Intensity-Modulated Radiation Therapy With Dose Painting: A Brain-Sparing Technique for Intracranial Germ Cell Tumors.
We sought to assess patterns of failure in pediatric patients with intracranial germ cell tumors (GCT) treated with intensity-modulated radiation therapy with dose painting (DP-IMRT). Between July 2007 and October 2013, 11 patients with localized GCT-five germinomas and six nongerminoma GCT (NGGCT)-received definitive treatment with DP-IMRT. Three representative patients were selected for replanning with (i) whole ventricular irradiation (WVI) with opposed lateral beams plus IMRT to the primary tumor and (ii) sequential IMRT. These plans were compared to the patients' original DP-IMRT plans for dosimetric analyses. Four patients with germinoma received radiation therapy alone: 45 Gy in 1.8 Gy fractions to the primary tumor and 25 Gy in 1.0 Gy fractions to whole ventricles using a dose-painting plan. One patient with germinoma received a reduced dose of 30.6 Gy to the primary tumor after neoadjuvant chemotherapy. Patients with NGGCT (n = 6) underwent multimodality treatment including chemotherapy (n = 6) and surgery (n = 3). These patients received 54 Gy to the primary tumor and 32.4-36 Gy to the whole ventricles. Dosimetric analyses showed DP-IMRT delivered decreased mean dose to whole brain, temporal lobes, hippocampi, cochleae, and optic nerves. With median follow-up of 4 years, 3-year failure-free survival was 100% for patients with germinoma and 67% for patients with NGGCT. One patient with a pineal NGGCT experienced a local recurrence within the high dose-volume while another experienced an isolated biochemical failure. DP-IMRT is dosimetrically superior to standard IMRT techniques for sparing of normal tissues. Disease control in this small series appears at least comparable to published results.


Posaconazole.
Posaconazole is a triazole antifungal agent, administered as an oral suspension, with an extended spectrum of in vitro activity. Posaconazole 800 mg/day demonstrated clinically relevant activity against a range of fungi in patients with invasive fungal infections who were refractory to, or intolerant of, other antifungal therapy in an open-label, multicentre, phase III study (330 patients received posaconazole and 279 patients served as external controls). In aspergillosis, the global response success rate at the end-of-therapy visit (primary endpoint) was significantly higher in posaconazole recipients than in external controls (42% vs 26%). Posaconazole was also associated with overall success rates of 54% in zygomycosis, 46% in fusariosis, 43% in Pseudallescheria infection, 80% in phaeohyphomycosis and 100% in histoplasmosis. Success rates were 48% in refractory candidiasis, 69% in refractory coccidioidomycosis, 48% in refractory cryptococcal infection and 82% in refractory chromoblastomycosis or mycetoma. Posaconazole also demonstrated potential in febrile neutropenia in an open-label phase II study (success rate of 81% 7 days after the end of treatment). In a noncomparative, multicentre, phase III study in patients with advanced HIV infection who had azole-refractory oropharyngeal and/or oesophageal candidiasis, posaconazole 400 or 800 mg/day resulted in a clinical response in 132 of 176 patients (75%). Oral posaconazole suspension was generally well tolerated in patients with invasive fungal infections, including patients who received treatment for >or=1 year.


Involvement of TWEAK/Fn14 interaction in the synovial inflammation of RA.
TWEAK, TNF-like weak inducer of apoptosis, induces not only apoptosis of some tumour cells, but also proliferation of endothelial cells, and angiogenesis. It is known that TWEAK induces production of cytokines that are involved in the pathogenesis of RA. However, it is not clear how TWEAK takes part in the synovitis of RA. In this study, we investigated the role of TWEAK/fibroblast growth factor-inducible 14 (Fn14) interaction in the synovitis of RA. TWEAK and Fn14 expression on RA and OA synovial cells (SCs) were analysed by FACS. Synovial fibroblasts (SFs) or freshly isolated SCs were cultured in the presence or absence of recombinant TWEAK (rTWEAK) and anti-TWEAK or anti-Fn14 mAbs. Cell proliferation, cytokine/chemokine production and intercellular adhesion molecule (ICAM-1) expression were measured by WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium monosodium salt], ELISA and FACS, respectively. TWEAK expression was detected on CD45-positive population in RA synovium, whereas Fn14 was detected on both CD45-positive and CD45-negative populations. Cultured RA and OA SFs showed higher proliferation and produced IL-6, IL-8 and MCP-1 in response to rTWEAK. Cell proliferation and cytokine production of freshly isolated SCs from RA patients were suppressed by anti-TWEAK and anti-Fn14 mAbs. ICAM-1 expression on RA, but not OA, SFs was up-regulated by rTWEAK. These data suggest that TWEAK/Fn14 interaction plays a substantial role in the synovitis of RA, by directly inducing the proliferation of SFs, and by up-regulating the production of inflammatory cytokines/chemokines as well as the expression of ICAM-1.


Socioeconomic and psychosocial mechanisms underlying racial/ethnic disparities in cognition among older adults.
Objective: Racial/ethnic disparities in cognitive aging are only partly attributable to socioeconomic indicators. Psychosocial factors, such as discrimination and perceived control, also differ across racial/ethnic groups, and emerging literature highlights their potential role in contributing to cognitive disparities in addition to socioeconomic status. Method: 1,463 older adults (51% Hispanic, 27% non-Hispanic Black, and 22% non-Hispanic White) in the Washington Heights-Inwood Columbia Aging Project completed cognitive and psychosocial measures, including a comprehensive neuropsychological battery, Everyday and Major Experiences of Lifetime Discrimination scales, and the Perceived Control scale. Mediation models quantified separate indirect effects of Black race and Hispanic ethnicity on global cognitive composite scores through education, income, discrimination, and external perceived control. Results: Educational attainment, income, and perceived control each mediated racial/ethnic disparities in global cognition. Socioeconomic indicators (i.e., lower education and lower income) explained approximately 50% of the Black-White and Hispanic-White disparities in global cognition, and more external perceived control explained an additional 5%-8%. Hispanics reported the lowest levels of discrimination, while non-Hispanic Blacks reported the highest levels. However, neither everyday nor major lifetime discrimination was associated with global cognition. Significant racial/ethnic disparities in global cognition remained after accounting for the included socioeconomic and psychosocial factors. Conclusions: This study suggests that psychosocial factors may explain racial/ethnic disparities in cognitive aging above and beyond socioeconomic indicators. More external perceived control, which could reflect chronic exposure to interpersonal and institutional marginalization, may be a particularly salient psychosocial risk factor for poorer cognitive aging among non-Hispanic Black and Hispanic older adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Freely Chosen Cadence is Increased during Repeated Bouts of Submaximal Ergometer Pedalling.
It was investigated whether the phenomenon of repeated bout rate enhancement occurs during submaximal ergometer cycling. Repeated bout rate enhancement is defined as an increase of the freely, or spontaneously, chosen cadence during repeated bouts of pedalling and has previously been reported for finger tapping. This is relevant to study since cadence can affect biomechanical and physiological responses. Recreationally active individuals (n=27) performed five consecutive 5-min bouts of cycling at 100 W using freely chosen cadence. All bouts were separated by 10-min rest. Cadence, pedal force profile characteristics, heart rate, tympanic temperature, and rate of perceived exertion were determined during cycling. The primary result was that cadence at the end of 5. bout was statistically significantly higher than at the end of all other bouts. Overall, the cadence at the end of 5. bout was 15.6%±20.4% higher than at the end of 1. bout. The altered rhythmic motor behaviour was accompanied by a statistically significant effect of bout on the pedal force profile. Also, there was a statistically significant effect of bout on heart rate, which amounted to 125±17 and 131±26 beats/min at the end of 1. and 5. bout, respectively. Perhaps the observed increase of cadence occurred as a nonconscious rhythmogenesis process in form of a net excitation of relevant parts of the nervous system. In conclusion, repeated bout rate enhancement during submaximal ergometer cycling occurred. The freely chosen cadence showed an increase of on average about 15%, or 10 rpm, as accumulated values across five bouts of cycling.


The DNP Graduate and the Potential to Advance Nursing: An Interview With Thought Leader Michael Bleich, PhD, RN, FAAN, by Carol Bradley, MSN, RN, FAONL.
This column is an interview of Michael Bleich PhD, RN, FAAN and focuses on the current state of DNP education. As a thought leader in nursing education, Michael shares his views on the state of DNP nursing education and the opportunity it provides to transform health care through nursing.


