Proteomic analysis of the Simkania-containing vacuole: the central role of retrograde transport.
Simkania negevensis is an obligate intracellular bacterial pathogen that grows in amoeba or human cells within a membrane-bound vacuole forming endoplasmic reticulum (ER) contact sites. The membrane of this Simkania-containing vacuole (SnCV) is a critical host-pathogen interface whose origin and molecular interactions with cellular organelles remain poorly defined. We performed proteomic analysis of purified ER-SnCV-membranes using label free LC-MS(2) to define the pathogen-containing organelle composition. Of the 1,178 proteins of human and 302 proteins of Simkania origin identified by this strategy, 51 host cell proteins were enriched or depleted by infection and 57 proteins were associated with host endosomal transport pathways. Chemical inhibitors that selectively interfere with trafficking at the early endosome-to-trans-Golgi network (TGN) interface (retrograde transport) affected SnCV formation, morphology and lipid transport. Our data demonstrate that Simkania exploits early endosome-to-TGN transport for nutrient acquisition and growth.


Shift of µ-opioid Receptor Signaling in the Dorsal Reticular Nucleus Is Implicated in Morphine-induced Hyperalgesia in Male Rats.
Increased descending pain facilitation accounts for opioid-induced hyperalgesia, but the underlying mechanisms remain elusive. Given the role of µ-opioid receptors in opioid-induced hyperalgesia in animals, the authors hypothesized that the dorsal reticular nucleus, a medullary pain facilitatory area, is involved in opioid-induced hyperalgesia through altered µ-opioid receptor signaling. The authors used male Wistar rats (n = 5 to 8 per group), chronically infused with morphine, to evaluate in the dorsal reticular nucleus the expressions of the µ-opioid receptor and phosphorylated cAMP response element-binding, a downstream marker of excitatory µ-opioid receptor signaling. The authors used pharmacologic and gene-mediated approaches. Nociceptive behaviors were evaluated by the von Frey and hot-plates tests. Lidocaine fully reversed mechanical and thermal hypersensitivity induced by chronic morphine. Morphine-infusion increased µ-opioid receptor, without concomitant messenger RNA changes, and phosphorylated cAMP response element-binding levels at the dorsal reticular nucleus. µ-opioid receptor knockdown in morphine-infused animals attenuated the decrease of mechanical thresholds and heat-evoked withdrawal latencies compared with the control vector (von Frey [mean ± SD]: -17 ± 8% vs. -40 ± 9.0%; P < 0.001; hot-plate: -10 ± 5% vs. -32 ± 10%; P = 0.001). µ-opioid receptor knockdown in control animals induced the opposite (von Frey: -31 ± 8% vs. -17 ± 8%; P = 0.053; hotplate: -24 ± 6% vs. -3 ± 10%; P = 0.001). The µ-opioid receptor agonist (D-ALA2,N-ME-PHE4,GLY5-OL)-enkephalin acetate (DAMGO) decreased mechanical thresholds and did not affect heat-evoked withdrawal latencies in morphine-infused animals. In control animals, DAMGO increased both mechanical thresholds and heat-evoked withdrawal latencies. Ultra-low-dose naloxone, which prevents the excitatory signaling of the µ-opioid receptor, administered alone, attenuated mechanical and thermal hypersensitivities, and coadministered with DAMGO, restored DAMGO analgesic effects and decreased phosphorylated cAMP response element-binding levels. Chronic morphine shifted µ-opioid receptor signaling from inhibitory to excitatory at the dorsal reticular nucleus, likely enhancing descending facilitation during opioid-induced hyperalgesia in the rat.


The use of unlicensed assistive personnel: an update and skeptical look at a role that may present more problems than solutions.
Patients implicitly rely on nurses to be their advocate. They trust nurses for health care information (92%). Approximately three fourths of Americans rated nurses' honesty and ethics as either "high" or "very high, placing them above any other profession. It is time to reconsider the full implication of Florence Nightingale's admonition to do the sick no harm in terms of staffing.


Magnetic resonance imaging in the diagnosis of periodontal and periapical disease.
Early pre-clinical inflammatory changes in periodontal and/or periapical lesions, which typically precede bone loss, are challenging to diagnose using ionizing-radiation-based imaging modalities. MRI provides relevant additional diagnostic information of inflammatory processes in soft and hard tissues. The aim of the present study is to undertake a systematic review of the literature on MRI in the diagnosis of periodontal and/or periapical disease. The PubMed/MEDLINE and Scopus bibliographic databases were searched (2000-2021) using the search string: ("MRI" or "magnetic resonance imaging") and ("periodontitis" or "periodontal" or "apical pathology" or "endodontic pathology" or "periapical" or "furcation" or "intrabony"). The search was limited to studies published in English. The studies were assessed independently by three reviewers, focusing on the MRI sequences, imaging modalities (radiographs, cone beam CT (CBCT), and MRI), disease definition, assessed parameters, and outcome measurements. The search strategy yielded 34 studies, from which 13 were included. Overall, the findings of MRI were in agreement with CBCT. The studies showed that MRI provided diagnostic information of the hard and soft tissue components affected by periodontal and/or periapical disease with a fairly high sensitivity and specificity. However, the assessed parameters (e.g. MRI acquisition protocols, and disease definition) differed substantially. The included studies indicate that the use of MRI in the diagnosis of periodontal and/or periapical disease is feasible and promising. More studies are needed to define the accuracy of this non-ionizing-radiation-based diagnostic modality, in the assessment of periodontal and/or periapical lesions.


A revised home treatment algorithm for Fabry disease: influence of antibody formation.
Enzyme replacement therapy for Fabry disease, consisting of biweekly infusions, interferes daily life. Home treatment proved beneficial. We evaluated a previously reported home treatment algorithm aiming to shorten the period of in-hospital infusions, while ascertaining patient safety. Retrospective analysis on clinical records of treated Fabry patients. Potentially predictive factors for infusion associated reactions (IARs) were studied: agalsidase antibodies, agalsidase product and dose, FOS-SSI scores, and GLA activity and mutation. A questionnaire evaluated patient satisfaction and compliance. Seventy-nine patients were included (41 males, 46% agalsidase antibody positive (AB+)). 85% received home treatment. Home treatment complications were erroneous fast infusion rates (n=4) causing IARs and, rarely, venous access problems. The single SAE was unrelated to home treatment. IgG antibody status was significantly associated with IARs (89% vs. 26% p-value<0.01). Negative antibody status did not preclude IARs. Except for three AB+ patients, all first IARs occurred within 13 infusions. IARs occurred more frequently in patients using agalsidase beta 1.0 mg/kg/eow than agalsidase alpha or beta 0.2 mg/kg/eow, but the time to first IAR did not differ between groups. Four AB+ males experienced IARs after a dose increase. Compliance between home and in-hospital treatment was similar. Most patients preferred home treatment. In this study home therapy for Fabry disease was safe and improved patient satisfaction. We propose a revised algorithm which allows safe home-treatment in all male patients after 13 instead of 26 infusions, irrespective of ERT preparation or dose. Furthermore, AB+ patients with dosage increase may experience new or increased IARs, necessitating in-hospital observations.


Endoscopic Endonasal Approach to Multilobular Giant Pituitary Adenoma with Cavernous Sinus Invasion and Petroclival Extension.
Giant pituitary adenomas are considered a surgical challenge. Their invasiveness, irregular growth, and extensions make this surgery critical. Because of this reason, the radical resection rate is low in such pathology. The endoscopic endonasal approach pushes its limits to get successful results in skull base lesions. Irregular shape, cavernous sinus invasion, and extensions are being successfully resected during the last decades. Lateral extension, especially posterolateral extension, of this tumor makes them impossible to radical resection. In this video case, we try to present an expanded endonasal approach to the irregular giant pituitary adenoma with a 360° cavernous sinus invasion and petroclival extension of the tumor. We are presenting a patient with an irregular-shaped giant pituitary adenoma who underwent an expanded endonasal approach for this reason. This is a 27-year-old male patient admitted with right-sided ophthalmoplegia and visual deterioration mainly in the left eye. Multilobular giant pituitary adenoma with right cavernous sinus involvement presented on magnetic resonance imaging. Right internal carotid artery (ICA) encased 360° with the tumor. The tumor extends to the petroclival region on the right side and compresses the brainstem. Anteriorly, tumor extends to the gyrus rectus and compresses the left optic nerve. 0:45: As usual we are preparing a wide nasoseptal flap for the reconstruction at the end of the surgery. We do it routinely in cases of giant pituitary adenoma surgery to avoid cerebrospinal fluid leak after the surgery. 1:00: The next step is drilling the anterior wall of the sphenoid sinus and opening the corridor to achieve enough space that lets us maneuver at the skull base. It is important to make a wide exposure to gain a high control of important anatomic structures at the skull base. 1:15: After the opening of the sellar floor, we made a "U-shaped" incision on the dura, taking a biopsy for the histopathological investigation and started debulking the tumor. The tumor tissue is soft and it is possible to remove it with suction. 2:08: Although the sellar part is removed, we are trying to remove the tumor from the posterior and superior part of the cavernous sinus. 2:28: To achieve access to the anterior part of the cavernous sinus we are drilling the bone overlying the anterior wall of the cavernous sinus on the right side. Then we are using micro-Doppler to identify the location of ICA. We made an incision lateral to the ICA, to widen the dural opening. To avoid possible carotid injury we are placing a cottonoid under the dura. Then we enter the space and remove the tumor inside the cavernous sinus as much as possible. 3:54: Removing the periosteum covering the sellar floor makes us reach the posterior clinoidal process. In order to gain an access to petroclival regoin inferior wall of sellar floor drilled out and middle and posterior clinoidal processes were removed by drilling. Removal of anterior petrous process has been done so manipulation of tumor would become easy. Now we can see the paraclival petrosal dura lying posterior to the ICA, at the foramen lacerum. 4:48: We are cutting the dura and widening the defect to enter the petroclival region. After entering the space we are trying to dissect out surrounding neurovascular tissue. Although the tumor is located inferior to the entering point and because mobilization of the tumor inferiorly is unachievable, we are pulling the tumor capsule to remove the soft component of the tumor with suction. As you can see, the tumor removed totally, and the tumor capsule is resected for achieving radical resection. 6:17: After complete resection of the extended part of the tumor to the posterior fossa we are inspecting the surgical area. 6:34: After the removal of the tumor as the last step, we are packing the cavity with fat graft and covering with vascularized nasoseptal flap. Postoperative first day magnetic resonance imaging shows near-total removal of the tumor. The patient did well after surgery. He had no hypopituitarism and diabetes insipidus after the surgery. Cerebrospinal fluid leak was not observed. Unfortunately, oculomotor palsy did not improve after surgery (Video 1).


