Point-of-care antithrombotic monitoring in children.
The use of oral anticoagulant therapy is increasing in children. Managing anticoagulant therapy in children presents unique challenges, including poor venous access. The advent of point-of-care (POC) monitoring of anticoagulant therapy offers a potential solution to this challenge. This paper reviews the published literature relating to POC monitoring of oral anticoagulant therapy in children. A Medline search was conducted and identified key publications. Papers were reviewed with respect to their objectives, populations and POC device investigated. Study limitations were identified. Five publications and one abstract were identified, reporting studies using five different POC monitors. Three studies had a strong clinical management focus. Outcome measures assessed included target therapeutic range achievement and frequency of adverse events. Correlation between POC and laboratory-based results ranged from 0.83 to 0.96. Home monitoring and self-management using POC monitors were both reported to be preferred compared to standard laboratory testing. POC monitoring of oral anticoagulant therapy in children offers considerable advantages. The reviewed literature would suggest such monitoring can be performed accurately and reliably. The impact of quality control issues, such as calibration of thromboplastin ISI in POC devices, has not been explored in a paediatric population. Further studies are needed to clarify such issues and confirm the safety, reliability and efficacy of POC monitoring of oral anticoagulant therapy in children, including its home monitoring and self-management programs.


Long-term quality of life outcome after spondylodiscitis treatment.
Spondylodiscitis is the most common spinal infection of which the incidence has increased and the peak prevalence is between 50 and 70 years of age. Spondylodiscitis is often a complication of a distant infection. Early diagnosis can be challenging, and although improvements in diagnostic techniques and modern therapy have diminished the mortality of the disease, current literature about the outcome of spondylodiscitis is scarce. To evaluate the long-term clinical outcome of patients who suffered from spondylodiscitis. A two-center cross-sectional study. Patients with spondylodiscitis in two large teaching hospitals in the Netherlands between 2003 and 2017. Visual Analogue Scale (VAS) for back pain, Oswestry Disability Index (ODI) for function, and Short Form 36 (SF-36) for general quality of life of spondylodiscitis patients. Eligible patients were identified from electronic patient databases and completed multiple patient reported outcome measures after obtaining informed consent. General demographic and clinical information (age, sex, medical history) were extracted from the patient records. SF-36 domain scores of spondylodiscitis patients were compared with a nationwide population sample. 183 patients were treated for spondylodiscitis; additional questionnaires were received from 82 patients. After a median follow-up of 63 months, the overall mortality was 28%. The mean VAS for back pain was 3.5, and the mean ODI score was 22. In all SF-36 domains a significantly lower score was found in the spondylodiscitis group compared with a normative national Dutch cohort. There was a strong correlation between back pain and ODI scores (ρ=0.81, p<.05). Our study confirms that spondylodiscitis is a disease causing a profound impact on back pain, function and quality of life. The results suggest that chronic back pain is a debilitating problem, as it has an extensive influence on daily activities and social and psychological well-being, causing significant disability.


Adsorption characteristics of haloacetonitriles on functionalized silica-based porous materials in aqueous solution.
The effect of the surface functional group on the removal and mechanism of dichloroacetonitrile (DCAN) adsorption over silica-based porous materials was evaluated in comparison with powdered activated carbon (PAC). Hexagonal mesoporous silicate (HMS) was synthesized and functionalized by three different types of organosilanes (3-aminopropyltriethoxysilane, 3-mercaptopropyltrimethoxysilane and n-octyldimethysilane). Adsorption kinetics and isotherm models were used to determine the adsorption mechanism. The selective adsorption of five haloacetonitriles (HANs) in the single and mixed solute systems was also studied. The experiments revealed that the surface functional groups of the adsorbents largely affected the DCAN adsorption capacities. 3-Mercaptopropyl-grafted HMS had a high DCAN adsorption capacity compared to PAC. The adsorption mechanism is believed to occur via an ion-dipole electrostatic interaction in which water interference is inevitable at low concentrations of DCAN. In addition, the adsorption of DCAN strongly depended on the pH of the solution as this related to the charge density of the adsorbents. The selective adsorption of the five HANs over PAC was not observed, while the molecular structure of different HANs obviously influenced the adsorption capacity and selectivity over 3-mercaptopropyl-grafted HMS.


Lumbar spine instrumented fusion surgery under spinal anaesthesia versus general anaesthesia-A retrospective study of 239 cases.
Conventionally spinal surgeries are done under general anaesthesia (GA). Plenty of literature is available on lumbar spine non-instrumented surgeries under spinal anaesthesia (SA) but handful of literature is there on lumbar spinal instrumented fusion surgeries under SA. We retrospectively analysed the data of 131 patients operated under SA and 108 patients under GA. Aim of the study was to evaluate the safety, advantages and disadvantages of doing lumbar spine instrumented fusion surgeries under SA.In time of COVID-19 pandemic, aerosol generating procedure like intubation, can be avoided if lumbar spine instrumented fusion surgeries are performed under SA. 239 patients aged between 20 and 79 years operated from January 2014 to December 2019 were included in this study. Indications for surgery were lumbar canal stenosis, degenerative or lytic spondylolisthesis. They underwent L4-L5 or L5-S1 fusion surgeries either TLIF or pedicle screw fixation postero lateral fusion (PLF) and decompression. Out of 239 patients,131 were operated under SA and 108 patients under GA. Heart rate, mean arterial pressure (MAP), blood loss, operating room time, post-op pain relief and need of analgesics, cost of surgery and anaesthesia related complications were analysed. The study found significantly less blood loss (p<.05), less OR time, better post-op analgesia and lesser incidence of nausea and vomiting in SA (8.4%) than GA (29.6%). We observed average 10% cost reduction in SA. This study did not find any prone position related complication in regional anaesthesia but one transient brachial plexus palsy and one post-op shoulder pain in GA group. SA is a safe alternative to GA for lumbar spine instrumented fusion surgery with significant less blood loss, OR time, better post-op analgesia, average 10% overall cost reduction and no reported prone-position related complications.


Differential sensitivity of various markers of platelet activation with adenosine diphosphate.
A number of techniques have been available to assess platelet activation, but their relative sensitivity is unknown and their usage is variable and not based on any rational criteria. Here, we compared the ability of several techniques based on morphological and biochemical markers to detect the first signs of ADP-induced platelet activation. Scanning electron microscopy of platelets was performed in parallel with flow cytometry to quantify the surface expression of P-selectin (marked by labeled anti-CD62P antibodies), active αIIbβ3-intergrin (assessed by the binding of labeled fibrinogen) and phosphatidylserine (assessed by the binding of labeled Annexin V). When expressed as a fraction of activated platelets, shape changes were the most sensitive to a low ADP concentration compared to the biochemical markers in the following order of sensitivity: morphological changes>fibrinogen binding capacity>P-selectin expression> phosphatidylserine exposure. These results suggest the greater sensitivity of platelet microscopy and the importance of its combination with flow cytometry used to detect surface expression of the molecular markers of platelet activation.


Diagnostic tools in coronavirus disease 2019 associated mucormycosis - do we need three-dimensional computed tomography?
Three-dimensional computed tomography reconstruction of the face has recently been presented as a newer diagnostic tool in coronavirus disease 2019 associated mucormycosis. This study was conducted to compare three-dimensional computed tomography reconstruction with conventional two-dimensional computed tomography in coronavirus disease 2019 associated mucormycosis. A total of 123 mucormycosis patients underwent three-dimensional computed tomography reconstruction after a comprehensive clinical investigation. The involvement of the facial skeleton was noted. The anterior maxillary wall was most commonly involved (9.8 per cent). Involvement of the lateral maxillary wall was noted in 6.5 per cent of patients. Sixty-seven patients (54.5 per cent) underwent endoscopic surgery, 22 (17.9 per cent) underwent open surgical procedures, and 12 (9.8 per cent) had combined endoscopic and open surgical procedures. In 21 patients (17.1 per cent), open surgery was performed in the first instance based on additional three-dimensional computed tomography findings, and revision surgical procedures were avoided. Three-dimensional computed tomography of the face was found to be superior in determining the extent of disease. It reduces delays in diagnosis, facilitates surgical planning and minimises the need for multiple surgical procedures.


Patient perspectives on non-response to psychotherapy for borderline personality disorder: a qualitative study.
Despite increasing evidence for the effectiveness of psychotherapy for Borderline Personality Disorder (BPD), estimates show that approximately half of those in treatment do not clinically improve or reach reliable change criteria. There are limited qualitative descriptions of treatment factors associated with non-response from the perspectives of those struggling to improve. Eighteen people (72.2% female, mean age 29.4 (SD = 8)) with experience of receiving psychotherapeutic treatment for BPD were interviewed to obtain their perspectives on hindering factors in treatment and what may be helpful to reduce non-response. The data in this qualitative study was analysed thematically. Four domains were created from the insights patients shared on non-response and what may be needed to mitigate it. The focus of Domain 1 was that therapy cannot be effective until two factors are in place. First, the patient needs sufficient safety and stability in their environment in order to face the challenges of therapy. Second, they need to be able to access therapy. Domain 2 described factors the patients themselves contribute. The themes in this domain were described as phases that need to be progressed through before therapy can be effective. These phases were ceasing denial that help is warranted and deserved, taking responsibility for behaviours that contribute to unwellness, and committing to the hard work that is required for change. Domain 3 described how the lack of a safe alliance and ruptures in the safety of the relationship with the therapist can contribute to non-response. Domain 4 was comprised of factors that patients identified as supportive of moving through the barriers to response. The first theme in this domain was prioritising the safety of the therapy relationship. The second theme was giving a clear diagnosis and taking a collaborative approach in sessions. The final theme described the importance of focusing on practical goals with the patient to create tangible life changes. This study found that non-response is complex and multifaceted. First, it is clear that systems need to be in place to support access to adequate care and foster life stability. Second, considerable effort may be needed at the engagement phase of therapy to clarify expectations. Third, attention to specific interpersonal challenges between patients and therapists is an important focus. Finally, structured work to improve relationships and vocational outcomes is indicated.


