Patient reported outcomes after risk-reducing surgery in patients at increased risk of ovarian cancer.
To describe the quality of life of women at an increased risk of ovarian cancer undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). Patients evaluated in our gynecologic oncology ambulatory practice between January 2018-December 2019 for an increased risk of ovarian cancer were included. Patients received the EORTC QLQ-C30 and PROMIS emotional and instrumental support questionnaires along with a disease-specific measure (PROM). First and last and pre- and post-surgical PROM responses in each group were compared as were PROMs between at-risk patients and patients with other ovarian diseases. 195 patients with an increased risk of ovarian cancer were identified, 155 completed PROMs (79.5%). BRCA1 or BRCA2 mutations were noted in 52.8%. Also included were 469 patients with benign ovarian disease and 455 with ovarian neoplasms. Seventy-two at-risk patients (46.5%) had surgery and 36 had both pre- and post-operative PROMs. Post-operatively, these patients reported significantly less tension (p = 0.011) and health-related worry (p = 0.021) but also decreased levels of health (p = 0.018) and quality of life <7d (0.001), less interest in sex (p = 0.014) and feeling less physically attractive (p = 0.046). No differences in body image or physical/sexual health were noted in at-risk patients who did not have surgery. When compared to patients with ovarian neoplasms, at-risk patients reported lower levels of disease-related life interference and treatment burden, less worry, and better overall health. In patients with an increased risk of ovarian cancer, RRBSO is associated with decreased health-related worry and tension, increased sexual dysfunction and poorer short-term quality of life. Patients with ovarian neoplasms suffer to a greater extent than at-risk patients and report higher levels of treatment burden and disease-related anxiety.


Three new tools for parathyroid surgery: expensive and unnecessary?
The intraoperative quick parathyroid hormone assay, the intraoperative gamma probe, and endoscopic parathyroidectomy are three very new techniques developed to facilitate parathyroid surgery. Some hospitals do not have the necessary equipment, and many, like ours, continue to operate in the time-honored way. We performed a retrospective chart review of 34 such operations, done with the use of Sestamibi scans, but entirely without the newer modalities. Four-gland exploration was carried out on all patients. Operative times ranged from 15 to 165 minutes, with a mean of 47 minutes, and incision lengths ranged from 2 to 3 cm, with a mean of 2.8 cm. There was no mortality, no reoperation, and no vocal cord or recurrent laryngeal nerve injury. Our cure rate was 100%, as determined by a fall in postoperative calcium and parathormone levels. In our view, the intraoperative parathyroid hormone assay, gamma probe, and endoscopic parathyroidectomy add an entirely unnecessary cost to an operation that can be completed satisfactorily with a preoperative Sestamibi scan and a thorough four-gland exploration.


Mechanical properties, corrosion and degradation behaviors, and in vitro cytocompatibility of a biodegradable Zn-5La alloy for bone-implant applications.
Zinc (Zn) and its alloys are used in bone-fixation devices as biodegradable bone-implant materials due to their good biosafety, biological function, biodegradability, and formability. Unfortunately, the clinical application of pure Zn is hindered by its insufficient mechanical properties and slow degradation rate. In this study, a Zn-5 wt.% lanthanum (Zn-5La) alloy with enhanced mechanical properties, suitable degradation rate, and cytocompatibility was developed through La alloying and hot extrusion. The hot-extruded (HE) Zn-5La alloy showed ultimate tensile strength of 286.3 MPa, tensile yield strength of 139.7 MPa, elongation of 35.7%, compressive yield strength of 262.7 MPa, and microhardness of 109.7 HV. The corrosion resistance of the HE Zn-5La in Hanks' and Dulbecco's modified Eagle medium (DMEM) solutions gradually increased with prolonged immersion time. Further, the HE Zn-5La exhibited an electrochemical corrosion rate of 36.7 μm/y in Hanks' solution and 11.4 μm/y in DMEM solution, and a degradation rate of 49.5 μm/y in Hanks' solution and 30.3 μm/y in DMEM solution, after 30 d of immersion. The corrosion resistance of both HE Zn and Zn-5La in DMEM solution was higher than in Hanks' solution. The 25% concentration extract of the HE Zn-5La showed a cell viability of 106.5%, indicating no cytotoxicity toward MG-63 cells. We recommend the HE Zn-5La alloy as a promising candidate material for biodegradable bone-implant applications. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion and degradation behaviors, in vitro cytocompatibility and antibacterial ability of biodegradable Zn-5La alloy for bone-implant applications. Our findings demonstrate that the hot-extruded (HE) Zn-5La alloy showed an ultimate tensile strength of 286.3 MPa, a yield strength of 139.7 MPa, an elongation of 35.7%, compressive yield strength of 262.7 MPa, and microhardness of 109.7 HV. HE Zn-5La exhibited appropriate degradation rates in Hanks' and DMEM solutions. Furthermore, the HE Zn-5La alloy showed good cytocompatibility toward MG-63 and MC3T3-E1 cells and greater antibacterial ability against S. aureus.


Effect of DDT exposure on lipids and energy balance in obese Sprague-Dawley rats before and after weight loss.
Dichlorodiphenyltrichloroethane (DDT) and its metabolites accumulate in adipose tissue through dietary exposure, and have been proposed to contribute to the development of abdominal obesity, insulin resistance and dyslipidemia. Toxicity may also result when DDT and its metabolites are released from adipose tissue into the bloodstream as a result of rapid weight loss. We hypothesized that DDT-exposed rats fed a high fat diet (HFD) followed by 60% calorie restriction would have an adverse metabolic response to rapid weight loss. To test this, we exposed obese Sprague-Dawley (SD) rats to DDT and a HFD over one month followed by 60% calorie restricted diet for two weeks, and examined metabolic parameters throughout the study. During the HFD feeding period, DDT-exposed rats had significantly elevated postprandial non-esterified fatty acids (NEFAs) and decreased body temperature compared with control rats. During calorie restriction, DDT-exposed rats had lowered food efficiency (weight gained/calories consumed), body temperature, and circulating TSH. Our findings suggest that exposure to DDT may impairs metabolic substrate utilization in rats during dynamic periods of weight gain and weight loss.


Growth Hormone-induced STAT5B Regulates Star Gene Expression Through a Cooperation With cJUN in Mouse MA-10 Leydig Cells.
Leydig cells produce androgens that are essential for male sex differentiation and reproductive function. Leydig cell function is regulated by several hormones and signaling molecules, including growth hormone (GH). Although GH is known to upregulate Star gene expression in Leydig cells, its molecular mechanism of action remains unknown. The STAT5B transcription factor is a downstream effector of GH signaling in other systems. While STAT5B is present in both primary and Leydig cell lines, its function in these cells has yet to be ascertained. Here we report that treatment of MA-10 Leydig cells with GH or overexpression of STAT5B induces Star messenger RNA levels and increases steroid hormone output. The mouse Star promoter contains a consensus STAT5B element (TTCnnnGAA) at -756 bp to which STAT5B binds in vitro (electrophoretic mobility shift assay and supershift) and in vivo (chromatin immunoprecipitation) in a GH-induced manner. In functional promoter assays, STAT5B was found to activate a -980 bp mouse Star reporter. Mutating the -756 bp element prevented STAT5B binding but did not abrogate STAT5B-responsiveness. STAT5B was found to functionally cooperate with DNA-bound cJUN. The STAT5B/cJUN cooperation was only observed in Leydig cells and not in Sertoli or fibroblast cells, indicating that additional Leydig cell-enriched transcription factors are required. The STAT5B/cJUN cooperation was lost only when both STAT5B and cJUN elements were mutated. In addition to identifying the Star gene as a novel target for STAT5B in Leydig cells, our data provide important new insights into the mechanism of GH and STAT5B action in the regulation of Leydig cell function.


Enlarged perivascular spaces mimicking multicystic brain tumors. Report of two cases and review of the literature.
The authors present two cases in which enlarged Virchow-Robin spaces were located in the basal ganglia and the thalamomesencephalic region. The incidence of such huge cystic lesions is extremely rare. The expanding nature of these lesions, demonstrated by the patients' progressive symptoms due to compression of the adjacent brain parenchyma and obstructive hydrocephalus, mimicked that of brain tumors. The two patients were successfully treated by neuroendoscopic cystocisternostomy or ventriculocystostomy. To the authors' knowledge there have been only two published reports on expanding Virchow-Robin spaces that produced a compressive effect or consequent hydrocephalus and were directly fenestrated using neuroendoscopic techniques. Neuroendoscopy appears to offer an effective surgical option in the treatment of symptomatic Virchow-Robin spaces.


Local cerebral blood flow in spontaneously breathing rats subjected to graded isobaric hypoxia.
Local cerebral blood flow (l-CBF) was measured with an autoradiographic technique in spontaneously breathing rats exposed to air or gas mixtures of O2 and N2, giving inspired oxygen fractions (FiO2) ranging from 0.21 to 0.07. The arterial O2 tension (PaO2) changed from 10.9 +/- 0.3 (FiO2 0.21) to 3.9 kPa (FiO2 0.07) (82 +/- 2 to 29 mmHg). Hypoxia caused hyperventilation, and the arterial CO2 tension (PaCO2) fell from 5.21 +/- 0.05 kPa (FiO2 0.21) to 3.27 kPa (FiO2 0.07) (39.1 +/- 0.4 to 24.5 mmHg). The hyperventilatory response was markedly augmented when changing FiO2 from 0.13 to 0.11, causing a fall in PaCO2 of 0.75 kPa and a shift in arterial pH from 7.45 +/- 0.01 (FiO2 0.13) to 7.54 +/- 0.01 (FiO2 0.11). The l-CBF response to hypoxia was found to be biphasic for all the observed regions. At FiO2 0.13, l-CBF was measured about 75% above control but at FiO2 0.11, only 30% above control. A further reduction in FiO2 to 0.07 caused a marked increase in l-CBF, at least 240% of control; however, the applied CBF technique did not admit quantitation. These results suggest that the mechanisms controlling the cerebrovascular response to hypoxia and changes in arterial CO2 tensions are different. The results also indicate that hyperventilation might be harmful to the patient suffering from acute hypoxia.


