Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy.
Pharmacogenetics aims to elucidate how genetic variation affects the efficacy and side effects of drugs, with the ultimate goal of personalizing medicine. Clinical studies of the genetic variation in the uridine 5'-diphosphoglucuronosyltransferase gene have demonstrated how reduced-function allele variants can predict the risk of severe toxicity and help identify cancer patients who could benefit from reduced-dose schedules or alternative chemotherapy. Candidate polymorphisms have also been identified in vitro, although the functional consequences of these variants still need to be tested in the clinical setting. Future approaches in uridine 5'-diphosphoglucuronosyltransferase pharmacogenetics include genetic testing prior to drug treatment, genotype-directed dose-escalation studies, study of genetic variation at the haplotype level and genome-wide studies.


Risk analysis of herbicide quinclorac residues in irrigated rice areas, Santa Catarina, Brazil.
Deterministic and probabilistic risk analyses were carried out for seven hydrographic basins in the State of Santa Catarina (Brazil), where irrigated rice is cultivated. Monitoring studies conducted in 1998/1999 and 1999/2000 had found that the herbicide quinclorac was the most frequently detected agrochemical residue, occurring in five of the seven hydrographic basins. In order to assess the ecological risk posed by quinclorac, median lethal concentration (LC(50)) and median effective concentration (EC(50)) data were obtained for quinclorac in toxicity tests with organisms routinely used in Brazil for this purpose. Experiments were carried out on microcosms associated with the irrigated rice crop to evaluate the effects of the herbicide on the natural plankton community. The deterministic analyses showed that the risk presented by the herbicide residues to the phytoplankton require mitigating action, while the probabilistic analysis revealed that the levels of risk for the aquatic community were acceptable. Field experiments showed that the recommended application concentration of the product directly affects phytoplankton and has an indirect, short-term effect on the zooplankton community.


A polarity dependent fluorescence "switch" in live cells.
The spectroscopic properties, ultrafast kinetics and utilization of a photochromic molecule as a bi-stable fluorescing sensor of polarity in live cells are described. This molecule is a photochromic fulgimide, 2,3-dialkylidenesuccinimide, which emits fluorescence that can be switched optically on and off. The fluorescence intensity is a function of the polarity of the molecular environment, namely it fluoresces strongly when the molecule is in its polar isomeric structure form. We demonstrate that this molecule enters live cells without inducing damage, it binds primarily to internal membranous organelles (mitochondria) and its fluorescence can be switched optically "on" and "off" repeatedly while inside the living cell. A possible use as a bi-stable, on/off sensor is discussed.


Flexor pollicis longus tendon rupture: a case series on palmaris longus tendon graft reconstruction after volar plate fixation.
Flexor pollicis longus (FPL) tendon rupture is a debilitating condition that can impair hand function. This case series study aimed to evaluate the outcomes of FPL tendon rupture and subsequent palmaris longus (PL) tendon graft reconstruction. Three cases of FPL tendon rupture in patients who had previously undergone open reduction and internal fixation with a volar plate were included. The surgical intervention involved volar plate removal, tenolysis and PL tendon graft reconstruction. Follow-up assessments showed gradual improvement in wrist function, with no post-operative complications or infections observed. These findings suggest that PL tendon grafting can be an effective surgical technique for FPL tendon rupture. Further research is needed to determine optimal surgical approaches and post-operative rehabilitation protocols for this condition.


Correlations and synchrony in threshold neuron models.
We study how threshold models and neocortical neurons transfer temporal and interneuronal input correlations to correlations of spikes. In both, we find that the low common input regime is governed by firing rate dependent spike correlations which are sensitive to the detailed structure of input correlation functions. In the high common input regime, the spike correlations are largely insensitive to the firing rate and exhibit a universal peak shape. We further show that pairs with different firing rates driven by common inputs in general exhibit asymmetric spike correlations.


Comparison of the fixed ratio and the Z-score of FEV1/FVC in the elderly population: a long-term mortality analysis from the Third National Health and Nutritional Examination Survey.
Despite the ongoing intense debate on the definition of airflow limitation by spirometry in the elderly population, there have only been few studies comparing the fixed ratio and the Z-score of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) in terms of long-term mortalities. In this study, we aimed to identify the proper method for accurately defining the airflow limitation in terms of long-term mortality prediction in the elderly population. Data were collected from the Third National Health and Nutrition Examination Survey in the US. Non-Hispanic Caucasians aged 65-80 years were included. The receiver operating characteristic (ROC) curves of both methods were plotted and compared for 10-year all-cause, respiratory, and COPD mortalities. Of 1,331 subjects, the mean age was 71.7 years and 805 (60.5%) were males. For the 10-year all-cause mortality, the area under the curve (AUC) of the fixed ratio was significantly greater than that of the Z-score of FEV1/FVC, but both showed poor prediction performance (0.633 vs 0.616, p<0.001). For the 10-year respiratory and COPD mortalities, both the fixed ratio and the Z-score of FEV1/FVC showed comparable prediction performance with greater AUCs (0.784 vs 0.778, p=0.160, and 0.896 vs 0.896, p=0.971, respectively). Interestingly, the conventional cutoff of 0.7 in the fixed ratio was consistently higher than the optimal for the 10-year all-cause, respiratory, and COPD mortalities (0.70 vs 0.69, 0.62, and 0.61, respectively), whereas that of -1.64 in the Z-score of FEV1/FVC was consistently lower than the optimal cutoff (-1.64 vs -1.31, -1.47, and -1.41, respectively). In the elderly population, both the fixed ratio and the Z-score of FEV1/FVC showed comparable prediction performance for the 10-year respiratory and COPD mortalities. However, the conventional cutoff of neither 0.70 in the fixed ratio nor -1.64 in the Z-score of FEV1/FVC was optimal for predicting the long-term mortalities.


Medawar's Paradox and Immune Mechanisms of Fetomaternal Tolerance.
Brazilian-born British biologist Dr. Peter Medawar played an integral role in developing the concepts of immunologic rejection and tolerance, which led to him receiving the Nobel Prize "for the discovery of acquired immunologic tolerance" and eventually made organ transplantation a reality. However, at the time of his early work in tolerance, a paradox to his theories was brought to his attention; how was pregnancy possible? Pregnancy resembles organ transplantation in that the fetus, possessing paternal antigens, is a semi-allogeneic graft that can survive without immunosuppression for 9 months. To answer this question, Medawar proposed three hypotheses of how a mother supports her fetus in utero, now known as "Medawar's Paradox." The mechanisms that govern fetomaternal tolerance are still incompletely understood but may provide critical insight into how to achieve immune tolerance in organ transplantation. Here, we review current understanding of the immune factors responsible for fetomaternal tolerance during pregnancy and discuss the potential implications for advances in transplantation science.


Harming the non-conscious.
Peter Singer has argued that nothing done to a fetus before it acquires consciousness can harm it. At the same time, he concedes that a child can be harmed by something done to it when it was a non-conscious fetus. But this implies that the non-conscious fetus can be harmed. The mistake lies in thinking that, since existence can be instrinsically bad for a being only if it is conscious, it can be harmed only if it is conscious. In fact, its being harmed only implies that it could have been conscious (and led a good life).


[Kaposis sarcoma in a renal graft].
Kaposi's sarcoma is an infrequent tumor of unknown cause, but with a higher impact in immune depressed individuals, particularly in HIV and transplant patients. It usually appears as a benign cutaneous lesions, while the invasive visceral form is uncommon with malignant evolution and wit rare remission. We present a patient with a Kaposi's sarcoma localised in a renal graft and bad response even when immuno suppression was discontinued.


Neglected wardens: T lymphocyte ryanodine receptors.
Ryanodine receptors (RyRs) are intracellular Ca2+ release channels ubiquitously expressed in various cell types. RyRs were extensively studied in striated muscle cells due to their crucial role in muscle contraction. In contrast, the role of RyRs in Ca2+ signalling and functions in non-excitable cells, such as T lymphocytes, remains poorly understood. Expression of different isoforms of RyRs was shown in primary T cells and T cell lines. In T cells, RyRs co-localize with the plasmalemmal store-operated Ca2+ channels of the Orai family and endoplasmic reticulum Ca2+ sensing Stim family proteins and are activated by store-operated Ca2+ entry and pyridine nucleotide metabolites, the intracellular second messengers generated upon stimulation of T cell receptors. Experimental data indicate that together with d-myo-inositol 1,4,5-trisphosphate receptors, RyRs regulate intercellular Ca2+ dynamics by controlling Ca2+ concentration within the lumen of the endoplasmic reticulum and, consequently, store-operated Ca2+ entry. Gain-of-function mutations, genetic deletion or pharmacological inhibition of RyRs alters T cell Ca2+ signalling and effector functions. The picture emerging from the collective data shows that RyRs are the essential regulators of T cell Ca2+ signalling and can be potentially used as molecular targets for immunomodulation or T cell-based diagnostics of the disorders associated with RyRs dysregulation.


Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes.
The study was undertaken to determine the risks of adverse obstetric outcomes in pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) and/or human chorionic gonadotropin (hCG) and to determine whether these risks vary by prepregnancy risk status. All women who underwent double-marker screening (MSAFP+hCG) between 1994 and 2000 and were delivered of an infant in Nova Scotia, Canada, during this period were identified from a hospital serum screening database and a provincial perinatal database. Patients with inaccurate dating, major structural anomalies, or chromosomal abnormalities were excluded. The primary outcomes studied were preeclampsia, abruptio placentae, fetal growth restriction, fetal death, and preterm birth. Women with medical or previous obstetric complications were designated high risk. Logistic regression, controlling for confounding factors, was used to estimate the relative risks (RRs) and 95% CI for elevated levels of MSAFP and/or hCG and each of the outcomes. Among the 14,374 women who met the study criteria, 5,789 were designated high risk. Except for abruptio placentae, unexplained elevated MSAFP or elevated hCG levels were independently associated with all the outcomes in both high- and low-risk women. Elevated screening values were associated with increased risk of abruptio placentae among low-risk women only. Particularly large RRs were seen for fetal death in both high- and low-risk women (RR=4.9, 95% CI 2.7-8.7 for elevated MSAFP or hCG in high- and low-risk women combined). Unexplained elevated levels of MSAFP and/or hCG are associated with an increased risk of most pregnancy complications. Increased antenatal surveillance of these patients is important regardless of prepregnancy risk status.


