The importance of treating the field in actinic keratosis.
Actinic keratoses (AKs) are intraepithelial atypical proliferations of keratinocytes that develop in skin that has undergone long-term exposure to ultraviolet radiation. Given the ageing population and an increasing prevalence of AK, the socio-economic burden of AK is likely to rise over the coming years. Areas of subclinical (non-visible) sun damage in the periphery of visible AK lesions contain the same genetic changes as those found in the lesions themselves, and are known as areas of field cancerization. AK lesions and the field are associated with an increased risk of skin cancer, including invasive squamous cell carcinoma. Although effective in clearing visible AK, lesion-directed therapies do not address field cancerization and can lead to high recurrence rates. In contrast, field-directed therapies, such as ingenol mebutate, imiquimod and diclofenac, can clear both visible and subclinical AK lesions and reduce the development of new lesions in the treated field. Additionally, preclinical studies suggest that field therapy may prevent or delay the recurrence of non-melanoma skin cancer. AK treatment guidelines now recognize the importance of treating the field in patients with AK, and adaptation of treatment guidelines into clinical practice is warranted. Physician and patient education around the consequences of leaving the field of cancerization untreated is necessary in order to reduce the increasing burden associated with AK.


[Young syndrome. Chronic sino-pulmonary infection and infertility].
Young's syndrome is a combination of chronic sinopulmonary infections and obstructive azoospermia in men. Cystic fibrosis and the "immotile cilia syndrome" must be ruled out. The most important methods in differential diagnosis are determination of sweat chloride and sodium levels, investigation of cilia ultrastructure and analysis of semen samples. A case of Young's syndrome in a 42-year-old patient is reported.


Combined surgical therapy of temporomandibular joint ankylosis and secondary deformity using intraoral distraction.
Temporomandibular joint (TMJ) ankylosis is a pathological process caused by damage of the mandibular condyle. When this event takes place in subjects during the developmental age, it results in an alteration of the entire maxillofacial complex. Therefore, surgical methods able to remove the temporomandibular ankylosis also include necessary operations to correct the secondary maxillofacial deformity. The distraction osteogenesis has induced our center to modify the surgical protocol for the therapy of patients who have developed TMJ ankylosis and secondary maxillomandibular deformity. We have treated four patients with monolateral ankylosis of the TMJ and serious deformities of the maxillomandibular complex secondary to functional limitation. During the same operation, arthroplasty was performed with the removal of the ankylotic block and the interposition of a temporal muscle flap in the new articular space; an intraoral osteodistractor was also positioned to lengthen the mandible. All patients showed recovery of the eurhythmy of the face and good re-establishment of the symmetry. An average 12-month follow-up showed the average opening of the mouth to be at least 35 mm. The combination of TMJ arthroplasty and intraoral osteodistraction provides good functional and aesthetic results in patients affected by ankylosis who have developed secondary maxillofacial deformities.


Early assessment of axillary response with ¹⁸F-FDG PET/CT during neoadjuvant chemotherapy in stage II-III breast cancer: implications for surgical management of the axilla.
If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography-computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential (18)F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II-III breast cancer. A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUVmax) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard. A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUVmax was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68-0.92) and 0.65 (95 % confidence interval 0.52-0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %-that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy. (18)F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.


Interferon production in sickle cell disease.
There is limited data on cytokine production in sickle cell disease (SCD). In this study, both alpha (Poly IC-induced) and gamma (PHA-induced) interferon (IFN) were measured in 62 SCD steady state patients, and 21 in the crisis state associated with infections. Comparable normal controls (30 healthy and 14 with infections) were assessed in a similar manner. Gamma IFN production in both SCD groups, steady state (35 +/- 6 U/ml) and crisis state (24 +/- 11 U/ml) was significantly diminished when compared to the normal healthy controls (65 +/- 14 U/ml) with P less than .005. Both SCD groups were also less than normals with infections (56 +/- 23 U/ml) with P less than .005. On closer analysis of individual titers, 15/62 (24%) in the steady state, 11/21 (52%) of SCD patients with infection and 2/14 (14%) of normals with infection, showed impaired gamma IFN when compared to normals without infection (range 27-2187 U/ml). Alpha IFN production in the SCD groups; steady state (512 +/- 113 U/ml) and SCD crisis with infection (559 +/- 110 U/ml) was virtually equivalent to normals (524 +/- 170 U/ml) and normals with infection (509 +/- 116 U/ml). Analysis of individual titers, in contrast to gamma IFN, also showed no significant differences. These results indicate that a significant percentage of SCD patients in both the steady state and infectious state associated with crisis, have impaired gamma IFN production. In view of the known immunomodulatory functions of gamma IFN, this apparent defect may be another factor to explain the increased frequency and severity of infections in SCD.


Nonfatal Strangulation: More Than Meets the Eye.
Nonfatal strangulation is a relatively newly recognized mechanism of injury that may not be taken seriously because of lack of physical injuries that many times accompany it. This comparison case series supports the importance of considering not only visually detected injuries but also symptoms the patient may be experiencing when determining diagnostics necessary to guide a treatment plan. A visually detectable injury is dependent on multiple factors. Bruises may occur with minimal pressure but may not be visible immediately after assault. Contrary to this, extensive bruising of the neck is not an accurate indicator of damage to underlying structures. The authors' experiences in these two cases signify the necessity of a comprehensive assessment utilizing both physical symptoms and assessments as the basis for determining nonfatal strangulation treatment plans.


Long non-coding RNA DGCR5 is involved in the regulation of proliferation, migration and invasion of lung cancer by targeting miR-1180.
Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), including small non-coding RNAs (small ncRNAs) and long non-coding RNAs (lncRNAs), are involved in tumor growth in lung cancer (LC). However, the specific role of DGCR5 in LC progression is not yet clear. In the present study, we found that DGCR5 was downregulated and miR-1180 was upregulated in the sera and tissues of LC patients and was correlated with poor prognosis. We also found that DGCR5 suppressed proliferation, migration and invasion of LC cell lines H520 and H1299. In addition, a luciferase reporter gene assay was used to investigate the regulatory relationship between DGCR5 and miR-1180. Furthermore, we suggested that DGCR5 inhibited the expression of AKT, GSK-3β, and β-catenin by targeting miR-1180. Based on these findings, DGCR5 might serve as a potential target for the development of effective anti-neoplastic therapies in lung cancer.


Radiation dose-reduction techniques in North American dental schools.
The purpose of this investigation was to describe the extent to which dental schools use materials, equipment, and quality-assurance protocols that reduce radiation exposure to patients. Questionnaires soliciting information regarding intraoral and extraoral radiographic practices and quality-assurance procedures were sent to the directors of oral and maxillofacial radiology (OMR) at the 65 schools of dentistry in the United States and Canada. The response rate was 100%. E-speed film is used at 86% of institutions. Direct digital radiography is used at 58% of institutions for intraoral imaging and 11% for extraoral radiography. Other dose-reducing techniques include long source-film distances (88%), rectangular beam limitation (47%), leaded aprons (95% for extraoral films; 85% with thyroid collars for intraoral films), and rare earth intensifying screens (100%). The most commonly used tube potential is 70 kVp (88%). The director of OMR is solely responsible for radiographic policies at approximately 75% of institutions. Regular tests for film fog, speed, and contrast are done at roughly 75% of schools, while over 90% test darkroom lighting and x-ray equipment. Some dose-reducing strategies are commonly used in dental schools, while others have not gained wide acceptance.


[Evaluation of the effect of diet composition and its supplementation with selected B vitamins on distribution of calcium and magnesium in the body].
The aim of the study was to estimate, on an animal model, the influence of diet composition and its supplementation with selected B vitamins on distribution of calcium and magnesium in the body. The change in diet composition was found to significantly reduce the calcium contents in the liver and blood of males as well as in the liver and kidney of females. The change enhanced calcium and magnesium accumulation in the skeletal muscles of the animals examined. In females, the effect was augmented by supplementation. The vitamin supplementation applied was conducive to incorporation into the bones calcium in males and magnesium in females, respectively. Analysis of the results allows to conclude that both the change in the diet composition and the supplementation of the diet modified by selected B vitamins significantly affected distribution of calcium and magnesium between different organs and tissues of the animals examined and probably modified the functional status of the organs and tissues in question. The magnitude and direction of the changes in most parameters analysed were sex-dependent.


Clinical assessment of postoperative sensitivity in posterior composite restorations.
This incidence of postoperative sensitivity was evaluated in resin-based posterior restorations. Two hundred and ninety-two direct restorations were evaluated in premolars and molars. A total of 143 Class I and 149 Class II restorations (MO/OD and MOD) were placed in patients ranging in age from 30 to 50 years. After the cavity preparations were completed, a rubber dam was placed, and the preparations were restored using a total-etch system (Prime & Bond NT) and a resin-based restorative material (TPH Spectrum). The patients were contacted after 24 hours and 7, 30 and 90 days postoperatively and questioned regarding the presence of sensitivity and the stimuli that triggered that sensitivity. The Chi-square and Fisher's Exact Test were used for statistical analysis. Evaluation at 24 hours after restorative treatment revealed statistically significant differences among the types of cavity preparations restored and the occurrence of postoperative sensitivity (p = 0.0003), with a higher frequency of sensitivity in Class II MOD restorations (26%), followed by Class II MO/DO (15%) and Class I restorations (5%). At 7, 30 and 90 days after restorative treatment, there was a decrease in the occurrence of sensitivity for all groups. The percentage of sensitivity among the groups was not significantly different. This study shows that the occurrence of sensitivity is correlated with the complexity of the restoration.


[Analysis on the secondary attack rates of SARS-CoV-2 Omicron variant and the associated factors].
Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q1, Q3) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q1, Q3) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.


Mechanism of production of midsystolic click in a prolapsed mitral valve.
In order to examine the production mechanism of the midsystolic click in cases of a midsystolic click and a late systolic murmur, the relationship between the click and the motion of the mitral apparatus was studied by means of ultrasono-cardiotomography and the simultaneous recording of phonocardiograms and ultrasono-cardiograms (UCGs). It was found that the systolic click occurred in exact coincidence with the time at which the hump of the echo of the unusual early systolic anterior motion (early SAM) took its backmost position. This coincidence was found when the click was shifted either by postural changes or inhalation of amyl nitrite. The present ultrasono-cardiotomographic study demonstrated that the echo source of the early SAM could be attributed to the protrusion into the left ventricular outflow tract of the slackened elongated chordae tendineae in systole. The anterior leaflet moved suddenly to the position of maximal prolapse when the slackened chordae tendineae were stretched taut in midsystole. In other words, the midsystolic click occurred when the anterior leaflet prolapsed and the tension exerted on the chordae tendineae was at its maximum.


