Healthy doctors, healthy communities.
Promoting health and eliminating disease are goals of Healthy People 2010, a national initiative for all communities. Physician-directed interventions that advance these principles are most effective when directed by clinicians who regularly participate in such healthy behaviors themselves. This pilot study describes an 8-week intervention, "Well-being for You and Your Patients," for first-year medical students to experience health behavior change. In the 2-hour sessions, students set goals for changing health behavior in 6 dimensions of wellness; report their progress; and enjoy a 30-minute change-of-pace wellness activity. The authors recommend adapting the course for medical student alumni to facilitate health behavior change with small groups of adults, school-age children, teens, and elders in churches, schools, community health centers, and other community-based organizations. Through continuing medical education and Grand Rounds, residents and physicians in practice could also be trained to implement specific behavioral change strategies.


[Effect of dauricine on apoptosis and expression of apoptogenic protein after transient focal cerebral ischemia-reperfusion injury in rats].
To investigate the effect of dauricine on the apoptosis of neuronal cells and the expression of apoptosis-related proteins in the brain penumbra of rats induced by transient focal cerebral ischemia-reperfusion injury. Male SD rats were randomly divided into five groups: sham group (Sham), model group (Model), and Dauricine groups of low, middle and high doses. To make the transient focal cerebral ischemia-reperfusion injury model, the middle cerebral artery on the right side of rat was occluded by inserting a nylon suture through the internal carotid artery for 1 h, followed by reperfusion for 24 h after withdrawing the suture. Dauricine groups, different doses of Dauricine (2.5, 5, 10 mg x kg(-1) as low, middle and high dose respectively) were administered intraperitoneally at the beginning of the cerebral ischemia, and at 11 h and 23 h after reperfusion. At the same time, Sham group and Model group was administered saline as controls. Brain samples of rats were treated with paraformaldehyde perfusion fixation 24 h after blood reperfusion and then collected for making pathological sections. Apoptotic changes of neuronal cells in the brain penumbra of rat were evaluated in situ by terminal deoxyribonucleotidyl transferasemediated dUTP-digoxigenin nick end-labelling (TUNEL). Cytochrome C (Cyt-C) release and the expression of caspase -3 and caspase -9 proteins of the ischemic-reperfusion brain tissue were determined by immunohistochemistry assay. TUNEL-positive cells in groups of middle and high doses of dauricine (18.9 +/- 2.02 and 15.9 +/- 2.9 cells/mm2 respectively) decreased significantly compared with model group (25.5 +/- 3.3 cells/mm2, P<0.05). Cyt-C release and the expression of caspase-3 and caspase-9 proteins in groups of middle and high doses of dauricine were also inhibited compared with Model group (P<0.01). The mechanism of the neuroprotective effect of dauricine after cerebral ischemia-reperfusion injury may parly, related with an inhibition of neuronal cells apoptosis in the penumbra.


Recurrent angioedema caused by circulating immune complexes containing antibodies against bovine proteins.
A 27-year-old woman with severe recurrent angioedema and urticaria since 5 years was found to have high levels of circulating immune complexes in the peripheral blood. These immune complexes contained antibodies against bovine serum albumin. Elimination of bovine products from the diet resulted in disappearance of immune complexes within 2 days and addition again to the diet led to reappearance within 24 h. The patient has now been in complete remission during 4.5 years under treatment with a diet free of bovine proteins but containing products from chicken, egg, pork and fish. The immune complexes have not reappeared. Thus, immune complexes containing antibodies against alimentary antigens can provoke acute vascular damage manifested as angioedema and urticaria. In such cases, elimination of the causative antigen from the diet can result in patient being cured.


Physical therapists' use of therapeutic exercise for patients with clinical knee osteoarthritis in the United kingdom: in line with current recommendations?
Physical therapists have an important role in the management of clinical knee osteoarthritis (OA) through designing and supervising exercise programs. This study explored whether their current use of therapeutic exercise for patients with this condition is in line with recent recommendations. A cross-sectional survey was conducted with a random sample of chartered (licensed) physical therapists (N=2,000) practicing in the United Kingdom. This survey included a vignette describing a patient with clinical knee OA as well as clinical management questions relating to the respondents' use of therapeutic exercise. The questionnaire response rate was 58% (n=1,152), with 538 respondents stating they had treated a patient with clinical knee OA in the preceding 6 months. In line with recent recommendations, 99% of the physical therapists stated they would use therapeutic exercise for this patient population, although strengthening exercises were favored over aerobic exercises. Although nearly all physical therapists would monitor exercise adherence, only 12% would use an exercise diary. Seventy-six percent of physical therapists would provide up to 5 treatment sessions, and only 34% would offer physical therapy follow-up after discharge. The measure of physical therapists' current clinical practice was self-reported clinical behavior on the basis of a vignette. Although this is a valid measure of clinical behavior, in practice, physical therapists may use therapeutic exercise differently. There are disparities between physical therapists' current use of therapeutic exercise for clinical knee OA and recent recommendations. Identifying potential ways to overcome these disparities is an important step toward optimizing the outcome from therapeutic exercise for patients with clinical knee OA.


Anxiety in Parkinson's Disease: A Systematic Review of Neuroimaging Studies.
The mechanisms and neuronal networks associated with anxiety in Parkinson's disease (PD) are incompletely understood. One of the best tools for investigating both component function and neuronal networks associated with psychiatric symptoms is functional MRI (fMRI). Unlike structural scans, functional scans, whether task-based or resting-state, are more likely to be clinically relevant and sensitive to changes related to treatment. The investigators provide a comprehensive review of and present results for imaging studies of anxiety in PD. A systematic review of the literature on fMRI and anxiety in PD was conducted, and the quality of all included studies was simultaneously assessed. Eighteen studies were included: 15 studies assessed anxiety directly, and three evaluated emotional processing. Imaging methodology and behavioral assessments varied across studies, preventing direct comparison of results in most cases. There was a convergence in findings across methods, implicating involvement of the amygdala, caudate, and putamen in association with anxiety in PD. For both task-based activation and resting-state connectivity, dopamine medication status was associated with differences in activation and behavioral function. Although there is little consensus in the current fMRI literature studying anxiety in PD, these results suggest an overlap between structures classically involved in the brain's fear circuit (particularly the amygdala) and the alterations in the nigro-striatal system (e.g., the caudate and putamen and on-off dopamine findings) related to PD and its dopaminergic treatments.


[In vitro activity of anidulafungin. Comparison with the activity of other echinocandins].
Anidulafungin is a new echinocandin that acts by inhibiting (1,3)-beta-D-glucan synthesis in the fungal cell wall. This agent is a semisynthetic lipopeptide synthesized from a fermentation product of Aspergillus nidulans. The spectrum of activity of anidulafungin includes Candida and Aspergillus, the two main etiological agents causing invasive fungal infections. This drug is also active against strains of these genera resistant to azoles or amphotericin B. However, anidulafungin is not active against Cryptococcus spp., Trichosporon spp., Fusarium spp. or Mucorales spp. Data on the activity of this drug against other species are limited and do not allow conclusions to be drawn or recommendations to be made. Echinocandin resistance is uncommon and has little clinical relevance.


Stress fracture of the proximal phalanx of the great toe.
Three cases of stress fracture of the proximal phalanx of the great toe occurring in a 12-year-old female volleyball player, a 17-year-old female long distance runner, and a 12-year-old male soccer player are reported. This condition probably develops after repeated forced dorsiflexion of the first metatarsophalangeal joint with changing steps. When athletes who repeatedly run and jump complain of pain in the first metatarsophalangeal joint, and there is no history of trauma, this condition should also be considered.


Heat-induced oxidative stress and inflammation involve in cadmium pollution history in the spleen of zebrafish.
Zebrafish were exposed to 0, 2.5 and 5 μg/L cadmium (Cd) for 10 weeks, and then each group was exposed to 26 °C(control) and 32 °C (high temperature) for 7 days. 22 indicators were compared between 26 °C and 32 °C in the spleen, including body weight, LPO and NO levels, activity levels of Cu/Zn-SOD, CAT and iNOS, MTs protein levels, and mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1, MTs, IL-6, IL-10, IL-1β, TNF-α, iNOS and NF-κB. Most indicators were not significantly affected by heat in fish from no Cd pollution. However, almost all of indicators were responsive to heat in fish pre-exposed to Cd. Several indicators were sensitive to heat in fish pre-exposed to 2.5 μg/L Cd such as iNOS activities, and mRNA levels of iNOS and IL-10. Most other indicators were sensitive to heat in fish pre-exposed to 5 μg/L. The mRNA levels of HSP70 and MTF-1 were up-regulated by heat in fish pre-exposed to 0, 2.5 and 5 μg/L Cd. However, the magnitude of increase was the greatest in fish pre-exposed to 5 μg/L Cd. These differences between control and high temperature would serve as biomarkers to distinguish healthy from Cd-polluted group. The findings imply that metal pollution history should be carefully considered when screening heat biomarkers in fish.


Leukocyte Behavior in Mesenteric Microcirculation upon Experimental By Leishmania Spp. in BALB/c Mice.
We aimed to determine the cellular recruitment (leukocyte rolling and adhesion) by which the Leishmania (Viannia) braziliensis, L. (Leishmania) amazonensis, and L. (Leishmania) major species in the mesenteric microcirculation of BALB/c mice. Five experimental groups were considered: group 1 (L. braziliensis); group 2 (L. amazonensis); group 3 (L. major); group 4 (control group with PBS); group 5 (negative control group), analyzed 3, 6, 12, and 24 h after parasite inoculation. Infections by the different Leishmania species caused an increase in the number of rolling leukocytes: L. braziliensis a peak at 6 h; L. amazonensis and L. major a peak at 3 h. The Leishmania infections induced leukocyte adhesion: L. major and L. amazonensis showed an increase after 3 and 6 h, respectively. The kinetics of cellular recruitment in Leishmania infections, leading to infection susceptibility or resistance, indicates that distinct mechanisms regulate the initial response to Leishmania infection and determine its course.


