Regulated conformation of myosin V.
We have found that myosin V, an important actin-based vesicle transporter, has a folded conformation that is coupled to inhibition of its enzymatic activity in the absence of cargo and Ca(2+). In the absence of Ca(2+) where the actin-activated MgATPase activity is low, purified brain myosin V sediments in the analytical ultracentrifuge at 14 S as opposed to 11 S in the presence of Ca(2+) where the activity is high. At high ionic strength it sediments at 10 S independent of Ca(2+), and its regulation is poor. These data are consistent with myosin V having a compact, inactive conformation in the absence of Ca(2+) and an extended conformation in the presence of Ca(2+) or high ionic strength. Electron microscopy reveals that in the absence of Ca(2+) the heads and tail are both folded to give a triangular shape, very different from the extended appearance of myosin V at high ionic strength. A recombinant myosin V heavy meromyosin fragment that is missing the distal portion of the tail domain is not regulated by calcium and has only a small change in sedimentation coefficient, which is in the opposite direction to that seen with intact myosin V. Electron microscopy shows that its heads are extended even in the absence of calcium. These data suggest that interaction between the motor and cargo binding domains may be a general mechanism for shutting down motor protein activity and thereby regulating the active movement of vesicles in cells.


Mannose-binding lectin deficiency and predisposition to recurrent infection in adults.
The effects of mannose-binding lectin (MBL) deficiency are well known in children and in those with a compromised immune system. However, its effects in adults are debateable, with little research having been carried out in the UK regarding infection risk in otherwise healthy adults with an MBL deficiency. Using an ELISA, we investigated the prevalence of MBL deficiency in both healthy adults and those with recurrent infection. The aim was to determine first if there was a disparity in MBL levels between the two groups and second to investigate the effect of severe deficiency. Overall, the difference between the two groups for MBL level was found not to be statistically significant (p=0.203); however, there was a higher prevalence of severe deficiency (MBL<75 ng/mL) in the patients with recurrent infection (p=0.03). It was concluded that there is justified reason for continuing to perform the MBL test in adult patients suffering recurrent infection.


Oxygen Consumption by Desulfovibrio Strains with and without Polyglucose.
The kinetics of oxygen reduction by Desulfovibrio salexigens Mast1 and the role of polyglucose in this activity were examined and compared with those of strains of D. desulfuricans and D. gigas. Oxidation rates were highest at air saturation (up to 40 nmol of O(2) min mg of protein) and declined with decreasing oxygen concentrations. Studies with cell extracts (CE) indicated that NADH oxidase was entirely responsible for the oxygen reduction in strain Mast1. In D. desulfuricans CSN, at least three independent systems appeared to reduce oxygen. Two were active at all oxygen concentrations (NADH oxidase and NADPH oxidase), and one was maximally active at less than 10 muM oxygen. In contrast to D. gigas and D. salexigens strains, the D. desulfuricans strains also contained NADH peroxidase and NADPH peroxidase activities and did not accumulate polyglucose under nonlimiting growth conditions. At air saturation, initial activities of the oxidases and peroxidases of cells harvested at the end of the log phase were on the order of 20 to 140 nmol of O(2) min mg of protein. In all strains, these enzymes were relatively stable but were susceptible to inactivation as soon as substrates were added to the assay mixture. Under those conditions, all oxidation activity disappeared after ca. 1 h of incubation. The same finding was observed with whole cells of D. desulfuricans CSN and D. desulfuricans ATCC 27774, but inactivation was less pronounced with cells of D. salexigens Mast1. It appeared that the presence of polyglucose in the whole cells retarded the process of inactivation of NADH oxidase, but this property was lost in crude CE. In spite of the effect of polyglucose on the oxidative potential, oxygen-dependent growth of D. salexigens Mast1 could be demonstrated neither in batch nor in continuous culture.


Tissue expression of the hepatitis C virus NS3 protein does not correlate with histological or clinical features in patients with chronic hepatitis C.
In chronic hepatitis B, the HBcAg viral protein in liver tissue demonstrates a positive correlation with serum aminotransferase levels, serum hepatitis B viral DNA, and histological activities. Little is known if similar relationships exist for chronic hepatitis C. This study attempted to determine if expression of the hepatocyte NS3 protein of the hepatitis C virus (HCV-NS3) was correlated with the serum HCV-RNA load, hepatitis activity, or other clinical parameters. Clinical and histological data of 214 patients with chronic hepatitis C were retrospectively reviewed. A mouse monoclonal antibody was used to detect HCV-NS3 in hepatocytes. The staining intensity was scored semiquantitatively as 0~3+, and its correlations with the serum HCV-RNA load, hepatitis activity, and other clinical parameters were analyzed. In total, 202 (94%) of the 214 liver biopsies were positive for HCV-NS3, and the intensity of HCV-NS3 staining was 0 in 12 (6%), 1+ in 181 (84%), and 2+ in 21 patients (10%). The intensity of HCV-NS3 expression in the samples did not correlate with patient age (p = 0.302, ANOVA), patient gender (p = 0.130, Fisher's exact test), the alanine transaminase level (p = 0.177, ANOVA), serum HCV-RNA level (p = 0.305, ANOVA), HCV antibody titer (p = 0.139, Chi-squared test), hepatitis activity index score (p = 0.861, Chisquared test), or sustained viral response rate (p = 0.861, Chi-squared test). This HCV-NS3 immunohistochemical staining method was reliable for detecting HCV in liver specimens. Hepatocyte expression of HCV-NS3 was not correlated with the serum viral load, severity of hepatic injury, or treatment response.


[Primary Small Bowel Tumor with Simultaneous Lung Metastases from Rectal Cancer - A Case Report].
A 56-year-old woman was diagnosed with rectal cancer and liver metastases(Stage IV), and underwent low anterior resection and laparoscopic partial hepatectomy. The patient received adjuvant chemotherapy(mFOLFOX6 for 24 weeks), but developed multiple lung metastases 11 months later. Before undergoing a pulmonary resection, the patient presented with acute small bowel obstruction. Abdominal computed tomography showed small bowel stenosis due to a tumor, and we suspected peritoneal metastases from the rectal tumor. We performed partial resection of the small intestine, and histopathological examination revealed a primary small bowel tumor. The patient was discharged to her home without complications, and later underwent pulmonary resections for bilateral lung metastases. We usually suspect that small bowel obstruction is due to peritoneal metastases in patients with advanced colorectal tumors, but must consider the rare possibility of a separate primary small bowel tumor, especially in patients with a solitary lesion. We report a rare primary small bowel tumor after FOLFOX treatment in a patient with Stage IV rectal cancer.


Sampled-data filtering framework for cardiac motion recovery: optimal estimation of continuous dynamics from discrete measurements.
Quantitative and noninvasive estimation of cardiac kinematics has significant physiological and clinical implications. In this paper, a sampled-data filtering framework is presented for the recovery of cardiac motion and deformation functions from periodic medical image sequences. Cardiac dynamics is a continuously evolving physical/physiological process, whereas the imaging data can provide only sampled measurements at discrete time instants. Given such a hybrid paradigm, stochastic multiframe filtering frameworks are constructed to couple the continuous dynamics with the discrete measurements, and to coordinately deal with the parameter uncertainty of the biomechanical constraining model and the noisy nature of the imaging data. The state estimates are predicted according to the continuous-time biomechanically constructed state equation between observation time points, and then updated with the new imaging-derived measurements at discrete time instants, yielding physically more meaningful and more accurate estimation results. Both continuous-discrete Kalman filter and sampled-data Hinfinity filter are applied for motion recovery. While Kalman filter is the optimal estimator under Gaussian noises, the Hinfinity scheme can give robust estimation results when the types and levels of model uncertainties and data disturbances are not available a priori. The strategies are validated through synthetic data experiments to illustrate their advantages and on canine MR phase contrast images and human MR tagging data to show their clinical potential.


The aid of microsurgical instruments in nasolabial cyst enucleation. A report of two cases with critical review of the therapeutic approach.
Nasolabial cysts are rare non-odontogenic cysts related to epithelial remnants of the nasolacrimal duct, slowly enlarging and provoking extraoral swelling in the nasolabial fold with obstruction of the naris. Two patients of large unilateral nasolabial cysts are reported, appearing as cosmetically unappealing distention of the nasolabial fold. Diagnosis is based on clinical characteristics. Computed tomography imaging reveals the dimensions of the cyst, the correlation to the nasal cavity and might depict a depression on the labial surface of the maxilla. Intraoral surgical enucleation of the cystic wall or nasal marsupialization is the main treatment modalities. However, both procedures are related to a small percentage of recurrence. Microsurgical instruments were used to dissect the cystic wall from the nasal mucosa. The aim of this paper is to stress the implementation of microsurgical instruments to separate the cystic wall of the nasolabial cyst from the thin and friable nasal mucosa to avoid recurrence.


Neuroendocrine lung cancer presenting as a breast lump.
We report the case of a 54-year-old woman presenting to our attention for a palpable breast lump. The mammographic examination showed multiple round/oval areas of increased opacity spread on both breasts. The ultrasonographic examination showed multiple hypo-anechoic nodularities without retro-tumor acoustic shadowing. The mammo/ultrasonographic findings were worthy of histological analysis, thus we performed a ultrasound (US)-guided core-biopsy, obtaining a histological diagnosis of neuroendocrine carcinoma, probably originating from the lungs. The subsequent whole body CT scan, performed to search the primary neoplasm, put in evidence a neoplasm in the left lung, involving the pulmonary hilum, and infiltrating the bronchial branches. Moreover, there were multiple secondary lesions involving adrenal glands, brain and bowel. A review of the literature confirmed that breast lumps may be the first manifestation of a metastatic disease.