Frontal plane compensatory strategies associated with self-selected walking speed in individuals post-stroke.
Approximately two out of three individuals post-stroke experience walking impairments. Frontal plane compensatory strategies (i.e. pelvic hiking and circumduction) are observed in post-stroke gait in part to achieve foot clearance in response to reduced knee flexion and ankle dorsiflexion. The objective of this study was to investigate the relationship between self-selected walking speed and the kinematic patterns related to paretic foot clearance during post-stroke walking. Gait analysis was performed at self-selected walking speed for 21 individuals post-stroke. Four kinematic variables were calculated during the swing phase of the paretic limb: peak pelvic tilt (pelvic hiking), peak hip abduction (circumduction), peak knee flexion, and peak ankle dorsiflexion. Paretic joint angles were analyzed across self-selected walking speed as well as between functionally relevant ambulation categories (Household <0.4m/s, Limited Community 0.4-0.8m/s, Community >0.8m/s). While all subjects exhibited similar foot clearance, slower walkers exhibited greater peak pelvic hiking and less knee flexion, ankle dorsiflexion, and circumduction compared to faster walkers (P<.05). Additionally, four of the fastest walkers compensated for poor knee flexion and ankle dorsiflexion through large amounts of circumduction. These findings suggest that improved gait performance after stroke, as measured by self-selected walking speed, is not necessarily always accomplished through gait patterns that more closely resemble healthy gait for all variables. It appears the ability to walk fast is achieved by either sufficient ankle dorsiflexion and knee flexion to achieve foot clearance or the employment of circumduction to overcome a deficit in either ankle dorsiflexion or knee flexion.


High Glucose Up-regulates ADAM17 through HIF-1α in Mesangial Cells.
We previously showed that ADAM17 mediates high glucose-induced matrix production by kidney mesangial cells. ADAM17 expression is increased in diabetic kidneys, suggesting that its up-regulation may augment high glucose profibrotic responses. We thus studied the effects of high glucose on ADAM17 gene regulation. Primary rat mesangial cells were treated with high glucose (30 mm) or mannitol as osmotic control. High glucose dose-dependently increased ADAM17 promoter activity, transcript, and protein levels. This correlated with augmented ADAM17 activity after 24 h versus 1 h of high glucose. We tested involvement of transcription factors shown in other settings to regulate ADAM17 transcription. Promoter activation was not affected by NF-κB or Sp1 inhibitors, but was blocked by hypoxia-inducible factor-1α (HIF-1α) inhibition or down-regulation. This also prevented ADAM17 transcript and protein increases. HIF-1α activation by high glucose was shown by its increased nuclear translocation and activation of the HIF-responsive hypoxia-response element (HRE)-luciferase reporter construct. Assessment of ADAM17 promoter deletion constructs coupled with mutation analysis and ChIP studies identified HIF-1α binding to its consensus element at -607 as critical for the high glucose response. Finally, inhibitors of epidermal growth factor receptor (EGFR) and downstream PI3K/Akt, or ADAM17 itself, prevented high glucose-induced HIF-1α activation and ADAM17 up-regulation. Thus, high glucose induces ADAM17 transcriptional up-regulation in mesangial cells, which is associated with augmentation of its activity. This is mediated by HIF-1α and requires EGFR/ADAM17 signaling, demonstrating the potentiation by ADAM17 of its own up-regulation. ADAM17 inhibition thus provides a potential novel therapeutic strategy for the treatment of diabetic nephropathy.


Daily remote peritoneal dialysis monitoring: an adjunct to enhance patient care.
Peritoneal dialysis (PD) is the preferred dialysis modality in children, but it relies on the patient or caregiver to perform dialysis daily at home. We describe the utilization of a modem transmission system in 2 pediatric PD patients to improve communication with the dialysis team, monitor compliance via frequent remote data collection, and decrease dialysis-related complications. A home dialysis modem was provided for each patient and connected to the home telephone line by the dialysis nurse. PD treatment data were transmitted daily to the dialysis unit, records entered into the patient's electronic medical record, and reviewed by the patient's PD nurse and/or pediatric nephrologist and adjustments made accordingly. This resulted in improved medical outcomes specifically related to fluid balance and cardiovascular health, ultimately facilitating renal transplantation in each case. In summary, the use of the ProCard (Baxter Healthcare, Deerfield, Illinois, USA) has improved the ability to monitor home PD patients effectively. However, the additional use of the modem to transmit data on a more frequent basis can further enhance the care of chronic continuous cycling PD patients and should be considered in more challenging medical situations.


HIV type 1 subtypes in Malaysia, determined with serologic assays: 1992-1996.
We investigated the molecular epidemiology of HIV-1 subtypes in Malaysia among injecting drug users (IDUs) and sexual transmission risk groups, using serologic and genetic techniques. Frozen sera collected at a general hospital, a blood bank, several drug treatment centers, and an STD clinic in Kuala Lumpur, between 1992 and 1996, were investigated retrospectively. V3 peptide serotyping and monomeric gp120 capture serotyping were used to study 89 known HIV-1-infected subjects. The methods differentiate subtypes B, E, and C. V3 peptide and gp120 capture results were comparable. No subtype C-specific reactive sera were found; one specimen was dually reactive for subtypes C and B, using the V3 peptide ELISA; and four were durally reactive for subtypes E and C using this assay. Genotypic analysis of HIV-1 gag RNA in serum was done on a subset of subjects and confirmed serologic findings. HIV-1 subtypes differed significantly by risk category: of 53 IDUs, 29 (55%) were infected with subtype B and 19 (36%) were infected with subtype E, 3 (6%) were dually reactive, and 2 (4%) were not typable. Of 36 persons with heterosexual risks, 29 (81%) were infected with subtype E, 5 (14%) were infected with subtype B, and 2 (5%) were not typable. Persons with IDU risks were significantly more likely to be infected with subtype B than were those with sexual risks (OR 5.89; 95% CI, 1.94-18.54; p < 0.001). Subtypes B and E of HIV-1 appear to predominate in Malaysia; subtype B was more prevalent among IDUs; subtype E was more prevalent among all other groups. These results may have important HIV-1 vaccine implications.


Diverse antigen specificity of erythrocyte-reactive monoclonal autoantibodies from NZB mice.
The specificities of a panel of erythrocyte-reactive MoAbs derived from NZB mice with autoimmune haemolytic anaemia (AIHA) were determined by immunoprecipitation and immunoblotting. Of the eight antibodies, two (IgG1 MoAb 105-2H and IgG2a MoAb 34-3C) immunoprecipitated a 105-kD component identified as the erythrocyte anion channel band 3. A similar band was also immunoprecipitated by the IgG2b MoAb 34-2B when used at relatively high concentrations, but none of the remaining hybridoma antibodies precipitated any labelled erythrocyte components. In immunoblotting experiments only 34-2B reacted with band 3, indicating that the epitope recognized by this MoAb is robust and differs from the determinant(s) recognized by 105-2H and 34-3C. The remaining MoAbs to react by immunoblotting were the IgM antibodies IE10 and 4C8, both of which bound to a doublet corresponding to band 4.1 from the internal erythrocyte membrane skeleton. Of the three MoAbs which gave negative results in immunoprecipitation and immunoblotting, the IgM antibodies 103-7E and 106-10E reacted poorly with intact erythrocytes by flow cytometry, but the IgG1 antibody 31-9D bound well. ELISAs demonstrated that all four IgM MoAbs are polyreactive, since they bound to histones from a panel of nuclear antigens, and additionally 103-7E reacted with phosphatidyl choline. It is concluded that band 3 is an important autoantigen in NZB AIHA. However, since 3/5 haemolytic MoAbs failed to participate this antigen, either these antibodies represent minor components of the total autoantibody response, or responses to diverse possibly non-protein surface antigens also contribute to the pathogenesis of the disease.


gcr2, a new mutation affecting glycolytic gene expression in Saccharomyces cerevisiae.
Screening of a mutagenized strain carrying a multicopy ENO1-'lacZ fusion plasmid revealed a new mutation affecting most glycolytic enzyme activities in a pattern resembling that caused by gcr1: levels in the range of 10% of wild-type levels on glycerol plus lactate but somewhat higher on glucose. The recessive single nuclear gene mutation, named gcr2-1, was unlinked to gcr1, and GCR1 in multiple copies did not restore enzyme levels. GCR2 was obtained by complementation from a YCp50 genomic library; the complemented strain had normal enzyme levels, as did a strain with GCR2 in multiple copies. GCR2 in multiple copies did not suppress gcr1. A chromosomal gcr2 null mutant was constructed; its pattern of enzyme activities resembled that of the gcr2-1 mutant and, like the gcr2-1 mutant, its growth defect on glucose was only partial (in contrast to the glucose negativity of the gcr1 mutant). Northern (RNA) analysis showed that gcr2 and gcr1 affect ENO1 mRNA levels.


A novel transcriptional activator, tubX, is required for the stability of Bacillus sphaericus mosquitocidal plasmid pBsph.
Stable maintenance of the low-copy-number plasmid pBsph in Bacillus sphaericus requires a partitioning (par) system that consists of a filament-forming protein, B. sphaericus TubZ (TubZ-Bs); a centromere-binding protein, TubR-Bs; and a centromere-like DNA site, tubC, composed of three blocks (I, II, and III) of 12-bp degenerate repeats. Previous studies have shown that mini-pBsph replicons encoding the TubZ system are segregationally highly unstable, whereas the native pBsph is stably maintained. However, the mechanism underlying the stability discrepancy between pBsph and its minireplicon is poorly understood. Here orf187 (encoding TubX), a gene downstream of tubZ-Bs, was found to play a role in plasmid stabilization. Null mutation or overexpression of tubX resulted in a defect in pBsph stability and a significant decrease in the level of tubRZ-Bs expression, and the TubX-null phenotype was suppressed by ectopic expression of a wild-type copy of tubX and additional tubRZ-Bs. An electrophoresis mobility shift assay (EMSA) and a DNase I footprinting assay revealed that the TubX protein bound directly to five 8-bp degenerate repeats located in the par promoter region and that TubX competed with TubR-Bs for binding to the par promoter. Further studies demonstrated that TubX significantly stimulated the transcription of the par operon in the absence of tubR-Bs, and a higher level of gene activation was observed when tubR-Bs was present. These results suggested that TubX positively regulates tubRZ-Bs transcription by interfering with TubR-Bs-mediated repression and binding directly to the tubRZ-Bs promoter region.


