Medical and radiological aspects of emergency preparedness and response at SevRAO facilities.
Regulatory cooperation between the Norwegian Radiation Protection Authority and the Federal Medical Biological Agency (FMBA) of the Russian Federation has the overall goal of promoting improvements in radiation protection in Northwest Russia. One of the projects in this programme has the objectives to review and improve the existing medical emergency preparedness capabilities at the sites for temporary storage of spent nuclear fuel and radioactive waste. These are operated by SevRAO at Andreeva Bay and in Gremikha village on the Kola Peninsula. The work is also intended to provide a better basis for regulation of emergency response and medical emergency preparedness at similar facilities elsewhere in Russia. The purpose of this paper is to present the main results of that project, implemented by the Burnasyan Federal Medical Biophysical Centre. The first task was an analysis of the regulatory requirements and the current state of preparedness for medical emergency response at the SevRAO facilities. Although Russian regulatory documents are mostly consistent with international recommendations, some distinctions lead to numerical differences in operational intervention criteria under otherwise similar conditions. Radiological threats relating to possible accidents, and related gaps in the regulation of SevRAO facilities, were also identified. As part of the project, a special exercise on emergency medical response on-site at Andreeva Bay was prepared and carried out, and recommendations were proposed after the exercise. Following fruitful dialogue among regulators, designers and operators, special regulatory guidance has been issued by FMBA to account for the specific and unusual features of the SevRAO facilities. Detailed sections relate to the prevention of accidents, and emergency preparedness and response, supplementing the basic Russian regulatory requirements. Overall it is concluded that (a) the provision of medical and sanitary components of emergency response at SevRAO facilities is a priority task within the general system of emergency preparedness; (b) there is an effective and improving interaction between SevRAO and the local medical institutions of FMBA and other territorial medical units; (c) the infrastructure of emergency response at SevRAO facilities has been created and operates within the framework of Russian legal and normative requirements. Further proposals have been made aimed at increasing the effectiveness of the available system of emergency preparedness and response, and to promote interagency cooperation.


Application of chitin and chitosan derivatives in the pharmaceutical field.
Chitin and chitosan derivatives are used as excipients and drug carriers in the pharmaceutical field. Their derivatization contributed to expansion of application and decrease toxicity. Chitosan is used as an excipient in oral dosage form. Chitosan tablet can exhibit a sustained drug release compared to commercial products. Films prepared using chitin or chitosan have been developed as wound dressings, oral mucoadhesive and water-resisting adhesive by virtue of their release characteristics and adhesion. Intratumoral administration of gadopentetic acid-chitosan complex nanoparticles (approximately 430 nm in diameter) has been more effective for gadolinium neutron-capture therapy compared with a group treated with the solution. Compared to intragastrical feeding with diphtheria toxoid (DT) in PBS, a strong enhancement of the systemic (IgG) and local (IgA) immune responses against DT has been observed in mice fed with DT loaded chitosan microparticles (approximately 4.7 microm in size). When DNA-loaded chitosan microspheres (1.15 - 1.28 microm) were intramuscularly administrated into mice, high beta-galactosidase and luciferase productions were obtained even after a long post-transfection period (12 weeks). N-Succinyl-chitosan (Suc-Chi) has been studied for cancer chemotherapy as a drug carrier and the conjugates of mitomycin C with Suc-Chi exhibited good antitumor activities against various tumors. Furthermore, trimethyl-chitosan and monocarboxymethyl-chitosan has been shown to be effective as intestinal absorption enhancers due to their physiological properties. Chitosan-thioglycolic acid conjugates has been found to be a promising candidate as scaffold material in tissue engineering due to their physicochemical properties. This review summarizes the application of chitin and chitosan derivatives for hospital preparations and drug carriers.


Deep posterior compartment strength and foot kinematics in subjects with stage II posterior tibial tendon dysfunction.
Tibialis posterior muscle weakness has been documented in subjects with Stage II posterior tibial tendon dysfunction (PTTD) but the effect of weakness on foot structure remains unclear. The association between strength and flatfoot kinematics may guide treatment such as the use of strengthening programs targeting the tibialis posterior muscle. Thirty Stage II PTTD subjects (age; 58.1 +/- 10.5 years, BMI 30.6 +/- 5.4) and 15 matched controls (age; 56.5 +/- 7.7 years, BMI 30.6 +/- 3.6) volunteered for this study. Deep Posterior Compartment strength was measured from both legs of each subject and the strength ratio was used to compare each subject's involved side to their uninvolved side. A 20% deficit was defined, a priori, to define two groups of subjects with PTTD. The strength ratio for each group averaged; 1.06 +/- 0.1 (range 0.87 to 1.36) for controls, 1.06 +/- 0.1 (range, 0.89 to 1.25), for the PTTD strong group, and 0.64 +/- 0.2 (range 0.42 to 0.76) for the PTTD weak group. Across four phases of stance, kinematic measures of flatfoot were compared between the three groups using a two-way mixed effect ANOVA model repeated for each kinematic variable. Subjects with PTTD regardless of group demonstrated significantly greater hindfoot eversion compared to controls. Subjects with PTTD who were weak demonstrated greater hindfoot eversion compared to subjects with PTTD who were strong. For forefoot abduction and MLA angles the differences between groups depended on the phase of stance with significant differences between each group observed at the pre-swing phase of stance. Strength was associated with the degree of flatfoot deformity observed during walking, however, flatfoot deformity may also occur without strength deficits. Strengthening programs may only partially correct flatfoot kinematics while other clinical interventions such as bracing or surgery may also be indicated.


[Development of renal function in the transplanted patient with renal hypertension treated with enalapril].
We report our experience with a converting-enzyme inhibitor, enalapril, as antihypertensive agent in eighteen patients with hypertension after renal transplantation. Renal function was prospectively followed up. Six patients demonstrated an acute renal failure episode (defined by a 25% increase of serum creatinine during enalapril therapy). Renal failure was always reversible with interruption or dosage reduction of the drug. We recommend to start therapy with low dose and to closely monitor renal function.


Right ventricular remodeling in idiopathic pulmonary arterial hypertension: adaptive versus maladaptive morphology.
Although increased pulmonary pressure is caused by changes in the pulmonary vasculature, prognosis in idiopathic pulmonary arterial hypertension (IPAH) is strongly associated with right ventricular (RV) function. The aim of this study was to describe the best RV adaptive remodeling pattern to increased afterload in IPAH. In 60 consecutive patients with IPAH, RV morphologic and functional features were evaluated by echocardiography and cardiac magnetic resonance imaging. To address the question of the best RV adaptation pattern, we divided the study population into two groups by the median value of RV mass/volume ratio (0.46) because this parameter allows the distinction between RV eccentric (≤0.46) and concentric hypertrophy (>0.46). The two groups were compared for RV remodeling and systolic function parameters, World Health Organization class, pulmonary hemodynamics, and 6-minute walk test. Despite similar pulmonary vascular resistance, mean pulmonary pressure, and compliance, patients with eccentric hypertrophy had advanced World Health Organization class and worse 6-minute walk test, hemodynamics, RV remodeling, and systolic function parameters compared with patients with concentric hypertrophy. The group with concentric hypertrophy had higher RV to pulmonary arterial coupling compared with the group with eccentric hypertrophy (1.24 ± 0.26 vs 0.83 ± 0.33, p = 0.0001), indicating higher RV efficiency. A significant correlation was found between pulmonary vascular resistance and RV to pulmonary arterial coupling (r = -0.55, r(2) = 0.31, p = 0.0001), with patients with RV mass/volume ratio > 0.46 at the higher part of the scatterplot, confirming more adequate RV function. Concentric hypertrophy might represent a more favorable RV adaptive remodeling pattern to increased afterload in IPAH because it is associated with more suitable systolic function and mechanical efficiency.


RetroBioCat Database: A Platform for Collaborative Curation and Automated Meta-Analysis of Biocatalysis Data.
Despite the increasing use of biocatalysis for organic synthesis, there are currently no databases that adequately capture synthetic biotransformations. The lack of a biocatalysis database prevents accelerating biocatalyst characterization efforts from being leveraged to quickly identify candidate enzymes for reactions or cascades, slowing their development. The RetroBioCat Database (available at retrobiocat.com) addresses this gap by capturing information on synthetic biotransformations and providing an analysis platform that allows biocatalysis data to be searched and explored through a range of highly interactive data visualization tools. This database makes it simple to explore available enzymes, their substrate scopes, and how characterized enzymes are related to each other and the wider sequence space. Data entry is facilitated through an openly accessible curation platform, featuring automated tools to accelerate the process. The RetroBioCat Database democratizes biocatalysis knowledge and has the potential to accelerate biocatalytic reaction development, making it a valuable resource for the community.


Antitumor effects are produced by forced expression of membrane-bound but not soluble Fas ligand in murine lung carcinoma cells.
Interaction of Fas and Fas ligand (FasL) in immunocompetent cells plays a crucial role(s) in their effector functions and in the regulation of host immune responses. Expression of FasL in tumors possibly counteracts Fas-positive effector T cells that infiltrate into tumors and consequently the Fas/FasL interaction can contribute to the escape of tumor cells from systemic immune systems. However, forced expression of FasL in tumors unexpectedly induced migration of neutrophils into the tumors and the FasL-expressing tumors were rejected due to the inflammatory reaction. Since FasL is released from the cell surface, we examined whether soluble or membrane-bound FdsL molecules produced such antitumor effects. Fas-positive B cells were effectively killed by membrane-bound but not soluble FasL in which the leader sequence of interleukin-4 was ligated with the extracytoplasmic portion of FasL. Mice inoculated with A11 murine lung cancer cells expressing membrane-bound FasL did not develop tumors and had few spontaneous lung metastatic foci. In contrast, mice injected with A11 cells secreting soluble FasL developed tumors; the growth of the tumors and the number of lung metastatic foci from subcutaneous tumors were not different from those of parent tumors. The chemotactic activity of FasL, tested by intraperitoneal injection of parent and the FasL-expressing A11 cells, showed that the level of neutrophil migration by A11 cells secreting soluble FasL was greater than that by parent cells but was not as significant as that by A11 cells expressing membrane-bound FasL. The antitumor activity induced by expressed FasL seems to be correlated with the apoptosis-inducing activity through the Fas/FasL interaction but not directly with the chemotactic activity for neutrophils.


