Surgical Outcomes After Treatment of Urethral Complications Following Metoidioplasty in Transgender Men.
Several treatment options for urethral complications following metoidioplasty in transmen are described in the literature, yet little is known with regard to the surgical outcomes. The aim of this study was to analyze the surgical outcomes after treatment of urethral strictures and urethral fistulas following metoidioplasty. A multicenter retrospective cohort study was conducted with transmen treated for strictures and fistulas after metoidioplasty in 3 tertiary referral centers. The primary outcome was the recurrence-free rate after surgical treatment of urethral strictures and urethral fistulas over a time period of 3 years postoperatively. Of 96 transmen included in this study with a urethral complication, 44 (46%) experienced a urethral fistula, 31 (32%) a urethral stricture, and 21 (22%) both complications simultaneously. The recurrence-free rate for urethral strictures following endoscopic management (ie, urethral dilation or direct visual internal urethrotomy) was 61% after 1, 50% after 2, and 43% after 3 years, compared to 82% following open treatment options after 1, 2, and 3 years (P = .002). Open treatment options were Heineke-Mikulicz procedure (7/9, 78% success), excision and primary anastomosis (3/3, 100%), 2-stage without graft (9/9, 100%), pedicled flap urethroplasty (1/1, 100%), and buccal mucosa graft urethroplasty (2/4 [50%] single-stage, 1/1 [100%] 2-stage). The recurrence-free rate for small urethral fistulas located at the pendulous urethra was 79% after 1, and 72% after 2 and 3 years, compared to 45% after 1, and 41% after 2 and 3 years for large fistulas, generally located at the urethral anastomoses of the fixed urethra. Treatment options for urethral fistulas were fistulectomy (26/48, 54%), fistulectomy & (redo) colpectomy (7/11, 64%), buccal mucosa graft urethroplasty (1/1, 100%), and retubularization of the urethral plate (3/4, 75%). A colpectomy before or during reoperation of a urethral fistula at the proximal urethral anastomosis showed higher success rates compared to without a colpectomy (7/11 [64%] vs 2/13 [15%] respectively, P = .03). This study provides insight in the treatment possibilities and corresponding outcomes of urethral complications following metoidioplasty in transmen. Strengths were the relatively large sample size and the overview of multiple treatment options available. Limitations were the heterogeneity of the cohort, underexposure of some surgical modalities, and absence of patient-reported outcomes. Open surgical techniques show better long-term outcomes in the management of urethral strictures compared to endoscopic options, and a colpectomy is beneficial before or during urethral fistula repair at the proximal urethral anastomosis. de Rooij FPW, Falcone M, Waterschoot M, et al. Surgical Outcomes After Treatment of Urethral Complications Following Metoidioplasty in Transgender Men. J Sex Med 2022;19:377-384.


Hospital factors and metastatic surgery in colorectal cancer patients, a population-based cohort study.
Only a limited proportion of patients with metastatic colorectal cancer (mCRC) receives metastatic surgery (including local ablative therapy). The aim was to investigate whether hospital volume and hospital level were associated with the chance of metastatic surgery. This national cohort retrieved from the CRCBaSe linkage included all Swedish adult patients diagnosed with synchronous mCRC in 2009-2016. The association between annual hospital volume of incident mCRC patients and the chance of metastatic surgery, and survival, were assessed using logistic regression and Cox regression models, respectively. Hospital level (university/non-university) was evaluated as a secondary exposure in a similar manner. Both uni- and multivariable (adjusted for sex, age, Charlson comorbidity index, year of diagnosis, cancer characteristics and socioeconomic factors) models were fitted. A total of 1,674 (17%) out of 9,968 mCRC patients had metastatic surgery. High hospital volume was not associated with increased odds of metastatic surgery after including hospital level in the model, whereas hospital level was (odds ratio (OR) (95% confidence interval (CI)): 1.94 (1.68-2.24)). All-cause mortality was lower in university versus non-university hospitals (hazard ratio (95% CI): 0.83 (0.78-0.88)). Patients with mCRC initially cared for by a university hospital experienced a greater chance to receive metastatic surgery and had superior overall survival. High hospital volume in itself was not associated with a greater chance to receive metastatic surgery nor a greater survival probability. Additional efforts should be imposed to provide more equal care for mCRC patients across Swedish hospitals.


Characteristics of the spin-trapping reaction of a free radical derived from AAPH: further development of the ORAC-ESR assay.
The characteristics of the spin-trapping reaction in the oxygen radical absorbance capacity (ORAC)-electron spin resonance (ESR) assay were examined, focusing on the kind of spin traps. 2,2-Azobis(2-amidinopropane) dihydrochloride (AAPH) was used as a free radical initiator. The spin adducts of the AAPH-derived free radical were assigned as those of the alkoxyl radical, RO· (R=H(2)N(HN)C-C(CH(3))(2)). Among the spin traps tested, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), 5,5-dimethyl-4-phenyl-1-pyrroline N-oxide (4PDMPO), 5-(2,2-dimethyl-1,3-propoxycyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO), and 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO) were applicable to the ORAC-ESR assay. Optimal formation of spin-trapped radical adduct was observed with 1 mM AAPH, 10 mM spin trap, and 5 s UV irradiation. The calibration curve (the Stern-Volmer's plot) for each spin trap showed good linearity, and their slopes, k (SB)/k (ST), were estimated to be 87.7±2.3, 267±15, 228±9, and 213±16 for DMPO, 4PDMPO, CYPMPO, and DEPMPO, respectively. Though the k (SB)/k (ST) values for selected biosubstances varied with various spin traps, their ratios to Trolox (the relative ORAC values) were almost the same for all spin traps tested. The ORAC-ESR assay also had a very good reproducibility. The ORAC-ESR assay was conducted under stoichiometric experimental conditions. The present results demonstrate the superiority of the ORAC-ESR assay.


Development of a gas chromatography/mass spectrometry method to quantify several urinary monohydroxy metabolites of polycyclic aromatic hydrocarbons in occupationally exposed subjects.
The aim of this study was the development of a method for the determination of 12 urinary monohydroxy metabolites of PAHs, namely 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene. Analytes were determined in the presence of deuterated analogues as internal standards, by GC/MS operating in the electron impact mode. Sample preparation was performed by enzymatic hydrolysis of glucoronate and sulphate conjugates of hydroxy metabolites of PAHs, liquid-liquid extraction with n-hexane, and derivatization with a silylating reagent. The method is very specific, limits of quantification are in the range 0.1-1.4 microg/l, and range of linearity is from limit of detection to 208 microg/l. Within- and between-run precision, expressed as coefficient of variation, are <20%; accuracy for most analytes is within 20% of the theoretical value. An application of the proposed method to the analysis of 10 urine samples from coke-oven workers shows that 1-hydroxynaphthalene and 2-hydroxyfluorene were the most abundant compounds (median 61.4 and 69.7 microg/l, respectively), while 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene were always below the quantification limit.


Does a Survivorship Model of Opioid Use Disorder Improve Public Stigma or Policy Support? A General Population Randomized Experiment.
The chronic disease model of opioid use disorder (OUD) is promoted by many public health authorities, yet high levels of stigma persist along with low support for policies that would benefit people with OUD. Determine if a survivorship model of OUD, which does not imply a chronic, relapsing disease state, compared to a chronic disease model improves public stigma and support for opioid-related policies. Explore if race or gender moderates any effect. Online, vignette-based randomized study. US adults recruited through a market research firm. Participants viewed one of 8 vignettes depicting a person with OUD in sustained remission. Vignettes varied in terms of the OUD model (survivorship, chronic disease) and vignette individual's race (Black, White) and gender (man, woman). (1) Public stigma measured by desire for social distance, perceptions of dangerousness, and overall feelings toward the vignette individual. (2) Support for 7 opioid-related policies. Overall feelings were measured on a feelings thermometer (0/cold-100/warm). Stigma and policy support responses were measured on Likert scales dichotomized to indicate a positive (4, 5) or negative/indifferent (1-3) response. Of 1440 potential participants, 1172 (81%) were included in the analysis. Exposure to the survivorship model resulted in warmer feelings (mean 72, SD 23) compared to the chronic disease (mean 67, SD 23; difference 4, 95%CI 1-6). There was no effect modification from the vignette individual's race or gender. There was no significant difference between OUD models on other measures of public stigma or support for policies. The survivorship model of OUD improved overall feelings compared to the chronic disease model, but we did not detect an effect of this model on other domains of public stigma or support for policies. Further refinement and testing of this novel, survivorship model of OUD could improve public opinions.


Ruptured intracranial dermoid cyst associated with rupture of cerebral aneurysm.
Many tumors have been reported to coexist with cerebral aneurysm. However, intracranial dermoid cysts associated with cerebral aneurysm are very rare. We report a case in which rupture of a cerebral aneurysm resulted in a ruptured dermoid cyst. We present this interesting case and review current literature about the relationship between tumors and aneurysm formation.


Studies on the mechanism of metabolic stimulation in polymorphonuclear leucocytes during phagocytosis. II. Presence of the NADPH2 oxidizing activity in a myeloperoxidase-deficient subject.
1. The biochemical properties of leucocytes from a myeloperoxidase-deficient subject were compared with those of leucocytes from healthy subjects. 2. Myleoperoxidase-deficient leucocytes responded to phagocytosis of heat-killed bacteria with increased respiration, increased oxidation of glucose through the hexose monophosphate shunt and increased production of H2O2 as normal leucocytes do. 3. The ability of granules isolated from myeloperoxidase-deficient leucocytes to oxidize nicotinamide coenzymes was comparable to that of granules isolated from normal leucocytes. 4. The results argue against the hypothesis that oxidation of NADPH2 in leucocytes is performed by myeloperoxidase.


A challenging abdomino-scrotal hydrocele-successful resolution with the help of interventional radiology guided sclerosis.
Abdomino-scrotal hydrocele is a rare condition that presents in male infants. There is no consensus in the literature over treatment. We present the case of a 4-year-old boy with what was thought to be a straight forward congenital hydrocele that persisted despite ligation of a patent processus vaginalis and a Jaboulay procedure. A subsequent Magnetic Resonance Imaging scan identified a large intra-abdominal component connecting to the scrotum. Laparoscopic excision of the intra-abdominal component was performed successfully, but the hydrocele persisted. The hydrocele resolved without complication following two episodes of image intensifier guided sclerotherapy carried out by the interventional radiology team.