Cooperative function of Aml1-ETO corepressor recruitment domains in the expansion of primary bone marrow cells.
AML1-ETO is an oncoprotein that can promote self-renewal of primary hematopoietic cells by opposing the activity of AML1. Two domains, Nervy-homology(NH) 2 and NH4, have been implicated in the recruitment of corepressors by AML1-ETO, but the relative roles of NH2 and NH4 vary in different cell lines and have not been examined in nonimmortalized cells. Here, we have used a series of differentiation, proliferation, and self-renewal assays in an effort to determine the roles of the NH domains using progenitor-enriched primary bone marrow cells. In these assays, deletion of NH2 or NH4, individually, has a minimal effect on AML1-ETO function, and the mutants retain the ability to promote long-term expansion of cells. In contrast, the double deletion of NH2 and NH4 eliminates the activity of the fusion protein. Thus, the double deletion of NH2 and NH4 produces a functional deficit greater than the sum of the individual deletions. These findings suggest that the NH2 and NH4 domains function cooperatively in the corepressor environment of primary bone marrow cells.


Update on pancreatic cancer.
Pancreatic cancer is one of the commonest causes of cancer death worldwide. Patients with pancreatic cancer benefit from resectional surgery (improved quality of life) and adjuvant treatment (enhanced survival). This review covers advances in the understanding of the development of pancreatic cancer, state-of-the-art clinical management and, finally, novel treatment and screening techniques.


First-principles study of benzo[a]pyrene-7,8-dione and DNA adducts.
Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in environments, and some of them are causative agents of human cancer. Previous studies concluded that benzo[a]pyrene-7,8-dione (BPQ), which is one kind of carcinogenic PAH metabolites, forms covalently bonded adducts with DNA, and the major adduct formed is a deoxyguanosine adduct. In this work, we investigate the interactions between BPQ and DNA molecules via first-principles calculations. We identify six possible DNA adducts with BPQ. In addition to the four adducts forming covalent bonds, there are two adducts bound purely by van der Waals (vdW) interactions. Remarkably, the two vdW-bound adducts have comparable, if not larger, binding energies as the covalent adducts. The results may help us gain more understanding of the interactions between PAH metabolites and DNA.


Overexpression of MDM2, p53, and NCAM proteins in human radiation-induced skin ulcers.
Using immunohistochemistry, we studied the overexpression of MDM2, p53, and NCAM proteins in human radiation-induced skin ulcers. We found that the positive rate of overexpression of MDM2, p53, and NCAM was 36%, 8%, and 32%, respectively. The overexpression of MDM2 protein was mainly observed in the nuclei of fibroblasts in the deeper part of the ulcer; that of p53 protein was in the nuclei of the epidermis and in the cytoplasm of fibroblasts and endothelial cells, whereas that of NCAM was located in the cytoplasm of squamous epithelial cells of the epidermis and in fibroblasts, fibrocytes, endothelial cells, and leiomyocytes in the media of arteriolar walls. The overexpression of MDM2, p53, and NCAM may be related to the poor healing of radiation-induced skin ulcers and the cancer transformation.


Small-molecule Inhibitors of Epigenetic Mutations as Compelling Drugtargets for Myelodysplastic Syndromes.
Involvement of mutations in epigenetic mechanism in the development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described in >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression. Preclinical and clinical trials have already been initiated for some synthetic and natural products and established proof-of-concept for mitigation of mutagenic effects. The present review article entails the mutational signatures in DNA-methylation and hydroxymethylation, histone acetylation and Deacetylation, polycomb repressor complex (PRC2), and small molecule inhibitors of these mutational expressions. Information has been collected from the recently published literature available mainly through Google search in Medline and PubMed database. Special emphasis was paid on the literature available during 2009-2016. The up-to-date information accumulated on signature-mutations and their inhibitors has to integrate the function of clonal hematopoiesis of indeterminate potential (CHIP) and mutational complexities for re-defining MDS-genesis. Nevertheless, molecular understanding of MDS heterogeneity and its transformation to AML is expanding at fast pace with expanding knowledge on abundant non-coding RNAs (ncRNAs), which forms the basis of targeted drug-tailoring, and will further develop personalized medicines based on individual genetic blue-prints. Mutation-specific targeted epigenetic drugs, which have already sensitized drug-makers and regulators, may promise attestation of 'del5q and lenalidomide'-like specific drugs for every mutational signature independently or in combination with standard therapeutic elements used for MDS-management, and that will add to understand their antagonistic/synergistic effects.


Microbial ecology of the terrestrial subsurface.
We have presented a current view of the microbial ecology of the terrestrial subsurface by considering primarily the ecology of shallow aquifer sediments. The properties of the aquifer sediments and groundwater determine their ability to support microbial life and control the abundance and activities of microorganisms. Pore size, nutrient limitations, availability of electron acceptors, and large surface area for attachment all may have major effects on microbial abundance and activities in aquifer material. Microorganisms are the predominant forms of life in the subsurface. They will be found wherever enough space, nutrients, and water are available for them to live. Environmental factors such as pH, temperature, hydrostatic pressure, and dissolved salts also may influence subsurface microbial populations, but these factors do not exhibit great extremes in shallow water table aquifers, and thus only in very deep formations might they limit diversity or preclude the existence of microorganisms. Although the presence and activity of microorganisms in most subsurface environments are predictable, only recently have subsurface microbial populations in shallow subsurface zones been characterized. Aseptic sampling methods have been employed and microbiological and biochemical methods have been adapted to determine the types, abundance, and metabolic activities of microorganisms in subsurface material. Bacteria dominate, but eukaryotic microorganisms also are present. Vertical profile studies of a shallow aquifer in Oklahoma showed that active microbial biomass declined with depth to the unsaturated zone, but was variable in saturated sediments. Such a distribution of active biomass may be common in shallow aquifers. Studies on the lateral distribution of microorganisms in shallow and deep aquifers suggest that microorganisms are transported or migrate over fairly long distances in aquifer sediments. Surficial aquifers may be colonized by vertical or lateral transport and migration of surface microorganisms from recharge areas, but microorganisms could also have colonized when sediments were originally deposited. The biological and physical mechanisms controlling the migration of microorganisms in aquifers are not well understood. The function of shallow aquifers was considered with regard to nutritional ecology. Most pristine aquifers are oligotrophic. Heterotrophic life in these unique ecosystems is supported by secondary organic compounds that filter down from the soil above. The quantity and quality of organic nutrients depend on the age of water and rate of recharge of the aquifer.(ABSTRACT TRUNCATED AT 400 WORDS)


Changes in leukocyte subsets of pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus and relationships with viral load and fetal outcome.
In spite of more than two decades of extensive research, the understanding of porcine reproductive and respiratory syndrome virus (PRRSv) immunity is still incomplete. A PRRSv infection of the late term pregnant female can result in abortions, early farrowings, fetal death, and the birth of weak, congenitally infected piglets. The objectives of the present study were to investigate changes in peripheral blood mononuclear cell populations in third trimester pregnant females infected with type 2 PRRSv (NVSL 97-7895) and to analyze potential relationships with viral load and fetal mortality rate. PRRSv infection caused a massive, acute drop in total leukocyte counts affecting all PBMC populations by two days post infection. Except for B cells, cell counts started to rebound by day six post infection. Our data also show a greater decrease of naïve B cells, T-helper cells and cytolytic T cells than their respective effector or memory counterparts. Absolute numbers of T cells and γδ T cells were negatively associated with PRRSv RNA concentration in gilt serum over time. Additionally, absolute numbers of T helper cells may be predictive of fetal mortality rate. The preceding three leukocyte populations may therefore be predictive of PRRSv-related pathological outcomes in pregnant gilts. Although many questions regarding the immune responses remain unanswered, these findings provide insight and clues that may help reduce the impact of PRRSv in pregnant gilts.


Reducing post-catheterization bladder dysfunction by reconditioning.
The purpose of this study was to determine the effect of reconditioning upon bladder dysfunction caused by prolonged catheterization. Eight women undergoing surgery with baseline residual urine volumes (RUVs) not greater than 25 ml and catheterization durations of 36 to 106 hours qualified as subjects. Immediately prior to catheter removal, the four treatment group subjects received reconditioning, a procedure in which their catheters were clamped for three hours followed by five minutes of urinary drainage. This cycle was repeated twice more, totaling nine hours, ten minutes. The four control group subjects received no reconditioning. After catheter removal, reconditioned subjects resumed natural micturition significantly sooner than non-reconditioned subjects (t = -2.82, df = 6, p less than 0.05). A t test showed no significant differences between the groups in post-indwelling catheterization RUVs following the first micturition, probably due to the small number of subjects, since the control group's mean post-catheterization RUV increased to a physiologically abnormal level (42.25 ml), while the reconditioned group's mean RUV stayed within normal limits. This study should be repeated to test for statistical significance in larger samples.


Tourniquet pain: calf versus ankle tourniquet.
The tourniquet pain during 30 minutes after the application of calf tourniquet and ankle tourniquet were assessed and compared in 63 healthy volunteers, 32 males and 31 females whose ages ranged from 21-36 (average, 24) years. The visual analogue pain score assessed at 0, 1, 3, 5, 10, 20, 30 minutes of adequate tourniquet pressure application and after removal of the tourniquet at 0, 5 and 30 minutes were recorded. The results revealed significant less visual analogue pain scores with the ankle tourniquet group (range, 0-4.4 mmHg) than the calf tourniquet group (range, 0-6.7 mmHg) at all time-points of evaluations and the tourniquet pain was also diminished faster in the ankle tourniquet group after the tourniquet was removed. It was also found a significant higher minimal tourniquet pressure required for the vascular occlusion distal to the tourniquet sites detected by a pulse oximeter in the ankle tourniquet group (mean, 310.8 +/- 40.8 mmHg) than the calf tourniquet group (mean, 272.5 +/- 36.9 mmHg, p = 0.024). The present study supports the use of ankle tourniquet to minimize tourniquet pain for foot surgery.


