Chondrolipoma in the pelvic cavity: a case report.
A chondrolipoma is an extremely rare form of a benign mesenchymal tumor containing mature cartilage and fatty tissue. Chondrolipomas may be found in almost any part of the body, particularly in the connective tissue of the breast, head and neck area, as well as in the skeletal muscle. However, to the best of our knowledge, chondrolipomas located in the pelvic cavity have not been reported. In this case report, we describe a case of a chondrolipoma in the pelvis, and show that it has its own characteristic imaging findings, which included the composition of fatty tissue and calcification in most parts, as well as some focal areas of chondroid tissue based on the CT and MR findings.


Executive function, more than global cognition, predicts functional decline and mortality in elderly women.
Functional impairment in community-dwelling older adults is common and is associated with poor outcomes. Our goal was to compare the contribution of impairment in executive function or global cognitive function to predicting functional decline and mortality. We studied 7717 elderly women enrolled in a prospective study (mean age 73.3 years) and identified women with poor baseline executive function (score > 1 standard deviation [SD] below the mean on the Trail Making Test B (Trails B; n = 957, 12.4%), poor global cognitive function (score > 1 SD below the mean on a modified Mini-Mental State Examination [mMMSE], n = 387, 5.0%), impairment in both (n = 249, 3.2%), or no impairment (n = 6124, 79.4%). We compared level of functional difficulty (Activities of Daily Living [ADLs] and Instrumental ADLs [IADLs]) at baseline and at 6-year follow-up and survival at follow-up. We also determined if the association was independent of age, education, depression, medical comorbidities, and baseline functional ability. At baseline, women with Trails B impairment only or impairment on both tests reported the highest proportion of ADL and IADL dependence compared to the other groups. At the 6-year follow-up after adjusting for age, education, medical comorbidities, depression, and baseline ADL or IADL, women with only Trails B impairment were 1.3 times more likely to develop an incident ADL dependence (adjusted odds ratio [OR] = 1.34; 95% confidence interval [CI], 1.07-1.69) and 1.5 times more likely to develop a worsening of ADL dependence (adjusted OR = 1.48; 95% CI, 1.16-1.89) when compared to women with no impairment on either test. In addition, women with only Trails B impairment had a 1.5-fold increased risk of mortality (adjusted hazard ratio [HR] = 1.48; 95% CI, 1.21-1.81). In contrast, women with impairment on only mMMSE were not at increased risk to develop incident ADL or IADL dependence, a worsening of ADL or IADL dependence, or mortality. Compared to women with no impairment, women with executive function impairment had significantly worse ADL and IADL function cross-sectionally and over 6 years. Individuals with executive dysfunction also had increased risk of mortality. These results suggest that screening of executive function can help to identify women who are at risk for functional decline and decreased survival.


Synthesis of Tricyclic Spiranoid Lactones via I2/Sm(II)- and I2/Pd(0)-Mediated Cyclizations of a Common Cycloalkylmethylene Precursor.
A general synthesis of phylogenetically and structurally different tricyclic angularly fused spiranoid lactones, frequently observed as scaffold segments of various biochemical compounds and drugs of natural origin, is demonstrated via controlled cyclization of simple and easily accessible cycloalkylmethylene key precursors. The rapid composition of the key architecture yields an assembly of stable bicyclic iodolactones, which are converted to form a wide range of angularly fused tricyclic scaffolds.


Decalcification prevention around orthodontic brackets bonded to bleached enamel using different topical agents.
The present study was conducted to evaluate the effect of different topical agents utilized for prevention of enamel decalcification around orthodontic brackets bonded to bleached and non-bleached enamel. Human maxillary premolars (n = 120) were divided into two equal groups. Teeth in group I were left without bleaching while those in group II were bleached with Vivastyle gel. Metal brackets were bonded to all the teeth using light-cured adhesive. Each group was divided into six equal subgroups (A, B, C, D, E, and F). In subgroup A, no material was applied (control). In subgroups B, C, D, E, and F, the following materials were applied respectively: Profluorid varnish, Enamel Pro Varnish, Ortho-Choice Ortho-Coat, GC Tooth Mousse, and GC MI Paste Plus. All teeth were cycled in a demineralization solution/artificial saliva for 15 days. Laser fluorescence was used to measure the level of enamel mineralization. The data were statistically analyzed. Regarding the non-bleaching subgroups, all studied material revealed significant demineralization reduction in comparison to the control subgroup (P < 0.05). Ortho-Choice Ortho-Coat revealed the highest significant effect while GC Tooth Mousse showed the least effect. In bleached subgroups, Profluorid varnish, Enamel Pro Varnish, and Ortho-Choice Ortho-Coat significantly reduced demineralization (P < 0.05) while either GC MI Paste Plus or GC Tooth Mousse had no significant effects (P > 0.05). Ortho-Choice Ortho-Coat, and Profluorid and Enamel Pro varnishes could be utilized successfully to reduce enamel demineralization around brackets bonded to either bleached or non-bleached enamel. GC MI Paste Plus and GC Tooth Mousse were effective only in non-bleached enamel.


Pulmonary arteriovenous malformations: therapeutic options.
We have treated 21 patients (13 female, 8 male) with pulmonary arteriovenous malformations (PAVMs). Mean age at diagnosis was 37.5 years (range, 15 to 72 years). Presenting symptoms included dyspnea on exertion (67%), hereditary hemorrhagic telangiectasia (57%), and major neurologic events (33%). In our early experience, 8 patients had no specific treatment; their case histories illustrate the major neurologic complications of untreated PAVMs. Nine patients (8 primarily, 1 after recurrence) underwent conservative surgical excision; 4 had lobectomy, and 5 had segmentectomy or subsegmental excision. One patient underwent staged bilateral thoracotomies for multiple bilateral lesions. The arterial oxygen tension was found to increase after excision of large or solitary PAVMs. All surgically treated patients were relieved of dyspnea, and none had postoperative recurrence of PAVMs or neurologic complications related to PAVMs. Five patients underwent balloon occlusion of PAVMs. Two patients chose to have solitary PAVMs occluded rather than undergo thoracotomy. One underwent surgical excision 5 years later, and the other required repeat balloon embolization 4 years later when recanalization of the PAVMs was documented. Three patients with numerous PAVMs received palliation with multiple balloon embolizations. The high incidence of associated major neurologic complications mandates aggressive treatment of PAVMs whenever feasible. Conservative surgical resection remains the treatment of choice. Balloon embolization offers an alternative therapy for patients who are poor surgical risks or those whose lesions are too numerous to resect.


The awareness of novelty for strangely familiar words: a laboratory analogue of the déjà vu experience.
Déjà vu is a nebulous memory experience defined by a clash between evaluations of familiarity and novelty for the same stimulus. We sought to generate it in the laboratory by pairing a DRM recognition task, which generates erroneous familiarity for critical words, with a monitoring task by which participants realise that some of these erroneously familiar words are in fact novel. We tested 30 participants in an experiment in which we varied both participant awareness of stimulus novelty and erroneous familiarity strength. We found that déjà vu reports were most frequent for high novelty critical words (∼25%), with low novelty critical words yielding only baseline levels of déjà vu report frequency (∼10%). There was no significant variation in déjà vu report frequency according to familiarity strength. Discursive accounts of the experimentally-generated déjà vu experience suggest that aspects of the naturalistic déjà vu experience were captured by this analogue, but that the analogue was also limited in its focus and prone to influence by demand characteristics. We discuss theoretical and methodological considerations relevant to further development of this procedure and propose that verifiable novelty is an important component of both naturalistic and experimental analogues of déjà vu.


Engineering high-potency R-spondin adult stem cell growth factors.
Secreted R-spondin proteins (RSPOs1-4) function as adult stem cell growth factors by potentiating Wnt signaling. Simultaneous binding of distinct regions of the RSPO Fu1-Fu2 domain module to the extracellular domains (ECDs) of the LGR4 G protein-coupled receptor and the ZNRF3 transmembrane E3 ubiquitin ligase regulates Wnt receptor availability. Here, we examine the molecular basis for the differing signaling strengths of RSPOs1-4 using purified RSPO Fu1-Fu2, LGR4 ECD, and ZNRF3 ECD proteins in Wnt signaling and receptor binding assays, and we engineer novel high-potency RSPOs. RSPO2/3/4 had similar signaling potencies that were stronger than that of RSPO1, whereas RSPO1/2/3 had similar efficacies that were greater than that of RSPO4. The RSPOs bound LGR4 with affinity rank order RSPO4 > RSPO2/3 > RSPO1 and ZNRF3 with affinity rank order RSPO2/3 > > RSPO1 > RSPO4. An RSPO2-4 chimera combining RSPO2 ZNRF3 binding with RSPO4 LGR4 binding was a "Superspondin" that exhibited enhanced ternary complex formation and 10-fold stronger signaling potency than RSPO2 and efficacy equivalent to RSPO2. An RSPO4-1 chimera combining RSPO4 ZNRF3 binding with RSPO1 LGR4 binding was a "Poorspondin" that exhibited signaling potency similar to RSPO1 and efficacy equivalent to RSPO4. Conferring increased ZNRF3 binding upon RSPO4 with amino acid substitutions L56F, I58L, and I63M enhanced its signaling potency and efficacy. Our results reveal the molecular basis for RSPOs1-4 activity differences and suggest that signaling potency is determined by ternary complex formation ability, whereas efficacy depends on ZNRF3 recruitment. High-potency RSPOs may be of value for regenerative medicine and/or therapeutic applications.


The effect of backpack load on muscle activities of the trunk and lower extremities and plantar foot pressure in flatfoot.
[Purpose] The purpose of this study was to investigate the changes in muscle activation of the trunk and lower extremities and plantar foot pressure due to backpack loads of 0, 10, 15, and 20% of body weight during level walking in individuals with flatfoot. [Methods] Fourteen young flatfoot subjects and 12 normal foot subjects participated in this study. In each session, the subjects were assigned to carry a backpack load, and there were four level walking modes: (1) unloaded walking (0%), (2) 10% body weight (BW) load, (3) 15% BW load, and (4) 20% BW load. Trunk and lower extremity muscle activities were recorded by surface EMG, and contact area and plantar foot pressure were determined using a RS scan system. [Results] The erector spinae, vastus medialis, tibialis anterior and gastrocnemius muscle activities, but not the rectus femoris and rectus abdominis muscle activities of flatfoot subjects significantly and progressively increased as load increased in flatfoot subjects. Contact area and pressure of the lateral and medial heel zones were significantly increased too. [Conclusion] Based on this data, the weight of a backpack could influence muscle activation and plantar foot pressure in flatfoot.