Hydronephrosis due to ureteral endometriosis treated by transperitoneal laparoscopic ureterolysis.
Ureteral obstruction secondary to endometriosis is relatively uncommon. We present a 43-year-old multiparous woman who suffered from periodic left loin pain in the terminal period of her menstruation. Excretory urogram demonstrated left hydronephrosis and hydroureter and obstruction of the lower left ureter just inferior to the left sacroiliac joint without urolithiasis. An enhanced computed tomography scan showed soft tissue density mass around the left ureter at the level of the stenosis. She underwent transperitoneal laparoscopic ureterolysis and adhesiotomy of the left ureter under the diagnosis of ureteral endometriosis. Because blueberry spots were clearly observed on the pelvic brim, the fibrous tissue surrounded the ureter was removed with peritoneal bleeding spots. Histological examination of the surrounding tissue confirmed the ectopic endometriosis. Even though retroperitoneoscopy is frequently used for ureteral lesion, transperitoneal laparoscopy has an advantage for resection of ectopic endometriosis surrounding the ureter.


[Key role of plasma membrane receptor domains in carcinogenesis].
Within the limits of the previously proposed conception concerning the dynamical domain organization of receptor molecules in biological membranes the possible role of receptor domains (RD) of plasma membranes in the mechanism of carcinogenesis is discussed. On the basis of extensive experimental material accumulating to present by study of different aspects of carcinogenesis, and based on the key role of receptor domains of plasma membranes in this process the attempt has been made to build the general theory of carcinogenesis. Particular attention is given to the analysis of possible genetically depended changes in the system of cell division and cell differentiation control, which may be responsible for the appearance of non-malignant and malignant tumours in the organism, and also to the consideration of the conditions of the appearance of clones of transformed cells with uncontrolled growth in the organism. Differences in the molecular mechanisms of the appearance of non-malignant and malignant tumours are explained.


[Development and validation of the University of Tokyo Occupational Mental Health leadership checklist among occupational health specialists].
Recently, occupational health specialists (OHS) are expected to exert leadership to develop high-quality occupational health activities. This study aimed to develop and investigate the reliability and validity of a scale to measure leadership preparation among OHS (The University of Tokyo Occupational Mental Health [TOMH] Leadership Checklist; TLC). Based on literature reviews and interviews among OHS, we created potential items consisting of 54 items with six factors (10 items for self-awareness, 10 items for situational awareness, 9 items for vision, 12 items for mindset, 3 items for performance of one's duties, and 10 items for relationship-building). An online survey was conducted with 300 OHS in Japan to verify the scale's reliability and validity. Consequent to the exploratory factor analysis, using the principal factor method and promax rotation, 51 items across the following five factors were identified; "self-awareness", "situational awareness", "vision", "mindset", and "performance of one's duties". The confirmatory factor analysis showed good fit indices; CFI = 0.877, SRMR = 0.050, and RMSEA = 0.072. Cronbach's α ranged from 0.93-0.96. Additionally, the scores of the TLC were significantly positively correlated with work engagement, job satisfaction, and self-efficacy; contrastingly, they were significantly negatively correlated with psychological distress (p < .05). Furthermore, the participants who had experience leadership without authority indicated significantly higher scores of the TLC and its subscales than those who did not (p < .001). The newly developed TLC appeared to have acceptable levels of reliability and validity. It would be beneficial for OHS to show good leadership.


[Assay of erythropoietin in serum with short term enzyme linked immunosorbent assay method--the clinical significance, Part 1: Relation to anemia in renal failure and hematological disorders].
With a newly developed enzyme linked immunosorbent assay kit TOYOBO Co. in which 2 anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from normal adults, 168 patients with renal failure and 333 patients with hematological disorders. In the patients with renal failure, serum EPO level was normal (52.9%) or reduced (42.9%), and there was no correlation to their hematocrits. However, there was an increment in EPO concentration correlated to their severity of anemia in the most patients with hematological disorders, such as iron deficiency anemia (correlation coefficient r = -0.74), aplastic anemia (r = -0.89), leukemia (r = -0.81), and MDS (r = -0.65). On the other hand, EPO concentration in sera from all the untreated patients with polycythemia vera were significantly low level. But the concentrations of EPO from the patients successfully treated, with normal hematocrit were recovered to normal level. In the patients with secondary polycythemia, there were much varieties in EPO level. Assay of EPO in blood is important not only for diagnosis of polycythemia but also for the analysis of anemia and clinical use of EPO in vivo. The method described here is accurate and technically not complicated, and could be widely induced in most laboratories.


The nature and management of labor pain: part I. Nonpharmacologic pain relief.
Pain in labor is a nearly universal experience for childbearing women. A recent evidence-based symposium on the nature and management of labor pain brought together family physicians, obstetricians, midwives, obstetric anesthesiologists, and childbirth educators to discuss a series of commissioned systematic reviews. Although management of labor pain plays a relatively minor role in a woman's satisfaction with childbirth compared with the quality of the relationship with her maternity caregiver and the degree of participation she has in decision making, it is an important topic for women and their caregivers. Nonpharmacologic methods of pain relief such as labor support, intradermal water blocks, and warm water baths are effective techniques for management of labor pain. An increased availability of these methods can provide effective alternatives for women in labor.


Spirituality in nursing: what are the issues?
This article describes the author's attempt to highlight the problem areas associated with providing spiritual care for patients. The focus of this work is to discuss the following areas of interest: What is spirituality? The issue of spirituality in nursing. The impact of spirituality for the patient. The relevance or irrelevance of religion. The concept of serenity as a goal for nursing practice. The author provides examples, specifically regarding older people, explaining why spiritual care of patients is decidedly problematic in the British healthcare system and provides suggestions as to how to reintegrate this essential part of caregiving back into daily practice.


New mechanistic insights of integrin β1 in breast cancer bone colonization.
Bone metastasis is a frequent and life-threatening complication of breast cancer. The molecular mechanisms supporting the establishment of breast cancer cells in the skeleton are still not fully understood, which may be attributed to the lack of suitable models that interrogate interactions between human breast cancer cells and the bone microenvironment. Although it is well-known that integrins mediate adhesion of malignant cells to bone extracellular matrix, their role during bone colonization remains unclear. Here, the role of β1 integrins in bone colonization was investigated using tissue-engineered humanized in vitro and in vivo bone models. In vitro, bone-metastatic breast cancer cells with suppressed integrin β1 expression showed reduced attachment, spreading, and migration within human bone matrix compared to control cells. Cell proliferation in vitro was not affected by β1 integrin knockdown, yet tumor growth in vivo within humanized bone microenvironments was significantly inhibited upon β1 integrin suppression, as revealed by quantitative in/ex vivo fluorescence imaging and histological analysis. Tumor cells invaded bone marrow spaces in the humanized bone and formed osteolytic lesions; osteoclastic bone resorption was, however, not reduced by β1 integrin knockdown. Taken together, we demonstrate that β1 integrins have a pivotal role in bone colonization using unique tissue-engineered humanized bone models.


A Novel Biodegradable and Thermosensitive Poly(Ester-Amide) Hydrogel for Cartilage Tissue Engineering.
Thermosensitive hydrogels are attractive alternative scaffolding materials for minimally invasive surgery through a simple injection and in situ gelling. In this study, a novel poly(ester-amide) polymer, methoxy poly(ethylene glycol)-poly(pyrrolidone-co-lactide) (mPDLA, P3L7) diblock copolymer, was synthesized and characterized for cartilage tissue engineering. A series of amphiphilic diblock copolymers was synthesized by ring-opening polymerization of mPEG 550, D,L-lactide, and 2-pyrrolidone. By dynamic light scattering analysis and tube-flipped-upside-down method, viscoelastic properties of the mPDLA diblock copolymer solution exhibited sol-gel transition behavior as a function of temperature. An in vitro degradation assay showed that degradation acidity was effectively reduced by introducing the 2-pyrrolidone monomer into the polyester hydrogel. Besides, mPDLA exhibited great biocompatibility in vitro for cell encapsulation due to a high swelling ratio. Moreover, cell viability and biochemical analysis proved that the mPDLA hydrogel presented a great chondrogenic response. Taken together, these results demonstrate that mPDLA hydrogels are promising injectable scaffolds potentially applicable to cartilage tissue engineering.


[Cohort study on the association between hyperopia reserve and myopia incidence in primary school students: the Anyang Childhood Eye Study].
Objective: To analyze the longitudinal association between hyperopia reserve and the cumulative incidence of myopia in grade 1 primary school students. Methods: Cohort study. This study included 2 628 grade 1 primary school students (2 628 eyes) who without myopic at baseline from the Anyang Childhood Eye Study. There were 1 515 male and 1 113 female, aged(7.16±0.40) years. Every year, cycloplegic autorefraction was performed with 1% cyclopentolate eye drops to obtain data of hyperopia reserve. Students with different ranges of hyperopia reserve at baseline were analyzed. Axial length, anterior chamber depth, corneal curvature, lens thickness, and other parameters were obtained by ocular biometrics and compared by the independent sample t test. Qualitative data were described by frequency and percentage, and comparison between groups was performed by the Chi-square test or exact probability method. Linear regression was used to analyze the association between baseline hyperopia reserve and spherical equivalent at 5 years. Results: The average hyperopia reserve was (+1.09±0.78) diopters (D) in grade 1 non-myopic children. Axial length, anterior chamber depth, corneal radius of curvature, and lens thickness were (22.66±0.72), (2.88±0.24), (7.80±0.25) and (3.62±0.19) mm, respectively. The cumulative incidence of myopia among non-myopic grade 1 primary school students was 8.5%, 21.5%, 35.6%, 47.6% and 64.1% at 1, 2, 3, 4 and 5 years, respectively. The incidence of myopia in girls was significantly higher than that in boys at 3, 4 and 5 years. The 5-year cumulative incidence of myopia was 4.6%, 26.3%, 52.3%, 78.6%, 92.6% and 94.3%, respectively, corresponding to students with baseline hyperopia reserve of >+2.00 D,+1.50 D to +2.00 D,+1.00 D to +1.50 D,+0.50 D to +1.00 D, 0.00 D to +0.50 D and -0.50 D to 0.00 D, and the difference was statistically significant (χ²=490.59, P<0.001). The regression equation between baseline hyperopia reserve and 5-year spherical equivalent was as follows: 5-year spherical equivalent=-3.135+1.692·baseline hyperopia reserve (R2=0.454, P<0.001). Conclusions: The lower the hyperopia reserve, the higher the incidence of myopia. Monitoring children's hyperopia reserve and early protection to reduce its consumption and timely detection of children at high risk of myopia are of great significance to prevent the occurrence and development of myopia.(This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on March 15, 2022).