Advances in management of type 1 diabetes mellitus.
Treatment of type 1 diabetes mellitus has always posed a challenge to balance hyperglycemia control with hypoglycemia episodes. The quest for newer therapies is continuing and this review attempts to outline the recent developments. The insulin molecule itself has got moulded into different analogues by minor changes in its structure to ensure well controlled delivery, stable half-lives and lesser side effects. Insulin delivery systems have also consistently undergone advances from subcutaneous injections to continuous infusion to trials of inhalational delivery. Continuous glucose monitoring systems are also becoming more accurate and user friendly. Smartphones have also made their entry into therapy of diabetes by integrating blood glucose levels and food intake with calculated adequate insulin required. Artificial pancreas has enabled to a certain extent to close the loop between blood glucose level and insulin delivery with devices armed with meal and exercise announcements, dual hormone delivery and pramlintide infusion. Islet, pancreas-kidney and stem cells transplants are also being attempted though complete success is still a far way off. Incorporating insulin gene and secretary apparatus is another ambitious leap to achieve insulin independence though the search for the ideal vector and target cell is still continuing. Finally to stand up to the statement, prevention is better than cure, immunological methods are being investigated to be used as vaccine to prevent the onset of diabetes mellitus.


Mimotope/anti-mimotope probing of structural relationships in platelet glycoprotein Ib alpha.
A bacteriophage library displaying random decapeptides was used to characterize the binding preference of C-34, a monoclonal antibody originally raised against platelet-type von Willebrand disease platelets heterozygous for the mutation 23OWKQ (G --> V)233V234 in the alpha chain of glycoprotein Ib (GPIb alpha). Three rounds of biopanning C-34 against the library resulted in striking convergence upon the sequence WNWRYREYV. Since no portion of this sequence corresponds to a recognizable peptide sequence within human platelet GPIb alpha, it may be considered a "mimotope" of the naturally occurring C-34 epitope, presumably bearing similarity to it in three-dimensional structure. Synthetic AWNWRYREYV peptide preincubated with C-34 fully neutralized the ability of C-34 to inhibit platelet aggregation, with an IC50 of approximately 6 microg/ml. When biotinylated AWNWRYREYV was subsequently bioparmed against the original decapeptide library, the sole clone demonstrating inhibitory activity above background level in a functional platelet assay displayed the sequence RHVAWWRQGV, and chemically synthesized peptide fully inhibited ristocetin-induced aggregation, with an IC50 of 200-400 microg/ml. Synthesized RHVAWWKQGV peptide exerted only slight inhibition, whereas RHVAWWKQVV peptide showed potent inhibitory activity. Moreover, whereas synthesized wild-type 228YVWKQGVDVK237 GPIb alpha peptide was virtually without inhibitory activity, the 228YVWKQ(G -->V) 233VDVK237 peptide fully inhibited ristocetin-induced aggregation, with an IC50 of approximately 400 microg/ml. These studies raise the possibility of an intramolecular association of peptide regions within GPIb alpha that may play a role in the regulation of von Willebrand factor-dependent platelet aggregation.


Bolometric detectors: optimization for differential radiometers.
A differential radiometer can be constructed by placing two matched bolometric detectors in an ac bridge, thus producing a signal that is proportional to the difference in power incident on the two detectors. In conditions of large and time-varying common-mode radiative load, the common-mode response resulting from imperfectly matched detectors can limit the stability of the difference signal. For semiconductor thermistor bolometers we find that the bridge can always be trimmed to null the common-mode response for a given instantaneous value of the radiative load. However, subsequent changes in the commonmode radiative load change the operating point of the detectors, giving rise to a second-order common-mode response. This response can be minimized by increasing the electrical-power dissipation in the detectors at the cost of sensitivity. For the case that we are analyzing, and for mismatches in detector parameters that are typical of randomly paired detectors, common-mode rejection ratios in excess of 10(3) can be achieved under 20% changes in radiative load.


Benzothiazolyl and Benzoxazolyl Hydrazones Function as Zinc Metallochaperones to Reactivate Mutant p53.
We identified a set of thiosemicarbazone (TSC) metal ion chelators that reactivate specific zinc-deficient p53 mutants using a mechanism called zinc metallochaperones (ZMCs) that restore zinc binding by shuttling zinc into cells. We defined biophysical and cellular assays necessary for structure-activity relationship studies using this mechanism. We investigated an alternative class of zinc scaffolds that differ from TSCs by substitution of the thiocarbamoyl moiety with benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones. Members of this series bound zinc with similar affinity and functioned to reactivate mutant p53 comparable to the TSCs. Acute toxicity and efficacy assays in rodents demonstrated C1 to be significantly less toxic than the TSCs while demonstrating equivalent growth inhibition. We identified C85 as a ZMC with diminished copper binding that functions as a chemotherapy and radiation sensitizer. We conclude that the benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones can function as ZMCs to reactivate mutant p53 in vitro and in vivo.


[Pretreatment and resource utilization of industrial effluent with benzoic acid].
Extraction equilibrium of benzoic acid were studied using 20%, 30% and 50% tributyl phosphate (TBP) in kerosene, 1-octanol and toluene as the extractants, to investigate the efficient method of recovering benzoic and acetic acid in the industrial effluent and meeting the requirement of the terminal wastewater treatment. The CODCr value in residual phase and the recovery of benzoic acid in various extractants were measured. The results showed that the recovery of benzoic acid was closed to 100% with 50% TBP/kerosene system, and depended on the polarity of extractant for pure solvent system. The recovery with 1-octanol was equivalent to the one with 30% TBP. The CODCr value in the residual phase depended on the CODCr value from benzoic acid and the solubility of extractant, which does not depend on the benzoic acid concentration in the residue phase apparently, and shown 50% TBP approximately equal to 30% TBP > 1-octanol > 20% TBP > toluene. Meanwhile, the profitable diagram of pretreatment of industrial effluent with benzoic acid was suggested, i.e. firstly, extract benzoic acid with toluene and return the toluene to the benzoic acid reactor, then, extract acetic acid with trialkylphosphine oxide and back-extract the acetic acid with CaO or MgO to produce calcium magnesium acetate.


Association of Electronic Cigarette Use with Respiratory Symptom Development among U.S. Young Adults.
Rationale: Electronic cigarette (e-cigarette) use is highly prevalent among young adults. However, longitudinal data assessing the association between e-cigarette use and respiratory symptoms are lacking. Objectives: To determine whether e-cigarette use is associated with the development of respiratory symptoms in young adults. Methods: Data are derived from the PATH (Population Assessment of Tobacco and Health) study waves 2 (2014-2015), 3 (2015-2016), 4 (2016-2018), and 5 (2018-2019). Young adults aged 18-24 years at baseline with no prevalent respiratory disease or symptoms were included in the analyses. Binary logistic regression models with a generalized estimating equation were used to estimate time-varying and time-lagged associations of e-cigarette use during waves 2-4, with respiratory symptom development approximately 12 months later at waves 3-5. Measurements and Main Results: The per-wave prevalence of former and current e-cigarette use was 15.2% and 5.6%, respectively. Former e-cigarette use was associated with higher odds of developing any respiratory symptom (adjusted odds ratio [aOR], 1.20; 95% confidence interval [CI], 1.04-1.39) and wheezing in the chest (aOR, 1.41; 95% CI, 1.08-1.83) in multivariable adjusted models. Current e-cigarette use was associated with higher odds for any respiratory symptom (aOR, 1.32; 95% CI, 1.06-1.65) and wheezing in the chest (aOR, 1.51; 95% CI, 1.06-2.14). Associations persisted among participants who never smoked combustible cigarettes. Conclusions: In this nationally representative cohort of young adults, former and current e-cigarette use was associated with higher odds of developing wheezing-related respiratory symptoms, after accounting for cigarette smoking and other combustible tobacco product use.


Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy.
Parathyroid hormone (PTH), PTH-derived peptides, and new PTH assays in renal osteodystrophy. Reliable measurements of parathyroid hormone (PTH) concentrations in serum or plasma are critical for the appropriate diagnosis and management of patients with renal osteodystrophy. With the introduction of second generation immunometric assays for PTH, it is now possible to measure exclusively full-length, biologically active PTH(1-84). In contrast, first generation immunometric assays that have been used widely for many years detect not only PTH(1-84), but also other large amino-terminally-truncated, PTH-derived peptides. This development will require a careful re-evaluation of PTH measurements, as determined by either first or second generation immunometric assays, and their relationship to bone histology and bone remodeling rates in patients with end-stage renal disease (ESRD). Such information is essential for proper clinical management, but only limited bone biopsy data are available to guide the interpretation of PTH results using second generation PTH assays. The different performance characteristics of first and second generation immunometric PTH assays also makes it possible to quantify the plasma levels of amino-terminally-truncated, PTH-derived peptides, which may accumulate disproportionately in patients with ESRD. Recent experimental evidence indicates that one or more of these peptides can modify bone cell activity and skeletal remodeling, possibly by interacting with a PTH receptor distinct from the type I PTH receptor that binds to the amino-terminal portion of PTH and mediates the classical biological actions of the hormone. The putative C-PTH receptor interacts with mid- and/or carboxyterminal regions of PTH and other amino-terminally-truncated PTH-derived peptides; signaling through it may contribute to the skeletal resistance to PTH that characterizes ESRD. The current review discusses certain aspects of the molecular structure of PTH and its interaction with various receptors, briefly comments about selected components of PTH secretion, highlights recent technical advances in PTH assays, and summarizes the effects of various PTH-derived peptides on bone cells and on skeletal metabolism.


Astrocytic clasmatodendrosis in the cerebral cortex of methamphetamine abusers.
Postmortem investigation of methamphetamine (MA) abuse is an important task in forensic pathology. The present study investigated morphological changes in the astrocytes in the parietal cerebral cortex of MA abusers. Glial fibrillary acidic protein immunoreactivity in the cerebral cortex was examined in forensic autopsy cases for MA-detected group and control group. Clasmatodendrotic astrocytes (including those with swollen cell bodies and disintegrating distal processes) were frequently observed in the cerebral cortex of MA abusers. Quantitative analysis using a colour image processor showed a concomitant increase in the astrocyte area and astrocyte-to-vessel area ratio (size and number of astrocytes) in the grey matter in acute MA fatality and other MA-involved cases, although the astrocyte area (size) was also increased in cases of asphyxiation. The total astrocyte area (size) in the white matter was significantly higher in MA fatalities and asphyxia than in the other groups involving MA abusers. Those indices were independent of blood MA level, age, sex, survival or postmortem time. These observations suggest the increasing number and hypertrophic changes of astrocytes in the grey matter in MA abusers can be the outcome of long-term abuse, while disintegrating distal processes may exist only in acute fatal MA intoxication.


