Electron spin relaxation of iron-sulphur proteins studied by microwave power saturation.
The electron-spin relaxation of iron-sulphur centres in a range of simple proteins (ferredoxin, high-potential iron-sulphur protein and rubredoxin) was investigated by means of the temperature dependence and microwave power saturation of the EPR signal. The proteins containing [2Fe-2S] centres all showed temperature optima higher than those for [4Fe-4S] centres, but the difference between the slowest-relaxing [4Fe-4S] protein (Chromatium high-potential iron-sulphur protein) and the fastest-relaxing [2Fe-2S] protein (Halobacterium halobium ferredoxin) was small. A greater distinction was seen in the power saturation behaviour at low temperature (10--20 K). The behaviour of the signal intensity as a function of microwave power was analyzed in terms of the power for half saturation P 1/2 and the degree of homogeneous/inhomogeneous broadening. The effect of distorting the protein structure by salts, organic solvents and urea was to decrease the electron-spin relaxation rate as shown by a decreased value of P 1/2. The addition of Ni2+ as a paramagnetic perturbing agent caused an increase in the electron-spin relaxation rate of all the proteins, with the exception of adrenal ferredoxin, as shown by an increased P 1/2 and, in a few cases, broadening of the linewidth. Ferricyanide, a commonly used oxidizing agent, has similar effects. These results are discussed in relation to the use of paramagnetic probes to determine whether iron-sulphur centres are near to a membrane surface. Spin-spin interactions between two paramagnetic centres in a protein molecule such as a 2[4Fe-4S] ferredoxin, lead to more rapid electron-spin relaxation. This method was used to detect a spin-spin interaction between molybdenum V and centre Fe-SI in xanthine oxidase.


The management of healthcare employees' job satisfaction: optimization analyses from a series of large-scale surveys.
Measuring employees' satisfaction with their jobs and working environment have become increasingly common worldwide. Healthcare organizations are not extraneous to the irreversible trend of measuring employee perceptions to boost performance and improve service provision. Considering the multiplicity of aspects associated with job satisfaction, it is important to provide managers with a method for assessing which elements may carry key relevance. Our study identifies the mix of factors that are associated with an improvement of public healthcare professionals' job satisfaction related to unit, organization, and regional government. Investigating employees' satisfaction and perception about organizational climate with different governance level seems essential in light of extant evidence showing the interconnection as well as the uniqueness of each governance layer in enhancing or threatening motivation and satisfaction. This study investigates the correlates of job satisfaction among 73,441 employees in healthcare regional governments in Italy. Across four cross sectional surveys in different healthcare systems, we use an optimization model to identify the most efficient combination of factors that is associated with an increase in employees' satisfaction at three levels, namely one's unit, organization, and regional healthcare system. Findings show that environmental characteristics, organizational management practices, and team coordination mechanisms correlates with professionals' satisfaction. Optimization analyses reveal that improving the planning of activities and tasks in the unit, a sense of being part of a team, and supervisor's managerial competences correlate with a higher satisfaction to work for one's unit. Improving how managers do their job tend to be associated with more satisfaction to work for the organization. The study unveils commonalities and differences of personnel administration and management across public healthcare systems and provides insights on the role that several layers of governance have in depicting human resource management strategies.


Examining how and why polygenic dopamine composite levels moderate adolescents' vulnerability to peer victimization.
Extensive literature documents that dopaminergic genes play an important role in the link between adverse environments and adolescents' problem behavior. However, little is known about the potential mechanism underlying adolescents' vulnerability to peer victimization. The current study examined the effect of the interplay between a polygenic dopamine composite (i.e., COMT Val158Met and DRD2-141C Ins/Del polymorphisms) and peer victimization on adolescents' externalizing problems as well as the mediating role of emotion dysregulation in the interactive effects in a sample of 393 Chinese adolescents (Mean age = 14.71 years; 50.1% girls). A significant moderation of dopaminergic genetic composite was observed in girls but not in boys. In addition, emotion dysregulation partially explained the moderating effect of dopaminergic genes. Specifically, girls with genic composite indexing low dopamine activity reported a higher level of emotion dysregulation when faced with more peer victimization. More difficulties with emotion regulation, in turn, predicted more pronounced externalizing problems in girls. This study underscores polygenic underpinnings of adolescent vulnerability to negative peer experiences and suggests the importance of considering sex differences when investigating genic influence on the relationship between adverse environments and externalizing problems.


A high performance liquid chromatography method for the analysis of total and free indomethacin in serum.
A simple rapid and sensitive HPLC technique for the analysis of total and free plasma indomethacin concentrations in neonates is described. The advantages of the technique are small sample volumes (50 microL) enabling the use of capillary samples, direct extraction, low limits of detection (20 ng/mL) and good precision (CV less than 7% between-batch). Indomethacin and the internal standard (flufenamic acid) eluted within 12 min and the peaks were unaffected by indomethacin metabolites or by a number of commonly used drugs. The technique is suitable for the investigation into the pharmacokinetics of total and free indomethacin, in neonates with patent ductus arteriosus, and could be used to define a therapeutic window for free indomethacin levels to enable therapeutic drug monitoring to occur in this condition.


Monochorionic-triamniotic triplet pregnancy after intracytoplasmic sperm injection, assisted hatching, and two-embryo transfer: first reported case following IVF.
BACKGROUND: We present a case of monochorionic-triamniotic pregnancy that developed after embryo transfer following in vitro fertilization (IVF). METHODS: After controlled ovarian hyperstimulation and transvaginal retrieval of 22 metaphase II oocytes, fertilization was accomplished with intracytoplasmic sperm injection (ICSI). Assisted embryo hatching was performed, and two embryos were transferred in utero. One non-transferred blastocyst was cryopreserved. RESULTS: Fourteen days post-transfer, serum hCG level was 423 mIU/ml and subsequent transvaginal ultrasound revealed a single intrauterine gestational sac with three separate amnion compartments. Three distinct foci of cardiac motion were detected and the diagnosis was revised to monochorionic-triamniotic triplet pregnancy. Antenatal management included cerclage placement at 19 weeks gestation and hospital admission at 28 weeks gestation due to mild preeclampsia. Three viable female infants were delivered via cesarean at 30 5/7 weeks gestation. CONCLUSIONS: The incidence of triplet delivery in humans is approximately 1:6400, and such pregnancies are classified as high-risk for reasons described in this report. We also outline an obstetric management strategy designed to optimize outcomes. The roles of IVF, ICSI, assisted embryo hatching and associated laboratory culture conditions on the subsequent development of monozygotic/monochorionic pregnancy remain controversial. As demonstrated here, even when two-embryo transfer is employed after IVF the statistical probability of monozygotic multiple gestation cannot be reduced to zero. We encourage discussion of this possibility during informed consent for the advanced reproductive technologies.


Lifestyle approach for type 2 diabetes and metabolic syndrome.
Recent changes in lifestyle, including physical inactivity and unhealthy diets, are likely to have played an important role in the global epidemic of obesity, type 2 diabetes, and metabolic syndrome. Implementation of a healthier lifestyle, with an increase in physical activity and a reduction of body weight, based on the regulation of calories and fat intake, are the basis for the prevention and treatment of both type 2 diabetes and metabolic syndrome. Intervention studies based on changes in lifestyle in individuals at risk found that diabetes incidence was reduced by 42% to 63%. Similarly, intensive lifestyle changes in patients with the metabolic syndrome have been shown to reduce the prevalence of the syndrome by 20% to 48%. Reduction of body weight, improvement of the quality of diet, and promotion of physical activity are the main approaches to prevent and treat patients with type 2 diabetes or metabolic syndrome.


Platypnoea Orthodeoxia Syndrome and Patent Foramen Ovale Closure: Single-Centre Experience and Long-Term Follow-Up.
Platypnoea orthodeoxia syndrome (POS) is an uncommon condition characterised by dyspnoea and arterial desaturation induced by an upright position and relieved in the supine position, usually due to a patent foramen ovale (PFO). Percutaneous closure of a PFO is the preferred treatment to cure POS. This study aimed to evaluate the clinical and gasometrical characteristics and to describe the long-term outcomes of percutaneous PFO closure in a group of patients with POS. Patients with POS and a PFO treated by percutaneous intervention from 2010-2020 were reviewed. The primary efficacy outcome was the arterial oxygen pressure to fraction of inspired oxygen (PaO2/FiO2) ratio before and 24 hours after the procedure. Total clinical success was considered if the arterial oxygen saturation measured by pulse oximetry (SpO2) improved to >94% in the supine and sitting positions without supplemental oxygen, while partial success was considered if SpO2 improved from baseline but still required oxygen to achieve >94%. Secondary outcomes were an absolute improvement in SpO2 and sense of dyspnoea, without significant residual shunt on transthoracic echocardiography (TTE) at follow-up. Of 168 patients undergoing PFO or atrial septal defect closure, 14 had POS (8.3%). Percutaneous PFO closure was successfully performed in all patients with a single device. Twelve of 14 patients had total clinical success (86%) and one patient had partial success. The PaO2/FiO2 ratio increased from 155.9±50.6 to 318.3±73.4 after PFO closure (p=0.002). All patients with total clinical success had a successful secondary efficacy outcome with an absolute improvement in SpO2 and complete resolution of dyspnoea, which was maintained at follow-up (37±20 months; range, 11 months to 6 years). None had a significant residual shunt between 12 and 24 months of follow-up. The PFO percutaneous closure was a successful, durable and safe method for patients presenting with POS; it achieved major improvements in both gasometrical parameters and quality of life.


Prognostic impact of circulating tumor cells detected with the microfluidic "universal CTC-chip" for primary lung cancer.
Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, "CTC-chip," for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM-chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression-free survival (P = .037) and cancer-specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression-free survival was worse in CTC-positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM-chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.