Antigenic determinants of infective and inactivated human rhinovirus type 2.
Treatment of human rhinovirus type 2 (HRV 2) virions at pH 5, at 56 C or in 2 M urea, produces one or both of two types of subviral particles. These subviral particles sediment at 135S or at 80S and both share what have been designated as C-antigenic determinants; the determinants of native virions have been designated D. These sets of determinants have been contrasted by the techniques of immunodiffusion, complement fixation, and serum blocking, and the results indicate that many or most of the D-determinants are lost in the conversion to C antigenicity. Some of the HRV 2 C-determinants also react, in immunodiffusion and in complement fixation tests, with antisera produced against HRV 1A virions. The inverse reaction has also been detected by complement fixation. Purified natural top component (NTC) of HRV 2 contains C- and, to a lesser extent, D-determinants. The D-determinants of NTC are also, like those of virions, lost upon treatment at pH 5. These results are discussed in terms of a conformational model for the D- to C-antigenic conversion.


Patient participation in colon cancer screening programs.
The objectives of this study were to survey compliance and identify factors that influence continued participation with periodic colon cancer screening guidelines once patients are seen for their first screening. The study group consisted of 95 patients who had initial fecal occult blood tests (FOBT) and flexible sigmoidoscopy (FS) in 1991 as part of a gastroenterologist-directed, aggressively managed colon cancer screening registry. Regular notices are sent to patients and their primary care provider for annual FOBT and FS at 3- to 5-year intervals. Of 70 (74%) reviewed, 2 had died and 3 were having colonoscopic surveillance. Thirty-two of the 65 (49%) contacted eligible study subjects were no longer participating. Reasons stated were as follows: unaware that screening was due (14), too busy (6), unpleasant experience (3), and change to insurance provider that did not cover screening (9 [commercial-3, managed care-1, Medicare-5]). Despite aggressive program management, 44% of nonparticipators reported that they were unaware that screening was due. Sixteen percent of those who did not continue to participate had graduated to Medicare, which did not cover screening costs. Factors that influence continued participation need to be considered in the design of public education and marketing promotions.


Up-regulation of adiponectin, its isoforms and receptors in end-stage kidney disease.
Despite the favourable effects of adiponectin on the vasculature and insulin resistance (IR), levels are increased in patients with end-stage kidney disease (ESKD), in whom both IR and atherosclerosis are prevalent. To investigate this paradox, we examined the distribution of adiponectin isoforms, the expression of adiponectin receptor (AdipoR) mRNA on peripheral blood mononuclear cells (PBMC) in 41 patients with ESKD on haemodialysis and 41 matched controls, and its function by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation of AdipoR on PBMC. We also compared the expression of AdipoR on PBMC with that on muscle and subcutaneous and visceral fat in 10 patients undergoing elective cholecystectomy. The proportion of the high molecular weight (HMW) isoform of adiponectin was increased in the dialysis group (P = 0.001), even though these patients were significantly insulin resistant compared with controls (P = 0.006). AdipoR1 and AdipoR2 on PBMC were also increased in patients with ESKD (P < 0.05 and P = 0.007, respectively), but levels did not correlate with IR, the HMW isoform or other anthropometric measurements. There was a strong correlation between AdipoR1 and AdipoR2 on PBMC in ESKD and in subcutaneous and visceral fat in controls. However, there was no relationship between AdipoR in PBMC, muscle or visceral fat. Phosphorylation of AMPK by recombinant adiponectin showed that AdipoR on PBMC, from controls and ESKD patients, were equally functional. IR in ESKD is not explained by the change in isoformic distribution, or by AdipoR down-regulation or dysfunction. Rather, this receptor-ligand axis is up-regulated and may be a beneficial response to the inflammatory milieu of ESKD.


[Clinical study of eosinophilic gastroenteritis].
To study the clinical symptoms, diagnosis and treatment of eosinophilic gastroenteritis (EG). A total of 44 cases of EG admitted to our hospital were studied respectively in clinical manifestations, laboratory examinations, endoscopic signs and treatment. (1) The presenting symptoms of EG patients was abdominal pain. (2) The endoscopic signs of EG were mucosal pathological changes of hyperemia, erosion and hyperplasia. A certain number of eosinophilic granulocytes were detected in pathological examination. (3) The hormones were effective and had quick onsets. While, based on different clinical symptoms, the traditional medicine was dosed by oral administration and intestinal enema. In TCM group (n = 22), 20 patients had a relief of clinical symptoms, 4 cases of recurrence and 16 of cure. In comparison, in hormone group (n = 18), 17 patients had a relief of clinical symptoms, 6 cases of recurrence and 12 of cure. The results showed that two groups had no statistical difference in relief of clinical symptoms, recurrence and hormonal cure (all P > 0.05). But it will be more readily accepted. The incidence of EG is low in clinical practice because of its non-specific clinical and endoscopic manifestations. An elevated count of eosinophilic granulocytes in peripheral blood, ascitic fluid and tissues of mucous membrane are key diagnostic points. The hormonal treatment is both fast and effective. But traditional medicine will have a brighter clinical prospect.


[Dissecting aneurysm of the middle cerebral artery with subarachnoid hemorrhage showing complete occlusion at the M2 portion of the middle cerebral artery on preoperative angiograms: case report].
We present a surgical case of a dissecting aneurysm of the middle cerebral artery associated with subarachnoid hemorrhage and intracranial hemorrhage. A 29-year-old man suddenly fell into a comatose state, and was referred to our hospital. CT scan showed diffuse subarachnoid hemorrhage and an intracerebral hematoma with marked midline shift located in the right frontal lobe. The right carotid angiogram revealed complete occlusion at the M2 portion of the middle cerebral artery, but failed to reveal any aneurysms in the rest of the intracranial circulation. We undertook emergent surgery to evacuate the hematoma and to confirm whether it was a dissecting aneurysm or not. After evacuation of the hematoma of the right frontal lobe, the Sylvian fissure was noticed to be widely opened. We detected a large dissecting aneurysm with a dark-purplish wall arising from the right M2 trunk, and we trapped the aneurysm. The postoperative course was uneventful and the patient gradually improved and was discharged without neurological deficits. We presented this case with a review of the literature.


Diastereoselective Hartwig-Buchwald reaction of chiral amines with rac-[2.2]paracyclophane derivatives.
A Hartwig-Buchwald addition of a variety of chiral amines to rac-4-bromo-[2.2]paracyclophane and rac-trifluoromethanesulfonic acid (4-[2.2]paracyclophane) ester was performed with high diastereoselectivities. Kinetic racemic resolution of the starting materials was achieved, providing a rapid access to enantiomerically enriched 4-bromo-[2.2]paracyclophane and the corresponding enantiomerically pure [2.2]paracyclophane amines. Additionally, the first reaction of a secondary amine with a [2.2]paracyclophane halide was achieved.


[A case of esophageal actinomycosis in a patient with normal immunity].
Actinomycosis is a chronic suppurative disease and caused by Actinomycosis species, principally Actinomyces israelii, which are part of the normal inhabitant on the mucous membrane of the oropharynx, gastrointestinal tract, and urogenital tract. It usually affects cervicofacial, thoracic and abdominal tissue. Cervicofacial type has the highest percentage of occurrence with 50%. Actinomycosis frequently occurs following dental extraction, jaw surgery, chronic infection or poor oral hygiene. It may also be considered as an opportunistic infection in immunocompromised patients such as malignancy, human immunodeficiency virus infection, diabetes mellitus, steroid usage or alcoholism. But, actinomycosis rarely occurs in adults with normal immunity and rare in the esophagus. We report an unusual case of esophageal actinomycosis which was developed in a patient with normal immunity and improved by therapy with intravenous penicillin G followed oral amoxicillin, and we also reviewed the associated literature.


Between pandemics: sex worker, sexual minority, and transgender activism from HIV to COVID-19.
Public health crises alter political landscapes. This article investigates social movement strategies during and between the HIV and COVID-19 pandemics. We conducted a set of eighteen in-depth interviews with eleven leaders of organisations working with sex workers, sexual minorities, and transgender people around India, all of whom had been actively involved in HIV prevention programs, before and after the arrival of COVID-19 in India. First HIV, and then COVID-19, altered the political landscape for these groups in relation to three types of institutions: (1) donors (by creating dramatic increases and decreases in the amount, type, and conditions of global funding and deepening inequalities among organisations) (2) the state (by shifting the balance of advocacy and human rights work toward immediate relief); and (3) other social movements (by expanding solidarities across groups but also placing them in competition for limited resources). We argue that, to weather these dramatic shifts, organisations relied on internal alliances and resources built in and after periods of crisis. In this way, despite the differences between the two pandemics, the legacies of HIV shaped the response to COVID-19. Though responses to COVID-19 seem improvised and temporary, they build on a longer-term social movement infrastructure.


Probing colloidal particle aggregation by light scattering.
The present article reviews recent progress in the measurement of aggregation rates in colloidal suspensions by light scattering. Time-resolved light scattering offers the possibility to measure absolute aggregation rate constants for homoaggregation as well as heteroaggregation processes. We further discuss the typical concentration dependencies of the aggregation rate constants on additives. Addition of simple salts containing monovalent counterions leads to screening of the electrostatic repulsion of the charged particles and a transition from slow to rapid aggregation. Addition of salts containing multivalent counterions may lead to a charge reversal, which results in a sequence of two instability regions. Heteroaggregation rates between oppositely charged particles decrease with increasing salt level. This decrease is caused by screening of the electrostatic attraction between these particles.


Bioinformatics analysis of carotid vulnerable plaques associated with the SARS-CoV-2 pattern.
The rupture of carotid artery vulnerable plaque plays a critical role in ischemic stroke, and the widely spread new coronavirus in recent years plays a certain role in the development of human carotid artery vulnerable plaque, we screened out 27 differential expression genes (DEGs) of stable plaque and vulnerable plaque associated with the new coronavirus. Through the construction of the protein-protein interaction (PPI) network, the Cathepsin B (CTSB) and Niemann-Pick Disease Type 2 (NPC2) were identified as crucial expression genes, and further, we confirmed the validity of core gene expression in two validation sets. Additionally, we discovered a significant connection between CTSB, NPC2 and 28 different kinds of immune cells in carotid plaque tissue. We screened out 65 target interacting drugs based on 10 differentially expressed genes through online tools and finally verified the high expression of 2 core genes in fragile plaques through clinical sample experiments. These findings imply that two core genes may be novel targets for molecular diagnostics and immunotherapy of vulnerable plaques.


