Primary radial nerve palsy in patients with acute humeral shaft fractures.
The primary aim was to report on the recovery of radial nerve function in patients with acute closed humeral shaft fractures and associated primary radial nerve palsy. The secondary aim was to report on the long-term functional outcome and health-related quality of life (HRQoL) in patients with this specific injury. Six major hospitals in Stockholm County. Descriptive study. Retrospective assessment of radial nerve recovery and fracture healing. Prospective assessment of functional outcome and HRQoL. Thirty-three patients with acute radial nerve palsy and a closed humeral shaft fracture in a population of 358 patients with 361 humeral shaft fractures. Nonoperative or operative treatment as per decision of the attending orthopedic surgeon. Recovery of the radial nerve, fracture healing, functional outcome according to the Short Musculoskeletal Function Assessment (SMFA) and the Disabilities of the Arm, Shoulder and Hand (DASH). HRQoL according to Short Form 36 (SF-36). Among the 18 patients treated nonoperatively, 16 (89%) displayed a complete recovery from their radial nerve palsy while 2 (11%) presented minor sequelae. In 11 (73%) of the 15 patients treated primarily operatively, the nerve function recovered completely while 2 patients (13%) had minor sequelae and 2 (13%) had major sequelae, i.e. 1 partial nerve palsy and 1 total radial nerve palsy. Sixteen patients (48%) were available for assessment of the long-term functional outcome and HRQoL at a mean of 7 years (range, 6 to 8 years). The range of motion and the muscular strength of the injured arm, the functional outcome according to the SMFA, and HRQoL according to the SF-36 showed results comparable to those previously reported for patients with healed humeral shaft fractures without associated radial nerve palsy. This study confirms the high spontaneous recovery rate of primary radial nerve palsies in patients with closed humeral shaft fractures. Primary radial nerve palsy should not be regarded as an isolated indication for primary surgical intervention.


Three-dimensional confocal laser scanning DNA ploidy cytometry in thick histological sections.
DNA ploidy measurement by flow (FCM) or image cytometry (ICM) of single cell suspensions of solid tumour has prognostic value, but it would be a definite advantage if the assessment could be done on histological sections. However, this is usually not possible by means of standard ICM, due to the capping of nuclei in thin sections, or overlap in thick sections. Three-dimensional (3D) microscopy by means of confocal laser scanning microscopy (CLSM) could solve this problem in theory but the results published so far are not very satisfactory. A new method has been developed in which the DNA content of haploid (human testis spermatozoa), diploid, tetraploid, octaploid (human and rat liver and human spermatogonia), and near-triploid (human breast cancer) nuclei stained with YOYO-1 iodide has been measured by a newly developed 3D image cytometry method (3DICM) in 20 microns thick histological sections. YOYO-1 iodide is a new highly sensitive, specific, stoichiometric, and stable fluorescent dye for DNA. DNA ploidy of a breast cancer which was near-triploid with FCM and ICM was also assessed with 3DICM in a tissue section adjacent to the section used for FCM and ICM and the results were compared. The integrated 3DICM fluorescence intensity showed good linearity (r = 0.99) with the real DNA content of all nuclei analysed. In human tissue, the coefficient of variation of 3DICM for haploid (n = 12), diploid (n = 63), triploid (n = 13), tetraploid (n = 12), and octaploid (n = 3) ploidy distributions was 5.1, 6.6, 4.2, 4.0, and 0.6 per cent, respectively (n = the number of nuclei). For the rat liver, the CV of the diploid (n = 21), tetraploid (n = 31), and octaploid (n = 3) peaks was 6.7, 4.8, and 1.6 per cent, respectively. Repeated "blind' measurements of nuclei with different DNA indices showed excellent reproducibility between different observers (r = 0.98). It is concluded that the 3DICM method used is accurate, reproducible, and clinically feasible in thick histological sections. This is especially important in small lesions, or if the results of DNA ploidy measurement of single cell suspensions (by FCM) or imprints (by ICM) are inadequate.


How scientists use social media to communicate their research.
Millions of people all over the world are constantly sharing an extremely wide range of fascinating, quirky, funny, irrelevant and important content all at once. Even scientists are no strangers to this trend. Social media has enabled them to communicate their research quickly and efficiently throughout each corner of the world. But which social media platforms are they using to communicate this research and how are they using them? One thing is clear: the range of social media platforms that scientists are using is relatively vast and dependent on discipline and sentiment. While the future of social media is unknown, a combination of educated speculation and persuasive fact points to the industry's continual growth and influence. Thus, is that not only are scientists utilizing social media to communicate their research, they must. The ability to communicate to the masses via social media is critical to the distribution of scientific information amongst professionals in the field and to the general population.


Egg-Independent Influenza Vaccines and Vaccine Candidates.
Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.


Effect of trypsin inhibitors on acrosome reaction of guinea pig spermatozoa.
Synthetic trypsin inhibitors known to inhibit acrosin were incubated with capacitated guinea pig spermatozoa to determine their possible effects on the membrane vesiculation and acrosomal matrix dispersion steps of the acrosome reaction. As seen by phase-contrast microscopy, the inhibitors nitrophenyl p-guanidinobenzoate, benzamidine and p-aminobenzamidine delayed acrosome reactions induced synchronously in capacitated spermatozoa. Electron microscopy revealed that the membrane vesiculation step of the acrosome reaction was unaffected by treatment of the spermatozoa with trypsin inhibitors, but that dispersion of the acrosomal matrix was blocked in the inhibitor-treated spermatozoa. These results suggest that in the guinea pig, proteinase activity (most likely that of acrosin) is involved in the dispersion of the acrosomal matrix following the membrane vesiculation step of the acrosome reaction, but not in membrane vesiculation.


HIF-1 Interacts with TRIM28 and DNA-PK to release paused RNA polymerase II and activate target gene transcription in response to hypoxia.
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that acts as a regulator of oxygen (O2) homeostasis in metazoan species by binding to hypoxia response elements (HREs) and activating the transcription of hundreds of genes in response to reduced O2 availability. RNA polymerase II (Pol II) initiates transcription of many HIF target genes under non-hypoxic conditions but pauses after approximately 30-60 nucleotides and requires HIF-1 binding for release. Here we report that in hypoxic breast cancer cells, HIF-1 recruits TRIM28 and DNA-dependent protein kinase (DNA-PK) to HREs to release paused Pol II. We show that HIF-1α and TRIM28 assemble the catalytically-active DNA-PK heterotrimer, which phosphorylates TRIM28 at serine-824, enabling recruitment of CDK9, which phosphorylates serine-2 of the Pol II large subunit C-terminal domain as well as the negative elongation factor to release paused Pol II, thereby stimulating productive transcriptional elongation. Our studies reveal a molecular mechanism by which HIF-1 stimulates gene transcription and reveal that the anticancer effects of drugs targeting DNA-PK in breast cancer may be due in part to their inhibition of HIF-dependent transcription.


Effect of Nitrous Oxide on Pulpal Anesthesia: A Preliminary Study.
To compare the success of perceived pulpal anesthesia between groups using nitrous oxide/oxygen (N2O/O2) and oxygen (O2) in children premedicated with ibuprofen with symptomatic irreversible pulpitis permanent teeth. Thirty-three children (mean age 10.4 ± 1.9 years) with 33 symptomatic irreversible pulpitis permanent teeth were included in this preliminary study. All children were premedicated with ibuprofen and randomly assigned to receive either N2O/O2 (17 participants) or O2 (16 participants). Four percent articaine with epinephrine 1:100,000 was administered, and vital pulp therapy was performed. Children used the Wong-Baker FACES Pain Rating Scale (WBFPS) to report their pain at baseline as well as during carious dentin removal, pulpal exposure, and pulpal tissue removal steps. The success was determined when the reported WBFPS score was ≤4. The chi-square test was used to compare the success between both groups. The success of pulpal anesthesia was 71% (12/17) and 19% (3/16) in the N2O/O2 and O2 groups, respectively. The success in the N2O/O2 group was 52% higher than that in the O2 group (confidence interval = 22.9% to 80.7%; significant difference p = .003). From the result of this preliminary study, N2O/O2 significantly increased the success of perceived pulpal anesthesia in children premedicated with ibuprofen with symptomatic irreversible pulpitis permanent teeth. However, further study with a larger sample is required to confirm this result.


Traumatic urethral injuries: does the digital rectal examination really help us?
The digital rectal examination (DRE) has been commonly employed as a trauma screening tool since the inception of the ATLS program. Because of weak evidence, its utility as a screening test has recently been questioned. The primary goal of this study was to identify the sensitivity of the DRE for detecting blunt urethral injuries in a level 1 trauma center. The secondary goal was to evaluate the interaction of DRE with additional clinical indices of urethral trauma. A retrospective review of all blunt injured patients diagnosed with a urethral disruption at an urban level 1 trauma center from 1995 to 2008 was performed. Urethral injuries were diagnosed by retrograde urethrogram, urethroscopy and operative exploration. Demographics and injury data were collected. The value of the DRE in diagnosing urethral trauma was assessed (p=0.05). Urethral injuries were diagnosed in 41 male patients (mean age=39 years), 34 (83%) of whom were injured via a motor vehicle (median ISS=21). Associated injuries were present in 40 (95%) patients, including 39 (95%) pelvic fractures. No clinical signs of urethral injury were evident on initial examination in 25 (61%) patients. All patients had hematuria after catheter insertion. An abnormal prostate on DRE, blood at the urethral meatus, and hematuria prior to catheter insertion was present in 1 (2%), 8 (20%) and 7 (17%) patients, respectively. Both meatal blood and hematuria were better screening tests than the DRE (p<0.05). The sensitivity of the DRE for identifying urethral disruption is 2%. The majority of patients with urethral trauma undergo urinary catheterization prior to diagnosis of the injury. Additional signs of disruption including meatal blood and hematuria detected prior to catheter insertion are also infrequent. While the DRE remains clinically indicated in patients with penetrating trauma in the vicinity of the rectum, pelvic fractures, and spinal cord injuries, it appears to be insensitive for detecting blunt urethral injuries.