Identification and characterization of a potent and selective inhibitor of human urate transporter 1.
Selective inhibitors of human urate transporter 1 (hURAT1) are considered to be effective treatment for hyperuricemia and gout, which can reduce the reabsorption of more than 90% of uric acid in the proximal tubule of the kidney. We aimed to design and synthesize a more potent hURAT1 based on the structure of Lesinurad (LU), which was reported to lower uric acid levels with IC50 value of hURAT1 (about 60μM). A cell model was conducted and characterized via Real-time qRCR and Western blot. We synthesized and identified a new midazole analogue of LU. Cells stably-expressing hURAT1 or human organic anion transporter 1 (hOAT1) were used in the [14C] urate or 6-carboxyfluorescein (6-CF) uptake assays to test the activities of the newly synthesized compound. The uric acid lowering effects of LU and LUM and their effects on urea nitrogen and creatinine in potassium oxonate-induced hyperuricemic rats were analyzed. The [14C] Urate uptake assay using hURAT1 stably transfected MDCK cells indicated that LUM was more potent than LU against hURAT1, with IC50 values of 3.22μM and 65.47μM, respectively. LU and LUM also effectively suppressed hOAT1-mediated 6-CF uptake, and the IC50 hURAT1/IC50 hOAT1 of LU and LUM was1.49 and 0.35 respectively, indicating a better selectivity for LUM than LU. In vivo, LUM-Na (40mg/kg) showed more potent activity in reducing serum uric acid levels in potassium oxonate-induced hyperuricemic rats, compared to similar doses of LU-Na. LUM was demonstrated to be as potent a uricosuric drug as LU.


Compassion for simulation.
This topic for debate explores how simulation based education has become an area where Higher Education providers look to deliver on an agenda of recruiting, educating and assessing for compassion. This paper offers that rather than SBE being a forum for developing and promoting compassion it may actually be achieving the opposite both for those we educate and those they in turn care for. It does this through introducing two ideas, near enemies and Jung's shadow and uses these ideas to explore our understanding and expression of compassion through simulation.


Gut-Brain-Skin Axis in Psoriasis: A Review.
Psoriasis is a common skin disease, with chronic inflammation and a complex etiology. It has long been recognized that chronic skin conditions and mental health disorders are often co-morbid. Thus, the concept of the gut-brain-skin axis emphasized in mental health disorders may also regulate the health of skin. The gut microbiota has been found to be the bridge between the immune system and nervous system. By leveraging clinical cases and animal models of psoriasis, an important communication pathway has been identified along the gut-brain-skin axis that is associated with the modulation of neurotransmitters from the microbiota. Furthermore, mammalian neurotransmitters, including dopamine, serotonin, or γ-aminobutyric acid (GABA), can be produced and/or consumed by several types of bacteria. Other studies suggest that manipulating these neurotransmitters by bacteria may have an effect on host physiology, and the levels of neurotransmitter can be altered by microbiota-based interventions. Nonetheless, it is unknown whether or not the manipulation of neurotransmitter levels by bacteria can affect the occurrence and development of psoriasis. Notably, preliminary experiments found that oral consumption of probiotics improves the clinical symptoms in patients with psoriasis, perhaps correlated with the gut microbiome-mediated crosstalk between the immune system and the nervous system by secreting neurotransmitters in psoriasis. In this review, the communication along the gut-brain-skin axis is discussed.


Dual-task performance and the hick-hyman law of choice reaction time.
The slope, intercept, and linearity of the function relating RT and stimulus information reflect different aspects of information processing. This experiment determined which aspects of information processing are affected by the presence of a secondary task. Subjects (n = 12) performed a one-dimensional tracking task concurrently with a choice RTtask. Subjects also performed each task singly. Half of the subjects performed under dual-task conditions with adjacent displays, half with separated displays. For the adjacent group the tracking task had no reliable effect on either the slope, intercept, or linearity of the relation. Scanning affected only the intercept for the separated group. Error on the tracking task was found to increase linearly with increased processing load on the choice RT task for both groups. The results are interpreted as supporting a modified single-channel theory.


Analysis of the Li-Fraumeni Spectrum Based on an International Germline TP53 Variant Data Set: An International Agency for Research on Cancer TP53 Database Analysis.
Li-Fraumeni syndrome is a cancer predisposition syndrome that is associated with a high, lifelong risk of a broad spectrum of cancers that is caused by pathogenic TP53 germline variants. A definition that reflects the broad phenotypic spectrum that has evolved since the gene discovery is lacking, and mechanisms leading to phenotypic differences remain largely unknown. To define the phenotypic spectrum of Li-Fraumeni syndrome and conduct phenotype-genotype associations across the phenotypic spectrum. We analyzed and classified the germline variant data set of the International Agency for Research on Cancer TP53 database that contains data on a cohort of 3034 persons from 1282 families reported in the scientific literature since 1990. We defined the term Li-Fraumeni spectrum to encompass (1) phenotypic Li-Fraumeni syndrome, defined by the absence of a pathogenic/likely pathogenic TP53 variant in persons/families meeting clinical Li-Fraumeni syndrome criteria; (2) Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in persons/families meeting Li-Fraumeni syndrome testing criteria; (3) attenuated Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in a person/family with cancer who does not meet Li-Fraumeni syndrome testing criteria; and (4) incidental Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in a person/family without a history of cancer. Data analysis occurred from November 2020 to March 2021. Differences in variant distribution and cancer characteristics in patients with a germline TP53 variant who met vs did not meet Li-Fraumeni syndrome testing criteria. Tumor spectra showed significant differences, with more early adrenal (n = 166, 6.5% vs n = 0), brain (n = 360, 14.17% vs n = 57, 7.46%), connective tissue (n = 303, 11.92% vs n = 56, 7.33%), and bone tumors (n = 279, 10.98% vs n = 3, 0.39%) in patients who met Li-Fraumeni syndrome genetic testing criteria (n = 2139). Carriers who did not meet Li-Fraumeni syndrome genetic testing criteria (n = 678) had more breast (n = 292, 38.22% vs n = 700, 27.55%) and other cancers, 45% of them occurring after age 45 years. Hotspot variants were present in both groups. Several variants were exclusively found in patients with Li-Fraumeni syndrome, while others where exclusively found in patients with attenuated Li-Fraumeni syndrome. In patients who met Li-Fraumeni syndrome genetic testing criteria, most TP53 variants were classified as pathogenic/likely pathogenic (1757 of 2139, 82.2%), whereas 40.4% (404 of 678) of TP53 variants identified in patients who did not meet the Li-Fraumeni syndrome genetic testing criteria were classified as variants of uncertain significance, conflicting results, likely benign, benign, or unknown. The findings of this cohort study suggest that this new classification, Li-Fraumeni spectrum, is a step toward understanding the factors that lead to phenotypic differences and may serve as a model for other cancer predisposition syndromes.


Prediction of SYNTAX score II improvement by adding temporal heart rate changes between discharge and first outpatient visit in patients with acute myocardial infarction.
The prognostic ability of the temporal changes in resting heart rate (ΔHR) in patients with acute myocardial infarction (AMI) for cardiovascular (CV) mortality and clinical outcomes is rarely examined. This study investigated the predictive value of ΔHR using models with SYNTAX score II (SxS-II) for the long-term prognosis of patients with AMI. Six hundred five AMI patients with vital signs recorded at the first outpatient visit (2-4 weeks after discharge) were retrospectively recruited into this study. The changes between discharge and outpatient resting heart rate (D-O ΔHR) were calculated by subtracting the HR at the first post-discharge visit from the value recorded at discharge. The major adverse cardiovascular and cerebrovascular events (MACCE) include cardiovascular death, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predictive values and reclassification ability of the different models were assessed using a likelihood ratio test, Akaike's information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During the follow-up period, a drop-in resting heart rate (RHR) from discharge to first outpatient visit was independently associated with less risk of CV mortality [D-O ΔHR: hazards ratio (HR) = 0.97, 95% CI = 0.96-0.99, P < 0.001] and MACCE (HR = 0.98, 95% CI = 0.97-0.99, p = 0.001). The likelihood test indicated that the combined model of SxS-II and D-O ΔHR yielded the lowest AIC for CV mortality and MACCE (P < 0.001). Moreover, D-O ΔHR alone significantly improved the net reclassification and integrated discrimination of the models containing SxS-II for CV mortality and MACCE (CV mortality: NRI = 0.5600, P = 0.001 and IDI = 0.0759, P = 0.03; MACCE: NRI = 0.2231, P < 0.05 and IDI = 0.0107, P < 0.05). The change in D-O ΔHR was an independent predictor of long-term CV mortality and MACCE. The D-O ΔHR combined with SxS-II could significantly improve its predictive probability.


Determination of acid value during edible oil storage using a portable NIR spectroscopy system combined with variable selection algorithms based on an MPA-based strategy.
The acid value is an important indicator for evaluating the quality of edible oil during storage. This study employs a portable near-infrared (NIR) spectroscopy system to determine the acid value during edible oil storage. Four MPA-based variable selection methods, namely competitive adaptive reweighted sampling (CARS), the variable iterative space shrinkage approach (VISSA), iteratively variable subset optimization (IVSO), and bootstrapping soft shrinkage (BOSS) were introduced to optimize the preprocessed NIR spectra. Support vector machine (SVM) models based on characteristic spectra obtained by different selection methods were then established to achieve quantitative detection of the acid value during edible oil storage. The results revealed that, compared with the full-spectrum SVM model, the SVM models established by the characteristic wavelengths optimized by the variable selection methods based on the MPA strategy exhibit a significant improvement in complexity and generalization performance. Furthermore, compared with the CARS, VISSA, and IVSO methods, the BOSS method obtained the least number of characteristic wavelength variables, and the SVM model established based on the optimized features of this method exhibited the optimal prediction performance. The root mean square error of prediction (RMSEP) was 0.11 mg g-1, the coefficient of determination (Rp2) was 0.92 and the ratio performance deviation (RPD) was 2.82, respectively. The overall results indicate that the variable selection methods based on the MPA strategy can select more targeted characteristic variables. This has good application prospects in NIR spectra feature optimization. © 2020 Society of Chemical Industry.


