Myristic acid-conjugated polyethylenimine for brain-targeting delivery: in vivo and ex vivo imaging evaluation.
To investigate the potential of myristic acid (MC) to mediate brain delivery of polyethylenimine (PEI) as a gene delivery system, a covalent conjugate (MC-PEI) of MC, and PEI was synthesized. A near-infrared fluorescence probe, IR820 was conjugated to MC-PEI to explore its in vivo distribution after intravenous (i.v.) administration in mice. The brain targeting ability of MC-PEI was evaluated by near-infrared fluorescence imaging and analyzed semiquantitatively by fluorescence intensity, respectively. Significant NIR fluorescent signal was detected in the brain 12 h after i.v. administration and further confirmed by imaging the whole brain and brain slices. Semiquantitative results from fluorescence intensity further supported the successful brain delivery of MC-PEI which led to a very significant increase ( approximately 200%) in the brain uptake after i.v. injection in comparison with unmodified PEI. The capability of MC-PEI to condense DNA was further confirmed using agarose gel retardation assay, indicating its potential for gene delivery. The significant in vivo and ex vivo results suggest that MC-PEI is a promising brain-targeting drug delivery system, especially for gene delivery.


Relationship between Anti-Thyroid Peroxidase Antibody and Thyroid Function Test.
Anti-thyroid peroxidase antibody (anti-TPO antibody) is a member of thyroid autoantibodies which are important in inducing and also diagnosing autoimmune thyroid diseases. Thyroid autoimmunity can cause several forms of thyroiditis and abnormal thyroid functions, ranging from hypothyroidism to hyperthyroidism. To evaluate the relationship between serum levels of anti-TPO antibody and thyroid function test parameters (T3, T4, and TSH) in patients with thyroid disease. In 2425 subjects suspected of having thyroid disease referred to Yazd central medical laboratory by physicians during a 2 year period, the concentrations of serum anti-TPO antibody (ELISA) and T3, T4, and TSH (RIA) were measured. 53.53% of the patients were 20 to 39 years old. 2135 patients (88.04%) were female and 290 (11.96%) were male. The levels of T3, T4, and TSH in individuals with normal and raised anti-TPO antibody titers was significantly different (p<0.0001). A correlation between TSH and T4 levels and abnormal anti-TPO antibody was detected (p=0.002). Our results confirm the correlation between thyroid function test and anti-TPO antibody values, indicating the clinical significance of this antibody and suggesting a through clinical examination and follow up of individuals with high anti-TPO antibody titer.


Group identification and college adjustment: the experience of encountering a novel stereotype.
Previous research has investigated members of stigmatized groups by studying the consequences of encountering stereotypes for performance and self-esteem. The present study extends these findings by examining the experience of entering a new environment and encountering a negative stereotype for the first time (i.e., a novel stereotype). Participants were students admitted "provisionally" to a large state university. Results suggest that, when encountering a novel stereotype, targets of stereotypes differed in their identification with the group, and that this identification moderated the consequences of the stereotype for performance and self-esteem. Implications for future research are discussed. These data also suggest that a college-based intervention program can provide a buffer against negative stereotypes by reducing the perceived applicability of the stereotype.


Confusion/delirium following cataract surgery: an incidence study of 1-year duration.
Delirium is frequently observed in clinical practice, particularly in medical and surgical wards and more so among patients at risk, especially elderly with preexisting central nervous system impairments. Despite the severe consequences of delirium, epidemiological data relating to incidence of delirium following "minor" surgery are lacking. The aim of the present study was to evaluate the incidence of delirium following cataract surgery in community-dwelling patients. For purposes of the present study, the Confusion Rating Scale was used. Of 296 patients fulfilling the inclusion criteria, 13 (4.4%) had had immediate postoperative delirium. The two variables that significantly differentiated between delirious and nondelirious patients were older age (82.1 vs. 73.06 years; p < .001) and more frequent use of benzodiazepine premedication (69% vs. 39.9%; p < .002). These findings suggest that the incidence of delirium following cataract surgery requires greater awareness, possibly changes in premedication, and a longer observation period in the very old.


Specific immune recognition of pancreatic carcinoma by patient-derived CD4 and CD8 T cells and its improvement by interferon-gamma.
Pancreatic carcinoma is a very aggressive disease and little is known about its immunobiology. We here describe the presence in pancreatic cancer patients of spontaneously induced functional CD4 and CD8 memory/effector T cells reactive to autologous tumor cells or to the pancreatic cancer associated antigen, MUC-1. Such specific cells were present in the bone marrow or peripheral blood of most of the 23 tested patients. Low dose stimulation of primary cultures of pancreatic cancer cells with 500 IU/ml IFN-gamma for 72 h enhanced HLA-I expression and induced the de novo expression of HLA-II molecules. This led to a much better immune recognition by autologous HLA-I restricted and purified CD8 T cells and allowed tumor cell recognition by HLA-II restricted purified CD4 T-helper cells. Thus, interferon-gamma appears to be a useful adjuvant cytokine to enhance the immunogenicity of a patients' tumor cells and their recognition by tumor reactive immune cells.


Video-assisted neck surgery for thyroid and parathyroid diseases.
Endoscopic surgery has now become a well-established modality for the treatment of various organ diseases. In the present study, we analyzed the surgical results achieved by video-assisted neck surgery (VANS) in thyroid and parathyroid diseases. From January 2000 to April 2002, 87 patients (eight males and 79 females) with a mean age of 49 years underwent VANS. The preoperative diagnoses of these patients included 37 benign thyroid tumors, 30 Graves' diseases, 17 parathyroid adenomas and three thyroid cancers. The mean operative time of VANS was 165 min for a hemithyroidectomy, 287 min for a subtotal thyroidectomy, and 157 min for a parathyroidectomy. The mean intraoperative blood loss was 60, 183 and 23 g for a hemithyroidectomy, subtotal thyroidectomy and parathyroidectomy, respectively. No conversion from VANS to conventional surgery was experienced. Three patients (3.4%) had temporary palsy of the recurrent laryngeal nerve. Otherwise, the postoperative courses were uneventful. VANS for thyroid and parathyroid diseases was found to be safe and effective. From a cosmetic point of view, a high degree of patient satisfaction was obtained. VANS is thus considered to be an excellent option for selected patients with thyroid and parathyroid diseases.


Cardiac sarcoidosis completely mimicking biventricular arrhythmogenic cardiomyopathy.
Cardiac sarcoidosis (CS) is a chameleon of cardiology, and it can mimic different cardiac diseases; among them is arrhythmogenic cardiomyopathy (ACM). We admitted a 70-year-old female patient with heart failure symptoms in 2015, who fulfilled all major ECG and non-invasive imaging criteria of biventricular ACM. She was well with the recommended medications for 3 years, showing only isolated cardiac involvement, but in 2018, cervical and mediastinal lymphadenopathy appeared and cervical lymph node core biopsy histology, bronchoalveolar lavage flow cytometry strongly suggested extracardiac sarcoidosis. Therefore, our suspicion was that sarcoidosis is responsible for the cardiac involvement, which was not confirmed by PET-CT and gallium scintigraphy examinations. At the end of 2018, she died in septicaemia with multiorgan failure, and only autopsy verified her CS. A new ECG algorithm published in 2021 for the differential diagnosis of CS and biventricular ACM, when applied on her ECGs recorded in 2015, suggested the diagnosis of CS.


[Effect of fluid resuscitation guided by pulse contour cardiac output monitoring technology on organ function in extremely severe burn patients].
Objective: To investigate the effect of fluid resuscitation guided by pulse contour cardiac output (PiCCO) monitoring technology on the organ function in extremely severe burn patients. Methods: From May 2015 to March 2019, 52 patients with extremely severe burn hospitalized in Tongren Hospital of Wuhan University & Wuhan Third Hospital, meeting the inclusion criteria, were recruited to conduct a prospectively randomized control study. The patients were divided into PiCCO monitoring rehydration group (25 cases, 17 males and 8 females) and traditional rehydration group (27 cases, 20 males and 7 females) according to the random number table, with the ages of (47±9) and (49±8) years respectively. After admission, all the patients were rehydrated according to the rehydration formula of the Third Military Medical University during shock stage. In traditional rehydration group, fluid resuscitation of the patients was performed by monitoring the traditional shock indicators such as urine volume and central venous pressure, while PiCCO monitoring was performed in patients in PiCCO monitoring rehydration group, and the global end-diastolic volume index combined with the other relevant indicators of PiCCO monitoring were used to guide rehydration on the basis of the monitoring indicators of traditional rehydration group. The rehydration coefficients and urine volumes per kilogram of body weight per hour during the first and second 24 h post injury were compared between the two groups, which were compared with the corresponding rehydration scheme value of the Third Military Medical University (hereinafter referred to as the scheme value) at the same time. The total rehydration volumes within post injury hour (PIH) 8 and during the first and second 24 h post injury, the urine volumes per hour during the first and second 24 h post injury, and the levels of creatinine, urea nitrogen, lactate clearance rate, procalcitonin, creatine kinase isoenzyme (CK-MB) in blood and mean arterial pressure (MAP) on post injury day (PID) 1, 2, and 3 were measured. The incidence of complications, the application case number of mechanical ventilation, and the mechanical ventilation time within PID 28 were analyzed. Data were statistically analyzed with analysis of variance for repeated measurement, t test, Bonferroni correction, Mann-Whitney U test, chi-square test, and Fisher's exact probability method test. Results: During the second 24 h post injury, the rehydration coefficient of patients in traditional rehydration group was significantly higher than the scheme value (t=5.120, P<0.01). During the first and second 24 h post injury, the rehydration coefficients of patients in PiCCO monitoring rehydration group were significantly higher than the scheme values (t=3.655, 10.894, P<0.01) and those in traditional rehydration group (t=3.172, 2.363, P<0.05 or P<0.01). Within PIH 8, the total rehydration volumes of patients between the two groups were similar. During the first and second 24 h post injury, the total rehydration volumes of patients in PiCCO monitoring rehydration group were significantly higher than those in traditional rehydration group (t=4.428, 3.665, P<0.01). During the first and second 24 h post injury, the urine volumes per kilogram of body weight per hour of patients in traditional rehydration group were significantly higher than the schema values (t=4.293, 6.362, P<0.01), and the urine volumes per kilogram body weight per hour of patients in PiCCO monitoring rehydration group were significantly higher than the schema values (t=6.461, 8.234, P<0.01). The urine volumes per kilogram of body weight per hour and urine volumes per hour of patients in PiCCO monitoring rehydration group during the second 24 h post injury were significantly higher than those in traditional rehydration group (t=2.849, 3.644, P<0.05 or P<0.01). The creatinine levels of patients between the two groups on PID 1, 2, and 3 were similar. The urea nitrogen levels of patients in PiCCO monitoring rehydration group on PID 1, 2, and 3 were (6.8±1.5), (5.6±1.4), (4.4±1.4) mmol/L respectively, which were significantly lower than (8.6±1.8), (6.6±1.5), (5.5±1.4) mmol/L in traditional rehydration group (t=3.817, 2.511, 2.903, P<0.05 or P<0.01). The lactate clearance rates of patients in PiCCO monitoring rehydration group on PID 1, 2, and 3 were significantly higher than those in traditional rehydration group (t=2.516, 4.540, 3.130, P<0.05 or P<0.01). The procalcitonin levels of patients in PiCCO monitoring rehydration group on PID 2 and 3 were significantly lower than those in traditional rehydration group (Z=-2.491, -2.903, P<0.05). The CK-MB level of patients in PiCCO monitoring rehydration group on PID 3 was (35±10) U/L, which was significantly lower than (51±16) U/L in traditional rehydration group (t=4.556, P<0.01). The MAP levels of patients between the two groups on PID 1, 2, and 3 were similar. Within PID 28, the incidence of complications of patients in traditional rehydration group was significantly higher than that in PiCCO monitoring rehydration group (χ(2)=4.995, P<0.05), and the application case number of mechanical ventilation and the mechanical ventilation time of patients between the two groups were similar. Conclusions: The use of PiCCO monitoring technology to guide the early fluid resuscitation of extremely severe burn patients is beneficial for accurate determination of the fluid volume required by the patients and reduction of organ injury caused by improper rehydration.