Relationship of EMAST and microsatellite instability among patients with rectal cancer.
Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in 60% of sporadic colon cancers and may be linked with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI-H) in which hypermethylation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and subsequent relaxation of MMR function with the biological consequences not known. We evaluated the prevalence of EMAST and MSI in a population-based cohort of rectal cancers, as EMAST has not been previously determined in rectal cancers. We analyzed 147 sporadic cases of rectal cancer using five tetranucleotide microsatellite markers and National-Cancer-Institute-recommended MSI (mononucleotide and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the polymerase chain reaction products and determined positive if at least two loci were found to have frame-shifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage and examined the samples for lymphocyte infiltration. Among this cohort of patients with rectal cancer (mean age 62.2 ± 10.3 years, 36% female, 24% African American), 3/147 (2%) showed MSI (three males, two African American) and 49/147 (33%) demonstrated EMAST. Rectal tumors from African Americans were more likely to show EMAST than Caucasians (18/37, 49% vs. 27/104, 26%, p = 0.014) and were associated with advanced stage (18/29, 62% EMAST vs. 18/53, 37%, non-EMAST p = 0.02). There was no association between EMAST and gender. EMAST was more prevalent in rectal tumors that showed peri-tumoral infiltration compared to those without (30/49, 60% EMAST vs. 24/98, 25% non-EMAST, p = 0.0001). EMAST in rectal cancer is common and MSI is rare. EMAST is associated with African-American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST are under investigation, but its association with immune cell infiltration suggests that inflammation may play a role for its development.


Baicalin can scavenge peroxynitrite and ameliorate endogenous peroxynitrite-mediated neurotoxicity in cerebral ischemia-reperfusion injury.
Baicalin is one of the principal flavonoids isolated from the dried root of Scutellaria baicalensis Georgi that has long been used to treat ischemic stroke. However, its neuroprotective mechanisms against cerebral ischemia injury are poorly understood. To explore the neuroprotective mechanisms of baicalin against cerebral ischemia reperfusion injury. In chemical systems, we conducted electron paramagnetic resonance (EPR) spin trapping experiments to evaluate the scavenging effects of baicalin on superoxide and nitric oxide, and mass spectrometry (MS) studies on the reaction of baicalin and peroxynitrite. In cellular experiments, we investigated the effects of baicalin against extraneous and endogenous peroxynitrite mediated neurotoxicity in SH-SY5Y cells treated with peroxynitrite donor, synthesized peroxynitrite and exposed to oxygen glucose deprivation and reoxygenation (OGD/RO) in vitro. Moreover, we studied the neuroprotective effects of baicalin by using a rat model of middle cerebral artery occlusion in vivo. FeTMPyP, a peroxynitrite decomposition catalyst, was used as positive control. Cell viability and apoptotic cell death was accessed by MTT assay and TUNEL assay respectively; 3-nitrotyrosine formation and infarction volume were detected by immunostaining experiments and TTC staining respectively. Baicalin revealed strong antioxidant ability by directly scavenging superoxide and reacting with peroxynitrite. Baicalin protected the neuronal cells from extraneous and endogenous peroxynitrite-induced neurotoxicity. In ischemia-reperfused brains, baicalin inhibited the formation of 3-nitrotyrosine, reduced infarct size and attenuated apoptotic cell death, whose effects were similar to FeTMPyP. Baicalin can directly scavenge peroxynitrite and the peroxynitrite-scavenging ability contributes to its neuroprotective mechanisms against cerebral ischemia reperfusion injury.


Solitary plasmacytoma of the sacrum treated with microwave ablation in conjunction with high dose of dexamethasone: A case report and review of the literature.
Plasma cell neoplasms are characterized by the neoplastic proliferation of a single clone of plasma cells. Solitary plasmacytomas most often occur in bone, but they can also be found in soft tissues. A 53-year-old male presented with localized sacral pain and urinary incontinence. His radiographic studies showed a solitary sacral plasmacytoma (i.e., involving the bone). He was successfully managed with high-dose dexamethasone and microwave ablation (MWA). Plasmacytomas of bone can be occasionally successfully managed with MWA, adjuvant cytoreduction therapy, and high doses of dexamethasone.


Differential stability of E. coli ribosomal particles and free RNA towards thermal degradation studied by microcalorimetry.
We investigated the thermal degradation of E. coli ribosomes by differential scanning microcalorimetry. The 70S particles show two distinctive and irreversible peaks upon thermal degradation. Free rRNA in solution produces, on the contrary, an unstructured denaturation profile. The thermal analysis of 50S particles shows a profile substantially identical to that observed in 70S, while 30S particles produce an unstructured denaturation pattern. Therefore the thermal behavior of the 70S particle is essentially attributable to the denaturation of the 50S subunit. Our data validate previous observations that the 50S has a more rigid structure as compared to 30S, which behaves as a 'floppy' particle. In addition our data suggest that protein/RNA interactions play a significant role to stabilize three-dimensional structures of the ribosome.


Cellular compartmentalization of salt ions and protective agents with respect to freezing tolerance of leaves : Investigations with the Halophyte Halimione portulacoides (L.) aellen.
Evidence was given that the freezing tolerance of Halimione portulacoides, a wintergreen halophyte, can be explained by protection of sensitive cellular membranes in vivo. Experiments were done with cloned cuttings of a plant from the German North Sea coast. One series received no NaCl (O-plants) the other 3% NaCl (NaCl-plants) in the nutrient solution. During the annual course Na+ and Cl- of the O-plant leaves remained on a nearly constant low level. In the leaves of the NaCl-plants Na+ and Cl- concentrations changed strongly during year and reached a maximum in winter. Potassium was always on a low level. The freezing tolerance curves showed a minimum in summer and a maximum in winter. The small difference between the freezing tolerance peaks of the NaCl- and O-plants indicated that the increased salt stress did not affect freezing tolerance very much. Freezing stress in cellular membranes, like thylacoids, acts in the same way as increasing salt concentration; consequently both together must amplify the stress. For the analysis of their ion contents chloroplasts of H. portulacoides were non-aqueously isolated from leaves with different freezing tolerance during the year. In midwinter, when freezing tolerance was highest, the chloroplasts of the NaCl-plants contained about 250 mM chloride (O-plants c. 150 mM), while the non-plastidic fraction of the cell contained about 1 M (O-plants c. 400 mM) chloride. On the other hand citrate reached high concentrations in the chloroplasts in winter. Non-volatile organic acids like citrate are known to compensate colligatively the injurious action of the inorganic salt ions on thylacoids in vitro (Heber and Santarius, 1976). The molar proportion between chloride and citrate in H. portulacoides chloroplasts decreased with increasing freezing tolerance and reached values which were protective on chloroplast membranes in vitro. This relationship in vivo with H. portulacoides provides evidence supplying the concept of colligative protection of cellular membranes. Besides citrate also malate may act as a colligatively protecting agent against the amplified salt stress by freezing.


A clinical pathological study of a granulosa cell tumor with a fatal course: case report.
The authors report a case of a granulosa cell tumor with a rapidly fatal course in a young girl of 12. The pathological characteristics (a high degree of anaplasia) are analyzed and a critical review is made, stressing the particular aspects of the case as compared with others reported in literature.


Voluntary vacation attachments to rural general practitioners: experience with pre-clinical medical students.
In view of the continuing maldistribution of medical manpower away from rural practice, a voluntary vacation rural general practitioner attachment scheme was established for pre-clinical students. The responses of the students and preceptors to these attachments are discussed.


[The influence of capillary permeability on the extravascular protein quantities as measured in situ (author's transl)].
The extravascular protein contents in the perivascular connective tissue of a rat's mesenterial plate was measured ultramicrospectrophotometrically in situ and in vivo after changing the hydrostatic and colloidosmotic pressures of the blood. We analized the perivascular area of the different microcirculatory vessels, arterioles, capillaries and venules. The perivascular protein contents, which corresponds besides arterioles to 40% and besides venules to 59% in comparison to the intravascular blood plasma, decreased in a comparison group under the osmotic influence of the perfusion liquid on the mesenterial plate. An injection of an isotonic saline solution is followed only by small fluctuations of the perivascular protein contents during one hour. After blood loss a transitional increase of extravascular protein at the perivenular area was observed indicating the mobilisation of protein depots. Around arterioles the extravascular protein contents did not change significantly. An intravenous injection of albumin solution was followed by a short-termed increase of tissue protein around the arterioles. Around the venules after 50 minutes the extravascular protein contents increased significantly. Within one hour after the changes of the permeability conditions the maximal induceable protein movements in the perivascular space were calculated as +/- 1.35 g% plasma protein concentration corresponding to a maximun protein exchange of +/- 3.1 mg ml(-1) tissue.


A simple and convenient method for producing anti-activated lymphocyte alloantisera which does not require prior absorption.
A BALB/c B cell lymphoma, 2PK-3, was found to be activation lymphocyte alloantigen (Ala-1)-positive by virtue of its ability to absorb out the cytotoxic anti-Ala-1.1-like antibody activity of an antiserum against activated BALB/c (Ala-1.1) lymphocytes. Injection of 2PK-3 cells from the spleens or ascites of lymphomatous BALB/c mice into H-2d compatible DBA/2 mice led to the rapid development of an antiserum with properties identical to anti-Ala-1.1 alloantisera. Thus, it did not significantly kill normal spleen cells from any one of 7 different strains tested, but killed over 85% of Con A- or LPS-stimulated spleen cells of 4 Ala-1.1 positive strains; activated lymphocytes of Ala-1.2 were not affected. Furthermore, these properties were seen with unabsorbed antisera. The results indicate that the Ala-1 phenotype may, in some cases, be retained on neoplastic lymphocytes and that such cells, being rapidly and easily obtained in vivo in large quantities, can serve as a convenient source of immunogen for the development of anti-Ala-1 alloantisera in certain donor-recipient combinations.


