Defensive applications of gene transfer technology in the face of bioterrorism: DNA-based vaccines and immune targeting.
Gene transfer involves the introduction of an engineered gene into a person's cells with the expectation that the protein expressed from the gene will produce a therapeutic benefit. Strategies based on this principle have led to the approval of > 600 clinical trials and enrollment of approximately 3500 subjects worldwide in attempts to treat diseases ranging from cancer to AIDS to cystic fibrosis. While gene therapy has met with limited success and still has many hurdles to overcome before it sees wide application, it may be useful as a defensive strategy against bioterrorism agents including infectious microbes and toxins. Although many defensive strategies are possible, immunological strategies are currently the most developed and are being actively applied to the development of strategies against several of the most virulent potential bio-weapons. While most of these strategies are not yet ready for human application, DNA-based vaccines appear to be among the most promising in the fight against bioterrorism.


Technology Myth Busters for Nurse Leaders.
Technology is frequently viewed as a barrier to workflow and efficiency rather than as a tool that can be used to improve the quality of our care, increase efficiency, or enhance patient outcomes. However, when technology is applied effectively, nurse leaders can leverage tools such as clinical decision support to avoid errors, inform decision making, and boost provider and patient satisfaction. These topics were discussed at the AONE annual meeting in a preconference session. In this article, AONE session leaders detail ways to ensure that information technology is a valuable tool-and not an obstacle-for effective nursing practice.


Engaging the next generation of physician-informaticians through early exposure to the field: successes and challenges associated with starting a novel clinical informatics interest group.
Clinical informatics remains underappreciated among medical students in part due to a lack of integration into undergraduate medical education (UME). New developments in the study and practice of medicine are traditionally introduced via formal integration into undergraduate medical curricula. While this path has certain advantages, curricular changes are slow and may fail to showcase the breadth of clinical informatics activities. Less formal and more flexible approaches can circumvent these drawbacks. Interest groups (IGs), which are organized through the Association of American Medical College Careers in Medicine (CiM) program, exemplify the informal approach. CiM IGs are student-led groups that provide exposure to different specialty options, acting as an adjunct to the traditional medical curriculum. While the primary purpose of these groups is to assist students applying to residency programs, we took a novel approach of using an IG to increase student exposure to an area of medicine that had not yet been formally integrated at our institution. IGs provide unique advantages to formal integration into a curriculum as they can be more easily setup and can quickly respond to student interests. Furthermore, IGs can act synergistically with UME, acting as proving grounds for ideas that can lead to new courses. We believe that the lessons and takeaways from our experience can act as a guide for those interested in starting similar organizations at their own schools.


Cancer-Associated Fibroblast Risk Model for Prediction of Colorectal Carcinoma Prognosis and Therapeutic Responses.
Colorectal carcinoma (CRC) is a malignant tumor of the digestive system. Cancer-associated fibroblasts (CAFs) are important cellular elements in the tumor microenvironment of CRC, which contribute to CRC progression and immune escape. To predict the survival outcome and therapeutic responses of CRC patients, we identified genes connected with stromal CAF and generated a risk model. In this study, we used multiple algorithms to reveal CAF-related genes in the Gene Expression Omnibus and The Cancer Genome Atlas datasets and construct a risk model composed by prognostic CAF-associated genes. Then, we evaluated whether the risk score could predict CAF infiltrations and immunotherapy in CRC and confirmed the expression of the risk model in CAFs. Our results showed that CRC patients with high CAF infiltrations and stromal score had worse prognosis than those with low-CAF infiltrations and stromal score. We obtained 88 stromal CAF-associated hub-genes and generated a CAF risk model consisting of ZNF532 and COLEC12. Compared with low-risk group, the overall survival in high-risk group was shorter. The relationship between risk score, ZNF532 and COLEC12, and stromal CAF infiltrations and CAF markers was positive. In addition, the effect of immunotherapy in the high-risk group was not as good as that in the low-risk group. Patients with the high-risk group were enriched in chemokine signaling pathway, cytokine-cytokine receptor interaction, and focal adhesion. Finally, we confirmed that the expressions of ZNF532 and COLEC12 in risk model were widely distributed in fibroblasts of CRC, and the expression levels were higher in fibroblasts than CRC cells. In conclusion, the prognostic CAF signature of ZNF532 and COLEC12 can be applied not only to predict the prognosis of CRC patients but also to evaluate the immunotherapy response in CRC patients, and these findings provide the possibility for further development of individualized treatment for CRC.


Recent advances in CO2 capture and reduction.
Given the continuous and excessive CO2 emission into the atmosphere from anthropomorphic activities, there is now a growing demand for negative carbon emission technologies, which requires efficient capture and conversion of CO2 to value-added chemicals. This review highlights recent advances in CO2 capture and conversion chemistry and processes. It first summarizes various adsorbent materials that have been developed for CO2 capture, including hydroxide-, amine-, and metal organic framework-based adsorbents. It then reviews recent efforts devoted to two types of CO2 conversion reaction: thermochemical CO2 hydrogenation and electrochemical CO2 reduction. While thermal hydrogenation reactions are often accomplished in the presence of H2, electrochemical reactions are realized by direct use of electricity that can be renewably generated from solar and wind power. The key to the success of these reactions is to develop efficient catalysts and to rationally engineer the catalyst-electrolyte interfaces. The review further covers recent studies in integrating CO2 capture and conversion processes so that energy efficiency for the overall CO2 capture and conversion can be optimized. Lastly, the review briefs some new approaches and future directions of coupling direct air capture and CO2 conversion technologies as solutions to negative carbon emission and energy sustainability.


Metallothionein and copper in liver disease with copper retention--a histopathological study.
We have examined the relationship between (a) histochemically demonstrable copper using rubeanic acid, (b) copper-associated protein (CAP) using orcein, and (c) immunoreactive metallothionein (MT) using DNP hapten sandwich staining and have correlated these with histological lesions in 95 liver biopsies from patients with conditions associated with hepatic copper retention, 4 fetal livers, and 25 histologically normal adult controls. No copper or CAP was present in normal adult liver but periportal CAP was present in fetal liver. MT was present in hepatocytes of normal livers with a predominantly perivenular (centrilobular) cytoplasmic distribution varying in staining intensity; all fetal hepatocytes stained strongly for MT. Fifty-two of 95 (55 per cent) abnormal livers contained CAP and 42 (44 per cent) contained both CAP and copper. In CAP-positive livers, the commonest histological lesions were piecemeal necrosis and cholestasis. CAP was present in (a) 15/15 cases of primary biliary cirrhosis including early cases with minimal pathology; and (b) 5/5 cases of Wilson's disease, 6/6 cases of biliary atresia, and 3/9 cases of sclerosing cholangitis. In other conditions, it was present in 25-50 per cent of cases. MT distribution was abnormal in most CAP-positive livers. Necrotic hepatocytes were intensely MT-positive and in Wilson's disease had a characteristic appearance.


Revision of the Oriental species of Polypedilum Kieffer (Diptera: Chironomidae) with their phylogenetic relationship.
Imagines and pupae of new species Polypedilum (Pentapedilum) retusum are described from India. Three species, P. (Polypedilum) tamanigrum Sasa, 1983, P. (Pentapedilum) anale (Freeman, 1954), and P. (Tripodura) conghuaense Zhang, Song, Qi and Wang, 2016 with pupa are recorded firstly in the subcontinent. Hypopygia of P. (P.) ascium Chaudhuri, Guha and Das Gupta, 1981, P. (T.) conghuaense, P. (T.) lineatum Chaudhuri, Guha and Das Gupta, 1981 and P. (P.) nudiceps Chaudhuri, Guha and Das Gupta, 1981 are redescribed. Polypedilum (P.) exterflexum Hazra, Sanyal and Brahma, 2015, P. clavipennae Hazra, Sanyal and Brahma, 2015 and P. aduncum Konar and Hazra, 2017 are proposed here to transfer to the genus Stictochironomus Kieffer, 1919. Polypedilum (P.) insolitum Chaudhuri, Guha and Das Gupta, 1981 is here stated as junior synonym of Zavreliella marmorata (Wulp, 1859). In addition, some biogeographic and taxonomic remarks including DNA barcoding for selected species are given. Cladistic analysis of the Oriental species of Polypedilum Kieffer is made to hypothesise their possible relationship. A new dichotomous key of the Oriental species of Polypedilum is presented here.


Wigner crystals of 229Th for optical excitation of the nuclear isomer.
We have produced laser-cooled Wigner crystals of 229Th3+ in a linear Paul trap. The magnetic dipole (A) and electric quadrupole (B) hyperfine constants for four low-lying electronic levels and the relative isotope shifts with respect to 232Th3+ for three low-lying optical transitions are measured. Using the hyperfine B constants in conjunction with prior atomic structure calculations, a new value of the spectroscopic nuclear electric quadrupole moment Q=3.11(16) eb is deduced. These results are a step towards optical excitation of the low-lying isomer level in the 229Th nucleus.


Large Bowel Ischemia/Infarction: How to Recognize It and Make Differential Diagnosis? A Review.
Ischemic colitis represents the most frequent form of intestinal ischemia occurring when there is an acute impairment or chronic reduction in the colonic blood supply, resulting in mucosal ulceration, inflammation, hemorrhage and ischemic necrosis of variable severity. The clinical presentation is variable and nonspecific, so it is often misdiagnosed. The most common etiology is hypoperfusion, almost always associated with generalized atherosclerotic disease. The severity ranges from localized and transient ischemia to transmural necrosis of the bowel wall, becoming a surgical emergency, with significant associated morbidity and mortality. The diagnosis is based on clinical, laboratory suspicion and radiological, endoscopic and histopathological findings. Among the radiological tests, enhanced-CT is the diagnostic investigation of choice. It allows us to make the diagnosis in an appropriate clinical setting, and to define the entity of the ischemia. MR may be adopted in the follow-up in patients with iodine allergy or renal dysfunctions, or younger patients who should avoid radiological exposure. In the majority of cases, supportive therapy is the only required treatment. In this article we review the pathophysiology and the imaging findings of ischemic colitis.