Sarcomatoid renal cell carcinoma: a case report and literature review.
Renal cell carcinoma (RCC) is the most common malignancy of the kidney and consists of multiple subtypes. The sarcomatoid variety, while previously considered a distinct histologic subtype, is now categorized as a form of dedifferentiated carcinoma. When present, it is associated with a significant decrease in patient survival due to its rapid growth and intrusive behavior. Preoperative knowledge of this diagnosis may be beneficial to clinicians in order to modify treatment options and follow-up protocols. This report describes a case of sarcomatoid renal cell carcinoma in which the patient initially presented with flank pain. We then discuss the clinical features of sarcomatoid renal cell carcinoma and its imaging appearance on computed tomography (CT), and succinctly review the subtypes of renal cell carcinoma and their imaging characteristics.


Rheumatology. Part 2: The role of medication.
Rheumatoid arthritis is a chronic, long-term inflammatory disease. Symptom relief can be achieved with analgesia and NSAIDs. The only way to influence its progress is by administering disease-modifying anti-rheumatic drugs.


Intraoperative assessment of mitral valve and peri-operative results of surgical treatment of mitral valve disease in patients who previously underwent closed surgical and percutaneous transluminal mitral commissurotomy.
Surgical open or closed mitral commisurotomy and percutaneous transluminal mitral commissurotomy (PTMC) are the well-established therapies in patients with mitral valve stenosis. However, due to various factors the long-term effects may not be optimal in some patients, so they should undergo surgical mitral valve replacement. The intra-operative assessment of the morphology of mitral valve and the evaluation of the peri-operative results of surgical treatment in patients with mitral valve disease who previously underwent closed surgical commissurotomy followed by PTMC. Twenty one patients (20 males, mean age 49 years) who underwent surgery due to mitral valve disease after closed mitral commissurotomy and PTMC, are presented. The time from closed mitral commissurotomy to PTMC was 3-42 years, and the time from PTMC to mitral valve replacement - 9 days to almost 9 years. One patient died on the second day after the operation because of left ventricular failure. The outcome of the remaining patients was good. Advanced changes of the mitral valve and subvalvular apparatus were present in the majority of patients. The results of the implantation of mitral valve prosthesis in patients who previously underwent closed surgical mitral commissurotomy and PTMC are good. In some patients with a history of closed surgical mitral commissurotomy, PTMC delays surgical replacement of the mitral valve. Advanced changes in the mitral valve leaflets and subvalvular apparatus are the causes of PTMC failure.


Total Synthesis of (±)-Waihoensene.
The first total synthesis of waihoensene, a tetracyclic diterpene containing an angular triquinane and a six-membered ring, with four contiguous quaternary carbon atoms, was achieved through the tandem cycloaddition reaction of an allenyl diazo substrate containing a six-membered ring via trimethylenemethane (TMM) diyl intermediate.


Electrochemical Preparation of Poly(3,4-Ethylenedioxythiophene) Layers on Gold Microelectrodes for Uric Acid-Sensing Applications.
Two different methods for the synthesis of poly(3,4-ethylenedioxythiophene) (PEDOT) on gold electrodes are described, using electropolymerization of 3,4-ethylenedioxythiophene (EDOT) monomer in an aqueous and an organic solution. Cyclic voltammetry (CV) was used in the synthesis of PEDOT thin layers. Lithium perchlorate (LiClO4) was used as a dopant in both aqueous (aqueous/acetonitrile (ACN)) and organic (propylene carbonate (PC)) solvent systems. After the PEDOT layer was created in the organic system, the electrode surface was acclimatized by successive cycling in an aqueous solution for use as a sensor for aqueous samples. The use of an aqueous-based electropolymerization method has the potential benefit of removing the acclimatization step to have a shorter sensor preparation time. Although the aqueous method is more economical and environmentally friendly than the organic solvent method, superior PEDOT formation is obtained in the organic solution. The resulting PEDOT electrode surfaces were characterized by scanning electron microscopy (SEM), which showed the constant growth of PEDOT during electropolymerization from the organic PC solution, with rapid fractal-type growth on gold (Au) microelectrodes.


Duloxetine and Amitriptyline Reduce Neuropathic Pain by Inhibiting Primary Sensory Input to Spinal Dorsal Horn Neurons via α1- and α2-Adrenergic Receptors.
Antidepressants, such as duloxetine and amitriptyline, are effective for treating patients with chronic neuropathic pain. Inhibiting norepinephrine and serotonin transporters at presynaptic terminals raises extracellular concentrations of norepinephrine. The α1- and α2-adrenergic receptor agonists inhibit glutamatergic input from primary afferent nerves to the spinal dorsal horn. However, the contribution of spinal α1- and α2-adrenergic receptors to the analgesic effect of antidepressants and associated synaptic plasticity remains uncertain. In this study, we showed that systemic administration of duloxetine or amitriptyline acutely reduced tactile allodynia and mechanical and thermal hyperalgesia caused by spinal nerve ligation in rats. In contrast, duloxetine or amitriptyline had no effect on nociception in sham rats. Blocking α1-adrenergic receptors with WB-4101 or α2-adrenergic receptors with yohimbine at the spinal level diminished the analgesic effect of systemically administered duloxetine and amitriptyline. Furthermore, intrathecal injection of duloxetine or amitriptyline similarly attenuated pain hypersensitivity in nerve-injured rats; the analgesic effect was abolished by intrathecal pretreatment with both WB-4101 and yohimbine. In addition, whole-cell patch-clamp recordings in spinal cord slices showed that duloxetine or amitriptyline rapidly inhibited dorsal root-evoked excitatory postsynaptic currents in dorsal horn neurons in nerve-injured rats but had no such effect in sham rats. The inhibitory effect of duloxetine and amitriptyline was abolished by the WB-4101 and yohimbine combination. Therefore, antidepressants attenuate neuropathic pain predominantly by inhibiting primary afferent input to the spinal cord via activating both α1- and α2-adrenergic receptors. This information helps the design of new strategies to improve the treatment of neuropathic pain.


"No, It's You:" Dyadic perceived need for change predicts relationship education outcomes.
Relationship education (RE) efforts have been shown to help couples and individuals with a variety of family relationships. However, much still needs to be identified in terms of what factors are salient to outcomes. Drawing on therapeutic models of change, we have identified perceived need for change as one such potential factor. Using data from a couple RE course (n = 447 couples), we assessed how dyadic congruence and average ratings of each partner's need for change were associated with change in three RE outcomes: knowledge, communication, and commitment. In general, the more partners perceived that their partner needed to change, above and beyond what their partner thought, the less change occurred. Implications for RE programming and implementation are discussed, as well as the potential role of therapeutic models and techniques in RE.


Success of Occlusal Aperture Access for Endodontic Therapy of Canine Teeth in Dogs.
The objective of this study was to determine the success of the natural crowns of endodontically treated canine teeth in pet dogs, instrumented and obturated using rotary driven non-taper nickel titanium files, through an occlusal access preparation, without the placement of a prosthetic cast metal crown. A search of medical records at a private veterinary dental referral practice was conducted to identify pet dogs having had endodontic treatment of one or more canine teeth over an eleven-year period (2007-2018). Follow up, performed by the same veterinary dental specialist, included a complete oral health assessment under general anesthesia and included intraoral radiography thereby allowing close visual examination of the crown and restoration as well as assessing endodontic success. Time to follow up was between two and nine years after treatment with a mean of 4.5 years. Analysis revealed that 29/29 (100%) of the treated crowns maintained their stability and did not require extraction. 5/29 (17.2%) of the treated teeth had an enamel fracture requiring additional treatment to the crown after the initial treatment; 1/29 (3.4%) had additional abrasion but did not require treatment and 23/29 (79.3%) were found to have sustained no additional damage. This study supports endodontic treatment without the placement of a prosthetic crown in canine teeth in pet dogs when an occlusal access site is used as described in this paper. Further study is required on the increased risk of fracture of the remaining unaltered canine teeth.


In vivo pressure measurements of lithotripsy shock waves in pigs.
Stone comminution and tissue damage in lithotripsy are sensitive to the acoustic field within the kidney, yet knowledge of shock waves in vivo is limited. We have made measurements of lithotripsy shock waves inside pigs with small hydrophones constructed of a 25-microm PVDF membrane stretched over a 21-mm diameter ring. A thin layer of silicone rubber was used to isolate the membrane electrically from pig fluid. A hydrophone was positioned around the pig kidney following a flank incision. Hydrophones were placed on either the anterior (shock wave entrance) or the posterior (shock wave exit) surface of the left kidney. Fluoroscopic imaging was used to orient the hydrophone perpendicular to the shock wave. For each pig, the voltage settings (12-24 kV) and the position of the shock wave focus within the kidney were varied. Waveforms measured within the pig had a shape very similar to those measured in water, but the peak pressure was about 70% of that in water. The focal region in vivo was 82 mm x 20 mm, larger than that measured in vitro (57 mm x 12 mm). It appeared that a combination of nonlinear effects and inhomogeneities in the tissue broadened the focus of the lithotripter. The shock rise time was on the order of 100 ns, substantially more than the rise time measured in water, and was attributed to higher absorption in tissue.


Direct Oral Anticoagulant Failures in Atrial Fibrillation With Stroke: Retrospective Admission Analysis and Novel Classification System.
Breakthrough acute ischemic stroke (AIS) in patients with known, nonvalvular Atrial Fibrillation (AF), on Direct Oral Anticoagulants (DOAC), is an ongoing clinical conundrum. Switching anticoagulants was shown to be ineffective in preventing recurrent AIS. Systematic, patient-level chart review of so-called "DOAC failures" may offer insight into this phenomenon. We conducted an IRB-approved, 6-year, retrospective study of AIS admissions, already prescribed DOAC for known AF. We sought plausible, alternative reasons for the AIS using a novel classification schema, CLAMP: C for Compliance concerns, L for Lacunes (small-vessel disease), A for Arteriopathy (atherosclerosis, web, or vasculitis), M for Malignancy, and P for Patent Foramen Ovale (PFO). These categories were labeled as DOAC "Pseudo-failures." Conversely, absence of CLAMP variables were labeled as DOAC "Crypto-failures" conceivably from AF itself ("atriopathy") or pharmacokinetic/pharmacogenomic dysfunction (ie, altered DOAC absorption, clearance, metabolism, or genetic polymorphisms). Forward logistic regression analysis was performed on prespecified DOAC subgroups. Of 4890 AIS admissions, 606 had AF, and 87 were previously prescribed DOAC (14.4% overall DOAC failure rate, 2.4% annualized over 6 years). Pseudo-failures comprised 77%: Compliance concerns (48.9%), Lacunes (5.7%), Arteriopathy (17.0%), Malignancy (26.1%), and PFO (2.3%). Crypto-failures comprised 23%, had lower CHADSVASc scores (AOR = .65, P = .013), and occurred more with rivaroxaban (41%) than apixaban (16%) or dabigatran (5.6%). In AIS patients with known AF, DOAC Pseudo-failures, with identified alternate etiologies, are 3 times more likely than DOAC Crypto-failures. The CLAMP schema represents a novel approach to diagnostic classification and therapeutic adjustments in patients already prescribed DOAC for AF.