Diabetes and inflammation: fundamental aspects and clinical implications.
The aim of this paper is to provide the fundamental background of the inflammation theory associated with type 2 diabetes, to discuss the clinical consequences of low-grade inflammation, particularly in terms of cardiovascular risk, and to infer some clinical therapeutic strategies deriving from drugs that already exist or are in development. This non-exhaustive work is the result of a Pubmed(®) research, based on requests including the following keywords: diabetes, inflammation, innate immunity, obesity, reticulum endoplasmic stress, cytokines, endothelial dysfunction. Obesity and type 2 diabetes are linked with a low-grade inflammation state that reflects the activation of innate immunity where metabolic, environmental and genetic factors are implicated. The role of endoplasmic reticulum stress and unfold protein response is underlined. Inflammation markers are predictive for the risk to develop diabetes, and are associated with an increased cardiovascular risk. While lifestyle modifications are followed by an improvement in inflammation markers, treatments inferred from the inflammation theory are of great interest, although quite moderate effects on glycaemic control have been observed with some of them. The development of molecules targeting different inflammatory mechanisms could lead in diabetic patients to improvement of both glycaemia and cardiovascular prognosis.


Modulation of phospholipase A2 activity in human endometrium and amniotic membrane by steroid hormones.
Phospholipase A2 (PLA2) activity was measured in endometrium and amnion by a double isotope ratio technique using 1-palmitoyl-2-oleoyl phosphatidylcholine as substrate in the presence and absence of a range of unconjugated steroids and steroid sulphates (0.2-6.4 X 10(-4) M). In the presence of 0.1% Triton, PLA2 activity was inhibited by the majority of steroids tested, pregnenolone sulphate being the most effective (12.9 +/- 3.0% control activity) while oestradiol sulphate, oestrone and testosterone had only a minimal or no effect (99.1 +/- 19.0, 85.4 +/- 4.4 and 104.2 +/- 16.3% control respectively). In the absence of Triton, the inhibitory effect of the free steroids was reduced or absent but oestradiol sulphate and testosterone sulphate stimulated activity by 2-13 and 1.5-3 times respectively. The effect was dose related, linear with time and independent of the stage of the menstrual cycle. Inhibition by pregnenolone sulphate, dehydroepiandrosterone (DHA sulphate and oestrone sulphate was maintained in the absence of Triton (24.9 +/- 3.8, 67.1 +/- 10.1 and 87.2 +/- 13.8% control respectively). In amnion all 5 steroid sulphates caused a marked stimulation of PLA2 activity in both the presence and absence of Triton. The effect was greatest without Triton and at 6.4 X 10(-4) M, testosterone, pregnenolone, oestrone, DHA and oestradiol sulphates increased PLA2 activity 20, 15, 12, 10 and 6-fold respectively. These findings indicate a direct action of steroid sulphates on PLA2 activity in endometrium and amnion.


Temporal dynamics and metabolic correlation between lactate-producing and hydrogen-producing bacteria in sugarcane vinasse dark fermentation: The key role of lactate.
This study aimed to better understand the role of different microbial groups and the determining fermentation pathways in a biohydrogen (bioH2)-producing reactor fed with sugarcane vinasse by using next-generation sequencing and principal component analysis (PCA). Both microbial structure and dynamics were characterized. The highest bioH2 production levels were associated with the Thermoanaerobacterium genus, whilst lactate-producing bacteria comprised the dominant genera (e.g. Lactobacillus and Leuconostoc) within the reactor at both stable and unstable bioH2-producing periods. PCA further revealed that the fermentation of lactate played a dual role in the reactor, as both bioH2-producing (acetate+lactate→butyrate+bioH2) and non-bioH2-producing (lactate→propionate+acetate) routes could be observed. Overall, the results suggested that lactate is the primary alternative carbon source in vinasse-fed systems subjected to carbohydrate-shortage conditions.


[The recasting of the job reference system, what are the stakes for training?]
Expected for many months, even years, the reform of the nursing profession is on its way. However, it will be necessary to determine which gradation of the evolution of competences will be arbitrated in order to guarantee the conceptual acceptance of the approach by all the actors and to answer the modernized stakes of the nurse's role. The subject of a renewed elaboration of the decree of acts dating from 2004 remains at the heart of the debates. But on what legal basis will it be necessary from now on to recognize and develop the disciplinary field of nursing sciences? A decree on competencies and a definition of the profession by mission are the first avenues suggested. The possibility of a national license, replacing the degree, should also be discussed during the work on training, with a view to establishing the academic branch of the discipline.


Concurrent IgG4-related hypophysitis and clinically nonfunctioning gonadotroph pituitary neuroendocrine tumor.
Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET. A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-β and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels. This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging.


Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer.
Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated "M@P-PDR"), which acted as "Nano-targeted cells" to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with "Nano-targeted cells"-based cocktail therapy. "Nano-targeted cells"-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.


In silico and in vitro analyses of the angiotensin-I converting enzyme inhibitory activity of hydrolysates generated from crude barley (Hordeum vulgare) protein concentrates.
Angiotensin-I-converting enzyme (ACE-I) plays a key role in control of hypertension, and type-2 diabetes mellitus, which frequently co-exist. Our current work utilised in silico methodologies and peptide databases as tools for predicting release of ACE-I inhibitory peptides from barley proteins. Papain was the enzyme of choice, based on in silico analysis, for experimental hydrolysis of barley protein concentrate, which was performed at the enzyme's optimum conditions (60 °C, pH 6.0) for 24 h. The generated hydrolysate was subjected to molecular weight cut-off (MWCO) filtration, following which the non-ultrafiltered hydrolysate (NUFH), and the generated 3 kDa and 10 kDa MWCO filtrates were assessed for their in vitro ACE-I inhibitory activities. The 3 kDa filtrate (1 mg/ml), that demonstrated highest ACE-I inhibitory activity of 70.37%, was characterised in terms of its peptidic composition using mass spectrometry and 1882 peptides derived from 61 barley proteins were identified, amongst which 15 peptides were selected for chemical synthesis based on their predicted ACE-I inhibitory properties. Of the synthesized peptides, FQLPKF and GFPTLKIF were most potent, demonstrating ACE-I IC50 values of 28.2 μM and 41.2 μM respectively.


Determination of cyclopiazonic acid in white mould cheese by liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) using a novel internal standard.
For the determination of cyclopiazonic acid (CPA) in food and feed samples a simple and accurate LC-MS/MS method, which does not require extensive sample clean-up steps, was developed and validated. A fully carbon-13-labelled internal standard was used to compensate for matrix effects. Briefly, the samples were extracted with 1% formic acid in acetonitrile and directly analysed with HPLC-MS/MS. The following MS/MS transitions were used: m/z 337/196 and 337/182 for cyclopiazonic acid; m/z 357/210 and 357/191 for (13)C20-cyclopiazonic acid. Applying this optimised method, LODs down to 0.2μgkg(-1) and LOQs down to 0.5μgkg(-1) were determined in the validated matrices. The focus of this study was testing different types of white mould cheese but other complex samples could also be analyzed successfully with this method. It was interesting to find out, that in some commercially available white mould cheese, high concentrations of CPA (up to 3700μgkg(-1)) could be found.


Synchronous reconstruction of the floor of mouth and chin with a single skin island fibular free flap.
The goal this presentation is to: 1) Review the reconstructive options for anterior mandible through-and-through composite defects and 2) Instruct the audience in the application of the double-skin paddle fibular flap in selected patients. Case presentation with review of the literature. A 70-year old male with an anterior floor of mouth squamous cell carcinoma underwent composite resection that included resection of a 5-cm ovoid component of overlying chin skin. The defect was reconstructed with a fibular osteocutaneous flap with a double skin paddle technique. Several reconstructive options have been described in the literature for extended oral cavity defects including the use of multiple free flaps, combinations of regional and distant flaps, and sequential reconstruction. This case report reviews the use of a single flap reconstruction of these defects for selected patients.


Occurrence and spatial characteristics of polychlorinated biphenyls (PCBs) in sediments from rivers in the western Niger delta of Nigeria impacted by urban and industrial activities.
The characteristic concentrations of 28 PCB congeners, their spatial distributions, sources, and associated risks to the ecosystem were investigated in sediments of some rivers around a glass industry and power generating plant in the Niger Delta of Nigeria. Gas chromatography-mass spectrometry (GC-MS) was applied for the identification and quantification of PCBs in sediments from these rivers. The Ʃ28 PCB concentrations (dry weight) in sediments ranged from 1520 to 3540 ng g-1 for the Afiesere River, 976-5670 ng g-1 for the Edor River, and from 1440 to 6340 ng g-1 for the Okpare River. The homologue distribution patterns in sediments from these rivers indicated that low-chlorinated (2 Cl to 5 Cl) PCBs were more dominant than high-chlorinated (6 Cl to 10 Cl) PCBs with tri-, penta- and deca-PCBs as the top homologues. The PCB source analyses suggested that the PCB contamination of these river sediments could have originated from Aroclor mixtures, paints, pigments and other inadvertent sources. The risk assessment indicated a high risk to the ecosystem.


Adenosine deaminase 2 from chicken liver: purification, characterization, and N-terminal amino acid sequence.
Adenosine deaminase (ADA) is involved in purine metabolism and plays an important role in the mechanism of the immune system. ADA activity is composed of two kinetically distinct isozymes, which are referred to as ADA1 and ADA2. ADA1 is widely distributed in many animals and well characterized. On the contrary, relatively little is known about ADA2. In this study, we first purified ADA2 to homogeneity from chicken liver. The purified enzyme had a molecular mass of approximately 110 kDa on gel filtration. Also, the enzyme was shown to be a homodimer with an estimated molecular mass of 61 kDa on SDS-PAGE. Following treatment with N-glycosidase, the molecular mass of ADA2 changed to 55 kDa. Several properties of the highly purified ADA2 were also investigated in this study. Furthermore, the N-terminal amino acid sequence of ADA2 was determined.