Laparoscopic management of cholecystocolic fistula.
Cholecystocolic fistula is a rare complication of gallbladder disease. Its clinical presentation is variable and nonspecific, and the diagnosis is made, mostly, incidentally during intraoperative maneuver. Cholecystectomy with closure of the fistula is considered the treatment of choice for the condition, with an increasingly reproducible tendency to the use of laparoscopy. To describe the laparoscopic approach for cholecystocolic fistula and ratify its feasibility even with the unavailability of more specific instruments. After dissection of the communication and section of the gallbladder fundus, the fistula is externalized by an appropriate trocar and sutured manually. Colonic segment is reintroduced into the cavity and cholecystectomy is performed avoiding the conversion procedure to open surgery. Laparoscopy for resolution of cholecystocolic fistula isn't only feasible, but also offers a shorter stay at hospital and a milder postoperative period when compared to laparotomy.


[Phytoplankton in Yangtze River estuary and its adjacent waters in spring in 2009: species composition and size-fractionated chlorophyll a].
Based on the multidisciplinary cruise investigation in the Yangtze River estuary and its adjacent waters in April 2009, the phytoplankton species and their abundance were analyzed by the Utermöhl method, and the size-fractionated chlorophyll a concentrations were determined. In the meantime, the relationships between the dominant phytoplankton species and environmental physicochemical factors were explored by Canonical Correspondence Analysis (CCA). A total of 3 phyla, 46 genera, and 64 species (not including uncertain species) were found, mostly diatoms and dinoflagellates, with diatoms dominant. Most of these species were temperate and coastal, but a few brackish and oceanic species also presented. There were 33 diatom genera including 45 species. The dominant species were Skeletonema dohrnii, Paralia sulcata, Thalassionema nitzschioides, Pseudo-nitzschia pungens, Melosira granulata var. angustissima, Pseudo-nitzschia delicatissima, and Guinardia delicatula. The phytoplankton cell abundance ranged from 0.3 to 13447.7 cells x ml(-1), with an average of 1142.385 cells x ml(-1). Concerning the horizontal distribution, cell abundance was the highest in the middle-northern part of the survey area, with S. dohrnii dominant. The phytoplankton cell abundance was high in the surface layer water, and decreased with increasing depth. The Shannon diversity index and Pielou evenness index were consistently low in the middle-northern part of the survey area, in contrast to the trend of phytoplankton cell abundance. The chlorophyll a concentrations ranged from 0.34 to 29 g x L(-1), with an average of 3.3 g x L(-1), consistent with the cell abundance distribution. Size-fractionated chlorophyll a results showed that the biomass in the middle-northern part of the survey area was mainly composed of microphytoplankton (> 20 microm), while that in offshore waters was mainly composed of nanophytoplankton (2-20 microm) and picophytoplankton (< 2 microm). The CCA showed that the distribution of predominant species S. dohrnii was mainly affected by the water nitrate content, pH value, and microzooplankton grazing. On the contrary, the distribution of other common species including dinoflagellates was mainly associated with water salinity, and phosphate and silicate contents. The paper also compared the differences in the methods of phytoplankton quantification used by the present study and by the previous studies based on net samples. It was suggested that in future work, the autecological study of genus Skeletonema in the Yangtze River estuary and its adjacent waters should be strengthened.


Endogenous Selection Bias: The Problem of Conditioning on a Collider Variable.
Endogenous selection bias is a central problem for causal inference. Recognizing the problem, however, can be difficult in practice. This article introduces a purely graphical way of characterizing endogenous selection bias and of understanding its consequences (Hernán et al. 2004). We use causal graphs (direct acyclic graphs, or DAGs) to highlight that endogenous selection bias stems from conditioning (e.g., controlling, stratifying, or selecting) on a so-called collider variable, i.e., a variable that is itself caused by two other variables, one that is (or is associated with) the treatment and another that is (or is associated with) the outcome. Endogenous selection bias can result from direct conditioning on the outcome variable, a post-outcome variable, a post-treatment variable, and even a pre-treatment variable. We highlight the difference between endogenous selection bias, common-cause confounding, and overcontrol bias and discuss numerous examples from social stratification, cultural sociology, social network analysis, political sociology, social demography, and the sociology of education.


The role of calcineurin in the lung fibroblasts proliferation and collagen synthesis induced by basic fibroblast growth factor.
To investigate the role of calcineurin (CaN) in the lung fibroblast proliferation and collagen synthesis induced by basic fibroblast growth factor (bFGF). We used Western blot and immunohistochemical methods for investigating the content and distribution of calcineurin in the lung tissue. Calcineurin activity in different tissues was measured using (32)P-labelled substrate. In the primary culture of lung fibroblasts, (3)H-thymidine ((3)H-TdR) and (3)H-proline incorporation methods were used to study the effect of cyclosporin A (CsA), an inhibitor of calcineurin, on the lung fibroblast DNA and collagen synthesis stimulated by bFGF. We found that calcineurin was expressed in lung tissue and has phosphatase activity (7.1 +/- 2.0 pmol Pi/mg pr/min). CsA (10(-8) - 10(-6) mol/L) inhibited lung fibroblast (3)H-TdR incorporation induced by bFGF in a dose-dependent manner, with the inhibitory rates by 20%, 46% and 66% (P < 0.01). CsA (10(-7) - 10(-6) mol/L) inhibited (3)H-proline incorporation in lung fibroblasts stimulated by bFGF, with the inhibitory rates by 21% and 37% (P < 0.01). In a culture medium, CsA (10(-8) - 10(-6) mol/L) inhibited (3)H-proline secretion induced by bFGF in a dose-dependent manner, with the inhibitory rates by 19%, 29% (P < 0.05) and 56% (P < 0.01). CsA (10(-7) mol/L) could inhibit calcineurin activity by 44% in lung fibroblasts (P < 0.01). Calcineurin is expressed in lung tissue and has phosphatase activity. It is involved in the bFGF stimulated lung fibroblast DNA and collagen synthesis.


Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure.
Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed. Based on well-established renal physiological principles, an equation was derived to predict net sodium output using a spot urine sample obtained 1 or 2 hours after loop diuretic administration. This equation was then prospectively validated in 50 acute decompensated heart failure patients using meticulously obtained timed 6-hour urine collections to quantify loop diuretic-induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2-4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91; P<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (area under the curve =0.95, 95% confidence interval 0.89-1.0; P<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66; P<0.001) and lesser ability to predict poor natriuretic response (area under the curve =0.76, 95% confidence interval 0.63-0.89; P=0.002). In patients being treated for acute decompensated heart failure, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample.


[Atelectasis - bronchoscopy and unilateral ventilation].
Atelectasis in the postsurgical patient or patients on artificial ventilation problems is a frequently occurring complication. Bronchoscopy, local secretion removal by suction, lavage and vigorous positive pressure ventilation in many cases fail to re-expand the collapsed lung. Intubation after bronchoscopy by a double lumen tube permits systematic overinflation of the collapsed lung whereas the other lung is open to atmospheric pressure. In this manner the opening pressure of the collapsed lung can be overcome without overdistension of the other lung. The result is a marked improvement of oxygenation by reducing the venous admixture in lung.


Endosseous implant placement in conjunction with inferior alveolar nerve transposition: an evaluation of neurosensory disturbance.
This retrospective study evaluated neurosensory dysfunction and the implant success rate associated with 64 implants placed in 15 patients following transposition of the inferior alveolar nerve. A total of 21 inferior alveolar nerve mobilization surgeries were performed. The mean postoperative follow-up time was 41.3 months, with a range of 10 to 67 months. The effects of surgical technique and implant surface geometry on neurosensory dysfunction were evaluated by using light touch, brush stroke direction, and two-point discrimination. The implant success rate was 93.8% (60/64). The surgical technique that involved detaching the mental foramen resulted in a significantly greater incidence of neurosensory disturbance (77.8%, 7/9) than did the technique that left the bony foramen intact (33.3%, 4/12). The overall incidence of neurosensory disturbance was 52.4% (11/21).


Imaging moiré deformation and dynamics in twisted bilayer graphene.
In 'magic angle' twisted bilayer graphene (TBG) a flat band forms, yielding correlated insulator behavior and superconductivity. In general, the moiré structure in TBG varies spatially, influencing the overall conductance properties of devices. Hence, to understand the wide variety of phase diagrams observed, a detailed understanding of local variations is needed. Here, we study spatial and temporal variations of the moiré pattern in TBG using aberration-corrected Low Energy Electron Microscopy (AC-LEEM). We find a smaller spatial variation than reported previously. Furthermore, we observe thermal fluctuations corresponding to collective atomic displacements over 70 pm on a timescale of seconds. Remarkably, no untwisting is found up to 600 ∘C. We conclude that thermal annealing can be used to decrease local disorder. Finally, we observe edge dislocations in the underlying atomic lattice, the moiré structure acting as a magnifying glass. These topological defects are anticipated to exhibit unique local electronic properties.


The diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists: an assessment of interobserver variability and associated morphologic features.
The purposes of this study are to assess the level of interobserver variability in the diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists based purely on their morphologic features and to comparatively describe the cases of putative clear cell carcinoma (CCC) with and without significant interobserver variability. A total of 35 endometrial carcinomas (1 slide per case) were reviewed by 11 gynecologic pathologists (median experience: 10 y) from 11 North American institutions. The cases were selected from the files of 3 institutions on the basis of the presence of at least focal clear cells and had previously been classified as a variety of histotypes at these institutions. Diagnoses were rendered in a blinded manner and without predetermined diagnostic criteria or categories. The κ values between any pair of observers ranged from 0.18 to 0.69 (combined 0.46), which was indicative of a "moderate" level of interobserver agreement for the group. Subgroups of "confirmed CCC" [cases diagnosed as such by at least 8 (73%) of the 11 observers, n=14] and "possible CCC" (cases diagnosed as CCC by ≥1 but <8 observers, n=13) were compared with regard to a variety of semiquantified morphologic features. By combining selected morphologic features that displayed statistically significant differences between the 2 groups on univariate analyses, the following approximate morphologic profile emerged for the confirmed CCC group: papillae with hyalinized cores in ≥33% of the lesion, clear cells in ≥33% of the lesion, hyperchromasia in ≥33% of the lesion, the absence of nuclear pseudostratification in >3 cells on the papillae, the absence of nuclear pseudostratification in glands in ≥33% of the lesion, the absence of diffuse grade 3 nuclei, the absence of long and slender papillae in ≥33% of the lesion, and glands and papillae lined by cuboidal to flat, noncolumnar cells. In a backward stepwise logistic regression analysis, features from the profile that predicted the confirmed CCC group included: (1) absence or minimality of diffuse sheets of grade 3 nuclei [P=0.025; 95% confidence interval (CI), 0.0266-0.363]; (2) absence or minimality of nuclear stratification in glands and papillae (P=0.040; 95% CI, -0.228 to -0.0054); and (3) glands and papillae lined by cuboidal to flat, noncolumnar cells (P=0.008; 95% CI, 0.0911-0.566). The 2 groups displayed significant overlap regarding a wide variety of features, and no single case displayed a full complement of potentially diagnostic features. Morphologic patterns associated with cases with very high levels of interobserver variability (defined as cases with ≥4 different diagnoses rendered for them, n=9) included the near-exclusive or exclusively solid pattern of clear cells (3/9) and glandular/papillary proliferations whose only CCC-like feature was the presence of clear cells (2/9). In conclusion, the diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists is associated with a moderate level of interobserver variability. However, there is a morphologic profile that characterizes cases that gynecologic pathologists more uniformly classify as CCC, and the presence of these features is supportive of a CCC diagnosis in an endometrial carcinoma with clear cells. Cases that display broad and significant qualitative deviations from the aforementioned profile should prompt the consideration of a diagnosis other than CCC.


Not all asthma inhalers are the same: factors to consider when prescribing an inhaler.
National and international asthma guidelines stress that before making changes to patients' therapy their compliance and inhaler technique should be checked. This review addresses these issues and highlights the differences between inhalers in terms of inhaler technique, individual ability/competence, and ease of use. The advantages and disadvantages of metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) are presented. The reformulation of beclometasone MDIs is discussed since there has been some confusion over prescribing and Regulatory Authorities have recommended that these should be prescribed by brand name and not generically. This review should provide prescribers with an update to help them appreciate the differences between inhalers thereby optimising each patient's inhaled treatment.


Systemic circulation of poly(L-lysine)/DNA vectors is influenced by polycation molecular weight and type of DNA: differential circulation in mice and rats and the implications for human gene therapy.
Effective gene therapy for diseases of the circulation requires vectors capable of systemic delivery. The molecular weight of poly(L-lysine) (pLL) has a significant effect on the circulation of pLL/DNA complexes in mice, with pLL(211)/DNA complexes displaying up to 20 times greater levels in the blood after 30 minutes compared with pLL(20)/DNA. It is shown that pLL(20)/DNA complexes fix mouse complement C3 in vitro, independent of immunoglobulin binding; are less soluble in the blood in vivo; bind erythrocytes; are rapidly removed by the liver, where they associate predominantly with Kupffer cells; and result in a rapid increase in hepatic leukocytes expressing high levels of complement receptor 3 (CR3). The circulation properties of these complexes are also dependent on the type of DNA used, with circular plasmid DNA complexes exhibiting increased circulation compared with linear DNA. PLL(211)/DNA complexes bind erythrocytes and associate with Kupffer cells but, in contrast, do not fix mouse complement in vitro and are unaffected by the type of DNA used. In rats, both types of complexes produce hematuria and are rapidly removed from the circulation. Correlation of in vivo and in vitro results suggests that the solubility of complexes in physiological saline and species-matched complement fixation and erythrocyte lysis may correlate with systemic circulation. Analysis using human blood in vitro shows no hemolysis, but both types of complexes fix complement and bind IgG, suggesting that pLL/DNA complexes may be rapidly cleared from the human circulation.


Fast generation of 3-D deformable moving surfaces.
Dynamic surface modeling is an important subject of geometric modeling due to their extensive applications in engineering design, entertainment and medical visualization. Many deformable objects in the real world are dynamic objects as their shapes change over time. Traditional geometric modeling methods are mainly concerned with static problems, therefore unsuitable for the representation of dynamic objects. Apart from the definition of a dynamic modeling problem, another key issue is how to solve the problem. Because of the complexity of the representations, currently the finite element method or finite difference method is usually used. Their major shortcoming is the excessive computational cost, hence not ideal for applications requiring real-time performance. We propose a representation of dynamic surface modeling with a set of fourth order dynamic partial differential equations (PDEs). To solve these dynamic PDEs accurately and efficiently, we also develop an effective resolution method. This method is further extended to achieve local deformation and produce n-sided patches. It is demonstrated that this new method is almost as fast and accurate as the analytical closed form resolution method and much more efficient and accurate than the numerical methods.


Mazabraud's Syndrome: A Case Report and Up-To-Date Literature Review.
Mazabraud's syndrome is a rare form of bone fibrous dysplasia associated with intramuscular myxomas. Fibrous dysplasia, is generally localized to pelvis and femur and it results in a fragile bone with deformities, pain, pathological fractures and functional impairment. Intramuscular myxomas, are rare benign mesenchymal neoplasms that exceptionally may evolve to malignant forms. This case report describes a 66-year-old woman with Mazabraud's Syndrome (MS), characterized both by monostotic right femur fibrous dysplasia and by a solitary intramuscular myxoma at the right quadriceps muscle, that underwent a long-term treatment (4 years) with intravenous zoledronic acid. Zoledronic acid therapy rapidly lowered bone pain together with a reduction of intramuscular myxoma volume, but did not affect the extension of fibrous dysplasia. No adverse effects have been observed during treatment. Highly active bisphosphonates are commonly used for the treatment of bone metabolic disorders and they are generally well tolerated. Zoledronic acid may represent a promising alternative to surgical intervention in MS, although its use in rare form of bone fibrous dysplasias is still controversial.


IgE antibodies to Staphylococcus aureus. Prevalence in patients with atopic dermatitis.
We determined the prevalence of IgE antibodies to Staphylococcus aureus by optimized immunoradiometric assay methods in serum specimens from 69 patients with atopic dermatitis. All patients had positive aerobic cultures for S aureus from skin. Significant binding attributable to IgE antibodies was noted in three of 25 patients with atopic dermatitis and superimposed impetiginization or pustules, but antibodies were not detected in the remaining 44 patients whose lesions were colonized with S aureus. By comparison, IgE antibodies to S aureus were uniformly present in high titer in serum samples from patients with the hyperimmunoglobulin E syndrome. We conclude that most patients with atopic dermatitis do not have detectable levels of IgE antibodies to S aureus.


Talking to the family after an autopsy.
Few physicians have opportunities that can match the pathologist's to bring compassion and understanding to the bereaved by means of the postautopsy consultation with families. The emotional responses of survivors are often dominated by guilt. Practical guidelines for talking to the bereaved consist of the honesty , compassion, and common sense of the pathologist.


Components of delay time in suspected acute myocardial infarction with particular emphasis on patient delay.
Two hundred and thirty-four patients admitted to a coronary care unit (CCU) were interviewed a few days after arrival in hospital to determine reasons for patient delay and the various components of total delay time from onset of symptoms to arrival in CCU. Of the three major components of delay, decision time (time from onset of symptoms to decision to go to hospital), and hospital procedure time (time from arrival in hospital to arrival in the CCU), were of the same magnitude, 1 h 15 min and 1 h 30 min (median), whereas the median time for preparation and transportation to hospital was somewhat shorter, being 45 min. Decision time appeared to be similar in patients with confirmed and non-confirmed acute myocardial infarction (AMI) and was not associated with intensity of pain or infarct size. Half of the patients hesitated to go to hospital, which resulted in a prolonged decision delay (3 h). It is concluded that patient indecision to seek medical help is the most important reason for delay in hospital arrival in patients with suspected AMI.


Role of Absorbing Nanocrystal Cores in Soft Photonic Crystals: A Spectroscopy and SANS Study.
Periodic superstructures of plasmonic nanoparticles have attracted significant interest because they can support coupled plasmonic modes, making them interesting for plasmonic lasing, metamaterials, and as light-management structures in thin-film optoelectronic devices. We have recently shown that noble metal hydrogel core-shell colloids allow for the fabrication of highly ordered 2-dimensional plasmonic lattices that show surface lattice resonances as the result of plasmonic/diffractive coupling (Volk, K.; Fitzgerald, J. P. S.; Ruckdeschel, P.; Retsch, M.; König, T. A. F.; Karg, M. Reversible Tuning of Visible Wavelength Surface Lattice Resonances in Self-Assembled Hybrid Monolayers. Adv. Optical Mater. 2017, 5, 1600971, DOI: 10.1002/adom.201600971). In the present work, we study the photonic properties and structure of 3-dimensional crystalline superstructures of gold hydrogel core-shell colloids and their pitted counterparts without gold cores. We use far-field extinction spectroscopy to investigate the optical response of these superstructures. Narrow Bragg peaks are measured, independently of the presence or absence of the gold cores. All crystals show a significant reduction in low-wavelength scattering. This leads to a significant enhancement of the plasmonic properties of the samples prepared from gold-nanoparticle-containing core-shell colloids. Plasmonic/diffractive coupling is not evident, which we mostly attribute to the relatively small size of the gold cores limiting the effective coupling strength. Small-angle neutron scattering is applied to study the crystal structure. Bragg peaks of several orders clearly assignable to an fcc arrangement of the particles are observed for all crystalline samples in a broad range of volume fractions. Our results indicate that the nanocrystal cores do not influence the overall crystallization behavior or the crystal structure. These are important prerequisites for future studies on photonic materials built from core-shell particles, in particular, the development of new photonic materials from plasmonic nanocrystals.