Changes in shoulder muscle activities and glenohumeral motion after rotator cuff repair: an assessment using ultrasound real-time tissue elastography.
Although rotator cuff repair is performed to restore the function of the rotator cuff muscles and glenohumeral (GH) joint motion, little has been known regarding the recovery process. The purpose of this study was (1) to investigate changes over time in activities of the supraspinatus and deltoid muscles assessed by ultrasound real-time tissue elastography (RTE) after rotator cuff repair and (2) to determine contributions of the activities of these muscles to the GH joint motion. Twenty patients after rotator cuff repair and 13 control participants were enrolled in this study. Elasticity of the supraspinatus and middle deltoid muscles were measured at rest and 30° of humerothoracic elevation in the scapular plane (scaption) by using RTE. The elasticity at 30° of scaption was normalized to that at rest in each muscle to quantify their muscle activities. In addition, the supraspinatus-to-middle deltoid (SSP/MD) ratio for the normalized elasticity was calculated. The GH elevation angle was measured with a digital inclinometer, which was calculated by subtracting the scapular upward rotation angle from 30° of scaption. For patients after rotator cuff repair, all measurements were performed at 6 weeks, 8 weeks, 3 months, and 6 months after surgery. Rotator cuff integrity was examined with magnetic resonance imaging at 6 months after surgery. Fifteen of 20 patients who remained intact at 6 months after surgery completed this study. The supraspinatus activity at 6 weeks was significantly smaller than that at 3 months (P = .006) and 6 months (P = .010). There was no significant difference in the supraspinatus activity between the patients at 3 months and the control participants (P = .586). The middle deltoid activity at 6 weeks was significantly greater than that at 6 months (P = .003). There was positive correlation between GH elevation angle and the activity of the supraspinatus relative to the deltoid at 6 weeks (r = 0.75, P = .001) and 8 weeks (r = 0.53, P = .041). The supraspinatus activity increased from 6 weeks to 3 months after surgery. The supraspinatus activity at 3 months after surgery was the same level as that in healthy individuals. On the other hand, the deltoid activity decreased from 6 weeks to 6 months after surgery. The increase in activity of the supraspinatus relative to the deltoid was likely to be related to the increase in GH elevation during postoperative at 8 weeks.


High-dimensional analyses reveal a distinct role of T-cell subsets in the immune microenvironment of gastric cancer.
To facilitate disease prognosis and improve precise immunotherapy of gastric cancer (GC) patients, a comprehensive study integrating immune cellular and molecular analyses on tumor tissues and peripheral blood was performed. The association of GC patients' outcomes and the immune context of their tumors was explored using multiplex immunohistochemistry (mIHC) and transcriptome profiling. Potential immune dysfunction mechanism/s in the tumors on the systemic level was further examined using mass cytometry (CyTOF) in complementary peripheral blood from selected patients. GC cohorts with mIHC and gene expression profiling data were also used as validation cohorts. Increased CD4+FOXP3+ T-cell density in the GC tumor correlated with prolonged survival. Interestingly, CD4+FOXP3+ T cells had a close interaction with CD8+ T cells rather than tumor cells. High densities of CD4+FOXP3+ T cells and CD8+ T cells (High-High) independently predicted prolonged patient survival. Furthermore, the interferon-gamma (IFN-γ) gene signature and PDL1 expression were up-regulated in this group. Importantly, a subgroup of genomically stable (GS) tumors and tumors with chromosomal instability (CIN) within this High-High group also had excellent survival. The High-High GS/CIN tumors were coupled with increased frequencies of Tbet+CD4+ T cells and central memory CD4+ T cells in the peripheral blood. These novel findings identify the combination of CD8+ T cells and FOXP3+CD4+ T cells as a significant prognostic marker for GC patients, which also could potentially be targeted and applied in the combination therapy with immune checkpoint blockades in precision medicine.


Distribution, risk assessment, and source apportionment of polycyclic aromatic hydrocarbons (PAHs) using positive matrix factorization (PMF) in urban soils of East India.
This study investigated 16 United States environmental protection agency priority PAHs profiles and their sources in 40 urban soils collected from two industrialised cities, Jamshedpur and Bokaro, in east India and assessed their health risk to humans. The results showed the predominance of high molecular weight (HMW) PAHs (4-5 rings). The total PAHs concentration in surface soils ranged from 2223 to 11,266 ng/g and 729 to 5359 ng/g (dw), respectively, for Jamshedpur and Bokaro. Higher concentrations of PAHs were recorded at the selected industrial areas and heavy traffic zones of both cities. In JSR city 4-ring PAHs contributed 43% of total PAHs trailed by 5-ring PAHs 27.2%. Similarly, in BKR city 4-ring PAHs contributed 34% of the total PAHs, followed by 3-ring PAHs 28.9% and 5-ring PAHs 22.9%. Total organic carbon in surface soils exhibited moderate correlation with the low molecular weight (ΣLMW) PAHs (R2 = 0.69) and a comparatively strong correlation with the ΣHMW PAHs (R2 = 0.89), suggesting strong adsorption of HMW PAHs to urban soils. The Diagnostic and PMF modelling analysis indicated that the major sources of PAHs contamination in soils were petroleum combustion, vehicular emissions, biomass, and coal combustion. The health risk assessment shows that the cumulative probability of carcinogenic risks was under the acceptable limits of 10-4 to 10-6. At some sampling areas in both cities, the maximum value of total exposure cancer risk slightly exceeded the acceptable limits indicating some carcinogenic risk for adults.


Ganglioside composition of human neuroblastomas. Correlation with prognosis. A Pediatric Oncology Group Study.
The ganglioside composition of neuroblastoma samples from 53 patients was determined. Tumor sites included the adrenals (15), and the thoracic (20), abdominal (15), and pelvic (3) areas. Age of the patients at the time of surgery ranged from 1 day to over 10 years and the Stage of the tumors from A to D. Differences in ganglioside patterns were observed, with neuroblastomas from patients who were either disease positive or dead of disease tending to have more monosialogangliosides and fewer gangliotetraose gangliosides of the B series (formula; see text) than tumors from patients who were disease-free. More specifically, six of the seven patients lacking GT1b died of disease, suggesting that the absence of GT1b is indicative of a poor prognosis.


Posterior hinge fixation for the treatment of unstable traumatic sacroiliac joint injuries.
Posterior hinge fixation (PHF) is a sacroiliac joint fixation method indicated for the surgical treatment of unstable pelvic ring fractures (tile C). PHF yields good functional outcomes based on the Majeed score at more than 1 year of follow-up. A single-center, retrospective study of patients who had a Tile C pelvic ring fracture, who were operated by PHF and who were evaluated at a minimum follow-up of 1 year. The functional outcome was determined using the Majeed score and pain was evaluated by the patients using a visual analog scale (VAS). The preoperative, intraoperative and postoperative data, complications and sequelae were documented. A CT-scan was done at least 1 year after the surgical treatment to determine the SI joint's reduction and fusion. Included were 22 patients (59% men) who had a mean age of 37.3±11.9 years; 21 of these patients were reviewed at a mean of 4.8±4 years. The mean Majeed score at the final assessment was 76.4 points±15.3, with 24% of patients having excellent results (n=5), 53% having good results (n=11), 19% having average results (n=4) and 5% having poor results (n=1). The mean pain level on VAS was 28±23mm. Of the eight surgical site infections, seven occurred in the PHF (88%). CT-scans taken at 1 year postoperative were compared to the preoperative scans. The pelvic opening was reduced by -9±6 (p<0.01), SI diastasis by -11mm±9 (p<0.001), vertical displacement by-7mm±8 (p<0.001), symphysis opening by -15mm±15 (p<0.001), median transverse diameter by -10mm±9 (p<0.001) and bispinal diameter by -5mm±7 (p<0.001). SI fusion was confirmed in 43% of patients (n=9). PHF is a surgical instrumentation method that provides satisfactory long-term reduction of Tile C pelvic ring fractures. The clinical outcomes are good or excellent in 77% of cases. The perioperative morbidity is marked by surgical site infections, all of which healed. IV; retrospective, non-comparative cohort study.


Reversible splenial lesion after surgery for distant arteriovenous malformation: a case report.
Isolated lesions of the corpus callosum are rare and may represent permanent but also transient responses to various pathology termed "reversible splenial lesion syndrome" (RESLES) when in light of relevant clinical presentation. We present the first case of the RESLES after elective surgery for distant arteriovenous malformation (AVM), followed by a slight speech disturbance and MRI verified small, oval, well-circumscribed area of apparent cytotoxic edema in the center of the corpus callosum splenium, which completely resolved within 15 days. Surgery for AVM is followed by the complex adaptation to a new vascular pattern, RESLES might develop, and should be suspected.


Tumor-necrosis-factor and DNA topoisomerase-ii inhibitors in human ovarian-cancer - potential role in chemotherapy.
Seven ovarian and one cervical human cancer cell lines were examined far their sensitivity or resistance to tumor necrosis factor, to three topoisomerase II inhibitors and to cisplatin. Only one line exhibited the multidrug-resistance phenotype and another one an 'atypical'-MDR phenotype. The combination of TNF and topoisomerase-II inhibitors produced enhanced cytotoxicity and overcame the MDR and the atypical resistance. No potentiation of cisplatin cytotoxicity was observed. These findings suggest that TNF enhances the activity of DNA topoisomerase II both in TNF resistant and sensitive cells.


Microstructure of polyelectrolyte nanoaggregates studied by fluorescence probe method.
The microstructure of water soluble nanoaggregates based on polyelectrolyte complex formed by the cationic comb-type copolymer poly(acrylamide -co-[3- (methacryloyl-amino)propyl] trimethylammonium chloride)-graft- polyacrylamide [P(AM-co-MAPTAC)-g-PAM] and the anionic linear polyelectrolyte sodium polyacrylate (NaPA) was investigated using the fluorescence probe technique. The fluorescence probe were 1-anilinonaphthalene-8-sulfonic acid (ANS), pyrene (Py) and 1,10-bis(1-pyrene) decane (PD). The fluorescence properties in polyelectrolyte complex solutions, which are sensitive to either micropolarity (ANS, Py) or microviscosity (PD), were related to the quantities obtained in different pure or mixed solvents. Micropolarities were quantified utilizing the polarity common index (Reichardt) E(T)(30). ANS and Py showed a variation of the micropolarity with the charge ratio of the two polymers, with the lowest polarity reached at the complex neutralization. The PD probe, by its excimer-to-monomer fluorescence intensities ratio, enabled us to evidence the effect of the composition and the comb-type copolymer grafting density on the microviscosity of the interpolyelectrolytes aggregates. It has been found that the microviscosity increased with the density of the grafting PAM chains.


Nitrate contamination of coastal groundwater: Sources and transport mechanisms along a volcanic aquifer.
Groundwater is the sole water supply source on Jeju volcanic island in Korea and increasing levels of nitrate contamination have raised serious public concerns. This study was objected to understand the nitrate contamination mechanisms of the coastal groundwater overlain by a low-permeability layer in the western part of the island. The 2-yrs of quarterly groundwater monitoring from Sep. 2016 to Oct. 2018 revealed that NO3-N concentrations of 60.7% of sampled wells exceeded 10 mg/L, and those of 17.8% in the range of 3-10 mg/L, indicating those wells are already contaminated or under influence of potential sources. The spatio-temporal variation of groundwater chemistry and stable isotopic signatures suggested that nitrate originated mainly from chemical fertilizers due to agricultural activities and in part from liquefied manure affected by local livestock industries. Two transport processes appeared to be responsible for the nitrate in the confined coastal aquifer: 1) the direct penetration from the land surface through the wellbore leakage at incompletely grouted wells, and 2) the addition of nitrate-contaminated groundwater from upgradient areas where the confining layer is pinched out. Presently the potential nitrate sources are distributed up to 600 m above mean sea level(amsl), and the isotopic signatures implies that the provenance of coastal groundwater could be upland areas of up to 1280 m amsl. Subsequently, nitrate sources at upland areas could be picked up and carried down to the coastal groundwater under the confined condition of the basaltic aquifer that the regional groundwater recharge occurs. Consequently, groundwater contamination in the coastal aquifer should be considered in the big picture of groundwater system accommodating both regional and local flows.


