Exploring differences between the ICD-11 and DSM-5 models of PTSD: Does it matter which model is used?
Alternative symptom profiles for posttraumatic stress disorder (PTSD) are presented in the DSM-5 and ICD-11. This study compared DSM-5 PTSD symptom profiles with ICD-11 PTSD symptom profiles among a large group of trauma-exposed individuals from Denmark. Covariates, and rates of co-occurrence with other psychiatric disorders were also investigated. A sample of treatment-seeking adult survivors of childhood sexual abuse (n=434) were assessed using self-report measures of PTSD and other psychiatric disorders. A significantly larger proportion of individuals met caseness for DSM-5 PTSD (60.0%) compared to ICD-11 PTSD (49.1%). This difference was largely attributable to low endorsement of the ICD-11 re-experiencing criteria. Replacement of the 'recurrent nightmares' symptom with the 'recurrent thoughts/memories' symptom seemed to balance the proportion of individuals meeting caseness for both taxonomies. Levels of co-occurrence with anxiety and thought disorder were higher for the DSM-5 model of PTSD compared to the ICD-11 model. Current results merit careful consideration in the selection of symptom indicators for the new ICD model of PTSD, particularly with respect to the re-experiencing symptom category.


Thermal ablation combined with transarterial chemoembolization for hepatocellular carcinoma: What is the right treatment sequence?
The combination treatment regimen of thermal ablation (TA) and transarterial chemoembolization (TACE) has gained a place in treatment of hepatocellular carcinoma (HCC) lesions > 3 cm unsuitable for surgery. Despite a high heterogeneity in the currently used treatment protocols, the pooled results of combined treatments seem to outperform those of TA or TACE alone. TACE preceding TA has been studied extensively, while results of the reverse treatment sequence are lacking. In this retrospective cohort study we compared the two treatment sequences. 38 patients (median age: 68.5 yrs (range 40-84), male: 34, liver cirrhosis: 33, early stage HCC: 21, intermediate stage HCC: 17) were included in two tertiary referral centers, of whom 27 were treated with TA and adjuvant TACE (TA + TACE). The other 11 patients received TA with neoadjuvant TACE (TACE + TA). Overall survival (OS), time to progression (TTP) and local tumor progression (LTP) free survival were determined for the entire cohort and compared between the two treatment sequences. The median OS of all patients was 52.7 months and the median time to LTP was 11.5 months (censored for liver transplantation). No differences were found with respect to OS between the two treatment sequences. Median time to LTP for TACE + TA was 23.6 months and 8.1 months for TA + TACE (p = 0.19). No statistical differences were found for OS, TTP and time to LTP between patients treated with TA combined with neoadjuvant or adjuvant TACE.


Arsenic levels in ground water and cancer incidence in Idaho: an ecologic study.
Long-term exposure to arsenic above 50 microg/L in drinking water has been related to multiple types of cancers. Few epidemiologic studies conducted in the US have detected an association between regional exposures below this level in drinking water and corresponding cancer occurrence rates. This county-level ecologic study evaluates arsenic levels in ground water and its association with targeted cancer incidence in Idaho, where some regions have been found to contain higher arsenic levels. Using cancer incidence data (1991-2005) from the Cancer Data Registry of Idaho and arsenic data (1991-2005) from the Idaho Department of Environmental Quality, we calculated the age-adjusted incidence rate for cancers of the urinary bladder, kidney and renal pelvis, liver and bile duct, lung and bronchus, non-Hodgkin's lymphoma (NHL), and all malignant cancers according to arsenic levels in ground water. Multivariate regression analysis was applied to evaluate the relationship between arsenic levels in ground water and cancer incidence. For males, but not for females, age-adjusted incidence for lung cancer and all malignant cancers was significantly higher in the intermediate arsenic counties (2-9 microg/L, n = 16) and the high arsenic counties (>or=10 microg/L, n = 5) compared to the low arsenic counties (<2.0 microg/L, n = 23). When adjusted for race, gender, population density, smoking and body mass index (BMI), no relationship was found between arsenic levels in ground water and cancer incidence. In this ecological design, exposure to low-level arsenic in ground water is not associated with cancer incidence when adjusting for salient variables. For populations residing in southwestern Idaho, where arsenic has been found to exceed 10 microg/L in ground water, individual risk assessment is required in order to determine whether there is a link between long-term arsenic exposure at these levels and cancer risk.


Choline acetyltransferase and substance P-like immuno-reactivity in the human spinal cord: changes in amyotrophic lateral sclerosis.
The topographic location of the enzyme choline acetyltransferase (ChAT) has recently been determined within the human spinal cord. ChAT, which is regarded as a specific marker of cholinergic structures in nervous tissue, showed an area of high activity in the ventrolateral part of the ventral horn, probably related to motor neurons. In addition, an area of high ChAT activity was found in the apical part of the dorsal horn. As amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of the cortico-spinal tracts and the lower motor neurons, we considered it of value to investigate the involvement of spinal cholinergic structures in this disorder. Substance P is regarded as the transmitter of incoming pain signals to the dorsal horn of the spinal cord, a subject recently reviewed by Marx. As disturbed sensation of pain is not a symptom of ALS, there seemed reason to correlate the spinal concentration of this peptide with the activities of ChAT in ALS.


Anterograde axonal transport of the exogenous cellular isoform of prion protein in the chick visual system.
The cellular isoform of endogenous, newly synthesized prion protein (PrPc) can be transported by axons in the anterograde direction. To determine whether a mechanism exists for secreted PrPc to be internalized and then axonally transported, we analyzed internalization and anterograde axonal transport of radiolabeled recombinant PrPc after its intraocular injection in chick embryos. Internalization and axonal transport of exogenous PrPc to the midbrain by retinal ganglion cells (RGCs) is efficient, saturable and likely receptor-mediated. Ultrastructural quantitative localization of radiolabeled PrPc within RGC soma showed significant labeling of vesicular/endosomal compartments and much less labeling present over the Golgi apparatus and lysosomes, which indicates slow degradation of exogenous PrPc in this system. These data show that a mechanism exists to internalize a secreted form of PrPc and then to axonally transport such PrPc in an anterograde direction. This may provide an additional, novel mechanism for prion protein to spread among neurons.


Infliximab and surgical treatment of complex anal Crohn's disease.
Perianal fistulae in Crohn's disease are frequently complex, involve the anal sphincter complex and surgical treatment can be associated with poor healing of wounds and damage to the mechanism of continence. The aim of this study was to evaluate the efficacy and duration of response to infliximab in the long-term management of perianal fistulae in Crohn's disease in routine clinical practice. A prospectively maintained database was used to identify patients with Crohn's disease and complex anal fistulae who were treated with infliximab (primary treatment, three initial infusions followed by maintenance therapy). Patients who received infliximab for luminal disease or for enterocutaneous, peristomal or rectovaginal fistulae were excluded from this study. Fifty-two patients [25 male, median age 24 (range 15-72) years] were treated with infliximab for perianal Crohn's fistulae for a median of 66 (7-124) months. Twenty-six of the patients underwent pre-infliximab MRI scans and 38 had an examination under anaesthetic (EUA) prior to commencement of treatment, 22 of whom had seton(s) inserted into their fistulae. Maintenance therapy was possible in 42 (81%) of 52 patients. Twenty-two (42.3%) patients had a complete response to treatment, 23 (44.2%) had a partial response and 7 (13.5%) had no response. Less than complete response to infliximab was associated with a greater risk of requiring surgical intervention (Fisher's exact test, d.f. 1, P = 0.005). The response rates of Crohn's related complex perianal fistulae to infliximab are good. Complete response is associated with a reduced need for surgical intervention.


Vascular endothelial growth factor induces extracellular matrix proteins and osteopontin in the umbilical artery.
Vascular endothelial growth factor (VEGF) is a mitogenic, angiogenic, and potent mediator of vascular permeability. It plays a role in injuries, contributes to edema during the acute stage of tissue damage, and promotes repair during recovery. We recently showed that VEGF serum levels of burn patients with a considerable number of damaged vessels were significantly increased. Here, we study the effects of VEGF on healthy vessels treated with a comparable VEGF concentration achieved in patients suffering heavy burns. VEGF 165 (0.2 mL of 10 ng/mL) or vehicle (saline 0.9%) was intraluminally applied to umbilical arteries for 90 min at 37 degrees C. Then, the cord was perfused for 4 hr. During perfusion, functional and biochemical parameters were kept within normal physiological ranges. Afterward, the vessels were analyzed applying morphometry, sirius red staining, polarization microscopy, Western blot analysis, and immunohistochemistry. Moreover, cultured human umbilical vein endothelial cells (HUVECs) were treated with VEGF or vehicle for 90 min and 5.5 hr to examine extracellular matrix (ECM) proteins and receptor tyrosine kinases. VEGF-treated umbilical arteries showed significant tissue edema and simultaneously an enhancement of laminin and collagen types I, III, and IV compared with control arteries. We detected an increase in Flt-1, Flk-1, osteopontin, and ss(1)-integrin. VEGF induced laminin early in HUVECs as measured by flow cytometry. In parallel, VEGF induced a higher amount of osteopontin, ss(1)-integrin, and both receptor tyrosine kinases in endothelial cells within 90 min. Intraluminal application of VEGF enhances ECM protein, osteopontin, and ss(1)-integrin production of the endothelium, while it still generates tissue edema. VEGF initiates vascular remodeling as early as it generates edema, even if the target vessel is not damaged. Osteopontin and ss(1)-integrin, both induced by VEGF, may play an important role in the vascular remodeling process.


Continuous combined hormone replacement therapy with 1 mg 17beta-oestradiol and 5 mg dydrogesterone (Femoston-conti): endometrial safety and bleeding profile.
The aim of the study was to confirm the endometrial safety and describe the bleeding profile of continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone in post-menopausal women. An open, multicentre study was carried out in 290 healthy, non-hysterectomised post-menopausal women receiving oral continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone (Femoston-conti) for 1 year. Aspiration endometrial biopsies were performed at baseline and at the end of the study; those classified as hyperplasia or malignancy were considered treatment failures. Only one woman developed simple hyperplasia without atypia at the end of the study; the treatment failure rate was therefore 0.4%. Cross-sectional analysis showed that the percentage of women without bleeding increased from 71% during the first cycle to around 80% by the end of the study. Approximately 50% of the bleeding episodes occurred in the form of spotting; severe bleeding was rare and only seven women withdrew prematurely from the study due to uterine bleeding. Overall, 41% of the women were amenorrhoeic throughout the study. Continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone provides excellent endometrial safety and is associated with an acceptable bleeding profile.