Curcumin and its uses in active and smart food packaging applications - a comprehensive review.
Active and intelligent food packaging is an innovative technology to prevent food contamination and ensure food quality and safety. Active packaging protects the food from microbial contamination, while smart or intelligent packaging enables monitoring the freshness of the food or quality change in real-time. Curcumin, one of the most well-known natural colorants, has received a lot of attention for its excellent functional properties and ability to change color with changes in pH. Curcumin, the golden component of turmeric, a spice widely used in food since ancient times, is a cost-effective and abundant biomaterial with various biological properties such as antioxidant, antibacterial, antiviral, antitumor, and anti-inflammatory. Recently, active packaging or intelligent packaging systems have been actively developed using the functional properties of curcumin. In this review, we briefly reviewed curcumin's basic biological functions and discussed comprehensive and recent progress in using curcumin in various polymer-based active and smart food packaging applications.


N-terminal tau truncation in the pathogenesis of Alzheimer's disease (AD): Developing a novel diagnostic and therapeutic approach.
Tau truncation occurs at early stages during the development of human Alzheimer's disease (AD) and other tauopathy dementias. Tau cleavage, particularly in its N-terminal projection domain, is able to drive per se neurodegeneration, regardless of its pro-aggregative pathway(s) and in fragment(s)-dependent way. In this short review, we highlight the pathological relevance of the 20-22 kDa NH2-truncated tau fragment which is endowed with potent neurotoxic "gain-of-function" action(s), both in vitro and in vivo. An extensive comment on its clinical value as novel progression/diagnostic biomarker and potential therapeutic target in the context of tau-mediated neurodegeneration is also provided.


Structure and dynamics of the core US air travel markets: A basic empirical analysis of domestic passenger demand.
The air transportation industry in the US has undergone significant restructuring since 2001. While adjustments in costs have been the focus of the industry, changes in the demand structure have also occurred. This paper analyses the structure and dynamics of the origin and destination of core air travel market demand using 1995-2006 US quarterly time-series data. Despite the industry consolidating its network following the terrorist attacks of 2001, passenger travels in core markets have exhibited strong growth in recent years. This increase was driven mostly by the gains in the larger markets. When segmented by types of markets, super-thin markets are seen to have lost services while other markets gained. A majority of passengers use the thick markets that account for only a small portion of all markets and their demand has continued to grow. Relatively fewer passengers fly in the thin and super-thin markets, but they account for a substantial portion of all markets. Empirical estimates align well with the events and adjustments that have been experienced during the time series we examined.


Circulating endocannabinoids in insulin sensitive vs. insulin resistant obese postmenopausal women. A MONET group study.
To measure the circulating levels of endocannabinoids and related molecules at fasting, after acute hyperinsulinemia and after weight loss in insulin sensitive vs. insulin resistant obese postmenopausal women. The sample consisted of 30 obese postmenopausal women (age: 58.9 ± 5.2 yrs; BMI: 32.9 ± 3.6 kg/m(2) ). Subjects underwent a 3-hour hyperinsulinaemic-euglycaemic clamp (HEC) (glucose disposal rate (M-value): 10.7 ± 3.3 mg min(-1) kg(-1) FFM) and 6-month weight loss intervention. Participants were classified as insulin sensitive obese (ISO) or insulin resistant obese (IRO) based on a predefined cutoff. Plasma levels of the endocannabinoids, anandamide (AEA), 2-arachidonoylglycerol (2-AG), and of the AEA-related compounds, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), were measured by liquid chromatography-mass spectrometry. IRO presented higher levels of 2-AG (P < 0.05) independently of the HEC and weight loss, whereas the HEC had an independent inhibitory effect on AEA, PEA, and OEA levels (P < 0.05) in both groups. Furthermore, there was an independent stimulatory effect of weight loss only on PEA levels in both groups (P < 0.05). This study is the first to show that higher circulating levels of the endocannabinoid 2-AG are found in IRO compared to ISO postmenopausal women, and that weight loss is associated with an increase in PEA, a PPAR-α ligand.


[Head and neck localizations of hydatid cyst: A series of 17 cases].
Head and neck localizations of hydatid cyst are very rare (1% of human cases) even in countries where echinococcosis is endemic (human sites). Our objective was to report the epidemiological, and clinical characteristics and the management of head and neck localizations of hydatid cyst. A retrospective descriptive study of 17 cases of head and neck hydatid cysts taken in charge in our department between 2000 and 2014 was conducted. The mean age was 35 years. Male were slightly predominant (sex ratio: 1.12). Eighty-eight percent of the patients had regular contact with dogs and 53% were of rural origin. The soft tissues of the head and neck were involved in six patients, the parotid gland in 6 patients, the thyroid in 4 patients and the submaxillary gland in one patient. Complete surgical resection of the lesions was systematically done. Hydatid disease was confirmed in all the cases by histology. The outcome was uneventful in all the patients with a mean follow-up of 2 years. Given the lack of recommendations for the surgical treatment of head and neck hydatid cysts, we advocate a total resection of the affected organ if there is no functional risk. Otherwise, an excision of the cyst and of the surrounding tissues combined with an abundant washing-out of the residual cavity must be done, especially in case of intraoperative breaking of the cyst.


Light controlled signaling initiated by subretinal semiconducting-polymer layer in developing-blind-retina mimics the response of the neonatal retina.
Optoelectronic semiconducting polymer material interfaced with a blind-developing chick-retina (E13-E18) in subretinal configuration reveals a response to full-field flash stimulus that resembles an elicited response from natural photoreceptors in a neonatal chick retina. The response manifests as evoked-firing of action potentials and was recorded using a multi-electrode array in contact with the retinal ganglion layer. Characteristics of increasing features in the signal unfold during different retina-development stages and highlight the emerging network mediated pathways typically present in the vision process of the artificial photoreceptor interfaced retina.


Neutrophil-mediated transport of liposomes across the Madin Darby canine kidney epithelial cell monolayer.
Targeted drug delivery to peripheral blood neutrophils (PMNs) should be of therapeutic potential in various disease states. In addition, substances taken up by PMNs in the circulation may be delivered to an extravascular site via the naturally occurring cell infiltration. The present study employs an in vitro chemotaxis model to test whether particulate drug carriers such as liposomes can be transported across a cellular barrier by migrating PMNs. The system contained 10(7) human PMNs/ml, 0.3-micron liposomes at a total lipid concentration of 2.5 mM, and 10% autologous human serum in the apical side of a confluent Madin Darby canine kidney (MDCK) epithelial cell monolayer of 4.71 cm2. The MDCK cells were grown on a polycarbonate membrane with 3-micron pores without any extracellular matrix, and 10(-7) M f-Met-Leu-Phe was added to the basolateral side as a trigger of chemotaxis. The aqueous phase of the reverse-phase evaporation vesicles (REVs) contained lucifer yellow CH (LY) and [14C]sucrose. The lipid bilayer of the REVs was spiked with [3H]dipalmitoylphosphatidylcholine (DPPC). Transmission electron micrographs showed that, in response to the formyl peptide, PMNs adhered to the apical surface of MDCK cells, emigrated across the MDCK cell layer, passed through the 3-micron pores in the polycarbonate membrane, and finally, appeared in the bottom well. Epifluorescence micrographs showed that most, if not all, of the migrated PMNs contained punctate fluorescence derived from LY. Transport data over a 3.5-hr period indicated that those markers that appeared in the basal side were indeed transported by phagocytosis of REVs by PMNs and that intact serum was an essential component in the process.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficient charge separation in sulfur doped AgFeO2 photocatalyst for enhanced photocatalytic U(VI) reduction: The role of doping and mechanism insights.
Photocatalytic reduction of U(VI) in aqueous solutions has been considered as an efficient and promising technology to solve radioactive U pollution. In this work, density functional theory (DFT) calculations were firstly employed to optimize and compare the adsorption configurations combined uranium with four given photocatalysts, then their adsorption energies were - 0.97 eV for AgFeO2, - 1.15 eV for Zn doped AgFeO2, - 1.73 eV for Cu doped AgFeO2 and - 2.66 eV for S doped AgFeO2, respectively, indicating the sulfur doping plays a major role in U(VI) photoreduction. Herein, a visible light responsive efficient sulfur doped AgFeO2 photocatalyst (S doped AgFeO2) was synthesized and utilized to photocatalytic reduction of U(VI) in aqueous solutions. According to XRD, XPS and TEM analysis, the sulfur was successfully doped in AgFeO2 via the hydrothermal method. The batch experimental showed that S doping enhanced the U(VI) photoreduction activity of AgFeO2, and the S-AFO-3 photocatalyst exhibited the highest photocatalytic activity (92.57%), which was 1.5 times than that of pure AgFeO2. ESR, PL and DFT results demonstrated that the enhancement of adsorbed U(VI) photoreduction was attributed to the own unique effect of oxygen vacancy defects and efficient charge separation of S doped AgFeO2 photocatalyst. Due to its higher adsorption energies, fast-U(VI) photoreduction rate and superior chemical stability, the sulfur doped AgFeO2 photocatalyst is hoped for water remediation containing U(VI) wastewater.


The autonomously replicating sequence (ARS) of the yeast Saccharomyces exiguus Yp74L-3.
Fragments containing ARSes were cloned from the genomic DNA of the yeast Saccharomyces exiguus Yp74L-3, and the essential regions for ARSes were restricted for these fragments. Mapping studies of ARS-acting sequences in one of these fragments suggested that S. exiguus recognizes a sequence as an ARS that is different from that recognized by Saccharomyces cerevisiae. Two ARS essential regions of S. exiguus were sequenced, and an ARS core consensus sequence of S. exiguus was deduced to be MATTAMWAWWTK. This sequence differs significantly from that of S. cerevisiae in two positions, suggesting that these nucleotide substitutions cause the difference in the ARS-recognition modes between S. exiguus and S. cerevisiae.


