Gemination of a permanent lateral incisor- a case report with special emphasis on management.
The purpose of this case report is to describe the successful endodontic treatment and surgical management of a unesthetic geminated permanent maxillary lateral incisor tooth. Geminated maxillary incisor clinically revealed bifid crown with coronal groove and intraoral periapical radiograph showing radiolucent lesion with sclerotic border. orthograde root canal treatment was performed. surgery was done by reflecting limited thickness mucoperiosteal flap, cyst enucleated, root end resected and retrograde filling done using mineral trioxide aggregate. During the follow up examination, post operative intra oral periapical radiographs revealed healing of periapical lesion. Key words:Gemination, Periapical Cyst, Retrograde Filling. How to cite this article: Sharada H L, Deo B, Briget B. Gemination of a Permanent Lateral Incisor - A Case Report with Special Emphasis on Management. J Int Oral Health 2013; 5(2):55-59.


Cyanobacterium-Derived Extracellular Carbohydrate Polymer for the Controlled Delivery of Functional Proteins.
The unicellular cyanobacterium Cyanothece sp. CCY 0110 is a highly efficient producer of extracellular polymeric substances (EPS), releasing up to 75% of the polymer to the culture medium. The carbohydrate polymer released to the medium (RPS) was previously isolated and characterized; it is composed of nine different monosaccharides including two uronic acids, and also containing peptides and sulfate groups. Here it is shown that the RPS spontaneously assembles with proteins at high concentrations leading to a phase transition. The proteins are released progressively and structurally intact near physiological conditions, primarily through the swelling of the polymer-protein matrix. The releasing kinetics of the proteins can be modulated through the addition of divalent cations, such as calcium. Notably, the polymer is not toxic to human dermal neonatal fibroblasts in vitro at RPS concentrations bellow 0.1 mg mL-1 . The results show that this polymer is a good candidate for the delivery of therapeutic macromolecules.


Best Practice (Efficient) Immunohistologic Panel for Diagnosing Metaplastic Breast Carcinoma.
Immunohistochemistry (IHC) plays a key role in the diagnosis of metaplastic breast carcinomas (MBCs), particularly the spindle cell variant. The most efficient immunopanel has yet to be developed. We studied the immunoprofile of 45 MBCs including 23 matrix-producing MBCs, 11 squamous cell carcinomas, 6 spindle cell carcinomas, and 5 mixed-subtypes (2 cases including spindle cell components). Representative sections from mastectomy or core biopsy specimens were subject to IHC using a list of antibodies including OSCAR, a recently developed antibody against pooled cytokeratins. The staining was interpreted as positive when >1% of tumor cells demonstrated unequivocal staining. As a result, OSCAR showed similar sensitivity to AE1/AE3 and CAM 5.2 (89.1% vs. 89.4% vs. 89.4%) for MBCs, but the former showed more diffuse pattern of staining, particularly in spindle cell carcinomas. High molecular weight cytokeratin CK14, CK5, and CK17 were positive in 91.3%, 87.2%, and 73.3% of MBCs, respectively. CK7 was much less likely to be positive in spindle cell carcinomas (37.5%) than in other variants of MBCs (97.4%). P63 and CK14 were the most useful markers for spindle cell carcinomas, positive in 87.5% and 85.7% of cases, respectively. GATA 3 was positive in 63% MBCs, and nonspecific staining for vimentin and smooth muscle actin were common. Random combination of up to 3 antibodies against keratins including p63 showed sensitivities ranging from 80.9% to 97.9%. Our results suggested the combination of OSCAR, CK14 and p63 is the most efficient panel (sensitivity 97.9%) for diagnosing MBCs.


Revealing ecological networks using Bayesian network inference algorithms.
Understanding functional relationships within ecological networks can help reveal keys to ecosystem stability or fragility. Revealing these relationships is complicated by the difficulties of isolating variables or performing experimental manipulations within a natural ecosystem, and thus inferences are often made by matching models to observational data. Such models, however, require assumptions-or detailed measurements-of parameters such as birth and death rate, encounter frequency, territorial exclusion, and predation success. Here, we evaluate the use of a Bayesian network inference algorithm, which can reveal ecological networks based upon species and habitat abundance alone. We test the algorithm's performance and applicability on observational data of avian communities and habitat in the Peak District National Park, United Kingdom. The resulting networks correctly reveal known relationships among habitat types and known interspecific relationships. In addition, the networks produced novel insights into ecosystem structure and identified key species with high connectivity. Thus, Bayesian networks show potential for becoming a valuable tool in ecosystem analysis.


Diagnostic value of contrast-enhanced CT scans in identifying lung adenocarcinomas manifesting as GGNs (ground glass nodules).
This study aimed to explore the value of contrast-enhanced computed tomography (CT) scans in the differential diagnosis of atypical adenomatous hyperplasia, adenocarcinoma in situ, minimal invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC), which manifested as ground glass nodules (GGNs) or mixed GGNs.Unenhanced and contrast-enhanced presurgical CT images of 136 cases of GGNs were compared. The nodules were diagnosed based on their solid portions and maximum dimensions, and the findings obtained using both contrast-enhanced and unenhanced CT images were analyzed in corroboration with the pathological diagnosis.Most (53/56) preinvasive nodules showed increased mean CT values after contrast administration. In the MIA group, after contrast administration, enlargements of the solid portions were seen in 48 nodules (48/60), and the elevation of the mean CT value was observed in 12 nodules (12/60). The vast majority of IAC nodules (29/30) showed enlargement of the solid portions after contrast administration. Moreover, for group differences, findings obtained using this approach statistically match the pathological findings.Contrast-enhanced CT scans are more useful than unenhanced CT scans for the diagnosis of GGNs, especially for pure GGNs, before surgery.


Artefactually-normal automated platelet counts due to malaria-infected RBC.
Protein aggregates, red cell or white cell fragments are known to interfere with platelet counts in automated blood analysers, both by aperture impedance and optical technologies. When a falsely high value is suspected, interference by pseudo-platelet particles can be confirmed by systematic examination of stained blood films. The method that best avoids these sources of interference is the reference, immunological platelet count. We describe a case of treated malaria with a false normal platelet count. The blood smear revealed small red cells, infected by trophozoites of Plasmodium falciparum, that interfered with the platelet count. The Cell Dyn 4000 shows different patterns of interference by infected red cells in its impedance and optical counts, and thrombocytopenia was suspected immediately. This was confirmed by a phase-contrast microscopic platelet count.


[The Role of Nrf2 Pathway Activation in Hippocampal Neuron Injury of Neonatal Rats with Bilirubin Encephalopathy].
To explore the effect of nuclear factor-erythroid 2-related factor (Nrf2) pathway activation on hippocampal neuron damage in neonatal rats with bilirubin encephalopathy. Neonatal rats were randomly assigned to a control group (Control), a model group (Model) and an Nrf2 activator TBHQ (tert-Butylhydroquinone) group (TBHQ), with 20 rats in each group. Bilirubin solution was injected through the cerebellomedullary cistern to establish the neonatal rat model of bilirubin encephalopathy. Neurobehavioral changes were observed in rats and the water content of the brain tissue was measured. Nissl staining was done to observe the damage of hippocampal neurons. TUNEL staining was used to observe the apoptosis of hippocampal neurons. Colorimetric analysis was done to determine the Caspase-3 activity in the hippocampus. The content of malondialdehyde (MDA) and reduced glutathione (GSH) and the activity of superoxide dismutase (SOD) in the hippocampus were examined by chemical analysis. qRT-PCR and Western blot were done to measure the expression of Nrf2 and heme oxygenase-l (HO-1) mRNA and proteins in the hippocampus. After injection of bilirubin into the cerebellomedullary cistern, the young rats in the Model group and the TBHQ group showed different degrees of neurological abnormalities, while those in the control group showed no significant neurobehavioral abnormalities. Compared with the Control group, the Model group had severe neuronal damage, and the water content of brain tissue, the apoptosis of hippocampal neurons, the activity of Caspase-3 and the content of MDA content significantly increased ( P<0.01), while the SOD activity, GSH content, the expression of Nrf2 and HO-1 mRNA and proteins significantly decreased ( P<0.05). Compared with the Model group, neuronal damage was improved in the TBHQ group, and the water content of brain tissue, apoptosis of hippocampal neurons, activity of Caspase-3 and MDA content were all significantly reduced ( P<0.01), while SOD activity, GSH content and the expression of Nrf2 and HO-1 mRNA and proteins were significantly increased ( P<0.05). Activation of the Nrf2 pathway can improve hippocampal neuronal damage in neonatal rats with bilirubin encephalopathy and inhibit neuronal apoptosis and the oxidation reaction.


Sample preparation for plasma measurement of plasminogen activator inhibitor-1 antigen in large population studies.
Plasminogen activator inhibitor-1 is important in regulating fibrinolysis and may be an important cardiovascular risk factor. Because of this, there is increased interest in performing plasminogen activator inhibitor-1 assays in large epidemiologic studies. Our aim in this study was to determine the simplest blood collection methods that yield accurate results with our plasminogen activator inhibitor-1 antigen assay. Our results indicate that the following issues are important: (1) since there is a large circadian variation in plasminogen activator inhibitor-1 plasma levels, a target time frame must be established; (2) commercially available citrate collection tubes are adequate, if sample processing is rapid; (3) careful venipuncture is necessary, with freely flowing collection; hemolysis must be avoided; and (4) centrifugation of at least 30,000 g.min is required to avoid platelet contamination.


A UV-LED module that is highly effective at inactivating human coronaviruses and HIV-1.
Ultraviolet (UV) light has previously been established as useful method of disinfection, with demonstrated efficacy to inactivate a broad range of microorganisms. The advent of ultraviolet light-emitting diodes provides advantages in ease of disinfection, in that there can be delivery of germicidal UV with the same light unit that delivers standard white light to illuminate a room. Herein we demonstrate the efficacy and feasibility of ultraviolet light-emitting diodes as a means of decontamination by inactivating two distinct virus models, human coronavirus 229E and human immunodeficiency virus. Importantly, the same dose of ultraviolet light that inactivated human viruses also elicited complete inactivation of ultraviolet-resistant bacterial spores (Bacillus pumilus), a gold standard for demonstrating ultraviolet-mediated disinfection. This work demonstrates that seconds of ultraviolet light-emitting diodes (UV-LED) exposure can inactivate viruses and bacteria, highlighting that UV-LED could be a useful and practical tool for broad sanitization of public spaces.


