Optical direct intensity modulation of a 79GHz resonant tunneling diode-photodetector oscillator.
We report on the direct intensity modulation characteristics of a high-speed resonant tunneling diode-photodetector (RTD-PD) with an oscillation frequency of 79 GHz. This work demonstrates both electrical and optical modulation and shows that RTD-PD oscillators can be utilized as versatile optoelectronic/radio interfaces. This is the first demonstration of optical modulation of an RF carrier using integrated RTD-PD oscillators at microwave frequencies.


Variability in the Preparation, Reporting, and Use of Bone Marrow Aspirate Concentrate in Musculoskeletal Disorders: A Systematic Review of the Clinical Orthopaedic Literature.
Interest in the therapeutic potential of bone marrow aspirate concentrate (BMAC) has grown exponentially. However, comparisons among studies and their processing methods are challenging because of inconsistent reporting of protocols, as well as poor characterization of the composition of the initial bone marrow aspirate and of the final products delivered. The purpose of this study was to perform a systematic review of the literature to evaluate the level of reporting related to the protocols used for BMAC preparation and the composition of BMAC utilized in the treatment of musculoskeletal diseases in published clinical studies. A systematic review of the literature was performed by searching PubMed, MEDLINE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials from 1980 to 2016. Inclusion criteria were human clinical trials, English language, and manuscripts that reported on the use of BMAC in musculoskeletal conditions. After a comprehensive review of the 986 identified articles, 46 articles met the inclusion criteria for analysis. No study provided comprehensive reporting that included a clear description of the preparation protocol that could be used by subsequent investigators to repeat the method. Only 14 (30%) of the studies provided quantitative metrics of the composition of the BMAC final product. The reporting of BMAC preparation protocols in clinical studies was highly inconsistent and studies did not provide sufficient information to allow the protocol to be reproduced. Moreover, comparison of the efficacy and yield of BMAC products is precluded by deficiencies in the reporting of preparation methods and composition. Future studies should contain standardized and stepwise descriptions of the BMAC preparation protocol, and the composition of the BMAC delivered, to permit validating and rationally optimizing the role of BMAC in musculoskeletal care.


Braving the Element: Pancreatic β-Cell Dysfunction and Adaptation in Response to Arsenic Exposure.
Type 2 diabetes mellitus (T2DM) is a serious global health problem, currently affecting an estimated 451 million people worldwide. T2DM is characterized by hyperglycemia and low insulin relative to the metabolic demand. The precise contributing factors for a given individual vary, but generally include a combination of insulin resistance and insufficient insulin secretion. Ultimately, the progression to diabetes occurs only after β-cells fail to meet the needs of the individual. The stresses placed upon β-cells in this context manifest as increased oxidative damage, local inflammation, and ER stress, often inciting a destructive spiral of β-cell death, increased metabolic stress due to further insufficiency, and additional β-cell death. Several pathways controlling insulin resistance and β-cell adaptation/survival are affected by a class of exogenous bioactive compounds deemed endocrine disrupting chemicals (EDCs). Epidemiological studies have shown that, in several regions throughout the world, exposure to the EDC inorganic arsenic (iAs) correlates significantly with T2DM. It has been proposed that a lifetime of exposure to iAs may exacerbate problems with both insulin sensitivity as well as β-cell function/survival, promoting the development of T2DM. This review focuses on the mechanisms of iAs action as they relate to known adaptive and maladaptive pathways in pancreatic β-cells.


Harmonization, regulation, and trade: interactions in the pharmaceutical field.
This article aims to draw attention to the process of harmonization of requirements for drug registration (the so-called ICH process) and to examine how it may affect access to medicines in developing countries. The ICH process, especially when seen in conjunction with the World Trade Organization's Agreement on Technical Barriers to Trade, may create additional barriers to would-be entrants on the global pharmaceutical market, notably large generic manufacturers in developing countries-the very companies that can create credible price competition for the innovative industry and, thus, increase access to medicines. These barriers could help maintain the status quo by insulating well-established companies from competition, thereby forming a further obstacle to lower drug prices and to access to medicines, especially in developing countries. Developing countries should therefore carefully consider the implications of the positioning of ICH standards as global standards, and be vigilant with regard to their possible incorporation, whether explicitly or not, in international trade agreements.


Immunopharmacological activities of 2-keto-3-deoxyoctonic acid-(alpha 2----6)-linked 4-O-phosphono-D-glucosamine derivatives carrying N- and 3-O-acyl substituents.
The immunopharmacological activities of 2-keto-3-deoxyoctonic acid (KDO)-(alpha 2----6)-linked lipid A-subunit analogs, 4-O-phosphono-D-glucosamine derivatives carrying N- and 3-O-acyl substituents, were compared with those of the corresponding analogs without KDO, GLA-27, GLA-47, and GLA-60. Among the analogs tested, GLA-60, a 4-O-phosphono-D-glucosamine carrying N-3-hydroxytetradecanoyl and 3-O-3-tetradecanoyloxytetradecanoyl groups, exhibited the most intensive activities in terms of mitogenicity, adjuvanticity, and mediator (tumor necrosis factor and colony-stimulating factor) induction. Binding (alpha 2----6) of KDO to GLA-60 failed to enhance the activities. Similarly, the activities of GLA-27 and GLA-47 were also decreased by introduction of KDO to the O-6 of the analogs. This indicates that the strengths of the activities of the subunit analogs depend on the kinds of N- and 3-O-linked acyl substituents and not on the presence of the KDO linked to the O-6.


Modulation of prolactin expression by xenoestrogens.
Xenoestrogens are widely used environmental chemicals that have recently been under scrutiny because of their possible role as endocrine disrupters. Among them are endosulfan and chlordane, two persistent insecticides suspected to act as estrogens in living organisms. To test and better understand the potential estrogenic activity of these chemicals, we used a pituitary cell line (GH(3)) known to respond to estrogens by increasing its secretion of prolactin (PRL), a hormone that is well known for its many physiological functions, especially in fetal growth, development, and reproduction. We measured the levels of PRL secretion and PRL mRNA transcription using immunometric tests, Northern blots, and relative quantitative RT-PCR. We also employed the XTT proliferation assay to compare the growth of GH(3) cells stimulated with 17-beta estradiol and endosulfan or chlordane. Our results show that endosulfan and chlordane are able to induce a substantial increase of PRL expression while these two chemicals do not increase cell growth. Together, our results suggest that endosulfan and chlordane could indeed modulate an estrogen-inducible gene such as PRL, possibly acting via second messenger-mediated cellular mechanisms instead of solely competing with estrogens for the nuclear estrogen receptor sites.


[Evaluation of the results of the prevention program "Protect your voice" implemented by The Greater Poland Center of Occupational Medicine of Poznan].
The aim of the study was to evaluate the rationale for training in voice emission and voice prophylaxis among teachers and to assess the effects of voice disorders rehabilitation in the selected group of teachers participating in the program "Protect your voice." An anonymous survey was conducted among 463 teachers participating in the training part of the program. The effectivness of rehabilitation of teachers with occupational voice disorders was evaluated among 51 subjects (average age: 43 years) taking part in diagnostic and rehabilitation part of the program. Phonation voice exercises with speech therapist and physiotherapy (iontophoresis, inhalations and elektrostimulation) were administered. Evaluation of rehabilitation was based on phoniatric examination, including videostroboscopy and statistical calculations. The survey showed that among teachers there is high demand (98%) for training in proper voice emission, hygiene and prevention of voice. The effectiveness of rehabilitation has been confirmed by the observed improvements in phonatory activities of larynx, proper breathing during phonation (p = 0.0000), the voice quality (p = 0.0022), prolonged phonation time (an average of 1.39 s), increased number of people who correctly activated resonators (p = 0.0000) and increased number of people with phonation without excesive muscle tension of the neck. The results indicate that among all the professionally active teachers, there is a need for regular training of proper voice emission and vocal hygiene and then conduct individually phonation and breathing exercises, supported by the physiotherapy. This should be an effective method of voice disorders prevention in teachers. Med Pr 2017;68(5):593-603.


School-based youth health nurses: roles, responsibilities, challenges, and rewards.
A case study and focus-group discussions were conducted with 10 youth health nurses (nurses) employed in the recently introduced School-Based Youth Health Nurse Program (SBYHNP) to identify their roles, responsibilities, and professional development needs. Major roles are support, referral, health promotion, and marketing. Clients include high school students, teachers, and parents; the majority of whom are female and aged 13-16 years. Health issues addressed during individual consultations are predominantly psychosocial but also include medical, sexual health and sexuality issues, health surveillance, and risk-taking behaviors. Nurses also provide clients with health information and promote enhanced personal skill development during these consultations. Health promotion strategies undertaken by nurses were predominantly health education and health information displays. Nurses reported marketing their role and function within the school to be an essential and often difficult aspect of their role. Professional development through the SBYHNP was excellent; however, there was concern relating to the availability of future educational opportunities. The SBYHNP provides nurses with a new, challenging, autonomous role within the school environment and the opportunity to expand their role to incorporate all aspects of the health-promoting schools' framework.


The phylogenetic relationships of Kronborgia (Platyhelminthes, Fecampiida) based on comparison of 18S ribosomal DNA sequences.
Approximately 580 bp at the 5' end of the small subunit RNA gene were amplified by PCR for 19 platyhelminth taxa, and Homo and Artemia were used as outgroups. These were analysed to test the hypothesis that fecampiids and Neodermata are sister groups. No evidence was found that the fecampiid Kronborgia isopodicola is closely related to the Neodermata or to the Rhabdocoela (in which the fecampiids are usually included). Morphological, including ultrastructural, characters and DNA data do not support a close relationship of fecampiids with any other platyhelminth taxon, although the DNA sequence analysis provides some evidence that the Acoela and Tricladida are closest. Fecampiids are sufficiently different from any other platyhelminth group to warrant establishment of a class, Fecampiida, for them. A diagnosis of the new class is given.