[Noninvasive studies of dynamic left ventricular outflow obstruction in patients with sigmoid septum].
In order to evaluate the clinical significance of the markedly protruding interventricular septum into the left ventricular (LV) cavity (sigmoid septum), we performed non-invasive studies including amyl nitrite (AN) inhalation in 21 patients (pts) with two-dimensional echocardiographic (2DE) documentations. LV outflow tract (LVOT) obstruction was determined by the presence at least three of the following findings at rest or during AN inhalation: 1) a loud apical ejection systolic murmur (ESM), 2) a midsystolic dip in the carotid pulse, 3) systolic anterior motion (SAM) of the mitral valve (MV) or chordae tendineae, and 4) systolic semiclosure of the aortic valve (AV). The 21 pts were subdivided into six pts (group I) with resting (two pts) or provocative (four) obstruction, and 15 pts (group II) without obstruction. Their ages ranged from 40 to 85 years with an average of 65. No pt had evidence of hypertrophic cardiomyopathy. Results were as follows: In five pts of group I a long ESM with a mid-systolic peak was recorded near the apex. After AN inhalation, this murmur was markedly intensified. On the contrary, all pts of group II had a short and early systolic murmur, which was not markedly intensified by AN. In contrast to group II, group I pts had a significantly smaller LV end-diastolic dimension, a smaller LVOT dimension, higher percent thickening of the LV posterior wall, higher fractional shortening and decreased aorto septal angle (the angle between the anterior aortic wall and the interventricular septum by 2DE). On 2DE, each pt of group I showed significant narrowing between the protruded septum and the hypercontractile LV posterior wall with the papillary muscle. Anteriorly shifted chordae tendineae noted as the SAM on the M-mode echocardiogram might also play an important role on the genesis of obstruction. The signs of LVOT obstruction at rest disappeared following oral administration of propranolol in two pts of group I. These observations suggested that LVOT obstruction might occur in some pts with sigmoid septum and the hypercontractile state, and that a systolic murmur observed in this condition should be differentiated from a functional murmur in the aged or a systolic murmur in hypertrophic obstructive cardiomyopathy.


Investigation of Anticancer Properties of Monoterpene-Aminopyrimidine Hybrids on A2780 Ovarian Cancer Cells.
The present study aimed to characterize the antiproliferative and antimetastatic properties of two recently synthesized monoterpene-aminopyrimidine hybrids (1 and 2) on A2780 ovary cancer cells. Both agents exerted a more pronounced cell growth inhibitory action than the reference agent cisplatin, as determined by the MTT assay. Tumor selectivity was assessed using non-cancerous fibroblast cells. Hybrids 1 and 2 induced changes in cell morphology and membrane integrity in A2780 cells, as evidenced by Hoechst 33258-propidium iodide fluorescent staining. Cell cycle analysis by flow cytometry revealed substantial changes in the distribution of A2780 ovarian cancer cells, with an increased rate in the subG1 and G2/M phases, at the expense of the G1 cell population. Moreover, the tested molecules accelerated tubulin polymerization in a cell-free in vitro system. The antimetastatic properties of both tested compounds were investigated by wound healing and Boyden chamber assays after 24 and 48 h of incubation. Treatment with 1 and 2 resulted in time- and concentration-dependent inhibition of migration and invasion of A2780 cancer cells. These results support that the tested agents may be worth of further investigation as promising anticancer drug candidates.


The Influencing Factors of Haze Tolerance in China.
Haze pollution has become the most serious environmental risk in China and generated a large amount of public concerns. Influencing almost all the citizens in the polluted area, it is necessary and important to take public perception as an essential element in haze abatement. From the perspective of social psychology, this paper explores haze tolerance in Beijing, Shanghai, and Guangzhou, also the key influential factors on haze tolerance from four dimensions: political trust, perceived risk, cost perception, and haze knowledge. Based on the sample of 517 respondents, the results show that compared with Shanghai and Guangzhou, Beijing residents had the lowest tolerance level of haze pollution but have the highest levels of trust in the government's capacity to control haze and self-evaluation of their own haze knowledge. People in Shanghai had the lowest cost perception and the strongest willingness to acquire haze knowledge. Meanwhile, the empirical analysis revealed that political trust and cost perception could enhance the public's haze tolerance while perceived risk and haze knowledge had negative impacts on tolerance. Also, our research could provide some suggestions to government officials when making policies for abating haze pollution from the perspective of social risk control. Policy makers are supposed to launch various policy instruments to control haze effectively and engage the citizens in the decision-making process to improve their political trust, and publicize the knowledge of haze pollution to help the public to acquire objective and scientific knowledge and diminish unnecessary worries.


Noninvasive measurement of intra-aneurysmal pressure and flow pattern using phase contrast with vastly undersampled isotropic projection imaging.
Currently, more reliable parameters to predict the risk of aneurysmal rupture are needed. Intra-aneurysmal pressure gradients and flow maps could provide additional information regarding the risk of rupture. Our hypothesis was that phase contrast with vastly undersampled isotropic projection reconstruction (PC-VIPR), a novel 3D MR imaging sequence, could accurately assess intra-aneurysmal pressure gradients in a canine aneurysmal model when compared with invasive measurements. A total of 13 surgically created aneurysms in 8 canines were included in this study. Pressure measurements were performed in the parent vessel, aneurysm neck, and 5 regions within the aneurysmal sac with a microcatheter. PC-VIPR sequence was used to obtain cardiac-gated velocity measurements in a region covering the entire aneurysm. The velocity and pressure gradient maps derived from the PC-VIPR data were then coregistered with the anatomic DSA images and compared with catheter measurements. In 7 of the bifurcation aneurysms, the velocity flow maps demonstrated a recirculation flow pattern with a small neck-to-dome pressure gradient (mean, +0.5 mm Hg). In 1 bifurcation aneurysm, a flow jet extending from the neck to the dome with significantly greater pressure gradient (+50.2 mm Hg) was observed. All sidewall aneurysms had low flow in the sac with intermediate pressure gradients (mean, +8.3 mm Hg). High statistical correlation existed between PC-VIPR aneurysmal pressures and microcatheter pressure measurements (R = 0.82, P < .01). PC-VIPR can provide anatomic as well as noninvasive quantitative and qualitative hemodynamic information in the canine aneurysm model. The PC-VIPR intra-aneurysmal pressure measurements correlated well with catheter measurements.


Specific skin lesions as the presenting symptom of hairy cell leukemia.
A 68-year-old Japanese man with a chief complaint of eczema-like dermatosis was diagnosed as having B-cell hairy cell leukemia (HCL) by demonstration of hairy cells in the skin lesions as well as in blood and bone marrow. He was treated with alpha-interferon, resulting in disappearance of skin lesions and reduction of his massive splenomegaly from 18 to 5 cm in about 14 months. Although specific skin lesions in HCL, shown by a review of the literature to occur in about 8% of cases, are not as uncommon as generally assumed, it is rare for HCL to present with specific skin lesions, the present case being only the second of its type mentioned in the literature.


Electrokinetic Manipulation Integrated Plasmonic-Photonic Hybrid Raman Nanosensors with Dually Enhanced Sensitivity.
To detect biochemicals with ultrahigh sensitivity, efficiency, reproducibility, and specificity has been the holy grail in the development of nanosensors. In this work, we report an innovative type of photonic-plasmonic hybrid Raman nanosensor integrated with electrokinetic manipulation by rational design, which offers dual mechanisms that enhance the sensitivity for molecule detection directly in solution. For the first time, we integrate large arrays of synthesized plasmonic nanocapsules with densely surface distributed silver (Ag) nanoparticles (NPs) on lithographically patterned photonic crystal slabs via electric-field assembling. With the interdigital microelectrodes, the applied electric fields not only assemble the hybrid plasmonic nanocapsules on photonic crystal slabs, but also generate electrokinetic flows that focus analyte molecules to the Ag hot spots on the nanocapsules for surface-enhanced Raman scattering (SERS) detection. The synergistic effects of plasmonic-photonic resonance and the electrokinetic molecular focusing can promote the SERS enhancement factor (EF) robustly to ∼2 × 109. Various molecules including SERS probing molecules, nucleobases, and unsafe food additives can be detected directly from suspension. The innovative mechanism, design, and fabrication reported in this work can inspire a new paradigm for achieving high-performance Raman nanosensors, which is pivotal for lab-on-chip disease diagnosis and environmental protection.


Periostin promotes chronic allergic inflammation in response to Th2 cytokines.
Allergic inflammation triggered by exposure of an allergen frequently leads to the onset of chronic inflammatory diseases such as atopic dermatitis (AD) and bronchial asthma. The mechanisms underlying chronicity in allergic inflammation remain unresolved. Periostin, a recently characterized matricellular protein, interacts with several cell surface integrin molecules, providing signals for tissue development and remodeling. Here we show that periostin is a critical mediator for the amplification and persistence of allergic inflammation using a mouse model of skin inflammation. Th2 cytokines IL-4 and IL-13 stimulated fibroblasts to produce periostin, which interacted with αv integrin, a functional periostin receptor on keratinocytes, inducing production of proinflammatory cytokines, which consequently accelerated Th2-type immune responses. Accordingly, inhibition of periostin or αv integrin prevented the development or progression of allergen-induced skin inflammation. Thus, periostin sets up a vicious circle that links Th2-type immune responses to keratinocyte activation and plays a critical role in the amplification and chronicity of allergic skin inflammation.