Sawtooth faceting in silicon nanowires.
We observe in situ the vapor-liquid-solid (VLS) growth of Si nanowires, in UHV-CVD using Au catalyst. The nanowire sidewalls exhibit periodic sawtooth faceting, reflecting an oscillatory growth process. We interpret the facet alternation as resulting from the interplay of the geometry and surface energies of the wire and liquid droplet. Such faceting may be present in any VLS growth system in which there are no stable orientations parallel to the growth direction. The sawtooth structure has important implications for electronic mobility and scattering in nanowire devices.


[Dumai moxibustion combined with low-dose tadalafil for erectile dysfunction: Evaluation of therapeutic effect].
To investigate the clinical effect of dumai (governor meridian) moxibustion combined with low-dose tadalafil in the treatment of ED with decline of vital gate fire. We enrolled in this study 130 ED patients with decline of vital gate fire who met the inclusion criteria and equally randomized them into a control and an experimental group, the former treated with low-dose tadalafil tablets at 5 mg once a day while the latter by dumai moxibustion once a week in addition, all for 4 weeks. Of the total number of subjects, 62 in the control group and 63 in the experimental group completed the experiment. We recorded the scores on IIEF-5, Erection Quality Scale (EQS), Erection Hardness Scale (EHS), TCM symptoms and Treatment Satisfaction Scale (TSS) as well as the penile hemodynamic parameters peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) before and after treatment and compared them between the two groups. The total response rate was significantly higher in the experimental group than in the control (87.30% vs 66.13%, P < 0.05). IIEF-5, EQS, EHS and TSS scores, PSV and RI were markedly increased while TCM symptoms and EDV remarkably decreased in both groups after treatment (P < 0.05), even more significantly in the experimental than in the control group (P < 0.05). Dumai moxibustion combined with low-dose tadalafil can improve erectile function, increase penile blood flow velocity and alleviate clinical symptoms in ED patients with decline of vital gate fire, with definite clinical effect and safety.


Evaluation of hydrophilic surface osseointegration in low-density bone: Preclinical study in rabbits.
The aim of this study was to evaluate the osseointegration of a hydrophilic surface (blasting + acid etching + immersion in isotonic solution) in comparison with that of a control surface (blasting + acid etching) using an experimental model of low-density bone. To perform the study, 24 rabbits were submitted to the installation of 4 implants in the iliac bone bilaterally: 2 implants with a control surface and 2 implants with a hydrophilic surface. The rabbits were euthanized at 2, 4, and 8 weeks after implant installation. After euthanasia, one implant from each surface was used to perform the removal torque analysis, and the other implant was used for the execution of non-decalcified histological sections and evaluation of the bone implant contact (% BIC) as well as the fraction of bone tissue area between the implant threads (% BBT). The implants with a hydrophilic surface presented higher %BIC (42.92 ± 2.85% vs. 29.49 ± 10.27%) and % BBT (34.32 ± 8.52% vs. 23.20 ± 6.75%) (p < 0.05) in the 2-week period. Furthermore, the hydrophilic surface presented higher removal torque in the 8-week period (76.13 ± 16.00 Ncm2 vs. 52.77 ± 13.49 Ncm2) (p<0.05). Implants with a hydrophilic surface exhibited acceleration in the process of osseointegration, culminating in greater secondary stability in low-density bone than in implants with a control surface.


Becoming a Faithful Defender: Traditional Chinese Medicine against Coronavirus Disease 2019 (COVID-19).
The outbreak caused by COVID-19 is causing a major challenge to clinical management and a worldwide threat to public health. So far, there is no specific anti-coronavirus therapy approved for the treatment of COVID-19. Recently, as the efficacy and safety of traditional Chinese medicine (TCM) is widely acknowledged, it has been brought to a crucial status by the public, governments, and World Health Organization (WHO). For a better popularization of TCM, governments have made several advances in regulations and policies for treatment and measures of novel coronavirus pneumonia (NCP). Therefore, on the basis of epidemiology and virology information, we reviewed relevant meta-analysis and clinical studies of anti-coronavirus therapeutics by TCM, in the aspect of mortality, symptom improvement, duration and dosage of corticosteroid, incidence of complications and the like. In addition, we also summarized preclinical rationale for anti-coronavirus activity by TCM in terms of virion assembly and release, as well as viral entry and replication, which could be a useful contribution for figuring out effective Chinese herbal medicine (CHM) for coronavirus, including ingredients from single monomeric compounds, Chinese herbs, Chinese herb extracts and Chinese herb formulas, or potential targets for medicine. We would like to see these relevant studies, ranging from basic researches to clinical application, could provide some idea on effects of CHM to combat COVID-19 or other coronaviruses, and also offer new thinking for the exploration of therapeutic strategies under the guidance of TCM.


[Successful hypnotherapy in an intellectually disabled patient with drug treatment resistant epilepsy].
The possibility of psychogenic non-epileptic seizures (PNES) should be considered in patients with treatment-resistant epilepsy for whom hypnotherapeutic approach may be tried as one treatment option. Multimodal epileptic seizures as well as various behavioral and dyskinetic disorders are commonly associated with intellectual disabilities. Differentiation of brain derived epileptic seizures from other non-epileptic seizures requires an extensive anamnesis, clinical follow-up of the patient and video-EEG recording of seizures. We describe a patient with mild intellectual disability whose almost daily, drug-resistant epileptic attacks were found to be psychogenic. Hypnotherapeutic relaxation initiated upon mother's suggestion turned out to be useful.


Intensive insulin treatment induces insulin resistance in diabetic rats by impairing glucose metabolism-related mechanisms in muscle and liver.
Insulin replacement is the only effective therapy to manage hyperglycemia in type 1 diabetes mellitus (T1DM). Nevertheless, intensive insulin therapy has inadvertently led to insulin resistance. This study investigates mechanisms involved in the insulin resistance induced by hyperinsulinization. Wistar rats were rendered diabetic by alloxan injection, and 2 weeks later received saline or different doses of neutral protamine Hagedorn insulin (1.5, 3, 6, and 9 U/day) over 7 days. Insulinopenic-untreated rats and 6U- and 9U-treated rats developed insulin resistance, whereas 3U-treated rats revealed the highest grade of insulin sensitivity, but did not achieve good glycemic control as 6U- and 9U-treated rats did. This insulin sensitivity profile was in agreement with glucose transporter 4 expression and translocation in skeletal muscle, and insulin signaling, phosphoenolpyruvate carboxykinase/glucose-6-phosphatase expression and glycogen storage in the liver. Under the expectation that insulin resistance develops in hyperinsulinized diabetic patients, we believe insulin sensitizer approaches should be considered in treating T1DM.


Complete genome sequence of Treponema pallidum strain DAL-1.
Treponema pallidum strain DAL-1 is a human uncultivable pathogen causing the sexually transmitted disease syphilis. Strain DAL-1 was isolated from the amniotic fluid of a pregnant woman in the secondary stage of syphilis. Here we describe the 1,139,971 bp long genome of T. pallidum strain DAL-1 which was sequenced using two independent sequencing methods (454 pyrosequencing and Illumina). In rabbits, strain DAL-1 replicated better than the T. pallidum strain Nichols. The comparison of the complete DAL-1 genome sequence with the Nichols sequence revealed a list of genetic differences that are potentially responsible for the increased rabbit virulence of the DAL-1 strain.


Mental health service utilisation among transgender women sex workers who are at risk of mental health problems in Shenyang, China: An application of minority stress theory.
Transgender women sex workers (TGSW), as a highly stigmatised population, are at substantial risk for mental health problems but lack access to mental health care. This study investigated factors of mental health service utilisation (MHSU) behaviour and related behavioural intention among TGSW who were at risk of mental health problems in the past year [subsample 1: scored above the cut-off for probable depression or probable anxiety or had suicidal ideation (N = 126); subsample 2: perceived needs for mental health services (N = 109)]. A cross-sectional survey was conducted among TGSW in Shenyang, China during 2017-2018. Data on minority stress, coping, mental health and MHSU were collected. 10.3% of participants in subsample 1 and 14.7% in subsample 2 had sought help from mental health professionals in the last year. Unwillingness to disclose minority identity and gender non-affirmation were negatively associated with MHSU. Factors for behavioural intention of MHSU included unwillingness to disclose minority identity and social support for both subsamples and adaptive coping for subsample 2. Confidentiality concern, discrimination and cost were the most frequently endorsed barriers to mental health services. Interventions should promote gender affirmation, social support and adaptive coping as well as remove stigma to increase health service access and utilisation among minority populations.


Treatment of acute transverse myelitis and its early complications.
Acute transverse myelitis (ATM) has many potential etiologies, but a significant proportion of cases are categorized as idiopathic despite thorough evaluation. Clinical presentation of ATM typically includes some combination of motor weakness, sensory symptoms, and bowel and bladder dysfunction. Prompt recognition, even before a final etiologic diagnosis is reached, is critical to initiating early therapeutic intervention to reduce the harmful effects of inflammation. Acute therapeutic options for ATM include corticosteroids, plasma exchange, IV immunoglobulin, and chemotherapeutic agents such as cyclophosphamide. In some instances, combinations of these therapies are used. This article examines the therapeutic approach to ATM and its various acute clinical manifestations.


Boxing: medical care in and out of the ring.
Boxing may well be the oldest sport known to mankind and probably the most controversial. Injuries are common in boxing, occurring most often to the head, neck, face, and hands. Brain injury, both acute and chronic, is the major risk for potential catastrophe. Medical care for the boxer extends beyond the competition in the boxing ring; the ringside physician is responsible for protecting both boxers and must make quick decisions about their continued participation based upon a limited examination. A thorough knowledge of the rules and regulations of boxing is necessary for the ringside physician to effectively care for the athlete. In spite of the perceived brutality associated with the sport, most injuries are minor, although serious injuries and deaths do occur, most commonly due to brain injury. Given the potential for catastrophic injury, the ringside physician must be prepared and equipped to care for the boxer.