Sublingual administration of captopril versus nitroglycerin in patients with severe congestive heart failure.
Angiotensin-converting enzyme inhibition has proven to be a successful approach for the long-term treatment of patients with congestive heart failure. This investigation compared the acute hemodynamic changes after sublingual administration of the angiotensin-converting enzyme inhibitor captopril with those after nitroglycerin. A total of 24 patients with severe left heart failure (New York Heart Association classes III and IV) were given 25 mg captopril and 0.8 mg nitroglycerin sublingually in this randomized, cross-over study. Hemodynamic monitoring revealed a clear improvement in pre- and afterload parameters for both drugs (P less than 0.01 and P less than 0.001), while captopril induced a higher increase in cardiac index (+49.2% vs. +25%), stroke volume index (+53.5% vs. +25.7%), and stroke work index (+55% vs. +28%) than nitroglycerin (P less than 0.001). Although not statistically significant, the onset of change for most hemodynamic parameters was measured earlier after nitroglycerin (after 12-19 vs. 16-22 minutes). Captopril revealed later peak effects (after 47-84 vs. 25-55 minutes, P less than 0.001) and a longer sustained improvement in hemodynamic values (return to baseline values after 117-162 vs. 68-120 minutes, P less than 0.001). No side effects occurred after either captopril or nitroglycerin in this study. Thus, these results indicate there is an early improvement in hemodynamic parameters after the sublingual administration of both drugs in patients with severe congestive heart failure, and that captopril induces a more pronounced and prolonged improvement than nitroglycerin.


The Canadian medicinal plant Heracleum maximum contains antimycobacterial diynes and furanocoumarins.
Heracleum maximum is amongst the most commonly used plants by the indigenous peoples of North America. The First Nations of the eastern Canada use infusions of Heracleum maximum roots for the treatment of respiratory ailments including tuberculosis. Previous investigations of extracts derived from the roots of Heracleum maximum have shown it to possess antimycobacterial activity. To isolate and identify antimycobacterial constituents from the roots of Heracleum maximum. A methanolic extract of Heracleum maximum roots was subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The antimycobacterial constituents were identified by NMR, MS and polarimetry. The polyacetylene (3R,8S)-falcarindiol and the furanocoumarins bergapten, isobergapten, angelicin, sphondin, pimpinellin, isopimpinellin and 6-isopentenyloxyisobergapten were isolated from the Heracleum maximum root extract. (3R,8S)-Falcarindiol and 6-isopentenyloxyisobergapten exhibited MICs of 24 μM and 167 μM and IC50s of 6 μM and 27 μM against Mycobacterium tuberculosis H37Ra respectively. The remaining furanocoumarins bergapten, isobergapten, angelicin, sphondin, pimpinellin, and isopimpinellin were less active, with MICs of 925, 1850, 2149, 1859, 812 and 1625 μM and IC50s of 125, 344, 350, 351, 389 and 406 μM. (3R,8S)-Falcarindiol, bergapten, isobergapten, angelicin, sphondin, pimpinellin, isopimpinellin and 6-isopentenyloxyisobergapten were identified as the principal constituents responsible for the antimycobacterial activity of the roots of Heracleum maximum. This work supports the ethnopharmacological use of Heracleum maximum by Canadian First Nations and Native American communities as a treatment for infectious diseases, specifically tuberculosis.


Obstructive airway diseases in women exposed to biomass smoke.
The majority of women living in rural areas in Turkey use biomass fuels for domestic energy and are exposed to high levels of indoor air pollution every day. The objective of this study was to compare the presence of chronic airway diseases (CAD) in two groups of nonsmoking women older than 40 years with (exposed group, n=397) and without a history of exposure to biomass cooking (liquid petroleum gas (LPG); control group, n=199), in 2002 in Kirikkale, Turkey. Detailed respiratory symptoms were collected with a standard questionnaire adapted from that of the British Medical Research Council. Exposure was calculated as the average hours spent daily for cooking multiplied by the number of years. CAD were defined as either chronic airway obstruction (CAO; (forced expiratory volume in 1s/forced vital capacity)<0.70), chronic bronchitis, or chronic bronchitis with CAO. The prevalence of CAD in the exposed group was found to be higher than that in the LPG group (28.5% vs. 13.6%, crude odds ratios (ORs) 2.5 (1.5--4.0), P=0.0001). The fraction of CAD attributed to exposure to biomass smoke after adjusting for possible confounding factors was 23.1% (95% confidence interval (CI) 13.4--33.2). Acute symptoms during exposure to biomass smoke were important predictors for the presence of CAD. Biomass smoke pollution is an important contributing factor in the development of CAD in nonsmoking women living in a rural area. The presence of acute symptoms during cooking in women in rural areas should signal to general practitioners the possibility of CAD.


Trans-fused iridoid glycosides from Penstemon mucronatus.
Two new trans-fused iridoid glycosides (5 alpha H)-6 alpha-8-epidihydrocornin and (5 alpha H)-6 alpha-8-hydroxy-8-epiloganin, were isolated from Penstemon mucronatus, along with cornin, penstemoside and three hastatosides. The trans-fused iridoids are only the second and third known among over 900 described cis-fused iridoid glycosides. Two pairs of iridoids, identical except for the stereochemistry at C-8, were found. Structures were determined by spectroscopic methods.


Regulation of parathyroid hypertensive factor secretion by Ca2+ in spontaneously hypertensive rat parathyroid cells.
Elevated parathyroid hypertensive factor (PHF) has been suggested to play a causal role in the pathogenesis of hypertension. Previous studies have indicated that PHF secretion is stimulated by low extracellular (EC) Ca2+. Therefore, we hypothesized that the calcium-sensing receptor (CaR) is involved in regulation of PHF release. Parathyroid gland (PTG) organ and cell cultures derived from spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats were exposed to low and normal EC Ca2+ and PHF release measured by ELISA. Expression of CaR protein was assessed by Western blot. Low EC Ca2+ stimulated both SHR and WKY PTG organ cultures to secrete more PHF, first observable after 60 min incubation. After 4 h, PHF secretion was stimulated (66-fold v 24-fold stimulation for SHR and WKY, respectively). Cultured SHR and WKY parathyroid cells were also stimulated, but to a lesser extent (2.63-fold v 3.75-fold stimulation for SHR and WKY respectively). After 24 h the stimulation by low EC Ca2+ was no longer apparent. Expression of CaR is elevated in the SHR relative to WKY PTG. In both strains expression is higher under conditions of normal (1.5 mmol/L) EC Ca2+ and it increases with incubation time. The apparent suppression of PHF release by normal (1.5 mmol/L) EC Ca2+ is blocked by pre-exposure of the PTG cells to anti-CaR antibody. Low EC Ca2+ stimulated rapid PHF release from both SHR and WKY PTG. Changes in CaR expression may account for different sensitivity to EC Ca2+ of the two strains and over time.


[Goals and methodology of research on the rehabilitation of psychiatric patients as a comprehensive interdisciplinary project--content and system of data processing].
The authors describe and discuss the problems of a current long term international comparative study on rehabilitation for the mentally ill. Above all methodology of computerized data sampling should not interfere with the complex holistic structure of the underlying theory of rehabilitation. Thus first theoretical assumptions are explained emphasizing a holistic approach. With critical reference to earlier efforts and studies elsewhere structure of data organization is described with direct reference to the documentary sheets for case documentation use. The documentation form developed enhances precision of task definition, interdisciplinary work, self control for the professional, and the establishing of new hypothesis.


Tensile bond strength of different adhesive systems between bone and composite compared: an in vitro study.
The aim was to compare tensile bond strength of three dentine adhesive systems (Excite, Clearfil New Bond, Etch & Prime 3.0) and two cyanoacrylate adhesives (Cyano Veneer, Histoacryl) to animal bone in vitro. Specimens from five porcine mandibles (diameter 9 mm) with a total thickness of 4mm (+/-0.5mm) and a cortical layer of 1.5mm (+/-0.2mm) were prepared using trephine burs under constant water cooling and under standardized conditions. They were assigned to five experimental groups. Tensile bond strength of five different adhesive agents (Clearfil New Bond, Etch & Prime 3.0, Excite, Histoacryl and Cyano Veneer was measured 15 min after application and after light curing of a composite material (Tetric Ceram, colour A2) added thereupon using a universal testing machine. Qualitative control was performed by scanning electron microscopy, while examining loaded and unloaded specimens. The measured tensile bond strength was as follows: Clearfil New Bond 8.00 MPa (+/-1.36 MPa), Etch & Prime 3.0 4.05 MPa (+/-1.52 MPa), Excite 2.96 MPa (+/-1.34 MPa), Histoacryl 5.22 MPa (+/-2.00 MPa), Cyano Veneer 4.56 MPa (+/-0.76 MPa). Clearfil New Bond showed significantly higher bond strength than the other four adhesives. Scanning electron microscopy analysis of unloaded specimens showed mixed modes of fracture. As regards the loaded specimens, no tag formation as known for dentine was found. Within the limitations of an in vitro investigation it can be concluded that dentine adhesive systems might be useful for bone bonding. Tensile bond strength of the dentine adhesive systems tested on bone is comparable to that evaluated for dentine in earlier investigations.


Net Clinical Benefit of Left Atrial Appendage Closure Versus Warfarin in Patients With Atrial Fibrillation: A Pooled Analysis of the Randomized PROTECT-AF and PREVAIL Studies.
Background The PROTECT-AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trials demonstrated noninferiority of left atrial appendage closure (LAAC) to warfarin for the composite end point of stroke, systemic embolism, or cardiovascular death. This study aims to quantify the net clinical benefit (NCB) of LAAC versus warfarin, accounting for differences in clinical impact of different event types. Methods and Results We performed a post hoc analysis of the PROTECT-AF and PREVAIL trials, which randomized atrial fibrillation patients to LAAC or warfarin in a 2:1 fashion. The trials enrolled patients in the United States and Europe between 2005 and 2012 with paroxysmal, persistent, or permanent atrial fibrillation and CHADS2 risk scores ≥1. Relative to an index weight for death (1.0), events were assigned weights based on their disabling effect: (1) stroke event weights were based on modified Rankin scores in the base case analyses, and (2) major bleed (0.05) and pericardial effusion (0.05). NCB was calculated as the sum of weight-adjusted events per 100 patient-years. Among 1114 randomized subjects, the NCB of LAAC was 1.42% per year (95% CI 0.01-2.82, P=0.04) and a relative risk of 0.74 (95% CI 0.56-1.00). NCB point estimates favored warfarin early in follow-up, but trended in favor of LAAC after 1 to 2 years. The benefit of LAAC was preserved across subgroups, with particular benefit observed in the subgroup of prior stroke and without diabetes mellitus. Conclusions This analysis demonstrates long-term NCB of LAAC with Watchman over warfarin therapy, as the upfront risk of periprocedural events is counterbalanced over time by reduced bleeding events and mortality. Clinical Trial Registration UR: http://www.clinicaltrials.gov. Unique identifiers: NCT01182441 and NCT00129545.