Oral prednisolone and triamcinolone injection for gastric stricture after endoscopic submucosal dissection.
The expansion of the indications for endoscopic submucosal dissection (ESD) to include early gastric cancers has enabled extensive resection. However, post-ESD stenosis after large resections applied to the gastric cardia or pylorus is often difficult to manage. The aim of this study was to evaluate the benefit of oral prednisolone and triamcinolone injection for stenosis after gastric ESD. Eight patients who underwent ESD for large neoplastic lesions that extended more than three-fourths of the luminal circumference were enrolled in this study. Four patients underwent ESD for gastric cardia cancer, and four patients were treated for pyloric lesions. To prevent post-ESD stricture, oral prednisolone was started at 30 mg daily on the second day after ESD and then tapered gradually in two cases, while topical injection of 80 mg triamcinolone was performed once immediately after ESD in six cases. Endoscopic balloon dilatation (EBD) was used for stricture-related symptoms or signs including nausea, vomiting, or food residuals observed on endoscopy. EBD was also applied if a 10-mm-diameter endoscope was not able to pass through the lumen. The incidence of stenosis, the frequency and period required for EBD, the duration required for ulcer healing after ESD, and the incidences of post-procedural bleeding and perforation were assessed. One of the eight patients had post-ESD stenosis requiring EBD. The median ulcer healing period after ESD was 87.5 (range, 56-133) days. No patients experienced post-procedural bleeding or perforation. There were no adverse events due to steroid therapy. The results of the present study showed the safety and usefulness of steroid therapy for management of stenosis after large ESD in the gastric cardia or pylorus.


Regional Nerve Block Complication Analysis Following Peripheral Nerve Block During Foot and Ankle Surgical Procedures.
Background Foot and ankle surgeries are frequently accompanied by a peripheral nerve block in order to reduce postoperative pain. Higher than expected complication rates with peripheral nerve blocks have led to increased concern among surgeons and patients. To our knowledge, no study conducted by the treating surgeon has identified risk factors that may predispose a patient to complications. Our goal was to attempt to identify those risk factors. Methods We reviewed patient charts of those who underwent an orthopedic foot and ankle procedure between 2013 and 2018, as performed by the senior author. This yielded 992 procedures performed across four surgical locations. Of these procedures, 137 procedures were removed because no block was used. The remaining cases were analyzed for nerve complications, defined as sensory or motor deficits along the distribution of a nerve. The patients were divided into those with and without complications and were evaluated for differences. Statistical analysis was performed using the SAS® software (SAS Institute Inc., Cary, North Carolina, USA). Results The overall short-term complication rate was 10.1% and the long-term complication rate was 4.3%, with a total of 855 blocks given. Electromyographies (EMGs) were performed on 24.4% of the patients with a complication. Of the EMGs, 95.2% confirmed nerve complications in the distribution of the blocked nerve. The significant factors associated with complications were age, BMI, location, and smoking status. A regression analysis was performed to determine the odds ratio for individual factors. Those with significantly higher odds ratio were between 40 and 65 years of age, had normal or underweight BMI, underwent surgery at an outpatient surgery center, and were current smokers. Conclusions Our study suggests that there are significant epidemiological factors in predicting postoperative complications related to a peripheral nerve block. The study also shows a similar short-term complication rate but a higher long-term complication rate than other studies. This data are important because it allows for an informed decision to be made between a surgeon, anesthesiologist, and the patient regarding the safety and necessity of delivering a preoperative peripheral nerve block based on patient risk factors.


Preparation of Shell-Core Cu(2)O-Cu Nanocomposite Particles and Cu Nanoparticles in a New Microemulsion System.
Shell-core Cu(2)O-Cu nanocomposite particles and metal Cu nanoparticles are synthesized in a new microemulsion system which consists of saturated Cu(2+) salt aqueous solution dispersed in isopropanol and stabilized by polyvinylalcohol (PVA). The size of the composite particles and the thickness of the Cu(2)O shell layer can be controlled by the volume ratio of isopropanol to H(2)O (the ratio is defined as R). When R >/= 1000, it is available to obtain metal Cu nanoparticles. Copyright 1999 Academic Press.


GRA9, a new Toxoplasma gondii dense granule protein associated with the intravacuolar network of tubular membranes.
Important components of the parasitophorous vacuole in which the intracellular protozoan parasite Toxoplasma gondii develops, comprise proteins secreted from apicomplexan specific secretory organelles named the dense granules. Here, we confirm by immunofluorescence and by cryo-electron microscopy that the recently isolated B10 protein (318 amino acids, 41kDa) is a new dense granule protein that should now be referred to as GRA9. Within the vacuolar compartment, GRA9, like GRA2, GRA4 and GRA6, associates with the network of tubular membranes connected to the parasitophorous vacuole delimiting membrane. Like the other GRA proteins, GRA9 is secreted into the vacuole from the anterior end of the parasite. However, unlike GRA2 or GRA6, GRA9 does not transit by the posterior invaginated pocket of the parasite where the network first assembles. Within the dense granules, GRA9 exists in both a soluble and an insoluble state. Like the other GRA proteins, GRA9 is secreted as a soluble form only and like most of the GRA proteins, two forms of GRA9 of the similar molecular weight are detected within the vacuolar space: a soluble form and a membrane associated form. The dual properties of GRA9 are not only ascribed by the presence of amphipathic and hydrophobic alpha-helices but also by the fact that the protein is mainly hydrophilic.


CT diagnosis of pedunculated liver tumours.
Liver tumours with extrahepatic location are uncommon. They show specific CT criteria with respect to blood supply. Various CT criteria have been analysed in 10 tumours, including three hepatocellular adenomas, two focal nodular hyperplasias, four cavernous haemangiomas and one hepatocellular carcinoma. Correct diagnosis was obtained only in haemangiomas with their characteristic hyperdense blood pools, and in one hepatocellular carcinoma. CT criteria of the ten pedunculated tumours are discussed, to with the aim of adding to our knowledge of the diagnostic relevance of CT.


Quantitative evaluation of modified advanced platelet-rich fibrin buffy coat among diabetic patients and tobacco smokers with chronic periodontitis.
The use of biofuel like platelet-rich fibrin (PRF) may enhance the healing potential of the tissues in tobacco smokers and diabetic patients. To evaluate the modified advanced PRF (A-PRF) buffy coat quantitatively in uncontrolled type-2 diabetic patients and tobacco smokers with chronic periodontitis by determining the size outcome of the buffy coat, the platelet and leukocyte concentration, and also to find out the influence of gender on these parameters. In this cross-sectional study, 180 generalized chronic periodontitis patients (46-55 years) were enrolled, Group 1 (Control group): 60 systemically healthy subjects; Group 2 (Test group): 60 Heavy tobacco smokers; and Group 3 (Test group): 60 uncontrolled type 2 diabetic patients. 15 ml of blood was drawn from all subjects to assess the size outcome, platelet, and leukocyte concentration also to find out the influence of gender on the various parameters of the prepared modified (A-PRF) membrane. Uncontrolled type-2 diabetic patients had maximum height (23.39 ± 1.69 mm) and width (7.26 ± 0.16 mm) of modified (A-PRF) clot when compared to healthy individuals and tobacco smokers. The total number of platelet (245.38 ± 40.72 1000/ul) and leukocyte count (6.11 ± 0.60 1000/ul) and their percentage of concentration were 95.21 ± 2.16% and 77.25% ±1.98%, respectively, and is significantly higher in uncontrolled type-2 diabetic patients (P ≤ 0.05). Females were associated with the larger sized modified (A-PRF) clot with more number of platelets and leukocytes count than males. Size outcome of modified (A-PRF) clot was found to be comparatively larger in uncontrolled type-2 diabetic patients particularly in females of all the groups when compared to males. Among the hematological parameters, the total count as well as the percentage of platelet and leukocyte in modified (A-PRF) membrane was found to be higher in uncontrolled type-2 diabetic patients. Female subjects exhibited higher platelet and leukocyte concentration than males.