The Diagnosis and Management of Airway Complications Following Lung Transplantation.
Airway complications following lung transplantation result in considerable morbidity and are associated with a mortality of 2% to 4%. The incidence of lethal and nonlethal airway complications has decreased since the early experiences with double- and single-lung transplantation. The most common risk factor associated with post-lung transplantation airway complications is anastomotic ischemia. Airway complications include the development of exophytic granulation tissue, bronchial stenosis, bronchomalacia, airway fistula, endobronchial infection, and anastomotic dehiscence. The broadening array of bronchoscopic therapies has enhanced treatment options for lung transplant recipients with airway complications. This article reviews the risk factors, clinical manifestations, and treatments of airway complications following lung transplantation and provides our expert opinion when evidence is lacking.


LMWH in IVF - Biomarkers and benefits.
There is biological plausibility that coagulation activation underlies a proportion of in vitro fertilisation IVF failures and recurrent early clinical pregnancy loss (RPL). However, low-molecular-weight heparin (LMWH) use, based upon previous clinical outcome alone, is not effective in preventing RPL. RPL is heterogeneous in mechanism. Identifying those with an underlying thrombotic mechanism would allow stratification for LMWH treatment. Annexin A5 is an anticoagulant protein expressed on the trophoblast surface. The annexin A5 M2 haplotype (ANXA5 M2) is associated with several placenta mediated pregnancy complications (PMPC) and poor IVF outcome. It is transmitted equally by males and females. A pragmatic observational study of IVF couples screened for M2 carriage and treated with LMWH achieved a 37.9% live birth rate, similar to an unscreened and untreated group with fewer adverse risk factors for conception and a better prognosis from assisted conception. This suggests that LMWH may counteract the adverse effects of M2 carriage. Using this biomarker to stratify IVF and PMPC patients for LMWH treatment merits further evaluation.


Robust real-time imaging through flexible multimode fibers.
Conventional endoscopes comprise a bundle of optical fibers, associating one fiber for each pixel in the image. In principle, this can be reduced to a single multimode optical fiber (MMF), the width of a human hair, with one fiber spatial-mode per image pixel. However, images transmitted through a MMF emerge as unrecognizable speckle patterns due to dispersion and coupling between the spatial modes of the fiber. Furthermore, speckle patterns change as the fiber undergoes bending, making the use of MMFs in flexible imaging applications even more complicated. In this paper, we propose a real-time imaging system using flexible MMFs, but which is robust to bending. Our approach does not require access or feedback signal from the distal end of the fiber during imaging. We leverage a variational autoencoder to reconstruct and classify images from the speckles and show that these images can still be recovered when the bend configuration of the fiber is changed to one that was not part of the training set. We utilize a MMF 300 mm long with a 62.5 μm core for imaging [Formula: see text] cm objects placed approximately at 20 cm from the fiber and the system can deal with a change in fiber bend of 50[Formula: see text] and range of movement of 8 cm.


A case of Mollitias and Fragilitas Ossium - unusual presentation of hairy cell leukaemia followed by the diagnosis of nonsecretory myeloma.
Hairy cell leukaemia (HCL) is a B-cell malignancy with a late developmental arrest. This report describes a patient that presented with leucocytosis and splenomegaly. The abnormal leucocytes showed typical morphology and expressed CD103, CD11c, CD19 and CD20 but not CD25 by immunophenotyping. The patient failed to respond to splenectomy and then developed lytic bone lesions and pathological fractures, which progressed despite a single course of cladribine chemotherapy. Review of the pathology of the bone reamings showed nonsecretory myeloma of the same kappa-light chain isotype. He went on to receive induction chemotherapy in preparation for an autologous stem-cell transplant but failed to mobilize sufficient numbers of stem cells. He has had two localized relapses with bony lesions, one within 6 weeks of stopping chemotherapy for which he received localized radiotherapy and thalidomide consolidation. Sequential myeloma has been described in HCL. There is controversy whether this represents clonal evolution or a secondary malignancy. An increased rate of secondary malignancies has been reported by some, but not other, authors in long-term survivors of HCL. This case illustrates the value of a repeat pathological review in case of unexpected complications.


Mothers grieving the death of a child. Case reports of maternal grief.
Research has shown that the experience of losing a child is by far the most painful. It is documented that bereaved parents have more intense symptomatology than adults grieving other types of loss, such as the loss of a spouse or parent. However, there are fewer studies that focus on parental grief than on other types of grief. This article presents case reports of two mothers grieving the deaths of their children. This presentation is unique because grief as a process is explicated from the perspective of the mothers by means of qualitative and quantitative analysis. Taped semistructured interview sessions were conducted monthly and analyzed using grounded theory. These results were compared to results obtained from the analysis of two quantitative symptom inventories--the SCL-90-R, a psychological distress scale, and the GEI, a 135 item grief experience inventory. The experience of maternal grief that is presented through case examples will enable practitioners to connect theory with practical application to ease the suffering of grieving parents.


Leaf Spectral Reflectance Shows Thalassia testudinum Seedlings More Sensitive to Hypersalinity than Hyposalinity.
Thalassia testudinum (turtle grass) is the dominant and climax-successional seagrass species in the subtropical/tropical Atlantic and Caribbean region. Two die-offs of T. testudinum in Florida Bay, United States have raised concerns regarding the resilience of this species to environmental disturbances. Seedlings are important in recovery of T. testudinum, following disturbance events. Leaf spectral reflectance [R(λ)] was measured in T. testudinum seedlings exposed for 2 weeks to three salinities (20, 35, and 50) and two light levels (full sun and 50-70% light reduction) in experimental mesocosms. Multivariate analyses indicated that hypersalinity had a greater effect on spectral reflectance than hyposalinity or light reduction. There was an increase in variability and flattening of reflectance spectra at the highest salinity. All three salinity treatments had distinct reflectance spectra across green wavelengths (530-580 nm), with additional discrimination between 20 versus 50 and 35 versus 50 treatments across red wavelengths (630-690 nm). Red:Green reflectance ratios were highest and photochemical reflective index values were lowest for the salinity 50 treatment, but were not significantly different between the salinity 20 and 35 treatments. The changes in the R(λ) spectra for the salinity 50 seedlings were consistent with previously observed reductions in leaf pigments and maximum photochemical efficiency of photosystem II. These observations indicate that leaf spectral reflectance is a sensitive indicator of plant stress in T. testudinum seedlings and that seedlings are more sensitive to short-term exposures to hypersalinity than hyposalinity.


Enantioselective Ir-Catalyzed Allylic Alkylation of Racemic Allylic Alcohols with Malonates.
Ir-catalyzed enantioselective allylic alkylation of branched racemic allylic alcohols with malonates is described. Enabled by Carreira's chiral Ir/(P, olefin) complex, the method described allows allylic substitution with various aromatic alcohols and malonates with excellent enantioselectivity. The malonates could be used directly as efficient nucleophiles without the need of preactivation.


Phototherapy for neonatal hyperbilirubinemia in "healthy" and "ill" infants.
The effectiveness of phototherapy for nonhemolytic hyperbilirubinemia was evaluated in two groups of closely matched newborns, one group consisting of "healthy" and the other "ill" infants. Phototherapy was equally effective in reducing bilirubin levels in both groups of infants. It would seem to be the treatment of choice in all infants with nonhemolytic hyperbilirubinemia, especially ill infants in whom its simplicity, safety, and effectiveness would make it an ideal form of therapy.


Engineering oncogene-targeted anisamide-functionalized pBAE nanoparticles as efficient lung cancer antisense therapies.
Non-small cell lung cancer (NSCLC) is one of the leading causes of worldwide death, mainly due to the lack of efficient and safe therapies. Currently, NSCLC standard of care for consist on the use of traditional chemotherapeutics, non-selectively distributed through the whole body, thus causing severe side effects while not achieving high efficacy outcomes. Consequently, the need of novel therapies, targeted to modify specific subcellular routes aberrantly expressed only in tumor cells is still urgent. In this context, the delivery of siRNAs that can know-down overexpressed oncogenes, such as mTOR, could become the promised targeted therapy. However, siRNA effective delivery remains a challenge due to its compromised stability in biological fluids and its inability to cross biological and plasmatic membranes. Therefore, polymeric nanoparticles that efficiently encapsulate siRNAs and are selectively targeted to tumor cells could play a pivotal role. Accordingly, we demonstrate in this work that oligopeptide end-modified poly(beta aminoester) (OM-pBAE) polymers can efficiently complex siRNA in small nanometric particles using very low polymer amounts, protecting siRNA from nucleases attack. These nanoparticles are stable in the presence of serum, advantageous fact in terms of in vivo use. We also demonstrated that they efficiently transfect cells in vitro, in the presence of serum and are able to knock down target gene expression. Moreover, we demonstrated their antitumor efficacy by encapsulating mTOR siRNA, as a model antisense therapy, which showed specific lung tumor cell growth inhibition in vitro and in vivo. Finally, through the addition of anisamide functionalization to the surface of the nanoparticles, we proved that they become selective to lung tumor cells, while not affecting healthy cells. Therefore, our results are a first step in the discovery of a tumor cell-targeted efficient silencing nanotherapy for NSCLC patients survival improvement.


CORM-2 Pretreatment Attenuates Inflammation-mediated Islet Dysfunction.
During the process of human islet isolation a cascade of stressful events are triggered and negatively influence islet yield, viability, and function, including the production of proinflammatory cytokines and activation of apoptosis. Carbon monoxide-releasing molecule 2 (CORM-2) is a donor of carbon monoxide (CO) and can release CO spontaneously. Accumulating studies suggest that CORM-2 exerts cytoprotective and anti-inflammatory properties. However, the effect of CORM-2 on islet isolation is still unclear. In this study, we found that CORM-2 pretreatment significantly decreased the expression of critical inflammatory genes, including tissue factor, intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2, C-X-C motif chemokine 10, Toll-like receptor 4, interleukin-1β, interleukin-6, and tumor necrosis factor-α (TNF-α). The isolated islets of the CORM-2 pretreatment group showed reduced apoptotic rate, improved viability, and higher glucose-stimulated insulin secretion, and functional gene expression in comparison to control group. Importantly, CORM-2 pretreatment prevented the impairment caused by TNF-α, evidenced by the improved glucose-stimulated index and transplantation outcomes. The present study demonstrated the anti-inflammatory property of CORM-2 during human islet isolation, and we suggest that CORM-2 pretreatment is an appealing treatment to mitigate inflammation-mediated islet dysfunction during isolation and culture ex vivo and to preserve long-term islet survival and function.