Exploiting a Phage-Bacterium Interaction System as a Molecular Switch to Decipher Macromolecular Interactions in the Living Cell.
Pathogenicity islands of Staphylococcus aureus are under the strong control of helper phages, where regulation is communicated at the gene expression level via a family of specific repressor proteins. The repressor proteins are crucial to phage-host interactions and, based on their protein characteristics, may also be exploited as versatile molecular tools. The Stl repressor from this protein family has been recently investigated and although the binding site of Stl on DNA was recently discovered, there is a lack of knowledge on the specific protein segments involved in this interaction. Here, we develop a generally applicable system to reveal the mechanism of the interaction between Stl and its cognate DNA within the cellular environment. Our unbiased approach combines random mutagenesis with high-throughput analysis based on the lac operon to create a well-characterized gene expression system. Our results clearly indicate that, in addition to a previously implicated helix-turn-helix segment, other protein moieties also play decisive roles in the DNA binding capability of Stl. Structural model-based investigations provided a detailed understanding of Stl:DNA complex formation. The robustness and reliability of our novel test system were confirmed by several mutated Stl constructs, as well as by demonstrating the interaction between Stl and dUTPase from the Staphylococcal ϕ11 phage. Our system may be applied to high-throughput studies of protein:DNA and protein:protein interactions.


Biochemical and immunocytochemical characterization of olfactory marker protein in the rodent central nervous system.
Olfactory marker protein (OMP), previously thought to be expressed only by olfactory receptor neurons and their processes, was localized anatomically with immunocytochemical techniques to a number of brain regions in three rodent species, the mouse, rat, and hamster. In addition, the amount of antigen was quantified by radioimmunoassay (RIA) and characterized by an immunoblot procedure. In all three species the antigen could be detected immunocytochemically in the preoptic region and hypothalamus. The rat did not exhibit immunostaining in any other brain region. However, in the mouse neuronal labelling was observed throughout the neural axis, including cellular labelling in the bed nucleus of the anterior commissure, the median preoptic nucleus, the bed nucleus of the stria terminalis, the periventricular region, the anterior parvicellular subnucleus of the paraventricular nucleus, around the dorsomedial hypothalamic nucleus (pars compacta), the subincertal region, the arcuate nucleus, the anterior cortical nucleus of the amygdala, the suprageniculate nucleus, the lateral lemniscal nuclei, the lateraldorsal and lateralventral central gray, the posterior aspects of the commissural and marginal nuclei of the inferior colliculus, the paragenule nucleus, the A-5 region, the area postrema, the ventromedial nucleus of the solitary tract, area X, the spinal trigeminal nucleus (pars zonale), and superficial laminae of the spinal cord. The hamster displayed a different pattern of labelling including cells in the periventricular gray, the pontine reticular tegmental nucleus, the A-5 region, the medial vestibular complex, the prepositus hypoglossal nucleus, the parvicellular reticular nucleus, the lateral paragigantocellular nucleus, the raphe obscuras, the lateral reticular nucleus, and the lateral nucleus of the cerebellum. Immunostaining was seen in fibers within the red nucleus and within mossy fibers of the cerebellum. OMP levels could only be quantified by radioimmunoassay in the olfactory bulb of the three species and in the hamster cerebellum where they were 1/1,000 of those determined in the olfactory bulb. The authenticity of OMP measured in the RIA and detected immunocytochemically was verified by a double-antibody immunoisolation/immunodetection procedure, which confirmed that the antigen being visualized had the molecular properties expected for OMP. In summary, these experiments demonstrate that authentic OMP exists in small groups of neurons in many areas of the central nervous system.


Ovarian Teratoid Carcinosarcoma Is an Aggressive Tumor of Probable Mullerian Derivation with a Carcinosarcomatous and Mixed Germ-Cell Morphology.
Ovarian carcinosarcoma is also referred to as malignant mixed Mullerian tumor (MMMT). It is a rare neoplasm, and although it represents less than 5% of malignant ovarian tumors, it remains generally well-known among clinicians and pathologists. Rarer yet is ovarian teratoid carcinosarcoma, defined as carcinosarcoma with the added feature of immature neuroectodermal tissue, with or without elements of primitive germ cell tumor. To our knowledge, six ovarian teratoid carcinosarcomas have been reported in the literature [Matsuura et al. J Obstet Gynaecol Res. 2010 Aug; 36(4): 907-11]. These tumors resemble nasopharyngeal tumors of the same name. We report a 55-year-old woman seen at Orlando Health's division of gynecological oncology whose pathology showed ovarian teratoid carcinosarcoma, and present what we believe to be a seventh report of this entity.


A note on the stability of team performance.
Yearly winning percentages of 23 professional basketball teams over a 10-year period were used to evaluate the stability of team performance. The intercorrelation matrix produced by these data is characterized by strong, positive correlations in adjacent time periods. As the number of intervening time periods increased, however, the observed correlations systematically decreased and ultimately became negative. Significant negative correlations of earlier performance with later performance are almost never observed with typical time-related performance data. Possible explanations and boundary conditions for these atypical results are discussed.


[The effect of coffee and tea upon lower esophageal sphincteric function.].
The effects of coffee and tea upon lower esophageal sphincteric (LES) function were examined in a blinded crossover study of 12 healthy subjects. Lower esophageal sphincter pressure (LESP) and lower esophageal (LE) pH were measured simultaneously by a sleeve sensor and a pH probe for 20 minutes before and 90 minutes after intragastric instillation of four test solutions, which contained either regular coffee (C), decaffeinated coffee (D), tea (T) or water (W). C and T solutions had the same caffeine content, 160 mg. As compared with control (W), LESP was significantly lower after C and T, but not after D. The data for LE pH paralleled those for LESP. Thus, the greatest number of reflux episodes occurred after T and C. Difference from control (W) was statistically significant for T but not for C. We conclude that both regular coffee and tea have adverse effects upon LES function, whereas decaffeinated coffee does not. This study provides a rational basis for limiting intake of both caffeinated coffee and tea in patients with clinically important gastroesophageal reflux.


Relationship between coronary risk factor and arteriographic feature of coronary atherosclerosis.
Coronary arteriography was performed in 1,029 consecutive patients with ischemic heart disease and the relationship between the arteriographic features of coronary atherosclerosis and coronary risk factors was analyzed by case control studies. Patients were divided into four groups according to coronary arteriographic findings. Patients with normal or near normal coronary arteriograms (Group I) showed a high prevalence of smoking habit and a higher value of serum uric acid compared with the control group, so smoking and hyperuricemia were considered to be the risk factors for coronary atherosclerosis in patients of group. Four selected variables: smoking, hyperuricemia, hypertension and hyperlipidemia, were identified to be risk factors for the patients with minor plaques in the coronary arteries (Group II). As in Group I, smoking and hyperuricemia had a close relationship to solitary tight plaque in a branch of the coronary artery (Group III). Multiple tight stenoses in the coronary arteries (Group IV) correlated closely with smoking, hyperuricemia, hypertension, hyperlipidemia and diabetes mellitus. Thus, there were many strong risk factors for patients with diffuse, extended coronary atherosclerosis (Group II and Group IV), while only two factors, smoking and hyperuricemia, were considered to be risk factors for the patients with near normal coronary arteries ies or a solitary plaque in a branch of the coronary artery. These findings suggest that the role of the coronary risk factors on the pathogenesis of coronary atherosclerosis is not uniform but variable depending on the morphologic variability of the coronary atherosclerosis and on the pathophysiology of the ischemic heart disease.


Gamma probe-guided lymph node dissection ('gamma picking') in differentiated thyroid carcinoma.
The prognostic significance and the optimal management of regional lymph node metastases in patients with well-differentiated thyroid carcinoma continue to be controversial. The current surgical approach for nodal metastases is removal of grossly involved lymph nodes ("berry picking"). In patients with papillary thyroid cancer, this intraoperative sampling technique reveals tumor in only 15% to 60% of excised nodes. However, if a more extensive nodal dissection is undertaken, at least 70% of patients are found to have nodal disease. The authors have successfully used a gamma probe-guided lymph node dissection technique ("gamma picking") to identify visually undetectable micrometastatic lymph nodes at the time of surgical exploration. The authors used this technique in a 52-year-old man with papillary carcinoma of the thyroid that was diagnosed by fine-needle aspiration. Eighteen hours before the planned total thyroidectomy, the patient was given 1 mCi I-123 orally. Operative exploration revealed multiple tumor nodules in both lobes but no palpable lymph nodes in the neck. Total thyroidectomy was performed with complete extracapsular removal of both lobes and isthmus. The thyroid bed and the central and lateral nodal basins were scanned using a gamma probe (Neoprobe). Hot spots were identified, and these counts were compared with that of the background activity in the strap muscles. The gamma probe revealed four distinct foci of increased activity (10 times more than the background). These were resected and labeled separately for histopathologic study. Histologic analysis revealed bilateral, multifocal well-differentiated papillary carcinoma, with the largest tumor focus measuring 0.6 cm. Two of the four hot spots proved to be metastatic foci in small lymph nodes measuring less than 0.5 cm. The other two hot spots were thyroid remnants with no associated nodal tissue.


Exercise and drug therapy alter recovery from labyrinth lesion in humans.
Acute unilateral vestibular failure is characterized by rotatory vertigo, horizontal-rotatory nystagmus, and postural imbalance, all of which last from days to weeks. These signs and symptoms are caused by a vestibular tone imbalance between the two labyrinths. Recovery results from a combination of peripheral restoration of labyrinthine function (usually incomplete) and central vestibular compensation (CVC) of the vestibular tone imbalance. Acute unilateral failure is most often caused by vestibular neuritis, which is most likely due to the reactivation of a latent HSV-1 infection. Therefore, therapeutic strategies to improve the outcome of VN are theoretically based on two principles: (a) vestibular exercises and drugs to improve CVC and (b) drug treatment of the assumed viral inflammation. The following conclusions can be drawn from studies in animals and/or humans: (1) There is strong evidence that vestibular exercises may improve vestibulo-spinal compensation. These exercises should begin as early as possible after symptom onset. Moreover, slower exercises are likely to be more effective than faster exercises because slower ones seem to depend more on the vestibular system. (2) Despite extensive data from animal experiments indicating that drugs have a favorable effect on CVC, this has not been clinically proven and thus cannot be recommended yet. (3) Preliminary results of an interim analysis from an ongoing randomized, prospective study showed that methylprednisolone (plus an antiviral agent?) may be useful for improving peripheral vestibular function in vestibular neuritis.