New electrocardiographic criteria for diagnosing right ventricular hypertrophy in mitral stenosis--comparison with the Bonner's and Mortara's criteria.
New criteria for the diagnosis of right ventricular hypertrophy (RVH) using a point scoring system were developed after analyzing standard 12-lead ECGs in 155 patients with mitral stenosis verified by cardiac catheterization and 155 age and sex-matched apparently normal healthy subjects. ECGs were evaluated to identify criteria that provided maximum sensitivity and at least a 95% specificity: (1) the R wave magnitude in V1 had to be greater than 0.7 mV; (2) the S wave magnitude in V6 had to be greater than 0.3 mV; (3) the S wave magnitude in V1 less than 0.5 mV; (4) the R wave magnitude in V1 plus the S wave magnitude in V6 minus the S wave magnitude in V1 must be greater than 0 mV; and (5) the degree of frontal QRS axis had to be greater than 90 degrees. Application of these criteria achieved 25% (39 of 155) sensitivity in patients with RVH, significantly better (p less than 0.01) than the 17% sensitivity (17 of 155) of Bonner's criteria for the automated ECG. The specificity of the proposed criteria was 98% (152 of 155), significantly better (p less than 0.01) than the 90% specificity (139 of 155) of Mortara's criteria. Thus, it was evident that the accuracy of the proposed criteria was the highest among those criteria used in a point scoring system including the currently used automated ECG criteria for the diagnosis of RVH.


In situ nitrogen-doped, defect-induced carbon nanotubes as an efficient anode for sodium-ion batteries.
The incorporation of heteroatoms and defects in carbonaceous material is a well-known approach to improve the electrochemical performance of the anode in a sodium-ion battery (NIB). However, previous works aimed to use either heteroatom-doped or defect-enriched carbon material. The present work focuses on nitrogen-doped, defect-induced surface-modified carbon nanotubes (MN-BCNT) having the synergy of both the effects to improve the electrochemical performance of the NIB. Initially, in situ nitrogen-doped CNTs were grown using a scalable, cost-effective and green synthesis technique. In situ nitrogen doping introduces lattice defects resulting in bamboo-shaped CNTs. The defects were further enriched by opening the ends of the tubes and also by shortening them. This structure demonstrates the high capacity of 278 mA h g-1 at a current density of 50 mA g-1, which is more than double compared to conventional CNTs. The improved performance of MN-BCNT is attributed to the improved electrical conductivity due to nitrogen doping and the availability of significant active sites as a result of tube shortening. Moreover, the designed structure shows good cyclic stability at 200 mA g-1 accompanied with excellent rate capability.


The effect of labetalol and propranolol on the development of hypertension in spontaneously hypertensive rats.
The effect of long-term administration of propranolol (0.2 and 0.4 mg/kg-1 p.o.) and that of labetalol (2.0, 4.0 and 8.0 mg/kg-1 p.o. and 1 mg/kg-1 i.p.) on the development of hypertension was studied in female rats of SHR/N/Ibn strain. The experiment was started on 6-week-old animals. Rats received the tested drugs once daily between 11 and 12 o'clock. From the 29th day on (i.e. after the age of 10 weeks) the arterial blood pressure was measured bloodlessly twice weekly 2 hours before the daily dose of the drug. Labetalol given p.o. in a dose of 2 mg/kg-1 had no effect on the development of hypertension, while the doses 4.0 and 8.0 mg/kg-1 decreased the arterial pressure by about 4 kPa (30 mm Hg). After drug withdrawal a rapid rise was observed in the arterial pressure to values approaching the values recorded in control animals. In the animals receiving labetalol parenterally (1 mg/kg-1 i.p.) the blood pressure was significantly lower than in control rats. After drug withdrawal the blood pressure increased gradually, however, even on the 54th day of the experiment it was slightly below that in controls. Propranolol given orally in doses of 0.2 mg/kg-1 delayed the development of hypertension, while in the dose of 0.4 mg/kg-1 it prevented its development. After withdrawal of the lower drug dose the blood pressure remained for about 2 weeks at a level similar to the previous one, later on it increased steeply to the values observed in controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia.
This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.


Aluminum determination in whole blood, dialysis solution, and tap water samples from Maracaibo dialysis units (Venezuela) by graphite furnace atomic absorption spectrometry.
Patients with chronic renal failure (CRF) on periodical hemodialysis may accumulate aluminum in tissues and show typical disorders such as dialysis encephalopathy, osteodystrophy, and microcytic anemia. Aluminum contamination of the water used to prepare the dialysis solution (dialysate) is one of the metal sources that may affect people under hemodialysis, especially in units in which untreated water is used. Graphite furnace atomic absorption spectrometric methods for aluminum determination in whole blood, dialysis solution, and tap water samples from CRF patients were developed, based upon the use of the same furnace temperature program. Samples were diluted 4-fold with 0.6% triton X-100 (whole blood) or with 0.01 mol/L nitric acid (dialysis solution and tap water) and analyzed by aqueous standard (blood and tap water) or matrix-matching standard (dialysis solution) calibration curves. The characteristic masses were 33.8, 11.3, and 19.5 pg Al/0.0044 A.s for whole blood, dialysate, and tap water, respectively. In the diluted solutions, the detection limits (2 sigma) for the described methods were 0.5 microgram/L Al (whole blood), 0.4 microgram/L Al (dialysate), and 0.4 microgram/L Al (tap water). The methods were applied to samples from several CRF patients under hemodialysis at Maracaibo University hospital. The data revealed extremely high aluminum levels, which corresponded to the symptoms of dialysis encephalopathy and/or osteodystrophy showed by some of them. The proposed methods are reliable and reproducible.


Spectroscopic study of a UV-photostable organic-inorganic hybrids incorporating an Eu3+ beta-diketonate complex.
New europium and gadolinium tris-beta-diketonate complexes have been prepared and incorporated in sol-gel-derived organic-inorganic hybrids, named di-ureasils. The general formula [Ln(btfa)3(4,4'-bpy)(EtOH)] (Ln=Eu, Gd; 4,4'-bpy=4,4'-bipyridine; btfa=4,4,4-trifluoro-1-phenyl-1,3-butanedione) for the complexes was confirmed by X-ray crystallography and elemental analysis. The ground-state geometry of the Eu3+ complex was calculated from the Sparkle/AM1 model. The calculated quantum yield obtained from the Sparkle model and from the crystal structure (both 46%) are in satisfactory agreement with the experimental value (38+/-4%). In the isolated complex the most efficient luminescence channel is S0-->S1-->T-->(5D1, 5D0)-->7F0-6, where the exchange mechanism dominates in the energy-transfer channel T-->(5D1, 5D0). For the Eu3+-based di-ureasils a 50% quantum yield enhancement compared to the Eu3+ complex is observed, which suggests an effective hybrid host-metal ion interaction and an active energy-transfer channel between the hybrid host and the Eu3+ complex. The Eu3+-based di-ureasils are photostable under UVA (360 nm) excitation, whereas under UVB (320 nm) and UVC (290 nm) photodegradation occurs.


Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish.
Comprehension of compound interactions in mixtures is of increasing interest to scientists, especially from a perspective of mixture risk assessment. However, most of conducted studies have been dedicated to the effects on gonads, while only few of them were. interested in the effects on the central nervous system which is a known target for estrogenic compounds. In the present study, the effects of estradiol (E2), a natural estrogen, and genistein (GEN), a phyto-estrogen, on the brain ER-regulated cyp19a1b gene in radial glial cells were investigated alone and in mixtures. For that, zebrafish-specific in vitro and in vivo bioassays were used. In U251-MG transactivation assays, E2 and GEN produced antagonistic effects at low mixture concentrations. In the cyp19a1b-GFP transgenic zebrafish, this antagonism was observed at all ratios and all concentrations of mixtures, confirming the in vitro effects. In the present study, we confirm (i) that our in vitro and in vivo biological models are valuable complementary tools to assess the estrogenic potency of chemicals both alone and in mixtures; (ii) the usefulness of the ray design approach combined with the concentration-addition modeling to highlight interactions between mixture components.


[Adverse health effects of cadmium and related factors].
Cd is a very toxic chemical to animal and human beings. Cd contamination has been ubiquitous because of industry and the human activities. Cd not only affects adversely the growth, yield and quality of crops but also effects on the health of animal and human being. The damage of Cd on bone, kidney, liver, immune and procreation systems as well possible factors that influence Cd absorption, accumulation and damage in the body are summarized in this paper.


Coverage of ethics within the artificial intelligence and machine learning academic literature: The case of disabled people.
Disabled people are often the anticipated users of scientific and technological products and processes advanced and enabled by artificial intelligence (AI) and machine learning (ML). Disabled people are also impacted by societal impacts of AI/ML. Many ethical issues are identified within AI/ML as fields and within individual applications of AI/ML. At the same time, problems have been identified in how ethics discourses engage with disabled people. The aim of our scoping review was to better understand to what extent and how the AI/ML focused academic literature engaged with the ethics of AI/ML in relation to disabled people.Of the n = 1659 abstracts engaging with AI/ML and ethics downloaded from Scopus (which includes all Medline articles) and the 70 databases of EBSCO ALL, we found 54 relevant abstracts using the term "patient" and 11 relevant abstracts mentioning terms linked to "impair*", "disab*" and "deaf". Our study suggests a gap in the literature that should be filled given the many AI/ML related ethical issues identified in the literature and their impact on disabled people.


Community knowledge and perceptions on malaria prevention and house screening in Nyabondo, Western Kenya.
Screening of houses to prevent mosquito entry is increasingly being recommended as an effective and practical method against malaria transmission through reduced human-mosquito contact. The objective of the study was to assess community knowledge and perceptions on malaria prevention and house screening in a malaria endemic area of Western Kenya. A cross-sectional household survey was conducted in 2017 in Nyabondo area of western Kenya. A total of 80 households were randomly selected to participate in the study within 16 villages. Structured questionnaires, focus group discussions and key informant interviews were used to collect data. A total of 80 respondents participated in the survey and more than half (53.8%) reported to have attained primary education. About 91% of the respondents had previously seen or heard malaria messages and this was associated with the respondents level of education (χ2 = 10.163; df 4; P = 0.038, 95% CI). However, other variables like gender, marital status, religion and occupation were not significantly associated with knowledge in malaria. Insecticide treated mosquito nets was by far the most reported known (97.4%) and applied (97.6%) personal protective while only 15.6% respondents were aware of house screening. The major reason given for screening doors, windows and eaves was to prevent entry of mosquito and other insects (> 85%). Lack of awareness was the major reason given for not screening houses. Grey colour was the most preferred choice for screen material (48%), and the main reason given was that grey matched the colour of the walls (21%) and did not 'gather' dust quickly. House screening was not a common intervention for self-protection against malaria vectors in the study area. There is need to advocate and promote house screening to increase community knowledge on this as an additional integrated vector management strategy for malaria control.