The hemoglobins of the bullfrog, Rana catesbeiana. The cDNA-derived amino acid sequences of the alpha chains of adult hemoglobins B and C: their roles in deoxygenation-induced aggregation.
The adult bullfrog (Rana catesbeiana) has two major tetrameric hemoglobins, B and C, which share a common beta chain but have different alpha chains. Components B and C associate upon deoxygenation to form a complex of the form BC2, a trimer of tetramers that depends on contacts between the alpha B and alpha C chains. Nucleotide sequences of cDNA transcripts for these chains have been determined. Transcripts were identified by analysis of the amino acid compositions of the tryptic peptides of the components and by partial amino acid sequencing. These results, together with the amino acid sequence of the beta chain (Tam, L.-T., Gray, G. P., and Riggs, A. F. (1986) J. Biol. Chem. 261, 8290-8294), permit an analysis of the structures of the alpha 2 beta 2 tetramers of hemoglobins B and C. Molecular modeling suggests possible residues at the alpha B-alpha C interfaces in the BC2 trimer and additional alpha C-alpha C contacts that would form a closed ring of six alpha chain subunits that would further stabilize the BC2 trimer. Phylogenetic analysis of the alpha B sequence suggests that it may be a "tadpole" chain, the temporal expression of which has shifted from larva to adult.


Effectiveness of low-carbohydrate diets for long-term weight loss in obese individuals: A meta-analysis of randomized controlled trials.
To assess whether low-carbohydrate (LC) diets are associated with differences in weight loss and well-being in people with obesity, and their cardiovascular and renal safety. A meta-analysis of randomized controlled trials longer than 3 months, retrieved through an extensive search on MedLine and Embase databases, comparing weight loss with LC and control diets in people with body mass index (BMI) greater than 30 kg/m2 , was conducted. We retrieved 25 trials. Compared with controls, LC diets were associated with significant reduction of body weight at 3-4 (MD -2.59 [-3.93, -1.25] kg) and 6-8 months (MD -2.64 [-4.32, -0.95]), but no difference at 10-14 and 18-30 months, and significantly greater BMI reduction at 3-4 months (-1.66 [-2.70, -0.61] kg/m2 ), but not at other time points. Because only four trials reported data on renal function and psychological variables, renal safety and impact on well-being could not be assessed. Differences in fasting plasma glucose at any time point were not statistically significant. No significant differences in total or LDL cholesterol or blood pressure were found in the long term, whereas a long-term reduction of triglycerides (23.26 [-45.53, -0.98] mg/dl at 18-30 months), and increase of HDL cholesterol (MD 4.94 [0.30, 9.57] mg/dl at 18-30 months), were observed. LC diets are associated with greater short-term weight loss than non-carbohydrate-restricted diets and a longer term favourable effect on cardiovascular risk factors. Further evidence on long-term efficacy and renal safety is needed before LC diets can be recommended as the preferred diets in obese people.


Proton-Conducting Hydrogen-Bonded 3D Frameworks of Imidazo-Pyridine-Based Coordination Complexes Containing Naphthalene Disulfonates in Rhomboid Channels.
Coordination complexes of an olefinic molecule (PIP) containing pyridine and imidazopyridine moieties with ZnII /NiII metal salts were shown to exhibit appreciable proton conductivity. These complexes form 3D-hydrogen bonded frameworks containing rhomboidal channels that are occupied by uncoordinated 1,5-naphthalenedisulfonate (NDS). The extensive hydrogen bonding between the frameworks and NDS resulted in thermally stable and water-insoluble materials. Irrespective of the metal atom present, both complexes exhibited moderate to high proton conduction in the range of 10-5 to 0.5×10-3 S cm-1 depending on the temperature and humidity levels.


Artificial intelligence in diabetic retinopathy screening: clinical assessment using handheld fundus camera in a real-life setting.
Diabetic retinopathy (DR) represents the main cause of vision loss among working age people. A prompt screening of this condition may prevent its worst complications. This study aims to validate the in-built artificial intelligence (AI) algorithm Selena+ of a handheld fundus camera (Optomed Aurora, Optomed, Oulu, Finland) in a first line screening of a real-world clinical setting. It was an observational cross-sectional study including 256 eyes of 256 consecutive patients. The sample included both diabetic and non-diabetic patients. Each patient received a 50°, macula centered, non-mydriatic fundus photography and, after pupil dilation, a complete fundus examination by an experienced retina specialist. All images were after analyzed by a skilled operator and by the AI algorithm. The results of the three procedures were then compared. The agreement between the operator-based fundus analysis in bio-microscopy and the fundus photographs was of 100%. Among the DR patients the AI algorithm revealed signs of DR in 121 out of 125 subjects (96.8%) and no signs of DR 122 of the 126 non-diabetic patients (96.8%). The sensitivity of the AI algorithm was 96.8% and the specificity 96.8%. The overall concordance coefficient k (95% CI) between AI-based assessment and fundus biomicroscopy was 0.935 (0.891-0.979). The Aurora fundus camera is effective in a first line screening of DR. Its in-built AI software can be considered a reliable tool to automatically identify the presence of signs of DR and therefore employed as a promising resource in large screening campaigns.


Exploration of promising optical and electronic properties of (non-polymer) small donor molecules for organic solar cells.
Non-fullerene based organic compounds are considered promising materials for the fabrication of modern photovoltaic materials. Non-fullerene-based organic solar cells comprise of good photochemical and thermal stability along with longer device lifetimes as compared to fullerene-based compounds. Five new non-fullerene donor molecules were designed keeping in view the excellent donor properties of 3-bis(4-(2-ethylhexyl)-thiophen-2-yl)-5,7-bis(2ethylhexyl) benzo[1,2-:4,5-c']-dithiophene-4,8-dione thiophene-alkoxy benzene-thiophene indenedione (BDD-IN) by end-capped modifications. Photovoltaic and electronic characteristics of studied molecules were determined by employing density functional theory (DFT) and time dependent density functional theory (TD-DFT). Subsequently, obtained results were compared with the reference molecule BDD-IN. The designed molecules presented lower energy difference (ΔΕ) in the range of 2.17-2.39 eV in comparison to BDD-IN (= 2.72 eV). Moreover, insight from the frontier molecular orbital (FMO) analysis disclosed that central acceptors are responsible for the charge transformation. The designed molecules were found with higher λmax values and lower transition energies than BDD-IN molecule due to stronger end-capped acceptors. Open circuit voltage (Voc) was observed in the higher range (1.54-1.78 V) in accordance with HOMOdonor-LUMOPC61BM by designed compounds when compared with BDD-IN (1.28 V). Similarly, lower reorganization energy values were exhibited by the designed compounds in the range of λe(0.00285-0.00370 Eh) and λh(0.00847-0.00802 Eh) than BDD-IN [λe(0.00700 Eh) and λh(0.00889 Eh)]. These measurements show that the designed compounds are promising candidates for incorporation into solar cell devices, which would benefit from better hole and electron mobility.


Metabolism of all-trans-retinol and all-trans-retinoic acid in rabbit tracheal epithelial cells in culture.
As reported previously squamous cell differentiation of rabbit tracheal epithelial (RTE) cells in culture is a multi-step process. This program of differentiation is inhibited by retinoic acid and retinol; retinoic acid is about 100 times more effective than retinol. To examine the metabolism of these agents in this in vitro model system, RTE cells were grown in the presence of all-trans-[3H]retinol or all-trans-[3H]retinoic acid and their metabolites analyzed by high-pressure liquid chromatography. RTE cells converted most of the retinol to retinyl esters, predominantly retinyl palmitate. A small fraction was metabolized to polar compounds, one of which coeluted with retinoic acid. After methylation this compound eluted as 13-cis-methyl retinoate and as all-trans-methyl retinoate. Conversion to 13-cis-retinol was also observed. All-trans-retinoic acid was rapidly taken up by RTE cells and converted to more polar (peak 1) and less polar (peak 3) metabolites. A proportion of all-trans-[3H]retinoic acid was metabolized to 13-cis-[3H]retinoic acid. These metabolic reactions appeared to be constitutive and were not induced by pretreatment with retinoic acid. The peak 1 metabolites were rapidly secreted into the medium whereas the peak 3 metabolites were retained by the cells and were not detected in the medium. Alkaline hydrolysis of the metabolites in peak 3 yielded retinoic acid, indicating the formation of retinoyl derivatives. Our results establish that RTE cells can convert all-trans-retinol to 13-cis-retinol and retinoic acid. RTE can metabolize all-trans-retinoic acid to 13-cis-retinoic acid and to an unidentified ester of retinoic acid.


[The role of public health service in prevention and control of infectious diseases in the Federal Republic of Germany. Tasks, structures and responsibilities--an overview].
The goal is to describe the structure of administration for the control of infectious diseases in the German states. Internationally there is an increasing risk of potentially global transmission of infectious diseases and therefore increasing need for improved control mechanisms which are viable locally, regionally and internationally. The international public health community must ensure that responses to infectious disease with a potential impact on more than one county entail concerted action, clear communication and decision making by diverse administration agencies. Given Germany's federal structure, the 16 states have differing protocols delineating responsibilities for infection control systems. This paper provides an overview, going into detail only with regard to the administration structure in Hesse. In 2001, the German law governing infectious disease control was amended and significantly expanded. With regard to protection of humans from infectious disease, each state must define its schedule of responsibilities on the resulting scope of duties. Each state in Germany has entrusted the local public health service at the county level with the responsibility for infection prevention and control. As a rule, at the state level both an expert agency and one or more district administration agencies have been installed; these work directly with the Ministry of Health at the state level. In addition to this, Hesse has established a "centre of competence for highly contagious diseases." In the event of an infectious emergency, this network provides special treatment of highly infectious patients and expertise for public health services and the Ministry of Health on a 24-h shift basis. In times of ongoing structural transformation, it is important to emphasize that expertise at the state level is not an alternative to maintaining enough specialised personnel in the public health services themselves. Specialized practitioners are needed to ensure professional and fast-acting responses, both for the prevention and control of infectious diseases.