Ultrastructure of fetal spinal cord and cortex implants into adult rat spinal cord.
The ultrastructure of cortex and spinal cord from 11-, 12-, and 15-day-old fetuses implanted into the spinal cord of adult rats was studied over 3 months. Under deep Chloropent anesthesia, a 0.5 X 1.0-mm square of fetal cortex or a 1.0-mm segment of fetal spinal cord was implanted subpially between the left dorsal column and the dorsal horn of 70 adult rats. Implants grew toward gray matter, usually interfacing with the host at the isthmus between the horns of the spinal cord. However, implants were observed that occupied the entire left dorsal and ventral horns of the left half of the host spinal cord. Implants had concentric zones: A central zone with basal lamina lined joined channels and subjacent neuroglia; a zone of differentiating implant nervous system; a zone with basal lamina lined implant with overlying pial cells on the dorsal and lateral surfaces of the implant; a zone that interfaced with the host with overlapping neuropil on the lateral and ventral surfaces of the implant. Neuron types were typical for cortical or spinal implants. Implants survived for 3 months and reached stages of neuronal and neuroglial maturation similar to controls. Both fetal spinal cord and brain were successful as implants, had delayed differentiation, and formed complex neuropils. The zone of overlapping interface of the donor and host is an anatomical indication of physiological and functional integration.


Quantitative in vitro vasoactivity of 5-hydroxytryptamine on the human basilar artery.
The importance of autacoidal substances in the genesis of cerebral vascular constriction and spasm is an unresolved issue. Comparative vasoactivity of 5-hydroxytryptamine (5HT) and norepinephrine (NE) on the human basilar artery was quantitatively assessed in vitro. 5HT was decidedly more vasoactive in this preparation. Three patterns of vasoactivity were noted with 5HT. Type I was an immediate sustained increase in tension lasting more than 30 minutes. Average increase in tension was 2988 mg (range 120-8600). Type II consisted of a sharp immediate increase in tension to average 1555 mg (range 240-4500) followed by gradual dissipation to base-line levels within 15 minutes. Type III pattern was a lesser immediate increase (372 mg; range 100-850) and more rapid dissipation over ten minutes. NE-induced Type I and Type III activity was present in only six of 20 segments. This study demonstrates that 5HT is vasoactive in human cerebral arteries. Type I sustained contractions may possibly be implicated in spasm. It is hypothesized that such autacoid-induced contraction may contribute to vascular wall ischemia, necrosis, and irreversible constriction as seen in human vasospasm.


Corticotropin-releasing factor synapses within the paraventricular nucleus of the hypothalamus.
Corticotropin-releasing factor (CRF) regulates the release of adrenocorticotropin (ACTH) from the anterior pituitary and these neurosecretory neurons reside in the paraventricular nucleus of the hypothalamus (PVN). In addition to its role as an ACTH secretogogue, exogenously administered CRF can act centrally to modify sympathetic outflow, alter various stress-induced behaviors and modulate its own secretion. Some of these effects might be mediated by CRF acting synaptically within the PVN as the nucleus is known to play a major role in integration of autonomic function. The current ultrastructural immunocytochemical study was designed to examine the range of synaptic relationships that CRF terminals make within the PVN. CRF-positive synapses were numerous, particularly in the periventricular zone. The majority of terminals formed axo-dendritic synapses and of these over 85% were the Gray's type II (symmetrical) class. Axo-somatic terminals were also encountered and both parvicellular and magnocellular neurons were innervated. Once again most of the terminals were Gray's type II. Although an innervation of unidentified structures was the most common, CRF synapses onto CRF neurons and dendrites were observed. All CRF/CRF interactions had symmetrical membrane specializations. These studies indicate that CRF could play a prominent role in the modulation of both parvicellular and magnocellular neurons within the paraventricular nucleus, including modulation of its own neurosecretory activity.


[Isolated Displaced Fracture of the Acromion - Case Report].
Displaced fractures of the acromion are rare injuries. A 45-year-old lady presented with an isolated acromion fracture (type III, Kuhn classification) resulting from a direct blow to the top of her right shoulder in a fall while skiing. After standard clinical and radiological examination of the shoulder, an open reduction and internal plate fixation using a postero-superior approach to the scapula was performed. Early rehabilitation of the arm and shoulder was initiated. At 50 days after surgery the patient achieved a full range of motion in her right shoulder and muscle strength equal to that of the contralateral extremity. By 12 weeks radiographic union of the fracture was recorded. The final functional outcome after open reduction and internal plate fixation of the fracture was comparable with results reported in the literature and, in comparison with conservative treatment, the risk of non-union was significantly reduced. acromion fracture, scapula, osteosynthesis.


Identification of candidate genes involved in gonocyte development.
Several germ cell tumors that occur in adult men likely originate from gonocytes that are impaired in their development. To select candidate genes that are involved in the normal development of the gonocytes, we constructed a complementary DNA (cDNA) library from rat gonocytes as well as from single, paired, and aligned A spermatogonia (A(s), A(pr), and A(all) spermatogonia, respectively), their direct descendants. Five hundred gonocyte clones were differentially screened using both libraries. Successive verification by dot blot assays yielded 7 clones that were consistently highly abundant only in the gonocyte cDNA library. Also, in situ hybridization of these clones confirmed their differential expression. They encoded for, respectively, succinate dehydrogenase, ribosomal protein S15a, and the 65-kilodalton scaffolding subunit (a isoform) of protein phosphatase 2A. No clues regarding the nature of the remaining four clones could be found. Hence, using differential screening on both constructed cDNA libraries, we were able to select several genes that are interesting candidates for studying the molecular mechanisms of normal gonocyte development.


Expression patterns of angiopoietin-1, -2, and tie-2 receptor in ulcerative colitis support involvement of the angiopoietin/tie pathway in the progression of ulcerative colitis.
The active stage of ulcerative colitis (UC) involves transmigration of polymorphonuclear (PMN) cells to colonic epithelia. The angiopoietin (Ang) pathway plays a role as the regulator of PMN transmigration. To clarify the role of the Ang/Tie pathway in the activation of UC, especially in cypt abscess formation, 67 tissue samples were obtained from patients with UC and ten controls without UC for immunohistochemical analysis for the expression of Ang-1, -2, or Tie-2. The epithelia of crypt abscess was strongly positive for Ang-1 and -2 for all 57 samples derived from patients with active UC, though the colorectal epithelium without crypt abscess showed minimal expression of Ang-1, -2, and Tie-2. Numerous transepithelial migrating PMN cells in crypt abscesses also expressed Tie-2. The specimens of UC patients in remission showed significantly less immunoreactivity for Ang-1, -2, or Tie-2. These findings suggest that the Ang/Tie pathway may play a role in the progression of UC.


A Wireless Visualized Sensing System with Prosthesis Pose Reconstruction for Total Knee Arthroplasty.
The surgery quality of the total knee arthroplasty (TKA) depends on how accurate the knee prosthesis is implanted. The knee prosthesis is composed of the femoral component, the plastic spacer and the tibia component. The instant and kinetic relative pose of the knee prosthesis is one key aspect for the surgery quality evaluation. In this work, a wireless visualized sensing system with the instant and kinetic prosthesis pose reconstruction has been proposed and implemented. The system consists of a multimodal sensing device, a wireless data receiver and a data processing workstation. The sensing device has the identical shape and size as the spacer. During the surgery, the sensing device temporarily replaces the spacer and captures the images and the contact force distribution inside the knee joint prosthesis. It is connected to the external data receiver wirelessly through a 432 MHz data link, and the data is then sent to the workstation for processing. The signal processing method to analyze the instant and kinetic prosthesis pose from the image data has been investigated. Experiments on the prototype system show that the absolute reconstruction errors of the flexion-extension rotation angle (the pitch rotation of the femoral component around the horizontal long axis of the spacer), the internal-external rotation (the yaw rotation of the femoral component around the spacer vertical axis) and the mediolateral translation displacement between the centers of the femoral component and the spacer based on the image data are less than 1.73°, 1.08° and 1.55 mm, respectively. It provides a force balance measurement with error less than ±5 N. The experiments also show that kinetic pose reconstruction can be used to detect the surgery defection that cannot be detected by the force measurement or instant pose reconstruction.


Vagal Paraganglioma: Surgical Removal with Superior Laryngeal Nerve Preservation.
Vagal paragangliomas (VPGLs) represent <5% of all head and neck paragangliomas (PGLs) and show a 17% to 20% risk of malignancy. We present a rare case of a 50-year-old gender with a left VPGL in her neck. To date, approximately 200 cases have been reported. The tumor showed web-like adhesions and arterial supply from the external carotid artery. We performed en bloc resection including a part of the vagus nerve. The superior laryngeal nerve was preserved with the "human communicating nerve" which maintains neural communication in >70% of humans, providing motor fibers to the larynx. The patient recovered uneventfully and was discharged on the 3rd postoperative day. These tumors are therapeutically challenging owing to their proximity to vital neck and skull base structures. Early detection decreases surgical morbidity and mortality. Preservation of viable neural tissue is important in advanced disease.


Increased creatine kinase activity in pituitary tumours of rat and man.
The demonstration that phosphocreatine is used as an energy source by rat PRL-secreting pituitary tumours prompted the study of the enzyme creatine kinase in both rat and human pituitary tumours. Rats treated with diethylstilbestrol developed greatly enlarged pituitaries and hyperprolactinaemia. Total creatine kinase was significantly increased and fractionation on diethylaminoethyl Sephadex showed that the 'brain' form was increased, whereas the 'muscle' and mitochondrial forms showed no change. Exposure to large concentrations of oestradiol caused similar changes in creatine kinase which increased over a period of 25 weeks. The total creatine kinase content of a series of human pituitary tumours was highly variable, but the mean value of 183 +/- 46 (SEM) units per gram protein was significantly higher than the mean for normal pituitary tissues (28.4 +/- 2.9). The brain:muscle isozyme ratio was measured in six human PRL-secreting tumours with a mean of 3.47 +/- 0.73, significantly higher than in 'non-functional' tumours (1.57 +/- 0.29) or normal tissue (1.77 +/- 0.28). Three of four GH-secreting tumours had a ratio below 0.6. The highest ratio found (8.66) was in an ACTH-secreting tumour. Previous reports have shown that oestradiol rapidly induces brain creatine kinase in oestrogen responsive tissues. This is not the case with the rat pituitary gland or oestrogen responsive human tumour cells in culture. Chronic oestrogen treatment, however, does increase creatine kinase in the proliferating gland and many human pituitary tumours have increased enzyme activity. These results suggest that the phosphocreatine/ATP system and in particular the brain isozyme of creatine kinase are of particular importance in lactotropes.