Accumulation of cadmium by channel catfish (Ictalurus punctatus): influx from environmental solutions.
1. The accumulation of cadmium (Cd) from external environmental solutions was measured in channel catfish (Ictalurus punctatus) with the aid of 109Cd and by direct analysis of tissues. 2. Acute uptake (with 109Cd) was concentration dependent and was increased by changing the external pH from 7.3 to 5.0 and decreased by raising the Ca concentration from 0.1 mM to 3.0 mM. 3. The presence of external Zn did not change the uptake of the Cd. 4. In chronic 7-day experiments, fasted catfish were found to accumulate the toxic metal in their liver and kidneys from external media with Cd concentrations as low as 10(-9) M (about 0.1 microgram/l). 5. Concentrations were greater in the kidneys than the liver. 6. Detectable amounts of Cd (less than 0.03 microgram/g net wt) were not found in muscle in this time at external concentrations of Cd less than 10(-5) M (less than 1.0 mg/l).


Studies on the nucleic acid sequences of Kirsten sarcoma virus: a model for formation of a mammalian RNA-containing sarcoma virus.
The genetic information contained in the Kirsten and Moloney strains of mammalian RNA-containing sarcoma viruses has been analyzed by RNA . (3)H-DNA hybridization. Kirsten sarcoma virus has been found to possess two distinct sets of nucleic acid sequences. One set of sequences is contained in murine type C helper virus, and the other set is contained in rat type C helper virus. Moloney sarcoma virus contains sequences of murine type C helper virus but not of rat type C helper virus. The results indicate that Kirsten sarcoma virus arose through a process of recombination between Kirsten murine leukemia virus and nucleic acid sequences found in rat cells. A model is suggested for the formation of transforming type C viruses involving the transduction of oncogenic information.


Thrombotic thrombocytopenic purpura as a rare complication in childhood systemic lupus erythematosus: case report and literature review.
Thrombotic thrombocytopenic purpura is a rare but serious condition in childhood. It can be idiopathic or a complication of other diseases or drug therapy. We report on a 12-year-old Chinese girl who presented with fulminant systemic lupus erythematosus with progressive renal failure, pancytopenia, and cerebral dysfunction due to thrombotic thrombocytopenic purpura. The patient also had Pneumocystis carinii pneumonia, Pseudomonas septicaemia, and Herpes zoster infections as a result of immunosuppressive treatment. She responded to combined therapy with pulse methylprednisolone, cyclophosphamide, plasmapheresis, and intensive care support, and completely recovered renal and neurological function. A review of the English-language medical literature since 1968 identified 20 other paediatric cases of systemic lupus erythematosus and thrombotic thrombocytopenic purpura. Clinical features, treatment, and outcome of these cases are presented and discussed. Early recognition is important, and although plasmapheresis is not of proven benefit in severe cases of systemic lupus erythematosus, it is life-saving in lupus-related thrombotic thrombocytopenic purpura and must be instituted early to avoid a poor outcome.


Resonant absorption induced fast melting studied with mid-IR QCLs.
We demonstrate the use of a pump-probe setup based on two mid-infrared quantum cascade lasers (QCLs) to investigate the melting and crystallization of materials through resonant absorption. A combination of pump and probe beams fulfills the two-color synchronous detection. Furthermore, narrow linewidth advances the accuracy of measurements and the character of broad tuning range of QCLs enables wide applications in various sample and multiple structures. 1-Eicosene was selected as a simple model system to verify the feasibility of this method. A pulsed QCL was tuned to the absorption peak of CH2 bending vibration at 1467 cm-1 to resonantly heat the sample. The other QCL in continuous mode was tuned to 1643 cm-1 corresponding the C=C stretching vibration to follow the fast melting dynamics. By monitoring the transmission intensity variation of pump and probe beams during pump-probe experiments, the resonant absorption induced fast melting and re-crystallization of 1-Eicosene can be studied. Results show that the thermal effect and melting behaviors strongly depend on the pump wavelength (resonant or non-resonant) and energy, as well as the pump time. The realization and detection of melting and recrystallization can be performed in tens of milliseconds, which improves the time resolution of melting process study based on general mid-infrared spectrum by orders of magnitude. The availability of resonant heating and detections based on mid-infrared QCLs is expected to enable new applications in melting study.


Suicide prevention program for at-risk groups: pointers from an epidemiological study.
The aim of this paper is to identify at-risk groups for a focused suicide prevention program for Malaysia. Data from 20,552 persons aged 16 years and above (males 45.9%), was obtained using stratified, random sampling in a national survey of psychiatric morbidity using locally validated General Health Questionnaire (GHQ-28) which included questions on suicidal ideation. The overall prevalence of suicidal ideation (SI) was 6.3%, CI 6.1-6.8 (n=1288). Logistic regression analysis was performed with age, ethnicity, gender, urban/rural residence, age group, marital status, household income, type of household, presence of chronic pain, social dysfunction, somatic, anxiety or depressive symptoms, obesity, and chronic medical illnesses as independent variables. Only Insomnia, Religion, Marital Status, Depression, Social Dysfunction and Anxiety were seen to be significant predictors. Prevalence of SI was significantly higher among Indians (11.0%, CI 9.5-12.5), especially those of the Hindu faith (12.2%, CI 10.5-14.0), Chinese (9.7%, CI 8.8-10.7) and those having depressive symptoms. In a developing country with competing priorities, prudent allocation of resources requires focusing suicide prevention efforts on treating depression in vulnerable groups.


Dermatophytoses in Mexico City.
We analysed 2350 biological samples from patients with a clinical diagnosis of superficial mycoses who attended outpatient services over a 7-year period. Samples of scales were processed by direct microscopic examination with 15% KOH and cultured on Sabouraud glucose agar with chloramphenicol and cycloheximide. Laboratory examination confirmed dermatophytosis in 860 (36.6%) cases, of which 80.9% were caused by Trichophyton rubrum. The most frequently observed dermatophytoses were tinea unguium (60%) and tinea pedis (25.6%). In agreement with previous observations, we demonstrate that T. rubrum continues to increase in Mexico.


The Combined Use of Copper Sulfate and Trichlorfon Exerts Stronger Toxicity on the Liver of Zebrafish.
In aquaculture, copper sulphate and trichlorfon are commonly used as disinfectants and insecticide, sometimes in combination. However, improper use can result in biotoxicity and increased ecological risks. The liver plays a crucial role in detoxification, lipid metabolism, nutrient storage, and immune function in fish. Selecting the liver as the main target organ for research helps to gain an in-depth understanding of various aspects of fish physiology, health, and adaptability. In the present study, zebrafish were exposed to Cu (0.5 mg/L) and Tri (0.5 mg/L) alone and in combination for 21 days. The results demonstrate that both Cu and Tri caused hepatocyte structure damage in zebrafish after 21 days of exposure, with the combination showing an even greater toxicity. Additionally, the antioxidant and immune enzyme activities in zebrafish liver were significantly induced on both day 7 and day 21. A transcriptome analysis revealed that Cu and Tri, alone and in combination, impacted various physiological activities differently, including metabolism, growth, and immunity. Overall, Cu and Tri, either individually or in combination, can induce tissue damage by generating oxidative stress in the body, and the longer the exposure duration, the stronger the toxic effects. Moreover, the combined exposure to Cu and Tri exhibits enhanced toxicity. This study provides a theoretical foundation for the combined use of heavy metal disinfectants and other drugs.


The Development of the Military Service Identification Tool: Identifying Military Veterans in a Clinical Research Database Using Natural Language Processing and Machine Learning.
Electronic health care records (EHRs) are a rich source of health-related information, with potential for secondary research use. In the United Kingdom, there is no national marker for identifying those who have previously served in the Armed Forces, making analysis of the health and well-being of veterans using EHRs difficult. This study aimed to develop a tool to identify veterans from free-text clinical documents recorded in a psychiatric EHR database. Veterans were manually identified using the South London and Maudsley (SLaM) Biomedical Research Centre Clinical Record Interactive Search-a database holding secondary mental health care electronic records for the SLaM National Health Service Foundation Trust. An iterative approach was taken; first, a structured query language (SQL) method was developed, which was then refined using natural language processing and machine learning to create the Military Service Identification Tool (MSIT) to identify if a patient was a civilian or veteran. Performance, defined as correct classification of veterans compared with incorrect classification, was measured using positive predictive value, negative predictive value, sensitivity, F1 score, and accuracy (otherwise termed Youden Index). A gold standard dataset of 6672 free-text clinical documents was manually annotated by human coders. Of these documents, 66.00% (4470/6672) were then used to train the SQL and MSIT approaches and 34.00% (2202/6672) were used for testing the approaches. To develop the MSIT, an iterative 2-stage approach was undertaken. In the first stage, an SQL method was developed to identify veterans using a keyword rule-based approach. This approach obtained an accuracy of 0.93 in correctly predicting civilians and veterans, a positive predictive value of 0.81, a sensitivity of 0.75, and a negative predictive value of 0.95. This method informed the second stage, which was the development of the MSIT using machine learning, which, when tested, obtained an accuracy of 0.97, a positive predictive value of 0.90, a sensitivity of 0.91, and a negative predictive value of 0.98. The MSIT has the potential to be used in identifying veterans in the United Kingdom from free-text clinical documents, providing new and unique insights into the health and well-being of this population and their use of mental health care services.


Practices and issues of moulting programs for laying hens: a review.
1. Moulting is a natural physiological process in birds when they shed their old feathers and replace them with new ones, and it is followed by reproductive quiescence resulting in reduced egg production. Different birds undergo moulting at different points in their life. Some birds have seasonal moulting while some moult at the end of their breeding cycle. This review will mainly focus on moulting practices associated with commercial layer birds because, in all other bird types, this is not managed.2. Commercial farms commonly analyse the cost-benefit ratio to decide the time and method to adopt for moulting. Commercial layer farms adopt different practices to force birds out of moult and restart the production cycle. Animal welfare groups consider this as stressful and against animal welfare, raising questions about the ethics of this practice.3. Many studies have been conducted using complete or partial feed withdrawal and non-feed withdrawal programs to measure their effectiveness in maintaining animal welfare, economy, and post-moult performance in mind.4. Animal welfare should not be compromised during moulting. The United States Egg Producers and other such groups from the United Kingdom and Europe have decided to sell eggs produced only through a non-feed withdrawal moulting programs.