The Hsp90 chaperone complex as a novel target for cancer therapy.
Heat shock protein 90 (Hsp90) is responsible for chaperoning proteins involved in cell signaling, proliferation and survival. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is an anticancer agent currently in phase I trials in the USA and UK. It represents a class of drugs, the benzoquinone ansamycin antibiotics, capable of binding and disrupting the function of Hsp90, leading to the depletion of multiple oncogenic client proteins. Studies were identified through a PubMed search, review of bibliographies of relevant articles and review of abstracts from national meetings. Preclinical studies have demonstrated that disruption of many client proteins chaperoned by Hsp90 is achievable and associated with significant growth inhibition, both in vitro and in tumor xenografts. Following an overview of the mechanism of action of ansamycin antibiotics and the pathways they disrupt, we review the current clinical status of 17-AAG, and discuss future directions for combinations of traditional antineoplastics with 17-AAG. 17-AAG represents a class of drugs capable of affecting multiple targets in the signal transduction pathway involved in tumor cell proliferation and survival. Early results from phase I studies indicate that 17-AAG administration results in an acceptable toxicity profile while achieving in vivo disruption of client proteins.


[Canine osteosarcoma as a model in comparative oncology].
Osteogenic sarcomas constitute 80% of all bone tumors in dogs, i.e. approximately 4% of canine tumors. Canine and human osteosarcomas have many clinical and pathological features in common. Epidemiological studies have provided interesting data: larger canine breeds are subject to excess risk of primary bone sarcoma, probably as high as thirty times the risk in small dogs. The appendicular skeleton, namely the metaphyses of long bones, is a preferential initial site of the tumor, and this involvement increases with the weight class of the animals. These data suggest that body size, weight or growth rate may act as factors of bone sarcoma development. Therapeutic trials on canine osteosarcoma are ongoing and could be used as models for the human counterpart.


Loop-mediated isothermal amplification of specific endoglucanase gene sequence for detection of the bacterial wilt pathogen Ralstonia solanacearum.
The increased globalization of crops production and processing industries also promotes the side-effects of more rapid and efficient spread of plant pathogens. To prevent the associated economic losses, and particularly those related to bacterial diseases where their management relies on removal of the infected material from production, simple, easy-to-perform, rapid and cost-effective tests are needed. Loop-mediated isothermal amplification (LAMP) assays that target 16S rRNA, fliC and egl genes were compared and evaluated as on-site applications. The assay with the best performance was that targeted to the egl gene, which shows high analytical specificity for diverse strains of the betaproteobacterium Ralstonia solanacearum, including its non-European and non-race 3 biovar 2 strains. The additional melting curve analysis provides confirmation of the test results. According to our extensive assessment, the egl LAMP assay requires minimum sample preparation (a few minutes of boiling) for the identification of pure cultures and ooze from symptomatic material, and it can also be used in a high-throughput format in the laboratory. This provides sensitive and reliable detection of R. solanacearum strains of different phylotypes.


De novo drug designing coupled with brute force screening and structure guided lead optimization gives highly specific inhibitor of METTL3: a potential cure for Acute Myeloid Leukaemia.
Expression of METTL3, a SAM dependent methyltransferase, which deposits m6A on mRNA is linked to poor prognosis in Acute Myeloid Leukaemia and other type of cancers. Down regulation of this epitranscriptomic regulator has been found to inhibit cancer progression. Silencing the methyltransferase activity of METTL3 is a lucrative strategy to design anticancer drugs. In this study 3600 commercially available molecules were screened against METTL3 using brute force screening approach. However, none of these compounds take advantage of the unique Y-shaped binding cavity of the protein, raising the need for de novo drug designing strategies. As such, 125 branched, Y-shaped molecules were designed by "stitching" together the chemical fragments of the best inhibitors that interact strongly with the METTL3 binding pocket. This results in molecules that have the three-dimensional structure and functional groups which enable it to fit in the METTL3 cavity like fingers in a glove, having unprecedented selectivity and binding affinities. The designed compounds were further refined based on Lipinski's rule, docking score and synthetic accessibility. The molecules faring well in these criteria were simulated for 100 ns to check the stability of the protein inhibitor complex followed by binding free energy calculation.Communicated by Ramaswamy H. Sarma.


Inverted valve after initially successful transfemoral aortic valve implantation.
A 73-year-old woman with severe aortic stenosis was accepted for transcatheter aortic valve implantation. There was minimal paravalvular leakage after the implantation, and the patient was stable. Twelve minutes after the implantation, the arterial pressure suddenly dropped. Transesophageal echocardiography showed severe left ventricular dysfunction. Cardiopulmonary resuscitation was started, and initially was successful with a systolic blood pressure of 90 mm Hg. However, despite initiation of extracorporeal circulation support, the patient deteriorated, pulmonary edema developed, and she died. Autopsy revealed an inverted aortic valve. The reasons why the patient had cardiac arrest and an inverted transfemoral aortic valve remain unclear.


Functional complementation between bacterial MDR-like export systems: colicin V, alpha-hemolysin, and Erwinia protease.
The antibacterial protein Colicin V (ColV) is secreted from gram-negative bacteria by a signal sequence-independent pathway. The proteins that mediate the export of ColV share sequence similarities with components from other signal sequence-independent export systems such as those for alpha-hemolysin (Hly) and Erwinia protease (Prt). We report here that the intact HlyBD export system can export active ColV from Escherichia coli strains lacking the ColV export proteins CvaA and CvaB. The individual Hly export genes complement mutations in their respective ColV homologs, but do so at a lower efficiency. When CvaA or CvaB is expressed along with the intact HlyBD exporter, the Cva export protein interferes with export of ColV through the HlyBD system. Gene fusions and point mutations in the ColV structural gene were used to define signals in ColV recognized by the Hly exporter. An export signal in ColV recognized by HlyBD is localized to the amino-terminal 57 amino acids of the protein. In addition, mutations in the ColV export signal differentially affect export through CvaAB and HlyBD, suggesting differences in signal specificity between the Cva and Hly systems. The three Erwinia protease export proteins can also export active ColV, and interference is seen when CvaA or CvaB is expressed along with the intact Prt exporter. Functional complementation is not reciprocal; alpha-hemolysin is not exported through either the ColV system or the Prt system.


Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract.
Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.


In Situ Cross-Linking Strategy to Enable Highly Stable Perovskite Solar Cells.
The perovskite solar cells (PSCs) have achieved great success in power conversion efficiency due to their excellent optoelectrical properties of perovskite. However, the instability of PSCs severely impedes their commercialization. Recently, in situ cross-linking strategy has been proposed to mitigate stability issues of PSCs, enabling highly efficient and stable PSCs. Here, the critical factors that lead to the degradation of PSCs are first outlined. Then, a comprehensive review of in situ cross-linking strategy in perovskite to enhance the moisture, thermal, illumination, and bending stress resistance properties of PSCs is presented. Furthermore, the detailed mechanism underlying these advantageous effects is discussed pertaining to crystallization regulation, immobilization of ions, water resistance, and release of unfavorable stress. Finally, the current challenges and further development trends of in situ cross-linking strategy in PSCs and extension to other optoelectronic devices are prospected.


Nontuberculous mycobacteria isolated from specimens of pulmonary tuberculosis suspects, Northern Tunisia: 2002-2016.
Reports on the worldwide ascending trend of pulmonary nontuberculous mycobacteria (NTM) isolation rates and their effective role in respiratory tract infections are compelling. However, as yet, there are no such data relating to Tunisia. Here we carried out a retrospective review of mycobacterial cultures originating from Northern Tunisia, which have been processed in the laboratory of mycobacteria of the Institut Pasteur de Tunis, during the time period 2002-2016. All pulmonary NTM (PNTM) isolates available for culture were characterized phenotypically and their taxonomic status was further established based on polymorphisms in rpoB, 16S rRNA, hsp65, and sodA DNA gene sequences. Of the 10,466 specimens collected from HIV-negative Tunisian patients with presumptive clinical pulmonary TB, 60 (0.6%) yielded PNTM isolates. An overall annual PNTM isolation prevalence of 0.2/100,000 was estimated. As far as could be ascertained, this isolation rate accounts amongst the lowest reported hitherto throughout the world. Among the 30 NTM isolates that were available for culture, 27 (90.0%) have been identified to the species level. The most commonly encountered species was Mycobacterium kansasii (23.3%) subtype 1. Strikingly, all M. kansasii cases were male patients originating from Bizerte, an industrialized region particularly known for iron industry. The remaining NTM species were M. fortuitum (16.6%), M. novocastrense (16.6%), M. chelonae (10.0%), M. gordonae (6.6%), M. gadium (6.6%), M. peregrinum (3.3%), M. porcinum (3.3%), and M. flavescens (3.3%). There were no bacteria of the M. avium complex, the most frequently isolated NTM globally, and the main driver of the rise of NTM-lung diseases. This study uncovered an exceptional low prevalence of PNTM isolation among HIV-negative TB suspects in Northern Tunisia, suggesting a very low burden of NTM pulmonary disease. However, the frequent isolation of M. kansasii subtype 1, the most pathogenic subtype, particularly from the industrialized region of Bizerte, strongly suggests its effective involvement in a typical pulmonary disease.