Coronary artery disease grading by cardiac CT for predicting outcome in patients with stable angina.
The coronary atheroma burden drives major adverse cardiovascular events (MACE) in patients with suspected coronary heart disease (CHD). However, a consensus on how to grade disease burden for effective risk stratification is lacking. The purpose of this study was to compare the effectiveness of common CHD grading tools to risk stratify symptomatic patients. We analyzed the 5-year outcome of 381 prospectively enrolled patients in the CORE320 international, multicenter study using baseline clinical and cardiac computer-tomography (CT) imaging characteristics, including coronary artery calcium score (CACS), percent atheroma volume, "high-risk" plaque, disease severity grading using the CAD-RADS, and two simplified CAD staging systems. We applied Cox proportional hazard models and area under the curve (AUC) analysis to predict MACE or hard MACE, defined as death, myocardial infarction, or stroke. Analyses were stratified by a history of CHD. Additional forward selection analysis was performed to evaluate incremental value of metrics. Clinical characteristics were the strongest predictors of MACE in the overall cohort. In patients without history of CHD, CACS remained the only independent predictor of MACE yielding an AUC of 73 (CI 67-79) vs. 64 (CI 57-70) for clinical characteristics. Noncalcified plaque volume did not add prognostic value. Simple CHD grading schemes yielded similar risk stratification as the CAD-RADS classification. Forward selection analysis confirmed prominent role of CACS and revealed usefulness of functional testing in subgroup with known CHD. In patients referred for invasive angiography, a history of CHD was the strongest predictor of MACE. In patients without history of CHD, a coronary calcium score yielded at least equal risk stratification vs. more complex CHD grading.


Ani s 1 and Ani s 7 recombinant allergens are able to differentiate distinct Anisakis simplex-associated allergic clinical disorders.
Diagnosis in gastro-allergic anisakiasis (GAA) is straightforward, when clinical history is combined with further allergological evaluation of specific IgE by means of skin prick test and serum specific IgE. In Anisakis simplex sensitisation associated chronic urticaria (CU+), clinical evaluation of possible previous parasitism is difficult, and positive serum specific IgE could be due to cross-reactivity or other unknown factors. In this study, we evaluated the association between IgE seropositivity to the recombinant allergens Ani s 1 and Ani s 7 and several A. simplex-associated allergic disorders. Twenty-eight patients with GAA and 40 patients with CU+ were studied and their IgE responses were compared with a control group composed of patients with chronic urticaria not sensitized to A. simplex (CU-) according to the skin prick test, as well as a group of 15 healthy subjects not referring urticaria or currently A. simplex associated symptoms. 82.1% of GAA patients and 42.5% of CU+ patients were positive for Ani s 1 (P < 0.001), while the Ani s 7 allergen was recognized by 92.9 and 92.5% of sera from patients with GAA and CU+, respectively. The combined positivity obtained for both allergens reached 100% in GAA, and 95% in CU+. IgE determinations to Ani s 1 and Ani s 7 allergens are useful to diagnose the Anisakis infections and to differentiate among several A. simplex-associated allergic disorders. The IgE responses to Ani s 1 are mainly associated with GAA, while this molecule cannot be considered a major allergen in CU+ patients.


Detection of increased intracranial pressure in trans-oral robotic thyroidectomy using optic nerve sheath diameter measurement.
During transoral robot-assisted thyroidectomy, there is a risk of increasing intracranial pressure because the site of CO2 insufflation is narrow and close to the brain. We analyzed the pre- to post-CO2 neck insufflation change in the optic nerve sheath diameter during transoral robot-assisted thyroidectomy. Changes in vital-signs, airway pressure, and arterial carbon dioxide pressure were analyzed along with postoperative complications. Among the 30 participants, the post-CO2 inflation mean optic nerve sheath diameter (5.64 ± 0.54 mm) was higher than the pre-induction diameter (4.81 ± 0.37 mm) with a mean difference of 0.83 (95% CI, 0.69-0.97; p < 0.001), but returned to baseline after CO2 deflation in most cases. One participant had sustained increased optic nerve sheath diameter (6.35 mm) associated with severe new-onset postoperative headache. Transient elevation in the intracranial pressure during low-pressure CO2 neck insufflation in the transoral robot-assisted thyroidectomy did not appear to adversely affect patients.


High-resolution magic angle spinning NMR of the neuronal tau protein integrated in Alzheimer's-like paired helical fragments.
HRMAS NMR of tau paired helical fragments assembled with heparin show an intensity decrease for those amino acids that are incorporated into the rigid core region, whereas the N-terminal amino acids maintain their full mobility.


Stimulus motion and retrospective time judgments.
The effect of stimulus motion on retrospective time judgments was investigated in four experiments. Subjects reproduced the duration of a 32-s interval which was filled by either a stationary or moving visual element presented on a computer monitor. In Experiments 1 and 4, the element moved horizontally back and forth, and in Experiments 2 and 3 it traced a circular pathway. In Experiments 1 and 2, the element moved at speeds of either 5 or 20 cm/s. In Experiment 3, it moved at a constant speed, alternating direction between clockwise and anti-clockwise rotation once every 1, 4, 8 or 16 s. In Experiment 4 the element moved at linear speeds of 1, 2, 4, 8 or 16 cm/s back and forth along a 16 cm horizontal path thereby alternating between left- and rightward motion-directions once every 16, 8, 4, 2 and 1 s, respectively. Temporal reproductions were not systematically influenced by stimulus speed. Rather, the pattern of results indicated a nonmonotonic relationship between remembered duration and the frequency of motion-direction changes; whereas remembered duration was unaffected by either infrequent or very frequent rates of changes, moderate rates of motion-changes lengthens remembered duration. These findings are discussed in relation to the change models of retrospective timing, and the claim that stimulus speed, as distinct from changes in the direction of stimulus motion, is not an important determinant of retrospective timing.


Tbx15/18/22 shares a binding site with Tbx6-r.b to maintain expression of a muscle structural gene in ascidian late embryos.
The ascidian larval tail contains muscle cells for swimming. Most of these muscle cells differentiate autonomously. The genetic program behind this autonomy has been studied extensively and the genetic cascade from maternal factors to initiation of expression of a muscle structural gene, Myl.c, has been uncovered; Myl.c expression is directed initially by transcription factor Tbx6-r.b at the 64-cell stage and then by the combined actions of Tbx6-r.b and Mrf from the gastrula to early tailbud stages. In the present study, we showed that transcription of Myl.c continued in late tailbud embryos and larvae, although a fusion protein of Tbx6-r.b and GFP was hardly detectable in late tailbud embryos. A knockdown experiment, reporter assay, and in vitro binding assay indicated that an essential cis-regulatory element of Myl.c that bound Tbx6-r.b in early embryos bound Tbx15/18/22 in late embryos to maintain expression of Myl.c. We also found that Tbx15/18/22 was controlled by Mrf, which constitutes a regulatory loop with Tbx6-r.b. Therefore, our data indicated that Tbx15/18/22 was activated initially under control of this regulatory loop as in the case of Myl.c, and then Tbx15/18/22 maintained the expression of Myl.c after Tbx6-r.b had disappeared. RNA-sequencing of Tbx15/18/22 morphant embryos revealed that many muscle structural genes were regulated similarly by Tbx15/18/22. Thus, the present study revealed the mechanisms of maintenance of transcription of muscle structural genes in late embryos in which Tbx15/18/22 takes the place of Tbx6-r.b.


Urgent Dental Care During Italian Lockdown: A Cross-sectional Survey.
On March 9, 2020, the Italian government imposed a nationwide lockdown to contain the spread of coronavirus disease 2019. Oral health services were limited to only essential services. Nonurgent treatments were postponed. This study described the management of urgent dental care in northern Italy during the lockdown, with a particular focus on the province of Brescia. A cross-sectional survey was administered to Italian dentists at the end of the lockdown (May 3, 2020). A total of 1407 dentists answered the survey. A total of 1205 dentists were included. Most of the respondents were dental owners (73.6%). About 79.7% of the dentists handled urgencies during the lockdown. The number of urgencies treated weekly was lower than that generally handled before the coronavirus disease 2019 outbreak (P < .001). Many dentists (81.2%) provided telephone consultations to evaluate symptoms. Pulpitis and abscesses were the most common urgencies (44.7% and 40.2%, respectively). Furthermore, 95% of dentists wore masks, protective eyewear, and surgical gloves while delivering nonpostponable treatments. The filtering facepiece 2 mask was used by 41.8% and 41.7% of owners and dental assistants, respectively. Financial concerns, risk of contagion, and personal protective equipment supply were indicated as the main current concerns. Our survey showed that Italian dentists took protective measures during the lockdown, thus minimizing the risk of contagion for dental health care personnel and patients. Many precautionary guidelines are now available, but a high uncertainty persists about dental health delivery during the pandemic.


Motor Difficulties and Their Effect on Participation in School-Aged Children.
The purpose was to examine whether children diagnosed with motor problems in the preschool period still exhibit motor problems at school age and the impact of these difficulties on participation. The study group comprised 60 children 7-12 years old who were referred to occupational therapy 4-6 years prior to study initiation due to motor difficulties. The control group comprised 28 age-matched children with typical development. Parents completed the Participation, Developmental Coordination Disorder and Performance Skill Questionnaire 4-6 years after treatment. Significant differences were found between children with and without motor difficulties in motor function, but not in any of the participation domains except for parental satisfaction. Children in the control group had significantly higher scores than children with motor difficulties in motor and process skills. Motor difficulties persist into school years. Children with motor difficulties manifest performance skill problems, however they succeed in narrowing the gap and participate similar to their peers.


Adequate intake to allow optimum development. Feeding and elimination in SCBU.
There are a number of options available for babies who cannot feed orally, but all babies receiving critical care must be carefully monitored for both feeding and elimination.