Single-molecule manipulation quantification of site-specific DNA binding.
The execution of functions on DNA relies on complex interactions between DNA and proteins in a sequence and structure dependent manner. Accurate quantification of the affinity and kinetics of these interactions is critical for understanding the molecular mechanisms underlying their corresponding biological functions. The development of single-molecule manipulation technologies in the last two decades has made it possible to apply a mechanical constraint to a single DNA molecule and measure the end-to-end extension changes with nanometer resolution in realtime. While it has been shown that such technologies can be used to investigate binding of ligands, which can be proteins or other molecules, to DNA in a fluorescence-label free manner, a systematic review on such applications has been lacking. Here, we provide a review on some of recently developed methods for fluorescence-label free single-molecule quantification of site-specific DNA binding by ligands and demonstrate their wide scope of applications using several examples of binding of ligands to dsDNA and ssDNA binding sites.


Supraphysiologic extracellular pressure inhibits intestinal epithelial wound healing independently of luminal nutrient flow.
Luminal pressure may injure the gut mucosa in obstruction, ileus, or inflammatory bowel disease. We formed Roux-en-Y anastomoses in 19 mice, creating proximal and defunctionalized partially obstructed limbs and a distal limb to vary luminal pressure and flow. We induced mucosal ulcers by serosal acetic acid, and assessed proliferation (proliferating cell nuclear antigen) and ERK (immunoblotting). Parallel studies compared Caco-2 enterocyte migration and proliferation after pressure and/or ERK blockade. At 3 days, anastomoses were probe-patent, proximal and distal limbs contained chyme, and defunctionalized limbs were empty. The proximal and defunctionalized limbs showed increased pressure and slower healing despite increased proliferation, ERK protein, and ERK activation. In vitro, pressure decreased Caco-2 migration across collagen or fibronectin, stimulated proliferation, and activated ERK. However, ERK blockade did not prevent pressure effects. Luminal pressure during obstruction or ileus may impair mucosal healing independently of luminal flow despite increased mitosis and ERK activation.


Granulovacuolar degeneration in pyramidal cells of the hippocampus.
We have shown that as the number of granulovacuolar bodies in affected pyramidal cells of the hippocampus increases so cytoplasmic RNA contant is reduced. Prior to its degeration, the nucleolus is increased in volume while that of the nucleus remains unchanged in size throughout. The effects of these degenerative changes are to bring about a progressive decline in the capacity for nerve cell function, leading eventually to the death of the cell.


3D printed implantable drug delivery devices for women's health: Formulation challenges and regulatory perspective.
Modern pharmaceutical interventions are shifting from traditional "one-size-fits-all" approaches toward tailored therapies. Following the regulatory approval of Spritam®, the first marketed drug manufactured using three-dimensional printing (3DP) technologies, there is a precedence set for the use of 3DP in the manufacture of pharmaceutical products. The involvement of 3DP technologies in pharmaceutical research has demonstrated its capabilities in enabling the customisation of characteristics such as drug dosing, release characteristics and product designs on an individualised basis. Nonetheless, research into 3DP implantable drug delivery devices lags behind that for oral devices, cell-based therapies and tissue engineering applications. The recent efforts and initiatives to address the disparity in women's health is overdue but should provide a drive for more research into this area, especially using new and emerging technologies as 3DP. Therefore, the focus of this review has been placed on the unique opportunity of formulating personalised implantable drug delivery systems using 3DP for women's health applications, particularly passive implants. An evaluation of the current landscape and key formulation challenges for achieving this is provided supplemented with critical insight into the current global regulatory status and its outlook.


Comparison among three polymerase chain reaction assays on detection of DNA from Leishmania in biological samples from patients with American cutaneous leishmaniasis.
The study analyzed positivity of polymerase chain reaction (PCR) on detection of DNA from Leishmania in patients' samples. Extracted DNA was submitted to L150/L152, 13Y/13Z, and seminested PCR (snPCR). Results were evidenced by bands of approximately 120, 720, and 670 bp for L150/L152, 13Y/13Z, and snPCR, respectively. L150/L152, 13Y/13Z, and snPCR positivity indexes were 76.9, 56.4, and 9.2 (p>0.05), respectively, for suspected and 93.7, 68.7, and 84.4 (p<0.05), respectively, for confirmed. Preliminary results showed that these assays, mainly L150/L152 and snPCR, can detect Leishmania DNA and carry potential on laboratory diagnosis of leishmaniasis.


Atree, a remarkable new genus of the subfamily Brachistinae (Hymenoptera: Braconidae) and the first report of the tribe Diospilini from India.
The braconid tribe Diospilini (subfamily Brachistinae) is reported for the first time from India with the description of a new genus, Atree, along with the description of a new species A. rajathae from south India. The newly described genus belongs to the Aspigonus genus group showing the presence of a wide, deep sculptured groove on the propleuron. Based on morphological affinities, two species reported from Taiwan which were earlier included in the genus Diospilus have been transferred to the new genus, as A. improcerus (Chou Hsu, 1998) comb. nov. and A. validus (Chou Hsu, 1998) comb. nov. A key to the Indomalayan and Palaearctic genera of Diospilini is provided along with the key to the species of Atree gen. nov.


Architecture of the human XPC DNA repair and stem cell coactivator complex.
The Xeroderma pigmentosum complementation group C (XPC) complex is a versatile factor involved in both nucleotide excision repair and transcriptional coactivation as a critical component of the NANOG, OCT4, and SOX2 pluripotency gene regulatory network. Here we present the structure of the human holo-XPC complex determined by single-particle electron microscopy to reveal a flexible, ear-shaped structure that undergoes localized loss of order upon DNA binding. We also determined the structure of the complete yeast homolog Rad4 holo-complex to find a similar overall architecture to the human complex, consistent with their shared DNA repair functions. Localized differences between these structures reflect an intriguing phylogenetic divergence in transcriptional capabilities that we present here. Having positioned the constituent subunits by tagging and deletion, we propose a model of key interaction interfaces that reveals the structural basis for this difference in functional conservation. Together, our findings establish a framework for understanding the structure-function relationships of the XPC complex in the interplay between transcription and DNA repair.


Incidence of pulmonary cement embolism after real-time CT fluoroscopy-guided vertebroplasty.
To prospectively evaluate the incidence of pulmonary cement embolism (PCE) after vertebroplasty in procedures performed under real-time computed tomographic (CT) fluoroscopy guidance. A total of 85 vertebroplasties were performed in 51 consecutive patients (31 women, 20 men; mean age, 71.9 y; range, 48-92 y) in 51 sessions. The needle was inserted with guidance from intermittent single-shot CT scans, and intermittent CT fluoroscopy was used during cement injection only. To reduce the risk of extravertebral or extraosseous leakage, several procedures (cement injection stopping/slowing, needle position changes) were employed. The chest and treated bone were scanned immediately after vertebroplasty. These CT images included the entire thorax as well as the treated vertebrae. No cement emboli were observed on CT after vertebroplasty. After 85 vertebroplasty procedures, 44 extravertebral leaks were detected. Epidural leaks were observed on CT in six treated vertebrae (7%), in 12 cases in the anterior external venous plexus (14.1%), in five in the azygos vein (5.8%), in 19 in the disc space (22%), and in two in the foraminal space (2.3%). On a per-patient basis, the odds of leaks increased with the number of vertebroplasties (P = .05) and the volume of cement used (P = .0412). There was also a higher probability of leak (P < .05) for osteoporotic vertebral compression fractures (67.9%; 95% confidence interval, 47.7%-84.1%) than osteolytic spinal metastases (34.8%; 16.4%-57.3%). PCE did not occur after vertebroplasty under CT fluoroscopy guidance. Further larger prospective vertebroplasty studies are needed to compare the rates of PCE for CT versus conventional fluoroscopic guidance.


The effects of abamectin on oxidative stress and gene expression in rat liver and brain tissues: Modulation by sesame oil and ascorbic acid.
The present work was designed to assess the modulatory effects of sesame oil (SO) and ascorbic acid (AA) on abamectin (ABM)-induced oxidative stress and altered gene expression of hepatic cytochrome P450 2E1 (CYP-2E1), p38 MAPK, and caspase-3 and cerebral P-glycoprotein (Abcb1a receptor). Male rats were distributed into five groups (6 rats/group), receiving distilled water, ABM 2 mg/kg bwt 1/5 LD50 orally for 5 days, ABM + AA 100 mg/kg bwt orally, ABM + SO 5 ml/kg bwt orally, or ABM + SO + AA at the aforementioned doses. Nineteen compounds were identified in the SO sample by GC-MS analysis, including tetradecane,2,6,10-trimethyl, octadecane, 1-hexadecanol,2-methyl, and octadecane,6-methyl. Abamectin significantly upregulated the hepatic CYP-2E1 expression with excess generation of oxidative radicals, as evident by the significant depletion of reduced glutathione and elevation of malondialdehyde concentration (p ≤ 0.05) in rat liver and brain tissues. Further, ABM significantly increased TNF-α concentration, the expression of caspase-3 and p38 MAPK in the liver, as well as p-glycoprotein and GABA-A receptor in the brain. These results were in line with the observed histopathological changes. Sesame oil and/or AA supplementation alleviated ABM-induced cell damage by modulating all tested parameters. In conclusion, ABM induces oxidative stress and increases the expression of CYP-2E1, caspase-3, and p38 MAPK in the liver, as well as P-gp and GABA-A receptor in the brain. These effects could be ameliorated by SO and AA, alone and in combination, probably due to their anti-oxidant, anti-apoptotic, and gene-regulating activities.