Methylation of microinjected isoaspartyl peptides in Xenopus oocytes. Competition with protein carboxyl methylation reactions.
Xenopus oocytes possess a highly conserved protein carboxyl methyltransferase postulated to function in the repair or metabolism of age-damaged protein aspartyl residues (O'Connor, C. M. (1987) J. Biol. Chem. 262, 10398-10403). Three hexapeptides of the general sequence Val-Tyr-Pro-isoAsp-X-Ala, in which isoAsp represents an L-isoaspartyl residue and X represents Gly, Ser, or Ala, are methylated with the same order of preference following their microinjection into oocytes as in a purified system containing bovine brain protein carboxyl methyltransferase and S-adenosyl-L-[methyl-3H]methionine. The affinities of the enzyme for the glycyl, seryl, and alanyl variants of the peptides in vitro are 4.25, 3.04, and 1.67 microM, respectively. A nonapeptide of the sequence Lys-Ala-Ser-Ala-isoAsp-Leu-Ala-Lys-Tyr is a higher affinity substrate for the methyltransferase in vitro, characterized by a Km of 0.88 microM, but it is modified to a lesser extent in oocytes, partially because of its reduced stability in cytoplasm. The hexapeptide Val-Tyr-Pro-Asp-Gly-Ala, which contains an aspartyl residue in the usual stereoconfiguration, is not methylated either in vitro or in intact oocytes. Microinjection of any of the four isoaspartyl-containing peptides greatly stimulates total carboxyl methylation in oocytes, with rate increases ranging from 19- to 51-fold after the injection of 30 pmol of peptide. The protein ovalbumin is also modified following its microinjection into oocytes to near its calculated methyl-accepting capacity. Each of the isoaspartyl peptides can act as a competitive inhibitor of ovalbumin methylation both in vitro and in microinjected oocytes. The inhibitory potencies of the peptides parallel their specific methyl-accepting activities. The results demonstrate that the oocyte may be a useful model for studying the significance of protein carboxyl methylation because of the large functional excess of methylation capacity and the fidelity of the reactions compared to those observed in purified systems. This excess capability may have physiological significance when structurally abnormal proteins accumulate as a result of cellular stress and or aging.


Amino acid sequences in fibrinogen mediating its interaction with its platelet receptor, GPIIbIIIa.
Platelet membrane GPIIbIIIa is a member of the family receptors named integrins that recognize RGD sequences in their ligands. GPIIbIIIa interacts with at least three different adhesive ligands: fibrinogen, fibronectin, and von Willebrand factor. These interactions are inhibited by RGD-containing peptides and by peptides corresponding to a sequence unique to fibrinogen in the COOH-terminal domain of its gamma chain (HLGGAKQAGDV). Two RGD sequences are present in fibrinogen A alpha chain: an RGDS sequence at A alpha 572-575, and an RGDF sequence at A alpha 95-98. Polyclonal antibodies raised against the RGDF sequence and the gamma COOH-terminal domain both reacted specifically with fibrinogen in solid phase enzyme-linked immunosorbent assays and immunoprecipitated the protein in solution. The Fab fragments prepared from these antibodies inhibited fibrinogen-platelet interaction and aggregation. These results demonstrate that these two sequences are both accessible within the fibrinogen molecule and are both implicated in ligand binding and cell-cell interaction. In addition, by further examining the interaction of the gamma chain peptide with platelets, it was found that RGDF and the gamma peptide produced a similar dose-dependent inhibition of the binding of the labeled gamma peptide to ADP-stimulated platelets. These results provide evidence that the RGDF sequence present at the A alpha 95-98 constitutes with the gamma 401-411 sequence two recognition sites interacting with the same site or with mutually exclusive sites on GPIIbIIIa.


Acute promyelocytic leukemia, study of predictive factors for Differentiation Syndrome, single center experience.
Reports about patients with acute promyelocytic leukemia from the Middle East are few; in this study we are reporting our single center experience of treating 29 patients over 6years. Acute promyelocytic leukemia treatment response is markedly improved after the introduction of ATRA. Treatment related complication is still an important issue particularly Differentiation Syndrome. Prediction to its occurrence has been tried by other groups. We aimed to study all the possible predictive factors of acute promyelocytic leukemia. Our chemotherapy induction protocol is AIDA protocol which includes ATRA 45mg/m(2)/d in divided doses every12h, and Idarubicin 12mg/m(2)/d IV on days 3, 5, 7, and 9. Differentiation Syndrome occurred in 48.3% of patients and was mainly presented by pulmonary symptoms in 55.2%, 6 cases died during induction. None of the predictive factors studied showed a statistically significant difference between patients who developed Differentiation Syndrome and those who did not. Differentiation Syndrome did not affect overall survival. Cox regression showed an inverse yet a non significant association between PETHEMA and overall survival probability (P=0.168). In conclusion, Differentiation Syndrome has no clear predictive factor to date. The best approach is to hold ATRA and give dexamethasone which is quite effective as reported in the literature. PETHEMA risk model has a moderately significant prognostic value.


An enzyme-linked immunosorbent assay for plasma-paraquat levels of poisoned patients.
To investigate the efficacy of medical treatments, plasma-paraquat levels were measured in patients who had ingested the liquid weedkiller, Gramoxon, containing paraquat. We determined the levels by an enzyme-linked immunosorbent assay (ELISA) using a murine paraquat-specific monoclonal antibody developed by Niewola et al. (Clin. Chim. Acta, 148 (1985) 149-156). Using this ELISA, concentrations of paraquat in the range 1.56-100 ng/ml could be measured. This assay method had good precision and was suitable for measurement of low levels of paraquat. The therapeutic treatments were most effective on the day of admission. The plasma-paraquat levels of poisoned patients decreased significantly. However, the levels tended to increase again during the pause period of the haemoperfusion and this increase was serious for fatal cases. It is clear that elimination of poison not only from blood but also from tissues is necessary to lower the mortality rate.


Periampullary mass--a rare presentation of poorly differentiated neuroendocrine cancer of duodenum in a young adult: a case report and review of literature.
Poorly differentiated neuroendocrine tumour in the periampullary region of the duodenum is a rare entity. This entity usually present in old men. Here we report a periampullary poorly differentiated neuroendocrine cancer (PDEC) of duodenum presenting in a young man with subacute history of jaundice, abdominal pain, pancreatitis and constitutional symptoms. MRI localised the tumour and endoscopy-guided biopsy of the lesion proved the diagnosis. Although palliative surgery and chemotherapy were planned, the patient opted to leave against medical advice.


ELISA for human pancreatic elastase 1.
A sandwich-type ELISA for human pancreatic elastase 1 was developed and assessed for clinical feasibility. Using highly purified reagents, the test seems to be as sensitive and specific as the well-documented Radio-immunoassay (RIA) for the detection of elevated elastase 1 serum levels and, consequently, would have the same indications described for the RIA. In addition, the ELISA could be valid as a screening test for cystic fibrosis. Because ELISA reagents are relatively stable, the assay is always ready to use and can be performed without special equipment.


Apobec-1 increases cyclooxygenase-2 and aggravates injury in oxygen-deprived neurogenic cells and middle cerebral artery occlusion rats.
Given that cyclooxygenase-2 (COX-2) plays a crucial role during cerebral ischemia and Apobec-1 is a critical regulator of COX-2 mRNA stabilization in gastrointestinal settings, the correlation of COX-2 and Apobec-1 was investigated in neurogenic cells and rat model of cerebral ischemia. After neurogenic SH-SY5Y, NG108-15 and PC12 cells were exposed to oxygen-glucose deprivation, cell viability, LDH leakage and Apobec-1 expression were determined. The effect of Apobec-1 overexpression on injury severity of oxygen-glucose deprivation, COX-2 expression, C-to-U editing of COX-2 mRNA were measured in vitro. Then the correlation of Apobec-1 level and injury severity was analyzed in cells with oxygen-glucose deprivation and in rats with middle cerebral artery occlusion. Apobec-1 expression was elevated along with upregulation of COX-2 and injury severity of oxygen-glucose deprivation in the three cell lines. Apobec-1 overexpression aggravated injury of oxygen-glucose deprivation in vitro and could be correlated to injury severity in vivo. Meanwhile, Apobec-1 increased COX-2 expression and COX-2 mRNA stabilization in neurogenic cells, and failed to catalyze C-to-U editing of COX-2 mRNA. Apobec-1 could upregulate COX-2 expression in neurogenic cells by stabilizing COX-2 mRNA, and might aggravate injury of oxygen-glucose deprivation in neurogenic cells as well as in rats with cerebral ischemia.


Overview of the microfluidic diagnostics commercial landscape.
Since its birth in the late 1980s, the field of microfluidics has continued to mature, with a growing number of companies pursuing diagnostic applications. In 2009 the worldwide in vitro diagnostics market was estimated at >$40 billion USD, and microfluidic diagnostics are poised to reap a significant part of this market across a range of areas including laboratory diagnostics, point-of-care diagnostics, cancer diagnostics, and others. The potential economic advantages of microfluidics are numerous and compelling: lower reagent and/or sample volumes, lower equipment costs, improved portability, increased automation, and increased measurement speed. All of these factors may help put more information in the hands of doctors and patients sooner, enabling earlier disease detection and more tailored, effective treatments. This chapter reviews the microfluidic diagnostics commercial landscape and discusses potential commercialization challenges and opportunities.


Melatonin modulates diacylglycerol and arachidonic acid metabolism in the anterior pituitary of immature rats.
In pituitary glands of immature rats prelabeled in vitro with [3H]arachidonic acid, melatonin diminished the luteinizing hormone-releasing hormone (LHRH)-induced increase in [3H]diacylglycerol accumulation as well as [3H]arachidonic acid release from the tissue. Melatonin reduced also LHRH-stimulated incorporation of [3H]glycerol into pituitary [3H]diacylglycerol. The effect was day-time dependent: in the evening experiment melatonin was effective at 0.1 nM concentration while in the morning it had no effect even at 10 nM concentration. The effect of melatonin was also abolished by pretreatment with pertussis toxin. Diacylglycerol and/or arachidonic acid might serve as 2nd messengers transducing the effect of melatonin at the cellular level.


Defective low-density cells of dendritic morphology from the blood of patients with common variable hypogammaglobulinaemia: low immunoglobulin production on stimulation of normal B cells.
Low-density cells (LDC) of dendritic morphology from the blood of patients with common variable (late-onset) hypogammaglobulinaemia (CVH) did not induce allogeneic immunoglobulin production by normal B cells unlike LDC from normal blood. When LDC from patients were treated with pokeweed mitogen (PWM), a lower allogeneic secretion of IgM and IgG was induced in normal B cells than that induced by allogeneic normal LDC treated with PWM. B cells from hypogammaglobulinaemic patients were non-responsive to both normal and patient LDC treated with PWM under all conditions tested.


[Partially pigmented vitreous cyst].
Free-floating iris pigment epithelial cysts in the vitreous are very rare. We report the case of a partially pigmented cyst found on routine examination in the vitreous of a 51-year-old asymptomatic patient. Usually, non-pigmented cysts are derived from the hyaloid system. Pigmented cysts, however, are derived from the iris pigment epithelium. When they are not dislodged, these cysts can be confused with iris melanoma or primary stromal cysts. Treatment is usually unnecessary, unless they become symptomatic.