Bosma arrhinia microphthalmia syndrome in a Mexican patient with a molecular analysis of PAX6.
The association of anophthalmia, arrhinia, and hypogonadism constitutes the major clinical features for Bosma arrhinia microphthalmia syndrome. However, there is variability in the presentation of this disease; arrhinia is the most constant clinical feature, which is then combined with a spectrum of anophthalmia/microphthalmia and/or hypogonadism. This rare entity is not associated with any specific genes, but the genes that are related to arrhinia and anophthalmia have been studied in an attempt to explain this phenomenon. We analyzed the PAX6 gene in a Bosma arrhinia microphthalmia syndrome patient but found no variation or mutation that could constitute or establish a causal association in our patient.


A potential metallographic technique for the investigation of pipe bombings.
This study was conducted in an attempt to develop a metallographic method for the investigation of pipe bombings. Three common pipe materials, ASTM A53 steel, AISI 304L stainless steel, and 6061-T6 aluminum, were shock-loaded using five high explosives and three propellants. The explosives used were ANFO, Composition C4, C6 detasheet, nitroglycerine-based dynamite, and flake TNT. The propellants used were FFFFg black powder. Red Dot smokeless powder, and Turbo Fuel A. The post-blast microstructure, hardness, and, in the case of 304L, transformed martensite content were examined for each test. The damage done to the microstructure was found to increase with increasing detonation velocity of the explosives and increase in pressure generated by the shock-metal interaction. Material hardness and, in the case of 304L, martensite content showed a sharp increase followed by a plateau as the shock pressure and detonation velocity increased.


Sphingolipid-gated Ca2+ release from intracellular stores of endothelial cells is mediated by a novel Ca(2+)-permeable channel.
Sphingolipid-gated Ca2+ signaling is mediated through Ca(2+)-permeable channels. In this report, we characterize the properties of the channel in a human endothelial cell line (EA.hy926). Ca2+ release from intracellular stores is not antagonized by nifedipine, omega conotoxin G-VIa, or heparin. To further characterize the molecular properties of the channel, we developed a novel assay to directly measure efflux of Ca2+ from intracellular stores of permeabilized Xenopus oocytes. Following size fractionation by sucrose gradient, poly(A)+ RNA from EA.hy926 cells is microinjected into oocytes of Xenopus laevis. We find that the mRNA encoding Ca2+ release activity is approximately 1.5-2.0 kilobases in length. The sphingolipid-gated Ca(2+)-permeable channel is thus likely to be a novel Ca(2+)-permeable channel distinct from other characterized intracellular Ca2+ channels such as the ryanodyne receptor and the inositol 1,4,5-trisphosphate receptor. The method described here provides a new approach to further characterizing this channel and other intracellular Ca2+ channels.


Lower urinary tract dysfunction and disability status in patients with multiple sclerosis.
To investigate the correlation between neurologic and urologic status in patients with multiple sclerosis (MS). Between January 1993 and December 1995, 116 patients with MS symptoms were fully assessed neurologically and urologically with urodynamic studies. Urodynamic abnormalities were detected in 104 patients (89.6%). Several significant relationships between urinary tract findings and neurologic dysfunction were: (1) the relation between voiding disorder as the presenting symptom of the disease and a higher severity of bladder dysfunction; (2) the relation between reduced bladder sensation and longer duration of voiding disorders, lower detrusor uninhibited contractions threshold, and lower bladder capacity; and (3) the relation between voiding disorders and cerebellar system score. Finally, a significant inverse relationship was found between detrusor hypocontractility and neurologic status (from the Expanded Disability Status Scale, pyramidal system score, and Barthel Index). In this series a high incidence of patients reported voiding disorder as the presenting symptom of MS. These patients also showed a higher severity of urodynamic disorders. They should be rigorously followed up. Furthermore, our data suggest that although the most common cause of altered bladder control in MS is spinal cord pathology, involvement of cortical centers and/or peripheral neuronal lesions may occur.


[Immunocorrection of the physiologic status of white rats by sidnofen conjugates with bovine serum albumin].
The effect of immunisation by covalent conjugates of known psychostimulant and antidepressant sydnophen with bovine serum albumin (BSA) on behaviour, formation of conditioned reflex reactions and alcoholization of white rats has been studied. The immunization of sydnophen with BSA by conjugates permits to obtain a long-term alteration of the emotional status: suppression of behavioral activity, learning and alcohol attraction of rats similar in some elements to the action of neuroleptic drugs. The direction of these alterations is opposite to ones caused by the action of sydnophen. It gives possibility to consider fruitful the conception on the ways of long-term immunocorrection of the physiological status of organism.


Bilateral Testicular Loss due to Dog Bite in a Child.
Although animal bites are common, genital trauma caused by animal bites is rare. Here we report a case of bilateral testicular loss in an infant due to a dog bite. The patient was bitten by a friend's dog while his mother was intoxicated and, therefore, did not receive immediate medical attention. Although initial treatment with subsequent genital reconstruction and hormone replacement is important for children with genital trauma, it is too important to make home safe for them.


Synthesis and Photophysical and Photocatalytic Properties of a Highly Fluorinated and Durable Phthalocyanine-Peptide Bioconjugate for Potential Theranostic Applications.
The functionalized, asymmetric fluoro-fluoroalkyl scaffold F48H7COOHPcZn (3) was used to prepare F48H7COOPcZn-6-amino-hexanoate-CTVALPGGYVRVC (5), a Pep42 peptide bioconjugate envisioned for photodynamic therapy, which can specifically target the GRP78 chaperone protein overexpressed and exclusively localized on some cancer cell surfaces. The analogous F48H7COOHPcCu (4) has also been prepared, and its single-crystal X-ray structure was elucidated. Despite reduced steric hindrance relative to the nonfunctionalized, single-site complexes of the F64Pc scaffold, no aggregation was detected in solution via UV-vis spectroscopy, for either 3, 4, or 5, consistent with the lack of π stacking observed for the crystalline 4. The 6-aminohexanoic acid-Pep42 moiety diminishes the fluorescence efficiency of 5, relative to 3, but for singlet oxygen (1O2) generation, photochemical hydroperoxidation of β-(-)-citronellol using 5 and 3 occurs with comparable substrate turnover efficiency, albeit at a slower initial triplet oxygen uptake for 5. The bioconjugate 5 is durable; it does not decompose under 1O2 photoreaction conditions. These results suggest a synthetic coupling pathway for obtaining diverse biotargeting polypeptide-fluorinated phthalocyanine bioconjugates of potential utility as both fluorescence reporters and photocatalysts and highlight the importance of fluorinated scaffolds for generating chemically resilient, catalytic, theranostic materials.


Analysis of the myoglobin gene in Tibetans living at high altitude.
Myoglobin, a protein with an important role in muscle oxidative metabolism, is increased in high altitude residents. In the closely related hemoglobins, mutations cause or contribute to human disease. Furthermore, heme-containing proteins may be involved in oxygen sensing. We therefore tested the hypotheses that myoglobin allele frequencies differed in Tibetans, a long-resident human high-altitude population, compared with sea-level residents, and varied in relation to altitude among Tibetans. We obtained the sequence of exon 2 of the myoglobin gene in 146 Tibetans with greater than three generations of stable residence at altitude in rural Tibet. We compared the frequency of known polymorphic sites in this gene among Tibetans living at altitudes of 3000, 3700, and 4500 m and to allele frequencies previously obtained in 525 residents of Dallas, Texas. We also examined the association between different myoglobin genotypes and hemoglobin concentration, used as an index of myoglobin levels. The frequency of the myoglobin 79A allele was higher in the high altitude compared with the sea-level residents, but unchanged with increasing altitude among Tibetans. There was no significant deviation from Hardy-Weinberg equilibrium in any of the Tibetan altitude groups, nor was there any association between myoglobin genotype and hemoglobin concentration. Screening of exon 2 of the myoglobin gene in high altitude Tibetans does not show novel polymorphism or selection for specific myoglobin alleles as a function of altitude of residence or hypoxic challenge.


Microsystems in health care: Part 5. How leaders are leading.
Leading and leadership by formal and informal leaders goes on at all levels of microsystems--the essential building blocks of all health systems--and between them. It goes on between microsystems and other levels of the systems in health care. This series on high-performing clinical microsystems is based on interviews and site visits to 20 clinical microsystems in the United States. This fifth article in the series describes how leaders contribute to the performance of those microsystems. Interviews of leaders and staff members offer a rich understanding of the three core processes of leading. Building knowledge requires many behaviors of leaders and has many manifestations as leaders seek to build knowledge about the structure, processes, and patterns of work in their clinical microsystems. Taking action covers many different behaviors--making things happen, executing plans, making good on intentions. It focuses action on the way people are hired and developed and involves the way the work gets done. Reviewing and reflecting provides insight as to how the microsystem's patterns, processes, and structure enable the desired work to get done; what success looks like; and what will be next after that "success" is created. The focus on the processes of leading is intended to enable more people to develop into leaders and more people to share the roles of leading.


[Meniscuses and ligaments injuries in tibial plateau fractures in comparative evaluation of clinical, intraoperative and MR examination].
The diagnosis of the meniscal and ligament injuries accompanying the tibial plateau fractures is difficult and unconvincing. Thus the capsular, ligament and meniscal injuries coexisting with this kind of fractures were questioned for many years. Introducing of MR afforded for the precise evaluation of the bone as well as the soft tissue injury. This article demonstrates the results of MR images of 112 patients with the acute proximal tibia fractures. The number and the degree of the meniscal and ligament injury were estimated and intraoperative verification of MR was made in 66 patients qualified for an operative procedure. The attempt to find the correlation between the type of the fracture and the meniscal and ligament injury was made according to Schatzker classification. MR images revealed that the bone injury was accompanied by the ligament or meniscal injury in 88%. Most commonly the partial tears (77% considering ligament injuries and 70% considering meniscal injuries) occurred. The most frequent extracapsular and intracapsular injury was MCL tear (70%) and LM tear (56%) respectively. No correlation between the type of the fracture and the soft tissue injury was found.