D-dimers, thrombin-antithrombin complexes, and risk factors for thromboembolism in hospitalized patient.
There is lack of data about the correlation between hemostatic markers and the clinical and biological risk factors (RFs) for venous thromboembolism (VTE) in medical inpatients without suspicion of acute VTE. To evaluate the coagulation activation status in patients with current known RFs for VTE, the authors measured 2 markers of hypercoagulability, thrombin antithrombin (TAT) complexes and D-dimers, at day 1 in 165 patients hospitalized in internal medicine wards without suspected acute VTE. All known RFs for VTE were systematically assessed at admission and classified in a chronological way as permanent or transient. Surprisingly, TAT values followed a multimodal distribution. D-dimers showed a normal distribution after a logarithmic transformation (P = .34, Shapiro-Wilk test). Interestingly, a significant progression in D-dimer levels was found according to the chronological classification of RFs. D-dimer variations on multivariate analysis (not applicable for TAT because of the multimodal distribution) correlated independently with a recent inability to walk and an increase in C reactive protein level more than 10 mg/L. (a) this study is the first to describe the variations of hypercoagulability markers according to a systematic screening of RFs for VTE in inpatients without suspicion of acute VTE, (b) TAT appeared as a less relevant marker of hypercoagulability than D-dimers in internal medicine inpatients, (d) the chronological classification of RFs identified clearly groups at risk for the prethrombotic state, and (d) an increased hypercoagulability state was demonstrated in patients with an association between a recent immobility and increased inflammatory markers.


Tissue-Specific Effects of Esophageal Extracellular Matrix.
Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate repair or remodeling of numerous tissues, including the esophagus. The theoretically ideal scaffold for tissue repair is the ECM derived from the particular tissue to be treated, that is, site-specific or homologous ECM. The preference or potential advantage for the use of site-specific ECM remains unknown in the esophageal location. The objective of the present study was to characterize the in vitro cellular response and in vivo host response to a homologous esophageal ECM (eECM) versus nonhomologous ECMs derived from small intestinal submucosa and urinary bladder. The in vitro response of esophageal stem cells was characterized by migration, proliferation, and three-dimensional (3D) organoid formation assays. The in vivo remodeling response was evaluated in a rat model of esophageal mucosal resection. Results of the study showed that the eECM retains favorable tissue-specific characteristics that enhance the migration of esophageal stem cells and supports the formation of 3D organoids to a greater extent than heterologous ECMs. Implantation of eECM facilitates the remodeling of esophageal mucosa following mucosal resection, but no distinct advantage versus heterologous ECM could be identified.


BET 2: Twist score in cases of suspected paediatric testicular torsion.
A shortcut review of the literature was carried out to establish whether the Testicular Workup for Ischemia and Suspected Torsion (TWIST) score was reliable and accurate enough to rule out testicular torsion in the paediatric population.Four papers were found to be relevant to the clinical question following the below-described search strategies. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of those best papers are tabulated. It is concluded that based on the currently available evidence, a low-risk TWIST score has a high sensitivity and can be used in line with clinical judgement to rule out testicular torsion.


Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial.
Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future.


Health survey of former workers in a Norwegian coke plant: Part 2. Cancer incidence and cause specific mortality.
A Norwegian coke plant that operated from 1964 to 1988 was investigated to ascertain whether the male workers in this plant had increased morbidities of cancer or increased mortality from specific causes, particularly associated with specific exposures at the coke plant. Personal data on all the employees of the plant were obtained from the plant's archives. With additional data from the Norwegian Bureau of Statistics we identified 888 male former workers at the plant. Causes of death were obtained from the Norwegian Bureau of Statistics, and cancer diagnoses from the Norwegian Cancer Registry. The results were compared with national averages adjusted for age. Specific exposures were estimated with records of actual measurements done at the plant and interviews with former workers at the plant. A significant excess of stomach cancer (standardised incidence ratio (SIR) 2.22, 95% confidence interval (95% CI) 1.01 to 4.21) was found. Mortality from ischaemic heart disease and sudden death was positively associated with work in areas which entailed peak exposures to CO. When considering work in such areas the past 3 years before death, the association was significant (p = 0.01). The last result is based on only two deaths. Considering the short follow up time and the small size of the cohort the results should be interpreted with a certain caution. The positive results would justify a re-examination of the cohort at a later date.


Impact of microfinance health interventions on health-related outcomes among female informal workers in Pakistan: a retrospective quasi-experimental study.
The purpose of this study is to assess the impact of microfinance health interventions (health insurance and health-awareness programmes) on health-related outcomes among female informal workers in Pakistan. We conducted a retrospective, quasi-experimental study among a total of 442 female borrowers from seven microfinance providers (MFPs) across four provinces of Pakistan in 2018. A standardised tool was used for data collection. Probit regression was used to identify the probability of female borrowers gaining improvements in health outcomes based on their sociodemographic characteristics. Propensity score matching (PSM) was used to assess the overall impact of health interventions. Four health-related outcomes reported by the women were used: perception of good health overall, ability to visit a general practitioner, ability to purchase prescribed medicine and intake of multivitamins. We found that women receiving health interventions had a greater probability of better health outcomes when they were from Punjab province, borrowing in groups and attending monthly meetings at MFPs. Even with a small loan amount, all four health-related outcomes were significantly associated with receiving health insurance and health-awareness programmes. PSM results show a greater likelihood of overall perceived good health (nearest neighbour matching (NNM) =17.4%; kernel matching (KM) =11.8%) when health insurance is provided and a significant improvement in the ability to purchase prescribed medicine when a health-awareness programme is provided (NNM=10.1%; KM=11.7%). Health and social policies are vital to secure health and well-being among poor women working in the informal sector. Targeting improved equity across female population groups for health interventions will in the long run improve poor women's health, income-earning abilities and capacity expansion for small businesses.


Accuracy of data on influenza vaccination status at four Vaccine Safety Datalink sites.
Studies of influenza vaccination using electronic medical records rely on accurate classification of vaccination status. Vaccinations not entered into electronic records would be unavailable for study. This study evaluated the sensitivity and negative predictive value (NPV) of electronic records for influenza vaccination and factors associated with failure to capture vaccinations. In four diverse medical care organizations in the Vaccine Safety Datalink, those aged 50-79 years with no influenza vaccination record during the 2007-2008 season were surveyed by telephone, and electronic records were analyzed in 2008. The sensitivity and NPV of electronic records were estimated, using survey responses as the gold standard. Logistic regression models determined associations between 1-NPV and demographic factors, risk of influenza complications, and healthcare utilization levels. Data were obtained for 933 survey participants and 1,085,916 medical care organization members. Sites varied significantly in the sensitivity (51%, 68%, 79%, 89%) and NPV (46%, 62%, 66%, 87%) of electronic records. In multivariate analysis, the rate of failure to capture vaccinations was significantly higher for those aged 65-79 years than for those aged 50-64 years at three sites. Of vaccinations not captured by electronic records, 58% were reportedly administered in nontraditional settings, usually workplaces; the rest were given within the sites. Influenza vaccination studies relying on electronic records may misclassify substantial proportions of vaccinated individuals as unvaccinated, producing biased estimates of vaccine effectiveness. Sites with limited sensitivity to capture vaccinations administered within their organization should seek possible remedies. More complete capture of vaccinations administered to older patients and in nontraditional settings would further reduce misclassification.


EBRA Migration Analysis of a Modular, Distally Fixed Stem in Hip Revision Arthroplasty: A Clinical and Radiological Study.
Background: Massive osteolysis of the proximal femur makes stem revision a challenging procedure. EBRA-FCA provides the opportunity to determine stem migration, which is considered a predictive factor for implant survival. In this study, we aimed to analyze the migration behavior of a modular, distally fixed reconstruction prosthesis. Methods: Applying a retrospective study design, we reviewed all consecutive patients who received a cementless MP reconstruction prosthesis (Waldemar Link GmbH & Co. KG, Hamburg, Germany) at our Department between 2005 and 2019. We reviewed medical histories and performed radiological measurements using EBRA-FCA software. Results: A total of 67 stems in 62 patients (female 26; male 36) fulfilled our inclusion criteria. Mean age at surgery was 68.0 (range 38.7−88.44) years. EBRA migration analysis showed a median subsidence of 1.6 mm (range 0.0−20.6) at 24 months. The angle between stem and femur axis was 0.3° (range 0.0°−2.9°) at final follow-up. No correlation between body mass index and increased subsidence was found (p > 0.05). Overall revision-free rate amounted to 92.5% and revision-free rate for aseptic loosening to 98.5%. Furthermore, no case of material breakage was detected. Conclusions: In summary, the MP reconstruction prosthesis showed low subsidence and reduction in the migration rate over the investigated follow-up. Based on this, the modular stem can be considered as a good therapy option in challenging stem revisions offering various options to address the individual anatomical situation.