In vitro evaluation of the release of albuterol sulfate from polymer gels: effect of fatty acids on drug transport across biological membranes.
In this investigation, the diffusion of the beta 2 agonist albuterol sulfate (ABS) across several membranes (cellulose, hairless mouse skin, human cadaver skin) from polymer gels was studied, and the effects of several fatty acids on drug permeation through skin were evaluated. The results were then used to predict whether transdermal delivery would be appropriate for ABS. All in vitro release studies were carried out at 37 degrees C using modified Franz diffusion cells. In preliminary studies, ABS release through cellulose membranes was studied from two polymeric gels, Klucel (hydroxypropylcellulose) and Methocel (hydroxypropylmethylcellulose). Three polymer concentrations were used for each gel (0.5%, 1.0%, and 1.5%). From these experiments, Klucel 0.5% was selected as the optimal formulation to study ABS diffusion across hairless mouse skin. Experiments were conducted to evaluate the effects of capric acid, lauric acid, and myristic acid as penetration enhancers. The results suggested that lauric acid preferentially enhanced ABS diffusion compared to the other fatty acids studied, and follow-up studies were done to evaluate the release through human cadaver skin from a donor containing 2% ABS and lauric acid in 0.5% Klucel. These experiments showed that a 2:1 (lauric acid:ABS) molar ratio gave the best ABS release rates. The release rate across human cadaver skin declined slowly over 24 hr, and an average flux over 24 hr of approximately 0.09 mg/hr cm2 was measured. Using this value as a steady-state flux, extrapolations predicted that transdermal delivery can be used to maintain therapeutic ABS plasma levels (6-14 ng/mL) for extended periods. The results of this research suggest that ABS is a good candidate for transdermal drug delivery.


Biological factors in human sexuality.
This paper considers a number of key concepts relevant to biological determinants of human sexuality, including sexual differentiation, brain mechanisms involved in sexual response, the role of sex hormones, and the sexual effects of drugs. The paper concludes with consideration of how little is known about the interaction between biology and culture in shaping human sexuality, and the need for research in this area.


House refuses to remove ban on abortions in overseas military hospitals.
On June 15 (1995), the House voted 300-126 to adopt the Department of Defense (DOD) authorization bill (HR 1530), which approves $267 billion for fiscal year 1996. During debate, members rejected an amendment to maintain the current policy allowing privately funded abortions at overseas military hospitals. Offered by pro-choice Representative Rosa DeLauro (D-CT), the amendment was defeated 196-230; the National Security Committee had rejected an identical proposal in a 20-32 vote on May 24. The final bill revises the existing statutory ban on the use of agency funds to "perform abortions except where the life of the mother would be endangered" by explicitly expanding it to encompass "medical treatment facilities or other facilities of the [DOD]." In previous years, the prohibition on non-life-saving abortions at overseas military hospitals was implemented through a 1988 agency memo interpreting the funding ban to extend to military facilities outside of the continental US. In January 1993, President Clinton reversed that interpretation.


Intestinal brush-border membrane enzyme activities and transport functions during prenatal development of pigs.
Enzyme activities and rates of leucine and glucose uptake were measured using brush-border membrane vesicles prepared from the small intestine of 7-, 8-, 10-, and 12-week fetal (43, 49, 61, and 74% of gestation) and unsuckled, neonatal pigs. Lactase was detected in 7-week fetuses, with a large increase in activity between 10 weeks of gestation and birth. gamma-Glutamyltranspeptidase activity was stable throughout gestation, whereas sucrase activity was not detected. Active L-leucine uptake was already present at 7 weeks of gestation, with an increasing distal-to-proximal gradient observed at birth. D-glucose uptake was low at 7 weeks, but by 8 weeks it exhibited a typical overshoot phenomenon and established a decreasing proximal-to-distal gradient by 12 weeks. D-glucose uptake at all ages was directly related to incubation temperature, but less so for 7- and 10-week fetuses. By 12 weeks strict Na(+)-dependency of D-glucose uptake was observed along the entire length of the small intestine. Kinetic analysis of Na(+)-D-glucose cotransport showed a shift from the presence of both high- and low-affinity systems at 8 weeks of gestation to a single high-affinity Michaelian component at birth. In light of similarities with human fetuses, the pig may be a valuable model for studying development of intestinal transport during gestation, particularly during the final trimester, when availability of human tissue is limited.


Enhancing COVID Rehabilitation with Technology (ECORT): protocol for an open-label, single-site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms.
As of May 2022, Ontario has seen more than 1.3 million cases of COVID-19. While the majority of individuals will recover from infection within 4 weeks, a significant subset experience persistent and often debilitating symptoms, known as "post-COVID syndrome" or "Long COVID." Those with Long COVID experience a wide array of symptoms, with variable severity, including fatigue, cognitive impairment, and shortness of breath. Further, the prevalence and duration of Long COVID is not clear, nor is there evidence on the best course of rehabilitation for individuals to return to their desired level of function. Previous work with chronic conditions has suggested that the addition of electronic case management (ECM) may help to improve outcomes. These platforms provide enhanced connection with care providers, detailed symptom tracking and goal setting, and access to relevant resources. In this study, our primary aim is to determine if the addition of ECM with health coaching improves Long COVID outcomes at 3 months compared to health coaching alone. The trial is an open-label, single-site, randomized controlled trial of ECM with health coaching (ECM+) compared to health coaching alone (HC). Both groups will continue to receive usual care. Participants will be randomized equally to receive health coaching (± ECM) for a period of 8 weeks and a 12-week follow-up. Our primary outcome is the WHO Disability Assessment Scale (WHODAS), 36-item self-report total score. Participants will also complete measures of cognition, fatigue, breathlessness, and mental health. Participants and care providers will be asked to complete a brief qualitative interview at the end of the study to evaluate acceptability and implementation of the intervention. There is currently little evidence about the optimal treatment of Long COVID patients or the use of digital health platforms in this population. The results of this trial could result in rapid, scalable, and personalized care for people with Long COVID which will decrease morbidity after an acute infection. Results from this study will also inform decision making in Long COVID and treatment guidelines at provincial and national levels. ClinicalTrials.gov NCT05019963. Registered on 25 August 2021.


Alanine mutagenesis of surfactant protein A reveals that lipid binding and pH-dependent liposome aggregation are mediated by the carbohydrate recognition domain.
The carbohydrate recognition domain (CRD) of surfactant protein A (SP-A) is critical for the modulation of surfactant secretion from isolated type II cells and for the Ca(2+)-dependent aggregation of surfactant liposomes, but the domains of SP-A that mediate lipid binding have not been precisely mapped. To determine the role of the CRD in lipid interactions and other functions, the conserved amino acids of the putative Ca2+ and carbohydrate binding site (Glu195, Glu202, Asn214, Asp215) were substituted with alanine. The wild-type recombinant protein, SP-Ahyp, and mutant SP-As SP-Ahyp,E195A, SP-Ahyp,E202A, SP-Ahyp,N214A, and SP-Ahyp,D215A, were expressed in insect cells using baculovirus vectors and compared functionally. The Ca(2+)-dependent binding and aggregation of liposomes at pH 7.0 by SP-Ahyp,N214A were comparable to SP-Ahyp, but these activities were blocked in SP-Ahyp,E195A, SP-Ahyp,E202A, and SP-Ahyp,D215A. In contrast, the SP-Ahyp,D215A but not the other mutant proteins induced the Ca(2+)-independent aggregation of phospholipid liposomes at pH 4.0. The mutant recombinant proteins did not compete with 125I-labeled rat SP-A for high-affinity receptor occupancy on isolated type II cells and were much less potent than SP-Ahyp as regulators of surfactant secretion and uptake from type II cells. We conclude that (1) lipid binding and pH-dependent liposome aggregation are mediated by the CRD of SP-A, (2) distinct but overlapping domains within the CRD are required for pH- and Ca(2+)-dependent liposome aggregation, and (3) conserved acidic and polar residues of the carbohydrate binding site of SP-A are essential for interactions with type II cells.


The Anti-Proliferative and Apoptotic Effects of Rutaecarpine on Human Esophageal Squamous Cell Carcinoma Cell Line CE81T/VGH In Vitro and In Vivo.
The overall five-year survival rate for patients with esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages. Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on tumor cells. However, the mechanisms by which RTP confer these effects and its importance in esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP's effects on tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2, caspase-3, caspase-9, and PCNA in CE81T/VGH cells or the tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G2/M phase, and induces apoptosis. Consistently, the in vivo study showed that tumor size, tumor weight, and proliferating cell nuclear antigen protein expression in tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax proteins, while inhibiting the expression of Bcl-2 in cancer cells. In addition, RTP significantly increases the expression of cleaved caspase-9 and cleaved caspase-3 proteins in tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as caspase-9 and caspase-3.


Mary, a 4-year-old with oppositional defiant disorder.
Examine the treatment course of a 4-year-old girl with oppositional defiant disorder, which developed in the context of her father's deployment to Bosnia. A case report of the interventions made with this patient and her clinical outcomes. The patient's behavior improved substantially with regular therapy sessions and with a designated playtime with her mother. One possible cause of oppositional defiant disorder is a parent-child attachment deficit. In this case, the child's parents are both active duty service members and her father was deployed overseas. Young children have difficulty verbalizing feelings of loss and may respond behaviorally by exerting control over their immediate environment. Some children may respond to unstructured play sessions in which they are able to express feelings and gain some control in their interactions with adults.


An ESR study of the radicals in X-irradiated L-alpha-amino-n-butyric acid HCl containing 1.5% L-cysteine HCl.
After X-irradiation at room temperature, the radicals in L-alpha-amino-n-butyric acid HCl are CH3CH2CHCOOH. The beta- and alpha-hyperfine constants are typical of those found in amino acid radicals. On annealing at temperatures near 100 degrees C this carbon-centered radical in samples containing 1.5% cysteine converts to a perthiyl radical, RCH2S(1)S(2). The g-values for the perithiyl radical are 2.0024, 2.0257, and 2.0557. When the field is in the minimum g-value direction, the hyperfine splittings are 50 G for 33S(2) and 32 G for 33S(1).