Functional muscarinic M2 and M3 receptors and beta-adrenoceptor in cultured rat bladder smooth muscle.
A highly purified rat urinary bladder smooth muscle cell culture was obtained by a modified enzymic isolation method, and the presence of functional muscarinic as well as beta-adrenergic receptors were subsequently determined. At 7-10 days of culture, cells became elongated and spindle-shaped showing a typical "hills and valleys" form. They were stained with anti-alpha-actin and anti-myosin antibodies. Radiolabeled ligand binding using [3H]N-methylscopolamine and [3H]CGP12177 showed that these cells expressed muscarinic and beta-adrenergic receptors. Stimulation of cultured cells with carbachol inhibited the forskolin-stimulated cyclic AMP formation, caused an elevation of intracellular Ca2+ concentration measured by fura-2 fluorometry. The latter response was almost completely blocked by 4-DAMP, a selective muscarinic M3 antagonist. On the other hand, stimulation of cultured cells with isoproterenol enhanced the basal cyclic AMP formation, which was reversed by carbachol. Therefore, the presence of functional muscarinic (both M2 and M3) as well as beta-adrenergic receptors was confirmed in pure culture of the rat bladder smooth muscle cells obtained by using an enzymic isolation method.


CD47 and PD-L1 overexpression in proliferating human hepatocytes attenuated immune responses and ameliorated acute liver injury in mice.
Hepatocyte transplantation has the potential to treat acute liver failure and correct liver-based metabolic disorders. Proliferating human hepatocytes (ProliHHs) provide a large-scale source as an alternative to primary human hepatocytes. However, host rejection led to inefficient graft survival and function, which hindered the clinical application of cell therapy. Herein, we employed the lentiviral system to overexpress immunomodulatory factors programmed death-ligand 1 (cluster of differentiation 274) (CD274) and cluster of differentiation 47 (CD47) in ProliHHs. CD47+274 overexpression inhibited macrophage and T cell responses in vitro. After transplantation into mice via the spleen without immunosuppression, CD47+274 ProliHHs accumulation in the liver significantly increased for 48 hours compared with ProliHHs. Consistent with the in vitro results, CD47+274 ProliHHs were less aggregated and infiltrated by macrophages and also recruited fewer T cells in the liver. Seven days after transplantation, the human albumin level of engineered ProliHHs doubled compared with control group. CD47+274 ProliHHs further ameliorated the liver injury induced using concanavalin A. Overall, our results suggested CD47+274 overexpression reduced innate and adaptive immune responses during hepatocyte transplantation, and the survival rate and graft function of transplanted hepatocyte-like cells were all significantly improved.


Informing common pool resource problems: a survey of preference for catchment management strategies amongst farmers and the general public in the Ythan river catchment.
In principle the protection of environmental resources is in every ones interest, yet it is evident that this is not what often occurs. In some cases there is an identifiable person or corporation, whose environmental impact can be tractably regulated either politically or via market forces. In other cases there is cumulative impact on a commonly held or "common pool" resource, from a variety of users, making establishing rights and responsibilities for resource management more difficult. The water of the Ythan catchment is one such 'Common Pool Resource' (CPR). An intensively farmed catchment also sustaining a sizable population, the consequent nitrate inputs to the water are believed to be the cause of algal matting at the estuary mouth, an internationally designated wildlife reserve. This led to its designation as Scotland's first Nitrate Vulnerable Zone (NVZ). Supported by the EU Life Environment fund, the Ythan Project attempted to foster co-operation between farmers and the wider community of the Ythan catchment to protect and restore the river environment. Throughout the project surveys were undertaken concerning the popularity of the Ythan Project's voluntary approach compared with more individualist or state-organised approaches. Taking CPR theory as a framework, key findings from those surveys are presented and discussed as to their implications for organisational intervention in CPR problems.


HLA status following fetal liver transplantation in aplastic anaemia and acute myeloid leukaemia.
Fetal liver infusion (FLI) was tried as an alternate mode of therapy in 40 patients with aplastic anaemia and in 16 patients with acute myeloid leukaemia. The fetal HLA typing carried out on spleen and thymus cells revealed that, while it was more difficult to HLA type the thymus than the spleen cells, 'full house' antigens could be determined only in fetuses of 18 weeks or older. No special effort was made to transfuse HLA- matched or partially matched donor cells into the recipient. The recipients were HLA typed at varying time intervals following FLI in an attempt to document a possible chimerism. None of the patients revealed a 'shift' in their HLA antigen profile and there was no evidence of any donor cell engraftment. No relationship between the HLA match of donor and recipient, and the general condition, the prognosis or the total survival of the patient was evidenced. These data indicate that, even though fetal liver cells express HLA antigens, these cells are functionally incompetent to cause an apparent graft-versus-host disease in the host.


Maxillary Impacted Canine and Upper Lateral Incisor Agenesis Treatment with "Canine First Technique" and Clear Aligners: A Case Report.
The aim of this study was to show a case of an impacted canine in an adult patient with agenesis of the maxillary lateral incisor treated with clear aligners (CA). A 19-year-old male with a persistence of 5.3 and absence of 1.2 came to our department of the School of Orthodontics at the University of Federico II in Naples and asked for an aesthetic treatment. The Canine First approach was used to surgically expose the canine and pull it into the dental arch. In order to ensure long-term aesthetic, periodontal, and occlusal results, a treatment with CAs to close the space through the mesial placement of the canine and the enameloplasty of the tooth crown was performed. At the end of the treatment, the occlusal objectives were achieved.


Maternal hemoglobin and risk of gestational diabetes mellitus in Chinese women.
To examine the relationship between high maternal hemoglobin concentration at the initial antenatal visit and occurrence of gestational diabetes mellitus (GDM) in the third trimester in nonanemic women. In a prospective observational study, 762 nondiabetic Chinese women with singleton pregnancies, whose initial visit hemoglobin concentration and mean cell volume were 10 g/dL or more and 80 fL or more, respectively, recruited at 28-30 weeks, had blood drawn for repeat measurement of hemoglobin concentration and iron parameters. These women were categorized by their initial visit hemoglobin concentration into quartiles, and the incidence of GDM was analyzed together with the maternal characteristics and iron status. The final study sample comprised 730 women. Compared with the rest, the group in the highest hemoglobin quartile (more than 13 g/dL) had a significantly higher incidence of GDM (18.7% versus 10.9%, P =.007), as well as greater age, weight, and serum ferritin and iron concentrations. Logistic regression was used to examine the effects of high body mass index (more than 25 kg/m(2)), advanced age (older than 34 years), parity of 1 or more, and hemoglobin in the highest quartile, on the incidence of GDM. Only advanced age (odds ratio 3.79, 95% confidence interval 2.33, 6.17) and hemoglobin in the highest quartile (odds ratio 1.73, 95% confidence interval 1.08, 2.78) emerged to be significant factors. A high maternal hemoglobin (more than 13 g/dL) at the initial prenatal visit in Chinese women is an independent risk factor for GDM. This may reflect a better nutritional status in these women, as suggested by the increased iron status.


Changes in rapidly transported proteins in the auditory nerve after hair cell loss.
In an effort to further characterize the proteins of the auditory nerve, the effects of hair cell loss on rapidly transported proteins of the auditory nerve were studied. The effects were studied in the waltzing guinea pig, a genetically deaf animal which displays an age-dependent loss of sensory cells, and in normal guinea pigs treated with neomycin. In both cases hair cell loss is followed by a slow degeneration of spiral ganglion cells and corresponding auditory nerve fibers. Rapidly transported proteins in the cochlear nucleus were analyzed by two dimensional electrofocusing/electrophoresis 3 h after cochlear injection of [35S]methionine. In both the waltzing guinea pig and the neomycin-treated animals, a significant increase in labeling of two series of polypeptides (average molecular weights of 27,000 and 36,000 daltons) was apparent. Quantitation of the 36,000 dalton protein by extracting from dried gels showed a 2-fold increase in the 10-day-old waltzing guinea pig and a 6-fold increase in the 80-day-old waltzing guinea pig. Further analysis shows these proteins to be membrane-associated glycoproteins.


Systematic review with meta-analysis: age-related malignancy detection rates at upper gastrointestinal endoscopy.
Age is an important and objective risk factor for upper gastrointestinal (GI) malignancy. The accuracy of various age limits to detect upper GI malignancy is unclear. Determination of this accuracy may aid in the decision to refer symptomatic patients for upper GI endoscopy. The aim of this analysis was to synthesize data on upper GI malignancy detection rates for various age limits worldwide through meta-analysis. We searched MEDLINE, EMBASE, and Web of Science in November 2018. Selection criteria included studies addressing malignant findings at upper GI endoscopy in a symptomatic population reporting age at time of diagnosis. Meta-analyses were conducted to derive continent-specific cancer detection rates. A total of 33 studies including 346,641 patients across 21 countries fulfilled the inclusion criteria. To detect >80% of malignant cases all symptomatic patients over 40 years of age should be investigated in Africa, over 50 years of age in South America and Asia, and over 55 years of age in North America and Europe. This systematic review and meta-analysis provides data on intercontinental variation in age at time of upper GI malignancy diagnosis in symptomatic patients referred for upper GI endoscopy. Guideline recommendations for age-based selection should be tailored to local age-related detection rates.


Anti-tumor properties of human-activated macrophages produced in large scale for clinical application.
When properly activated, macrophages can be tumoricidal. To harness the therapeutic potential of these cells, we have developed a process for ex vivo production of large numbers of IFN-gamma-activated monocyte-derived macrophages. These monocyte-derived activated killer (MAK) cells have been safely administered to cancer patients with minimal residual disease in phase I/II clinical studies. To evaluate efficacy of treatment with MAK cells, phase III clinical studies are necessary. The process of MAK cell production has been further optimized and qualified for use in large cohorts of patients. In this study, we characterized MAK cells produced in large scale by studying their phenotype and functions. MAK cells were shown to exert anti-tumor activity by killing tumor cells and inhibiting their proliferation. These activities were enhanced by activation with IFN-gamma and addition of anti-tumor antibodies. Tumor necrosis factor-alpha (TNF-alpha) was one of the mediators used by MAK cells to inhibit tumor proliferation. To facilitate logistics of clinical trials, a process for MAK cell cryopreservation has been developed. We verified in vitro that cryopreserved cells retained the activity of fresh cells and were stable during storage. The safety and efficacy of cryopreserved MAK cells (Bexidem) are currently being assessed on superficial bladder cancer patients in a phase II/III clinical trial.