Molecular and morphological differentiation between species of the Plagiorchis vespertilionis group (Digenea, Plagiorchiidae) occurring in European bats, with a re-description of P. vespertilionis (Müller, 1780).
The taxonomic history of the species of Plagiorchis Lühe, 1899 occurring in European bats has been very confused because of high morphological similarity between different forms/species and the inadequate initial description of P. vespertilionis (Müller, 1780). As morphological data alone have not provided enough convincing arguments to solve the problem, the sequences from the nuclear rDNA ITS region (ITS1, 5.8S and ITS2) of three species of the P. vespertilionis group (P. vespertilionis, P. muelleri Tkach & Sharpilo, 1990 and P. koreanus Ogata, 1938) occurring in European bats were used to test the validity of these species and evaluate some of the morphological characters used for the species differentiation within this group. P. elegans from birds was used as the outgroup in the analysis. All three ingroup species were clearly distinguishable using ITS sequences. Among them, P. koreanus occupied a basal position, while P. vespertilionis and P. muelleri appeared as a cluster of two closely related, derived species. ITS sequences of the specimens obtained from different hosts and/or geographical areas did not exhibit any intraspecific variability. Morphological study of the material in collections revealed characters which enable the species of Plagiorchis from bats in Europe to be distinguished. Taking into account that the type-material of P. vespertilionis. described during the 18th Century, has been lost, for nomenclatural stability, a neotype is established and described. An amended description of the type-material of P. muelleri and keys for the determination of Plagiorchis spp. from European bats are presented.


Rituximab therapy for refractory biliary strictures in immunoglobulin G4-associated cholangitis.
Biliary strictures occur in a third of patients with autoimmune pancreatitis and have been termed immunoglobulin G subclass 4 (IgG4) associated cholangitis (IAC). IAC often responds to steroid therapy. A patient with autoimmune pancreatitis and (IAC) refractory to steroids and 6-mercaptopurine was treated with rituximab, a monoclonal antibody directed against the CD20 antigen on B lymphocytes. The patient's biliary strictures improved after rituximab therapy, permitting removal of his biliary stents. Systemic manifestations of IgG4-associated disease also improved. Rituximab may be a treatment option for patients with refractory or recurrent autoimmune pancreatitis or IAC.


Comparison of an online self-referral tool with a physician-based referral strategy for early recognition of patients with a high probability of axial spa.
The diagnostic delay in axial spondyloarthritis (axial SpA) remains unacceptably high, with one of the reasons being a late referral. Structured physician-based referral programs are able to improve early diagnosis, but lack of implementation is still an issue. The objective of this study was to evaluate an online self-referral (OSR) tool for patients with back pain and to compare it to an established physician-based referral tool. Patients with back pain were included if they either fulfilled the requirements of the OSR tool or were referred by a physician using the Berlin referral tool. Rheumatologists in the specialized center performed a structured assessment in all patients that resulted in the final diagnosis of axial SpA / no axial SpA. Furthermore, we attempted to optimize the OSR tool in terms of maximizing the specificity constrained by a sensitivity of at least 90% of the original strategy. 361 consecutive patients (180 via the OSR and 181 via the Berlin referral tool) were included in the study. A total of 35 patients (19.4%) in the self-referral group and 71 patients (39.2%) in the physician-referral group were finally diagnosed with axial SpA. Axial SpA patients from the OSR group were more often HLA-B27 negative, females, and were more frequently at a non-radiographic stage as compared to axial SpA patients who came via the physician-based tool. Both groups had, however, a similar disease burden. According to the pre-defined selection criterion we identified an optimized combination of ≥2 IBP parameters and ≥1 other SpA parameters (in addition to both stem parameters). Despite the better performance of the physician-based referral strategy, the proportion of axial SpA among self-referred patients (19.4%) was clearly higher than the assumed 5% prevalence of axial SpA in patients with chronic back pain. Based on our data driven approach the performance of the OSR strategy could be further improved if at least two IBP parameters plus one additional SpA parameter had to be present in addition to the stem parameters. The OSR tool can be used in specialized centers in addition to a physician-based referral strategy to improve early diagnosis and to increase awareness of axial SpA.


Cutaneous nitrogen excretion in the African clawed frog Xenopus laevis: effects of high environmental ammonia (HEA).
Ammonia is a highly toxic molecule and often introduced in considerable amounts into aquatic environments due to anthropogenic activities. Many aquatic and semi-aquatic amphibians utilize, in addition to their kidneys, the skin for osmoregulation and nitrogen excretion. In the present study the effects of prolonged (7-21 days) exposure to high environmental ammonia (HEA, 1 mmol l(-1) NH4Cl) on cutaneous nitrogen excretion and gene expression of key-transporters involved in nitrogen excretion and acid-base regulation were investigated in the fully aquatic African clawed frog, Xenopus laevis. The study revealed that X. laevis excretes predominately ammonia of which approximately 50% is excreted via the skin. Both the ventral and dorsal skin were capable to generate a net ammonia efflux, which was significantly activated by 10 mmol l(-1) of the phosphodiesterase blocker theophylline. The obtained data further suggest that the ammonia efflux was promoted by an acidification of the unstirred boundary layer, likely generated by an apical localized V-ATPase, with NH3 being transported via cutaneous expressed ammonia transporters, Rhbg and Rhcg. Prolonged HEA exposure did significantly reduce the net-flux rates over the ventral skin with Vmax changing from 256 nmol cm(-2) h(-1) in control frogs to 196 nmol cm(-2) h(-1) in HEA exposed animals. Further, prolonged HEA exposure caused a decrease in mRNA expression levels of the ammonia transporter Rhbg, Na(+)/K(+)-ATPase (α-subunit) and V-ATPase (subunit H) in the ventral and dorsal skin and the kidney. In contrast, Rhcg expression levels were unaffected by HEA in skin tissues.


Biological activities of lipopolysaccharide fractionated by preparative acrylamide gel electrophoresis.
Lipopolysaccharide from a smooth strain of Salmonella minnesota was fractionated into two major fractions and one intermediate fraction by using sodium dodecylsulfate-polyacrylamide gel electrophoresis. On the basis of the study by Hitchcock and Brown, it was deduced that the top fraction was mainly long O-side chain LPS and the bottom fraction was O-side chain-less LPS. The middle fraction was a mixture of both short O-side chain LPS and O-side chain-less LPS. The antigenic properties and biological activities were not altered in this fractionation procedure. Comparison of the biological activities of the top fraction with those of the bottom fraction revealed that the bottom fraction had higher activity in polyclonal B-cell activation and spleen-swelling effect and that there was no significant difference in adjuvant activity, ability to render macrophages cytotoxic, induction of colony-stimulating factor and the ability to induce the Schwartzmann reaction. It was suggested that O-side chain makes no contribution to the latter biological activities including adjuvant activity of S. minnesota LPS.


Relevance of in vitro SCREENIT results for drug-induced QT interval prolongation in vivo: a database review and analysis.
The use of an isolated rabbit heart model (SCREENIT) to predict drug-induced QTc prolongation in animals was assessed using hERG and telemetry data. We compiled data from (i) hERG assay (IC50s), (ii) SCREENIT assay (APD60) and (iii) in vivo non-rodent telemetry studies (QTc interval) and evaluated the reliability of APD60 to fit with IC50s and QTc prolongation using the ratio to free plasma level (FPL). Eighty-two compounds were separated into three classes based on hERG IC50s (class I: IC50s< or =1 microM, n=7; class II: IC50s>1 microM to < or =10 microM, n=15; class III: IC50s>10 microM, n=60). Three class I compounds did not prolong QTc at the FPL equivalent to their IC50s (43% hERG false positives). There were no false positives in SCREENIT. Six class II compounds prolonged the QTc interval. Results showed 40% hERG false negatives and no SCREENIT false negatives. Nine compounds had no effect on QTc, and two prolonged APD60 at an equivalent concentration/FPL (13% false positives). Three class III compounds prolonged QTc at an FPL lower than maximum SCREENIT concentrations (5% false negatives). Four other compounds generated SCREENIT false positive results (7%). SCREENIT increased the predictability of preclinical results for QTc prolongation without generating any false positive results in class I (13% in class II). Making decisions without isolated heart data increases the risk for eliminating efficient drugs displaying hERG inhibition.


Interfacial behavior of polar, weakly polar, and nonpolar compounds bound to activated carbons.
Detailed analysis of the interfacial behavior of water and weakly polar or nonpolar organics adsorbed alone or co-adsorbed onto activated carbons (AC) at different temperatures is a complex problem important for practical applications of adsorbents. Interaction of water, 1-decanol, and n-decane with AC possessing highly developed porosity (pore volume Vp≈1.4-2.3 cm(3)/g, specific surface area S(BET)≈1500-3500 m(2)/g) was studied over a broad temperature range using differential scanning calorimetry (DSC), thermoporometry, (1)H NMR spectroscopy, cryoporometry, and temperature-programmed desorption with mass-spectrometry control methods. Comparison of the pore size distributions (PSD) calculated using the DSC thermoporometry, NMR cryoporometry, and nitrogen adsorption isotherms allows us to determine localization of adsorbates in different pores, as well as changes in the PSD of AC due to freezing of adsorbates in pores. Theoretical calculations (using ab initio HF/6-31G(d,p), DFT B3LYP/6-31G(d,p), and PM7 methods) explain certain aspects of the interfacial behavior of water, decane, and decanol adsorbed onto AC that appear in the experimental data. Obtained results show strong temperature dependence (above and below the freezing point, Tf, of bulk liquids) of the interfacial behavior of adsorbates on the textural characteristics and hydrophilic/hydrophobic properties of AC and the adsorbate amounts that affect the distributions of adsorbates unfrozen at T<Tf in pores of different sizes.


Inhibition of endogenous CO by ZnPP protects against stress-induced gastric lesion in adult male albino rats.
Carbon monoxide (CO) has been found to be produced in every living cell in a biochemical reaction catalyzed by heme-oxygenase (HO) enzyme which degrades heme into biliverdin, CO, and iron. Endogenous CO is not a waste product, but acts as a chemical messenger mediating and modulating many intracellular biochemical reactions that regulate physiological functions. This study was designed to investigate the effect of inhibition of endogenous CO production by zinc protoporphyrin (ZnPP), an HO inhibitor, on the gastric secretion and ulceration induced by cold-restraint stress (CRS) in adult male albino rats. Rats were pylorically ligated and divided randomly into the following groups (six rats each): control, ZnPP treated (50 μmol/kg/day, s.c. for 10 days), CRS, and stressed ZnPP treated groups. Blood samples were collected from the retro-orbital sinus of anesthetized rats for determination of CO concentration. We found that ZnPP pretreatment significantly decreased HO-1 level, CO level, and volume of gastric juice as compared to the control non-stressed rats. In the present study, ZnPP pretreatment proved to be protective against development of ulcerative lesions in CRS model as evidenced by reduction of the ulcer index, and this could be mediated through reduction of free and total acidity of gastric secretion and decreased lipid peroxidation but with significantly decreased gastric protective nitric oxide and prostaglandin E(2) levels. In conclusion and according to our results, the protective effect of ZnPP on CRS-induced gastric ulcers despite of inhibition of endogenous CO could be attributed to the presence of zinc which is known to have a protective anti-ulcer effect.