Antibiotics in a seasonal ice-sealed reservoir: Occurrence, temporal variation, prioritization, and source apportionment.
Antibiotics are prevalent in the aquatic environment as emerging contaminants. Their knowledge of seasonal ice-sealed reservoirs, however, is limited. The occurrence, temporal variation, and prioritization of twenty-three antibiotics in Shitoukoumen Reservoir during its ice-free and ice-sealed periods, as well as the source apportionment of the high-priority antibiotics, were investigated in this study. The results showed that florfenicol was the dominant antibiotic in Shitoukoumen Reservoir, with different median concentrations of 75.0 ± 6.5 ng L-1 and 7.0 ± 1.7 ng kg-1 in the water and ice, respectively. The concentrations of florfenicol, sulfaguanidine, and sulfamonomethoxine in the water of the reservoir water varied over time, but their monthly mass loads from inflow rivers were similar during ice-free and ice-sealed periods. This indicated that other factors, such as aquacultural practice, non-point source rain runoff, and the blocking effect of ice, determined the temporal variations of the three antibiotics and resulted in their relatively high concentrations during the ice-free period. High-priority antibiotics included erythromycin, florfenicol, ofloxacin, sarafloxacin, sulfaquinoxaline, thiamphenicol, and tylosin. Aquaculture was the primary source of high-priority antibiotics, accounting for 67.3 % and 59.4 % of the total high-priority antibiotic concentrations during ice-free and ice-sealed periods, respectively. The findings suggest that aquaculture, rain runoff, and ice blocking should all be considered as factors influencing antibiotic variations in a seasonal ice-sealed reservoir.


A new species of Hypocristata (Nematoda, Trichostrongyuna, Heligmosomoidea) a parasite of Sigmodon hispidus (Cricetidae, Sigmodontinae) from Venezuela.
Description of Hypocristata tercera n. sp. (Heligmonellidae, Nippostrongylinae) a parasite of the small intestine of Sigmodon hispidus (Rodent, Sigmodontinae) from Venezuela. Two other species were described in the genus, both from Colombia and parasitic in Sigmodontinae. H. thomosomysi Durette-Desset, 1970, a parasite of Thomasomys sp. has about the same number of cuticular ridges at mid-body but differs by ridges having chitinoid struts, a caudal bursa pattern of type 2-2-1 (vs 1-3-1). H. anguillula Durette-Desset, 1970, a parasite of Sigmodontomys alfari (= Nectomys alfari) has the same caudal bursa pattern (type 1-3-1) but differs by the presence of ridges at mid-body in both sexes (absent at that level in H. tercera) and by ridges having chitinoid struts in female. This is the first report of the genus Hypocristata Durette-Desset, 1971 in Venezuela and in the genus Sigmodon (Sigmodontinae).


Propagation of polarized light through two- and three-layer anisotropic stacks.
The extended Jones formulation is used to investigate propagation at nonnormal incidence through two- and three-layer systems of birefringent material in which the optic axes of the individual layers are in the plane of the layers. Such systems are equivalent to two optical elements in series-an equivalent retardation plate and a polarization rotator. Analytical solutions are obtained for the equivalent retardation and rotation. The major finding is that, in general, there are two nonnormal incidence directions for which the retardation vanishes; therefore these two directions are optic axes of the composite system. These simple layered systems therefore behave in a manner similar to biaxial crystals. Moreover, the results illustrate the fact that even if the optic axes of individual layers in composite systems are in the plane of the layers, the optic axes of the system are, in general, out of this plane.


Impaired bone formation with a high-protein diet in rats with adriamycin-induced nephrotic syndrome.
The purpose of the study was to investigate the effects of a high-protein (HP) diet on bone metabolism in rats with adriamycin (ADR)-induced nephrotic syndrome. Nephrotic syndrome was established by weekly injections of ADR (2 mg/kg, i.p.) for 6 weeks. After a final injection, we confirmed that nephrotic syndrome had developed. Then, the rats were divided into two groups for the dietary treatments, namely the HP diet (30% of calories from protein) and the low-protein (LP) diet (7% of calories from protein), and were fed an isocaloric diet for the following 5 weeks. Urinary protein and phosphate excretion were significantly greater in the HP diet group than in the LP diet group (p < 0.05). Serum parathyroid hormone and osteocalcin levels were significantly higher and lower, respectively, in the HP diet group (p < 0.05). Femur weight, femur mass index and femur calcium contents were significantly lower in the HP diet group than in the LP diet group (p < 0.05). Bone mineral density was significantly lower in the HP diet group than in the LP diet group (p < 0.05); however, bone mineral content did not differ between the two groups. We confirmed that an HP diet negatively affects bone mineral metabolism and bone density in ADR-induced nephrotic syndrome rats.


Restrictive cardiomyopathy: from genetics and clinical overview to animal modeling.
Restrictive cardiomyopathy (RCM), a potentially devastating heart muscle disorder, is characterized by diastolic dysfunction due to abnormal muscle relaxation and myocardial stiffness resulting in restrictive filling of the ventricles. Diastolic dysfunction is often accompanied by left atrial or bi-atrial enlargement and normal ventricular size and systolic function. RCM is the rarest form of cardiomyopathy, accounting for 2-5% of pediatric cardiomyopathy cases, however, survival rates have been reported to be 82%, 80%, and 68% at 1-, 2-, and 5-years after diagnosis, respectively. RCM can be idiopathic, familial, or secondary to a systemic disorder, such as amyloidosis, sarcoidosis, and hereditary hemochromatosis. Approximately 30% of cases are familial RCM, and the genes that have been linked to RCM are cTnT, cTnI, MyBP-C, MYH7, MYL2, MYL3, DES, MYPN, TTN, BAG3, DCBLD2, LNMA, and FLNC. Increased Ca2+ sensitivity, sarcomere disruption, and protein aggregates are some of the few mechanisms of pathogenesis that have been revealed by studies utilizing cell lines and animal models. Additional exploration into the pathogenesis of RCM is necessary to create novel therapeutic strategies to reverse restrictive cardiomyopathic phenotypes.


Reproducibility of retinal thickness measurements in normal eyes using optical coherence tomography.
To determine the reproducibility of retinal thickness measurements in normal eyes using optical coherence tomography (OCT). Multiple 3.20-mm vertical cross-sectional images through the center of fixation of consecutive patients with normal results on ocular examinations were obtained. Each image was divided into seven 320-micron segments. Regional retinal thicknesses for each section were measured using both the manually assisted (requiring observer localization of reflectivity peaks) and the automated modes (observer-independent measurement) of the computer software. Eighteen right eyes were studied. The mean coefficient of variation was less than 10% for all locations using the manually assisted method (average standard deviation less than 17 microns [range 9 to 16 microns]). The automated method was less reliable, with a coefficient of variation greater than 10% for locations within 500 microns of fixation. Automated measurements at fixation were the least reproducible because of poor internal limiting membrane reflectivity. OCT is capable of reproducible measurement of retinal thickness in normal eyes. Computer-driven, automated measurement of retinal thickness within 500 microns of fixation needs to be refined and its reproducibility reassessed in this region.


CT, MR, and angiography findings of a solitary fibrous tumor of the larynx: a case report.
This report details the CT, MR, and angiography findings of a solitary fibrous tumor involving the larynx of a 34-year-old man. A precontrast CT scan revealed a well-defined isodense mass in the submucosal region of the supraglottic larynx. The tumor appeared as a mixed intensity lesion on the T1- and T2-weighted MR images. A T2-weighted MR image showed a central, round, and low signal intensity area within the mass. For both the CT and MR images, the mass demonstrated heterogeneous enhancement following the administration of contrast material. The angiography showed a hypervascular tumor with heterogeneous persistent staining.


Prostaglandin E2 and Receptors: Insight Into Tumorigenesis, Tumor Progression, and Treatment of Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is a common primary liver cancer with ∼750,000 annual incidence rates globally. PGE2, usually known as a pro-inflammatory cytokine, is over-expressed in various human malignancies including HCC. PGE2 binds to EP receptors in HCC cells to influence tumorigenesis or enhance tumor progression through multiple pathways such as EP1-PKC-MAPK, EP2-PKA-GSK3β, and EP4-PKA-CREB. In the progression of hepatocellular carcinoma, PGE2 can promote the proliferation and migration of liver cancer cells by affecting hepatocytes directly and the tumor microenvironment (TME) through ERK/COX-2/PGE2 signal pathway in hepatic stellate cells (HSC). For the treatment of hepatocellular carcinoma, there are drugs such as T7 peptide and EP1 antagonist ONO-8711 targeting Cox-2/PGE2 axis to inhibit tumor progression. In conclusion, PGE2 has been shown to be a traditional target with pleiotropic effects in tumorigenesis and progression of HCC that could be used to develop a new potential clinical impact. For the treatment study focusing on the COX-PGE2 axis, the exclusive usage of non-steroidal anti-inflammatory agents (NSAIDs) or COX-2-inhibitors may be replaced by a combination of selective EP antagonists and traditional anti-tumoral drugs to alleviate severe side effects and achieve better outcomes.


Are the common genetic variants associated with colorectal cancer risk for DNA mismatch repair gene mutation carriers?
Genome-wide association studies have identified at least 15 independent common genetic variants associated with colorectal cancer (CRC) risk. The aim of this study was to investigate whether 11 of these variants are associated with CRC risk for carriers of germline mutations in DNA mismatch repair (MMR) genes. A total of 927 MMR gene mutation carriers (360 MLH1, 442 MSH2, 85 MSH6 and 40 PMS2) from 315 families enrolled in the Colon Cancer Family Registry, were genotyped for the single nucleotide polymorphisms (SNPs): rs16892766 (8q23.3), rs6983267 (8q24.21), rs719725 (9p24), rs10795668 (10p14), rs3802842 (11q23.1), rs4444235 (14q22.2), rs4779584 (15q13.3), rs9929218 (16q22.1), rs4939827 (18q21.1), rs10411210 (19q13.1) and rs961253 (20p12.3). We used a weighted Cox regression to estimate CRC risk for homozygous and heterozygous carriers of the risk allele compared with homozygous non-carriers as well as for an additive per allele model (on the log scale). Over a total of 40,978 person-years observation, 426 (46%) carriers were diagnosed with CRC at a mean age of 44.3 years. For all carriers combined, we found no evidence of an association between CRC risk and the total number of risk alleles (hazard ratio [HR] per risk allele=0.97, 95% confidence interval [CI]=0.88-1.07, p=0.52). We found no evidence that the SNPs associated with CRC in the general population are modifiers of the risk for MMR gene mutation carriers overall, and therefore any evidence of proven clinical utility in Lynch syndrome.