A method for measuring cyto-adherence on frozen tissue sections.
A simple method for quantifying the cells adhering to frozen sections of mouse spleen using a microscope equipped with a drawing tube attachment, and a planimeter is described. It is a straightforward and reproducible technique which was been preliminarily employed to study optimal binding conditions for Esheep and EoxAC.


A heterogeneous "resting" pool of synaptic vesicles that is dynamically interchanged across boutons in mammalian CNS synapses.
Using pHluorin-tagged synaptic vesicle proteins we have examined the partitioning of these probes into recycling and nonrecycling pools at hippocampal nerve terminals in cell culture. Our studies show that for three of the major synaptic vesicle components, vGlut-1, VAMP-2, and Synaptotagmin I, approximately 50-60% of the tagged protein appears in a recycling pool that responds readily to sustained action potential stimulation by mobilizing and fusing with the plasma membrane, while the remainder is targeted to a nonrecycling, acidic compartment. The fraction of recycling and nonrecycling (or resting) pools varied significantly across boutons within an individual axon, from 100% resting (silent) to 100% recycling. Single-bouton bleaching studies show that recycling and resting pools are dynamic and exchange between synaptic boutons. The quantitative parameters that can be extracted with the approaches outlined here should help elucidate the potential functional role of the resting vesicle pool.


Interferon-gamma responses to ESAT-6 in tuberculosis patients early into and after anti-tuberculosis treatment.
To investigate T-cell responses to ESAT-6 by an interferon-gamma (IFN-gamma) ex vivo enzyme-linked immunospot (ELISpot) assay in tuberculosis (TB) patients early during treatment and in patients who have completed a course of anti-tuberculosis chemotherapy. T-cell responses following overnight stimulation with 6-kD early secretory antigenic target (ESAT-6) antigen were compared to responses obtained using cells cultured with ESAT-6 for 6 days, using an ELISpot assay. In the ex vivo ELISpot assay, the median IFN-gamma responses in TB patients, irrespective of treatment status, were significantly higher than in healthy BCG-vaccinated controls. In the 6-day ELISpot assay, median IFN-gamma responses were significantly higher in TB patients who had completed treatment than in patients early during therapy. There was considerable individual variability in the degree of expansion of ESAT-6 specific T-cells from day 1 to day 6 in both treatment groups. Further studies are required to assess which type of assay provides the best indicator of a memory T-cell response and how ESAT-6 specific T-cells relate to protective immunity in TB infection.


Evaluation of fetal heart serum amyloid a concentrations in infectious cattle abortion cases.
Serum amyloid A (SAA) concentrations have been investigated in diseases of human and domestic animals and increased SAA levels have been reported in infectious diseases. In the present study, we determined the fetal heart blood SAA concentrations in aborted bovine fetuses and investigated the relationship between the level of SAA and causative infectious agents. A total of 46 heart blood samples were collected from aborted bovine fetuses between July 2018 and July 2019 and were assigned to two groups according to microbiological, pathological and molecular results. Group 1: An infectious disease was diagnosed by detecting a microorganism (21 cases); Group 2: An infectious or inflammatory disease was not detected (25 cases). The fetal heart blood SAA concentrations were measured by commercial ELISA test. Serum amyloid A concentrations in aborted bovine fetuses were elevated from 6.1 to ≥40 mg/L in 17 of 21 cases in group 1. In group 2, SAA concentrations were less than 2.5 mg/L in 23 of 25 cases. This difference was statistically significant between group 1 and group 2. These findings suggest that SAA concentrations in fetal heart blood from bovine fetuses is potentially a novel marker for distinguishing between infectious and non-infectious bovine abortion cases.


Ultrathin Double-Shell Capsules for High Performance Photon Upconversion.
Triplet-fusion-based photon upconversion capsules with ultrathin double shells are developed through a single dripping instability in a microfluidic flow-focusing device. An inner separation layer allows use of a brominated hydrocarbon oil-based fluidic core, demonstrating significantly enhanced upconversion quantum yield. Furthermore, a perfluorinated photocurable monomer serves as a transparent shell phase with remote motion control through magnetic nanoparticle incorporation.


Impaired left ventricular function has a detrimental effect on image quality in multi-detector row CT coronary angiography.
To determine whether there is a relationship between left ventricular (LV) haemodynamic parameters, circulation times, and arterial contrast opacification that might affect the image quality of computed tomography (CT) coronary angiography. Thirty-six patients were included in the study: 18 with cardiomyopathy (CM) and LV dilatation of suspected ischaemic aetiology [age 57.9+/-13.7 years, range 30-77 years; 14 male, four female; body mass index (BMI)=27.7+/-4.5, range 25.5-31.8] and 18 controls (age 62.3+/-9.4 years, range 47-89 years; 10 male, eight female; BMI 27.8+/-6.6; range 19.2-33.6). Coronary artery image quality was assessed using a three-point visual scale; contrast medium circulation times, aortic root contrast attenuation, and LV functional parameters were studied. Visually reduced contrast opacification impaired image quality more often in the CM group than the control group (27.4 versus 5.1%). A total of 55.6% CM patients had a contrast transit time ranging from 30-75 s; the number of "unassessable" segments increased with increasing transit time conforming to a fitted quadratic model (R2=0.74). The relationship between LV ejection fraction and contrast attenuation may also conform to a quadratic model (R2=0.71). LV haemodynamics influence coronary artery opacification using cardiac CT, and users imaging this subgroup must do so with the knowledge of this potential pitfall. The results indicate the need for further studies examining CT protocols in this clinical subgroup.


Does Exercise Improve False Episodic Memory in Dementia?
Ageing is a risk factor involved in decline in cognitive function, particularly in executive function, processing speed and episodic memory [...].


Prevalence of genetic mutations in alpha-1 antitrypsin deficiency (aatd) in patients with chronic obstructive pulmonary disease in Colombia.
Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder associated mainly with pulmonary emphysema and Chronic Obstructive Pulmonary Disease (COPD). All individuals with COPD regardless of age or ethnicity should be tested for AATD, but in Colombia its prevalence in unknown. To determine the prevalence of the genetic mutations, present in AATD in adult patients with COPD in Colombia, using a genotyping test on cells from the oral mucosa. This was a multicentre, observational, cross-sectional study which included adult patients attending seven COPD care centres in Colombia. Demographic data, medical history, including history of exposure to smoking and biomass smoke, most recent spirometry, pharmacological and non-pharmacological treatment received, serum AAT levels, and mutations detected by the genotyping test were recorded for all the recruited patients. For the comparison of variables between the groups with and without mutation, we used the X2 test for the qualitative variables and the Student's t-test or Mann-Whitney U test according to their distribution. We collected a sample of 1,107 patients, the median age was 73.8 years (87.6-79.9). Mutations were documented in 144 patients (13.01%), the majority had the M/S mutation (78.50%), followed by M/Z (9.72%). One patient had a ZZ mutation and two patients had null alleles. In total, 23 patients had mutations associated with serum AAT deficiency (levels below 60 mg/dl). Genetic mutations were documented in 13.01% of patients with COPD in Colombia and 2.07% were AATD-related, showing that there is a significant number of underdiagnosed patients.


Maxillofacial Injuries due to Bear Mauling.
Bear bite injuries have become a common occurrence as the forest covers and natural habitats are diminishing. Patients injured in bear attack present with different patterns of injuries. A common protocol may not be suitable for the management of injuries inflicted by these large wild animals. These animals usually attack in remote areas where composite trauma centres do not exist and urgent referrals of these patients will have significant effect on the final outcome. Limited literature is available describing bear bite management in maxillofacial practice. The goal of the present case reports is to document the injuries suffered in bear mauling and to add to the literature on the conservative management with minimal complications.


Postoperative Cerebral Ischemia Due to Hypotension in Moyamoya Patient with Autonomic Dysfunction.
Hypotension is a significant risk factor for the development of ischemic complication following revascularization surgery for moyamoya disease (MMD). However, it is currently unknown whether autonomic dysfunction also plays a role. Here we report a case of MMD in which hypotension due to autonomic dysfunction caused postoperative cerebral ischemia. A 30-year-old female patient with MMD had a history of transient right hemiparesis following laughter. Single-photon emission computed tomography showed impaired cerebral blood flow (CBF) in both cerebral hemispheres, so she underwent revascularization surgery in her left cerebral hemisphere. She awoke from anesthesia uneventfully; however, 1 hour after the surgery her blood pressure suddenly dropped to 90/40 mm Hg and she became comatose. A perfusion computed tomography scan demonstrated a widespread reduction in CBF in the left hemisphere. Bezold-Jarisch reflex was thought to be the cause of the hypotension. Following treatment with a vasopressor agent, her BP increased and her consciousness rapidly recovered. The reduced CBF had almost completely recovered the next day. Head-up tilt test conducted 2 weeks after surgery demonstrated latent vasopressor-type autonomic dysfunction, which was possibly another cause of the hypotension. She was discharged from the hospital, and the laughter-induced hemiparesis gradually resolved. Situational neurologic deterioration in patients with MMD suggests latent autonomic dysfunction, which may be a risk factor for postoperative ischemic complications.


HER2 genomic heterogeneity is a frequent event in gastroesophageal adenocarcinoma and correlates with tumor morphology.
To characterize a cohort of gastro-esophageal adenocarcinomas (GEA) evaluated for HER2 gene amplification using bright field in situ hybridization (ISH) following the 2016 guidelines for GEA and correlating the results with clinico-pathological features. It was also aimed to evaluate the effect of applying the ISH criteria from the 2018 guidelines for breast cancer (BC) in the same GEA cases. 159 GEA cases collected in a period of 59 months were evaluated for HER2 gene amplification by ISH according to GEA and BC guidelines. All cases were reviewed for histological type, grading and presence of signet ring cells. Most of the cases refereed to ISH were HER2 equivocal (57.9 %) by immunohistochemistry. According to the GEA guideline, 131 cases were HER2-negative (87.3 %) and 19 cases were HER2-positive (12.7 %). According to the BC guideline, 133 cases were HER2-negative (88.7 %) and 17 cases were HER2-positive (11.3 %), being statistically similar to the results obtained with the GEA guideline. HER2 genomic heterogeneity was detected in 31.6 % of the HER2-positive cases, almost exclusively in tubular adenocarcinoma. We observed a significant association between HER2 gene amplification and tubular adenocarcinomas, and absence of signet ring cells. The only case with HER2 gene amplification and presence of signet ring cells was a mixed carcinoma, where the signet ring cells represented the non-amplified component. HER2 positivity rate was similar when applying the GEA or the BC guidelines. We also establish a tight association between morphology and HER2 gene amplification.