New indices in predicting cardiometabolic risk and its relation to endothelial dysfunction in adolescents: The HELENA study.
Blood pressure (BP) changes and insulin resistance (IR) are important cardiometabolic risk (CMR) factors; their early identification can contribute to the reduction of cardiovascular events in adulthood. This necessitates the search for more accessible and easily applied indicators for their prediction. Therefore, this study aimed to evaluate the predictive power of the indices, TyG, TG/HDL-c, height-corrected lipid accumulation product (HLAP), and visceral adiposity index (VAI), in identifying the CMR obtained by high BP and IR and to verify their relationship with biomarkers of endothelial dysfunction (ED) in European adolescents. The anthropometric data and blood biomarkers of 744 adolescents (343 boys and 401 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS), with a mean age of 14.67 (SD 1.15) years, were assessed. The adolescents were then classified according to the presence or absence of high BP and IR. The cut-off points of the indices evaluated for the identification of CMR were determined. The relationship between CMR diagnosed using these indices and ED biomarkers was tested. The HLAP and TG/HDL-c were fair predictors of CMR obtained by IR in male adolescents. These indices showed association with hsCRP in sVCAM-1 in boys, but it lost significance after adjusting for age and body mass index. TG/HDL-c and HLAP indices showed a fair performance in predicting CMR, obtained by IR, in male adolescents. ED showed no association with the CMR identified by the indices.


[Tuberculous meningoencephalitis from personal material].
Clinical characteristics of 6 patients with tuberculous meningoencephalitis is presented. The increased morbidity of tuberculosis in recent years makes it necessary to consider this etiology in the diagnosis of CNS infections especially with severe atypic and long lasting course. In the case when tuberculous etiology is suspected the anti tuberculous treatment should be applied. Using new and modern diagnostic methods of CSF will allow to diagnose tuberculous meningoencephalitis earlier and will improve prognosis in this disease.


A PCR-Based Molecular Detection of Strongyloides stercoralisin Human Stool Samples from Tabriz City, Iran.
Strongyloides stercoralis is a nematode causing serious infections in immunocompromised patients. In chronically infected patients, the low parasitic content as well as the resemblance of the larvae to several other species make diagnosis basedonmorphology difficult. In the present study, a PCR-based method targeting the internal transcribed sequence 2 (ITS2) of the rDNA region was examined for the molecular detection of S. stercoralis infection from the stool samples. A total of 1800 patients were included. Three fresh stool samples were collected per patient, and S. stercoralis isolates were identified by the morphological method. A subset of isolates was later used in the PCR-based method as positive controls. Additionally, negative and no-template controls were included. Data analysis was accomplished using an x² test. Ap-value less than 0.05 was considered significant. In total, fivestool samples were found to be infected with S. stercoralis using the morphology method. PCR method detected S. stercoralis DNA target from all of the fiveDNA samples extracted from positive fecal samples. The PCR method used for amplifying a short fragment was successful for diagnosis of S. stercoralis in fecal samples and can be reliable for directly detecting the parasite bypassing morphological method.


Cancer-causing human papillomavirus E6 proteins display major differences in the phospho-regulation of their PDZ interactions.
Previous studies have shown that the cancer-causing high-risk human papillomavirus (HPV) E6 oncoproteins have PDZ binding potential, an activity which is important for their ability to support the viral life cycle and to cooperate in the induction of malignancy. However, PDZ interactions are not constitutive, and they can be negatively regulated by phosphorylation within the E6 PDZ binding motif (PBM). In this study, we have investigated the differential regulation of the HPV E6 PBMs from diverse high-risk HPV types. We show that, depending on the HPV type, PDZ binding activity can be regulated by phosphorylation with protein kinase A (PKA) or AKT, which, in turn, inhibits PDZ recognition. Such regulation is highly conserved between E6 proteins derived from HPV-16, HPV-18, and HPV-58 while being somewhat weaker or absent from other types such as HPV-31, HPV-33, and HPV-51. In the case of HPV31, PKA phosphorylation occurs within the core of the E6 protein and has no effect on PDZ interactions, and this demonstrates a surprising degree of heterogeneity among the different high-risk HPV E6 oncoproteins in how they are regulated by different cellular signaling pathways. This study demonstrated that the cancer-causing HPV E6 oncoproteins are all subject to posttranslational modification of their extreme C-terminal PDZ binding motifs through phosphorylation. However, the identities of the kinase are not the same for all HPV types. This demonstrates a very important divergence between these HPVs, and it suggests that changes in cell signaling pathways have different consequences for different high-risk virus infections and their associated malignancies.


Aerosol assisted chemical vapor deposition of In2O3 films from Me3In and donor functionalized alcohols.
The reaction of Me3In and ROH (R = CH2CH2NMe2, CH(CH3)CH2NMe2, C(CH3)2CH2OMe, CH2CH2OMe) in toluene under aerosol assisted chemical vapor deposition (AACVD) conditions leads to the production of indium oxide thin films on glass. The indium oxide films were deposited at 550 degrees C and analyzed by scanning electron microscopy (SEM), X-ray powder diffraction, wavelength dispersive analysis of X-rays (WDX), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. This CVD technique offers a rapid, convenient route to In2O3, which presumably involves the in situ formation of dimethylindium alkoxides, of the type [Me2InOR]2. In order to identify compounds present in the aerosol mist, the solution-phase reaction between Me3In and ROH (R = CH2CH2NMe2, C(CH3)2CH2OMe, CH(CH3)CH2NMe2, CH(CH2NMe2)2) at room temperature in toluene was carried out. Dimeric indium alkoxides, of the type [Me2In(OR)]2, were isolated, and their structures were determined by X-ray crystallography.


Traversing the nucleation-growth landscape through heterogeneous random walks.
The nucleation-growth process is a crucial component of crystallization. While previous theoretical models have focused on nucleation events and postnucleation growth, such as the classical nucleation theory and Lifshitz-Slyozov-Wagner model, recent advancements in experiments and simulations have highlighted the inability of classical models to explain the transient dynamics during the early development of nanocrystals. To address these shortcomings, we present a model that describes the nucleation-growth dynamics of individual nanocrystals as a series of reversible chain reactions, with the free energy landscape extended to include activation-adsorption-relaxation reaction pathways. By using the Monte Carlo method based on the transition state theory, we simulate the crystallization dynamics. We derive a Fokker-Planck formalism from the master equation to describe the nucleation-growth process as a heterogeneous random walk on the extended free energy landscape with activated states. Our results reveal the transient quasiequilibrium of the prenucleation stage before nucleation starts, and we identify a postnucleation crossover regime where the dynamic growth exponents asymptotically converge towards classical limits. Additionally, we generalize the power laws to address the dimension and scale effects for the growth of large crystals.


The relationship between anaesthetic technique, clinicopathological characteristics and the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colon cancer.
The magnitude of the postoperative systemic inflammatory response (SIR) is now recognised to be associated with both short and long-term outcomes in patients undergoing surgery for colon cancer. During such surgery, it is unclear whether the anaesthetic regimens influence the magnitude of the postoperative SIR, independent of other factors. The aim of the present study was to examine the association between anaesthetic agents, clinicopathological characteristics and the magnitude of the postoperative SIR in patients undergoing elective surgery for colon cancer. Patients with colon cancer who underwent elective open or laparoscopic surgery between 2008 and 2016 (n = 409) were studied at a single center. The relationship between type of anaesthesia, surgical technique; open (n = 241) versus laparoscopic (n = 168) and clinicopathological characteristics was examined by using chi-square testing. The chi-square test was used to determine which anaesthetic group influences the POD 2 CRP for only patients undergoing elective open colon surgery. The majority of patients were <75 years old, male, normal weight or obese, underwent open surgery and had regional anaesthesia, in particular an epidural approach. There was a significant association between type of anaesthesia and post-operative CRP on day 2 (p <0.001) in patients undergoing open surgery but not laparoscopic surgery. Other factors associated with type of anaesthesia included; year of operation (p <0.01), surgical technique (p <0.001), and preoperative dexamethasone (p <0.01). In patients undergoing surgery for elective colon cancer, the type of anaesthesia varied over time. The type of anaesthesia appears to influence the magnitude of the postoperative SIR on post-operative day 2 in open surgery but not laparoscopic surgery. Future work using prospective study design is required to better define this relationship.


When to p and when not to p.
The p-value was proposed in the early 20th century as a potentially useful metric for statistical inference and was defined as "the probability of the observed result, plus more extreme results, if the null hypothesis were true," in the context of a formal statistical testing process. A century later, the scientific community uses it extensively, mostly inappropriately, and often interprets it incorrectly. This editorial briefly reviews the history of the p-value, provides how to properly interpret it, and recommends when to use it and when not to use it.


Neonatal Bartter syndrome diagnosed by rapid genomics following low risk pre-conception carrier screening.
Advances in the speed and accessibility of genomic sequencing are broadening the application of this technology to rapid, acute care diagnostics and pre-conception carrier screening. In both circumstances, genetic counselling plays a critical role in preparing couples for the strengths and limitations of the testing. For pre-conception carrier screening in particular, it is important that parents and clinicians are aware that even in the absence of an identified risk for recessive disease, a baby with a genetic condition may still be conceived. As an example, we present the genomic journey of a couple who underwent pre-conception carrier screening and following a low-risk result, delivered a baby boy who was diagnosed with Type 1 Bartter syndrome. Ultra-rapid, post-natal, trio whole genome sequencing resolved both parents as carriers of pathogenic variants in SLC12A1, a gene not included in the original pre-conception screening panel. This family's story highlights (i) the intricacy of gene selection for pre-conception screening panels, (ii) the benefits of high-quality pre-test genetic counselling in supporting families through adverse genomic findings and (iii) the role rapid genomics can play in resolving uncertainty for families and clinicians in circumstances where suspicion of genetic disease exists. This article is accompanied by a Patient Voice perspective written by the child's parents, placing emphasis on the essential role genetic counselling played in their journey.