Extremely Low Contact Resistance on Graphene through n-Type Doping and Edge Contact Design.
The effects of graphene n-doping on a metal-graphene contact are studied in combination with 1D edge contacts, presenting a record contact resistance of 23 Ω μm at room temperature (19 Ω μm at 100 K). This contact scheme is applied to a graphene-perovskite hybrid photodetector, significantly improving its performance (0.6 → 1.8 A W(-1) in photoresponsivity and 3.3 × 10(4) → 5.4 × 10(4) Jones in detectivity).


Retinoids: a journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects.
Retinoids are a class of compounds derived from vitamin A or having structural and/or functional similarities with vitamin A. They are classified into three generations based on their molecular structures. Inside the body, retinoids bind to several classes of proteins including retinoid-binding proteins and retinoid nuclear receptors. This eventually leads to the activation of specific regulatory regions of DNA - called the retinoic acid response elements - involved in regulating cell growth, differentiation and apoptosis. Several clinical trials have studied the role of topical and systemic retinoids in disease, and research is still ongoing. Currently, retinoids are used in several fields of medicine. This paper aims to review the structure, mechanisms of action, and adverse effects of retinoids, as well as some of their current uses in Dermatology.


Screening and health education practices related to cardiovascular risk factors among adults: results of a households survey in Sousse, Tunisia.
In Tunisia, despite the implementation of national strategies to prevent some of cardiovascular risk factors, these diseases still represent the leading cause of death. The current study aimed to determine the prevalence of cardiovascular risk factors and assess the screening and health education practices related to these factors among the adults of Sousse (Tunisia). A cross-sectional study was conducted in 1000 households in Sousse, Tunisia. To collect data, a team of trained medical doctors administered by interview a pre-tested questionnaire and performed blood pressure and anthropometric measures at the participants' homes. In total, 1977 adults participated in the study. Their mean age was 39.8 (± 13.8) years. The Females/Males sex ratio was 1.5. Weight excess and lack of physical activity were found in 65.4% and 60.7% of participants. Screening for obesity and android obesity were reported by 36.6% and 5.7% of health services users. Advices from a healthcare professional to practice the recommended physical activity and eat healthily were reported by less than a third of these latter. Screening and health education practices related to cardiovascular risk factors should be reinforced in the Tunisian healthcare facilities. The implementation of multisectoral actions is necessary at the national level in order to obtain an environment that promotes a healthy lifestyle.


Laparoscopic Ultra-radical Lymph Node Debulking Using Yasargil Clamps for Gynecological Malignancies: Results from a Large, Multicenter, Retrospective Analysis.
Resection of bulky lymph nodes in gynecologic oncology is a challenging procedure. Considering the risk of intraoperative vascular injury, a technique to avoid severe complications is mandatory. In this study, we aimed to analyze the feasibility of laparoscopic ultraradical lymph node debulking using Yasargil clamps in patients with gynecologic cancer with bulky lymph node metastases. Multicenter retrospective case series (ClinicalTrialg.gov ID: NCT05318170), between September 2010 and April 2020. Units of Gynecologic Oncology. Patients with gynecologic cancer with bulky lymph node metastases. Laparoscopic ultraradical lymph node debulking using Yasargil clamps. Forty-three patients with gynecologic cancer with bulky pelvic and/or aortic lymph nodes metastases undergoing laparoscopic lymph node debulking surgery using Yasargil clamps were included. Median surgical time was 300 minutes (range, 120-550 minutes); median estimated blood loss was 170 mL (range, 0-700 mL). Median size of lymph nodes was 50 mm (range, 25-100). R0 resection was achieved in all cases. Four intraoperative complications (9.3%) occurred. No conversion to open surgery was required. There were 8 postoperative complications, classified grade 2 or worse. There were no cases with intra- or postoperative mortality. In our experience, in carefully selected patients with gynecologic cancer with bulky lymph nodes, laparoscopic lymph node debulking using Yasargil clamps could be considered a valid option to avoid potential severe vascular intraoperative complications.


[The prognosis for children of mothers with preeclampsia. Part 2: long-term effects].
Preeclampsia affects between 4% to 8% of all human pregnancies. It compromised both mothers and offspring beyond perinatal period. This is the second of two papers devoted to show the available evidence about the effect of preeclampsia on offsprings beyond perinatal period from cohort studies, some over 60-years follow-up. From this perspective, these children are at great risk to develop cardiovascular disorders as hypertension, as well as other disorders, as cancer or neuropsychiatric ones.


Misreporting of myocardial infarction end points: results of adjudication by a central clinical events committee in the PARAGON-B trial. Second Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network Trial.
Myocardial (re)infarction (MI), a common trial end point, can be difficult to identify because of inconclusive signs and symptoms. We examined disagreement between investigator and clinical events committee (CEC) reporting of MIs in an international, randomized trial. The primary end point of the PARAGON-B trial was a 30-day composite of death, MI (CEC adjudicated), or ischemia-driven intervention. If CEC and investigator determinations of MI differed, we sent investigators event summaries and rationales for CEC decisions and asked whether they now agreed with the CEC assessment. If they still disagreed, they were to provide a rationale and supporting data. Such cases were reviewed, and a final decision was made. Overall, 1736 of 5225 (33%) patients had suspected MIs; the CEC adjudicated 483 of 1736 (28%) as MIs. In 404 patients (23%), investigator and CEC assessments of MI differed; 270 MIs were identified by the CEC but not investigators, and 134 were identified by investigators but not the CEC. Most disagreements concerned periprocedural MIs, but some reflected clinical ischemia and enzyme elevations. Letters for 382 disagreements were sent and returned by investigators, and investigators came to agree with CEC assessments in 307 cases (80%). For the other 75 cases (20%), after review the investigators' assessments were confirmed in 10 cases, and the original CEC decisions were supported in the other 65 cases. Investigators misreport MI end points, but most later agree with CEC assessments. These data support standard, independent adjudication of suspected MIs for accurate reporting, which may affect evaluations of therapies, sample-size calculations, and event-rate comparisons across trials.


The interaction of adenosine diphosphoribosyl transferase (ADPRT) with a cruciform DNA.
Adenosine Diphosphoribosyl Transferase is a eucaryotic nuclear protein that catalyses the transfer of ADP-ribose moiety of NAD+ to itself and other cellular proteins. DNA is required for this post-translational modification process. We present novel evidence that Adenosine Diphosphoribosyl Transferase interacts with the base of plasmid pUC7 cruciform. We speculate that, unlike a sequence-specific DNA binding protein, the transferase may recognize an unusual DNA conformation.


Targeted therapy for renal cell carcinoma: focus on 2nd and 3rd line.
Second- and third-line treatments are more and more frequently administered to metastatic renal cell carcinoma (mRCC) patients. Here we discuss the various levels of evidence supporting presently available recommendations, trying to address a number of as yet unanswered issues, and also to take a glowing glance at the future. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for relevant studies. Until recently, with regard to choosing the second line treatment after the failure of therapy with vascular endothelial growth factor receptors-tyrosine kinase inhibitors (VEGFR-TKIs), the continued inhibition of the VEGF/VEGR pathway, or else the switch to an mTOR inhibitor, is recommended. These two options are characterized by partly different targets, completely different toxicity profiles, but a comparable efficacy. This scenario will change soon, after the publication of two randomized, controlled, phase III trials in which cabozantinib and nivolumab proved to be superior as compared to everolimus. As regards third line treatment, where a sequence of two VEGFR-TKIs has been used beforehand, the choice is represented by the mTOR inhibitor everolimus, whilst if a VEGFR-TKI followed by everolimus has been chosen, a return to VEGF pathway inhibition is suggested.


Newly diagnosed ANCA-associated vasculitis after COVID-19 infection: a case report.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic autoimmune disease characterized by mononuclear cell infiltration and small and medium-sized blood vessel destruction leading to renal failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to have the potential to induce the presentation or exacerbation of autoimmune disease. This report describes the clinical features of a case of newly diagnosed ANCA-associated vasculitis after COVID-19 Infection. During the COVID-19 pandemic, a 67- year-old female Japanese was undergoing treatment for interstitial pneumonia, diabetes mellitus, and hypertension at her local doctor. About 2 months ago, she was diagnosed with COVID-19 and went to a hotel for treatment, and her condition improved. But a month later, after her COVID-19 infection, she presented with a fever and cough and visited Yodogawa Christian Hospital in Osaka, Japan. The reverse transcription-polymerase chain reaction was negative. She underwent extensive radiological and laboratory investigations. Serologies revealed a high perinuclear-ANCA titer with a specific anti-myeloperoxidase antibody titer of 31.7 units/mL. We suspected ANCA-associated vasculitis and performed a renal biopsy. Renal biopsy showed evidence of crescentic glomerulonephritis, which was consistent with ANCA-associated vasculitis. The patient was referred to the Department of Rheumatology and Clinical Immunology for steroid pulse and cyclophosphamide treatment. Delayed screening may lead to progression of the autoimmune disease, so prompt diagnosis is necessary. In this case, we could make an immediate diagnosis and refer the patient to the Department of Rheumatology and Clinical Immunology.


[Injuries in nursing homes. Hospital-based registration of injuries of patients in nursing homes].
109 patients were registered in a prospective study of accidents occurring in geriatric nursing homes and treated in Harstad Hospital. In more than 50% the seriousness of the injury was so high that in-patient treatment was necessary. More than 90% of the patients had fallen and 50 patients had suffered fracture of the proximal femur. The incidence of injury is higher than the estimated 13% average, and the seriousness of the injury is substantially higher than the average for all age groups.


Optimal Design of Honeycomb Material Used to Mitigate Head Impact.
This paper presents a study of the impact resistance of honeycomb structure with the purpose to mitigate impact forces. The objective is to aid in the choice of optimal parameters to minimize the thickness of the honeycomb structure while providing adequate protection to prevent injury due to head impact. Studies are presented using explicit finite element analysis representing the case of an unprotected drop of a rigid impactor onto a simulated floor consisting of vinyl composition tile and concrete. Analysis of honeycomb material to reduce resulting accelerations is also presented where parameters such as honeycomb material modulus, wall thickness, cell geometry and structure depth are compared to the unprotected case. A simplified analysis technique using a genetic algorithm is presented to demonstrate the use of this method to select a minimum honeycomb depth to achieve a desired acceleration level at a given level of input energy. It is important to select a minimum material depth in that smaller dimensions lead toward more aesthetic design that increase the likelihood of that the device is used.