COVID Arm: Delayed Hypersensitivity Reactions to SARS-CoV-2 Vaccines Misdiagnosed as Cellulitis.
The term "COVID arm" has been coined to describe a harmless delayed hypersensitivity reaction occurring approximately a week after administration of the novel SARS-CoV-2 mRNA vaccine. It appears as a red, warm, pruritic, indurated, or swollen area in the vicinity of the vaccine site. These reactions, especially if accompanied by systemic symptoms, have been mistaken for cellulitis. We report 3 cases of COVID arm, 2 of which were mistaken for cellulitis. Distinguishing features of COVID arm from cellulitis include pruritus as a common finding, occurrence approximately a week after vaccination, a lack of progression of symptoms, rapid response to topical steroids, and/or spontaneous resolution usually over 4 to 5 days.Practice Points:• Patients receiving SARS-CoV-2 vaccines may experience delayed hypersensitivity reactions characterized by erythema, swelling, and itching occurring near the vaccination site (COVID arm), approximately a week after vaccination.• Clinicians can distinguish SARS-CoV-2 vaccine reactions from cellulitis by the time of onset (approximately a week vs 5 days), by the lack of progression of symptoms, and resolution over 4 to 5 days.• Severe cases of COVID arm may be treated with topical steroids.


Lipidomics characterization of the mechanism of Cynomorium songaricum polysaccharide on treating type 2 diabetes.
Although Cynomorium songaricum Rupr. polysaccharide (CSP) has been examined for its effects on glucose regulation, its underlying mechanism is still unclear. To address this issue, a MS-based lipidomics strategy was developed to gain a system-level understanding of the mechanism of CSP on improving type 2 diabetes mellitus (T2DM). UPLC-QTOF/MS and multivariate statistical tools were used to identify the alteration of serum metabolites associated with T2DM and responses to CSP treatment. As a result, 35 potential biomarkers were found and identified in serum, amongst which 26 metabolites were regulated to normal like levels after the administration of CSP. By analyzing the metabolic pathways, glycerophospholipid metabolism was suggested to be closely involved. These results indicated that the intake of CSP exhibited promising anti-diabetic activity, largely due to the regulation of phospholipid metabolism, including phosphatidylcholines, lysophosphatydylcholines, phosphtatidylethanolamines and sphingomyelins.


A novel human monoclonal antibody rapidly induces homotypic cell aggregation and promotes antibody-secreting activity by human B lymphoblastoid cell line IM-9.
A human monoclonal antibody (mAb), designated mNKES, was generated by fusing B cells isolated from an enlarged cervical lymph node of a patient with a carotid body tumor (CBT), with human myeloma cell line KR-12 (6TG). The reactivity of mNKES was tested by the indirect immunofluorescence method. The antigen defined by mNKES was expressed on Burkitt's lymphoma cell lines Raji, Daudi, and Ramos and on B lymphoblastoid cell line IM-9. In addition, mNKES reacted with T cells stimulated with recombinant interleukin-2 (rIL-2) obtained from normal healthy donors. However, mNKES did not react with normal resting human T, B, or adherent cells (monocytes/macrophages). When the reactivity of mNKES and mouse mAbs recognizing the human adhesion-associated antigen (CD10, CD11a, CD11b, CD11c, CD14, CD16, CD18, CD23, CD28, CD29, CD31, CD43, CD44, CD45RA, CD50, CD54, CD58, CD80, CD102, CD106, and HLA class I, and HLA class II antigen) with various cell lines was compared, mNKES reactivity was found to be unique, not resembling that of any of these mouse mAbs. Interestingly, mNKES specifically and rapidly (within 2 hr) induced homotypic cell aggregation of IM-9 cells. This mNKES-induced cell aggregation was completely blocked by the addition of EDTA and when incubated at 4 degrees C. The mAbs reactive with CD11a/CD18 (leukocyte function-associated antigen-1; LFA-1) and CD54 (intercellular adhesion molecule-1; ICAM-1) completely blocked the IM-9 cell aggregation induced by mNKES, and induction of IM-9 cell aggregation by mNKES was significantly blocked in the presence of the protein kinase C inhibitors sphingosine and H-7 and completely blocked by cytochalasin B and cytochalasin D, which inhibit microfilament formation. Regarding biological function, IM-9 cells bearing surface IgG (sIgG) effectively promoted IgG-secreting activity underlying the homotypic cell aggregation induced by mNKES. The surface antigen recognized by mNKES has a molecular size of about 55 kDa, as determined by immunoblotting analysis. These findings indicate that mNKES recognizes a novel adhesion-associated antigen distinct from any previously reported adhesion-associated antigens in terms of pattern of cellular distribution and biological function and that mNKES is the first human mAb found that rapidly induces homotypic cell aggregation and effectively promotes the IgG-secreting activity of human B lymphoblastoid cell line IM-9.


Reduced mate preference for dominant over subordinate males in old female Syrian hamsters (Mesocricetus auratus).
Why some females choose to mate with a 'preferred' male, whereas others choose to mate with an 'inferior' male is not always clear. Generally, the choosiness of females is thought to decline with advanced age, but relatively few studies have investigated this concept, and reports of this phenomenon in mammals are lacking. To address this deficiency, young and old female golden hamsters were evaluated for their preference for dominant vs. subordinate males. Females observed male dyads as a dominance relationship was established. Dominant and subordinate males were then placed within enclosures at the opposite ends of a Y-maze, and the first approach, scent marking, and time spent near each male were evaluated in young and old females during pro-oestrus-a time when females solicit visits by prospective mates by leaving vaginal and flank scent marks. Whereas the proportion of time spent near the dominant male was significantly greater than random for both young and old females, the proportions of vaginal and flank scent marks left for the dominant male were significantly greater than random for young females, but not for old females. Overall, these results are consistent with a decline in the preference for dominant males by old female hamsters.


Toothpaste factors related to dentine tubule occlusion and dentine protection against erosion and abrasion.
To investigate the effect of toothpastes on dentine surface loss and tubule occlusion, and the association of toothpaste-related factors to each of the outcomes. One hundred and sixty human dentine specimens were randomly distributed into 10 groups, according to different toothpastes. The specimens were submitted to artificial saliva (60 min), citric acid (3 min), and brushing abrasion (25 s; totalizing 2 min in toothpaste slurries). This was repeated five times and two outcome variables were analyzed: dentine surface loss (dSL; μm) and tubule occlusion by measurement of the total area of open tubules (Area-OT; μm2). Data were analyzed with Kruskal-Wallis and Mann-Whitney tests (α = 0.05); bivariate and multivariate regressions were used to model the association of the chemical (pH, concentration of F-, Ca2+, and PO43- and presence of Sn2+) and physical (% weight of solid particles, particle size, and wettability) factors of the toothpastes to both outcome variables. Toothpastes caused different degrees of dSL and did not differ in Area-OT. All chemical and physical factors, except the presence of Sn2+, were associated with dSL (p < 0.001). Area-OT was associated only with the presence of Sn2+ (p = 0.033). Greater dSL was associated with lower pH, lower concentration of F-, higher concentration of Ca2+ and PO43-, greater % weight of solid particles, smaller particle size, and lesser wettability, whereas tubule occlusion was associated with the presence of Sn2+. Depending on their chemical and physical composition, toothpastes will cause different degrees of dentine tubule occlusion and dentine surface loss. This could, in turn, modulate dentine hypersensitivity.


Ghrelin in Type 2 diabetes mellitus and metabolic syndrome.
The increasing prevalence of metabolic syndrome and the consequent cardiovascular diseases, like atherosclerotic diseases and Type 2 diabetes has stimulated an active search for novel risk factors. The hormones regulating energy balance are of special interest as potential risk factors for metabolic syndrome and Type 2 diabetes. Ghrelin is a peptide hormone from stomach with growth hormone releasing activity. It is also able to modify glucose and insulin metabolism, blood pressure levels, adipogenesis, and inflammatory processes in experimental conditions. Whether ghrelin has a role in the development metabolic syndrome and the associated diseases, is not known. This review will report the evidence for the role of ghrelin in the clustering of the components of the metabolic syndrome.


Effect of glenoid component inclination on its fixation and humeral head subluxation in total shoulder arthroplasty.
To investigate the effect of glenoid component inclination angle on the fixation of cemented glenoid-bone structures and humeral head subluxation. Results of shoulder replacements, in terms of glenoid component fixation and joint functionality, are bad and must be improved. Repeated glenoid component tilting, a result of eccentric contact forces harms glenoid component fixation. However, the effect of glenoid component inclination is unknown. Keeled glenoid components are cemented into bone substitutes and positioned under inclination angles varying between -4.5 degrees and +4.5 degrees . For each inclination angle 5 glenoid specimens are loaded by a horizontal, constant joint compression force (725 (SD 10) N) and a vertical, superior directed subluxation force (shear force), cyclically varying between 0 and 350 (SD 1) N. After 200,000 load cycles, the upper and lower glenoid component rim-displacements are measured during 1500 additional load cycles by custom made displacement sensors. The maximal superior rim-displacement significantly increased and the minimal inferior rim-displacement dramatically decreased for increasing glenoid component inclination angles up to +4.5 degrees . Maximal ratio of subluxation force over compression force significantly decreased for increasing glenoid component inclination. According to this study, decreasing glenoid component inclination angle decreases glenoid component tilting and humeral head subluxation and the results can be used to improve total shoulder replacements. Better understanding of the effect of glenoid component inclination on glenoid component tilting and humeral head subluxation may be useful information for the surgeon to improve results of the total shoulder arthroplasty, when replacing the glenoid surface.