Uptake of high-density lipoprotein by scavenger receptor class B type 1 is associated with prostate cancer proliferation and tumor progression in mice.
High-density lipoprotein (HDL) metabolism is facilitated in part by scavenger receptor class B, type 1 (SR-B1) that mediates HDL uptake into cells. Higher levels of HDL have been associated with protection in other diseases, however, its role in prostate cancer is not definitive. SR-B1 is up-regulated in prostate cancer tissue, suggesting a possible role of this receptor in tumor progression. Here, we report that knockout (KO) of SR-B1 in both human and mouse prostate cancer cell lines through CRISPR/Cas9-mediated genome editing reduces HDL uptake into the prostate cancer cells and reduces their proliferation in response to HDL. In vivo studies using syngeneic SR-B1 WT (SR-B1+/+) and SR-B1 KO (SR-B1-/-) prostate cancer cells in WT and apolipoprotein-AI KO (apoA1-KO) C57BL/6J mice revealed that WT hosts, containing higher levels of total and HDL-cholesterol, grew larger tumors than apoA1-KO hosts with lower levels of total and HDL-cholesterol. Furthermore, SR-B1-/- prostate cancer cells formed smaller tumors in WT hosts than SR-B1+/+ cells in the same host model. Increased tumor volume was overall associated with reduced survival. We conclude that knocking out SR-B1 in prostate cancer tumors reduces HDL-associated increases in prostate cancer cell proliferation and disease progression.


Structural analysis of cortical porosity applied to HR-pQCT data.
The investigation of cortical porosity is an important aspect of understanding biological, pathoetiological, and biomechanical processes occurring within the skeleton. With the emergence of HR-pQCT as a noninvasive tool suitable for clinical use, cortical porosity at appendicular sites can be directly visualized in vivo. The aim of this study was to introduce a novel topological analysis of the cortical pore network for HR-pQCT data and determine the influence of resolution on measures of cortical pore network microstructure and topology. Cadaveric radii were scanned using HR-pQCT at two different voxel sizes (41 and 82 μm) and also using μCT at a voxel size of 18 μm. HR-pQCT and μCT image sets were spatially coregistered. Segmentation and quantification of cortical porosity (Ct.Po) and mean pore diameter (Ct.Po.Dm) were achieved using an established extended cortical analysis technique. Topological classification of individual pores was performed using topology-preserving skeletonization and multicolor dilation algorithms. Based on the pore skeleton topological classification, the following parameters were quantified: total number of planar surface-skeleton canals (N.Slabs), tubular curve-skeleton canals (N.Tubes), and junction elements (N.Junctions), mean slab volume (Slab.Vol), mean tube volume (Tube.Vol), mean slab orientation (Slab.θ), mean tube orientation (Tube.θ), N.Slabs/N.Tubes, and integral (total) slab volume/integral tube volume (iSlab.Vol/iTube.Vol). An in vivo reproducibility study was also conducted to assess short-term precision of the topology parameters. Precision error was characterized using root mean square coefficient of variation (RMSCV%). Correlations to μCT values for Ct.Po were significant for both the 41 and 82 μm HR-pQCT data (41: r(2) = 0.82, p < 0.001, 82: r(2) = 0.75, p < 0.001). For Ct.Po.Dm, only the 41 μm data were significantly predictive of μCT values (r(2) = 0.72, p < 0.01) Data at both HR-pQCT voxel sizes were strongly predictive of the μCT values for N.Slabs (41: r(2) = 0.93, p < 0.001; 82: r(2) = 0.84, p < 0.001), N.Tubes (41: r(2) = 0.94, p < 0.001; 82: r(2) = 0.84, p < 0.001), and N.Junctions (41: r(2) = 0.93, p < 0.001; 82: r(2) = 0.78, p < 0.001), though proportional bias was evident in these correlations. Weak correlations were seen for iSlab.Vol/iTube.Vol at both voxel sizes (41: r(2) = 0.52, p < 0.01; 82: r(2) = 0.39, p < 0.05). Slab.Vol was significantly correlated to μCT data at 41 μm (r(2) = 0.60, p < 0.01) but not at 82 μm, while Tube.Vol was significantly correlated at both voxel sizes (41: r(2) = 0.79, p < 0.001; 82: r(2) = 0.68, p < 0.01). In vivo precision error for these parameters ranged from 2.31 to 9.68 RMSCV%. Strong correlations between μCT- and HR-pQCT-derived measurements were found, particularly in HR-pQCT images obtained at 41 μm. These data are in agreement with our previous study investigating the effect of voxel size on standard HR-pQCT metrics of trabecular and cortical microstructure, and extend our previous findings to include topological descriptors of the cortical pore network.


Molecular weight and related properties of lily amylose determined by monitoring of elution from TSK-GEL PW high performance gel chromatography columns by the low-angle laser light scattering technique and precision differential refractometry.
Amylose was fractionated according to its molecular weight by high performance gel chromatography using columns of a TSK-GEL PW series. Elution from the columns was monitored with a low-angle laser light scattering photometer and a precision differential refractometer. The following results were obtained indicating that the procedure is highly efficient for characterizing an amylose preparation with respect to its molecular weight: 1) the weight-average molecular weight of lily amylose used as a test material was determined to be 786,000 +/- 26,000 (n = 7); 2) the molecular weight distribution curve of the amylose was worked out from the chromatographic data; and 3) based on the concept of the universal calibration curve, the Mark-Houwink-Sakurada equation of the amylose was presumed to be [eta] = 2.27 X 10(-4)M0.62 (dl/g). The technique saves time and sample significantly compared with the conventional ones, and consequently enables the characterization of amylose in aqueous solvents without either the degradation or association peculiar to the amylose molecule.


One-Year Multicenter Randomised Controlled Trial Comparing OT Equator® and Locator Attachments to Retain an Early Loaded Implant Overdenture on Two Implants.
This investigation aimed to compare the effectiveness of the OT Equator® (Rhein, Bologna, Italy) and the Locator attachment systems used to retain early loaded implant-retained overdentures. This study was designed as a multicenter randomised controlled trial of parallel groups. After implant placement, the patients were randomised to receive OT Equator® attachments in the test group or Locator attachments in the control group. The outcome measures were implant and prosthetic success and survival rates, any biological and technical complication, marginal bone loss, patients' satisfaction, and periodontal parameters. Overall, 42 patients were consecutively enrolled and treated. One implant was lost in the control group, while no implants were lost in the test group. No prostheses failed in both groups. Only a few complications were experienced in both groups. The main was represented by loss of retention of the attachments (retentive caps). The OT Equator® attachment showed statistically lower periodontal parameters. In conclusion, both attachment systems were suitable for overdenture implant retention.


Steroid-responsive multifocal motor neuropathy with cranial manifestations - a case report.
The typical presentation of multifocal motor neuropathy (MMN) is progressive asymmetric limb weakness. Cranial neuropathy is rare. We report a 28-year-old woman with cranial and bulbar palsies but with typical electrophysiological features of MMN by multifocal motor conduction blocks and serological markers of anti-ganglioside GM1 antibodies. The previous consensus on the treatment of MMN is intravenous immunoglobulins, but our patient responded to oral steroids and had clinical and electrophysiological improvement under continuous low-dose prednisolone treatment. In summary, MMN is a treatable chronic inflammatory disease of peripheral nerves. Cranial neuropathies can be its initial presentations. Electromyography studies are crucial for MMN diagnosis and helpful in monitoring disease activity and treatment responses. Although the previous guideline did not suggest using steroids for MMN, with careful patient selection, low-dose oral steroids can be an effective treatment in patients with relatively minor symptoms. Keywords: Multifocal motor neuropathy, conduction block, bulbar palsy, cranial nerve, cranial neuropathy.


Dental care of the polymedication patient.
With increasing frequency, ambulatory patients maintained on multiple medications are seeking dental care. Because new medications are approved for use each year and new interactions and side effects are regularly exposed for existing medications, it is important to keep current in this area. With the availability of regularly updated computer programs to help analyze accurate patient medication lists, the treatment of the polymedication patient has become much easier. The close, careful attention to patient medications should help prevent medical problems as well as reveal much about the patient's ability to withstand dental procedures.


[Effect of prolactin on CD40/CD154 expression on peripheral blood mononuclear cells in patients with systemic lupus erythematosus].
To investigate the effect of prolactin on CD40 and CD154 expressions on the surface of peripheral blood mononuclear cells in patients with systemic lupus erythematosus (SLE) and explore the role of prolactin in the pathogenesis of SLE. The serum prolectin level was detected in 30 SLE patients and 20 healthy volunteers, from whom peripheral blood mononuclear cells (PBMCs) were also isolated to examine the expressions of CD40 and CD154 using flow cytometry. CD154 significantly increased on the PBMCs in SLE patients with high serum prolectin level in comparison with that in patients with normal prolactin level or the normal controls (P<0.05). When the PBMCs were incubated with recombinant human prolactin, CD154 expression was significantly increased in SLE patients with normal serum prolactin level (P<0.05), but not in the normal control group (P>0.05). Incubation of the PBMCs in the presence of bromocriptine did not result in significantly decreased CD154 expression in SLE patients irrespective of the prolactin level, nor was significant difference found in CD40 expression on the surface of PBMCs between SLE patients and the normal controls(P>0.05). Prolactin plays an important role in the pathogenesis of SLE by increasing CD154 expression on the PBMCs, and bromocriptine produces no significant inhibitory effect on either endogenous or exogenous prolectin.


Electrospray ionization and time-of-flight mass spectrometric method for simultaneous determination of spermidine and spermine.
A sensitive method for the determination of polyamines in mammalian cells was described using electrospray ionization and time-of-flight mass spectrometer. This method was 50-fold more sensitive than the previous method using ionspray ionization and quadrupole mass spectrometer. The method employed the partial purification and derivatization of polyamines, but allowed a measurement of multiple samples which contained picomol amounts of polyamines. Time required for data acquisition of one sample was approximately 2 min. The method was successfully applied for the determination of reduced spermidine and spermine contents in cultured cells under the inhibition of aminopropyltransferases. In addition, a new proper internal standard was proposed for the tracer experiment using (15)N-labeled polyamines.