Simultaneous separation and identification of all structural isomers and enantiomers of aminobutyric acid using a highly sensitive chiral resolution labeling reagent.
Aminobutyric acid has structural isomers (α-, β-, and γ-aminobutyric acids) and enantiomers (D/L-forms) with various unique functions. Therefore, a quantitative method for determining the content of each aminobutyric acid must be developed. In general, quantitative simultaneous analysis of multiple compounds is conducted via high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). However, simultaneous separation and highly sensitive detection of all aminobutyric acids are complicated, so highly sensitive analytical methods for the separation and identification of each compound have not yet been established. We previously developed highly sensitive chiral resolution labeling reagents. Herein, we propose a highly sensitive analytical method for the simultaneous separation and identification of all aminobutyric acids via LC-MS and labeling with our original highly sensitive chiral resolution labeling reagent, 1-fluoro-2,4-dinitrophenyl-5-L-valine-N,N-dimethylethylenediamine amide (L-FDVDA). The labeling reagent was completely bound to all aminobutyric acids through incubation overnight (>15 h) at 50 °C. Additionally, the labeled aminobutyric acids could be stored for at least 1 week at 4 °C. Furthermore, we demonstrated simultaneous separation and identification of aminobutyric acids in biological samples and foods through LC-MS using a C18 column after labeling with L-FDVDA. Our method is expected to be adopted for the analysis of the contents of all aminobutyric acids in biological and clinical samples as well as various foods.


[Dimensional measures in autism spectrum disorders: do we know what we measure?].
In the last decades, researchers often used measures to quantify autism spectrum disorder (ASD) traits, paralleling the tendency to describe psychiatric and developmental disorders more dimensionally. The broader autism phenotype (BAP) concept originates from this kind of research. The primary aim of our studies was to study the existence of the BAP and the familial transmission of quantitative autism traits (QAT). We measured ASD-traits with interviews and questionnaires in all members of 170 families with at least one child with ASD. We confirmed the existence of the BAP in fathers, as well as the familial transmission of QAT. The results also suggest that what is measured with these questionnaires might depend on the population and the context. Based on our results and additional data from scientific literature, we reflect on the interpretations of research results and the use of quantitative scales in both research and clinical practice.


Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper, canine parvovirus infection and rabies.
Wild dogs Lycaon pictuis (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.


Concurrent and predictive validities of the Bayley Motor Scale and the Peabody Developmental Motor Scales.
Concurrent and predictive validities of the Bayley Motor Scale and the Peabody Developmental Motor Scales were examined by administering both tests to 23 full-term and 21 healthy premature infants at 12, 15, and 18 months of age. For both groups, a correlation analysis of age-equivalent scores indicated Bayley scores had good to high correlation with Peabody gross motor scores (range, r = .78 to r = .96) and unacceptable correlation with Peabody fine motor scores (range, r = .20 to r = .57). When results were reported using standardized quotients, mean Bayley quotients for the full-term infant group were significantly higher than Peabody gross motor quotients. Prediction of motor development at 18 months of age was limited (range, r = .25 to r = .60), with the exception of Peabody fine motor scores for the premature infant group (r = .75). This study provides evidence of concurrent validity between Bayley motor and Peabody gross motor age-equivalent scores, and it suggests the need for further testing, using separate assessments of gross motor and fine motor ability, to determine motor development at later ages.


Co-actors Exhibit Similarity in Their Structure of Behavioural Variation That Remains Stable Across Range of Naturalistic Activities.
Human behaviour, along with any natural/biological behaviour, has varying degrees of intrinsic 'noise' or variability. Many studies have shown that the structure or patterning of this variability is sensitive to changes in task and constraint. Furthermore, two or more humans interacting together often begin to exhibit similar structures of behavioural variability (i.e., the patterning of their behavioural fluctuations becomes aligned or matched) independent of any moment-to-moment synchronization (termed complexity matching). However, much of the previous work has focused on a subset of simple or contrived behaviours within the context of highly controlled laboratory tasks. In the current study, individuals and pairs performed five self-paced (unsupervised), semi-structured activities around a university campus. Empatica E4 wristbands and iPhones were used to record the participants' behavioural activity via accelerometers and GPS. The results revealed that the structure of variability in naturalistic human behaviour co-varies with the task-goal constraints, and that the patterning of the behavioural fluctuations exhibited by co-acting individuals does become aligned during the performance of everyday activities. The results also revealed that the degree of complexity matching that occurred between pairs remained invariant across activity type, indicating that this measure could be employed as a robust, task-independent index of interpersonal behaviour.


Network-Level Structure-Function Relationships in Human Neocortex.
The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between structural and functional connections, much less is known about how large-scale coherent functional network patterns emerge from the topology of structural networks. In the present study, we deploy a multivariate statistical technique, partial least squares, to investigate the association between spatially extended structural networks and functional networks. We find multiple statistically robust patterns, reflecting reliable combinations of structural and functional subnetworks that are optimally associated with one another. Importantly, these patterns generally do not show a one-to-one correspondence between structural and functional edges, but are instead distributed and heterogeneous, with many functional relationships arising from nonoverlapping sets of anatomical connections. We also find that structural connections between high-degree hubs are disproportionately represented, suggesting that these connections are particularly important in establishing coherent functional networks. Altogether, these results demonstrate that the network organization of the cerebral cortex supports the emergence of diverse functional network configurations that often diverge from the underlying anatomical substrate.


Processing directed acyclic graphs with recursive neural networks.
Recursive neural networks are conceived for processing graphs and extend the well-known recurrent model for processing sequences. In Frasconi et al. (1998), recursive neural networks can deal only with directed ordered acyclic graphs (DOAGs), in which the children of any given node are ordered. While this assumption is reasonable in some applications, it introduces unnecessary constraints in others. In this paper, it is shown that the constraint on the ordering can be relaxed by using an appropriate weight sharing, that guarantees the independence of the network output with respect to the permutations of the arcs leaving from each node. The method can be used with graphs having low connectivity and, in particular, few outcoming arcs. Some theoretical properties of the proposed architecture are given. They guarantee that the approximation capabilities are maintained, despite the weight sharing.


Meta‑analysis of single-incision laparoscopic versus multi-trocar laparoscopic totally extraperitoneal inguinal hernia repair.
Whether single-incision laparoscopic totally extraperitoneal (SIL-TEP) inguinal hernia repair is similar or superior to multi-trocar laparoscopic totally extraperitoneal (MTL-TEP) inguinal hernia repair is controversial. We conducted this meta-analysis to compare the safety, efficacy and cosmetic effect of the two surgical methods. We systematically searched the Cochrane Library, Embase database and PubMed database for published studies on SIL-TEP and MTL-TEP inguinal hernia repair. The studies were screened and evaluated for quality according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for meta-analysis. Twenty studies were included, including 7 randomized controlled studies and 13 nonrandomized controlled studies. Meta-analysis revealed no significant difference between SIL-TEP and MTL-TEP inguinal hernia repair in terms of unilateral operation time (P = 0.12), bilateral operation time (P = 0.72), pain score on the first day after operation (P = 0.61], chronic pain rate (P = 0.61), total complication rate (P = 0.26), hospital stay (P = 0.72), and recurrence rate (P = 0.83), but the cosmetic effect score (P = 0.002) was higher in the former. These findings demonstrate that SIL-TEP inguinal hernia repair is safe, reliable and feasible. In addition, it can result in a better cosmetic effect of the incision than MTL-TEP inguinal hernia repair. SIL-TEP inguinal hernia repair should be considered for patients with stricter cosmetic requirements.Clinical trial registration: INPLASY2022110085.


Protective effect of a 43 kD protein from the leaves of the herb, Cajanus indicus L on chloroform induced hepatic-disorder.
Cajanus indicus is a herb with medicinal properties and is traditionally used to treat various forms of liver disorders. Present study aimed to evaluate the effect of a 43 kD protein isolated from the leaves of this herb against chloroform induced hepatotoxicity. Male albino mice were intraperitoneally treated with 2 mg/kg body weight of the protein for 5 days followed by oral application of chloroform (0.75 ml/kg body weight) for 2 days. Different biochemical parameters related to physiology and pathophysiology of liver, such as, serum glutamate pyruvate transaminase and alkaline phosphatase were determined in the murine sera under various experimental conditions. Direct antioxidant role of the protein was also determined from its reaction with Diphenyl picryl hydroxyl radical, superoxide radical and hydrogen peroxide. To find out the mode of action of this protein against chloroform induced liver damage, levels of antioxidant enzymes catalase, superoxide dismutase and glutathione-S-transferase were measured from liver homogenates. Peroxidation of membrane lipids both in vivo and in vitro were also measured as malonaldialdehyde. Finally, histopathological analyses were done from liver sections of control, toxin treated and protein pre- and post-treated (along with the toxin) mice. Levels of serum glutamate pyruvate transaminase and alkaline phosphatase, which showed an elevation in chloroform induced hepatic damage, were brought down near to the normal levels with the protein pretreatment. On the contrary, the levels of antioxidant enzymes such as catalase, superoxide dismutase and glutathione-S-transferase that had gone down in mice orally fed with chloroform were significantly elevated in protein pretreated ones. Besides, chloroform induced lipid peroxidation was effectively reduced by protein treatment both in vivo and in vitro. In cell free system the protein effectively quenched diphenyl picryl hydroxyl radical and superoxide radical, though it could not catalyse the breakdown of hydrogen peroxide. Post treatment with the protein for 3 days after 2 days of chloroform administration showed similar results. Histopathological studies indicated that chloroform induced extensive tissue damage was less severe in the mice livers treated with the 43 kD protein prior and post to the toxin administration. Results from all these data suggest that the protein possesses both preventive and curative role against chloroform induced hepatotoxicity and probably acts by an anti-oxidative defense mechanism.