Reporting Erectile Function Outcomes After Radiation Therapy for Prostate Cancer: Challenges in Data Interpretation.
Choice of prostate cancer treatment is frequently influenced by the expected chance of treatment-induced side effects such as erectile dysfunction (ED). However, great discrepancy in cited ED rates exists in the contemporary radiation therapy literature. To analyze the reported ED rates and cause of discrepancies and explore the strengths and limitations in the literature on radiation-induced ED. We performed a PubMed literature search and reviewed the literature on ED rates associated with external-beam radiotherapy and brachytherapy from the past 10 years. Eighteen studies were eligible for inclusion and subsequently reviewed. Variables required for interpretation of erectile function outcomes, including patient demographics, treatment characteristics, and sexual function outcomes. A large variety in the reported incidence of ED was found among studies. In part, these differences resulted from large variations in (i) study populations, (ii) patient characteristics, (iii) treatment characteristics, (iv) prescription of androgen deprivation therapy, (v) means of data acquisition, (vi) definitions of ED, (vii) temporal considerations, and (viii) erectile aid use. Relevant data required for adequate appraisal of sexual function outcomes were not always reported. Based on the present findings, we present general recommendations for reporting of erectile function outcomes after radiotherapy for prostate cancer. These should improve future reports. This is the first report that presents general requirements on reporting erectile function outcomes in the setting of radiotherapy for prostate cancer. We did not conduct a formal meta-analysis because we focused on concepts of research design; this might be considered a limitation. In this review, we have highlighted the strengths and deficiencies of the current literature on ED after external-beam radiotherapy and brachytherapy for prostate cancer. We have made general recommendations to achieve some degree of standardization among reports and improve clinical interpretability. Wortel RC, Incrocci L, Muhall JP. Reporting Erectile Function Outcomes After Radiation Therapy for Prostate Cancer: Challenges in Data Interpretation. J Sex Med 2017;14:1260-1269.


Oil-based or water-based contrast for hysterosalpingography in infertile women: a cost-effectiveness analysis of a randomized controlled trial.
To determine the cost effectiveness of the use of oil-based versus water-based contrast in infertile women undergoing hysterosalpingography (HSG). Economic evaluation alongside a multicenter randomized trial. Hospitals. Infertile women with an ovulatory cycle, 18-39 years of age, low risk of tubal pathology. Use of oil-based versus water-based contrast during HSG. Costs per additional ongoing pregnancy and per live birth within 6 months of randomization, incremental cost-effective ratios (ICERs). A total of 1,119 women were randomized to HSG (oil-based contrast, n = 557; water-based contrast, n = 562). After HSG, most women had no additional treatment; a minority had IUI or IVF. In the oil group, 39.7% women had an ongoing pregnancy within 6 months of randomization versus 29.1% women in the water group. There was a 10.7% increase in the live birth rate in the oil group. For ongoing pregnancy, the mean costs per couple were US$2,014 in the oil group and US$1,144 in the water group, with a corresponding ICER of US$8,198 per additional ongoing pregnancy. For live birth, the mean costs per couple were US$11,532 in the oil group and US$8,310 in the water group, with a corresponding ICER of US$30,112 per additional live birth. Hysterosalpingography with oil-based contrast results in higher 6-month ongoing pregnancy and live birth rate. If society is willing to pay US$8,198 for an additional ongoing pregnancy, HSG with oil-based contrast is a cost-effective strategy compared with HSG with water-based contrast for infertile, ovulatory women at low risk for tubal pathology. Dutch Trial Register, NTR 6577 (www.trialregister.nl).


Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model.
Previous studies suggested that endothelin-1 (ET-1) may play a pathophysiological role in myocardial ischemia/reperfusion injury. This study was designed to investigate the effects of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia in a heterotopic rat heart transplantation model. Isogenic intraabdominal heterotopic transplantation was performed in Lewis rats. After 1 h of cold ischemic preservation reperfusion was started either after application of placebo (control), BQ123 (3 mumol/kg/min). BQ788 (3 mumol/kg/min), ET-1 (8 pmol/kg/min) or simultaneous infusion of BQ123 or BQ788 and ET-1, respectively (n = 12 each). An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Myocardial blood flow (MBF) was assessed by the hydrogen-clearance method. Measurements were taken after 1 and 24 h of reperfusion. Endothelium-dependent vasodilation to acetylcholine (ACH) and endothelium-independent vasodilation to sodium nitroprusside were also determined. Both BQ123 and BQ788 significantly improved myocardial and endothelial functional recovery during early reperfusion, whereas ET-1 significantly impaired myocardial and endothelial function. Simultaneous infusion of ET-1 diminished the effects of BQ123 and BQ788. Although myocardial function and baseline MBF were similar in all groups after 24 h of reperfusion, endothelium dependent vasodilation to ACH was still significantly higher in the BQ123 and BQ788 groups and lower in the ET-1 groups (p < 0.05). These results suggest that endogenous ET release is involved in the pathogenesis of reperfusion injury after heart transplantation. ET-A and ET-B receptor antagonists may be useful to reduce ischemia/reperfusion injury.


Nontraumatic rupture of the globe secondary to orbital cellulitis.
A 53-year-old woman had a spontaneous nontraumatic rupture of the globe secondary to severely increased orbital pressure from an orbital cellulitis. To our knowledge this is the first such case reported.


Simultaneous quantification of specific food allergen proteins using a fluorescent multiplex array.
The aim was to develop a fluorescent multiplex array for simultaneously measuring regulated food allergens using specific allergen protein molecules from peanut, tree nut, cow's milk, egg, soy, fish, shellfish, sesame, mustard and celery. Microspheres coupled to specific monoclonal antibodies were used for allergen detection, with purified allergens as reference standards.Standard curves for 17 allergens covered a 5-log dynamic range. Intra- and inter-assay acceptance criteria were within 70-130% recovery and a CV of ≤15%. Food reference materials contained high levels of their respective major allergens (2000-175,000 µg/g), Similar high allergen levels were found in 10 selected foods analysed using a 9-plex array. Egg, milk, peanut, hazelnut and walnut allergens were detectable in chocolate bars with incurred allergens at 3, 10, 30, and 100 ppm. The multiplex array is an efficient tool for measuring specific food allergens, with applications for risk assessment and standardization of therapeutic products for food allergy.


Modifying sucrose esters oleogels properties using different structuration routes.
Sucrose esters (SE) have been widely studied as emulsifiers to tailor crystallization in fats. Nevertheless, few studies have assessed the potential of SEs as oleogelators to structure oleogels. This study aimed to evaluate alternative routes that would improve the oleogelation capacity of commercial SEs with different Hydrophilic-lipophilic balance (HLB) values and evaluate the physical properties of the oleogels produced by different routes. Four SEs were evaluated (SP10-HLB2, SP30-HLB6, SP50-HLB11, and SP70-HLB15) using three oleogelation routes (traditional or melting, ethanol, and foam-template). Of all evaluated samples, only the SP50 ethanol route with 10 % SE showed a solid-like structure. This sample presented the highest hardness (0.4 ± 0.1 N) and elastic modulus (4589 ± 89 Pa). SP70 showed a potential oleogel after foam-template approach due to the higher oil binding capacity. SP10 was the only directly completely soluble SE in oil, although it formed a very liquid gel. SP30 did not show a potential or oleogel structure for any of the routes tested.


SASC: A simple approach to synthetic cohorts for generating longitudinal observational patient cohorts from COVID-19 clinical data.
One of the impacts of the coronavirus disease 2019 (COVID-19) pandemic has been a push for researchers to better exploit synthetic data and accelerate the design, analysis, and modeling of clinical trials. The unprecedented clinical efforts caused by COVID-19's emergence will certainly boost future robust and innovative approaches of statistical sciences applied to clinical fields. Here, we report the development of SASC, a simple but efficient approach to generate COVID-19-related synthetic clinical data through a web application. SASC takes basic summary statistics for each group of patients and attempts to generate single variables according to internal correlations. To assess the "reliability" of the results, statistical comparisons with Synthea, a known synthetic patient generator tool, and, more importantly, with clinical data of real COVID-19 patients are provided. The source code and web application are available on GitHub, Zenodo, and Mendeley Data.


Peripheral nerve ischemia: Part 2. Accumulation of organelles.
Following simultaneous ligation of the aorta and femoral artery in the cat, organelles accumulated in distal portions of the sciatic nerve and in lower portions of the tibial and peroneal nerves. The accumulations were located in the proximal and distal ends of the nerve infarction and delineated the borders of the necrotic area. Topographical analysis of the necrosis and organelle accumulations following ligation of these main arteries showed the larger nerve fascicles to be more sensitive to ischemia than the smaller ones. The center of a nerve fascicle was more sensitive than the periphery. The organelles accumulated in ischemic nerves during the first hours after arterial ligation, presumably as a result of lack of energy for fast axoplasmic transport. Later accumulations reflected mechanical block of axoplasmic transport due to focal necrosis of the nerve. The content of organelle accumulations was similar to that found in lesions resulting from transection except for the presence of 60 to 70 A filaments at the distal end of the infarction.


Anatomical insights into disrupted small-world networks in schizophrenia.
Schizophrenia is characterized by lowered efficiency in distributed information processing, as indicated by research that identified a disrupted small-world functional network. However, whether the dysconnection manifested by the disrupted small-world functional network is reflected in underlying anatomical disruption in schizophrenia remains unresolved. This study examined the topological properties of human brain anatomical networks derived from diffusion tensor imaging in patients with schizophrenia and in healthy controls. We constructed the weighted brain anatomical network for each of 79 schizophrenia patients and for 96 age and gender matched healthy subjects using diffusion tensor tractography and calculated the topological properties of the networks using a graph theoretical method. The topological properties of the patients' anatomical networks were altered, in that global efficiency decreased but local efficiency remained unchanged. The deleterious effects of schizophrenia on network performance appear to be localized as reduced regional efficiency in hubs such as the frontal associative cortices, the paralimbic/limbic regions and a subcortical structure (the left putamen). Additionally, scores on the Positive and Negative Symptom Scale correlated negatively with efficient network properties in schizophrenia. These findings suggest that complex brain network analysis may potentially be used to detect an imaging biomarker for schizophrenia.


Isolable fluorinated triphenylmethyl cation salts of [HCB11Cl11]-: demonstration of remarkable hydride affinity.
Significantly fluorinated triarylmethyl cations have long attracted attention as potentially accessible highly reactive carbocations, but their isolation in a convenient form has proved elusive. We show that abstraction of chloride with a cationic silylium reagent leads to the facile formation of di-, tetra-, and hexafluorinated trityl cations, which could be isolated as analytically pure salts with the [HCB11Cl11]- counterion and are compatible with (halo)arene solvents. The F6Tr+ cation carrying six meta-F substituents was computationally predicted to possess up to 20% higher hydride affinity than the parent triphenylmethyl cation Tr+. We report that indeed F6Tr+ displays reactivity unmatched by Tr+. F6Tr+ at ambient temperature abstracts hydrides from the C-H bonds in tetraethylsilane, mesitylene, methylcyclohexane, and catalyzes Friedel-Crafts alkylation of arenes with ethylene, while Tr+ does none of these.