Energy balance of nutrition and activity in a group of nursing students.
This descriptive study presents a profile of energy balance, nutrition, and activity in a group of baccalaureate nursing students (N = 21). Self-reported, consecutive, three-day food and physical activity records as well as a background questionnaire served as the instruments for data collection. Findings revealed that energy intakes were adequate to meet recommended nutrient intakes for all nutrients except carbohydrate, but insufficient to meet their levels of energy expenditure. Student involvement in a range of activities that required substantial energy expenditure, coupled with weight-loss dieting by several students appear to explain this observed energy imbalance. Increased carbohydrate intake and decreased fat intake would seem to be recommended nutritional modifications warranted for this group of nursing students.


The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment.
Serotonin toxicity (or serotonin syndrome) has become an increasingly common and important clinical problem in medicine over the last 15 years with the introduction of many new antidepressants that can cause increased levels of serotonin (5-HT) in the central nervous system (CNS). Severe and life-threatening cases are almost exclusively a result of combinations of antidepressants (usually monoamine oxidase inhibitors and selective serotonin reuptake inhibitors). Unfortunately, the term serotonin syndrome has a number of quite different meanings, and many people writing on this subject have failed to differentiate them. This has led to false conclusions regarding the 5-HT receptor subtypes responsible for the life-threatening effects in animal and human toxicity, and suggestions of ineffective treatment strategies. This review primarily addresses the serotonin receptor subtypes that underlie the clinical manifestations of excess CNS serotonin in humans and animals, and their implications for diagnosis and treatment. More specific diagnostic criteria for serotonin toxicity are required to identify situations when specific antidotes are likely to be useful. However, the mainstay of treatment of severe cases is good supportive care and early intubation and paralysis in life-threatening serotonin toxicity.


The influence of chosen metals administration in drinking water on magnesium balance in rats.
The aim of our study was to estimate the influence of chromium, lead and aluminium on the magnesium level in serum and tissues of rats. Male Wistar rats received Cr, Pb and Al at the concentration of 500 mg of metal x dm(-3) in the form of drinking water for three or six weeks. After the period of administration the animals were sacrificed under ketamine narcosis and blood from the heart as well as the tissues of the liver, kidney, brain, spleen, femoral muscle and heart muscle were collected. Magnesium concentration was measured in serum and tissue homogenates. Chromium caused the increase of Mg level in some tissues after six weeks and no changes in serum. Lead influenced Mg level in serum and tissues mainly after six weeks but the changes were more diverse and depending on the tissue. After six weeks' administration aluminium caused the magnesium release from serum and its storage in tissues.


Evaluation of asymmetric liposomal nanoparticles for encapsulation of polynucleotides.
Conventional lipid bilayer liposomes have similar inner and outer leaflet compositions; asymmetric liposomes have different lipid leaflet compositions. The goal of this work is to place cationic lipids in the inner leaflet to encapsulate negatively charged polynucleotides and to place neutral/anionic lipids on the outer leaflet to decrease nonspecific cellular uptake/toxicity. Inverse emulsion particles have been developed with a single lipid leaflet of cationic and neutral lipids surrounding an aqueous core containing a negatively charged 21-mer DNA oligo. The particles are accelerated through an oil-water interface, entrapping a second neutral lipid to form oligo encapsulated unilamellar liposome nanoparticles. Inverse emulsion particles can be consistently produced to encapsulate an aqueous environment containing negatively charged oligo. The efficiency of encapsulated liposome formation is low and depends on the hydrocarbon used as the oil phase. Dodecane, mineral oil, and squalene were tested, and squalene, a branched hydrocarbon, yielded the highest efficiency.


Pre-target neural oscillations predict variability in the detection of small pitch changes.
Pitch discrimination is important for language or music processing. Previous studies indicate that auditory perception depends on pre-target neural activity. However, so far the pre-target electrophysiological conditions which enable the detection of small pitch changes are not well studied, but might yield important insights into pitch-processing. We used magnetoencephalography (MEG) source imaging to reveal the pre-target effects of successful auditory detection of small pitch deviations from a sequence of standard tones. Participants heard a sequence of four pure tones and had to determine whether the last target tone was different or identical to the first three standard sounds. We found that successful pitch change detection could be predicted from the amplitude of theta (4-8 Hz) oscillatory activity in the right inferior frontal gyrus (IFG) as well as beta (12-30 Hz) oscillatory activity in the right auditory cortex. These findings confirm and extend evidence for the involvement of theta as well as beta-band activity in auditory perception.


Localized Epidermal Cysts as a Radiation Recall Phenomenon in a Melanoma Patient Treated with Radiotherapy and the BRAF Inhibitor Vemurafenib.
BRAF inhibitors are broadly used for metastatic melanoma with BRAF mutations. Their use results in various cutaneous side effects, such as the development of keratoacanthomas and squamous cell carcinomas. We report a patient with metastatic melanoma treated with vemurafenib who developed dozens of histologically confirmed epidermal cysts within 2 months after initiation of vemurafenib administration. The cystic lesions were observed only in the localized area where a large exophytic melanoma tumor mass had been previously irradiated. Localized epidermal cysts may constitute an unusual radiation recall reaction in patients treated with BRAF inhibitors.


Are adult cardiocytes still able to proliferate?
In all mammals including humans, adult cardiocytes become post mitotic cells, while cardiac non muscle cells still have the capacity to proliferate, and cardiac hypertrophy in adults is known to be due to cardiocyte hypertrophy and non muscle cell hyperplasia. Such a dogma was supported by several, rather ancient, observations, and has been recently challenged by two different groups. Several new paradigms in cell biology have modified these views: the entire determinants of the cell cycle are now entirely known; apoptosis, and cardiac apoptosis, is central in the process of cell division, and has a rather complicated significance; telomeres are specialized DNA-protein structures that prevent end-to-end chromosome fusion, and are rather characteristic of germ and stem cells, these structures are maintained by telomerase. Using several markers, including telomerase activity, endogenous self-renewing, clonogenic and multipotent stem cells were identified in the adult myocardium in human, mice and rat. These cells are activated during cardiac overload or ischemia to produce new cardiocytes. New endothelial cells also appeared, and are likely to have a circulatory origin. The physiological importance of these new cells is debatable at the moment. Nevertheless, these findings provide an important new basis for cell cardiomyoplasty. It is also possible to envisage stimulation of the production and activity of these new cells to compensate for the lack of substance after myocardial infarction.


Copper-Assisted Amination of Boronic Acids for Synthesis of Bulky Diarylamines: Experimental and DFT Study.
Comparative investigation of copper-assisted oxidative and reductive amination showed that the latter was preferable for the synthesis of bulky diarylamines. DFT estimation of the mechanism of copper(I)-assisted reductive amination of boronic acids with aryl nitroso compounds was performed and possible active species were identified. DFT estimation of the steric penalty revealed that the barrier for the transmetalation step for the hindered nitroso compound was almost the same as that for the unsubstituted one, whereas a bulky group in the boronic acid increased the activation energy. A DFT study of the influence of the electronic properties of the substituents in both reactants on the activation energy revealed that the optimal combination for the synthesis of unsymmetrical diarylamines to provide better yields was an electron-rich aryl boronic acid and an electron-deficient nitroso compound. By using these helpful guidelines, a series of new bulky diarylamines were obtained and fully characterized.


The AgED Study. Age-related eye disease (AgED) in South Australian general practice: are we blind to early detection and intervention?
The AgED Study aimed to evaluate the detection, awareness and management of age-related eye disease (AgED) in South Australian general practice. Three South Australian metropolitan general practices were recruited and all patients aged 75 years and older were invited to participate. A cross-sectional postal questionnaire and retrospective audit of consenting patients' medical records was performed. On average, patients had their last eye check 9 months ago; the majority (64.9%) performed by an optometrist. Only 7.6% had visited their GP for their last eye check, mostly (90.5%) for a mandatory 'Fitness to Drive' medical assessment. There were marked differences in GP recording v. self-reported AgED and a marked discrepancy in the prevalence rates of AgED, visual impairment and blindness in this study compared with Australian population-based prevalence surveys. Despite the lack of GP documentation of eye disease, the majority of patients engaged in timely eye checks with either an optometrist or ophthalmologist, and their overall visual function and vision-related quality of life (QoL) were satisfactory.


Vagal afferent activation decreases brown adipose tissue (BAT) sympathetic nerve activity and BAT thermogenesis.
In urethane/α-chloralose anesthetized rats, electrical stimulation of cervical vagal afferent fibers inhibited the increases in brown adipose tissue sympathetic nerve activity and brown adipose tissue thermogenesis evoked by cold exposure, by nanoinjection of the GABAA receptor antagonist, bicuculline, in the dorsomedial hypothalamus, and by nanoinjection of N-methyl-D-aspartate in the rostral raphe pallidus. Vagus nerve stimulation-evoked inhibition of brown adipose tissue sympathetic nerve activity was prevented by blockade of ionotropic glutamate receptors in the termination site of vagal afferents in the nucleus of the solitary tract, and by nanoinjection of GABAA receptor antagonists in the rostral raphe pallidus. In conclusion, the brown adipose tissue sympathoinhibitory effect of cervical afferent vagal nerve stimulation is mediated by glutamatergic activation of second-order sensory neurons in the nucleus of the solitary tract and by a GABAergic inhibition of brown adipose tissue sympathetic premotor neurons in the rostral raphe pallidus, but does not require GABAergic inhibition of the brown adipose tissue sympathoexcitatory neurons in the dorsomedial hypothalamus.


Possible risk considerations for toxic risk assessment.
The concepts of 'negligible', 'tolerable' and 'unacceptable' risk are considered in the context of 'voluntary' and 'involuntary' risks. Levels of risk for different ill health consequences are examined in relation to the various types of risk associated with standard setting and, in particular, for standards relevant to workplace ill-health.


Olaparib Keeps Hereditary Breast Tumors in Check.
In the phase III OlympiAD study, tumors shrank in about 60% of women with BRCA mutation-associated metastatic breast cancer who received the PARP inhibitor olaparib compared with 29% who received chemotherapy; the median time to disease progression was 7 months compared with 4.2 months, respectively. These findings are the first to demonstrate that a PARP inhibitor can improve progression-free survival in metastatic, hereditary breast cancer.