Ahemeral lighting of turkey breeder hens. 1. Cycle length effects on egg production and egg characteristics.
A study was conducted to determine the effective range of light-dark cycle lengths for reproductive performance in turkey hens. The treatments consisted of seven different light-dark cycle lengths: 21, 23, 24, 26, 27, 28, and 30 h each with a 15-h photophase per cycle. Data were collected for BW, feed intake, livability, onset and rate of egg production, egg weight (EW), shell thickness, and weight of egg components. The results indicate that turkey hens can be induced to lay eggs with light-dark cycle lengths other than 24 h (ahemeral) with practical extremes being about 23 to 28 h. Egg production in the ahemeral treatments never significantly exceeded that occurring in the 24 h group and the percentage of floor eggs increased at cycle lengths greater than 26 h and at 21 h. Cycle lengths of 21 and 30 h provided the most extreme deviations in the quantity and quality of eggs from those obtained on a 24 h cycle length. Shell thickness increased consistently as cycle lengths increased from 23 to 30 h. Egg weight increased in a curvilinear manner as cycle lengths increased or decreased from 24 h. This increase was associated with increases in shell, yolk, and albumen weight; however, the contribution by each was inconsistent, varying by cycle length as well as time on treatment. It may be concluded that an effective practical range of light-dark cycles for turkeys is 23 to 28 h and that 28 h is a reasonable limit to maximize EW and shell thickness while minimizing a reduction in egg production.


Perturbed nuptiality, delayed fertility: childbirth effects of Covid19.
An aspect of the Covid-19 pandemic that merits attention is its effects on marriage and childbirth. Although the direct fertility effects of people getting the virus may be minor, the impact of delayed marriages due to the first preventive lockdown, such as that imposed in Pakistan from March 14 to May 8 2020, and the closure of marriage halls that lasted till September 14 may be non-negligible. These demographic consequences are of particular import to developing countries such as Pakistan where birth rates remain high, marriage is nearly universal, and almost all child-bearing takes place within marriage. Based on historic marriage patterns, we estimate that the delay in nuptiality during the first wave of the coronavirus outbreak may affect about half of the marriages that were to take place during the year. In Pakistan, childbearing begins soon after marriage, and about 37% of Pakistani married women give birth to their first child within twelve months of marriage. A sizeable number out of these, around 400,000 annual births that occur within twelve months of the marriage, may consequently be delayed. Postponement of marriages due to the accompanying difficult economic situation and employment precariousness will accentuate this fertility effect. The net fertility impact of the Covid-19 outbreak will ultimately depend not only on the delay in marriages but also on the reproductive behavior of existing couples.


The Ability of Adults of Different Size to Egress Through Confined Space Apertures.
To determine minimum egress apertures in healthy adults of different body size. Body space requirements have traditionally been considered from an industrial perspective, facilitating safe confined-space working. However, increased typical body size resulting from global obesity renders traditional assumptions of body size inappropriate. This has potentially far-reaching consequences for evacuation planning, due to diminished clearance space, slower movement, and increased chance of physical entrapment. Critically, no current literature describes the minimum apertures adults can negotiate. Forty-eight men and 40 women underwent anthropometric and 3-D scanning assessments from which anatomical dimensions were extracted. Additionally, a wall egress task was undertaken through an aperture that was progressively narrowed until individuals failed to pass. Minimum egress aperture was predicted from anatomical variables using backwards elimination regression. Minimum wall egress was best predicted from mass, abdominal depth, bideltoid breadth and chest depth. Passes and fails, discriminated using binary logistic regression, identified chest depth and abdominal depth as influential for wall egress success at selected apertures, with a gender interaction manifest at abdominal depth. Minimum egress aperture relates to body size and can be predicted from anatomical variables; however, men and women display subtle differences in egress capability. In public and industrial settings, egress capability in restricted spaces is affected by size and gender, with profound implications for safety, which relate to increased typical body size associated with global obesity.


Targeted inhibition of transient activation of the EGFR-mediated cell survival pathway enhances paclitaxel-induced ovarian cancer cell death.
Emerging studies have suggested that transient activation of the cell survival pathway may be the strategy for cancer cells to fight against chemotherapy and eventually mysteriously evade paclitaxel-induced cell death. Modulation of the EGFR-mediated survival pathway in addition to the utilization of paclitaxel renders a promise of better clinical management. The objective of this study was to understand the molecular mechanism of transient induction of EGFR-mediated cell survival by paclitaxel. We utilized ovarian cancer cell line, Caov3, cells to investigate the effect of paclitaxel on EGFR-mediated MAP kinase and AKT activation, and the expression of survivin. We found that paclitaxel transiently induced EGFR phosphorylation and ERK and AKT activation but not JNK and p38. Paclitaxel-induced ERK and AKT activity was inhibited by the EGFR inhibitor, PD153035; ERK inhibitor, U0126; and PI3 kinase inhibitor, LY294002, respectively. We observed that paclitaxel transiently induced expression of survivin in the early hours of treatment. Paclitaxel-induced survivin expression was inhibited by the EGFR inhibitor, PD153035. Inhibitors of EGFR, ERK and PI3 kinase all enhanced paclitaxel-induced cell death. We conclude that paclitaxel transiently transactivates EGFR, leading to activation of cell survival factors, such as ERK and AKT, and expression of survivin, which are all inclusively accountable for ovarian cancer cell resistance to paclitaxel treatment. A combination of these inhibitors with paclitaxel may be a better option for ovarian cancer treatment.


Isolation and species distribution of staphylococci from animal and human skin.
From April 1999 to December 2000, a survey was made on the distribution of Staphylococcus species on the skin of 7 kinds of animals and humans. Staphylococci were isolated from 12 (100%) of 12 pigs, 17 (89.5%) of 19 horses, 30 (100%) of 30 cows, 73 (90.1%) of 81 chickens, 10 (40%) of 25 dogs, 23 (76.7%) of 30 laboratory mice, 20 (52.6%) of 38 pigeons, and 80 (88.9%) of 90 human beings. The predominant staphylococci isolated from a variety of animal species were novobiocin-resistant species, S. xylosus and S. sciuri regardless of the animal host species. The novobiocin-resistant species including S. xylosus and S. sciuri were only occasionally isolated from human skin. The predominant staphylococci found on human skin were novobiocin-sensitive species, S. epidermidis (63.8%), followed by S. warneri (28.8%) and S. hominis (13.8%). The results suggest that the staphylococcal flora inhabiting animal skin are different from those of human skin in regard to the predominant species isolated. In this study, we used pulsed-field gel electrophoresis to examine the chromosomal polymorphisms of S. epidermidis isolated most frequently from human skin. Strains of S. epidermidis showed the greatest genomic diversity in their fragment patterns.


The motor syndrome associated with exaggerated inhibition within the primary motor cortex of patients with hemiparetic.
Following transcranial magnetic stimulation (TMS) at stimulation strength of 1.5 times the resting motor threshold, a silent period (SP) of approximately 180 ms duration can be observed in surface EMG-registrations of tonically activated small hand muscles. This SP is believed to be generated cortically and can be prolonged in stroke patients, but it is not known whether a prolongation of the SP has any functional significance. In order to answer the question of whether enhanced cortical inhibition can contribute to pathophysiology of motor dysfunction we studied stroke patients with clearly prolonged SP durations in the first dorsal interosseus muscle (> 2 times that of the intact side), but with normal magnetically evoked motor potentials. Sixteen patients out of a cohort of 174 consecutive patients presenting with acute hemiparetic stroke fulfilled the inclusion criteria. Serial TMS investigations were performed for up to 2 years post-stroke. In all patients, the SP duration decreased in parallel with clinical improvement. In two patients, intermittent clinical deterioration was accompanied by an increase in the SP duration. In four patients, in addition to a markedly prolonged SP duration, the phenomenon of a complete inability to initiate voluntary muscle activity for several seconds, following TMS, could be observed in a number of trials ('motor arrest'). Detailed clinical analysis revealed that, in addition to hemiparesis, distinct motor disturbances in patients with SP prolongation could be observed. These motor disturbances resembled those of motor neglect and were characterized by motivationally dependent under-utilization of the affected arm, impairment of movement initiation, inability to maintain a constant force level and to scale forces, and impairment of individual finger movements. In 12 of the 16 patients at least one additional behavioural manifestation of neglect was present. We suggest that in stroke patients severe motor dysfunction may be caused by hyperactivity of cortical inhibitory interneurons rather than by direct lesions of descending motor tracts. Cortical hyperinhibition may, in turn, result from damage to any of a number of afferent pathways to the motor cortex which modulate local interneuronal activity.


Statistical analysis of molecular signal recording.
A molecular device that records time-varying signals would enable new approaches in neuroscience. We have recently proposed such a device, termed a "molecular ticker tape", in which an engineered DNA polymerase (DNAP) writes time-varying signals into DNA in the form of nucleotide misincorporation patterns. Here, we define a theoretical framework quantifying the expected capabilities of molecular ticker tapes as a function of experimental parameters. We present a decoding algorithm for estimating time-dependent input signals, and DNAP kinetic parameters, directly from misincorporation rates as determined by sequencing. We explore the requirements for accurate signal decoding, particularly the constraints on (1) the polymerase biochemical parameters, and (2) the amplitude, temporal resolution, and duration of the time-varying input signals. Our results suggest that molecular recording devices with kinetic properties similar to natural polymerases could be used to perform experiments in which neural activity is compared across several experimental conditions, and that devices engineered by combining favorable biochemical properties from multiple known polymerases could potentially measure faster phenomena such as slow synchronization of neuronal oscillations. Sophisticated engineering of DNAPs is likely required to achieve molecular recording of neuronal activity with single-spike temporal resolution over experimentally relevant timescales.


Profiles of Coping Strategies in Resilient Adolescents.
To understand how resilient adolescents adapt to adverse situations, this study examined resilient adolescents and their coping strategies. Resilience is the phenomenon characterized by good outcomes despite serious threats to adaptation and/or development. The current study aimed to identify the coping strategy profiles that distinguish a resilient group from three other groups-struggling, competent, and vulnerable-specifically to differentiate the resilient group from the competent group. Descriptive discriminant analysis results indicated that resilient adolescents simultaneously utilized not only problem-focused but also the emotion-focused coping strategies. The competent group primarily used problem-focused coping, while the struggling group primarily used emotion-focused strategies. Finally, the vulnerable adolescents used neither problem-focused nor emotion-focused strategies. Practical implications of the results were discussed to guide professionals.


Localized hypertrophy of hand in syringomyelia.
Segmental amyotrophy is a common feature resulting from extension of the syrinx into the anterior horns. Segmental hypertrophy in the form of chiromegaly/podomegaly or limb and hemi-hypertrophy are rare but well recognized clinical feature of syringomyelia. We report a case of hand hypertrophy secondary to syringomyelia. Hypertrophy of the hands is a rare but interesting feature of syringomyelia and in all cases of enlargements of hands syringomyelia should be considered in the differential diagnosis.