Mediating effects of group cohesion on physical activity and diet in women of color: health is power.
To determine the effects and mediating factors of a physical activity (PA) or vegetable and fruit (VF) group cohesion intervention. Longitudinal design. Harris County and Travis County, Texas. Community-dwelling African-American and Hispanic or Latina women. Three hundred ten women were randomized to a PA (n = 204) or VF (n = 106) intervention group. Women met in groups six times over the course of 6 months and were exposed to a group cohesion intervention to promote walking or to increase VF consumption. Women completed the International PA Questionnaire, National Cancer Institute VF and fat screeners, PA Group Environment Questionnaire, and 7-day accelerometer protocol at baseline and post-intervention. The direct and mediated effects of the intervention on outcomes were evaluated using a mediational chain model, controlling for baseline values and covariates using path analysis. Women were middle aged (mean = 44.4 years) and overweight or obese (mean body mass index = 34.0 kg/m(2)). PA increased and fat consumption decreased for both groups, whereas VF consumption increased for women in VF group only (all p < .05). Increased task cohesion led to hypothesized increases in psychosocial factors in the PA group but not to behavioral changes. Group cohesion interventions may have psychological and physical health benefits for African-American and Hispanic or Latina women, but refinement of measures and intervention delivery is needed to determine whether hypothesized mediational pathways are valid.


Elastin--lipid interaction action in the arterial wall. Part 1. Extraction of elastin from human aortic intima.
Elastin was extracted from human aortic plaque and adjacent grossly normal intima by the following methods: (1) 0.1 N NaOH at 100 degrees C, (2) hot NaOH and 0.2 M EDTA, (3) 5 M guanidine--HCl and collagenase, (4) guanidine--collagenase and dithioerythritol--urea--sodium dodecyl sulfate, (5) guanidine--collagenase and EDTA, (6) 10% NaCl and collagenase, and (7) NaCl--collagenase and EDTA. All elastin samples contained small amounts of carbohydrate and hydroxyproline. The lipid content of non-plaque intimal elastin samples was small (2--3%), whereas it increased to 4--6% in plaque intima. The lipid composition of elastin preparations varied significantly with the extraction procedure. Elastin from plaque intima contained significantly more cholesterol (50--60%) and less triglyceride and phospholipid than elastin of non-plaque intima (30--50% cholesterol). The contents of free and esterified cholesterol were comparable in all preparations. The main phospholipid in all samples was sphingomyelin, which comprised between 50 and 80% of the total phospholipid. Compared with NaOH-purified elastin, the other elastin samples were characterized by an increased phosphatidyl--choline content, while they all contained an almost equal amount of phosphatidylethanolamine. In elastin samples from plaque intima, the polar amino acids were increased, whereas cross-linking amino acids were decreased. The polarity and hydroxyproline content of elastin samples were slightly decreased after treatment with EDTA or dithioerythritol--urea--sodium dodecyl sulfate.


Cross-talk between angiotensin II and interleukin-6-induced signaling through Stat3 transcription factor.
In cultured neonatal rat cardiac fibroblasts and CHO-K1 cells expressing angiotensin II (Ang II) type 1 receptors (AT1) (T3CHO/AT1A cell line), Ang II induced a delayed tyrosine phosphorylation of Stat3 (Signal Transducers and Activators of Transcription) with maximal activation at 2 h. This was in contrast to the rapid tyrosine phosphorylation (15-30 min) of Stat3 by the cytokine interleukin-6 (IL-6). Using T3CHO/AT1A cells, we tested the hypothesis that the delayed tyrosine phosphorylation of Stat3 by Ang II resulted from the induction of an inhibitory pathway (0-30 min) prior to activation (1-2 h). In support of this hypothesis, we observed that a short treatment of cells with Ang II transiently inhibited the IL-6-induced Stat3 tyrosine phosphorylation. The inhibitory effect of Ang II could be attenuated by exposing the cells to a specific inhibitor of MAP kinase kinase 1, PD98059. Such modulatory cross-talk between Ang II and IL-6 may have relevance in pathophysiological conditions such as cardiac hypertrophy, and in acute phase and inflammatory responses.


Electrochemical determination of anaerobic microbial decay coefficients.
The biokinetics of attached and suspended bacteria are an essential component of activated sludge models, anaerobic digestion models and biofilm models. These parameters are often assumed or "confirmed" based on the goodness-of-fit of the bioprocess models. Using a microbial fuel cell with a baffled reactor chamber, the attached- and mixed-growth microbial decay coefficients were evaluated under anaerobic conditions. The capability for real-time voltage recording allows easy and accurate measurement of the anaerobic microbial decay coefficients (b(L), lysis-regrowth approach), which were determined to be 0.11+/-0.01 and 0.15+/-0.01 d(-1) for attached (to anode) and mixed (present in the anode chamber) growth microorganisms, respectively. The corresponding half-saturation constants using glucose as a substrate were 204+/-10 and 123+/-1 mg COD l(-1). Hence, like an oxygen uptake rate-based approach to measure the microbial kinetics under aerobic conditions, the electrochemical recording provides an attractive method to measure anaerobic microbial decay coefficients.


Evaluation of the stability of neuropsychological functioning after acute episodes of schizophrenia: one-year followup study.
Few studies have evaluated the longitudinal stability of neuropsychological deficits in schizophrenia. In the present study, 39 inpatients with DSM-III-R schizophrenia were administered a comprehensive battery of neuropsychological tests after achieving sufficient clinical recovery to warrant discharge, and again 1 year after the first assessment during a nonacute period. Significant improvement in neuropsychological functioning from the first to the second assessment was observed on several tasks, including the following: Trails A and B, Digit Symbol, Judgment of Line Orientation, recognition memory on the Rey Auditory Verbal Learning Test, the Wisconsin Card Sort, and Finger Tapping. These improvements were unrelated to treatment history, and were similar in first episode and chronic cases. For many patients, the improvement in functioning brought test performance into line with normative scores from test standardization samples. These results indicate that considerable improvement in neuropsychological functioning can occur in schizophrenic patients over the months following an acute episode of illness, and that recovery of cognitive functioning can occur after substantial clinical recovery from an acute episode of illness has already been achieved.


Silicone oil tamponade in eyes with posterior staphyloma and retinal detachment caused by macular hole.
A retinal detachment caused by a macular hole in an eye with a posterior staphyloma presents a therapeutical challenge. Vitrectomy and silicone oil tamponade might be a therapeutic strategy in such eyes. We report on three eyes of three patients with retinal detachment caused by a macular hole in the presence of a posterior staphyloma, where a vitrectomy and a silicone oil filling was performed. In all three eyes the retina could be reattached. After oil removal, the retina remained attached in all three eyes until the end of the follow-up period (mean 18.7 months). In all three eyes, visual acuity improved, no major complications were noted. The use of silicone oil in eyes with retinal detachment caused by a macular hole in the presence of a posterior staphyloma presents a therapeutic option and we discuss this strategy as a primary treatment for these eyes.


Intuitionistic Fuzzy Synthetic Measure on the Basis of Survey Responses and Aggregated Ordinal Data.
The paper addresses the problem of complex socio-economic phenomena assessment using questionnaire surveys. The data are represented on an ordinal scale; the object assessments may contain positive, negative, no answers, a "difficult to say" or "no opinion" answers. The general framework for Intuitionistic Fuzzy Synthetic Measure (IFSM) based on distances to the pattern object (ideal solution) is used to analyze the survey data. First, Euclidean and Hamming distances are applied in the procedure. Second, two pattern object constructions are proposed in the procedure: one based on maximum values from the survey data, and the second on maximum intuitionistic values. Third, the method for criteria comparison with the Intuitionistic Fuzzy Synthetic Measure is presented. Finally, a case study solving the problem of rank-ordering of the cities in terms of satisfaction from local public administration obtained using different variants of the proposed method is discussed. Additionally, the comparative analysis results using the Intuitionistic Fuzzy Synthetic Measure and the Intuitionistic Fuzzy TOPSIS (IFT) framework are presented.


A computational framework for particle and whole cell tracking applied to a real biological dataset.
Cell tracking is becoming increasingly important in cell biology as it provides a valuable tool for analysing experimental data and hence furthering our understanding of dynamic cellular phenomena. The advent of high-throughput, high-resolution microscopy and imaging techniques means that a wealth of large data is routinely generated in many laboratories. Due to the sheer magnitude of the data involved manual tracking is often cumbersome and the development of computer algorithms for automated cell tracking is thus highly desirable. In this work, we describe two approaches for automated cell tracking. Firstly, we consider particle tracking. We propose a few segmentation techniques for the detection of cells migrating in a non-uniform background, centroids of the segmented cells are then calculated and linked from frame to frame via a nearest-neighbour approach. Secondly, we consider the problem of whole cell tracking in which one wishes to reconstruct in time whole cell morphologies. Our approach is based on fitting a mathematical model to the experimental imaging data with the goal being that the physics encoded in the model is reflected in the reconstructed data. The resulting mathematical problem involves the optimal control of a phase-field formulation of a geometric evolution law. Efficient approximation of this challenging optimal control problem is achieved via advanced numerical methods for the solution of semilinear parabolic partial differential equations (PDEs) coupled with parallelisation and adaptive resolution techniques. Along with a detailed description of our algorithms, a number of simulation results are reported on. We focus on illustrating the effectivity of our approaches by applying the algorithms to the tracking of migrating cells in a dataset which reflects many of the challenges typically encountered in microscopy data.


Primary endometrioid adenocarcinoma of the cervix with widespread squamous metaplasia--a potential diagnostic pitfall.
Uterine or endocervical biopsies that contain endometrioid adenocarcinoma with widespread squamous metaplasia are usually of endometrial origin. The presence of squamous metaplasia is said to be helpful in distinguishing endocervical from endometrial adenocarcinomas in small biopsy samples. A 51-year-old woman presented with post-coital and post-menopausal bleeding. Biopsy of a friable lesion in the proximal endocervical canal revealed an endocervical adenocarcinoma of endometrioid type with widespread squamous metaplasia. The latter feature initially raised the possible diagnosis of a primary endometrial adenocarcinoma. However, immunohistochemical marker studies indicated a diagnosis of primary endocervical adenocarcinoma of endometrioid type and this was confirmed at hysterectomy. Squamous differentiation is not well documented in endocervical adenocarcinomas of endometrioid type and, when widespread, may represent a diagnostic pitfall for pathologists. Interpretation of small biopsies from the endocervical canal on the basis of morphology alone may lead to misdiagnosis and inappropriate surgical management.