Time course of urinary excretion of intraportal ammonia as uric acid and ammonia in chickens fed low- or high-protein diet.
15N-ammonia was intraportally infused for 6 hr into chickens fed 5% or 20% protein diet to examine the time course of urinary excretion of intraportal ammonia and dietary effects on it. Urinary ammonia increased linearly for the first hour to the same extent in both dietary groups and thereafter further in the low-protein group. Urinary uric acid derived from the intraportal ammonia adaptively increased and reached a steady state level within 1.5 hr. This level was four times higher in the high-protein group. The infused ammonia was excreted into urine as both ammonia and uric acid, in relatively high proportions in the chickens fed the low-protein diet but was almost all excreted as uric acid in those fed the high-protein diet.


A Hypothetical Model Suggesting Some Possible Ways That the Progesterone Receptor May Be Involved in Cancer Proliferation.
Cancer and the fetal-placental semi-allograft share certain characteristics, e.g., rapid proliferation, the capacity to invade normal tissue, and, related to the presence of antigens foreign to the host, the need to evade immune surveillance. Many present-day methods to treat cancer use drugs that can block a key molecule that is important for one or more of these characteristics and thus reduce side effects. The ideal molecule would be one that is essential for both the survival of the fetus and malignant tumor, but not needed for normal cells. There is a potential suitable candidate, the progesterone induced blocking factor (PIBF). The parent 90 kilodalton (kDa) form seems to be required for cell-cycle regulation, required by both the fetal-placental unit and malignant tumors. The parent form may be converted to splice variants that help both the fetus and tumors escape immune surveillance, especially in the fetal and tumor microenvironment. Evidence suggests that membrane progesterone receptors are involved in PIBF production, and indeed there has been anecdotal evidence that progesterone receptor antagonists, e.g., mifepristone, can significantly improve longevity and quality of life, with few side effects.


Suppression of immunopathology in schistosomiasis by interleukin-2-targeted fusion toxin, DAB389IL-2. I. Studies of in vitro and in vivo efficacy.
Schistosomiasis causes pathology in an estimated 200 million individuals. Clinical disease is caused by a complex immunopathologic response to the parasite ova, which are deposited in the host tissues. This immunopathologic response is caused by T lymphocytes which express the high-affinity IL-2 receptor (IL-2R). DAB389IL-2 is a diphtheria toxin-IL-2 fusion toxin protein which functionally inactivates or kills cells which bear the high-affinity IL-2R. DAB389IL-2 has been used in man to suppress IL-2R-dependent immune reactivity. Therefore, we reasoned that DAB389IL-2 might suppress immunopathology in schistosomiasis. In these studies we assessed the in vitro and in vivo effects of DAB389IL-2 on the development of immunopathology in murine schistosomiasis. DAB389IL-2 suppressed IL-2, lectin mitogen (Con A), and soluble Schistosoma mansoni egg antigen-induced lymphocyte proliferation and in vitro granuloma formation. In addition, DA-B389IL-2 suppressed in vitro IL-2R expression. DA-B389IL-2 also suppressed the development of granulomas and collagen deposition in vivo in the livers of infected animals. Therefore, DAB389IL-2 may have potential for the targeted reduction of immunopathology due to schistosomiasis in man.


[Cerebral schistosomiasis with a huge calcification. A case report].
A case of cerebral schistosomiasis with a huge calcification and with a long clinical course was reported. A 39-year-old male developed ataxic gait gradually associated with headache and general fatigability. According to the past history, the patient had suffered from severe meningitis with disturbance of consciousness for 2 weeks when he was 10 years of age. Neurological examination revealed positive Romberg's sign and left homonymous hemianopsia. Plain craniogram showed a large calcification occupying the whole right occipital region. This calcification was lobulated in shape and was 11 X 9 X 9 cm in size. CT scan demonstrated calcification and remarkable hydrocephalus. This calcification had no mass effect. Left vertebral angiogram revealed the right parieto-occipital artery to be stretched and slightly displaced toward midline. Hematological analysis disclosed no abnormality except for eosinophilia (10%). Pre-operative diagnosis was an old calcified granuloma of unknown origin. For the purpose of biopsy, a right occipital craniotomy was performed. On reflecting the dura, fibrous adhesion and vascular network were seen between the inner table of the dura and the arachnoid. Subarachnoid space was enlarged and all cortical vessels were narrow in their diameters. By a corticotomy, a whitish-yellow calcified mass was seen in the depth of 2 mm. The yellowish gelatinous content poured out of the mass. A piece of calcification and a small amount of content were taken as specimen. Microscopic study of the calcified tissue showed many egg shells of schistosoma japonica, necrotic tissues and infiltration of small round cells.


Increased Cu/Zn superoxide dismutase-like immunoreactivity in the swollen axons of rats intoxicated chronically with beta,beta'-iminodipropionitrile.
Demonstration of a genetic linkage between the Cu/Zn superoxide dismutase (SOD1) gene and familial amyotrophic lateral sclerosis (ALS) has aroused interest in the role of SOD1 in spinal motoneuronal death. We used chronically beta,beta'-iminodipropionitrile (IDPN)-intoxicated rats as a model of ALS and investigated SOD1 changes in the spinal cord by immunocytochemical and in situ hybridization techniques. Compared with control rats, SOD1-like immunoreactivity (SOD1-IR) increased in swollen axons of the proximal spinal roots, but not in motoneuronal and dorsal root ganglion neuronal cell bodies where SOD1 gene transcription did not increase. The present data indicate that treatment with IDPN induces accumulation of SOD1 in the swollen axons by blocking slow axonal flow, suggesting the possibility that increased SOD1-IR in ALS is induced by axonal flow blockade.


Minimally invasive plate osteosynthesis for short oblique diaphyseal tibia fractures: does fracture site affect the outcomes?
To report the results of patients with short oblique diaphyseal tibia fractures treated with minimally invasive plate osteosynthesis (MIPO). The secondary aim was to understand the effect of fracture location (midshaft or distal 1/3) on outcomes. Twenty-eight patients with short oblique (>30°) tibial shaft fractures (AO/OTA 42A2) treated with plate and MIPO technique between 2015 and 2019 were retrospectively assessed. Age, gender, follow-up time, fracture type (open or closed), operation time, postoperative infection rate, union time, ankle joint range of motion, and complications were analyzed. Patients' radiographs at a minimum 1-year follow-up were evaluated for malunion, nonunion, and implant-related complications. Mean age and follow-up time were 47.0 ± 15.7 years and 18.3 ± 12.1 months, respectively. Mean bone union time was 3.66 ± 1.04 months in middle 1/3 diaphysis and 4.23 ± 1.48 months in distal 1/3 tibia fractures. Seven (25%) patients developed superficial infections. Mean union time, malunion rate, coronal and sagittal angulation, operation length, and infection rate were similar between the groups. MIPO is an effective method for treatment of short oblique diaphyseal tibia fractures, and results in few complications. Both distal and midshaft fractures have similar union and malunion rates.


Age-dependent characterization of carotid and cerebral artery geometries in a transgenic mouse model of sickle cell anemia using ultrasound and microcomputed tomography.
To define morphological changes in carotid and cerebral arteries in sickle cell transgenic mice (SS) as they age, a combination of ultrasound and microcomputed tomography of plastinated arteries was used to quantify arterial dimensions and changes in mice 4, 12, and 24 weeks of age. 12-week SS mice had significantly larger common carotid artery diameters than AS mice, which continued through to the extracranial and intracranial portions of the internal carotid artery (ICA). There were also side specific differences in diameters between the left and right vessels. Significant ICA tapering along its length occurred by 12- and 24-weeks in SS mice, decreasing by as much as 70%. Significant narrowing along the length was also measured in SS anterior cerebral arteries at 12- and 24-weeks, but not AS. Collectively, these findings indicate that sickle cell anemia induces arterial remodeling in 12- and 24-weeks old mice. Catalog of measurements are also provided for the common carotid, internal carotid, anterior cerebral, and middle cerebral arteries for AS and SS genotypes, as a reference for other investigators using mathematical and computational models of age-dependent arterial complications caused by sickle cell anemia.


[Evaluation of a hospitalization unit opened during the winter influenza epidemic of 1999-2000].
Last winter, a great many patients with influenza-like infection were admitted to our hospital, leading us to open a specific unit for 6 weeks. We report the evaluation of medical care given to these patients. Useful data for evaluating care to patients presenting respiratory infections were determined beforehand by the retrospective analysis of patients' charts. Fifty-seven out of 185 admitted patients (31%) had infectious respiratory symptoms. The mean age was 81 years. Six cases of influenza virus infection, 43 cases of viral bronchitis, six cases of bacterial pneumonia, one superinfected asthma and one septic shock were diagnosed. All patients presented with cardiac and/or chronic pulmonary diseases. Influenza vaccination had been performed in 28 patients (49%). Before hospitalisation, 30 patients (52%) had received antibiotics, and 17 (30%) a steroid therapy. In contrast, only 12 patients (21%) have received anti-infective agents during the hospitalisation. Twenty-five patients were able to go back home and a nursing home was required for 27 patients (47%); five patients died. Tools for improving this specific department in a public hospital are discussed. Vaccinations in the elderly appear to be poorly utilized; meanwhile, antibiotic treatments, as well as steroid therapy, are overused. Managing epidemic infections requires attention from the public hospital system.


Assessment of lung cancer risk factors by histologic category.
The patterns of risk by histologic type of lung cancer were analyzed with the use of data from a large hospital-based case-control study (7,804 cases and 15,207 controls) of lung cancer performed in Western Europe. Relative risks (RR) increased with duration of cigarette use for all histologic types, although the gradients of risk were greater for Kreyberg I cell types, particularly squamous cell carcinoma (SCC), than for adenocarcinoma (AC). Risks also declined more sharply with years since cessation of smoking for all Kreyberg I cell types, in particular for SCC, rather than for AC. After adjustment for duration of use, the RR associated with number of cigarettes smoked per day, frequency and depth of inhalation, and fraction of cigarette consumed were not consistently different by cell type, suggesting that intensity-related measures of cigarette exposure have less effect on cell type than duration-related factors. Among those who never smoked there were marked cell type differences by sex, with a greater proportion of AC compared to SCC for females (45 vs. 25%) than for males (35 vs. 33%). Review of limited work histories indicated that occupational associations also were more strongly related to Kreyberg I than to Kreyberg II tumors.


Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer and the Dutch Belgian Hemato-Oncology Cooperative Group.
We conducted a prospective randomized multicenter clinical trial comparing the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to intensive chemotherapy in patients of 61 years and older with untreated newly diagnosed acute myeloid leukemia (AML). Patients were randomized to either receive daunomycin-cytosine arabinoside with GM-CSF or daunomycin-cytosine arabinoside (control arm). Based on the rationale that GM-CSF might sensitize the leukemic cells to the cytotoxicity of chemotherapy as well as enhance white blood cell regeneration, GM-CSF was given during chemotherapy as well as after chemotherapy. Patients were treated with one, and in case of a partial response, with two remission induction cycles. When a complete remission was attained they received one additional cycle of consolidation therapy. Of 318 evaluable patients with a median age of 68 years, 157 were randomized to receive GM-CSF and 161 were assigned to control therapy. The effect of GM-CSF on treatment was evaluated according to intention-to-treat. Complete remission was achieved in 56% of the patients in the GM-CSF group and 55% of the control patients (P = .98). Recovery of neutrophils was significantly faster in GM-CSF-treated patients. The median time of recovery of neutrophils towards 0.5 x 10(9)/L was 23 days in the GM-CSF group versus 25 days in the control group (P = .0002) with the percentages of patients who recovered being 81% and 71%, respectively. With a median follow-up of 36 months, the probabilities of survival at 2 years after randomization were estimated at 22% for individuals assigned to the GM-CSF treatment as well as for control patients (P = .55). Disease-free survival at 2 years compared 15% and 19% for the two treatment groups (P = .69). The number of nights spent in the hospital, number of transfusions, and frequencies and types of hemorrhages and infections did not differ either. The cytogenetic results at diagnosis of this study in elderly AML shows that there is a relatively high numerical representation of patients with abnormal cytogenetics (55% of documented cases), who showed significantly inferior response rates and survival duration. We conclude that, except for a faster neutrophil recovery, GM-CSF during and after induction chemotherapy does not improve the clinical outcome of elderly patients with AML.


Enhanced anticaries efficacy of a 0.243% sodium fluoride/10% xylitol/silica dentifrice: 3-year clinical results.
To evaluate the efficacy of a sodium fluoride (NaF)/silica/xylitol dentifrice compared with that of a positive control NaF/silica dentifrice on caries increments in school children over a 3-year period in an area without an optimal level of fluoride in the drinking water (mean level <0.1 ppm). A 3-year, double-blind clinical caries study was conducted in 2,630 children initially aged 8-10 years at 17 schools in the San Jose, Costa Rica metropolitan area. Clinical dental examinations were performed at participating schools utilizing portable dental equipment. Caries evaluations employed conventional tactile/visual methodology consisting of artificial light, dental mirrors and single-edge #23 explorers. Children accepted into the study were stratified by age and sex into two balanced groups within each school, and randomly assigned to use either a positive control dentifrice containing 0.243% NaF/silica or a test dentifrice containing 0.234% NaF/silica/10% xylitol. Children were instructed to brush with the assigned dentifrice twice daily. Caries evaluations were conducted at baseline, 2 years, and 3 years. After 3 years, subjects using the 0.234% NaF/silica/10% xylitol dentifrice had statistically significantly reduced decayed/filled surfaces (DFS; -12.3% reduction; P < or = 0.001) and decayed/filled buccal and lingual surfaces (DFS-BL; -10.5% reduction; P < or = 0/01).


Peritoneal dialysis: myths, barriers, and achieving optimum outcomes.
Peritoneal dialysis provides an excellent alternative to in-center hemodialysis but the development of successful programs is often plagued by myths and misinformation. A review of recent literature can dispel some of the common myths and help understand the barriers to this modality. In addition, achieving optimum outcomes in peritoneal dialysis program requires an active continuous quality improvement team.


Current issues and future perspectives of gastric cancer screening.
Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries, which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques, namely, upper gastrointestinal endoscopy, serological testing, and "screen and treat" method were extensively reviewed. Moreover, the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand, serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date, the effectiveness of new techniques for gastric cancer screening has remained limited. However, endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening. To effectively introduce new techniques for gastric cancer screening in a community, incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies. In addition to effectiveness evaluation, the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening.


Revision Total Hip and Knee Arthroplasty are Associated With Lower Hospital Consumer Assessment of Healthcare Providers and Systems Patient Satisfaction Scores Compared With Primary Arthroplasty.
As rates of primary total joint arthroplasty continue to rise, so do rates of revision. Revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) are more frequently done at larger centers, are associated with higher morbidity, and may have different patient satisfaction outcomes. This study compares the survey results of Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) between patients who underwent primary versus revision THA or TKA. All adult patients who underwent inpatient, elective, primary, and revision THA or TKA at a single institution were selected for retrospective analysis. Patient demographics, comorbidities, functional status, surgical variables, 30-day outcomes, and HCAHPS scores were assessed. Univariate and multivariate analyses were done to determine correlations between the aforementioned variables and top-box HCAHPS survey scores for primary versus revision THA and TKA. Of 2,707 patients who met the inclusion criteria and had returned the HCAHPS survey, primary THA was documented in 1,075 patients (39.71%), revision THA in 75 (2.77%), primary TKA in 1,497 (55.30%), and revision TKA in 60 (2.22%). Revision THA patients were more functionally dependent, and TKA patients had higher American Society of Anesthesiologists score than their primary comparators. Revisions had longer hospital length of stay for both procedures. For THA, revision THA patients demonstrated lower total top-box rates compared withprimary THA patients (71.64% versus 75.67% top-box, P < 0.001) and lower scores on the care from doctors subsection (76.26% versus 85.34%, P < 0.001) of the HCAHPS survey. Similarly, for TKA, revision TKA patients demonstrated lower total top-box rates (76.13% versus 79.22%, P < 0.013) and lower scores on the care from doctors subsection (66.28% versus 83.65%, P < 0.001) of the HCAHPS survey. For both THA and TKA, revision procedures were associated with lower total HCAHPS scores and rated care from doctors. This suggests that HCAHPS scores may be biased by factors outside the surgeon's control, such as the complexity associated with revision procedures. Level III.


beta-Amyloid and endoplasmic reticulum stress responses in primary neurons: effects of drugs that interact with the cytoskeleton.
In vitro studies designed to probe the cellular mechanisms underlying beta-amyloid (Abeta) toxicity in neurons have implicated several processes, including hyperphosphorylation of the microtubule (MT)-associated protein tau, loss of MT stability, and increased cytosolic calcium levels. Given that Alzheimer's disease involves accumulation of aggregates of two different proteins, the potential involvement of the unfolded protein response (UPR) and endoplasmic reticulum (ER) dysfunction has been suggested to lead to cell death. The relationship between these apparently divergent factors and pathways in Abeta toxicity is still unclear. In these studies we investigated the relationship between MT stability and the ER stress response in primary neurons exposed to toxic Abeta peptides in culture. In addition, nocodazole (ND) was used to determine if direct disruption of MT organization activated the UPR. Pretreatment of neurons with MT-stabilizing drugs paclitaxel (Taxol) and epothilone A prevented the induction of three indicators of the UPR induced by Abeta, ND, and thapsigargin, a compound known to inhibit the sarco-ER Ca(2+)-ATPase and deplete ER calcium stores, resulting in initiation of the UPR. In addition, treatment with MT-stabilizing drugs blocked cell death and the cytoskeletal disorganization induced by these insults. The results suggest that loss of cytoskeletal integrity is a very early step in the response to a variety of toxic stimuli and that preservation of MT stability might be important in preventing the induction of ER dysfunction and subsequent cell death by Abeta in neurons.


Tumor necrosis factor mediates apoptosis via Ca++/Mg++ dependent endonuclease with protein kinase C as a possible mechanism for cytokine resistance in human renal carcinoma cells.
Because renal cell cancers have been found to be resistant to numerous chemotherapeutic agents, other agents including tumor necrosis factor are now being considered for clinical use. In this study, we used 2 renal cancer cell lines. SK-RC-42 and SK-RC-49, and determined the cytotoxic effects of tumor necrosis factor (TNF) and the possible mechanism of TNF resistance. Cytotoxic assays, comparative reverse transcriptase-polymerase chain reaction (RT-PCR) and nuclease digestion analyses were used. Cytotoxic assays with SK-RC-42 demonstrated that TNF at 50 ng./ml. for 24 hours resulted in 19% cytotoxicity of the cells. Similar assay with SK-RC-49 only demonstrated less than 4% cytotoxicity. Based on these results, we defined our TNF-sensitive cells as SK-RC-42 and SK-RC-49 as our TNF-resistant cells. To determine whether protein kinase C (PKC), which is involved in the signal transduction pathway of a cell, could regulate endogenous basal TNF mRNA levels, comparative PCR analyses for TNF expression were used. The PCR results demonstrated that the TNF-resistant cell, SK-RC-49, had a higher basal expression of TNF mRNA than the TNF-sensitive cell SK-RC-42. With PMA, a PKC activator, for various time points, both cell lines demonstrated an induction of endogenous TNF mRNA. To further confirm our findings that PKC may regulate endogenous TNF expression, a PKC inhibitor, staurosporine, was used. When the cells were treated with staurosporine prior to PMA stimulation, no increase in TNF mRNA expression was seen. To determine whether PKC is involved in providing resistance against TNF, we incubated the SK-RC-42 and SK-RC-49 cells with staurosporine at 100 nM. and TNF at 50 ng./ml. for 24 hours. After factoring out the cytotoxicity of staurosporine, the TNF-mediated cytotoxicity increased to 39.3% and 28.7% for the SK-RC-42 and SK-RC-49 cells, respectively. Furthermore, by using a nuclease digestion assay, we demonstrated that TNF activated a Ca++/Mg++ dependent endonuclease responsible for programmed cell death or apoptosis. Our data suggest that protein kinase C may play a role in protecting renal cancer cells from undergoing cytokine-mediated apoptosis.