An integrated optimization model and metaheuristics for assortment planning, shelf space allocation, and inventory management of perishable products: A real application.
Product category management (PCM) plays a pivotal role in today's large stores. PCM manages to answer questions such as assortment planning (AP) and shelf space allocation (SSA). AP problem seeks to determine a list of products and suppliers, while SSA problem tries to design the layout of the selected products in the available shelf space. These problems aim to maximize the retailer sales under different constraints, such as limited purchasing budget, limited space of classes for displaying the products, and having at least a certain number of suppliers. This paper makes an attempt to develop an integrated mathematical model to optimize integrated AP, SSA, and inventory control problem for the perishable products. The objective of the model is to maximize the sales and retail profit, considering the costs of supplier contracting/selecting and ordering, assortment planning, holding, and procurement cost. GAMS BARON solver is hired to solve the proposed model in small and medium scales. However, because the problem is NP-hard, an evolutionary genetic algorithm (GA), and an efficient local search vibration damping optimization (VDO) algorithm are proposed. A real case study is considered to evaluate the effectiveness and capabilities of the model. Besides, some test problems of different sizes are generated and solved by the proposed metaheuristic solvers to confirm the efficient performance of proposed algorithms in solving large-scale instances.


[Feasibility of using amplitude-integrated electroencephalogram to identify epileptic seizures by pediatric intensive care unit medical staff independently].
Objective: To evaluate the feasibility of using amplitude-integrated electroencephalogram (aEEG) to identify epileptic seizures by physicians and nurses in pediatric intensive care unit (PICU) independently. Method: Six testees (two PICU physicians versus one EEG physician and two PICU nurses versus one EEG technician) accepted a short-term training, then interpreted aEEG in a single blinded way. These aEEG recordings with synchronous VEEG monitoring were done from January 2013 to May 2015 in PICU. The testees should recognize and mark both the seizure type and the seizure duration from the two-channel recorder (C3/C4) of aEEG (short-term seizure or status epilepticus (SE)). Using raw VEEG monitoring as a gold standard to determine a seizure, the accuracy, missing and error rate of each testees were confirmed, and the reasons of the latter two situations were analyzed by rank sum test and inter-testee agreement (k) . Result: Eighty-two aEEG recordings from 56 patients were interpreted. Thirty-two recordings had 141 epileptic seizures confirmed by VEEG, including 119 short-term seizures and 22 SE. There were 50 recordings without seizure. As for the short-term seizures, the average accuracy of 6 testees by aEEG alone was (66±4)%. The accuracy for SE was 100% in three testees and 95% in the other three. Missing rate of the seizures were 24.1%-32.6% in all 6 testees. Those missed seizures were all short-term (duration less than 20 seconds) but one SE. The average error rate was (19±9) times (P=0.000). These false interpretations were misunderstanding, many kinds of artifacts were regarded as epileptic seizures. The accuracy and missing rate among the testees had no significance(P=0.930, 0.996), but the error rate had(P=0.000). The inter-testee agreement (k) between two physicians in PICU and the EEG doctor were 0.700 and 0.687 respectively (P<0.01), which is good. As for two nurses and the EEG technician, the inter-testee agreement (k) was 0.705 and 0.396 respectively (P<0.01). Conclusion: Most of the seizures especially status epilepticus can be detected by PICU staff after short term training. The accuracy of identification of epileptic seizures was similar among observers from PICU and EEG, although some short-term seizures may be missed, and artifacts are mistaken.It's necessary to communicate with EEG doctors and compare with the row VEEG when physicians in PICU find suspicious events.


The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells.
The association of the murine motheaten phenotype of severe hemopoietic dysregulation with loss of PTP1C tyrosine phosphatase activity indicates a critical role for this SH2 domain-containing phosphotyrosine phosphatase in the regulation of hemopoietic cell growth and differentiation. To explore the molecular basis for PTP1C effects on hematopoiesis, we have investigated the possibility that this enzyme interacts with the product of the Vav proto-oncogene, a putative guanine nucleotide exchange factor expressed exclusively in hemopoietic cells. Our data indicate that PTP1C physically associates with Vav in murine spleen cells and in EL4 T lymphoma and P815 mastocytoma cells, and that this interaction is increased following mitogenic stimulation and the induction of both PTP1C and Vav tyrosine phosphorylation. The results also reveal tyrosine phosphatase activity to be present in Vav immunoprecipitates from stimulated splenic and P815 cells and suggest that a major portion of total cellular PTP1C catalytic activity is associated with Vav. As Vav-associated tyrosine phosphatase activity was not detected in PTP1C-deficient motheaten splenic cells, it appears that PTP1C accounts for most, if not all, Vav-coprecipitable tyrosine phosphatase activity in normal cells. The data also demonstrate the capacity of the Vav SH2 domain alone to bind to PTP1C in activated P815 cells, but suggest a role for the two Vav SH3 domains in enhancing this interaction. In addition, the results reveal PTP1C association with two other molecules implicated in Ras activation, the Grb2 adaptor protein and mSos1, a GTP/GDP exchanger for Ras. PTP1C therefore has the capacity to bind and potentially modulate various signaling effectors involved in activation of Ras or Ras-related proteins, and, accordingly, regulation of Ras activation represents a possible mechanism whereby PTP1C influences hemopoietic cellular responses.


Sudden unexplained death in Asian immigrants: recognition of a syndrome in metropolitan Toronto.
To determine the number of Southeast Asians in Ontario who died of the sudden unexplained death syndrome in Asian immigrants. Retrospective review. Ontario. All deaths reported to the Office of the Chief Coroner for Ontario from 1992 to 1995. Age, residence and country of origin of people who died of sudden unexplained death syndrome in Asian immigrants, as defined by standard criteria, autopsy findings and social history of cases. Eight cases of sudden unexplained death in Asian immigrants were reported during the study period. All involved men, and the mean age at death was 34 (standard error of the mean 7) years (range 23 to 44 years). All of the people were residents of metropolitan Toronto. Four were from Vietnam, three from China and one from the Philippines. Seven people lived with family members; the eighth was unemployed and lived alone. Death occurred during sleep or in the waking hours of the morning in six cases; in two of these cases the person's spouse was awakened by loud, laboured breathing. Two men experienced chest pain, and one of them also had sudden-onset dyspnea. There was no prodromal illness in any case. The only consistent autopsy finding was acute nonspecific pulmonary edema and congestion. Analysis of heart weights failed to reveal signs of significant cardiomegaly. Men from Southeast Asia aged 20 to 45 years are at risk of sudden unexplained death, which usually occurs during sleep. No specific factors have been found that could be used to identify people at risk.


Processing of fear and anger facial expressions: the role of spatial frequency.
Spatial frequency (SF) components encode a portion of the affective value expressed in face images. The aim of this study was to estimate the relative weight of specific frequency spectrum bandwidth on the discrimination of anger and fear facial expressions. The general paradigm was a classification of the expression of faces morphed at varying proportions between anger and fear images in which SF adaptation and SF subtraction are expected to shift classification of facial emotion. A series of three experiments was conducted. In Experiment 1 subjects classified morphed face images that were unfiltered or filtered to remove either low (<8 cycles/face), middle (12-28 cycles/face), or high (>32 cycles/face) SF components. In Experiment 2 subjects were adapted to unfiltered or filtered prototypical (non-morphed) fear face images and subsequently classified morphed face images. In Experiment 3 subjects were adapted to unfiltered or filtered prototypical fear face images with the phase component randomized before classifying morphed face images. Removing mid frequency components from the target images shifted classification toward fear. The same shift was observed under adaptation condition to unfiltered and low- and middle-range filtered fear images. However, when the phase spectrum of the same adaptation stimuli was randomized, no adaptation effect was observed. These results suggest that medium SF components support the perception of fear more than anger at both low and high level of processing. They also suggest that the effect at high-level processing stage is related more to high-level featural and/or configural information than to the low-level frequency spectrum.


Biochemical analysis of the immune B cell defect in xid mice.
Previous studies have shown that B cells from xid immune defective CBA/N mice that are unresponsive do not proliferate after stimulation with unconjugated anti-Ig. The experiments in this manuscript demonstrate that dextran-anti-Ig conjugates, which induce extensive and prolonged sIg cross-linking, are able to stimulate proliferation of xid B cells. The ability of these conjugates to stimulate proliferation of xid B cells is not related to their ability to stimulate higher levels of PIP2 breakdown. Thus, high concentrations of unconjugated anti-Ig antibody, which are nonmitogenic for xid B cells, stimulate higher levels of PIP2 breakdown and of calcium transients than lower concentrations of dextran-conjugated anti-Ig, which are mitogenic. Although unconjugated anti-Ig does not provide a fully competent signal to stimulate proliferation of xid B cells, it induces a sufficiently stimulatory signal to enable them to enter DNA synthesis in the presence of the protein kinase C activator, indolactam. This suggests that the extent or duration of activation of protein kinase C by anti-Ig may be limiting in xid B cells. To examine whether another recently described pathway of B cell activation is defective in these mice, we studied the induction of early anti-Ig-mediated tyrosine kinase activity in xid B cells. Both unconjugated and dextran-conjugated anti-Ig antibody stimulated comparable but not identical patterns of tyrosine phosphorylation. These data taken together with other findings that the combination of phorbol ester and calcium ionophore stimulates high levels of proliferation in xid B cells suggests that the immune defect of xid B cells may be distal to surface Ig-mediated activation of tyrosine kinase and of PIP2 breakdown but proximal to PKC activation. Alternatively, the xid immune defect may not result from abnormalities in the early signal transduction pathways, but rather from more distal and/or as yet undefined pathways leading to B cell activation.


Oncometabolites: Unconventional triggers of oncogenic signalling cascades.
Cancer is a complex and heterogeneous disease thought to be caused by multiple genetic lesions. The recent finding that enzymes of the tricarboxylic acid (TCA) cycle are mutated in cancer rekindled the hypothesis that altered metabolism might also have a role in cellular transformation. Attempts to link mitochondrial dysfunction to cancer uncovered the unexpected role of small molecule metabolites, now known as oncometabolites, in tumorigenesis. In this review, we describe how oncometabolites can contribute to tumorigenesis. We propose that lesions of oncogenes and tumour suppressors are only one of the possible routes to tumorigenesis, which include accumulation of oncometabolites triggered by environmental cues.


PRECISION.seq: An R Package for Benchmarking Depth Normalization in microRNA Sequencing.
We present a new R package PRECISION.seq for assessing the performance of depth normalization in microRNA sequencing data. It provides a pair of microRNA sequencing data sets for the same set of tumor samples, additional pairs of data sets simulated by re-sampling under various patterns of differential expression, and a collection of numerical and graphical tools for assessing the performance of normalization methods. Users can easily assess their chosen normalization method and compare its performance to nine methods already included in the package. PRECISION.seq enables an objective and systematic evaluation of normalization methods in microRNA sequencing using realistically distributed and robustly benchmarked data under a wide range of differential expression patterns. To our best knowledge, this is the first such tool available. The data sets and source code of the R package can be found at https://github.com/LXQin/PRECISION.seq.