Primary mouse brain pericytes isolated from transgenic Alzheimer mice spontaneously differentiate into a CD11b+ microglial-like cell type in vitro.
Alzheimer's disease (AD) is characterized by amyloid-β plaques, tau pathology and vascular impairment including pericyte damage. Pericytes are perivascular cells of the blood-brain barrier and can differentiate into different cell types in vitro including microglia. The aim of the present study is to explore if primary mouse brain pericytes isolated and cultured from transgenic AD (APP_SweDI) mice can differentiate into CD11b+ (integrin alpha M) microglia in vitro. We show that primary pericytes (passage 5) isolated from wildtype C57BL6 mice differentiated into CD11b+ microglia (Type B, >90%), when exposed to a differentiation factor mix of FGF-2, cAMP and fibronectin. This differentiation was time-dependent and seen as a large 80 kDa CD11b fragment (days 1-8) and a smaller 50 kDA CD11b fragment (>4 days). These pericytes did not differentiate into neurons, astroglia or oligodendroglia. However, pericytes isolated from transgenic AD mice differentiated into CD11b+ microglia (Type A, <10%) without addition of exogenous differentiation factors, displayed moderate Iba1+ immunostaining and phagocytic activity, but were still positive for PDGFRβ. In conclusion, we show for the first time that primary mouse pericytes from AD mice have the potential to spontanously differentiate in vitro into a CD11b+ microglial-like (Type A) cell type, but we do not provide evidence that these pericytic microglia display a full active microglial cell.


Different effects of I-wave periodicity repetitive TMS on motor cortex interhemispheric interaction.
Activity of the neural circuits in the human motor cortex can be probed using transcranial magnetic stimulation (TMS). Changing TMS-induced current direction recruits different cortical neural circuits. I-wave periodicity repetitive TMS (iTMS) substantially modulates motor cortex excitability through neural plasticity, yet its effect on interhemispheric interaction remains unclear. To explore the modulation of interhemispheric interaction by iTMS applied in different current directions. Twenty right-handed healthy young volunteers (aged 27.5 ± 5.0 years) participated in this study with three visits. On each visit, iTMS in posterior-anterior/anterior-posterior direction (PA-/AP-iTMS) or sham-iTMS was applied to the right hemisphere, with corticospinal excitability and intracortical facilitation of the non-stimulated left hemisphere evaluated at four timepoints. Ipsilateral silent period was also measured at each timepoint probing interhemispheric inhibition (IHI). PA- and AP-iTMS potentiated cortical excitability concurrently in the stimulated right hemisphere. Corticospinal excitability of the non-stimulated left hemisphere increased 10 min after both PA- and AP-iTMS intervention, with a decrease in short-interval intracortical facilitation (SICF) observed in AP-iTMS only. Immediately after the intervention, PA-iTMS tilted the IHI balance toward inhibiting the non-stimulated hemisphere, while AP-iTMS shifted the balance toward the opposite direction. Our findings provide systematic evidence on the plastic modulation of interhemispheric interaction by PA- and AP-iTMS. We show that iTMS induces an interhemispheric facilitatory effect, and that PA- and AP-iTMS differs in modulating interhemispheric inhibition.


Type IIb von Willebrand disease: role of qualitative defects in atherosclerosis and endothelial dysfunction.
To verify whether a hereditary bleeding tendency, such as von Willebrand disease (vWD) type IIB, protects against the onset of atherosclerosis. Twenty-four patients with vWD type IIB and 24 healthy controls, matched for common atherosclerotic risk factors. All patients were evaluated by color Doppler ultrasound of the common carotid, carotid bifurcation, common femoral artery, brachial artery, and abdominal aorta, investigating intima-media thickness (IMT) and presence of plaques in each arterial district. Flow mediated dilation (FMD) of the brachial artery was used to test endothelial function. vWD type IIB patients presented no significant difference in IMT in any arterial district. FMD showed no differences between the 2 groups. The quantitative clotting defect characteristic of vWD type IIB does not seem to protect against atherosclerosis.


Anaerobic Capacity is Associated with Metabolic Contribution and Mechanical Output Measured During the Wingate Test.
The study aimed to investigate the relationship between anaerobic capacity, mechanical and anaerobic contribution during the 30-s Wingate Anaerobic Test (30sWAnT). After familiarization, fifteen, male recreational mountain biking practitioners underwent the following sequence of tests: 1) a graded exercise test to determine maximal oxygen uptake and associated intensity i V ˙ O 2 m a x ; 2 and 3) supramaximal exhaustive effort at 115% of iVO2max and 30sWAnT, performed randomly. The glycolytic and phosphagen pathways measured during the supramaximal effort were significantly correlated with peak power (r = 0.85; p < 0.01 and r = 0.57; p = 0.02, respectively), mean power (r = 0.78; p < 0.01 and r = 0.69; p < 0.01, respectively), and total work (r = 0.78; p < 0.01 and r = 0.69; p< 0.02, respectively) measured during the 30sWAnT. A significant correlation was also found between anaerobic capacity and peak power (r = 0.88; p < 0.01), mean power (r = 0.89; p < 0.01), and total work (r = 0.89; p < 0.01). Additionally, anaerobic capacity estimated during the supramaximal effort and the anaerobic contribution measured during the 30sWAnT were not different (p = 0.44) and presented significant good reliability and association (ICC = 0.84; p = 0.001) and good agreement, evidenced by the mean of differences and 95% limits of agreement near to zero (mean bias = 0.11). The results suggest that glycolytic and phosphagen capacity were associated with mechanical performance in the 30sWAnT. In addition, anaerobic contribution during the 30sWAnT seems to be valid for estimating anaerobic capacity in recreational mountain bike cyclists, as well as to estimate the glycolytic and phosphagen contributions.


Surgery in patients aged 80 years and over. A retrospective comparative study from 1981 and 1987.
This is a retrospective study from a general surgical unit to evaluate the profile of surgery in patients aged greater than or equal to 80 years in the years 1981 and 1987. The proportion of admissions of such patients rose from 9.6% in 1981 to 15.7% in 1987. There was a twofold increase in emergency admissions and an increase of 30-40% in early (within 24 hours) interventions among the emergency cases of this age group. The postoperative mortality was concentrated to the emergency cases. In more than half of the admittances as well as of the postoperative fatalities the main diagnosis was a benign disease. The surgical procedure was considered to be curative or beneficial in 72% of the patients. To improve the efficiency of surgical therapy in this age group higher priority should be given to elective operations in order to avoid emergency interventions.


[Clinical picture of spinal tumors].
Spinal tumors may present with symptoms such as pain and motor and sensory deficits. Sphincter dysfunction may also occur. The clinical picture depends upon the size and localization of the tumor in relation to the cross section and the height along the longitudinal axis of the spinal cord. Typical symptoms due to transverse damage of the spinal cord are complete lesion, Brown-Sequard syndrome, a lesion of the central spinal cord, and posterior cord syndrome. Tetraparesis, spastic, or flaccid paraparesis result from lesions at the cervical spine, thoracic spine, or below the first lumbar vertebral body, respectively.


A new norditerpenoid alkaloid from Aconitum taipaicum.
To investigate the chemical constituents of the roots of Aconitum taipaicum, silica gel column chromatography was used for the isolation and purification of compounds. A new norditerpenoid alkaloid, isodelelatine (1), along with five known alkaloids, atisine (2), delfissinol (3), liangshanine (4), hypaconitine (5) and delelatine (6) were isolated and identified. The structure of the new compound was elucidated on the basis of spectral data.


Application of neutron imaging in observing various states of matter inside lithium batteries.
Lithium batteries have been essential technologies and become an integral part of our daily lives, powering a range of devices from phones to electric vehicles. To fully understand and optimize the performance of lithium batteries, it is necessary to investigate their internal states and processes through various characterization methods. Neutron imaging has been an indispensable complementary characterization technique to X-ray imaging or electron microscopy because of the unique interaction principle between neutrons and matter. It provides particular insights into the various states of matter inside lithium batteries, including the Li+ concentration in solid electrodes, the Li plating/stripping behavior of Li-metal anodes, the Li+ diffusion in solid ionic conductors, the distribution of liquid electrolytes and the generation of gases. This review aims to highlight the capabilities and advantages of neutron imaging in characterizing lithium batteries, as well as its current state of application in this field. Additionally, we discuss the potential of neutron imaging to contribute to the ongoing development of advanced batteries through its ability to visualize internal evolution.


[The clinical importance of histocompatibility antigens and their combinations in the diagnosis of chronic pyelonephritis].
Distribution of histocompatibility antigens and combinations thereof were investigated in citizens of St. Petersburg. All the examinees suffered from chronic pyelonephritis (CPN). The occurrence of antigens A1 and B17 in the patients was significantly high and associated with increased risk and etiological fraction. Combinations of antigens were frequently encountered in one locus: A1, A2, interlocus combinations A1, B5, A1, B7, A1, B17. Combinations of these antigens (especially A1 + B17) were indicative of high CPN risk. Frequent incidence of antigens A1, B7; A1, B5 may be due to the fact that in the above combinations they are responsible for higher CPN-risk. Increased incidence rate of antigens HLA-A1 and HLA-B17 evidences their involvement into CPN pathogenesis. Strong association of the disease with antigens A1, B17 seems to be typical for St. Petersburg citizens.


The use of allograft and recombinant human bone morphogenetic protein for instrumented atlantoaxial fusions.
Iliac crest autograft is the historic gold standard for bone grafting, but is associated with a significant patient morbidity. Fusion rates of C1-C2 up to 88.9% using allograft and 96.7% using autologous iliac crest bone graft can be achieved when combined with rigid screw fixation. We sought to determine our fusion rate when combining allograft with recombinant human bone morphogenetic protein-2 (rh-BMP2) and rigid screw fixation. We reviewed our experience using allograft, bone morphogenetic protein (rh-BMP2) and screw fixation of C1-C2 in 52 patients and examined indications, surgical technique, fusion rates, and complications. In 28 patients, corticocancellous allograft pieces were laid along decorticated bone after a C2 neurectomy was performed. In 24 patients, unicortical iliac crest allograft was precision-cut to fit between the C1 lamina and C2 spinous processes. Fifty-two C1-C2 fusions were performed with allograft, rh-BMP2, and rigid screw fixation. There were 25 female and 27 male patients ranging in age from 6 to 92 years (mean, 65.8 years). Operative indications included trauma (56%), degenerative disease (21%), rheumatoid arthritis (15%), congenital anomalies (6%), and synovial cyst (2%). The mean follow-up was 23.9 ± 2.1 months (range, 2-55 months). The mean dose of rh-BMP2 used for all patients was 4.5 mg (range, 2.2-12 mg). In patients who achieved sufficient follow-up, 100% achieved solid fusion: 45/50 Lenke A, 5/50 Lenke B. There were no known complications attributable to the use of rh-BMP2. The use of small doses of rh-BMP2 added to allograft in addition to rigid screw fixation is a safe and highly effective means of promoting a solid fusion of the atlantoaxial complex and spares the patient the morbidity of iliac crest harvest.