Within-Person Dynamics of Objective and Subjective Social Isolation in Midlife and Later Life.
ObjectivesTo investigate the within-person dynamics of objective and subjective social isolation among U.S. middle-aged and older adults and to explore gender differences in this relationship. Methods: Four waves of data from the Health and Retirement Study (HRS, 2006-2018, N = 5437) and the multiple group random intercept cross-lagged panel model were used. Results: Within-person deviation in expected subjective isolation predicted deviation in expected objective isolation years later. No corresponding cross-lagged effect of objective isolation on subjective isolation was found. Gender differences were detected: the within-person cross-lagged positive effect of subjective isolation on objective isolation was significant for men but not for women. Discussion: This study provides evidence for a unidirectional relationship between subjective and objective isolation at the within-person level: higher than expected increase in subjective isolation predicts higher than expected increase in subsequent objective isolation. This within-person process is more salient in men than in women.


Selective stimulation of nociceptive small fibers during intraepidermal electrical stimulation: Experiment and computational analysis.
Electrical stimulation of skin nociceptors is gaining attention in pain research and peripheral neuropathy diagnosis. However, the optimal parameters for selective stimulation are still difficult to determine because they require simultaneous characterization of the electrical response of small fibers (Aδ- and C-fibers). In this study, we measured the in vivo electrical threshold responses of small fibers to train-pulse stimulation in humans for the first time. We also examined selective stimulation via a computational model, which combines electrical analysis, and terminal fiber and synaptic models, including the first cutaneous pain C-fiber model. Selective stimulation of small fibers is performed by injecting train-pulse stimulation via coaxial electrodes with an intraepidermal needle tip at varying pulse counts and frequencies. The activation Aδ- or C-fibers was discriminated from the differences in reaction time. Aδ-fiber elicited a pinpricking sensation with a mean reaction time of 0.522 s, and C-fiber elicited a tingling sensation or slight burning itch with a mean reaction time of 1.243 s. The implemented multiscale electrical model investigates synaptic effects while considering stimulation waveform characteristics. Experimental results showed that perception thresholds decreased with the number of consecutive pulses and frequency up to convergence (five pulses or 70 Hz) during the selective stimulation of Aδ- and C-fibers. Considering the synaptic properties, the optimal stimulus conditions for selective stimulation of Aδ- vs. C-fibers were train of at least four pulses and a frequency of 40-70 Hz at a pulse width of 1 ms. The experimental results were modeled with high fidelity by incorporating temporal synaptic effects into the computational model. Numerical analysis revealed terminal axon thickness to be the most important biophysical factor affecting threshold variability. The computational model can be used to estimate perception thresholds while understanding the mechanisms underlying the selective stimulation of small fibers. The parameters derived here are important in exploring selective stimulation between Aδ- and C-fibers for diagnosing neuropathies.


Reducing the risk of pesticide exposure among children of agricultural workers: how nurse practitioners can address pesticide safety in the primary care setting.
Studies have shown that exposure to agricultural pesticides can result in serious acute and chronic health effects in humans. While pesticide exposure may occur in many different settings, agricultural workers and their families are at greatest risk. Children of agricultural workers are at particular risk because of their smaller size, higher metabolic rates, immature body systems, and behavioral and developmental patterns. Health care providers working in rural and agricultural areas are most likely to work with families and children at greatest risk for pesticide exposure. Many health care professionals do not feel adequately prepared to address safety, prevention, and education regarding pesticide exposure. This article reviews current studies on reducing pesticide exposure in children of agricultural workers and outlines a list of recommendations and guidelines for health care professionals working with this population. These guidelines address the particular vulnerabilities and risks of children at all stages of their development and ways in which health care professionals can address these risks with agricultural workers and their families in the primary care setting.


Effects of BabyDance Lubricant on Sperm Parameters.
Semen analysis is a common test conducted for diagnosing the cause of male infertility, so using an innocuous lubricant can be beneficial to reduce the semen collection difficulties. In this study, the effects of BabyDance™ lubricant gel, a paraben-free lubricant, on sperm parameters were investigated. It was a prospective study and a total of 45 individuals were enrolled. First, the semen samples of 20 patients referred to Royan Research Institute were incubated with different concentrations of gel, and subsequently, the sperm motility and vitality were evaluated. In the second phase, 25 individuals who had a spermogram test were asked to apply the gel in the new semen examination. Obtained data were statistically analysed using SPSS software. The results of the in vitro phase revealed that this gel does not affect the pH, sample colour, viability, total motility and progressive and non-progressive motility of spermatozoa at any concentration. The second phase results also represented no difference in spermatozoal characteristics with and without gel use. Moreover, 100% of the participants in the second phase were satisfied with the gel and recommended that to other patients. It was concluded that this gel can be considered a harmless product to sperm and can be a beneficial option for clients referring to infertility centres that facilitate the semen collection process.


Effect of phacoemulsification on facility of outflow.
Phacoemulsification has been shown to reduce intraocular pressure (IOP). The mechanism of action is thought to be via increased trabecular outflow facility. However, studies on the relationship between phacoemulsification and outflow facility have been inconsistent. This study intended to examine the change in electronic Schiotz tonographic outflow facility (TOF) and IOP measurements following phacoemulsification. Patients who were due to undergo a standard clear corneal incision phacoemulsification with intraocular lens (IOL) implantation, at St Thomas' Hospital, were invited to participate in this study. IOP was measured using Goldmann's applanation tonometer, and TOF was measured by electronic Schiotz tonography at baseline and at 3, 6 and 12 months postoperatively. Forty-one patients were recruited. Tonography data for 27 patients were reliable and available at all time points. Eleven cases had primary open angle glaucoma and cataract, while 16 patients had cataract only. Mean IOP reduced at every time point postoperatively significantly compared with baseline. TOF improved significantly after cataract extraction at all time points (baseline of 0.14±0.06 vs 0.18±0.09 at 3 months, P=0.02 and 0.20±0.09 at 6 months, P=0.003, 0.17±0.07 µL/min mmHg at 12 months, P=0.04). Five contralateral eyes of patients with cataracts only who did not have any intraocular surgery during the follow-up period were used as comparison. Their IOP and TOF did not change significantly at any postoperative visits. This is the first study using electronic Schiotz tonography with documented anterior chamber depth and gonioscopy after modern cataract surgery (CS) with phacoemulsification and IOL implantation. We demonstrated that phacoemulsification increases TOF and this fully accounts for the IOP reduction following CS. ISRCTN04247738.


Iconicity and sign vocabulary acquisition.
This study was designed to investigate learning and retention of isolated sign vocabulary as a function of sign classification (iconic, opaque, or abstract). The subjects were 28 hearing college students naive to sign vocabulary. They were drilled with 30 signs from American Sign Language that had been classified as iconic, opaque, or abstract. Training was conducted using two different media: computer-assisted instruction and videotaped presentation. Performance scores for the three types of signs were significantly different. Scores were consistently higher for iconic signs, regardless of the training mode. The videotaped presentation mode produced the greatest consistency in scores. The results of this study support the notion that it is easier for beginning students of sign language to learn and retain iconic signs.


Serum levels of CD8 antigen in childhood lymphoid malignancies: a possible indicator of increased suppressor cell activity in poor-risk patients.
Serum concentrations of CD8 antigen were measured at diagnosis with an enzyme-linked immunoassay in children with acute lymphoblastic leukemia (n = 344) or non-Hodgkin's lymphoma (n = 65). All patients had detectable levels of the serum antigen, which in its soluble nonreduced form appeared to be a 52-Kd homodimer as compared with the 66-Kd surface membrane component on most thymocytes and on a subset of functionally distinct T cells (suppressor/cytotoxic). Increased serum levels of CD8 in leukemia patients were significantly related to recognized high-risk prognostic features: high leukocyte count, large liver and spleen size, high serum lactic dehydrogenase level, T-cell immunophenotype, presence of a mediastinal mass, pseudodiploid karyotype, DNA index less than 1.16, and chromosomal translocation. Children with serum CD8 levels greater than or equal to 450 U/mL were more likely to fail treatment than were those with lower levels (P = .002), even in the group with non-T-cell leukemia (P = .003). In a multivariate analysis, serum CD8 antigen contributed independent prognostic information beyond that conveyed by age, leukocyte count, and race (P = .02). High serum CD8 antigen levels also correlated with advanced stages of disease in children with non-Hodgkin's lymphoma or B-cell leukemia. Children with higher serum CD8 antigen levels (greater than or equal to 700 U/mL) had a poorer treatment outcome (P = .003), even after results were adjusted for disease stage and serum lactic dehydrogenase level (P = .05). Measurement of serum levels of CD8 antigen not only has important prognostic value in childhood lymphoid malignancies but also could be useful in assessing the immunoregulatory role of T cells in patients with cancer.


Promoting Pulmonary Arterial Growth via Right Ventricle-to-Pulmonary Artery Connection in Children With Pulmonary Atresia, Ventricular Septal Defect, and Hypoplastic Pulmonary Arteries.
Complete repair of pulmonary atresia (PA) ventricular septal defect (VSD) with hypoplastic or absent native pulmonary arteries, often with major aortopulmonary collateral arteries (MAPCAs), involves construction of an adequate sized pulmonary arterial tree. We report our results with a previously described staged strategy using initial right ventricle (RV)-to-reconstructed pulmonary arterial tree (RV-PA) connection to promote pulmonary arterial growth and facilitate later ventricular septation. We retrospectively reviewed data for all patients (N = 10) with initial echocardiographic diagnosis of PA-VSD and hypoplastic pulmonary arteries operated in our center from October 2008 to August 2016. Pulmonary arterial vessel size measured on preoperative and postoperative angiography was used to calculate Nakata index. Seven patients had PA-VSD, three had virtual PA-VSD, and seven had MAPCAs. All underwent creation of RV-PA connection at a median age of 7.5 days and weight 3.6 kg. Eight patients had RV-PA conduits, two had a transannular patches, and seven had major pulmonary artery reconstruction simultaneously. There were no deaths or serious morbidity; one conduit required revision prior to complete repair. Complete repair with ventricular septation and RV pressure less than half systemic was achieved in all patients at a median age of 239 days. Nakata index in neonatal period was 54 mm2/m2 (range 15-144 mm2/m2) and at time of septation 184 mm2/m2 (range 56-510 mm2/m2; P = .004). Growth rates of right and left branch pulmonary arteries were similar. The 10 patients underwent 28 catheterizations with 13 interventions in 8 patients prior to full repair. Early palliative RV-PA connection promotes pulmonary arterial growth and facilitates eventual full repair with VSD closure with low RV pressure and operative risk.