IL-1α reversibly inhibits skeletal muscle ryanodine receptor. a novel mechanism for critical illness myopathy?
Critical illness myopathies in patients with sepsis or sustained mechanical ventilation prolong intensive care treatment and threaten both patients and health budgets; no specific therapy is available. Underlying pathophysiological mechanisms are still patchy. We characterized IL-1α action on muscle performance in "skinned" muscle fibers using force transducers and confocal Ca(2+) fluorescence microscopy for force/Ca(2+) transients and Ca(2+) sparks. Association of IL-1α with sarcoplasmic reticulum (SR) release channel, ryanodine receptor (RyR) 1, was investigated with coimmunoprecipitation and confocal immunofluorescence colocalization. Membrane integrity was studied in single, intact fibers challenged with IL-1α. IL-1α reversibly stabilized Mg(2+) inhibition of Ca(2+) release. Low Mg(2+)-induced force and Ca(2+) transients were reversibly abolished by IL-1α. At normal Mg(2+), IL-1α reversibly increased caffeine-induced force and Ca(2+) transients. IL-1α reduced SR Ca(2+) leak via RyR1, as judged by (1) increased SR Ca(2+) retention, (2) increased IL-1α force transients being reproduced by 25 μM tetracaine, and (3) reduced Ca(2+) spark frequencies by IL-1α or tetracaine. Coimmunoprecipitation confirmed RyR1/IL-1 association. RyR1/IL-1 immunofluorescence patterns perfectly colocalized. Long-term, 8-hour IL-1α challenge of intact muscle fibers compromised membrane integrity in approximately 50% of fibers, and confirmed intracellular IL-1α deposition. IL-1α exerts a novel, specific, and reversible interaction mechanism with the skeletal muscle RyR1 macromolecular release complex without the need to act via its membrane IL-1 receptor, as IL-1R membrane expression levels were not detectable in Western blots or immunostaining of single fibers. We present a potential explanation of how the inflammatory mediator, IL-1α, may contribute to muscle weakness in critical illness.


Nanoparticle-based delivery system for application of siRNA in vivo.
Small interfering RNAs (siRNAs) silence the expression of specific target genes by mediating RNA interference (RNAi) in mammalian cells. siRNAs have not only been widely used as a valuable tool for functional genomics research, but they also have demonstrated great potential in biomedical therapeutic applications for diseases caused by abnormal gene overexpression or mutation. One of the most important issues to overcome before full clinical application is the development of effective administration methods for siRNAs to the target tissue or cells in vivo, which is highly dependent on the delivery system. Currently, there are two major kinds of in vivo delivery systems: viral or nonviral. As one of the nonviral carrier systems, nanoparticles, combinations of liposomes and cationic polymer complexes, have exhibited improved in vivo stability, target specificity, and cell/tissue uptake and internalization of the encapsulated RNAi oligos, which result in more effective silencing with less cellular toxicity and immune stimulation. This review will discuss the latest advancements in nanoparticle-mediated RNAi delivery systems, including nano-materials, preparation, and characteristics. In conjunction, the clinical trial cases related to the nanoparticle-siRNA complexes will be highlighted. The safety issues of nanoparticles used in vivo will also be mentioned. Finally, this review will summarize the perspectives for future applications of nanoparticle-mediated RNAi delivery systems.


Mannose 6-phosphate receptors are sorted from immature secretory granules via adaptor protein AP-1, clathrin, and syntaxin 6-positive vesicles.
The occurrence of clathrin-coated buds on immature granules (IGs) of the regulated secretory pathway suggests that specific transmembrane proteins are sorted into these buds through interaction with cytosolic adaptor proteins. By quantitative immunoelectron microscopy of rat endocrine pancreatic beta cells and exocrine parotid and pancreatic cells, we show for the first time that the mannose 6-phosphate receptors (MPRs) for lysosomal enzyme sorting colocalize with the AP-1 adaptor in clathrin-coated buds on IGs. Furthermore, the concentrations of both MPR and AP-1 decline by approximately 90% as the granules mature. Concomitantly, in exocrine secretory cells lysosomal proenzymes enter and then are sorted out of IGs, just as was previously observed in beta cells (Kuliawat, R., J. Klumperman, T. Ludwig, and P. Arvan. 1997. J. Cell Biol. 137:595-608). The exit of MPRs in AP-1/clathrin-coated buds is selective, indicated by the fact that the membrane protein phogrin is not removed from maturing granules. We have also made the first observation of a soluble N-ethylmaleimide-sensitive factor attachment protein receptor, syntaxin 6, which has been implicated in clathrin-coated vesicle trafficking from the TGN to endosomes (Bock, J.B., J. Klumperman, S. Davanger, and R.H. Scheller. 1997. Mol. Biol. Cell. 8:1261-1271) that enters and then exits the regulated secretory pathway during granule maturation. Thus, we hypothesize that during secretory granule maturation, MPR-ligand complexes and syntaxin 6 are removed from IGs by AP-1/clathrin-coated vesicles, and then delivered to endosomes.


The 17β-hydroxysteroid dehydrogenase type 3 deficiency: a case report of an 18-year patient and review of the literature.
Deficiency of 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3), an enzyme converting androstenedione (A) to testosterone (T), is a rare cause of autosomal recessive 46,XY disorder of sexual development (DSD). A 18-years phenotypically female patient from southern Italy presented with primary amenorrhea. She had deep voice, macrocephaly, enlarged and bulbous nasal tip, macrostomia, facial acne, breast asymmetry, hypoplasia of the first finger of right hand, proximal implant of the fifth metatarsus bilaterally as well as an increased muscle mass and hirsutism, with hair distribution on face, neck, chest, abdomen, pubic region and on upper and lower limbs. Genital exam showed thickened labra majora with absence of labra minora and a blind-ending pseudo-vagina with clitoris enlargement. Karyotype analysis showed a male genotype (46,XY). Hormonal evaluation showed decreased T (188 ng/dL-6.5 nmol/L) and increased A (10 ng/mL-34,96 nmol/L), considering male reference ranges, resulting in a decreased T/A ratio (0,186). MRI identified testicles in inguinal regions. Human Chorionic Gonadotropin test showed T/A ratio permanently under 0,8. These evidences were suggestive of a 46,XY DSD due to 17βHSD3 deficiency. An homozygous mutation (IVS3 -1 G>C or c.326-1G>C) of the 17βHSD3 gene was discovered. Psychologist identified a well determined female gender identity. It was decided to proceed with gonadectomy and vaginal enlargement by use of dilatators. The case described represents a new case of DSD due to 17βHSD3 deficiency. This patient, raised as a girl, is diagnosed in a very late stage. The identified mutation, previously reported only in Dutch and Brazilian population, is one of 27 presently known mutations of 17βHSD3 gene and is never reported in Italian population.


Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers.
Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers have generated enormous interest, because they predict for sensitivity to TK inhibitors (TKIs). While mutational status is of great importance in determining response to TKIs, it is not the sole factor, and evidence is accumulating that EGFR gene amplification, other members of the EGFR family (HER2, HER3) and genes downstream of EGFR signaling (KRAS, BRAF), may be involved in cancer pathogenesis and the response of TKIs. EGFR mutations occur in highly selected subpopulations of lung cancer patients: adenocarcinoma histology, never-smoker status, East Asian ethnicity and female gender. The recent finding of "a resistance associated" mutation for TKIs also provides new insights into this complicated mechanism. Thus, molecular-based studies to analyze the biological functions and to assess TKI sensitivity depending on the type of mutations are required. Epidemiological studies to identify possible carcinogenic factor(s) affecting different subpopulations are also of interest. In addition, for optimal therapeutic approach a comprehensive understanding of the genes related to EGFR signaling pathway, including RAS/RAF/MAPK and PI3K-AKT pathways, are required.


Histamine release from leucocytes during migraine attack.
Spontaneous histamine release (SHR) from leucocytes (basophils) of 27 migraine patients was investigated during various phases of attack. Mean SHR during the first 3 h of attack (33.7%) was increased compared with the mean SHR from leucocytes of healthy persons (15.9%), but differed insignificantly from the mean SHR in symptom-free periods. Histamine release (HR) from leucocytes of healthy persons suspended in migraine sera from different time-periods of attack was also increased compared with HR in control sera, i.e. high HR could be induced by passive transfer of serum. But the mean HRs in sera from different time-periods of attack were insignificantly different from the mean HR in sera from symptom-free periods. The increased SHR may contribute to vascular hyperreactivity in migraine.


Why training and specialization is needed for peer review: a case study of peer review for randomized controlled trials.
The purpose and effectiveness of peer review is currently a subject of hot debate, as is the need for greater openness and transparency in the conduct of clinical trials. Innovations in peer review have focused on the process of peer review rather than its quality. The aims of peer review are poorly defined, with no evidence that it works and no established way to provide training. However, despite the lack of evidence for its effectiveness, evidence-based medicine, which directly informs patient care, depends on the system of peer review. The current system applies the same process to all fields of research and all study designs. While the volume of available health related information is vast, there is no consistent means for the lay person to judge its quality or trustworthiness. Some types of research, such as randomized controlled trials, may lend themselves to a more specialized form of peer review where training and ongoing appraisal and revalidation is provided to individuals who peer review randomized controlled trials. Any randomized controlled trial peer reviewed by such a trained peer reviewer could then have a searchable 'quality assurance' symbol attached to the published articles and any published peer reviewer reports, thereby providing some guidance to the lay person seeking to inform themselves about their own health or medical treatment. Specialization, training and ongoing appraisal and revalidation in peer review, coupled with a quality assurance symbol for the lay person, could address some of the current limitations of peer review for randomized controlled trials.