Three-channel Lissajous' trajectory of human auditory brain stem evoked potentials.
By simultaneously recording from 3 orthogonal electrode montages, and plotting the 3 voltage-time records on three-dimensional voltage-voltage-voltage coordinates, a spatial Lissajous' trajectory is obtained. This 3-Channel Lissajous' Trajectory (3CLT) represents the simultaneous voltage values from 3 independent montages and, assuming a uniform volume conductor, it includes all the information required for calculation of the dipole equivalent of surface-recorded activity. In 3CLT time is not explicitly graphed, but is implied as motion along the trajectory. Thanks to the small distribution of the generators of BAEPs, relative to their distance from the recording electrodes, 3CLT of BAEPs holds the promise of summarizing all activity from the surface. Comparing 3CLT of BAEPs to left vs. right ear stimulation has confirmed the lateralization of components I and III, but has also shown lateralization for the other components, which detailed surface mapping studies had overlooked. 3CLT may offer a more sensitive, yet less cumbersome, alternative to detailed surface mapping of BAEPs. The full promise of 3CLT can only be evaluated after quantitative indices of the trajectory are developed.


Multiple interactions between the alpha 2C- and beta1-adrenergic receptors influence heart failure survival.
Persistent stimulation of cardiac beta1-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the alpha 2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (ADRB1 and ADRA2C, respectively) on the risk of death/transplant in heart failure patients. Sixteen sequence variations in ADRA2C and 17 sequence variations in ADRB1 were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation. Three polymorphisms in ADRA2C and five polymorphisms in ADRB1 were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18) relative to all other genotype classes. Multiple polymorphisms act synergistically between the ADRA2C and ADRB1 genes to increase risk of death or cardiac transplant in heart failure patients.


Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus.
Gastroparesis is a common gastrointestinal complication in diabetes mellitus, whereas dysfunction in the other gastrointestinal organs has been less thoroughly investigated. Furthermore, it is not known whether there is any relationship between motility and dysmotility between these organs. The aim of this study was to examine whether diabetic patients with gastrointestinal symptoms also have motility disturbances in the oesophagus and stomach and, if so, whether there are any associations between these disturbances. Thirty-one patients with diabetes mellitus who complained of gastrointestinal symptoms were asked to complete a questionnaire about their symptoms. They were further investigated with oesophageal manometry and gastric emptying scintigraphy. Fifty-eight per cent of the patients had abnormal oesophageal function, and 68% had delayed gastric emptying. Abdominal fullness was the only symptom that related to any dysfunction, and it was associated with delayed gastric emptying (P = 0.02). We did not find any relationship in motility or dysmotility between the oesophagus and the stomach. Oesophageal dysmotility, as well as gastroparesis, are common in patients with diabetes who have gastrointestinal symptoms. It is important to investigate these patients further, to be able to reach an accurate diagnosis and instigate appropriate treatment. Our findings indicate that the oesophagus and the stomach function as separate organs and that pathology in one does not necessarily mean pathology in the other.


Exploiting the potential of fabric phase sorptive extraction for forensic food safety: Analysis of food samples in cases of drug facilitated crimes.
Drug-facilitated crimes (DFCs) entail the use of a single drug or a mixture of drugs to render a victim unable. Traditionally, biological samples have been gathered from victims and conducting analysis to establish evidence of drug administration. Nevertheless, the rapid metabolism of various drugs and delays in analysis can impede the identification of such substances. For this, the present article describes a rapid, sustainable, highly efficient and miniaturized protocol for the identification and quantification of three sedative-hypnotic drugs namely diazepam, chlordiazepoxide and ketamine in alcoholic beverages and complex food samples (cream of biscuit, flavoured milk, juice, cake, tea, sweets and chocolate). The methodology involves utilizing fabric phase sorptive extraction (FPSE) to extract diazepam (DZ), chlordiazepoxide (CDP), and ketamine (KET), Subsequently, the extracted sample are subjected to analysis using gas chromatography-mass spectrometry (GC-MS). Several parameters, including type of membrane, pH, agitation time and speed, ionic strength, sample volume, elution volume and time, and type of elution solvent, were screened and thoroughly optimized. Sol-gel Carbowax 20M (CW-20M) has demonstrated most effective extraction efficiency for the target analytes among all evaluated membranes. Under optimal conditions, the method displayed linearity within the range of 0.3-10 µg mL-1 (or µg g-1), exhibiting a coefficient of determination (R2) ranging from 0.996 to 0.999. The limits of detection (LODs) and limits of quantification (LOQs) for liquid samples ranging between 0.020 and 0.069 µg mL-1 and 0.066-0.22 µg mL-1, respectively. Correspondingly, the LODs for solid samples ranged from 0.056 to 0.090 µg g-1, while the LOQs ranged from 0.18 to 0.29 µg g-1. Notably, the method showcased better precision, with repeatability and reproducibility both below 5% and 10%, respectively. Furthermore, the FPSE-GC-MS method proved effective in determining diazepam (DZ) in forensic food samples connected to drug-facilitated crimes (DFCs). Additionally, the proposed method underwent evaluation for its whiteness using the RGB12 algorithm.


Characterization of spontaneous and chemically induced cardiac lesions in rodent model systems: the national toxicology program experience.
Induction of heart disease can be related to exposure to a number of agents, including environmental chemicals. Studies with laboratory rodents are commonly used to identify cardiotoxic agents and to investigate mechanisms of toxicity. This study was conducted to characterize spontaneous and chemically-induced rodent heart lesions. A retrospective light-microscopic evaluation was performed on the hearts of F344 rats and B6C3F1 mice from National Toxicology Program studies of six chemicals in which chemically-induced myocardial toxicity was present: oxymetholone, monochloroacetic acid, 3,3'-4,4'- tetrachoroazoxybenzene, diethanolamine, urethane, and methyl bromide. Two myocardial lesions were observed: cardiomyopathy (multifocal myofiber degeneration that could occur spontaneously or as a treatment effect) and degeneration (diffuse myofiber degeneration that was clearly related to treatment). Oxymetholone produced cardiotoxicity that was apparent as an increase in the incidence and average severity of cardiomyopathy. The remaining five chemicals produced degeneration, which appeared morphologically similar with each of the chemicals. Based on available information concerning possible mechanisms by which each of these chemicals may induce cardiotoxicity, this evaluation indicated it may be possible to place the chemicals into two main categories: (1) those that primarily affected the coronary vasculature with secondary effects on the myocardium (oxymetholone), and (2) those that had a direct toxic effect on the myocardial cells (the remaining five chemicals). Beyond this, however, light-microscopic findings did not indicate any specific mechanisms. Additional morphologic evaluations, such as electron microscopy or special histochemical or immunostains, may help identify specific subcellular sites of toxic damage, which in turn can indicate appropriate types of molecular mechanistic studies.


High-resolution ultrasound-guided percutaneous needle biopsy and intraoperative ultrasonography of a cervical parathyroid adenoma in a patient with persistent hyperparathyroidism.
We present a case of persistent hyperparathyroidism in which high-resolution real-time ultrasonography was used to perform a percutaneous needle biopsy of a parathyroid tumor. Additionally, intraoperative ultrasonography was valuable in the precise localization of the tumor and thereby reduced the need for extensive surgical reexploration.


The object of this investigation was to find out what significance the agglutinin Anti-AHP (Prokop et al., 1968a) has for the postembryonal development of Helix pomatia. 1. The agglutinin Anti-AHP, beside its significance as an immunobiological protection for the living egg, has a conserving and protective function for dead eggs. Dead eggs do not become in any way tainted nor do they rot. 2. A direct relation between Anti-AHP and the postembryonal development could not be found. The reaction disappears between the ninth and sixteenth day of live and does not reappear till the snails have a fully developed reproductive system. An indirect relation exists in so far as dead eggs strongly promote the growth of young snails which feed on them.


The median to ulnar cross-sectional surface area ratio in carpal tunnel syndrome.
To investigate the use of a sonographic median-to-ulnar cross-sectional area ratio (MUR) in diagnosis of carpal tunnel syndrome (CTS); and to compare the MUR with currently used sonographic parameters, and electrophysiology. Subjects with CTS and healthy volunteers underwent ultrasound studies of the median and ulnar nerves in the wrist and forearm. Various sonographic parameters and ratios were calculated, and compared between CTS patients and controls. The sensitivity and specificity of the different parameters were compared by plotting receiver operator characteristic curves. Correlations of sonographic results with electrophysiologic studies were calculated. The MUR was increased in patients with CTS, in comparison with controls. A cut-point of >2.09 yielded a sensitivity of 86% and specificity of 84%. This was comparable to the currently used ultrasound metrics for CTS. The MUR also correlated with electrophysiologic severity. The MUR is an effective means of diagnosing CTS and correlates with electrophysiologic severity. This report provides support for the use of the MUR in the sonographic diagnosis of CTS.