Characterization of the cyclophilin of Trichophyton mentagrophytes.
A genetic approach to cyclophilins in a dermatophyte, Trichophyton mentagrophytes, was carried out. The nucleotide and deduced amino acid sequences of the cyclophilin of T. mentagrophytes shared about 70% sequence similarity with those of Schizosaccharomyces pombe, Saccharomyces cerevisiae and Candida albicans. However, the first 21 amino acid and the C-terminal amino acid regions of 188 to 226 of the T. mentagrophytes cyclophilin were distinct from those of the other fungal cyclophilins. The recombinant glutathione S-transferase (GST)-T. mentagrophytes cyclophilin fusion protein produced by Escherichia coli was purified. The protease digest of the fusion protein had a molecular weight of about 13 kDa and peptidyl-prolyl cis-trans isomerase (PPI) activity. This digest protein from T. mentagrophytes was confirmed to be cyclophilin by proving PPI activity.


[Assessment of neoplastic pancreatic focal injury by multidetector computed tomography].
pancreatic focal neoplastic lesions (PFNL) should be characterized through image methods to differentiate from no neoplastic lesions, suggesting one or more probable diagnosis, and staging of malignant lesions, in order to help define the estrategy of medial or surgical management. The multidetector computed tomography (MDCT) offers multiple properties and advantages that enable adequate characterization of the PFNL. The objective of this study is to evaluate de usefulness of MDCT in characterizing PFNL. a descriptive, retrospective caseseries study has been conducted. It consisted of reviewing MDCT studies in which PFNL were found, over a period of 4 years 11 months from January 2006 to November 2010. we obtained 54 cases of PFNL which were characterized by MDCT; 75.9% for a specific diagnosis, and were categorized as indeterminate 24.1%, considering more than one possible diagnosis. The most frequent PFNL type was pancreatic ductal adenocarcinoma in 51.9%. Pancreatic cystic neoplasms accounted for 16.7%. MDCT is useful for identifying and characterizing LFNP, this means the possibility of establishing one or more diagnostic possibilities and guide medical management.


Isolation of 4-methylthio-3-butenyl glucosinolate from Raphanus sativus sprouts (kaiware daikon) and its redox properties.
The most promising among glucosinolates (GLs) are those bearing in their aglycon an extra sulfur function, such as glucoraphasatin (4-methylthio-3-butenyl GL; GRH) and glucoraphenin (4-methylsulfinyl-3-butenyl GL; GRE). The GRE/GRH redox couple is typically met among secondary metabolites of Raphanus sativus L. and, whereas GRE prevails in seeds, GRH is the major GL in full-grown roots. During the 10 days of sprouting of R. sativus seeds, the GRE and GRH contents were determined according to the Eurpean Union official method (ISO 9167-1). In comparison to the seeds, the GRE content in sprouts decreased from about 90 to about 12 micromol g(-1) of dry weight (dw), whereas a 25-fold increase--from about 3 to 76 micromol g(-1) of dw--of the GRH content was measured. An efficient pure GRH gram-scale production process from R. sativus (kaiware daikon) sprouts resulted in significant yield improvement of up to 2.2% (dw basis). The reaction of GRH with both H2O2 and ABTS*+ radical cation was investigated. Whereas H2O2 oxidation of GRH readily resulted in complete transformation into GRE, ABTS*+ caused complete decay of the GL. Even though not directly related to its radical scavenging activity, the assessed reducing capacity of GRH suggests that R. sativus sprouts might possess potential for health benefits.


Characterization and location of secretory phospholipase A2 groups IIE, V, and X in the rat brain.
Secretory phospholipases A(2) (sPLA(2)) form a diverse family of enzymes involved in a variety of physiologic and pathologic processes. Common among all sPLA(2) is the ability to cleave the second position of phospholipids, thereby releasing fatty acid and a lysophospholipid. Several sPLA(2) have been cloned and characterized in various tissues and receptors have been identified. In the nervous system, sPLA(2) groups IB, IIA, IIE, IIF, V, and XII have been identified, and binding sites for sPLA(2) have been found. Here, we report sPLA(2)-IIE and sPLA(2)-X in rat brain as well as in neurons in primary culture. We furthermore confirm the presence of sPLA(2)-V in rat brain and demonstrate the presence of sPLA(2)-V in primary neuronal cultures. The distribution of sPLA(2)-IIE, V, and -X seems to be mainly neuronal, with the highest abundance occurring in the cerebral cortex and hippocampus. We also find that sPLA(2)-IIE, -V, and -X are differentially induced by kainic acid. This study supports the concept that sPLA(2) heterogeneity in brain is functionally relevant and responsive to seizures.


Lin28B is a novel prognostic marker in gastric adenocarcinoma.
Lin28B, a homologue of Lin28, represses biogenesis of let-7 microRNAs with a role in tumorigenesis and is considered a potential therapeutic target for various human cancers. The aim of the study was to identify the clinical significance of Lin28B in gastric adenocarcinoma (GAC). We examined the expression of Lin28B in 97 human gastric cancer samples with 32 samples of non-dysplastic tissues by immunohistochemistry. In the 97 GAC cases, 42 were with high Lin28B expression. The expression levels of Lin28B proteins in GAC were higher than in corresponding adjacent normal tissues (P=0.001). Significant correlations were noted between Lin28B expression and lymph node status (P=0.005), TNM stage (P < 0.001), tumor invasion (P=0.036), and differentiation (P=0.001) of GAC patients. The Kaplan-Meier estimates showed a negative correlation of overall 5-year survival rate with Lin28B expression where higher expression resulted in poorer prognosis in GAC. In univariate analysis, lymph node metastasis, TNM stage, serosal invasion, Lin28B expression as well as differentiation grade could predict the prognosis of GAC patients (P=0.002, P < 0.001, P=0.003, P < 0.001, P=0.001, respectively). Multivariate analysis revealed that the expression level of Lin28B (P < 0.001), TNM stage (P < 0.001) as well as differentiation grade (P < 0.001) were the three potential independent prognostic factors in our study [Hazard ratio (HR)=2.108 and P=0.017, HR=1.994 and P=0.018, HR=1.939 and P=0.046, respectively]. Our findings point to the prognostic role of Lin28B in GAC, and indicate Lin28B as a potential therapeutic target of GAC patients.


[Effectiveness analysis established in Russia and hygienic standards for the use of food dyes].
Analysis of the income of diet and frequency of use of food additives--dyes in food production showed that established in Russia hygienic standards provide compliance with acceptable doses of these substances. For the first time in Russia an assessment of dietary intake of several food dyes, possessing biological activity is conducted. The average daily intake by using such substances can reach (as % of physiological needs of the adult population): riboflavin--180%, curcumin--60%, beta-carotene--25%, anthocyanins--10%, canthaxanthin (lutein, lycopene)--5%.


Osmosis and diffusion conceptual assessment.
Biology student mastery regarding the mechanisms of diffusion and osmosis is difficult to achieve. To monitor comprehension of these processes among students at a large public university, we developed and validated an 18-item Osmosis and Diffusion Conceptual Assessment (ODCA). This assessment includes two-tiered items, some adopted or modified from the previously published Diffusion and Osmosis Diagnostic Test (DODT) and some newly developed items. The ODCA, a validated instrument containing fewer items than the DODT and emphasizing different content areas within the realm of osmosis and diffusion, better aligns with our curriculum. Creation of the ODCA involved removal of six DODT item pairs, modification of another six DODT item pairs, and development of three new item pairs addressing basic osmosis and diffusion concepts. Responses to ODCA items testing the same concepts as the DODT were remarkably similar to responses to the DODT collected from students 15 yr earlier, suggesting that student mastery regarding the mechanisms of diffusion and osmosis remains elusive.


A survey of the first complication of newly implanted CSF shunt devices for the treatment of nontumoral hydrocephalus. Cooperative survey of the 1991-1992 Education Committee of the ISPN.
The results of an international multicenter study concerning the first complication of newly implanted cerebrospinal fluid shunts in nontumoral hydrocephalus are the subject of the present report. The authors have collected information on 773 cases from four continents. In particular, the following data were evaluated in relation to the general incidence of complications recorded in the first follow-up year: the patient's age at the operation, the etiology of hydrocephalus, the type of CSF shunt device used, and the modality of the surgical procedures. The overall complication rate in the series was 29%. Age and etiology of hydrocephalus appear to play a major role in influencing the complication rate; on the other hand, the choice of a specific CSF shunt device seems to be less important in this respect.


Staff reactions to the closing of a community mental health center.
Many community mental health centers face seriuos financial problems as they near the end of the federal funding period. The author describes the developments surrounding an extended financial crisis at an inner-city mental health center that eventually was forced to close. Using a crisis theory framework, she examines staff reactions to the crisis and proposes an intervention model in which a consultant is employed to help staff identify and avoid maladaptive coping behavior.