[Effect of the pho85 mutation on the catabolite repression of the CIT1 gene in yeasts Saccharomyces cerevisiae].
The Krebs cycle is one of the major metabolic pathways in a cell, which includes both catabolic and anabolic reactions. The first enzyme of the Krebs cycle, citrate synthase, catalyzes one of a few irreversible reactions of the cycle, citrate formation from acetyl-CoA and oxaloacetate. Expression of the CIT1 gene encoding the mitochondrial form of this enzyme in Saccharomyces cerevisiae is repressed on glucose- and glutamate-containing medium and activated on the raffinose-containing medium. In this work, the dependence of glucose repression of the CIT1 gene on the content of phosphate in the medium was studied. On the phosphate-deficient medium, the level of the CIT1 gene expression was increased twice. A low-molecular-weight (about 34 kDa) protein was identified and shown to interact with a region of the CIT1 gene promoter (from -367 to -346 bp), which controls the glucose repression. The results obtained suggest that the Pho4 protein is involved in regulation of the CIT1 gene expression on the glucose-containing and phosphate-deficient medium. Disruption of the PHO85 gene encoding phosphoprotein kinase (Pho4p is the substrate of this enzyme) leads to alleviation of glucose repression of the CIT1 gene. Thus, in yeast cells grown in the presence of glucose, the PHO85 gene mediates downregulation of the CIT1 expression.


Two groups of TH-like immunoreactive neurons in the frog (Rana pipiens) retina.
The morphology and distribution of TH-like immunoreactive (TH-IR) cells in the retina of Rana pipiens were studied in retinal whole mounts and in radial and horizontal sections. A large majority (96%) of the immunoreactive cells were found in the inner nuclear layer while a few cells were found in the ganglion cell layer. All TH-IR cells had round to oval somata with average diameter of 10 microm. The 2-4 primary processes of these cells distributed extensively to sublamina 1 of the inner plexiform layer (IPL) and sparsely to sublamina 5. Two groups of TH-IR cells were distinguished: one, designated thin cells, had only thin (<2 microm diameter) primary processes; the second, designated thick cells, had one or more primary processes with diameter(s) exceeding 2 microm for a distance of 5 microm or more from the soma. The thin cells did not significantly differ from the thick cells in soma diameter, number of primary processes, horizontal spread of processes or vertical lamination of processes. Nearest neighbor analyses of the two types revealed that the population of TH-IR cells (thick and thin together) have an orderly distribution while the thick cells alone are more randomly distributed, indicating that the thick cells do not comprise a functional population. The total number of TH-IR cells varied between retinas; the variability was due principally to variation of thin cell density. It is hypothesized that the thick cells are a subpopulation of the TH-IR cells which are in a particular physiological state at the time of fixation.


Presymptomatic Retinal Sensitivity Changes in Intermediate Age-Related Macular Degeneration Associated With New Retinal Fluid.
To determine whether change in retinal sensitivity in areas with subretinal or intraretinal fluid secondary to age-related macular degeneration (AMD) precedes visual symptoms. If confirmed, retinal sensitivity testing could be used for home monitoring in AMD. Individuals with intermediate AMD enrolled in a longitudinal study were seen every 6 months and underwent best-corrected visual acuity testing (BCVA), spectral domain-optical coherence tomography (SD-OCT), and microperimetry. Asymptomatic individuals who developed incidental, reading center-determined retinal fluid detected on SD-OCT were identified. The point-wise sensitivity (PWS) at the time of fluid detection was compared with 6 and 12 months prior. Fourteen of 161 individuals developed fluid without symptoms. PWS over fluid areas at detection was reduced compared with 6 (difference -2.04 dB, P < 0.001) and 12 months (-2.27 dB, P < 0.001) prior. PWS over fluid areas was reduced compared with perifluid areas (difference -1.02 dB, P = 0.03), peripheral areas (-1.51 dB, P < 0.001), nonprogressed fellow eyes (-1.49 dB, P = 0.006), and nonprogressed age-matched intermediate AMD eyes (-2.29 dB, P = 0.001). No difference in BCVA was observed in eyes developing fluid compared to eyes that do not develop fluid (P = 0.76). Retinal areas with fluid on SD-OCT had a corresponding reduction in retinal sensitivity at the time of fluid detection compared with 6 and 12 months prior, in asymptomatic intermediate AMD without change in BCVA. Development of self-monitoring tools to detect changes in retinal sensitivity may be helpful for early detection of retinal fluid suggestive of progression to neovascular AMD before acuity is affected.


Experimental studies of herbivory and algal competition in a low intertidal habitat.
Ecological factors regulating the species composition and abundance of the plant assemblage in the low intertidal zone were studied in the semiprotected San Juan Islands in Washington state. In particular, the roles of an abundant herbivore (the chiton Katharina tunicata) and competition among plants were evaluated experimentally. Densities of Katharina were manipulated in large areas to establish 3 treatments: Katharina removals (N=2), controls (N=2), and Katharina addition (N=1). These sites were monitored for 4 years. Over this time, algal abundance and diversity increased in the Katharina-removal areas; algae in most functional groups proliferated, and a multi-storied intertidal kelp bed eventually developed. In the Katharina-addition, the abundance of all plants except crusts, diatoms, and surfgrass decreased, and overall diversity declined. Control sites underwent year-to-year fluctuation in the abundance of the most conspicuous alga, Hedophyllum sessile, but remained otherwise unchanged.At the end of the third year, the dominant space occupiers (the large brown algae) were removed from half of each of the Katharina removal and control areas. These kelps positively affect abundances of Katharina but are negatively correlated with limpet numbers. In the absence of competition from the kelps, the abundance and diversity of most other algal groups increased. This change was especially dramatic in the areas lacking both chitons and kelps, indicating that herbivory and competition have negative, additive effects on smaller algae. However, even in the absence of Katharina, abiotic disturbance (desiccation and storms) apparently mediates the competitive dominance of the kelps.


Crystal structures of [Met5] and [(4-bromo)Phe4,Met5]enkephalins: formation of a dimeric antiparallel beta-structure.
The crystal structure of [(4-bromo)Phe4,Met5]enkephalin (Tyr-Gly-Gly-(4-bromo)-Phe-Met) shows two independent molecular conformations. The molecules are arranged in parallel in a head-to-tail fashion and form an antiparallel beta-sheet structure involving intermolecular hydrogen bonds. This dimeric beta-structure is also observed in the [Met5]enkephalin crystal, in spite of their different crystal packing environments, which shows the energetic stability of this molecular conformation. The three-dimensional similarity between the dimeric beta-structure and the beta-turn form is discussed in the relation to the opioid delta and mu receptors.


Dissociated vertical deviation in patients with intermittent exotropia.
To determine whether the age of strabismus onset and the degree of stereopsis are related to the development of dissociated vertical deviation (DVD) in patients with intermittent exotropia and to describe the characteristics of DVD in patients with intermittent exotropia and DVD. Retrospective record review of patients with (1) intermittent exotropia with DVD; (2) infantile esotropia with DVD; and (3) intermittent exotropia without DVD. Age of strabismus onset, stereopsis, strabismus measurements, and the response of DVD to the Bielschowsky head-tilt test were compared among the three groups. Fifty-two children with intermittent exotropia and DVD were identified. In patients with intermittent exotropia with DVD and intermittent exotropia without DVD group, the mean age of strabismus onset was 12.7 months and 28.9 months, respectively (p = 0.03), and mean stereopsis was 147 arcsec and 65 arcsec (p = 0.02). In patients with intermittent exotropia with DVD and infantile esotropia with DVD, the mean amount of DVD was 9.7(Delta) and 17.2(Delta), respectively (p < 0.01). Bielschowsky head-tilt test showed an increase of DVD on ipsilateral head tilt in 91% and 63.3%, respectively. Intermittent exotropia with DVD is characterized by earlier onset of strabismus and worse stereopsis, suggesting that these factors may be related to the development of DVD in patients with intermittent exotropia. Unlike DVD in infantile esotropia, DVD in intermittent exotropia was smaller in amount and demonstrated a more uniform response to the Bielschowsky head-tilt test.


Persistence of combat-related posttraumatic stress symptoms for 75 years.
Investigations of the duration of combat-related posttraumatic stress symptoms have focused mainly on survivors of World War II and the Vietnam War, with little attention to surviving veterans of World War I. The authors describe a case in which posttraumatic stress symptoms persisted for 75 years in a World War I combat veteran and increased in frequency toward the end of his life accompanied by advancing dementia and hospitalization. The case illustrates that posttraumatic stress symptoms may be lifelong and exacerbated by various consequences of aging, even if they are not disabling.


Shear's role in non-union. Measuring mean angle of long bone multi-fragmentary non-unions.
Both mechanical and biological theories have been proposed in the development of non-union. The mechanical theory suggests that a high strain environment in a fracture will predispose it to non-union. While in simple fractures and wedge fractures there are only one and two primary fracture planes respectively, in multi-fragmentary fractures there are many and a non-union may form along any of the original fracture lines, however the plane which experiences the highest strain is at 45O - the shear plane. We hypothesise that in multi-fragmentary fractures the initial fracture line that most often fails to unite will tend towards the plane with the highest strain. 1) Define the mean non-union angle in a cohort of multi-fragmentary tibial and femoral fractures. 2) In wedge-like fractures within the cohort, define and compare the mean angle of initial fracture planes which go on to form a non-union to those that unite 3) In comminuted fractures within the cohort, define the mean non-union angle DESIGN: Retrospective cohort study SETTING: Level-1 trauma centre METHODOLOGY: Fractures were categorised into wedge-like and comminuted. A published technique was utilised to measure fracture and non-union angles. In wedge-like fractures, united and non-united initial planes were compared. In comminuted fractures only the mean non-union angle was defined. Demographic patient data was also collected. 183 non-unions were screened, 68 patients were included. The mean non-union angle was 56°(SD 18) across all fractures. In wedge-like fractures the mean non-union angle was 59°(SD 18). In comminuted fractures the mean non-union angle was 50°(SD 19). Non-united initial fracture planes in wedge-like fractures showed a peaked distribution about a mean of 58° while united fracture planes were distributed at the extremities of the range. In patients with multi-fragmentary fractures resulting in non-union, the mean tibial non-union angle was 52° while the mean femoral non-union angle was 65°. In wedge-like fractures, non-unions occurred more commonly than appropriate union in fractures between 41°-80°. The non-union angle is closer to 45° in comminuted fractures than in wedge-like fractures. These results support the mechanical theory that strain from the shear plane is an important factor in the formation of non-unions. Prognostic level 3.


