrition phase (milk intake 10-20 mL/kg/day): 71% [40-100], median [IQR], of the prescribed enteral milk was administered. The full prescribed amount was less likely administered if a higher volume of gastric residual was aspirated or if the infant did not pass stool during the same day. Longer opiate use, patent ductus arteriosus, respiratory distress syndrome and slower passage of the first meconium associated with slower enteral feeding progression. Enteral feeding of a VLBW infant is often not administered as prescribed, which possibly plays a significant role in the slow progression of enteral feeding.


Predictors of Future Deep Brain Stimulation Surgery in de novo Parkinson's Disease.
Deep brain stimulation (DBS) surgery is offered to a subset of Parkinson's disease (PD) patients. It is unclear if there are features at diagnosis that predict future DBS surgery. To assess predictors of eventual DBS surgery in de novo PD patients. Subjects from the Parkinson's Progression Marker Initiative (PPMI) database with newly diagnosed, sporadic PD (n = 416) were identified and stratified by their eventual DBS status (DBS+, n = 43; DBS-, n = 373). A total of 50 baseline clinical, imaging, and biospecimen features were extracted for each subject and cross-validated lasso regression was used for feature reduction. Multivariate logistic regression assessed their relationship with DBS status and a receiver operating characteristic curve evaluated model performance. Linear mixed effect models assessed disease progression over 4 years in DBS+ and DBS- patients. Age at symptom onset, Hoehn and Yahr (H&Y) stage, tremor score, and ratio of CSF Tau to amyloid-beta 1-42 (Tau: Ab) were identified as important baseline features for predicting DBS surgery. Each independently predicted DBS surgery (area under the curve = 0.83). DBS- patients had faster memory decline (P < 0.05), while DBS+ patients had faster decline in H&Y stage (P < 0.001) and motor scores (P < 0.05) prior to surgery. The identified features may be used for early identification of patients who may be surgical candidates during the course of their disease. Disease progression in these groups reflects surgical eligibility criteria, with DBS- patients having more rapid decline in memory while DBS+ patients experienced a faster decline in motor scores prior to DBS surgery.


Use of granulocyte colony-stimulating factor in ART treatment does not increase the risk of adverse perinatal outcomes.
Granulocyte colony-stimulating factor (G-CSF) acts on reproductive function at different stages, but its effects on the early stages of embryo development are unknown. The aim of this study was to assess the effect of G-CSF administration during treatment with assisted reproductive technologies (ART) and early pregnancy on newborns. Retrospective study in women undergoing egg donation, with a study group including 33 live-born children from a pregnancy in which G-CSF was administered, and a control group of 3798 children in which this medication was not ordered during pregnancy. The analysis was of perinatal outcomes resulting from G-CSF treatment administered off-label compared with a control group. No significant differences were found in maternal age (40.9 ± 0.1 versus 38.9 ± 1.8, P = 0.055), body mass index (23.2 ± 0.2 versus 22.6 ± 1.5, P = 0.503), infant birthweight (2952 ± 200 versus 3145 ± 270 g, P = 0.184), gestational age (38 ± 1 versus 37 ± 1 weeks, P = 0.926) or length (50.2 ± 1.5 versus 48.7 ± 2.7 cm, P = 0.678) (between the control group and women treated with G-CSF, respectively). The prematurity rates of births before week 36 (10.0% versus 9.5%, P = 0.783) or week 32 (2.2% versus 0.0%, P = 0.585) were similar in the control and study groups, respectively. The incidence of low birthweight (<2500 g; 19.6% versus 11.8%, P = 0.570) or very low birthweight (1500 g; 2.5% versus 0.0%, P = 0.454) was not significantly different between non-treated and G-CSF-treated women, respectively. Administration of G-CSF at embryo transfer and during early pregnancy in recurrent miscarriage patients with KIR-HLA-C mismatch undergoing egg donation ART treatment does not convey a higher risk of perinatal complications.


Neuroscience-Inspired, Behavioral Change Program for University Students.
It is clear that environmental influences impact the structure and function of the human brain, and thus, thoughts, actions, and behaviors. These in turn influence whether an individual engages in high-risk (drugs, alcohol, violence) or health-promoting (exercise, meditation, music) activities. The developmental mismatch between cortical and subcortical maturation of the transitional age brain places college students at risk for negative outcomes. This article argues that the prescription of incentive-based behavioral change and brain-building activities simply make good scientific, programmatic, and financial sense for colleges and universities. The authors present University of Vermont Wellness Environment as an example.


Separation and determination of cysteine enantiomers in plasma after derivatization with 4-fluoro-7-nitrobenzofurazan.
The importance of D-amino acids in mammals associated with enantio-dependent biological functions has been increasingly highlighted. In addition to naturally occurring, D-amino acid supplementation could have a positive biological impact, including cytoprotective implications. In this context, supplementation with D-cysteine has revealed beneficial effects. Quantification of cysteine enantiomers in rodent plasma has been achieved by using 4-fluoro-7-nitrobenzofurazan derivatization of the target analytes. Cystine, the main form of cysteine in the plasma, was initially reduced to cysteine using DL-dithiothreitol. Baseline enantioseparation was then achieved in less than 3 min using a (R,R)-Whelk-O 1 stationary phase and isocratic elution using CH3OH-H2O 90:10 (v/v) with 15 mM ammonium formate (apparent pH 6.0) at 0.5 mL/min. The derivatives were then detected using negative ESI-MS in SRM mode. An external calibration was employed for D-cysteine, while L-cysteine quantification, as an endogenous analyte, was addressed using a background subtraction strategy. The method was validated. Response functions were obtained from 0 to 300 µM and from 0 to 125 µM for D-cysteine and L-cysteine, respectively. The trueness ranged from 96% to 105% for both enantiomers with repeatability and intermediate precision lower than 8% and 15% for the D-form and the endogenous L-form, respectively. The method was successfully applied for determining D- and L-cysteine in mouse plasma after D-cysteine administration.


Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats decreases during high salt intake.
Dahl salt-sensitive rats, but not salt-resistant rats, develop hypertension in response to high salt intake. We have previously shown an inverse relationship between plasma 25-hydroxyvitamin D (25-OHD) concentration and blood pressure of Dahl salt-sensitive rats during high salt intake. In this study, we report on the relationship between high salt intake and plasma 24,25-dihydroxyvitamin D (24,25-(OH)(2)D) concentration of Dahl salt-sensitive and salt-resistant rats. Rats were fed a high salt diet (8%) and sacrificed at day 2, 7, 14, 21, and 28. Plasma 24,25-(OH)(2)D concentrations of salt-sensitive rats were reduced to 50% of that at baseline at day 2-when blood pressure and plasma 25-OHD concentration were unchanged, but 25-OHD content in the kidney was 81% of that at baseline. Plasma 24,25-(OH)(2)D concentration was reduced further to 10% of that at baseline from day 7 to 14 of high salt intake, a reduction that was prevented in rats switched to a low salt (0.3%) diet at day 7. Exogenous 24,25-dihydroxycholecalciferol (24,25-(OH)(2)D(3)), administered at a level that increased plasma 24,25-(OH)(2)D concentration to five times normal, did not attenuate the salt-induced hypertension of salt-sensitive rats. Plasma 24,25-(OH)(2)D concentration of salt-resistant rats was gradually reduced to 50% of that at baseline at day 14 and returned to baseline value at day 28 of high salt intake. We conclude that the decrease in plasma 24,25-(OH)(2)D concentration in salt-sensitive rats during high salt intake is caused by decreased 25-OHD content in the kidney and also by another unidentified mechanism.


Defective monocyte function in acquired immune deficiency syndrome (AIDS): evidence from a monocyte-dependent T-cell proliferative system.
T-cell proliferative responses to the mitogenic monoclonal antibody anti-Leu 4 were assessed in healthy controls, lymphadenopathy syndrome (LAS) patients, and acquired immune deficiency syndrome (AIDS) patients. While 19% of the control group showed low anti-Leu 4 responses (less than 12,000 cpm), 60% of the LAS patients, 71% of the AIDS-opportunistic infection patients, and 50% of the AIDS-Kaposi's sarcoma patients showed low responses. T-cell responsiveness in healthy low responders was greatly enhanced by the addition of monocytes from an anti-Leu 4 high responder (responder monocytes). We therefore sought to determine if the low-responder state in LAS and AIDS patients was also mediated by monocytes and, thus, correctable by the addition of responder monocytes. In the LAS low-responder group, the level of enhancement by healthy responder monocytes was similar to that observed for the healthy low-responder group. In the AIDS low-responder group, however, the level of enhancement was significantly lower than that observed in the healthy low-responder and LAS low-responder groups. These findings suggest that impaired proliferation to anti-Leu 4 in LAS patients may be due to a monocyte defect similar to the monocyte defect responsible for low anti-Leu 4 responses in healthy controls. AIDS patients, however, show additional defects in anti-Leu 4-induced proliferation that are not fully corrected by the addition of responder monocytes.