Emergence and Spread of Extended Spectrum β-Lactamase Producing Enterobacteriaceae (ESBL-PE) in Pigs and Exposed Workers: A Multicentre Comparative Study between Cameroon and South Africa.
Extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) represent a significant public health concern globally and are recognized by the World Health Organization as pathogens of critical priority. However, the prevalence of ESBL-PE in food animals and humans across the farm-to-plate continuum is yet to be elucidated in Sub-Saharan countries including Cameroon and South Africa. This work sought to determine the risk factors, carriage, antimicrobial resistance profiles and genetic relatedness of extended spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE) amid pigs and abattoir workers in Cameroon and South Africa. ESBL-PE from pooled samples of 432 pigs and nasal and hand swabs of 82 humans were confirmed with VITEK 2 system. Genomic fingerprinting was performed by ERIC-PCR. Logistic regression (univariate and multivariate) analyses were carried out to identify risk factors for human ESBL-PE carriage using a questionnaire survey amongst abattoir workers. ESBL-PE prevalence in animal samples from Cameroon were higher than for South Africa and ESBL-PE carriage was observed in Cameroonian workers only. Nasal ESBL-PE colonization was statistically significantly associated with hand ESBL-PE (21.95% vs. 91.67%; p = 0.000; OR = 39.11; 95% CI 2.02⁻755.72; p = 0.015). Low level of education, lesser monthly income, previous hospitalization, recent antibiotic use, inadequate handwashing, lack of training and contact with poultry were the risk factors identified. The study highlights the threat posed by ESBL-PE in the food chain and recommends the implementation of effective strategies for antibiotic resistance containment in both countries.


Mortality following Campylobacter infection: a registry-based linkage study.
Campylobacteriosis is one of the most commonly identified causes of bacterial diarrheal disease and a common cause of gastroenteritis in travellers from developed nations. Despite the widespread occurrence, there is little information on Campylobacter mortality. Mortality among a cohort of Campylobacter cases were compared with the general population 0-1, 1-3, 3-12 and more than 12 month after the onset of the illness. The cases were sub-grouped according to if they had been infected domestically or abroad. The standardized mortality ratio for cases infected domestically was 2.9 (95% CI: 1.9-4.0) within the first month following the illness. The risk then gradually diminished and approached 1.0 after one year or more have passed since the illness. This initial excess risk was not attributable to any particular age group (such as the oldest). In contrast, for those infected abroad, a lower standardized mortality ratio 0.3 (95% CI: 0.04-0.8) was shown for the first month after diagnosis compared to what would be expected in the general population. Infection with Campylobacter is associated with an increased short-term risk of death among those who were infected domestically. On the contrary, for those infected abroad a lower than expected risk of death was evident. We suggest that the explanation behind this is a "healthy traveler effect" among imported cases, and effects of a more frail than average population among domestic cases.


Type III Monteggia fracture with posterior interosseous nerve injury in a child: A case report.
Elbow injury in children by improper treatment or a delay of more than 3 weeks could lead to old unreduced Monteggia fracture, which are difficult to manage. Conservative or normal surgical methods usually fail. Herein, we present a 6-year-old boy with sustaining injury approximately 1 month to his left elbow. Activity in his elbow was restricted, and his ability to extend his wrist and fingers was impaired. Type III Monteggia elbow fracture-dislocation consisting of radial head dislocation and malunion of the ulna associated with posterior interosseous nerve palsy were confirmed, which requiring surgical treatment. A closed reduction was performed with hyperplastic scar tissues erased and the radial head relocated. Follow-up 4 months later showed satisfactory recovery of function. Forearm fractures in children may be misjudged, and that early anatomical reduction rather than conservative treatment may be required.


One Pass Thalamic and Subthalamic Stimulation for Patients with Tremor-Dominant Idiopathic Parkinson Syndrome (OPINION): Protocol for a Randomized, Active-Controlled, Double-Blinded Pilot Trial.
Besides fluctuations, therapy refractory tremor is one of the main indications of deep brain stimulation (DBS) in patients with idiopathic Parkinson syndrome (IPS). Although thalamic DBS (ventral intermediate nucleus [Vim] of thalamus) has been shown to reduce tremor in 85-95% of patients, bradykinesia and rigidity often are not well controlled. The dentato-rubro-thalamic tract (DRT) that can directly be targeted with special diffusion tensor magnetic resonance imaging sequences has been shown as an efficient target for thalamic DBS. The subthalamic nucleus (STN) is typically chosen in younger patients as the target for dopamine-responsive motor symptoms. This study investigates a one-path thalamic (Vim/DRT) and subthalamic implantation of DBS electrodes and possibly a combined stimulation strategy for both target regions. This study investigates a one path thalamic (Vim/DRT) and subthalamic implantation of DBS electrodes and a possibly combined stimulation strategy for both target regions. This is a randomized, active-controlled, double-blinded (patient- and observer-blinded), monocentric trial with three treatments, three periods and six treatment sequences allocated according to a Williams design. Eighteen patients will undergo one-path thalamic (Vim/DRT) and STN implantation of DBS electrodes. After one month, a double-blinded and randomly-assigned stimulation of the thalamic target (Vim/DRT), the STN and a combined stimulation of both target regions will be performed for a period of three months each. The primary objective is to assess the quality of life obtained by the Parkinson's Disease Questionnaire (39 items) for each stimulation modality. Secondary objectives include tremor reduction (obtained by the Fahn-Tolosa-Marin tremor rating scale, video recordings, the Unified Parkinson's disease rating scale, and by tremor analysis), psychiatric assessment of patients, and to assess the safety of intervention. At the moment, the recruitment is stopped and 12 patients have been randomized and treated. A futility analysis is being carried out by means of a conditional power analysis. The approach of the OPINION trial planned to make, for the first time, a direct comparison of the different stimulation conditions (Vim/DRT, compared to STN, compared to Vim/DRT+STN) in a homogeneous patient population and, furthermore, will allow for intraindividual comparison of each condition with the "quality of life" outcome parameter. We hypothesize that the combined stimulation of the STN and the thalamic (Vim/DRT) target will be superior with respect to the patients' quality of life as compared to the singular stimulation of the individual target regions. If this holds true, this work might change the standardized treatment described in the previous section. ClinicalTrials.gov: NCT02288468; https://clinicaltrials.gov/ct2/show/NCT02288468 (Archived by WebCite at http://www.webcitation.org/6wlKnt2pJ); and German Clinical Trials Register: DRKS00007526; https://www.drks.de/drks_ web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00007526 (Archived by WebCite at http://www.webcitation.org/6wlKyXZZL).


Glenoid bone-grafting in total shoulder arthroplasty.
Abnormal glenoid architecture resulting from loss of bone usually is listed among the contraindications to total shoulder arthroplasty using an unconstrained prosthesis. However, in a series of 463 consecutive replacement procedures that were performed between 1973 and 1985, in only two patients did the lack of bone make the implantation of a glenoid component impossible. Of the remaining sixty-five shoulders that had an abnormal glenoid, twenty were successfully treated with a large, internally fixed bone graft or grafts and forty-five, with smaller bone grafts that were not internally fixed. Nineteen of the twenty shoulders that had a large graft or grafts were followed for two years or more (average, 4.4 years). The clinical results were judged to be excellent in sixteen and satisfactory in one, and the desired limited goals were obtained in two. Two fixation screws broke and one screw was worn by contact with the humeral component. None of the glenoid components clinically loosened or migrated, and no patient has needed further surgical treatment. Although bone-grafting was necessary in only twenty (4.3 per cent) of the 463 replacement procedures, this procedure provided sufficient osseous support to allow implantation of a component in a severely damaged glenoid.


Giant Intrathoracic Goiter of Atypical Presentation: A Case Report.
The term goiter is used to describe any abnormal growth of the thyroid gland, which can be diffuse or nodular, and can be associated with normal, diminished, or increased thyroid function. Multinodular goiter is a common disease whose prevalence increases at age 50. Clinical manifestations can be due to thyroid function impairment or related to size and location of the gland with compressive symptoms. Intrathoracic location is less frequent, can be mistaken with pulmonary lesions and usually implies a difficult surgical approach. A 66-year-old woman with a history of subtotal thyroidectomy presented with 7-month dyspnea, dry cough. There was no evidence of neck masses, or jugular engorgement. Physical examination was normal. Chest x-ray showed an 11 cm mass in the upper right hemithorax. Computed tomography (CT)-scan, showed calcifications, and compression of the superior vena cava without infiltration, the right subclavian vein and left displacement of the trachea. Distinction between intrapulmonary or mediastinal location was not clear. Biopsy showed thyroid origin, and bilateral thoracotomy was performed with confirmation of a giant multinodular goiter. Intrathoracic goiter should undergo surgical or ablative management if compressive symptoms of the airway and cervical or thoracic vessels are present. The large size of the tumor along with the presentation after thyroidectomy and the seeming location in the right upper lobe made this particular case striking. Specially in the elderly, multidisciplinary perioperative management is key for a successful recovery.


Parsimonious Charge Deconvolution for Native Mass Spectrometry.
Charge deconvolution infers the mass from mass over charge (m/z) measurements in electrospray ionization mass spectra. When applied over a wide input m/z or broad target mass range, charge-deconvolution algorithms can produce artifacts, such as false masses at one-half or one-third of the correct mass. Indeed, a maximum entropy term in the objective function of MaxEnt, the most commonly used charge deconvolution algorithm, favors a deconvolved spectrum with many peaks over one with fewer peaks. Here we describe a new "parsimonious" charge deconvolution algorithm that produces fewer artifacts. The algorithm is especially well-suited to high-resolution native mass spectrometry of intact glycoproteins and protein complexes. Deconvolution of native mass spectra poses special challenges due to salt and small molecule adducts, multimers, wide mass ranges, and fewer and lower charge states. We demonstrate the performance of the new deconvolution algorithm on a range of samples. On the heavily glycosylated plasma properdin glycoprotein, the new algorithm could deconvolve monomer and dimer simultaneously and, when focused on the m/z range of the monomer, gave accurate and interpretable masses for glycoforms that had previously been analyzed manually using m/z peaks rather than deconvolved masses. On therapeutic antibodies, the new algorithm facilitated the analysis of extensions, truncations, and Fab glycosylation. The algorithm facilitates the use of native mass spectrometry for the qualitative and quantitative analysis of protein and protein assemblies.


Heterocyclic compounds with different moieties: synthesis and evaluation of biological activities assisted with the computational study.
In the present work, heterocyclic compounds containing different moieties, such as pyrazole and thiophene, were synthesized and screened for inhibitory potency against medicinal enzymes and bacterial and cancer (breast and cervical) cell lines. The synthesized compounds have exhibited inhibitory capability against the studied enzymes. Among substances, C3 compound showed AChE and BChE inhibitory potency with the lowest IC50 value of 3.72 ± 0.57 and 1.66 ± 0.22 µM, respectively, in comparison to the standard tacrine. These analogs indicated varying degrees of tyrosinase inhibitory potencies ranging from 1.12 ± 0.50 to 7.70 ± 0.88 µM, and substance C4 was more potent against the enzyme than the reference compound, kojic acid. All four compounds have IC50 values between 37.11 ± 1.56-124.8 ± 2.09 µM for α-glucosidase. It was found that compound C1 exhibited a better antiproliferative activity compared to other substances, with IC50 values at 5.068 and 6.460 µg mL-1 for MCF-7 and HeLa cells, respectively. C1 and C2 compounds had good inhibitory ability against E. faecalis with a MIC value (16 µg mL-ˡ). Molecular docking analysis showed that C3 has the lowest binding score against α-glucosidase (-8.617 kcal/mol).Communicated by Ramaswamy H. Sarma.