A Novel Biphenyl-based Chemotype of Retinoid X Receptor Ligands Enables Subtype and Heterodimer Preferences.
The nuclear retinoid X receptors (RXRs) are key ligand sensing transcription factors that serve as universal nuclear receptor heterodimer partners and are thus involved in numerous physiological processes. Therapeutic targeting of RXRs holds high potential but available RXR activators suffer from limited safety. Selectivity for RXR subtypes or for certain RXR heterodimers are promising strategies for safer RXR modulation. Here, we report systematic structure-activity relationship studies on biphenyl carboxylates as new RXR ligand chemotype. We discovered specific structural modifications that enhance potency on RXRs, govern subtype preference, and vary modulation of different RXR heterodimers. Fusion of these structural motifs enabled specific tuning of subtype preferential profiles with markedly improved potency. Our results provide further evidence that RXR subtype selective ligands can be designed and present a novel chemotype of RXR modulators that can be tuned for subtype and heterodimer preferences.


Characterization of the AB (AF-1) region in the muscle-specific retinoid X receptor-gamma: evidence that the AF-1 region functions in a cell-specific manner.
The retinoid X receptors alpha, beta and gamma (RXRs) share a highly conserved 'C' region or DNA binding domain (DBD). The conserved 'DE' region or ligand binding domain (LBD) of the RXRs is functionally complex, mediating dimerization and a ligand-dependent activation function (AF-2). The AB or N-terminal region of the RXRs is poorly conserved and encodes a ligand-independent activation function (AF-1). RXR gamma mRNA is preferentially expressed in skeletal and cardiac muscle, however, cell-specific steroid receptor-mediated trans-activation is a poorly understood phenomenon. We utilized the GAL4 hybrid assay system and have demonstrated that RXR gamma contains two functional domains in the AB and DE regions that activate transcription in a ligand-independent and -dependent manner respectively. The functions of the AB (AF-1) and DE (AF-2) domains were regulated by cAMP-dependent protein kinases, furthermore, the function of AF-2 in the LBD was activated by 8-Br-cAMP, independent of 9-cis-retinoic acid treatment. Deletion analysis demonstrated that the AF-1 of RXR gamma, is located between amino acids 1 and 103 and contained multiple motifs that were targets of cAMP-dependent protein kinases. Transfection analyses in non-muscle and myogenic cells clearly demonstrated that: (i) the AF-1 of RXR gamma functions in a muscle-specific manner and is required for optimal ligand-dependent trans-activation from an RXRE; (ii) RXR gamma trans-activates more efficiently in a myogenic background.


The Lipid Raft Proteome of African Trypanosomes Contains Many Flagellar Proteins.
Lipid rafts are liquid-ordered membrane microdomains that form by preferential association of 3-β-hydroxysterols, sphingolipids and raft-associated proteins often having acyl modifications. We isolated lipid rafts of the protozoan parasite Trypanosoma brucei and determined the protein composition of lipid rafts in the cell. This analysis revealed a striking enrichment of flagellar proteins and several putative signaling proteins in the lipid raft proteome. Calpains and intraflagellar transport proteins, in particular, were found to be abundant in the lipid raft proteome. These findings provide additional evidence supporting the notion that the eukaryotic cilium/flagellum is a lipid raft-enriched specialized structure with high concentrations of sterols, sphingolipids and palmitoylated proteins involved in environmental sensing and cell signaling.


Alteration in isotopic composition of gross rainfall as it is being partitioned into throughfall and stemflow by xerophytic shrub canopies within water-limited arid desert ecosystems.
Isotopic composition of gross rainfall has been extensively used as a conservative tracer to track water movement and other hydrological processes in vegetated ecosystems. Recent studies from forest ecosystems, however, demonstrated that vegetation canopies can alter the isotopic composition of rainwater during rainfall partitioning into throughfall and stemflow, likely leading to errors and biases in aforementioned studies. No known studies, to date, had investigated this topic in shrub-dominated arid and semi-arid ecosystems where water is typically the driving factor in ecological, hydrological and biogeochemical processes. In this study, event-based gross rainfall, the throughfall and stemflow induced by shrubs of Caragana korshinskii were measured and samples were collected within a water-limited arid desert ecosystem of northern China, and their water stable isotopes (18O and 2H) were also analyzed in the laboratory. We mainly aimed to investigate whether there is an isotopic enrichment or depletion in stemflow and throughfall in comparison to gross rainfall, and to evaluate the possible underlying mechanisms. Our results indicated an enrichment of both isotopes in stemflow, while a general more depletion in throughfall than in gross rainfall, which is presumably affected by a combinative effects of canopy evaporation, isotopic exchange, and selective canopy storage. Deuterium excess of stemflow were found to be significantly higher (P < 0.05) than that of gross rainfall and throughfall. Moreover, we detected the pronounced "amount effect", with a significant (P < 0.05) negative relationship between isotopic composition and the amount of gross rainfall, throughfall, and stemflow, respectively. Our study is expected to contribute to an improved understanding of physical processes and water routing in shrub canopies within vast arid desert ecosystems.


[Experience and comparison of antihypertensive effect of ace inhibitor spirapril and calcium antagonist amlodipinein standard and chronotherapeutic prescription mode].
Arterial pressure is an effect of many physiologic processes of organism effected by daily rhytmus. The introduction of round the 24-hour monitoring of arterial pressure enabled to detect arterial pressure circular fluctuation. Chronotherapy with the application of amlodipin and spirapril due to the data of round the 24-hour arterial pressure monitoring increases the effectiveness of antihypertensive therapy.


Relationship between pre-anesthetic and intra-anesthetic airway resistance in patients undergoing general anesthesia: A prospective observational study.
Surgery patients in Japan undergo routine spirometry testing prior to general anesthesia. The use of a flow sensor during general anesthesia has recently become common. However, it is not certain whether the information derived from flow-volume curves is being adequately used for mechanical ventilation management during general anesthesia. So far, there have been no attempts to calculate airway resistance using flow-volume curves. Therefore, we performed a prospective, observational study to investigate the relationship between pre-anesthetic and intra-anesthetic airway resistance in patients scheduled for surgery under general anesthesia. We calculated pre-anesthetic and intra-anesthetic airway resistance in each patient, based on the slopes of flow-volume curves obtained prior to and during general anesthesia. We also calculated endotracheal tube resistance to correct the intra-anesthetic airway resistance values calculated. A total of 526 patients were included in the study, and 98 patients had a forced expiratory volume in the first second/forced vital capacity ratio of < 70%. Pre-anesthetic airway resistance was significantly higher in patients with airflow obstruction than in those without airflow obstruction (p < 0.001), whereas no significant difference in intra-anesthetic airway resistance was found between patients with and without airflow obstruction during mechanical ventilation (p = 0.48). Pre-anesthetic and intra-anesthetic airway resistance values were closer to each other in patients without airflow obstruction, with a mean difference < 1.0 cmH2O L-1s-1, than in those with airflow obstruction, although these respiratory parameters were significantly different (p < 0.001). Intra-anesthetic airway resistance was not related to the FEV1/FVC ratio, regardless of the degree to which the FEV1/FVC ratio reflected pre-anesthetic airway resistance. As compared with patients with airflow obstruction, the mean difference between pre-anesthetic and intra-anesthetic airway resistance was small in patients without airflow obstruction.


Influence of human urine on the in vitro activity and postantibiotic effect of ciprofloxacin against Escherichia coli.
The purpose of this investigation was to study the effects of human urine on the minimum inhibitory concentration (MIC) and the postantibiotic effect (PAE) of ciprofloxacin against Escherichia coli. MICs and the PAE were performed in Mueller-Hinton broth (MHB; pH 7.3 and 5.5) and in human urine (pH 5.5 and 7.3). In urine, pH 5.5, MICs increased 64-fold (from 0.016 to 1.024 micrograms/ml) and the PAE was abolished (from 101.6 to 3.7 min), when compared to MHB, pH 7.3. An acidic pH demonstrated the greatest effect on reduced susceptibility and PAE. Using ciprofloxacin concentrations adjusted for a higher MIC obtained in pH-adjusted urine and MHB, PAE values were similar for urine and MHB (approximately 280 min at 40 x MIC). This study demonstrated that the MIC and PAE of ciprofloxacin against E. coli are influenced by human urine and in particular its pH.


The silent witness: using dive computer records in diving fatality investigations.
Downloaded data from diving computers can offer invaluable insights into diving incidents resulting in fatalities. Such data form an essential part of subsequent investigations or in legal actions related to the diving incident. It is often tempting to accept the information being displayed from a computer download without question. However, there is a large variability between the makes and models of dive computer in how the data are recorded, stored and re-displayed and caution must be employed in the interpretation of the evidence. In reporting on downloaded data, investigators should be fully aware of the limitations in the data retrieved. They should also know exactly how to interpret parameters such as: the accuracy of the dive profile; the effects of different mode settings; the precision of displayed water temperatures; the potential for misrepresenting breathing rates where there are data from integrated monitoring systems, and be able to challenge some forms of displayed information either through re-modelling based on the pressure/time profiles or by testing the computers in standardised conditions.


Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum.
Malaria invasion of red blood cells involves multiple parasite-specific targets that are easily accessible to inhibitory compounds, making it an attractive target for antimalarial development. However, no current antimalarial agents act against host cell invasion. Here, we demonstrate that the clinically used macrolide antibiotic azithromycin, which is known to kill human malaria asexual blood-stage parasites by blocking protein synthesis in their apicoplast, is also a rapid inhibitor of red blood cell invasion in human (Plasmodium falciparum) and rodent (P. berghei) malarias. Multiple lines of evidence demonstrate that the action of azithromycin in inhibiting parasite invasion of red blood cells is independent of its inhibition of protein synthesis in the parasite apicoplast, opening up a new strategy to develop a single drug with multiple parasite targets. We identified derivatives of azithromycin and erythromycin that are better invasion inhibitors than parent compounds, offering promise for development of this novel antimalarial strategy. Safe and effective macrolide antibiotics with dual modalities could be developed to combat malaria and reduce the parasite's options for resistance.