No difference in joint awareness after mobile- and fixed-bearing total knee arthroplasty: 3-year follow-up of a randomized controlled trial.
To compare the patients ability to forget the artificial knee joint in everyday life who were randomized to be operated for mobile- or fixed-bearing total knee arthroplasty (TKA). This single-center randomized controlled trial evaluated the 3-year follow-up of the cemented mobile- and fixed-bearing TKA from the same brand in a series of 41 patients. Clinical examination was during the pre-, 6-week, 6-month, 1-, 2- and 3-year follow-up containing multiple patient-reported outcome measures (PROMs) including the 12-item Forgotten Joint Score (FJS-12) at 3 years. Effect size was calculated for each PROM at 3-year follow-up to quantify the size of the difference between both bearings. At 3-year follow-up, general linear mixed model analysis showed that there were no significant or clinically relevant differences between the two groups for all outcome measures. Calculated effect sizes were small (<0.3) for all the PROMs except for the FJS-12; these were moderate (0.5). The results of this study demonstrate that joint awareness was slightly lower in patients operated with the MB TKA with comparable improved clinical outcome and PROMs at 3-year follow-up. Measuring joint awareness with the FJS-12 is useful and provides more stringent information at 3-year follow-up compared to other PROMs and should be the PROM of choice at each follow-up after TKA. Level I, randomized controlled trial.


Activation of PKR/eIF2α signaling cascade is associated with dihydrotestosterone-induced cell cycle arrest and apoptosis in human liver cells.
Androgen receptor (AR) signaling plays an important role in the development and progression of several liver diseases, including hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease (NAFLD). Dihydrotestosterone (DHT) is the active metabolite of the major circulating androgen, testosterone. In this study, we investigated the effect of DHT on human liver cells. We found that DHT not only induces cell cycle arrest but also initiates apoptosis in androgen-sensitive liver cells, such as SMMC-7721 and L02. Importantly, DHT/AR induces the activation of RNA-dependent protein kinase (PKR)/eukaryotic initiation factor-2 alpha (eIF2α) cascades in androgen-sensitive liver cells. PKR/eIF2α activation-induced growth arrest and DNA damage-inducible gene 153 (GADD153) and heat shock protein 27 (Hsp27) expression contribute to cell cycle arrest in response to DHT. It is notable that DHT administration results in androgen-sensitive liver cells apoptosis, at least in part, through PKR/eIF2α/GADD153 cascades. These results suggest that the androgen/AR pathway plays a pivotal role in liver cell growth and apoptosis regulating, whose deregulation might be involved in the pathogenesis of liver diseases.


Successful tongue cancer surgery under general anesthesia in a 99-year-old patient in Okinawa, Japan: A case report and review of the literature.
As advances in the medical field have resulted in increased life expectancy, performing surgery under general anesthesia in elderly patients has become an important issue. A 99-year-old Okinawan female was admitted to the hospital presenting with pain in the tongue. Following physical examination, a clinical diagnosis of early stage tongue cancer (T2N0Mx) was confirmed. Early stage tongue cancer is particularly easy to access for surgical resection. By contrast, later stages of tongue cancer are associated with pain, dysphagia and throat obstruction. The patient and their family agreed to surgery due to the worsening pain associated with the tumor and gave informed consent for surgery. Following consultation with a cardiologist and an anesthesiologist, the tongue tumor was surgically resected under general anesthesia. Subsequent to surgery, the patient experienced pain relief and was discharged from the hospital on day 14 post-surgery. The patient was able to maintain the same quality of life, and lived for 5 years and 2 months longer without evidence of disease, surviving to the age of 104 years old. The present case demonstrates that surgery under general anesthesia may be appropriate in patients of an advanced age, with a treatment plan that should ideally be based on careful assessment of the wishes of the patient and their family, medical risks, and benefits and economic costs of alternative treatments, in addition to consideration of the patient's culture.


Amyloid Typing by Mass Spectrometry in Clinical Practice: a Comprehensive Review of 16,175 Samples.
To map the occurrence of amyloid types in a large clinical cohort using mass spectrometry-based shotgun proteomics, an unbiased method that unambiguously identifies all amyloid types in a single assay. A mass spectrometry-based shotgun proteomics assay was implemented in a central reference laboratory. We documented our experience of typing 16,175 amyloidosis specimens over an 11-year period from January 1, 2008, to December 31, 2018. We identified 21 established amyloid types, including AL (n=9542; 59.0%), ATTR (n=4600; 28.4%), ALECT2 (n=511; 3.2%), AA (n=463; 2.9%), AH (n=367; 2.3%), AIns (n=182; 1.2%), KRT5-14 (n=94; <1%), AFib (n=71; <1%), AApoAIV (n=57; <1%), AApoA1 (n=56; <1%), AANF (n=47; <1%), Aβ2M (n=38; <1%), ASem1 (n=34; <1%), AGel (n=29; <1%), TGFB1 (n=29; <1%), ALys (n=15; <1%), AIAPP (n=13; <1%), AApoCII (n=11; <1%), APro (n=8; <1%), AEnf (n=6; <1%), and ACal (n=2; <1%). We developed the first comprehensive organ-by-type map showing the relative frequency of 21 amyloid types in 31 different organs, and the first type-by-organ map showing organ tropism of 18 rare types. Using a modified bioinformatics pipeline, we detected amino acid substitutions in cases of hereditary amyloidosis with 100% specificity. Amyloid typing by proteomics, which effectively recognizes all amyloid types in a single assay, optimally supports the diagnosis and treatment of amyloidosis patients in routine clinical practice.


Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling.
N-alpha-acetyltransferase 60 (NAA60) is the most recently discovered N-terminal acetyltransferase and found only in multicellular eukaryotes. NAA60 localizes to the Golgi complex and is one of the only two N-terminal acetyltransferases known to localize to an organelle. Furthermore, NAA60 possesses a unique ability of catalyzing the acetylation of membrane-anchored proteins at the N-terminus and histones at the lysine side chains. Herein, we demonstrate that NAA60 exhibits proviral properties during influenza A virus (IAV) infection by interfering with the interferon (IFN) α signaling. We found that the depletion and overexpression of NAA60 reduced and enhanced, respectively, the IAV growth in a cell type- and IAV strain-independent manner. Mechanistically, the IAV-induced expression of IFNα was increased and decreased in NAA60-depleted and -overexpressing cells, respectively. Furthermore, the depletion of NAA60 enhanced the level of phosphorylated STAT1 transcription factor as well as the expression of several IFN-stimulated genes (ISGs) such as MX1, CH25H, IFITM3, ISG15 and viperin in infected cells. Whereas the overexpression of NAA60 produced opposite results. Finally, similar results were obtained when the NAA60-depleted cells were treated with purified IFNα. These findings, in conjunction with our recent findings where N-terminal acetylation of many host proteins increased in response to the IAV infection, indicate an important role of N-terminal acetylation during IAV replication.


Field comparison of manual and semi-automatic methods for the measurement of total gaseous mercury in ambient air and assessment of equivalence.
The manual and semi-automatic methods for the measurement of total gaseous mercury in ambient air have been compared in a field trial for the first time. The comparison results have shown that whilst the expected random scatter is present, there was no significant systematic bias between the two methods, whose operational differences have also been outlined and analysed in this work. Furthermore it has been observed that because variation in instrument sensitivity is largely random in nature there is little effect on the results of the comparison if the period between instrument calibrations is altered. When the manual and semi-automatic methods are compared according to guidelines produced by the European Commission the results presented here, taken together with other supporting evidence, strongly suggest that the two methods are equivalent.


A Case of Laryngeal Tuberculosis, Endobronchial Tuberculosis and Pulmonary Tuberculosis Coexistent in an Immunocompetent Host.
Historically associated with poor prognosis seen in advanced disease, laryngeal tuberculosis (LTB) now represents only 1% of all cases of tuberculosis (TB). The incidence of LTB has decreased drastically with the introduction of anti-tubercular drugs. LTB can be primary or secondary to pulmonary tuberculosis. LTB can mimic laryngeal cancer. We present a case of primary laryngeal TB with descending tracheobronchial spread in an immunocompetent 71-year-old female who developed progressive dysphonia over several months with unintentional weight loss and non-productive cough. Non-contrast enhanced computed tomography (CT) revealed clustering of subcentimeter stellate nodules in the right upper lung field with an enlarging ground-glass opacity in the right lower lung but did not show structural abnormalities within the neck. Positron emission tomography (PET) showed pathologic fluorodeoxyglucose (FDG) uptake within the larynx and trachea with extension into the left mainstream bronchus as well as the proximal left upper and lower lobe bronchi. Diffuse standardized uptake value (SUV) was greatest in the larynx (20.5). Polymerase chain reaction (PCR) on bronchoscope sputum specimen confirmed Mycobacterium tuberculosis. Findings were consistent with primary laryngeal TB with endobronchial extension. She was started on a four-drug regimen comprising of isoniazid, rifampin, ethambutol, and pyrazinamide with a good response. Her close contacts were treated as well. This case highlights the unusual spread of primary laryngeal TB in an immunocompetent host. Early diagnosis can limit adverse complications and unnecessary exposure to healthcare workers. To our knowledge, this is the first case of primary LTB with proximal spread to the tracheobronchial and pulmonary tuberculosis.


A descriptive analysis of wounds among U.S. Marines treated at second-echelon facilities in the Kuwaiti theater of operations.
Medical data from 120 U.S. Marine Corps trauma admissions to second-echelon facilities during Operation Desert Shield/Storm were examined. Sixty-five percent of the admissions occurred between February 22 and February 28, the time frame corresponding to the ground war and the preliminary mobilization period. Penetrating wounds were the most prevalent types of injury, followed by lacerations, open fractures, and closed fractures. The most frequent anatomical regions sustaining injuries were the leg, head, hand, and arm. Fragments were the causative agent of 63% of the admissions that had this variable recorded, while gunfire was the cause in 20% of the cases. The median injury-to-admission interval increased from 0.67 hours in the non-ground war period to 4.41 during the ground war.