The effect of audio-visual video with korotkoff sounds on anxiety levels and blood pressure measurement skills of nursing students: A randomized controlled study.
This study was aimed to determine the effect of the audio-visual video created with korotkoff sounds on the anxiety levels and blood pressure measurement skills of nursing students. Blood pressure measurement is the basis of nursing care and clinical decision. For this reason, it is stated that nursing students should specialize in this skill. This research was conducted as a randomized controlled experimental study. This research was conducted with 130 (intervention group: 67, control group: 63) nursing students in the nursing department of a university in March 2022. Before the skill practice, the students in the intervention group listened to the korotkoff sounds using an audio-visual video containing the korotkoff sounds and then the practice was made. Data of the study were collected using the short version of the State-Trait Anxiety Inventory, the student introduction form and the blood pressure measurement evaluation form. The mean age of the students was 19.41 (SD 1.75) in the intervention group and 19.20 (SD 1.04) in the control group. The State-Trait Anxiety Inventory mean scores of both groups were similar before the skill practice. At the end of the skill practice, the state anxiety score of the intervention group 0.56 (SD 1.03) was lower than the control group 1.30 (SD 1.81) and the difference was statistically significant (p < 0.05). When the blood pressure measurements of the students in both groups were compared, the rate of hearing korotkoff sounds and measuring blood pressure correctly was higher in the students in the intervention group and the difference was statistically significant (p < 0.05). The korotkoff sounds presented with audio-visual video increased the skill levels of the students and reduced the anxiety level. In this direction; it is recommended to use audio-visual video containing korotkoff sounds for students to gain blood pressure measurement skills.


Evidence of specialized conduction cells in human pulmonary veins of patients with atrial fibrillation.
Specialized Conducting Cells in Human PV. Depolarizations similar to those from the sinus node have been documented from the pulmonary veins after isolation procedures. We assessed the hypothesis that sinus node-like tissue is present in the pulmonary veins of humans. Pulmonary vein tissue was obtained from five autopsies (four individuals with a history of atrial fibrillation and one without a history of atrial arrhythmias) and five transplant heart donors. Autopsy veins were fixed in formaldehyde and processed for light microscopy to identify areas having possible conductive-like tissue. Areas requiring additional study were extracted from paraffin blocks and reprocessed for electron microscopy. Donor specimens were fixed in formaldehyde for histologic sections and glutaraldehyde for electron microscopy. Myocardial cells with pale cytoplasm were identified by light microscopy in 4 of the 5 autopsy subjects. Electron microscopy confirmed the presence of P cells, transitional cells, and Purkinje cells in the pulmonary veins of these cases. Our report is the first to show the presence of P cells, transitional cells, and Purkinje cells in human pulmonary veins. Whether these cells are relevant in the genesis of atrial fibrillation requires further study.


Rapid method for determination of dioxin-like polychlorinated biphenyls and other congeners in marine sediments using sonic extraction and photodiode array detection.
A rapid method has been developed to measure dioxin-like polychlorinated biphenyl (PCB) congeners as well as other selected PCBs in sediment. The analytes were extracted from sediment by sonication with dichloromethane, and the PCBs were separated from interfering compounds on a gravity-flow cleanup column packed with acidic, basic, and neutral silica gels eluted with 1:1 hexane:pentane (v/v). Subsequently, the dioxin-like PCB congeners were resolved from nonplanar PCBs and other chlorinated compounds by high-performance liquid chromatography (HPLC). Two important advantages of PDA over conventional UV detection are the ability to identify individual analytes by comparing their UV spectra with those of reference standards and the ability to establish the spectral homogeneity (purity) of the analytes by comparing spectra within a peak to the apex spectrum. The HPLC-PDA method was tested with reference and marine sediment samples. Concentrations of selected dioxin-like PCBs, selected nonplanar PCBs, and summed PCBs in sediments and National Institute of Standards and Technology standard reference materials determined by our rapid HPLC-PDA method were comparable with the levels in the same samples analyzed by alternative comprehensive methods (i.e., gas chromatography-electron capture detection or high-resolution gas chromatography-high-resolution mass spectrometry).


Thymosin alpha 1-induced modulation of cellular responses and functional T-cell subsets in mice with experimental autoimmune thyroiditis.
The effects of Ta-1, a peptide constituent of thymosin fraction 5, were studied on murine autoimmune thyroiditis using two congenic strains of mice, B10.Br (Br) and B10.D2 (D2), which are sensitive and resistant to experimental autoimmune thyroiditis (EAT) induction, respectively. EAT was induced by either 2 weekly iv injections of mouse thyroglobulin with adjuvant lipopolysaccharide (LPS) or intradermal injection of thyroglobulin mixed with complete Freund's adjuvant (CFA). The criteria for induction and intensity of thyroiditis were the level of lymphoid infiltration in the thyroid gland and the titer of anti-thyroglobulin antibodies. Ta-1 was given in 5 or 10 daily sc injections in doses ranging from 0.0001 to 0.1 microgram/injection. The injections were commenced at varying intervals from the 1st to the 4th week after immunization. T-Cell subsets in the spleens were determined 2 weeks after the first antigen injection and thyroid infiltration was determined 3 weeks later. Treatment with Ta-1 between the two antigen injections increased the level of thyroiditis in resistant mice, but had no effect in sensitive mice. Treatment for the first 2 weeks had similar effects in resistant mice, but also suppressed thyroiditis in the sensitive strain. Later treatments, during the 3rd and 4th weeks after immunization also revealed immunomodulating properties of Ta-1, with a suppressing effect on thyroiditis in sensitive mice and an enhancing effect in the resistant strain. Both effects of Ta-1 were dose dependent. The effects of Ta-1 on the individual phenotypes were also dose dependent. The dose of 0.01 microgram greatly lowered the percentages of Lyt-2+3+ cells in D2 mice and mildly increased the percentages in Br mice, but did not change the Lyt-1+ cell level in either strain. On the other hand, the dose of 0.001 microgram greatly increased the percentage of Lyt-1+ cells in D2 mice and mildly decreased it in the Br strain, but did not alter the Lyt-2+3+ cell subset in either strain. Thus, both doses of Ta-1 modulated Lyt-1+/2+3+ ratios, with each dose affecting a different T-cell subset. The changes in the response to thyroglobulin are apparently exerted through the regulation of the functional T-cell subset balance.


Effect of yoga and mindfulness on psychological correlates in young athletes: A meta-analysis.
This meta-analysis planned to assess the impact of yoga and mindfulness practice in reducing stress and anxiety to improve athletes' sports performance. Several databases were electronically searched for eligible articles till September 2022. Participants aged 18-45 yrs, male and female, and recreational athletes from different sports were included. Athletes' stress, competitive anxiety, and sports performance were measured. The mean difference or standardized mean difference with a 95% confidence interval was calculated in RevMan software 5.4. The fixed effect model was applied to test the statistical significance difference and heterogeneity (p < 0.05). The GRADE pro evidence was also created to assess the quality of evidence. Results were analyzed with pooled data from fifteen articles. Forest plots showed an overall significant effect of yoga and mindfulness on Mindfulness [Z = 4.13 (p < 0.0001)] [(I2 = 48%), MD -2.6, (95% CI, -3.85, -1.37)] and flow state [Z = 9.49 (p < 0.00001)] [(I2 = 85%), SMD 3.13, (95% CI, 2.48, 3.77)]. The insignificant effects were noted on attention and awareness [Z = 1.51 (p = 0.13)] [(I2 = 25%), SMD -0.26, (95% CI, -0.60, 0.80)], and action and acceptance [Z = 0.43 (p = 0.67)] [(I2 = 0%), MD 0.20, (95% CI, -0.69, 1.08)]. We also observed a significant effect for the comparison of stress [Z = 6.56 (p < 0.00001)] [(I2 = 76%), SMD -0.74, (95% CI, -0.97, 0.52)] and an insignificant effect for comparing anxiety [Z = 1.62 (p = 0.11)] [(I2 = 14%), SMD -0.31, (95% CI, -0.69, 0.07)]. The findings of this meta-analysis provides valuable insights to the beneficial or complementary effects of yoga and mindfulness on athletes' psychological health and sports performance.


Two β-strands of RAGE participate in the recognition and transport of amyloid-β peptide across the blood brain barrier.
Amyloid-β (Aβ) peptide is central to the development of brain pathology in Alzheimer disease (AD) patients. Association with receptors for advanced glycation end-products (RAGE) enables the transport of Aβ peptide from circulating blood to human brain, and also causes the activation of the NF-κB signaling pathway. Here we show that two β-strands of RAGE participate in the interaction with Aβ peptide. Serial deletion analysis of the RAGE V domain indicates that the third and eighth β-strands are required for interaction with Aβ peptide. Site-directed mutagenesis of amino acids located in the third and eighth β-strands abolish the interaction of RAGE with Aβ peptide. Wild-type RAGE activates the NF-κB signaling pathway in response to Aβ peptide treatment, while a RAGE mutant defective in Aβ binding does not. Furthermore, use of peptide for the third β-strand or a RAGE monoclonal antibody that targets the RAGE-Aβ interaction interface inhibited transport of the Aβ peptide across the blood brain barrier in a mice model. These results provide information crucial to the development of RAGE-derived therapeutic reagents for Alzheimer disease.