[Cranial bone graft in oral and maxillofacial surgery].
The sufficient donor bone volume is important to restore congenital, developmental and accidented defects of facial skeleton. In recent years, the outer table of cranial bone, as a better donor source, has been used in maxillofacial and craniofacial surgery extensively. But no clinical report was found in China. In this paper 16 cases were reported (5 cases of alveolar cleft, 5 cases of secondary deformity after cleft palate and ankylosis of TMJ, 6 cases of developmental deformity of jaws). All of these cases were treated by using cranial bone graft in strips or bone dust during orthognathic operations. The result showed no any complications in all cases. Compared with iliac and rib grafts, the outer table of cranial bone graft showed distinct advantages: greater graft volume survival, little postoperative pain at the donor site, and the skin incision within the hairline.


Early-Life Iron Deficiency Anemia Programs the Hippocampal Epigenomic Landscape.
Iron deficiency (ID) anemia is the foremost micronutrient deficiency worldwide, affecting around 40% of pregnant women and young children. ID during the prenatal and early postnatal periods has a pronounced effect on neurodevelopment, resulting in long-term effects such as cognitive impairment and increased risk for neuropsychiatric disorders. Treatment of ID has been complicated as it does not always resolve the long-lasting neurodevelopmental deficits. In animal models, developmental ID results in abnormal hippocampal structure and function associated with dysregulation of genes involved in neurotransmission and synaptic plasticity. Dysregulation of these genes is a likely proximate cause of the life-long deficits that follow developmental ID. However, a direct functional link between iron and gene dysregulation has yet to be elucidated. Iron-dependent epigenetic modifications are one mechanism by which ID could alter gene expression across the lifespan. The jumonji and AT-rich interaction domain-containing (JARID) protein and the Ten-Eleven Translocation (TET) proteins are two families of iron-dependent epigenetic modifiers that play critical roles during neural development by establishing proper gene regulation during critical periods of brain development. Therefore, JARIDs and TETs can contribute to the iron-mediated epigenetic mechanisms by which early-life ID directly causes stable changes in gene regulation across the life span.


Promoting Self-Determination in Parents With Mental Illness in Adult Mental Health Settings.
This article reports a strengths-based intervention to support parents with mental illness and their children in adult mental health settings: "Let's Talk About Children" (LTC) intervention. A qualitative methodology was adopted with parent participants receiving LTC in adult mental health and family services. The benefits for parents receiving LTC were described through in-depth interviews with 25 parents following the delivery of the program. Interview data identified an impact on parental self-regulation-mainly through a change in a sense of agency as a parent-and skill building, once a clearer picture of their child's everyday life was understood. This study outlines the benefits of talking with parents about the strengths and vulnerabilities of their children during routine mental health treatment. The role for self-determination of parents in preventive interventions for children is an important consideration for mental health recovery, and it also helps to break the cycle of transgenerational mental illness within families.


Impaired Development of Early Endometriotic Lesions in CD44 Knockout Mice.
Previous studies have shown endometrial cell (EC) CD44 and peritoneal mesothelial cell (PMC)-associated hyaluronan (hyaluronic acid [HA]) are involved in the attachment of endometrial stroma and epithelial cells to peritoneal mesothelium. Here we assess the CD44-HA interaction in the formation of the early endometriotic lesion using CD44(-/-) (knockout) mice. Using an established murine model and crossover technique, endometrial tissue from donor mice (wild type [WT] and CD44(-/-)) was used to induce endometriosis in recipient mice (WT and CD44(-/-)). Endometriotic lesions were visualized by fluorescent microscopy and confirmed by hematoxylin and eosin staining. Early endometriotic lesions were decreased when CD44(-/-) endometrium was placed in WT recipients and when WT endometrium was placed in CD44(-/-) recipients (P = .002). Early endometriotic lesions were also significantly decreased when both peritoneal and endometrial tissues lacked CD44 expression (P < .01). These studies demonstrate that both EC and PMC CD44 play a role in the development of early endometriotic lesion.


I-cell disease: report of an autopsy case.
The history and findings at autopsy of a 9-year-old female with I-cell disease are reported. She manifested gargoyle face, progressive psychomotor retardation, and increased serum levels of lysosomal enzymes with decreased activities in peripheral blood lymphocytes. She received a bone marrow transplantation from her HLA-mismatched father when she was 8 years old. Rejection followed, and 9 months later, she died of cardiac failure secondary to aortic regurgitation. The characteristic inclusion bodies, ultrastructurally corresponding to double-membranous lamellar vacuoles and empty single membrane-bound vacuoles, were identified in dermal fibro blasts, macrophages, glomerular epithelial cells, cardiomyocytes and smooth muscle cells. Pale bodies, faintly eosinophilic cytoplasmic globular inclusions immunoreactive for plasma proteins, were observed in hepatocytes and renal collecting tubular epithelial cells. Enzyme histochemical analyses were performed for N-acetyl-beta-glucosaminidase, beta-glucuronidase, nonspecific esterase and acid phosphatase. Decreased activities of the acid hydrolases and their diffusion in the cytoplasm were seen in Kupffer's cells. Ultrastructural localization of acid phosphatase activity suggested the labilization of the lysosomal membrane. The abnormality in the intracellular transport of the acid hydrolases into the lysosomes in I-cell disease is briefly reviewed and discussed.


Seminal plasma and cryopreservation alter ram sperm surface carbohydrates and interactions with neutrophils.
Spermatozoa deposited vaginally must navigate the physical, chemical and immune barriers of the cervix to reach the site of fertilisation. Characteristics that favour successful cervical transit remain largely unknown beyond the obvious factors of motility and viability. Epididymal and cryopreserved ram spermatozoa demonstrate poor cervical transit, for unknown reasons. We hypothesised that seminal plasma exposure and cryopreservation alter the surface sugars of these sperm populations and, consequently, their interaction with immune cells, both potential factors for successful cervical transit. The carbohydrate profiles of epididymal, ejaculated and frozen-thawed ram spermatozoa were assessed by flow cytometry and western blotting using lectins for galactose, sialic acid, N-acetylglucosamine and mannose. Seminal plasma exposure and cryopreservation caused significant changes to the relative amounts of surface sugars detected by flow cytometry and lectin blotting. Immune cell interaction was characterised using a neutrophil-binding assay. Seminal plasma acted as a robust protective mechanism, limiting binding of spermatozoa, whereas the media used for cryopreservation caused a significant disruption to opsonin-mediated binding. We were unable to demonstrate a link between changes to surface sugars and neutrophil susceptibility. Seminal plasma and cryopreservation clearly alter the sperm glycocalyx, as well as the interaction of spermatozoa with immune cells.


Hypertensive Disorders of Pregnancy and Symptoms of Depression and Anxiety as Related to Gestational Age at Birth: Findings From the All Our Families Study.
The aim of the study was to investigate whether symptoms of depression or state anxiety changed the strength or nature of the association between hypertensive disorders of pregnancy (HDP) and gestational age at birth. We conducted a secondary analysis of data from the All Our Families Cohort, a prospective pregnancy cohort study based in Calgary, Alberta, Canada. Self-reported depressive symptoms and state anxiety were assessed between 3 and 5 months of gestation, and obstetrical information, including diagnosis of HDP, parity, type of delivery, and gestational age at birth, was retrieved from the maternal discharge abstract. All models were adjusted for sociodemographic and obstetric confounders. Of 2763 women who had a singleton pregnancy and live birth, 247 (9%) were diagnosed with HDP. Women with HDP had significantly shorter gestational length relative to those without the diagnosis (M = 37.87 versus M = 38.99 weeks of gestation), t(2761) = 9.43, p < .001. Moderation analyses showed significant HDP by depressive symptoms and HDP by state anxiety interactions, such that the strength of the association between HDP and gestational age at birth increased alongside greater depressive symptom and state anxiety severity. Results suggest that depressive symptoms and state anxiety may add to the increased risk for shortened gestation associated with HDP. Women at high risk of cardiovascular complications during pregnancy may benefit from additional resources to manage symptoms of depression or anxiety.


Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression.
Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability. A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability. Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls. After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory. The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.


Phase I study of paclitaxel and cisplatin for patients with advanced or recurrent gastric cancer.
The present phase I study was planned to define the toxicities, maximum tolerated dose (MTD), and pharmacokinetics of the combination of paclitaxel and cisplatin in patients with advanced or recurrent gastric cancer, and to recommend a dose for the phase II study. Patients were required to have performance status of 0 to 1, to be between 15 and 74 years of age, and to have adequate organ function. The cisplatin was administered at a fixed dose of 25mg/m2 and paclitaxel was administered at four dose levels (60, 70, 80, and 90mg/m2). Plasma sampling was performed to characterize the pharmacokinetics and pharacodynamics of paclitaxel. All of the 15 patients entered were assessable for toxicity and response and were subject to analysis of dose-limiting toxicity (DLT) and MTD. Neutropenia (grade 4, for 3 days or more; n=2) indicated DLT at dose level 4 (90mg/m2). The MTD for this regimen was 90mg/m2/week of paclitaxel for 3 weeks. Tumor response occurred in 7 of the 15 patients and the overall response rate was 57.1%. The pharmacokinetic profiles of paclitaxel were similar to those observed after the administration of each dose as a single agent. Our study demonstrated that the level 3 dosage (80mg/m2 of paclitaxel and 25mg/m2 of cisplatin) is recommended for this combination chemotherapy. This phase I study showed favorable antitumor activity and fewer adverse reactions relative to other types of chemotherapy.