Application of image analysis technique to determine cleaning of ohmic heating system for milk.
Cleaning of equipment is one of the major areas of concern in food industry. Image analysis technique was used to assess the cleaning effectiveness and optimize the CIP protocol for ohmic heating setup. Process parameters selected for optimization of cleaning were caustic concentration (1.0, 1.5, 2.0 and 2.5%), caustic temperature (70, 75, 80 and 85 °C), acid concentration (0.00, 0.25, 0.5 and 0.75%), and acid temperature (40, 50, 60 and 70 °C). Time for caustic treatment was varied from 5 to 20 min at an interval of 5 min, while time acid treatment was kept at a constant of 10 min. Taguchi orthogonal array design was used generate different combinations of acid and alkali concentration and temperature. Images of ohmic heating plates were taken before and after the cleaning procedure. MATLAB program was developed to analyze and extract Gray-Level Co-occurrence (GLCM) matrix properties from the image. Optimized combination was selected based on the highest value of desirability factor among all the experimental set of trials. Treatment with 1.5% caustic concentration at 70 °C for 5 min followed by 0.5% nitric acid concentration at 60 °C was found optimum effective CIP of the heating plates used in ohmic heating setup. GLCM properties correlation, cluster prominence, cluster shade, entropy, homogeneity and inverse difference moment normalized were found suitable for analysis of cleaning effectiveness and optimization of the CIP protocol.


Morphofunctional organization of sinoatrial node in rat heart.
The distribution of pacemaker cells along the sinus node artery was studied under conditions of short-term culturing using intracellular glass microelectrodes. The functional borders of the central and peripheral parts of the sinoatrial node were determined. The relationship between the position of the central part of the sinoatrial node and the patterns of the sinus node artery branching were analyzed.


Incidence of recurrent or residual stenosis after carotid endarterectomy.
The incidences of recurrent and residual stenosis after carotid endarterectomy have been controversial. Duplex scanning has recently provided an accurate noninvasive method of quantifying areas of arterial narrowing, and this technique was used in 122 postendarterectomy vessels from 71 men and 35 women with a mean age of 65.2 years. The average time interval between operation and scanning was 26.3 months (range 1 month to 11.76 years). Postoperative examination of the internal carotid artery revealed no stenosis in 78 vessels, less than 50 percent area reduction in 17 vessels, 50 to 75 percent stenosis in 11 vessels, more than 75 percent area reduction in 9 vessels, and total occlusion in 7 vessels. Thus, 22 percent of the vessels (27 of 122) had total occlusion or more than 50 percent area reduction after carotid endarterectomy. This is a higher rate of recurrent stenosis than was diagnosed by oculoplethysmography, where 7 of 52 vessels (13 percent) had a positive oculoplethysmogram after operation. These data show that the reported incidence of residual or recurrent stenosis after carotid endarterectomy is heavily dependent on the testing method used. Duplex scanning documents a 22 percent frequency of residual or recurrent stenosis, a figure higher than has been reported with less sensitive tests.


Impairment of superoxide dismutase activation by N-terminally truncated prion protein (PrP) in PrP-deficient neuronal cell line.
Previous studies have reported a neuroprotective role for cellular prion protein (PrP(C)) against apoptosis induced by serum deprivation in an immortalized prion protein gene (Prnp)-deficient neuronal cell line, but the mechanisms remain unclear. In this study, to investigate the mechanisms by which PrP(C) prevents apoptosis, the authors compared apoptosis of Prnp(-/-) cells with that of Prnp(-/-) cells expressing the wild-type PrP(C) or PrP(C) lacking N-terminal octapeptide repeat region under serum-free conditions. Re-introduction of Prnp rescued cells from apoptosis, upregulated superoxide dismutase (SOD) activity, enhanced superoxide anion elimination, and inhibited caspase-3/9 activation. On the other hand, N-terminally truncated PrP(C) enhanced apoptosis accompanied by potentiation of superoxide production and caspase-3/9 activation due to inhibition of SOD. These results suggest that PrP(C) protects Prnp(-/-) cells from apoptosis via superoxide- and caspase-3/9-dependent pathways by upregulating SOD activity. Furthermore, the octapeptide repeat region of PrP(C) plays an essential role in regulating apoptosis and SOD activity.


Relationship between body mass index and pediatric urologic diagnoses.
We had the clinical impression that children with certain urological diagnoses were thinner and others were heavier. We therefore reviewed body mass index (BMI) in children with a variety of urological diagnoses. The data from all pediatric patients treated as outpatients in our office between 1 Jan and 30 Sept 2004 were analyzed retrospectively. The patients were counted only once, even if they came back to the office several times. They were grouped by the principal billing diagnosis, but groups of less than nine patients were excluded. BMI percentiles were determined based on data from the Centers for Disease Control and compared to diagnosis codes. The data from 1054 patients were analyzed: 53% were female, mean age was 8.0+/-3.7, mean BMI was 18.7+/-5.1 and mean BMI percentile was 64+/-31%. BMI varied significantly by diagnosis. Children with hernias and penile problems had the lowest BMI percentile and those with urinary infection and incontinence the highest, e.g. the mean BMI percentile was 46+/-31% for children with a hernia but 71+/-27% for those patients with nocturnal enuresis. The rate of obesity varied considerably based on pediatric urological diagnosis. Diet and personality may be part of the etiology for some urological disorders. It is possible that lifestyle changes may benefit urological patients who are obese.


Light energy allocation at PSII under field light conditions: how much energy is lost in NPQ-associated dissipation?
In the field, plants are exposed to fluctuating light, where photosynthesis occurs under conditions far from a steady state. Excess energy dissipation associated with energy quenching of chlorophyll fluorescence (qE) functions as an efficient photo-protection mechanism in photosystem II. PsbS is an important regulator of qE, especially for the induction phase of qE. Beside the regulatory energy dissipation, some part of energy is lost through relaxation of excited chlorophyll molecules. To date, several models to quantify energy loss through these dissipative pathways in PSII have been proposed. In this short review, we compare and evaluate these models for PSII energy allocation when they are applied to non-steady state photosynthesis. As a case study, an investigation on energy allocation to qE-associated dissipation at PSII under non-steady state photosynthesis using PsbS-deficient rice transformants is introduced. Diurnal and seasonal changes in PSII energy allocation in rice under natural light are also presented. Future perspective of studies on PSII energy allocation is discussed.


Amentoflavone mitigates doxorubicin-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation through inhibition of the STING/NLRP3 signalling pathway.
Doxorubicin (DOX) is a potent anticancer chemotherapeutic agent whose clinical application is substantially constrained by its cardiotoxicity. The pathophysiology of DOX-induced cardiotoxicity manifests as cardiomyocyte pyroptosis and inflammation. Amentoflavone (AMF) is a naturally occurring biflavone possessing anti-pyroptotic and anti-inflammatory properties. However, the mechanism through which AMF alleviates DOX-induced cardiotoxicity remains undetermined. This study aimed at investigating the role of AMF in alleviating DOX-induced cardiotoxicity. To assess the in vivo effect of AMF, DOX was intraperitoneally administered into a mouse model to induce cardiotoxicity. To elucidate the underlying mechanisms, the activities of STING/NLRP3 were quantified using the NLRP3 agonist nigericin and the STING agonist amidobenzimidazole (ABZI). Primary cardiomyocytes isolated from neonatal Sprague-Dawley rats were treated with saline (vehicle) or DOX with or without AMF and/or ABZI. The echocardiogram, haemodynamics, cardiac injury markers, heart/body weight ratio, and pathological alterations were monitored; the STING/NLRP3 pathway-associated proteins were detected by western blot and cardiomyocyte pyroptosis was analysed by immunofluorescence staining of cleaved N-terminal GSDMD and scanning electron microscopy. Furthermore, we evaluated the potential of AMF in compromising the anticancer effects of DOX in human breast cancer cell lines. AMF substantially alleviated cardiac dysfunction and reduced heart/body weight ratio and myocardial damage in mice models of DOX-induced cardiotoxicity. AMF effectively suppressed DOX-mediated upregulation of IL-1β, IL-18, TNF-α, and pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and cleaved N-terminal GSDMD. The levels of apoptosis-related proteins, namely Bax, cleaved caspase-3, and BCL-2 were not affected. In addition, AMF inhibited STING phosphorylation in DOX-affected hearts. Intriguingly, the administration of nigericin or ABZI dampened the cardioprotective effects of AMF. The in vitro anti-pyroptotic effect of AMF was demonstrated in attenuating the DOX-induced reduction in cardiomyocyte cell viability, upregulation of cleaved N-terminal GSDMD, and pyroptotic morphology alteration at the microstructural level. AMF exhibited a synergistic effect with DOX to reduce the viability of human breast cancer cells. AMF alleviates DOX-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation via inhibition of the STING/NLRP3 signalling pathway, thereby validating its efficacy as a cardioprotective agent.


A prospective, matched comparison of ultra-low and standard-dose computed tomography for assessment of renal colic.
To determine the diagnostic accuracy of ultra-low-dose computed tomography (ULDCT) compared with standard-dose CT (SDCT) in the evaluation of patients with clinically suspected renal colic, in addition to secondary features (hydroureteronephrosis, perinephric stranding) and additional pathological entities (renal masses). A prospective, comparative cohort study was conducted amongst patients presenting to the emergency department with signs and symptoms suggestive of renal or ureteric colic. Patients underwent both SDCT and ULDCT. Single-blinded review of the image sets was performed independently by three board-certified radiologists. Among 21 patients, the effective radiation dose was lower for ULDCT [mean (SD) 1.02 (0.16) mSv] than SDCT [mean (SD) 4.97 (2.02) mSv]. Renal and/or ureteric calculi were detected in 57.1% (12/21) of patients. There were no significant differences in calculus detection and size estimation between ULDCT and SDCT. A higher concordance was observed for ureteric calculi (75%) than renal calculi (38%), mostly due to greater detection of calculi of <3 mm by SDCT. Clinically significant calculi (≥3 mm) were detected by ULDCT with high specificity (97.6%) and sensitivity (100%) compared to overall detection (specificity 91.2%, sensitivity 58.8%). ULDCT and SDCT were highly concordant for detection of secondary features, while ULDCT detected less renal cysts of <2 cm. Inter-observer agreement for the ureteric calculi detection was 93.9% for SDCT and 87.8% for ULDCT. ULDCT performed similarly to SDCT for calculus detection and size estimation with reduced radiation exposure. Based on this and other studies, ULDCT should be considered as the first-line modality for evaluation of renal colic in routine practice.