Studies on porcine pancreatic elastase activity. I. Radioimmunoassay of porcine pancreatic elastase.
An improved method of radioimmunoassay was devised to offer a successful formula for determining blood concentration of elastase. With porcine pancreatic elastase as the antigen, rabbits were immunized to obtain antiserum. Iodinated elastase labeled by the chloramine-T procedure using 131I (or 125I) had a specific activity of 200-300 mCi/mg. The double antibody method was used for BF separation. While the usual method of radioimmunoassay was not always successful in obtaining accurate serum concentration of elastase, the use of diisopropyl fluorophosphate (DFP) was able to eliminate the disturbing influence of intra-serious inhibitors, alpha 1-AT and alpha 2-M, eventually producing satisfactory results. With the use of DFP, the elastase standard curve and the porcine serum dilution curve had a statistically significant correlation; precision and recovery were both satisfactory; cross-reactivity of the antiserum with trypsin and chymotrypsin was less than 0.001%. The minimal detectable concentration of elastase was 5 ng/ml, and the range of normal fasting porcine serum level was 70-100 ng/ml.


4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis.
Cell signaling pathways include a complex myriad of interconnected factors from the membrane to the nucleus, such as erbB family receptors and the phosphoinositide-3-kinase/Akt/mTOR and Ras-Raf-ERK cascades, which drive proliferative signals, promote survival, and regulate protein synthesis. To find pivotal factors in these pathways, which provide prognostic information in malignancies, we studied 103 human breast tumors with an immunohistochemical profile, including total and phosphorylated (p) proteins: human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, Akt, 4E-binding protein 1 (4EBP1), eukaryotic initiation factor 4E, phosphorylated ribosomal protein S6 kinase 1, phosphorylated ribosomal protein S6, and Ki67. Western blot and reverse lysate protein arrays were also done in a subset of tumors. Significantly, activation of the phosphoinositide-3-kinase/Akt/mTOR cascade was detected in a high proportion of tumors (41.9%). Tumors with HER2 overexpression showed higher p-Akt as compared with negative tumors (P < 0.001). Levels of p-Akt correlated with the downstream molecules, p-4EBP1 (P = 0.001) and p-p70S6K (P = 0.05). Although 81.5% of tumors expressed p-4EBP1, in 16.3% of these tumors, concomitant activation of the upstream factors was not detected. Interestingly, p-4EBP1 was mainly expressed in poorly differentiated tumors (P < 0.001) and correlated with tumor size (P < 0.001), presence of lymph node metastasis (P = 0.002), and locoregional recurrences (P = 0.002). Coexpression of p-4EBP1 and p-eIF4G correlated with a high tumor proliferation rate (P = 0.012). In this study, p-4EBP1 was the main factor in signaling pathways that associate with prognosis and grade of malignancy in breast tumors. Moreover, p-4EBP1 was detected in both HER2-positive and HER2-negative tumors. This factor seems to be a channeling point at which different upstream oncogenic alterations converge and transmit their proliferative signal, modulating protein translation.


Halogen-Bonding Interactions of Polybrominated Diphenyl Ethers and Thyroid Hormone Derivatives: A Potential Mechanism for the Inhibition of Iodothyronine Deiodinase.
Polybrominated diphenyl ethers (PBDEs) increase flame resistance in consumer goods, but these compounds and their hydroxylated derivatives (OH-BDEs) impair normal thyroid function. Halogen bonding (XB) of PBDEs to an active site selenocysteine may prevent iodothyronine deiodinase(Dio)-catalyzed activation/deactivation of thyroid hormone (TH) derivatives. In this study, we compare the strength of the XB interactions of TH derivatives, iodine-based contrast agents and PBDEs/OH-BDEs with a methylselenolate model of the Dio active site using density functional theory calculations. The strength of the XB interaction depends upon the acceptor halide, the position of the halide, the number of ring substituents, and the proximity of hydroxyl groups to the XB site. The weaker Se⋅⋅⋅Br interactions relative to Se⋅⋅⋅I interactions are consistent with a model of competitive inhibition that blocks binding of THs at elevated PBDE/OH-BDE concentrations. XB interactions were generally more favorable at ortho and meta positions and in substrates with more electron-withdrawing substituents. PBDEs/OH-BDEs that mimic the binding behavior of THs, that is, containing ortho and meta bromides and adjacent hydroxyl groups, may be the most effective inhibitors. Highly-brominated PBDEs/OH-BDEs have comparable interaction energies to THs and may undergo debromination. These results may also suggest that XB strength must exceed a threshold value in order for PBDEs/OH-BDEs to undergo nucleophilic attack by Dio.


[Progress in research on imprinted gene associated with male infertility].
The connection between male infertility and abnormal methylation of imprinted genes has attracted much attention. Some imprinted genes, e.g., H19, MEG3, MEST and SNRPN, are known to be related with male infertility. Abnormal imprinted information may influence sperm concentration, motility and morphology, but the mechanism is still unclear. Sperm genomic imprinting reconstruction and erase respectively occur at the time of spermatogenesis and before embryo transfer. Many studies have shown that the probability of imprinting disorder syndrome of offspring born through assisted reproductive technology (ART) was significantly higher, leading to the worry about the safety of ART and speculation that the operation and in vitro environment may affect sperm imprinted information, which in turn may lead to imprinting diseases in the offspring. However, above connection still lacks convincing evidence. This paper has conducted a literature review of recent literature and explored the impact of abnormal methylation of imprinted genes on male fertility and the offspring.


Outcome of patients with hepatocellular carcinoma referred to a tertiary centre with availability of multiple treatment options including cadaveric liver transplantation.
Hepatocellular carcinoma (HCC) is a primary cancer of the liver with an established causal link to viral hepatitis and other forms of chronic liver disease. The aim of this study was to analyse the determinants of outcome in patients with HCC referred to a tertiary centre for management. Two hundred and thirty-five prospective patients with HCC and minimum 12-month follow-up were studied. The cohort was heterogeneous, with 52% Caucasian, 40% Asian and 5% of Middle-Eastern origin. Independent predictors of outcome included tumour size and number, the presence of ascites or portal vein thrombosis, alpha-foetoprotein >50 U/L and an impaired performance status. Treatment was determined on an individual case basis by a multidisciplinary tumour team. Surgical resection was primary treatment in 43 patients, liver transplantation in 40 patients, local ablation (percutaneous radiofrequency ablation or alcohol injection) in 33 patients, transarterial chemoembolisation in 33 patients, chemotherapy or other systemic therapy in 30 patients and no treatment in 56 patients. After adjustment for significant covariates, both liver transplantation (P<0.001) and surgical resection (P=0.029) had a significant effect on patient survival compared with no treatment, but local ablation (P=0.410) and chemoembolisation (P=0.831) did not. Liver transplantation resulted in superior overall and, in particular, disease-free survival compared with surgical resection (disease-free survival 84 vs 15% at 5 years). In conclusion, both surgical resection and liver transplantation significantly improve the survival of patients with HCC, but improvements need to be made to the delivery of loco-regional therapy to enhance its effectiveness.


TEMPERATURE EFFECTS AND GENOTYPE-BY-ENVIRONMENT INTERACTIONS IN HYBRIDS: HALDANE'S RULE IN FLOUR BEETLES.
When males of the flour beetle, Tribolium castaneum, are crossed to females of its close relative T. freemani, the sex ratio of the hybrids is female biased, owing in part to hybrid male mortality. Morphological abnormalities are also frequent in the surviving hybrid males, but not in the hybrid females. The finding that the heterogametic sex (male) is more adversely affected in interspecific crosses than the homogametic sex is consistent with Haldane's rule, which predicts that hybrid dysfunction should emerge as an indirect byproduct of divergent adaptation to differing environments. If so, environmental effects and genotype-by-environment interactions (GEI) should characterize the expression of Haldane's rule and interspecific hybrid traits in general. We used two wild-collected populations of T. castaneum (from Infantes, Spain, and Madagascar) to investigate the effects of environmental variation on the expression of Haldane's rule. Males from each population were mated to several T. freemani females and the half-sibling hybrid progenies were reared across a series of temperature regimes. For both populations, we found that hybrids raised at higher temperatures exhibited a more extreme expression of Haldane's rule: The hybrid sex ratios were more biased toward females and hybrid males had a much higher incidence of morphological abnormalities. The average response to temperature, the norm of reaction for Haldane's rule, varied between the two populations, and we found considerable and significant GEI for both hybrid traits within both populations. The evolutionary implications of these findings are discussed in the context of speciation arising as an indirect effect of local adaptation.


[On myositis ossificans localisata and its operative treatment (author's transl)].
We observed 52 patients with myositis ossificans localisata partly of a traumatic, neurogenic or morbid (inflammable) origin. The fact that preferably young men are concerned in cases of traumatic and neurogenic myositis ossificans localisata is certainly not only caused by their increased exposition to trauma, but also by disposition. For indication and operative treatment it is necessary to classify as well as radiologically III different stages of development as respective groups of muscles. In posttraumatic and neurogenic cases relapses post operationem may probably be avoided in case, there is a radiological stage III (total development of muscle ossification).


On-Surface Photochemistry of Pre-Ordered 1-Methyl-2-phenyl-acetylenes: C-H Bond Activation and Intermolecular Coupling on Highly Oriented Pyrolytic Graphite.
In this contribution we report on light-induced metal-free coupling of propynylbenzene molecular units on highly oriented pyrolytic graphite. The reaction occurs within the self-assembled monolayer and leads to the generation of covalently coupled 1,5-hexadiyne and para-terphenyl derivatives under topological control. Such photochemical uncatalysed pathway represents an original approach in the field of topological C-C coupling at the solid/liquid interface and provides new insight into the low temperature formation of aromatic compounds at the surface of carbonaceous supports.


Secretory activity in salt glands of birds and turtles: stimulation via cyclic AMP.
O2 consumption in tissue slices from the nasal salt gland of the duck and the lachrymal salt gland of Malaclemys is stimulated by methacholine, a stimulation that is inhibited by bumetanide and by ouabain. In addition, the calcium ionophore A23187 mimics the action of methacholine in stimulating this secretion-related O2 consumption in both glands, suggesting a second-messenger role for this ion in the cholinergic response. However, the adenylate cyclase activator, forskolin, and the cyclic AMP analogue, 8-cpt-cAMP, also stimulate ouabain-sensitive and bumetanide-sensitive O2 consumption in both the duck gland and the Malaclemys gland. It is suggested that the mechanism of salt secretion in the Malaclemys lachrymal gland conforms to that previously described for other extrarenal salt-secreting tissues in nonmammalian vertebrates and, as in the bird gland, is subject to a cholinergic regulation potentially acting via changes in intracellular calcium. In addition to this, secretory activity in both the avian and the turtle glands can be stimulated by a previously undisclosed adenylate cyclase-cyclic AMP system. The identity of the primary signal for such a system is not known, nor is the nature of any interrelationship between the two second-messenger systems that have been identified in these glands.