[Staged surgery of Sanders type Ⅳ calcaneal fractures with soft tissue three-degree swelling].
To compare the clinical efficacy of staged surgery on Sanders Ⅳ calcaneal fractures with soft tissue Ⅲ swelling. The clinical data of 76 patients with Sanders type Ⅳ closed calcaneal fracture with soft tissue three-degree swelling treated from June 2017 to May 2020 was retrospectively analyzed, including 54 males and 22 females, aged from 25 to 50 (38.16±10.24) years. The patients were divided into observation group and control group according to different treatment methods. Twenty-four patients in the observation group were treated by staged surgery stageⅠclosed prying traction reduction and Kirschner wire fixation, stageⅡopen reduction and internal fixation with titanium plate, including 17 males and 7 females, aged from 25 to 50 (36.12±9.56) years. There were 52 patients in the control group, including 37 males and 15 females, aged from 25 to 50 (38.32±10.67) years, these patients were treated with open reduction and internal fixation with titanium plate after the dermatoglyphic signs appeared. The swelling subsidence time, the length of hospitalization days, and the incidence of postoperative incision complications were compared between two groups. The Bhler angle, Gissane angle, and calcaneal varus angle were measured by X-ray before and 6 months after operation. American Orthopedic Foot and Ankle Society (AOFAS) about the ankle hindfoot score was used to evaluate the clinical efficacy. All 76 patients were followed up for 8 to 12 (9.52±2.01) months. The swelling subsidence time and hospitalization days in observation group were (12.12± 3.24) d and (24.53±6.44) d, respectively, which in control group were (15.16±4.16) d and (29.46±9.61) d, with statistical difference between two groups (P<0.05). Postoperative 6 months, Bhler angle, Gissane angle and calcaneal varus angle were (31.33±10.15)°, (145.34±8.04) ° and (10.31±3.23) ° in observation group, while those in control group were (20.24±8.23) °, (165.28±10.29) °and (21.24±5.27) °, with statistical difference between two groups (P<0.05). And there was significant difference in all patients between before and 6 months after operation (P<0.05). The AOFAS score of the observation group and control group were 71.76±9.84 and 57.23±10.76 at 6 months after operation, with significant different between two groups (P< 0.05). The excellent rate of observation group was significantly higher than that of control group (P<0.05). Compared with open reduction and internal fixation with titanium plate after the appearance of dermatoglyphic signs, staged surgery for Sanders type Ⅳ calcaneal fractures with soft tissue three-swelling does not increase the risk of soft tissue complications, and can significantly shorten the patient's swelling subsidence time and hospitalization days, improve the quality of fracture reduction and short term function, and relieve pain.


Small bowel metastases of lung cancer as unique metastatic lesions: CT, MRI and small bowel enema findings. a case report.
Small bowel metastases of lung cancer as unique secondary lesions are a very rare occurrence and may be clinically missed due to the aspecificity of the symptoms. Diagnosis is usually made at acute abdominal symptomatology that requires emergency surgical treatment. We report a case of 69-year-old woman, previously treated for epidermoid lung carcinoma, complaining only of aspecific asthenia; blood cell count and chemistry showed a moderate but progressive anemia; no signs of small bowel occlusion were present. The follow-up CT scan showed two large masses at the small bowel level, without any evidence of hepatic, lung, adrenal or brain metastases. MRI and small bowel enema confirmed the presence of the masses, and the diagnosis of small bowel metastases was hypothesized. Surgical specimens of the masses confirmed the radiological suspicion.


The discriminative stimulus effects of diazepam in rats at two training doses.
Two groups of rats were trained to discriminate either a low (1 mg/kg) or a high (10 mg/kg) intraperitoneal dose of diazepam from vehicle injections in a two-lever, food-reinforcement procedure. Comparison of the dose-response curves demonstrated a difference in the intensity of the stimulus effects. A number of benzodiazepine agonists and partial agonists were tested for stimulus generalization. The stimulus effect in both groups of rats generalized fully to triazolam, alprazolam, adinazolam and pentobarbital. Ro 17-1812 occasioned nearly full generalization in both groups of rats with a shallow dose-response slope. The low-, but not the high-dose stimulus effect generalized to the following compounds: CL 218872, ZK 91296 (ethyl-5-benzyloxy-4-methoxymethyl-B-carboline-3-carboxylate), CGS 20625 (2-(4-methoxyphenyl)-2,3,5,6,7,8,9,10-octahydrocyclohepta(b)pyrazo lo(3,4- d)pyridin-3-one) and U-78875 (3-(5-cyclo-propyl-1,2,4-oxadiazol-3-yl)-5-(1- methylethyl)imidazol(1,5-a)quinoxalin-4(5H)-o-ne). Flumazenil, FD-7142 (N-methyl-beta-carboline-3-carboxamide), buspirone and morphine occasioned predominantly vehicle-appropriate responses in both groups of rats. In the low-dose group, pretreatment with flumazenil (10 mg/kg) reduced responding on the diazepam-lever for the following compounds: diazepam, Ro 17-1812 (cyclopropylmethyl-(S)-8-chloro-12,12a-dihydro- 9-oxo-9H,11H-aceto(2,1-C)imidazo(1,5-a)(1,4)benzo-diazepine-1-carboxylat e), ZK 91296, CGS 20625, CL 218872 and U-78875.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term behavioral adaptation of Oldowan toolmakers to resource-constrained environments at 2.3 Ma in the Lower Omo Valley (Ethiopia).
The long stratigraphic sequence of the Shungura Formation in the Lower Omo Valley documents 3 million years (Ma) of hominin evolution, which, when combined with detailed paleo-depositional environmental data, opens new perspectives for understanding the complex interactions between hominin landscape use and the development of stone tool-mediated activities. Stone tool assemblages produced by Paranthropus aethiopicus and/or a species of early Homo from ~ 2.3 Ma, reflect their ability to deal with the raw material scarce environment of the Lower Omo Valley. It remains to be seen whether this activity can be related to a single, brief occupation event or the expression of an emergent new adaptation. Here we report on the newly investigated site complex of OMO 79, which produced the first evidence for multiple phases of hominin tool-making and use in the Shungura Formation. The development of this long-lasting techno-economic behavior marks a cognitive tipping point around 2.3 Ma in the Lower Omo Valley, evidenced by the adaptability of the early hominins to resource-constrained environments.


Charged bipolar suramin derivatives induce aggregation of the prion protein at the cell surface and inhibit PrPSc replication.
The conversion of the cellular prion protein (PrPc) into a pathogenic isoform (PrP(Sc)) is one of the underlying events in the pathogenesis of the fatal transmissible spongiform encephalopathies (TSEs). Numerous compounds have been described to inhibit prion replication and PrP(Sc) accumulation in cell culture. Among these, the drug suramin induces aggregation and re-targeting of PrPc to endocytic compartments. Plasma membrane and sites of conversion into PrP(Sc) are thereby bypassed. In the present study, a library of suramin analogues was tested as a potential class of new anti-prion compounds and the molecular mechanisms underlying these effects were analysed. Treatment of prion-infected neuroblastoma cells with compounds containing symmetrical aromatic sulfonic acid substitutions inhibited de novo synthesis of PrP(Sc) and induced aggregation and reduction of the half-life of PrPc without downregulating PrPc cell surface expression. Half-molecule compounds lacking the symmetrical bipolar structure or the anionic groups had no effect on PrP(Sc) synthesis or PrPc solubility. Cell surface expression of PrPc was necessary for the activity of effective compounds. Suramin derivatives did not induce aggregation of PrPc when transport along the secretory pathway was compromised, suggesting that their effects occur at a post trans-Golgi network (TGN) site, possibly close to the compartment of conversion into PrP(Sc). In vitro studies with recombinant PrP demonstrated that the inhibitory effect correlated with direct binding to PrP and induction of insoluble PrP aggregates. Our data reveal an anti-prion effect that differs from those characterising other sulphated polyanions and is dependent on the presence of the symmetrical anionic structure of these molecules.


Stabilization of L-asparaginase modified with comb-shaped poly(ethylene glycol) derivatives, in vivo and in vitro.
L-Asparaginase from Escherichia coli was coupled with two types of comb-shaped copolymer of poly-(ethylene glycol) derivative and maleic anhydride (activated PM), having molecular weights of 13,000 and 100,000 (activated PM13 and PM100, respectively) with multivalent reaction sites. After single intravenous injections of PM100-asparaginase and nonmodified asparaginase into rats, the enzymic activity of PM100-asparaginase in serum was well retained for at least 11 days, and the serum L-asparagine concentration remained undetectable for 27 days. The half-lives of PM100-asparaginase and nonmodified asparaginase were 50 and 1.5 h, respectively. Stabilization of L-asparaginase toward heat, urea, and acidity was caused by modifying the enzyme with activated PM13 and PM100. Especially, PM100-asparaginase retained high enzymic activity toward heat and urea, compared with PM13-asparaginase. It was suggested that these modifiers with a comb-shaped form and with multivalent reactive sites cover the whole surface of the asparaginase molecule and stabilize its conformation possibly through multiple covalent bindings and through various noncovalent interactions.