Complete Laparoscopic Nephroureterectomy for the Upper Urinary Tract Urothelial Carcinoma in a Female Patient with Severe Senile Kyphosis: An Initial Case Report.
Kyphosis is usually described as the deformity of the spine that results in an abnormally round back. Patients with kyphosis form a challenging group to laparoscopic surgeons because of difficulties in positioning and abdominal approach. The narrow abdomen causes difficulty with trocar insertion and some operative procedures. Here we report the transperitoneal complete laparoscopic nephroureterectomy in a case of kyphosis. An 81-year-old woman underwent this operation for urothelial carcinoma of the upper urinary tract. We took best care of the positioning and the trocar insertion; we could have accomplished utilizing four ports at semilateral position without any troubles and complications. This procedure is safe and feasible, and not thought to be a contraindication for the patients with senile kyphosis.


High-resolution computed tomographic evaluation of airway distensibility and the effects of lung inflation on airway caliber in healthy subjects and individuals with asthma.
The effects of a deep inspiration (DI) in individuals with asthma differ from those observed in healthy subjects. It has been postulated that the beneficial effect of lung inflation is mediated by airway stretch. One hypothesis to explain the defects in the function of lung inflation in asthma is that a DI may be unable to stretch the airways. This may result from attenuation of the tethering forces between the airways and the surrounding parenchyma. In the current study, we used high-resolution computed tomography (HRCT) to examine the ability of a DI to distend the airways of subjects with asthma (n = 10) compared with healthy subjects (n = 9) at baseline and after increasing airway tone with methacholine (MCh). We found that both at baseline and after the induction of smooth muscle tone with MCh, a DI distended the airways of healthy and asthmatic subjects to a similar extent, indicating that abnormal interdependence between the lung parenchyma and the airways is unlikely to play a major role in the loss or attenuation of the beneficial effect of lung inflation that characterizes asthma. Furthermore, we observed that after constriction had already been induced by MCh, following a DI, bronchodilation occurred in the healthy subjects but further bronchoconstriction occurred in the subjects with asthma. Our findings suggest that an abnormal excitation contraction mechanism in the airway smooth muscle of subjects with mild asthma counteracts the bronchodilatory effect of a DI. Therefore, the mechanism for reduced bronchodilation after DIs in subjects with mild asthma could be intrinsic to the airway smooth muscle.


A pandemic influenza modeling and visualization tool.
The National Strategy for Pandemic Influenza outlines a plan for community response to a potential pandemic. In this outline, state and local communities are charged with enhancing their preparedness. In order to help public health officials better understand these charges, we have developed a visual analytics toolkit (PanViz) for analyzing the effect of decision measures implemented during a simulated pandemic influenza scenario. Spread vectors based on the point of origin and distance traveled over time are calculated and the factors of age distribution and population density are taken into effect. Healthcare officials are able to explore the effects of the pandemic on the population through a geographical spatiotemporal view, moving forward and backward through time and inserting decision points at various days to determine the impact. Linked statistical displays are also shown, providing county level summaries of data in terms of the number of sick, hospitalized and dead as a result of the outbreak. Currently, this tool has been deployed in Indiana State Department of Health planning and preparedness exercises, and as an educational tool for demonstrating the impact of social distancing strategies during the recent H1N1 (swine flu) outbreak.


The human imperative of stabilizing global climate change at 1.5°C.
Increased concentrations of atmospheric greenhouse gases have led to a global mean surface temperature 1.0°C higher than during the pre-industrial period. We expand on the recent IPCC Special Report on global warming of 1.5°C and review the additional risks associated with higher levels of warming, each having major implications for multiple geographies, climates, and ecosystems. Limiting warming to 1.5°C rather than 2.0°C would be required to maintain substantial proportions of ecosystems and would have clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where the escalation of climate-related risks may prevent the achievement of the United Nations Sustainable Development Goals.


Formerly Homeless People Had Lower Overall Health Care Expenditures After Moving Into Supportive Housing.
The provision of supportive housing is often recognized as important public policy, but it also plays a role in health care reform. Health care costs for the homeless reflect both their medical complexity and psychosocial risk factors. Supportive housing attempts to moderate both by providing stable places to live along with on-site integrated health services. In this pilot study we used a mixture of survey and administrative claims data to evaluate outcomes for formerly homeless people who were living in a supportive housing facility in Oregon between 2010 and 2014. Results from the claims analysis showed significantly lower overall health care expenditures for the people after they moved into supportive housing. Expenditure changes were driven primarily by reductions in emergency and inpatient care. Survey data suggest that the savings were not at the expense of quality: Respondents reported improved access to care, stronger primary care connections, and better subjective health outcomes. Together, these results indicate a potential association between supportive housing and reduced health care costs that warrants deeper consideration as part of ongoing health care reforms.


Effect of cold nerve allograft preservation on antigen presentation and rejection.
Nerve allotransplantation provides a temporary scaffold for host nerve regeneration and allows for the reconstruction of significant segmental nerve injuries. The need for systemic immunosuppression, however, limits the current clinical utilization of nerve allografts, although this need is reduced by the practice of cold nerve allograft preservation. Activation of T cells in response to alloantigen presentation occurs in the context of donor antigen presenting cells (direct pathway) or host antigen-presenting cells (indirect pathway). The relative role of each pathway in eliciting an alloimmune response and its potential for rejection of the nerve allograft model has not previously been investigated. The objective of this investigation was to study the effect of progressive periods of cold nerve allograft preservation on antigen presentation and the alloimmune response. The authors used wild type C57Bl/6 (B6), BALB/c, and major histocompatibility Class II-deficient (MHC-/-) C57Bl/6 mice as both nerve allograft recipients and donors. A nonvascularized nerve allograft was used to reconstruct a 1-cm sciatic nerve gap. Progressive cold preservation of donor nerve allografts was used. Quantitative assessment was made after 3 weeks using nerve histomorphometry. The donor-recipient combination lacking a functional direct pathway (BALB/c host with MHC-/- graft) rejected nerve allografts as vigorously as wild-type animals. Without an intact indirect pathway (MHC-/- host with BALB/c graft), axonal regeneration was improved (p < 0.052). One week of cold allograft preservation did not improve regeneration to any significant degree in any of the donor-recipient combinations. Four weeks of cold preservation did improve regeneration significantly (p < 0.05) for all combinations compared with wild-type animals without pretreatment. However, only in the presence of an intact indirect pathway (no direct pathway) did 4 weeks of cold preservation improve regeneration significantly compared with 1 week and no preservation in the same donor-recipient combination. The indirect pathway may be the predominant route of antigen presentation in the unmodified host response to the nerve allograft. Prolonged duration of cold nerve allograft preservation is required to significantly attenuate the rejection response. Cold preservation for 4 weeks improves nerve regeneration with a significant effect on indirect allorecognition.


Predicting Fusarium head blight epidemics with boosted regression trees.
Predicting major Fusarium head blight (FHB) epidemics allows for the judicious use of fungicides in suppressing disease development. Our objectives were to investigate the utility of boosted regression trees (BRTs) for predictive modeling of FHB epidemics in the United States, and to compare the predictive performances of the BRT models with those of logistic regression models we had developed previously. The data included 527 FHB observations from 15 states over 26 years. BRTs were fit to a training data set of 369 FHB observations, in which FHB epidemics were classified as either major (severity ≥ 10%) or non-major (severity < 10%), linked to a predictor matrix consisting of 350 weather-based variables and categorical variables for wheat type (spring or winter), presence or absence of corn residue, and cultivar resistance. Predictive performance was estimated on a test (holdout) data set consisting of the remaining 158 observations. BRTs had a misclassification rate of 0.23 on the test data, which was 31% lower than the average misclassification rate over 15 logistic regression models we had presented earlier. The strongest predictors were generally one of mean daily relative humidity, mean daily temperature, and the number of hours in which the temperature was between 9 and 30°C and relative humidity ≥ 90% simultaneously. Moreover, the predicted risk of major epidemics increased substantially when mean daily relative humidity rose above 70%, which is a lower threshold than previously modeled for most plant pathosystems. BRTs led to novel insights into the weather-epidemic relationship.


Relating middle-ear acoustic performance to body size in the cat family: measurements and models.
Is the acoustic performance of the mammalian middle ear dependent on body size? We focus on the cat family, because of its qualitatively uniform (and distinctive) middle-ear structure, large size range, and the extensive data available from domestic cats which provide a framework for relating middle-ear acoustics to structure. We report measurements of acoustic admittance in 17 live adult ears of 11 exotic species, ranging in size from sand cat (3 kg) to tiger (180 kg). For low frequencies, the middle-ear response is compliant for all species and generally increases with size. The compliance of the middle-ear air space increases with size, but the compliance of the tympanic membrane and ossicular chain is not correlated with size. Structure-based rules are developed to represent some features of middle-ear performance: (1) low-frequency sensitivity increases with size; and (2) the frequency of a prominent notch in admittance decreases with size. Although some species deviate from the rules, the data generally support the idea that in larger felids the middle-ear response is shifted to lower frequencies. Thus, in the cat family, body size partly describes variations in auditory features. More speculatively, ethological pressures which might influence hearing performance are discussed.