Lack of impact of OCTN1 gene polymorphisms on clinical outcomes of gabapentinoids in Pakistani patients with neuropathic pain.
Gabapentinoids are the first-line drugs for neuropathic pain. These drugs are the substrate of organic cation transporter (OCTN1) for renal excretion and absorption across the intestinal epithelium. Gabapentinoids exhibit wide interindividual variability in daily dosage and therapeutic efficacy which makes titration regimens prolonged for optimal efficacy. The present study aimed to investigate the possible influence of the single nucleotide polymorphism (SNP) of OCTN1 on therapeutic efficacy and safety of gabapentinoids in neuropathic pain patients of the Pakistani population. Four hundred and twenty-six patients were enrolled in the study. All participants were genotyped for OCTN1 rs1050152 and rs3792876 by PCR-RFLP method and followed up for eight weeks. The therapeutic outcomes of gabapentinoids, reduction in pain score, inadequate or complete lack of response, adverse events (AEs) in responders and discontinuation of treatment on account of AEs were recorded for all patients. There was no significant association of genotypes and alleles of both SNPs on the clinical response of gabapentinoids (P ˃ 0.05). Similarly, significant differences were not found in the reduction of pain scores and AEs among different genotypes in the responders. The present study has reported the association of OCTN1 rs1050152 and rs3792876 polymorphisms with clinical outcomes of gabapentinoids for the first time in the real-world clinical setting. Our results suggest a lack of influence of OCTN1 genetic variants in the determination of clinical response to gabapentinoids in patients with neuropathic pain in the Pakistani population. These findings signify the role of renal functions in predicting the interindividual variability to therapeutic responsiveness of gabapentinoids.


A sectional stock tray system for making impressions.
This article describes a sectional stock tray system developed by the authors for making preliminary impressions. It may be used not only for individual dental arches but also for patients with microstomia or constricted oral openings. This system allows many combinations of right and left tray sizes and forms to be assembled into a well-fitted anatomically-conforming tray in spite of individual anatomic discrepancies.


Current trends in epigenetic, cellular and molecular pathways in management of rheumatoid arthritis.
Rheumatoid arthritis is a systemic chronic polyarticular autoimmune disorder of joints and joint membrane mainly affecting feet and hands. The pathological manifestation of the disease includes infiltration of immune cells, hyperplasia of the lining of synovium, formation of pannus and bone and cartilage destruction. If left untreated, the appearance of small focal necrosis, adhesion of granulation, and formation of fibrous tissue on the surface of articular cartilage is noted. The disease primarily affects nearly 1% of the population globally, women being more affected than men with a ratio 2:1 and can initiate regardless of any age. The synovial fibroblast in rheumatoid arthritis individuals exhibits an aggressive phenotype which upregulates the manifestation of protooncogenes, adhesive compounds, inflammatory cytokines and matrix-deteriorating enzymes. Apart from the inflammatory effects of cytokines, chemokines are also noted to induce swelling and pain in arthritic individuals by residing in synovial membrane and forming pannus. The current treatment of rheumatoid arthritis includes treatment with non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, treatment with biologics such as inhibitors of TNF-α, interleukins, platelet activating factor, etc. which provides significant relief from symptoms and aids in management of the disease. The current review highlights the pathogenesis involved in the onset of rheumatoid arthritis and also covers epigenetic, cellular and molecular parameters associated with it to aid better and advanced therapeutic approaches for management of the debilitating disease.


Patellar Fracture Fixation Using Suture Tape Cerclage.
Transverse patellar fractures are a relatively common injury and typically require surgical fixation. An adequate restoration of patella integrity is essential for proper functioning of the extensor mechanism of the knee and for the prevention of patellofemoral osteoarthritis. Currently, the treatment of transverse fractures of the patellar bone involves several surgical techniques, most of which involve the use of metallic implants. Despite good clinical results following surgery, numerous complications exist, including primarily symptomatic hardware following surgical treatment. The purpose of this article is to describe the technique for treatment of a transverse patellar fracture using a high-resistance tape (FiberTape; Arthrex) and a tensioner (Arthrex) instead of traditional metallic implants.


Metabolic imaging by positron emission tomography early after myocardial infarction as a predictor of recovery of myocardial function after reperfusion.
Myocardial ischemia leads to alterations in myocardial substrate metabolism that have been shown to reflect severity of ischemic injury. The purpose of this study was to correlate oxidative metabolism with recovery of contractile function in patients with acute myocardial infarction. Regional blood flow and oxidative metabolism were assessed by dynamic positron emission tomography early after myocardial infarction treated with thrombolytic therapy in 18 patients. The extent of myocardial perfusion abnormally (carbon 11-labeled acetate uptake; relative amplitude < or = 50%) was inversely correlated with the ejection fraction obtained within 8 hours of the onset of chest pain (r = -0.81; p - 0.01) but not clearly with that at follow-up 1 week later (r = 0.64; p = 0.09). Oxidative metabolism (carbon 11-labeled acetate; monoexponential clearance) was higher in periinfarct territories with early or late recovery of contractile function than in those without, but there was a large overlap in absolute values limiting the predictive power of a single measurement. Relatively preserved oxidative metabolism compared with perfusion in low-flow areas was predictive of early (day 1 to 1 week) and delayed (week 1 to beyond 1 month) recovery. Normal resting perfusion with regionally decreased oxidative metabolism predicted early recovery of contractile function. Thus in patients studied with positron emission tomography early after myocardial infarction, comparison of regional perfusion and oxidative metabolism was more predictive of recovery in contractile function than was assessment of either one alone.


Grafting of short elastin-like peptides using an electric field.
Surface-grafted elastin has found a wide range of uses such as sensing, tissue engineering and capture/release applications because of its ability to undergo stimuli-responsive phase transition. While various methods exist to control surface grafting in general, it is still difficult to control orientation as attachment occurs. This study investigates using an electric field as a new approach to control the surface-grafting of short elastin-like polypeptide (ELP). Characterization of ELP grafting to gold via quartz crystal microbalance with dissipation, atomic force microscopy and temperature ramping experiments revealed that the charge/hydrophobicity of the peptides, rearrangement kinetics and an applied electric field impacted the grafted morphology of ELP. Specifically, an ELP with a negative charge on the opposite end of the surface-binding moiety assembled in a more upright orientation, and a sufficient electric field pushed the charge away from the surface compared to when the same peptide was assembled in no electric field. In addition, this study demonstrated that assembling charged ELP in an applied electric field impacts transition behavior. Overall, this study reveals new strategies for achieving desirable and predictable surface properties of surface-bound ELP.


Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: an observational study.
Waning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population. We estimated these population immunities in Qatar's population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case-control studies. Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped after Omicron emergence from 88.3% (95% CI: 84.8-91.0%) in November 2021 to 51.0% (95% CI: 48.3-53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0-85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5-58.2%) by November 2021. Effectiveness declined linearly by ∼1 percentage point every 5 days. After Omicron emergence, effectiveness dropped from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped after Omicron emergence from 83.0% (95% CI: 65.6-91.6%) in November 2021 to 32.9% (95% CI: 26.7-38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration. High population immunity against infection may not be sustained beyond a year, but population immunity against severe COVID-19 is durable with slow waning even after Omicron emergence. The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.


Genome-wide association study for systemic lupus erythematosus in an egyptian population.
Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.


Variance of age-specific log incidence decomposition (VALID): a unifying model of measured and unmeasured genetic and non-genetic risks.
The extent to which known and unknown factors explain how much people of the same age differ in disease risk is fundamental to epidemiology. Risk factors can be correlated in relatives, so familial aspects of risk (genetic and non-genetic) must be considered. We present a unifying model (VALID) for variance in risk, with risk defined as log(incidence) or logit(cumulative incidence). Consider a normally distributed risk score with incidence increasing exponentially as the risk increases. VALID's building block is variance in risk, Δ2, where Δ = log(OPERA) is the difference in mean between cases and controls and OPERA is the odds ratio per standard deviation. A risk score correlated r between a pair of relatives generates a familial odds ratio of exp(rΔ2). Familial risk ratios, therefore, can be converted into variance components of risk, extending Fisher's classic decomposition of familial variation to binary traits. Under VALID, there is a natural upper limit to variance in risk caused by genetic factors, determined by the familial odds ratio for genetically identical twin pairs, but not to variation caused by non-genetic factors. For female breast cancer, VALID quantified how much variance in risk is explained-at different ages-by known and unknown major genes and polygenes, non-genomic risk factors correlated in relatives, and known individual-specific factors. VALID has shown that, while substantial genetic risk factors have been discovered, much is unknown about genetic and familial aspects of breast cancer risk especially for young women, and little is known about individual-specific variance in risk.


Effective embryo production from Holstein cows treated with gonadotropin-releasing hormone during early lactation.
The low efficiency of embryo production in Holstein cows during early lactation presents many challenges for animal production. To improve its efficiency, the outcomes of single GnRH injections 48 hours before each of three cycles of ovum pick up (OPU; weeks 2, 4, and 6) were compared with three cycles of unstimulated OPU (controls; weeks 1, 3, and 5) in 35 Holstein cows during 6 weeks of early lactation (40-80 days postpartum). More total follicle numbers (19.5 vs. 16.0; P < 0.05) but fewer dominant follicles (0.5 vs. 1.4; P < 0.01) were observed by ultrasound, and more cumulus-oocyte complexes were collected in a single OPU in the treatment cycles compared with controls (15.3 vs. 11.5; P < 0.05). The numbers of morphologically "good" cumulus-oocyte complexes graded A and B in the stimulated OPUs were significantly greater than in controls (2.8 vs. 1.7 and 5.8 vs. 4.2, respectively; P < 0.05). Significantly, more oocytes stained positively with brilliant cresyl blue after GnRH treatment compared with the control cycles (13.7 vs. 9.6; P < 0.05). After in vitro fertilization, embryos in the treatment cycles had improved development (P < 0.01) during each developmental stage compared with the controls (9.0 vs. 6.2 two-cell embryos; 4.7 vs. 3.0 four-cell embryos; 3.3 vs. 2.0 morulae; and 3.0 vs. 1.7 blastocysts, respectively). Moreover, there was no significant difference in pregnancy rate of the recipient cows after embryo transfer (57.1% vs. 42.1%; P > 0.05) no matter if the embryos came from the GnRH-treated cycles or not. Thus, GnRH-stimulated OPUs improved the efficiency of embryo production in Holstein cows during early lactation. This novel method for in vitro embryo production should benefit the dairy industry.