Pregnancy-Associated Chest Pain: A Case of Spontaneous Coronary Artery Dissection.
Spontaneous Coronary Artery Dissection (SCAD) is an important cause of myocardial infarction that typically affects women without traditional cardiovascular risk factors. It is the most common cause of myocardial infarction in pregnant and postpartum women. SCAD is often underdiagnosed due to the lack of clinician familiarity, and patients with pregnancy-associated SCAD often have more severe clinical presentations than those without. We present a case of SCAD in a multiparous woman who presented with acute chest pain in the postpartum period.


Detecting impaired vision caused by AMD from gaze data.
Age Related Macular Degeneration (AMD) is the third leading cause of blindness and the first one in the elderly. AMD usually causes central blindness due to loss of photoreceptor cell . In this paper, we propose to detect AMD caused vision impairment from gaze data. Compared with the current methods, e.g., Amsler grid, Microperimetry and Preferential Hyperacuity Perimetry, to detect vision impairments, the proposed method has several advantages. 1) It does not require the patient to stare at a fixed position throughout the test. 2) It does not require the patient to orally or manually report / mark out the vision impairment. 3) It is easy to operate thus a trained nurse is capable of operating the test. We collect gaze data while the patient is performing fixation and smooth pursuit. Features describing the gaze properties are extracted and SVM with linear kernel is trained to detect AMD impaired vision. To implement the proposed method, we collected gaze data of 74 eyes of 57 patients, who are diagnosed as AMD patient by clinicians. Nidek Microperimetry is adopted as gold standard. 57 eyes with normal vision and 17 eyes with impaired vision (blind at more than half test points in Nidek test) are used for test. The result verifies the effectiveness of detecting vision impairment from gaze data.


Apo, Zn2+-bound and Mn2+-bound structures reveal ligand-binding properties of SitA from the pathogen Staphylococcus pseudintermedius.
The Gram-positive bacterium Staphylococcus pseudintermedius is a leading cause of canine bacterial pyoderma, resulting in worldwide morbidity in dogs. S. pseudintermedius also causes life-threatening human infections. Furthermore, methicillin-resistant S. pseudintermedius is emerging, resembling the human health threat of methicillin-resistant Staphylococcus aureus. Therefore it is increasingly important to characterize targets for intervention strategies to counteract S. pseudintermedius infections. Here we used biophysical methods, mutagenesis, and X-ray crystallography, to define the ligand-binding properties and structure of SitA, an S. pseudintermedius surface lipoprotein. SitA was strongly and specifically stabilized by Mn2+ and Zn2+ ions. Crystal structures of SitA complexed with Mn2+ and Zn2+ revealed a canonical class III solute-binding protein with the metal cation bound in a cavity between N- and C-terminal lobes. Unexpectedly, one crystal contained both apo- and holo-forms of SitA, revealing a large side-chain reorientation of His64, and associated structural differences accompanying ligand binding. Such conformational changes may regulate fruitful engagement of the cognate ABC (ATP-binding cassette) transporter system (SitBC) required for metal uptake. These results provide the first detailed characterization and mechanistic insights for a potential therapeutic target of the major canine pathogen S. pseudintermedius, and also shed light on homologous structures in related staphylococcal pathogens afflicting humans.


Intrauterine insemination with ultrasound guidance in the long-tailed macaque (Macaca fascicularis).
Techniques used for the artificial insemination of macaques have primarily involved instillation of the ejaculate into the vagina or cervical canal. Intrauterine insemination has been performed previously but only as a surgical procedure. The application of ultrasound-guided techniques for this purpose provides a method for efficiently inseminating macaques in a relatively noninvasive fashion. This report describes the successful transabdominal ultrasound-guided insemination of the long-tailed macaque and the potential application of this procedure to a variety of nonhuman primate species.


The Cell Wall Proteome of Marchantia polymorpha Reveals Specificities Compared to Those of Flowering Plants.
Primary plant cell walls are composite extracellular structures composed of three major classes of polysaccharides (pectins, hemicelluloses, and cellulose) and of proteins. The cell wall proteins (CWPs) play multiple roles during plant development and in response to environmental stresses by remodeling the polysaccharide and protein networks and acting in signaling processes. To date, the cell wall proteome has been mostly described in flowering plants and has revealed the diversity of the CWP families. In this article, we describe the cell wall proteome of an early divergent plant, Marchantia polymorpha, a Bryophyte which belong to one of the first plant species colonizing lands. It has been possible to identify 410 different CWPs from three development stages of the haploid gametophyte and they could be classified in the same functional classes as the CWPs of flowering plants. This result underlied the ability of M. polymorpha to sustain cell wall dynamics. However, some specificities of the M. polymorpha cell wall proteome could be highlighted, in particular the importance of oxido-reductases such as class III peroxidases and polyphenol oxidases, D-mannose binding lectins, and dirigent-like proteins. These proteins families could be related to the presence of specific compounds in the M. polymorpha cell walls, like mannans or phenolics. This work paves the way for functional studies to unravel the role of CWPs during M. polymorpha development and in response to environmental cues.


Bilaminar Palatal Connective Tissue Grafts Obtained With the Modified Double Blade Harvesting Technique: Technical Description and Case Series.
The purpose of this case series is to present a technique to harvest palatal connective tissue grafts (CTGs) that concurrently provides several advantages over previously described techniques when applied to treat gingival recessions. Twenty patients were treated with root coverage procedures using CTGs harvested with the modified double blade harvesting technique (MDBHT). A double blade knife with two surgical blades set 1 mm apart was used in this case series. The palatal connective tissue was accessed through a horizontal incision and an envelope flap that was closed by primary intention. The grafts were measured immediately after harvesting with a periodontal probe. The overall mean length was 28.8 ± 7.8 mm and graft thickness was homogeneous and near to 1 mm in all the cases. Graft mean apicocoronal height was 5.0 ± 0.8 mm and 5.3 ± 1 mm at the molar and premolar levels, respectively. Clinical wound healing was evaluated at 7 days post-surgically and showed a modified early-wound healing index mean value of 3.0 ± 1.0. The introduced MDBHT consistently rendered grafts of uniform thickness and sufficient dimensions, while excluding epithelial tissue and the deeper aspects of the submucosa, thus avoiding rich fatty and glandular tissues. MDBHT allowed for donor site healing with minimal discomfort and without complications.


Delivering mental health awareness training to police officers.
Police officers regularly come into contact with people with mental health problems but receive relatively little training on the issue. This article outlines an initiative to deliver awareness training to officers, and explores the benefits of such programmes. It also gives details of the evaluation carried out.


Identification of the site of interaction of the 14-3-3 protein with phosphorylated tryptophan hydroxylase.
The 14-3-3 protein family plays a role in a wide variety of cell signaling processes including monoamine synthesis, exocytosis, and cell cycle regulation, but the structural requirements for the activity of this protein family are not known. We have previously shown that the 14-3-3 protein binds with and activates phosphorylated tryptophan hydroxylase (TPH, the rate-limiting enzyme in the biosynthesis of neurotransmitter serotonin) and proposed that this activity might be mediated through the COOH-terminal acidic region of the 14-3-3 molecules. In this report we demonstrate, using a series of truncation mutants of the 14-3-3 eta isoform expressed in Escherichia coli, that the COOH-terminal region, especially restricted in amino acids 171-213, binds indeed with the phosphorylated TPH. This restricted region, which we termed 14-3-3 box I, is one of the structural regions whose sequence is highly conserved beyond species, allowing that the plant 14-3-3 isoform (GF14) could also activate rat brain TPH. The 14-3-3 box I is the first functional region whose activity has directly been defined in the 14-3-3 sequence and may represent a common structural element whereby 14-3-3 interacts with other target proteins such as Raf-1 kinase. The result is consistent with the recently published crystal structure of this protein family, which suggests the importance of the negatively charged groove-like structure in the ligand binding.


Effect of Light on Chemical Modification of Chloroplast Ferredoxin-NADP Reductase.
Chemical modification of spinach chloroplasts by phenylglyoxal and dansyl chloride resulted in inhibition of NADP photoreduction. The rate of inactivation was higher with both reagents when modification was carried out in the light with methylviologen or phenazine methosulfate present. Uncouplers prevent the effect of light. Electron transport from water to methylviologen was not affected by the modifiers.The presence of 10 millimolar NADP completely protected the membrane-bound reductase against inactivation by phenylglyoxal. With lower concentrations, protection was higher in the light than in the dark. The apparent dissociation constants of the enzyme-substrate complex for NADP were 0.9 and 0.1 millimolar for the dark and light inactivation, respectively. Inactivation of NADP photoreduction by dansyl chloride was completely prevented by ferredoxin, but only partially by nucleotides.The diaphorase activity was inhibited in chloroplasts modified by phenylglyoxal, but not when modified by dansyl chloride.The results suggest that energizing thylakoid membranes by light induces a conformational change in membrane-bound ferredoxin-NADP reductase, and that the reductase is an allotopic enzyme.


Epidermoid cyst in Meckel's cave with unusual computed tomography and magnetic resonance imaging findings. Case report.
A 27-year-old woman presented with headache and occasional numbness over her right face. Computed tomography revealed a hypodense mass in the middle cranial fossa and another adjacent hyperdense mass in the posterior fossa with erosion of the right petrous apex. Magnetic resonance imaging revealed the lesion in the middle cranial fossa as iso- to hypointense on T(1)-weighted and hyperintense on T(2)-weighted imaging, with peripheral enhancement after gadolinium administration, and the adjacent lesion in the posterior fossa as hyperintense on T(1)-weighted and hypointense on T(2)-weighted imaging. During surgery, these lesions mimicking two adjacent distinct tumors were revealed to connect through Meckel's cave. The hypodense lesion in the middle cranial fossa consisted of pearly-like solid contents, and the hyperdense lesion in the posterior cranial fossa consisted of viscid dark-green materials. The tumors were gross totally resected with endoscopic assistance. Histological examination confirmed that the tumor was an epidermoid cyst. The present case cyst indicates that although the diffusion-weighted imaging sequence is useful for detection of intracranial epidermoid cysts, epidermoid cysts including viscous materials with unusual radiological findings could complicate the preoperative diagnosis.