[Personality disorders in the elderly: diagnostic aspects].
This article describes the usefulness of the DSM personality disorders. In conclusion the presence of personality disorders during a lifetime is not always an enduring pattern of (the same) conduct disorders. Despite this, the DSM describes a static course of mainly interpersonal behaviour. Next to this, the utility of the DSM-Axis-II assessment and general personality assessment in relation to older adults will be discussed. In general these instruments are not very suitable for the assessment of the disposition and gravity of personality disorders in the elderly. It is proposed to develop specific profiles with regard to personality disorders in the elderly by applying the Delphi-technique on existing personality assessment. A Delphi panel of experts in the field of personality pathology in older adults can be asked to mention a certain personality disorder and describe this on a certain personality selfreport list, like the shortened version of the TCI.


Peri-operative complications of sphenopalatine artery ligation: a 10-year series from two secondary care centres.
There is currently limited evidence regarding the potential complications of sphenopalatine artery ligation. The post-operative outcomes at two secondary care centres over a 10-year period were reviewed. A retrospective review was undertaken of patients undergoing emergency and elective sphenopalatine artery ligation between January 2011 and January 2021. Their demographics, peri-operative care and post-operative outcomes were recorded. The median follow-up time was 54 days (range, 0-2657 days). Ninety-one patients were included. Four patients (4.4 per cent) had a septal perforation at post-operative review. Nineteen patients (20.9 per cent) had post-operative bleeding that extended their in-patient stay, with five patients (5.5 per cent) requiring revision surgery. Pre-operative non-dissolvable nasal packing was used a median of 1 time (range, 0-8 times). Further research on outcomes of sphenopalatine artery ligation is needed. Pre-operative non-dissolvable nasal packing, concurrent septal surgical procedures, surgical techniques, and co-morbidities such as hypertension represent potential confounding factors that could not be further assessed in this small, retrospective study.


Echocardiographic and Electrocardiographic Determinants of Atrial Cardiomyopathy Identify Patients with Atrial Fibrillation at Risk for Left Atrial Thrombogenesis.
Objective: Atrial cardiomyopathy (ACM) is associated with development of AF, left atrial (LA) thrombogenesis, and stroke. Diagnosis of ACM is feasible using both echocardiographic LA strain imaging and measurement of the amplified p-wave duration (APWD) in digital 12-lead-ECG. We sought to determine the thresholds of LA global longitudinal strain (LA-GLS) and APWD that identify patients with AF at risk for LA appendage (LAA) thrombogenesis. Methods: One hundred and twenty-eight patients with a history of AF were included. Left atrial appendage maximal flow velocity (LAA-Vel, in TEE), LA-GLS (TTE), and APWD (digital 12-lead-ECG) were measured in all patients. ROC analysis was performed for each method to determine the thresholds for LA-GLS and the APWD, enabling diagnosis of patients with LAA-thrombus. Results: Significant differences in LA-GLS were found during both rhythms (SR and AF) between the thrombus group and control group: LA-GLS in SR: 14.3 ± 7.4% vs. 24.6 ± 9.0%, p < 0.001 and in AF: 11.4 ± 4.2% vs. 16.1 ± 5.0%, p = 0.045. ROC analysis revealed a threshold of 17.45% for the entire cohort (AUC 0.82, sensitivity: 84.6%, specificity: 63.6%, Negative Predictive Value (NPV): 94.3%) with additional rhythm-specific thresholds: 19.1% in SR and 13.9% in AF, and a threshold of 165 ms for APWD (AUC 0.90, sensitivity: 88.5%, specificity: 75.5%, NPV: 96.2%) as optimal discriminators of LAA-thrombus. Moreover, both LA-GLS and APWD correlated well with the established contractile LA-parameter LAA-Vel in TEE (r = 0.39, p < 0.001 and r = −0.39, p < 0.001, respectively). Conclusion: LA-GLS and APWD are valuable diagnostic predictors of left atrial thrombogenesis in patients with AF.


The evocative power of enactments.
The inevitability of analytic enactments, defined as symbolic interactions between patient and analyst, is discussed. Clinical material from the psychoanalysis of a latency-age child is presented to illustrate the role of enactments and to demonstrate their usefulness in furthering the analytic work.


Formin family proteins in cytoskeletal control.
Functions of the cell cortex, including motility, adhesion, and cytokinesis, are mediated by the reorganization of the actin cytoskeleton. The assembly of the cytoskeletal components at cortical sites is regulated dynamically in a temporal and spatial manner. Recent evidence indicates that the formin family proteins play a crucial role in the reorganization of the cytoskeleton. In this review, recent advance in the understanding of the functions of formin family proteins is discussed.


Effect of oxygen in a thin-film rotating disk photocatalytic reactor.
A novel experimental procedure was developed to measure oxygen mass transfer during the oxygenation of water in a thin film of a rotating disk photocatalytic reactor (RDPR). The increase in dissolved oxygen (DO) of initially deaerated water was monitored with time in the reactor vessel at different disk angular velocities after exposure of the reactor to the atmosphere. Oxygenation was predominantly achieved by oxygen mass transport through the thin liquid film carried by the disk and to a much lesser extent by direct oxygenation of the water in the reactor vessel via a surface renewal mechanism. A mathematical model was developed to simulate the phenomenon considering both cases of presence and absence of oxygen mass transport limitations. In the latter case, the model considered that the amount of liquid carried by the disk was saturated with oxygen when returning to the reactor vessel. On the basis of the model and the experimental data, it was proven that mass-transfer limitations existed until the water in the reactor vessel became saturated with oxygen. Results obtained from the model were validated by an alternative analysis using dimensionless groups characteristic to the system. The study revealed that the mass-transfer coefficient increased linearly with disk angular velocity and thus disk Reynolds number. The results showed that oxygen mass-transfer limitations decreased with increasing disk angular velocity, mainly due to an increase in the overall mass-transfer coefficient. In the presence of UV radiation, the influence of oxygen on the photocatalytic oxidation of 4-chlorobenzoic acid was investigated in the RDPR operated in batch and continuous mode. The photocatalytic reactions occurred in a thin film of liquid carried by the disk in the presence of UV radiation and ST-B01 composite spherical ceramic (SiO2/Al2O3) balls coated with anatase TiO2 catalyst. It was found that the initial degradation rate followed Langmuir kinetics with respect to oxygen concentration in the gas phase. When the oxygen concentration in the gas phase surpassed that in air, the degradation rates did not improve significantly, suggesting that operation with air instead of oxygen is most probably a more realistic practical choice. Measurements of DO during the presence and absence of UV radiation suggested that the photocatalytic reactions were mainly oxygen concentration-limited rather than oxygen mass-transfer-limited.


Monte Carlo simulation of cylinders with short-range attractions.
Cylindrical or rod-like particles are promising materials for the applications of fillers in nanocomposite materials and additives to control rheological properties of colloidal suspensions. Recent advances in particle synthesis allows for cylinders to be manufactured with short-ranged attractions to study the gelation as a function of packing fraction, aspect ratio and attraction strength. In order to aid in the analysis of small-angle scattering experiments of rod-like particles, computer simulation methods were used to model these particles with specialized Monte Carlo algorithms and tabular superquadric potentials. The attractive interaction between neighboring rods increases with the amount of locally-accessible surface area, thus leading to patchy-like interactions. We characterize the clustering and percolation of cylinders as the attractive interaction increases from the homogenous fluid at relatively low attraction strength, for a variety of aspect ratios and packing fractions. Comparisons with the experimental scattering results are also presented, which are in agreement.


Which person is my trainer? Spontaneous visual discrimination of human individuals by bottlenose dolphins (Tursiops truncatus).
Bottlenose dolphins are known to use signature whistles to identify conspecifics auditorily. However, the way in which they recognize individuals visually is less well known. We investigated their visual recognition of familiar human individuals under the spontaneous discrimination task. In each trial, the main trainer appeared from behind a panel. In test trials, two persons (one was the main trainer) appeared from the left and right sides of the panel and moved along the poolside in opposite directions. Three of the four dolphins spontaneously followed their main trainers significantly above the level of chance. Subsequent tests, however, revealed that when the two persons wore identical clothing, the following response deteriorated. This suggests that dolphins can spontaneously discriminate human individuals using visual cues, but they do not utilize facial cues, but body area for this discrimination.


Double Face Mask Use for COVID-19 Infection Prevention and Control Among Medical Students at Makerere University: A Cross-Section Survey.
The second wave of COVID-19 greatly affected the health care and education systems in Uganda, due to the infection itself and the lockdowns instituted. Double masking has been suggested as a safe alternative to double-layered masks, where the quality of the latter may not be guaranteed. This study aimed to determine patterns of double mask use among undergraduate medical students at Makerere University, Uganda. We conducted a descriptive cross-sectional study using an online questionnaire. All students enrolled at the College of Health Sciences; Makerere University received the link to this questionnaire to participate. Logistic regression analysis was used to assess factors associated with double mask use. A total of 348 participants were enrolled. The majority (61.8%) were male; the median age was 23 (range: 32) years. Up to 10.3%, 42%, and 4.3% reported past COVID-19 positive test, history of COVID-19 symptoms, and having comorbidities, respectively. Up to 40.8% had been vaccinated against COVID-19. More than half (68.7%) believed double masking was superior to single masking for COVID-19 IPC, but only 20.5% reported double masking. Participants with a past COVID-19 positive test [aOR: 2.5; 95% CI: 1.1-5.8, p = 0.026] and participants who believed double masks had a superior protective advantage [aOR: 20; 95% CI: 4.9-86.2, p < 0.001] were more likely to double mask. Lack of trust in the quality of masks (46.5%) was the most frequent motivation for double masking, while excessive sweating (68.4%), high cost of masks (66.4%), and difficulty in breathing (66.1%) were the major barriers. Very few medical students practice double masking to prevent COVID-19. Coupled with inconsistencies in the availability of the recommended four-layered masks in Uganda and increased exposure in lecture rooms and clinical rotations, medical students may be at risk of contracting COVID-19.


Inorganic ions in the skin: Allies or enemies?
Skin constitutes a barrier protecting the organism against physical and chemical factors. Therefore, it is constantly exposed to the xenobiotics, including inorganic ions that are ubiquitous in the environment. Some of them play important roles in homeostasis and regulatory functions of the body, also in the skin, while others can be considered dangerous. Many authors have shown that inorganic ions could penetrate inside the skin and possibly induce local effects. In this review, we give an account of the current knowledge on the effects of skin exposure to inorganic ions. Beneficial effects on skin conditions related to the use of thermal spring waters are discussed together with the application of aluminium in underarm hygiene products and silver salts in treatment of difficult wounds. Finally, the potential consequences of dermal exposure to topical sensitizers and harmful heavy ions including radionuclides are discussed.