[Management of micro-inflammation in uremia].
Chronic micro-inflammation is commonly observed in patients with chronic renal failure. However, the causes of this micro-inflammation remain mainly indeterminated. Therefore, the appropriate therapeutic management of uremic microinflammation is not yet established. Meanwhile, it appears to be reasonable to use current non-specific anti-inflammatory therapies (e.g. ACEI, statins) in order to reduce uremic micro-inflammation. However, it is clear that such an approach is not sufficient, and further strategies (e.g. vitamin E) are warranted to optimize uremic micro-inflammation prevention.


Toward a definition of masked hypertension and white-coat hypertension among hemodialysis patients.
Among people with essential hypertension, ambulatory BP measurement is superior to BP obtained in the clinic in predicting cardiovascular outcomes. In part, this is because it can detect white-coat hypertension and masked hypertension. Whether the same is true for hemodialysis patients is not known. Using a threshold of 140/80 mmHg for median midweek dialysis-unit BP and 135/85 mmHg for 44-hour ambulatory BP, we defined four categories of BP: sustained normotension (SN), white-coat hypertension (WCH), masked hypertension (MHTN), and sustained hypertension (SHTN). Among 355 long-term hemodialysis patients, the prevalence of SN was 35%, WCH 15%, MHTN 15%, and SHTN 35%. Over a mean follow-up of 29.6 (SD 21.7) months, 102 patients died (29%), yielding a crude mortality rate of 121/1000 patient-years. Unadjusted and multivariate-adjusted analyses showed increasing all-cause mortality with increasing severity of hypertension (unadjusted hazard ratios from SN, WCH, MHTN, SHTN: 1, 1.12, 1.70, 1.80, respectively [P for trend < 0.01]; adjusted hazard ratios: 1, 1.30, 1.36, 1.87, respectively [P for trend 0.02]). When a predialysis BP threshold of 140/90 mmHg was used to classify patients into BP categories, the prevalence of SN was 24%, WCH 26%, MHTN 4%, and SHTN 47%. Hazard ratios for mortality were similar when compared with median midweek dialysis-unit BP. As in the essential hypertension population, MHTN and WCH have prognostic significance. The prognostic value of BP obtained in the dialysis unit can be refined with ambulatory BP monitoring.


Weakened untuned gain control is associated with schizophrenia while atypical orientation-tuned suppression depends on visual acuity.
Perceptual distortions are core features of psychosis. Weakened contrast surround suppression has been proposed as a neural mechanism underlying atypical perceptual experiences. Although previous work has measured suppression by asking participants to report the perceived contrast of a low-contrast target surrounded by a high-contrast surround, it is possible to modulate perceived contrast solely by manipulating the orientation of a matched-contrast center and surround. Removing the bottom-up segmentation cue of contrast difference and isolating orientation-dependent suppression may clarify the neural processes responsible for atypical surround suppression in psychosis. We examined surround suppression across a spectrum of psychotic psychopathology including people with schizophrenia (PSZ; N = 31) and people with bipolar disorder (PBD; N = 29), first-degree biological relatives of these patient groups (PBDrel, PSZrel; N = 28, N = 21, respectively), and healthy controls (N = 29). PSZ exhibited reduced surround suppression across orientations; although group differences were minimal at the condition that produced the strongest suppression. PBD and PSZrel exhibited intermediate suppression, whereas PBDrel performed most similarly to controls. Intriguingly, group differences in orientation-dependent surround suppression magnitude were moderated by visual acuity. A simulation in which visual acuity and/or focal attention interact with untuned gain control reproduces the observed pattern of results, including the lack of group differences when orientation of center and surround are the same. Our findings further elucidate perceptual mechanisms of impaired center-surround processing in psychosis and provide insights into the effects of visual acuity on orientation-dependent suppression in PSZ.


EyePACS: an adaptable telemedicine system for diabetic retinopathy screening.
Annual retinal screening of patients with diabetes is the standard clinical practice to prevent visual impairment and blindness from diabetic retinopathy. Telemedicine-based diabetic retinopathy screening (DRS) in primary care settings can effectively detect sight-threatening retinopathy and significantly increase compliance with annual retinal exams. EyePACS is a license-free Web-based DRS system designed to simplify the process of image capture, transmission, and review. The system provides a flexible platform for collaboration among clinicians about diabetic retinopathy. Primary clinic personnel (i.e., nursing, technical, or administrative staff) are trained and certified by the EyePACS program to acquire retinal images from standard digital retinal cameras. Relevant clinical data and eight high-resolution images per patient (two external and six retinal images) are encrypted and transmitted to a secure Internet server, using a standard computer and Web browser. Images are then interpreted by certified EyePACS reviewers or local eye care providers who are certified through the EyePACS Retinopathy Grading System. Reports indicating retinopathy level and referral recommendations are transmitted back to primary care providers through the EyePACS Web site or through interfaces between EyePACS and Health Level 7-compliant electronic medical records or chronic disease registries. The pilot phase of the EyePACS DRS program in California (2005-2006) recorded 3562 encounters. Since 2006, EyePACS has been expanded to over 120 primary care sites throughout California and elsewhere recording over 34,000 DRSs. The overall rate of referral is 8.21% for sight-threatening retinopathy and 7.83% for other conditions (e.g., cataract and glaucoma). The use of license-free Web-based software, standard interfaces, and flexible protocols has allowed primary care providers to adopt retinopathy screening with minimal effort and resources.


Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus.
Susceptibility to systemic lupus erythematosus is associated with major histocompatibility complex (MHC)--encoded genes. We have used nucleotide sequence analysis to better define the disease-associated MHC alleles. HLA-DR2, DQw1, and especially the rare allele DQ beta 1. AZH confer high relative risk (RR = 14) for lupus nephritis in a Caucasian population of patients. Pilot studies using historical controls suggest that these genes also confer a high risk in non-Caucasian ethnic groups (RR = 24-78). We have found that DR4 is significantly decreased in patients with lupus nephritis. Fifty percent of the patients with lupus nephritis had either the DQ beta 1.1, the DQ beta 1.AZH, or the DQ beta 1.9 alleles. These alleles share amino acid residues that have been predicted to be the contact points for antigen and the T cell receptor. These HLA alleles appear to have a direct role in the predisposition to lupus nephritis, whereas DR4 may have a "protective" effect.


[Vitamin D3 poisoning and irreversible sequela].
Twenty-four children with vitamin D intoxication and a follow-up of one to thirteen years old (means: four years and seven months) are reviewed. Over-dosage was prescribed by medical order in 66.6% of patients and by the mother herself in 16.6%. Intensity of clinical symptoms (renal, neurologic, digestive) were related with daily dose administered whilst final secuelae depends on duration of overdosage. Hipercalcemia was easily corrected by association of low calcium diet, corticoesteroids and/or furosemide in least than a month in 81% of cases. Two patients died during the acute fase and 22.7% remain with permanent damage (five in chronic renal failure, one in haemodialysis and three with low IC).


Phototransformation of propiconazole in aqueous media.
The photolysis of propiconazole in pure water, in water containing humic substances, and in natural water was investigated. The reaction rates were determined, and the main photoproducts were identified with the help of HPLC-mass spectrometry and by NMR. The quantum yield for direct photolysis was 0.11 +/- 0.01 at the maximum of absorption (269 nm). Photocyclization after HCl elimination and photohydrolysis of the cyclized intermediate were the main reaction pathways at 254 nm. By contrast, oxidation prevailed over dechlorination in simulated or natural solar light. Humic substances (10 mg x L(-)(1)) and naturally occurring chromophores contained in natural water enhanced the rate of propiconazole photodegradation in solar light. Half-life in June in Clermont-Ferrand (latitude 46 degrees N) was found to be 85 +/- 10 h in pure water and 60 +/- 10 h in natural water; showing that photodegradation of propiconazole in natural waters involves both direct photolysis and photoinduced reactions.


New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma.
Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma. A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis. Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed. A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.


Regulation of renal tubular bile acid transport in the early phase of an obstructive cholestasis in the rat.
In obstructive liver diseases, urinary excretion of bile acids is markedly enhanced. The mechanism of this effect is not entirely clear. The aim of the present study was to assess the glomerular and tubular factors involved in the renal handling of bile acids during the early phase of an obstructive cholestasis induced by a 24-hour bile duct ligation in rats. In addition to conventional clearance experiments, taurocholate transport was studied on proximal tubular cells freshly isolated from rat kidneys. The expression of the taurocholate transport protein was determined in these cells by immunoblotting. Glomerular filtration rate and arterial blood pressure were not significantly affected by the cholestasis induced. The (3)H-taurocholate and (3)H-cholate clearances significantly increased whereas the fractional tubular reabsorption rates of these bile acids significantly fell. Probenecid did not affect the (3)H-taurocholate and (3)H-cholate clearances. By employing S0960, a specific inhibitor of the sodium-dependent bile salt transporter ASBT, it could be shown that this transporter mediates (3)H-taurocholate uptake into the proximal tubular cells. The bile duct ligation caused a significant decrease of the V(max) value of the taurocholate transporter indicating a downregulation of this transporter in cholestasis. The downregulation occurred without a change of the ASBT protein content of the proximal tubular cells. The results demonstrate that there is a functional adaptive downregulation of renal tubular bile acid transport enhancing renal clearance of bile acids during the early phase of an obstructive cholestasis.


Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease.
Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month-old APP(SweLon)/PS1(M146L), a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared with age-matched control mice. We then developed a method of 3-D microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganization of glucose uptake in relation to cerebral amyloidosis.


Community health center integration: experience in the State of Ohio.
In the face of severe financial challenges and demands to improve quality and service to patients, many community health centers (CHCs) have aligned or integrated with other CHCs, physician groups, or hospitals. Yet the nature of and rationale for these organizational decisions are not well understood. Our research applied an organizational theoretical framework to test whether strategic adaptation theory or institutional theory best describes the integration activity of CHCs in Ohio. We collected primary data from case studies of seven CHCs selected for geographic representation and studied December 2000-January 2001. Semi-structured interviews and a case study database supported our chain of evidence. We found that CHC integration activity was substantial (five of seven CHCs integrated) and extremely varied. Consistent with strategic adaptation theory, we determined that CHC integration actions were predominantly center-specific, rational responses to environmental challenges and were initiated to improve operations or financial performance. Rarely did CHCs initiate major organizational change merely to mimic other CHC actions, as might have been expected of highly institutionalized organizations. Understanding the basis for CHCs' strategic decisions while monitoring financial health will remain critical as lawmakers and administrators work to develop policies that both maintain progress made and improve primary care access for the poor, the uninsured, and those with special health care needs served by these important safety net providers.