Scleral fixation without conjunctival dissection.
Scleral fixation of intraocular lenses (IOLs) and adjunctive capsular devices can be performed under the protection of a scleral flap. A modification of this technique uses a scleral pocket initiated through a peripheral clear corneal incision. Full-thickness passage of a double-armed suture through the scleral pocket and conjunctiva, with subsequent retrieval of the suture ends through the external incision for tying, facilitates scleral fixation. This modification offers several advantages over traditional methods: It eliminates the need for conjunctival dissection and scleral cauterization; a scleral pocket affords a greater surface area for suture placement through an ab externo or ab interno approach; retrieval of the sutures through the external corneal incision and subsequent tying allows the suture knot to pass under the protective roof of the scleral pocket, negating the need for suture knot rotation; and the architecture of the scleral pocket eliminates the need for sutured wound closure. Suture retrieval and scleral fixation through a corneoscleral pocket offers a refined method for fixation of IOLs and other intraocular adjunctive devices.


Red eye and a rodent ulcer.
A 58-year-old woman presented with a 1-week history of poor vision in the right eye associated with a red eye. She was transferred for vitreoretinal management of suspected endophthalmitis. On examination, she had extensive ulceration of her forehead, exposing a pulsating mass covered with white antiseptic powder. The ulcer extended to involve the nose and right upper eyelid. Computed tomography demonstrated widespread erosion of the frontal bone, exposing the dura; histopathology confirmed the lesion to be basal cell carcinoma. The ulcer had slowly progressed for 30 years, but the patient was in denial about her condition. She had kept the ulcer well hidden by combing her hair forward over it. She was married, with an adult child, and was employed as a courier. Despite three assessments of her eye by medical staff in the preceding 24 hours, the diagnosis of the extensive basal cell carcinoma had been missed as she had refused to lift her hair for a complete examination.


Tantalum tracheography in upper airway obstruction: 100 experiences in adults.
A total of 100 tantalum cine laryngotracheograms were performed in adults with documented or suspected upper airway obstruction. With appropriate precautions, tantalum powder proved to be a safe material for delineating tracheal and laryngeal abnormalities. A cine recording to document tracheomalacia as well as a careful evaluation of the larynx are useful extensions of examination of patients with suspected upper airway obstruction. Tracheomalacia was found in 35% of our series; 29% showed laryngeal abnormalities. With modifications to correct for magnification, the tantalum tracheogram gives the surgeon the exact length of trachea to be resected. When tantalum becomes approved by the Food and Drug Administration, we expect that tantalum cine laryngotracheography will be the preferred means for study of upper airway obstruction.


[Combined use of microbiological methods for the intraspecific differentiation of Shigella sonnei. The use of the S. sonnei phage typing method in the People's Republic of Bulgaria].
The data on the use of the method for S. sonnei phage typing in Bulgaria during the period of 1973-1980 were analyzed. The comparative study with the use of two sets of phages (international and Bulgarian) were carried out. 9360 S. sonnei strains isolated in various districts of the country, mainly during epidemic outbreaks, were subjected to phage typing. 31 phage types corresponding to the international scheme were revealed; of these, 15 phage types could be subdivided into phage subtypes by means of Bulgarian phages. In systematic epidemiological study the combined use of both the sets of phages was shown to enhance the effectiveness of the method. The necessity of using, simultaneously with phage typing, the methods of biotyping, colicin and antibiotic typing, as well as the method of studying the properties of R-plasmids, is emphasized. This is based on the established correlation between different types and phage type changes occurring due to the action of R-plasmids.


High Expressed Emotion and Warmth among Families of Patients with Schizophrenia in Greece.
Expressed emotion (EE) is an established prognostic factor for relapse in schizophrenia. Through critical comments (CC), hostility (H) and emotional overinvolvement (EOI), a relative can be rated as high or low EE, but the role of warmth should also be evaluated in order to consider the influence of a positive affect within the family context. In this study, EE was assessed in a sample of 48 relatives of patients with schizophrenia using the Camberwell Family Interview (CFI). Questionnaires assessing coping (brief-COPE), their wellbeing (World Health Organization Well-Being Index WHO-5) and the socio-demographic variables were also administered. Relatives who expressed a higher level of warmth were found to make fewer CC (5.2 ± 4.6 vs. 8.4 ± 4.6, p = 0.009) and have, on average, higher EOI scores (3.2 ± 1.0 vs. 1.9 ± 1.1, p = 0.002) than those who expressed no or very little warmth. High EE was found to be associated with having fewer family members (p = 0.035), while relatives with a higher level of education expressed less warmth (p = 0.007). Relatives with a low level of warmth had higher maladaptive coping scores and tended to score worse for their overall wellbeing in comparison to relatives who showed a higher level of warmth (28.4 ± 5.0 vs. 24.1 ± 5.2, p = 0.006 and 39.1 ± 20.4 vs. 51.3 ± 22.0, p = 0.073, respectively). Since the role of warmth is important, it should be taken into account when designing family interventions, independently from lowering EE. Customized interventions to promote warmth and the routine screening of relatives are recommended.


[Application of multiple post labeling delay time arterial spin labeling imaging in the quantitative blood flow analysis of brain subregions in healthy adults].
Objective: To explore the normal ranges of perfusion parameters between cerebral hemisphere, cerebellar hemisphere and brain anatomical subregions (56 pairs) in different gender and age groups with multiple post labeling delay time (Multi-PLD) arterial spin labeling (ASL) imaging. Methods: From November 2020 to December 2020, 42 healthy adult volunteers (Male 25, Female 17) were recruited to perform 7 PLD ASL imaging, including 21 young adults (15 males and 6 females, aged 23-35 years) and 21 seniors (10 males and 11 females, aged 36-74 years). The data was processed offline by Cereflow software to obtain arterial arrival time (ATT) and corrected cerebral blood flow (CBF) and cerebral blood volume (CBV) perfusion parameters. SimpleITK standardization function was used to standardize the calculated perfusion image according to the anatomical automatic labeling (AAL) template. Therefore, CBF, ATT, CBV perfusion values of brain subregions were obtained. Paired samples t test, Wilcoxon rank sum test, independent samples t test and Mann-Whitney U test were used to compare the differences of perfusion parameters in the cerebral hemisphere, the cerebellar hemisphere, brain subregions depending on side, gender and age. Pearson correlation analysis was used to compare the correlations of perfusion parameters with age. Results: CBF in 62.5% (35/56) subregions and CBV in 44.6% (25/56) subregions were higher in right side than those in left side. ATT in most brain anatomical subregions (16/56) were higher in left side. The CBF [(35.30±8.31) vs. (34.34±7.53) ml·100g-1·min-1, P=0.021], CBV [(0.47±0.11) vs. (0.45±0.09) ml/100g, P<0.001], ATT [(1.30±0.10) vs. (1.24±0.11) s, P<0.001] in left cerebellar hemisphere were higher than that of right side. The CBF (28/56) of cerebral hemisphere, cerebellar hemisphere and brain subregions was higher in females than that in males, while ATT in 83.9% (47/56) subregions was lower than that in males (all P<0.05). CBV in female subjects was higher only in 5 brain regions (superior occipital gyrus, middle occipital gyrus, inferior occipital gyrus, superior parietal gyrus and cerebelum_7b) (all P<0.05). In young subjects, CBF in 44.6% (25/56) subregions and CBV in 33.9% (19/56) subregions were higher than those in the senior group (all P<0.05). The ATT in most subregions in young group were lower than those in senior group, but the difference was statistically significant only in rectus gyrus (P=0.026) and paracentral lobule (P=0.006). The CBF (r=-0.430, P=0.005) and CBV (r=-0.327, P=0.035) of cerebral hemisphere were negatively correlated with age. The CBF (24/25, r range:-0.497 --0.343, all P<0.05) and CBV (16/19, r range:-0.474 --0.322, all P<0.05) in most subregions were negatively correlated with age, while ATT was positively correlated (gyrus rectus: r=0.311, P=0.045; paracentral lobule: r=0.392, P=0.010). Conclusions: Multi-PLD ASL imaging could be applied for quantitative analysis of brain perfusion. The perfusion parameters of anatomical subregions are different depending on side, gender, and age.


Inhibitory effect of cholesteryl gamma-aminobutyrate on evoked activity in rat hippocampal slices.
Cholesteryl gamma-aminobutyrate (C-G) readily crosses the blood-brain barrier and has properties that suggest that it may be a potential gamma-aminobutyric acid (GABA)-mimetic compound. The effect of this compound on the orthodromically-evoked discharge of hippocampal pyramidal cells was investigated using slices of rat hippocampus maintained in vitro. The compound produced dose-dependent inhibition of the discharge of pyramidal cells. The magnitude of the inhibitory effect was somewhat less than that produced by a similar dose of GABA, but the duration of the inhibition was prolonged by about 10-fold over that produced by GABA. The inhibition produced by cholesteryl gamma-aminobutyrate was blocked by the addition of picrotoxin to the incubation medium, and by replacement of chloride with isethionate. In addition, pretreatment of slices with the irreversible esterase inhibitor, phenylmethylsulfonylfluoride, attenuated the effects of cholesteryl gamma-aminobutyrate, but not that of GABA. These results suggest that cholesteryl gamma-aminobutyrate has GABA-like actions in the CNS, and that its activity is largely dependent upon enzymatic release of GABA from the compound by esterases present in the tissue.


Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with cobas 4800 HPV and Hybrid Capture 2 tests for detection of high-grade lesions of the uterine cervix.
The triage of women with high-risk (HR) human papillomavirus (HPV)-positive smears for atypical squamous cells of undetermined significance (ASC-US) to colposcopy is now an integrated option in clinical guidelines. The performance of cobas 4800 HPV and that of Hybrid Capture 2 (HC2) for HR HPV DNA detection in cervical samples in PreservCyt were compared in 396 women referred to colposcopy for ASC-US. Of these, 316 did not have cervical intraepithelial neoplasia (CIN), 47 had CIN1, 29 had CIN2 or CIN3 (CIN2+), and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 149 (37.6%) samples with HC2 and cobas 4800 HPV, respectively (P = 0.15). The clinical sensitivities and specificities for detecting CIN2+ were 89.7% (95% confidence interval [CI], 72.8 to 97.2%) and 66.7% (95% CI, 61.7 to 71.3%) with cobas 4800 HPV and 93.1% (95% CI, 77.0 to 99.2%) and 72.2% (95% CI 67.4 to 76.5%) with HC2. The performance of cobas 4800 HPV was similar to that of HC2 for identifying women with ASC-US who would benefit the most from colposcopy.