Reduced severity of liver ischemia/reperfusion injury following hepatic resection in humans is associated with enhanced intrahepatic expression of Th2 cytokines.
Based on previous studies in experimental models, pro-inflammatory Th1 cytokines (i.e. TNF-alpha and IFN-gamma) are thought to play a pathogenic role in hepatic ischemia/reperfusion injury, while anti-inflammatory Th2 cytokines (i.e. IL-4 and IL-10) have been associated with reduced liver disease severity. To test the relevance of these concepts in humans, cytokine expression profiles were characterized in liver biopsies from patients undergoing hepatic resection following intermittent portal clamping. Twelve patients were analyzed for the intrahepatic expression of TNF-alpha, IFN-gamma, IL-4 and IL-10 before and about 90min after the last reperfusion. In addition, parameters of liver damage including sALT and serum levels of TNF-alpha were analyzed at 2, 24 and 48h after surgery. When compared with pre-reperfusion liver specimens, all post-reperfusion biopsies showed significantly increased levels of TNF-alpha and IFN-gamma mRNAs. Conversely IL-4 and IL-10 mRNA levels were significantly increased in only seven patients. A negative correlation was observed between Th2 cytokines (IL-4, IL-10) and ALT and serum levels of TNF-alpha. Furthermore, the presence of hepatic steatosis was significantly associated with lower intrahepatic contents of IL-4 and IL-10. The results suggest that the local early expression of Th2 cytokines may contribute to attenuate liver injury following ischemia reperfusion in humans. The early imbalance between pro- and anti-inflammatory cytokines seen in steatotic liver subjected to I/R could explain, at least partially, the decreased tolerance of steatotic livers to I/R injury.


Eruption of the maxillary canines in relation to skeletal maturity.
Our aim in this study was to assess the relationship between the eruption of the permanent maxillary canines and skeletal maturity in subjects with different skeletal relationships in the sagittal and vertical planes. A sample of 152 subjects (63 boys, 89 girls) with erupting permanent maxillary canines was analyzed. On the lateral cephalograms, the stage of cervical vertebral maturation was assessed. Then the subjects were divided into prepeak (before the pubertal growth spurt, cervical stage [CS]1 and CS2), peak (during the pubertal growth spurt, CS3 and CS4), and postpeak (after the pubertal growth spurt, CS5 and CS6) groups. Skeletal relationships in the sagittal and vertical planes were evaluated, and relationships to timing of canine eruption were tested statistically. The prepeak group comprised 86 subjects, the peak group 66 subjects, and the postpeak group 0 subjects. The differences in prevalence rates between either the prepeak or peak groups and the postpeak group were statistically significant (P < 0.001). The prevalence rate for hyperdivergent subjects showing eruption of the permanent maxillary canine in the prepeak group (37.2%) was significantly higher than in the reference orthodontic population (21%). The eruption of the permanent maxillary canine can occur at any stage in skeletal maturation before the end the pubertal growth spurt (CS1-CS4), with hyperdivergent subjects more frequently having prepubertal canine eruption.


Localization of Leu-enkephalin in dense core vesicles of axon terminals.
The localization of enkephalins by immunofluorescence has already shown that these pentapeptides are largely distributed in the central nervous system. In order to clearly identify the structures and organelles containing enkephalins, an immunohistochemical localization of Leu-enkephalin was performed at the ultrastructural level. Leu-enkephalin was detected in dense core vesicles (70--100 nm in diameter) of many nerve fibers in the substantia gelatinosa of the spinal cord, the globus pallidus and the nucleus papabrachialis. These findings support the hypothesis that Leu-enkephalin could act as a neuromodulator.


Sevoflurane anesthetic preconditioning protects the lung endothelial glycocalyx from ischemia reperfusion injury in an experimental lung autotransplant model.
The glycocalyx is a glycoprotein-polysaccaride layer covering the endothelium luminal surface, and plays a key regulatory role in several endothelial functions. Lung ischemia reperfusion (IR) is a clinical entity that occurs in everyday thoracic surgery and causes glycocalix destruction and a florid local and systemic immune response. Moreover, sevoflurane is able to modulate the inflammatory response triggered by IR lung injury. In this study, we evaluated the protective effects of sevoflurane on the pulmonary endothelial glycocalyx in an in-vivo lung autotransplant model in pigs. Sixteen Large White pigs underwent pneumonectomy plus lung autotransplant. They were divided into two groups depending on the hypnotic agent received (propofol or anesthetic preconditioning with sevoflurane). Glycocalyx components (syndecan-1 and heparan sulphate), cathepsin B, chemokines (MCP-1, MIP-1, and MIP-2) and adhesion molecules (VCAM and ICAM-1) were measured at four different timepoints using porcine-specific enzyme-linked immunosorbent assay (ELISA) kits. There were no differences between groups in weight or in surgical and one-lung ventilation time. Greater glycocalyx destruction and higher chemokine and adhesion molecule expression were observed in the group that did not receive sevoflurane. Heparan sulphate and serum syndecan levels were higher in the propofol group (P < 0.0001) after reperfusion, as was cathepsin B activity (P < 0.015). MCP-1, MIP-1, MIP-2, VCAM, and ICAM-1 levels were also higher in the propofol group (P < 0.006). Sevoflurane preconditioning protects pulmonary glycocalyx and reduces expression of leukocyte chemokines in an in-vivo model of pulmonary IR.


Sequence polymorphisms of Der f 1, Der p 1, Der f 2 and Der p 2 from Korean house dust mite isolates.
Amino acid sequence variations have possible influences on the allergenicity of allergens and may be important factors in allergen standardization. This study was undertaken to investigate the sequence polymorphisms of group 1 and 2 allergens from Korean isolates of the house dust mites Dermatophagoides farinae and D. pteronyssinus. cDNA sequences encoding group 1 and 2 allergens were amplified by RT-PCR and compared the deduced amino acid sequences. Der f 1.0101, which appeared in 64.0 % of the 50 sequences analyzed, was found to be predominant. Among the Der p 1 sequences, Der p 1.0102 and 1.0105 were predominant (58 %). Among the Der f 2 sequences, Der f 2.0102 (40.7 %) and a new variant with Gly at position 42 (27.8 %) were predominant. The deduced amino acid sequences of 60 Der p 2 clones were examined, and 28 variants with 1-5 amino acid substitutions were found. Interestingly, all of the Der p 2 sequences had Thr instead of Lys at position 49. Two variants (Leu40, Thr49, and Asn114 (26.6 %); Val40, Thr49, and Asn114 (20.0 %)) were found to be the most predominant forms of Der p 2. Der p 1 has a high rate of sporadic substitutions and the group 2 allergens show a more regular pattern with orderly associations of amino acid substitutions. Der f 1 and Der p 2 from Korean mite isolates have unique amino acid sequence polymorphisms. These findings provide important data for house dust mite allergen standardization.


Differential expression of invertase genes in internal and external phloem tissues of potato (Solanum tuberosum L.).
The cloning of promoter sequences of two invertase genes from potato (Solanum tuberosum L.) is described. Histochemical analysis of series of reporter transgenic lines reveals phloem-specific expression from both promoters, with one expressed preferentially in internal phloem and the other in external phloem of stem vascular bundles.


Tree species (Picea abies and Fagus sylvatica) effects on soil water acidification and aluminium chemistry at sites subjected to long-term acidification in the Ore Mts., Czech Republic.
The effect of European beech (Fagus sylvatica) and Norway spruce (Picea abies) on acid deposition and soil water chemistry was studied at a site in the Ore Mts., Czech Republic, that has been subjected to decades of elevated acidic deposition. Dry deposition onto the spruce canopy significantly increased acid input to the soil in comparison to the beech canopy. As a result soil waters were more acidic; Al, SO4(2-), and NO3- concentrations were significantly higher; and Ca and K concentrations were lower in the spruce stand than in the beech stand. The concentrations of potentially toxic inorganic aluminium (Al(in)) were, on average, three times higher in the spruce stand than in the beech stand. Thus, Al played a major role in neutralizing acid inputs to mineral soils in the spruce stand. Despite the higher dissolved organic carbon (DOC) concentrations in spruce organic soil solutions, organic Al (Al(org)) accounted for only 30% of total Al (Al(tot)), whereas in beech organic soil solutions Al(org) was 60% of Al(tot). Soil waters in the beech stand exhibited Al(in) concentrations close to solubility with jurbanite (Al(SO4)OH.5H2O). The more acidic soil waters in the spruce stand were oversaturated with respect to jurbanite. The Bc/Al(in) ratio (Bc = Ca + Mg + K) in O horizon leachate was 4.6 and 70 in spruce and beech stands, respectively. In beech mineral soil solutions, the Bc/Al(in) ratio declined significantly to about 2. In the spruce stand, mineral soil solutions had Bc/Al(in) values below the critical value of 1. The observed Bc/Al(in) value of 0.4 at 30 cm depth in the spruce stand suggests significant stress for spruce rooting systems. A more favourable value of 31 was observed for the same depth in the beech stand. The efficiency of the spruce canopy in capturing acidic aerosols, particulates, and cloud water has resulted in the long-term degradation of underlying soils as a medium for sustainable forest growth.