NAD(P)H:quinone oxidoreductase 1-compromised human bone marrow endothelial cells exhibit decreased adhesion molecule expression and CD34+ hematopoietic cell adhesion.
NAD(P)H:quinone oxidoreductase 1 (NQO1) deficiency resulting from a homozygous NQO1*2 polymorphism has been associated with an increased risk of benzene-induced myeloid toxicity and a variety of de novo and therapy-induced leukemias. Endothelial cells in human bone marrow form one of the two known hematopoietic stem cell microenvironments and are one of the major cell types that express NQO1 in bone marrow. We have used a transformed human bone marrow endothelial cell (TrHBMEC) line to study the potential impact of a lack of NQO1 activity on adhesion molecule [endothelial leukocyte adhesion molecule 1 (E-selectin), vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1] expression and functional adhesion to bone marrow progenitor cells. We used both 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), a mechanism-based inhibitor of NQO1, and anti-NQO1 small interfering RNA to abrogate NQO1 activity. Real-time reverse transcription-polymerase chain reaction data demonstrated a significant inhibition of tumor necrosis factor (TNF)alpha-induced E-selectin mRNA levels after ES936 pretreatment. Immunoblot assays demonstrated a significant reduction in TNFalpha-stimulated E-selectin, VCAM-1, and ICAM-1 proteins after inhibition or knockdown of NQO1. The mechanisms underlying this effect remain undefined, but modulation of nuclear factor-kappaB (p65), c-Jun, and activating transcription factor 2, transcriptional regulators of adhesion molecules, were observed after inhibition or knockdown of NQO1. Decreased level of E-selectin, VCAM-1, and ICAM-1 also resulted in a functional deficit in adhesion. A parallel plate flow chamber study demonstrated a marked reduction in CD34(+) cell (KG1a) adhesion to NQO1-deficient TrHBMECs relative to controls. The reduced adhesive ability of TrHBMECs may affect the function of the vascular stem cell niche and also may contribute to the increased susceptibility of polymorphic individuals lacking NQO1 to leukemias and hematotoxicants such as benzene.


[A young man with painful feet].
We present a 28-year-old plasterer with symptomatic pes planus due to bilateral calcaneonavicular coalition. Computed tomography revealed an osseous calcaneonavicular bar of the right foot and a fibrous calcaneonavicular coalition of the left foot. Treatment options include conservative measures and surgical treatment consisting of a calcaneonavicular bar resection.


Single-villus analysis of disaccharidase expression by different regions of the mouse intestine.
1. The present results describe how a new technique of whole-tissue cytochemistry can be combined with automatic scanning of microdissected villi to measure the capacity of individual villi to hydrolyse disaccharides in different parts of the small intestine. 2. Intact villi from the mouse proximal jejunum are found to be eight times more effective than ileal villi in hydrolysing 2-naphthyl-alpha-D-glucoside, an artificial substrate for enzymes normally hydrolysing sucrose, maltose, isomaltose and trehalose in adult intestine. Homogenates of jejunal scrapings are four times more effective than ileal homogenates in hydrolysing this substrate. This discrepancy arises from relating enzyme activities to homogenate protein in cases where intestinal structure changes. 3. The eightfold difference in villus alpha-glucosidase activity is associated with a threefold difference in villus surface area. This discrepancy in turn reflects changes in the capacity of individual enterocytes to express alpha-glucosidase during migration along the crypt-villus axis. These results emphasize the futility of trying to gauge intestinal function from measurement of intestinal structure. 4. Differences between ileal and jejunal villus alpha-glucosidase activities have been further partitioned into those depending on villus structure and those depending on enterocyte development. Present results are discussed in relation to the ability of luminal nutrition to maintain a proximal-distal gradient of digestive enzyme function in the small intestine. The general applicability of this method of analysis to other studies of adaptive response is also emphasized.


Age, gender, and race/ethnic differences in total body and subregional bone density.
Total body bone density of adults from National Health and Nutrition Examination Survey (NHANES) 1999-2004 differed as expected for some groups (men>women and blacks>whites) but not others (whites>Mexican Americans). Cross-sectional age patterns in bone mineral density (BMD) of older adults differed at skeletal sites that varied by degree of weight-bearing. Total body dual-energy X-ray absorptiometry (DXA) data offer the opportunity to compare bone density of demographic groups across the entire skeleton. The present study uses total body DXA data (Hologic QDR 4500A, Hologic, Bedford MA, USA) from the NHANES 1999-2004 to examine BMD of the total body and selected skeletal subregions in a wide age range of adult men and women from three race/ethnic groups. Total body, lumbar spine, pelvis, right leg, and left arm BMD and lean mass from 13,091 adults aged 20 years and older were used. The subregions were chosen to represent sites with different degrees of weight-bearing. Mean BMD varied in expected ways for some demographic characteristics (men>women and non-Hispanic blacks>non-Hispanic whites) but not others (non-Hispanic whites>Mexican Americans). Differences in age patterns in BMD also emerged for some characteristics (sex) but not others (race/ethnicity). Differences in cross-sectional age patterns in BMD and lean mass by degree of weight-bearing in older adults were observed for the pelvis, leg, and arm. This information may be useful for generating hypotheses about age, race, and sex differences in fracture risk in the population.


Western and Mediterranean Dietary Patterns and Physical Activity and Fitness among Spanish Older Adults.
Objectives: To assess prevailing food patterns, and its association with physical activity and fitness among Spanish older adults. Methods: Cross-sectional study in Spain, collecting data from a sample (n = 380; 54% female) aged 55-80 years (men) and 60-80 years (women) with no previously documented cardiovascular disease. Body weight, body fat and waist circumference were assessed. Physical activity performed was measured using the Minnesota Leisure-time Physical Activity Questionnaire (LTPA). Physical fitness was assessed using a validated physical fitness test battery. Food consumption was assessed by a validated semi-quantitative food-frequency questionnaire. Factor analysis identified two major dietary food patterns: "Western" (WDP) and "Mediterranean" (MDP) dietary patterns. Results: Participants in MDP's fourth quartile were classified in the second (men) and third (men and women) tertile of LTPA. After adjusting for age, body fat, waist-to-height ratio, and METs, in both sexes, a negative significant association was found between 30-s Chair stand and 6-min walking test, a positive significant association was found between 30-m Gait speed and 8-foot Time Up-and-Go (except in men) tests with WDP. The 30-m Gait speed test was negatively associated with MDP in men. Conclusions: MDP is associated with more time spent on LTPA, and this association was independent of body composition and a fast gait speed in men. WDP is associated with slower gait speed and lower body strength, agility and aerobic endurance. MDP has protective effect on healthy physical fitness, and WDP may be a contributor to frailty.


Risk Areas for Influenza A(H5) Environmental Contamination in Live Bird Markets, Dhaka, Bangladesh.
We evaluated the presence of influenza A(H5) virus environmental contamination in live bird markets (LBMs) in Dhaka, Bangladesh. By using Bernoulli generalized linear models and multinomial logistic regression models, we quantified LBM-level factors associated with market work zone-specific influenza A(H5) virus contamination patterns. Results showed higher environmental contamination in LBMs that have wholesale and retail operations compared with retail-only markets (relative risk 0.69, 95% 0.51-0.93; p = 0.012) and in March compared with January (relative risk 2.07, 95% CI 1.44-2.96; p<0.001). Influenza A(H5) environmental contamination remains a public health problem in most LBMs in Dhaka, which underscores the need to implement enhanced biosecurity interventions in LBMs in Bangladesh.


Spontaneous Redox-Reaction-Driven Growth of Ag Nanoparticles on Co(OH)2 Nanoflower Arrays for Surface-Enhanced Raman Scattering.
A simple and reliable method is developed to fabricate Ag-nanoparticle-decorated Co(OH)2 nanoflowers grafted on polyacrylonitrile (PAN) nanopillar arrays as uniform and sensitive surface-enhanced Raman scattering (SERS) substrates. First, Co(OH)2-nanosheet-assembled nanoflowers are achieved on the highly uniform PAN nanopillar arrays via electrochemical deposition. Then, Ag nanoparticles (Ag-NPs) are decorated onto the Au-nanoparticle-precoated Co(OH)2 nanoflowers based on a spontaneous redox reaction (SRR) between the silver ions and Co(OH)2 nanosheets at room temperature. Ag-NPs can be successfully in situ synthesized on the Co(OH)2 nanoflowers, and Au nanoparticles precoated on the surface of the Co(OH)2 nanosheets can ensure that the Co(OH)2 nanoflower structure does not collapse. Because of the highly uniform PAN nanopillar arrays and the high-density sub-10 nm gaps between the neighboring Ag-NPs on the surface of the Co(OH)2 nanoflowers, the hierarchical three-dimensional Ag@Co(OH)x grown on PAN nanopillar arrays can produce a reproducible and sensitive SERS effect. To verify the SERS performance of the substrate, 4-aminothiophenol (4-ATP) is used as the probe molecule, and the Ag@Co(OH)x grown on PAN nanopillar arrays is employed as the SERS substrate. As a result, 4-ATP concentrations as low as 10-10 M can still be identified, exhibiting high SERS activity. Additionally, the relative standard deviation value of the main characteristic peak of 10-5 M 4-ATP is 9.43%, indicating good uniformity of the SERS signal of the substrate. The SRR between silver ions and Co(OH)2 can provide a simple route to prepare heterostructures as SERS substrates, which has great potential for application in the field of analysis.


Design of Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS).
Cryptogenic ischemic strokes constitute 20-30% of ischemic strokes, the majority of which are embolic strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid. The Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent stroke and to characterize the safety of dabigatran in this setting. Prospective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with embolic stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-months and up to approximately three-years. It is an event-driven trial aiming for 353 adjudicated primary outcome events. The primary efficacy outcome is time to first recurrent stroke (ischemic, hemorrhagic, or unspecified). Key secondary outcomes are time to first ischemic stroke and time to first occurrence in the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death. The primary safety outcome is major hemorrhage, including symptomatic intracranial hemorrhage. Acetylsalicylic acid is the most common antithrombotic given to patients with embolic strokes of undetermined source to reduce recurrence risk. This trial will determine whether anticoagulation with dabigatran is more effective than acetylsalicylic acid, and acceptably safe.