Measles (rubeola) susceptibility among elementary schoolchildren.
Measles (rubeola) immunity among 479 elementary schoolchildren from suburban Minneapolis was serologically surveyed in December 1971. Of the 479 children, 25 (5.2%) had hemagglutination-inhibition (HI) titers less than 2. These children were considered susceptible to measles. For the 233 immunized children with no measles history, 13 (5.6%) had rubeola HI titers less than 2 while 5 (5.1%) of the 98 youngsters with a history of clinical measles had rubeola HI titers less than 2. Of the 454 immune children, 73 (16%) had measles HI titers between 2 and 8. These findings confirm durable immunity and a low rate of vaccine failure following live attenuated measles vaccination but demonstrate the importance of testing sera beginning at a dilution of 2 in order to detect children with low antibody levels. This survey also suggests that maternal antibody interferes with the active immune response in youngsters immunized when less than 1 year of age because this group of children had significantly lower geometric mean titers and significantly more susceptibles than the children immunized when greater than or minus 2 years.


Understanding practice: factors that influence physician hand hygiene compliance.
To identify the behavioral determinants--both barriers and enablers--that may impact physician hand hygiene compliance. A qualitative study involving semistructured key informant interviews with staff physicians and residents. An urban, 1,100-bed multisite tertiary care Canadian hospital. A total of 42 staff physicians and residents in internal medicine and surgery. Semistructured interviews were conducted using an interview guide that was based on the theoretical domains framework (TDF), a behavior change framework comprised of 14 theoretical domains that explain health-related behavior change. Interview transcripts were analyzed using thematic content analysis involving a systematic 3-step approach: coding, generation of specific beliefs, and identification of relevant TDF domains. Similar determinants were reported by staff physicians and residents and between medicine and surgery. A total of 53 specific beliefs from 9 theoretical domains were identified as relevant to physician hand hygiene compliance. The 9 relevant domains were knowledge; skills; beliefs about capabilities; beliefs about consequences; goals; memory, attention, and decision processes; environmental context and resources; social professional role and identity; and social influences. We identified several key determinants that physicians believe influence whether and when they practice hand hygiene at work. These beliefs identify potential individual, team, and organization targets for behavior change interventions to improve physician hand hygiene compliance.


Effectiveness of capillary electrophoresis fluoroimmunoassay of blood PrpSc for evaluation of scrapie pathogenesis in sheep.
Management of prion diseases in livestock would benefit greatly from availability of a validated blood test. A promising immunocapillary electrophoresis technique (also known as capillary electrophoresis fluoroimmunoassay) to detect abnormal prion protein in blood from live sheep is evaluated here. Capillary electrophoresis fluoroimmunoassay was applied to analysis of extracted blood from scrapie-exposed sheep (n = 87; 347 samples) at various stages of incubation, and to control sheep (n = 194; 489 samples). Overall, test values for the control and test populations were not significantly different, and a similar proportion of control (7%) and test (10%) sheep were classified as positive. Over 2-3 month intervals from birth until clinical disease, test specificity and sensitivity ranged from 66.7% to 100% and 0% to 66.7%, respectively, indicating poor diagnostic performance at all stages of pathogenesis. In routine application, in its present form, the capillary electrophoresis fluoroimmunoassay procedure proved to be insufficiently robust for use as a blood test for scrapie diagnosis.


Design, characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting.
Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra. The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson's drug ropinirole (RH) to the brain using polymeric nanoparticles. Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration. The RH-CSNPs showed sustained release profiles for up to 18 h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210 ± 0.52), followed by kidneys (6.862 ± 0.62), intestine (4.862 ± 0.45), and lungs (4.640 ± 0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251 ± 0.09 and 0.386 ± 0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5 h are indicative of direct nose to brain transport, bypassing the blood-brain barrier (BBB). The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.


Pharmacology and clinical use of bivalirudin.
To review the primary literature describing the pharmacology and clinical uses of bivalirudin. A MEDLINE search (January 1966-May 2001) was conducted that used bivalirudin, hirulog, and direct thrombin inhibitor as key words. References from retrieved articles and unpublished information acquired from the manufacturer and the Internet were also used. All acquired articles that discussed the pharmacology, pharmacokinetics, and clinical efficacy of bivalirudin were reviewed. Articles were selected based on content regarding the pharmacology and clinical use of bivalirudin. Given the paucity of data pertaining to the clinical use of bivalirudin, most articles were used, including abstracts and communications with the manufacturer. Bivalirudin is a direct thrombin inhibitor that inactivates both unbound and fibrin-bound thrombin. Bivalirudin rapidly induces anticoagulation and has a relatively short duration of action. Bivalirudin displays linear kinetics and is primarily eliminated renally. Bivalirudin was proven effective in preventing postprocedural ischemic complications in patients with unstable or postinfarction angina who received percutaneous transluminal coronary angioplasty (PTCA). Yet, further investigations that include less critically ill patients and use the current clinical practice of administering glycoprotein IIb/IIIa antagonists and/or inserting intracoronary stents are needed to fully evaluate its efficacy. Bivalirudin has also induced early patency in patients with myocardial infarction in combination with streptokinase, but its use with newer thrombolytics needs to be studied. Bivalirudin has been used in patients with immunologically mediated, heparin-induced thrombocytopenia (HIT) without complications. Bleeding is the major adverse effect and occurs more commonly in patients with renal dysfunction. At present, bivalirudin is worthy of consideration in patients requiring PTCA who have HIT. Advocating the routine use of bivalirudin in patients experiencing an acute coronary syndrome or HIT is premature.


Pediatricians' attitudes toward maternal employment and substitute child care.
In 1979 more than 54% of women with children less than 18 years old were in the labor force. The purpose of this study was to study the attitudes of pediatricians toward maternal employment and substitute child care arrangements. To survey their attitudes toward maternal employment and substitute child care, we sent a questionnaire to 476 North Carolina pediatricians. The response rate was 50%. On the issue of maternal employment the attitudes were 46% favorable, 35% neutral, and 19% unfavorable. Corresponding attitudes for substitute child care were 53%, 30%, and 17%.


Outbreak of multidrug-resistant Pseudomonas aeruginosa colonization and infection secondary to imperfect intensive care unit room design.
Pseudomonas aeruginosa has been increasingly recognized for its ability to cause significant hospital-associated outbreaks, particularly since the emergence of multidrug-resistant strains. Biofilm formation allows the pathogen to persist in environmental reservoirs. Thus, multiple hospital room design elements, including sink placement and design, can impact nosocomial transmission of P. aeruginosa and other pathogens. From December 2004 through March 2006, 36 patients exposed to the intensive care unit or transplant units of a tertiary care hospital were infected with a multidrug-resistant strain of P. aeruginosa. All phenotypically similar isolates were examined for genetic relatedness by means of pulsed-field gel electrophoresis. Clinical characteristics of the affected patients were collected, and a detailed epidemiological and environmental investigation of potential sources was carried out. Seventeen of the infected patients died within 3 months; for 12 (71%) of these patients, infection with the outbreak organism contributed to or directly caused death. The source of the outbreak was traced to hand hygiene sink drains, where biofilms containing viable organisms were found. Testing by use of a commercial fluorescent marker demonstrated that when the sink was used for handwashing, drain contents splashed at least 1 meter from the sink. Various attempts were made to disinfect the drains, but it was only when the sinks were renovated to prevent splashing onto surrounding areas that the outbreak was terminated. This report highlights the importance of biofilms and of sink and patient room design in the propagation of an outbreak and suggests some strategies to reduce the risks associated with hospital sinks.


Cluster-selective 57Fe labeling of a Twitch-domain-containing radical SAM enzyme.
57Fe-specific techniques such as Mössbauer spectroscopy are invaluable tools in mechanistic studies of Fe-S proteins. However, they remain underutilized for proteins that bind multiple Fe-S clusters because such proteins are typically uniformly enriched with 57Fe. As a result, it can be unclear which spectroscopic responses derive from which cluster, and this in turn obscures the chemistry that takes place at each cluster. Herein, we report a facile method for cluster-selective 57Fe enrichment based on exchange between the protein's Fe-S clusters and exogenous Fe ions. Through a combination of inductively coupled plasma mass spectrometric and 57Fe Mössbauer spectroscopic analysis, we show that, of the two [Fe4S4] clusters in BtrN (a Twitch-domain-containing radical S-adenosyl-l-methionine (SAM) enzyme), the Fe ions in the SAM-binding cluster undergo faster exchange with exogenous Fe2+; the auxiliary cluster is essentially inert under the reaction conditions. Exploiting this rate difference allows for either of the two [Fe4S4] clusters to be selectively labeled: the SAM-binding cluster can be labeled by exchanging unlabeled BtrN with 57Fe2+, or the auxiliary cluster can be labeled by exchanging fully labeled BtrN with natural abundance Fe2+. The labeling selectivity likely originates primarily from differences in the clusters' accessibility to small molecules, with secondary contributions from the different redox properties of the clusters. This method for cluster-selective isotopic labeling could in principle be applied to any protein that binds multiple Fe-S clusters so long as the clusters undergo exchange with exogenous Fe ions at sufficiently different rates.


Micro electrical impedance spectroscopy on a needle for ex vivo discrimination between human normal and cancer renal tissues.
The ex-vivo discrimination between human normal and cancer renal tissues was confirmed using μEoN (micro electrical impedance spectroscopy-on-a-needle) by measuring and comparing the electrical impedances in the frequency domain. To quantify the extent of discrimination between dissimilar tissues and to determine the optimal frequency at which the discrimination capability is at a maximum, discrimination index (DI) was employed for both magnitude and phase. The highest values of DI for the magnitude and phase were 5.15 at 1 MHz and 3.57 at 1 kHz, respectively. The mean magnitude and phase measured at the optimal frequency for normal tissues were 5013.40 ± 94.39 Ω and -68.54 ± 0.72°, respectively; those for cancer tissues were 4165.19 ± 70.32 Ω and -64.10 ± 0.52°, respectively. A statistically significant difference (p< 0.05) between the two tissues was observed at all the investigated frequencies. To extract the electrical properties (resistance and capacitance) of these bio-tissues through curve fitting with experimental results, an equivalent circuit was proposed based on the μEoN structure on the condition that the μEoN was immersed in the bio-tissues. The average and standard deviation of the extracted resistance and capacitance for the normal tissues were 6.22 ± 0.24 kΩ and 280.21 ± 32.25 pF, respectively, and those for the cancer tissues were 5.45 ± 0.22 kΩ and 376.32 ± 34.14 pF, respectively. The electrical impedance was higher in the normal tissues compared with the cancer tissues. The μEoN could clearly discriminate between normal and cancer tissues by comparing the results at the optimal frequency (magnitude and phase) and those of the curve fitting (extracted resistance and capacitance).