Identification of KD5170: a novel mercaptoketone-based histone deacetylase inhibitor.
We report the identification of KD5170, a potent mercaptoketone-based Class I and II-histone deacetylase inhibitor that demonstrates broad spectrum cytotoxic activity against a range of human tumor-derived cell lines. KD5170 exhibits robust and sustained histone H3 hyperacetylation in HCT-116 xenograft tumors following single oral or i.v. dose and inhibition of tumor growth following chronic dosing.


Antibiotics Utilization for Community Acquired Pneumonia in a Community Hospital Emergency Department.
A local health authority in Canada implemented its own Antimicrobial Stewardship Program (ASP) which provide guidelines to clinicians to utilize when treating infectious diseases such as community-acquired pneumonia (CAP). Objectives: The primary objective is to describe antibiotic usage patterns at the community hospital's emergency department (ED) and to analyze the patterns in relation to ASP goals of reducing risk of infections, adverse drug events and antibiotic resistance, and to identify potential areas of improvement. This retrospective chart review included 156 adult patients with a diagnosis of CAP admitted to a community hospital ED from December 1, 2015 to November 30, 2016. 50.6% patients were prescribed moxifloxacin across all severity of CAP patients. Low and moderate severity CAP patients were most often prescribed antibiotic duration > 7 days. In low, moderate and high severity CAP patients who were treated using ceftriaxone, 100%, 88.9% and 66.6% patients were treated with ceftriaxone 2000 mg daily respectively. Antibiotic prescribing patterns suggest fluoroquinolones were frequently being over-prescribed, ceftriaxone dosages were often too high, and duration of antibiotics for low and moderate severity CAP were too long. More efforts are needed to promote appropriate antibiotic usage and optimize patient care.


Creation of consensus recommendations for collaborative practice in the Malaysian psychiatric system: a modified Delphi study.
There is strong evidence that collaborative practice in mental healthcare improves outcomes for patients. The concept of collaborative practice can include collaboration between healthcare workers of different professional backgrounds and collaboration with patients, families and communities. Most models of collaborative practice were developed in Western and high-income countries and are not easily translatable to settings which are culturally diverse and lower in resources. This project aimed to develop a set of recommendations to improve collaborative practice in Malaysia. In the first phase, qualitative research was conducted to better understand collaboration in a psychiatric hospital (previously published). In the second phase a local hospital level committee from the same hospital was created to act on the qualitative research and create a set of recommendations to improve collaborative practice at the hospital for the hospital. Some of these recommendations were implemented, where feasible and the outcomes discussed. These recommendations were then sent to a nationwide Delphi panel. These committees consisted of healthcare staff of various professions, patients and carers. The Delphi panel reached consensus after three rounds. The recommendations include ways to improve collaborative problem solving and decision making in the hospital, ways to improve the autonomy and relatedness of patients, carers and staff and ways to improve the levels of resources (e.g. skills training in staff, allowing people with lived experience of mental disorder to contribute). This study showed that the Delphi method is a feasible method of developing recommendations and guidelines in Malaysia and allowed a wider range of stakeholders to contribute than traditional methods of developing guidelines and recommendations.Trial registration Registered in the National Medical Research Register, Malaysia, NMRR-13-308-14792.


Additional Benefits Conferred by Endoscopic Sclerotherapy to Liver Cirrhosis Patients Receiving Endoscopic Variceal Ligation.
Gastroesophageal varices are a direct consequence of portal hypertension in cirrhosis. The management of gastroesophageal varices has evolved over the last decade resulting in reduced mortality and morbidity rates. The study was aimed to analyze the short-term and long-term efficacy of different endoscopic methods in the treatment of gastric varices in cirrhotic patients. From January 2016 to December 2019, 135 patients with liver cirrhosis and gastric varices undergoing different endoscopic treatment protocols were retrospectively analyzed. The patients were divided into three groups according to endoscopic variceal ligation, endoscopic sclerotherapy, and a combination of both, respectively. Main outcomes including the overall response rate, hemostasis, short- and long-term rebleeding (3 months before and after treatment), complication, blood pressure, heart rate, portal venous pressure (PVP), portal vein diameter (PVD), portal vein velocity (PVV), portal vein blood flow (PVF) detected by ultrasound, recurrence rate, and mortality were analyzed after treatments. The overall response rate in the combined group was higher than that in the ligation group and the sclerotherapy group (P < 0.05). The incidence rate of complications in the combined group and the ligation group was lower than that in the sclerotherapy group (P < 0.05). After treatment, the PVP, PVD, and PVF were reduced in the combined group compared with the ligation group and the sclerotherapy group, while the PVV was not (P < 0.05). Lower rates of long-term rebleeding, recurrence, and mortality were noted in the combined group compared to the ligation group and the sclerotherapy group (P < 0.05). Endoscopic variceal ligation combined with endoscopic sclerotherapy is more effective than both alone in treating liver cirrhosis and gastric varices. The combined therapy contributed to reduced short-term and long-term rebleeding rate, decreased long-term recurrence rate, and mortality.


A systematic review of mixed studies on malaria in Colombia 1980-2022: what the "bifocal vision" discovers.
Mixed methods are essential in public health research and malaria control, because they allow grasping part of the complexity and diversity of the factors that determine health-disease. This study analyzes the mixed studies on malaria in Colombia, 1980-2022, through a systematic review in 15 databases and institutional repositories. The methodological quality was assessed with Mixed Methods Appraisal Tool (MMAT), STrengthening the Reporting of OBservational studies in Epidemiology (STROBE), and Standards for Reporting Qualitative Research (SRQR). The qualitative and quantitative findings were grouped into a four-level hierarchical matrix. The epidemiological profile of malaria morbidity, from traditional epidemiology, has been sustained by environmental problems, armed conflict, individual risk behaviors, and low adherence to recommendations from health institutions. However, the qualitative component reveals deeper causes that are less studied, of greater theoretical complexity, and that reflect challenges to design and implement health interventions, such as socioeconomic and political crises, poverty, and the neoliberal orientation in the malaria control policy; the latter reflected in the change in the role of the State, the fragmentation of control actions, the predominance of insurance over social assistance, the privatization of the provision of health services, the individualistic and economistic predominance of health, and low connection with popular tradition and community initiatives. The above confirms the importance of expanding mixed studies as a source of evidence to improve malaria research and control models in Colombia, and to identify the underlying causes of the epidemiological profile.


Higher seroprevalence of Helicobacter pylori infection in Korean adolescent athletes compared to age- and sex-matched non-athletes.
Poor living conditions, such as overcrowding and bed-sharing, are reported to be significant risk factors for Helicobacter pylori infection throughout childhood. We investigated the prevalence of H. pylori infection in Korean athletes who are obliged to live together in training camps for more than 6 months in a year. Blood sampling and surveying through questionnaire were performed on 440 students from a regular high school (228 boys and 212 girls) and 220 athletes (148 boys and 72 girls) of a physical education high school. We measured serum immunoglobulin G antibody (IgG Ab) to H. pylori in order to compare the prevalence of H. pylori infection between normal adolescents and athletes. In addition, we conducted a nutritional analysis and questionnaire survey for socioeconomic status in order to compare other risk factors that might influence H. pylori infection between groups. The prevalence of H. pylori infection in athletes (43.2%) was higher than that in the controls (22.7%). No significant differences in the nutritional factors or socioeconomic status, such as Hollingshead index, type of house, number of siblings, and crowding index, were found between the groups. Multivariate analysis showed that crowding and the difference in school type were the significant predictors of H. pylori seropositivity after controlling for dietary and socioeconomic factors. The seroprevalence of H. pylori infection was higher in adolescent athletes than in age- and sex-matched regular students. Further prospective study is needed to confirm the observation.


The number of risk factors not at target is associated with cardiovascular risk in a type 2 diabetic population with albuminuria in primary cardiovascular prevention. Post-hoc analysis of the NID-2 trial.
Nephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes. Intervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0-1 risk factor (absent/low); 2-3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase. Absent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04-3.52, P = 0.038 and 1.96, 95%CI 1.02-3.8, P = 0,045, respectively, vs absent/low risk group). This post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk. ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925.


Promoting effects of combined antioxidant and sodium nitrite treatment on forestomach carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine.
The effects of sodium nitrite (NaNO2), in combination with one of three antioxidants, tert-butylhydroquinone (TBHQ), alpha-tocopherol (alpha-Toc) and propyl gallate (PG), on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stomach carcinogenesis were investigated in F344 rats. Groups of 15 male rats were treated with an intragastric dose of 150 mg/kg body weight of MNNG, and starting 1 week later, were treated with 0.5% TBHQ, 1% alpha-Toc, 1% PG or basal diet with or without 0.2% NaNO2 in their drinking water until they were killed at the end of week 36. Macroscopically, in MNNG-treated animals, combined administration of alpha-Toc or PG with NaNO2 significantly increased the areas and numbers of forestomach nodules as compared with the respective antioxidant alone values. Microscopically, in MNNG-treated animals, treatment with TBHQ significantly increased the incidence and multiplicity of forestomach papillomas as compared with basal diet alone value. Combined administration of alpha-Toc with NaNO2 significantly raised the multiplicity of forestomach papillomas, with a tendency to elevation in the incidence as compared with the group given alpha-Toc alone. Incidences of forestomach moderate and/or severe hyperplasias were significantly higher in the TBHQ or PG plus NaNO2 groups than in the single compound groups. In rats without MNNG treatment, combined treatment of antioxidants with NaNO2 significantly increased the incidences of mild or moderate hyperplasia. In the glandular stomach, although the incidence of atypical hyperplasia showed a non-significant tendency for decrease with TBHQ treatment, additional administration of NaNO2 caused significant increase. These results indicate that co-administration of NaNO2 with alpha-Toc, TBHQ or PG and particularly the first, promotes forestomach carcinogenesis. Concurrent alpha-Toc, TBHQ or PG treatment with NaNO2 is likely to induce forestomach tumors in the long term.