Identification of novel omega-3 fatty acid-derived bioactive metabolites based on a targeted lipidomics approach.
Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid have beneficial effects in many inflammatory disorders. Although the mechanism of eicosapentaenoic acid and docosahexaenoic acid action is still not fully defined in molecular terms, recent studies have revealed that, during the course of acute inflammation, omega-3 polyunsaturated fatty acid-derived anti-inflammatory mediators including resolvins and protectins are produced. This review presents recent advances in understanding the formation and action of these mediators, especially focusing on the LC-MS/MS-based lipidomics approach and recently identified bioactive products with potent anti-inflammatory property.


Lesion Material From Treponema-Associated Hoof Disease of Wild Elk Induces Disease Pathology in the Sheep Digital Dermatitis Model.
A hoof disease among wild elk (Cervus elaphus) in the western United States has been reported since 2008. Now present in Washington, Oregon, Idaho, and California, this hoof disease continues to spread among elk herds suggesting an infectious etiology. Causing severe lesions at the hoof-skin junction, lesions can penetrate the hoof-horn structure causing severe lameness, misshapen hooves, and in some cases, sloughed hooves leaving the elk prone to infection, malnutrition, and premature death. Isolated to the feet, this disease has been termed treponeme-associated hoof disease due to the numerous Treponema spp. found within lesions. In addition to the Treponema spp., treponeme-associated hoof disease shares many similarities with digital dermatitis of cattle and livestock including association with several groups of anaerobic bacteria such as Bacteroides, Clostridia, and Fusobacterium, neutrophilic inflammatory infiltrate, and restriction of the disease to the foot and hoof tissues. To determine if there was a transmissible infectious component to this disease syndrome, elk lesion homogenate was used in a sheep model of digital dermatitis. Ten animals were inoculated with lesion material and lesion development was followed over 7 weeks. Most inoculated feet developed moderate to severe lesions at 2- or 4-weeks post-inoculation timepoints, with 16 of 18 feet at 4 weeks also had spirochetes associated within the lesions. Histopathology demonstrated spirochetes at the invading edge of the lesions along with other hallmarks of elk hoof disease, neutrophilic inflammatory infiltrates, and keratinocyte erosion. Treponema-specific PCR demonstrated three phylotypes associated with elk hoof disease and digital dermatitis were present. Serum of infected sheep had increased anti-Treponema IgG when compared to negative control sheep and pre-exposure samples. Analysis of the bacterial microbiome by sequencing of the bacterial 16S rRNA gene showed a community structure in sheep lesions that was highly similar to the elk lesion homogenate used as inoculum. Bacteroidies, Fusobacterium, and Clostridia were among the bacterial taxa overrepresented in infected samples as compared to negative control samples. In conclusion, there is a highly transmissible, infectious bacterial component to elk treponeme-associated hoof disease which includes several species of Treponema as well as other bacteria previously associated with digital dermatitis.


COVID-19 pandemic outbreak: the Brazilian reality from the first case to the collapse of health services.
Coronavirus is associated with several infectious diseases that cause outbreaks in humans, such as SARS in 2002-2003 and MERS in 2012. In December 2019, COVID-19, promoted by the SARS-CoV-2 virus, was first reported in Wuhan (China) as a new coronavirus disease. This outbreak quickly reached a pandemic status, affecting at least 185 countries and territories to date on all continents. The first case of COVID-19 reported in São Paulo city (Brazil) occurred in February 26th. Days later, 182 suspected cases in 16 states were being monitored. In May 30th, 514,849 cases and 29,314 deaths were confirmed in Brazil comprising all 26 states and Federal District. The primary measure in order to contain the spread of SARS-CoV-2 involved social isolation. At that time there were not enough diagnostic tests to identify infected individuals and data were strongly associated with sub notifications. Nevertheless, the effectiveness of this measure largely depends on the individual's social responsibility. This measure has a severe economic and social impact, as in other countries. In this review, we present an overview and scientific perspectives of the evolution of COVID-19 from Brazilian databases in which climate and economic situations differ from China, European countries, and the USA.


Accuracy of a diagnostic strategy combining aortic dissection detection risk score and D-dimer levels in patients with suspected acute aortic syndrome.
The European Society of Cardiology recently proposed a novel diagnostic algorithm combining the aortic dissection detection (ADD) risk score with D-dimer level assessment for detecting acute aortic syndromes (AASs) in patients presenting with chest pain. The diagnostic accuracy of this strategy is yet to be validated. We retrospectively identified 376 patients with chest pain and available D-dimer on admission to the emergency department of our institution between January 2011 and May 2014. The ADD risk score was calculated using retrospective blinded chart review. A score ⩽1 was defined as 'low probability', whereas a score >1 as 'high probability'. AASs were diagnosed in 85 (22.6%) patients. Patients with AAS more frequently had a 'high probability' score than AAS-negative patients (63.5% vs 1.0%; P<0.001). An ADD risk score ⩾1 had a sensitivity of 98.8% and a specificity of 64.6% for diagnosing AAS with a failure rate of 0.5%, whereas an ADD risk score ⩾2 had a sensitivity of 63.5% and a specificity of 98.9% with a failure rate of 9.7%. Among the patients with a 'low probability' score, D-dimer had a sensitivity and specificity for the detection of AAS, respectively, of 93.5% and 63.2%, with a negative predictive value of 98.9% and a failure rate of 1.1%. A 'high probability' ADD score detected AAS with good specificity. A 'low probability' score combined with negative D-dimer safely and efficiently ruled out AAS with a low failure rate.


Initiation of antiretroviral therapy at high CD4+ cell counts is associated with positive treatment outcomes.
There is limited research investigating the possible mechanisms of how starting combination antiretroviral therapy (cART) at a higher CD4 cell count decreases mortality. This study investigated the association between initiating cART with short-term and long-term achievement of viral suppression; emergence of any drug resistance and of an AIDS-defining illness (ADI); long-term treatment adherence; and all-cause mortality. This retrospective cohort study included 4120 naive patients who initiated cART between 2000 and 2012. Patients were followed until 2013, death or until the last contact date (varied by outcome). The main exposure was the interaction between period of cART initiation (2000-2006 and 2007-2012) and CD4 cell count at cART initiation (<500 versus ≥500 cells/μl). We considered both baseline and longitudinal covariates. We fitted different multivariable models using cross-sectional and longitudinal statistical methods, depending on the outcome. Patients who initiated cART with a CD4 cell count at least 500 cells/μl in 2007-2012 had an increased likelihood of achieving viral suppression at 9 months and of maintaining an adherence level of at least 95% over time, and the lowest probability of developing any resistance and an ADI during follow-up. These patients were not the ones with the highest likelihood of maintaining viral suppression over time, most likely due to viral load blips experienced during the follow-up. The outcomes in this study likely play an important role in explaining the positive impact of early cART initiation on mortality. These results should alleviate some of the concerns clinicians may have when initiating cART in patients with high CD4s as recommended by current treatment guidelines.


Key genes differential expressions and pathway involved in salt and water-deprivation stresses for renal cortex in camel.
Camels possess the characteristics of salt- and drought-resistances, due to the long-time adaption to the living environment in desert. The camel resistance research on transcriptome is rare and deficient, especially reabsorption in renal cortex. Non-coding RNAs are normally considered as the RNA molecules that are not translated into proteins, their current roles remain mostly in regulation of information flux from DNA to protein, further on normal life activities and diseases. In order to reveal the mysterious veil of the post-transcriptional regulation of ncRNAs in renal cortex for the first time as far as we know, we designed and carried out the experiment of salt stress and water-deprivation stress in camel. By means of RNA-seq in renal cortex of Alxa Bactrian Camel (Camelus bactrianus), we identified certain significantly differential RNAs, including 4 novel lncRNAs, 11 miRNAs and 13 mRNAs under salt stress, 0 lncRNAs, 18 miRNAs and 14 mRNAs under water-deprivation stress. By data analysis, the response pathway of post-transcriptional regulation concerning salt and water-deprivation stresses was put forward, involving preventing sodium from entering the cell, purifying of water and compensating neutral amino acids by miR-193b, miR-542-5p interaction with SLC6A19 mRNA. Based on the resistance-related lncRNAs, miRNAs, and mRNAs, we proposed the post-transcriptional regulation pathway to explain how camels respond to salt and water-deprivation stresses in the ncRNAs regulation level of renal cortex for the first time, thus hoping to provide a theoretical basis for therapy of disease that is similar to high blood pressure in humans.


Molecular cloning and characterization of senescence-related genes from carnation flower petals.
The senescence of carnation (Dianthus caryophyllus L.) flower petals is associated with increased production of ethylene which plays an important role in regulating this developmental event. Three senescence-related cDNA clones were isolated from a cDNA library prepared from mRNA isolated from senescing petals. These cDNAs are representative of two classes of mRNAs which increase in abundance in senescing petal tissue. The mRNA for one class is present at low levels during the early stages of development and begins to accumulate in mature petals prior to the increase in ethylene production. The accumulation of this mRNA is reduced, but not eliminated, in petals treated with aminooxyacetic acid, an inhibitor of ethylene biosynthesis, or silver thiosulfate, an ethylene action inhibitor. In contrast, expression of the second class of mRNAs appears to be highly regulated by ethylene. These mRNAs are not detectable prior to the rise in ethylene production and increase in abundance in parallel with the ethylene climacteric. Furthermore, expression of these mRNAs is significantly inhibited by both aminooxyacetic acid and silver thiosulfate. Expression of these mRNAs in vegetative and floral organs was limited to floral tissue, and predominantly to senescing petals.


Application of Molecular Pathology in Endocrine Pathology.
Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values.