Determination of Vancomycin in Human Serum by Cyclodextrin-Micellar Electrokinetic Capillary Chromatography (CD-MEKC) and Application for PDAP Patients.
A simple and sensitive cyclodextrin-micellar electrokinetic capillary chromatography (CD-MEKC) method with UV detection was developed and validated for the determination of vancomycin (VCM) in serum. The separation was achieved in 14 min at 25 °C with a fused-silica capillary column of 40.2 cm × 50 mm i.d. (effective length 30.2 cm) and a run buffer containing 25 mM borate buffer with 50 mM sodium dodecylsulfonate (SDS) (pH 9.5) and 2% sulfobutyl-β-cyclodextrin (sulfobutyl-β-CD). Under optimal conditions for biological samples, good separations with high efficiency and short analysis time were achieved. Several parameters affecting the drug separation from biological matrices were studied, including buffer types, concentrations, and pHs. The methods were validated over the range of 0.9998-99.98 µg/mL. Calibration curves of VCM also showed good linearity (r² > 0.999). Intra- and interday precisions (relative standard deviation, RSD) were less than 5.80% and 7.38%, and lower limit of quantification (LLOQ) were lower than 1.0 μg/mL. The mean recoveries ranged between 84.03% and 91.69%. The method was successfully applied for monitoring VCM concentrations in serum of patients with peritoneal dialysis-associated peritonitis (PDAP). The assay should be applicable to pharmacokinetic studies and routine therapeutic drug monitoring of this drug in serum.


Clinical significance of altered S100A2 expression in gastric cancer.
The S100A2 gene has been reported to be a putative tumor‑suppressor gene. Nevertheless, overexpression of S100A2 has been found in certain types of cancer. This study investigated S100A2 expression in tissue specimens of gastritis, intestinal metaplasia, adenomatous dysplasia and gastric cancer to determine its association with clinical features. A serial of tissue samples (gastritis, intestinal metaplasia, adenomatous dysplasia and gastric cancer samples) were used for quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), western blotting and immunohistochemical analyses of S100A2 expression. The data revealed that there was a gradual loss of S100A2 expression from gastritis, intestinal metaplasia and dysplasia to cancer tissue specimens (p<0.001). In gastric cancer samples, loss of S100A2 expression was associated with increased tumor size, depth of invasion, lymph node metastasis and a poor prognosis (p<0.001). However, the intestinal type of gastric cancer expressed more S100A2 protein than the diffuse type (p<0.001). In conclusion, data from the present study demonstrated that loss of S100A2 expression contributes to gastric cancer development and progression; therefore, the determination of S100A2 expression levels may help to predict the carcinogenesis and aggressiveness of gastric cancer as well as patient survival.


Capecitabine for the treatment of gastric cancer.
Capecitabine is an orally administered prodrug of 5-fluorouracil (5-FU) and was designed to specifically affect tumor cells more than normal tissues. Capecitabine is as effective and well tolerated as infusional 5-FU in the treatment of advanced gastric cancer (AGC). Following the REAL-2 and ML17032 studies, capecitabine has replaced infusional 5-FU for treating GC. Capecitabine plus platinum is one of the most widely used regimens for the first-line treatment of AGC, regardless of HER2 status. The adjuvant capecitabine/oxaliplatin regimen is one therapeutic option for resectable gastric cancer, especially after D2 resection. Compared with S-1, capecitabine has been shown to have a similar efficacy, but is associated with fewer ethnic differences than S-1, which accounts for the more widespread usage of capecitabine worldwide.


The effect of acute uremia on liver mitochondrial activity.
The effect of acute uremia on the liver mitochondrial activity was studied in Swiss albino mice subjected to complete urethral obstruction and sacrificed at different time intervals. The specific respiratory coefficient (measured as microliters of oxygen utilized per milligram of total proteins X 10(-1)) was similar in uremic and sham-operated control groups. The utilization of succinate as substrate was also similar in uremic and controls. There was a tendency for decreasing utilization of alpha-glutarate as substrate by the uremic group, particularly after 48 h of total urinary obstruction. There was no correlation between the retention of urea and the degree of mitochondrial respiratory inhibition.


Volatiles Emitted at Different Flowering Stages of Jasminum sambac and Expression of Genes Related to α-Farnesene Biosynthesis.
Fresh jasmine flowers have been used to make jasmine teas in China, but there has been no complete information about volatile organic compound emissions in relation to flower developmental stages and no science-based knowledge about which floral stage should be used for the infusion. This study monitored volatile organic compounds emitted from living flowers of Jasminum sambac (L.) Ait. 'Bifoliatum' at five developmental stages and also from excised flowers. Among the compounds identified, α-farnesene, linalool, and benzyl acetate were most abundant. Since α-farnesene is synthesized through the Mevalonate pathway, four genes encoding 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), farnesyl pyrophosphate synthase, and terpene synthase were isolated. Their expression patterns in living flowers at the five stages and in excised flowers coincided with the emission patterns of α-farnesene. Application of lovastatin, a HMGR inhibitor, significantly reduced the expression of the genes and greatly decreased the emission of α-farnesene. The sweet scent was diminished from lovastatin-treated flowers as well. These results indicate that α-farnesene is an important compound emitted from jasmine flowers, and its emission patterns suggest that flowers at the opening stage or flower buds 8 h after excision should be used for the infusion of tea leaves.


Ganglioside GM3 exerts opposite effects on motility via epidermal growth factor receptor and hepatocyte growth factor receptor-mediated migration signaling.
The ganglioside GM3 exerts its different effects via various growth factor receptors. The present study investigated and comparatively analyzed the opposing effects exerted by GM3 on the migration of mouse hepatocellular carcinoma Hepa1‑6 cells via epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR/cMet). The results demonstrated that GM3 inhibited EGF‑stimulated motility, but promoted HGF‑stimulated motility of the Hepa1‑6 cells via phosphatidylinositol 3‑kinase/Akt‑mediated migration signaling. It is well established that the main cytokines modulating cell proliferation, invasion and metastasis are different in different types of tumor. This difference may, at least in part, explain why GM3 exerted its actions in a tumor‑type specific manner.


Changes in humeral torsion and shoulder rotation range of motion in high school baseball players over a 1-year period.
The torsional stress on a baseball player's throwing limb has been theorized to affect humeral retrotosion during skeletal maturity. This study investigated 1) changes in humeral retrotorsion and shoulder rotation range of motion over a 1-year period in high school baseball players, and 2) relationship between a 1-year change in dominant limb retrotorsion and the number of seasons participants played on organized baseball teams. Humeral retrotorsion and shoulder range of motion were measured a year apart in a total of 138 high school baseball players. Baseball participation history over the year was captured using a questionnaire. Changes in bilateral humeral retrotorsion and range of motion over a year and effects of baseball participation on changes in humeral retrotorsion and range of motion were assessed using analysis of variance models. Humeral retrotorsion did not significantly change over the year regardless of the number of seasons participants played baseball (P>0.05). The participants' dominant limb internal rotation range of motion decreased slightly over a year (2.0°, P=0.015), while external rotation (7.8°, P<0.01) and total rotation (11.9°, P<0.01) range of motion decreased bilaterally among the participants who only played baseball in 1 season. Adaptation in humeral retrotorsion seems to occur prior to high school age. Our observations suggest that change in shoulder range of motion in high school baseball players are attributed to soft tissue contracture. This provides a support that stretching exercises should be implemented when significant changes in range of motion are identified in high school baseball players.


Effects of different segmental spinal stabilization exercise protocols on postural stability in asymptomatic subjects: randomized controlled trial.
The aim was to assess and compare the postural stability effects of the "Progressive Dynamic Spine Stabilization Exercise Protocols" (PDSSEP) which were designed for different spinal segments. The asymptomatic, sedentary, and female volunteers (21.26 ± 1.30 years old) were allocated randomly into Cervical (n=22), Lumbar (n=21), Thoracic (n=20), Combined (n=20), and Control (n=21) Groups. All training groups participated into the related PDSSEP for six weeks, 3 days/week. The assessments were carried out at the baseline, after 6(th) week, and on the 12(th) week. "Tetrax Interactive Posturography and Balance System" (Tetrax System, Ramat Gan, Israel) was used to assess the overall postural stability (SI), weight distribution (WDI) and somatosensory reactions. "Kruskal Wallis Test" for the differences of the pre-6th weeks, pre-12(th) weeks within the groups, "Mann-Whitney U Test" for control and inter-group comparisons were used. The differences were observed for eyes closed SI, and WDI in head right rotated position (p< 0.05) between the baseline and after completing the programs. Eyes closed SI in solid surface was shown statistically different in Thoracic group in comparison to controls (p< 0.02). SI on soft surface, SI head left rotated position and somatosensory reactions with head flexed position improved in Thoracic Group at the 12(th) week (p< 0.01). WDI significantly improved in Cervical Group (p< 0.01). Thoracic spine can be considered as a hidden source for improving overall postural stability. It may be appropriate to focus on thoracic region in the kinetic chain for the treatment or training. A prospective randomized controlled trial, Level 1.


Multifactorial discrimination as a fundamental cause of mental health inequities.
The theory of fundamental causes explains why health disparities persist over time, even as risk factors, mechanisms, and diseases change. Using an intersectional framework, we evaluated multifactorial discrimination as a fundamental cause of mental health disparities. Using baseline data from the Project STRIDE: Stress, Identity, and Mental Health study, we examined the health effects of discrimination among individuals who self-identified as lesbian, gay, or bisexual. We used logistic and linear regression to assess whether multifactorial discrimination met the four criteria designating a fundamental cause, namely that the cause: 1) influences multiple health outcomes, 2) affects multiple risk factors, 3) involves access to resources that can be leveraged to reduce consequences of disease, and 4) reproduces itself in varied contexts through changing mechanisms. Multifactorial discrimination predicted high depression scores, psychological well-being, and substance use disorder diagnosis. Discrimination was positively associated with risk factors for high depression scores: chronic strain and total number of stressful life events. Discrimination was associated with significantly lower levels of mastery and self-esteem, protective factors for depressive symptomatology. Even after controlling for risk factors, discrimination remained a significant predictor for high depression scores. Among subjects with low depression scores, multifactorial discrimination also predicted anxiety and aggregate mental health scores. Multifactorial discrimination should be considered a fundamental cause of mental health inequities and may be an important cause of broad health disparities among populations with intersecting social identities.