Functional residual capacity and respiratory mechanics as indicators of aeration and collapse in experimental lung injury.
Increased functional residual capacity (FRC) and compliance are two desirable, but seldom measured, effects of positive end-expiratory pressure (PEEP) in mechanically ventilated patients. To assess how these variables reflect the morphological lung perturbations during the evolution of acute lung injury and the morphological changes from altered PEEP, we correlated measurements of FRC and respiratory system mechanics to the degree of lung aeration and consolidation on computed tomography (CT). We used a porcine oleic acid model with FRC determinations by sulfur hexafluoride washin-washout and respiratory system mechanics measured during an inspiratory hold maneuver. Within the first hour, during constant volume-controlled ventilation with PEEP 5 cm H(2)O, FRC decreased by 45% +/- 15% (P = 0.005) and compliance decreased by 35% +/- 12% (P = 0.005). Resistance increased by 60% +/- 62% (P = 0.005). Only the FRC changes correlated significantly to the decreased aeration (R(2) = 0.56; P = 0.01) and the increased consolidation (R(2) = 0.43; P = 0.04) on CT. When the PEEP was changed to either 10 or 0 cm H(2)O, there were larger changes in FRC than in compliance. We conclude that, in our model, FRC was a more sensitive indicator of PEEP-induced aeration and recruitment of lung tissue and that FRC may be a useful adjunct to PaO(2) monitoring. Lung injury was quantified on computed tomography and related to monitored values of functional residual capacity and mechanical properties of the respiratory system. We found the functional residual capacity to be a more sensitive marker of the lung perturbations than the compliance. It might be of value to include functional residual capacity in the monitoring of acute lung injury.


Electron spin resonance (ESR) spectrum of paraffin embedded human liver tissue. A possible method for the estimation of copper content.
Human liver tissues embedded in paraffin wax for histological examination have been studied by Electron Spin Resonance (ESR) spectroscopy. A signal was detected at g approximately 2.05 section of the spectrum. The amplitude of this signal was correlated with the copper content of the embedded specimens measured by flame atomic absorption technique. The positive correlation which has been found can make ESR spectroscopy suitable for estimating the copper content of tissues without damaging the sample. The limits and errors of this method have also been analysed.


Uncovering undernutrition in chronic obstructive pulmonary disease: Beyond body mass index.
Undernutrition, a common but treatable complication of chronic obstructive pulmonary disease (COPD), contributes to poor outcomes but is under-detected. Improved detection could prompt dietary intervention which may improve outcomes. We investigated whether adding a measure of muscle mass (fat-free mass index, FFMI) or a malnutrition screening tool (Mini Nutritional Assessment, MNA®) to the commonly used measure of body mass index (BMI), helps detect undernutrition in COPD. We conducted a retrospective chart review of 86 outpatients with COPD. Demographic and disease severity data were collected, and nutritional status assessed using BMI, FFMI and MNA®. Patients comprised 55% males with median age 71.5 years, severe COPD (median FEV1 = 0.74 (30.5% predicted)) and high symptom impact (median COPD Assessment Test (CAT) = 23). Twenty-eight percent of patients had low BMI, 27% had low FFMI, 22% were MNA®-classified malnourished and 43% were MNA®-classified at risk of malnutrition. MNA® correlated moderately with BMI and classified 55% of patients with healthy/high BMI as either malnourished or at risk of malnutrition. FFMI and BMI correlated strongly, and low FFMI was present in 5% of patients with healthy/high BMI. The undernutrition measures also showed weak to moderate correlations with disease severity (spirometry data) and MNA® weakly correlated with symptom impact (CAT). The MNA® identified more undernourished patients than FFMI or BMI. It also correlated with disease severity and broader symptom burden. The MNA® appears to be a simple tool for earlier detection of patients who may benefit from dietary intervention, potentially enhancing their quality of life.


Rational design of antimicrobial peptide conjugated graphene-silver nanoparticle loaded chitosan wound dressing.
Wound dressing with poor antibacterial properties, the tendency to adhere to the wound site, poor mechanical strength, and lack of porosity and flexibility are the major cause of blood loss, delayed wound repair, and sometimes causes death during the trauma or injury. In such cases, hydrogel-based antibacterial wound dressing would be a boon to the existing dressing as the moist environment will maintain the cooling temperate and proper exchange of atmosphere around the wound. In the present study, the multifunctional graphene with silver and ε-Poly-l-lysine reinforced into the chitosan matrix (CGAPL) was prepared as a nanobiocomposite wound dressing. The contact angle measurement depicted the hydrophilic property of CGAPL nanobiocomposite dressing (water contact angle 42°), while the mechanical property was 78.9 MPa. The antibacterial and cell infiltration study showed the antimicrobial property of CGAPL nanobiocomposite wound dressing. It also demonstrated no cytotoxicity to the L929 fibroblast cells. Chorioallantoic Membrane (CAM) assay showed the pro-angiogenic potential of CGAPL nanobiocomposite wound dressing. In-vitro scratch wound assay confirmed the migration of cells and increased cell adhesion and proliferation within 18 h of culture on the surface of CGAPL nanobiocomposite dressing. Later, the in-vivo study in the Wistar rat model showed that CGAPL nanobiocomposite dressing significantly enhanced the wound healing process as compared to the commercially available wound dressing Tegaderm (p-value <0.01) and Fibroheal@Ag (p-value <0.005) and obtained complete wound closure in 14 days. Histology study further confirmed the complete healing process, re-epithelization, and thick epidermis tissue formation. The proposed CGAPL nanobiocomposite wound dressing thus offers a novel wound dressing material with an efficient and faster wound healing property.


Temperature insensitivity of short-term adaptation in single-units of the chick cochlear nerve.
Short-term adaptation in acoustically stimulated chick cochlear nerve fibers has recently been shown to have similar kinetics as the readily-releasable vesicle pool in patch-clamped chick hair cells, suggesting that short-term adaptation depends on the dynamics of hair cell exocytosis. Our understanding of the relationship between these two phenomena has been hampered by differences in the temperatures at which the two types of data have been collected. In this report, the effect of temperature on short-term adaptation was studied in single-units of the chick cochlear nerve. Compared to units recorded at 38-41 degrees C, spontaneous and evoked firing rates were markedly decreased when the temperature was lowered to 28-32 degrees C, but the rate of short-term adaptation during 100 ms tone bursts was relatively unchanged, with a temperature Q(10), of approximately 1.2. The continued similarity of the adaptation time-constant of cooled units to vesicle depletion kinetics in chick hair cells measured at room temperature suggests that comparison of in vitro hair cell exocytosis and in vivo cochlear nerve firing properties may not be confounded by temperature differences between the two approaches.


Psychometric assessment of the Adolescent Physical Activity Perceived Benefits and Barriers Scales.
The purpose of this study was to psychometrically test the Adolescent Physical Activity Perceived Benefits and Barriers Scales developed for middle-school-age youth. A total of 206 racially diverse 6th, 7th, and 8th graders completed questionnaires at two time points (2 weeks apart). For the 10-item Perceived Benefits Scale and the 9-item Perceived Barriers Scale, test-retest reliability (r = .70; r = .71, respectively) and internal consistency (Cronbach's alpha was .80 and .79, respectively, at time 1) were supported. Principal components analysis with Varimax rotation was employed to assess construct validity. A 2-factor solution emerged for each scale as predicted. The relationship between both scale scores and self-reported physical activity provided additional evidence of validity. Both instruments were found to be reliable and valid for measuring the perceived benefits of and barriers to physical activity in middle school youth.


Microarray Developed on Plastic Substrates.
There is a huge potential interest to use synthetic polymers as versatile solid supports for analytical microarraying. Chemical modification of polycarbonate (PC) for covalent immobilization of probes, micro-printing of protein or nucleic acid probes, development of indirect immunoassay, and development of hybridization protocols are described and discussed.


Clinical course of cuffitis in ulcerative colitis patients with restorative proctocolectomy and ileal pouch-anal anastomoses.
Cuffitis, considered a form of reminiscent ulcerative colitis (UC), is one of the common complications of ileal pouch-anal anastomosis (IPAA) and its disease course has not been systematically characterized. The aim was to examine the disease course of cuffitis in a large historical cohort. All patients with cuffitis diagnosed based on a combined evaluation of symptom and pouch endoscopy at the initial visit to our Pouchitis Clinic were included. Pouch patients with diagnoses other than cuffitis served as controls. Patients with familial adenomatous polyposis were excluded. A total of 120 patients with cuffitis were included. The control group consisted of 811 patients (normal pouch, n = 85; irritable pouch syndrome, n = 155; acute pouchitis, n = 170; chronic pouchitis, n = 128; Crohn's disease [CD] of the pouch, n = 185; and surgical complications, n = 88). After a median follow-up of 6 years (interquartile range: 3-10 years) after pouch construction, there were 40 (33.3%) having 5-aminosalicylate (5-ASA)/steroid-responsive cuffitis; 22 (18.3%) having 5-ASA/steroid-dependent cuffitis, and 58 (48.4%) developing 5-ASA/steroid-refractory cuffitis. Further investigation of the 58 patients with refractory cuffitis showed that 19 (32.8%) had CD of the pouch and 14 (24.1%) had surgical complications including fistulae and anastomotic sinuses. There were 16 (13.3%) cuffitis patients who developed pouch failure during the follow-up period. Cuffitis may represent a spectrum of diseases. In patients with refractory cuffitis, a diagnosis of CD or surgery-associated anal transitional zone complications should be considered.