[Endoparasites of calves in large herds].
The authors present preliminary results of the coprological examination of calves in large-capacity calf-houses. In a new large-capacity calf-house in the Benesov district in the Central-Bohemian region, 200 samples of faeces were examined according to Breza (1957) and further examinations were performed regularly in a group of 42 calves from the age of 0.5 to 6 months. The tests revealed 13 species of endoparasites, including eight species of coccidia: Eimeria auburnensis, E. alabamensis. E. bovis, E. cylindrica, E. elliposidalis, E. subspherica, E. zuernii, Isospora spp., and five species of helminths: Strongyloides papillosus, Oesophagostomum radiatum, Trichocephalus ovis, Cooperia spp., and Ascaris suum. The following conclusions were derived from these findings: 1. The calves may carry the germs of coccidia and helminths on their hooves already during transportation to the new calf-house; 2. twelve- to twenty-day-old calves, coming to the calf-houses, are often already attacked by several species of coccidia and helminths; 3. the number of parasite species increases and the extensity of invasion rises with age; 4. it has been demonstrated that the invasion process of eight species of coccidia and five species of worms can take place under the conditions of modern calf-house; 5, stronglyloidosis, oesophagostomosis, and trichocephalosis can be treated as typical stable helminthoses; 6. some other speceis of helminths and coccidia occur in calves after transition to green forage with which they are probably carried to the calf-house.


Brain-bladder control network: the unsolved 21st century urological mystery.
A review of functional brain imaging studies of bladder control in participants with normal control and pathological conditions. In the normal condition, bladder and urethral afferents received in the periaqueductal gray relay the information to the insula, the anterior cingulate cortex and the prefrontal cortex. During the storage phase, these superior regions control the pontine micturition center to inhibit voiding. In overactive bladder patients, brain responses are different. Cortical responses become exaggerated, especially in the anterior cingulate cortex and the supplementary motor area. That is what presumably evokes the "urgency". The supplementary motor area is activated during contraction of the pelvic floor muscles, and provides protection against incontinence. We believe that functional brain imaging studies are promising not only for the understanding of bladder dysfunction, but also as an aid to the development of therapeutic options for chronic disorders.


Age and sex specific target of blood pressure for the prevention of cardiovascular event among the treatment naive hypertensive patients.
The time at which hypertension treatment should be initiated for different age groups and sexes remains controversial. We aimed to determine whether the association between blood pressure (BP) and major adverse cardiovascular events (MACE) varies with age and sex. This study enrolled 327,328 subjects who had not taken antihypertensive medication in the Korean National Health Service-National Health Screening Cohort between 2002 and 2003. Participants were categorized into four groups according to 2017 American College of Cardiology/American Heart Association hypertension guideline. Primary outcome was MACE characterized by cardiovascular mortality, myocardial infarction, unstable angina, and stroke. During a 10-year follow-up, a significant increase in MACE risk was observed from the stage 1 hypertension group (hazard ratio [HR], 1.23; 95% CI 1.15-1.32; P < 0.001) in time-varying Cox analysis. This relationship was persistent in subjects aged < 70 years, but increased MACE risk was observed only in the stage 2 hypertension group in ≥ 70 years (HR, 1.52; 95% CI 1.32-1.76, P < 0.001). When categorized as per sex, both men and women showed significant MACE risk from stage 1 hypertension. However, on comparing the sexes after stratifying by age, a significantly increased risk of MACE was shown from stage 1 hypertension in men aged < 50 years, but from stage 2 hypertension in men aged ≥ 50 years. Meanwhile, increased MACE risk was observed from stage 2 hypertension in women aged < 60 years, but from stage 1 hypertension in women aged ≥ 60 years. Thus, young male subjects had higher MACE risk than young female subjects, but this difference gradually decreased with age and there was no difference between sexes in subjects aged ≥ 70 years. Therefore, our results suggest that hypertension treatment initiation may need to be individualized depending on age and sex.


Congenital hypothyroidism in Calabria: epidemiological and clinical aspects.
Neonatal screening of congenital hypothyroidism (CH), carried out on all newborns 3rd -5th day of life, has a very important priority because the incidence of this disease is the highest of all congenital diseases involving brain damage which can be preventable with early specific treatment. In recent years, the values of TSH that were considered pathological were modified and the TSH cut-off, the title of hormone to be taken as the limit of significance for determining a subject suffering from CH, has been progressively lowered. In Calabria the introduction of the new value of TSH cut-off on blood spot, has led to a considerable increase in the frequency of CH, particularly in the case of the thyroid in situ normal ultrasound and of the diagnosis of transitional forms of CH.


Synthesis and magnetic properties of Gd doped EuS nanocrystals with enhanced Curie temperatures.
EuS nanocrystals (NCs) were doped with Gd resulting in an enhancement of their magnetic properties. New EuS and GdS single source precursors (SSPs) were synthesized, characterized, and employed to synthesize Eu(1-x)Gd(x)S NCs by decomposition in oleylamine and trioctylphosphine at 290 °C. The doped NCs were characterized using X-ray diffraction, transmission electron microscopy, and scanning transmission electron microscopy, which support the uniform distribution of Gd dopants through electron energy loss spectroscopy (EELS) mapping. X-ray absorption spectroscopy (XAS) revealed the dopant ions in Eu(1-x)Gd(x)S NCs to be predominantly Gd(3+). NCs with a variety of doping ratios of Gd (0 ≤ x < 1) were systematically studied using vibrating sample magnetometry and the observed magnetic properties were correlated with the Gd doping levels (x) as quantified with ICP-AES. Enhancement of the Curie temperature (T(C)) was observed for samples with low Gd concentrations (x ≤ 10%) with a maximum T(C) of 29.4 K observed for NCs containing 5.3% Gd. Overall, the observed T(C), Weiss temperature (θ), and hysteretic behavior correspond directly to the doping level in Eu(1-x)Gd(x)S NCs and the trends qualitatively follow those previously reported for bulk and thin film samples.


Induction of nephroblastoma-like renal tumours in rats by a single dose of 1,2-dimethylhydrazine.
A single injection of 1,2-dimethylhydrazine (200 mg/kg s.c.) resulted in the development of renal tumours in 70 per cent of treated rats within 1 year. The tumours were frequently bilateral (36 per cent) and grew to a large size (up to 100 g) before causing death. Lung metastases were found in one case. Histologically, the majority of the tumours (73 per cent) exhibited the classical triphasic morphological features of nephroblastoma (Wilms' tumour) with varying proportions of epithelial (glomeruloid and tubular structures), stromal (fibrous tissue, smooth muscle, cartilage) and blastematous elements. This pathological resemblance to human nephroblastoma suggests the possibility of using dimethylhydrazine-induced renal tumours as a model of Wilms' tumour.


Differential expression of surface membrane growth hormone receptor on human peripheral blood lymphocytes detected by dual fluorochrome flow cytometry.
Although several reports indicate proliferative and functional effects of human GH (hGH) on peripheral blood lymphocytes (PBL), no information is available about hGH receptor (GHR) expression in PBL subsets. Here, the surface membrane GHR levels were investigated in different human PBL subpopulations using a fluorescein isothiocyanate (FITC)-conjugated monoclonal antibody specific for the GHR (mAb263) in dual fluorochrome flow cytometric assays. Strong GHR expression was found in B-cells (CD20+), whereas CD2+ lymphocytes, including T-cells as well as natural killer cells, exhibited considerably lower levels of receptor expression. Similarly, using FITC-labeled recombinant hGH, receptor expression on CD20+ cells was significantly higher than that on CD2+ cells. Abundant expression of GHR in B-lymphocytes was confirmed by reverse transcriptase-polymerase chain reaction analysis of GHR messenger ribonucleic acid from isolated B-cells. Accordingly, the B-cell merits greater consideration as a GH target cell. The use of FITC-labeled mAb263 and hGH is of potential use for the study of GHR levels in patients exhibiting different types of growth disorders. Because of its high specificity for GHR, FITC-labeled mAb263 is also of considerable value for specifically demonstrating the presence of GHR, because hGH may interact with and act through PRL receptor, as shown previously in human neutrophils.


[When does an autoimmune disease begin? Importance of the early diagnosis].
In autoimmune diseases, such as type I diabetes mellitus, systemic autoimmune diseases and the early phase of rheumatoid arthritis, before the development of a definitive disease, clinical and laboratory alterations can be observed. Being aware of these symptoms is crucial both for family practitioners and specialists, handling autoimmune and early arthritis patients. The early recognition and prognosticating of the disease and sending the patient immediately to a specialist will lead to the exponential improvement of the patient's life expectancies and will also help to avoid complications. The need for special diagnostics, care and treatment made the development of national immunological and rheumatological centers imperative, where sufficient experience and professional knowledge helps the proper medical attendance.


Roy's adaptation model: a guide for rehabilitation nursing practice.
Roy's Adaptation Model provides a framework for holistic rehabilitation nursing practice. In this article, the model is applied to a rehabilitation patient with a spinal cord injury for the assessment of behaviors and stimuli influencing the behaviors and also for planning and evaluating nursing care.


[Methods of estimating concentration of the D-dimers used in venous thromboembolism diagnosis].
D-dimers (DD) are final products of stabilized fibrin degradation process. Elevated level of DD indicates parallel activation of both coagulation and fibrinolysis. D-dimers play important role in the diagnosis of deep vein thrombosis and pulmonary embolism. All diagnostic methods detecting DD are based on monoclonal antibodies. There are three basic techniques used to measure DD: latex agglutination, full blood agglutination and immunoenzymatic methods. Nowadays new methods based on in vivo detection of DD using antibodies labeled with technetium are under clinical evaluation.