Endoscopic submucosal dissection for gastric indefinite for neoplasia: which lesions should be resected?
The management plan for gastric indefinite for neoplasia is undetermined, and endoscopic forceps biopsy might be inconclusive in ascertaining whether a resection is required. This study aimed to evaluate the clinical outcomes of endoscopic submucosal dissection (ESD) for gastric indefinite for neoplasia and to identify the factors highly predictive of true neoplasia. This retrospective study was conducted in a single, tertiary, referral hospital between November 2008 and December 2015. A total of 109 gastric indefinite for neoplasia lesions from endoscopic forceps biopsy that were resected by ESD were included in the study. The clinical outcomes and endoscopic factors for prediction of true neoplasia were analyzed. A total of 99 patients (90.8%) were diagnosed with definite neoplasia after ESD and were classified as category 3 (n = 42), category 4 (n = 50), and category 5 (n = 7) according to the revised Vienna classification. The mean age of the patients was 65.8 ± 9.8 years. The mean lesion size was 10.7 ± 6.1 mm. The patient population predominantly consisted of male patients (70.6%). The en bloc and complete endoscopic resection rates were 98.2% and 94.5%, respectively. Factors associated with true neoplastic lesions were male sex (odds ratio [OR] 8.596, p = 0.008) and lesion size ≥ 5 mm (OR 11.355, p = 0.003). Factors associated with category 4-5 were male sex (OR 3.165, p = 0.021) and erosive change (OR 2.841, p = 0.031). Endoscopic resection for indefinite for neoplasia with larger lesions size and erosive changes, especially in males, should be considered when possible.


A preliminary investigation of noise impact within metro stations in the urban city of Guangzhou, China.
The noise in the metro station is synthesized from a variety of different noise sources. Excessive noise exposure will bring serious impacts on humans' health. To alleviate the shortage of the urban land, most metro stations are planning to develop convenience stores and shopping malls. In order to evaluate the potential noise impact on humans' comfort in the metro stations, this study selected four representative stations of Guangzhou Metro Line 1 to carry out a preliminary questionnaire survey of 226 respondents for the perception and perform a noise measurement. Additionally, platform screen doors as a potential method for noise mitigation were examined. The results show that the noise caused by trains was dominant in the metro stations; however, the noise impact by public broadcast and passengers cannot be ignored. The noise levels of the transfer stations were obviously greater than the normal stations, especially during the peak hours. In addition, people in the metro stations have potential exposure to noise that the noise levels exceed the criteria limit of China, which would bring discomfort for humans; however, the normal activities of people would not be impacted. The platform screen doors should be further improved or relevant noise mitigation methods should be taken into account to reduce the noise level within the criteria limit.


The kinetics of the BOLD response depend on inter-stimulus time.
Numerous parameters such as subject age, region of activation, and stimulus timing are known to affect the BOLD signal following neural activation. Here, we investigated how differences in the rest time between successive long visual stimuli alter the kinetics of the BOLD signal in the visual cortex. We found that the BOLD rise time varies with the inter-stimulus interval. By taking this into account when performing statistical analyses of BOLD data, we show that a roughly 20% increase in statistical power can be achieved. In addition, the dependence of the BOLD signal rise time on the inter-stimulus interval provides insight into the physiology underlying the post-stimulus undershoot.


Dialysis arthropathy: outcome after renal transplantation.
Patients treated by long-term maintenance hemodialysis frequently develop a form of chronic arthropathy that is strongly associated with beta 2-microglobulin amyloid deposition and related, at least in part, to beta 2-microglobulin retention. Successful renal transplantation is followed by a rapid fall in serum beta 2-microglobulin levels and might allow dissolution of amyloid deposits. The purpose of this work was to investigate the effects of renal transplantation on dialysis arthropathy. Fourteen renal transplant recipients were selected on the basis of previous hemodialysis treatment for at least 10 years (mean 16) and a history of chronic joint pain prior to transplantation. They all received 10 to 17.5 mg/d of prednisone. Posttransplant rheumatologic manifestations were studied prospectively and compared to pretransplant rheumatologic manifestations recorded in medical charts and reported during patient interviews. Pretransplant and posttransplant articular roentgenograms were separately analyzed by three observers who were blinded to timing of the films. Beta 2-microglobulin amyloid was identified by Congo red staining and immunohistology. After a mean posttransplant interval of 54 months (range 12 to 121), the articular condition was improved in 10 patients, unchanged in 1, and worsened in 3, according to patients' assessments. The number of painful joints decreased significantly (P < 0.05) as compared to the pretransplant period. However, the number and size of subchondral bone erosions remained unchanged, destructive arthropathies generally worsened, and articular beta 2-microglobulin amyloid deposits were identified in 2 patients, 2 and 10 years after renal transplantation, respectively. Renal transplantation appeared to arrest progression of beta 2-microglobulin amyloid in dialysis patients, but it neither led to dissolution of deposits nor prevented progression of destructive arthropathies. Most articular symptoms were improved, probably as a result of corticosteroid therapy.


Application of the Stage, Size, Grade, and Necrosis (SSIGN) Score for Clear Cell Renal Cell Carcinoma in Contemporary Patients.
The tumor stage, size, grade, and necrosis (SSIGN) score was originally defined using patients treated with radical nephrectomy (RN) between 1970 and 1998 for clear cell renal cell carcinoma (ccRCC), excluding patients treated with partial nephrectomy (PN). To characterize the original SSIGN score cohort with longer follow-up and evaluate a contemporary series of patients treated with RN and PN. Retrospective single-institution review of 3600 consecutive surgically treated ccRCC patients grouped into three cohorts: original RN, contemporary (1999-2010) RN, and contemporary PN. RN or PN. The association of the SSIGN score with risk of death from RCC was assessed using a Cox proportional hazards regression model, and predictive ability was summarized with a C-index. The SSIGN scores differed significantly between the original RN, contemporary RN, and contemporary PN cohorts (p<0.001), with SSIGN ≥4 in 53.5%, 62.7%, and 4.7%, respectively (p<0.001). The median durations of follow-up for these groups were 20.1, 9.2, and 7.6 yr, respectively. Each increase in the SSIGN score was predictive of death from RCC (hazard ratios [HRs]: 1.41 for original RN, 1.37 for contemporary RN, and 1.70 for contemporary PN; all p<0.001). The C-indexes for these models were 0.82, 0.84, and 0.82 for original RN, contemporary RN, and contemporary PN, respectively. After accounting for an era-specific improvement in survival among RN patients (HR: 0.53 for contemporary vs original RN; p<0.001), the SSIGN score remained predictive of death from RCC (HR: 1.40; p<0.001). The SSIGN score remains a useful prediction tool for patients undergoing RN with 20-yr follow-up. When applied to contemporary RN and PN patients, the score retained strong predictive ability. These results should assist in patient counseling and help guide surveillance for ccRCC patients treated with RN or PN. We evaluated the validity of a previously described tool to predict survival following surgery in contemporary patients with kidney cancer. We found that this tool remains valid even when extended to patients significantly different than were initially used to create the tool.


How Much Does Presenteeism Change in Response to Interventions or Alterations in Health Status? A Systematic Review and Meta-Analysis Using the COSMIN Methodology.
Purpose The purpose of this study was to estimate the extent to which measures of presenteeism among workers change in response to alterations in health status induced by treatment or natural history. Methods We searched eight databases in August 2020 for studies published since 2012 measuring presenteeism longitudinally. Two independent reviewers screened the titles, abstracts, and full-text articles and performed data extraction. Studies were stratified into longitudinal studies using presenteeism as an outcome and measurement studies designed to test the responsiveness of presenteeism measures. We appraised the methodological quality of the measurement studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist. Standardized response means (SRMs) for interventional studies where participants reported improvement on anchor measures were quantitatively pooled.Results Our searches returned 2882 results. Eleven measurement studies and 126 longitudinal studies were included. Of the measurement studies (n = 2625 participants), 7 had adequate study quality and 4 studies were deemed doubtful. Anchors and responsiveness methods varied considerably. Our estimate of responsiveness from 5 measurement studies and 4 presenteeism measures is an SRM of 0.85 (95% CI 0.77, 0.92) and Cohen's d of 0.54 (95% CI 0.49, 0.58), translating to an average important change of 17/100. For deterioration, the value is - 17/100. Conclusions We found considerable variation regarding how responsiveness data was reported in measurement studies. There is evidence that responsiveness is strong for four presenteeism measures: the Work Productivity Survey, the Work Functioning Impairment Scale, the Work Role Functioning Questionnaire, and the Nurses Work Functioning Questionnaire.


White matter alterations in the corpus callosum of adolescents with first-admission schizophrenia.
Several diffusion tensor imaging (DTI) studies involving adults and adolescents with schizophrenia have examined fractional anisotropy (FA) in the corpus callosum (CC) with conflicting findings. This may be due to confounding factors such as the chronicity of the disorder, long-term medication with psychotropics or methodological differences. To provide a clearer picture of early alterations, we examined 13 adolescents with first-admission schizophrenia and 13 healthy controls using a region-of-interest approach based on probabilistic voxel classification. We quantified FA in four subdivisions of the CC and hypothesized that adolescents with schizophrenia display a reduced FA in the genu associated with 'hypofrontality' and a reduced FA in the body of the CC linked to the heteromodal association cortex. Fiber integrity measurements revealed significant FA decreases in the genu and body of the CC in adolescents with schizophrenia compared to healthy controls. These findings emphasize the central role of the CC in even the early stages of schizophrenia and lend weight to hypotheses about frontal alterations and the central role of the heteromodal association cortex in the aetiopathogenesis of the disorder.


Chemopreventive and antitumor effects of benzyl isothiocynate on HCC models: A possible role of HGF /pAkt/ STAT3 axis and VEGF.
Benzyl isothiocyanate (BITC) is a member of the isothiocyanate compounds that found in cruciferous vegetables. BITC has a potential anticancer effect in different types of tumors. Few studies referred to the antineoplastic effect of BITC against HCC. The mechanism of BITC concerning retardation of HCC progression is incompletely understood. This study evaluated the role of HGF, pAkt and STAT3 in BITC induced HCC growth retardation. HCC was induced in mice using diethylnitrosamine (DEN) 75 mg/kg once a week for 4 weeks. BITC 10 and 20 mg/kg was given to mice orally each day for 10 weeks. The HCC cell lines HepG2 and Huh-7 were also used to evaluate the effect of BITC on tumor cells behavior. Immunoassay was used to detect expressions of caspase-3 activity, VEGF, MMP-2, TNF-α, HGF and pAkt. STAT3 expression was detected in liver tissues using immunohistochemical staining. BITC has a potential role in suppressing hepatic precancerous lesion progression in mice. The drug increased caspase-3 activity in tumor cells and inhibited the angiogenic marker VEGF. It also decreased the metastatic marker MMP-2. This anticancer effect of BITC was observed in DEN treated mice as well as in hepatoma cell lines. The reported antineoplastic activity was correlated with downregulation of HGF and its downstream molecules pAkt and STAT3. The effect of BITC on HGF /pAkt/ STAT3 axis has a potential role in both chemopreventive and chemotherapeutic effects of BITC.