Treatment of iron overload in adults with continuous parenteral desferrioxamine.
Adult patients with transfusional hemosiderosis were given ascorbic acid and treated with the iron chelator, desferrioxamine B. The drug was administered by continuous subcutaneous or intravenous infusions using a light weight portable constant infusion device. On this regimen, four of the five patients studied were able to excrete significant amounts of iron (greater than 35 mg/da) when receiving a daily desferrioxamine dose of 1.5 to 2.2 g. Continuous subcutaneous infusion was well tolerated and about 80 per cent as effective as intravenous therapy in chelating iron. The number of prior transfusions, the hepatic iron content and the serum ferritin levels appear to be useful in predicting which patients will respond to iron chelation therapy, especially if there is little bone marrow erythropoietic activity. One patient with ineffective erythropoiesis did not have significantly increased hepatic iron stores but responded to the administration of desferrioxamine. Continuous subcutaneously administered desferrioxamine may prove to be adaptable for long-term outpatient therapy, allowing patients with ongoing transfusion requirements to go into negative iron balance. Long-term studies will be needed to demonstrate reversal of endocrine, hepatic and cardiac dysfunction secondary to iron deposition in these patients.


Axial movements are relatively preserved with respect to limb movements in aphasic patients.
Apraxia is commonly manifested during the acute stage following left hemisphere cerebrovascular accident and typically co-occurs with aphasia. We examined 30 acute stroke patients with aphasia and apraxia in order to determine if such patients show evidence of preservation of selective subclasses of movements. Although Geschwind noted the preservation of axial movements to command in aphasic apraxic patients, his views were subsequently refuted. However, we found that aphasic apraxic patients of varying degrees of severity, including patients with global aphasia, showed relative preservation of axial movements to command and imitation. Theoretical interpretations and implications for acute neurologic rehabilitation are discussed.


Feasibility of PET for the management of coronary artery disease: Comparison between CFR and FFR.
Myocardial perfusion imaging using positron emission tomography (PET) allows both qualitative and quantitative measurement. The quantitative myocardial blood flow and coronary flow reserve (CFR) are reliable indices for evaluating functional severity, influenced by both epicardial stenosis and microvascular disease. Fractional flow reserve (FFR) also reflects physiological stenosis, which measures the pressure differences across a coronary artery stenosis during maximum hyperemia. Discordance between CFR and FFR has been noticed in estimating the functional significance of coronary stenosis. In this review, we summarize the feasibility of PET for the management of coronary artery disease compared to FFR.


Marine natural products that inhibit osteoclastogenesis and promote osteoblast differentiation.
Osteoporosis is a disease that affects the quality of life of elderly people. The balance between bone formation mediated by osteoblasts and bone resorption by osteoclasts is important to maintain the normal bone condition. Therefore, the promotion of osteoblast differentiation and the suppression of osteoclastogenesis are effective strategies for osteoporosis treatment. Marine organisms are a promising source of biologically active and structurally diverse secondary metabolites, and have been providing drug leads for the treatment of numerous diseases. We describe the marine-derived secondary metabolites that can inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and promote osteoblast differentiation.


When self-report diverges from performance: the usage of BIS-11 along with neuropsychological tests.
Impulsivity has been fractionated into multiple independent, but correlated, components. Personality and neuropsychological studies have consistently shown its multidimensional nature. Each theoretical approach uses different techniques such as self-report questionnaires and neuropsychological tests to assess impulsivity, respectively. Our main objective was to investigate if there is evidence of convergent validity for impulsivity as assessed by both types of measures. We administered the Barratt Impulsivity Scale 11 and two neuropsychological tests (Iowa Gambling Task and Continuous Performance Task) to 266 participants to measure inhibition control and non-planning impulsivity dimensions. Results from an exploratory factorial analysis and group comparison indicated there was little evidence of convergent validity between the two types of measures. These findings are discussed in terms of impulsivity as a multi-factorial construct as well as the specific instruments used for assessment. Implications for psychological theory and impulsivity assessment were also proposed.


Comparison of mild ovarian stimulation with conventional ovarian stimulation in poor responders.
To compare the IVF outcomes of mild ovarian stimulation with conventional ovarian stimulation in poor responders. From 2004 to 2009, 389 IVF cycles in 285 women showed poor responses (defined as either a basal FSH level ≥12 mIU/mL, or the number of retrieved oocytes ≤3, or serum E(2) level on hCG day <500 pg/mL) were analyzed, retrospectively. In total, 119 cycles with mild ovarian stimulation (m-IVF) and 270 cycles with conventional ovarian stimulation (c-IVF) were included. Both groups were divided based on their age, into groups over and under 37 years old. The m-IVF group was lower than the c-IVF group in the duration of stimulation, total doses of gonadotropins used, serum E(2) level on hCG day, the number of retrieved oocytes, and the number of mature oocytes. However, there was no significant difference in the number of good embryos, the number of transferred embryos, the cancellation rate, or the clinical pregnancy rate. In the m-IVF group over 37 years old, the clinical pregnancy rate and live birth rate were higher when compared with the c-IVF group, but this result was not statistically significant. In poor responder groups, mild ovarian stimulation is more cost effective and patient friendly than conventional IVF. Therefore, we suggest that mild ovarian stimulation could be considered for poor responders over 37 years old.


Identification and characterization of the gltK gene encoding a membrane-associated glucose transport protein of pseudomonas aeruginosa.
The Pseudomonas aeruginosa oprB gene encodes the carbohydrate-selective OprB porin, which translocates substrate molecules across the outer membrane to the periplasmic glucose-binding protein. We identified and cloned two open reading frames (ORFs) flanking the oprB gene but are not in operonic arrangement with the oprB gene. The downstream ORF encodes a putative polypeptide homologous to members of a family of transcriptional repressors, whereas the oprB gene is preceded by an ORF encoding a putative product, which exhibits strong homology to several carbohydrate transport ATP-binding cassette (ABC) proteins. The genomic copy of the upstream ORF was mutagenized by homologous recombination. Analysis of the deletion mutant in comparison with the wild type revealed a significant reduction in [14C] glucose transport activity in the mutant strain, suggesting that this ORF likely encodes the inner membrane component of the glucose ABC transporter. It is thus designated gltK gene to reflect its homology to the Pseudomona fluorescens mtlK and its involvement in the high-affinity glucose transport system. Multiple alignment analysis revealed that the P. aeruginosa gltK gene product is a member of the MalK subfamily of ABC proteins.


Outcomes of bridging versus mesh augmentation in laparoscopic repair of small and medium midline ventral hernias.
Bridging of the hernia defect in laparoscopic repair (sIPOM) technique does not fully restore the abdominal wall function. Closure of hernia defect in IPOM-plus technique leads to the restoration of abdominal wall function and improved long-term treatment outcomes. Against the expectations, the studies confirm the formation of intraabdominal adhesions to the mesh. Regardless of the above, the search of the proper technique for mesh implantation and fixation is still ongoing. There have also been attempts to identify groups of patients who may still benefit from IPOM procedure. Patients with midline abdominal wall hernias up to 10 cm wide were enrolled in the study except for subxiphoid and suprapubic hernias. Between 2011 and 2014 we performed 82 hernia repairs using the laparoscopic technique with Physiomesh. Patients were divided into sIPOM and IPOM-plus groups. The study included 44M and 38F patients aged 27-84 years. After 12-months and again in August 2015 a survey was posted to all patients with questions regarding potential recurrence. After 12 months, eight patients (20 %) in sIPOM group reported subjectively perceived recurrence and none in IPOM-plus group (p = 0.002). Six patients (14.3 %) in sIPOM group reported suspected recurrence, as compared to three patients (7.1 %) in IPOM-plus group (p = 0.13). These patients were invited for a follow-up physical examination and sonography. Eventually, four cases of hernia recurrence were confirmed in sIPOM group (10 %) and none in IPOM-plus group (p = 0.018). Other patients presented with mesh bulging. Laparoscopic ventral hernia repair is generally safe and is associated with the low recurrence rate. Closure of fascial defects before mesh insertion offers better treatment outcomes. Non-closure of fascial defects with only bridging of the hernia defect (sIPOM) causes more frequent recurrence and bulging. As a result, patient satisfaction with treatment is lower, and they are concerned about hernia recurrence.


A comparison of Sysmex-XN 2000 and Yumizen H2500 automated hematology analyzers.
A complete blood count is a highly automated laboratory test. The use of highly advanced measurement methods increases the accuracy and sensitivity of the determination of individual hematological parameters, especially in the case of white blood cells differentiation. Therefore, it is necessary to make comparative analyses, which involve performance of the analyzers used in daily work. The aim of the study was to indicate whether the results obtained using two compared analyzers show significant differences. In this study a comparative analysis of 241 peripheral blood samples from adult patients was performed. The complete blood count results were obtained using two automated hematology analyzers: Sysmex XN-2000 and Horiba Yumizen H2500. The Passing-Bablok regression method and Bland- Altman analysis were also used to evaluate the results received for both analyzers. Statistically significant differences were found for four hematological parameters: eosinophil count, immature granulocytes, mean corpuscular hemoglobin concentration (MCHC) and platelet distribution width (PDW). The P value for MCHC was 0.01. Sysmex XN-2000 and Horiba Yumizen H2500 also showed disagreement in plate platelet distribution width (PDW) (P = 0.04). For other parameters both analyzers showed good agreement. Based on the results of the study, it was shown that there are significant differences in the measurements of hematological parameters between compared analyzers.


Multipara with utero-vesical fistula following repeat cesarean section: a rare iatrogenic complication.
Utero-Vesical fistulas are the rarest of all urogenital fistulas, with most cases occurring after cesarean section. Its prevalence is increasing worldwide because of the increasing indications of cesarean section. Patient usually presents with urine leak, amenorrhea and cyclic hematuria. Herein, we present a case of patient presenting with complain of severe urinary tract infection following cesarean section. Review and update of recent literature regarding the diagnostic imaging of this entity are described.


Attentional orienting and reorienting is indicated by human event-related brain potentials.
We investigated event-related potential indications for the orienting towards task-irrelevant, distracting aspects of stimulation and for the subsequent reorienting towards task-related aspects of stimulation. An identical experimental protocol was run in three conditions manipulating the task relevance of the sounds. As to be expected, distractors elicited the MMN (reflecting the brain's pre-attentive change detection) in each condition (even when the sounds were ignored) and subsequent N2b and P3 (reflecting orienting towards the distractor) when the sounds were attended. A late negativity was confined to a condition in which subjects discriminating long from short sounds were distracted by task-irrelevant frequency deviations. The 'reorienting negativity' (RON) probably reflects processes in the context of reorienting towards task-relevant aspects of stimulation following distraction.