Discovery of novel potent and selective dipeptide hepatitis C virus NS3/4A serine protease inhibitors.
Starting from the previously reported HCV NS3/4A protease inhibitor BILN 2061, we have used a fast-follower approach to identify a novel series of HCV NS3/4A protease inhibitors in which (i) the P3 amino moiety and its capping group have been truncated, (ii) a sulfonamide is introduced in the P1 cyclopropyl amino acid, (iii) the position 8 of the quinoline is substituted with a methyl or halo group, and (iv) the ring size of the macrocycle has been reduced to 14 atoms. SAR analysis performed with a limited set of compounds led to the identification of N-{17-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]-2,14-dioxo-3,15-diazatricyclo [188.8.131.52 [Bartenschlager, R.; Lohmann, V. J. Gen. Virol. 2000, 81, 1631; Vincent Soriano, Antonio Madejon, Eugenia Vispo, Pablo Labarga, Javier Garcia-Samaniego, Luz Martin-Carbonero, Julie Sheldon, Marcelle Bottecchia, Paula Tuma, Pablo Barreiro Expert Opin. Emerg. Drugs, 2008, 13, 1-19]]octadec-7-ene-4-carbonyl}(1-methylcyclopropyl)(1-methylcyclopropyl)sulfonamide 19l an extremely potent (K(i)=0.20 nM, EC(50)=3.7 nM), selective, and orally bioavailable dipeptide NS3/4A protease inhibitor, which has features attractive for further preclinical development.


Geobacter anodireducens sp. nov., an exoelectrogenic microbe in bioelectrochemical systems.
A previously isolated exoelectrogenic bacterium, strain SD-1(T), was further characterized and identified as a representative of a novel species of the genus Geobacter. Strain SD-1(T) was Gram-negative, aerotolerant, anaerobic, non-spore-forming, non-fermentative and non-motile. Cells were short, curved rods (0.8-1.3 µm long and 0.3 µm in diameter). Growth of strain SD-1(T) was observed at 15-42 °C and pH 6.0-8.5, with optimal growth at 30-35 °C and pH 7. Analysis of 16S rRNA gene sequences indicated that the isolate was a member of the genus Geobacter, with the closest known relative being Geobacter sulfurreducens PCA(T) (98% similarity). Similar to other members of the genus Geobacter, strain SD-1(T) used soluble or insoluble Fe(III) as the sole electron acceptor coupled with the oxidation of acetate. However, SD-1(T) could not reduce fumarate as an electron acceptor with acetate oxidization, which is an important physiological trait for G. sulfurreducens. Moreover, SD-1(T) could grow in media containing as much as 3% NaCl, while G. sulfurreducens PCA(T) can tolerate just half this concentration, and this difference in salt tolerance was even more obvious when cultivated in bioelectrochemical systems. DNA-DNA hybridization analysis of strain SD-1(T) and its closest relative, G. sulfurreducens ATCC 51573(T), showed a relatedness of 61.6%. The DNA G+C content of strain SD-1(T) was 58.9 mol%. Thus, on the basis of these characteristics, strain SD-1(T) was not assigned to G. sulfurreducens, and was instead classified in the genus Geobacter as a representative of a novel species. The name Geobacter anodireducens sp. nov. is proposed, with the type strain SD-1(T) ( = CGMCC 1.12536(T) = KCTC 4672(T)).


Carbonyl- and Nitrogen-Embedded Multi-Resonance Emitter with Ultra-Pure Green Emission and High Electroluminescence Efficiencies.
Multi-resonance thermally activated delayed fluorescence (MR-TADF) emitters with narrow emission spectra have garnered significant attention in future organic light-emitting diode (OLED) displays. However, current C=O/N-embedded MR-TADF systems still lack satisfactory performance in terms of electroluminescence bandwidths and external quantum efficiencies (EQEs). In this study, a C=O/N-embedded green MR-TADF emitter, featuring two acridone units incorporated in a sterically protected 11-ring fused core skeleton, is successfully synthesized through finely controlling the reaction selectivity. The superior combination of multiple intramolecular fusion and steric wrapping strategies in the design of the emitter not only imparts an extremely narrow emission spectrum and a high fluorescence quantum yield to the emitter but also mitigates aggregation-induced spectral broadening and fluorescence quenching. Therefore, the emitter exhibits leading green OLED performance among C=O/N-based MR-TADF systems, achieving an EQE of up to 37.2%, a full width at half maximum of merely 0.11 eV (24 nm), and a Commission Internationale de l'Éclairage coordinate of (0.20, 0.73). This study marks a significant advance in the realization of ideal C=O/N-based MR-TADF emitters and holds profound implications for the design and synthesis of other MR-TADF systems.


Primary vs. post-chemotherapy retroperitoneal lymph node dissection (RPLND) in patients with presence of teratoma at orchiectomy.
The presence of teratoma in the primary orchiectomy specimen creates controversies for subsequent management. Although predominant teratoma is less likely to metastasize, teratoma in the retroperitoneum may be less amenable to chemotherapy. In order to elucidate the issues about teratoma in the primary tumor, we reviewed differences between primary retroperitoneal lymph node dissection (P-RPLND) vs. post-chemotherapy RPLND (PC-RPLND) in patients with teratoma at orchiectomy. Patients who had undergone RPLND at our institution from 2001 to 2008 were identified, and clinical charts reviewed. Eighty-three patients with teratoma at orchiectomy were identified and perioperative data were obtained. Of the 83 patients with teratoma at orchiectomy who underwent RPLND, 44 (53%) and 39 (47%) underwent primary and PC-RPLND, respectively. Median follow-up was 1.4 years. Of the 83 patients with primary teratoma at orchiectomy, there were 7 (8%) patients with pure teratoma and 76 (92%) patients with mixed histology. Of the patients with mixed histology, 72 (87%) patients had embryonal carcinoma and 36 (43%) had LVI. There were 19 (43%) positive lymph nodes for P-RPLND, of which 13 (30%) contained teratoma. For the PC-RPLND group, 30 (77%) of lymph nodes were positive, of which 28 (72%) contained teratoma. There were 3 (4%) recurrences overall, all of which recurred in the PC-RPLND group. There were 11 (13%) perioperative complications total. There were no deaths in either group. Patients with teratoma at orchiectomy were associated with other high risk features and are at significant risk for metastatic disease. Patients with post-chemotherapy retroperitoneal findings are at significant risk for viable GCT and/or teratoma and should undergo PC-RPLND.


Accurate age classification of 6 and 12 month-old infants based on resting-state functional connectivity magnetic resonance imaging data.
Human large-scale functional brain networks are hypothesized to undergo significant changes over development. Little is known about these functional architectural changes, particularly during the second half of the first year of life. We used multivariate pattern classification of resting-state functional connectivity magnetic resonance imaging (fcMRI) data obtained in an on-going, multi-site, longitudinal study of brain and behavioral development to explore whether fcMRI data contained information sufficient to classify infant age. Analyses carefully account for the effects of fcMRI motion artifact. Support vector machines (SVMs) classified 6 versus 12 month-old infants (128 datasets) above chance based on fcMRI data alone. Results demonstrate significant changes in measures of brain functional organization that coincide with a special period of dramatic change in infant motor, cognitive, and social development. Explorations of the most different correlations used for SVM lead to two different interpretations about functional connections that support 6 versus 12-month age categorization.


[Return to work and cardiovascular status after myocardial infarction].
110 male subjects, under 60, admitted for myocardial infarction in 1980 and 1981, have been considered. 85 answers to the questionnaire, sent by post have been obtained, 6 pertaining to patients who died in the meanwhile. Among the 79 living patients who replied, 57 (72.1%) had resumed work within the average time of 4.8 months (min. 0.5-max. 12). Return to work has been significantly higher among self-employed people than employees; only 15 subjects had changed job or task. The subjective rating of the actual health status, two years after the infarction, has been satisfactory in 90.5% of cases, in spite of 56.5% complaining of heartburn, 38.1% of dyspnea and 35.7% of palpitation. The work-load has been rated as tiring only by 12.6% of them, while 65.6% have maintained unchanged their work capacity. Electrocardiographic monitoring (by the Holter method), during a normal workday, showed no significant differences between working and retired subjects and, also, in work and normal activity periods. 19 subjects (47.5%) presented ventricular arrhythmias, in 12 cases at high risk, most of them being unaware of it. These arrhythmias were more frequent during wake periods, but not strictly connected to the type and the quality of the work activity. The patients subjected to rehabilitation showed no differences in the cardiovascular patterns during the ergometric test and ECG monitoring when compared to those not subjected to rehabilitation.