High-resolution differentiation of transmissible spongiform encephalopathy strains by quantitative N-terminal amino acid profiling (N-TAAP) of PK-digested abnormal prion protein.
New forms of transmissible spongiform encephalopathy (TSE) continue to be identified, and consequently sensitive differential diagnosis is increasingly important both for the management of disease in humans and livestock and in providing confidence in the safety of the food chain. TSE diseases are associated with accumulation of protease-resistant prion protein (PrP(Sc)) and detection of this marker protein is central to diagnosis. Proteolysis by proteinase K (PK) generates protease-resistant products (PrP(res)) with partially variable N-termini. The conformation(s) of PrP(Sc) and thus the points of PK cleavage are thought to be dependent on the strain of prion disease. Western blot (WB) analysis of PrP(res) gives characteristic migration patterns that can be used to diagnose TSEs, but the relatively low resolution of this technique limits its ability to differentiate certain disease strains. Mass spectrometry (MS) has the capability to resolve these various PK cleavage sites to the level of individual amino acid residues. In the present study multiple selected reaction monitoring (mSRM) was used to detect and quantify PrP(res) N-terminal tryptic peptides by MS and thus to define the N-terminal amino acid profiles (N-TAAPs) of PrP(res) characteristic for various TSEs in sheep. The fragmentation behaviour of the N-terminal tryptic peptides was studied to allow selection of the transitions specific for each peptide. Different PrP(res) preparation methods were evaluated and the most effective approach applied to differentiate the N-TAAPs corresponding to various sheep TSE isolates. Marked differences were identified between the N-TAAPs of bovine spongiform encephalopathy (BSE) and classical scrapie, and between classical scrapie and the experimental strains SSBP/1 and CH1641, thereby validating this approach as a means of TSE-strain specific diagnosis.


In vivo toxicological effects of rel A antisense phosphorothioates in CD-1 mice.
To characterize the in vivo toxicity of phosphorothioate antisense oligonucleotides against rel A (p65 subunit of NF-kappa B transcription factor), forty-eight 6-week-old CD-1 mice were split into 4 groups (6/sex/group) receiving vehicle (phosphate-buffered saline) or doses of 50, 100, and 150 mg/kg of rel A antisense oligonucleotides intraperitoneally 3 times weekly for 2 weeks. Clinical signs of toxicity included weakness, and decreased motor activity and food consumption with body weight loss. Mortality occurred in 7 of 12 mice in the 150-mg/kg group and in 2 of 12 mice in the 100-mg/kg group, most of which died within the first 2 to 4 days of treatment. The remaining mice were necropsied on day 15. The major hematological finding was severe dose-dependent thrombocytopenia. The liver enzyme levels were mildly elevated in the serum of mid- and high-dose animals. At necropsy, increased spleen and liver weights were observed in treated mice, some of which also had mild pleural and/or peritoneal effusions. Histopathological examination revealed the likely cause of death to be acute renal failure due to renal cortical or tubular necrosis. Treatment-related changes were also found in the liver, spleen, bone marrow, and several other organs. In summary, the kidney, liver, and bone marrow (megakaryocytic lineage) were identified as the major target organs for toxicity with rel A antisense therapy.


Beryllium bis(diazaborolyl): old neighbors finally shake hands.
The synthesis of a linear beryllium bis(diazaborolyl) compound featuring the first non-cluster bond between boron and beryllium has been achieved through the reaction of Yamashita's lithium diazaborolide and BeCl2. In accord with the established chemistry of beryllium, the bonding is polar covalent in character, as determined by structural and spectroscopic analysis, as well as reactivity studies.


[Comparison of risk factors for serrated polyps and conventional adenoma and the suitable age to start colorectal cancer screening].
To compare the risk factors associated with serrated polyps (SPs) and conventional adenoma (CA). One hundred and three healthy control subjects, 100 patients with pathologically confirmed SPs and 115 with CA were randomly selected from individuals undergoing colonoscopy in Nanfang Hospital from 2012 to 2015. The demographic and clinical data were collected from the subjects, including age, gender, height, weight, hypertension, diabetes, smoking status, alcohol use, family history of colorectal cancer (CRC) and blood lipids. Among the enrolled subjects, the mean onset age of SPs was 48.87 years (95%CI: 47.22-50.52 years), significantly younger than that of CA (P%0.038). The risk factors both for SPs and CA include an advanced age, a male gender (OR%2.75 [95%CI: 1.50-5.07] for SPs, and OR%2.19 [95%CI: 1.22-3.95] for CA), and a high body mass index (OR%1.18 [95%CI: 1.06-1.30] for SPs and OR%1.20 [95%CI: 1.09-1.32] for CA. Relative to the young individuals (below 45 years of age), the middle-aged individuals (45-60 years of age) had increased risks for SPs and CA by 2.31 [95% CI: 1.46-3.65] folds and 4.10 [95%CI: 2.50-6.72] folds, respectively, and in the elderly (beyond 60 years of age), the risks further increased by 2.77 [95%CI: 1.52-5.04] folds for SPs and by 6.00 [95%CI: 3.26-11.05] folds for CA. Age was more strongly associated with CA than with SPs (OR%2.14 [95%CI: 1.21-3.78], the elderly vs the young, P%0.009). SPs and CA have common risk factors, thus the screening strategy for CA may also be applicable to SPs. As the mean onset age of SPs is earlier than 50 years and SPs may rapidly progress to a carcinogenic state, an earlier screening age needs to be considered.


A Pricing Model for Groundwater Rights in Ningxia, China Based on the Fuzzy Mathematical Model.
To reduce groundwater overexploitation and alleviate water shortages, market mechanisms are introduced to allocate water rights. Scientific and reasonable pricing of groundwater rights is key to ensuring the effectiveness of the groundwater market. Because of the complexity and uncertainty of water resources, this study calculates the price of groundwater rights based on the value of water resources with an evaluation indicator system. The system includes 14 indicators developed with a fuzzy mathematics model addressing three dimensions: environment, society, and economy. The weights of the indicators are determined through the analytic network process (ANP) and the entropy method. The results show that the price of groundwater rights in Ningxia, China increased from 5.11 yuan/m3 to 5.73 yuan/m3 between 2013 and 2017; this means the price was basically stable, with a slight increase. The ratio of residents' water fee expenditures to real disposable income also remained essentially stable, fluctuating around 0.37%, far below the normal level. These data demonstrated that the current regional water price policy does not reflect the true value of groundwater resources; there is room to increase urban water prices. Local governments need speed up water price system reforms and adopt water rights systems to optimize water resource allocations.


Electron transport in disordered graphene nanoribbons.
We report an electron transport study of lithographically fabricated graphene nanoribbons (GNRs) of various widths and lengths. At the charge neutrality point, a length-independent transport gap forms whose size is inversely proportional to the GNR width. In this gap, electrons are localized, and charge transport exhibits a transition between thermally activated behavior at higher temperatures and variable range hopping at lower temperatures. By varying the geometric capacitance, we find that charging effects constitute a significant portion of the activation energy.


Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81.
Lactic acid is a well known metabolic by-product of intense exercise, particularly under anaerobic conditions. Lactate is also a key source of energy and an important metabolic substrate, and it has also been hypothesized to be a signaling molecule directing metabolic activity. Here we show that GPR81, an orphan G-protein-coupled receptor highly expressed in fat, is in fact a sensor for lactate. Lactate activates GPR81 in its physiological concentration range of 1-20 mM and suppresses lipolysis in mouse, rat, and human adipocytes as well as in differentiated 3T3-L1 cells. Adipocytes from GPR81-deficient mice lack an antilipolytic response to lactate but are responsive to other antilipolytic agents. Lactate specifically induces internalization of GPR81 after receptor activation. Site-directed mutagenesis of GPR81 coupled with homology modeling demonstrates that classically conserved key residues in the transmembrane binding domains are responsible for interacting with lactate. Our results indicate that lactate suppresses lipolysis in adipose tissue through a direct activation of GPR81. GPR81 may thus be an attractive target for the treatment of dyslipidemia and other metabolic disorders.


Early neuropathologic effects of mild or moderate hypoxemia after controlled cortical impact injury in rats.
Hypoxemia has detrimental effects after traumatic brain injury (TBI) in both experimental models and humans. The purpose of this study was to determine the effect of mild or moderate hypoxemia on early histologic and motor functional outcome after controlled cortical impact (CCI) in rats. Anesthetized rats underwent CCI and were randomized to receive mild (FiO2 = 13%, n = 6), moderate (FiO2 = 11%, n = 9), or no (FiO2 = 33%, n = 6) hypoxemia for 30 min after trauma. Sham-operated rats without hypoxemia (n = 7) were used as controls. Motor function (beam balance latency) was assessed on days 0-5. Rats were killed 7 days after injury and their brains removed for assessment of survival of hippocampal neurons and contusion volume. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL) was performed on brain sections from rats killed at 6, 24, and 72 h after CCI and moderate hypoxemia to assess DNA fragmentation in situ. Mild and moderate hypoxemia augmented motor function deficits after CCI in a dose-dependent manner. Moderate hypoxemia after CCI reduced 7-day survival of CA3 neurons but not CA1 neurons vs. sham (55 [46-86] vs. 99 [95-130], p < 0.05, and 79 [63-86] vs. 101 [81-123], NS, respectively; % uninjured hemisphere, median [range]). The addition of mild or moderate hypoxemia did not increase contusion volume. TUNEL-positive neurons were seen in ipsilateral cortex and dentate gyrus at 6, 24, and 72 h after trauma, and in ipsilateral CA3 hippocampal neurons and thalamus at 24 and 72 h. Moderate hypoxemia augments CA3 neuronal death and early motor functional deficits after CCI. The pattern of DNA fragmentation in selectively vulnerable neurons suggests that apoptosis may play a role in the delayed neuronal death seen after TBI.