COPD and disease-specific health status in a working population.
It has been debated whether treatment should be started early in subjects with mild to moderate COPD. An impaired health status score was associated with a higher probability of being diagnosed with COPD as compared with undiagnosed COPD. To investigate the health status in a healthy working population, to determine reference scores for healthy non-smoking subjects, and to investigate the relationship between their health status and airflow limitation. A total of 1333 healthy industrial workers aged ≥40 years performed spirometry and completed the St. George's Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT). The prevalence of COPD defined by the fixed ratio of the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was 10.9%, and the prevalence defined by the Lower Limit of Normal was 5.0%. All SGRQ and CAT scores were skewed to the milder end. In 512 non-smoking subjects with normal spirometry, the mean SGRQ score was 5.7, and the mean CAT score was 5.8. In 145 people with COPD defined by the fixed ratio, the mean SGRQ score was 7.9, with a zero score in 6.9% of the subjects. Using the CAT, the mean score was 7.3, with 7.6% of the scores being zero. The scores in patients identified using the Lower Limit of Normal approach were: SGRQ 8.4 (13.4% had a score of zero) and CAT 7.4 (13.4% had a score of zero). Although the 95th percentiles of the Total, Symptoms, Activity, and Impact scores of the SGRQ and CAT sores were 13.8, 34.0, 23.4, 7.2 and 13.6 in the 512 healthy non-smoking subjects, respectively, they were also distributed under their upper limits in over 80% of the COPD subjects. The COPD-specific health status scores in a working population were good, even in those with spirometrically diagnosed COPD. All scores were widely distributed in both healthy non-smoking subjects and in subjects with COPD, and the score distribution overlapped remarkably between these two groups. This suggests that symptom-based methods are not suitable screening tools in a healthy general population.


Identification and expression analysis of genes with pathogen-inducible cis-regulatory elements in the promoter regions in Oryza sativa.
Complex co-regulatory networks in plants may elicit responses during pathogen infections. A number of genes are activated when these responses take place. Identification of these genes would shed new light on understanding the mechanisms of rice response to pathogen infections and the elucidation of crosstalk among diverse signaling networks in rice disease resistance/susceptibility. Here we report the identification of genes with pathogen-inducible cis-regulatory elements (PICEs) (AS-1, G-box, GCC-box, and H-box) in the promoter regions in rice. Our results showed that a set of 882 rice genes contained these four elements in their promoter regions. Of these genes, 190 encode disease resistance/susceptibility related proteins, and 70 encode transcription factors. Analyses of the available microarray data demonstrated that 357 transcripts were differentially expressed after pathogen infections. 48 out of 53 differentially expressed transcription factors are up-regulated or down-regulated by more than 1.1-fold in response to pathogen infections. Analyses of the public mRNA-Seq data showed that 327 transcripts were differently expressed after pathogen infections. A total of 100 up-regulated genes and 37 down-regulated genes were found in common between the microarray and mRNA-Seq data. We report here a set of rice genes that contain the four PICEs, i.e., AS-1, G-box, GCC-box, and H-box, in their promoter regions, of which, 53.5% were up- or down-regulated when pathogens attack. The PICEs in the gene promoters are critical for rice response to pathogen infections. They are also useful markers for identification of rice genes involved in response to pathogen infections.


Aneurysmal remnants after microsurgical clipping: classification and results from a prospective angiographic study (in a consecutive series of 305 operated intracranial aneurysms).
The aim of this prospective study, carried out in a consecutive series of 305 microsurgically clipped aneurysms, was to check the absence of an aneurysmal remnant on post-operative angiography, and if a remnant was found to quantify its size in order to consider additional clipping to avoid the risk of rebleeding. Out of the 305 aneurysms, 292 (96%) were located in the anterior and 13 (4%) in the posterior circulation. Post-operative angiography was performed on average two weeks after surgery. Determination of the presence or not of an aneurysmal remnant and its quantification was done by an independent observer (JCA). Aneurysmal remnants were classified into 5 grades: grade I: less than 50% of neck size, grade II: more than 50% of neck size, grade III: residual lobe of a multilobulated sac, grade IV: residual sac of less than 75% of aneurysmal size and grade V: residual sac of more than 75% of aneurysmal size. Correlations between presence (and size) of the remnant and anatomical-surgical data obtained from the operative report were studied. Clipping was considered incomplete in 18 of the 305 aneurysms (5.9%). The group with residual neck only (grade I = 8 cases, Grade II = 4 cases) amounted to 4% of the whole series, whereas the group with residual neck + sac (grade III = 4, grade IV = 1, Grade V = 1) to 1.9%. Only this latter group was amenable to re-operation for complementary clipping without creating a stenosis of the parent artery. Our results are in the range of those of other published series. Anatomical-surgical factors for predisposition to incomplete clipping are discussed. The rates of sac obliteration using microsurgical clipping are to be compared with those recently achieved by electrically detachable coiling. The classification which we have developed is proposed for future comparison with endovascular results.


Prevention and control of HPV and HPV-related cancers in France: the evolving landscape and the way forward - a meeting report.
Misinformation regarding HPV vaccine safety and benefits has resulted in low coverage within the eligible French population. HPV vaccination is safe and efficacious in preventing HPV infections in adolescents. However, reaching optimal coverage in countries such as France is challenging due to misinformation, among other factors. Moreover, disparities exist in cervical cancer screening programs. To support the government health promotion policy aimed at improving prevention and control of HPV-related cancers in France, the Human Papillomavirus Prevention and Control Board (HPV-PCB), in collaboration with local experts, held a meeting in Annecy, France (December 2021).HPV-PCB is an independent, multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV control programs.After a one-and-a-half-day meeting, participants concluded that multi-pronged strategies are required to expand vaccination coverage and screening. Vaccine acceptance could be improved by: 1) strenghtening existing trust in clinicians by continuous training of current and upcoming/pre-service healthcare professionals (HCPs), 2) improving health literacy among adolescents and the public through school and social media platforms, and 3) providing full reimbursement of the gender-neutral HPV vaccine, as a strong signal that this vaccination is essential.The discussions on HPV infections control focused on the need to: 1) encourage HCPs to facilitate patient data collection to support performance assessment of the national cervical cancer screening program, 2) advance the transition from cytology to HPV-based screening, 3) improve cancer prevention training and awareness for all HCPs involved in screening, including midwives, 4) identifying patient barriers to invitation acceptance, and 5) promoting urine or vaginal self-sampling screening techniques to improve acceptability, while establishing appropriate follow-up strategies for HPV-positive women. This report covers some critical findings, key challenges, and future steps to improve the status of HPV prevention and control measures in the country.


[The Knowledge Gained from Questionnaire Survey of the Patients Fall in the Radiological Examinations -Focus on the Severity Due to Fall Accidents].
The purpose of this study is to analyze the factors of patient's fall that causes serious injury in the radiological examinations. We conducted a questionnaire survey on cases of medical accidents occurring in the radiological examination department in medical institutions. The number of responses to the questionnaire surveys was 372. Among them, 197 cases were related to fall. The incident influence classification divided into eight clusters (0, 0H, 1, 2, 3a, 3b, 4, 5) was divided into three clusters (tiny, moderate, serious injury) depending on severity. We analyzed the factors that cause serious injury. In the case of patient's fall, several factors have been found to cause serious injury. The factors were general radiography, standing position, outside working hours. All falls can cause serious injury. To reduce falls, it is important to analyze what kind of patient and in what situation tend to fall, and prevent falls in advance.


Self-Assembly of Multifunctional DNA Nanohydrogels with Tumor Microenvironment-Responsive Cascade Reactions for Cooperative Cancer Therapy.
A DNA structure-based nanoreactor has emerged as a promising biomaterial for antitumor therapy with its intrinsic biodegradability, biocompatibility, and tunable multifunctionality. Herein, the intelligent DNA nanohydrogel was reported to target cancer cells, control the size, be pH-responsive, and be loaded with glucose oxidase (GOx). Two kinds of X-shaped DNA monomers and DNA linkers were assembled to form a DNA nanohydrogel by hybridization. GOx was successfully encapsulated in the DNA nanohydrogel. The DNA linker was designed with i-motif sequences and modified with ferrocene (Fc). The i-motif-like quadruplex structures were formed in acidic tumor microenvironments, resulting in the disassembly of the DNA nanohydrogel to release GOx. The GOx could oxidize the intratumoral glucose to produce gluconic acid and H2O2. The generated H2O2 was catalyzed by Fc to induce toxic hydroxyl radicals (•OH), which could effectively kill cancer cells. Both the in vitro and the in vivo results demonstrated that the multifunctional DNA nanohydrogel had high-efficiency tumor suppression through combined chemodynamic and starvation cancer therapies.


Development of a scrotal vasocutaneous fistula producing viable spermatozoa 9 years after vasectomy.
To describe a case of scrotal vasocutaneous fistula discharging viable sperm. Case report. A hospital-based assisted conception center. A 37-year-old male presenting for fertility treatment 9 years after vasectomy with a scrotal vasocutaneous fistula that caused a painful, intermittently rupturing, subcutaneous cyst. Analysis of fistula discharge and planned fistula resection with vasovasostomy. Diagnostic semen analysis to determine presence or absence of spermatozoa in fistula discharge. A very low concentration of live spermatozoa were identified in the fistula discharge. We believe this is the first time that live spermatozoa, potentially suitable for assisted conception treatment using intracytoplasmic sperm injection have been identified in the discharge from a vasocutaneous fistula.


Randomized scheduling feasibility study of S-1 for adjuvant chemotherapy in advanced head and neck cancer.
The purpose of this study was to determine the feasible adjuvant therapy administration schedule of S-1 for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Patients receiving definitive treatments were randomly assigned to either arm A (51 cases) receiving oral S-1 of 2-week administration followed by 1-week rest for 6 months, or arm B receiving S-1 of 4-week administration followed by 2-week rest for 6 months. Planned treatment was given in 40% of patients in arm A and 29% in arm B. The cumulative rates of the relative total administration dose of S-1 at 100% were 54.9% (95% CI: 40.1-69.7%) in arm A and 34.3% (95% CI: 21.1-47.4%) in arm B, respectively (P=0.054). Adverse events were recorded in 41 patients (82.0%) in arm A and 48 patients (94.1%) in arm B (P=0.060). The incidences of diarrhoea (10 vs 28%; P<0.05) and skin toxicities (18 vs 37%; P<0.05) were significantly higher in arm B. One-year disease-free survival was similar in both arms: arm A 81.2% (95% CI: 70.0-92.4%); arm B 77.0% (95% CI: 65.0-89.0%). The schedule of 2-week administration followed by 1-week rest seems to be more feasible for oral 6-month administration of S-1 in adjuvant chemotherapy of locoregionally advanced SCCHN.