Optical coherence tomography-based misdiagnosis and morphological distinction in pachychoroid neovasculopathy vs. polypoidal choroidal vasculopathy.
To evaluate the rate of misdiagnosis of aneurysmatic pachychoroid type 1 choroidal neovascularization/polypoidal choroidal vasculopathy (PAT1/PCV) among cases diagnosed as non-aneurysmatic pachychoroid neovasculopathy (PNV) and to define optical coherence tomography (OCT) features facilitating their distinction. The database of the Department of Ophthalmology, Ludwig-Maximilians University Munich, was screened for patients diagnosed with PNV. Multimodal imaging was screened for the presence of choroidal neovascularization (CNV) and aneurysms/polyps. Imaging features facilitating the diagnosis of PAT1/PCV were analysed. In total, 49 eyes of 44 patients with a clinical PNV diagnosis were included, of which 42 (85.7%) had PNV and 7 (14.3%) represented misdiagnosed PAT1/PCV. SFCT was comparable (PNV: 377 ± 92 vs. PAT1/PCV: 400 ± 83 µm; p = 0.39). Whereas no difference was detected in total pigment epithelium detachment (PED) diameter (p = 0.46), maximum PED height was significantly higher in the PAT1/PCV group (199 ± 31 vs. 82 ± 46, p < 0.00001). In a receiver operating characteristic (ROC) analysis, the optimum cutoff for defining "peaking PED" was 158 µm with an area under the curve of 0.969, a sensitivity of 1.0 (95% CI: 0.59-1.0), and a specificity of 0.95 (95% CI: 0.84-0.99). Sub-retinal hyperreflective material (SHRM; p = 0.04), sub-retinal ring-like structures (SRRLS; p < 0.00001), and sub-RPE fluid (p = 0.04) were significantly more frequent in eyes with PAT1/PCV. A relevant percentage of eyes diagnosed with PNV might instead suffer from PAT1/PCV. The detection of a maximum PED height ("peaking PED") exceeding approximately 150 µm, SHRM, SRRLS, and sub-RPE fluid might greatly aid in the production of a more accurate diagnosis.


Contribution of hydroxyapatite to the tensile strength of the isobutyl-2-cyanoacrylate-bone bond.
The bonding strength between bone and alpha-2-cyanoacrylate polymers, with or without the addition of powdered hydroxyapatite, was determined. The tensile strength of a bone-cyanoacrylate bond was measured for each polymer: 4.31 +/- 0.88 MPa (methyl-), 5.74 +/- 0.62 MPa (ethyl-), and 8.33 +/- 0.41 MPa (isobutyl-). The tensile strength of the isobutyl-2-cyanoacrylate bond increased to 12.03 +/- 0.72 MPa with the addition of 10% (w/v) hydroxyapatite before decreasing to 7.89 +/- 0.58 MPa on addition of 15% (w/v) hydroxyapatite. An optimal concentration of hydroxyapatite significantly increased the tensile strength of a bone-cyanocacrylate bond in vitro in a manner comparable to reinforced bone replacement materials.


Are major histocompatibility system class III products independent markers for susceptibility to rheumatoid arthritis?
Three components of the complement pathway C2, Factor B, and C4 are coded for by four genes C2, Bf, C4A, and C4B in the class III region of the major histocompatibility system in man. Studies of the polymorphism of these plasma proteins have shown associations of BfS, C2C, and C4B3 (2.9) with RA. Family studies have shown that these markers occur together, usually on DR4 positive haplotypes and in particular on the A2-Cw3-Bw62-C4B3-C4A3-BfS-C2C-DR4 haplotype. It is argued that Class III gene products are unlikely to be independent markers of susceptibility to RA.


Obstetric and parental psychiatric variables as potential predictors of autism severity.
Associations between obstetric and parental psychiatric variables and subjects' Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) domain scores were examined using linear mixed effects models. Data for the 228 families studied were provided by the Autism Genetic Resource Exchange. Hypertension (P = 0.002), preeclampsia (P = 0.021) and generalized edema (P = 0.011) were associated with higher ADI-R communication scores. Hypertension (P = 0.011), albuminuria (P = 0.039) and generalized edema (P = 0.009) were associated with higher ADI-R repetitive behaviors scores. Parent depression was associated with higher ADI-R repetitive behaviors scores (P = 0.005), and parent anxiety with lower ADOS social/communication composite scores (P = 0.025). The associations between hypertension-related obstetric conditions and autistic severity warrant further investigation and raise intriguing questions regarding potential causal and modifying factors in autism.


The Efficacy of Primary Interventional Urethral Realignment for the Treatment of Traumatic Urethral Injuries.
To evaluate the efficacy of primary interventional urethral realignment (PIUR) in patients with traumatic urethral injuries. This retrospective study included 13 patients with traumatic urethral injuries who were treated with PIUR between September 2008 and February 2014. All 13 patients were men with the mean age of 56.3 years. Technical success rate of PIUR, time to PIUR, required procedure time, length of hospital stay, duration of urethral catheterization, and complications after PIUR were investigated. PIUR was technically successful in 12 of 13 patients (92.3%). The mean time from trauma to PIUR was 44 hours (range, 1-240 h). The mean procedure time was 20.2 minutes (range, 3-90 min). The median length of hospital stay was 15 days (range, 1-60 d). The mean duration of urethral catheterization after PIUR was 25 days (range, 9-65 d). There were no immediate complications related to PIUR, although 6 of 12 patients developed symptomatic urethral stricture after PIUR. The mean time to stricture development after PIUR was 4.3 months (range, 2-12 mo). Of the 6 patients, 2 were treated with endoscopic internal urethrotomy, and 4 were treated with interventional radiologic urethral balloon dilation. PIUR can be safe and effective for patients with traumatic urethral injuries. However, symptomatic stricture formation occurred in one-half of the successful realignment procedures.


Renal secretion of diphosphonates in rats.
Diphosphonates, characterized by a P--C--P bond, are relatively new experimental drugs used for the treatment of myositis ossificans, dental calculus, nephrolithiasis and Paget's disease. These compounds are not metabolized and the fraction which is not taken up by the skeleton is excreted unchanged in the urine. In the present study, the renal clearances of two 14C-labelled diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (CEHDP) and disodium dichloromethylene diphosphonate (CC12MDP) have been measured in conscious rats. The clearances have been found to be higher than the glomerular filtration rate (GFR), Cdiphosphonate/GFR being about 1.5. This observation indicates net tubular secretion of both drugs. High plasma concentration of EHDP or Cl2MDP significantly depressed CEHDP, whereas CEHDP was not influenced by varying urine pH, by infusing NH4Cl or NaHCO3, or by simultaneous administration of high doses of para-aminohippurate (PAH), probenecid, N-methylnicotinamide or Ca-EDTA. High plasma concentration of inorganic phosphate depressed CEHDP and also depressed the in vitro ultrafiltrability of EHDP. In conclusion, these results provide evidence of an active renal transport of diphosphonates which appears distinct from the mechanisms handling organic acids, organic bases and EDTA in the rat kidney.


Psychological distress among religious nonbelievers: a systematic review.
Studies of religious belief and psychological health are on the rise, but most overlook atheists and agnostics. We review 14 articles that examine differences between nonbelievers and believers in levels of psychological distress, and potential sources of distress among nonbelievers. Various forms of psychological distress are experienced by nonbelievers, and greater certainty in one's belief system is associated with greater psychological health. We found one well-documented source of distress for nonbelievers: negative perceptions by others. We provide recommendations for improving research on nonbelievers and suggest a model analogous to Pargament's tripartite spiritual struggle to understand the stresses of nonbelief.


Evaluation of uncertainties in environmental impact assessment of naturally occurring radiation exposure situations on example of undisturbed and legacy NORM sites in the Fen Complex, Norway.
The risk from naturally occurring radioactive materials (NORM) has been extensively assessed, and this has led to the integration of specific NORM radiation protection requirements within the latest EU Directive 2013/59. Nevertheless, it has been internationally recognised that remaining NORM knowledge gaps and uncertainties now present similarly significant issues in addressing recent regulatory requirements. The multi-tiered nature of environmental impact assessment (EIA) implies per se possibility for uncertainties, but when EIA at radiation exposure sites includes consideration of sites with multiple radiation and contamination sources, different ecosystem transport pathways, effects and risks by applying different parameters and models, level of overall uncertainty increases. The results of EIA study in the Fen area in Norway, comprised of undisturbed and legacy NORM sites, have been evaluated in this analysis, in order to identify all existing input uncertainties and how they may impact the final conclusions, and thus, influence any subsequent decision-making. The main uncertainties have been identified in the measurement and exposure analysis tier, and were related to the heterogeneous distribution of radionuclides, radionuclide speciation, as well as to generic variability issues in the concepts used for mobility and biota uptake analysis (such as distribution coefficient, transfer factors and concentration ratios) as well as radioecological modelling. The uncertainties in the input values to the calculation of the dose arising from radon exposure in the Fen area led to an overall elevated uncertainty of the magnitude of the radiation exposure dose of humans. It has been concluded that an integrated, ecosystem-based approach with consideration of complexity of prevailing environmental conditions and interconnections must be applied to fully understand possible radiation effects and risks.


Familial Hypercholesterolemia and Lipoprotein(a): Two Partners in Crime?
Familial hypercholesterolemia is a high cardiovascular risk disorder. We will review the role of lipoprotein(a) in cardiovascular risk and in aortic valve stenosis in familial hypercholesterolemia, as well as its association with their phenotype, and strategies to identify this high-risk population. Patients with familial hypercholesterolemia have higher lipoprotein(a) levels mainly due to an increased frequency of LPA variants, and the cardiovascular risk is increased twofolds when both conditions coexist. Also, an increased risk for aortic valve stenosis and valve replacement has been observed with high lipoprotein(a) levels. Assessment of lipoprotein(a) during the cascade screening for familial hypercholesterolemia is a good opportunity to identify this high-risk population. High cardiovascular risk in familial hypercholesterolemia is increased even more when lipoprotein(a) is also elevated. Measurement of lipoprotein(a) in these patients is crucial to identify those subjects who need to intensify LDL-cholesterol reduction pending availability of lipoprotein(a)-specific treatments.