A novel HD-ZIP IV/MIXTA complex promotes glandular trichome initiation and cuticle development in Artemisia annua.
Glandular trichomes and cuticles are both specialized structures that cover the epidermis of aerial plant organs. The former are commonly regarded as 'biofactories' for producing valuable natural products. The latter are generally considered as natural barriers for defending plants against abiotic and biotic stresses. However, the regulatory network for their formation and relationship remains largely elusive. Here we identify a homeodomain-leucine zipper (HD-ZIP) IV transcription factor, AaHD8, directly promoting the expression of AaHD1 for glandular trichome initiation in Artemisia annua. We found that AaHD8 positively regulated leaf cuticle development in A. annua via controlling the expression of cuticle-related enzyme genes. Furthermore, AaHD8 interacted with a MIXTA-like protein AaMIXTA1, a positive regulator of trichome initiation and cuticle development, forming a regulatory complex and leading to enhanced transcriptional activity in regulating the expression of AaHD1 and cuticle development genes. Our results reveal a molecular mechanism by which a novel HD-ZIP IV/MIXTA complex plays a significant role in regulating epidermal development, including glandular trichome initiation and cuticle formation.


Epidemiology, clinical features and outcomes of incident tuberculosis in children in Canada in 2013-2016: results of a national surveillance study.
Childhood tuberculosis disease is difficult to diagnose and manage and is an under-recognised cause of morbidity and mortality. Reported data from Canada do not focus on childhood tuberculosis or capture key epidemiologic, clinical and microbiologic details. The purpose of this study was to assess demographics, presentation and clinical features of childhood tuberculosis in Canada. We conducted prospective surveillance from 2013 to 2016 of over 2700 paediatricians plus vertical tuberculosis programmes for incident tuberculosis disease in children younger than 15 years in Canada using the Canadian Paediatric Surveillance Program (CPSP). In total, 200 cases are included in this study. Tuberculosis was intrathoracic in 183 patients of whom 86% had exclusively intrathoracic involvement. Central nervous system tuberculosis occurred in 16 cases (8%). Fifty-one per cent of cases were hospitalised and 11 (5.5%) admitted to an intensive care unit. Adverse drug reactions were reported in 9% of cases. The source case, most often a first-degree relative, was known in 73% of cases. Fifty-eight per cent of reported cases were Canadian-born Indigenous children. Estimated study rates of reported cases (per 100 000 children per year) were 1.2 overall, 8.6 for all Indigenous children and 54.3 for Inuit children. Childhood tuberculosis may cause significant morbidity and resource utilisation. Key geographies and groups have very high incidence rates. Elimination of childhood tuberculosis in Canada will require well-resourced community-based efforts that focus on these highest risk groups.


Trends in cigarette smoking among high school students--United States, 1991-2001.
Cigarette smoking among adolescents is one of the 10 Leading Health Indicators that reflect the major health concerns in the United States. To examine changes in cigarette smoking among U.S. high school students during 1991-2001, CDC analyzed data from the national Youth Risk Behavior Survey (YRBS). This report summarizes the results of the analysis, which found that although cigarette smoking rates increased during most of the 1990s, they have declined significantly since 1997. If this pattern continues, the United States could achieve the national health objective for 2010 of reducing current smoking rates among high school students to < or = 16% (objective no. 27-2b).


Trigeminal ganglion neuron density and regulation of anterior choroid artery vasospasm: In a rabbit model of subarachnoid hemorrhage.
Subarachnoid hemorrhage (SAH) is associated with severe vasospasm caused by a variety of neurochemical mechanisms. The anterior choroid arteries (AChAs) are innervated by vasodilated fibers of the trigeminal ganglion (TGG). The goal of this study was to determine whether there is a relationship between the neuron density of the TGG and the severity of AChAs vasospasm with SAH. Thirty-two rabbits were used for the study; eight served as the baseline control group, seven as a SHAM group, with injections of 1 cc of isotonic saline solution, and 17 rabbits were included in the experimental SAH group, with injection of homologous blood into the cisterna magna. After 10 days, the histopathology of the AChAs and TGGs were examined. The AChAs vasospasm index (VSI) of the external/internal diameter and the neuron density of the ophthalmic root of the TGGs were evaluated stereologically. The AChAs VSI was preferred -- a measure of the degree of vasospasm. As the VSI increased, the degree of arterial vasospasm increased. The results were statistically analyzed. The mean AChAs VSI was significantly higher and the mean neuronal density of the ophthalmic root of the TGG was significantly lower in the group with severe vasospasm associated with SAH compared to the controls, SHAM, and the group with mild vasospasm associated with SAH (P< 0.05). The ophthalmic root of the TGG neuron density in the 7 rabbits that developed severe vasospasm was statistically less than that observed in the 10 rabbits with mild vasospasm. There was a linear relationship between the low neuronal density in the ophthalmic root of the TGG and the severity of the AChA vasospasm. The trigeminal ganglion neuron density may be an important factor in the regulation of AChAs diameter and cerebral blood flow. Low neuron density of the ophthalmic root of the TGG may play a role in the pathogenesis of AChAs vasospasm associated with SAH.


Recent advances in protection against doxorubicin-induced toxicity.
Anthracycline antibiotics are among the most effective and commonly used anticancer drugs. Unfortunately, their clinical use is restricted by dose-dependent toxicity. Doxorubicin is an anthracycline antibiotic and cytotoxic (antineoplastic) agent. It is commonly used against ovarian, breast, lung, uterine and cervical cancers, Hodgkin's disease, soft tissue and primary bone sarcomas, as well against in several other cancer types. It has been shown that free radicals are involved in doxorubicin-induced toxicity. Doxorubicin causes the generation of free radicals and the induction of oxidative stress, associated with cellular injury. This review illustrates recent applications of different natural products, drugs, drug delivery systems, and approaches for protection against doxorubicin-induced toxicity (2006-present).


A factor from neurons increases the number of acetylcholine receptor aggregates on cultured muscle cells.
There is an increase in the number of acetylcholine (AcCho) receptor aggregates on striated embryonic mouse myotubules when they are cocultured with clonal neuroblastoma-glioma hybrid cells. Medium conditioned by hybrid cells contains a factor which increases the number of AcCho receptor aggregates on myotubes cultured from mouse, rat or chick muscle. AcCho receptor-aggregating activity was present in medium conditioned by the neuroblastoma parent clone but was not detected in medium conditioned by cells of the parent glioma clone, fibroblasts, or HeLa cells. The factor increased the aggregation of AcCho receptors within 24 hr without a significant increase in the total number of AcCho receptors, and its action did not depend on myotube protein synthesis. The factor appears to rearrange the distribution of myotube AcCho receptors either by aggregating mobile AcCho receptors or by stabilizing labile receptor aggregates.


Psychiatric disorders in patients with intractable dizziness in the department of otolaryngology.
Vertigo and dizziness are often not fully explained by organic illnesses, but instead may be related to psychiatric disorders. It is important to determine the types of psychiatric comorbidities that are frequent in cases of intractable dizziness. The study subjects were 90 patients who had experienced intractable dizziness for more than three months and were referred to a psychiatrist when their symptoms could not be fully explained based on their physical illness. The patients' final diagnosis and questionnaire (DHI,SDS and STAI) scores were evaluated. Seventy percent (63/90) of patients with intractable dizziness had been diagnosed as having psychiatric conditions by the study psychiatrists. The most common diagnosis was unspecified depressive disorder. Psychiatric comorbidities seem to be more prevalent in certain subgroups of organic dizziness. We found a higher rate of depressive disorders in the sequelae of sudden deafness and migraine-related dizziness.


[Stratification of thoracic pain with modified HEART score and its relationship to short term cardiovascular events].
Chest pain is a major reason for emergency room care worldwide. The relationship between the Modified Heart Score and the presence of major cardiac events at 30 days after emergency admission was evaluated. Retrospective, observational study in a single centre on patients older than 18 years, who were treated for chest pain. The Modified HEART Score was applied at admission and related to the presence of major cardiac events (myocardial infarction, death, hospital re-admission due to cardiac causes, and percutaneous or surgical coronary revascularisation) at 30 days of follow-up. Of 158 patients analysed, 17 (10.8%) adverse events were found at follow-up. The modified HEART score could predict adverse events in 4%; 21.4%, and 100% of patients with scores 0-3; 4-6, and 7-10, respectively (P=.0001). A modified HEART score greater than or equal to 4 was associated with more adverse events (OR: 4.52; 95% CI 2.76-7.39) with a sensitivity of 70% and specificity of 84%. The application of the modified HEART score is useful for stratifying patients with chest pain into low, moderate, and high risk of cardiovascular complications, which should help the emergency units to improve their protocols for triage and diagnosis of acute coronary syndromes.


Thrombocytopenia in cirrhosis: Impact of fibrinogen on bleeding risk.
To investigate the relationship between baseline platelet count, clauss fibrinogen, maximum amplitude (MA) on thromboelastography, and blood loss in orthotopic liver transplantation (OLT). A retrospective analysis of our OLT Database (2006-2015) was performed. Baseline haematological indices and intraoperative blood transfusion requirements, as a combination of cell salvage return and estimation of 300 mls/unit of allogenic blood, was noted as a surrogate for intraoperative bleeding. Two groups: Excessive transfusion (> 1200 mL returned) and No excessive transfusion (< 1200 mL returned) were analysed. All data analyses were conducted using IBM SPSS Statistics version 23. Of 322 OLT patients, 77 were excluded due to fulminant disease; redo transplant or baseline haemoglobin (Hb) of < 80 g/L. One hundred and fourteen (46.3%) were classified into the excessive transfusion group, 132 (53.7%) in the no excessive transfusion group. Mean age and gender distribution were similar in both groups. Baseline Hb (P ≤ 0.001), platelet count (P = 0.005), clauss fibrinogen (P = 0.004) and heparinase MA (P = 0.001) were all statistically significantly different. Univariate logistic regression with a cut-off of platelets < 50 × 109/L as the predictor and Haemorrhage as the outcome showed an odds ratio of 1.393 (95%CI: 0.758-2.563; P = 0.286). Review of receiver operating characteristic curves showed an area under the curve (AUC) for platelet count of 0.604 (95%CI: 0.534-0.675; P = 0.005) as compared with AUC for fibrinogen level, 0.678 (95%CI: 0.612-0.744; P ≤ 0.001). A multivariate logistic regression shows United Kingdom model for End Stage Liver Disease (P = 0.006), Hb (P = 0.022) and Fibrinogen (P = 0.026) to be statistically significant, whereas Platelet count was not statistically significant. Platelet count alone does not predict excessive transfusion. Additional investigations, e.g., clauss fibrinogen and viscoelastic tests, provide more robust assessment of bleeding-risk in thrombocytopenia and cirrhosis.