Assessment of severity and change in obsessive compulsive disorder.
Useful clinician-rated measures of OCD are now available. The Y-BOCS and NIMH Global OC both seem suitable for monitoring outcome in drug trials of OCD. These two scales seem relatively specific for symptoms of OCD and are sensitive to drug-induced changes in symptoms. Neither the Y-BOCS nor the NIMH Global OC confuse trait with state. There are ample data suggesting that the Y-BOCS is reliable and valid scale. Unlike some of the symptom inventories, such as the LOI and MOCI, final scores on the NIMH Global OC and Y-BOCS are not influenced directly by the type or number of obsessions and compulsions present. A computer-administered version of the Y-BOCS has been developed. Currently available patient-rated instruments suffer from serious shortcomings, including insensitivity to change and poor representation of patients with mono-symptomatic clinical pictures (e.g., hoarding alone). Some rating scales have been adapted for use in children with OCD. Several groups, including our own, have elected to use change scores on the 10-item Y-BOCS and a global measure of OCD, such as the NIMH Global OC or modified OGI, as the principal outcome variables in drug trials in patients with OCD. Several studies have selected a 35% decrease in Y-BOCS scores from baseline as indicative of clinically significant improvement. A limitation of all single-item global measures is that they cannot be resolved into smaller components. The more fine-grained analysis that is possible with the multi-item Y-BOCS makes it more desirable as a primary outcome measure, with a global scale as a secondary outcome measure.


Management of a child with acute thyroxine ingestion.
We report a case of thyroxine overdose in a child. Despite extremely high thyroxine (T4RIA) levels on admission, the patient's only symptoms were mild hypertension and tachycardia. Both symptoms responded to propranolol, with a drop in pulse rate and a decrease in blood pressure to normal levels. After four days of cardiac monitoring, the patient was released and received propranolol for five additional days as an outpatient.


Triple framework interpenetration and immobilization of open metal sites within a microporous mixed metal-organic framework for highly selective gas adsorption.
A three-dimensional triply interpenetrated mixed metal-organic framework, Zn(2)(BBA)(2)(CuPyen)·G(x) (M'MOF-20; BBA = biphenyl-4,4'-dicarboxylate; G = guest solvent molecules), of primitive cubic net was obtained through the solvothermal reaction of Zn(NO(3))(2), biphenyl-4,4'-dicarboxylic acid, and the salen precursor Cu(PyenH(2))(NO(3))(2) by a metallo-ligand approach. The triple framework interpenetration has stabilized the framework in which the activated M'MOF-20a displays type-I N(2) gas sorption behavior with a Langmuir surface area of 62 m(2) g(-1). The narrow pores of about 3.9 Å and the open metal sites on the pore surfaces within M'MOF-20a collaboratively induce its highly selective C(2)H(2)/CH(4) and CO(2)/CH(4) gas separation at ambient temperature.


Insight into the characteristics of carbonaceous aerosols at urban and regional sites in the downwind area of Pearl River Delta region, China.
Carbonaceous aerosols (CAs) take up a substantial fraction of fine particle (PM2.5) in the atmosphere, yet high temporal resolution and seasonal variations of their emission sources and formation mechanisms are still poorly characterized in the regions with strong anthropogenic activities. In this study, the spatiotemporal characteristics of CAs and their subfractions, i.e., organic carbon (OC) and elemental carbon (EC), were studied in one of China's key city clusters, the Pearl River Delta (PRD) region. Results show that the annual mean OC and EC concentrations are 5.89 ± 3.32 μg/m3 and 1.60 ± 1.00 μg/m3 at the urban site, respectively. Such levels are consistently higher than those at the regional site (4.94 ± 3.34 μg/m3 of OC and 1.45 ± 0.82 μg/m3 of EC), suggesting the strong impact of human activities on OC and EC concentration. Moreover, the OC concentration peak sharply appears at 19:00 across all seasons at the urban site due to the direct influence of traffic exhaust and cooking activities. At regional site, OC peaks in fall afternoon due to intensive photochemical reactions derived combustion-related secondary organic carbon (SOCcom) contributions to the downwind PRD region. Correlations between SOCcom and influence factors were found at both regional and urban sites, suggesting that SOCcom formation is more regionally homogenous and mainly originates from the Zhaoqing-Foshan-Jiangmen belt. In addition, there are significantly different formation mechanisms of non-combustion-related secondary organic carbon (SOCnon-com) in the downwind PRD region. This study provides a solid evidence for collaborative efforts in the mitigation of secondary aerosols in the PRD region.


Long response to immune checkpoint inhibitors in metastatic NSCLC despite EGFR germline mutation. A case report.
First-line therapy in advanced non-small-cell-lung-cancer (NSCLC) is based on chemotherapy except for patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab is administrated. However, patients with somatic-EGFR-mutated tumors had usually been excluded from clinical applications of immune checkpoint inhibitors (ICIs). Germline-EGFR-mutated-patients are known to not respond to EGFR-Tyrosine-Kinase-inhibitors (TKIs). But what about germline EGFR mutations and response to ICIs? Herein, we describe the case of a long response to ICIs treatment in a complex metastatic NSCLC with co-occuring EGFR germline and KRAS somatic mutations, high PD-L1 score and a smoking history.


Impact of Demographics and Clinical Features on Initial Treatment Pathway for Vestibular Schwannoma.
To identify demographic and clinical features impacting initial treatment pathway for vestibular schwannoma. Retrospective chart review. Tertiary care academic medical center. Patients diagnosed with vestibular schwannoma between 2009 and 2019. Observation, stereotactic radiosurgery, or microsurgical resection. χ 2 Test, one-way analysis of variance, and multivariate logistic regression were used to correlate demographic and clinical factors with initial treatment pathway for 197 newly diagnosed vestibular schwannoma patients. Among 197 patients, 93 (47%) were initially treated with observation, 60 (30%) with stereotactic radiation (Gamma Knife) and 44 (22%) with surgical resection. Age univariately had no statistically significant impact on initial pathway, but those undergoing surgery trended toward a younger demographic (49.1 yr [surgery] versus 57.2 yr [observation] versus 59.0 yr [Gamma Knife]). Men were more likely to be initially observed than women ( p = 0.04). Patients initially observed were more likely to have a lower Koos classification ( p < 0.001) and have better tumor-ear hearing ( p = 0.03). Only 34.4% of patients living outside the local geographic region were initially observed compared with 53.0% living locally ( p = 0.055). Surgeon correlated with initial treatment ( p = 0.04) but did not maintain significance when adjusting for hearing level or tumor size. A multiple linear regression model found age, maximum tumor diameter, and Koos class to correlate with initial treatment pathway ( p < 0.0001, r2 = 0.42). Initial treatment pathway for newly diagnosed vestibular schwannoma is impacted by demographic factors such as age, sex, and geographic proximity to the medical center. Clinical features including hearing level and tumor size also correlated with initial treatment modality.


Spacer transfer RNAs in ribosomal RNA transcripts of E. coli: processing of 30S ribosomal RNA in vitro.
At least three different transfer RNAs are produced by in vitro processing of 30S ribosomal RNA which accumulates in RNAase III- strains of E. coli. Two of these tRNAs, tRNAGlu2 and tRNAIle1, have previously been shown to be "spacer tRNAs"--that is, genes for their synthesis are located in rRNA transcription units between the cistrons for 16S and 23S rRNAs (Lund et al., 1976). The third tRNA whose sequences are contained in 30S rRNA is tRNAAla1B. In addition to the tRNAs, 5S rRNA and several other 4S fragments are produced. Some of these 4S fragments may represent additional spacer tRNAs. One fragment, about 70 nucleotides long, arises from the 5' end of the 17S precursor of 16S rRNA. Four or five other tRNAs are hydrogen-bonded to 30S rRNA as we prepare it; one or more of these tRNAs may also be a spacer tRNA. The enzymes that process tRNAs out of 30S rRNA are associated with ribosomes, but can be removed from them by washing in 0.2 M NH4Cl; the enzymes required for 5S rRNA processing remain bound to the 0.2 M NH4Cl-washed ribosomes. Treatment of 30S rRNA with purified RNAase III produces 6-8S fragments which contain the sequences of tRNAGlu2, tRNAAla1B and 5S rRNA.


Comparison of metrizamide and iodophendylate for cerebral ventriculography: a long-term ultrastructural study of the ventricular wall in the rat.
Cerebral ventriculography was performed on adult albino rats to compare the effect of metrizamide and iodophendylate on the ependymal wall. The animals were killed by vascular perfusion 1 month and 4 months after ventriculography. The ependymal layer and the underlying brain tissue were examined with the electron microscope. After the use of metrizamide the tissue appeared completely normal. The use of iodophendylate provoked accumulation of phagocytozing macrophages on the ependymal wall and storage of iodophendylate in the ependyma and underlying brain tissue. These changes were present both 1 and 4 months after ventriculography.


Contamination by moulds of grape berries in Slovakia.
This paper describes the first map, albeit partial, of toxigenic fungi re-isolated from grape berries collected in three out of the six most important Slovakia winemaking areas in two different periods of the harvest year 2008. Low temperatures and high relative humidity during July 2008 favoured the development of grape fungal diseases that cause rots such as Plasmopara, Uncinula, Botrytis, Metasphaeria, Elsinoë, and Saccharomycetes. In the analysed samples, the following genera of toxigenic fungi were identified in the range of 1-4%: Aspergillus, Alternaria, Cladosporium, Epicoccum, Fusarium, Penicillium, Rhizopus, Ulocladium, and Trichoderma Trichothecium, while the genera Aspergillus, Alternaria, Fusarium, and Penicillium were in the range 11-29%. A. niger, A. carbonarius, some strains of A. carbonarius-with 'crystals' and strains of A. uvarum-uniseriate were identified; these species are considered ochratoxigenic (able to produce variable amounts of toxins). In addition, a non-ochratoxigenic strain of A. ibericus and a Fusarium strain able to biosynthesize small amount of fumonisins, beauvericin, and enniatins were identified. P. expansum, able to produce citrinin, represents 29.7%, of the Penicillium genus together with P. verrucosum, P. glabrum, P. citrinum, and P. crustosum. An analysis for the identification and quantification of the main toxins: ochratoxin A, fumonisins, beauvericin, enniatins, and fusaproliferin was performed on grape samples; it was consistent with the results of the mycological analysis. Toxigenic fungi should be checked throughout the years and their occurrence compared with all environmental factors to avoid health risks.