Surgical management of worm volvulus.
A retrospective study of 50 consecutive patients with small-bowel volvulus complicating intestinal ascariasis is reported. The commonest presenting features were abdominal distension (44 patients) and abdominal pain (38 patients). Thirty-three patients presented with vomiting, of whom 8 vomited worms. Twenty-five patients presented with peritonitis. In 33 patients there was evidence of worm infestation on radiographs while volvulus was diagnosed radiographically in 16 patients. Thirty-two patients required emergency surgery, while 16 were observed for a mean of 2.6 days before surgery. Thirty-nine patients had gangrenous bowel that required resection. The overall mortality rate was 14.5% and all deaths were from the gangrenous group. The results show that volvulus complicating ascariasis still carries a high mortality and morbidity rate. We stress the importance of early detection and early operative intervention.


Crystal structure of UDP-N-acetylglucosamine enolpyruvyltransferase, the target of the antibiotic fosfomycin.
The ever increasing number of antibiotic resistant bacteria has fuelled interest in the development of new antibiotics and other antibacterial agents. The major structural element of the bacterial cell wall is the heteropolymer peptidoglycan and the enzymes of peptidoglycan biosynthesis are potential targets for antibacterial agents. One such enzyme is UDP-N-acetylglucosamine enolpyruvyltransferase (EPT) which catalyzes the first committed step in peptidoglycan biosynthesis: the transfer of the enolpyruvyl moiety of phosphoenolpyruvate (PEP) to the 3-hydroxyl of UDP-N-acetylglucosamine (UDPGlcNAc). EPT is of potential pharmaceutical interest because it is inhibited by the broad spectrum antibiotic fosfomycin. The crystal structure of substrate-free EPT has been determined at 2.0 A resolution. The structure reveals a two-domain protein with an unusual fold (inside out alpha/beta barrel) which is built up from the sixfold repetition of one folding unit. The only repetitive element in the amino acid sequence is a short motif, Leu-X3-Gly(Ala), which is responsible for the formation of hydrogen-bond interactions between the folding units. An enzyme which catalyzes a similar reaction to EPT, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), has a very similar structure despite an amino acid sequence identity of only 25%. To date, only these two enzymes appear to display this characteristic fold. The present structure reflects the open conformation of the enzyme which is probably stabilized through two residues, a lysine and an arginine, located in the cleft between the domains. Binding of the negatively charged UDPGlcNAc to these residues could neutralize the repulsive force between the two domains, thereby allowing the movement of a catalytically active cysteine residue towards the cleft.


Cell membrane stretch and chest blow-induced ventricular fibrillation: commotio cordis.
Commotio cordis, sudden cardiac death secondary to blunt nonpenetrating chest blows in sports, is reported with increasing frequency. In a swine model, ventricular fibrillation (VF) is induced by a baseball blow to the chest, and the initiation of VF is related to the peak left ventricular (LV) pressure produced by the blow. LV pressure changes likely result in cell membrane stretch and mechanical activation of ion channels. Disruption of cell cytoskeleton that anchors the cell membrane prior to precordial blows offers the opportunity to explore whether cell membrane deformation is critical to commotio cordis. Twelve juvenile swine (mean 12.7 +/- 1.6 kg) were randomized to intravenous normal saline (control, n = 6) or 10 mg of intravenous colchicine (n = 6), which is known to depolymerize microtubules. Animals were given up to six blows timed to the vulnerable portion of the cardiac cycle with a 30 mph baseball on the chest directly over the cardiac silhouette. VF was initiated by 14 of the 29 (48%) impacts in the colchicine-treated animals compared with only 3 of 28 (11%) in the controls (P = 0.002). The peak generated LV pressure did not differ between colchicine animals (405 +/- 61 mmHg) and controls (387 +/- 115) (P = 0.47). However, animals administered colchicine were more likely to have VF generated by the chest blow at all pressures. The initiation of VF by chest blows is significantly increased by selective disruption of the cytoskeleton, suggesting that mechanical deformation of the cell membrane is fundamental to the activation of ion channels and underlies the mechanism of VF in commotio cordis.


Luteimonas cucumeris sp. nov., isolated a from cucumber leaf.
A Gram-negative, aerobic and non-motile rod, designated Y4(T), was isolated from a cucumber leaf from Pinggu District, east Beijing, PR China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Y4(T) was most closely related to Luteimonas aquatica RIB1-20(T) (96.7% 16S rRNA gene sequence similarity). DNA-DNA relatedness between strain Y4(T) and L. aquatica RIB1-20(T) was 42.5 ± 3.9%. The predominant fatty acids were iso-C(15:0), iso-C(17:1)ω9c, iso-C(16:0) and iso-C(17:0). The major ubiquinone was Q-8. The DNA G+C content of the type strain was 69.9 mol%. Based on the evidence above, strain Y4(T) represents a novel species of the genus Luteimonas, for which the name Luteimonas cucumeris sp. nov. is proposed. The type strain is Y4(T) ( = CGMCC 1.10821(T) = KCTC 23627(T)).


Computational studies and peptidomimetic design for the human p53-MDM2 complex.
The interaction between human p53 and MDM2 is a key event in controlling cell growth. Many studies have suggested that a p53 mimic would be sufficient to inhibit MDM2 to reduce cell growth in cancerous tissue. In order to design a potent p53 mimic, molecular dynamics (MD) simulations were used to examine the binding interface and the effect of mutating key residues in the human p53-MDM2 complex. The Generalized Born surface area (GBSA) method was used to estimate free energies of binding, and a computational alanine-scanning approach was used to calculate the relative effects in the free energy of binding for key mutations. Our calculations determine the free energy of binding for a model p53-MDM2 complex to be -7.4 kcal/mol, which is in very good agreement with the experimentally determined values (-6.6--8.8 kcal/mol). The alanine-scanning results are in good agreement with experimental data and calculations by other groups. We have used the information from our studies of human p53-MDM2 to design a beta-peptide mimic of p53. MD simulations of the mimic bound to MDM2 estimate a free energy of binding of -8.8 kcal/mol. We have also applied alanine scanning to the mimic-MDM2 complex and reveal which mutations are most likely to alter the binding affinity, possibly giving rise to escape mutants. The mimic was compared to nutlins, a new class of inhibitors that block the formation of the p53-MDM2 complex. There are interesting similarities between the nutlins and our mimic, and the differences point to ways that both inhibitors may be improved. Finally, an additional hydrophobic pocket is noted in the interior of MDM2. It may be possible to design new inhibitors to take advantage of that pocket.


The primary pathway for lactate oxidation in Desulfovibrio vulgaris.
The ability to respire sulfate linked to lactate oxidation is a key metabolic signature of the Desulfovibrio genus. Lactate oxidation by these incomplete oxidizers generates reductants through lactate dehydrogenase (LDH) and pyruvate-ferredoxin oxidoreductase (PFOR), with the latter catalyzing pyruvate conversion into acetyl-CoA. Acetyl-CoA is the source of substrate-level phosphorylation through the production of ATP. Here, we show that these crucial steps are performed by enzymes encoded by a nonacistronic transcriptional unit named now as operon luo (for lactate utilization operon). Using a combination of genetic and biochemical techniques, we assigned a physiological role to the operon genes DVU3027-28 and DVU3032-33. The growth of mutant Δ26-28 was highly disrupted on D-lactate, whereas the growth of mutant Δ32-33 was slower on L-lactate, which could be related to a decrease in the activity of D-lactate or L-lactate oxidase in the corresponding mutants. The DVU3027-28 and DVU3032-33 genes thus encode functional D-LDH and L-LDH enzymes, respectively. Scanning of the genome for lactate utilization revealed several lactate permease and dehydrogenase homologs. However, transcriptional compensation was not observed in any of the mutants except for lactate permease. Although there is a high degree of redundancy for lactate oxidase, it is not functionally efficient in LDH mutants. This result could be related to the identification of several operon enzymes, including LDHs, in the PFOR activity bands, suggesting the occurrence of a lactate-oxidizing supermolecular structure that can optimize the performance of lactate utilization in Desulfovibrio species.


[Effect of Enterobacter cloacae thermolabile enterotoxin on immune system of mice].
To study the effect of Enterobactercloacae thermolabile enterotoxin (LT-enterotoxin) on different arms of immune system of mice. Proprietary clinical strain E. cloacae 258 was used and intraperitoneal inoculation of outbred white mice with LT-enterotoxin-producing E. cloacae comprised experimental model. Phagocytic and lysosomal activity of peritoneal macrophages as well as level of APC to sheep erythrocytes were measured, spontaneous and induced NBT tests were also performed. Pleiotropic immunotoxic effect of LT-enterotoxin of studied bacteria was established, which characterized by suppres- sion of antigen-presenting and antigen-processing functions of macrophages, stimulation of mitotic activity of lymphocytes, decrease of activity of hexose monophosphate shunt enzymes in peritoneal macrophages as well as abnormalities in formation of specific B-lymphocytes. Obtained data allowed to reveal separate steps in pathogenesis of infectious process caused by LT-enterotoxin-producing bacteria from Enterobacter genus.


Early detection of prostate cancer. Decreasing the mortality rate.
In conclusion, prostate cancer is a major menace to Western society. Since prostate cancer is asymptomatic in the early stages and no curative therapy exists for the advanced stages, our only hope for decreasing the mortality rate from prostate cancer is through early detection programs. Young men with life expectancies of 15 years or more should participate in early detection efforts. These men should be evaluated diligently, through the combined use of DRE and the newly described age-specific reference ranges. Radical prostatectomy, when performed on a man with a life expectancy of 30 to 35 years who has organ-confined prostate cancer, is an effective treatment for the No. 1 cancer in men today. With limited health care dollars available in the future for the diagnosis and management of prostate cancer, physicians will be forced to become selective with their diagnostic and therapeutic efforts. It is much less expensive to treat a young man with early-stage, curable prostate cancer than to manage an elderly man terminally ill from advanced prostate cancer. Without question, young men will be the target of our early detection efforts and the ones who will benefit.