[Family dysfunction in adolescents with suicidal behavior and in adolescents with conduct disorders].
The period of life known as adolescence generally refers to transition from childhood to adulthood. Adolescents' progress toward autonomy involves remaining connected with, as well as separated from parents. Young people and their parents usually have mixed feelings about adolescent autonomy and attachment. An estimated 50% of children born in the 80-s have spent part of their developmental years in single-parent households. Divorce is almost always a stressful event in children's lives. Youthful suicide rate has increased dramatically and is the third leading cause of death among 15-19 year olds. Conduct disorder is one of the mostfrequently diagnosed conditions in adolescents. Suicidal adolescents and adolescents with conduct disorder are much more likely than their peers to have grown up in disrupted, disorganized homes with lack of attachment between parents and their children. This prospective study was carried out during 2002, 2003, and 2004. The research included 60 adolescents treated at the Center for Child and Adolescent Psychiatry in Novi Sad, 30 with diagnosed conduct disorder and 30 with suicidal behavior. Along with other kinds of distress, suicidal adolescents have experienced an escalation of family problems a few months prior to attempted suicide. Divorce and life in singe-parent households is almost always a stressful period in children's lives. Conduct disorder and suicidal behavior represent a desperate cryfor help. Conclusion Most adolescents in both groups live in single-parent households. These young people have frequently passed into adolescence with little reason to feel that they could rely on their parentsfor support, or on their home as a place of sanctuary.


Cross-hybridization between HPV genotypes in the Linear Array Genotyping Test confirmed by Next-Generation Sequencing.
Linear Array Genotyping Test (LA) is one of the gold standards used for Human Papillomavirus (HPV) genotyping, however, since its launching in 2006, new HPV genotypes are still being characterized with the use of high specificity techniques such as Next-Generation Sequencing (NGS). Derived from a previous study of the IMSS Research Network on HPV, which suggested that there might be cross-reaction of some HPV genotypes in the LA test, the aim of this study was to elucidate this point. Double stranded L1 fragments (gBlocks) from different HPVs were used to perform LA test, additionally, 14 HPV83+ and 26 HPV84+ cervical samples determined with LA, were individually genotyped by NGS. From the LA HPV83+ samples, 64.3% were truly HPV83+, while 42.9% were found to be HPV102+. On the other hand, 69.2% of the LA HPV84+ samples were HPV84+, while 3.8, 11.5 and 30.8% of the samples were indeed HPV 86, 87 and 114 positive, respectively. Additionally, novel nucleotide changes in L1 gene from HPV genotypes 83, 84, 87, 102 and 114 were determined in Mexican cervical samples, some of them lead to changes in the protein sequence. We demonstrated that there is cross-hybridization between alpha3-HPV genotypes 86, 87 and 114 with HPV84 probe in LA strips and between HPV102 with HPV83 probe; this may be causing over or under estimation in the prevalence of these genotypes. In the upcoming years, a switch to more specific and sensitive genotyping methods that detect a broader spectrum of HPV genotypes needs to be implemented.


Non-specific X-linked mental retardation: background, types, diagnosis and prevalence.
This paper reviews non-specific X-linked mental retardation (X-linked MR), a heterogeneous group of X-linked recessive disorders which are controlled by one or more genes located on the X chromosome. Presently, there are at least three major subdivisions of X-linked MR. The IQ of affected males is variable. Carrier females usually have normal intelligence but some do show partial expression resulting in retardation. Genetics units can diagnose affected males utilizing pedigree analysis, clinical evaluation and cytogenetic testing (fragile X-linked MR type only). Projections indicate X-linked MR may be as common in males as Down syndrome and could account for 25% of the retarded male population.


Hierarchical assembly of extended coordination networks constructed by novel metallacalix[4]arenes building blocks.
Five interesting metal-organic nanostructures and networks, [Ni(4)(HL)(4)(bpy)(py)(H(2)O)(5)](2) x 0.5 H(2)O (1), [Co(4)(HL)(4)(bpy)(py)(H(2)O)(5)](2) x 0.5 H(2)O (2), [Ni(4)(HL)(4)(H(2)O)(7)](n) x nH(2)O (3), [Ni(4)(HL)(4)(bpy)(2)(H(2)O)(4)](n) (4), and [Cd(4)(HL)(4)(H(2)O)](n) (5), were synthesized hydrothermally [H(3)L = 2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylate acid, py = pyridine, and bpy = 4,4'-bipyridine]. Intriguingly, all compounds consist of novel metallacalix[4]arene building blocks M(4)(HL)(4), where doubly deprotonated HL in the same bichelating fashion of mu-kN,N':kO,N'' displays a strong coordination orientation by cooperation of the 4,5-imidazoledicarboxylate and 2-pyridyl groups. Very interestingly, the symmetry of M(4)(HL)(4) and the linkage styles between metal nodes and HL in M(4)(HL)(4) are sensitive to the reaction conditions, and the resulting structural motifs vary with secondary ligands and metal nodes. In 1 and 2, two C(1)-symmetric M(4)(HL)(4) units are bpy-bridged into dimeric chiral nanomolecules with two different cavities. As deprotonated with NaOH, the combination of Ni(II) and HL forms a pseudo-S(4)- or S(4)-symmetric M(4)(HL)(4), which further assembles into 1D chiral crystals 3 or rare 3D crystals 4 of bpy-bridged 5-fold interpenetrating diamondoid architecture with metallacalix[4]arene building blocks as novel 4-connecting nodes, and the combination of Cd(II) and HL forms an 8-connected C(2)-symmetric M(4)(HL)(4) that fabricates the alpha-Po net of 5. Notably, those large M(4)(HL)(4) units are potentially highly connected building blocks in a hierarchical assembly of metal-organic networks. Magnetic studies disclose antiferromagnetic interactions in M(4)(HL)(4) of 1-4. The magnetic data for 1, 3, and 4, all containing isomeric Ni(4)(HL)(4) units, are analyzed by an equilateral quadrangle isotropic model combined with the molecular-field approximation with J = -4.00(2), -3.39(2), and -2.72(3) cm(-1), respectively, presenting a stronger comparison between the structure and magnetism. The emission of 5 is odd, which perhaps is relative to the bichelating fashion of ligand HL and a rare coordination geometry of Cd(II). Moreover, the thermal stability and gas sorption properties of these compounds were measured.


Enhancement of metastatic and invasive capacity of gastric cancer cells by transforming growth factor-beta1.
Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, exerts contradictory roles in different kinds of cells. A number of studies have revealed its involvement in the progression of many types of tumors. To investigate the effect of TGF-beta on gastric carcinoma, SGC7901, BGC823 and MKN28 (a TGF-beta-resistant cell line) adenocarcinoma clones were used. After pretreatment in serum-free medium with or without 10 ng/ml TGF-beta1, their experimental metastatic potential, chemotaxis, and invasive and adhesive ability were measured. Furthermore, zymography for gelatinase was processed. Liver colonies were also measured 4 weeks after inoculation of SGC7901, BGC823 and MKN28 in Balb/c nude mice, and an increase in the number of surface liver metastases was seen in SGC7901 (from 11.0+/-3.0 to 53.3+/-3.3) and BGC823 (from 9.3+/-2.5 to 60.0+/-2.8) groups, whereas there was no difference between MKN28 groups (from 35.2+/-3.8 to 38.5+/-2.7). In vitro experiments showed that TGF-beta1 increased the adhesion capacity of SGC7901 and BGC823 cells to immobilized reconstituted basement membrane/fibronectin matrices and promoted their penetration through reconstituted basement membrane barriers. Zymography demonstrated that enhanced invasive potential was partly due to the increased type IV collagenolytic (gelatinolytic) activity, but there was no difference in type IV collagenolytic activity and other biological behaviors between MKN28 groups. These results suggested that TGF-beta1 might modulate the metastatic potential of gastric cancer cells by promoting their ability to break down and penetrate basement membrane barriers and their adhesive and motile activities. We speculated that TGF-beta1 might act as a progression-enhancing factor in gastric cancer. Therefore blockage of TGF-beta or TGF-beta signaling might prevent gastric cancer cells from invading and metastasizing.


Ecological analysis of the association between mortality and major risk factors of cardiovascular disease. The World Health Organization MONICA Project.
The WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project has been established to measure trends in cardiovascular mortality and coronary heart disease and cerebrovascular disease morbidity and to assess the extent to which these trends are related to changes in known risk factors at the same time in defined communities in different countries. This cross-sectional study is based on data from the early part of the Project and assesses the association between mortality and population risk factor levels. Thirty-five populations of men and women aged 35-64 years are used in correlation analyses between four mortality measures (deaths from all causes, cardiovascular diseases, ischaemic heart disease and stroke) and three cardiovascular risk factors (regular cigarette smoking, blood pressure and total cholesterol). In male populations all-causes mortality and stroke mortality had more than 39% of their variance explained by the three risk factors but all cardiovascular and ischaemic heart disease mortality had less than 25% of their variance explained. For female populations each mortality measure except ischaemic heart disease mortality had more than 33% of their variances accounted for by the three risk factors. For both the male and female populations each of the mortality measures shows strong associations with high blood pressure but the associations with smoking and high cholesterol are generally weaker and much less consistent. This analysis has shown that accepted cardiovascular mortality risk factors measured cross-sectionally at the population level do not reflect well the variation in mortality between populations.