Cerebrospinal fluid viscosity: a novel diagnostic measure for acute meningitis.
Early diagnosis of acute meningitis has paramount importance in clinical practice because of mortality and morbidity of the disease. Examination of cerebrospinal fluid (CSF) has critical value for the diagnosis of acute meningitis and discrimination of bacterial and aseptic meningitis. It has been previously reported that plasma viscosity can be used as an inflammatory marker. In this study we aimed to evaluate the role of CSF viscosity as a complementary measure for diagnosis of meningitis in suspected patients. Forty-one consecutive patients who underwent lumbar puncture to rule out meningitis were studied prospectively. Twenty-seven patients were diagnosed with meningitis, of whom 13 patients had aseptic meningitis and 14 patients had bacterial meningitis. Meningitis was ruled out in 14 patients. CSF protein and CSF viscosity were significantly higher in patients with meningitis compared to nonmeningitis. Receiver operator characteristic (ROC) analysis revealed that CSF viscosity was highly sensitive (100%) and specific (93%); measures for the diagnosis of meningitis in the study population was comparable to those of CSF protein. Additionally, patients with meningitis were also divided into two groups as having bacterial and aseptic meningitis. CSF viscosity also significantly differed between bacterial and aseptic meningitis. The CSF viscosity is a simple and easy method and can be used as an adjunctive measure for the diagnosis of meningitis. With the support of further and larger clinical studies, CSF viscosity may have a role in the discrimination of bacterial versus aseptic meningitis.


Treatment of osteoporosis in men with bisphosphonates: rationale and latest evidence.
Osteoporosis in men contributes to significant morbidity and mortality. Hip fractures in men are associated with greater mortality compared with women, with a mortality rate of up to 37.5% within a year following the fracture. Its timely diagnosis and treatment are therefore essential. However, despite one-third of all hip fractures worldwide occurring in men, osteoporosis in men remains an immensely under-recognized and undertreated public health problem. Bisphosphonates are well studied first-line treatments for postmenopausal women with osteoporosis and have been shown to reduce fragility fractures at all clinically important sites (vertebral, nonvertebral, hip and wrist). However, the majority of studies of oral or intravenous bisphosphonate therapy in men with osteoporosis report effects on surrogate markers, including bone mineral density (BMD) and biochemical bone turnover markers, rather than on fragility fractures. Oral or intravenous bisphosphonate therapy increases spinal, total hip and femoral neck BMD compared with placebo in men with osteoporosis. Both bone resorption and bone formation markers are decreased following bisphosphonate therapy, with the onset of the decrease in bone formation markers being delayed. In a study of intravenous zoledronic acid given to older men and women following a hip fracture, any clinical vertebral and nonvertebral fractures were all reduced compared with placebo infusions. In addition, mortality was reduced in patients who received zoledronic acid. Recent studies in men with osteoporosis have increasingly reported reductions in incident vertebral fractures with oral or intravenous bisphosphonate therapy, although all studies have been underpowered to detect effects on nonvertebral and hip fracture outcomes. Bisphosphonates have a role as monotherapy, as consolidative therapy after a course of teriparatide therapy, or in combination with testosterone replacement in men with hypogonadism and osteoporosis. Bisphosphonate therapy is validated and important in the treatment of osteoporosis in men.


The chromatin remodeller CHD8 is required for E2F-dependent transcription activation of S-phase genes.
The precise regulation of S-phase-specific genes is critical for cell proliferation. How the repressive chromatin configuration mediated by the retinoblastoma protein and repressor E2F factors changes at the G1/S transition to allow transcription activation is unclear. Here we show ChIP-on-chip studies that reveal that the chromatin remodeller CHD8 binds ∼ 2000 transcriptionally active promoters. The spectrum of CHD8 target genes was enriched in E2F-dependent genes. We found that CHD8 binds E2F-dependent promoters at the G1/S transition but not in quiescent cells. Consistently, CHD8 was required for G1/S-specific expression of these genes and for cell cycle re-entry on serum stimulation of quiescent cells. We also show that CHD8 interacts with E2F1 and, importantly, loading of E2F1 and E2F3, but not E2F4, onto S-specific promoters, requires CHD8. However, CHD8 recruiting is independent of these factors. Recruiting of MLL histone methyltransferase complexes to S-specific promoters was also severely impaired in the absence of CHD8. Furthermore, depletion of CHD8 abolished E2F1 overexpression-dependent S-phase stimulation of serum-starved cells, highlighting the essential role of CHD8 in E2F-dependent transcription activation.


The attitudes of people with sarcoma and their family towards genomics and incidental information arising from genetic research.
The study aimed to examine attitudes of individuals diagnosed with sarcoma and their family members towards genetics, genomic research and incidental information arising as a result of participating in genetic research. A questionnaire was administered to 1200 individuals from the International Sarcoma Kindred Study (ISKS). Respondents were divided into three groups: individuals affected with sarcoma (probands), their spouses and family members. Approximately half of all research participants felt positively towards new discoveries in human genetics. Overall, more were positive in their attitudes towards genetic testing for inherited conditions (60%) but family members were less so. Older participants reported more highly positive attitudes more often than younger participants. Males were less likely to feel positive about new genetic discoveries and more likely to believe they could modify genetic risk by altering lifestyle factors. Almost all ISKS participants believed participants would like to be given ancillary information arising as a result of participating in genetic research. The only difference between the study groups was the decreased likelihood of family members being highly positive about genetic testing. This may be important if predictive testing for sarcoma becomes available. Generally ISKS research participants supported the notion of returning incidental genetic information to research participants.


Hypertrophic neuropathies and malignant peripheral nerve sheath tumors in transgenic mice overexpressing glial growth factor beta3 in myelinating Schwann cells.
The neuregulin-1 (NRG-1) family of growth and differentiation factors exerts a variety of effects on Schwann cells and their precursors during nervous system development; however, NRG-1 effects on adult Schwann cells are poorly defined. Several lines of evidence suggest that NRG-1 actions on adult Schwann cells are distinct from those observed during development. To test this hypothesis, we generated transgenic mice overexpressing the NRG-1 isoform glial growth factor beta3 (GGFbeta3) in myelinating Schwann cells [protein zero (P0)GGFbeta3 mice]. P0-GGFbeta3 mice develop resting tremors, gait abnormalities, decreased hindlimb strength, and paralysis by approximately 7 months of age. Sciatic nerves from these animals show a hypertrophic neuropathy characterized by demyelination, remyelination, and "onion bulb" formation. Development of this hypertrophic neuropathy is preceded by Schwann cell hyperplasia that is prominent in 1-month-old mice and present but decreased in 2- and 4-month-old animals. P0-GGFbeta3 mice also develop peripheral ganglion-associated malignant peripheral nerve sheath tumors. Motor, sensory, and sympathetic ganglia from 1-, 2-, and 4-month-old P0-GGFbeta3 mice uniformly contain intraganglionic, likely preneoplastic, Schwann cell proliferations. Examination of bromodeoxyuridine incorporation and caspase-3 activation in sciatic nerves and trigeminal ganglia indicates that Schwann cell hyperplasia in P0-GGFbeta3 mice reflects increased proliferation rather than decreased apoptosis. These observations are consistent with the hypothesis that GGFbeta3 induces proliferation of adult Schwann cells and demyelination of peripheral nerve axons. Furthermore, overexpression of this NRG-1 isoform frequently induces neoplastic Schwann cell proliferation within PNS ganglia, suggesting that NRG-1 may contribute to human Schwann cell neoplasia.


The membrane topography of ecto-5'-nucleotidase in rat hepatocytes.
The transmembrane topography of the rat hepatocyte ectoenzyme 5'-nucleotidase was studied by the use of glycoprotein labelling and limited-proteolysis techniques. Comparison, by one-dimensional peptide mapping, of enzyme iodinated from outside the cell with that iodinated in the solubilized state showed that no additional iodination sites were revealed on solubilization. Incubation of newly synthesized enzyme in a microsomal membrane fraction with proteinase showed that the entire molecule of 5'-nucleotidase was protected from proteolysis. These data suggest that little, if any, of the 5'-nucleotidase molecule is present on the cytoplasmic side of the plasma membrane. No evidence was found for a previously proposed interaction between 5'-nucleotidase and actin, although the ability of preparations of 5'-nucleotidase to prevent inhibition of deoxyribonuclease I by actin was explained by minute traces of ATPase activity. Comparison of peptide maps of enzyme labelled by iodination or by methods specific for carbohydrate showed that in both cases predominantly one section of the molecule was labelled. It is proposed that the enzyme is a short-stalked integral membrane protein without a cytoplasmic domain in which about one-third of the molecule forms the accessible molecular surface.


Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children.
Attention-deficit/hyperactivity disorder (ADHD) is male predominated, and the etiology of this disorder remains unclear. Past studies have assessed the association of low-level organophosphate pesticide exposure with childhood ADHD cross-sectionally and prospectively. However, the results have been inconsistent. A first case-control study was performed to investigate the relationship between organophosphate pesticide exposure and ADHD with adjusted covariates. We recruited 97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age. Exposure was assessed using urinary levels of dialkylphosphate metabolites, which are biomarkers of OP pesticide exposure. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. The sociodemographics and lifestyles of the children and of the mothers during pregnancy were collected using a questionnaire. The blood lead levels of both groups were similar (1.57 ± 0.73 vs. 1.73 ± 0.77 μg/dL, p = 0.15). Significant urinary concentration differences in one of the six dialkylphosphate metabolites, dimethylphosphate (DMP), were found between ADHD and control subjects (322.92 ± 315.68 vs. 224.37 ± 156.58 nmol/g cr., p < 0.01). A dose-response relationship was found between urinary concentrations of DMP and ADHD in both crude and adjusted analyses (p for trend<0.05). Children with higher urinary DMP concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD. We report a dose-response relationship between child DMP levels and ADHD. Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD.