Acute renal failure caused by bilateral ureteral herniation through the sciatic foramen.
Ureteral herniation is rare. Only a few cases of bilateral ureterosciatic herniation have been reported. We report the case of a 74-year-old woman with flank pain and acute renal failure. The initial ultrasound scan showed bilateral hydronephrosis. Follow-up computed tomography imaging demonstrated sciatic herniation of both ureters, causing bilateral hydronephrosis and hydroureter. The patient underwent bilateral retrograde ureterography and ureteral stent placement, with improvement in renal function to normal limits. Observation after stent removal demonstrated recurrent sciatic herniation of both ureters. Definitive surgical correction was performed by way of laparoscopic bilateral ureterolysis and sciatic notch hernia repair using mesh.


An agent-based model of monocyte differentiation into tumour-associated macrophages in chronic lymphocytic leukemia.
Monocyte-derived macrophages help maintain tissue homeostasis and defend the organism against pathogens. In tumors, recent studies have uncovered complex macrophage populations, including tumor-associated macrophages, which support tumorigenesis through cancer hallmarks such as immunosuppression, angiogenesis, or matrix remodeling. In the case of chronic lymphocytic leukemia, these macrophages are known as nurse-like cells (NLCs) and they protect leukemic cells from spontaneous apoptosis, contributing to their chemoresistance. We propose an agent-based model of monocyte differentiation into NLCs upon contact with leukemic B cells in vitro. We performed patient-specific model optimization using cultures of peripheral blood mononuclear cells from patients. Using our model, we were able to reproduce the temporal survival dynamics of cancer cells in a patient-specific manner and to identify patient groups related to distinct macrophage phenotypes. Our results show a potentially important role of phagocytosis in the polarization process of NLCs and in promoting cancer cells' enhanced survival.


Development and application of SINE-based markers for genotyping of potato varieties.
Potato variety discrimination based on morphological traits is laborious and influenced by the environment, while currently applied molecular markers are either expensive or time-consuming in development or application. SINEs, short interspersed nuclear elements, are retrotransposons with a high copy number in plant genomes representing a potential source for new markers. We developed a marker system for potato genotyping, designated inter-SINE amplified polymorphism (ISAP). Based on nine potato SINE families recently characterized (Wenke et al. in Plant Cell 23:3117-3128, 2011), we designed species-specific SINE primers. From the resulting 153 primer combinations, highly informative primer sets were selected for potato variety analysis regarding number of bands, quality of the banding pattern, and the degree of polymorphism. Fragments representing ISAPs can be separated by conventional agarose gel electrophoresis; however, automation with a capillary sequencer is feasible. Two selected SINE families, SolS-IIIa and SolS-IV, were shown to be highly but differently amplified in Solanaceae, Solaneae tribe, including wild and cultivated potatoes, tomato, and eggplant. Fluorescent in situ hybridization demonstrated the genome-wide distribution of SolS-IIIa and SolS-IV along potato chromosomes, which is the basis for genotype discrimination and differentiation of somaclonal variants by ISAP markers.


Development of Activity-Based Proteomic Probes for Protein Citrullination.
Protein arginine deiminases (PADs) catalyze the post-translational deimination of peptidyl arginine to form peptidyl citrulline. This modification is increased in multiple inflammatory diseases and in certain cancers. PADs regulate a variety of signaling pathways including apoptosis, terminal differentiation, and transcriptional regulation. Activity-based protein profiling (ABPP) probes have been developed to understand the role of the PADs in vivo and to investigate the effect of protein citrullination in various pathological conditions. Furthermore, these ABPPs have been utilized as a platform for high-throughput inhibitor discovery. This review will showcase the development of ABPPs targeting the PADs. In addition, it provides a brief overview of PAD structure and function along with recent advances in PAD inhibitor development.


Severe restrictive pulmonary defect in a patient with adult-onset Still's disease.
Adult-onset Still's disease is characterized by seronegative arthritis, fever, and an evanescent skin rash. Earlier reports have described pneumonitis and pleuritis as manifestations of this disease. We report a patient with adult-onset Still's disease with severe restrictive ventilatory impairment and evidence of respiratory muscle weakness who responded to corticosteroid and aspirin therapy.


Echocardiographic study of a Mestizo-Mexican population with Marfan syndrome.
The cardiovascular manifestations of Marfan syndrome (MFS) are the main causes of morbidity and mortality. This study describes the clinical and echocardiographic findings in a Mestizo-Mexican population affected by the disease. A total of 166 patients previously diagnosed with MFS were recruited for the study, 114 of them underwent complete clinical history, with emphasis on Ghent nosology criteria, and transthoracic echocardiography, with 68 patients also undergoing transesophageal study. Major cardiovascular criteria from the Ghent nosology predominated in adults (P < 0.0001), minor criteria in children (P = 0.007). Among pediatric patients, 83% had a New York Heart Association (NYHA) functional class of I; however, 64% of the adult patients had an NYHA class ≥II, (P < 0.0001). Corrected aortic echocardiographic measurements of both groups demonstrated statistically significant differences. Children had a greater prevalence of mitral valve prolapse, while adults more frequently presented with aortic complications. Seven patients died during follow-up from aortic complications, one child and six adults. Based on the data, we can conclude that MFS in the Mestizo-Mexican population has a distinctly different clinical pattern in children and adults, and a graver prognosis in adults. Adult patients with MFS are significantly more likely, than children, to have aortic dilation, aortic aneurysm, aortic regurgitation, aneurysm rupture, aortic dissection, and fatal outcome. Children with MFS are more likely, than adults, to present with asymptomatic mitral and tricuspid prolapse and mitral valve regurgitation.


[Reproducibility of whole lower limb X-rays made in supine position after total knee replacement: comparison with reproducibility of whole lower limb X-rays of normal knees].
Outcomes after total knee replacement are correlated with the postoperative HKA angle. Therefore, it seems crucial to determine the precision of the whole lower limb X-rays which are currently used to determine the frontal knee alignment. The aim of the study was to analyze the precision of the whole lower limb X-Rays made in supine position, after total knee replacement. A prospective study included 100 knees which were analyzed with two whole lower limb X-rays made at eight days interval. Seventy knees were non-replaced and 30 had total replacement with a posterior stabilized knee prosthesis. The X-rays were made in supine position and neutral rotation using the patella as a reference mark. One independent observer compared the HKA angle on the two consecutive X-Rays in order to evaluate the reproducibility of the X-Rays. In the group of patients with total knee replacement, the reproducibility was poor with a low correlation coefficient (0.5) and a poor precision of 5 degrees . On the contrary, in the non-replaced knee group, the reproducibility was very good with a high correlation factor between the two X-rays (0.99, p<0.0001) and a very good precision of 1.7 degrees (p<0.05). The group of patients with an HKA angle of less than 8 degrees had a significantly better precision (1.5 degrees ) than the group of patients with an angle HKA above 8 degrees (3 degrees , p<0.04). Reproducibility and precision of whole lower limb X-rays made in supine position is poor in patients with total knee replacement. Thus, we should be very careful for the analysis of the influence of the mechanical axis on the outcomes after total knee replacement.


Access to heart failure care post emergency department visit: do we meet established benchmarks and does it matter?
The Canadian Cardiology Society recommends that patients should be seen within 2 weeks after an emergency department (ED) visit for heart failure (HF). We sought to investigate whether patients who had an ED visit for HF subsequently consult a physician within the current established benchmark, to explore factors related to physician consultation, and to examine whether delay in consultation is associated with adverse events (AEs) (death, hospitalization, or repeat ED visit). Patients were recruited by nurses at 8 hospital EDs in Québec, Canada, and interviewed by telephone within 6 weeks of discharge and subsequently at 3 and 6 months. Clinical variables were extracted from medical charts by nurses. We used Cox regression in the analysis. We enrolled 410 patients (mean age 74.9 ± 11.1 years, 53% males) with a confirmed primary diagnosis of HF. Only 30% consulted with a physician within 2 weeks post-ED visit. By 4 weeks, 51% consulted a physician. Over the 6-month follow-up, 26% returned to the ED, 25% were hospitalized, and 9% died. Patients who were followed up within 4 weeks were more likely to be older and have higher education and a worse quality of life. Patients who consulted a physician within 4 weeks of ED discharge had a lower risk of AEs (hazard ratio 0.59, 95% CI 0.35-0.99). Prompt follow-up post-ED visit for HF is associated with lower risk for major AEs. Therefore, adherence to current HF guideline benchmarks for timely follow-up post-ED visit is crucial.


Beclin1 controls caspase-4 inflammsome activation and pyroptosis in mouse myocardial reperfusion-induced microvascular injury.
Myocardial reperfusion injury is often accompanied by cell death and inflammatory reactions. Recently, pyroptosis is gradually recognized as pivotal role in cardiovascular disease. However, little is known about the regulatory role of beclin1 in the control of caspase-4 activation and pyroptosis. The present study confirmed whether beclin1 regulates caspase-4 mediated pyroptosis and thereby protects Human Cardiac microvascular endothelial cells (HCMECs) against injury. TTC and Evan's blue dye, western blot, immunofluorescence and immunohistochemistry staining were performed in wild mice and transgenic mice with overexpression of beclin 1(BECN1-Tg). CMECs were transfected with a beclin1 lentivirus. The cell cytotoxicity was analyzed by LDH-Cytotoxicity Assay Kit. The protein levels of autophagy protein (Beclin1, p62 and LC3II/LC3I) and caspase-4/GSDMD pathway were determined by western blot. Autophagic vacuoles in cells were monitored with RFP-GFP-LC3 using fluorescence microscope. I/R caused caspase-4 activity and gasdermin D expression increase in vivo and in vitro. Overexpression of beclin1 in heart tissue and CMECs suppressed the caspase-4 activity and decreased the levels of gasdermin D; meanwhile beclin1 overexpression also reduced IL-1β levels, promoted autophagy (p62 expression was inhibited while LC3II expression was increased) in the heart and CMECs. Interestingly, beclin1 overexpression increased animal survival and attenuated myocardial infarct size (45 ± 6.13 vs 22 ± 4.37), no-reflow area (39 ± 5.22 vs 16 ± 2.54) post-myocardial ischemia reperfusion. Induction of beclin-1 signaling can be a potential therapeutic target in myocardial reperfusion-induced microvascular injury. Video Abstract.