Group cognitive-behavior therapy with family involvement for middle-school-age children with obsessive-compulsive disorder: a pilot study.
Middle-school-aged children with obsessive-compulsive disorder (OCD) are poised in development between the dependency of elementary-school-aged children and growing independence of adolescence. OCD patients of this age group may differ from older ones in the quality of symptoms and level of insight. We report the results of a naturalistic, pilot study of group Cognitive-behavior Therapy (CBT) for school-aged children with OCD with parents involved. The authors predicted symptom improvement and format acceptability. Over a 1.5 year period, 14 children with OCD aged 8-14 years and their parents received 14-week group CBT based on March and Mulle's OCD in Children and Adolescents: A Cognitive-Behavioral Treatment Manual in three consecutive sessions of four to six families. Age of onset averaged 8.7 years, 36% had undergone at least one medication trial, and 36% had previous CBT experience. OCD symptoms measured by the Children's Yale-Brown Obsessive Compulsive Scale improved significantly, both statistically and clinically (25%) from moderate-severe to mild-moderate. Mean Clinical Global Impression of Impairment (NIMH-CGI) Impairment ratings fell from clinical to sub-clinical and CGI Improvement ratings were "much improved". Children's self-reported depression decreased significantly from pre- to post-group. Parent ratings of the negative impact of OCD symptoms on the Children's OCD Impact Scale and of behavior problems on the Child Behavior Checklist each improved significantly. This pilot study, which included a non-selected clinical sample, demonstrates that a manual-based treatment protocol may be effectively adapted for group treatment of different developmental levels and be exported for clinical use. Clinical improvement justifies further investigation in a controlled study.


Physical abuse of urban Native Americans.
To ascertain the extent of, and risk factors for, physical abuse among older urban American Indian/Alaska Natives (AI/ANs), we conducted a chart review of 550 urban AI/AN primary care patients >/=50 years old seen during 1 year. Mistreatment was documented in 10%. A logistic regression found younger age (P <.001), female gender (P <.001), current depression (P <.001), and dependence on others for food (P <.05) to be significant correlates of physical abuse. In only 31% of instances of definite abuse were the authorities notified. We conclude that providers should be alert to the possibility of physical mistreatment among older urban AI/ANs. Improvements in detection and management are sorely needed.


Characterization of Riboflavin-Producing Strains of Lactobacillus plantarum as Potential Probiotic Candidate through in vitro Assessment and Principal Component Analysis.
Lactic acid bacteria (LAB) are known for their probiotic properties, but only a few strains produce riboflavin. We evaluated the probiotic properties of four riboflavin-producing strains of Lactobacillus plantarum (BBC33, BBC32A, BIF43, and BBC32B) by using in vitro assessment and carried out multivariate principal component analysis (PCA) to select the best strain. Safety, antioxidant, and exopolysaccharide-producing properties were also studied. Lact. plantarum BBC33 showed better probiotic potential, followed by strain BIF43. Lact. plantarum BBC32A degraded mucin and excluded as a potential probiotic candidate. Lact. plantarum BIF43, BBC33, and BBC32A tolerated simulated gastrointestinal conditions and their overnight cell-free culture supernatants (CFSs, pH 4.0-4.3) inhibited the growth of Escherichia coli AF10, Salmonella Typhi MTCC98, Bacillus cereus NCDC250, and Pseudomonas aeruginosa NCDC105. Lact. plantarum BIF43 and BBC33 did not degrade mucin, adhered to human epithelial colorectal adenocarcinoma Caco-2 cells (22-25%), and aggregated with indicators (30-50%). Moreover, both were non-hemolytic and sensitive to most antibiotics tested. Of the two selected strains, BIF43 showed better exopolysaccharides (EPS) producing phenotype. The CFSs of all strains showed high (85-93%) 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. PCA confirmed the results obtained from in vitro probiotic experiments and supported the selection of Lact. plantarum BIF33 and BBC43, as potential probiotics.


Concentrated Bone Marrow Aspirate Is More Cellular and Proliferative When Harvested From the Posterior Superior Iliac Spine Than the Proximal Humerus.
The purpose of this study is to determine whether concentrated bone marrow aspirate (cBMA) from the posterior superior iliac spine (PSIS) or proximal humerus (PH) produces a more productive cellular harvest in patients undergoing arthroscopic rotator cuff repair. Patients under 80 years old undergoing surgery for arthroscopic rotator cuff repair were enrolled. Two 60 mL aliquots of BMA were harvested from each subject, one from the PSIS and one from the PH. Each aliquot was processed independently to create cBMA. Cellular composition was determined using an automated hemocytometer and proliferative potential was studied with colony forming unit (CFU) assays. Twelve patients were recruited (7 male, 5 female). The average age was 64.3 years (range 46.1-77.25 years) with body mass index of 26.8 (range 20.0-34.3). The average total nucleated cells (TNC) from PH was 18.7 × 106 cells/mL (95% confidence interval [CI], 4.4-33.0; standard deviation [SD], 24.8) with 3.9 CFU/mL (95% CI, 0.3-7.5, SD, 5.7). The average TNC count from the PSIS was 55.9 × 106 cells/mL (95% CI, 25.3-86.4; SD, 52.9) with 32.5 CFU/mL (95% CI, 11.5-53.5; SD, 33.1). The PSIS had a 3.0 times greater total nucleated cell yield (P = .014) and 8.3 times greater number of CFU/mL (P = .024) when compared to the PH. The average harvest time from the PSIS was 5.6 minutes and from the PH was 11.0 minutes (P = .043); harvest time did not account for additional time to prep and drape the PSIS. The cBMA harvested from the PSIS resulted in a 3.0 times greater cellular yield and an 8.3 times greater proliferative product than cBMA from the PH. When a more cellular cBMA product is sought to augment rotator cuff tear repair surgery, the PSIS is the preferred site for harvest.


Internal mammary blood supply for ileo-colon interposition in esophagogastroplasty: a case report.
We report on a clinical case where microsurgical techniques successfully supported traditional surgery in a wide reconstruction between the oropharynx and small bowel. Several years ago, the patient sustained a severe corrosive injury of the upper digestive tract with subsequent esophageal stricture and stiffening; at that time, an emergency gastrectomy was performed. In this case, the restoration of the defect could not rely on the classic colonic interposition. During the operation the ileo-colic flap, well-fitted for tension-free reconstruction, revealed the foreseen inadequacy of its vascularization based on the sole middle colic vascular pedicle. The blood supply to its proximal part was then increased by microanastomosis between the right internal mammary and ileo-colic vessels. The revascularization ensured the viability of the interposed tissue. Oral intake resumed after 3 weeks; nowadays the patient is able to maintain her ideal weight with adequate nutrition.


Regulation of brain-derived neurotrophic factor messenger RNA levels in avian hypothalamic slice cultures.
Mechanisms regulating the expression of brain-derived neurotrophic factor, a member of the neurotrophin family, have been extensively studied in the rat cerebral cortex, hippocampus and cerebellum. In contrast, little is known regarding the regulation of this growth factor in the hypothalamus. Here we present an analysis of the regulation of brain-derived neurotrophic factor messenger RNA levels in chick embryo hypothalamic slice cultures following exposure to potassium chloride, glutamate agonists and sex steroids. Following a week in chemically-defined media the tissue was depolarized by exposure to 50 mM potassium chloride for 6h, resulting in a significant 4.2-fold increase in the level of brain-derived neurotrophic factor messenger RNA. This result is consistent with studies of other brain regions. Similar 6-h acute exposures of the hypothalamic cultures to 25 microM N-methyl-D-aspartic acid, 25 microM kainic acid and 25 microM alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid also significantly increased messenger RNA levels 2.5-, 2.1- and 1.4-fold, respectively. It was previously reported that brain-derived neurotrophic factor levels within the rat cerebral cortex, olfactory bulb and hippocampus are altered by exposure to 17beta-estradiol. Here we show that in hypothalamic slice cultures neither acute nor chronic treatments with 10 and 100 nM 17beta-estradiol and 10nM testosterone significantly altered the steady-state level of this growth factor. These findings show that neuronal activity, induced by glutamate agonists and potassium chloride, can regulate brain-derived neurotrophic factor messenger RNA levels within embryonic hypothalamic slice cultures. This regulation could play a critical role in the modulation of programmed cell death and synaptic maturation during development of the hypothalamus.


Histochemical study of globules in accessory cells of sea-urchin ovary: in relation to jelly coat substance.
Accessory cells of the sea-urchin ovary were studied histologically and histochemically. Different types of globules in these cells were distinguished. Histochemical observations suggest that the accessory cells synthesize neutral mucosubstances, sulfo- and sialopolysaccharides, which might be precursors for jelly formation.


Predictors of Adverse Fetal Outcomes in Intrahepatic Cholestasis of Pregnancy (ICP): a Narrative Review.
Intrahepatic cholestasis of pregnancy (ICP) is a hepatic disorder in pregnancy linked with adverse fetal outcomes, which primarily manifests in the late second and third trimesters of pregnancy. This review aims to recapitulate the existing evidence on factors that can predict detrimental perinatal outcomes in pregnant women diagnosed with intrahepatic cholestasis of pregnancy. We searched PubMed, Web of Science, Cochrane Library, Scopus, Medline, and Embase databases and selected studies related to predictors of fetal outcome in intrahepatic cholestasis of pregnancy. Studies of the articles showed that predictors of an adverse fetal outcome include in vitro fertilization (IVF) pregnancy, multifetal pregnancy, biochemical markers, gestational age of ICP onset, presence of comorbidities (preeclampsia and gestational diabetes mellitus), maternal history of ICP, and hepatobiliary disease.Intrahepatic cholestasis of pregnancy (ICP) complicates the pregnancy. Hence, early assessment of low-risk and high-risk groups will help to administer definite management protocols and strategies to prevent adverse neonatal outcomes. Further research should concentrate on the number of conditions/factors and the predictive power of different factors to determine the most reliable predictors and biomarkers that can predict adverse fetal outcomes and improve the assessment of risk in pregnancy complicated with ICP.