Multispectral Live-Cell Imaging.
Fluorescent proteins and vital dyes are invaluable tools for studying dynamic processes within living cells. However, the ability to distinguish more than a few different fluorescent reporters in a single sample is limited by the spectral overlap of available fluorophores. Here, we present a protocol for imaging live cells labeled with six fluorophores simultaneously. A confocal microscope with a spectral detector is used to acquire images, and linear unmixing algorithms are applied to identify the fluorophores present in each pixel of the image. We describe the application of this method to visualize the dynamics of six different organelles, and to quantify the contacts between organelles. However, this method can be used to image any molecule amenable to tagging with a fluorescent probe. Thus, multispectral live-cell imaging is a powerful tool for systems-level analysis of cellular organization and dynamics. © 2018 by John Wiley & Sons, Inc.


Assessment of bone marrow involvement in patients with lymphoma: report on a consensus meeting of the Korean Society of Hematology Lymphoma Working Party.
In September 2011, the Korean Society of Hematology Lymphoma Working Party held a nationwide conference to establish a consensus for assessing bone marrow (BM) involvement in patients with lymphoma. At this conference, many clinicians, hematopathologists, and diagnostic hematologists discussed various topics for a uniform consensus in the evaluation process to determine whether the BM is involved. Now that the discussion has matured sufficiently to be published, we herein describe the consensus reached and limitations in current methods for assessing BM involvement in patients with lymphoma.


A comparison of nasal clearance after treatment of perennial allergic rhinitis with budesonide and mometasone.
Evidence in vitro suggests that benzalkonium chloride, a preservative in many intranasal preparations, interferes with ciliary function and thus could potentially interfere with mucociliary transport, the mechanism for clearing secretions from the nasal cavity. We performed a parallel randomized study with 10 subjects in each arm comparing Rhinocort AQUA (an intranasal steroid [budesonide] spray without benzalkonium chloride) and Nasonex (an intranasal steroid [mometasone furoate] spray with benzalkonium chloride). Before and after 2 weeks of treatment, subjects completed a Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and underwent a measurement of nasal clearance of a radioactive colloidal spray into the nose. The groups were matched at entry for nasal clearance, even though there was variability among subjects. The amount of change after 2 weeks of treatment (Delta before versus after treatment) showed a significant difference in nasal clearance favoring budesonide. After 2 weeks of treatment, both budesonide and mometasone demonstrated overall improvement in quality of life as assessed by the RQLQ. Both treatments were well tolerated. Our study extends the observation in vitro that demonstrates the adverse effect of benzalkonium chloride on cilia to a measurement in vivo of clearance. The effects after 2 weeks might not reflect changes after longer periods of treatment. To determine the clinical significance of the small improvement in mucociliary transport will require large clinical trials.


Cost-effectiveness of insulin detemir: a systematic review.
The prevalence of diabetes and cost of associated treatment are steadily increasing, as is the resulting burden on healthcare systems worldwide. Current treatment recommendations for Type 1 and Type 2 diabetes advise a prominent role for basal insulin. We examined the published health-economic literature pertaining to the basal insulin analog insulin detemir (IDet) to determine whether IDet is a cost-saving and/or cost-effective treatment for suboptimally controlled Type 1 or Type 2 diabetes. A total of 15 modeling studies were assessed, most of which found IDet to be cost effective compared with neutral protamine Hagedorn and as cost effective as insulin glargine. Those that did not find IDet to be cost effective set the disutility of hypoglycemic events to almost zero or assumed a higher dose of IDet with no difference in treatment effect, ignoring the clinical benefits and cost savings associated with IDet in studies demonstrating comparable or superior glycemic control with less hypoglycemia versus other basal insulins. The evidence suggests that IDet is cost effective versus neutral protamine Hagedorn and at least as cost effective as insulin glargine in the treatment of patients with suboptimally controlled Type 1 and Type 2 diabetes.


Preventing tobacco in vocational high schools: study protocol for a randomized controlled trial of P2P, a peer to peer and theory planned behavior-based program.
In France, the issue of youth smoking remains a major challenge for public health. School failure, socio-economic and socio-cultural backgrounds influence the initiation and maintenance of smoking behavior in adolescents. Vocational students are at particularly high risk of using psychoactive substances, including tobacco. One of the most important factors is the environment, whether family, friends or peers. Therefore, peer education has a positive potential to change smoking behavior of adolescents. It has also been demonstrated that the Theory of Planned Behavior (TPB) has yielded the best prediction of intentions and behavior, in several health domains, including on tobacco. However, it is usually confined to the measurement of processes by which interventions change behavior, rather than to the development of these interventions. The objective of this paper is to describe the protocol for a randomized controlled trial of a peer intervention based on the TPB on a highly exposed young population. This is a cluster randomized controlled trial comparing an intervention group to a control group, randomized into clusters (professional schools and classes) and stratified in three departments (Hérault, Aude and Gard) in the Languedoc-Roussillon region. The primary issue is the prevalence of daily smoking at 24 months, defined by a daily tobacco use of at least 1 cigarette, validated by CO levels in exhaled air. The primary hypothesis is that intervention will lead to decrease the daily smoking prevalence of 10% between the intervention group and the control group during a 2-year follow-up. The results from this trial will provide evidence on the effectiveness of an innovative peer-to-peer intervention based on the TPB. ISRCTN: 37336035 , Retrospectively registered 11/12/2015.


Effect of nanometric grain size on electronic-transport, magneto-transport and magnetic properties of La(0.7)Ba(0.3)MnO(3) nanoparticles.
We have investigated the effect of nanometric grain size on electronic-transport, magneto-transport and magnetic properties of single-phase La(0.7)Ba(0.3)MnO(3) (LBMO) nanoparticles having an average grain size in the nanometric regime (21-35 nm). We have observed that both the metal-insulator transition temperature (T(P)) and para-ferromagnetic transition temperature (T(C)) shift to lower temperature with a decrease in average grain size. For the entire series of samples, a distinct minima in resistivity at a temperature (T(min)) followed by an upturn at a very low temperature (≤47 K) is observed. We have attributed the steeper low temperature (∼47 K) resistivity upturn in the smaller grain size sample than that in the larger grain size sample below T(min) to the increased value of charging energy (E(C)). E(C) has been estimated to be 1.3, 0.56 and 0.04 K for an average grain size of 21, 25 and 30 nm, respectively. Magneto-transport measurements show that the magnitude of low field MR (LFMR) varies with average grain size. In order to investigate the MR behavior of LBMO nanoparticles, we have analyzed our data in the light of a phenomenological model, based on spin-polarized transport of conduction electrons at the grain boundaries. Magneto-transport measurements show that the magnitude of low field MR (LFMR), as well as of high field MR (HFMR), remains constant up to sufficiently high temperature (∼50 K) and then drops sharply with temperature. We found that this strange temperature dependence of MR is decided predominantly by the nature of the temperature response of the surface magnetization (M(S)) of nanosized magnetic particles.


Endogenous nitric oxide causes vasodilation in rat bone marrow, bone, and spleen during accelerated hematopoiesis.
There is a marked increase in blood flow to rat bone marrow during increased erythro- or granulopoiesis. Furthermore, stimulated erythropoiesis increases bone and splenic perfusion, whereas granulopoietic hyperactivity does not. The mechanism behind this hyperemia is unknown. Endogenous nitric oxide (NO) has been shown to be a potent vasodilator in many vascular beds, but its possible role in the regulation of bone marrow, bone, and spleen vascular resistance and perfusion has not been explored. With the radioactive microsphere method, we determined blood flow to bone marrow, bone, and spleen in awake rats. Eight rats were bled heavily (1.5% of body weight), eight others received 10 micrograms/kg recombinant human granulocyte colony-stimulating factor (rhG-CSF) subcutaneously, and eight other untreated rats served as controls. We used 300 micrograms/kg, intraaortal, of the potent NO synthase blocker N-monomethyl-L-arginine (L-NMMA) (Calbiochem, La Jolla, CA). The inhibition of NO formation was subsequently reversed with 1000 mg/kg intraaortal arginine. Marrow vascular resistance was reduced to approximately 30% of control baseline in the experimental rats 10 hours after hematopoietic stimulation with either bleeding or rhG-CSF. Concomitantly, marrow blood flow increased to about 260% of control baseline in the bled rats, while it almost tripled after rhG-CSF injection. Inhibition of NO formation increased marrow vascular resistance in all three groups. After L-NMMA treatment, marrow perfusion was reduced to about 50% of baseline in the bled and 75% in the rhG-CSF-treated rats, while perfusion in the controls remained apparently unaltered. These changes were completely reversed with arginine. The increases in vascular resistance after NO blockade could not be explained by a concomitant change in arterial blood pressure. L-NMMA increased the vascular resistance in the bone and spleen both in controls and in stimulated rats, but since arterial blood pressure rose proportionally, perfusion remained unchanged. We conclude that NO plays an important role in the regulation of both the normal bone marrow vascular tone and the vasodilation that occurs during accelerated hematopoiesis. NO apparently also regulates bone and splenic vascular tone, but less conspicuously than in the stimulated bone marrow.


The Usage of an SNP-SNP Relationship Matrix for Best Linear Unbiased Prediction (BLUP) Analysis Using a Community-Based Cohort Study.
Best linear unbiased prediction (BLUP) has been used to estimate the fixed effects and random effects of complex traits. Traditionally, genomic relationship matrix-based (GRM) and random marker-based BLUP analyses are prevalent to estimate the genetic values of complex traits. We used three methods: GRM-based prediction (G-BLUP), random marker-based prediction using an identity matrix (so-called single-nucleotide polymorphism [SNP]-BLUP), and SNP-SNP variance-covariance matrix (so-called SNP-GBLUP). We used 35,675 SNPs and R package "rrBLUP" for the BLUP analysis. The SNP-SNP relationship matrix was calculated using the GRM and Sherman-Morrison-Woodbury lemma. The SNP-GBLUP result was very similar to G-BLUP in the prediction of genetic values. However, there were many discrepancies between SNP-BLUP and the other two BLUPs. SNP-GBLUP has the merit to be able to predict genetic values through SNP effects.