Clinical and pharmacoeconomic evaluation of antifungal prophylaxis with continuous micafungin in patients undergoing allogeneic stem cell transplantation: A six-year cohort analysis.
Patients undergoing allogeneic stem cell transplantation (aSCT) are at high risk to develop an invasive fungal disease (IFD). Optimisation of antifungal prophylaxis strategies may improve patient outcomes and reduce treatment costs. To analyse the clinical and economical impact of using continuous micafungin as antifungal prophylaxis. We performed a single-centre evaluation comparing patients who received either oral posaconazole with micafungin as intravenous bridging as required (POS-MIC) to patients who received only micafungin (MIC) as antifungal prophylaxis after aSCT. Epidemiological, clinical and direct treatment cost data extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut) were analysed. Three hundred and thirteen patients (97 and 216 patients in the POS-MIC and MIC groups, respectively) were included into the analysis. In the POS-MIC and MIC groups, median overall length of stay was 42 days (IQR: 35-52 days) vs 40 days (IQR: 35-49 days; p = .296), resulting in median overall costs of €42,964 (IQR: €35,040-€56,348) vs €43,291 (IQR: €37,281 vs €51,848; p = .993), respectively. Probable/proven IFD in the POS-MIC and MIC groups occurred in 5 patients (5%) vs 3 patients (1%; p = .051), respectively. The Kaplan-Meier analysis showed improved outcome of patients in the MIC group at day 100 (p = .037) and day 365 (p < .001) following aSCT. Our study results demonstrate improved outcomes in the MIC group compared with the POS-MIC group, which can in part be explained by a tendency towards less probable/proven IFD. Higher drug acquisition costs of micafungin did not translate into higher overall costs.


Satellite observations estimating the effects of river discharge and wind-driven upwelling on phytoplankton dynamics in the Chesapeake Bay.
Phytoplankton growth in estuaries is regulated by a complex combination of physical factors with freshwater discharge usually playing a dominating role controlling nutrient and light availability. The role of other factors, including upwelling-generating winds, is still unclear because most estuaries are too small for upwelling to emerge. In this study, we used remotely sensed proxies of phytoplankton biomass and concentration of suspended mineral particles to compare the effect of river discharge with the effect of upwelling events associated with persistent along-channel southerly winds in the Chesapeake Bay, a large estuary where upwelling and its effects on biogeochemical dynamics have been previously reported. The surface chlorophyll-a concentrations (Chl-a) were estimated from Visible Infrared Imaging Radiometer Suite (VIIRS) satellite data using the Generalized Stacked-Constraints Model (GSCM) corrected for seasonal effects by comparing remotely sensed and field-measured data. Light limitation of phytoplankton growth was assessed from the concentration of suspended mineral particles estimated from the remotely sensed backscattering at blue (443 nm) wavelength bbp (443). The nine-year time series (2012-2020) of Chl-a and bbp (443) confirmed that a primary factor regulating phytoplankton growth in this nearshore eutrophic area is discharge from the Susquehanna River, and presumably the nutrients it delivers, with a time lag up to four months. Persistent southerly wind events (2-3 days with wind speed >4 m/s) affected the water column stratification in the central part of the bay but did not result in significant increases in remotely sensed Chl-a. Analysis of model simulations of selected upwelling-favorable wind events revealed that strong southerly winds resulted in well-defined lateral (East-West) responses but were insufficient to deliver high-nutrient water to the surface layer to support phytoplankton bloom. We conclude that, in the Chesapeake Bay, which is a large, eutrophic estuary, wind-driven upwelling of deep water plays a limited role in driving phytoplankton growth under most conditions compared with river discharge. Integr Environ Assess Manag 2022;18:921-938. © 2022 SETAC.


Auricular Acupressure Therapy for Patients with Cancer with Sleep Disturbance: A Systematic Review and Meta-Analysis.
We aim to provide available synthesized evidence of the efficacy and safety of auricular acupressure for cancer patients with sleep disturbance. Randomized controlled clinical trials (RCTs) were identified from PubMed, EMBASE, Web of Science, The Cochrane Library, PsycINFO, Chinese Biomedical Database, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang Data, and the search date ranged from the inception of the databases to May 2021. Literature screening and data extraction were independently performed by three researchers. The Cochrane collaboration's tool for assessing the risk of bias was applied to evaluate the risk of bias of the RCTs included. The extracted data were analyzed using Rev-Man 5.4.1 software. Nine trials involving 688 participants met the inclusion criteria and were included in the qualitative analysis; 6 trials involving 485 participants were included in the meta-analysis. Synthesized results showed that auricular acupressure had a significant effect on reducing the total Pittsburgh Sleep Quality Index (PSQI) score (MD = -3.88, 95% CI (-5.24, -2.53), P < 0.00001), and the scores of five PSQI components, sleep latency (MD = -0.53, 95% CI (-0.73, -0.32), P < 0.00001), subjective sleep quality (MD = -0.79, 95% CI (-1.05, -0.53), P < 0.00001), sleep duration (MD = -0.50, 95% CI (-0.69, -0.31), P < 0.0001), daytime dysfunction (MD = -0.53, 95% CI (-0.77, -0.29), P < 0.0001), and sleep disturbances (MD = -0.54, 95% CI (-0.60, -0.49), P < 0.00001), were also obviously decreased after the intervention of auricular acupressure. Shenmen and heart were the most commonly selected auricular acupoints, the main intervention durations ranged from 10 to 42 days, and the pressing times of auricular acupoints were 1-6 times a day, 1-5 min each time. One trial reported slight and transient pain caused by auricular acupressure, while the remaining 8 trials did not report obvious side effects. Auricular acupressure can significantly improve the sleep quality of cancer patients with sleep disturbance, with no obvious side effects. Rigorously designed clinical trials are necessary for the further support of the clinical application.


Update on Osteosarcoma.
Osteosarcoma (OSA) is the most common primary tumor of bone, mainly affecting children and adolescents. Here we discuss recent advances in surgical and systemic therapies, and highlight potentially new modalities in preclinical evaluation and prognostication. The advent of neoadjuvant and adjuvant chemotherapy has markedly improved the disease-free recurrence and overall survival of OSA. However, treatment efficacy has been stagnant since the 1980s. This plateau has prompted preclinical and clinical research into in precision surgery, inhaled chemotherapy to increase pulmonary drug concentration without systemic side effects, and novel immunomodulators intended to block molecular pathways associated with OSA proliferation and metastasis. With the advent of novel surgical techniques and new forms and vectors for chemotherapy, it is hoped that OSA treatment outcomes will exceed their currently sustained plateau in the near future.


Alternative splicing of cAMP-specific phosphodiesterase mRNA transcripts. Characterization of a novel tissue-specific isoform, RNPDE4A8.
In order to characterize the structure and regulation of members of the cAMP-specific phosphodiesterase (PDE) family (Type IV PDEs; PDE4 family), we have cloned from the rat a cDNA, pRPDE39, encoding a novel member of this family, which we call RNPDE4A8. Sequencing of the pRPDE39 cDNA shows it to be encoded by the rat PDE4A gene, but to differ from two other PDE4A transcripts, RD1 (pRPDE8; RNPDE4A1) and pRPDE6 (RNPDE4A5), by the presence of a unique region at its 5' end, consistent with alternative mRNA splicing. The pRPDE39 cDNA encodes a predicted protein of 763 amino acids, of which all but 21, located at the extreme amino terminus, are found in the pRPDE6 protein. Expression of pRPDE39 in COS cells produced a protein of 98 +/- 1.4 kDa, as determined by immunoblotting with an antiserum specific to the carboxyl-terminal regions of all PDE4A proteins, compared to a predicted value of 87.5 kDa. RNase protection analysis detected pRPDE39 mRNA only in testis. Immunoblotting of testis extracts demonstrated two bands of 97 +/- 2 and 87 +/- 3 kDa, the larger of which co-migrated with the band seen in COS cells expressing pRPDE39. COS cell expressed pRPDE39 partitioned between a high speed pellet (particulate) fraction (15% of protein; 8% of activity) and a cytosolic fraction. The particulate fraction had a Km for cAMP of 3.3 +/- 0.6 microM, and the cytosolic fraction a Km of 5.4 +/- 2.8 microM. The Vmax values for the pRPDE39 protein, relative to the RD1 protein, were 0.16 +/- 0.06 and 0.29 +/- 0.05 for the particulate and cytosolic forms, respectively. The pRPDE39-encoded PDE activity could not be removed from the particulate fraction by high salt concentrations, or by nonionic detergents. The pRPDE39-encoded enzyme was inhibited by rolipram at an IC50 of 0.5 +/- 0.2 microM for the particulate form and 1.0 +/- 0.2 microM for the cytosolic form, which are values typical of PDE4 family members. The highly tissue-specific distribution of the pRPDE39 mRNA suggest that the pRPDE39 protein functions to modulate a cAMP signaling pathway that is present largely, if not exclusively, in the testis.


Applicability of various estimation formulas to assess renal function in Chinese children.
This study was to evaluate the relative applicability of the most commonly used estimation formulas for renal glomerular filtration rate (GFR) of Chinese children with chronic kidney disease (CKD). One hundred CKD patients of less than 17 years old were divided into two groups by sex which was further categorized into five subgroups based on CKD staging according to the "reference" GFR (rGFR) determined by Tc-99m-DTPA renal dynamic imaging. Four GFR markers including serum cystatin C (CysC), β2-microglobulin, creatinine, and blood urea nitrogen were measured. Among all four markers, CysC best reflected the extent of glomerular damages for CKD stage 1. The value for estimation of GFR (eGFR) was derived from five different formulas either over-estimated or underestimated GFR as referenced to rGFR, and the extent of deviations was dependent on gender, age and CKD stage. The Counahan-Barratt formula and the Schwartz formula gave the most accurate estimations of GFR for CKD stages 1 and 2-3, respectively regardless of gender and age differences. Receiver operating characteristic analyses indicated that the Counahan-Barratt formula has the highest diagnostic accuracy. The Counahan-Barratt formula provides the best approximation to rGFR, thereby the highest applicability to Chinese children with CKD of different genders, ages and CKD stages.


Emergency non-ruptured abdominal aortic aneurysm.
To investigate symptoms and early mortality (<30 days) following open surgery for emergency, symptomatic non-ruptured abdominal aortic aneurysm (AAA). Retrospective cohort study. During the period 1983-1994, 129 patients had an emergency admission, followed by surgery, for symptomatic non-ruptured AAA. Sixty-one received surgery within 24 h of admission and 68 received surgery more than 24 h after admission (median 135 h, inter-quartile range: 51-239 h). During the same period 239 patients had elective surgery for non-ruptured AAA. Early mortality (<30 days), symptoms and co-morbidities were recorded. Data were retrieved from the patient records. Mortality (30 days) was 18% in the 61 patients having surgery within 24 h of emergency admission for non-ruptured AAA. Mortality following either delayed surgery (semi-elective) after emergency admission or elective surgery was 4.2% (p=0.0002). Four out of 11 patients who died within 30 days following an acute operation had previously been declared unfit for elective surgery. One additional emergency patient had been found unfit for open surgery, but survived a delayed operation. The high mortality rate of patients with non-ruptured, symptomatic AAA undergoing surgery within 24 h of admission appears to be influenced by several factors, including co-morbidities and the acute operation. We propose that the 30-day mortality for non-ruptured AAA should be reported in two categories: mortality rate for elective surgery and mortality for surgery performed within 24 h of emergency admission. The term 'emergency non-ruptured' is a suitable term for the latter group.