Autonomic dysregulation during sleep in Parkinsonian spectrum disorders - A proof of concept.
Autonomic dysfunction is common in α-synucleinopathies such as Lewy Body dementias (LBD), Parkinson's disease (PD), and isolated REM Sleep Behavior Disorder (iRBD). We analyzed pulse-rate changes during sleep to index autonomic nervous system (ANS) dysfunction in patients with α-synucleinopathies vs. non-synucleinopathy groups expected to have normal ANS function. Patients with LBD (n = 16), PD (PD, n = 14) or iRBD (n = 12) were compared to the non-synucleinopathy groups Alzheimers disease dementia (ADem, n = 26), mild cognitive impairment (MCI, n = 34) or controls (CG, n = 54). Sleep Profiler was used to derive a sleep autonomic activation index (AAI), i.e., ≥6 beat-per-minute increase/decrease, pulse rate coefficient of variation (PR-CV), and automated sleep staging with sleep-spindles and non-REM hypertonia (NRH). Analysis included statistical group comparisons and receiver operating characteristics curves to determine optimal classification of groups. AAI and PR-CV were moderately correlated across all recordings (rs = 0.58, P < 0.0001), except in the LBD and PD groups. AAI but not PR-CV differentiated the LBD, PD and iRBD from non-Parkinsonian groups. AAI was decreased in LBD and PD patients compared to the CG (p < 0.003) and MCI (p < 0.03). AAI decreased based on age and its receiver operating characteristic area under the curve ranged from 0.63 to 0.75. AAI had a weak negative correlation to NRH (rs ≤ -0.26) but not sleep-spindles. Synucleinopathy-related ANS dysfunction can reasonably discriminate prodromal and manifest PD/LBD diseased groups from non-synucleinopathies. Further studies incorporating AAI into a multivariate classifier of neurodegenerative disorders based on sleep characteristics acquired in the patient's home are planned.


The thermal effects of lavage on 57 ox femoral heads prepared for hip resurfacing arthroplasty.
Previously, we have documented surface temperatures recorded by thermography great enough to cause osteonecrosis of the femoral head during hip resurfacing. We now performed an in vitro investigation with 3 questions: (1) whether water irrigation reduced bone surface temperature, (2) whether external bone temperatures were similar to core temperatures, and (3) whether blunting of the reamer affected temperature generation. Using an ox-bone model, 57 femoral heads were peripherally reamed. The surface temperatures of bone were measured using a thermal camera and internal bone temperatures were measured using 2 theromocouples. We measured the effects of cooling with water at room temperature and with ice-cooled water. Progressive blunting of reamers was assessed over the 57 experiments. Mean and maximum temperatures generated during peripheral reaming were greater when no irrigation was used. Ice-cold saline protected femoral heads from thermal damage. External bone temperatures were much greater than internal temperatures, which were not sufficiently elevated to cause osteonecrosis regardless of lavage. Blunting of the reamer was not found to have a statistically significant effect in this study. Cooling with ice-cooled water is recommended. Internal bone temperatures are not elevated despite the high surface temperatures reached during femoral head resurfacing.


The Transmission of Gun and Other Weapon-Involved Violence Within Social Networks.
Fatal and nonfatal injuries resulting from gun violence remain a persistent problem in the United States. The available research suggests that gun violence diffuses among people and across places through social relationships. Understanding the relationship between gun violence within social networks and individual gun violence risk is critical in preventing the spread of gun violence within populations. This systematic review examines the existing scientific evidence on the transmission of gun and other weapon-related violence in household, intimate partner, peer, and co-offending networks. Our review identified 16 studies published between 1996 and 2015 that suggest that exposure to a victim or perpetrator of violence in one's interpersonal relationships and social networks increases the risk of individual victimization and perpetration. Formal network analyses find high concentrations of gun violence in small networks and that exposure to gun violence in one's networks is highly correlated with one's own probability of being a gunshot victim. Physical violence by parents and weapon use by intimate partners also increase risk for victimization and perpetration. Additional work is needed to better characterize the mechanisms through which network exposures increase individual risk for violence and to evaluate interventions aimed at disrupting the spread of gun and other weapon violence in high-risk social networks.


The Interdisciplinary Generalist Project at the University of Nebraska Medical Center.
The Interdisciplinary Generalist Curriculum (IGC) Project at the University of Nebraska College of Medicine (Nebraska) had three goals: (1) to increase first- and second-year students' exposure to primary care practice in the community; (2) to develop specific educational programs introducing these students to the principles and practices of primary care medicine; and (3) to establish a generalist coordinating council to provide leadership and to nurture generalist educational initiatives in the College of MEDICINE: Students at Nebraska were already required to spend three half-days a semester in a longitudinal clinical experience (LCE) and to complete a three-week primary care block experience in the summer between the first and second years. IGC Project funds were used increase the number of required LCE visits to five a semester and to develop curricular enhancements that would maximize the educational potential of community-based clinical experiences for first- and second-year students. Curricular elements developed included a focus on faculty development for preceptors and development of the Primary Care Introduction to Medicine Curriculum, an eight-week, interdisciplinary module scheduled late in the first year to help prepare students for intensive summer rotations. Other developments were the implementation of a pediatric physical examination experience for first-year students and the implementation of instruction in community-oriented primary care in the second year. Lessons learned are related to: (1) the value and power of early clinical experiences; and (2) the enhancing effect of a holistic, longitudinal view of the curriculum on the planning of early clinical experiences.


The murine serotonin syndrome - evaluation of responses to 5-HT-enhancing drugs in NMRI mice.
In humans, the ingestion of the combination of two or more serotonin (5-HT)-enhancing drugs but also of a single drug in overdose can induce serious adverse effects, which are characteristics of the serotonin syndrome (SS). In mice, acute administration of direct and indirect 5-HT agonists also leads to behavioral and autonomic responses, but in literature different responses are thought to be essential. In order to detect common behavioral SS responses induced by 5-HT-enhancing drugs with different mechanisms of action, we investigated the effects of the 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), and the monoaminooxidase (MAO) inhibitor tranylcypromine (TCP) in male NMRI mice. The drugs were administered alone or in combination to investigate additive effects or drug potentiation. Moreover, we compared the 5-HT responses to the effects induced by the dopamine, noradrenaline, and cholinergic agonists, apomorphine (APO), atomoxetine (ATO), and oxotremorine (OXO). Our results show that the studied 5-HT-enhancing drugs induced a different number of concomitant responses. The following five responses consistently and dose-dependently occurred in NMRI mice: flat body posture, hindlimb abduction, piloerection, tremor, and decreased rearings. Like in humans, the combination of 5-HT-enhancing drugs leads to a potentiation of drug effects. With the exception of flat body posture the responses are not specific for serotonergic hyperactivity. The findings demonstrate that the SS in NMRI mice is a suitable animal model for preclinical research, if it is taken into account that the spectrum of typical responses to 5-HT enhancing drugs may differ depending on drug and mouse strain and that some responses might be evoked by activation of other transmission systems, too.


Spontaneous release of lipopolysaccharide by Pseudomonas aeruginosa.
Pseudomonas aeruginosa PAO grown in glucose mineral salts medium released lipopolysaccharide which was chemically and immunologically similar to the cellular lipopolysaccharide. In addition, it possessed identical phage E79-inactivating properties. Through neutralization of phage activity and hemolysis inhibition assays, the organism was found to liberate lipopolysaccharide at a constant rate during log-phase growth equivalent to 1.3 to 2.2 ng/10(8) cells over a growth temperature range of 25 to 42 degrees C. At 19 degrees C, a lipopolysaccharide was released which was deficient in phage-inactivating activity but retained its immunological properties. Chemical analysis of lipopolysaccharide extracted from cells grown at 19 degrees C showed a deficiency in the O-side-chain component fucosamine. Gel exclusion chromatography of the polysaccharide fraction derived from lipopolysaccharide isolated from cells grown at 19 degrees C exhibited a decreased content of side-chain polysaccharide as well as a difference in the hexosamine:hexose ratio. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis confirmed these results as well as establishing that an essentially normal distribution of side-chain repeating unit lengths were to be found in the 19 degrees C preparation. These results suggest a decrease in the frequency of capping R-form lipopolysaccharide at 19 degrees C.


Reduction of residual excess noise in class-A lasers using two-photon absorption.
We demonstrate experimentally a significant reduction of the remaining excess intensity noise in a class-A semi-conductor laser. This is obtained by inserting into the laser cavity a buffer reservoir mechanism based on two-photon absorption in GaAs. The excess noise peaks at the laser-free spectral range, induced by the beating between the lasing mode and the amplified spontaneous emission in the adjacent non-oscillating modes, is reduced by 20 dB, while preserving the class-A dynamical behavior of the laser cavity.


Outcome-Driven Clustering of Acute Coronary Syndrome Patients Using Multi-Task Neural Network with Attention.
Cluster analysis aims at separating patients into phenotypically heterogenous groups and defining therapeutically homogeneous patient subclasses. It is an important approach in data-driven disease classification and subtyping. Acute coronary syndrome (ACS) is a syndrome due to sudden decrease of coronary artery blood flow, where disease classification would help to inform therapeutic strategies and provide prognostic insights. Here we conducted an outcome-driven cluster analysis of ACS patients, which jointly considers treatment and patient outcome as indicators for patient state. Multi-task neural network with attention was used as a modeling framework, including learning of the patient state, cluster analysis, and feature importance profiling. Seven patient clusters were discovered. The clusters have different characteristics, as well as different risk profiles to the outcome of in-hospital major adverse cardiac events. The results demonstrate cluster analysis using outcome-driven multi-task neural network as promising for patient classification and subtyping.