Multimodal imaging patterns predict survival in recurrent glioblastoma patients treated with bevacizumab.
Bevacizumab is a humanized antibody against vascular endothelial growth factor approved for treatment of recurrent glioblastoma. There is a need to discover imaging biomarkers that can aid in the selection of patients who will likely derive the most survival benefit from bevacizumab. The aim of the study was to examine if pre- and posttherapy multimodal MRI features could predict progression-free survival and overall survival (OS) for patients with recurrent glioblastoma treated with bevacizumab. The patient population included 84 patients in a training cohort and 42 patients in a testing cohort, separated based on pretherapy imaging date. Tumor volumes of interest were segmented from contrast-enhanced T1-weighted and fluid attenuated inversion recovery images and were used to derive volumetric, shape, texture, parametric, and histogram features. A total of 2293 pretherapy and 9811 posttherapy features were used to generate the model. Using standard radiographic assessment criteria, the hazard ratio for predicting OS was 3.38 (P < .001). The hazard ratios for pre- and posttherapy features predicting OS were 5.10 (P < .001) and 3.64 (P < .005) for the training and testing cohorts, respectively. With the use of machine learning techniques to analyze imaging features derived from pre- and posttherapy multimodal MRI, we were able to develop a predictive model for patient OS that could potentially assist clinical decision making.


Functional correlation among Gal11, transcription factor (TF) IIE, and TFIIH in Saccharomyces cerevisiae. Gal11 and TFIIE cooperatively enhance TFIIH-mediated phosphorylation of RNA polymerase II carboxyl-terminal domain sequences.
Saccharomyces cerevisiae Gal11, a component of the holoenzyme of RNA polymerase II, interacts through its functional domains A and B with the small (Tfa2) and large (Tfa1) subunits of the general transcription factor (TF) IIE, respectively. We have recently suggested that Gal11 functions through a common pathway with TFIIE in transcriptional regulation (Sakurai, H., and Fukasawa, T. (1997) J. Biol. Chem. 272, 32663-32669). Here, we report that the activity of the TFIIH-associated kinase, responsible for phosphorylation of the largest subunit of RNA polymerase II at the carboxyl-terminal domain (CTD), is enhanced cooperatively by Gal11 and TFIIE. The enhancement of CTD phosphorylation was observed in the holoenzyme of RNA polymerase II, but not in its core enzyme. The stimulatory effect was completely abolished in the absence of either domain B of Gal11 or the Tfa1 subunit of TFIIE, suggesting that the domain B-Tfa1 interaction is necessary, if not sufficient, for an extensive phosphorylation of the CTD by TFIIH. Stimulation of basal transcription by Gal11 was coupled with enhancement of TFIIH-catalyzed CTD phosphorylation in a cell-free transcription system, suggesting that Gal11 activates transcription by stimulating the CTD phosphorylation in the cell.


Divergence and Redundancy in CSLD2 and CSLD3 Function During Arabidopsis Thaliana Root Hair and Female Gametophyte Development.
The Arabidopsis cellulose synthase-like D (CSLD) 2 and 3 genes are known to function in root hair development. Here, we show that these genes also play a role in female gametophyte development because csld2 csld3 double mutants were observed to have low seed set that could be traced to defects in female transmission efficiency. Cell biological studies of csld2 csld3 ovules showed synergid cell degeneration during megagametogenesis and reduced pollen tube penetration during fertilization. Although CSLD2 and CSLD3 function redundantly in female gametophyte development, detailed analyses of root hair phenotypes of progeny from genetic crosses between csld2 and csld3, suggest that CSLD3 might play a more prominent role than CSLD2 in root hair development. Phylogenetic and gene duplication studies of CSLD2 and CSLD3 homologs in Arabidopsis lyrata, Populus, Medicago, maize, and Physcomitrella were further performed to investigate the course of evolution for these genes. Our analyses indicate that the ancestor of land plants possibly contained two copies of CSLD genes, one of which developed into the CSLD5 lineage in flowering plants, and the other formed the CSLD1/2/3/4 clade. In addition, CSLD2 and CSLD3 likely originated from a recent genome-wide duplication event explaining their redundancy. Moreover, sliding-window dN/dS analysis showed that most of the coding regions of CSLD2 and CSLD3 have been under strong purifying selection pressure. However, the region that encodes the N-terminus of CSLD3 has been under relatively relaxed selection pressure as indicated by its high dN/dS value, suggesting that CSLD3 might have gained additional functions through more frequent non-synonymous sequence changes at the N-terminus, which could partly explain the more prominent role of CSLD3 during root hair development compared to CSLD2.


Organometallic-Mediated Alternating Radical Copolymerization of tert-Butyl-2-Trifluoromethacrylate with Vinyl Acetate and Synthesis of Block Copolymers Thereof.
Organometallic-mediated radical polymerization (OMRP) has given access to well-defined poly(vinyl acetate-alt-tert-butyl-2-trifluoromethacrylate)-b-poly(vinyl acetate) and poly(VAc-alt-MAF-TBE) copolymers composed of two electronically distinct monomers: vinyl acetate (VAc, donor, D) and tert-butyl-2-trifluoromethacrylate (MAF-TBE, acceptor, A), with low dispersity (≤1.24) and molar masses up to 57 000 g mol-1 . These copolymers have a precise 1:1 alternating structure over a wide range of comonomer feed compositions. The reactivity ratios are determined as rVAc = 0.01 ± 0.01 and rMAF-TBE = 0 at 40 °C. Remarkably, from a feed containing >50% molar VAc content, poly(VAc-alt-MAF-TBE)-b-PVAc block copolymers are produced via a one-pot synthesis. Such diblock copolymers exhibit two glass transition temperatures attributed to the alternating and homopolymer sequences. The OMRP of this fluorine-containing alternating monomer system may provide access to a wide range of new polymer materials.


Self-healing Growth of LaNiO3 on a Mixed-Terminated Perovskite Surface.
Developing atomic-scale synthesis control is a prerequisite for understanding and engineering the exotic physics inherent to transition-metal oxide heterostructures. Thus, far, however, the number of materials systems explored has been extremely limited, particularly with regard to the crystalline substrate, which is routinely SrTiO3. Here, we investigate the growth of a rare-earth nickelate─LaNiO3─on (LaAlO3)(Sr2AlTaO6) (LSAT) (001) by oxide molecular beam epitaxy (MBE). Whereas the LSAT substrates are smooth, they do not exhibit the single surface termination usually assumed necessary for control over the interface structure. Performing both nonresonant and resonant anomalous in situ synchrotron surface X-ray scattering during MBE growth, we show that reproducible heterostructures can be achieved regardless of both the mixed surface termination and the layer-by-layer deposition sequence. The rearrangement of the layers occurs dynamically during growth, resulting in the fabrication of high-quality LaNiO3/LSAT heterostructures with a sharp and consistent interfacial structure. This is due to the thermodynamics of the deposition window as well as the nature of the chemical species at interfaces─here, the flexible charge state of nickel at the oxide surface. This has important implications regarding the use of a wider variety of substrates for fundamental studies on complex oxide synthesis.


Medical education research as translational science.
Research on medical education is translational science when rigorous studies on trainee clinical skill and knowledge acquisition address key health care problems and measure outcomes in controlled laboratory settings (T1 translational research); when these outcomes transfer to clinics, wards, and offices where better health care is delivered (T2); and when patient or public health improves as a result of educational practices (T3). This Commentary covers features of medical education interventions and environments that contribute to translational outcomes, reviews selected research studies that advance translational science in medical education at all three levels, and presents pathways to improve medical education translational science.


Characteristics and prognostic factors of node-negative non-small cell lung cancer larger than 5 cm.
In the 7th edition of the tumour, node and metastasis staging system, a primary tumour size larger than 5 cm was shifted to Stage II. Therefore, we aimed to evaluate the characteristics and prognostic factors of node-negative non-small cell lung cancer (NSCLC) larger than 5 cm. We included 109 patients who underwent curative resection and had pathologically confirmed node-negative NSCLC >5 cm (Group 1). We compared the clinicopathological characteristics and prognosis of these patients with 85 patients with node-positive NSCLC >5 cm (Group 2) and 383 patients who had node-positive NSCLC ≤5 cm (Group 3). Compared with Group 2, old age and absence of lymphovascular invasion was significantly more common in Group 1. Compared with Group 3, frequency of non-adenocarcinoma type and visceral pleural invasion were significantly higher in Group 1; however, the frequency of lymphovascular invasion was higher in Group 3. A Cox proportional hazards model showed that the maximized standardized uptake value and visceral pleural invasion was a statistically worse prognostic factor. Compared with Group 2, Group 1 showed significantly longer overall survival; however, there was no difference in recurrence-free survival. Compared with Group 3, there was no significant difference in recurrence-free survival and overall survival. In Group 1, recurrence in the contralateral lung was the most common recurrence pattern, and there was no metastasis in the mediastinal lymph nodes. Patients with node-negative NSCLC >5 cm had a lower incidence of lymphovascular invasion and a more common contralateral recurrence than patients with node-positive NSCLC, and visceral pleural invasion was identified as independent prognostic factors.


Patient-Reported Outcomes Are Associated With Enhanced Recovery Status in Patients With Bladder Cancer Undergoing Radical Cystectomy.
Bladder cancer is a disease of the elderly that is associated with high morbidity in those treated with radical cystectomy. In this observational study of patients with bladder cancer undergoing radical cystectomy, we analyzed and compared patient-reported outcomes from those treated with Enhanced Recovery After Surgery (ERAS) methods versus those who received traditional perioperative care. We enrolled patients who underwent radical cystectomy at a high-volume tertiary care referral center from November 2013 to December 2016, when the ERAS concept was being introduced into postoperative care at our institution. Patients reported symptom outcomes using the MD Anderson Symptom Inventory preoperatively and on postoperative days 1 to 5. Mann-Whitney U tests were used to compare symptom burden between the ERAS and traditional-care groups. General linear mixed-effects models were used for longitudinal data; linear regression models were used for multivariable analysis. Patients (N = 383) reported dry mouth, disturbed sleep, drowsiness, fatigue, pain, and lack of appetite as the most severe symptoms. Compared with the traditional-care group, the ERAS group had significantly less pain (est. = -0.98, P = .005), drowsiness (est. = -0.91, P = .009), dry mouth (est. = -1.21, P = .002), disturbed sleep (est. = -0.97, P = .01), and interference with functioning (est. = -0.70, P = .022) (adjusted for age, sex, surgical technique, and neoadjuvant chemotherapy status). These results suggest that ERAS practice significantly reduced immediate postoperative symptom burden in bladder cancer patients recovering from radical cystectomy, supporting the use of patient-reported symptom burden as an outcome measure in perioperative care.