The Probability of Resistant Hypertension During Dental Treatment of Chronic Kidney Disease Patients.
Oral rehabilitation in medically compromised patients like chronic kidney disease (CKD) needs special dental care. Many papers have been published on dental considerations for such individuals. However, literature citing oral care for patients with risk factors of CKD are scarce. Resistant hypertension, one such risk factor, is closely related to CKD. Furthermore, the associated increased prevalence and adverse renal/cardiac outcomes motivated the author to report its unexplored association/impact during dental care. The importance of assessing glomerular filtration rate is highlighted to better understand patients' medical conditions.


Profiling the transcription factor regulatory networks of human cell types.
Neph et al. (2012) (Circuitry and dynamics of human transcription factor regulatory networks. Cell, 150: 1274-1286) reported the transcription factor (TF) regulatory networks of 41 human cell types using the DNaseI footprinting technique. This provides a valuable resource for uncovering regulation principles in different human cells. In this paper, the architectures of the 41 regulatory networks and the distributions of housekeeping and specific regulatory interactions are investigated. The TF regulatory networks of different human cell types demonstrate similar global three-layer (top, core and bottom) hierarchical architectures, which are greatly different from the yeast TF regulatory network. However, they have distinguishable local organizations, as suggested by the fact that wiring patterns of only a few TFs are enough to distinguish cell identities. The TF regulatory network of human embryonic stem cells (hESCs) is dense and enriched with interactions that are unseen in the networks of other cell types. The examination of specific regulatory interactions suggests that specific interactions play important roles in hESCs.


Feasibility and Usability of Tele-interview for Medical Residency Interview.
Every year in the United States, medical students and residency programs dedicate millions of dollars to the residency matching process. On-site interviews for training positions involve tremendous financial investment, and time spent detracts from educational pursuits and clinical responsibilities. Students are usually required to fund their own travel and accommodations, adding additional financial burdens to an already costly medical education. Similarly, residency programs allocate considerable funds to interview-day meals, tours, staffing, and social events. With the rapid onslaught of innovations and advancements in the field of telecommunication, technology has become ubiquitous in the practice of medicine. Internet applications have aided our ability to deliver appropriate, evidence-based care at speeds previously unimagined. Wearable medical tech allows physicians to monitor patients from afar, and telemedicine has emerged as an economical means by which to provide care to all corners of the world. It is against this backdrop that we consider the integration of technology into the residency application process. This article aims to assess the implementation of technology in the form of web-based interviewing as a viable means by which to reduce the costs and productivity losses associated with traditional in-person interview days.


Endothelin-1 impairs glucose transporter trafficking via a membrane-based mechanism.
Endothelin-1 (ET-1) disrupts insulin-regulated glucose transporter GLUT4 trafficking. Since the negative consequence of chronic ET-1 exposure appears to be independent of signal disturbance along the insulin receptor substrate-1/phosphatidylinositol (PI) 3-kinase (PI3K)/Akt-2 pathway of insulin action, we tested if ET-1 altered GLUT4 regulation engaged by osmotic shock, a PI3K-independent stimulus that mimics insulin action. Regulation of GLUT4 by hyperosmotic stress was impaired by ET-1. Because of the mutual disruption of both insulin- and hyperosmolarity-stimulated GLUT4 translocation, we tested whether shared signaling and/or key phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated cytoskeletal events of GLUT4 trafficking were targets of ET-1. Both insulin and hyperosmotic stress signaling to Cbl were impaired by ET-1. Also, plasma membrane PIP2 and cortical actin levels were reduced in cells exposed to ET-1. Exogenous PIP2, but not PI 3,4,5-bisphosphate, restored actin structure, Cbl activation, and GLUT4 translocation. These data show that ET-1-induced PIP2/actin disruption impairs GLUT4 trafficking elicited by insulin and hyperosmolarity. In addition to showing for the first time the important role of PIP2-regulated cytoskeletal events in GLUT4 regulation by stimuli other than insulin, these studies reveal a novel function of PIP2/actin structure in signal transduction.


Seasonal height velocity variation in boys and girls 8-18 years.
This study investigated the seasonal variation in height velocity during the summer and winter months. The subjects were healthy children, 109 boys and 119 girls, 8.5-18.0 years of age who are part of an ongoing longitudinal study of bone mineral accrual. Anthropometric dimensions were taken twice a year, in the fall in conjunction with the annual bone assessment measures and 6 months later. Six-month velocities for height were calculated, which produced 982 velocities in boys and 1043 velocities in girls. Over the age range studied, summer velocities accounted for at least 67% of the total yearly growth in boys and 60% of the total yearly growth in girls. Separate two-way ANOVAs (season by age) were used to compare the summer and winter velocities over half-yearly age increments in both sexes. Season and age effects were significant (P < 0.01), but the interaction effect was not significant. The seasonal differences converged in the later years when the summer and winter velocities decreased to zero. The results demonstrate the importance of considering seasonal variation in height velocity in designing studies and in assessing and interpreting growth data. Am. J. Hum. Biol. 9:709-715, 1997. © 1997 Wiley-Liss, Inc.


A Case of Cardiac Calcified Amorphous Tumor Presenting with Concomitant ST-Elevation Myocardial Infarction and Occipital Stroke and a Brief Review of the Literature.
Cardiac calcified amorphous tumor (CAT) is an extremely rare benign intracavitary tumor of the heart. It may mimic other cardiac tumors and can present with signs or symptoms of systemic embolization. There are limited data regarding CAT in the literature. We report a case of a 68-year-old woman with a cardiac CAT and mitral annular calcification (MAC), who presented with acute ST-elevation myocardial infarction (STEMI) and occipital stroke. After extensive review of the literature, we believe that this case is possibly the first description of a cardiac CAT presenting with STEMI. The CAT was surgically removed, and the diagnosis was confirmed by histology. The patient tolerated the surgery and reported no events at 6-month follow-up.


A Giant Brunneroma Causing Gastrointestinal Bleeding and Severe Anemia Requiring Transfusion and Surgery.
Brunner's gland hamartoma, also called hyperplasia, adenoma, and Brunneroma, is an extremely rare benign proliferative lesion of Brunner's glands in the duodenum. While being mostly small and asymptomatic, they can result in gastrointestinal bleeding and obstruction. We report the case of a 54-year-old man presenting with melena and severe anemia requiring blood transfusion. CT scans showed a large mass of 8 cm in diameter, presumably arising in the duodenum. Endoscopic biopsies were not conclusive. As we were unable to determine the nature of the mass preoperatively and due to the severe symptoms, its size, and the uncertain malignant potential, a classic Whipple procedure was performed. The resected specimen showed extensive proliferation of Brunner's glands without signs of malignancy.


Nosocomial outbreak of infection with multidrug-resistant Acinetobacter baumannii in a medical center in Taiwan.
To investigate a nosocomial outbreak of infection with multidrug-resistant (MDR) Acinetobacter baumannii in the intensive care units at China Medical University Hospital in Taiwan. Prospective outbreak investigation. Three intensive care units in a 2,000-bed university hospital in Taichung, Taiwan. Thirty-eight stable patients in 3 intensive care units, all of whom had undergone an invasive procedure, were enrolled in our study. Ninety-four A. baumannii strains were isolated from the patients or the environment in the 3 intensive care units, during the period from January 1 through December 31, 2006. We characterized A. baumannii isolates by use of repetitive extragenic palindromic-polymerase chain reaction (REP-PCR) and random amplified polymorphic DNA (RAPD) fingerprinting. The clinical characteristics of the source patients and the environment were noted. All of the clinical isolates were determined to belong to the same epidemic strain of MDR A. baumannii by the use of antimicrobial susceptibility tests, REP-PCR, and RAPD fingerprinting. All patients involved in the infection outbreak had undergone an invasive procedure. The outbreak strain was also isolated from the environment and the equipment in the intensive care units. Moreover, an environmental survey of one of the intensive care units found that both the patients and the environment harbored the same outbreak strain. The outbreak strain of A. baumannii might have been transmitted among medical staff and administration equipment. Routine and aggressive environmental and equipment disinfection is essential for preventing recurrent outbreaks of nosocomial infection with MDR A. baumannii.


The Intersection of Gender and Other Social Institutions in Constructing Gender-Based Violence in Guangzhou China.
Although violence against women is illegal in China, few studies have been published concerning this issue in that country. This article is part of a program of research undertaken in one province of China. The purpose of this study was to understand, from the perspectives of women who have experienced gender-based violence (GBV), the intersections of gender and other social institutions in constructing GBV in Guangzhou, China. The research question was as follows: For women who have been unfortunate enough to be with a partner who is willing to use abuse, how is gender revealed in their discussion of the experience? Women participants (N = 13) were all over the age of 21, had experienced some form of abuse in an intimate relationship, and had lived in Guangzhou at least for a year prior to data collection. They had a variety of backgrounds and experiences. The majority spoke of GBV as common. "Saving face" was connected to fear of being judged and socially stigmatized which had emotional as well as material consequences. Eight situations in which social stigma existed and caused women to lose face were identified. Gender role expectations and gendered institutions played a part in family relationships and the amount of support a woman could expect or would ask for. The women in this study received very little support from systems in their society. A high proportion (67%) revealed symptoms of mental strain, and three talked about having depression or being suicidal. The results are discussed in terms of identifying the mechanisms by which systems interlock and perpetuate GBV.