Direct plate-reader measurement of nitric oxide released from hypoxic erythrocytes flowing through a microfluidic device.
The ability to perform a fluorescence-based quantitative determination of a biologically important analyte directly released from mammalian cells using a standard microtiter plate reader to measure wells integrated into a microfluidic device is reported. Specifically, the amount of nitric oxide (NO) released from flowing erythrocytes (ERYs) exposed to a hypoxic buffer is measured using a fluorescein-based probe. The ERYs are pumped through channels in one layer of the poly(dimethylsiloxane) (PDMS) device; as these cells release NO, it flows through a porous polycarbonate membrane to the probe. The device is then placed into a standard microtiter plate reader for measurement, with the entire calibration and analyte determination occurring simultaneously. Using this method, NO release from hypoxic ERYs was determined to be 6.9 +/- 1.8 microM, a significantly increased value in comparison to that from normoxic ERYs of 0.60 +/- 0.04 microM (p < 0.001, n = 4 rabbits). Furthermore, the reproducibility (reported as a %RSD) of measuring fluorescence standards was 3.5%. Detection limits, dynamic range, and optimal membrane pore diameters are also reported. This device enables the use of a standard high-throughput tool (the plate reader) to measure analytes in a microfluidic device, the ability to improve the quantitative determination of a relatively unstable molecule (NO), and the incorporation of a flow component and blood constituent into a system that can be combined with microtiter plate technology.


Chromosomal translocations involved in non-Hodgkin lymphomas.
The discovery that recurrent chromosomal translocations are involved in the pathogenesis of non-Hodgkin lymphomas has greatly improved our understanding of these diseases and revolutionized their diagnosis. To review the mechanisms by which chromosomal translocations occur and contribute to the pathogenesis of various types of non-Hodgkin lymphomas and to review the utility of molecular genetic methods for the assessment of these translocations. Primary research studies and reviews published in the English language that focus on chromosomal translocation and non-Hodgkin lymphomas. Chromosomal translocations, which usually result in oncogene activation, occur in many types of B- and T-cell lymphoma, and their detection is helpful for establishing an accurate diagnosis and monitoring disease following therapy. However, the precise mechanisms that explain how translocations occur remain unknown, although for some types of translocations a clear relationship has been established with immunoglobulin gene rearrangement mechanisms. In recent years, a number of genes deregulated by chromosomal translocations have been identified, and the detailed molecular mechanisms by which chromosomal translocations contribute to the pathogenesis of non-Hodgkin lymphoma are beginning to be elucidated. Molecular genetic analysis has played a major role in improving our understanding of B- and T-cell non-Hodgkin lymphomas and has allowed more precise definition of lymphoma types. Molecular genetic tests to detect these translocations are important ancillary tools for the diagnosis and classification of malignant lymphomas.


Adenosine receptor ligands-recent developments part I. Agonists.
Developments in the field of adenosine receptor (AR) agonists of the past years are presented and discussed. Four different AR subtypes, A(1), A(2A), A(2B), and A(3), have been cloned from different species including the human receptors. Recombinant ARs expressed in permanent mammalian cell lines have found wide application in the screening of new ligands. Considerable differences are observed among data from different laboratories, using recombinant receptors for the assays. Reevaluation of compounds at all four receptor subtypes has shown that agonists that were believed to be selective for either A(1) or A(2A) ARs may be potent A(3) agonists and thus, non-selective. Potent and selective agonists for two of the AR subtypes, A(1) and A(3), have been developed. Truly selective A(2A) AR agonists, however, are presently not available. Potent or selective A(2B) agonists are still lacking. Since the treatment with AR agonists may lead to fast desensitization of the receptors, partial agonists, and indirect AR agonists, such as adenosine kinase inhibitors, or allosteric enhancers of adenosine binding, are being developed as site- and event-specific agents.


Consumer participation in the employment rehabilitation process: contextual factors and implications for practice.
Rehabilitation models of practice have emerged that offer persons' with disabilities opportunities to have an active role in the work entry or re(entry) process. Despite the growth and interest in empowering client involvement in practice, consumer views on the determinants of participation are not fully understood. Thus, consumer feedback on using a self-directed approach to employment rehabilitation was elicited to identify factors integral to their participation in the process. Focus groups were conducted with 35 adult consumers with developmental, mental health, physical and learning disabilities to gain insights into their involvement in a participatory approach to find employment. Content analysis of data revealed barriers and facilitators, which hindered or enabled consumer involvement in the vocational service process. This article discusses the importance of considering issues across the rehabilitation system, practice and lived contexts when implementing participatory approaches in vocational rehabilitation settings.


Polynomial distance classifier correlation filter for pattern recognition.
We introduce what is to our knowledge a new nonlinear shift-invariant classifier called the polynomial distance classifier correlation filter (PDCCF). The underlying theory extends the original linear distance classifier correlation filter [Appl. Opt. 35, 3127 (1996)] to include nonlinear functions of the input pattern. This new filter provides a framework (for combining different classification filters) that takes advantage of the individual filter strengths. In this new filter design, all filters are optimized jointly. We demonstrate the advantage of the new PDCCF method using simulated and real multi-class synthetic aperture radar images.


The soil organic matter decomposition mechanisms in ectomycorrhizal fungi are tuned for liberating soil organic nitrogen.
Many trees form ectomycorrhizal symbiosis with fungi. During symbiosis, the tree roots supply sugar to the fungi in exchange for nitrogen, and this process is critical for the nitrogen and carbon cycles in forest ecosystems. However, the extents to which ectomycorrhizal fungi can liberate nitrogen and modify the soil organic matter and the mechanisms by which they do so remain unclear since they have lost many enzymes for litter decomposition that were present in their free-living, saprotrophic ancestors. Using time-series spectroscopy and transcriptomics, we examined the ability of two ectomycorrhizal fungi from two independently evolved ectomycorrhizal lineages to mobilize soil organic nitrogen. Both species oxidized the organic matter and accessed the organic nitrogen. The expression of those events was controlled by the availability of glucose and inorganic nitrogen. Despite those similarities, the decomposition mechanisms, including the type of genes involved as well as the patterns of their expression, differed markedly between the two species. Our results suggest that in agreement with their diverse evolutionary origins, ectomycorrhizal fungi use different decomposition mechanisms to access organic nitrogen entrapped in soil organic matter. The timing and magnitude of the expression of the decomposition activity can be controlled by the below-ground nitrogen quality and the above-ground carbon supply.


[Leptospira-Zebra under the "corona herd"].
This article reports an incidental finding of leptospirosis during a special consultation, which was initiated due to the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The focus on SARS-CoV‑2 and the uncharacteristic symptoms of these two diseases make it much more difficult to find the correct diagnosis. Leptospirosis is predominantly a tropical zoonosis but also occurs in Germany.


Ultrastructure and immunohistochemical characterization of proteins concerned with the secretory machinery in goat ceruminous glands.
The expression of soluble N-ethyl-maleimide sensitive fusion attachment protein receptor (SNARE) proteins in apocrine glands has not been fully elucidated. In addition to performing ultrastructural observation of the ceruminous glands in goats, our study focuses on the demonstration of β-defensins, SNARE proteins and Rab3D in these glands with the use of immunohistochemical methods. The secretory cells were equipped with two types of vesicles, Golgi apparatus and abundant rough endoplasmic reticulum (ER). Additionally, in some of them, the characteristic concentric structures composed of rough ER were observed in their circum- and infranuclear parts. The expression of phosphorylated inositol requiring enzyme 1a was also detected. These findings may indicate their ability to produce numerous secretory proteins and the maintenance of homeostasis in the glandular cells. Furthermore, β-defensins were demonstrated as products of the ceruminous glands. The present investigation also revealed the presence of SNARE proteins and Rab3D. It is suggested that these proteins are concerned with the secretory machinery of this gland type.


Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugs.
The prognostic role of high blood pressure and the aggressiveness of blood pressure lowering in dementia are not well characterized. To assess whether office blood pressure, ambulatory blood pressure monitoring, or the use of antihypertensive drugs (AHDs) predict the progression of cognitive decline in patients with overt dementia and mild cognitive impairment (MCI). Cohort study between June 1, 2009, and December 31, 2012, with a median 9-month follow-up of patients with dementia and MCI in 2 outpatient memory clinics. Cognitive decline, defined as a Mini-Mental State Examination (MMSE) score change between baseline and follow-up. We analyzed 172 patients, with a mean (SD) age of 79 (5) years and a mean (SD) MMSE score of 22.1 (4.4). Among them, 68.0% had dementia, 32.0% had MCI, and 69.8% were being treated with AHDs. Patients in the lowest tertile of daytime systolic blood pressure (SBP) (≤ 128 mm Hg) showed a greater MMSE score change (mean [SD], -2.8 [3.8]) compared with patients in the intermediate tertile (129-144 mm Hg) (mean [SD], -0.7 [2.5]; P = .002) and patients in the highest tertile (≥ 145 mm Hg) (mean [SD], -0.7 [3.7]; P = .003). The association was significant in the dementia and MCI subgroups only among patients treated with AHDs. In a multivariable model that included age, baseline MMSE score, and vascular comorbidity score, the interaction term between low daytime SBP tertile and AHD treatment was independently associated with a greater cognitive decline in both subgroups. The association between office SBP and MMSE score change was weaker. Other ambulatory blood pressure monitoring variables were not associated with MMSE score change. Low daytime SBP was independently associated with a greater progression of cognitive decline in older patients with dementia and MCI among those treated with AHDs. Excessive SBP lowering may be harmful for older patients with cognitive impairment. Ambulatory blood pressure monitoring can be useful to help avoid high blood pressure overtreatment in this population.