Quality of cowpea seeds: A food security strategy in the tropical environment.
What is the relation between seed quality and food security? Here we built a summary diagram that links the development stages of the seeds with their potential of providing grain yield. This idea was tested using cowpea as a model crop, grown in a tropical environment. Initially, seed quality attributes such as water content, dry weight, germination, vigor, and longevity were characterized during seed development. With this, we were able to elucidate at which point the late maturation phase and the acquisition of seed with superior physiological quality starts. From these data, the proposed summary diagram highlighted the seed quality as a technological basis for generating a more productive plant community. It also showed that only seeds with a high-quality profile have a better chance to establishment in an increasingly challenging agricultural environment. Overall, we bring the concept that cowpea seeds with superior quality besides being the essential input for tropical agriculture is also a strategy that can contribute food security.


Comparison of a commercial and an in-house T cell-based assay for the diagnosis of Mycobacterium tuberculosis infection.
Identification of individuals with a tuberculosis infection is a very important element for the control of tuberculosis. The currently used tuberculin skin test has poor sensitivity and specificity. Recently, an important advance in tuberculosis diagnosis occurred with the development of in vitro T cell-based IFN-gamma release assays. The aim of this study was to compare a RD1-based in-house ELISPOT-IFN-gamma assay with a commercial (T-SPOT.TB) assay for the diagnosis of tuberculosis infection. The results showed an almost complete concordance between the two assays, confirming that our restricted but highly selected pool of peptides is sufficient to detect tuberculosis infection.


Psychiatric problems during the COVID-19 pandemic in children with autism spectrum disorder.
Children with autism spectrum disorder (ASD) are at elevated risk for psychiatric problems in response to the COVID-19 pandemic. This risk is due to their high rates of pre-pandemic psychiatric comorbidities and the pandemic's disruption to routines and access to necessary supports. Prior research has indicated that children with ASD may experience a worsening of specific psychiatric symptoms in response to COVID-19, though this body of work is limited in scope. The present study expands this literature by examining specific types of psychiatric problems that emerged about 2 months after the onset of the pandemic, and risk factors predicting changes in these psychiatric symptoms. Parents of children with a confirmed ASD diagnosis (N = 257), who enrolled in a clinic registry at an outpatient specialty autism center, were included in this study. All data were gathered online via customized and standardized questionnaires. Results showed that 59% of children experienced either a worsening of their pre-pandemic psychiatric diagnoses and/or the development of new psychiatric symptoms during the pandemic. Multivariable regression models indicated that risk factors for increased psychiatric problems included child understanding of COVID-19, COVID-19 illness in the family, low family income, and elevated parental depression and anxiety symptoms (all p < 0.05). Findings from this study emphasize the urgent need to provide effective and accessible psychiatric services for children with ASD and their families during and after the pandemic. LAY SUMMARY: Children with ASD are at high risk for psychiatric problems during the COVID-19 pandemic. We found that 59% of children in our clinical sample are experiencing increased psychiatric problems. The child's understanding of COVID-19, COVID-19 illness in the family, low family income, and depression and anxiety symptoms in the parent increase the risk for poor mental health during the pandemic. These findings indicate the importance of helping children with ASD access mental health treatment during COVID-19.


Physiological status of broiler chicks at pulling time and the relationship to duration of holding period.
Newly hatched chicks may be held longer than 48 h and experience long periods of fasting in commercial hatcheries. Limited information is known about the physiological status of chicks in such situations, due to the difficulty of precisely recording time of hatch. This study investigated the effect of the time from hatch to pulling (holding period) on physiological measures/parameters in 109 broiler chicks. Fertile Ross 308 eggs were incubated in a custom built small-scale incubator. The individual hatching time of each focal chick was determined using eggshell temperature monitoring. At 'pulling' (512 h of incubation time), the quality of focal chicks was assessed using the chick scoring method and physiological parameters were measured including BW, organ (heart, liver and stomach) weights, blood values and plasma corticosterone level. The time from hatch to pulling varied from 7.58 to 44.97 h. Egg weight at setting was significantly correlated with chick BW and weight of organs at pulling, but had no effect on chick quality, blood values and plasma corticosterone. Relative BW at pulling was negatively associated with the duration of holding period (P=0.002). However, there was a positive correlation between relative stomach weight and the duration of the holding period (P<0.001). As the holding period duration increased, there was a trend that blood partial pressure of oxygen, haematocrit and haemoglobin also increased, and blood partial pressure of carbon dioxide, total carbon dioxide and bicarbonate decreased (P<0.05). A wide range of plasma corticosterone was observed from chicks that had experienced different durations of holding period. We conclude that shortening the hatch window and minimising the number of chicks that experience a long holding period before pulling may improve chick quality and physiological status, which may be due to unfavourable environmental conditions that include feed and water deprivation.


Impact of thymol in thyme extracts on their antispasmodic action and ciliary clearance.
Thyme is a herb with broncholytic und secretomotoric effects. Its activity on beta (2) receptors as a possible mechanism of action was demonstrated. Major components are thymol and carvacrol which are claimed to be responsible for its effects and, therefore, used for standardization in the German pharmacopoeia (0.03 % phenols calculated as thymol). Our aim was to investigate the impact of thymol by using thyme extracts with either normal or extremely low thymol concentrations (< 0.005 % or > 0.038 %). The antispasmodic effect on smooth muscles of the trachea and the ileum and the effect on ciliary activity (respiratory clearance) were investigated. In addition, pure thymol and carvacrol were investigated separately and in spiking experiments. Thymol and carvacrol had a concentration-dependent antispasmodic effect in the rat trachea either being stimulated by acetylcholine, K (+) or Ba (++). The same result was observed with respect to the increase of mucociliary transport in mice. Extracts with very low thymol contents are effective in all models used except acetylcholine-induced rat ileum contraction. When thyme extracts with normal thymol contents or with very low thymol contents were compared, the extract with normal thymol contents was more effective, both as a relaxant (rat ileum) and as an antispasmodic compound (rat trachea contraction induced by either acetylcholine, Ba (++) or K (+)) and in ciliary transport experiments. Thyme extracts with very low thymol contents (practically free of volatile oil) were equally effective with respect to endothelin effects. When an extract with very low thymol contents is spiked with increasing concentrations of thymol, a concentration-dependent increase concerning the antispasmodic effect (Ba (++)-induced trachea contraction) is observed. In conclusion, the data show that in various models of antispasmodic effect (ileum and trachea) and by measuring ciliary activity, thymol (and carvacrol) is (are) active, although other not identified components of thyme extract appear to be very important as well, since extracts with very low thymol contents are active. On the basis of these results the standardization on thymol alone appears not to be justified.


Controlling factors in the synthesis of cucurbituril and its homologues.
The acid-catalyzed synthesis of cucurbit[n]urils from formaldehyde and glycoluril is poorly understood. In this paper, we examine a wide range of reaction conditions that include the effects of acid type, acid concentration, reactant concentrations, and temperature to both probe the mechanism and optimize the yields of isolated cucurbit[n]urils, where n = 5-10. A mechanism for the formation of these cucurbit[n]urils is presented. Individual cucurbit[n]urils were unambiguously identified in reaction mixtures using ESMS and (13)C NMR.


Synergism between different germinant receptors in the germination of Bacillus subtilis spores.
Rates of commitment to germinate and germination of Bacillus subtilis spores with mixtures of low concentrations of germinants acting on different germinant receptors (GRs) were much higher than the sums of the rates of commitment and germination with individual germinants alone. This synergism with mixtures of nutrient germinants was not seen with spores lacking GRs responsible for recognizing one or several components of the germinant mixtures and was not eliminated by either a gerD mutation or overexpression of one of the GRs involved in this synergism. This synergism was also not seen between the germinant L-valine, which acts via a GR, and the germinant dodecylamine, which does not act via any GR. These results indicate that spores not only integrate but can also amplify signals from multiple germinants and multiple GRs in determining rates of commitment and overall spore germination. This amplification can be explained by a simple mechanism in which a single signal integrator triggers germination above an accumulation threshold. Direct cooperative action between GRs may further add to the synergism seen in germination triggered by multiple GRs. Further experiments and modeling are required to determine the relative contributions of these different mechanisms.


Molecular insights into cardiomyopathies associated with desmin (DES) mutations.
Increasing usage of next-generation sequencing techniques pushed during the last decade cardiogenetic diagnostics leading to the identification of a huge number of genetic variants in about 170 genes associated with cardiomyopathies, channelopathies, or syndromes with cardiac involvement. Because of the biochemical and cellular complexity, it is challenging to understand the clinical meaning or even the relevant pathomechanisms of the majority of genetic sequence variants. However, detailed knowledge about the associated molecular pathomechanism is essential for the development of efficient therapeutic strategies in future and genetic counseling. Mutations in DES, encoding the muscle-specific intermediate filament protein desmin, have been identified in different kinds of cardiac and skeletal myopathies. Here, we review the functions of desmin in health and disease with a focus on cardiomyopathies. In addition, we will summarize the genetic and clinical literature about DES mutations and will explain relevant cell and animal models. Moreover, we discuss upcoming perspectives and consequences of novel experimental approaches like genome editing technology, which might open a novel research field contributing to the development of efficient and mutation-specific treatment options.


Nutritional adaptation of women in contrasting agricultural environments in Tari, Papua New Guinea.
The energy expenditure, food consumption and anthropometry of two groups of Hull women are described. The group occupying the highly productive drained margins of the Haeapugua Swamp at Weinani have significantly higher intakes of energy and protein than those at Heli on the Paijaka Plateau. However, both groups of women expend similar amounts of time and energy in agricultural activities. The differences are explained by the contrasting quality of agricultural land at each place. Production per hectare at Heli is only around half of that at Weinani. It is concluded that the nutritional health of Heli women is compromised. This is probably the cause of the significantly lower mean birthweights of children born to women living on the Paijaka Plateau.