Structure and UV-vis spectrum of C(60) fullerene in ethanol: a sequential molecular dynamics/quantum mechanics study.
A molecular dynamics simulation combined with semiempirical quantum mechanics calculations has been performed to investigate the structure, dynamical, and electronic properties of pure C60 in liquid ethanol. The behavior of the fullerene alcoholic solution was obtained by using the NPT ensemble under ambient conditions, including one C60 fullerene immersed in 1000 ethanol molecules. Our analyzed center-of-mass pairwise radial distribution function indicated that, on average, there are 32, 72, 132, and 187 ethanol molecules around, respectively, the first, second, third, and fourth solvation shells of the C60 molecule. To investigate the UV-vis transition energies of C60 in the presence of ethanol, we have considered constituents of the time uncorrelated supramolecular structures of the first solvation shell, i.e., clusters of C60@{EtOH}32 types. The semiempirical calculations were performed at the intermediate neglect of differential overlap level with configuration interaction singles (INDO/CIS). Our results have pointed out that the characteristic C60 UV-vis absorbance peaks are slightly shifted to longer wavelengths, as compared to the isolated molecule. These findings are in connection with the weak donor-acceptor character of the interactions involving electron lone pairs of oxygen atoms on the solvent and the fullerene surface.


Does perceived stress moderate the association between depressive symptoms and socioemotional and behavioural strengths and difficulties in adolescence?
More and more students report high level of perceived stress during childhood and adolescence, which is associated with socioemotional and behavioural strengths and difficulties. This study aims-based on the cognitive vulnerability-transactional stress theory-to examine perceived stress in early adolescence as a potential moderator in the association between depressive symptoms and socioemotional and behavioural strengths and difficulties from early to middle adolescence. Results of latent moderated structural equations with questionnaire data from a longitudinal study with 1,088 German students (Time 1: Mage = 13.70, SD = 0.53; Time 2: N = 845, Mage = 15.32, SD = 0.49) indicate that perceived stress functions as a moderator in the above-mentioned association and dominates the interaction if perceived strongly.


Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study.
In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI). The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST-elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia. A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively). The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin.


Histopathological, Microbiological, and Radiographic Analysis of Antimicrobial Photodynamic Therapy for the Treatment of Teeth with Apical Periodontitis: A Study in Rats' Molars.
The aim of this study was to evaluate in vivo, by histological and radiographic analysis, the response of apical tissues of rats' teeth with experimentally induced apical periodontitis, after one- and two-session endodontic treatment with and without photodynamic therapy (PDT). A microbiological analysis was also performed to verify bacterial reduction after each treatment. Studies carried out in recent years highlighted the antibacterial potential of PDT when associated with conventional endodontic therapy in vitro. Although the antimicrobial effect of PDT is well-established, tissue response to PDT in teeth with apical periodontitis lacks studies. Thirty-two rats' root canals were assigned to four groups: one session/PDT-[chemomechanical preparation (CMP)+root canal filling (RCF)]; two sessions/PDT- [CMP+calcium hydroxide (CH) for 14 days+RCF]; one session/PDT+ [CMP+PDT+RCF], and two sessions/PDT+ [CMP+PDT+CH for 14 days+RCF]. For microbiological evaluation, samples were collected before and after proposed treatments. For radiographic and histological analysis, the animals were euthanized after 28 days and the mandibles surgically removed. PDT associated with conventional endodontic therapy was able to promote significant bacterial reduction in root canals with induced apical periodontitis, but this reduction was not significantly different to conventional endodontic therapy alone. Although radiographic evaluation showed no significant differences, histological analysis showed lower scores for neutrophils/eosinophils in PDT-treated groups and macrophages/giant cells in CH groups. The use of low-level laser as light source did not promote major improvement on radiographic and histological repair, but since the number of inflammatory cells slightly decreased, it may optimize repair by modulating inflammatory process. PDT may be indicated as an adjunct to conventional endodontic therapy for teeth with apical periodontitis, in association with an interappointment dressing with CH, in an attempt to produce better conditions to stimulate repair.


The role of genetically engineered soybean and Amaranthus weeds on biological and reproductive parameters of Spodoptera cosmioides (Lepidoptera: Noctuidae).
In soybean fields containing insecticide- and herbicide-resistant genetically engineered varieties, some weed species have increasingly become difficult to manage and may favor the population growth of secondary pests like Spodoptera cosmioides (Walker) (Lepidoptera: Noctuidae). To test this hypothesis, we measured life-history traits, population growth parameters and adult nutrient content of S. cosmioides reared on foliage from four Amaranthus species, from Cry1Ac Bt and non-Bt soybean varieties, and on meridic artificial diet. Larvae reared on A. palmeri and A. spinosus had a shorter development time (5-7 days) than larvae raised on the soybean varieties and A. hybridus. Armyworm survival probability was zero on A. viridis and highest (80% and 71%) on soybeans and A. palmeri. The latter and the artificial diet produced the heaviest larvae and pupae, in contrast to the non-Bt soybean variety. Body nutrient content diverged mostly for adults reared on artificial diet compared with those raised on the soybean varieties. The intrinsic rate of population increase (overall fitness) was 27.88% higher for the armyworms on A. palmeri, Cry1Ac Bt soybean and artificial diet compared with those on non-Bt soybean, A. spinosus and A. hybridus. Cry1Ac soybean fields infested by some Amaranthus weeds, especially A. palmeri, are conducive to the population growth of S. cosmioides. Integrated pest management programs may be needed to properly manage S. cosmioides in soybean fields, with surveillance for population peaks and judicious control measures when needed. © 2022 Society of Chemical Industry.


Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity.
Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC) of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.


Dimeric Le(a) (Le(a)-on-Le(a)) status of beta-haptoglobin in sera of colon cancer, chronic inflammatory disease and normal subjects.
The glycosyl epitope dimeric Lea (Lea-on-Lea), defined by mouse monoclonal antibody NCC-ST-421, was identified previously as tumor-associated antigen, expressed highly in various human cancer tissues and cell lines derived therefrom, but with minimal expression in various normal tissues. In the present study, we observed clearly higher expression of this epitope, defined by ST421, in beta-haptoglobin (beta-Hap) from sera of patients with colorectal cancer, compared to normal, healthy subjects or patients with chronic inflammatory processes (Crohn's disease, ulcerative colitis). We focused, therefore, on biochemical characterization of glycosyl epitope status expressed in beta-Hap. We concluded that the dimeric Lea epitope is carried by O-linked but not by N-linked structure, based on the following observations: i) Treatment of beta-Hap with alpha-L-fucosidase reduced its reactivity with ST421, but did not affect its reactivity with anti-Hap antibody. In contrast, treatment of purified beta-Hap with PNGase F, which releases N-linked glycans, had no effect on reactivity with ST421, but changed molecular mass from 40 kDa to 30 kDa. ii) Strong reactivity of Colo205 supernatant with ST421 was reduced clearly by pre-incubation of cells with benzyl-alpha-GalNAc.


Neurotrophin-3 promotes the differentiation of muscle spindle afferents in the absence of peripheral targets.
The neurons of the dorsal root ganglia (DRG) that supply muscle spindles require target-derived factors for survival. One necessary factor for these neurons is neurotrophin-3 (NT3). To determine whether NT3 can promote the survival of these neurons in the absence of other target-derived factors, we analyzed the effects of exogenous NT3 after early limb bud deletion in the chick. In control embryos, limb bud deletion eliminated approximately 90% of the trkC-positive (trkC+) neurons in lumbar DRG on the deleted side. In addition, the deletion led to a dramatic loss of collateral sensory projections to motoneurons. Exogenous NT3 restored a normal population of trkC+ neurons in lumbar DRG on the deleted side and increased the number of trkC+ neurons in DRG with normal targets (contralateral lumbar and thoracic). The effect was highly selective; NT3 increased the number of trkC+ neurons without significantly changing the number of either trkA+ or trkB+ neurons. The effect of NT3 was attributable to the rescue of DRG neurons from cell death, because exogenous NT3 reduced the number of pyknotic nuclei without significantly altering proliferation. Analysis of spinal projections showed further that many of the trkC+ neurons rescued by NT3 projected to the ventral spinal cord. These neurons thus had central projections characteristic of muscle spindle afferents. Together, our results indicate that NT3 signaling is both necessary and sufficient for the development of the proprioceptive phenotype, even in the absence of other signals from limb muscle.


Email consultations in general practice.
Email is an established method of communication in business, leisure and education but not yet health care. To evaluate an email service enabling communication between patients and their general practice regarding repeat prescriptions, appointment booking and clinical enquiries. Qualitative analysis of interactions and an electronic user survey. An urban practice in Dundee, Scotland. 150 patients aged 24 to 85. We set up a practice facility to allow our patients to use email to book appointments, order repeat prescriptions and consult their general practitioner (GP). Patient satisfaction with the service was very high. Patients specifically commended the practice for setting up a facility to allow communication outside standard working hours and for the ease of ordering repeat prescriptions. Patients were pleased to have a means of seeking their doctor's comment or opinion without bothering him or her by making and attending a formal face-to-face consultation. Email dialogue was polite, factual, but less formal than standard letters. Staff did not experience any perceptible rise in workload. Use of an email consultation facility worked well within an urban practice, was deemed helpful by patients, and resulted in no apparent increase in GP workload. Our results suggest that there may be an unmet need amongst patients for clinical email services, and that such services may have positive outcomes for patients and practices.