Comparison of ureteric stent removal procedures using reusable and single-use flexible cystoscopes following ureteroscopy and lasertripsy: a micro cost analysis.
Diagnostic pressure on endoscopy suite can lead to delay in flexible cystoscopic stent removal. We compare the cost and organizational impact of reusable flexible cystoscope versus single-use, flexible cystoscope with a built-in stent grasper (Isiris®). Data for the reusable cystoscopic stent removal performed in endoscopy room, group A (period 1) were compared to Isiris disposable stent removal performed in outpatient clinic, group B (period 2). We chose the same calendar months in successive years for these two different groups (9 months each). A micro cost analysis was performed evaluating the impact on costs, complications and organizational benefit. A total of 72 patients (37, group A; 35, group B) were included with no significant differences in age and gender ratio. The mean procedure time was 14.4 and 2.2 minutes, and the mean stent dwell time was 26.8 and 15.4 days in groups A and B respectively (p <0.001). In group A, 5 patients (14%) developed stent encrustation, of which 3 needed a ureteroscopic removal subsequently. No complication occurred in group B. More staff on average were needed for procedures done in group A, than group B (p <0.001).The number of patients who had cancer diagnostic wait of >2 weeks for flexible cystoscopy and the mean number of days they waited, reduced from 16 to 3, and 21 days to 3 days respectively between period 1 to period 2. The cost per procedure between group A and group B was £267.2 and £252.62 (p <0.05) if the cost of managing complications was not considered, and £365.40 and £252.62 (p <0.001) if the cost of managing complications was also considered. Isiris significantly reduced stent dwell time, procedural time and staff needed to carry out the stent removals. It also allowed the procedures to be done in the outpatient setting thereby reducing the organizational pressure on endoscopy related diagnostic procedures.


[Determination of the state of emaciation of eel (Anguilla Anguilla) in migration in coastal and estuary zones].
The objective of this work is to characterise the variations of the quality of the glass eels recruitment during a season of migration, from November till March and before and after the transition from marine to continental environment. The emaciation state measured from the ratio DNA/Dry weight and percentage of body water is analysed from a sampling of glass-eels collected at sea and in estuary, in the South of the Bay of Biscay during the migration period 1999/2000. The length and the mass are taken into account, they decrease during the season while the individuals are more and more pigmented. However, our work shows that groups of glass eels arriving on the coasts of the Bay of Biscay are homogeneous from the point of view of their energetic and hydride reserves with a high individual variability within these groups. Also no significant difference in losses of water and energetic reserve were observed among the individuals migrating at the beginning and during tide stream. Fluctuations of the biochemical indication and the percentage of water between the glass eels caught in sea and in estuary show that the transition between maritime and continental environment is not a mobilising event of a lot of energy for glass eels. Differences were only observed in December.


Socioeconomic and Demographic Factors for Spousal Resemblance in Obesity Status in China.
The purposes of this study were to explore the resemblance in the weight status within couples with different family contextual factors and analyze the influence of the level of overweight or obesity of a spouse on that of the other spouse. The data were from the sixth National Health Service Survey of Henan Province in 2018. After screening, 7432 eligible couples were finally included. Socioeconomic and demographic factors were compared by the χ2 test or nonparametric test. The difference in the body mass index (BMI) of spouses was assessed by a t-test. The Pearson correlation coefficient and kappa value were used as indicators of consistency in weight status. A logistic regression analysis was used to further explore the effect of a spouse's level of overweight/obesity on that of the other spouse. The results show that the prevalence of overweight/obesity in couples aged 20 or older is 33.76%. The Pearson correlation coefficient of the BMI within couples was 0.102 (95% CI: 0.076-0.120). The kappa coefficients suggested a low resemblance in the weight status within couples (k = 0.049, 95% CI: 0.031-0.069). Besides, the influence of the overweight/obesity status of the wives on that of the husbands (odds ratio (OR) = 1.411, 95% CI: 1.309-1.521) was slightly higher than that of the husbands on that of the wives (OR = 1.404, 95% CI: 1.302-1.514). We found that there was a moderate but significant resemblance in the body weight status between spouses, especially elderly couples with a low education level in rural areas. Health education activities for couple interventions can have a good effect of intervention.


Prenatal lipopolysaccharide exposure increases anxiety-like behaviors and enhances stress-induced corticosterone responses in adult rats.
Maternal infection during pregnancy may affect fetal brain development and lead to neurological and mental disorders. Previously, we used lipopolysaccharide [LPS, 33 μg/kg, intraperitoneal injection] exposure on gestation day 10.5 to mimic maternal bacterial infection in rats and found reduced dopaminergic and serotoninergic neurons in the offspring. In the present study, we examined the anxiety and stress responses of the affected offspring and the neurophysiological changes in their brains. Our results show that LPS rats displayed more anxiety-like behaviors and heightened stress responses. Dopamine (DA) in the nucleus accumbens and serotonin (5-HT) in the medial prefrontal cortex and the hippocampus were significantly reduced in LPS rats. Their glucocorticoid receptors in the dorsal hippocampus and the 5-HT(1A) receptors in the dorsal and ventral hippocampus were also reduced. In addition, chronic but not acute fluoxetine treatment reversed the behavioral changes and increased hippocampal 5-HT(1A) receptor expression. This study demonstrates that LPS exposure during a critical time of embryonic development could produce long-term reduction of DA and 5-HT and other neurophysiological changes; such alterations may be associated with the increases in stress response and anxiety-like behaviors in the offspring.


Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.
Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.


Comparison of the short-term efficacy of two inductive chemotherapy regimens for locally advanced nasopharyngeal caricinoma: docetaxal plus carboplatin versus 5-fluorouracil plus carboplatin.
The platinum-based chemotherapy combined with 5-fluorouracil (5-FU) is most frequently used for nasopharyngeal carcinoma (NPC), but the efficacy has been maintained at 50%-60%. Docetaxel is an effective drug for head and neck tumors, its administration is simple, and the administration time is short. This study was to compare the short-term efficacy and toxicity between TC regimen (inductive chemotherapy with docetaxol plus carboplatin) and FC regimen (5-FU plus carboplatin) in local advanced NPC so as to provide a new chemotherapeutic regimen for NPC. Fifty-eight local advanced NPC patients without previous treatment in Sun Yat-sen University Cancer Center were randomly assigned to receive either TC or FC regimen inductive chemotherapy, followed by concurrent chemoradiotherapy with two cycles of carboplatin (AUC=6) plus radiotherapy of 60-78 Gy to the nasopharynx and 60-70 Gy to the neck. The short-term efficacy and adverse events were observed. More chemotherapy cycles were finished in TC group than in FC group (3.31 vs. 2.83, P = 0.043). There was no significant difference in short-term efficacy and 1-year survival rate between the two groups (P > 0.05). More grades 3-4 neutropenia appeared in TC group than in FC group (72.4% vs. 37.9%, P < 0.05) , whereas less thrombocytopenia and emesis occurred in TC than in FC group (P = 0.013 and 0.018, respectively). The short-term efficacy of TC regimen in local advanced NPC is similar to that of FC regimen with tolerable adverse events. But the long-term outcomes and toxicities need to be further investigated.


Animal movement rates as behavioural bouts.
Johnson et al. (Journal of Animal Ecology, 2002, 71, 225-235) have proposed a new technique for identifying scales of movement in animals. Animals are located at certain time intervals, and movement rates between successive animal relocations are calculated. The null model of a nonscalar response predicts a decreasing linear relationship between log (frequency) vs. movement rate, while a scalar response predicts a monotonically decreasing curve with an inflection point at the separation between the processes. I tested this technique using three types of simulated movement paths: correlated random walks, directed walks, and movements in patchy habitat. None of the simulations showed the results expected by the technique. This occurs because the technique assumes that movement rates are exponentially distributed, which is highly unlikely. Thus before this technique can be applied to animal movement data we need to understand how spatial and temporal scale, as well as sampling interval, affect the frequency histogram of animal movement rates.


Entry of cholera toxin into polarized human intestinal epithelial cells. Identification of an early brefeldin A sensitive event required for A1-peptide generation.
The effect of brefeldin-A (BFA), a reversible inhibitor of vesicular transport, on cholera toxin (CT)-induced Cl- secretion (Isc) was examined in the polarized human intestinal cell line, T84. Pretreatment of T84 monolayers with 5 microM BFA reversibly inhibited Isc in response to apical or basolateral addition of 120 nM CT (2.4 +/- 0.5 vs. 68 +/- 3 microA/cm2, n = 5). In contrast, BFA did not inhibit Isc responses to the cAMP agonist VIP (63 +/- 7 microA/cm2). BFA had no effect on cell surface binding and endocytosis of a functional fluorescent CT analog or on the dose dependency of CT induced 32P-NAD ribosylation of Gs alpha in vitro. In contrast, BFA completely inhibited (> 95%) the ability of T84 cells to reduce CT to the enzymatically active A1-peptide. BFA had to be added within the first 10 min of CT exposure to inhibit CT-elicited Isc. The early BFA-sensitive step occurred before a temperature-sensitive step essential for apical CT action. These studies show that sequential steps are required for a biological response to apical CT: (a) binding to cell surfaces and rapid endocytosis; (b) early, BFA-sensitive vesicular transport essential for reduction of the A1-peptide; and (c) subsequent temperature-sensitive translocation of a signal (the A1-peptide or possibly ADP-ribose-Gs alpha) to the basolateral domain.


Congenital postauricular swelling in a child.
First branchial cleft cysts develop as a result of incomplete fusion of the cleft between the first and second branchial arches. In 1972, Work introduced a modified classification of these anomalies that recognized the existence of two types. Type I lesions, which are extremely rare, present as a cystic mass posterior to the pinna and concha. Type II lesions represent a duplication of both the membranous and cartilaginous portions of the external ear canal. They are associated with fistulas in the concha or in the external ear canal. Clinical and surgical management is often difficult because these anomalies have a variable relationship to the facial nerves. We describe a rare localization of a type I first branchial cleft cyst in a child and the clinical management with successive surgical treatment.