High-sensitivity C-reactive protein as a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy.
C-reactive protein (CRP) is an important biomarker of inflammation and plays a pivotal role in predicting the clinical prognosis of cardiovascular and cerebrovascular diseases. However, the mechanism of inflammation influencing the outcome of patients with ischemic stroke are unknown. We aim to investigate the association between hsCRP and mRS in 194 eligible patients by therapy-stratified analyses. The modification effects of antiplatelet therapy on the association between mRS and different exposure variables were analyzed. The retained variables were analyzed in the receiver operating characteristic (ROC) curve to discriminate patients with poor outcome. hsCRP was positively correlated with mRS in therapy-stratified analyses. There was a statistical modification effect of antiplatelet therapy on the association of hsCRP and mRS (P for interaction = 0.0101). The discriminative effect of poor outcome was further verified by ROC curve analyses (AUCwith from 0.758 to 0.872, AUCwithout from 0.709 to 0.713). hsCRP is correlated with the clinical outcome of patients treated with IVrt-PA, and may be a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy than in non-used patients.


Therapeutic potency of heat-shock protein-90 pharmacological inhibitors in the treatment of gastrointestinal cancer, current status and perspectives.
Heat-shock protein-90 (HSP90) chaperone machinery is critical to the folding, stability and activity of several client proteins including many responsible for tumour initiation, progression and metastasis. Overexpression of HSP90 is correlated with poor prognosis of GI cancer. Pharmacological inhibitors of HSP90 suppress tumorigenic effects of HSP90 by suppressing angiogenesis, survival, metastasis and drug resistance in GI cancer. This review summarizes the role of HSP90 inhibitors in the treatment of GI cancer. We have presented different antitumour mechanisms of HSP90 inhibitors in cancer treatment. Suppression of HSP90 signalling via specific and novel pharmacological inhibitors is a potentially novel therapeutic approach for patients with GI cancer for a better understanding and hence a better management of this disease.


An explicit formula for frequency changes in genetic algebras.
A general situation in population genetics is considered with any hereditary system described by a genetic algebra. It is assumed that there is random mating, no selection, and infinite population size. A formula is derived for the distribution of genetic types in the general jth generation given the distribution in the initial generation. Special attention is paid to the case of one locus with polyploidy and chromosome segregation. The calculations are carried out as far as possible in the situation with triploid gametes.


Heteropterys aphrodisiaca (extract BST0298): a Brazilian plant that improves memory in aged rats.
Literature report is lacking on pharmacological studies of the plant Heteropterys aphrodisiaca, endemic to the scrublands of Brazil. The present study was carried out to investigate the effects of oral dosing with extract BST0298 from this plant, on learning and on memory, in young (3-6-month-old) and aged (20-28-month-old) rats. The aged animals presented significant memory deficits in both the passive avoidance and T-maze left/right discrimination tests. Treatment for 7 days (50 mg/kg) or 26 days (100 mg/kg) with extract BST0298 restored the memory deficits in the passive avoidance test. However, no improvement in memory was observed after acute administration of extract BST0298 (100 mg/kg) in aged rats. An improvement in learning was also observed in the left/right discrimination test in aged rats treated for 109 days with BST0298 at a dose of 50 mg/kg. These results suggest that treatment for 7 days or more with H. aphrodisiaca improves learning and memory deficits in aged rats.


Automated detection of ripple oscillations in long-term scalp EEG from patients with infantile spasms.
Objective.Scalp high-frequency oscillations (HFOs) are a promising biomarker of epileptogenicity in infantile spasms (IS) and many other epilepsy syndromes, but prior studies have relied on visual analysis of short segments of data due to the prevalence of artifacts in EEG. Here we set out to robustly characterize the rate and spatial distribution of HFOs in large datasets from IS subjects using fully automated HFO detection techniques.Approach.We prospectively collected long-term scalp EEG data from 12 subjects with IS and 18 healthy controls. For patients with IS, recording began prior to diagnosis and continued through initiation of treatment with adrenocorticotropic hormone (ACTH). The median analyzable EEG duration was 18.2 h for controls and 84.5 h for IS subjects (∼1300 h total). Ripples (80-250 Hz) were detected in all EEG data using an automated algorithm.Main results.HFO rates were substantially higher in patients with IS compared to controls. In IS patients, HFO rates were higher during sleep compared to wakefulness (median 5.5 min-1and 2.9 min-1, respectively;p = 0.002); controls did not exhibit a difference in HFO rate between sleep and wakefulness (median 0.98 min-1and 0.82 min-1, respectively). Spatially, IS patients exhibited significantly higher rates of HFOs in the posterior parasaggital region and significantly lower HFO rates in frontal channels, and this difference was more pronounced during sleep. In IS subjects, ACTH therapy significantly decreased the rate of HFOs.Significance.Here we provide a detailed characterization of the spatial distribution and rates of HFOs associated with IS, which may have relevance for diagnosis and assessment of treatment response. We also demonstrate that our fully automated algorithm can be used to detect HFOs in long-term scalp EEG with sufficient accuracy to clearly discriminate healthy subjects from those with IS.


Management of a central corneal perforation in the emergency room: Tenon patch technique.
Corneal perforations are defined as a solution of continuity in the cornea. Usually, these cases evolve to the formation of a corneal-iridial scar or require surgical intervention. The tenon patch graft represents a good alternative to other methods and has many advantages. A 63-year-old patient who had been followed for severe dry eyes due to rheumatoid arthritis for 10 years presented to the emergency room with a central corneal perforation, partially sealed by the iris, accompanied by significant corneal edema in the right eye. Given the clinical picture that had been developing for 5 days, we decided to perform a tenon patch graft on the perforation. At 4 weeks of follow-up, globe integrity was maintained with a well-placed tenon patch. No evidence of leakage in the Seidel test was noted. The tenon patch graft represents a good alternative in the management of corneal perforations and has many advantages, among which the feasibility in an emergency, allowing a corneal graft afterwards.


Correction: Convenient C-alkylation of the [HCB11Cl11](-) carborane anion.
Correction for 'Convenient C-alkylation of the [HCB11Cl11](-) carborane anion' by Rodrigo Ramírez-Contreras and Oleg V. Ozerov, Dalton Trans., 2012, 41, 7842-7844.


Morphometric MRI features are associated with surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis.
Corticoamygdalohippocampectomy (CAH) improves seizure control, quality of life, and decreases mortality for refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). One-third of patients continue having seizures, and it is pivotal to determine structural abnormalities that might influence the postoperative outcome. Studies indicate that nonhippocampal regions may play a role in the epileptogenic network in MTLE-HS and could generate seizures postoperatively. The aim of this study is to analyze areas of atrophy, not always detected on routine MRI, comparing patients who became seizure free (SF) with those non seizure free (NSF) after CAH, in an attempt to establish possible predictors of surgical outcome. 105 patients with refractory MTLE-HS submitted to CAH (59 left MTLE; 46 males) and 47 controls were enrolled. FreeSurfer was performed for cortical thickness and volume estimation comparing patients to controls and SF versus NSF patients. The final sample after post processing procedures resulted in 99 patients. Cortical thickness analyses showed reductions in left insula in NSF patients compared to those SF. Significant volume reductions in SF patients were present in bilateral thalami, hippocampi and pars opercularis, left parahippocampal gyrus and right temporal pole. In NSF patients reductions were present bilaterally in thalami, hippocampi, entorhinal cortices, superior frontal and supramarginal gyri; on the left: superior and middle temporal gyri, temporal pole, parahippocampal gyrus, pars opercularis and middle frontal gyrus; and on the right: precentral, superior, middle and inferior temporal gyri. Comparison between SF and NSF patients showed ipsilateral gray matter reductions in the right entorhinal cortex (p=0.003) and contralateral parahippocampal gyrus (p=0.05) in right MTLE-HS. Patients NSF had a longer duration of epilepsy than those SF (p=0.028). NSF patients exhibited more extensive areas of atrophy than SF ones. As entorhinal cortex and parahippocampal gyrus are reduced in NSF patients compared to those SF these structures might be implicated in the network responsible for the maintenance of postoperative seizures. Duration of epilepsy is a predictor of seizure outcome.


Core muscles thickness is not associated with knee frontal plane projection angle during single-leg squat in healthy people.
Core muscles play an important role in lower limb stability and alignment, with their weakness being associated with poor alignment and, consequently, with injuries. Despite muscle structure being critical to muscle strength production, we did not find studies associating the morphology of the core muscles and lower limb alignment during functional tasks. Is there association between thickness of core muscles (external oblique - EO, internal oblique - IO, transversus abdominis - TrA and gluteus medius - GMed) and lower limb alignment during the single-leg squat in healthy subjects? Forty-six healthy participants (27 male and 19 female) performed the following evaluations: (i) measurements of muscle thickness of the EO, IO, TrA and GMed using ultrasound and (ii) measurements of lower limb alignment using the knee frontal plane projection angle (FPPA) during the single-leg squat. A Spearman rank correlation coefficient (rs) was performed between the thickness of selected core muscles (OE, OI, TrA and GMed) and the knee FPPA. In addition, a partial correlation (r) was performed, using sex, physical activity level and body mass index as control variables. We did not observe significant correlations between the knee FPPA and the thickness of the EO (rs = 0.194; p = 0.197), IO (rs = 0.182; p = 0.225), TrA (rs = 0.073; p = 0.627) and GMed (rs = -0.092; p = 0.542). When controlling for sex, physical activity level and body mass index, similar results were observed [EO (r = 0.157; p = 0.316), IO (r = 0.261; p = 0.092), TrA (r = 0.030; p = 0.850) and GMed (r = -0.144; p = 0.356)] SIGNIFICANCE: Our results demonstrated that core muscles' thickness is not associated with lower limb alignment during the single-leg squat in healthy people.


Metabolic depletion effect on serine/threonine- and tyrosine-phosphorylations of membrane proteins in human erythrocytes.
The response of serine/threonine-phosphorylation of the major transmembrane protein (band 3) in human erythrocytes to the metabolic state of the cells is different from that exhibited by the tyrosine-phosphorylation of the same protein. Precisely, both serine- and tyrosine-phosphorylation are decreased during metabolic depletion of the erythrocytes. However, the depletion-induced tyrosine-phosphorylation decrease of band 3 is not reversed by the subsequent metabolic repletion of the depleted cells, being accompanied by an irreversible inactivation of both membrane-bound and cytosolic tyrosine-protein kinase(s). By contrast, the depletion-induced phosphoserine-dephosphorylation is reversed by the following repletion, being accompanied by a reversible translocation of casein kinase(s) between cytosolic and membrane compartments. A possible functional correlation between the serine-phosphorylation state of band 3 protein and the band 3-mediated anion transport across the membrane is discussed.