Functional coupling of voltage-dependent L-type Ca2+ current to Ca2+-activated K+ current in pituitary GH3 cells.
Ca2+-activated K+ currents (I(K(Ca)) can contribute to action potential repolarization and after-hyperpolarization in GH3 cells. In this study, we examined how the activation of I(K(Ca) at the cellular level could be functionally coupled to Ca2+ influx through L-type Ca2+ channels. A 30-msec Ca2+ influx step to 0 mV was found to exhibit substantial contribution of Ca2+ influx through the activation of I(Ca,L) to the activation of I(K(Ca)). A bell-shaped relationship between the conditioning potentials and the integrated I(K(Ca)) was observed, suggesting that the magnitude of integrated I(Ca,L) correlates well with that of integrated I(K(Ca)) in the same cell. A linear relationship of integrated I(Ca,L) and integrated I(K(Ca)) was found with a coupling ratio of 69+/-7. The value of the coupling ratio was unaffected by the presence of Bay K 8644 or nimodipine, although these compounds could effectively affect the amplitudes of both I(K(Ca)) and I(Ca,L). However, tetrandrine could decrease the coupling ratio. Paxilline or intracellular Ca2+ buffer with EGTA decreased the coupling ratio, while apamin had no effect on it. Interestingly, phorbol 12-myristate 13-acetate also reduced the coupling ratio significantly, whereas thapsigargin increased this value. Thus, the present study indicates that the activation of I(K(Ca)) during brief Ca2+ influx, which is inhibited by paxilline, is coupled to Ca2+ influx primarily through the L-type channels. The selective modulation of I(K(Ca)) by second messengers or Ca2+ release from internal stores may affect the coupling efficiency and hence cellular excitability.


Socio-ecological Model as a Framework for Overcoming Barriers and Challenges in Randomized Control Trials in Minority and Underserved Communities.
Numerous barriers and challenges can hinder the successful enrollment and retention of study participants in clinical trials targeting minority populations. To conduct quality research, it is important to investigate these challenges, determine appropriate strategies that are evidence-based and continue seeking methods of improvement. In this paper, we report such experiences in a registered clinical trial in an underserved minority population in the Southern part of United States. This research study is a randomized double-blind controlled clinical trial that tests the efficacy of higher-strength as compared to low-strength/standard of care folic acid to prevent fetal body and brain size reduction in pregnant women who smoke. A unique approach in this socio-behavioral, genetic-epigenetic clinical trial is that we have adopted the socio-ecological model as a functional platform to effectively achieve and maintain high participant recruitment and retention rates. We highlight the barriers we have encountered in our trial and describe how we have successfully applied the socio-ecological model to overcome these obstacles. Our positive experience will be of utility to other researchers globally. Our fi ndings have far-reaching implications as the socio-ecological model approach is adaptable to developed and developing regions and has the potential to increase recruitment and retention of hard-to-reach populations who are typically under-represented in clinical trials.


HIV counseling, testing, and care of tuberculosis patients at chest clinics--Guyana, 2005-2006.
Tuberculosis (TB) is a leading cause of morbidity and mortality among persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). During 2004, Guyana had an estimated TB incidence rate of 140 per 100,000 population, the fourth highest rate in the Americas (after Haiti, Bolivia, and Peru); Guyana also had an estimated adult HIV prevalence of 2.5%, and 20% of TB patients were reported to be infected with HIV. In 2000, the Guyana Ministry of Health (MOH) began providing HIV counseling, testing, and referrals to HIV/AIDS programs at its six public chest clinics. At the end of 2005, chest clinics also began providing co-trimoxazole preventive therapy (CPT) to HIV-infected TB patients as a measure against common opportunistic infections. During February-June 2006, an international team assessed the extent to which MOH chest clinics in Guyana had implemented these interventions during July 2005-June 2006. This report summarizes the results of that assessment, which determined that, among 253 TB patients sampled, 174 (69%) initially did not know their HIV-infection status; 127 (73%) of those patients were offered HIV counseling and testing, and 115 (91%) accepted and were tested for HIV. Of the 115 who were tested, 11 (10%) were determined to be HIV infected; overall, 68 (35%) of the 194 patients whose HIV-infection status was known were HIV infected (i.e., 11 who were tested at the chest clinics plus 57 with preexisting knowledge of their HIV status). These results indicate both a high rate of HIV infection among TB patients in Guyana and the ability of chest clinics to provide HIV-related interventions in resource-limited settings.


Mid-radial portal for operative arthroscopy of the elbow: cadaveric and clinical description of a new portal.
We report a previously undescribed portal on the lateral aspect of the elbow-the mid-radial portal-and discuss the safety and use of this portal in a clinical practice via cadaveric dissection and retrospective review of 61 patients. It is located midway between the proximal anterolateral and the direct lateral portals at the level of the radiocapitellar joint and serves as a second portal on the lateral side of the elbow for use anteriorly or posteriorly. The portal penetrates the common extensor origin and courses between the radial and ulnar bands of the lateral collateral ligament complex prior to penetrating the joint capsule.In the clinical series, the mid-radial portal was used in 40 (66%) of 61 cases. The most common procedures involved removal of loose bodies and debridement in the radiocapitellar joint or posterolateral gutter. Follow-up in the clinical series averaged 6 months. No major and 2 minor complications, neither of which could be directly attributed to the use of the mid-radial portal, were found. Specifically, no cases of postoperative lateral instability existed. The previously undescribed mid-radial portal is a safe, effective option for arthroscopy on the lateral aspect of the elbow.


Organelle Membranes from Germinating Castor Bean Endosperm: II. ENZYMES, CYTOCHROMES, AND PERMEABILITY OF THE GLYOXYSOME MEMBRANE.
Glyoxysome ghosts were isolated from germinating castor bean endosperms using established methods. Electron microscopic examination showed that some matrix material was retained within the glyoxysomal membrane. Two cytochrome reductases and phosphorylcholine glyceride transferase co-sedimented with the alkaline lipase, a known component of the glyoxysome membrane, in sucrose gradient centrifugation of osmotically shocked glyoxysomes. The activities of these enzymes in the glyoxysome membranes were compared to those in the endoplasmic reticulum relative to phospholipid content. On this basis, the phosphorylcholine glyceride transferase was 10-fold more active in the endoplasmic reticulum, whereas the lipase was 50-fold more active in the glyoxysome membrane. The cytochrome reductases were only 2-fold more active in the endoplasmic reticulum, indicating that they are components of the two membranes. Difference spectroscopy of the glyoxysome membrane suspension revealed the presence of a b5-type cytochrome similar to that found in the endoplasmic reticulum. Since the glyoxysome membrane is apparently derived from the endoplasmic reticulum, components of the endoplasmic reticulum such as these are likely to be incorporated into the glyoxysome membrane during biogenesis.Enzyme activities involving the cofactors NADH or CoA were measurable in broken, but not in intact, glyoxysomes. Thus, it appears that cofactors for enzymes within the organelle cannot pass through the membrane.


Conformational disorder in energy transfer: beyond Förster theory.
Energy transfer in donor-acceptor chromophore pairs, where the absorption of each species is well separated while donor emission and acceptor absorption overlap, can be understood through a Förster resonance energy transfer model. The picture is more complex for organic conjugated polymers, where the total absorption spectrum can be described as a sum of the individual contributions from each subunit (chromophore), whose absorption is not well separated. Although excitations in these systems tend to be well localized, traditional donors and acceptors cannot be defined and energy transfer can occur through various pathways where each subunit (chromophore) is capable of playing either role. In addition, fast torsional motions between individual monomers can break conjugation and lead to reordering of excited state energy levels. Fast torsional fluctuations occur on the same timescale as electronic transitions leading to multiple trivial unavoided crossings between excited states during dynamics. We use the non-adiabatic excited state molecular dynamics (NA-ESMD) approach to simulate energy transfer between two poly-phenylene vinylene (PPV) oligomers composed of 3-rings and 4-rings, respectively, separated by varying distances. The change in the spatial localization of the transient electronic transition density, initially localized on the donors, is used to determine the transfer rate. Our analysis shows that evolution of the intramolecular transition density can be decomposed into contributions from multiple transfer pathways. Here we present a detailed analysis of ensemble dynamics as well as a few representative trajectories which demonstrate the intertwined role of electronic and conformational processes. Our study reveals the complex nature of energy transfer in organic conjugated polymer systems and emphasizes the caution that must be taken in performing such an analysis when a single simple unidirectional pathway is unlikely.


Genome-Wide Identification of JRL Genes in Moso Bamboo and Their Expression Profiles in Response to Multiple Hormones and Abiotic Stresses.
Jacalin-related lectins (JRLs) are a new subfamily of plant lectins that has recently been recognized and plays an important role in plant growth, development, and abiotic stress response. Although moso bamboo (Phyllostachys edulis) is an economically and industrially important bamboo worldwide, there has been no systematic identification of JRLs in this species. Here, we identified 25 JRL genes in moso bamboo, and these genes are unequally distributed among 10 genome scaffolds. Phylogenetic analysis showed that the moso bamboo JRLs were clustered into four JRL subgroups: I, II, V, and VII. Numerous stress-responsive and hormone-regulated cis-elements were detected in the upstream promoter regions of the JRLs. Genome collinearity analyses showed that the JRL genes of moso bamboo are more closely related to those of Brachypodium distachyon than to those of Oryza sativa and Zea mays. Sixty-four percent of the PeJRL genes are present as segmental and tandem duplicates. qRT-PCR expression analysis showed that JRL genes in the same subgroup were significantly downregulated in response to salicylic acid (SA), abscisic acid (ABA), and methyl jasmonate (MeJA) treatments and significantly upregulated under low temperature, drought, and salt stress; they also exhibited tissue-specific expression patterns. Subcellular localization experiments revealed that PeJRL04 and PeJRL13 were localized to the cell membrane, nucleus, and cytoplasm. Three dimensional structure prediction and yeast two-hybrid assays were used to verify that PeJRL13 exists as a self-interacting homodimer in vivo. These findings provide an important reference for understanding the functions of specific moso bamboo JRL genes and for the effective selection of stress-related genes.