Role of renal microcirculation in experimental renovascular disease.
Renal artery stenosis (RAS) causes renal injury partly via microvascular (MV) endothelial dysfunction and damage. Vascular endothelial growth factor (VEGF) is crucial for preservation of microvasculature and promotes vascular proliferation and endothelial repair. We have previously shown that MV rarefaction is associated with decreased VEGF in the kidney exposed to chronic RAS, accompanied by deteriorated renal function and fibrosis. We hypothesized that preserving the renal microcirculation in the stenotic kidney will halt the progression of renal damage. Unilateral RAS was induced in 16 pigs. In eight, VEGF (0.05 micrograms/kg) was infused intra-renally at the onset of RAS. After 6 weeks, single-kidney haemodynamics and function were assessed using in vivo multi-detector computed tomography (CT). Renal microvessels, angiogenic pathways and morphology were investigated ex vivo using micro-CT, real-time PCR and histology. Blood pressure and degree of RAS was similar in RAS and RAS + VEGF pigs. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in RAS compared to Normal (221.1 +/- 46.5 and 29.9 +/- 3.8 vs. 522.5 +/- 60.9 and 49.3 +/- 3.4 mL/min, respectively, P < 0.05), accompanied by decreased cortical MV density and increased renal fibrosis. Pre-emptive administration of VEGF preserved MV architecture, attenuated fibrosis and normalized RBF and GFR (510.8 +/- 50.9 and 39.9.1 +/- 4.1 mL/min, P = not significant vs. Normal). This study underscores the importance of the renal microcirculation in renovascular disease. Intra-renal administration of VEGF preserved renal MV architecture and function of the stenotic kidney, which in turn preserved renal haemodynamics and function and decreased renal fibrosis. These observations suggest that preventing renal MV loss may be a potential target for therapeutic approaches for patients with chronic renovascular disease.


Reduction of spherical and chromatic aberration in axial-scanning optical systems with tunable lenses.
Optical systems with integrated tunable lenses allow for rapid axial-scanning without mechanical translation of the components. However, changing the power of the tunable lens typically upsets aberration balancing across the system, introducing spherical and chromatic aberrations that limit the usable axial range. This study develops an analytical approximation for the tuning-induced spherical and axial chromatic aberration of a general optical system containing a tunable lens element. The resulting model indicates that systems can be simultaneously corrected for both tuning-induced spherical and chromatic aberrations by controlling the lateral magnification, coma, and pupil lateral color prior to the tunable surface. These insights are then used to design a realizable axial-scanning microscope system with a high numerical aperture and diffraction-limited performance over a wide field of view and deep axial range.


Frequencies of the MEFV Gene Mutations in Azerbaijan.
The MEFV (familial Mediterranean fever gene) researches were performed in the population of the Republic of Azerbaijan in 2016-2021. Seven mutations of the MEFV gene were identified in heterozygous, homozygous and compound homozygous conditions: R761H, M694I, M694V, V726A, R202Q, M680I and E148Q. The E148Q and R202Q mutations were discovered in exon 2 and R761H M694I, M694V, V726A, M680I were found in exon 10 in the population of the Republic of Azerbaijan. The highest gene frequency of the MEFV gene examined in 42 patients was 42.85% in the M694V mutations. The second highest frequency was the R761H and the third most frequent mutation was V726A. According to world literature, five mutations, M694V, V726A, M694I, R202Q, M680I and E148Q, constitute 75.0% of all mutations found today. In our studies, these five mutations belong to the same group, and makes up 57.6% of the total mutations found. In order to prevent hereditary disease such as the familial Mediterranean fever (FMF) in the population of the Republic of Azerbaijan, it is planned to carry out prenatal diagnosis (PND) of the at-risk families.


Comparative Study of Relative-Pose Estimations from a Monocular Image Sequence in Computer Vision and Photogrammetry.
Techniques for measuring the position and orientation of an object from corresponding images are based on the principles of epipolar geometry in the computer vision and photogrammetric fields. Contributing to their importance, many different approaches have been developed in computer vision, increasing the automation of the pure photogrammetric processes. The aim of this paper is to evaluate the main differences between photogrammetric and computer vision approaches for the pose estimation of an object from image sequences, and how these have to be considered in the choice of processing technique when using a single camera. The use of a single camera in consumer electronics has enormously increased, even though most 3D user interfaces require additional devices to sense 3D motion for their input. In this regard, using a monocular camera to determine 3D motion is unique. However, we argue that relative pose estimations from monocular image sequences have not been studied thoroughly by comparing both photogrammetry and computer vision methods. To estimate motion parameters characterized by 3D rotation and 3D translations, estimation methods developed in the computer vision and photogrammetric fields are implemented. This paper describes a mathematical motion model for the proposed approaches, by differentiating their geometric properties and estimations of the motion parameters. A precision analysis is conducted to investigate the main characteristics of the methods in both fields. The results of the comparison indicate the differences between the estimations in both fields, in terms of accuracy and the test dataset. We show that homography-based approaches are more accurate than essential-matrix or relative orientation-based approaches under noisy conditions.


Congenital Pseudarthrosis of the Tibia: Results, at Skeletal Maturity, of the Charnley-Williams Procedure.
This study assessed the outcomes, at skeletal maturity, for 34 patients in whom congenital pseudarthrosis of the tibia (CPT) had been treated with intramedullary (IM) rod fixation. The results in skeletally mature patients in whom type-4 CPT had been treated with an IM rod at an average of 11.9 years earlier were reviewed. The rod procedures varied according to whether both the tibia and the fibula were resected and both bones (type A) or just the tibia (type B) were fixed with an IM rod or whether only the tibia was resected and the fibula received no surgery (type C). Outcome grading ranged from unequivocal union with brace-free function (grade 1) to a functional limb with residual angulation or cortical defects (grade 2) to a severely impaired extremity with insufficient union or refracture (grade 3). Thirty-four patients were evaluated at a mean age of 16.9 years, a mean of 11.9 years after their initial surgical procedure. Seventeen patients had a grade-1 result; 11 patients, grade 2; and 6, grade 3. Thus, 82% (28) of the 34 patients had a functional extremity at maturity. All patients with a final grade-3 outcome eventually requested amputation. The final outcomes were not affected by the age at the initial fracture or surgery, the presence of neurofibromatosis-1, or cross-ankle fixation. A total of 58 IM rod procedures were performed in the 34 patients. Twenty-four (73%) of the 33 type-A procedures produced grade-1 or 2 outcomes, as did 14 (88%) of the 16 type-B procedures. Of the 9 type-C procedures, none produced a grade-1 result and 4 produced a grade-2 outcome. The results of types A and B combined were superior to those of type-C procedures (p = 0.03). Refracture occurred in 13 of 33 patients with initial stability/union after rod fixation, with 3 of those fractures remaining ununited at the latest follow-up. A dystrophic fibula had no effect on the eventual achievement of a grade-1 or 2 outcome. This review, in which all patients had reached skeletal maturity, documents functional (grade-1 or 2) outcomes in 82% of cases of IM rod fixation for CPT. This finding was almost identical to the result in our earlier report and confirms the long-term value of permanent IM rod fixation in maintaining union and function in patients with CPT. Procedures not addressing the fibula produced inferior results. Although 13 patients had a refracture following initial union, only 3 of these fractures failed to heal with additional treatment. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Cooperative Fusion Based Passive Multistatic Radar Detection.
Passive multistatic radars have gained a lot of interest in recent years as they offer many benefits contrary to conventional radars. Here in this research, our aim is detection of target in a passive multistatic radar system. The system contains a single transmitter and multiple spatially distributed receivers comprised of both the surveillance and reference antennas. The system consists of two main parts: 1. Local receiver, and 2. Fusion center. Each local receiver detects the signal, processes it, and passes the information to the fusion center for final detection. To take the advantage of spatial diversity, we apply major fusion techniques consisting of hard fusion and soft fusion for the case of multistatic passive radars. Hard fusion techniques are analyzed for the case of different local radar detectors. In terms of soft fusion, a blind technique called equal gain soft fusion technique with random matrix theory-based local detector is analytically and theoretically analyzed under null hypothesis along with the calculation of detection threshold. Furthermore, six novel random matrix theory-based soft fusion techniques are proposed. All the techniques are blind in nature and hence do not require any knowledge of transmitted signal or channel information. Simulation results illustrate that proposed fusion techniques increase detection performance to a reasonable extent compared to other blind fusion techniques.


Acute pancreatitis in a patient with familial benign hypercalcaemia.
A patient with familial benign hypercalcaemia (FBH) who developed relapsing pancreatitis is presented. She underwent distal partial pancreas resection with surgical removal of pancreatic duct stones, and a pancreaticojejunostomy. No further causes for the pancreatitis were found. The present case is remarkable since it is an example of the occurrence of pancreatitis in a previously known patient with hypercalcaemia, and it underlines the severity of the pancreatitis when it occurs in this syndrome.


Substance use among a sample of foreign- and U.S.-born southeast Asians in an urban setting.
Asian Americans (AA) are thought to have the lowest rates of substance use. This study examined substance use prevalence among 494 urban-dwelling Southeast Asians using snowball techniques. Prevalence estimates were age-adjusted proportionate to the U.S. Asian population. Findings show beer and alcohol consumption approximated the national percentage among 25-44 year olds. U.S.-born were about three times likelier to have past month substance use. Foreign-born Vietnamese were likelier than U.S.-born to use all substances except for beer. U.S.- and foreign-born beer consumption rates were similar. Future research is needed to delineate substance use determinants and patterns in foreign and U.S.-born AA sub-groups.


Preparation and standardization of a herbal agent for the therapeutic management of asthma.
This study aims to develop a suitable single tablet dosage form containing a mixture of hot water stem back extracts of Anogeissus leiocarpus and Prosopis africana (AA1), suitable for use in the therapeutic management of asthma. The compaction characteristics of the oven-dried hot water extract (HWE) were studied using the Heckel equation. The mechanical properties as well as disintegration and dissolution profile of the compacts were also assessed. The results showed that AA1 exhibited high densification due to dye filling while the subsequent rearrangement of the granules did not contribute, significantly, to their densification. The granules had enhanced plasticity as shown by the low yield point, Py. The tablets produced from the extract had good mechanical properties, with hardness increasing with compression pressure while the friability decreased. Of the four disintegrants tested, tablets containing Explotab had the shortest disintegration time of 11 min while tablets containing Prosolv had the longest disintegration time of 40 min. The order of disintegrant property is Explotab > Cellactose > Emcocel > Maize starch > Prosolv. Dissolution results (t(90%)) show that tablets containing Explotab released 100% of the drug in 20 min proving to be the most suitable in acute asthma attack. The order of dissolution is Explotab > Cellactose > Maize starch > Prosolv > Emcocel. It is concluded that incorporation of Explotab (10%w/w) as a disintegrant in AA1 preparation produced tablets of suitable compressional properties and ensured adequate drug release for the management of acute asthma.