Light microscopy techniques for the demonstration of silicone gel.
Because of the difficulty in identifying silicone gel in histologic and cytologic specimens by means of conventional light microscopy, we investigated alternative light microscopy techniques, as well as specimen staining and preparation. Specimens from six periprosthetic capsules, one silicone granuloma specimen, and one synovial biopsy specimen obtained from women with silicone breast implants were cut at 4-, 10-, 20-, and 30-microns sections, stained with a variety of common stains, and correlated with electron probe microanalysis. In addition, a commercial silicone gel and silicone gel extracted from a previously implanted silicone breast prosthesis were smeared and examined unstained or stained with Papanicolaou and Diff Quik. Silicone was noted to be refractile, nonpolarizable, and nonstainable. Thicker sections prevented silicone "dropout" during processing and increased the contrast between stained tissue and unstained silicone (negative staining). The relative ease of silicone identification was greatly increased with non-Koehler, phase contrast, and darkfield microscopy. Staining the mounting media of hematoxylin-eosin-stained sections with a nonparticulate commercial ink allowed enhanced negative staining detection of silicone gel.


Advances in Polatuzumab Vedotin-PIIQ Therapy: A Review of Treatment Efficacy in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma.
Polatuzumab vedotin (PV) is an antibody-drug conjugate that has shown promising results in the treatment of diffuse B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBCL). This abstract summarizes the current understanding of PV's use in these malignancies based on available clinical data. Multiple clinical trials have evaluated PV as a part of combination therapy regimens in relapsed/refractory DLBCL and HGBCL. The pivotal Phase II study, GO29365, demonstrated that PV in combination with bendamustine and rituximab (BR) significantly improved progression-free survival and overall survival compared to BR alone in patients with relapsed/refractory DLBCL who ineligible for stem cell transplantation were. Subsequently, the US Food and Drug Administration granted accelerated approval to PV in this setting. PV's mechanism of action involves targeting CD79b, a cell surface receptor expressed in B-cell malignancies, and delivering the cytotoxic agent monomethyl auristatin E to CD79b-expressing cells. This approach enhances the selective killing of cancer cells while sparing normal cells. The safety profile of PV is generally manageable, with adverse events including infusion-related reactions, cytopenia, peripheral neuropathy, and infections. Overall, PV has emerged as a valuable treatment option for patients with relapsed/refractory DLBCL and HGBCL, offering improved outcomes when combined with appropriate chemotherapy regimens. Ongoing research and clinical trials are further exploring PV's potential in various treatment settings, including frontline therapy and in combination with other novel agents.


[Insertion of a second electrode array-a rare complication of CI reimplantation. German version].
Due to a technical defect or a medical indication, it may be necessary to explant a cochlear implant. This case report shows that there is the risk of encountering a nonremovable electrode array-as described here from the scala tympani-during cochlear reimplantation. In the present case, insertion of a second electrode array into the free and nonobstructed scala vestibuli was successful. Nonetheless, the indication for reimplantation must be carefully considered, especially in patients with tolerable limitations with little or no loss of speech understanding. Furthermore, surgery should not be performed solely because an implant upgrade is desired.


LinkImputeR: user-guided genotype calling and imputation for non-model organisms.
Genomic studies such as genome-wide association and genomic selection require genome-wide genotype data. All existing technologies used to create these data result in missing genotypes, which are often then inferred using genotype imputation software. However, existing imputation methods most often make use only of genotypes that are successfully inferred after having passed a certain read depth threshold. Because of this, any read information for genotypes that did not pass the threshold, and were thus set to missing, is ignored. Most genomic studies also choose read depth thresholds and quality filters without investigating their effects on the size and quality of the resulting genotype data. Moreover, almost all genotype imputation methods require ordered markers and are therefore of limited utility in non-model organisms. Here we introduce LinkImputeR, a software program that exploits the read count information that is normally ignored, and makes use of all available DNA sequence information for the purposes of genotype calling and imputation. It is specifically designed for non-model organisms since it requires neither ordered markers nor a reference panel of genotypes. Using next-generation DNA sequence (NGS) data from apple, cannabis and grape, we quantify the effect of varying read count and missingness thresholds on the quantity and quality of genotypes generated from LinkImputeR. We demonstrate that LinkImputeR can increase the number of genotype calls by more than an order of magnitude, can improve genotyping accuracy by several percent and can thus improve the power of downstream analyses. Moreover, we show that the effects of quality and read depth filters can differ substantially between data sets and should therefore be investigated on a per-study basis. By exploiting DNA sequence data that is normally ignored during genotype calling and imputation, LinkImputeR can significantly improve both the quantity and quality of genotype data generated from NGS technologies. It enables the user to quickly and easily examine the effects of varying thresholds and filters on the number and quality of the resulting genotype calls. In this manner, users can decide on thresholds that are most suitable for their purposes. We show that LinkImputeR can significantly augment the value and utility of NGS data sets, especially in non-model organisms with poor genomic resources.


Agreement Between Cytology and Histopathology for Regional Lymph Node Metastasis in Dogs With Melanocytic Neoplasms.
Melanocytic neoplasms are common in dogs and frequently occur within the oral cavity or in haired skin. The behavior of melanocytic neoplasms is variable and depends on tumor location, size, and histopathologic features. This study compared cytopathology and histopathology of 32 lymph nodes from 27 dogs diagnosed with melanocytic neoplasms. Agreement between the original cytology report, cytology slide review, original histopathology report, and histopathology slide review was determined for each lymph node. A subset of lymph nodes was subjected to immunohistochemistry (Melan-A) and additional histochemical stains/techniques (Prussian blue, bleach) to assist in differentiation of melanocytes and melanophages. Agreement ranged from slight to fair for each of the variables evaluated with weighted kappa (κw) or kappa (κ) analysis (original cytology vs cytology review κw = 0.24; original cytology vs original histopathology κw = 0.007; original cytology vs histopathology review κw = 0.23; cytology review vs original histopathology κw = 0.008; cytology review vs histopathology review κw = 0.006; and original histopathology vs histopathology review κ = 0.18). The diagnoses (metastatic, equivocal, or negative for metastasis) of the original report and slide review for both cytology and histopathology were not significantly correlated with survival in this population of patients. Overall, agreement between cytology and histopathology was poor even with a single clinical or anatomic pathologist performing slide review. Consensus between routine cytology and histopathology for staging of lymph nodes in patients with melanocytic neoplasms is poor and does not correlate with survival.


Hdac8 Inhibitor Alleviates Transverse Aortic Constriction-Induced Heart Failure in Mice by Downregulating Ace1.
Heart failure is characterized by activation of the renin-angiotensin-aldosterone system, which is involved in the regulation of cardiac hypertrophy and hypertension. Recently, we reported that Hdac8 inhibition alleviates isoproterenol-induced and angiotensin II-induced cardiac hypertrophy or hypertension in mice. Here, the effect and regulatory mechanisms of the Hdac8 selective inhibitor PCI34051 on pressure overload-induced heart failure were examined. At week 6 posttransverse aortic constriction (TAC), mice were administered with PCI34051 (3, 10, or 30 mg/kg bodyweight/day) for 2 weeks. The therapeutic effects of PCI34051 on TAC-induced cardiac and lung hypertrophy were determined by examining the heart weight-to-bodyweight and lung weight-to-bodyweight ratios and the cross-sectional cardiomyocyte area. Echocardiography analysis revealed that PCI34051 mitigated TAC-induced decreased ejection fraction and fractional shortening. Additionally, the expression of Hdac8 was upregulated in the cardiac and pulmonary tissues of TAC mice. The expression levels of Ace1 and Agtr1 were upregulated, whereas those of Ace2 and Agtr2 were downregulated in TAC mice. PCI34051 treatment or Hdac8 knockdown alleviated inflammation as evidenced by Rela downregulation and Nfkbia upregulation in mice, as well as in cardiomyocytes, but not in cardiac fibroblasts. Hdac8 overexpression-induced Rela pathway activation was downregulated in Ace1 knockdown cells. Picrosirius red staining, real-time polymerase chain reaction, and western blotting analyses revealed that PCI34051 alleviated fibrosis and downregulated fibrosis-related genes. Moreover, PCI34051 or Hdac8 knockdown in rat cardiac fibroblasts alleviated cardiac fibrosis through the Tgfb1-Smad2/3 pathway. The results of overexpression and knockdown experiments revealed that Hdac8 and Ace1 promote inflammation and fibrosis. Treatment with PCI34051 enhanced cardiac and lung functions in the TAC-induced heart failure mouse model. These data suggest that HDAC8 is a potential novel therapeutic target for heart failure accompanied by pathological lung diseases.


Seeking a reading machine for the blind and discovering the speech code.
A machine that can read printed material to the blind became a priority at the end of World War II with the appointment of a U.S. Government committee to instigate research on sensory aids to improve the lot of blinded veterans. The committee chose Haskins Laboratories to lead a multisite research program. Initially, Haskins researchers overestimated the capacities of users to learn an acoustic code based on the letters of a text, resulting in unsuitable designs. Progress was slow because the researchers clung to a mistaken view that speech is a sound alphabet and because of persisting gaps in man-machine technology. The tortuous route to a practical reading machine transformed the scientific understanding of speech perception and reading at Haskins Labs and elsewhere, leading to novel lines of basic research and new technologies. Research at Haskins Laboratories made valuable contributions in clarifying the physical basis of speech. Researchers recognized that coarticulatory overlap eliminated the possibility of alphabet-like discrete acoustic segments in speech. This work advanced the study of speech perception and contributed to our understanding of the relation of speech perception to production. Basic findings on speech enabled the development of speech synthesis, part science and part technology, essential for development of a reading machine, which has found many applications. Findings on the nature of speech further stimulated a new understanding of word recognition in reading across languages and scripts and contributed to our understanding of reading development and reading disabilities.