Invitation strategies and coverage in the population-based cancer screening programmes in the European Union.
The aim of this study was to describe the compliance of the population-based cancer screening programmes in the European Union Member States to the invitation strategies enumerated in the European Guidelines and the impact of such strategies on the invitational coverage. Experts in screening programme monitoring from the respective countries provided data. Coverage by invitation was calculated as the proportion of individuals in the target age range receiving a screening invitation over the total number of annualized eligible population. The invitation strategies of 30 breasts, 25 cervical and 27 colorectal national or regional population-based screening programmes are described. Individual mail invitations are sent by 28 breasts, 20 cervical and 25 colorectal screening programmes. Faecal occult blood test kits are sent by post in 17 of the colorectal cancer screening programmes. The majority of programmes claimed to have a population registry, although some use health insurance data as the database for sending invitations. At least 95% invitation coverage was reached by 16 breast, six cervical and five colorectal screening programmes. Majority of the programmes comply with the invitation strategies enumerated in the European guidelines, although there is still scope for improvements. Coverage by invitation is below the desirable level in many population-based cancer screening programmes in European Union.


Inadvertent epidural infusion of paracetamol in a child.
An 11-year-old boy underwent lumbar epidural anesthesia under general anesthesia to provide intra- and postoperative analgesia for a severe burn of his lower limb. A dural tap at the L4-L5 space occurred during the epidural approach. A second attempt through the upper intervertebral space was successful. Postoperatively, the boy was given both continuous epidural analgesia and intravenous (i.v.) infusions. These latter were provided using two similar double track pumps. At the 36th postoperative hour a nurse injected paracetamol using inadvertently the epidural instead of the i.v. pump. The mistake was repeated 6 h later. The boy experienced both headache and vomiting. Symptoms seemed to be a mechanical rather than a toxic complication. They disappeared for 48 h under treatment including saline and caffeine. Neurological examinations stayed normal. No sequelae were noted. The frequency of this type of medication incident is probably underestimated. The literature notes a large list of injected drugs, but paracetamol had never been described.


Social mindfulness: skill and will to navigate the social world.
Although one may not always see it, social life often involves choices that make people act in ways that are mindful of others or not. We adopt an interdependence theoretical approach to the novel concept of social mindfulness, which we conceptualize in terms of other-regarding choices involving both skill (to see it, e.g., theory of mind, perspective taking) and will (to do it, e.g., empathic concern, prosocial orientation) to act mindfully toward another person's control over outcomes. We operationalized social mindfulness in a new social decision-making paradigm that focuses on leaving or limiting choice options for others that we tested across 7 studies. Studies 1a through 1c showed that people with other-oriented mindsets left interdependent others more choice than people with self-oriented and/or unspecified mindsets. Studies 2a and 2b revealed that people developed more favorable judgments of a socially mindful than of a socially unmindful person. Study 3 revealed that unknown others with trustworthy (vs. untrustworthy) faces were met with more social mindfulness. Study 4 revealed that social mindfulness could be traced in personality by being positively related to Honesty-Humility and Agreeableness (HEXACO Personality Inventory-Revised) as well as to Empathy (Interpersonal Reactivity Index) and a prosocial value orientation (SVO). Together, these studies contribute to explaining how social mindfulness can help people to navigate the social world by aiming to maximize other people's control over their situational outcomes.


Early effects of spinal cord transection on skeletal muscle properties.
Modulation of beta-adrenergic receptor (beta-AR) activity affects muscle mass and could have a role in the reduction of muscle mass observed following spinal cord transection (Tx). The aims of this study were to examine the early acute effects of Tx on muscle mass, total and myofibrillar protein concentrations, cytochrome c oxidase activity, and beta-AR density of skeletal muscle, to ascertain if any change in muscle properties could be related to beta-AR signalling events. Female Sprague-Dawley rats (n = 33; approximately 255 g) were randomly assigned to 4 experimental groups: control 4 d, control 8 d, Tx 4 d, and Tx 8 d. A complete Tx was performed surgically at the T10 cord level. Compared with controls, muscle mass and muscle - body mass ratios decreased significantly following Tx, with no significant change observed in total and myofibrillar protein concentrations. Spinal cord Tx also resulted in a significant decrease in plantaris cytochrome c oxidase activity by 24% at Tx 4 d and 28% at Tx 8 d (p < 0.05). Beta-AR density of the lateral gastrocnemius was unchanged; however, the beta-AR density of the forelimb triceps brachii m. was found to increase after Tx. Our results suggest that changes in muscle mass and cytochrome c oxidase activity rapidly occur after Tx and do not appear to be related to changes in beta-AR density.


Perioperative considerations in patients with cirrhotic cardiomyopathy.
This review aims to identify specific criteria for cirrhotic cardiomyopathy, examine the correlation with perioperative adverse outcomes and explore options for hemodynamic monitoring. Cirrhotic cardiomyopathy is characterized by an increase in cardiac output, blunted systolic contractile response to stress, diastolic dysfunction and electrophysiological abnormalities. Adverse events due to cirrhotic cardiomyopathy are not as well characterized, but evidence suggests that some cardiovascular complications during surgery and in the postoperative period are caused by an impaired response to physiological stress. New developments in hemodynamic monitoring using not only thermodilution technology provide more reliable information about cardiac performance than pressure-derived measures. Transesophogeal echocardiography also offers the physician new information including the ability to visualize heart structures, shape, and function. To detect cirrhotic cardiomyopathy, physicians must conduct a systematic examination of the patient. Overt manifestations of cirrhotic cardiomyopathy often only become evident after a patient is exposed to physiological or drug-induced stress. Appropriate hemodynamic monitoring is a cornerstone in the perioperative management of cirrhotic patients.


Combination of Stem Cells with Chinese Herbs for Secondary Depression in Neurodegenerative Diseases Based on Traditional Chinese Medicine Theories.
Depression is a common secondary symptom in neurodegenerative diseases (NDs) caused by the loss of neurons and glial cells. Recent research focuses on stem cell therapy to replace dead nerve cells, but the low efficiency of stem cell differentiation and short survival time are obstacles limiting the therapy's effectiveness. Clinically, patients with different diseases cannot obtain the same effect by using the same cell therapy. However, traditional Chinese medicine (TCM) often uses syndrome differentiation to determine the treatment plan for NDs. Based on TCM syndrome differentiation and treatment, this article summarizes the advantages of Chinese herbal medicine combined with stem cell therapy, mainly for the effects of various herbs on diseases and stem cells, including prolonging the survival time of stem cells, resisting inflammation, and antidepressant-like effects. In particular, it analyzes the unique pathways of the influence of drugs and acupuncture on different therapies, seeking to clarify the scientific TCM system. This review mainly elaborates on the treatment of secondary depression in TCM and the advantages of a herbal combined stem cell therapy in various methods. We believe it can provide a new clinical concept for secondary depression to obtain good clinical effects and reduce the risks borne by patients.


Attenuated Superoxide Dismutase 2 Activity Induces Atherosclerotic Plaque Instability During Aging in Hyperlipidemic Mice.
Atherosclerosis progression during aging culminates in the development of vulnerable plaques, which may increase the risk of cardiovascular events. Increased generation and/or decreased scavenging of reactive oxygen species in the vascular wall are major contributors to atherogenesis. We previously showed that superoxide dismutase 2 deficiency increased vascular oxidative stress and reduced aortic compliance in aged wild-type mice and that young Apoe-/-/Sod2+/- had increased mitochondrial DNA damage and atherosclerosis versus young Apoe-/- mice. Here we investigated the effects of superoxide dismutase 2 deficiency on atherosclerosis progression and plaque morphology in middle-aged Apoe-/- mice. Compared with Apoe-/-, middle-aged Apoe-/-/Sod2+/- mice had increased vascular wall reactive oxygen species (P<0.05) and higher atherosclerotic lesion area (P<0.001). The atherosclerotic plaques in middle-aged Apoe-/-/Sod2+/- mice had an increased necrotic core with higher inflammatory cell infiltration, a thinned fibrous cap with depleted smooth muscle content, and intraplaque hemorrhage. In addition, the plaque shoulder area had higher levels of calpain-2, caspase-3, and matrix metalloproteinase-2 in intimal smooth muscle cells and depleted fibrous cap collagen. Targeting mitochondrial reactive oxygen species with MitoTEMPO attenuated features of atherosclerotic plaque vulnerability in middle-aged Apoe-/-/Sod2+/- mice by lowering expression of calpain-2, caspase-3, and matrix metalloproteinase-2 and decreasing smooth muscle cell apoptosis and matrix degradation. Enhanced mitochondrial oxidative stress under hyperlipidemic conditions in aging induces plaque instability, in part by increasing smooth muscle cell apoptosis, necrotic core expansion, and matrix degradation. Targeting mitochondrial reactive oxygen species or its effectors may be a viable therapeutic strategy to prevent aging-associated and oxidative stress-related atherosclerosis complications.


Propagation of population pharmacokinetic information using a Bayesian approach: comparison with meta-analysis.
We investigated the propagation of population pharmacokinetic information across clinical studies by applying Bayesian techniques. The aim was to summarize the population pharmacokinetic estimates of a study in appropriate statistical distributions in order to use them as Bayesian priors in consequent population pharmacokinetic analyses. Various data sets of simulated and real clinical data were fitted with WinBUGS, with and without informative priors. The posterior estimates of fittings with non-informative priors were used to build parametric informative priors and the whole procedure was carried on in a consecutive manner. The posterior distributions of the fittings with informative priors where compared to those of the meta-analysis fittings of the respective combinations of data sets. Good agreement was found, for the simulated and experimental datasets when the populations were exchangeable, with the posterior distribution from the fittings with the prior to be nearly identical to the ones estimated with meta-analysis. However, when populations were not exchangeble an alternative parametric form for the prior, the natural conjugate prior, had to be used in order to have consistent results. In conclusion, the results of a population pharmacokinetic analysis may be summarized in Bayesian prior distributions that can be used consecutively with other analyses. The procedure is an alternative to meta-analysis and gives comparable results. It has the advantage that it is faster than the meta-analysis, due to the large datasets used with the latter and can be performed when the data included in the prior are not actually available.


Synthesis and Comparative Study of Anti-Adenoviral Activity of 6-Azacytidine and Its Analogues.
This paper presents the results of synthesis and study of cytotoxicity and the anti-adenoviral activity of new N4-derivatives of 6-azacytidine and its α-L-glycopyranosyl analogues obtained by the simplified one-pot version of the silyl condensation method. The resulting acylated 4-methylmercapto-1,2,4-triazin-3(2Н)-one glycosides then underwent the amination and/or ammonolysis to provide 6-azacytidine glycoside analogues (2-6, 12, 15, 17) and compounds with modifications at both base and sugar fragments (11, 15). The evaluation of cytotoxicity and antiviral activity of new compounds against AdV5 showed high selectivity indexes for N4-methyl-6-azacytidine (2) and N,O-tetraacetyl-6-azacytidine (8). High anti-adenoviral activity of N4-methyl-6-azacytidine as well as very low cytotoxicity may suggest its further investigation as potential compound for the therapy of AdV infection.