Musculoskeletal pain during and after SARS-CoV-2 infection and healthcare utilization: a cross-sectional study.
The COVID-19 pandemic necessitated the reorganization of health services to cater to the needs of individuals affected by the virus. This study aimed to examine the association between musculoskeletal pain during and after SARS-CoV-2 infection and the utilization of health services among adults in southern Brazil. METHODS: A cross-sectional study was conducted with individuals aged 18 years and older, who were diagnosed with COVID-19 between December 2020 and March 2021. Questionnaires were electronically collected using tablets through the REDCap platform via phone calls. The health service utilization outcomes assessed included Primary Health Care, general practitioners, private emergency care, and specialized services. The exposure variable was the presence of musculoskeletal pain during and after SARS-CoV-2 infection in different regions, such as cervical, upper limbs, thoracic, lumbar, and lower limbs. Poisson regression analysis was employed to assess the relationship between health service utilization during and after SARS-CoV-2 infection and musculoskeletal pain during and after the infection with SARS-CoV-2 among adults in southern Brazil. Data were analyzed using the Stata 16.1 statistical package. RESULTS: A total of 2,919 individuals were interviewed. Overall, individuals with musculoskeletal pain were found to utilize health services approximately 15 percentage points higher when compared to those without musculoskeletal pain. In adjusted analysis, individuals who reported musculoskeletal pain during and after SARS-CoV-2 infection were up to twice as likely to use health services. Among them, the emergency care unit was the most frequently used service, particularly in those with pain in the lower limbs (RP=2.19, 95% CI 1.66-2.87) and thoracic region (RP=2.04, 95% CI 1.47-2.84). Notably, the highest magnitudes of association were observed with emergency care units, specialist doctors, and specialized services, especially neurologists, who were two to three times more likely to be sought, followed by pulmonologists. CONCLUSION: Health service utilization was significantly associated with musculoskeletal pain during and after SARS-CoV-2 infection. All regions, except for the cervical region, showed a correlation with the use of Primary Health Care. The thoracic region featured an association with pulmonologists and emergency room utilization. Additionally, health services like emergency care units, specialist doctors, and specialized services, including cardiologists and neurologists, were commonly utilized across all regions in southern Brazil.


Phosphoinositides in Golgi complex function.
The Golgi complex is a ribbon-like organelle composed of stacks of flat cisternae interconnected by tubular junctions. It occupies a central position in the endomembrane system as proteins and lipids that are synthesized in the endoplasmic reticulum (ER) pass through the Golgi complex to undergo biosynthetic modification (mainly glycosylation) and to be sorted to their final destinations. In addition the Golgi complex possesses a number of activities, apparently not directly connected with its main role in trafficking and sorting, which have been recently reviewed in Wilson et al. 2011. In spite of the constant massive flux of material the Golgi complex maintains its identity and phosphoinositides (PIs), among other factors, play a central role in this process. The active metabolism of PIs at the Golgi is necessary for the proper functioning of the organelle both in terms of membrane trafficking/sorting and its manifold metabolic and signalling activities. Phosphatidylinositol 4-phosphate (PtdIns4P), in particular, is responsible for the recruitment of numerous cytosolic proteins that recognise and bind PtdIns4P via specific lipid-binding domains. In this chapter we will summarize the findings that have contributed to our current understanding of the role of PIs in the biology of the Golgi complex in terms of the regulation of PI metabolism and the functional roles and regulation of PtdIns4P effectors.


Yet uninfected? Resolving cell states of plants under pathogen attack.
Although we have made significant strides in unraveling plant responses to pathogen attacks at the tissue or major cell type scale, a comprehensive understanding of individual cell responses still needs to be achieved. Addressing this gap, Zhu et al. employed single-cell transcriptome analysis to unveil the heterogeneous responses of plant cells when confronted with bacterial pathogens.


Effects of a mitochondrial-targeted ubiquinol on vascular function and exercise capacity in chronic kidney disease: a randomized controlled pilot study.
Mitochondria-derived oxidative stress has been implicated in vascular and skeletal muscle abnormalities in chronic kidney disease (CKD). The purpose of this study was to investigate the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in CKD. In this randomized controlled trial, 18 patients with CKD (means ± SE, age: 62 ± 3 yr and estimated glomerular filtration rate: 45 ± 3 mL/min/1.73 m2) received 4 wk of 20 mg/day MitoQ (MTQ group) or placebo (PLB). Outcomes assessed at baseline and follow-up included macrovascular function measured by flow-mediated dilation, microvascular function assessed by laser-Doppler flowmetry combined with intradermal microdialysis, aortic hemodynamics assessed by oscillometry, and exercise capacity assessed by cardiopulmonary exercise testing. Compared with PLB, MitoQ improved flow-mediated dilation (baseline vs. follow-up: MTQ, 2.4 ± 0.3% vs. 4.0 ± 0.9%, and PLB, 4.2 ± 1.0% vs. 2.5 ± 1.0%, P = 0.04). MitoQ improved microvascular function (change in cutaneous vascular conductance: MTQ 4.50 ± 2.57% vs. PLB -2.22 ± 2.67%, P = 0.053). Central aortic systolic and pulse pressures were unchanged; however, MitoQ prevented increases in augmentation pressures that were observed in the PLB group (P = 0.026). MitoQ did not affect exercise capacity. In conclusion, this study demonstrates the potential for a MitoQ to improve vascular function in CKD. The findings hold promise for future investigations of mitochondria-targeted therapies in CKD.NEW & NOTEWORTHY In this randomized controlled pilot study, we investigated the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in chronic kidney disease. Our novel findings showed that 4-wk supplementation of MitoQ was well tolerated and improved macrovascular endothelial function, arterial hemodynamics, and microvascular function in patients with stage 3-4 chronic kidney disease. Our mechanistic findings also suggest that MitoQ improved microvascular function in part by reducing the NADPH oxidase contribution to vascular dysfunction.


Impact of rotavirus vaccine implementation on Israeli children: a comparison between pre- and post-vaccination era.
Worldwide rotavirus vaccination has resulted in a substantial decrease in rotavirus-induced severe gastroenteritis and related hospitalizations among children. Still, the characterization of patients warranting hospitalization needs to be further elucidated. The purpose of the study is to compare the clinical and laboratory features of children hospitalized with acute rotavirus infection before and after the introduction of routine vaccination. This is a retrospective observational study. Participants were pediatric patients who presented to the Bnai Zion Medical Center pediatric emergency department and were diagnosed with rotavirus acute gastroenteritis between 2017 and 2019. During the pre-vaccination period (2007-2009), 114 infants and young children (median age: 14 months, range: 1-72 months; 59 male, 55 female) were hospitalized for rotavirus-induced acute gastroenteritis with a rate of 11.71 positive rotavirus tests per 1000 emergency room visits. In the post-vaccination period (2012-2019), 168 infants and young children (median age: 17 months, range: 0-84 months; 90 male, 78 female) were hospitalized with a rate of 4.18 positive rotavirus tests per 1000 emergency room visits. There were no statistical differences between the two groups in gender, breast-feeding rates and sibling(s). The proportion of cases with moderate-to-severe dehydration was higher in the post-vaccination children than in the pre-vaccination children. Rates of rotavirus-attributed acute gastroenteritis hospitalizations declined from the pre- to the post-vaccination period. Higher rates of dehydration were found in the post-vaccination children. Ongoing surveillance is warranted to better understand the implications of the vaccine.


Experimental and Computational Studies Reveal Novel Interaction of Lymphocytes Antigen 6K to TGF-β Receptor Complex.
TGF-β signaling promotes migration, invasion, and distant colonization of cancer cells in advanced metastatic cancers. TGF-β signaling suppresses the anti-tumor immune response in a tumor microenvironment, allowing sustained tumor growth. TGF-β plays an important role in normal physiology; thus it is no surprise that the clinical development of effective and safe TGF-β inhibitors has been hampered due to their high toxicity. We discovered that increased expression of LY6K in cancer cells led to increased TGF-β signaling and that inhibition of LY6K could lead to reduced TGF-β signaling and reduced in vivo tumor growth. LY6K is a highly cancer-specific protein, and it is not expressed in normal organs except in the testes. Thus, LY6K is a valid target for developing therapeutic strategies to inhibit TGF-β signaling in cancer cells. We employed in vitro pull-down assays and molecular dynamics simulations to understand the structural determinants of the TGF-β receptor complex with LY6K. This combined approach allowed us to identify the critical residues and dynamics of the LY6K interaction with the TGF-β receptor complex. These data are critical in designing novel drugs for the inhibition of TGF-β in LY6K expressing cancer, induction of anti-tumor immune response, and inhibition of tumor growth and metastatic spread.


Chronic exposure to perfluorohexane sulfonate leads to a reproduction deficit by suppressing hypothalamic kisspeptin expression in mice.
Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid found as an environmental contaminant. This study aims to investigate the effects of PFHxS exposure on female reproduction and the underlying mechanism in mice. Eight-week-old ICR mice were divided randomly into four groups administered corn oil (vehicle) and PFHxS at doses of 0.5, 5, and 50 mg/kg/day for 42 days by intragastric administration. Body weight, ovarian weight, estrous cycle, follicle counts, and serum sex hormone levels were evaluated. The expression of kisspeptin and gonadotropin releasing hormone (GnRH) in the hypothalamus was also detected. Compared to vehicle exposure, 5 mg/kg/day PFHxS treatment prolonged the estrous cycle, especially the duration of diestrus, after 42 days of treatment. The numbers of secondary follicles, antral follicles and corpus lutea were significantly reduced in the PFHxS-treated mice. Moreover, compared with the control mice, the PFHxS-treated mice showed decreases in the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2), and reduced GnRH mRNA levels, along with the lack of an LH surge. Furthermore, the PFHxS-treated mice had lower levels of kisspeptin immunoreactivity and kiss-1 mRNA in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) than the control mice. After intraventricular administration of kisspeptin-10, the numbers of secondary follicles, antral follicles and corpus lutea recovered, along with the levels of GnRH mRNA, FSH, and LH in the mice treated with 5 mg/kg/day PFHxS. These results indicate that chronic exposure of mice to 5 mg/kg/day PFHxS affects reproductive functions by inhibiting kisspeptin expression in the ARC and AVPV regions, leading to deficits in follicular development and ovulation.