Long noncoding RNA DLX6-AS1 promotes liver cancer by increasing the expression of WEE1 via targeting miR-424-5p.
Long noncoding RNAs (lncRNAs) played an important role in tumorigenesis and development of hepatocellular carcinoma (HCC). In this study, we first demonstrated that lncRNA DLX6 antisense RNA 1 (DLX6-AS1) was upregulated in cancer tissues and cells lines compared with normal adjacent and cell line. Knock-down DLX6-AS1 by transfection with small interfering RNA (siRNA) suppressed cell proliferation, migration, and invasion of HCC cells. Cell cycle analysis showed that cells transfected with siRNA were arrested in G0/G1 phase. Then, we performed dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay to show that DLX6-AS1 could bind with miR-424-5p. And cotransfection inhibitor of miR-424-5p with siRNA of DLX6-AS1 could abolish the inhibitory effect of siRNA of DLX6-AS1 on cell proliferation, migration, and invasion. Moreover, we further demonstrated that the oncogene WEE1 G2 checkpoint kinase (WEE1) was the target of miR-424-5p and expression levels of WEE1 were positive correlation with that of DLX6-AS1. Taken together, these results suggested that upregulated DLX6-AS1 promoted cell proliferation, migration, and invasion of HCC through increasing expression of WEE1 via targeting miR-424-5p.


Higher prevalence and levels of Nosema ceranae than Nosema apis infections in Canadian honey bee colonies.
This study was conducted to determine the prevalence and infection levels of the microsporidia fungi Nosema apis and/or Nosema ceranae in honey bee colonies of two Canadian provinces. Three surveys were conducted in the springs of 2008, 2010 and 2012 and PCR identification of Nosema species were performed in samples from 169 and 181 Ontario colonies and from 76 Alberta colonies that tested positive to Nosema spp. Infection levels of positive colonies were determined by microscopy and analyzed by Nosema spp. Results showed that N. ceranae was the dominant species in all three surveys (prevalence range of 41-91 vs. 4-34 % for N. apis), whereas mixed infections were less frequent than single infections (5-25 %). Infection levels of colonies parasitized by N. ceranae were three to five times higher than those of colonies parasitized by N. apis in the three surveys whereas mixed infections showed the highest spore counts. This is the first field study demonstrating significantly higher infection levels in colonies parasitized with either N. ceranae only or with both, N. ceranae and N. apis, than in colonies parasitized with N. apis only. Taken together, these results suggest that N. ceranae may be more virulent and better adapted than N. apis in cold climates such as Canadian environments.


[Bodies and Political Orders. On the Role of Bodies in Modern Western Political Theory].
At first glance, it can be stated that bodies do not play an important role in modern Western political theory. They are mostly privatized and set as natural or prepolitical. This article argues, however, that bodies are not absent in modern political theory but that they play a crucial political role. They legitimize political orders in a subtle way. Through an examination of central arguments in the work of Thomas Hobbes, John Locke, Jean-Jacques Rousseau, Immanuel Kant, Hannah Arendt, John Rawls, and Jürgen Habermas, three ways are identified in which bodies shape modern Western political theory. First, bodies are used to legitimize the political order; second, they serve to determine political subjectivity; and third, body politics define politics. The text aims to highlight how a body-theoretical perspective that does not define the body as prepolitical but rather as a political construct is able to expand the scope of political theory.


Evidence that methylglyoxal and receptor for advanced glycation end products are implicated in bladder dysfunction of obese diabetic ob/ob mice.
Glycolytic overload in diabetes causes large accumulation of the highly reactive dicarbonyl compound methylglyoxal (MGO) and overproduction of advanced glycation end products (AGEs), which interact with their receptors (RAGE), leading to diabetes-associated macrovascular complications. The bladder is an organ that stays most in contact with dicarbonyl species, but little is known about the importance of the MGO-AGEs-RAGE pathway to diabetes-associated bladder dysfunction. Here, we aimed to investigate the role of the MGO-AGEs-RAGE pathway in bladder dysfunction of diabetic male and female ob/ob mice compared with wild-type (WT) lean mice. Diabetic ob/ob mice were treated with the AGE breaker alagebrium (ALT-711, 1 mg/kg) for 8 wk in drinking water. Compared with WT animals, male and female ob/ob mice showed marked hyperglycemia and insulin resistance, whereas fluid intake remained unaltered. Levels of total AGEs, MGO-derived hydroimidazolone 1, and RAGE in bladder tissues, as well as fluorescent AGEs in serum, were significantly elevated in ob/ob mice of either sex. Collagen content was also markedly elevated in the bladders of ob/ob mice. Void spot assays in filter paper in conscious mice revealed significant increases in total void volume and volume per void in ob/ob mice with no alterations of spot number. Treatment with ALT-711 significantly reduced the levels of MGO, AGEs, RAGE, and collagen content in ob/ob mice. In addition, ALT-711 treatment normalized the volume per void and increased the number of spots in ob/ob mice. Activation of AGEs-RAGE pathways by MGO in the bladder wall may contribute to the pathogenesis of diabetes-associated bladder dysfunction.NEW & NOTEWORTHY The involvement of methylglyoxal (MGO) and advanced glycation end products (AGEs) in bladder dysfunction of diabetic ob/ob mice treated with the AGE breaker ALT-711 was investigated here. Diabetic mice exhibited high levels of MGO, AGEs, receptor for AGEs (RAGE), and collagen in serum and/or bladder tissues along with increased volume per void, all of which were reduced by ALT-711. Activation of the MGO-AGEs-RAGE pathway in the bladder wall contributes to the pathogenesis of diabetes-associated bladder dysfunction.


The wax gourd genomes offer insights into the genetic diversity and ancestral cucurbit karyotype.
The botanical family Cucurbitaceae includes a variety of fruit crops with global or local economic importance. How their genomes evolve and the genetic basis of diversity remain largely unexplored. In this study, we sequence the genome of the wax gourd (Benincasa hispida), which bears giant fruit up to 80 cm in length and weighing over 20 kg. Comparative analyses of six cucurbit genomes reveal that the wax gourd genome represents the most ancestral karyotype, with the predicted ancestral genome having 15 proto-chromosomes. We also resequence 146 lines of diverse germplasm and build a variation map consisting of 16 million variations. Combining population genetics and linkage mapping, we identify a number of regions/genes potentially selected during domestication and improvement, some of which likely contribute to the large fruit size in wax gourds. Our analyses of these data help to understand genome evolution and function in cucurbits.


Limitations of electronic energy transfer in the determination of lipid nanodomain sizes.
Even though superresolution microscopy indicates that size of plasma membrane rafts is <20 nm, those structures have never been observed. Förster resonance energy transfer (FRET) is therefore still the most powerful optical method for characterization of such domains. In this letter we investigate relation between nanodomain affinity of a donor-acceptor (D/A) pair and the detectable nanodomain size/area. We show that probes with high affinity to the liquid-ordered (L(o)) phase are required for detecting domain sizes of a few nanometers, and/or domains that occupy a few percent of the bilayer area. A combination of donors and acceptors that prefer different phases is the more favorable approach. For instance, a D/A pair with the distribution constant of donors K(D) = 5 and acceptors K(A) = 0.01 can resolve a broad spectrum of nanodomain sizes. On the other hand, currently available donors and acceptors that prefer the same phase, either the liquid-disordered (L(d)) or L(o) phase, are not so convenient for determining domain sizes <20 nm. Here the detection limits of FRET experiments employing several commonly used D/A pairs have been investigated.


Diffusion tensor imaging (DTI) of human lower leg muscles: correlation between DTI parameters and muscle power with different ankle positions.
To compare diffusion tensor imaging (DTI) parameters in healthy adult human lower leg muscles and to determine the correlation between DTI parameters and muscle power measurements among different types of muscle contraction. DTI measurements of the unilateral lower leg muscles having three different types of contraction (non-contraction state, isometric contraction, and soleus shortening) were obtained from 10 healthy adults using a 3-T MRI scanner. DTI parameters (λ1, λ2, λ3, mean diffusivity, and fractional anisotropy) were calculated. The values of the DTI parameters and correlation between the DTI parameters and muscle power measurements (maximum power and maximum amount of work) obtained from a dynamometer were statistically compared among the different types of contraction. Intra- and inter-class correlation coefficients were calculated for analysis of reproducibility. The λ1, λ2, λ3, and mean diffusivity of the soleus muscle are significantly lower in the non-contraction state as compared with isometric contraction and soleus shortening (p < 0.05). A positive correlation of the soleus muscle in the non-contraction state was seen between the maximum power and the λ1, λ2, and mean diffusivity. There was a positive correlation between the maximum amount of work and fractional anisotropy in the non-contraction state for the soleus muscle. A negative correlation for the tibialis anterior muscle in the non-contraction state was seen between the maximum amount of work and fractional anisotropy. Overall reproducibility of the DTI parameters was excellent. DTI parameters were significantly changed depending on the ankle joint position and type of muscle contraction.


Molecular Markov processes.
Markov processes are encountered in many contexts in physics and chemistry. This review surveys the scope of their application.


Pigment gene expression in protan color vision defects.
We screened 150 male eye donors and identified four who did not have or express L pigment genes, consistent with each of them having a congenital protan color vision defect. One donor was identified as a protanope because he had and expressed a single X-chromosome photopigment gene that encoded an M pigment. Three were categorized as protanomalous because each expressed significant levels of genes specifying two spectrally different M pigments. The first gene in each of the protanomalous arrays was expressed the most and encoded an M pigment that differed in amino acid sequence from M pigments in color normal men.