Influences of γ-ray irradiation on physico-chemical, structural, X-ray diffraction, thermal and antimicrobial activity of some γ-irradiated N',N'''-((Z)-ethane-1,2-diylidine)bis(2-aminobenzohydrazide) metal complexes.
A series of Co(II), Ni(II), Cu(II), Th(IV) and UO2(II) complexes have been synthesized from reaction of nitrogen based ligand (L) i.e. N',N'''-((Z)-ethane-1,2-diylidine)bis(2-aminobenzohydrazide)(L) with their salts. Investigation of synthesized metal complexes was achieved by using elemental analyses, magnetic moment, molar conductance, FT-IR, UV/Vis. spectroscopy, thermal techniques and 3D molecular modeling. An octahedral geometry has been suggested for all complexes except for Ni(II) complex (2) which adopted tetrahedral geometry. To through a light on the probability of structure changes with γ-irradiation, the effect of gamma irradiation on powder samples of the complexes [Co(L)Cl2].4H2O (1); [Ni2(L)(OAc)4].5H2O (2) and [Cu(L)Br2].5H2O (3) was investigated after being exposed to high energetic γ-rays at 100 kGy dose (hereafter referred to as (1A,2A,3A, respectively). Spectral, thermal, magnetic susceptibility, molar conductance and powder X-ray diffraction patterns (XRD) were performed before and after irradiation. In addition, the in vitro antimicrobial activity of the complexes against Staphylococcus aureus as Gram-positive strain, Escherichia coli as Gram-negative strain and antifungal Candida albicans was performed for both unirradiated and irradiated samples. The obtained results showed that the irradiated complexes were affected, but not greatly by the applied γ-irradiation dose.


Identifying the palliative care role of the nurse working in community hospitals: an exploratory study.
to ascertain registered nurses' and GPs' perceptions of and influences on the nurse's role in providing palliative care in community hospitals. qualitative exploratory/descriptive study. two community hospital sites within Perth and Kinross, Scotland. taped semi-structured interviews with four registered nurses and two GPs. Participants' perceptions were sought on the roles of nursing and medical professionals and of factors facilitating and hindering the provision of palliative care within the community hospital setting. six key themes were identified through thematic analysis of the information: communication, teamwork and relationships, holistic care, resources, culture, professional role. the themes were inter-related and gave valuable insight into the multidimensional nature and significance of the nurse's role in palliative care in the community hospital setting.


Targeting the dysregulated mammalian target of rapamycin pathway in organ transplantation: killing 2 birds with 1 stone.
Dysregulation and hyperactivation of the mammalian target of rapamycin (mTOR) pathway define the molecular basis of the hamartoma syndromes, including Cowden syndrome, tuberous sclerosis complex (TSC)/lymphangioleiomyomatosis, and Peutz-Jeghers syndrome. Loss of the tumor suppressors phosphatase and tensin homolog (PTEN), TSC1, TSC2, and LKB1 results in uncontrolled growth of usually benign tumors in various organs that, however, frequently lead to organ failure. Therefore, organ transplantation is a common therapeutic option in distinct patients with hamartoma syndromes, especially those with TSC/lymphangioleiomyomatosis. mTOR inhibitors are currently used in allogeneic transplantation as immunosuppressants and for the treatment of a growing number of cancers with dysregulated mTOR/phosphoinositide 3-kinase pathway. This dual targeting provides the unique opportunity for mTOR inhibitors to affect hamartoma syndromes at the molecular level along with potent immunosuppression in transplanted individuals. Here, we review the molecular mechanisms of hamartoma syndromes and discuss the recent clinical progress in transplant patients with hamartomas. Combining the identification of novel molecular targets of the phosphoinositide 3-kinase/mTOR pathway with insights into the clinical effectiveness of current therapeutic strategies sets the stage for a broader translational potential essential for further progress both in the treatment of cancer and for transplantation.


Genitoplasty for congenital adrenal hyperplasia: anatomy and technical review.
There is variable virilisation in female pseudohermaphrodities with congenital adrenal hyperplasia, but they always have normal ovaries, uterus and upper part of the vagina. The various anatomical stages of virilisation are outlined and a historical review is given. For psychological and practical reasons it is generally accepted that the operation should be performed when the patient is between 6 and 18 months of age. The aim is to reduce the size of the clitoris and to expose the vagina so that it opens onto the perineum. Operative procedures are described. The child is reviewed at intervals to determine the size and shape of the vagina and clitoris. Adjustments can be made around the time of puberty but are rarely necessary.


Oxidative stress assessment and its relationship with the prevalence of atherogenic risk in patients with type 2 diabetes.
During diabetes, prolonged hyperglycemia is characterized by the generation of free radicals via multiple mechanisms leading to various diabetic complications including cardiovascular diseases. This study aims to determine the relationship between a deregulation of the oxidative state in type 2 diabetes patients and the prevalence of atheroma plate formation. This research was carried out at the Bouguerra Boulaares hospital and Alia Salah hospital in Tebessa, Algeria, on 560 patients with type 2 diabetes (300 women and 260 men), compared with 100 normal subjects (50 women and 50 men). For all subjects the following parameters were estimated: blood pressure, BMI (body mass index), glucose, glycated hemoglobin, total cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides, Creatinine, serum redox status indicators (GSH, GPx, GSTs, and MDA) and a complete blood count was performed. The findings of this study indicated a slight increase in arterial pressure in 336 diabetic patients (60%) with an HbA1c level between 7 and 9% (210 patients) and > 9% (126 patients); while the flow of the glomerular filtration remained within the norms for all the studied subjects. Patients showed an increase in blood glucose levels, disturbance of the lipid parameters with an increase in lipid peroxidation and a decrease in serum and erythrocyte antioxidant defense. It can be concluded that the formation of atheroma plate in diabetics is caused by the oxidation of circulating lipoproteins by free radicals generated following hyperglycemia, which can be avoided by supplementing antioxidant molecules such as antioxidant vitamins, trace elements.


CO2 reforming of methane to syngas over multi-walled carbon nanotube supported Ni-Ce nanoparticles: effect of different synthesis methods.
Several multi-walled carbon nanotubes supported Ni-Ce catalysts were synthesized, and their performance in carbon dioxide reforming of methane (CDRM) for syngas production was evaluated. The attachment of Ni-Ce nanoparticles to the functionalized carbon nanotube (fCNT) support was carried out using four synthesis routes, i.e., impregnation (I), sol-gel (S), co-precipitation (C), and hydrothermal (H) methods. Results indicated that synthesis method influences the properties of the NiCe/fCNT catalysts in terms of homogeneity of metal dispersion, size of crystallites, and metal-support interaction. The activity of the catalysts followed the order of NiCe/fCNT(H) > NiCe/fCNT(S) > NiCe/fCNT(C) > NiCe/fCNT(I). The NiCe/fCNT(H) catalyst exhibited the highest catalytic activity with CH4 and CO2 conversions of 92 and 96%, respectively, and resulted in syngas product with consistent H2/CO ratio of 0.91 at reaction temperature of 800 °C without notable deactivation up to 30 h of reaction. Moreover, the growth of carbon on the spent catalyst was only 2% with deposition rate of 4.08 mg/gcat·h; this was plausibly due to the well-dispersed distribution of nanoparticles on fCNT surface and abundant presence of oxygenated groups on the catalyst surface.


Identification and in silico functional prediction of lineage-specific SNPs distributed in DosR-related proteins and resuscitation-promoting factor proteins of Mycobacterium tuberculosis.
One-third of the world population is infected by Mycobacterium tuberculosis, which may persist in the latent or dormant state. Bacteria can shift to dormancy when encountering harsh conditions such as low oxygen, nutrient starvation, high acidity and host immune defenses. Genes related to the dormancy survival regulator (DosR) regulon are responsible for the inhibition of aerobic respiration and replication, which is required to enter dormancy. Conversely, resuscitation-promoting factor (rpf) proteins participate in reactivation from dormancy and the development of active tuberculosis (TB). Many DosR regulon and rpf proteins are immunodominant T cell antigens that are highly expressed in latent TB infection. They could serve as TB vaccine candidates and be used for diagnostic development. We explored the genetic polymorphisms of 50 DosR-related genes and 5 rpf genes among 1,170 previously sequenced clinical M. tuberculosis genomes. Forty-three lineage- or sublineage-specific nonsynonymous single nucleotide polymorphisms (nsSNPs) were identified. Ten nsSNPs were specific to all Mtb isolates belonging to lineage 1 (L1). Two common sublineages, the Beijing family (L2.2) and EAI2 (L1.2.1), differed at as many as 26 lineage- or sublineage-specific SNPs. DosR regulon genes related to membrane proteins and the rpf family possessed mean dN/dS ratios greater than one, suggesting that they are under positive selection. Although the T cell epitope regions of DosR-related and rpf antigens were quite conserved, we found that the epitopes in L1 had higher rates of genetic polymorphisms than the other lineages. Some mutations in immunogenic epitopes of the antigens were specific to particular M. tuberculosis lineages. Therefore, the genetic diversity of the DosR regulon and rpf proteins might impact the adaptation of M. tuberculosis to the dormant state and the immunogenicity of latency antigens, which warrants further investigation.


Knockdown of lncRNA RMST protect against myocardial infarction through regulating miR-5692 and MAGI3 axis.
Myocardial infarction is the leading cause of death worldwide. The aim of this study was to investigate the function and mechanism of lncRNA RMST in myocardial infarction. H/R and H2O2 models were established to assess the function of lncRNA RMST in vitro. Mouse myocardial infarction was used to analyze the function of lncRNA RMST in vivo. Bioinformatics analysis was performed to predict the potential binding target of lncRNA RMST. Rescue experiments were performed to verify the relationship between RMST and its target. The expression of lncRNA RMST was significantly increased with H/R or H2O2 treatment. Knockdown of lncRNA RMST improved cell death and protected mitochondria from H/R injury in vitro. In vivo, cardiac function was significantly attenuated by knockdown of lncRNA RMST. We also provided evidence that miR-5692 was a direct target of lncRNA RMST. Rescue experiments showed that knockdown of miR-5692 could restore the function of RMST. Our study is the first to prove the function and mechanism of lncRNA RMST in myocardial infarction. Thus, a deeper understanding of the role of lncRNA RMST in myocardial infarction may provide new insights for the clinical intervention of MI.