Accumulation of Antifreeze Proteins on Ice Is Determined by Adsorption.
Antifreeze proteins (AFPs) facilitate the survival of diverse organisms in frigid environments by adsorbing to ice crystals and suppressing their growth. The rate of AFP accumulation on ice is determined by an interplay between AFP diffusion from the bulk solution to the ice-water interface and the subsequent adsorption of AFPs to the interface. To interrogate the relative importance of these two processes, here, we combine nonequilibrium fluorescence experiments with a reaction-diffusion model. We find that as diverse AFPs accumulate on ice, their concentration in the aqueous solution does not develop a gradient but remains equal to its bulk concentration throughout our experiments. These findings lead us to conclude that AFP accumulation on ice crystals, which are smaller than 100 μm in radius, is not limited by the diffusion of AFPs, but by the kinetics of AFP adsorption. Our results imply that mass transport limitations do not hinder AFPs from performing their biological function.


A comparative study of the interaction of Tamiflu and Oseltamivir carboxylate with bovine serum albumin.
Oseltamivir phosphate (Tamiflu) is a pro-drug that is metabolized to its active form (Oseltamivir carboxylate), after oral administration. OC inhibits influenza A and B neuraminidases in vitro and OP inhibits influenza virus infection and replication in vitro. Serum albumin is the most abundant of the proteins in the circulatory system of a wide variety of organisms and plays an important role in the transport and deposition of many drugs. The aim of this study was to examine the interaction of BSA with Tamiflu and Oseltamivir carboxylate in aqueous solution at physiological conditions, using a constant protein concentration and various drug contents. FTIR, UV-Vis spectroscopic methods were used to determine the drugs binding mode, the binding constant and the effects of drug complexation on protein secondary structure. Structural analysis showed that OP and OC bind BSA with overall binding constants of K(OP-BSA)=1.88 (±0.16)×10(4)M(-1) and K(OC-BSA)=5.7 (±0.09)×10(2)M(-1). Drug complexation alters protein conformation by major reduction of α-helix and random coil and increase of β-sheet and turn structures that indicate a partial protein destabilization. The results suggest that BSA might act as carrier proteins for OP in delivering it to target molecules.


Pediatric dysphagia.
Feeding and swallowing disorders in the pediatric population are becoming more common, particularly in infants born prematurely and in children with chronic medical conditions. The normal swallowing mechanism is divided into 4 stages: the preparatory, the oral, the pharyngeal, and the esophageal phases. Feeding disorders have multiple causes: medical, nutritional, behavioral, psychological, and environmental factors can all contribute. Pathologic conditions involving any of the anatomic sites associated with the phases of swallowing can negatively impact the coordination of these phases and lead to symptoms of dysphagia and feeding intolerance.


The synaptinemal complex in Rhoeo spathacea.
The synaptinemal complex in meiocytes of Rhoeo spathacea is described. Unpaired zygotene chromosomes do not exhibit well defined axial cores under the ordinary fixations of electron microscopy and appear diffuse. However, the axial core is defined by ethanolic phosphotungstic acid (PTA) although it does not respond to uranyl-EDTA-lead. Thus the core appears to contain histone but not RNA and presents a condition which is modified later in pairing when lateral elements of the synaptinemal complex respond positively to both tests. The total number of attachments of synaptinemal complexes to the nuclear envelope was determined in several nuclei from serial sections. Eleven of the twelve possible attachments were found in one nucleus. It thus seems certain that all must be so attached. In the same manner all chromosomes can be seen to have an attachment to a chromocentre. Chromocentres are often very large and compound in that two kinds of heterochromatin can be distinguished. These states of chromatin within the chromocentre are considered to be a function of the degree of condensation. Segments of synaptinemal complexes are distributed randomly through sections of pachytene nuclei and long uncoiled segments of complexes are frequently found in or near the centres of median nuclear sections. Synaptinemal complexes are also found in chromocentres. Our findings suggest that on completion of pairing, which begins distally, homologous chromosomes in Rhoeo are paired throughout their entire lengths, rather than in small terminal segments only.


The 11S globulin Sin a 2 from yellow mustard seeds shows IgE cross-reactivity with homologous counterparts from tree nuts and peanut.
The 11S globulin Sin a 2 is a marker to predict severity of symptoms in mustard allergic patients. The potential implication of Sin a 2 in cross-reactivity with tree nuts and peanut has not been investigated so far. In this work, we studied at the IgG and IgE level the involvement of the 11S globulin Sin a 2 in cross-reactivity among mustard, tree nuts and peanut. Eleven well-characterized mustard-allergic patients sensitized to Sin a 2 were included in the study. A specific anti-Sin a 2 serum was obtained in rabbit. Skin prick tests (SPT), enzyme-linked immunosorbent assay (ELISA), immunoblotting and IgG or IgE-inhibition immunoblotting experiments using purified Sin a 2, Sin a 1, Sin a 3, mustard, almond, hazelnut, pistachio, walnut or peanut extracts were performed. The rabbit anti-Sin a 2 serum showed high affinity and specificity to Sin a 2, which allowed us to demonstrate that Sin a 2 shares IgG epitopes with allergenic 11S globulins from tree nuts (almond, hazelnut, pistachio and walnut) but not from peanut. All the patients included in the study had positive skin prick test to tree nuts and/or peanut and we subdivided them into two different groups according to their clinical symptoms after ingestion of such allergenic sources. We showed that 11S globulins contain conserved IgE epitopes involved in cross-reactivity among mustard, tree nuts and peanut as well as species-specific IgE epitopes. The allergenic 11S globulin Sin a 2 from mustard is involved in cross-reactivity at the IgE level with tree nuts and peanut. Although the clinical relevance of the cross-reactive IgE epitopes present in 11S globulins needs to be investigated in further detail, our results contribute to improve the diagnosis and management of mustard allergic patients sensitized to Sin a 2.


High mobility group box-1 (HMGB1) participates in the pathogenesis of alcoholic liver disease (ALD).
Growing clinical and experimental evidence suggests that sterile inflammation contributes to alcoholic liver disease (ALD). High mobility group box-1 (HMGB1) is highly induced during liver injury; however, a link between this alarmin and ALD has not been established. Thus, the aim of this work was to determine whether HMGB1 contributes to the pathogenesis of ALD. Liver biopsies from patients with ALD showed a robust increase in HMGB1 expression and translocation, which correlated with disease stage, compared with healthy explants. Similar findings were observed in chronic ethanol-fed wild-type (WT) mice. Using primary cell culture, we validated the ability of hepatocytes from ethanol-fed mice to secrete a large amount of HMGB1. Secretion was time- and dose-dependent and responsive to prooxidants and antioxidants. Selective ablation of Hmgb1 in hepatocytes protected mice from alcohol-induced liver injury due to increased carnitine palmitoyltransferase-1, phosphorylated 5'AMP-activated protein kinase-α, and phosphorylated peroxisome proliferator-activated receptor-α expression along with elevated LDL plus VLDL export. Native and post-translationally modified HMGB1 were detected in humans and mice with ALD. In liver and serum from control mice and in serum from healthy volunteers, the lysine residues within the peptides containing nuclear localization signals (NLSs) 1 and 2 were non-acetylated, and all cysteine residues were reduced. However, in livers from ethanol-fed mice, in addition to all thiol/non-acetylated isoforms of HMGB1, we observed acetylated NLS1 and NLS2, a unique phosphorylation site in serine 35, and an increase in oxidation of HMGB1 to the disulfide isoform. In serum from ethanol-fed mice and from patients with ALD, there was disulfide-bonded hyperacetylated HMGB1, disulfide-bonded non-acetylated HMGB1, and HMGB1 phosphorylated in serine 35. Hepatocytes appeared to be a major source of these HMGB1 isoforms. Thus, hepatocyte HMGB1 participates in the pathogenesis of ALD and undergoes post-translational modifications (PTMs) that could condition its toxic effects.


Clinical outcome of dental implants placed with high insertion torques (up to 176 Ncm).
Primary stability can be improved by using a tapered implant in a slightly underprepared implant site. This may lead to high compression forces and elevated insertion torques. It has been postulated that disturbance of the local microcirculation may occur, leading to necrosis of the osteocytes and bone resorption. Report on the clinical outcome of 42 implants placed with an insertion torque equal or greater than 70 Ncm and evaluate bone levels around these implants. This prospective study included 48 patients treated with 66 4.5 mm diameter Tapered Screw-Vent implants (Zimmer Dental®, Carlsbad, CA, USA). Maximum insertion torque (MIT) was recorded with an electronic torque measuring device (Tohnichi® STC200CN, Hitachi, Tokyo, Japan). Nine implants (control group) presented MIT between 30 and 50 Ncm (mean = 37.1 Ncm) and 42 implants (experimental group) MIT greater than 70 Ncm (mean = 110.6 Ncm, range: 70.8-176 Ncm). Marginal bone levels were recorded at the time of loading and 1 year later for the two groups. After 2-3 months of non-sumerged healing, all implants were clinically stable. Mean marginal bone resorption was 1.03 mm (SD = 0.44) for the control group (low torque) and 0.72 mm (SD = 0.56) for the experimental group (high torque) at time of loading, and 1.09 (SD = 0.62) and 1.24 mm (SD = 0.75), respectively, after 1 year. There were no significant differences between the two groups for bone stability and implant success rate. The use of high insertion torques (up to 176 Ncm) did not prevent osseointegration. Marginal bone levels in the control and experimental groups were similar both at the time of loading and 1 year later.