Simulator training enhances resident performance in transesophageal echocardiography.
Standardized training via simulation as an educational adjunct may lead to a more rapid and complete skill achievement. The authors hypothesized that simulation training will also enhance performance in transesophageal echocardiography image acquisition among anesthesia residents. A total of 42 clinical anesthesia residents were randomized to one of two groups: a control group, which received traditional didactic training, and a simulator group, whose training used a transesophageal echocardiography-mannequin simulator. Each participating resident was directed to obtain 10 commonly used standard views on an anesthetized patient under attending supervision. Each of the 10 selected echocardiographic views were evaluated on a grading scale of 0 to 10, according to predetermined criteria. The effect of the intervention was assessed by using a linear mixed model implemented in SAS 9.3 (SAS Institute Inc., Cary, NC). Residents in the simulation group obtained significantly higher-quality images with a mean total image quality score of 83 (95% CI, 74 to 92) versus the control group score of 67 (95% CI, 58 to 76); P = 0.016. On average, 71% (95% CI, 58 to 85) of images acquired by each resident in the simulator group were acceptable for clinical use compared with 48% (95% CI, 35 to 62) in the control; P = 0.021. Additionally, the mean difference in score between training groups was the greatest for the clinical anesthesia-1 residents (difference 24; P = 0.031; n = 7 per group) and for those with no previous transesophageal echocardiography experience (difference 26; P = 0.005; simulator n = 13; control n = 11). Simulation-based transesophageal echocardiography education enhances image acquisition skills in anesthesiology residents.


The chemokine SDF-1/CXCL12 contributes to T lymphocyte recruitment in human pre-ovulatory follicles and coordinates with lymphocytes to increase granulosa cell survival and embryo quality.
We investigated the production and the role of the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) in pre-ovulatory follicles of women undergoing in vitro fertilization. We detected CXCL12 and its receptor CXCR4 by flow cytometry, western blotting and RT-PCR. We tested cell migration in Transwell experiments. We measured apoptosis using delta psi m-sensitive fluorescent probe DiOC6(3) and we screened apoptosis-related gene expression with macro-arrays. Granulosa cells from follicular aspirates produce CXCL12 that contributes to T lymphocytes recruitment. CXCL12 reduces early apoptosis of granulosa cells. This effect is accompanied by a shift of bcl2/bax ratio, and decreased expression of p53-targeted genes (pig7, pig8, p21, gadd45). Removal of lymphocytes disables CXCL12-mediated anti-apoptotic effect on granulosa cells. Anti-apoptotic activity of CXCL12 is positively correlated to high quality of embryos. In conclusion, CXCL12 is locally produced by luteinizing granulosa cells. It specifically contributes to T lymphocytes recruitment and coordinates with local lymphocytes to increase granulosa cell survival and embryo quality.


Interventional radiology methods of treating ureteral strictures developed on anastomoses after the radical cystectomy in Mainz pouch II and ileal conduit derivation.
OBJECTIVE of this work is to evaluate interventional radiology modalities such as balloon catheter dilation (BCD) and stent insertion, as minimally invasive methods in treatment uretero-enteral anastomotic strictures. Retrospective study enrolled 26 patients (pts) in whom percutaneous BCD (17 pts) and metal stent implantation (9 pts) were done. Study was conducted from June 2005 till August 2007 and included total amount of 470 pts operated during 4 year period from 2003 till 2007. In 26 pts 35 ureteral units were treated, all of them in ambulatory conditions under oral analgosedation, monitored by fluoroscopy. Percutaneous BCD or stent implantation was performed in 24 pts and in 2 pts combined antegrade-retrograde approach for stent delivery, was applied. In all cases percutaneous nephrostomy (PCN) was left for 7 days period after procedure but in 6 units (5 pts) it remained permanent solution. First check up was done 7 days after by contrast media injection through nephrostomy tube prior to its extraction. Second control was done 30 days after by ultrasound exam and the last control (3 months after) by intravenous urography (IVU). In our specimen 17pts had strictures unilaterally (65.4%) and in 9 pts (34.6%) it occurred bilaterally. First check up revealed 82.7% success of BCD, in 17.3% BCD was repeated with the final success rate of 73.5% (19/26). In four pts (26.5%) after BCD reobliteration happened and PCN was left. Patent ureteral lumen was observed in 6 pts (85.7%) with stent inserted while one pt underwent surgical reintervention. No significant difference between BCD and stent insertion success rate was noticed, based upon morphological parameters (ureteral lumen diameter, pelvicaliceal system dilatation) and serum creatinin level. BCD and stent insertion showed satisfactory results (following 3 months) in ureteroenteral anastomotic stricture recanalization. They include ambulatory conditions, ability to repeat procedure, without complications -excluding restenosis which finally can be surgically treated.


Familiar words can serve as a semantic seed for syntactic bootstrapping.
Young children can exploit the syntactic context of a novel word to narrow down its probable meaning. But how do they learn which contexts are linked to which semantic features in the first place? We investigate if 3- to 4-year-old children (n = 60) can learn about a syntactic context from tracking its use with only a few familiar words. After watching a 5-min training video in which a novel function word (i.e., 'ko') replaced either personal pronouns or articles, children were able to infer semantic properties for novel words co-occurring with the newly learned function word (i.e., objects vs. actions). These findings implicate a mechanism by which a distributional analysis, associated with a small vocabulary of known words, could be sufficient to identify some properties associated with specific syntactic contexts.


The effect of temperature on bactericidal properties of 10% povidone-iodine solution.
Ten percent povidone-iodine (PVI) is commonly used as a bactericidal solution before amniocentesis is performed. Warming PVI may increase patient comfort; however, the effect of warming on its bactericidal properties is not known. The objective of this study was to determine the effect of warming 10% PVI on its bactericidal properties. Room temperature of PVI was 25 degrees C, and temperature in an ultrasonic gel warmer was 32 degrees C. In vitro experiments were conducted in 25 degrees C and 32 degrees C water baths. Nine milliliters of PVI at each temperature was added to 1 mL of bacteria (10(7) organisms/mL Staphylococcus aureus, Enterococcus species, Escherichia coli, group B Streptococcus). After 0.25, 0.5, 1, 2, 4, and 8 minutes, 1-mL samples were removed and added to 4 mL of 0.5% sodium thiosulfate (to neutralize the iodine and interrupt bactericidal action). The number of viable organisms was determined by plating 0.1-mL samples on trypticase soy agar plates. Plates were incubated at 37 degrees C for 24 hours and colony-forming units (CFUs) were counted. For in vivo experiments in 40 volunteers, a 9-cm2 area of the dorsum of each hand was wiped with a sterile cotton swab to obtain a sample of bacteria for culture. The area was then wiped for 15 seconds with PVI at 25 degrees C or 32 degrees C and recultured. The bactericidal properties of PVI at each temperature were compared. The Mann-Whitney U test was used as appropriate, and P <.05 was considered significant. In vitro, PVI was bactericidal against E coli, S aureus, Enterococcus species, and group B Streptococcus within 0.25 minutes at both 25 degrees C and 32 degrees C, with median bacterial growth of 0 CFU/plate for each species of bacteria studied (3 replicates at each temperature). Median bacterial growth from skin was 4 CFU/plate (range, 0 to >100). After hands were wiped with PVI at 25 degrees C and 32 degrees C, median bacterial growth was 0 CFU/plate (range, 0-8) and 0 CFU/plate (range, 0-15), respectively (not significant). PVI is as effective at 32 degrees C as it is at 25 degrees C. Use of PVI at 32 degrees C should be considered to increase patient comfort in procedures performed without the use of anesthetics.


Spatio-temporal changes of AOD in Xinjiang of China from 2000 to 2019: Which factor is more influential, natural factor or human factor?
Aerosol optical depth (AOD), which represents the optical attenuation, poses a major threat to the production activity, air quality, human health and regional sustainable development of arid and semi-arid areas. To some degree, AOD shows areal air pollution level and possesses obvious spatio-temporal characteristics. However, long-time sequences and detailed AOD information can not be provided due to currently limited monitoring technology. In this paper, a daily AOD product, MODIS-based Multi-angle Implementation of Atmospheric Correction (MAIAC), is deployed to analyze the spatio-temporal characteristics in Xinjiang Uygur Autonomous Region from 2000 to 2019. In addition, the importance of influencing factors for AOD is calculated through Random Forest (RF) Model and the propagation trajectories of pollutants are simulated through Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) Model. Spatio distribution of AOD presents a tendency that AOD value in northern Xinjiang is low while the value in southern Xinjiang is high. Regions with high AOD values are mainly concentrated in Tarim Basin. AOD in southern Xinjiang is the highest, followed by that in eastern Xinjiang and AOD value in northern Xinjiang is the lowest. Seasonal variation of AOD is significant: Spring (0.309) > summer (0.200) > autumn (0.161) > winter (0.158). Average AOD value in Xinjiang is 0.196. AOD appears wavy from 2000 to 2014 with its low inflection point (0.157) appearing in 2005, and then increases, reaching its peak in 2014 (0.223). The obvious downward tendency after 2014 shows that the use of coal to natural gas (NG) conversion project improves the conditions of local environment. According to RF Model, NG contributes most to AOD. HYSPLIT Model reveals that aerosol in southern Xinjiang is related to the short-distant carriage of dust aerosol from the Taklimakan Desert. Aerosol there can affect Inner Mongolia through long-distant transport. Blocked by the Tianshan Mountains, fine dust particles can not cross the Tianshan Mountains to become a factor contributing to AOD in northern Xinjiang.


Socioeconomic issues of United States military neurosurgery.
Although the practice of neurosurgery in the United States (US) Armed Forces is in many ways similar to the civilian practice of neurosurgery, there are many differences as well. The unique challenges, duties, and opportunities US military neurosurgeons are given, both in peacetime and in times of conflict, are discussed, as are pathways for entering into service. The advantages of military service for neurosurgeons include sponsored training, decreased direct exposure to tort actions, little involvement with third-party payers, significant opportunities for travel, and military specific experiences. The most appealing aspect of military practice is serving fellow members of the US Armed Forces. Disadvantages include the extreme gap between the military and civilian pay scales, lack of support personnel, and in some areas low surgery-related case volume. The greatest concern faced by the military neurosurgical community is the failure to retain experienced neurosurgeons after their obligated service time has been completed, for which several possible solutions are described. It is hoped that future changes will make the practice of military neurosurgery attractive enough so that it will be seen as a career in itself and not an obligation to endure before starting practice in the "real world."