Characterization of a Borna disease virus glycoprotein, gp18.
Borna disease virus is a nonsegmented negative-strand RNA virus that causes neurologic disease in a wide variety of animal hosts. Here we describe identification and characterization of the first glycoprotein in this viral system. The 18-kDa glycoprotein, gp18, has been purified from infected rat brain. Isolation and microsequencing of this protein allowed identification of a 16.2-kDa open reading frame in the viral antigenome. Lectin binding and endoglycosidase sensitivity assays indicate that gp18 is an unusual N-linked glycoprotein.


STXM and NanoSIMS investigations on EPS fractions before and after adsorption to goethite.
Extracellular polymeric substances (EPS) are expected to be an important source for the formation of mineral-organic associations in soil. Because such formations affect the composition of mobile and immobile organic matter as well as the reactivity of minerals, we investigated the composition of EPS before and after adsorption to goethite. Raman measurements on EPS extracted from Bacillus subtilis distinguished four fractions rich in proteins, polysaccharides, lipids, or lipids and proteins. Scanning transmission X-ray microscopy identified three different EPS-fractions that varied in their composition in proteins, nonaromatic proteins, and polysaccharides. Reaction of EPS with goethite led to a preferential adsorption of lipids and proteins. The organic coverage was heterogeneous, consisting of ~100 × 200 nm large patches of either lipid-rich or protein-rich material. Nanoscale secondary ion mass spectrometry showed a strong S enrichment in aggregates of ~400 nm in the goethite adsorbed EPS. From our simplified model system, we learned that only a small portion (<10%) of EPS was immobilized via adsorption to goethite. This fraction formed a coating of subμm spaced protein-rich and lipid-rich domains, i.e., of two materials which will strongly differ in their reactive sites. This will finally affect further adsorption, the particle mobility and eventually also colloidal stability.


Suicide following acute admissions for physical illnesses across England and Wales.
The study aim was to establish and quantify suicide risk following acute admissions for all major physical illnesses, for confirmatory purposes, from two independent information sources from different countries. Record linkage of inpatient and death certificate data for 11 004 389 acute admissions for physical illnesses in England and 713 496 in Wales. The main outcome measure was standardised mortality ratios (SMRs) for suicide at 1 year following discharge from hospital. There were 1781 suicides within 1 year of discharge in England (SMR = 1.7; 95% = 1.6-1.8) and 131 in Wales (SMR = 2.0; 1.7-2.3). Of 48 major physical illnesses that were associated with at least eight suicides in either country, there was high consistent suicide mortality (significant SMR >3) in both countries for constipation (SMR = 4.1 in England, 7.5 in Wales), gastritis (4.4 and 4.9) and upper gastrointestinal bleeding (3.4 and 4.5). There was high suicide mortality in one country for alcoholic liver disease, other liver disease and chronic pancreatitis; for epilepsy and Parkinson's disease; for diabetes, hypoglycaemia and hypo-osmolality & hyponatraemia; and for pneumonia, back pain and urinary tract infections. There is little or no increased suicide mortality following acute admissions for most physical illnesses. Much of the increased suicide mortality relates to gastrointestinal disorders that are often alcohol related or specific chronic conditions, which may be linked to side effects from certain therapeutic medications. Acute hospital admissions for physical illnesses may therefore provide an opportunity for targeted suicide prevention among people with certain conditions, particularly alcohol related disorders.


Does a kidney-sharing alliance have to sacrifice cold ischemic time for better HLA matching?
The Scotland-Northern Ireland Kidney Allocation Alliance was created in August 1998. The purpose was to optimize the transplant service through increased regional exchange, higher quality matched kidneys, and better organ distribution. An analysis was performed on prospectively collected data regarding retrieval and transplant activity. The degree of HLA matching, the cold ischemic time (CIT), the balance of exchange, and graft survival were analyzed for a 2-year period after the introduction of the new alliance and compared with the last year before alliance. There was a 17.7% increase in the number of transplants performed. In the 2-year period, 78% of kidneys were exported from the retrieving center compared with 55% in the prealliance year, (P<0.05, chi2). The proportion of 000 mismatched transplants and other favorable matches increased from 9.5 to 21% and from 52.5 to 61%, respectively. There was no significant difference between the CIT for the three study periods, nor between the CIT for locally used kidneys versus those exchanged within the Alliance (P>0.05, Student's t test). The largest center was a net importer of kidneys, whereas small and medium-sized centers balanced their exchange within the 2-year period. The 1-year transplant survival rate improved from 81.5% in the prealliance year to 88.4% at the end of the second year. The introduction of a regional kidney allocation alliance has improved the degree of HLA matching and increased the exchange of organs, without a significant increase in the CIT and any detrimental effect on graft survival.


Non-invasive in vivo imaging by confocal laser scanning microscopy of gingival tissues following natural plaque deposition.
Imaging with Confocal Laser Scanning Microscopy (CLSM) generates high-resolution images and may be well suited for basic research in Periodontology and Implant Dentistry. The present study was aimed to explore the in vivo application of CLSM in experimentally induced gingivitis. Ten subjects were recruited and were advised to stop any oral hygiene of the upper front teeth for 7 days. The gingival tissues were observed using a Heidelberg Retina Tomograph combined with a Rostock Cornea Module at baseline and day 7. The system used a laser of 670 nm and the contrast was given by backscattering from different tissues. Each examination created 800-1200 images that were descriptively analysed. After 7 days of abandoned oral hygiene, plaque scores and bleeding frequencies increased. By using CLSM images tooth hard substances, cells and plaque deposits were distinguishable. Increased epithelial cell irregularities, the apical migration of the sulcular epithelium, cellular infiltrates within the sulcus and plaque deposits were observed at day 7. The present study showed for the first time that CLSM is suitable for in vivo imaging of the gingival sulcus and adjacent tissues.


Optimizing treatment approaches in seborrheic dermatitis.
Seborrheic dermatitis is a chronic, recurring, cutaneous condition that causes erythema and flaking, sometimes appearing as macules or plaques with dry white or moist oily scales. In adults, it commonly occurs in areas with high concentrations of sebaceous glands. The face and scalp are the most frequently affected areas, and involvement of multiple sites is common. Dandruff is regarded as a mild noninflammatory form of seborrheic dermatitis. There is a high incidence of seborrheic dermatitis among persons with human immunodeficiency virus infection or Parkinson's disease. The cause of seborrheic dermatitis is not well understood, but appears to be related to the composition of the sebaceous gland secretions, the proliferation of Malessezia yeasts, and the host immune response. Treatment options for nonscalp and scalp seborrheic dermatitis include topical agents and shampoos containing antifungal agents, anti-inflammatory agents, keratolytic agents, and calcineurin inhibitors. Because multiple body sites are usually involved, the physician should examine all commonly affected areas. Patients should be made aware that seborrheic dermatitis is a chronic condition that will probably recur even after successful treatment.


Transient ordering in a quasi-two-dimensional binary liquid near freezing.
We report the results of a theoretical study of locally ordered fluctuations in a quasi-two-dimensional (quasi-2D) binary hard sphere mixture as monitored by the aperture cross-correlation function. Systems with thickness less than two large hard sphere diameters were studied, over a range of large hard sphere density and relative concentration of large and small hard spheres in the liquid state, for two ratios of sphere diameters, 0.2 and 0.3. In several major respects the occurrence and character of the structured fluctuations in a quasi-2D binary hard sphere mixture have similarities with those in a quasi-2D one-component hard sphere fluid, as reported by Sheu and Rice [J. Chem. Phys. 128, 244517 (2008)]. Specifically, our studies establish that structured fluctuations with both hexagonal and square symmetries can be found in the liquid phase well below the freezing density and that the occurrence of particular structured fluctuations is correlated with the symmetry of the solid to which the liquid freezes. However, there is also a major difference, specifically, the presence of the smaller spheres in the binary mixture can suppress the occurrence of all structured fluctuations. We attribute the affect of a small volume fraction of small spheres in a dense binary mixture of small and large spheres on the occurrence of structured fluctuations to the unfavorable entropy change associated with demixing of the small and large spheres.


Relationship between tidal volume and deadspace during high frequency ventilation.
Physiological (VDphys) and anatomical (VDanat) deadspaces were measured in seven anaesthetized, paralysed and intubated adult patients ventilated at normal and high frequencies. To maintain a constant PaCO2 while increasing the ventilation frequency from 15 to 120 b.p.m., the mean VT was decreased from 454 +/- 62 ml (mean +/- SD) to 117 +/- 9 ml. The mean VDanat and VDphys decreased from 130 +/- 11 ml to 74 +/- 12 ml and 165 +/- 24 ml to 92 +/- 3 ml, respectively, by 80 b.p.m., above which frequency there was no further significant reduction in either. The mean VD/VT ratio increased from 0.36 +/- 0.04 to 0.76 +/- 0.05. This study showed that the deadspace volume measured conventionally was not a constant factor, was mainly a function of VT and was a determinant of tidal and minute volume requirement even during high frequency ventilation. The variable VDphys showed a wide variation between subjects, and appeared to have a mean minimal value of approximately 1.1 ml kg-1 at 80 b.p.m. in adult human subjects with a tracheal tube in situ--a value about half the VDphys measured at conventional normal tidal volumes and ventilation frequencies.


Pharmacotherapy in tracheal stenosis.
From our experience in the treatment of immunological diseases with a tendency to the formation of granulomas, we conceived the idea of treating pharmacotherapeutically the scar-tissue formation in recurrent tracheal stenosis. We have combined two medicines with different modes of action, namely, klorokin and penicillamine. Two patients with recurrent tracheal stenosis have been treated with remarkable results. After several unsuccessful operations it has now been possible to decannulate both of them and enable them to regain a normal way of living.


Depletion by capsaicin of substance P-immunoreactivity and acetylcholinesterase activity from nerve fibres in the guinea-pig heart.
The sensitivity to capsaicin of substance P-immunoreactive nerve fibres in the hearts of guinea-pigs was examined. Capsaicin decreased considerably the substance P-immunoreactive material in nerve fibres of the parietal pericardium, atria, bicuspid and tricuspid valves. Pericardial and valvar nerve fibres localized by acetylcholinesterase (AChE) histochemistry had a distribution and density pattern similar to that of the substance P immunoreactive fibres. Capsaicin treatment also decreased the number of visible AChE-positive nerve fibres. It is known that capsaicin has a selective action on those substance P-immunoreactive fibres that are of sensory origin; thus, these results imply that substance P-immunoreactive fibres in the heart are sensory. Moreover, the results suggest that some of the nerve fibres localized in the heart by AChE histochemistry are substance P-containing sensory fibres.