The first SARS-CoV-2 wave among pregnant women in Italy: results from a prospective population-based study.
This study aimed to estimate the incidence of SARS-CoV-2 infection among pregnant women during the first pandemic wave in Italy, and to describe COVID-19 disease characteristics and maternal and perinatal outcomes. National population-based prospective cohort study collecting information on women with SARS-CoV-2 diagnosis, confirmed within 7 days from hospital admission. The national SARS-CoV-2 rate was 6.04 per 1,000 births (95% CI 5.62-6.49) among pregnant women and 7.54 (95% CI 7.47-7.61) among women in reproductive age. 72.1% of the cohort developed mild COVID-19 disease without pneumonia nor need for ventilatory support. Severe disease was significantly associated with women's previous comorbidities (OR 2.55; 95% CI 0.98-6.90), obesity (OR 4.76; 95% CI 1.79-12.66) and citizenship from High Migration Pressure Countries (OR 3.43; 95% CI 1.27-9.25). During the first pandemic wave in Italy, the SARS-CoV-2 rate among pregnant women was lower compared to that detected among women of reproductive age, and risks of severe COVID-19 disease and adverse maternal and perinatal outcomes were rare.


Induction of morphological transformation, anchorage-independent growth and plasminogen activators in non-tumorigenic human osteosarcoma cells by lead chromate.
The possible carcinogenicity of insoluble chromium (VI) compound, PbCrO4, in human cells has been tested using a nontumorigenic human osteosarcoma cell line (HOS, TE 85). Electron microscopic studies show that PbCrO4 is phagocytosed by HOS cells and accumulates within the vacuoles in the cytoplasm. A number of cell lines have been isolated following multiple treatment of HOS cells with PbCrO4. These cell lines are morphologically different from HOS cells, form anchorage-independent colonies in soft agar and form quickly regressing small tumor nodules in athymic nude mice. The cellular and secreted plasminogen activator (PA) levels of 5 cell lines isolated after PbCrO4 treatment are increased up to 8 fold and up to 10 fold respectively as compared to untreated HOS controls. SDS-PAGE analysis in the presence of copolymerized substrates is consistent with increase in 55 kDa urokinase-type PA (u-PA) and 68 kDa tissue-type PA (t-PA). These results show that PbCrO4 treatment leads to stable phenotypic changes indicative of the transformation of HOS cells.


Nitric oxide as an electron donor, an atom donor, an atom acceptor, and a ligand in reactions with atomic transition-metal and main-group cations in the gas phase.
The room-temperature reactions of nitric oxide with 46 atomic cations have been surveyed systematically across and down the periodic table using an inductively-coupled plasma/selected-ion flow tube (ICP/SIFT) tandem mass spectrometer. Rate coefficients and product distributions were measured for the reactions of first-row cations from K+ to Se+, of second-row cations from Rb+ to Te+ (excluding Tc+), and of third-row cations from Cs+ to Bi+. Reactions both first and second order in NO were identified. The observed bimolecular reactions were thermodynamically controlled. Efficient exothermic electron transfer was observed with Zn+, As+, Se+, Au+, and Hg+. Bimolecular O-atom transfer was observed with Sc+, Ti+, Y+, Zr+, Nb+, La+, Hf+, Ta+, and W+. Of the remaining 32 atomic ions, all but 8 react in novel termolecular reactions second order in NO to produce NO+ and the metal-nitrosyl molecule, the metal-monoxide cation and nitrous oxide, and/or the metal-nitrosyl cation. K+, Rb+, Cs+, Ga+, In+, Tl+, Pb+, and Bi+ are totally unreactive. Further reactions with NO produce the dioxide cations CaO2+, TiO2+, VO2+, CrO2+, SrO2+, ZrO2+, NbO2+, RuO2+, BaO2+, HfO2+, TaO2+, WO2+, ReO2+, and OsO2+ and the still higher order oxides WO3+, ReO3+, and ReO4+. NO ligation was observed in the formation of CaO+(NO), ScO+(NO), TiO+(NO), VO+(NO)(1-3), VO2+(NO)(1-3), SrO+(NO), SrO2+(NO)1,2, RuO+(NO)(1-3), RuO2+(NO)1,2, OsO+(NO)(1-3), and IrO+(NO). The reported reactivities for bare atomic ions provide a benchmark for reactivities of ligated atomic ions and point to possible second-order NO chemistry in biometallic and metal-surface environments leading to the conversion of NO to N2O and the production of metal-nitrosyl molecules.


3,5-Diiodo-L-thyronine (3,5-t2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male diet-induced obese mice.
Effective and safe antiobesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with T3 administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2-treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase activity after application of 3,5-T2 (2.5 μg/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether, the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity.


Disconnected in a connected world: knowledge and understanding of Web 2.0 tools at the University of Pennsylvania Medical Center.
This article outlines five Web 2.0 resources and looks at the use of these tools among medical and nursing professionals and students at the Hospital, Medical School, and Nursing School of the University of Pennsylvania. Questionnaires showed that a majority of the individuals surveyed were unfamiliar with Web 2.0 resources. Additional respondents recognized the tools but did not use them in a medical or nursing context, with a minimal number using any tools to expand their medical or nursing knowledge. A lack of time to set up and use the resources, difficulty of set-up and use, skepticism about the quality of user-generated medical content, and a lack of perceived need for Web 2.0 resources contributed substantially to non-use. The University of Pennsylvania Biomedical Library is responding by increasing the availability of basic, quick, and easy-to-use instructional materials for selected Web 2.0 resources.


Training and calibrating evaluators for a national private dental office assessment program.
The work described was conducted to train and calibrate ten general dentists to participate as evaluators in a national program in which methods were developed and tested for the in-office evaluation of private general dental practice. The methods used in conducting six days of initial training are described, as well as the approach taken in establishing the posttraining levels of individual and group calibration achieved. Training and calibration that occurred halfway through a two-year field experience also are described. Techniques employed included the use of slides in lecture format; review of records, radiographs, and other materials from dental offices; examination of patients; use of a videotaped simulation of an office visit; and evaluation of private dental offices by paired evaluators. Calculation of percent of comparability of evaluator performance was used in determining calibration levels. We concluded that evaluators can be trained in six days to achieve a high level of calibration. Additional benefits were derived from the additional training session at the midpoint of field activities. Evaluators perceived themselves to be well prepared as a result of the training described.


Immunosuppression, macroencapsulation and ultraviolet-B irradiation as immunoprotection in porcine pancreatic islet xenotransplantation.
Membrane encapsulation or ultraviolet-B irradiation, with or without mild immunosuppressive treatment, was applied in order to prolong the survival of xenogeneic porcine foetal pancreatic grafts. Non-diabetic C57BL/6 mice were transplanted with porcine islet-like cell clusters, either membrane-encapsulated in the epididymal fat pad, or non-encapsulated under the kidney capsule. The animals were treated with daily subcutaneous injections of either cyclosporin A (12.5 mg/kg b.wt.), 15-deoxyspergualin (5.0 mg/kg b.wt.), ethyl (E)-6- (1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl) -4-methyl-4- hexenoate. (RS-61443) (70 mg/kg b.wt.) or with cyclophosphamide (70 mg/kg b.wt.) every second day. A fulminant mononuclear cell infiltration was observed 14 days after transplantation both around the subcapsular graft and outside the membranes in the saline treated control group. The membrane had pores of 0.45 micron and was designed to allow macromolecule transport but prevents cells from crossing. Therefore, xenoantigens can escape from the membrane implants and cause an immune reaction. A significantly weaker mononuclear cell infiltration was, however, seen when the membrane barrier was combined with 15-deoxyspergualin, cyclophosphamide or RS-61443 treatment but the morphology of the encapsulated ICC was not improved. The best subcapsular, non-encapsulated graft survival was obtained in animals treated with 15-deoxyspergualin or cyclophosphamide and the graft insulin content measurements confirmed the morphological data. There was no prolongation of islet-like cell cluster graft survival under the kidney capsule after ultraviolet-B irradiation alone (650 J/m2 for 90 sec.), and no synergistic effect was observed when ultraviolet-B irradiation was combined with 15-deoxyspergualin therapy (2.0 mg/kg b.wt.).(ABSTRACT TRUNCATED AT 250 WORDS)


Microporous Cyclic Titanium-Oxo Clusters with Labile Surface Ligands.
By using ethylene glycol and monocarboxylic acid as surface ligands, a series of cyclic Ti-oxo clusters (CTOC) with permanent microporosity are successfully synthesized. With a cyclic {Ti32 O16 } backbone made of eight connected Ti4 tetrahedral cages that are arranged in a zigzag fashion, the clusters have a "donut" shape with an inner diameter of 8.3 Å, outer diameter of 26.9 Å and height of 10.4 Å. While both inner and outer walls of the "donut" clusters are modified by double-deprotonated ethylene glycolates, their upper and lower surfaces are bound by carboxylates and mono-deprotonated ethylene glycolates. The clusters are readily packed into one-dimensional tubes which are further arranged in two different modes into crystalline microporous solids with surface areas over 660 m2 g-1 , depending on the surface carboxylates. The solid with olefin-bearing carboxylates exhibits a superior CO2 adsorption capacity of 40 cm3 g-1 at 273 K under 1 atm. Moreover, the mono-deprotonated ethylene glycolates on the clusters are demonstrated to be highly exchangeable by other alcohols, providing a nice platform for creating microporous solids or films with a wide variety of surface functionalities.


Multiple equilibria in the complexation of dibenzylimidazolium bromide salts by cyclodextrins: toward controlled self-assembly.
In aqueous solution, dibenzylimidazolium bromide salts form dimeric assemblies by T-stacking between an acidic proton of the imidazolium and the benzyl aromatic ring of another cation. This dimeric association can be disturbed by the addition of native cyclodextrins. The control of the majority species in solution can be made by the judicious choice of cyclodextrin concentration and its macrocycle size. The dimer is complexed directly by beta-cyclodextrin, whereas in the presence of alpha-cyclodextrin, the dimer is dissociated to form a 1:1 inclusion complex; at higher concentration, this 1:1 complex can dimerize.