The switch from rapid-acting to concentrated regular insulin improves glucose control in type 2 diabetes patients on pump therapy: A cohort survey.
To evaluate the impact of switching from U-100 to U-500 insulin in patients with type 2 diabetes mellitus (T2DM) uncontrolled with continuous subcutaneous insulin infusion (CSII) by pump. We retrospectively collected data from patients with T2DM, treated by U-100 CSII, who were switched to U-500 regular insulin where haemoglobin A1c (HbA1c) was >8% and/or insulin total daily dose (TDD) was >100 UI/d. Data collection from patient medical records included HbA1c, lipid levels, liver biomarkers, weight, TDD, declared hypoglycaemic episodes and measured by continuous glucose monitoring (CGM). Sixty-five patients were included, aged 63.9 ± 8.6 years, insulin pump since 3.7 ± 3 years, TDD 186 ± 52 U/day, body mass index 39.4 ± 5.3 kg/m², HbA1c 9.03 ± 1.6%. After switching to U-500 insulin, HbA1c dropped by -0.96% (P < 0.0001) at one year with the effect maintained at three years (- 0.95%, P < 0.01). A subgroup analysis (n=42/65) using a severity score which covered the three previous years on U-100 and the next three years on U-500 insulin confirmed the latter's efficacy. Body weight increased by + 4.8 kg and TDD by 16% at three years. Declared non-severe hypoglycaemia increased significantly three- to four-fold during follow up, but % time-below-range at six months did not differ between the two treatments. Baseline HbA1c correlated with improved glucose control with U-500. U-100 to U-500 insulin switch improves glucose control in CSII T2DM patients, especially with high baseline HbA1c. Use of concentrated insulin in pumps may represent an advance in the strategy for treating T2DM insulin resistant states with uncontrolled hyperglycaemia after a switch from multiple daily injections to pump therapy.


Quantitative radiographic assessment of the anatomic attachment sites of the anterior and posterior complexes of the proximal tibiofibular joint.
Quantitative guidelines for radiographic identification of the anterior and posterior ligaments of the proximal tibiofibular joint have not been well defined. The purpose of this study was to provide reproducible, quantitative descriptions of radiographic landmarks identifying the anterior and posterior ligament complexes of the proximal tibiofibular joint. It was hypothesized that consistent quantitative data regarding the radiographic location of the anterior and posterior proximal tibiofibular joint ligament complexes could be identified. The footprint centers of the individual ligament bundles of the anterior and posterior complexes of the proximal tibiofibular joint were labeled with radio-opaque markers in ten non-paired, fresh-frozen cadaveric knee specimens. Anteroposterior (AP) and lateral radiographs of the proximal tibiofibular joint were obtained, and distances between the markers and pertinent radiographic landmarks were recorded. On AP radiographs, the tibial span of the anterior complex was 12.8 ± 3.9 mm and started at a median of 11.4 mm distal to the tibial plateau; the fibular span was 11.6 ± 6.8 mm and started at a median of 5.1 mm from the apex of the fibular styloid. The tibial span of the posterior complex was 11.7 ± 8.4 mm and began at a median of 12.1 mm distal to the tibial plateau; the fibular span was 11.8 ± 7.9 mm and began at a median of 3.1 mm distal to the apex of the fibular styloid. Values were similar for lateral radiographs. The attachment locations of the proximal tibiofibular anterior and posterior complexes could be quantitatively correlated to reliable osseous landmarks and radiographic lines. This information will allow for consistent radiographic assessments of proper tunnel placement intraoperatively and postoperatively during anatomic reconstructions of the proximal tibiofibular joint.


Extended X-ray absorption fine structure determination of iron nitrogen distances in haemoglobin.
EXAFS spectra have been obtained of oxy and deoxy complexes of haemoglobin and of the 'picket fence' porphyrin, using synchrotron radiation as a source of X rays. The fluorescence data were Fourier filtered to obtain distances to the first shell and corrections applied to remove contributions from the axial ligands. In this way, the iron to porphinato nitrogen distances were determined to be 1.98 +/- 0.01 A for both oxygenated complexes and 2.055 +/- 0.01 A for both deoxy forms.


Conventional optimization and characterization of microbial dextran using treated sugarcane molasses.
This study focuses the comparison on yield of microbial dextran using treated sugarcane molasses (SCM) as a feed stock from different treatment methods. The suitable method for treatment of SCM was identified on the basis of microbial dextran production. The different factors namely the concentrations of total sugars, nitrogen sources, inoculum size, shaking speed, initial medium pH, and phosphate sources influencing the production of microbial dextran were studied. The maximum yield of dextran was obtained to be 17.18 ± 0.08 g L-1 using the conventional optimization. The structural analysis of produced dextran from SCM with various treatment techniques was compared using Fourier-transform infra-red analysis and nuclear magnetic resonance spectroscopy. Later, the rheological behavior of produced microbial dextran was examined and found to be a non-Newtonian. To the best of our knowledge, the comparison on the production of microbial dextran through fermentation using SCM with various treatment strategies has not been performed yet.


Effects of glycation method on the emulsifying performance and interfacial behavior of coconut globulins-fucoidan complexes.
Coconut globulins (CG) possesses potential as an emulsifier but has not been utilized well. In this study, the emulsifying performance of glycated CG-fucoidan (CGF) complexes, and the relationship between emulsifying stability and interfacial behavior were investigated. The results showed that the grafting of fucoidan increased the molecular weight of CG, and decreased the zeta potential and fluorescence intensity. With the higher glycosylation degree, the fucoidan modified CG exhibited better emulsifying stability and higher viscosity. Moreover, the result of adsorption kinetics revealed that elasticity was the main property of the interface layer. Compared to CG, CGF complexes with high degree of glycosylation had thicker interfacial layer on the oil-water interface. A thicker elastic interfacial layer may be beneficial to the emulsion stability, owing to the strong interaction of electrostatic repulsion and steric hindrance between oil droplets. These findings may provide useful information for glycated CGF complexes as emulsifiers in functional food.


Preliminary Exploration of the Sequence of Nerve Fiber Bundles Involvement for Idiopathic Normal Pressure Hydrocephalus: A Correlation Analysis Using Diffusion Tensor Imaging.
The study preliminarily explored the sequence and difference of involvement in different neuroanatomical structures in idiopathic normal pressure hydrocephalus (INPH). We retrospectively analyzed the differences in diffusion tensor imaging (DTI) parameters in 15 ROIs [including the bilateral centrum semiovale (CS), corpus callosum (CC) (body, genu, and splenium), head of the caudate nucleus (CN), internal capsule (IC) (anterior and posterior limb), thalamus (TH), and the bilateral frontal horn white matter hyperintensity (FHWMH)] between 27 INPH patients and 11 healthy controls and the correlation between DTI indices and clinical symptoms, as evaluated by the INPH grading scale (INPHGS), the Mini-Mental State Examination (MMSE), and the timed up and go test (TUG-t), before and 1 month after shunt surgery. Significant differences were observed in DTI parameters from the CS (p FA1 = 0.004, p ADC1 = 0.005) and the genu (p FA2 = 0.022; p ADC2 = 0.001) and body (p FA3 = 0.003; p ADC3 = 0.002) of the CC between the groups. The DTI parameters from the CS were strongly correlated with the MMSE score both pre-operatively and post-operatively. There was association between apparent diffusion coefficient (ADC) values of anterior and posterior limbs of the IC and MMSE. The DTI parameters of the head of the CN were correlated with motion, and the ADC value was significantly associated with the MMSE score. The FA value from TH correlated with an improvement in urination after shunt surgery. We considered that different neuroanatomical structures are affected differently by disease due to their positions in neural pathways and characteristics, which is further reflected in clinical symptoms and the prognosis of shunt surgery.


Chronic hidradenitis suppurativa of the anal canal. A surgical skin disease.
Obstruction of the outlet of the apocrine duct adjacent to the skin surface, with subsequent rupture into the intradermal plane, initiates the inflammatory condition termed "hidradenitis suppurativa." The chronic manifestations of the process, indicated by recurrent abscess formation, draining sinuses, skin fistulas, and an intense cicatricial response, usually affect the distal two thirds of the anatomic anal canal because the proximal portion is devoid of hair follicles and accessory glands. An anal fistula that lacks continuity with the cryptoglandular units of the dentate margin or intersphincteric space (or both) is suggestive of the presence of hidradenitis. The fistula of chronic hidradenitis suppurativa can be diagnosed by a track that originates in a pitlike scar, usually epithelialized, within the skin of the distal anal canal, which then progresses beyond the anal verge superficial to the internal sphincter muscle. A group of 30 patients have been followed up from one to seven years and are without evidence of recurrent symptoms in the anal canal.