The vulnerable superhero-a qualitative study investigating how spinal cord injury peer mentors experience their role in Active Rehabilitation training programs.
Qualitative study. To explore how peer mentors with spinal cord injury (SCI) experience their role in Active Rehabilitation programs in Sweden. Community peer-based training programs in Sweden. Twenty active peer mentors were strategically selected and invited to participate. Nine individuals of diverse age, level of SCI and time since injury participated in semi-structured interviews via video link. Qualitative content analysis was used to analyze the data. The theme: Being a vulnerable superhero-a balancing act with rewards was based upon five categories: Being a suitable fit for a demanding culture, Offering a shortcut to coping with spinal cord injury life, Feeling rewarded by helping others, Building trust is reciprocal, and Constituting the norm in a temporary community. The peer mentors expressed vulnerability of sharing life experiences, being a role model and building relationships with mentees. The theme emerged from notions of high expectations and demands of the SCI peer mentor role. Being a peer mentor empowered, educated and inspired the peer mentors themselves. Peer mentors were continuously balancing between being open and vulnerable, and being strong and capable. Personality traits were reported as more important aspects of the role than physical skills. The individual mentor-mentee meetings and relationships were considered more important than the actual training sessions. Feeling part of a community and the norm through meeting others in a similar situation was perceived as a reward and motivation for participating as a peer mentor.


Kinesin-driven transport in cell-free environment.
Conventional kinesin is an ATPase-active motor protein that is involved in the microtubule-dependent transport of cytoplasmic cargoes. The present paper provides a condensed overview on kinesin-1 and its motility generation outside a living cell. Moreover, it demonstrates that the neuron-specific kinesin KIF5A enables the formation of microtubules under conditions where pure tubulin does not assemble.


Twenty-five cases of adult prostate sarcoma treated at a high-volume institution from 1989 to 2009.
To analyze the clinical characteristics, treatment modalities, and outcomes of adult prostate sarcoma treated at our institution. The medical records of 25 adult patients with prostate sarcoma were obtained from January 1989 to December 2009. The clinicopathologic parameters were evaluated to determine their effect on survival. The median age was 37 years (range 18-81). The median tumor size was 9.5 cm (range 4-25). The median serum prostate-specific antigen level was 1.39 ng/mL (range 0.39-33.20). The most common symptom was dysuria (72%). Transrectal ultrasound-guided needle biopsy was used to diagnose 22 sarcomas, transurethral resection of the prostate to diagnose 2, and open surgery to diagnose 1. The predominant histologic subtype was leiomyosarcoma (40%); 21 (88%) were high grade and 6 patients had metastatic disease. Surgical resection of curative intent was performed in 14 patients, with negative margins in 10. After a median follow-up of 21 months (range 5-63), 2 patients were disease free, 4 were alive with disease, and 19 had died of their disease. Overall, the 1-, 2-, 3-, and 5-year survival rate was 80.0%, 47.4%, 22.6%, and 11.3%, respectively, and the median survival time was 23 months. The median survival time after recurrence was 20 months (range 9-39) and that after metastasis was 10 months (range 3-23). Age >50 years, metastasis at presentation, and a lack of surgery with curative intent were independently predictive of an unfavorable outcome. Adult prostate sarcoma accounted for 0.7% of primary prostate malignancies and carried a poor prognosis. Early diagnosis and surgical resection with curative intent offer patients the best chance of survival.


Effect of actinomycin D or puromycin on microsomal testosterone hydroxylase activity enhanced by testosterone in female rat liver.
The injection of testosterone propionate for 4 successive days into female rats resulted in an increase of the in vitro conversion of the hydroxylated testosterones from testosterone by the hepatic microsomal fraction, but no change in the content of microsomal cytochrome P-450 occurred. Actinomycin D or puromycin, which was administered for 4 days with injections of testosterone propionate, prevented the enzyme induction.


Mutual Activation of Two Radical Trapping Agents: Unusual "Win-Win Synergy" of Resveratrol and TEMPO during Scavenging of dpph• Radical in Methanol.
The reaction of the 2,2'-diphenyl-1-picrylhydrazyl radical (dpph•) with resveratrol in methanol (kMeOH = 192 M-1 s-1) is greatly accelerated in the presence of stable nitroxyl radical TEMPO• (kmixMeOH = 1.4 × 103 M-1 s-1). This synergistic effect is surprising because TEMPO• alone reacts with dpph• relatively slowly (kS = 31 M-1 s-1 in methanol and 0.03 M-1 s-1 in nonpolar ethyl acetate). We propose a putative mechanism in which a mutual activation occurs within the acid-base pair TEMPO•/RSV to the resveratrol (RSV) anion and TEMPOH•+ radical cation, both being extremely fast scavengers of the dpph• radical. The fast initial reaction is followed by a much slower but continuous decay of dpph• because a nitroxyl radical is recovered from the TEMPOnium cation, which is reduced directly by RSV/RSV- to TEMPO• or recovered indirectly via a reaction with methanol, producing TEMPOH subsequently oxidized by dpph• to TEMPO•.


Significant rate of lower urinary tract dysfunction in patients with sacrococcygeal teratomas.
Sacrococcygeal teratoma (SCT) is the most commonly occurring presacral tumor and can affect the lower urinary tract by direct mass effect, or as a sequela from surgical resection. Despite the potential impact on urologic function, there is no current standard for urological involvement or follow-up for these patients. The purpose of this study was to evaluate the need for urologic involvement for lower urinary tract dysfunction (LUTD) in patients with SCTs at our institution. We performed a retrospective chart review of patients diagnosed with SCT and managed at our institution between 1990 and 2019. Data collected included: patient demographics, surgical and pathology reports, presence of tethered cord or anorectal malformation, and need for urologic involvement for LUTD. LUTD included acute urinary retention, need for chronic intermittent catheterization, and/or urinary incontinence. Acute urinary retention was defined as requiring catheterization to empty the bladder for a limited time (outside the standard post-operative indwelling catheter time period) and the eventual return to spontaneous voiding. Chronic intermittent catheterization was defined as those with urinary retention that has persisted and required continued catheterization at the time of chart review. Urinary incontinence was defined as urine leakage in children older than 3 years of age. Patients with unavailable records were excluded. Comparison between groups was performed with Mann Whitney and chi-squared tests. Forty-five patients with SCTs were identified. LUTD was identified in 23 patients (51%). The most common reason for LUTD was urinary retention (n = 16, 70%): 9 patients had acute retention and 7 had chronic retention (Fig. 1). Nine patients (39%) had urinary incontinence: 2 of these patients (4% of all SCT patients) had urinary fistulas (vesicovaginal (n = 1) and urethrovaginal (n = 1)). Only 5 patients (22%) had LUTD recognized preoperatively. Nine patients had concomitant tethered cord, and 7 of these (78%) had LUTD. Of patients with LUTD, Altman type IV was the most common location (n = 10, 43%). There was no significant difference in tumor type between those with and without LUTD. Patients without LUTD had significantly shorter follow-up. Greater than 50% of patients with SCTs have known LUTD. Two of these patients were found to have urinary fistulas requiring urinary diversion. A multidisciplinary team including urology should be involved upfront in the management of patients with SCTs, and LUTD should be routinely assessed at follow-up visits. Evaluation for a urinary fistula should occur in the presence of urinary incontinence.


Arrector pili muscles surround human facial vellus hair follicles.
Arrector pili muscles have been assumed to attach to one side of the hair follicle, specifically the posterior wall of the bulge area. In this study, we demonstrated immunohistochemically that desminreactive arrector pili muscle, admixed with the connective tissue sheath, is present around the entire circumference of the vellus hair follicle.


Reconstruction of a mandible after shotgun trauma: report of case.
A case of massive facial trauma secondary to a shotgun injury has been presented. The method for managing soft tissue and bony defects incurred is discussed, and a method for reconstruction of the mandible with both an alloplastic implant and autogenous bone graft is detailed.


Relationship between serum uric acid levels and the outcome of STN-DBS in Parkinson's disease.
Uric acid is a natural antioxidant and it has been shown that low levels of uric acid may be a risk factor for the development of Parkinson's disease. We aimed to investigate the relationship between uric acid and improvement of motor symptoms in patients with Parkinson's disease after subthalamic nucleus deep brain stimulation. We analyzed the correlation between serum uric acid levels in 64 patients with Parkinson's disease and the rate of improvement of motor symptoms 2 years after subthalamic nucleus deep brain stimulation. A non-linear correlation was observed between uric acid levels and the rate of motor symptom improvement after subthalamic nucleus deep brain stimulation, during both the drug-off and drug-on periods. Uric acid is positively associated with the rate of motor symptom improvement in subthalamic nucleus deep brain stimulation within a certain range.


Growth in children and adolescents with type 1 diabetes.
To investigate the effect of type 1 diabetes on growth and adult height. Data from 22 651 children (10 494 females) with type 1 diabetes documented at onset of the disease from specialized centers in Germany and Austria were analyzed. Patients of non-German and non-Austrian origin and patients with celiac disease were excluded from the analysis. Near-adult height data were available in 1685 patients. At the time of diagnosis of type 1 diabetes, the mean age of the 22 651 children was 8.8 ± 4.2 years, with a mean height SDS of 0.22 ± 1.0. The 1685 patients with diabetes onset before age 11 years reached a mean adult height of -0.16 ± 1.0 SDS. Mean adult height was was 167.1 ± 6.2 cm (-0.16 ± 0.97 SDS) in females (n = 846) and 179.6 ± 7.1 cm (-0.17 ± 1.0 SDS) in males (n = 839). Mean duration of diabetes was 9.1 ± 2.6 years, and mean Hemoglobin A1c concentration was 7.9% ± 1.2% (63 ± 10 mmol/mol). In a multivariate regression model, adult height was positively correlated with height at onset of diabetes (P < .0001) and negatively with mean Hemoglobin A1c (P < .0001) and duration of diabetes (P = .0015). Height at the time of diagnosis of type 1 diabetes is above average. Even with intensive insulin therapy, growth and adult height remain indicators of metabolic diabetes control in the 21st century.