Extinction learning before trauma and subsequent posttraumatic stress.
Fear conditioning theories propose that persistent stress reactions may occur as a result of impaired extinction learning, and a poor capacity for extinction learning may predispose some individuals to posttraumatic stress disorder development. This study indexed the extent to which deficits in extinction learning before trauma exposure are a risk factor for persistent posttraumatic stress after trauma exposure. Eighty-four firefighters were assessed during cadet training (before trauma) and 70 were reassessed within 24 months of commencing active firefighting duties (after trauma). Measures of posttraumatic stress were used before and after trauma exposure. In addition, skin conductance and corrugator electromyogram (EMG) responses were obtained during fear conditioning and extinction paradigms before trauma exposure. Reduced extinction of an aversively conditioned corrugator EMG response pretrauma predicted 31% of the variance in posttraumatic stress severity. This result provides preliminary support for reduced extinction of a conditioned emotional response as a vulnerability factor for posttraumatic stress.


Lift-(gasless) laparoscopic surgery under regional anesthesia.
The objective of this Chapter was to investigate the feasibility and outcome of gasless laparoscopy under regional anesthesia. A prospective evaluation of Lift-(gasless) laparoscopic procedures under regional anesthesia (Canadian Task Force classification II-1) was done at three endoscopic gynecology centers (franchise system of EndGyn(r)). Sixty-three patients with gynecological diseases comprised the cohort. All patients underwent Lift-laparoscopic surgery under regional anesthesia: 10 patients for diagnostic purposes, 17 for surgery of ovarian tumors, 14 to remove fibroids, and 22 for hysterectomies. All patients were operated without conversion to general anesthesia and without perioperative or anesthesiologic complications. Lift-laparoscopy under regional anesthesia can be recommended to all patients who desire laparoscopic intervention without general anesthesia. For elderly patients, those with cardiopulmonary risks, during pregnancy, or with contraindications for general anesthesia, Lift-laparoscopy under regional anesthesia should be the procedure of choice.


COVID-19 and Sepsis in an Atypical Case of Mixed Connective Tissue Disorder Presenting With a Myasthenic Crisis.
Myasthenia gravis (MG) is an autoimmune illness that causes neuromuscular junctions to be damaged by anti-acetylcholine receptor antibodies. It is a very rare condition that is more common among women. Fatigable fluctuating diplopia or ptosis is the characteristic early appearance of this condition. Dysphagia or dysphonia may be present in rare cases. This illness can affect any group of skeletal muscles, including those in the neck and upper limbs. It can also affect the muscles that help you breathe, which can lead to breathing failure. We present a case of a 20-year-old female diagnosed with mixed connective tissue disease presenting with acute respiratory failure as the initial presentation of MG. Clinicians have to have a high index of suspicion for myasthenia when patients arrive with fatigable muscle weakness. This will cut down on the amount of money spent on investigations and the risk of morbidity.


Imperforate hymen: report of an unusual familial occurrence.
Imperforate hymen is an uncommon obstructive anomaly of the female reproductive tract, which usually presents with intermittent and cyclical abdominal pain. Although it is usually sporadic, four cases of familial occurrence of imperforate hymen have been reported so far. Imperforate hymen is seldom associated with complications if it is detected early. In view of the possible familial occurrence, it is important to have a high index of suspicion in women who present with imperforate hymen. A detailed menstrual history of other female family members is necessary to enable early detection.


Arterialized venous flaps for reconstructing soft-tissue defects of the extremities.
Four cases of soft-tissue defects of the extremities are presented. Each defect was covered by a fasciocutaneous venous free flap in which arterial inflow relied solely on the venous pedicle. India ink injection of the saphenous vein in eight cadaver lower extremities revealed that only the subdermal venous plexus supplies the cutaneous island. Clinically, flaps ranged in size from 4 x 6 cm to 5 x 9 cm. Three flaps survived completely, while one flap lost the cutaneous portion of its skin island. However, the subcutaneous tissue survived. Although free venous fasciocutaneous flaps have a more tenuous blood supply in the immediate postoperative period, this flap can be transferred successfully without the sacrifice of a donor artery.


Brain SPECT analysis by 3D-SSP and clinical features of Parkinson's disease.
The aim of the present study is to investigate the association of symptoms in Parkinson's disease (PD) with cerebral perfusion on single photon emission computed tomography (SPECT). The clinical features of PD were compared with SPECT images of the brain obtained by three-dimensional stereotactic surface projection (3D-SSP) analysis. Thirty-eight patients who had PD without dementia (17 men and 21 women with a mean age of 68.6 +/- 4.7 years) were enrolled in this study. Their symptoms were rated using the unified Parkinson's disease rating scale (UPDRS). Within a week, all patients were examined by SPECT with 1-123, and reconstructed images were analyzed with 3D-SSP using an image-analysis software, iSSP ver. 3.5. Data on brain surface perfusion extracted by 3D-SSP analysis were compared between the PD patients and the normal control group. The same comparisons were made for subgroups of PD patients with severe symptoms, such as tremor, gait disturbance, bradykinesia, and the UPDRS motor score. Cerebral perfusion was decreased at the anterior cingulate cortex and occipital lobe of the PD patients compared with the normal controls. In the subgroups with severe gait disturbance and severe bradykinesia, additional hypoperfusion was seen at the lateral frontal association and lateral temporal association and the medial frontal gyrus, and by the pixel-by-pixel comparison, perfusion was significantly decreased (p < 0.05) at the medial frontal gyrus and anterior cingulate cortex compared with the normal control group. In PD patients, severe gait disturbance and bradykinesia may be correlated with hypoperfusion of the medial aspect of the frontal lobe. This suggests that functional disturbance of the supplementary motor area and other parts of the frontal lobe are involved in the development of gait disturbance and bradykinesia in PD.


T cell-specific inhibition of multiple apoptotic pathways blocks negative selection and causes autoimmunity.
T cell self-tolerance is thought to involve peripheral tolerance and negative selection, involving apoptosis of autoreactive thymocytes. However, evidence supporting an essential role for negative selection is limited. Loss of Bim, a Bcl-2 BH3-only protein essential for thymocyte apoptosis, rarely results in autoimmunity on the C57BL/6 background. Mice with T cell-specific over-expression of Bcl-2, that blocks multiple BH3-only proteins, are also largely normal. The nuclear receptor Nur77, also implicated in negative selection, might function redundantly to promote apoptosis by associating with Bcl-2 and exposing its potentially pro-apoptotic BH3 domain. Here, we report that T cell-specific expression of a Bcl2 BH3 mutant transgene results in enhanced rescue of thymocytes from negative selection. Concomitantly, Treg development is increased. However, aged BH3 mutant mice progressively accumulate activated, autoreactive T cells, culminating in development of multi-organ autoimmunity and lethality. These data provide strong evidence that negative selection is crucial for establishing T cell tolerance.


From a Low-Cost Air Quality Sensor Network to Decision Support Services: Steps towards Data Calibration and Service Development.
Air pollution is a widespread problem due to its impact on both humans and the environment. Providing decision makers with artificial intelligence based solutions requires to monitor the ambient air quality accurately and in a timely manner, as AI models highly depend on the underlying data used to justify the predictions. Unfortunately, in urban contexts, the hyper-locality of air quality, varying from street to street, makes it difficult to monitor using high-end sensors, as the cost of the amount of sensors needed for such local measurements is too high. In addition, development of pollution dispersion models is challenging. The deployment of a low-cost sensor network allows a more dense cover of a region but at the cost of noisier sensing. This paper describes the development and deployment of a low-cost sensor network, discussing its challenges and applications, and is highly motivated by talks with the local municipality and the exploration of new technologies to improve air quality related services. However, before using data from these sources, calibration procedures are needed to ensure that the quality of the data is at a good level. We describe our steps towards developing calibration models and how they benefit the applications identified as important in the talks with the municipality.


Evaluation of a Pharmacist-Driven Aldosterone Antagonist Stewardship Program in Patients With Heart Failure.
To evaluate the impact of a pharmacist-driven initiative to optimize aldosterone antagonist use in patients with heart failure with reduced ejection fraction (HFrEF) at a large community hospital. This single-center, retrospective cohort study compared patients with heart failure before and after the implementation of the initiative. Data for pre- and postinitiative patients were retrospectively collected to assess patient characteristics and aldosterone antagonist use. The primary outcome was a composite of eligible patients with heart failure discharged on aldosterone antagonist therapy or with a documented reason for ineligibility before and after commencement of pharmacist-driven aldosterone antagonist initiative. The preinitiative cohort included 96 patients and the postinitiative cohort contained 92 patients. When the 3 month pre- and postinitiative groups were assessed, the primary outcome was noted in 60 (63%) of 96 patients in the preinitiative group and 87 (95%) of 92 patients in the postinitiative group ( P < .0001). In patients with HFrEF, a pharmacist-driven aldosterone antagonist optimization initiative significantly increased appropriate prescribing and documentation for aldosterone antagonist therapy.


The Understanding of Medical Informatics among Dental and Medical Students.
Current medical care deeply relies on informatics during all stages of patient care, which is significantly enhanced due to its use. The healthcare professional's formation in medical informatics results crucial for their everyday practice. However, healthcare study programs not always provide education about the use of this wide variety of systems, and young professionals find that they need to learn about it over the experience. The aim of this study was to assess the understanding of medical and dental students regarding medical informatics and ICTs. A questionnaire was produced with 3 sections and a total of 24 questions. Students replied to the survey before and after taking the medical informatics course. A total of 719 students from second year of medical and dental school were recruited for the study between the period of September of 2017-May 2018, September 2018-May 2019, September 2019-May 2020, and September 2020-May 2021. Medical and dental students showed a good level of understanding regarding medical informatics, as well as a good perception of the relevance of ICT learning for the professional practice. Course attendance increased the percentage of students that felt confident of their knowledge about medical informatics. However, most students felt that little or no medical informatics education was lectured at their schools and that the University should adapt the academic program to include it. After taking the course, the student's perception on this matter was improved. Medical and dental students find medical informatics learning useful for their future professional practice and feel inclined to use it. However, they feel that Universities need to adapt their programs in order to include medical education courses and trainings; partly because they are not completely aware of the use of ICTs that already are established in their courses.