Techniques for improving cardiac performance with implantable devices.
A variety of pacing techniques are available to improve cardiac performance in patients who have bradyarrhythmias. These approaches include the preservation of AV synchrony and rate responsiveness, whereby pacing rate is varied according to some physiologic marker such as the atrial rate. New rate responsive pacemakers utilize other sensors to govern pacing rate and these units may monitor QT interval duration, respiratory rate, activity, venous oxygen saturation, temperature, or pH. Additional sensors are presently being investigated and prototype stroke volume and pressure monitoring devices should be available in the near future. All of these approaches require clinical evaluation and their eventual widespread application must be preceded by thorough studies of benefit, risk, and cost.


Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer.
In previous studies it has been found that in cell cultures of human adult ovaries there is a population of small stem cells with diameters of 2-4 μm, which are present mainly in the ovarian surface epithelium and are comparable to very small embryonic-like stem cells (VSELs) from bone marrow. These cells are not observed by histopathologists in the ovarian tissue due to their small size and unknown clinical significance. Because these cells express a degree of pluripotency, they might be involved in the manifestation of ovarian cancer. Therefore we studied the ovarian tissue sections in women with borderline ovarian cancer and serous ovarian carcinoma to perhaps identify the small putative stem cells in situ. In 27 women with borderline ovarian cancer and 20 women with high-grade serous ovarian carcinoma the ovarian tissue sections were stained, per standard practice, with eosin and hematoxylin staining and on NANOG, SSEA-4 and SOX2 markers, related to pluripotency, using immunohistochemistry. We focused on the presence and localization of small putative stem cells with diameters of up to 5 μm and with the nuclei spread over nearly the full cell volume. In ovarian sections of both borderline ovarian cancer and serous ovarian carcinoma patients we were able to identify the presence of small round cells complying with the above criteria. Some of these small cells were NANOG-positive, were located among epithelial cells in the ovarian surface epithelium and as a single cell or groups of cells/clusters in typical "chambers", were found only in the presence of ovarian cancer and not in healthy ovaries and are comparable to those in fetal ovaries. We envision that these small cells could be related to NANOG-positive tumor-like structures and oocyte-like cells in similar "chambers" found in sections of cancerous ovaries, which could support their stemness and pluripotency. Further immunohistochemistry revealed a similar population of SSEA-4 and SOX2-positive cells. We may conclude that putative small stem cells expressing markers, related to pluripotency, are present in the ovarian tissue sections of women with borderline ovarian cancer and high-grade serous ovarian carcinoma thus indicating their potential involvement in ovarian cancer.


Erythropoiesis during an erythroblastic phase of chronic myeloproliferative disorder associated with monosomy 7.
A chronic myeloproliferative disorder associated with monosomy 7 is described in a 3 1/2-year-old boy. His presenting features closely resembled those of juvenile chronic myeloid leukaemia (JCML). Cytogenetic study of bone marrow cells showed that all of the metaphases examined had chromosome 7 deletions. He developed an erythroblastic phase, characterized by anaemia, marked erythroid hyperplasia of bone marrow and the appearance of nucleated red blood cells in the peripheral blood. During the erythroblastic phase, blood transfusion resulted in a suppression of erythropoiesis as evidenced in both the peripheral blood and bone marrow. The in vitro culture studies showed that the erythroid precursor was dependent upon erythropoietin (Ep) for differentiation and proliferation during the erythroblastic phase. However, the Ep dose-response curve showed that a peak of erythroid colony formation occurred at a lower concentration than in the healthy controls. These findings suggest that although the erythroid precursor remains under the control of Ep, it has an increased sensitivity to Ep during the erythroblastic phase of monosomy 7.


Degradative properties and cytocompatibility of a mixed-mode hydrogel containing oligo[poly(ethylene glycol)fumarate] and poly(ethylene glycol)dithiol.
Our laboratory is currently exploring synthetic oligo(poly(ethylene glycol)fumarate) (OPF)-based biomaterials as a means to deliver fibroblasts to promote regeneration of central/partial defects in tendons and ligaments. In order to further modulate the swelling and degradative characteristics of OPF-based hydrogels, OPF crosslinking via a radically initiated, mixed-mode reaction involving poly(ethylene glycol) (PEG)-diacrylate and PEG-dithiol was investigated. Results demonstrate that mixed-mode hydrogels containing OPF can be formed and that the presence of 20 wt.% PEG-dithiol increases swelling and decreases degradation time vs. 10 wt.% PEG-dithiol and non-thiol-containing hydrogels (20% thiol fold swelling 28.7+/-0.8; 10% thiol fold swelling 11.6+/-1.4; non-thiol 8.7+/-0.2; 20% thiol-containing hydrogels degrade within 15 days in vitro). After encapsulation, tendon/ligament fibroblasts remained largely viable over 8 days of static culture. While the presence of PEG-dithiol did not significantly affect cellularity or collagen production within the constructs over this time period, image analysis revealed that the 20% PEG-dithiol gels did appear to promote cell clustering, with greater values for aggregate area observed by day 8. These experiments suggest that mixed-mode OPF-based hydrogels may provide an interesting alternative as a cell carrier for engineering a variety of soft orthopedic tissues, particularly for applications when it is important to encourage cell-cell contact.


Effect of protonation and deprotonation on the gas-phase reactivity of fluorinated 1,2,4-triazines.
Positive and negative electrospray mass spectrometry (MS), in-time and in-space MS(n) experiments, high-resolution and accurate mass measurements obtained with an Orbitrap, together with density functional theory calculations have been used to study the gas-phase ion chemistry of a series of fluorinated 1,2,4-triazines. As a result of low-energy collision-induced dissociations, occurring in an ion trap and in a triple quadrupole, their protonated and deprotonated molecules show interesting features depending on the nature and structure of the precursor ions. The occurrence of elimination/hydration reactions produced by positive ions in the ion trap is noteworthy. Decompositions of deprotonated molecules, initiated by elimination of a hydroxyl radical from [M-H](-), are dominated by radical anions. Theoretical calculations have allowed us to obtain information on atom sites involved in the protonation and deprotonation reactions.


Dynamic seal at the aortic neck-endograft interface studied using a novel method of cohesive zone modeling.
Endovascular aortic stent graft technology radically altered aortic aneurysm repair from a maximally invasive procedure to a minimally invasive approach. Whereas the overall principle of the repair remained the same, the surgeon ceded control of the proximal seal when suturing was eliminated. In endovascular aneurysm repair (EVAR), no longer does the surgeon control the precise placement of mechanical fasteners (sutures) between graft and tissue; rather, the graft is kept in place by creation of a seal zone that often lacks any mechanical fastening. The kinematic coupling condition is replaced by contact mechanics between the outer graft surface and the aorta. We develop a novel computational methodology to fully model and characterize the aorta-endograft seal zone within a fully integrated aorta-EVAR model. The aorta, endograft, and intraluminal thrombus are modeled by standard finite element analysis in the limit of elastic response under pressure loading conditions. The seal zone in our simulations is fully dynamic and modeled using the cohesive zone method. Our methodology allows full separation of the aorta and endograft, simulating loss of seal and endoleak. Using patient-specific geometry, we show that our approach is capable of predicting the location of rupture in an index patient who presented with a ruptured juxtarenal aneurysm. Applying our novel cohesive zone method analysis to the post-EVAR geometry, we studied the stability of the endograft under several seal zone strengths correlating to very weak, standard, and very strong seal. Loss of seal is shown to correlate to the propagation of an elastic front in the aortic neck. We propose that aortic neck dilation, which develops from graft deployment and pressurization, provides an energy release mechanism that drives seal zone failure: the elasto-adhesive seal model. We develop the first ever fully integrated computational model of aorta-endograft seal. Our elasto-adhesive seal model provides the first biomechanical model to evaluate seal loss. We hope that our method will provide a rich tool set with which to study the vexing problems of type I endoleak and help guide the development of technologies to optimize seal.


Clinical anatomy of the precuneus and pathogenesis of the schizophrenia.
Recent evidence has shown that the precuneus plays a role in the pathogenesis of schizophrenia. The precuneus is a structure of the parietal lobe's medial and posterior cortex, representing a central hub involved in multimodal integration processes. Although neglected for several years, the precuneus is highly complex and crucial for multimodal integration. It has extensive connections with different cerebral areas and is an interface between external stimuli and internal representations. In human evolution, the precuneus has increased in size and complexity, allowing the development of higher cognitive functions, such as visual-spatial ability, mental imagery, episodic memory, and other tasks involved in emotional processing and mentalization. This paper reviews the functions of the precuneus and discusses them concerning the psychopathological aspects of schizophrenia. The different neuronal circuits, such as the default mode network (DMN), in which the precuneus is involved and its alterations in the structure (grey matter) and the disconnection of pathways (white matter) are described.