Spontaneously Ruptured Giant Splenic Cyst with Elevated Serum Levels of CA 19-9, CA 125 and Carcinoembryonic Antigen.
Splenic cyst is a relatively rare disease; however, the occurrence of complications associated with its rupture is even more rare. A 20-year-old female patient who had severe abdominal and left shoulder pain was admitted to our hospital. The patient's abdomen was hard and tender to the touch and she presented with a high fever. The patient's serum levels of the tumor markers carbohydrate antigen 19-9, cancer antigen 125 and carcinoembryonic antigen were high. Ultrasonography and computed tomography of the abdomen showed an 11-cm multilocular cystic lesion in the spleen and the presence of free intraperitoneal fluid. Peritonitis with ruptured splenic cyst was diagnosed, and the patient underwent an emergency laparotomy. The abdominal cavity was filled with purulent fluid. The cyst was localized to the spleen and had already ruptured. Total splenectomy and cyst resection were performed. The postoperative course was uneventful. The patient was discharged on day 9 following surgery. The histological findings showed the lesion to be a benign epidermoid cyst completely lined with inner stratified squamous epithelium with a capsule of connective tissue. In the immunostaining analyses, the squamous epithelium was positive for carcinoembryonic antigen. A ruptured splenic cyst causes sudden onset of severe peritonitis and elevation of serous tumor markers. An emergency operation is indicated as the treatment for a ruptured splenic cyst with peritonitis, after which a favorable outcome can be expected.


Estimated 2017 refrigerant emissions of 2,3,3,3-tetrafluoropropene (HFC-1234yf) in the United States resulting from automobile air conditioning.
In response to recent regulations and concern over climate change, the global automotive community is evaluating alternatives to the current refrigerant used in automobile air conditioning units, 1,1,1,2-tetrafluoroethane, HFC-134a. One potential alternative is 2,3,3,3-tetrafluoropropene (HFC-1234yf, also known as HFO-1234yf). We have developed a spatially and temporally resolved inventory of likely future HFC refrigerant emissions from the U.S. vehicle fleet in 2017, considering regular, irregular, servicing, and end-of-life leakages. We estimate the annual leak rate emissions for each leakage category for a projected 2017 U.S. vehicle fleet by state, and spatially apportion these leaks to a 36 km square grid over the continental United States. This projected inventory is a necessary first step in analyzing for potential atmospheric and ecosystem effects, such as ozone and trifluoroacetic acid production, that might result from widespread replacement of HFC-134a with HFC-1234yf.


[Long term follow-up of non-symptomatic HBsAg carriers].
232 asymptomatic HBsAg carriers were controlled between May/1986 and May/1990. The were detected in our blood bank between 1974 and 1976 or during pregnancy or delivery period after 1981. 23 of 232 (10%) became negative during the follow-up, this happening more frequently in carriers after 5 years of follow-up. Only 2 of 209 carriers with HBsAg were HBeAg positive and 1 of these was also DNA-VHB positive. None of the HBeAg negative carriers showed DNA-VHB; only 5 had increased transaminases. 7 were anti-VHC positive, these individuals experiencing more frequent increases in transaminases. The results of this study suggests that the determination of transaminases, viral activity markers, anti-HD, anti-VHC in HBsAg carriers are enough to identify those with hepatic disease.


The biological and physiological responses of Leptinotarsa decemlineata Say (Col. Chrysomelidae) to different potato cultivars.
The use of pest-resistant or less susceptible plant varieties is of great importance for integrated pest management programs. This study was conducted to evaluate the resistance of seven potato cultivars to a major pest, namely the Colorado potato beetle (CPB), by measuring its bio-physiological aspects. The longest developmental time and the lowest survival rate of CPB were detected on cultivar 'Manitou.' Although the larvae fed voraciously, the food conversion efficiency was the lowest on this cultivar leading to the lowest relative growth rate. Furthermore, larvae reared on Manitou had the lowest total protease activity and specific activity values of cathepsin B compared to the larvae reared on other cultivars. Additionally, the cluster analysis showed that the Manitou cultivar was the least suitable (partially resistant) CPB. Moreover, the results indicated that the protein content was the lowest in the Manitou cultivar; conversely, this cultivar was rich in polyphenol and flavonoid compared to Agria and Santae cultivars. The overall results in this study indicated that the Manitou cultivar might be a good candidate to be incorporated into integrated pest management programs. © 2022 Society of Chemical Industry.


[Two newborns with both small-bowel atresia and cystic fibrosis].
Two newborn girls presented with congenital small-bowel atresia; in one case a high intestinal obstruction had been demonstrated by prenatal echography, while in the other case there were feeding problems and a failure to produce meconium. In both infants, the postoperative period was complicated by feeding problems, malabsorption and insufficient growth. Cystic fibrosis (CF) was then diagnosed in both patients. After modification of the diet, both showed rapid growth to a normal weight. The prevalence of CF in children with congenital small-bowel atresia is 6-13%, which is considerably higher than in a normal population. There is still no good explanation for this finding, but it is likely that CF contributes to the development of small-bowel atresia. In view of the high prevalence of CF in children with small-bowel atresia, children with congenital small-bowel atresia should be examined for CF.


Space-variant Fresnel transform optical correlator.
A space-variant optical correlator whose output depends on both the shape and the position of the input signal is introduced. This positionally sensitive correlator has potential applications in machine vision, cryptography, and optical logic. In this approach the input function undergoes a free-space Fresnel transform (which introduces the positional sensitivity) and is multiplied by an appropriate mask function. The Fourier transform of the product then obtains the desired output. The theoretical basis for the space-variant correlator, computer-simulated outputs, and experimental results for the case in which the mask is written onto a magneto-optic spatial light modulator are discussed.


Correlations of palatal surface area with anthropometric dimensions of the head and face.
Saliva distribution over the palatal surface plays an important role in the perception of dry mouth. It is envisaged that non-invasive estimation of the palatal surface area by anthropometric measurements of the head and face can be useful in the assessment of oral dryness. For this purpose, the relationship between the palatal surface area and anthropometric measurements of the head and face was investigated. The palatal surface was measured in 51 healthy volunteers using an intra-oral scanner. The distances between anthropometric landmarks of the head and face were determined using an anatomical sliding caliper. Correlations between the palatal surface area and the anthropometric landmarks were investigated. The median palatal surface area for the total study population was found to be 2120.6 mm2. Virtually, all anthropometric measurements showed significant differences between females and males. Various head and face measurements had a significant correlation with the palatal surface area. However, these correlations disappeared when the participants were stratified based on their sex, with the exception of mandibular length and palatal width in females. The surface area of the palate correlates with nearly all anthropometric measurements of the head and face included in this study. Yet, the clinical applicability seems limited to females.


[WHAT SHOULD BE KNOWN ABOUT PSORIATIC ARTHRITIS]?
Psoriatic arthritis (PsA) is chronic inflammatory arthropathy of peripheral joints and axial skeleton, occurring in 7% to 42% of patients with psoriasis. Arthritis might precede skin psoriatic lesion lesion in 13% to 17% cases. Patients present with pain and stiffness of the affected joins. A genetic factors play an important role (B27 has been associated with axial form, and DR4 with peripheral polyarticular form of PsA). Enthesopathy is a hallmark feature of PsA. It is an inflammation at the sites where tendons and ligaments attach to the bone. Extra-articular manifestations of disease are conjunctivitis and uveitis (occur in up to 1/3 of patients with PsA), heart disorder (aortic insufficiency), gut inflammation, urogenital inflammation. Treatment of PsA includes therapies for boths the skin and the joint disease. The treatment for the joint disease includes using NSAR (nonsteroidal anti-inflammatory drugs), DMARDs (disease-Modifying Antirheumatic Drugs) such as methotrexate (MTX), leflunomid, sulfasalasin and biological agents. Second-line therapy are: systemic glucocorticoids, retinoic acid derivatives/etretinate, photochemoterapy with MTX, physical therapy as an adjunct to drug therapy, and reconstructive surgery. The most important is that rheumatologist and dermatologist need to have some approach in management of PsA for optimal results.


Drain data to predict clinically relevant pancreatic fistula.
Post-operative pancreatic fistula (POPF) is a common and potentially devastating complication of pancreas resection. Management of this complication is important to the pancreas surgeon. The aim of the present study was to evaluate whether drain data accurately predicts clinically significant POPF. A prospectively maintained database with daily drain amylase concentrations and output volumes from 177 consecutive pancreatic resections was analysed. Drain data, demographic and operative data were correlated with POPF (ISGPF Grade: A--clinically silent, B--clinically evident, C--severe) to determine predictive factors. Twenty-six (46.4%) out of 56 patients who underwent distal pancreatectomy and 52 (43.0%) out of 121 patients who underwent a Whipple procedure developed a POPF (Grade A-C). POPFs were classified as A (24, 42.9%) and C (2, 3.6%) after distal pancreatectomy whereas they were graded as A (35, 28.9%), B (15, 12.4%) and C (2, 1.7%) after Whipple procedures. Drain data analysis was limited to Whipple procedures because only two patients developed a clinically significant leak after distal pancreatectomy. The daily total drain output did not differ between patients with a clinical leak (Grades B/C) and patients without a clinical leak (no leak and Grade A) on post-operative day (POD) 1 to 7. Although the median amylase concentration was significantly higher in patients with a clinical leak on POD 1-6, there was no day that amylase concentration predicted a clinical leak better than simply classifying all patients as 'no leak' (maximum accuracy = 86.1% on POD 1, expected accuracy by chance = 85.6%, kappa = 10.2%). Drain amylase data in the early post-operative period are not a sensitive or specific predictor of which patients will develop clinically significant POPF after pancreas resection.


[In vitro growth of human pathogenic fungi on different stocking fabrics].
Athlete's foot and onychomycosis can be aggravated due to inappropriate footwear. In this study we examined whether stockings of synthetic and mixed fabrics may influence the growth behaviour of the commonly isolated fungi Trichophyton rubrum, Trichophyton mentagrophytes and Candida albicans. A standardized suspension of each fungus was given to each sample of twelve stockings of different materials. The size of the growing colonies and the velocity of their growth were measured and compared to each other. Based on our data stockings depending on their fabric mixture seem to support or inhibit respectively the growth of fungi. Stockings composed of polyamide and a high percentage of polyurethane (Elasthan) and silk stockings as well may likely promote the fungal growth.