Determination of the optimal acquisition protocol of breath-hold PET/CT for the diagnosis of thoracic lesions.
The aim of this study was to determine the optimal acquisition scan protocol for deep inspiration breath-hold (BH) fluoro-2-deoxy-D-glucose positron emission tomography (PET) for the examination of thoracic lesions. We studied 32 thoracic lesions in 21 patients. Whole-body PET/computed tomography (CT) scanning with free breathing (FB) was performed for 3 min per bed position, followed by a BH-CT and five BH-PET for 20 s each. Summed BH images with total acquisition times of 40, 60, 80 and 100 s were generated (BH × 2, BH × 3, BH × 4 and BH × 5, respectively). The displacements between PET and CT images, the lesion volume of the PET image, the maximum standardized uptake value (SUVmax) and the quality of the PET image were assessed in relation to the clinical characteristics of each patient and the summation of the BH-PET images. BH-PET decreased the tumor volume significantly (FB: 7.23 ± 9.70 cm³, BH × 5: 4.71 ± 5.14 cm³, P<0.01) and increased the SUVmax (FB: 6.27 ± 5.41, BH × 5: 7.53 ± 6.28, P<0.01). The displacement between the PET and CT images was improved significantly in the BH scans (FB: 0.77 ± 0.53 cm, BH × 5: 0.36 ± 0.24 cm, P<0.01). In addition, aging and lung function of patients influenced the reproducibility of BH-PET. The summed BH-PET images, obtained by summation of three or more BH-PET images (total acquisition time of 60 s or more), achieved good image quality. BH-PET/CT improved the misregistration between PET and CT images and increased the SUVmax of thoracic lesions. The recommended number of BH-PET images for summation with 20 s of acquisition time is three or more.


Complete mitochondrial genome of Chinese big-headed turtle, Platysternon megacephalum, with a novel gene organization in vertebrate mtDNA.
The mitochondrial genome of the Chinese big-headed turtle, Platysternon megacephalum, was obtained using polymerase chain reaction (PCR). The entire mtDNA sequence, the longest mitochondrial genome in turtles reported so far, is 19161 bp. This mitochondrial genome exhibits a novel gene order, which greatly differs from that of any other vertebrates. It is characterized by four distinctive features: 1) the translocation of a gene cluster including three tRNA genes (tRNAHis, tRNASer, tRNALeu(CUN)) and ND5 gene, 2) two tRNAThr pseudogenes, 3) a duplication of pseudo tRNAThr/tRNAPro/D-loop region and 4) 3 non-coding spacers. These unique identities represent a new mitogenomic gene order in vertebrates. The TDRL model was proposed to account for the generation of the gene order in P. megacephalum.


Novel throughput phenotyping platforms in plant genetic studies.
Unraveling the genetic basis of complex traits in plants is limited by the lack of appropriate phenotyping platforms that enable high-throughput screening of many genotypes in multilocation field trials. Near-infrared spectroscopy on agricultural harvesters and spectral reflectance of plant canopies have recently been reported as promising components of novel phenotyping platforms. Understanding the genetic basis of complex traits is now within reach with the use of these new techniques.


Load-dependent dysfunction of the putamen during attentional processing in patients with clinically isolated syndrome suggestive of multiple sclerosis.
Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.


Emerging therapeutic concepts for muscle and bone preservation/building.
Loss of muscle or bone mass occurs with ageing, immobility and in association with a variety of systemic diseases. The interaction of these two processes is most evident in the major contribution of falls to the risk of fractures in the elderly population. Exercise and nutrition are key common physiological variables that allow for preservation or formation of greater muscle or bone mass. However, although several pharmacological approaches have the potential to benefit both muscle and bone health, for example vitamin D, selective androgen receptor modulators and ghrelin mimetics, clinical trials with appropriate primary outcomes are lacking. Conventional approaches to address muscle loss are being extended to include stem cell biology and conserved molecular mechanisms of atrophy/hypertrophy. Pharmacological interventions to reduce fracture risk are exploring new mechanisms of action, in particular the uncoupling of bone resorption and formation. Emerging key issues for clinical trial design include adequate phenotyping of patients (personalised medicine), optimisation of the physiological background (multimodal approach) and the use of meaningful and robust outcomes relevant to daily clinical practice. At present, effective treatments that combine beneficial effects on both muscle and bone are lacking, although this is an important target for the future. This review therefore considers current and developing strategies to improve muscle function and bone strength in separate sections.


Engineered Sphingomonas sp. KT-1 PahZ1 monomers efficiently degrade poly(aspartic acid).
In recent years, there has been an effort toward creating and utilizing novel biodegradable polymeric materials. As products become available, it is necessary to concurrently search for novel biodegradation catalysts and further investigate the properties of known biodegradation enzymes. Regarding the latter, we recently reported the crystal structure of a dimeric enzyme, Sphingomonas sp. KT-1 PahZ1, capable of degrading poly(aspartic acid), a green alternative to non-biodegradable polycarboxylates. However, the role of the dimeric state in catalytic function remained unclear. Here we report PahZ1KT-1 constructs with either single or multiple mutation(s) at the dimer interface yield active monomers. Our data indicates PahZ1KT-1 monomers and dimers catalyze PAA degradation at equivalent rates. Unfolding experiments reveal differences where the activation energy for monomers is ~ 46 kJ mol-1 lower than for dimers despite similar thermodynamic properties. Characterization of this biodegradation enzyme and others is critical for future protein engineering efforts toward polymer remediation.


A multidimensional computer adaptive test approach to dyspnea assessment.
To develop and test a prototype dyspnea computer adaptive test (CAT). Prospective study. Two outpatient medical facilities. A convenience sample of adults (N=292) with chronic obstructive pulmonary disease (COPD). Not applicable. We developed a modified and expanded item bank and CAT for the Dyspnea Management Questionnaire (DMQ), an outcome measure consisting of 4 dyspnea dimensions: dyspnea intensity, dyspnea anxiety, activity avoidance, and activity self-efficacy. Factor analyses supported a 4-dimensional model underlying the 71 DMQ items. The DMQ item bank achieved acceptable Rasch model fit statistics, good measurement breadth with minimal floor and ceiling effects, and evidence of high internal consistency reliability (α=.92-.98). With the use of CAT simulation analyses, the DMQ-CAT showed high measurement accuracy compared with the total item pool (r=.83-.97, P<.0001) and evidence of good to excellent concurrent validity (r=-.61 to -.80, P<.0001). All DMQ-CAT domains showed evidence for known-groups validity (P≤.001). The DMQ-CAT reliably and validly captured 4 distinct dyspnea domains. Multidimensional dyspnea assessment in COPD is needed to better measure the effectiveness of pharmacologic, pulmonary rehabilitation, and psychosocial interventions in not only alleviating the somatic sensation of dyspnea but also reducing dysfunctional emotions, cognitions, and behaviors associated with dyspnea, especially for anxious patients.


Bio and immuno-activity of FSH in serum after intramuscular injection of highly purified urinary human FSH in normal men.
The pharmacokinetics of a human FSH preparation widely used in clinical practice was evaluated in healthy male volunteers whose endogenous FSH was suppressed by 19-nortestosterone injections. 9.7 h following intramuscular injection of 150 IU FSH the mean immunoreactive peak concentration over baseline was 3.8 IU/1. Injection of 450 IU FSH led to a mean immunoreactive peak level of 10.4 IU/1 at 9.8 h. Mean half-life was 24.6 h (150 IU FSH) and 32.6 h (450 IU FSH). Serum bioFSH concentrations were suppressed below the detection limit after injection of the 19-nortestosterone and rose to preinjection levels after administration of FSH. Mean bioactive peak level for the 450 IU FSH was 7.3 IU/1 FSH at 7.4 h. The half-life of bioFSH was calculated to be 13.4 h and is considerably shorter than the half-life of immunoFSH. Serum inhibin levels were suppressed by 19-nortestosterone and did not change significantly after injection of the FSH preparation, suggesting that the FSH dose was insufficient to elicit this biological response. It is concluded that the currently used dose regimen for the treatment of male hypogonadism is inadequate for maintenance of serum bioFSH levels in the normal range.


Dynamic viscoelastic properties of processed soft denture liners: Part I--Initial properties.
This research evaluated the dynamic viscoelastic properties of 12 laboratory-processed soft denture liners. Specimens, 1.4 x 3 x 40 mm, were prepared according to the manufacturer's instructions. Five specimens of each material were tested under applied strain frequencies of 1, 5, or 10 Hz and temperatures of 23 degrees C and 37 degrees C. The values at 37 degrees C and 1 Hz were judged most important because they closely approximate the service environment; therefore material comparisons were made for these conditions. Samples were tested with a custom-made dynamic viscoelastometer. The statistical significance of the results was tested by ANOVA and Scheffe's intervals test. Large differences in the storage modulus (elastic stiffness) were found. One acrylic resin, Verno-Soft, showed significantly higher storage moduli than the other materials. The viscous behavior of the materials was reflected by the loss modulus; here large differences were also found. Verno-Soft again exhibited much higher values than all of the other materials. Three other acrylic resins (Super Soft, Soft-Pak, and Justi Soft) also showed significantly higher loss moduli than the other materials. Significant differences were found in the damping factor between many of the materials. Most of the acrylic and vinyl resins had higher damping factors than the silicone and polyphosphazine rubbers. The values of the storage moduli, loss moduli, and the damping factor were affected by temperature and by applied strain frequency with some materials.


Inhibition of the Caenorhabditis elegans cell-death protease CED-3 by a CED-3 cleavage site in baculovirus p35 protein.
The baculovirus protein p35 inhibits programmed cell death in such diverse animals as insects, nematodes and mammals. Here we show that p35 protein is a substrate for and inhibitor of the Caenorhabditis elegans cell-death protease CED-3 (refs 6, 7) and a substrate for four CED-3-like vertebrate cysteine protease activities implicated in apoptosis in mammals. A p35 mutation that greatly reduced p35 activity in vitro as a CED-3 substrate and inhibitor abolished p35 activity in vivo in protecting against cell death in C. elegans. Introduction of the CED-3 cleavage site in p35 into the cowpox virus protein crmA, which inhibits mammalian apoptosis but not programmed cell death in C. elegans, caused crmA to block CED-3-mediated cell death. These observations suggest that p35 may prevent programmed cell death in C. elegans and other species by acting as a competitive inhibitor of cysteine proteases.