C-Reactive Protein: An Aid For Diagnosis Of Acute Appendicitis.
Delayed or wrong diagnosis of acute appendicitis in patients results in complications like perforation, gangrene, etc. which carries a significant amount of morbidity and mortality to the patients. Thus, timely diagnosis of acute appendicitis is crucial to prevent these complications. Recently, it was found that serum C-reactive protein (CRP) individually can be a useful marker, thus in resource limited settings (i.e., access to ultrasonography) simple laboratory investigation can be of extreme utility for the diagnosis of acute appendicitis. Current study aimed to ascertain and determine the role of C Reactive Protein (CRP) as a complementary test to decrease the rate of negative appendectomies in tertiary care hospitals of Pakistan. Using non-probability consecutive sampling, 112 patients with the initial diagnosis of acute appendicitis on history and clinical examination were enrolled. A blood sample was taken for serum level of CRP. Mean age was 20.8±8.6 years and 51 (45.5 %) patients were males. Pathologic review revealed 100 cases (89.3%) of acute appendicitis, 4 patients (3.6%) had perforated appendix while 8 patients (7.1%) had normal appendix. Sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of C reactive protein >24 mg/lit taking histology as gold standard came out 25.9%, 100%, 100%, 9.4% and 31.25% respectively. It was concluded that CRP >48 mg/lit is an indication of perforated appendix and when the surgeon is in fix whether to go conservatively or apply some intervention, CRP can be a good diagnostic aid.


Effects of octreotide on hepatic glycogenesis in rats with high fat diet‑induced obesity.
Reduced hepatic glycogenesis is one of the most important causes of metabolic abnormalities in non‑alcoholic fatty liver disease. Octreotide, a somatostatin analogue, has been demonstrated to promote weight loss and improve metabolic disorders in mice with high fat diet (HFD)‑induced obesity. However, whether octreotide affects hepatic glycogenesis is unknown. The aim of the present study was to verify the effects of octreotide on hepatic glycogenesis in rats with HFD‑induced obesity. Male Sprague‑Dawley rats were fed a standard diet or a HFD for 24 weeks. Obese rats from the HFD group were further divided into a HFD‑control group and an octreotide‑administered group. Rats in the latter group were injected with octreotide for 8 days. Glucose and insulin tolerance tests were performed, and the area under the curve (AUC) was calculated. Following sacrifice, their body weights and lengths, fasting plasma glucose (FPG), fasting insulin (FINS), serum triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. In addition, Lee's index and the homeostatic model assessment index were calculated. Hepatic TG, FFA levels and glycogen content were first determined. Hepatic steatosis in the obese rats was assessed based on hematoxylin and eosin and Oil Red O staining. Human hepatoblastoma HepG2 cells were divided into a control group, a palmitate (PA)‑treated group and a PA + octreotide‑treated group. Establishment of the in vitro fatty liver model using HepG2 cells was confirmed by Oil Red O staining. The expression of phosphorylated Akt and glycogen synthase kinase 3β (GSK3β) was detected by western blotting, and glycogen synthase (GS) mRNA levels were detected by reverse transcription‑quantitative polymerase chain reaction. Compared with the control group, the body weight, Lee's index, AUC of the intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test, levels of FPG, FINS, TG, TC, FFA, ALT and AST, and HOMA index values were significantly increased in the obese rats. The body weight, levels of FPG and FINS, and the HOMA index were significantly reduced following octreotide treatment, whereas the decrease in Lee's index, the blood levels of ALT, AST, TC, TG and FFA, and the AUC did not reach statistical significance. Hepatic TG and FFA levels were significantly increased and hepatic glycogen content was significantly decreased in rats with HFD‑induced obesity when compared with those in the control group. Octreotide intervention restored these alterations. The expression levels of phosphorylated Akt and GSK3β protein expression, as well as GS mRNA levels in the HFD group were lower when compared with those in the control group, whereas octreotide treatment reversed these reductions. The in vitro experiments demonstrated that the reduced levels of phosphorylated Akt and GSK3β protein, and GS mRNA in the PA‑treated group were significantly reversed by octreotide treatment. In conclusion, the results indicate that octreotide improved hepatic glycogenesis and decreased FPG concentration in rats with HFD‑induced obesity. These mechanisms may be associated with increased GS activity via the promotion of GSK3β phosphorylation. Therefore, octreotide may be regarded as a novel therapeutic strategy for HFD‑induced obesity and obesity‑associated metabolic disorders.


Hybridization of glyceraldehyde-3-phosphate dehydrogenase.
1. Glyceraldehyde-3-phosphate dehydrogenases [EC 220.127.116.11] from rabbit, pig, lobster, yeast, E. coli, and B. stearothermophilus have been subjected to hybridization in 3M NaCL. 2. Suitable mixtures of electrophoretically distinct glyceraldehyde-3-phosphate dehydrogenases were found to give five-membered by electrophoresis on cellulose acetate. 3. The thermophile enzyme did not form hybrids with any of its mesophile counterparts, presumably because it does not dissociate under the conditions used. 4. Hybridization of pig enzyme with lobster enzyme that had been inactivated by selective carboxymethylation of Cystetramer containing only one active pig enzyme subunit. Individual subunits would thus appear to express their activity independently even within hybrid tetramers formed with subunits of another species. 5. The successful hybridization of glyceraldehyde-3-phosphate dehydrogenases from evolutionarily distant sources suggests that the tertiary and quaternary structures of the enzyme have been highly conserved.


[Erythrocyte membrane abnormality and hemolytic anemias].
Screening for hemolytic anemia was established in Fukuoka University Hospital based on automated analyses of enzymes and glycolytic intermediates in suspicious blood specimens. Using the screening system, we found more than ten hemolytic anemias due to abnormalities of membrane proteins, glycolytic enzymes and hemoglobin in the last two years. In the present report, we summarize the screening system for hemolytic anemias and present two types of hemolytic anemia due to abnormalities of band 3 protein and deficiencies in band 4.2 protein.


Ad libitum vs. restricted fluid replacement on hydration and performance of military tasks.
The primary objective was to evaluate the effect of ad libitum vs. restricted fluid replacement protocol on hydration markers and performance in selected military tasks. The secondary objective was to determine if 300 ml x h(-1) could be considered a safe minimum fluid intake under the experimental conditions. Data were collected simulating a route march over 16 km. There were 57 subjects who participated in the study. The mean pre-exercise body mass of the ad libitum group was 70.4 +/- 13.3 (SD) kg compared to 69.3 +/- 8.9 kg in the restricted group. The mean total fluid intake of the ad libitum group was 2.1 +/- 0.9 L compared to 1.2 +/- 0.0 L in the restricted group. The ad libitum and restricted intake groups, respectively, lost a mean of 1.05 kg +/- 0.77 (1.5%) and 1.34 kg +/- 0.37 (1.9%). Calculated sweat rate was 608 +/- 93 ml x h(-1) compared to 762 +/- 162 ml x h(-1) in the ad libitum group. There were no significant differences for either urine specific gravity (USG) or urine osmolality (UOsm) before or after the exercise. It is not clear whether fluid intake and calculated sweat rates are causally related or explained by their codependence on a third variable; for example, the exercising metabolic rate. Thus, 300 ml x h(-1) intake could be considered a current safe minimum water intake for soldiers of similar mass under similar experimental conditions, namely similar exercise durations at equivalent exercise intensities in a moderate, dry climate.


Chidamide Suppresses the Growth of Cholangiocarcinoma by Inhibiting HDAC3 and Promoting FOXO1 Acetylation.
Inhibitors for histone deacetylases (HDACs) have been identified as epigenetic drug targets to treat a variety of malignancies through several molecular mechanisms. The present study is aimed at investigating the mechanism underlying the possible antitumor effect of the HDAC inhibitor chidamide (CDM) on cholangiocarcinoma (CCA). Microarray-based gene expression profiling was conducted to predict the expression of HDACs in CCA, which was validated in clinical tissue samples from CCA patients. Next, the proliferation, migration, invasion, autophagy, and apoptosis of human CCA QBC939 and SNU308 cells were measured following treatment with CDM at different concentrations. The acetylation level of FOXO1 in the nucleus and cytoplasm of QBC939 and SNU308 cells was determined after overexpression and suppression of HDAC3. A QBC939-implanted xenograft nude mouse model was established for further exploration of CDM roles in vitro. HDAC3 was prominently expressed in CCA tissues and indicated a poor prognosis for patients with CCA. CDM significantly inhibited cell proliferation, migration, and invasion of QBC939 and SNU308 cells, while inducing their autophagy and apoptosis by reducing the expression of HDAC3. CDM promoted FOXO1 acetylation by inhibiting HDAC3, thereby inducing cell autophagy. Additionally, CDM inhibited tumor growth in vivo via HDAC3 downregulation and FOXO1 acetylation induction. Overall, this study reveals that CDM can exhibit antitumor effects against CCA by promoting HDAC3-mediated FOXO1 acetylation, thus identifying a new therapeutic avenue for the treatment of CCA.


The Place of Complementary Medicine in the Treatment of Autistic Children.
The purpose of this study is to achieve a vision for autistic children and their parents aimed at generating interest in ideas such as "Sanitas Per Aquam" (SPA), massage and music therapy, which has begun to have widespread use and to attract attention. This cross-sectional, descriptive study was carried out with autistic children and their parents from February to April 2015 in Muğla, Turkey. The study was began by interviewing experts in the field and by developing a suitable assessment questionnaire. In order to direct the flow of conversation between the researchers and the autisitc children and their parents, the researchers conducted semi-structured face to face interviews in a form that had been determined by using reports in the literature and the opinions of experts in the field. Forty two boys (84%) and eight girls (16%) with autism participated in our study. Children in the 0 ─ 7 age group spent long time in the bathroom (P = 0.001). Boys liked to be hugged more than girls (P = 0.01). Children ages 0 ─ 7 years liked bright lighting while those 15 years of age and older liked gloomy lighting (P = 0.009). Except for these statistically significant sex- and age-related differences, no other statistically significant differences were noted in the parameters of this study. Although the result was not statistically significant, more children with mild autism disorder obeyed commands like inhale or exhale (P = 0.051). Treatment for autism spectrum disorders is not yet fully possible, so many studies are being done to alleviate some symptoms and to improve the quality of life for individuals with autism and their families. As a result of our study, whether touching the areas the children want touched and listening to their favorite music are required to stimulate the brain remain as questions in our minds.