Phase I/II clinical trial of epirubicin and paclitaxel followed by granulocyte colony-stimulating factor in a 2-week schedule in patients with advanced or metastatic breast cancer.
Anthracyclines and taxanes are the most potent cytotoxic agents available for treating breast cancer. With combined therapy (either epirubicin or doxorubicin with paclitaxel [Taxol; Bristol-Myers Squibb Company, Princeton, NJ]), response rates of 70% to 90% have been reported. To achieve a maximal dose intensity per week, we decided to combine epirubicin 100 mg/m2 with escalating doses of paclitaxel, at successive dose levels of 135, 150, 165, and 180 mg/m2 in a 2-week schedule, with administration of subcutaneous granulocyte colony-stimulating factor 5 microg/kg from days 2 through 10. To date, 16 patients have been included, with six patients treated at level 1 (100/135 mg/m2 epirubicin/paclitaxel), four at level 2 (100/150 mg/m2), four at level 3 (100/165 mg/m2), and two at level 4 (100/180 mg/m2). The median age of all subjects is 55 years (range, 41 to 65 years). Five patients had received chemotherapy in the adjuvant setting. Of 79 treatment courses, 78 are evaluable for toxicity. The mean number of courses per patient is six (range, two to six courses). At dose level 1, one episode of febrile neutropenia with grade 4 thrombocytopenia occurred. No grade 4 extrahematologic adverse event has been noted so far. At dose level 2, we achieved a dose intensity per week of epirubicin 50 mg/m2 and paclitaxel 75 mg/m2, as expected. At dose level 3, the dose intensity per week was 47.5 mg/m2 and 78.8 mg/m2, respectively (expected 50 and 82.5 mg/m2). The current response rate, evaluated in 14 of 16 patients, is four complete remissions and eight partial remissions, for an overall response rate of 85%. Two patients had stable disease. Granulocyte colony-stimulating factor following epirubicin/paclitaxel on a 2-week schedule permits a very high dose intensity per week for both drugs and produces a high response rate in patients with advanced or metastatic breast cancer.


An overview of some studies of chronic myelogenous leukemia: biological-clinical observations and viewing the disease as a chaotic system.
While much is known about CML at both the clinical and molecular biological levels, the precise relationship between the disease at these two levels is unclear. The appearance of the fusion gene bcr-abl and disorders in the regulation of the myc gene, and perhaps other oncogenes which code for nucleoproteins, appear to play integral roles in the genesis of the chronic and blastic phases of the disease. The resistance of this disease to cytotoxic therapy appears to reflect both "classical" drug resistance and the ability of those cells which survive cytotoxic therapy to rapidly replace the killed cells thereby offsetting the effects of chemotherapy ("regrowth resistance"). The clinical evolution of the disease is compatible with two fundamentally different processes: one compatible with a deterministic chaotic model and the other involves two basically independent linear phenomena which overlap and intersect as the blastic phase appears and replaces the chronic phase.


Gender aspects in heart failure. Pathophysiology and medical therapy.
Gender differences in the syndrome of heart failure (HF) occur in etiology and pathophysiology and lead to differences in the clinical presentation and course of the syndrome. In addition, gender specific treatment responses and gender associated differences in the behavior of treating physicians are found. Hypertension and diabetes play a major role as causes of HF in women and both interact in their pathophysiology with the renin angiotensin system (RAS). Modulation of the RAS by estrogens explains specific differences between pre- and post-menopausal women and men. Myocardial growth processes and myocardial calcium handling are differentially regulated in female and male myocytes. Myocardial remodeling with age and as a consequence of mechanical load differs in women and men. For yet unknown reasons, HF with preserved systolic function seems to be more frequent in women than in men and the clinical course of systolic HF is different in both genders. Medical therapy in heart failure has usually not been specified according to gender and gender specific analysis has been neglected in most large survival trials. Only a post-hoc analysis of gender differences led to the recognition of increased mortality with digitalis therapy in women. Single studies on angiotensin converting enzyme inhibitors (ACEI) or beta-receptor blockers did not reach significant end points in women whereas meta-analyses showed overall positive effects. Side effects of ACEI are more common and pharmacokinetics of beta-blockers are different in women. Angiotensin receptor blockers (ARB) are equally well tolerated in women and men. RAS inhibition may be particularly advantageous in postmenopausal women in whom the natural modulation of the RAS by estrogens is lost.


Relative Protein Abundances and Biological Ageing in Whole Skeletal Elements.
Establishing biological age is an integral part of forensic investigations, currently achieved through morphological methods with varying degrees of accuracy. Furthermore, biological ageing is much easier in juveniles than in adults, at which point traditional ageing methods struggle. Therefore, biomolecular approaches are considered of great interest, with several protein markers already recognized for their potential forensic significance. However, previous studies have typically relied on subsampling different parts of skeletal elements. Here, we attempt to evaluate the proteome of complete elements using a rat model. In the analysis of specimens spanning beyond adulthood (1 week to 1.5 years), we observed 729 unique proteins across 33 samples (three for each sex for each of the five (female) or six (male)), five of which represent newly identified proteins in relation to age estimation: vimentin, osteopontin, matrilin-1, apolipoprotein A-I, and prothrombin. Most of these follow the trend of decreasing abundance through age, with the exception of prothrombin that increases. We consider the combined use of these relative abundances, along with those of previously noted fetuin-A, biglycan, albumin, and chromogranin-A signatures, as being of potential value to the development of an age estimation tool worthy of further evaluation in forensic contexts.


Detection and titration of bluetongue virus in Culicoides insect cell culture by an antigen-capture enzyme-linked immunosorbent assay.
Bluetongue virus (BTV) infects sheep, cattle and other ruminants and is transmitted by Culicoides spp. of biting midges. Virus is typically isolated and characterized by infection of susceptible vertebrate cells that undergo detectable and measurable cytopathic effects. Cell lines derived from C. sonorensis may be useful for virus isolation and studies to better understand BTV replication in the insect vector. However, their use is hampered because BTV infection does not produce significant cytopathic effects in these insect cell cultures. Detection of virus replication in these cells typically requires co-cultivation with susceptible vertebrate cell culture. This report describes the use of an antigen-capture enzyme-linked immunosorbent assay (Ag-Cap ELISA) for direct detection and titration of BTV in cultures of a Culicoides cell line. This assay should facilitate use of this cell line for virus isolation, titration and studies of BTV replication.


Blood lymphocyte T subsets reference values in blood donors by flow cytometry.
To determine region-specific reference ranges of lymphocyte T subsets in blood donors and to assess the influence of gender and age on lymphocyte T susbsets. Blood samples from 143 blood donors were collected in the Blood Transfusion Center of Sfax. Lymphocyte T subsets were analyzed using a dual-platform method with a flow cytometer (percentages) and an automated hematology analyzer (white blood cells and lymphocytes). ANOVA and Student's tests were used for data analysis. Reference values were expressed as mean and 95% confidence intervals for T cells: CD3+: 1415 ± 348 cells/μL [1357-1473], CD3+/CD4+: 786 ± 220 cells/μL [732.31-811.7], CD3+/CD8+: 639 ± 258 cells/μL [596-862] and CD4+/CD8+ ratio was 1.46 ± 0.77 [1.36-1.62]. Gender and age influenced blood lymphocyte T subsets. Our study leads to the establishment of peripheral blood lymphocyte T subset reference ranges in blood donors in the region of Sfax. A study on a more diversified population, including more important number of individuals from various regions of Tunisia and including enumeration of other lymphocyte subsets (B cells and NK cells) is required.


Generating Novel Male Sterile Tomatoes by Editing Respiratory Burst Oxidase Homolog Genes.
Hybrid breeding of tomatoes (Solanum lycopersicum), an important vegetable crop, is an effective way to improve yield and enhance disease and stress resistance. However, the efficiency of tomato hybridization is hindered by self-fertilization, which can be overcome using male sterile lines. It has been reported that reactive oxygen species (ROS) act as a key regulator for anther development, mediated by RBOH (Respiratory Burst Oxidase Homolog) genes. Here, two tomato anther-expressed genes, LeRBOH (Solyc01g099620) and LeRBOHE (Solyc07g042460), were selected to cultivate novel tomato male sterile strains. By using a CRISPR/Cas9 system with a two-sgRNA module, the lerboh, lerbohe, and lerboh lerbohe mutant lines were generated, among which the lerbohe and lerboh lerbohe mutants displayed complete male sterility but could accept wild-type pollens and produce fruits normally. Further analysis uncovered significantly decreased ROS levels and abnormal programmed cell death in lerboh lerbohe anthers, indicating a key role of ROS metabolism in tomato pollen development. Taken together, our work demonstrates a successful application of gene editing via CRISPR/Cas9 in generating male sterile tomatoes and afforded helpful information for understanding how RBOH genes regulating tomato reproduction process.


Selective nanoparticle heating: another form of nonequilibrium in dusty plasmas.
Nanoparticles produced in low-temperature plasmas (LTPs) are often found with crystalline structure, which suggests rather high temperatures during synthesis. This even applies to particles of high-melting-point materials, which is surprising, because the gas temperature in LTPs is often close to room temperature and particles may reside in the plasma only for a few milliseconds. In this paper, we present a numerical study of nanoparticle heating in plasmas through energetic surface reactions. We find that, under realistic plasma conditions, particle temperatures can exceed the gas temperature by many hundreds of kelvins. However, as the particle temperature is highly unsteady, it is more reasonable to consider particle temperature distribution functions. The dependence of the particle temperature distribution on particle size and particle density in a dusty LTP is discussed.