The performance and associated mechanisms of carbon transformation (PHAs, polyhydroxyalkanoates) and nitrogen removal for landfill leachate treatment in a sequencing batch biofilm reactor (SBBR).
A modified sequencing batch biofilm reactor (SBBR, adding a pre-anoxic phase before the aeration phase) was used to treat landfill leachate. The overall SBBR operation period was divided into a load-increasing period I (69 days) and a steady operation period II (41 days). In period I, the influent total nitrogen (TN) and chemical oxygen demand (COD) concentrations increased from approximately 60 and 400 mg L-1 to 1000 and 6500 mg L-1, respectively, and these were kept for period II. In period II, the COD and TN removal rates were 83-88% and 95-98%, with effluent COD and TN concentrations of less than 500-600 and 10-20 mg L-1, respectively. The end of pre-anoxic phase PHA (polyhydroxyalkanoate) content increased from 0.11 Cmol (start of period I) to 0.22 Cmol (end of period II). The contributions from simultaneous nitrification and denitrification (SND) and endogenous denitrification to the TN removal rate were approximately 60% and 40%, respectively. The mechanisms of carbon transformation and nitrogen removal were: (1) the synthesis of PHAs in the pre-anoxic phase; (2) short-range nitrification; (3) simultaneous nitrification and denitrification (SND); and (4) endogenous denitrification. Microbial diversity analysis revealed that Proteobacteria and Bacteroidetes accounted for 89.66% of the total bacteria. Ammonia-oxidizing bacteria (AOB, Nitrosomonas) and denitrifying bacteria with the ability to transform organic matter into PHAs (Paracoccus and Thauera) are the dominant bacterial communities.


Effects of skin-chamber fluids from human allergic reactions on neutrophil activation.
We have found activated neutrophils (PMNs) in skin chambers overlying the site of ongoing human allergic reactions. To determine whether this activation is due to component(s) released early in these IgE-mediated reactions, we investigated the in vitro effects of skin chamber fluids (CF) on resting blood PMNs. These skin CF had been previously obtained, at different time periods, at pollen-antigen-challenged or buffer-control-challenged sites in sensitive human subjects. PMNs incubated with CF obtained during the first hour of antigen challenge (first-hour CF) generated significantly more superoxide (O2-) than spontaneous production (p less than 0.001) and more than PMNs incubated with first-hour buffer-site CF (p less than 0.002). A pattern similar to O2- generation was observed in lactoferrin secretion during the incubation of the three cell aliquots described above (p less than 0.001). After these incubations, the subsequent responsiveness of the PMNs present in the cell buttons to opsonized zymosan, a PMN activator, was assessed. PMNs previously incubated with first-hour CF generated significantly more net O2- in response to opsonized zymosan than did PMNs previously incubated with first-hour buffer-site CF (p less than 0.001) or buffered saline (p less than 0.001). Again, a similar difference in the patterns of net lactoferrin secretion was observed (p less than 0.02). These events were not associated with PMN damage. Analogous studies with CF previously obtained during the second- to first-hour of antigen or buffer challenge stimulated much less than first-hour CF. We conclude that one or more components released early in IgE-mediated skin reactions can activate PMNs. The nature of the activating component(s) is unknown, with no evidence of activation by histamine, antigen, or other components found to date in first-hour CF.


Circadian typologies and insomnia in individuals with internet gaming disorder comorbid with attention deficit/hyperactivity disorder.
The alteration in circadian typology and insomnia were prevalent among both Individuals with IGD and those with attention deficit hyperactivity disorder (ADHD), the most comorbid psychiatric disorder of IGD. This study aimed to evaluate the relationships between circadian typologies, insomnia, and internet gaming disorder (IGD) and how ADHD affects this relationship. We recruited three groups of 69 young adults: an IGD group, a control group comprising age- and sex-matched nongamers, and a group of gamers without IGD through diagnostic interviews. The participants with IGD exhibited lower composite scale of morningness (CSM) scores and thus a higher eveningness preference In addition, the score of Pittsburgh insomnia rating scale-20-item version (PIRS_20) was significantly higher among those with IGD. The participants with IGD and ADHD exhibited lower CSM scores but higher PRIS_20 scores than the participants with IGD but without ADHD. The present findings indicate that participants with IGD exhibited a tendency of eveningness preference and experienced more severe insomnia. ADHD exacerbated the eveningness preference and insomnia of individuals with IGD. Close attention should be paid to sleep problems in individuals with IGD, particularly to those with ADHD.


Is conflict monitoring supramodal? Spatiotemporal dynamics of cognitive control processes in an auditory Stroop task.
The electrophysiological correlates of conflict processing and cognitive control have been well characterized for the visual modality in paradigms such as the Stroop task. Much less is known about corresponding processes in the auditory modality. Here, electroencephalographic recordings of brain activity were measured during an auditory Stroop task, using three different forms of behavioral response (overt verbal, covert verbal, and manual), that closely paralleled our previous visual Stroop study. As was expected, behavioral responses were slower and less accurate for incongruent than for congruent trials. Neurally, incongruent trials showed an enhanced fronto-central negative polarity wave (N(inc)), similar to the N450 in visual Stroop tasks, with similar variations as a function of behavioral response mode, but peaking ~150 ms earlier, followed by an enhanced positive posterior wave. In addition, sequential behavioral and neural effects were observed that supported the conflict-monitoring and cognitive adjustment hypothesis. Thus, while some aspects of the conflict detection processes, such as timing, may be modality dependent, the general mechanisms would appear to be supramodal.


Intermacrocyclic Interactions upon Stepwise Oxidations in a Monometallic Porphyrin Dimer: Ring versus Metal-Center Oxidations and Effect of Counter Anions.
The effect of intermacrocyclic interactions was studied by controlled and stepwise oxidations of a monometallic silver(II) porphyrin dimer that contains a highly flexible ethane bridge. Monometallic dimers are unique systems and behave differently from their dimetallic analogues on the basis of their available sites for storing oxidizing equivalents. UV-visible spectrometry, 1 H NMR spectroscopy, XPS and single crystal X-ray diffraction studies clearly suggest the removal of the first electron from the metal center. The removal of the second electron occurred from the ring center to form a π-cation radical and, thereby, form a very unique mixed-valent species. However, unlike in all other ethane-bridged metalloporphyrin dimers reported earlier, the 2e-oxidized species showed quite unusual structures depending on the nature of counter ions. Ions, such as SbF6 , SbCl6 and PF6 , are engaged in strong interactions with the porphyrin π-cation radical and causes substantial structural changes, including large deformation of the ring. The solid-state structure remains intact in solution as well. The observations are further supported by DFT calculations.


VEGF/CDK2 are involved in diabetic organ regeneration.
Diabetes is a hyperglycaemic disease treated by a set of allopathic drugs and natural biomolecules along with many variety of stem cell. We aim to investigate the role of these drugs in targeting common protein molecule in diabetes and its associated disease. We also aim to investigate the organ degeneration mechanistic pathway in diabetes. We have generated diabetes using streptozotocin injection and treated them using bone marrow transplantation and curcumin administration. The organs were studied histopathologically and by immunofluorescence analysis while drugs were studied Pharmacogenomically. Mice injected with streptozotocin have higher glucose and lower insulin, islet number/diameter, bone marrow cell number compared to control and bone marrow transplanted and curcumin administered mice. Histopathology staining demonstrates damaged morphology of pancreas, kidney, brain and cardiac muscle. Further, upon comparison of all allopathic and ayurvedic drugs used for diabetes several protein targets have been identified by reverse pharmacophore analysis using PharmMapper. VEGF, CDK2, insulin receptor, HSp90, eNOS, Fructose1,6 bisphosphatase, neprilysin, AchE, MAPK are several common protein targets of anti-diabetic drugs. This article demonstrates that VEGF and CDK2 are critical marker in organ damage in diabetes as well as organ regeneration.


The effect of form of carboxymethyl-chitosan dressings on biological properties in wound healing.
Chitosan and its derivative have been widely used for wound healing applications, but the effect of the chitosan form on wound healing related properties has been less exploited. To this aim, water-soluble carboxymethyl-chitosan (CMCS) crosslinked by 10 wt.% genipin was fabricated in three different forms of dressings, i.e. hydrogel, membrane and sponge. The properties of dressing were evaluated and compared in terms of surface morphology, mechanical properties, water absorption rate, gas permeability, coagulation performance and biological responses in vitro and in vivo. The results showed that the prepared CMCS sponge dressing with porous structure exhibited the best water absorption, gas permeability, hemostatic performance and promoting effect on human skin fibroblast proliferation. The sponge sample overall had the highest expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1), while the CMCS hydrogel was favorable for stimulating the expression of matrix metalloproteinase-1 (MMP-1). Furthermore, the CMCS sponge dressing demonstrated the best performance in wound closure and accelerating wound repair in-vivo, showing the fastest epithelization, and best healing performance with the well-structure of epidermis and well-arranged collagen in the dermis. On the other hand, the CMCS hydrogel and membrane also demonstrated good biocompatibility, hemostatic properties and the capability to promote wound healing. Overall, CMCS sponge dressing demonstrated the optimal biological performances and excellent potential for the clinical wound healing applications.


Canine transmissible venereal tumour: assessment of mast cell numbers as indicators of the growth phase.
Mast cells are immune cells that are involved mainly in type 1 hypersensitivity reactions, and they have been implicated in tumour angiogenesis. In this study we assessed the presence of mast cell numbers and microvessel density during the progression and regression stages of natural spontaneous canine transmissible venereal tumours (CTVT). Mast cells were demonstrated by histochemical staining with toluidine blue, alcian blue and safranin O. Microvessel counts were demonstrated by immunohistochemical labelling with an antibody against the endothelial cell marker factor VIII. Mitotic cells, apoptotic cells and tumour infiltrating lymphocytes were counted from haematoxylin-eosin-stained sections. Tumour fibrosis was evaluated on Masson's trichome-stained sections. The results showed that progressing tumours had significantly higher mast cell counts and microvessel counts at the invasive edges of the tumours than did regressing tumours. In both the progressing and regressing tumours, microvessel counts were significantly positively correlated with mast cell counts. Regressing tumours had significantly higher mast cell counts of the whole tumour than progressing tumours. The results also showed that progressing tumours had significantly higher mitotic rate than regressing tumours, and fibrosis and apoptosis were significantly higher in regressing tumours than progressing tumours. There were no significant differences between the biochemical and haematological values of dogs with progressing and regressing tumours. These results suggests that mast cells play a role in CTVT progression probably by promoting vascularization at the invasion front during the progression phase, and that mast cell count could be used as one of the histological factors to indicate growth stage of CTVT.