Heat-Introduced Formation of Acrylamide in Table Olives: Analysis of Acrylamide, Free Asparagine, and 3-Aminopropionamide.
Acrylamide was detected in considerable amounts in black table olives. In this study, besides black, also green and naturally black table olives were investigated for their acrylamide, free asparagine, and 3-aminopropionamide contents before and after heat treatment. Acrylamide amount was 208-773 μg/kg in black table olives and did not change due to heat treatment. In green and naturally black table olives acrylamide was ≤24 μg/kg before heat treatment and rose to 1200 μg/kg afterward. Asparagine content was 0.35-35 mg/kg in all samples before heat treatment and after heat treatment with no considerable change in the range. 3-Aminopropionamide showed amounts of ≤56 μg/kg in the unheated samples and increased up to 131 μg/kg due to heat impact. However, quantified asparagine and 3-aminopropionamide amounts were insufficient in almost all samples to explain the acrylamide quantities formed due to heat treatment based on the formation via the Maillard reaction.


[Effect of acupuncture on retinal and choroidal thickness in patients with optic atrophy].
To observe the effect of acupuncture on visual acuity, intraocular pressure, visual field, retinal and choroidal thickness on optic disc and macular area in patients with optic atrophy. A total of 33 patients with optic atrophy were treated with acupuncture. Acupuncture was given at Chengqi (ST 1), Shangjingming (Extra), Qiuhou (EX-HN 7) and Fengchi (GB 20) etc., 30 min each time, once a day, for 14 days. The visual acuity, intraocular pressure, visual field indexes (mean deviation [MD], pattern standard deviation [PSD] and visual field index [VFI]), optic disc retinal nerve fiber layer thickness, macular retinal thickness and choroidal thickness of optic disc and sub-foveal were compared before and after treatment. Compared before treatment, the visual acuity was increased (P<0.05), the MD value was decreased (P<0.05), the thickness of nerve fiber layer on the upper temporal side of optic disc was thinner (P<0.05), and the choroidal thickness of average, nasal side and lower temporal side of optic disc was increased (P<0.05). There was significant correlation between visual field MD and retinal nerve fiber layer thickness in different quadrants before and after treatment (P<0.01). Acupuncture could improve visual acuity, increase choroidal thickness in part of optic disc area in patients with optic atrophy.


Medical Outcomes in Women Who Became Pregnant after Vaccination with a Virus-Like Particle Experimental Vaccine against Influenza A (H1N1) 2009 Virus Tested during 2009 Pandemic Outbreak.
The clinical effects and immunological response to the influenza vaccine in women who later become pregnant remain to be thoroughly studied. Here, we report the medical outcomes of 40 women volunteers who became pregnant after vaccination with an experimental virus-like particle (VLP) vaccine against pandemic influenza A(H1N1)2009 (influenza A(H1N1)pdm09) and their infants. When included in the VLP vaccine trial, none of the women were pregnant and were randomly assigned to one of the following groups: (1) placebo, (2) 15 μg dose of VLP vaccine, or (3) 45 μg dose of VLP vaccine. These 40 women reported becoming pregnant during the follow-up phase after receiving the placebo or VLP vaccine. Women were monitored throughout pregnancy and their infants were monitored until one year after birth. Antibody titers against VLP were measured in the mothers and infants at delivery and at six months and one year after birth. The incidence of preeclampsia, fetal death, preterm delivery, and premature rupture of membranes was similar among groups. All vaccinated women and their infants elicited antibody titers (≥1:40). Women vaccinated prior to pregnancy had no adverse events that were different from the nonvaccinated population. Even though this study is limited by the sample size, the results suggest that the anti-influenza A(H1N1)pdm09 VLP experimental vaccine applied before pregnancy is safe for both mothers and their infants.


Effect of Ramadan fasting on glycemic control in patients with Type 2 diabetes.
Although Muslim patients with Type 2 diabetes may be exempt from fasting during Ramadan for medical reasons, a high proportion of them fast. To investigate the association between Ramadan fasting and glycemic control in patients with Type 2 diabetes. A prospective cohort clinical trial was designed. Eighty-eight patients with Type 2 diabetes (45 male, 43 female, age 51±10 yr) who opted to fast for at least 10 days during the month of Ramadan were recruited. Fasting blood samples were taken at the beginning and end of Ramadan, and 1 month after Ramadan, to assess fasting blood glucose (FBG), fasting insulin, full blood count, glycated hemoglobin (HbA(1c)) and fasting lipid profile. Insulin resistance was estimated using the homeostatic model assessment. Anthropometrics and blood pressure were also measured. There was a significant deterioration in FBG and HbA(1c) (p=0.002 and p≤0.001, respectively) and significant improvements in HDL and LDL cholesterol and body mass index after Ramadan (p<0.001). Interestingly, HbA(1c) showed a reduction 1 month after Ramadan (9.4±2% at the end of Ramadan vs 8.4±2.5% 1 month after Ramadan; p<0.001). Results from this study showed that fasting during Ramadan deteriorated the glycemic control in Type 2 diabetes patients. This was more evident in patients using oral hypoglycemic medication than diet- controlled patients. However, Ramadan fasting had small positive effects on lipid profile and body weight.


"Mucin types" in normal and neoplastic colonic goblet cells: a mucin histochemical study.
Goblet cells in normal colon mucosa from 100 individuals histochemically showed two major "mucin types" in sialic acid composition. One type revealed mixed reactivities for N-acetyl-neuraminic acid (NANA, abbreviated C0), 7-O- acylated NANA (C7) and 9-O-acylated NANA (C9), and represented 25% of the individuals examined. The other type of mucin, seen in 69% of the cases, exhibited reactivity for 8-O-acylated NANA or pluri-O-acylated NANA (C8). C0 and C8 were observed simultaneously in 5% of the individuals. In addition, 8% displayed a mosaic pattern in which isolated "blue" crypts containing sialic acids of the C0 + C7 + C9 type were detected in the "red" colonic mucosa, which was predominantly C8. Little correlation was found between the mucin types and their site in the colon, or with the age, sex, ABO blood groups and degree of sulphation. O-acylated NANA was also observed, though reduced in amount, in all 22 colonic adenocarcinomas in which evaluable numbers of neoplastic goblet cells were found. The mucin types in colon cancer were fundamentally indistinguishable from those seen in the surrounding noncancerous colonic mucosa.


Induction in myeloid leukemic cells of genes that are expressed in different normal tissues.
Using DNA microarray and cluster analysis of expressed genes in a cloned line (M1-t-p53) of myeloid leukemic cells, we have analyzed the expression of genes that are preferentially expressed in different normal tissues. Clustering of 547 highly expressed genes in these leukemic cells showed 38 genes preferentially expressed in normal hematopoietic tissues and 122 other genes preferentially expressed in different normal nonhematopoietic tissues, including neuronal tissues, muscle, liver, and testis. We have also analyzed the genes whose expression in the leukemic cells changed after activation of WT p53 and treatment with the cytokine IL-6 or the calcium mobilizer thapsigargin. Of 620 such genes in the leukemic cells that were differentially expressed in normal tissues, clustering showed 80 genes that were preferentially expressed in hematopoietic tissues and 132 genes in different normal nonhematopoietic tissues that also included neuronal tissues, muscle, liver, and testis. Activation of p53 and treatment with IL-6 or thapsigargin induced different changes in the genes preferentially expressed in these normal tissues. These myeloid leukemic cells thus express genes that are expressed in normal nonhematopoietic tissues, and various treatments can reprogram these cells to induce other such nonhematopoietic genes. The results indicate that these leukemic cells share with normal hematopoietic stem cells the plasticity of differentiation to different cell types. It is suggested that this reprogramming to induce in malignant cells genes that are expressed in different normal tissues may be of clinical value in therapy.


Unusual fragmentation pathways in collagen glycopeptides.
Collagens are the most abundant glycoproteins in the body. One characteristic of this protein family is that the amino acid sequence consists of repeats of three amino acids -(X-Y-Gly)n. Within this motif, the Y residue is often 4-hydroxyproline (HyP) or 5-hydroxylysine (HyK). Glycosylation in collagen occurs at the 5-OH group in HyK in the form of two glycosides, galactosylhydroxylysine (Gal-HyK) and glucosyl galactosylhydroxylysine (GlcGal-HyK). In collision induced dissociation (CID), collagen tryptic glycopeptides exhibit unexpected gas-phase dissociation behavior compared to typical N- and O-linked glycopeptides (i.e., in addition to glycosidic bond cleavages, extensive cleavages of the amide bonds are observed). The Gal- or GlcGal- glycan modifications are largely retained on the fragment ions. These features enable unambiguous determination of the amino acid sequence of collagen glycopeptides and the location of the glycosylation site. This dissociation pattern was consistent for all analyzed collagen glycopeptides, regardless of their length or amino acid composition, collagen type or tissue. The two fragmentation pathways-amide bond and glycosidic bond cleavage-are highly competitive in collagen tryptic glycopeptides. The number of ionizing protons relative to the number of basic sites (i.e., Arg, Lys, HyK, and N-terminus) is a major driving force of the fragmentation. We present here our experimental results and employ quantum mechanics calculations to understand the factors enhancing the labile character of the amide bonds and the stability of hydroxylysine glycosides in gas phase dissociation of collagen glycopeptides.


Characterization of a Salmonella choleraesuis mutant that cannot multiply within epithelial cells.
A mutant of Salmonella choleraesuis was identified that could invade (enter) and penetrate through polarized monolayers of Caco-2 and MDCK epithelial cells at normal levels but was defective for intracellular multiplication within these cells. It was also able to survive inside cultured J774 macrophage cells. These bacteria remained inside membrane-bound vacuoles, which coalesced at later times in the perinuclear region of the epithelial cell. This mutant exhibited slightly slower growth rates in rich or minimal media than the parental strain but was normal for iron usage, phosphate usage, and anaerobic growth and was a prototroph. The mutant was completely avirulent when administered orally or intravenously to susceptible mice. These results suggest that the ability to multiply within eukaryotic cells may contribute to S. choleraesuis virulence.