Crystallization-Enabled Stereoconvergent Michael Additions of β-Keto Esters to Nitroolefins.
Asymmetric Michael additions are powerful tools to meet the growing need for stereochemically complex products. While 1,3-dicarbonyls are common nucleophiles, the successful use of configurationally unstable β-keto esters in diastereoselective variants remains understudied. In this Letter, crystalline β-keto esters were leveraged in a two-phase, one-pot merger of an asymmetric Michael addition with a crystallization-induced diastereomer transformation. Tuning the crystallinity of β-keto ester adducts enabled stereoconvergence of the products, which were isolated by filtration.


Hemifacial Spasm: Comparison of Results between Patients Older and Younger than 70 Years Operated on with Microvascular Decompression.
The aim of the present study was to evaluate the efficacy and safety of microvascular decompression (MVD) for primary hemifacial spasm (HFS) in patients aged ≥70 years and to compare the outcome with a control cohort of younger patients(<70 years). In this retrospective study, subjects were divided into two groups: an elderly group (patients who were ≥70 years) and a younger group. We compared demographic and clinical data, surgical outcome, MVD-related complications, and duration of operation and hospitalization after MVD between the two groups. At a mean follow-up of 32 ± 4.2 months, 188 elderly patients (90.4%) reported an effective outcome without need for any medication versus 379 (91.1%) of the younger cohort. There was no mortality in both cohorts. The prevalence of delayed facial palsy was 4.8% in the elderly group and 4.1% in the younger group. One (0.5%) patient in the elderly group and 3 (0.7%) patients in the younger group suffered cerebrospinal fluid (CSF) leakage. There was no significant difference between the two groups in terms of MVD-related complications, such as delayed facial palsy, hearing impairment, CSF leakage, and hematoma. MVD is an effective treatment option in elderly patients with HFS as well as in younger patients. Age itself seems to be no relevant contraindication or, alternatively, risk factor regarding MVD.


Does the degree of polarization of vector beams remain unchanged on atmospheric propagation?
All roads lead to Rome. In this article we propose a novel theoretical framework to demonstrate vector beams whose degree of polarization does not change on atmospheric propagation. Inspired by the Fresnel equations, we derive the reflected and refracted field of vector beams propagating through a phase screen by employing the continuity of electromagnetic field. We generalize the conventional split-step beam propagation method by considering the vectorial properties in the vacuum diffraction and the refractive properties of a single phase screen. Based on this vectorial propagation model, we extensively calculate the change of degree of polarization (DOP) of vector beams under different beam parameters and turbulence parameters both in free-space and satellite-mediated links. Our result is that whatever in the free-space or satellite-mediated regime, the change of DOP mainly fluctuates around the order of 10-13 to 10-6, which is almost negligible.


Platelet and megakaryocyte dense granules contain glycoproteins Ib and IIb-IIIa.
Platelets contain two main types of secretory organelles, the dense granules and the alpha-granules. P-selectin, a specific receptor for leukocytes that is present in the alpha-granule membrane, has also been demonstrated to be associated with the dense granule limiting membrane, showing that a relationship exists between these two types of secretory granules. We have previously shown that the plasma membrane receptors glycoproteins (Gp) IIb-IIIa and Ib are also present in the alpha-granule membrane. To document further the composition of the dense granule membrane, we have used immunoelectron microscopy in the present work to determine if the dense granule membrane also contains these glycoproteins. First, the cytochemical method of Richards and Da Prada (J Histochem Cytochem 25:1322, 1977), which specifically enhances dense body electron density, was combined with immunogold-labeled anti-Gp IIb-IIIa or anti-Gp Ib antibody. A consistent and reproducible labeling for Gp IIb-IIIa, but less for Gp Ib, was found in the membrane of platelet dense granules. Subsequently, double immunogold labeling was performed on frozen thin sections of resting platelets using antibodies directed against the dense body components granulophysin or P-selectin, followed by anti-Gp IIb-IIIa or anti-Gp Ib. Consistent labeling for Gp IIb-IIIa and weaker labeling for Gp Ib were detected in dense bodies. The possibility that the granulophysin-positive structures could be lysosomes was excluded by the presence of P-selectin. Immunogold labeling of isolated dense granule fractions confirmed these results. Identical findings were made on human cultured megakaryocytes using double immunolabeling. In conclusion, this study demonstrates the presence of Gp IIb-IIIa and Gp Ib on the dense granule membrane. This observation provides additional evidence of similarities between the alpha-granule and dense granule membranes and raises the possibility of a dual mechanism responsible for the formation of dense granules similar to that of alpha-granules, ie, endogenous synthesis as well as endocytosis from the plasma membrane.


Highly selective reactions of C60Cl6 with thiols for the synthesis of functionalized [60]fullerene derivatives.
Chlorofullerene C(60)Cl(6) undergoes highly selective reactions with thiols forming compounds C(60)[SR](5)H with high yields. These reactions open up straightforward synthetic routes to many functionalized fullerene derivatives, e.g. water-soluble compounds showing interesting biological activities.


Structural polymorphism of V kappa 21 E and V kappa 21 D gene products in laboratory mice.
The aim of the present work was to study structural polymorphism of V kappa genes products. To this end we isolated immunoglobulins expressing the V kappa 21 D and V kappa 21 E gene products from the normal sera of several inbred strains of mice using a monoclonal antibody that selectively recognizes V kappa 21 D and V kappa 21 E subgroups. Analysis of the isoelectric focusing pattern of the light chain of these immunoglobulins revealed the existence of 3 clearly different phenotypes. The first one is shared by most inbred strains of mice, the second one is expressed by C58/J, AKR and PL/J and the third one defines V kappa 21 D-E light chains of SJL and SJA mice. Genetic analysis revealed that the locus controlling V kappa 21 D-E chain structure is closely linked to the Ly2-3 and to the Ig Kappa-Ef1 loci. Finally, using recombinant mouse strains, we could also order V kappa 21 D-E genes with respect to the known loci affecting V kappa polymorphism. Taken together our data argue against the possibility that the polymorphism observed results from strain-specific expression of V kappa genes common to all mice, but rather suggest that different allelic form of the same V kappa gene subgroup exist in different strains.


Laparoscopic Surgical Algorithm to Triage the Timing of Tumor Reductive Surgery in Advanced Ovarian Cancer.
To estimate the effects of a laparoscopic scoring algorithm to triage patients with advanced ovarian cancer to immediate or delayed debulking to improve complete gross surgical resection rates and determine the resulting clinical outcomes. We prospectively performed laparoscopic assessment on patients with suspected advanced-stage ovarian cancer from April 2013 to December 2016 to determine primary resectability at tumor reductive surgery. Patients with medically inoperable or distant metastatic disease received neoadjuvant chemotherapy. Two-surgeon scoring was performed in a blinded fashion using a validated scoring method. Patients with predictive index value scores less than 8 were offered primary surgery and those with scores 8 or greater received neoadjuvant chemotherapy. Univariate and multivariate analysis was performed for effects on progression-free survival. Six hundred twenty-one patients presenting with presumed advanced ovarian cancer were evaluated during the study period and 488 patients met inclusion criteria. Two hundred fifteen patients underwent laparoscopic scoring, of whom 125 had predictive index value scores less than 8 and 84 had predictive index value scores 8 or greater. Blinded two-surgeon predictive index value scoring resulted in bivariate discordance in only 2% of patients. Tumor cytoreduction led to no gross residual disease (R0 resection) in 88% of patients in the primary surgery group and 74% in the neoadjuvant chemotherapy group. Patients triaged to primary surgery had an improved progression-free survival of 21.4 months versus 12.9 months in those patients undergoing neoadjuvant chemotherapy (P<.001). Median progression-free survival by treatment group and residual disease status was as follows: primary surgery-R0 23.5 months; primary surgery-R1 (any gross residual disease) 17.6 months; neoadjuvant chemotherapy-R0 15.5 months; and neoadjuvant chemotherapy-R1 12.9 months (P<.001). On multivariate analysis for progression-free survival, baseline CA 125 (P=.001) and gross residual disease at tumor reductive surgery (P=.01) were significantly associated with progression-free survival. Laparoscopic triage assessment allowed for a personalized approach to the management of patients with advanced ovarian cancer and resulted in high complete surgical resection rates at tumor reductive surgery.


A histoquantitative study of the striate cortex and lateral geniculate body in normal, blind and demented subjects.
The amount of myelin in the outer band of Baillarger in the human visual cortex stained by Luxol Fast Blue MBS, has been measured in normal individuals of wide age range, in a group of blind and severely visually impaired but otherwise normal individuals and in a series of demented patients of the Alzheimer and multi-infarct type who were apparently visually normal. The amount of myelin is found to be significantly reduced in the blind and demented groups. Examination of the lateral geniculate body in the blind cases demonstrated slight reduction in neuron numbers and marked reduction in mean neuron diameter. Neuronal cytoplasmic ribonucleic acid, nucleolar volume and numbers of tetraploid glial nuclei in the blind or visually impaired cases were significantly reduced when compared with controls, indicating reduced function in these neurons. Similar results were obtained on examining this nucleus in Alzheimer and multi-infarct cases, suggesting that the visual pathways may be involved in these conditions. It is concluded that loss of myelin from the outer band of Baillarger occurs in association with reduced function of neurons in the lateral geniculate body.


Flap folds after femtosecond LASIK.
To report a case of bilateral flap folds after a laser-assisted in situ keratomileusis (LASIK) procedure in which the flap was created by the femtosecond laser. Retrospective chart review. A 43-year-old white woman underwent bilateral simultaneous LASIK. The corneal flap was created with the femtosecond laser. Postoperatively, the patient noted significantly decreased visual acuity, glare, and haloes. She was diagnosed with corneal flap striae, which were treated unsuccessfully with a lifting and stretching procedure, but responded to subsequent bilateral flap suturing. Despite the increased accuracy in flap creation with the femtosecond laser, large flap folds may develop.