Nonoperative Management of Blunt Hepatic Trauma: Comparison of Level I and II Trauma Centers.
Most blunt liver injuries are treated with nonoperative management (NOM), and angiointervention (AI) has become a common adjunct. This study evaluated the use of AI, blood product utilization, pharmacological venous thromboembolic prophylaxis (VTEp), and outcomes in severe blunt liver trauma managed nonoperatively at level I versus II trauma centers. American College of Surgeons Trauma Quality Improvement Program (TQIP) study (2013-2016), including adult patients with severe blunt liver injuries (AIS score>/= 3) treated with NOM, was conducted. Epidemiological and clinical characteristics, severity of liver injury (AIS), use of AI, blood product utilization, and VTEp were collected. Outcomes included survival, complications, failure of NOM, blood product utilization, and length of stay (LOS). Study included 2825 patients: 2230(78.9%) in level I and 595(21.1%) in level II centers. There was no difference in demographics, clinical presentation, or injury severity between centers. Angiointervention was used in 6.4% in level I and 7.2% in level II centers (P=.452). Level II centers were less likely to use LMWH for VTEp (.003). There was no difference in mortality or failure of NOM. In level II centers, there was a significantly higher 24-hour blood product utilization (PRBC P = .015 and platelets P = .002), longer ventilator days (P = .012), and longer ICU (P< .001) and hospital LOS (P = .024). The incidence of ventilator-associated pneumonia was significantly higher in level II centers (P = .003). Utilization of AI and NOM success rates is similar in level I and II centers. However, the early blood utilization, ventilator days, and VAP complications are significantly higher in level II centers.


[Medical Rehabilitation as an Attractive Field of Work for Medical Doctors? - A Qualitative Survey].
In the German Health system there is an increasing competition in the recruitment of specialised staff, especially for rehabilitation centres, which are deemed less attractive. Therefore, this study examines the attractiveness of the field of medical rehabilitation from the point of view of medical professionals. We conducted 16 semi-structured interviews with doctors from 7 rehabilitation centres with different medical specialisations. The interviews were digitized and transcribed. A structured content analysis was carried out using the software MAXQDA 11. 745 codes were identified and assigned to the categories "attractiveness", "unfavourable aspects" and "special features" of rehabilitation. Regarding medical rehabilitation, the interviewees appreciated especially the predictable, flexible working environment with little time pressure. Other than working with rehabilitative patients working as part of an interdisciplinary team was of high importance for the interviewees. Among the special features of rehabilitation in comparison with acute care were the higher relevance of the bio-psycho-social model of health and illness as well as the higher proportion of communication and organisation. Medical rehabilitation in Germany is an attractive field of work for medical doctors. This fact should be considered more with regards to rehabilitation's public image.


Enhanced stability of the optical responses from all-inorganic perovskite nanocrystals embedded in a synthetic opal matrix.
Nanostructured luminescent materials based on perovskite nanocrystals (p-NCs) are attractive since their optical properties can be tuned in a wide spectral range with high luminescence quantum yields and lifetimes, however, they lack stability. In this work, the optical properties of highly luminescent colloidal p-NCs (CsPbX3, where X = Cl/Br, Br, I) embedded in porous opal matrices are presented. It is shown that the photoluminescence of the p-NCs embedded into opal matrices possess increased longtime stability of its spectral and kinetic parameters under ambient conditions. LEDs based on the developed materials show pure color p-NC emission with stability of its parameters. The results of this work may expand the knowledge of interactions between luminescent nanoparticles within multicomponent nanostructured materials for further photonic applications.


[An orthogonal method for comparing extracting techniques of licorice root extract].
A L9(3(4)) form developed by the orthogonal method was used to study the size, extraction solvent and extraction frequency of licorice root extract, and taking the recovery of glycyrrhizic acid as the criteria, a comparison was made on the different ways of extracting the herb. The result showed the glycyrrhizic acid could be recovered over 10% (about 7% higher than that from water treatment) when the herb was cut into pieces and then extracted by fluxing for 3 times with 60% alcohol containing 0.3% ammonia.


Analysis of nuclear uracil-DNA glycosylase (nUDG) turnover during the cell cycle.
Uracil-DNA glycosylases (UDG/UNG) are enzymes that remove uracil from DNA and initiate base-excision repair. These enzymes play a key role in maintaining genomic integrity by reducing the mutagenic events caused by G:C to A:T transition mutations. The recent finding that a family of RNA editing enzymes (AID/APOBECs) can deaminate cytosine in DNA has raised the interest in these base-excision repair enzymes. The methodology presented here focuses on determining the regulation of the nuclear isoform of uracil-DNA glycosylase (nUDG), a 36,000 Da protein. In synchronized HeLa cells, nUDG protein levels decrease to barely detectable levels during the S phase of the cell cycle. Immunoblot analysis of immunoprecipitated or affinity-isolated nUDG reveals ubiquitin-conjugated nUDG when proteolysis is inhibited by agents that block proteasomal-dependent protein degradation.


Functional genomics bridges the gap between quantitative genetics and molecular biology.
Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field.


Anti-thrombotic therapy strategies with long-term anticoagulation after percutaneous coronary intervention - a systematic review and meta-analysis.
Background: Long-term oral anticoagulants (OAC) increases bleeding risk after the percutaneous coronary intervention (PCI) with dual antiplatelet therapy (DAPT) with Aspirin and P2Y12 inhibitors. We hypothesize that dual anti-thrombotic therapy (DATT) reduces bleeding without increased cardiovascular events. Objectives: DATT does not increase adverse cardiovascular events compared to triple anti-thrombotic therapy (TATT). Method: We searched MEDLINE, PUBMED, Google Scholar, Cochrane and EMBASE from inception to 6 April 2019 for randomized control trials (RCTs) comparing DATT to TATT after PCI. Results: We identified 641 citations (411 after excluding duplicates). Four RCTs with 5,317 patients (3,039 on DATT vs 2,278 on TATT) were included. DATT arm showed significantly reduced [total bleeding, 731 vs. 784, odds ratio [OR] = 0.51, Confidence Interval [CI] = 0.39-0.67, p < 0.00001, I2 = 71% (I2 = 0% without WOEST study)], [TIIMI major bleeding 60 vs. 80, OR = 0.56, CI = 0.4-0.79, p = 0.0009, I2 = 0%], and [TIIMI minor bleeding, 70 vs 126, OR = 0.43, CI = 0.32-0.59, p < 0.00001, I2 = 0%]. There was no difference in subsequent strokes, myocardial infarction, stent thrombosis, and mortality. A trend towards decreased non-cardiac deaths with DATT was observed, 14 vs 26, OR = 0.55, CI = 0.27-1.10, p = 0.09, I2 = 6%. Conclusions: DATT is associated with significantly reduced bleeding and a trend towards reduced non-cardiac death with no difference in adverse cardiovascular outcomes.


Calculation of Dipole-Forbidden 5f Absorption Spectra of Uranium(V) Hexa-Halide Complexes.
Restricted-active-space wave function calculations including spin-orbit coupling, in combination with Kohn-Sham density functional calculations of vibrational modes, were used to determine the vibronic and electronic absorption intensities of the near-infrared electric dipole-forbidden 5f-5f transitions of representative uranium(V) hexa-halide complex ions. The agreement with experimentally assigned vibronic and electronic transitions measured for powder or solution samples of salts of the complex ions is reasonable overall and excellent for the experimentally best-resolved E5/2u → E5/2u' bands. The intensity of the vibronic transitions may be borrowed from ligand-to-metal charge-transfer excitations as well as 5f-to-6d metal-centered transitions. Magnetically allowed electronic transitions contribute to the two lower-frequency bands of the ligand-field spectrum.


3PO as a Selective Inhibitor of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 in A375 Human Melanoma Cells.
The occurrence of BRAFV600E mutation causes an up-regulation of the B-raf kinase activity leading to the stabilization of hypoxia-inducible factor 1-alpha (HIF-1α) - the promoter of the 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) enzyme. The aim of the study was to examine the effect of the (2E)-3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), as an inhibitor of PFKFB3, on human melanoma cells (A375) with endogenous BRAFV600E mutation. A375 cells were exposed to different concentrations of 3PO and the following tests were performed: docking, cytotoxicity assay, immunocytochemistry staining glucose uptake, clonogenic assay, holotomography imaging, and flow cytometry. Our studies revealed that 3PO presents a dose-dependent and time-independent cytotoxic effect and promotes apoptosis of A375 cells. Furthermore, the obtained data indicate that 3PO induces cell cycle arrest in G1/0 and glucose uptake reduction. Taking all together, our research demonstrated a here should be proapoptotic and antiproliferative effect of 3PO on A375 human melanoma cells.


Antibiotic overuse after discharge from medical short-stay units.
Of 100 patients discharged from short-stay units (SSUs) with antibiotics, 47 had a skin and soft-tissue infection, 22 had pneumonia, and 21 had a urinary tract infection. Among all discharge antibiotic prescriptions, 78% involved antibiotic overuse, most commonly excess duration (54 of 100) and guideline discordant selection (44 of 100).


Concentration recovery for SPECT CNS dopamine-receptor studies for monkeys.
Most commercial SPECT scanners do not properly compensate for scattering and partial volume effects, which severely impacts the quantitation of clinical and research SPECT studies, especially in CNS dopamine studies. Hence, in this paper, a brain phantom containing a monkey skull was used to calibrate a Picker Prism 3000 SPECT camera for quantitative studies of 123I and 99mTc-labeled radiopharmaceuticals. In the calibration study, two small vials representing basal ganglia were inserted into a skull phantom. A series of images were taken with different concentration ratios between the basal ganglia and the other brain compartments to simulate the dynamic imaging study of the dopamine D2 receptor in a monkey brain. Based on this calibration, a simple method is proposed for count correction in the region of interest (ROI). This technique is superior to using a single calibration factor from a cylindrical uniform activity phantom since it can compensate for both the partial volume effect and the dynamically changing effect of scattering. A significant difference between the true and measured values was observed in the correction factors (by a factor as much as 3). Furthermore, a cylindrical phantom, approximately the size of a monkey's head and containing the same basal ganglia inserts, was used to investigate the feasibility of using a cylindrical phantom with the proposed correction method. The results indicate that it is feasible to use a cylindrical phantom for the case where the activity inside the brain cavity and the activity in the surrounding tissue are similar.