Epidemiological profile and transmission dynamics of COVID-19 in the Philippines.
The Philippines confirmed local transmission of COVID-19 on 7 March 2020. We described the characteristics and epidemiological time-to-event distributions for laboratory-confirmed cases in the Philippines recorded up to 29 April 2020 and followed until 22 May 2020. The median age of 8212 cases was 46 years (IQR 32-61), with 46.2% being female and 68.8% living in the National Capital Region. Health care workers represented 24.7% of all detected infections. Mean length of hospitalisation for those who were discharged or died were 16.00 days (95% CI 15.48-16.54) and 7.27 days (95% CI 6.59-8.24). Mean duration of illness was 26.66 days (95% CI 26.06-27.28) and 12.61 days (95% CI 11.88-13.37) for those who recovered or died. Mean serial interval was 6.90 days (95% CI 5.81-8.41). Epidemic doubling time prior to the enhanced community quarantine (ECQ; 11 February and 19 March) was 4.86 days (95% CI 4.67-5.07) and the reproductive number was 2.41 (95% CI 2.33-2.48). During the ECQ (20 March to 9 April), doubling time was 12.97 days (95% CI 12.57-13.39) and the reproductive number was 0.89 (95% CI 0.78-1.02).


Atomic force microscopy and light scattering of small unilamellar actin-containing liposomes.
Three-dimensional networks of filamentous actin (F-actin) encapsulated inside phosphatidylcholine liposomes are currently being used in an effort to model the cytoskeleton and plasma membrane of eukaryotic cells. In this article, unilamellar lipid vesicles consisting of egg yolk-derived phosphatidylcholine encapsulating monomeric actin (G-actin) were made via extrusion in low ionic strength buffer (G-buffer). Vesicle shape and structure in these dispersions was studied using a combination of fluid-tapping atomic force microscopy, and multiangle static light scattering. After subjecting the liposome dispersion to high ionic strength polymerization buffer (F-buffer) containing K(+) ions, atomic force microscopy imaging and light scattering of these liposomes indicated the formation of specialized structures, including an overall liposome structure transformation from spherical to torus, disk-shaped geometries and tubular assemblies. Several atomic force microscopy control measurements were made to ascertain that the specialized structures formed were not due to free G-actin and F-actin self-assembling on the sample surface, plain liposomes exposed to G- and F-buffer, or liposomes encapsulating G-actin. Liposomes encapsulating G-actin assumed mostly thin disk shapes and some large irregularly shaped aggregates. In contrast, liposomes encapsulating polymerized actin assumed mostly torus or disk shapes along with some high aspect ratio tubular structures.


The effect of heparin on lysosomes of the dog pancreas during acute experimental pancreatitis.
In 12 dogs with acute experimental pancreatitis (AEP) and 6 control animals the "free", "latent" and "total" activity of acid phosphatase, beta-glucuronidase and cathepsins in whole homogenates of the pancreas, in a lysosomal-enriched subfraction and the supernatant of pancreatic tissue was estimated. AEP was induced by injection of bile salts and thrombin solution into the pancreatic duct. In 6 dogs the protection with heparin (1.5 mg/kg/body weight) immediately after producing AEP was applied. In AEP without any protection the free activity of hydrolases in the whole homogenate (80--90%) and in the lysosomal enriched subfraction (75--90%) was higher than in the controls (60--70% and 55--75% respectively), suggesting an augmented lysosomal fragility during the course of AEP. Heparin depressed the free activity of hydrolases to 60--80% in whole homogenates, and 64--75% in the lysosomal enriched subfraction. The release of cathepsins during incubation of the lysosomal-enriched subfraction in acidic medium was lower in the group with heparin treatment. The data obtained suggest the stabilising effect of heparin on the lysosomes of the pancreas during acute experimental pancreatitis in dogs.


Unexpected factors affecting the excitability of human motoneurones in voluntary and stimulated contractions.
The output of human motoneurone pools decreases with fatiguing exercise, but the mechanisms involved are uncertain. We explored depression of recurrent motoneurone discharges (F-waves) after sustained maximal voluntary contractions (MVCs). MVC depressed the size and frequency of F-waves in a hand muscle but a submaximal contraction (at 50% MVC) did not. Surprisingly, activation of the motoneurones antidromically by stimulation of the ulnar nerve (at 20 or 40 Hz) did not depress F-wave area or persistence. Furthermore, a sustained (3 min) MVC of a hand muscle depressed F-waves in its antagonist but not in a remote hand muscle. Our findings suggest that depression of F-waves after voluntary contractions is not simply due to repetitive activation of the motoneurones but requires descending voluntary drive. Furthermore, this effect may depress nearby, but not distant, spinal motoneurone pools. There are major spinal changes induced by repetitive activity and fatigue that could contribute to 'central' fatigue but the mechanisms involved are poorly understood in humans. Here we confirmed that the recurrent motoneuronal discharge (F-wave) is reduced during relaxation immediately after a sustained maximal voluntary contraction (MVC) of an intrinsic hand muscle (abductor digiti minimi, ADM) and explored the relationship between motoneurone firing and the depression of F-waves in three ways. First, the depression (in both F-wave area and F-wave persistence) was present after a 10 s MVC (initial decrease 36.4 ± 19.1%; mean ± SD) but not after a submaximal voluntary contraction at 50% maximum. Second, to evoke motoneurone discharge without volitional effort, 10 s tetanic contractions were produced by supramaximal ulnar nerve stimulation at the elbow at physiological frequencies of 25 and 40 Hz. Surprisingly, neither produced depression of F-waves in ADM to test supramaximal stimulation of the ulnar nerve at the wrist. Finally, a sustained MVC (3 min) of the antagonist to ADM (4th palmar interosseous) depressed F-waves in the anatomically close ADM (20 ± 18.2%) but not in the more remote first dorsal interosseous on the radial side of the hand. We argue that depression of F-waves after voluntary contractions may not be due to repetitive activation of the motoneurones but requires descending voluntary drive. Furthermore, this effect may depress nearby, but not distant, spinal motoneurone pools and it reveals potentially novel mechanisms controlling the output of human motoneurones.


Rat antibodies as probes for the characterization of progesterone receptor A and B proteins from laying hen oviduct cytosol.
The chicken oviduct contains two different hormone binding forms of the progesterone receptor, A and B. We have prepared rat antisera against both forms of the receptor partially purified from laying hen oviduct. The anti-progesterone receptor A antiserum reacts with both receptor forms on Western blots, while the anti-progesterone receptor B antiserum reacts mainly with the B form. Both antisera also react with the native progesterone receptor proteins as shown by sedimentation analysis of the antibody-receptor complexes. Receptors A and B are recognized on Western blots of total protein from dissolved tissue, indicating that both forms are likely to be physiological components. Epitope mapping experiments show that immunogenicity of both receptor molecules is restricted to structurally related protein domains of 28 kDa in receptor A and of 52 kDa in receptor B.


Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin.
Photobleaching of rhodopsin in rod photoreceptors activates the visual cascade system leading to a decrease in cyclic GMP and the closure of cGMP-gated channels in the rod outer segment plasma membrane. Calcium plays an important role in the recovery of the rod outer segment to its dark state by regulating the resynthesis of cGMP by guanylate cyclase. Here we report that calmodulin, a Ca(2+)-binding protein present in the rod outer segment, increases the apparent Michaelis constant of the channel for cGMP. This results in a decrease in the rate of cation influx into the rod outer segment by two- to sixfold at low cGMP concentrations and has the effect of increasing the sensitivity of the channel to small changes in cGMP levels during phototransduction. Biochemical studies indicate that calcium-calmodulin binds to a protein of M(r) 240K which is tightly associated with the channel. On the basis of these studies, Ca2+ is suggested to play a central role in photorecovery and light adaptation, not only by regulating guanylate cyclase, possibly through recoverin, but also by modulating the cGMP-gated channel through calmodulin interaction with the 240K protein.


Risk perception and preventive behaviours of COVID-19 among university students, Gondar, Ethiopia: a cross-sectional study.
This study aimed to assess COVID-19 preventive behaviours and their associated factors among university students. An institution-based cross-sectional study was employed among 405 university students and the study participants were chosen using a stratified simple random selection procedure. A pretested self-administered questionnaire was used to assess participants' perception of and preventive behaviour towards COVID-19. A multivariable logistic regression analysis was employed to identify factors associated with COVID-19 preventive behaviour. A total of 405 students participated in this study with a response rate of 97.4%. The mean age of the participants was 23.6 (SD ±2.4, range 19-30) years. Two hundred and twenty of the participants (45.7% with 95% CI 41.0% to 51.0%) had good preventive behaviour towards COVID-19. COVID-19 preventive behaviour was significantly associated with age (adjusted OR (AOR)=1.1, 95% CI 1.00 to 1.2), female sex (AOR=1.6, 95% CI 1.02 to 2.60), knowing anyone infected with COVID-19 (AOR=4.05, 95% CI 1.9 to 8.8), participants who had high perceived susceptibility (AOR=2.14, 95% CI 1.44 to 3.35) and participants who were enrolled in health programmes (AOR=4.23, 95% CI 2.6 to 7.0). The overall COVID-19 preventive behaviour among university students is unsatisfactory. Students' COVID-19 preventive behaviour was influenced by age, sex, knowing a COVID-19 infected person, perceived susceptibility and the sort of programme in which they had enrolled. The findings revealed that health communication interventions aimed at changing people's perceptions of COVID-19 and related prevention strategies are urgently needed to improve this population's COVID-19 preventive behaviour.


Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives.
One-third of breast cancer (BC) cases worldwide occur in women aged 65 years and older, with 10 to 15% overexpressing the human epidermal growth factor receptor 2 (HER2). Although several HER2-targeted therapies have been developed, the lack of data regarding their use in older patients hampers evidence-based decision-making for this population. We review current evidence on the efficacy and safety of HER2-targeted therapies in older adults with BC, focusing on approved therapies such as trastuzumab, lapatinib, pertuzumab, ado-trastuzumab-emtansine, and neratinib. Additionally, we discuss drugs under development to target the HER2-receptor, and to overcome resistance to existing therapies. Finally, we highlight the cardiotoxicity of HER2-targeted drugs among older adults. Older adults are underrepresented in trials of HER2-targeted therapies in BC. We propose strategies to increase recruitment of older adults in clinical trials in order to increase the evidence base to treat this growing population.


Biofeedback modification of frontal EMG in normal subjects.
We carried out a controlled study on the voluntary control of the frontalis muscle by biofeedback procedures employing 20 normal subjects. Subjects were randomly divided into two groups of 10: (1) the biofeedback group and (2) the control group. Each of the two groups received five training sessions of about 40 minutes' duration each on different days. The results obtained are as follows: (1) In the biofeedback group, mean EMG levels decreased progressively and markedly from 2. 16 muVp-p min the first session to 1.54 muVp-p min in the last session. On the contrary, the control group did not show constant decreases in EMG levels over sessions. (2) The changes in the heart rate did not correlate with the changes in EMG activity. (3) The changes in the respiratory rate correlated with the changes in EMG activity.


Determination of mean whole body intracellular pH in unanesthetized dogs.
In order to determine mean whole body pHi in unanesthetized dogs, assumptions on the urinary and intestinal excretion of DMO, the total loss of an injected single dose of [14C] DMO, and the distribution kinetics of DMO were tested experimentally. Urinary excretion of DMO was almost negligible. The best assumption on the total loss of DMO was based on the exponential decay observed over a period of 1 to 4 weeks. The biological half-life of DMO was 5 days, the time constant being --0.14 d-1. The extracellular distribution of DMO was considered to equal that of [3H] inulin. Between 1 and 7 hours after an injection of inulin in nephrectomized dogs the distribution volume increased linearly from 16% of the body weight after 2 hours to 21% after 6 hours. Based on these experimental results, pHi was determined in 16 unanesthetized dogs. 120 min after the injection of DMO pHi was 7.05 and 430 min after the injection pHi was 7.11. It is concluded that the assumption made allow the estimation of pHi in unanesthetized dogs over a period of 1 to 7 hours.


The molecular basis of T helper cell function--I. Allotype- and MHC-linked determinants on antigen-specific, H-2-restricted T cell lines, hybridomas and lymphomas.
A T-cell hybridoma clone, which produces antigen-specific helper factors and a T-cell lymphoma clone which produces non-specific helper factors was used to study the expression of T-cell allotypes and Ia antigens. Use was made of rabbit antisera against isolated T-cell receptor material and of monoclonal mouse antibodies against isolated rat Ia antigen. The rabbit antisera detected endogenously produced determinants both on the membrane and on intracellular polypeptides of these cells. The monoclonal mouse anti-rat-Ia antibodies detected polymorphic determinants on mouse Ia antigens and reacted with endogenously produced molecules on the membrane and on intracellular molecules of the hybridoma and lymphoma cells. The molecules carrying Tcr allotypes were single-chain polypeptides with mol. wts of 60,000-70,000 and the molecules carrying Ia-like antigenic determinants were single-chain polypeptides with mol. wts of 40,000-50,000. Thus T-cell allotypes and Ia antigens were found on separate polypeptide chains. The role and genetic localization of allotype-like and Ia-like molecules in T-cell products is discussed.


Enzymatic oxidation of aqueous pentachlorophenol.
The influence of the nonionic surfactant Tween 80 on pentachlorophenol (PCP) oxidation catalyzed by horseradish peroxidase was studied. The surfactant was tested at concentrations below and above its critical micelle concentration (CMC). Enhancement of PCP removal was observed at sub-CMCs. The presence of Tween 80 in the reaction mixture reduced enzyme inactivation which occurred through a combination of free radical attack and sorption by precipitated products. A simple first-order model was able to simulate time profiles for enzyme inactivation in the presence or absence of Tween 80. At supra-CMCs, the surfactant caused noticeable reductions in PCP removal, presumably through micelle partitioning of PCP which precluded the hydrophobic PCP molecule from interacting with the enzyme.


Effects of acute valproate administration on carnitine metabolism in mouse serum and tissues.
Carnitine concentrations in serum, liver, kidney, muscle and heart were determined 30 min, 2 hr and 4 hr after administration of single 50 mg/kg doses of valproic acid (VPA) or octanoic acid (OTA) of fasting mice. Half an hour post-administration (p.a.) of VPA, free carnitine concentrations were smaller than in controls in serum, liver, kidney and heart. Four hr p.a., the effects of VPA had disappeared from all the carnitine sources, which now had concentrations that were not significantly different from those of controls. The effects of OTA are different from, and sometimes the opposite of, those of VPA, showing that the effects of VPA are specific to it. Hyperammonemia, on the other hand, was greatest 4 hr p.a. of VPA. These findings show that the effect of VPA on carnitine metabolism is immediate but transient, and accordingly suggest that the carnitine deficiency observed in patients under prolonged treatment with VPA-containing anticonvulsants must be due to a more complex mechanism than direct interaction between carnitine and VPA.


Platelet transfusion in the management of severe thrombocytopenia in neonatal intensive care unit patients.
Platelet transfusions are frequently given to neonatal intensive care unit (NICU) patients with severe thrombocytopenia (platelets less than 50 x 10(9) L(-1)) but no study has assessed whether this is clinically appropriate. To address this we conducted a retrospective review of platelet transfusion practice in patients developing severe thrombocytopenia over 3 years in a single NICU. Out of 901 admissions, 53 (6%) developed severe thrombocytopenia. Twenty-seven neonates received a total of 63 platelet transfusions, the main triggers being: platelet count less than 30 x 10(9) L(-1) (all patients), or less than 50 x 10(9) L(-1) in those with previous haemorrhage or clinical instability. No major haemorrhage occurred during severe thrombocytopenia either in neonates in whom platelet transfusions were withheld (26/53) or in neonates given platelets who survived to discharge (22/27). Five preterm neonates given platelets died but all had overwhelming sepsis or necrotizing enterocolitis and none died directly as a result of haemorrhage. Although the widely used liberal triggers for neonatal platelet transfusion highlighted in this review reflect available guidelines, and represent cautious ('safe') haemostatic practice, they are likely to result in unnecessary transfusion for a significant number of NICU patients. Improved practice requires definition of a safe lower limit for platelet count in stable neonates; effective platelet transfusion strategies for sick neonates; and improved therapies for conditions precipitating severe thrombocytopenia.


Lipid hydroperoxide decomposition in model emulsions stabilized with emulsifiers having various sizes of hydrophilic heads.
The vulnerability of oils in emulsions to oxidation depends on the structural and physicochemical properties of oil droplet interface. To evaluate the implications of the interfacial characteristics of emulsion droplets on lipid oxidation, particularly lipid hydroperoxide decomposition, emulsions were prepared using emulsifiers with various lengths of polar groups because the length of hydrophilic heads of emulsifiers could be an important factor in determining the thickness of the droplet surface. The decomposition rate constants of cumene hydroperoxide in emulsions showed that the cumene hydroperoxide in emulsions having a thick emulsion droplet interface was decomposed faster than in emulsions having a loosen one. Our findings also showed that the denseness of the droplet interface affected cumene hydroperoxide decomposition in emulsions. Conclusively, this study suggested that the interfacial thickness and denseness of the emulsion droplets influence oxidative stability of emulsions.


Homotypic versican G1 domain interactions enhance hyaluronan incorporation into fibrillin microfibrils.
Versican G1 domain-containing fragments (VG1Fs) have been identified in extracts from the dermis in which hyaluronan (HA)-versican-fibrillin complexes are found. However, the molecular assembly of VG1Fs in the HA-versican-microfibril macrocomplex has not yet been elucidated. Here, we clarify the role of VG1Fs in the extracellular macrocomplex, specifically in mediating the recruitment of HA to microfibrils. Sequential extraction studies suggested that the VG1Fs were not associated with dermal elements through HA binding properties alone. Overlay analyses of dermal tissue sections using the recombinant versican G1 domain, rVN, showed that rVN deposited onto the elastic fiber network. In solid-phase binding assays, rVN bound to isolated nondegraded microfibrils. rVN specifically bound to authentic versican core protein produced by dermal fibroblasts. Furthermore, rVN bound to VG1Fs extracted from the dermis and to nondenatured versican but not to fibrillin-1. Homotypic binding of rVN was also seen. Consistent with these binding properties, macroaggregates containing VG1Fs were detected in high molecular weight fractions of sieved dermal extracts and visualized by electron microscopy, which revealed localization to microfibrils at the microscopic level. Importantly, exogenous rVN enhanced HA recruitment both to isolated microfibrils and to microfibrils in tissue sections in a dose-dependent manner. From these data, we propose that cleaved VG1Fs can be recaptured by microfibrils through VG1F homotypical interactions to enhance HA recruitment to microfibrils.