Interactions between B lymphocytes and NK cells.
The ability of natural killer (NK) cells to secrete lymphokines confers upon them the potential to regulate cell types via mechanisms other than direct cytotoxicity. During the past few years increasing evidence has been accumulating to show that NK and B cells can interact productively. First, NK cells cocultured with B cells can induce them to initiate polyclonal Ig secretion. This help is mediated by a soluble factor (or factors) that appears to be different from any known cytokine. Second, preactivated B lymphocytes can induce NK cells to produce greater amounts of IFN-gamma via an interaction that requires direct cell contact. Third, in contrast to previous suggestions, NK cells do not have the ability to kill primary B lymphocytes regardless of their stage of differentiation. Evaluation of the in vivo relevance of these interactions revealed that activated NK cells can increase the IgG2a response to a specific protein antigen. Without activation, NK cells neither enhance nor inhibit B cell responses to antigens. The deviation of the isotype distribution may allow increased NK cell specificity for certain pathogens by enhancing antibody-dependent cytotoxicity.


iMap intravascular ultrasound evaluation of culprit and non-culprit lesions in patients with ST-elevation myocardial infarction.
The purpose of this study was to evaluate plaque characteristics of culprit and non-culprit lesions in ST-elevation myocardial infarction (STEMI) patients at the index procedure and 10 months later using iMap intravascular ultrasound (IVUS). The exact site of the plaque rupture or erosion in coronary arteries with subsequent thrombosis cannot be precisely defined. Our hypothesis is that in STEMI patients angiographically guided stenting could fail to identify necrotic tissue and thus may leave an uncovered significant amount of vulnerable plaque. In 63 consecutive STEMI patients the culprit artery was analyzed with iMap IVUS at the time of the index procedure and 10 months later. The most stenotic culprit segment was compared to the segment proximal to the culprit lesion. A high percentage of necrotic tissue was observed in the culprit lesion and a comparatively lower percentage of necrotic tissue was observed in the non-culprit lesions proximal to the culprit at the index procedure by iMap IVUS (31.9%±10.0% vs 27.8%±11.8%, p=0.012). The proportion of necrotic tissue in the segment proximal to the culprit lesion was unchanged at 10-month follow-up (27.1%±11.9% vs 25.5%±12.8%, p=0.147). The percentage of lipidic tissue in the proximal segment decreased at 10-month follow-up (9.8%±2.9% vs 8.8±3.0%, p=0.009). In STEMI patients, culprit lesion segments and non-culprit segments contain high proportions of necrotic tissue. However, a comparatively higher proportion of necrotic tissue was found in the culprit lesions according to iMap IVUS. The percentage of necrotic tissue remained high at 10-month follow-up in both culprit and non-culprit segments.


Accumulation of basophils and their chemotactic activity in the airways during natural airway narrowing in asthmatic individuals.
To investigate cellular differentials in natural airway narrowing of steroid-dependent asthmatic individuals, we performed bronchoalveolar lavage (BAL) on 10 inpatients with asthma treated only with bronchodilators during episodes of natural airway narrowing evaluated by serial monitoring of peak expiratory flow (PEF), and on nine normal volunteers. We confirmed that the airway narrowing was not completely reversed by salbutamol aerosol just before the BAL study, but was completely reversed by administration of systemic steroid after the BAL study. Thus, the natural airway narrowing investigated in this study consisted not only of the constriction of airway smooth muscle, but also of edema of the airway mucosa and/or secretion in airways. Both the numbers and percentages of eosinophils and alcian blue-positive cells in BAL fluids from the asthmatic subjects were significantly higher than those of normals, but the numbers and percentages of neutrophils, lymphocytes, and macrophages were not. Thus, eosinophils and alcian blue-positive cells selectively increased in the airways during the natural airway narrowing. Because we found that the metachromatic cells consisted of two types, with a single nucleus and with segmented nuclei, we further examined basophil chemotactic activity (BCA) in BAL fluids. We showed that BCA was significantly higher in the asthmatic (79.3 +/- 17.2 cells/5 hpf) than in the normal subjects (6.2 +/- 1.6 cells/5 hpf), and also that the activity was more strongly correlated with the cells having segmented nuclei (p = 0.95) than with all of the cells (p = 0.73).(ABSTRACT TRUNCATED AT 250 WORDS)


FSH is produced by GnRH-deficient men and is suppressed by testosterone.
Because there is an unexpected action of testosterone (T) to increase follicle-stimulating hormone (FSH) production in the absence of gonadotropin-releasing hormone (GnRH) in the rat, the effects of T treatment on circulating FSH were studied in men with GnRH deficiency. FSH immunoreactivity was identified in serum using a sensitive two-site immunoassay in each of five untreated GnRH-deficient men. Analysis by gel filtration chromatography revealed that circulating immunoreactive FSH coeluted with radiolabeled authentic FSH. T enanthate treatment suppressed serum FSH levels in each subject from (mean +/- standard error of the mean [SEM]) 1.02 +/- 0.94 to 0.26 +/- 0.21 mIU/ml (P = 0.061, Wilcoxon rank sum test). Thus, FSH is produced in GnRH-deficient men, but there is no evidence for the stimulatory effect of T on FSH production in the absence of GnRH, as observed in the rat. These preliminary data provide further evidence that male contraceptive strategies using GnRH antagonists to suppress LH and FSH production in normal men will not be counteracted by T replacement therapy, although the issue deserves further attention in that study population.


Ubiquitin Chain Enrichment Middle-Down Mass Spectrometry Enables Characterization of Branched Ubiquitin Chains in Cellulo.
Ubiquitin (Ub) has a broad functional range that has been ascribed to the formation of an array of polymeric ubiquitin chains. Understanding the precise roles of ubiquitin chains, however, is difficult due to their complex chain topologies. Branched ubiquitin chains are particularly challenging, as multiple modifications on a single ubiquitin preclude the use of standard bottom-up proteomic approaches. Developing methods to overcome these challenges is crucial considering evidence suggesting branched chains regulate the stability of proteins. In this study, we employ Ubiquitin Chain Enrichment Middle-down Mass Spectrometry (UbiChEM-MS) to identify branched chains that cannot be detected using bottom-up proteomic methods. Specifically, we employ tandem ubiquitin binding entities (TUBEs) and the K29-selective Npl4 Zinc Finger 1 (NZF1) domain from the deubiquitinase TRABID to enrich for chains from human cells. Minimal trypsinolysis followed by high resolution mass spectrometric analysis reveals that Ub chain branching can indeed be detected using both Ub binding domains (UBDs) tested at endogenous levels. We find that ∼1% of chains isolated with TUBEs contain Ub branch points, with this value rising to ∼4% after proteasome inhibition. Electron-transfer dissociation (ETD) analysis indicates the presence of K48 in these branched chains. The use of the NZF1 domain reveals that ∼4% of the isolated chains contain branch points with no apparent dependence on proteasome inhibition. Our results demonstrate an effective strategy for detecting and characterizing the dynamics of branched conjugates under different cellular conditions.


Reconciling the economic and biological fishery data gathered through the European Data Collection Framework: A new R-tool.
Fishing fleets and targeted stocks are the basis for the design of multiannual management plans at European or Mediterranean levels. Management Strategy Evaluation and bioeconomic modeling need data at a specific level of resolution in terms of time, area and type of fishing activity for analyzing measures for management procedures using simulations. Within the Data Collection Framework, data are to be aggregated at different levels, e.g.: fleet segment and métier, the former linked to the predominant gear and the size of the vessel and the latter to the activity itself. Fishing costs are collected by fleet segment, effort and landings by fleet segment and métier. Bioeconomic modeling for management purposes requires data at the same resolution. The aim of this paper is to describe a methodology, implemented in SECFISH R package, to disaggregate variable cost data from the fleet segment to the métier level. The presented tool allows to determine the correlation between the variable costs of a vessel and its activities to estimate costs at the activity level (e.g. métiers). The tool is applied to selected Italian fleet segments characterized by a variety of métiers and high dynamicity.


Single intraoperative infrared laser optimized bone repair in rat femoral osteotomies with experimentally induced osteoporosis.
This study aimed to evaluate the effect of infrared laser (IRL) on bone repair in ovariectomized rats subjected to femoral osteotomies. Of 32 rats, half underwent bilateral ovariectomy (OVX) and the other half underwent sham ovariectomy (SHAM). A period of 3 months was defined to observe the presence of osteoporosis. The rats were subjected to osteotomies in the femurs and then fixed with a miniplate and 1.5-mm system screws. Thereafter, half of the rats from both SHAM and OVX groups were not irradiated, and the other half were irradiated by IRL using the following parameters: wavelength, 808 nm; power, 100 mW; 60 s for each point; 6 J/point; and a total of 5 points of bone gap. All animals were euthanized 60 days after surgery. The femur gap was scanned using micro-computed tomography (micro-CT). The samples were then examined under a confocal laser microscope to determine the amounts of calcein and alizarin red. The slides were stained with alizarin red and Stevenel's blue for histometric analysis. In the micro-CT analysis, the OVX groups had the lowest bone volume (P < 0.05). When the laser was applied to the OVX groups, bone turnover increased (P < 0.05). New bone formation (NBF) was comparable between SHAM and OVX/IR (P > 0.05) groups; however, it was less in the OVX groups (P < 0.05). In conclusion, the results encourage the use of IRL intraoperatively as it optimizes bone repair, mainly in animals with low bone mineral density.


Mechanism of lunar polarization.
A theoretical model to explain the negative polarization of moonlight at small lunar phase angles is developed. The model is based on the polarization of light in the diffraction region bordering the geometric shadow of an opaque dielectric obstacle.


Selection of Candidate Reference Genes for Gene Expression Analysis in Kentucky Bluegrass (Poa pratensis L.) under Abiotic Stress.
Kentucky bluegrass (Poa pratensis L.) belong to Gramineae and is widely used in lawns, golf courses, landscapes, and sport fields as a prominent cool-season grass. Gene expression patterns during different stages of plant development can provide clues toward the understanding of its biological functions. The selection and validation of reference genes are the first steps in any real-time quantitative PCR gene expression study. Therefore, suitable reference genes are necessary for obtaining reliable results in real-time quantitative PCR analyses of Kentucky bluegrass. In the present study, 9 candidate reference genes were chosen, and their expression stability in the leaves and roots of Kentucky bluegrass under different stresses (drought, salt, heat, and cold) were evaluated using the GeNorm, NormFinder, BestKeeper, and RefFinder programs. The results showed that the expression stability of the candidate reference genes was dependent on the experimental conditions. The combination of SAM with GAPDH was the most stable in leaves under salt stress and cold stress, while TUB combined with ACT or GAPDH was stable in roots under salt or cold stress, respectively. ACT and SAM maintained stable expression in drought-treated leaves, and GAPDH combined with ACT was stable in drought-treated roots. SAM and TUB exhibited stable expression in heat-treated leaves. ACT and RPL were stable in heat-treated roots. In addition, the expression patterns of PpFEH in response to drought and cold stress were used to confirm the reliability of the selected reference genes, indicating that the use of an inappropriate reference gene as the internal control will cause erroneous results. This work is the first study on the expression stability of reference genes in Kentucky bluegrass and will be particularly useful in the selection of stress-tolerance genes and the identification of the molecular mechanisms conferring stress tolerance in this species.