Results of short term radiotherapy followed by radical surgery for rectal cancer: A long-term unicenter observational study.
Short-term radiotherapy (STR) for rectal cancer (RC) has rarely been used in Spain. The aim of the present study is to describe oncological results after RTC and surgery for RC. This is a retrospective analysis of a consecutive series of patients treated with STR and surgery for RC (1999-2012). Epidemiological data, staging, complications of STR, STR-surgery interval, surgical approach, rate of anastomotic/perineal wound dehiscence, and pathological data (regression degree and staging) were collected. Global survival, disease free survival, local recurrence rate and incidence of toxicity, response and complications of combined treatment are reported. Of 1229 patients treated, 209 patients received STR and surgery. The median follow-up was 6.2 years. Mean age was 68 years and 66% of the patients were men. A total of 88% were cT3-4 and 44% cN+17 (8.1%) patients had resectable synchronous metastases. Acute and chronic toxicity due to STR was <5%. In 75% of the cases the STR-surgery interval was <15 days, and in 9%> 4 weeks. Seven patients (3.3%) presented complete response. Nine (4.3%) patients presented an local recurrence rate. Global survival at 5, 10 and 15 years was 67.8, 49.2 and 37.5%, respectively. Disease free survival at 5, 10 and 15 years was 66.1, 47.1 and 33%, respectively. The results compare favorably with multicentric historical series. STR offers certain advantages that could be increased by increasing the STR-surgery interval and/or interspersed with sequential chemotherapy.


Geriatric conditions, medication use, and risk of adverse drug events in a predominantly male, older veteran population.
To determine whether geriatric conditions and functional impairment are independent risk factors for adverse drug events (ADEs). Prospective cohort study. Veterans Affairs Medical Center. Three hundred seventy-seven veterans aged 65 and older and taking five or more medications. Geriatric conditions and functional status were assessed using participant interviews and structured assessments at study baseline. ADEs were elicited during participant interviews 3 and 12 months after study enrollment using validated methods. The strong majority (97%) of participants were male, with a mean age of 74 ± 5; 123 (33%) had one or more dependencies in instrumental activities of daily living (IADLs). Over the 1-year study period, 126 participants (33%) developed 167 ADEs. Upon multivariable analysis, risk of ADEs was not associated with any of the geriatric conditions that there was sufficient power to evaluate, including IADL function, cognitive impairment, depression, visual impairment, incontinence, constipation, and a summative measure of geriatric burden comprising the above and history of falls or gait instability. In exploratory analyses, the strongest factor associated with ADEs was the number of drugs added to a participant's medication regimen during the 1-year study period (incidence rate ratio 1.11 per each added drug, 95% confidence interval=1.03-1.19). Common geriatric conditions and IADL function were not associated with ADEs in a predominantly male, older veteran population. Although it is important to consider the unique circumstances of each participant, excessive caution in prescribing to older adults with these geriatric conditions may not be warranted.


A new pathway for considering trigger factors based on parallel-serial connection models and displaying the relationships of causal factors in low-probability events.
To determine the effect size of observed factors considering trigger factors based on parallel-serial models and to explore how multiple factors can be related to the result of complex events for low-probability events with binary outcomes. A low-probability event with a true binary outcome can be explained by a trigger factor. The models were based on the parallel-serial connection of switches; causal factors, including trigger factors, were simplified as switches. Effect size values of an observed factor for an outcome were calculated as SAR = (Pe-Pn)/(Pe + Pn), where Pe and Pn represent percentages in the exposed and nonexposed groups, respectively, and SAR represents standardized absolute risk. The influence of trigger factors is eliminated by SAR. Actual data were collected to obtain a deeper understanding of the system. SAR values of < 0.25, 0.25-0.50, and > 0.50 indicate low, medium, and high effect sizes, respectively. The system of data visualization based on the parallel-serial connection model revealed that at least 7 predictors with SAR > 0.50, including a trigger factor, were needed to predict schizophrenia. The SAR of the HLADQB1*03 gene was 0.22 for schizophrenia. It is likely that the trigger factors and observed factors had a cumulative effect, as indicated by the parallel-serial connection model for binary outcomes. SAR may allow better evaluation of the effect size of a factor in complex events by eliminating the influence of trigger factors. The efficiency and efficacy of observational research could be increased if we are able to clarify how multiple factors can be related to a result in a pragmatic manner.


Invasive ductal carcinoma arising in phyllodes tumor with isolated tumor cells in sentinel lymph node.
Phyllodes tumor (PT) consists of stroma of variable grading and benign ductal epithelium. Although exceptional, carcinomas that arise from the epithelium in PTs do exist, and seem to behave less aggressively than the usually encountered breast carcinoma. To the best of our knowledge, among the invasive carcinomas that have arisen in PTs, only 1 has been proved to have metastatic carcinoma in the lymph nodes. Here, we describe the youngest woman to have invasive ductal carcinoma that arose in a borderline PT, with isolated carcinoma cells in the sentinel lymph node. Whether such a combined lesion carries a more indolent course is also discussed.


The analytical determination of isoprenoid intermediates from the mevalonate pathway.
In this article, assays on the analytical determination of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), two important isoprenoid intermediates at biochemically relevant branching points in the mevalonate pathway, are summarized and reviewed. There is considerable recent interest in the measurement of these two isoprenoids because of their direct involvement in several diseases, for example, statins lower cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase but equally affect other metabolite biosyntheses. The isoprenoids FPP and GGPP are key intermediates due to their role as CaaX-specific substrates for posttranslational modification of proteins (protein prenylation). Disease pathologies and therapeutic efficacy of different treatments (e.g., cholesterol-lowering drugs) may lead to a reduction in isoprenoid levels and an accompanying reduction in prenylation of specific proteins. To understand the exact biochemical role of the isoprenoids FPP and GGPP, we need to know their levels. Several recent studies have shown exact levels of FPP and GGP in plasma and relevant tissues and their modulation following treatment. Furthermore, by directly measuring the extent of protein prenylation and identifying target proteins, further insight into the exact biochemical nature of the pathology and regulatory mechanisms will be possible. This short review aims to highlight the relevant literature on the analytical determination of the free isoprenoids FPP and GGPP in biological tissue as well as techniques for directly measuring prenylated proteins.


Evaluation of the role and usefulness of clinical pharmacists at the Fangcang Hospital during COVID-19 outbreak.
Fangcang Hospitals (cabin hospitals) played a key role in isolation and control of the infection sources during COVID-19 epidemic. Many patients at Fangcang Hospitals had complications or mental stress. As the doctors, nurses and paramedics presented in the emergency, there was a growing demand for clinical pharmacists to provide pharmaceutical care for the affected patients with chronic diseases via telemedicine. This study was a retrospective study to evaluate the usefulness of clinical prevention and control measures of clinical pharmacists at Jianghan Fangcang Hospital. Besides, this study proposed innovative strategies for developing pharmacy services to ensure the medication compliance, accuracy and cure rates under the epidemic. A total of 374 patients filled in the questionnaires and 349 patients were enrolled in this study. Patients who refused to receive pharmaceutical care were not included in this study. The pharmaceutical care included medication education via broadcast station, medication reconciliation, optimisation of drug use, monitor of adverse drug events and psychological comfort via WeChat one-to-one service. The data were collected from patients' interviews and the questionnaires of inpatients and discharged patients. In Jianghan Fangcang Hospital, many patients had complications with hypertension (12.9%), hyperlipidaemia (9.2%), thyroid disease (8.9%), diabetes (7.2%), heart disease (3.4%), nephropathy (1.7%), cancer (1.1%) and other diseases (12.6%). After 35 days' pharmacy service, about 200 different questions had been solved by our clinical pharmacists, including drug usage (65.38%), medication reconciliation (55.13%), drug precautions (23.1%), adverse drug reactions (35.9%) and psychological counselling (32.05%). Most patients were satisfied with clinical pharmacist service (66.7% great, 18.0% good). The results of the retrospective study indicated that clinical pharmacist can effectively reduce and prevent drug-related, life-related and COVID-19-related problems for COVID-19 patients, which is important for the disease recovery. This study also demonstrated that clinical pharmacist played a key role for patients' healthcare during the pandemic.


Trajectories of illness in stage 5 chronic kidney disease: a longitudinal study of patient symptoms and concerns in the last year of life.
The illness trajectory in the last year of life in advanced (stage 5) chronic kidney disease is poorly understood. Mapping the trajectory of patient-centered outcomes could facilitate better care. The objectives of this study were to determine trajectories of symptoms and wider health-related concerns in the last year of life in stage 5 chronic kidney disease, managed without dialysis. A longitudinal symptom survey in three UK renal units was used, using the Memorial Symptom Assessment Scale-Short Form and core Palliative Care Outcome Scale. Average (using mean scores over time) and individual (using individual scores over time, with visual graphical analysis) trajectories were mapped. Seventy-four patients (mean age, 81 ± 6.8 years) were recruited; 49 died during follow-up. Average trajectories showed moderate symptom distress and health-related concerns, with marked increase in the last 2 months of life. Visual graphical analysis enabled stable, increasing, or fluctuant individual trajectories to be identified. The proportion following these trajectories varied between outcome measures; regarding symptoms, 50% followed a stable pattern, 24% increased, and 21% fluctuated compared with 26%, 57%, and 21%, respectively, for health-related concerns. Inter-rater agreement in grouping trajectories was high (κ statistic, 0.80 and 0.86, respectively). In the 2 months before death, patients reported a sharp increase in symptom distress and health-related concerns. Health care should anticipate and address this increase, which may indicate the patients is approaching death. Considerable individual variation and flexibility/responsiveness of care is important: one size of service does not fit all.


Hemoglobin A(1c) proportion, mortality rate, and risk factors for death in diabetic patients with severe hypoglycemia: a multicenter retrospective survey over ten years.
To investigate the HbA(1c) proportion and mortality rate across diabetic patients with severe hypoglycemia and the risk factors for death. All the diabetic patients with severe hypoglycemia were divided into HbA(1c)<6.5% group and HbA(1c)≥6.5% group. The proportion of HbA(1c), mortality rate and the risk factors for death were analyzed. Common causes for severe hypoglycemia were also analyzed. The percentages of HbA(1c) in the HbA(1c)<6.5% and HbA(1c)≥6.5% groups were 51.2% and 48.8%, respectively. The mortality rates were not significantly different between the 2 groups (5.3% vs. 5.1%, χ(2)=0.01, p=0.17). Binary logistic regression analysis revealed that in both groups, creatinine, aspartate aminotransferase, and uric acid levels were the risk factors for death. In the HbA(1c)<6.5% and HbA(1c)≥6.5% groups, 65.0% and 64.2% showed common causes of severe hypoglycemia, respectively. With respect to severe hypoglycemia, equal attention should be paid to patients with an HbA(1c) level of ≥6.5% and those with an HbA(1c) level of <6.5%. The mortality rate is approximately 5% in severe hypoglycemia no matter how the HbA(1c) level is. Creatinine, aspartate aminotransferase, and uric acid are the main risk factors in both groups. Two-thirds of severe hypoglycemia cases could be prevented.