[An adaptation of the CLAVIENDINDO classification of complications for contact ureterolithot- ripsy].
to study an adaptability of the Clavien-Dindo classification of complications for contact ureterolithotripsy. A total of 506 patients with ureteric stones who were undergone 545 endoscopic interventions in the Urologic Department of "MONIKI" named after M.F. Vladimirsky were included in retrospective analysis. Complications of grade 1, II, IIIa and IIIb were noted in 39 (7.1%), 24 (4.3%), 15 (2.8%) and 14 cases (2,6%), respectively. Among the complications of grade IVa, an acute pyelonephritis was complicated by the septic shock. The complication of grade IVb developed in 1 case (0.2%). There were no complications of Grade V. The Clavien-Dindo classification allows to grade only postoperative complications and attempts to adapt it for the assessment of intraoperative complications can lead to the distortion of study results. The uncontrolled use of the Clavien-Dindo classification in all areas of surgery can lead to a decrease in its accuracy, thereby reducing its value as fairly universal tool. In our opinion, a further work aimed to the development of strict criteria for the different grades of complications of the Clavien-Dindo classifications is needed. We believe it is possible and necessary to develop a single tool for the assessment of complications of typical interventions within a single surgical area.


Limited costs of wrong root placement in Rumex palustris in heterogeneous soils.
Nutrient hot spots in the soil have a limited life span, but the costs and benefits for root foraging are still underexposed. We assessed short-term costs that may arise when a nutrient-rich patch induces root proliferation, but then rapidly disappears. Rumex palustris plants were grown with a homogeneous or a heterogeneous nutrient application. After root proliferation in a nutrient-rich patch, nutrient supply was switched from homogeneous to heterogeneous, and vice versa, or the patch location was changed. R. palustris proliferated its roots in the rich patch. After switching, the relative growth rates of the roots were adjusted to the novel pattern of nutrient availability. However, the changes in local root biomass lagged behind the rapid shift in nutrient supply, because the root mass realized in specific sectors could not be rapidly relocated. Despite this, R. palustris did not exhibit costs of switching in terms of biomass or nitrogen uptake. Our data suggest that rapid shifts in uptake rate and redistribution of nitrogen within the plant may have lowered the costs of incorrect root placement.


Direct repeat-mediated deletion of a type IV pilin gene results in major virulence attenuation of Francisella tularensis.
Francisella tularensis, the causative agent of tularaemia, is a highly infectious and virulent intracellular pathogen. There are two main human pathogenic subspecies, Francisella tularensis ssp. tularensis (type A), and Francisella tularensis ssp. holarctica (type B). So far, knowledge regarding key virulence determinants is limited but it is clear that intracellular survival and multiplication is one major virulence strategy of Francisella. In addition, genome sequencing has revealed the presence of genes encoding type IV pili (Tfp). One genomic region encoding three proteins with signatures typical for type IV pilins contained two 120 bp direct repeats. Here we establish that repeat-mediated loss of one of the putative pilin genes in a type B strain results in severe virulence attenuation in mice infected by subcutaneous route. Complementation of the mutant by introduction of the pilin gene in cis resulted in complete restoration of virulence. The level of attenuation was similar to that of the live vaccine strain and this strain was also found to lack the pilin gene as result of a similar deletion event mediated by the direct repeats. Presence of the pilin had no major effect on the ability to interact, survive and multiply inside macrophage-like cell lines. Importantly, the pilin-negative strain was impaired in its ability to spread from the initial site of infection to the spleen. Our findings indicate that this putative pilin is critical for Francisella infections that occur via peripheral routes.


Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope.
We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein269-277 epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A∗02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as "variants of concern," was not recognized by the large CD8 T cell response seen across cohorts of HLA A∗02+ convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.


Dual lesion margins on fundus autofluorescence associated with paradoxical worsening following treatment for tubercular serpiginous-like choroiditis.
A 31-year-old male presented with decreased vision in the right eye associated with an active plaque-like serpiginoid choroiditis. The lesion showed a unique feature of dual margins of hyperautofluorescence of the lesion on fundus autofluoresence (FAF) imaging. Systemic investigations suggested a tubercular etiology. He was started on antitubercular treatment and a conventional dose of oral corticosteroids (1mg/kg body weight). However, the lesions showed paradoxical worsening and required increased immunosuppression in the form of local steroids and oral immunomodulators. The presence of dual margins of hyperautofluorescence could suggest increased inflammatory activity leading to paradoxical worsening on treatment requiring increased immunosuppression.


Bis(meta-phenylene)-32-crown-10-based cryptand/diquat inclusion [2]complexes.
Bis(meta-phenylene)-32-crown-10-based cryptands have been proved to complex diquat much more strongly than bis(meta-phenylene)-32-crown-10 itself; in fact, one containing a pyridyl moiety has one of the highest Ka values yet reported.


Robot-Assisted Surgery for Endometriosis Current and Future Perspectives.
Successful resection of all visible lesions may effectively treat endometriosis-related infertility and pelvic pain. Minimally invasive surgery provides significant advantages, with lower rates of surgical complications such as surgical trauma, infection, postoperative pain, and hospital stay. Robotic surgery is shown to have similar perioperative outcomes to conventional laparoscopy; however, complex stage III and IV endometriosis, especially cases requiring significant resection such as deep infiltrating endometriosis, widespread peritoneal implants, and urologic and intestinal involvement, may benefit most from a robotic approach. There are certain aspects of endometriosis surgery where utilization of robotic technology might provide an additional benefit. These include (1) heterogeneity of lesions, and thus difficulty in identification; (2) difficulty in accurately predicting surgical complexity; and (3) prolonged operative time for complex cases. The objective of this review is to describe the current and future perspectives of robotic surgery as it pertains to endometriosis.


Food choices of young African-American and Latino adolescents: where do parents fit in?
To gain insight into parents' perceptions of the food preferences of their young adolescents, and their negotiating and decision-making strategies around food purchasing and meals, four focus groups were held with 32 African-American parents and three focus groups with 14 Spanish-dominant, first-generation immigrant Latina mothers. Most participants were of low socioeconomic status and were single parents. Many African-American parents emphasized children's growing appetites and preferences for fast food. Many reported making weekday dinner decisions jointly with the child or allowing the child to eat a lunch-like alternative, and allowing serve-yourself meals on weekends. A few prepared traditional ethnic foods. Latina parents reported that their children liked ethnic foods and fast/junk foods. They emphasized buying foods their children wanted, making no eating restrictions, and preparing traditional ethnic dinners without alternatives. African-American and Latina parents displayed concern over whether to place restrictions on young adolescents' eating. Further research is needed on the ways in which socioeconomic inequalities compound barriers to healthful eating, with particular attention to low income and immigrant populations.


Efficient expression of EpEX in the cytoplasm of Escherichia coli using thioredoxin fusion protein.
Recombinant epithelial cell adhesion molecule extracellular domain (EpEX) has a high potential as a candidate for passive and active immunotherapy as well as cancer vaccination. In the present study, EpEX was expressed as a thioredoxin fusion protein in Escherichia coli (E. coli). The effect of different hosts and expression conditions on the expression level of the fusion protein was also evaluated. Moreover, the effect of temperature and isopropyl-β-d-thiogalactopyranoside (IPTG) concentration on protein solubility was assessed. The codon optimized-synthetic gene was cloned into pET32a (+) expression vector and transformed into E. coli BL21 (DE3), Rosetta™ (DE3), and Origami™ (DE3). The protein expression was confirmed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. Lowering the expression temperature to 16 °C and IPTG concentration to 0.5 mM also dramatically increased the volumetric productivity of the fusion protein. In optimum culture condition, high-level expression of the target fusion protein was detected in Rosetta™ (DE3) and Origami™ (DE3) (207 and 334 μg/mL, respectively), though they were expressed as inclusion bodies. No improvement was observed in the solubility of the fusion protein by reducing the temperature or IPTG concentration even when expressed in a TrxB/gor mutant strain. Results showed that Trx tag combined with other strategies utilized here could be effective to achieve high level of protein production but not effective in solubility improvement. However, new approaches might be necessary to enhance the solubility of EpEX in the E. coli system.


Using a Matlab implemented algorithm for UV-vis spectral resolution for pKa determination and multicomponent analysis.
A Matlab implemented computer code for spectral resolution is presented. The code enables the user to resolve the UV-visible absorption spectrum of a mixture of up to 3 previously known components, to the individual components, thus, evaluating their quantities. The resolving procedure is based on searching the combination of the components which yields the spectrum which is the most similar (minimal RMSE) to the measured spectrum of the mixture. Examples of using the software for pK(a) value estimation and multicomponent analysis are presented and other implementations are suggested.


Functional analysis of synthetic insectatachykinin analogs on recombinant neurokinin receptor expressing cell lines.
The activity of a series of synthetic tachykinin-like peptide analogs was studied by means of microscopic calcium imaging on recombinant neurokinin receptor expressing cell lines. A C-terminal pentapeptide (FTGMRa) is sufficient for activation of the stomoxytachykinin receptor (STKR) expressed in Schneider 2 cells. Replacement of amino acid residues at the position of the conserved phenylalanine (F) or arginine (R) residues by alanine (A) results in inactive peptides (when tested at 1microM), whereas A-replacements at other positions do not abolish the biological activity of the resulting insectatachykinin-like analogs. Calcium imaging was also employed to compare the activity of C-terminally substituted tachykinin analogs on three different neurokinin receptors. The results indicate that the major pharmacological and evolutionary difference between tachykinin-related agonists for insect (STKR) and human (NK1 and NK2) receptors resides in the C-terminal amino acid residues (R versus M). A single C-terminal amino acid change can turn an STKR-agonist into an NK-agonist and vice versa.