Ecdysone signaling and transcript signature in Drosophila cells resistant against methoxyfenozide.
Methoxyfenozide (RH-2485) is a non-steroidal ecdysteroid agonist with a dibenzoylhydrazine structure, representing a group used as novel biorational insecticides in the control of insect pests. Here we report on the selection of Drosophila melanogaster S2 cells for resistance to inhibition of cell proliferation by methoxyfenozide by ∼ 1000-fold over 4 months. Cells were exposed to gradually increasing concentrations of methoxyfenozide and selected out based on the ecdysteroid-sensitive response for cell proliferation. In the resistant cells, the ecdysteroid receptor (EcR/USP) complex was no longer active in the presence of methoxyfenozide. But when resistant cells were relaxed from pressure in methoxyfenozide-free medium, induction of the reporter construct was observed. In parallel, EcR/USP functionality was also restored when resistant cells were rescued by a Drosophila EcR plasmid. However, it was striking that in the resistant cells the ecdysteroid-sensitive response for cell proliferation was not restored upon methoxyfenozide withdrawal, indicating permanent changes in the physiology of the cells during selection. To investigate changes in gene expression caused by inactivation of the EcR/USP complex in resistant cells, Drosophila oligo 14kv1 microarrays were used and probed with cDNAs from resistant cells in the presence and absence of ecdysone agonist on one hand and from unselected sensitive cells on the other hand. A selection of 324 differentially expressed genes was assigned covering diverse functions as transport, enzyme activity, cytoskeleton organization, cell cycle machinery, transcription/translation and ecdysteroid signaling. Besides the identification of (primary and secondary) target genes of the EcR/USP signaling pathway, this analysis also allows to gain insights into the mechanism of resistance and on the crosstalk between ecdysteroid signaling and cell proliferation-linked processes.


Embodiment of motor skills when observing expert and novice athletes.
If people are shown a dynamic movie of an action such as kicking a soccer ball or hitting a tennis ball, they will respond to it faster if it requires the same effector. This standard congruency effect was reported to reverse when participants viewed static images of famous athletes not actually performing an action. It was suggested that the congruent response was inhibited because of a social contrast effect, based on an implied action, whereby responders viewed themselves as comparatively worse than the professional athlete. The present study recorded hand and foot responses when identifying static images of both famous and novice athletes in soccer and tennis. The action was either explicit or implied. In Experiment 1, a standard congruency effect was found for all images. In Experiment 2, when a response was based on the identity of the athlete rather than their expertise, the standard congruency effect was enhanced for images of novice athletes, but was eliminated for experts, suggesting a social contrast effect. Our study is the first to show that embodiment effects can be seen for implied and explicit action images of both novices and experts, and that static images are capable of eliciting priming effects associated with sport-relevant effector pairings.


What memory is-Not!
Rejecting the received account, which includes procedural and semantic memory, Stanley B. Klein claims that only episodic memory is genuine memory. This is so, he asserts, because only episodic memory is partly constituted by a quale, a Nagelian "what it is like" feeling of the past. However, his actual position reveals a very different set of claims about memory, one that involves a distinctive feel, distinct from Nagelian qualia and other versions of what qualia are. We argue that Klein's actual position significantly differs from what he claims memory is. And we try to describe what Kleinian qualia should feel like. We suspect that they might not feel like anything at all. This article is categorized under: Psychology > Memory Philosophy > Consciousness Philosophy > Psychological Capacities.


Reconstruction of endodontically treated posterior teeth--with or without post? Guidelines for the dental practitioner.
The clinical concepts regarding the restoration of root canal treated teeth are not clear today and often based on conjecture due to a lack of sound empirical data. The diversity of published opinions is confusing and may lead to less-than-optimal treatment selections. There is also emerging debate whether or not a post is necessary. The purpose of the present article is to organize this topic in evidence-based principles and provide dental practitioners with clear guidelines about restorative therapy for premolar and molar teeth. Two clinical reports are presented, to exemplify the different clinical situations. The first case highlights a conservative restoration of an endodontically treated molar, maintaining an adequate quantity of healthy residual tissue and only covering the cusp with restoration material, which was not sustained by healthy dentin. In the second case, the fact that the premolar was so badly damaged by carious pathology meant that it was necessary to use a pin to anchor the composite material, and the cusp was covered completely. Based on the two presented clinical reports and a literature review, the concept of fiber post application is explained. Searches by hand and MEDLINE were employed to identify peer-reviewed articles on reconstruction of endodontically treated posterior teeth. A total of 70 articles published between 1967 and 2008 were reviewed.


A kinetic model of the co-operative binding of calcium and ADP to scallop (Argopecten irradians) heavy meromyosin.
Analysis of the kinetics of ATP and ADP binding to scallop (Argopecten irradians) heavy meromyosin (HMM) showed that the only calcium-dependent process is the rate of ADP release. At physiological ionic strength calcium accelerated ADP release about 20-fold. Notably in the absence of calcium only one ADP bound HMM, with an affinity of 0.5-1 microM. The second nucleotide site remained unoccupied at up to 50 microM ADP yet could bind ATP rapidly. The calcium dependence of ADP-release rates showed that calcium binds co-operatively to scallop HMM with an affinity of 0.78 microM and a Hill coefficient of 1.9. Detailed interpretation of the data suggests that HMM exists in equilibrium between the on and off states and that calcium and ADP modulate the equilibrium between the two states. The on state is favoured in the presence of calcium and in the absence of both calcium and nucleotide. The off state is favoured by ADP (or ADP * P(i)) in the absence of calcium. A detailed co-operative model of the interaction of ADP and calcium with HMM is presented.


Water Calorimetry: The Heat Defect.
Domen developed a sealed water calorimeter at NIST to measure absorbed dose to water from ionizing radiation. This calorimeter exhibited anomalous behavior using water saturated with gas mixtures of H2 and O2. Using computer simulations of the radiolysis of water, we show that the observed behavior can be explained if, in the gas mixtures, the amount-of-substance of H2 and of O2 differed significantly from 50 %. We also report the results of simulations for other dilute aqueous solutions that are used for water calorimetry-pure water, air-saturated water, and H2-saturated water. The production of H2O2 was measured for these aqueous solutions and compared to simulations. The results indicate that water saturated with a gas mixture containing an amount-of-substance of H2 of 50 % and of O2 of 50 % is suitable for water calorimetry if the water is stirred and is in contact with a gas space of similar volume. H2-saturated water does not require a gas space but O2 contamination must be guarded against. The lack of a scavenger for OH radicals in "pure" water means that, depending on the water purity, some "pure" water might require a large priming dose to remove reactive impurities. The experimental and theoretical problems associated with air-saturated water and O2-saturated water in water calorimeters are discussed.


High-frequency follow-up studies in musculoskeletal disorders: a scoping review.
This scoping review identifies research in musculoskeletal disorders that uses high frequency follow-up of symptoms. The aim was to investigate whether symptom variability is investigated as a predictor of disease outcome and how intensive follow-up methods are used in musculoskeletal research. Embase, MEDLINE and PsycInfo were searched using OVID, and the Institute of Electrical and Electronic Engineers was also searched using the Institute of Electrical and Electronic Engineers Xplore search engine. Studies were systematically reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, but no meta-analysis was done because the priority in this study is to identify gaps in available literature. Twenty-one papers were included. There was a mean of 54 patients per study (s.d. of 27.7). Two-thirds of the papers looked at how a symptom influences another in the short-term (subsequent assessment in the same day or next day), but none looked at the long-term. Only one study considered symptom variability investigating how higher variability in pain (defined by the s.d.) is associated with higher average pain severity and lower average sleep quality. The methodology of musculoskeletal disorder research has changed from completing paper booklets to using electronic data capture (smartphones). There has also been a trend of collecting more intensive longitudinal data, but very little research utilizes these data to look at how symptom variability affects symptom outcomes. This demonstrates a gap in research where furthering understanding of this will help clinicians decide on the most important symptom to address in future patients.


Quantum Kramers model: Corrections to the linear response theory for continuous bath spectrum.
Decay of the metastable state is analyzed within the quantum Kramers model in the weak-to-intermediate dissipation regime. The decay kinetics in this regime is determined by energy exchange between the unstable mode and the stable modes of thermal bath. In our previous paper [Phys. Rev. A 42, 4427 (1990)PLRAAN1050-294710.1103/PhysRevA.42.4427], Grabert's perturbative approach to well dynamics in the case of the discrete bath [Phys. Rev. Lett. 61, 1683 (1988)PRLTAO0031-900710.1103/PhysRevLett.61.1683] has been extended to account for the second order terms in the classical equations of motion (EOM) for the stable modes. Account of the secular terms reduces EOM for the stable modes to those of the forced oscillator with the time-dependent frequency (TDF oscillator). Analytic expression for the characteristic function of energy loss of the unstable mode has been derived in terms of the generating function of the transition probabilities for the quantum forced TDF oscillator. In this paper, the approach is further developed and applied to the case of the continuous frequency spectrum of the bath. The spectral density functions of the bath of stable modes are expressed in terms of the dissipative properties (the friction function) of the original bath. They simplify considerably for the one-dimensional systems, when the density of phonon states is constant. Explicit expressions for the fourth order corrections to the linear response theory result for the characteristic function of the energy loss and its cumulants are obtained for the particular case of the cubic potential with Ohmic (Markovian) dissipation. The range of validity of the perturbative approach in this case is determined (γ/ω_{b}<0.26), which includes the turnover region. The dominant correction to the linear response theory result is associated with the "work function" and leads to reduction of the average energy loss and its dispersion. This reduction increases with the increasing dissipation strength (up to ∼10%) within the range of validity of the approach. We have also calculated corrections to the depopulation factor and the escape rate for the quantum and for the classical Kramers models. Results for the classical escape rate are in very good agreement with the numerical simulations for high barriers. The results can serve as an additional proof of the robustness and accuracy of the linear response theory.


Expression of Glucocorticoid Receptors GRα and GRβ in Bullous Pemphigoid.
First-line treatments of bullous pemphigoid (BP) are topical and systemic glucocorticoids (GC). The actions of GC are mediated by glucocorticoid receptors (GR), which exist in several isoforms, of which GRα and GRβ are the most important. In many inflammatory diseases, up-regulation of GRβ is associated with GC insensitivity. The aims of this study were to determine the expression of GRα and GRβ in patients with BP and to investigate the effect of prednisolone treatment on the expression of GR isoforms in BP. Quantitative real-time PCR (qPCR) analysis demonstrated that GR isoform mRNAs are expressed in peripheral blood mononuclear cells (PBMC) from patients with BP. Expression of GRα and GRβ protein was confirmed by immunohistochemical staining of BP skin biopsies and by Western blot analysis and flow cytometric analysis of PBMCs. During prednisolone treatment, GRα and GRβ expression varied markedly, but changes were not suitable as a clinical marker of GC sensitivity in patients with BP.