Comparison of clinical characteristics of combined hepatocellular-cholangiocarcinoma and other primary liver cancers.
Combined hepatocellular-cholangiocarcinoma (CHC) is a rare liver malignancy. In this study, we compared patient characteristics and outcomes for primary CHC, intrahepatic cholangiocarcinoma (ICC), and hepatocellular carcinoma (HCC). Medical records of patients with tissue-proven CHC (65 cases) treated at the Chang Gung Memorial Hospital between 1991 and 2005 were retrospectively reviewed. These records were compared to records of patients diagnosed with tissue-proven HCC (1985 cases) and ICC (127 cases) during the same period. Hepatitis B and C are major causes of CHC. CHC patients exhibited greater similarity to HCC than to ICC patients with respect to cirrhotic changes, age, and positive serology for hepatitis B surface antigen and anti-hepatitis C antibody. Survival was related to tumor characteristics and intervention therapies, but not to etiologies. The clinical characteristics of CHC are similar to those of HCC, but overall survival is more similar to that of ICC; survival may be related to tumor biology rather than the cause. Multimodal treatment with an initial aggressive therapeutic approach can improve survival.


Study of the peripheral and central auditory pathways in patients with mucopolysaccharidosis.
To investigate the peripheral and central auditory pathways in mucopolysaccharidosis (MPS) individuals. The research sample comprised 15 individuals (one female and 14 males), aged 8 to 46 years. The following procedures were used: medical history survey, otoscopy, speech and pure-tone threshold audiometry, acoustic immittance measures, and central auditory pathway assessment with brainstem auditory evoked potentials (BAEP) and long-latency auditory evoked potentials (LLAEP). The pure-tone audiometry identified hearing loss in 13 individuals, and more than 90 % of the hearing loss was sensorineural. The degree of hearing loss was between mild to moderately severe with descendent configuration. Type A tympanogram predominated, and acoustic reflexes were present according to the types and degrees of hearing loss. Among the individuals with abnormal BAEP, longer wave III and V absolute latencies were the main findings. In addition, the unilateral absence of wave I was observed in two cases. In the LLAEP, longer latencies were observed in 14 individuals, and the most impaired components were the P1 and P3 in children and adolescents and the P2, N2 and P3 in adult individuals. The peripheral auditory pathway assessment revealed a predominantly sensorineural hearing loss, affecting mainly high frequencies, and in the central pathway was observed abnormal brainstem and cortical auditory processing in individuals with MPS.


Crystallographic characterization of a Cu,Zn superoxide dismutase from Photobacterium leiognathi.
Crystals of a copper-zinc superoxide dismutase from Photobacterium leiognathi, a luminescent marine bacterium that is the species-specific symbiont of the ponyfish, have been obtained from 2-methyl-2,4-pentanediol solutions. The space group was determined using screenless small-angle precession photographs, and was confirmed by analyzing area detector diffraction data with the XENGEN programs for indexing and refinement. The crystals are monoclinic, space group C2 (a = 126.4 A, b = 87.0 A, c = 44.4 A, beta = 92.8 A), and have two 32,000 Mr dimers per asymmetric unit. The crystals diffract to at least 2.7 A resolution, are resistant to radiation damage, and are suitable for determination of the structure by X-ray diffraction.


Comparison of Mechanical Properties of Hemp-Fibre Biocomposites Fabricated with Biobased and Regular Epoxy Resins.
Bio- and green composites are mainly used in non-structural automotive elements like interior panels and vehicle underpanels. Currently, the use of biocomposites as a worthy alternative to glass fibre-reinforced plastics (GFRPs) in structural applications still needs to be fully evaluated. In the current study, the development of a suited biocomposites started with a thorough review of the available raw materials, including both reinforcement fibres and matrix materials. Based on its specific properties, hemp appeared to be a very suitable fibre. A similar analysis was conducted for the commercially available biobased matrix materials. Greenpoxy 55 (with a biocontent of 55%) and Super Sap 100 (with a biocontent of 37%) were selected and compared with a standard epoxy resin. Tensile and three-point bending tests were conducted to characterise the hemp-based biocomposite.


Carcinoma erysipeloides.
We report an 83-year-old woman with carcinoma erysipeloides due to an occult carcinoma. Immunohistochemical study of skin biopsies showed reactivity to S-100 protein and human milk fat globule antigen indicating that the tumour originated in the breast.


Switch-like control of helicase processivity by single-stranded DNA binding protein.
Helicases utilize nucleotide triphosphate (NTP) hydrolysis to translocate along single-stranded nucleic acids (NA) and unwind the duplex. In the cell, helicases function in the context of other NA-associated proteins such as single-stranded DNA binding proteins. Such encounters regulate helicase function, although the underlying mechanisms remain largely unknown. Ferroplasma acidarmanus xeroderma pigmentosum group D (XPD) helicase serves as a model for understanding the molecular mechanisms of superfamily 2B helicases, and its activity is enhanced by the cognate single-stranded DNA binding protein replication protein A 2 (RPA2). Here, optical trap measurements of the unwinding activity of a single XPD helicase in the presence of RPA2 reveal a mechanism in which XPD interconverts between two states with different processivities and transient RPA2 interactions stabilize the more processive state, activating a latent 'processivity switch' in XPD. A point mutation at a regulatory DNA binding site on XPD similarly activates this switch. These findings provide new insights on mechanisms of helicase regulation by accessory proteins.


The presence of semicarbazide in crustaceans collected from natural habitats in Thailand.
Semicarbazide (SEM) has been used as a marker residue of the banned veterinary drug nitrofurazone (NFZ). Although evidence indicates that SEM can be found in some natural crustaceans that have never been exposed to NFZ, such information is limited to a few species. The present study aimed to investigate the natural occurrence of SEM in wild crustaceans in Thailand. A total of 14 species, all economically important food animals, were captured from different regions of Thailand. Tissue-bound SEM and its parent drug NFZ were determined by the UPLC-MS/MS and LC-MS methods, respectively. The results showed that while NFZ was not detected in any samples, the tissue-bound SEM could be found in every natural crustacean species investigated. However, the prevalence and concentration varied greatly. The occurrence of SEM in the freshwater palaemonid Macrobrachium prawns is generally much higher than in the marine penaeid shrimps/prawns. SEM was found in 33% and 80% of the giant river prawn (Macrobrachium rosenbergii) muscles (<0.10-0.46 ng/g) and shells (3.68-13.22 ng/g), respectively. In contrast, SEM was not detected in the muscles of penaeid shrimps/prawns (with few exceptions), but it was occasionally found in the shells at low levels (usually <1 ng/g). The shells of saltwater crabs also contained higher levels of SEM than the muscles. For instance, the highest SEM levels detected in the mud crab (Scylla sp.) muscles and shells were 0.40 and 22.75 ng/g, respectively. However, the situation was reversed for the rice-field crab (Sayamia sp. and Esanthelphusa sp.), in which SEM was not detected in all shells but detected in the muscles (up to 1.46 ng/g). The fact that SEM is often found in wild crustaceans implies a natural origin of this substance. Consequently, using SEM as a marker residue of NFZ is controversial and should be reconsidered.


Association of circular RNAs and environmental risk factors with coronary heart disease.
Coronary heart disease (CHD) is a complex disease caused by multi-factors and a major threat to human health. Circular RNAs (circRNAs) have critical roles in various biological processes and diseases. This study explores the independent role of circRNAs and their interaction with environmental factors in CHD. A case-control study was conducted from March 2015 to September 2017 in Fuzhou, China. A total of 585 CHD patients and 585 gender- and age-matched healthy controls were enrolled. Questionnaire survey, health examination and molecular biology laboratory testing were conducted. Microarray technology and quantitative real-time polymerase chain reaction (PCR) were used to profile the expression levels of circRNAs. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to determine the diagnostic cut-offs. Multivariate logistic regression and multiplicative analysis were used to analyse the effects of environmental factors and hsa_circ_0008507, hsa_circ_0001946, hsa_circ_0000284 and hsa_circ_0125589 on CHD. The expression profile of circRNAs showed that 3423 circRNAs were differentially expressed at P < 0.05, but none pass multiple testing correction. qRT-PCR further confirmed the expression levels of hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 in peripheral blood leukocytes in CHD cases were higher than those in non-CHD subjects (All p < 0.05). Hsa_circ_0008507 (OR = 1.29; 95% CI: 1.11-1.50), hsa_circ_0001946 (OR = 1.20; 95% CI: 1.01-1.42) and hsa_circ_0000284 (OR = 2.05; 95% CI: 1.32-3.19) were independent risk factors for CHD after controlling other common environmental risk factors. The AUC for hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 was 0.75, 0.71 and 0.68, respectively. Compared with non-smoking individuals with low hsa_circ_0008507 expression, the smokers with high hsa_circ_0008507 expression showed the highest magnitude of OR in CHD risk. Additionally, a statistically significant multiplicative interaction was found between hsa_circ_0008507 and smoking for CHD. Hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 were closely related to the occurrence and development of CHD. The combination of smoking and high hsa_circ_0008507 expression causes the occurrence and development of CHD.


Cancer GAMAdb: database of cancer genetic associations from meta-analyses and genome-wide association studies.
In the field of cancer, genetic association studies are among the most active and well-funded research areas, and have produced hundreds of genetic associations, especially in the genome-wide association studies (GWAS) era. Knowledge synthesis of these discoveries is the first critical step in translating the rapidly emerging data from cancer genetic association research into potential applications for clinical practice. To facilitate the effort of translational research on cancer genetics, we have developed a continually updated database named Cancer Genome-wide Association and Meta Analyses database that contains key descriptive characteristics of each genetic association extracted from published GWAS and meta-analyses relevant to cancer risk. Here we describe the design and development of this tool with the aim of aiding the cancer research community to quickly obtain the current updated status in cancer genetic association studies.


The apparent digestibility of fibre in trotters when dietary soybean oil is substituted for an iso-energetic amount of glucose.
An attempt was made to quantify the effect of extra fat intake on fibre utilization in horses. In a 4 x 4 cross-over trial with feeding periods of 24 days each, eight mature trotting horses (age 4 to 12 years, 407 to 531 kg BW) were given four diets. The concentrates were formulated to contain either soybean oil or an iso-energetic amount of glucose or combinations of the two ingredients. The concentrates were fed in combination with the same amount of hay so that the whole diets contained 30, 50, 77 or 108 g EE/kg DM. Apart from the amounts of fat and glucose the four diets were identical. With an increase of 10 g/kg DM of soybean oil the apparent total tract digestibility of crude fibre was reduced with 0.9 percentage units. Extra fat intake also reduced apparent protein and NFE digestibility, but raised apparent fat digestibility. Although the present results may hold specifically for the conditions of this study, it is suggested that the observed interaction between fat content of the diet and macronutrient utilization might have consequences for practical horse feeding in that calculating the energy content of high-fat diets on the basis of feedstuff tables will lead to over- or underestimating the amount of energy provided by the various ingredients of the diets.