Percutaneous coronary intervention for stable coronary artery disease.
The adverse consequences of stable coronary artery disease (CAD) are death, myocardial infarction (MI) and angina. Trials in stable CAD show that percutaneous coronary intervention (PCI) does not reduce mortality. PCI does appear to reduce spontaneous MI rates but at the expense of causing some periprocedural MI. Therefore, the main purpose of PCI is to relieve angina. Indeed, patients and physicians often choose PCI rather than first attempting to control symptoms with anti-anginal medications as recommended by guidelines. Nevertheless, it is unclear how effective PCI is at relieving angina. This is because, whereas anti-anginal medications are universally required to be tested against placebo, there is no such requirement for procedural interventions such as PCI. The first placebo-controlled trial of PCI showed a surprisingly small effect size. This may be because it is overly simplistic to assume that the presence of a stenosis and inducible ischaemia in a patient means that the clinical chest pain they report is caused by ischaemia. In this article, we review the evidence base and argue that if we as a medical specialty wish to lead the science of procedures for symptom control, we should recognise the special merit of placebo-controlled experiments.


Pediatric Hip Disease Increases the Risk for Opioid Use in Adulthood: Long-term Burden of Pain and Depression.
Legg-Calvé-Perthes disease (LCPD) and slipped capital femoral epiphysis (SCFE) can result in painful deformation of the hip joint with impaired range of motion and early development of secondary osteoarthritis. It has not been investigated whether having LCPD or SCFE is associated with increased use of pain or antidepressant drug prescriptions later in life. With this study, we aimed to investigate if patients with a history of LCPD or SCFE have an increased risk of prescription analgesic or antidepressant drugs in adulthood compared with matched controls. The included patients were identified by the Swedish Patient Register and matched for age, gender, and residency with 10 control individuals not exposed to any of the mentioned pediatric hip diseases, by the Swedish National Population Register. This was a nationwide, registry-based cohort study which included 1,292 patients diagnosed with LCPD at age 2-15 years and 1,613 patients diagnosed with SCFE at age 5-16 years and > 17 years from 2005 through 2011. Prescription data of first-line analgesic drugs (acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids), or first-line antidepressant drugs (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants) were derived from the Swedish Prescribed Drugs Register. Conditional logistic regression models were fitted to estimate the relative risk for the prescription in exposed compared with unexposed individuals. Adjustment was performed for gender and birth year. In the group with an LCPD diagnosis, the adjusted odds ratio for analgesic prescriptions overall was 1.3 (95% CI, 1.2-1.5). For patients with an SCFE diagnosis, the adjusted odds ratio for analgesic prescriptions overall was 1.4 (95% CI, 1.3-1.6). Among patients with an LCPD diagnosis, the adjusted odds ratio for antidepressant prescriptions overall was 1.0 (95% CI, 0.8-1.2). For patients with an SCFE diagnosis, the adjusted odds ratio was 1.2 (95% CI, 1.1-1.4). As with all register studies, there are known associated biases such as selection, detection, and observational bias as well as the uncertain quality of input data. Further, the Swedish Prescribed Drugs Register only includes drugs that were prescribed by a physician and dispensed at a pharmacy. This is also a factor that may lead to underestimating the use of acetaminophen and nonsteroidal anti-inflammatory drugs, as these drugs can be acquired "over the counter." During childhood, patients with LCPD or SCFE seem to suffer long-term pain and have an increased risk of requiring analgesic medication in adulthood, including opioids. It is important to assess the causes, type, and severity of pain to optimize pain management to counteract possible overuse in these patients. Seemingly, patients with LCPD do not have an increased risk for antidepressant drug therapy in adulthood whereas we did see an increased risk for that in patients with previous SCFE compared with the general population.


[Intramedullary nailing of the tibia with the expert tibia nail].
Restoration of axis, length, and rotation of the lower leg. Sufficient primary stability of the osteosynthesis for functional aftercare. Early functional aftercare to maintain joint mobility. Good bony healing in closed and open fractures. All closed and open fractures of the tibia and complete lower leg fractures (AO 42). Certain extraarticular fractures of the proximal and distal tibia (AO 41 A2/A3; AO 43 A1/A2/A3). Segmental fractures of the tibia. Certain intraarticular fractures of the tibia with use of additional implants (AO 41 C1/C2; AO 43 C1/C2). Stabilization during and after segmental bone transport or callus distraction of the tibia. Patients in poor general condition (e.g., bedridden). Flexion of the knee of less than 90 degrees . Infection in the nail's insertion area. Infection of the tibial cavity. Complex articular fractures of the proximal or distal tibia with joint depression. Closed reduction of the fracture. If necessary, use of reduction clamps through additional stab incisions or open surgical procedures. In some cases, additional osteosynthesis procedures are necessary (e.g., screws). Positioning of the patient may be performed on a radiolucent table or a traction table. Opening of the proximal tibia in line with the medullary canal. Cannulated or noncannulated insertion of the Expert Tibia Nail((R)) with or without reaming of the medullary canal depending on the fracture type and soft-tissue condition. Control of axis, length, and rotation. Distal interlocking with the radiolucent drill and proximal interlocking with the targeting device. Immediate mobilization of ankle joint and knee joint. Depending on the type of fracture, mobilization with 20 kg partial weight bearing or pain-dependent full weight bearing with crutches. X-ray control 6 weeks postoperatively and increased weight bearing depending on the fracture status. In a prospective, international multicentric study, 181 patients with 186 fractures were included between July 2004 and May 2005. 57 of these fractures (30.7%) initially were graded open, 15 of them grade I, 32 grade II, and ten grade III. Most of the fractures (36%) were shaft fractures. After 1 year, 146 patients (81%) could be evaluated clinically and radiologically. The overall pseudarthrosis rate was 12.2% (18.2% for open and 9.7% for closed fractures). The risk for secondary operations or revisions (including dynamization of the nail) was 18.8%. Without consideration of dynamization procedures, revisions were necessary in only 5.4% of all patients. The risk for varus, valgus or antecurvation malalignment of more than 5 degrees in any plane on radiologic long leg views was 4.3% for shaft fractures, 1.5% for distal fractures, and 13.6% for proximal fractures. The implant-specific risk for bolt breakage was 3.2%.


The "Ozone Deficit" Problem: O2(X, v ge 26) + O(3P) from 226-nm Ozone Photodissociation.
Highly vibrationally excited O(2)(X(3)sigmag(-), v >/= 26) has been observed from the photodissociation of ozone (O(3)), and the quantum yield for this reaction has been determined for excitation at 226 nanometers. This observation may help to address the "ozone deficit" problem, or why the previously predicted stratospheric O(3) concentration is less than that observed. Recent kinetic studies have suggested that O(2)(X(3)sigmag(-), v >/= 26) can react rapidly with O(2) to form O(3) + O and have led to speculation that, if produced in the photodissociation of O(3), this species might be involved in resolving the discrepancy. The sequence O(3) + hv --> O(2)(X(3)sigmag(-), v >/= 26) + O; O(2)(X(3)sigmag(-), v >/= 26) + O(2) --> O(3) + O (where hv is a photon) would be an autocatalytic mechanism for production of odd oxygen. A two-dimensional atmospheric model has been used to evaluate the importance of this new mechanism. The new mechanism can completely account for the tropical O(3) deficit at an altitude of 43 kilometers, but it does not completely account for the deficit at higher altitudes. The mechanism also provides for isotopic fractionation and may contribute to an explanation for the anomalously high concentration of heavy O(3) in the stratosphere.


Anatomical total shoulder arthroplasty in young patients with osteoarthritis: all-polyethylene versus metal-backed glenoid.
Controversy about the use of an anatomical total shoulder arthroplasty (aTSA) in young arthritic patients relates to which is the ideal form of fixation for the glenoid component: cemented or cementless. This study aimed to evaluate implant survival of aTSA when used in patients aged < 60 years with primary glenohumeral osteoarthritis (OA), and to compare the survival of cemented all-polyethylene and cementless metal-backed glenoid components. A total of 69 consecutive aTSAs were performed in 67 patients aged < 60 years with primary glenohumeral OA. Their mean age at the time of surgery was 54 years (35 to 60). Of these aTSAs, 46 were undertaken using a cemented polyethylene component and 23 were undertaken using a cementless metal-backed component. The age, gender, preoperative function, mobility, premorbid glenoid erosion, and length of follow-up were comparable in the two groups. The patients were reviewed clinically and radiographically at a mean of 10.3 years (5 to 12, sd 26) postoperatively. Kaplan-Meier survivorship analysis was performed with revision as the endpoint. A total of 26 shoulders (38%) underwent revision surgery: ten (22%) in the polyethylene group and 16 (70%) in the metal-backed group (p < 0.0001). At 12 years' follow-up, the rate of implant survival was 74% (sd 0.09) for polyethylene components and 24% (sd 0.10) for metal-backed components (p < 0.0002). Glenoid loosening or failure was the indication for revision in the polyethylene group, whereas polyethylene wear with metal-on-metal contact, instability, and insufficiency of the rotator cuff were the indications for revision in the metal-backed group. Preoperative posterior subluxation of the humeral head with a biconcave/retroverted glenoid (Walch B2) had an adverse effect on the survival of a metal-backed component. The survival of a cemented polyethylene glenoid component is three times higher than that of a cementless metal-backed glenoid component ten years after aTSA in patients aged < 60 years with primary glenohumeral OA. Patients with a biconcave (B2) glenoid have the highest risk of failure. Cite this article: Bone Joint J 2018;100-B:485-92.


A novel nitrilase, arylacetonitrilase, of Alcaligenes faecalis JM3. Purification and characterization.
A new type of nitrilase, arylacetonitrilase, has been purified from isovaleronitrile-induced cells of Alcaligenes faecalis JM3 in four steps. The purity of the enzyme was confirmed by SDS/polyacrylamide gel electrophoresis, ampholyte electrofocusing and double immunodiffusion in agarose. The enzyme has a molecular mass of about 275 kDa and consists of six subunits of identical molecular mass. The purified enzyme exhibits a pH optimum of 7.5 and a temperature optimum of 45 degrees C. The enzyme is specific for arylacetonitriles such as 2-thiophenacetonitrile, p-tolyacetonitrile, p-chlorobenzylcyanide, p-fluorobenzylcyanide and 3-pyridylacetonitrile. The enzyme stoichiometrically catalyzes the hydrolysis of arylacetonitrile to arylacetic acid and ammonia, no formation of amide occurring. However, the enzyme does not attack nitrile groups attached to aromatic and heteroaromatic rings, which are hydrolyzed preferably by the nitrilases known previously. The enzyme requires thiol compounds such as dithiothreitol and 2-mercaptoethanol to exhibit its maximum activity.