Melanoma brain metastases: an unmet challenge in the era of active therapy.
Metastatic disease to the brain is a frequent manifestation of melanoma and is associated with significant morbidity and mortality and poor prognosis. Surgery and stereotactic radiosurgery provide local control but less frequently affect the overall outcome of melanoma brain metastases (MBM). The role of systemic therapies for active brain lesions has been largely underinvestigated, and patients with active brain lesions are excluded from the vast majority of clinical trials. The advent of active systemic therapy has revolutionized the care of melanoma patients, but this benefit has not been systematically translated into intracranial activity. In this article, we review the biology and clinical outcomes of patients with MBM, and the evidence supporting the use of radiation, surgery, and systemic therapy in MBM. Prospective studies that included patients with active MBM have shown clinical intracranial activity that parallels systemic activity and support the inclusion of patients with active MBM in clinical trials involving novel agents and combination therapies.


Temporal characteristics of proximally-induced accommodation.
This study sought to determine whether proximally-induced accommodation (PIA) is capable of sustaining an accommodative response over time. Accordingly, the steady-state PIA response was measured during the course of a continuous 5 min stimulus period for targets located at distances of 0.2 or 6 m. The vergence and accommodation loops were opened by subjects (n = 8) monocularly viewing the targets through a 0.5 mm pinhole, while accommodation was assessed using an objective, open-field, infrared optometer. The mean PIA response did not change significantly during the fixation period. This finding suggests that PIA is indeed capable of maintaining a sustained response. This observation is consistent with the constancy of apparent target distance perception during extended fixation of a stationary object of regard under these conditions.


Role of diffusion-weighted MR imaging in assessing malignant versus benign skull-base lesions.
This study was done to assess the role of diffusion-weighted magnetic resonance (MR) imaging in assessing malignant versus benign skull lesions. A retrospective analysis was undertaken of 45 patients (26 male, 19 female; age range 14-68 years, mean age 39 years) with skull-base lesions. Diffusion-weighted MR images were acquired with a b-factor of 500 and 1,000 s/mm(2) using single-shot echoplanar imaging. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the lesion was calculated. The mean ADC value of malignant tumours was (1.002 ± 0.21) × 10(-3) mm(2)/s and that of benign tumours was (1.63 ± 0.29) × 10(-3) mm(2)/s. There was a statistically significant difference (p=0.001) in the ADC value of malignant skull-base tumours versus benign lesions. Selection of (1.3) × 10(-3)mm(2)/s as a threshold value of ADC for differentiating benign from malignant tumours yielded the best result, with an accuracy of 94%, sensitivity of 94%, specificity of 93%, positive predictive value of 93%, negative predictive value of 94% and area under the curve of 0.932. We conclude that diffusion-weighted MR imaging is a promising, noninvasive approach that can be used to characterise skull-base lesions in that it can help differentiate malignant tumours from benign lesions and evaluate the pathological grading of malignant tumours.


Population dynamics and life history of a solitary coral, Balanophyllia elegans, from Central California.
Size-specific mortality rates and growth rates for the solitary coral Balanophyllia elegans are determined from size-frequency distributions of live corals from natural and artificial substrates, and from skeletons of dead corals found in rubble channels. Marked quadrats were monitored to measure actual recruitment and mortality for juveniles and adults. First year rate of mortality for juveniles is high, 56%; and mortality rate for adults is about 10% annually. Estimates of annual larval survivorship (44%) are incorporated in a life table, and other demographic parameters are calculated. B. elegans has a high intrinsic rate of increase apparently because of high larval survivorship and early onset of reproduction. Population growth is checked partly by high juvenile and random adult mortality. I estimate a 6-11 year average life span for B. elegans at the Hopkins Marine Life Refuge in Pacific Grove, California.


Structure and expression of integrated hepatitis B virus genes in an HBs antigen producing human cell line (huGK-14).
A human continuous cell line (huGK-14) within a lineage of passaged cultures was investigated in the mode of integration and expression of hepatitis B virus (HBV) genes. HBV DNA was integrated in eight different sites of the cellular DNA, in each of which HBV genome was rearranged, fragmented, and/or partly deleted. Complete HBV genome that may lead to production of infectious virus particles was not detected in the cells nor in the culture medium. Clones of cDNA containing a complete coding frame for small HBs antigen protein (type adr) were obtained from mRNA of the cells. The cells were stable over the period of six months of cultivation and more than 60 population doublings in the mode of HBV integration and HBs mRNA expression.These results provide substantial evidence for the absence of an ability for the integrated DNA to create an infectious product in the cell; for the stable production of HBs mRNA from the cells, and suggest the usefulness of this cell line as a substrate for HBV vaccine production.


Effect of anoxia on the urethral response to phenylephrine.
Smooth muscle requires oxygen for proper contractile function. In addition, anoxia has been shown to inhibit the contractile response to various forms of stimulation. Continence, at least in part, depends upon active alpha-adrenergic tone, which provides intraurethral tension during bladder filling. The current study was designed to determine the effect of anoxia on the ability of the urethra to sustain tension. Standard isolated urethral strip preparations were used to determine the effect of anoxia on the contractile response to phenylephrine; isolated whole urethra preparations were used to determine the effect of anoxia on the intraurethral pressure--flow characteristics. The peak tension responses of the female and male urethra to phenylephrine were significantly greater than the plateau tension. Anoxia induced an immediate decrease in phenylephrine-stimulated tonic tension to baseline tension. In the whole urethra preparation, phenylephrine increased opening pressure to a greater extent in the male urethra than in the female urethra. In both sexes, anoxia reduced the opening pressure and completely prevented phenylephrine stimulated increases in opening pressure. The tonic response to phenylephrine is lost virtually immediately upon the initiation of hypoxia. This suggests that hypoxia decreases the ability of the urethra to maintain a tonic response to alpha-adrenergic stimulation during bladder filling and may be a factor in incontinence, especially in females.


Getting back to dental practice.
The results from the survey 'The Provision of Dental Care by Women Dentists in England and Wales in 1985' indicated that the lack of a specific retraining course was a major barrier in preventing women who have left dental practice from returning to work. The need for a course also applied to men and women who have ceased to work because of ill-health.


Evaluation of a patient-centered integrated care program for individuals with frequent hospital readmissions and multimorbidity.
Managing patients with multimorbidity and frequent hospital readmissions is a challenge. Integrated care programs that consider their needs and allow for personalized care are necessary for their early identification and management. This work aims to describe these patients' clinical characteristics and evaluate a program designed to reducing readmissions. This prospective study analyzed all patients with ≥ 3 admissions to a medical department in the previous year who were included in the Internal Medicine Department chronic care program at the Lucus Augusti University Hospital (Lugo, Spain) between April 1, 2019 and April 30, 2021. A multidimensional assessment, personalized care plan, and proactive follow-up with a case manager nurse were provided via an advanced hospital system. Clinical and demographic variables and data on healthcare system use were analyzed at 6 and 12 months before and after inclusion. Descriptive and survival analyses were performed. One hundred sixty-one patients were included. Program participants were elderly (mean 81.4 (SD 11) years), had multimorbidity (10.2 (3) chronic diseases) and polypharmacy (10.6 (3.5) drugs), frequently used the healthcare system, and were highly complex. Most were included for heart failure. The program led to significant reductions in admissions and emergency department visits (p = .0001). A total of 44.7% patients died within 1 year. The PROFUND Index showed good predictive ability (p = .013), with high values associated with mortality (RR 1.15, p = .001). Patients with frequent hospital readmissions are highly complex and need special care. A personalized integrated care program reduced admissions and allowed for individualized decision-making.


Endocytosis and breakdown of ribonuclease oligomers by sinusoidal rat liver cells in vivo. II. Effect of charge.
Experiments presented in this paper suggest that sinusoidal rat liver cells recognize basic groups on proteins and that this recognition results in endocytosis of the proteins. Evidence for involvement of basic groups was obtained in two ways. Firstly, we changed the positively charged amino groups of the cross-linked ribonuclease molecules to neutral or negative by acetylation or succinylation, respectively. The modified proteins did not contain easily reducible disulfide bonds and they were not very sensitive to endoproteases, suggesting that they were not denatured by the acetylation procedures. Acetylation and succinylation reduced uptake of the injected cross-linked ribonuclease derivatives by liver and spleen and abolished their rapid clearance from plasma. In nephrectomized rats about 75% of the polymer, 36% of the acetylated polymer and 32% of the succinylated polymer were endocytosed by liver after 6 h. For the dimer fractions these values were 59%, 23% and 27%, respectively. Autoradiography and subcellular fractionation of liver 30 min post-injection localized the acetylated polymer in the lysosomal/microsomal fraction of sinusoidal liver cells, probably endothelial cells. Secondly, a positive correlation was found between binding of a number of ribonuclease derivatives to the cation exchanger SP-Sephadex G-25 and the rate of endocytosis by sinusoidal liver cells.