Automatic rib unfolding in postmortem computed tomography: diagnostic evaluation of the OpenRib software compared with the autopsy in the detection of rib fractures.
The main objective of this study was to evaluate the diagnostic performance of the OpenRib software against the gold standard of autopsy in the detection of rib fractures. The secondary objective was to measure inter-rater agreement between each radiological reader. Thirty-six subjects who underwent postmortem CT and autopsy were included in this study. Rib fractures were first assessed during the autopsy by carefully dissecting and examining each rib. They were also independently evaluated by three readers using OpenRib software. This software produces from postmortem CT images a reformat of the rib cage and a display of all ribs in a single plane. Each reader was asked to determine if the rib was fractured and, if so, whether the fracture was single or multiple. After exclusions, 649 ribs were included in the statistical analysis. The two readers with a similar level of experience showed a satisfactory inter-rater agreement and a sensitivity of 0.73 and 0.83 with a specificity of 0.95 and 0.91. However, the experienced reader diagnosed significantly more fractures than the autopsy and the other two readers (p < 0.001). The use of automatic rib unfolding software in postmortem CT allows an efficient and accurate assessment of rib fractures and enables the diagnosis of fractures that cannot be detected during a standard autopsy. For now, this method seems to be the simplest that can be routinely performed; however, it requires training time in order to be sufficiently effective.


Design, synthesis, and anticancer activity of C8-substituted-4'-thionucleosides as potential HSP90 inhibitors.
A series of C8-substituted-4'-thioadenosine analogs 3a-3g, 15, and 17 and their truncated derivatives 4a-4j, 23-25, and 27 have been successfully synthesized from d-ribose and d-mannose, respectively, employing Pummerer type or Vorbrüggen condensation reactions and the functionalization at the C8-position of nucleobase via Stille coupling or nucleophilic aromatic substitution reactions as key steps. All the synthesized compounds were assayed for their HSP90 inhibitory activity, but they were found to be inactive up to 100μM. However, the 8-iodo derivatives 15, 17, and 27 exhibited potent anticancer activity, indicating that different mechanism of action might be involved in their biological activity.


Cloning and expression analysis of interferon regulatory factor (IRF) 3 and 7 in large yellow croaker, Larimichthys crocea.
The interferon regulatory factor (IRF)3 and IRF7 are considered to play essential roles in innate immune system's antiviral responses. In this report, the full-length cDNA and genomic structure and immune response characterizations of IRF3 and IRF7 were investigated in large yellow croaker, Larimichthys crocea. The full-length cDNA of L. crocea (Lc)IRF3 was of 2204 bp, including a 5'-terminal untranslated region (UTR) of 41 bp, a 3'-terminal UTR of 774 bp and an open reading frame (ORF) of 1389 bp encoding a polypeptide of 462 amino acids residues. The full-length cDNA of LcIRF7 was of 1979 bp, including a 5'-terminal UTR of 47 bp, a 3'-terminal UTR of 636 bp and an ORF of 1296 bp encoding a polypeptide of 431 amino acids. The putative amino acid sequence of both LcIRF3 and LcIRF7 contained a typical IRF domain at the N-terminal and an IRF3 domain at the C-terminal. Furthermore, we obtained 4517 nucleotides (nt) LcIRF3 genome sequence based on the full-length cDNA, which contained 11 exons and 10 introns. The full-length genome sequence of LcIRF7 was of 3991 nucleotides, including 9 exons and 8 introns. Quantitative real-time reverse transcription PCR analysis revealed a broad expression of LcIRF3 and LcIRF7 with the most predominant expression of LcIRF3 and LcIRF7 in the liver and in the gill, respectively. The expression levels of LcIRF3 and LcIRF7 after challenged with LPS, poly I:C and Vibrio parahaemolyticus were tested in blood, spleen and liver. The results showed that the highest relative expression of LcIRF3 was in the liver at 24 h after poly I:C injection with 90 times greater than that of the non-injection group (p < 0.05). Moreover, LcIRF3 transcription increased significantly at most time point in blood and spleen tissue after poly I:C stimulation compared with that of the control group. After LPS injection, the peak value of LcIRF7 was in the liver with 207 times (at 3 h) as much as that in the control group (p < 0.05). In addition, LcIRF7 expression was significantly induced by poly I:C injection in spleen. Both LcIRF3 and LcIRF7 transcripts did not show significant change after V. parahaemolyticus stimulation. These results indicated that IRF3 and IRF7 might play an important role in large yellow croaker's defense against viral and bacterial infection.


Stroke size correlates with functional outcome on the simplified modified Rankin Scale questionnaire.
Acute stroke size is one of the factors impacting functional outcome. To further validate the simplified modified Rankin Scale questionnaire (smRSq), we tested its correlation with stroke size. We screened 60 ischemic stroke patients with acute brain images available for stroke volume measurement who were enrolled in 2 smRSq reliability studies. Inclusion criteria were acute ischemic stroke visible on computed tomography (CT) or magnetic resonance imaging (MRI) and the smRSq scored at least 3 months after stroke. We excluded patients with disabilities from a previous stroke. One investigator who was blinded to the functional outcomes measured stroke volumes with a specialized computer program (Analyze). We used MRI when both MRI and CT were available. We classified strokes into 2 size categories: lacunar type measuring ≤ 6.28 cm(3), which corresponds to a cylinder with a maximum diameter and height of 2.00 cm, or strokes >6.28 cm(3). The Spearman correlation analysis compared the smRSq between the lacunar type and the larger strokes. Thirty-two patients qualified for this analysis with a mean age of 59 ± 15 years, and 17 (53%) were men. Lacunar stroke volumes (n = 17) ranged from 0.03 to 4.58 cm(3), and the larger stroke volumes (n = 15) ranged from 11.52 to 250.02 cm(3). Lacunar strokes were associated with lower smRSq scores (median 1) than the larger strokes (median 4; r = 0.68; R(2) = 0.46; P < .001). Acute stroke size correlates well with the smRSq, supporting its validity in assessing functional outcome after stroke.


[The vision organ evaluation in children with heparin modified intraocular lens implants].
The aim of the work was to estimate the vision organ state in children with IOLs-PMMA and heparin modified IOLs operated on different types of cataract. Material comprised 65 eyes with congenital, traumatic and complicated cataract in patients aged from 3 months to 17 years. Visual acuity and anatomic state of eyes with IOLs were evaluated. Results indicate the suitability of heparin modified IOLs implantation in children with different types of cataract.


Where do we stand on vascular calcification?
Vascular disease, such as atherosclerosis and diabetic vasculopathy, is frequently complicated by vascular calcification. Previously believed to be an end-stage process of unregulated mineral precipitation, it is now well established to be a multi-faceted disease influenced by the characteristics of its vascular location, the origins of calcifying cells and numerous regulatory pathways. It reflects the fundamental plasticity of the vasculature that is gradually being revealed by progress in vascular and stem cell biology. This review provides a brief overview of where we stand in our understanding of vascular calcification, facing the challenge of translating this knowledge into viable preventive and therapeutic strategies.


Integrating Information from Existing Risk Prediction Models with No Model Details.
Consider the setting where (i) individual-level data are collected to build a regression model for the association between an event of interest and certain covariates, and (ii) some risk calculators predicting the risk of the event using less detailed covariates are available, possibly as algorithmic black boxes with little information available about how they were built. We propose a general empirical-likelihood-based framework to integrate the rich auxiliary information contained in the calculators into fitting the regression model, to make the estimation of regression parameters more efficient. Two methods are developed, one using working models to extract the calculator information and one making a direct use of calculator predictions without working models. Theoretical and numerical investigations show that the calculator information can substantially reduce the variance of regression parameter estimation. As an application, we study the dependence of the risk of high grade prostate cancer on both conventional risk factors and newly identified molecular biomarkers by integrating information from the Prostate Biopsy Collaborative Group (PBCG) risk calculator, which was built based on conventional risk factors alone.


A genome variation map provides insights into the genetics of walnut adaptation and agronomic traits.
Common walnut (Juglans regia L.) is one of the top four most consumed nuts in the world due to its health benefits and pleasant taste. Despite its economic importance, the evolutionary history and genetic control of its adaptation and agronomic traits remain largely unexplored. We report a comprehensive walnut genomic variation map based on whole-genome resequencing of 815 walnut accessions. Evolutionary analyses suggest that Chinese J. regia diverged from J. sigillata with extensive hybridizations after the split of the two species. In contrast to annual crops, the genetic diversity and heterozygous deleterious mutations of Chinese common walnut trees have continued to increase during the improvement process. Selective sweep analyses identify 902 genes uniquely selected in the improved common walnut compared to its progenitor population. Five major-effect loci are identified to be involved in walnut adaptations to temperature, precipitation, and altitude. Genome-wide association studies reveal 27 genomic loci responsible for 18 important agronomic traits, among which JrFAD2 and JrANR are the potentially major-effect causative genes controlling linoleic acid content and color of the endopleura of the nut, respectively. The largest genomic resource for walnuts to date has been generated and explored in this study, unveiling their evolutionary history and cracking the genetic code for agronomic traits and environmental adaptation of this economically crucial crop tree.


Simultaneous measurement of changes in current and tracer flux in voltage-clamped squid giant axon.
A method is described for the simultaneous measurement of changes in membrane current and unidirectional radiotracer flux in internally dialyzed voltage-clamped squid giant axons. The small currents that are produced by electrogenic transport processes or steady-state ionic currents can be resolved using this method. Because the use of grounded guard electrodes in the end pools is not, by itself, an adequate means of eliminating end-effects, two ancillary end pool clamp circuits are described to eliminate extraneous current flow from the ends of the axon. The end pool voltage-clamp circuits serve to minimize net current flow between the end pools and center pool, and employ stable, low-impedance calomel electrodes to monitor the potentials of the end and center pools. The adequacy of the method is demonstrated by experiments in which unidirectional 22Na efflux and current, flowing through tetrodotoxin (TTX)-sensitive Na channels into Na-free seawater, under K-free conditions, are shown to be equal. The equality of unidirectional TTX-sensitive flux and current is maintained over the entire range of membrane potentials examined (-60 to +20 mV). The method has been applied to a series of experiments in which the voltage dependence and stoichiometry of the Na/K pump have been measured (Rakowski et al., 1989), and can be applied in general to the simultaneous measurement of changes in current and flux of other electrogenic transport processes, and of currents through ionic channels that open under steady-state conditions.