Characterization of antisera to a synthetic carboxyl-terminal peptide of the glucose transporter protein.
Peptides corresponding to amino acid residues 1-12 of the amino terminal and 480-492 of the carboxyl terminal of the deduced sequence of the glucose transporter were synthesized and used to produce site-specific polyclonal antipeptide sera. In a solid-phase radioimmunoassay, antiserum to the carboxyl terminal recognizes peptide 480-492 and purified human erythrocyte glucose transporter, but not peptide 1-12. Antiserum to the amino terminal recognizes peptide 1-12 but neither peptide 480-492 nor the erythrocyte transporter. The antiserum to the carboxyl terminal specifically immunoblots the Mr 55,000 glucose transporter in erythrocyte membranes and the purified erythrocyte transporter. It also recognizes a Mr 40,000-60,000 polypeptide in membranes of cells derived from different mammalian species and tissues including insulin-sensitive rat adipocytes as well as a Mr 20,000 tryptic fragment of the transporter which contains the site for photolabeling by cytochalasin B. Antiserum to the carboxyl terminal of the transporter binds specifically to leaky erythrocyte membranes but not to intact erythrocytes. This binding is saturable and competitively inhibited by peptide 480-492. Using immunofluorescence microscopy, this antiserum detects glucose transporter protein in permeabilized erythrocytes, but not in intact erythrocytes. These studies provide immunochemical evidence in support of the predicted cytoplasmic orientation of the carboxyl terminus of the glucose transporter, allow us to suggest a spatial relationship of the cytochalasin B binding site to the carboxyl terminal of the glucose transporter and suggest that antisera directed to the carboxyl terminal domain of the protein may be useful for the immunocytochemical localization of the glucose transporter.


A biosensor based on catalase for determination of highly toxic chemical azide in fruit juices.
In this work, an amperometric biosensor based on catalase enzyme was developed for the determination of azide. The principle of the measurements was based on the determination of the decrease in the differentiation of oxygen level which had been caused by the inhibition of catalase in the bioactive layer of the biosensor by azide. Firstly, the optimum conditions for the inhibitor biosensor were established. In the optimization studies of the biosensor, the most suitable catalase and gelatin amounts and glutaraldehyde ratio were determined. Optimum catalase activity, optimum gelatin amount and glutaraldehyde percentage were 5000 Ucm(-2), 5.94 mgcm(-2) and 2.5%, respectively. Characterization studies of the biosensor such as optimum pH and optimum temperature were carried out. The repeatability experiments were done and the average value (x), standard deviation (S.D.) and variation coefficient (C.V.) were calculated as 98.6 microM, +/-4.16 microM and 4.23%, respectively. A good linear relationship with a correlation coefficient of 0.9902 was obtained over the concentration range of 25 microM to 300 microM azide. After the optimization and characterization studies the proposed biosensor was applied to the determination of azide in certain fruit juices.


Preclinical evidence for GABAB agonists as a pharmacotherapy for cocaine addiction.
A variety of studies indicate that GABA(B) receptor agonists may be useful in the treatment of addictive disorders. This brief review summarizes self-administration studies in rats which show that baclofen and other GABA(B) agonists may have specific effects on the reinforcing effects of cocaine. Preliminary clinical data with baclofen have also been encouraging. The obstacles and issues related to the use of GABA drugs in addiction therapy are briefly addressed.


On the paths of fluid particles in an axisymmetrical aneurysm.
The aim of this study is the characterization of the pulsatile flow field by demonstration of the paths of single particles in a model of an axisymmetric aneurysm. The detailed analysis of the flow field can give additional information on the flow pattern and the time of transition of blood particles in the segment. The basis of the calculations is the system of the Navier-Stokes equations for incompressible Newtonian fluid flow. To solve these equations numerically the finite element method was used. The trajectory equations for a fluid particle were solved by use of a predictor-corrector procedure. The results of the computer simulation demonstrate the development, shift and disappearance of vortices in the excavation and give references to zones of stasis. This behavior can be an important factor in thrombogenesis.


Microvessel density, cyclo-oxygenase 2 expression, K-ras mutation and p53 overexpression in colonic cancer.
Tumour angiogenesis, cyclo-oxygenase (COX) 2 expression, K-ras mutation and p53 overexpression are commonly involved in colorectal tumorigenesis, but their interrelationship and clinicopathological effects remain inconclusive. Clinicopathological data from 114 consecutive patients with primary stage III colorectal cancer were evaluated prospectively. Microvessel density (MVD) of the tumour was defined by counting the number of microvessels in hotspots, visualized by immunocytochemical staining of endothelial CD34. K-ras mutation was analysed by the restriction enzyme cleavage method. COX-2 expression and p53 overexpression were determined by immunocytochemistry. Increased MVD in hotspots was significantly associated with COX-2 expression (P < 0.001), K-ras mutation (P = 0.007) and p53 overexpression (P = 0.006). COX-2 expression was not associated with either K-ras mutation or p53 overexpression. Clinicopathologically, greater MVD and COX-2 expression were significantly associated with vascular invasion of cancer cells (MVD, P = 0.027 and COX-2 expression, P = 0.006), but p53 overexpression and K-ras mutation were not. Multivariate analysis indicated that greater MVD (P = 0.002) and p53 overexpression (P = 0.016) were significant independent predictors of tumour recurrence, whereas COX-2 expression (P = 0.634) and K-ras mutation (P = 0.356) were not. Tumour angiogenesis may be associated with tumour metastasis and is significantly influenced by K-ras mutation, p53 overexpression and COX-2 expression in patients with colonic cancer.


Health risk of consuming Sphoeroides spp. from the Navachiste Lagoon complex due to its trace metals and organochlorine pesticides content.
The Navachiste complex (NAV) is impacted by neighbored human activities and is located in the southwestern coastal zone of the Gulf of California. The study determines the trace metal (TM) and organochlorine pesticides (OCP) health risk content in the edible tissue of Sphoeroides spp. from NAV. The daily intakes (EDI), target hazard quotient (THQ), hazard index (HI), and carcinogenic and non-carcinogenic risks were calculated. Twenty OCP and seven TM were detected. Cd, Cu, Fe, Mn, Pb, and Zn were above MRLs. The γ‒Chlordane was the most frequent OCP. The highest average concentration was for α‒HCH, followed by γ‒chlordane. With the high ratios of γ‒HCH, p, p'‒ DDD and p, p'‒DDD, and the absence of p, p'‒ DDT, the higher ratios for dieldrin and endrin than for aldrin, α‒ chlordane, γ‒chlordane, heptachlor, and heptachlor epoxide indicates historical contamination. In contrast, the residual products of methoxychlor, endosulfan, and its isomers indicate endosulfan's recent use. The TM EDI, THQ > 1 (at 120 g day-1), and the ILCR (> 1 × 10-6) were above minimum levels, showing a high-risk potential for cancer development in the long term.


Enrichment of cadmium and selenium in soil-crop system and associated probabilistic health risks in black shale areas.
Selenium (Se) is the essential component of selenoenzymes and contributes to antioxidant defenses. The capability of Se to antagonize the toxicity of heavy metals makes it an essential trace element for human and plant health. Soils derived from black shales are naturally enriched with Se; however, these soils often contain high geological cadmium (Cd), due to the weathering of black shales rich in Cd and Se. Cadmium, as a known Group I carcinogen, could induce damage to various organs. This therefore poses a major challenge for safe cultivation of Se-rich land resources. In this study, a total of 247 paired soil-crop samples were collected from a typical farmland derived from black shales. The concentrations of Cd and Se in the samples were analyzed by inductively coupled plasma mass spectroscopy and atomic fluorescence spectrometry. Monte Carlo simulation was applied to evaluate potential health risks associated with Cd exposure. Cadmium was the critical pollutant in the study area, with the average value of 1.53 mg/kg. Moreover, both children and adults living in the area had a significant non-carcinogenic health risk. Additional health risk assessments revealed that diet was the main contributor for both children and adults among the four pathways (diet > soil ingestion > soil dermal adsorption > soil inhalation). Furthermore, our results revealed that leguminous vegetables and maize were ideal for this site due to their high Se and low Cd accumulation abilities. These findings provide support for adjusting planting structure by variety screening to mitigate the health risk induced by Cd.


Treatment of iatrogenic functional or morphologic bladder loss.
From 1984 to 1986, six children from 4 to 13 years of age, received a bladder augmentation by ileocecal cystoplasty (Mainz-pouch technique) because of an iatrogenic functional or morphologic bladder loss. Indications for operation were incontinence due to the low bladder capacity or threat to the upper urinary tract due to ureteral obstruction or vesicorenal reflux. Two of the children had already undergone supravesical urinary diversion by sigmoid conduit. After a follow-up period of 2 to 19 months, (mean 11 months), five of the six children are completely continent. One boy with a known weak sphincter still has slight, but decreasing, enuresis nocturna in periods of complete filling of the pouch, 1 month after the operation. All children are able to void their augmented bladders without residual urine.


In vitro study of smooth muscle cells on polycaprolactone and collagen nanofibrous matrices.
Biodegradable polycaprolactone and collagen nanofibers were produced by electrospinning, with fiber diameters of around 300-700nm and features similar to the extracellular matrix of natural tissue. Human coronary artery smooth muscle cells (SMCs) seeded on nanofibrous matrices tend to maintain normal phenotypic shape and growth tends to be guided by the nanofiber orientation. The SMC and nanofibrous matrix interaction was observed by SEM, MTS assay, trypan blue exclusion method and laser scanning confocal microscopy. The results showed that the proliferation and growth rate of SMCs were not different on polycaprolactone (PCL) nanofibrous matrices coated with collagen or tissue culture plates. PCL nanofibrous matrices coated with collagen showed that the SMCs migrated towards inside the nanofibrous matrices and formed smooth muscle tissue. This approach may be useful for engineering a variety of tissues in various structures and shapes, and also to demonstrate the importance of matching both the initial mechanical properties and degradation rate of nanofibrous matrices to the specific tissue engineering.


Social support for mothers in illness: a multifaceted phenomenon.
Many women privilege the mothering role over other areas of their lives, and for ill women, it can be difficult to relinquish maternal responsibility. Not being able to mother in their usual way can have consequences for women's wellbeing and view of themselves as 'good' mothers. In this study, 77 mothers of dependent children were interviewed about their experiences of illness, and the social support they received. Despite their illnesses, participants in this study continued to feel they were primarily responsible for the wellbeing and care of their children, and were distressed if they were unable to adequately fulfil the primary carer role. As participants sometimes found it difficult to care for their children, help with childcare emerged as an important element of social support. Seeking assistance with care for children revealed a tension between support that was accessible and support that was acceptable. Mothering while ill is difficult and women facing illness may need encouragement to accept help to continue to meet their maternal responsibilities. Nurses are in an excellent position to encourage women to identify and draw upon sources of support to assist them in maintaining their mothering role while ill.