Screening hub genes in coronary artery disease based on integrated analysis.
Coronary artery disease (CAD) is the leading cause of mortality worldwide. Identifying key pathogenic genes benefits the understanding molecular mechanism of CAD. In this study, 5 microarray data sets from the blood sample of 312 CADs and 277 healthy controls were downloaded. Limma and metaMA packages were used to identify differentially expressed genes. The functional enrichment analysis of differentially expressed genes was further performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Additionally, protein-protein interac-tion and transcript factors-target networks were performed based on top 10 up- and down-regulated differentially expressed genes to further study the biological function. Last, real-time quantitative poly-merase chain reaction (RT-qPCR) was used to validate the integrated analysis result. A total of 528 differentially expressed genes were obtained. All differentially expressed genes were significantly involved in signal transduction and the MAPK signaling pathway. Among MAPK signaling pathway, IL1R2, ARRB2 and PRKX were associated with CAD. Furthermore, there were 4 common differentially expressed genes including PLAUR, HSPH1, ZMYND11 and S100A8 in the protein-protein interaction and transcript factors-target networks, which played crucial roles in the development of CAD. In quantitative RT-qPCR, the expression of PRKX, HSPH1 and ZMYND11 was down-regulated and consistent with the integrated analysis. Identified 7 differentially expressed genes (IL1R2, ARRB2, PRKX, PLAUR, HSPH1, ZMYND11 and S100A8) may play crucial roles in the development of CAD.


Myristate and the ecology of AM fungi: significance, opportunities, applications and challenges.
A recent study by Sugiura and coworkers reported the non-symbiotic growth and spore production of an arbuscular mycorrhizal (AM) fungus, Rhizophagus irregularis, when the fungus received an external supply of certain fatty acids, myristates (C:14). This discovery follows the insight that AM fungi receive fatty acids from their hosts when in symbiosis. If this result holds up and can be repeated under nonsterile conditions and with a broader range of fungi, it has numerous consequences for our understanding of AM fungal ecology, from the level of the fungus, at the plant community level, and to functional consequences in ecosystems. In addition, myristate may open up several avenues from a more applied perspective, including improved fungal culture and supplementation of AM fungi or inoculum in the field. We here map these potential opportunities, and additionally offer thoughts on potential risks of this potentially new technology. Lastly, we discuss the specific research challenges that need to be overcome to come to an understanding of the potential role of myristate in AM ecology.


Setting Ideal Lubricant Mixing Time for Manufacturing Tablets by Evaluating Powder Flowability.
We investigated the effectiveness of using Carr's flowability index (FI) and practical angle of internal friction (Φ) as indexes for setting the target Mg-St mixing time needed for preparing tablets with the target physical properties. We used FI as a measure of flowability under non-loaded conditions, and Φ as a measure of flowability under loaded conditions for pharmaceutical powders undergoing direct compression with varying concentrations of Mg-St and mixing times. We evaluated the relationship between Mg-St mixing conditions and pharmaceutical powder flowability, analyzed the correlation between the physical properties of the tablets (i.e., tablet weight variation, drug content uniformity, hardness, friability, and disintegration time of tablets prepared using the pharmaceutical powder), and studied the effect of Mg-St mixing conditions and pharmaceutical powder flowability on tablet properties. Mg-St mixing time highly correlated with pharmaceutical powder FI (R 2 = 0.883) while Mg-St concentration has low correlation with FI, and FI highly correlated with the physical properties of the tablet (R 2 values: weight variation 0.509, drug content variation 0.314, hardness 0.525, friability 0.477, and disintegration time 0.346). Therefore, using pharmaceutical powder FI as an index could enable prediction of the physical properties of a tablet without the need for tableting, and setting the Mg-St mixing time by using pharmaceutical powder FI could enable preparation of tablets with the target physical properties. Thus, the FI of the intermediate product (i.e., pharmaceutical powder) is an effective index for controlling the physical properties of the finished tablet.


Molecular Mechanisms Underlying Intestinal Ischemia/Reperfusion Injury: Bioinformatics Analysis and In Vivo Validation.
BACKGROUND Intestinal ischemia/reperfusion (I/R) injury is a serious clinical complication. This study aimed to explore the hub genes and pathways of intestinal I/R injury. MATERIAL AND METHODS GSE96733 from the GEO website was extracted to analyze the differentially expressed genes (DEGs) of intestinal I/R injured and sham-operated mice at 3 h and 6 h after surgery. The DAVID and STRING databases were used to construct functional enrichment analyses of DEGs and the protein-protein interaction (PPI) network. In Cytoscape software, cytoHubba was used to identify hub genes, and MCODE was used for module analysis. Testing by qRT-PCR detected the expression of hub genes in intestinal I/R injury. Western blot analysis detected the key proteins involved with the important pathways of intestinal I/R injury. RESULTS IL-6, IL-10, CXCL1, CXCL2, and IL-1ß were identified as critical upregulated genes, while IRF7, IFIT3, IFIT1, Herc6, and Oasl2 were identified as hub genes among the downregulated genes. The qRT-PCR testing showed the expression of critical upregulated genes was significantly increased in intestinal I/R injury (P<0.05), while the expression of hub downregulated genes was notably reduced (P<0.05). The proteins of CXCL1 and CXCR2 were upregulated following intestinal I/R injury (P<0.05) and the CXCL1/CXCR2 axis was involved with intestinal I/R injury. CONCLUSIONS The results of the present study identified IL-6, IL-10, CXCL1, CXCL2, IL-1ß, IRF7, IFIT3, IFIT1, Herc6, and Oasl2 as hub genes in intestinal I/R injury and identified the involvement of the CXCL1/CXCR2 axis in intestinal I/R injury.


Predicting research use in a public health policy environment: results of a logistic regression analysis.
Use of research evidence in public health policy decision-making is affected by a range of contextual factors operating at the individual, organisational and external levels. Context-specific research is needed to target and tailor research translation intervention design and implementation to ensure that factors affecting research in a specific context are addressed. Whilst such research is increasing, there remain relatively few studies that have quantitatively assessed the factors that predict research use in specific public health policy environments. A quantitative survey was designed and implemented within two public health policy agencies in the Australian state of Victoria. Binary logistic regression analyses were conducted on survey data provided by 372 participants. Univariate logistic regression analyses of 49 factors revealed 26 factors that significantly predicted research use independently. The 26 factors were then tested in a single model and five factors emerged as significant predictors of research over and above all other factors. The five key factors that significantly predicted research use were the following: relevance of research to day-to-day decision-making, skills for research use, internal prompts for use of research, intention to use research within the next 12 months and the agency for which the individual worked. These findings suggest that individual- and organisational-level factors are the critical factors to target in the design of interventions aiming to increase research use in this context. In particular, relevance of research and skills for research use would be necessary to target. The likelihood for research use increased 11- and 4-fold for those who rated highly on these factors. This study builds on previous research and contributes to the currently limited number of quantitative studies that examine use of research evidence in a large sample of public health policy and program decision-makers within a specific context. The survey used in this study is likely to be relevant for use in other public health policy contexts.


Socio-demographic determinants of the knowledge and attitude of Nepalese healthcare workers toward human monkeypox: a cross-sectional study.
Human monkeypox is an infectious zoonotic disease and since May 2022, there has been a spike in cases worldwide. In this regard, a global health emergency has been declared by the World Health Organization (WHO) on July 23rd, 2022. Although there have been no confirmed human monkeypox cases in Nepal yet, the nation is undeniably at risk of an outbreak. Despite all preventive efforts and preparedness for monkeypox, there still remain several challenges including the literacy and knowledge of our healthcare workers regarding monkeypox. The aim of this study was to assess the level of knowledge and attitude of Nepalese healthcare workers regarding monkeypox. A cross-sectional study was performed on different healthcare workers at Tribhuvan University Teaching Hospital on the month of October 2022 using a set of validated questionnaires used previously in a Saudi Arabian study. An in-person survey was conducted where a total of 220 questionnaires were distributed. The response rate was 93%. Knowledge was categorized into high or low based on the mean knowledge score. The attitude was assessed using a 3-point Likert scale. The association of the knowledge and attitude of the respondents in accordance with their socio-demographics was statistically evaluated using Pearson's Chi-square test. The mean knowledge score was 13. A larger proportion of the respondents (60.4%) demonstrated a high knowledge and 51.1% demonstrated a positive attitude. Studying monkeypox during medical education possessed a significant difference in the attitude (p = 0.025). Knowledge did not vary based on socio-demographic characteristics. Despite almost half a year into the monkeypox outbreak, Nepalese healthcare workers still have an unsatisfying degree of knowledge and a negative attitude regarding its control which shows the need for education and awareness.


Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia (A-T) Patients Using a LC/MS-Based Label-Free Protein Quantification Technology.
Cerebrospinal fluid (CSF) has been used for biomarker discovery of neurodegenerative diseases in humans since biological changes in the brain can be seen in this biofluid. Inactivation of A-T-mutated protein (ATM), a multifunctional protein kinase, is responsible for A-T, yet biochemical studies have not succeeded in conclusively identifying the molecular mechanism(s) underlying the neurodegeneration seen in A-T patients or the proteins that can be used as biomarkers for neurologic assessment of A-T or as potential therapeutic targets. In this study, we applied a high-throughput LC/MS-based label-free protein quantification technology to quantitatively characterize the proteins in CSF samples in order to identify differentially expressed proteins that can serve as potential biomarker candidates for A-T. Among 204 identified CSF proteins with high peptide-identification confidence, thirteen showed significant protein expression changes. Bioinformatic analysis revealed that these 13 proteins are either involved in neurodegenerative disorders or cancer. Future molecular and functional characterization of these proteins would provide more insights into the potential therapeutic targets for the treatment of A-T and the biomarkers that can be used to monitor or predict A-T disease progression. Clinical validation studies are required before any of these proteins can be developed into clinically useful biomarkers.


Revealing the Sequence-Structure-Electronic Property Relation of Self-Assembling π-Conjugated Oligopeptides by Molecular and Quantum Mechanical Modeling.
Self-assembled nanoaggregates of π-conjugated synthetic peptides present a biocompatible and highly tunable alternative to silicon-based optical and electronic materials. Understanding the relationship between structural morphology and electronic properties of these assemblies is critical for understanding and controlling their mechanical, optical, and electronic responses. In this work, we combine all-atom classical molecular simulations with quantum mechanical electronic structure calculations to ascertain the sequence-structure-electronic property relationship within a family of Asp-X-X-quaterthiophene-X-X-Asp (DXX-OT4-XXD) oligopeptides in which X is one of the five amino acids {Ala, Phe, Gly, Ile, Val} ({A, F, G, I, V}). Molecular dynamics simulations reveal that smaller amino acid substituents (A, G) favor linear stacking within a peptide dimer, whereas larger groups (F, I, V) induce larger twist angles between the peptides. Density functional theory calculations on the dimer show the absorption spectrum to be dominated by transitions between carbon and sulfur p orbitals. Although the absorption spectrum is largely insensitive to the relative twist angle, the highest occupied molecular orbital strongly localizes onto one molecule within the dimer at large twist angles, impeding the efficiency of transport between molecules. Our results provide a fundamental understanding of the relation between peptide orientation and electronic structure and offer design precepts for rational engineering of these systems.


Gunther von Hagens and Body Worlds part 2: The anatomist as priest and prophet.
Part 1 of this two-part series highlighted tensions between the anatomical quest for scientific knowledge about the human interior and artistic representations of the anatomized body, contrasting the roles of Goethe's scientific Prosektor and humanistic Proplastiker-roles disturbingly fused in Gunther von Hagens. Part 2 first examines religious interpretations of the human body that fuel the tensions manifest in anatomy art. The body in Western cultures is a sacred text amenable to interpretation as handiwork of God, habitation for the soul, and vehicle for resurrection. As handiwork of God the body beckons the anatomist's scalpel, helping establish dissection as the hallmark of Western medicine. The body as divinely designed machine encompasses the idea of an indwelling soul expressing its will in actions mediated through the intricate network of muscles-an understanding reflected in the oft occurring muscle men of early anatomical textbooks. Interconnections of body and soul in medieval somatic spirituality are examined with reference to ideas of resurrection and their impact on anatomical illustration. Part 2 concludes with consideration of von Hagens as priest and prophet, culminating in the Promethean impulse that recognizes not God but ourselves as proper owners and molders of our destiny, embodied in the plastinator's visionary quest to create the superhuman.


Obtainment and Inoculation of Acinetobacter pittii Strain JJ-2, and Combined Action with Plants for Formaldehyde and CO2 Removal: A Research Study.
A formaldehyde-degrading bacterium JJ-2 was isolated from the rhizosphere of Chlorophytum and identified as Acinetobacter pittii by colony morphology and 16S rDNA sequence analysis. Further studies showed that under optimal conditions, JJ-2 could maintain activity for six cycles at an initial formaldehyde concentration of 450 mg L-1. At the same time, the complete degradation time was shortened from 12 to 6 h. When the JJ-2 strain was inoculated into sterile soil, the surface spray method had the best effect, and the removal efficiency of 5 ppm formaldehyde increased by 22.63%. In an actual potted plants system colonized with strain JJ-2, the first and second fumigations (without re-inoculation) increased removal by 1.36 times and 0.92 times during the day and 1.27 times and 2.07 times at night. In addition, in the second fumigation, the plant-bacteria combined system was 693.63 ppm and the plant system was 715.34 ppm, effectively reducing the CO2 concentration. This study provides an economical, ecological, and efficient approach to improve the combined system of plants and bacteria to remove gaseous formaldehyde from indoor air, with a positive impact on carbon neutrality.


Role of dopamine D1 receptors and extracellular signal regulated kinase in the motivational properties of acetaldehyde as assessed by place preference conditioning.
The role of dopamine D1 receptors and Extracellular signal Regulated Kinase (ERK) in the motivational properties of drugs can be studied by place-conditioning. Recent advances have shown that the motivational properties of ethanol, determined by place-conditioning, are mediated by its metabolic conversion into acetaldehyde. To date, the role of D1 receptors and ERK activation in acetaldehyde-elicited place preference has not been determined. The aim of this study was to assess the role of D1 receptors blockade and MEK inhibition in the acquisition of acetaldehyde-elicited conditioned place preference. Male Sprague-Dawley rats were subjected to repeated pairings with 1 compartment of the conditioning apparatus immediately following acetaldehyde (20 mg/kg i.g.) or ethanol (1 g/kg i.g.) administration. The D1 receptor antagonist, SCH 39166 (50 microg/kg s.c.), was administered 10 minutes before acetaldehyde or ethanol administration. In order to study the role of activated ERK in the acetaldehyde-elicited place preference, rats were administered the MEK inhibitor, PD98059 (1, 30, and 90 microg i.c.v.), 10 or 30 minutes before acetaldehyde. To verify the specificity of these effects, we also studied whether PD98059 pretreatment could affect morphine (1 mg/kg s.c.)-elicited place preference. Both acetaldehyde and ethanol elicited significant place preferences and these were prevented by pretreatment with SCH 39166. In addition, pretreatment with PD98059, dose (30 and 90 but not 1 microg i.c.v.) and time (10 but not 30 minutes before) dependently, prevented the acquisition of acetaldehyde- and significantly reduced the acquisition of morphine-elicited conditioned place preference. These results confirm that acetaldehyde and ethanol elicit conditioned place preference and demonstrate that D1 receptors are critically involved in these effects. Furthermore, the finding that PD98059 prevents the acquisition of acetaldehyde-elicited conditioned place preference highlights the importance of the D1 receptor-ERK pathway in its motivational effects.


Extracorporeal Membrane Oxygenation for COVID 2019-Acute Respiratory Distress Syndrome: Comparison between First and Second Waves (Stage 2).
We aimed to compare the outcomes of patients under veno-venous extracorporeal membrane oxygenation (V-V ECMO) for COVID-19-Acute Respiratory Distress Syndrome (CARDS) between the first and the second wave. From 1 March 2020 to 30 November 2020, fifty patients requiring a V-V ECMO support for CARDS were included. Patient demographics, pre-ECMO, and day one, three, and seven on-ECMO data and outcomes were collected. The 90-day mortality was 11% higher during the second wave (18/26 (69%)) compared to the first wave (14/24 (58%) (p = 0.423). During the second wave, all of the patients were given steroids compared to 16.7% during the first wave (p < 0.001). The second wave's patients had been on non-invasive ventilation support for a longer period than in the first wave, with the median time from ICU admission to ECMO implantation being significantly higher (14 (11-20) vs. 7.7 (5-12) days; p < 0.001). Mechanical properties of the lung were worsened in the second wave's CARDS patients before ECMO implantation (median static compliance 20 (16-26) vs. 29 (25-37) mL/cmH2O; p < 0.001) and during ECMO days one, three, and seven. More bacterial co-infections before implantation and under ECMO were documented in the second wave group. Despite a better evidence-driven critical care management, we depicted fewer encouraging outcomes during the second wave.


[Day-care clinics in mass screening of the population].
Day hospital at the out-patient department may be well included into the organizational and technological links of the dispensarization of population. The effective introduction of a day hospital into the dispensarization system does not take place automatically but require the complex of administrative pressures, regulation and purposeful completion of which is ensured by the use of organizational projecting technique.


Von Hippel-Lindau disease: when neurosurgery meets nephrology, ophthalmology and genetics.
Von Hippel-Lindau (VHL) disease is a dominantly inherited condition associated with tumors in multiple organs, whose treatment requires heightened multidisciplinary teamwork. Therefore, a document summarizing all the pertinent knowledge is needed to enhance coordination of care. A systematic review of the literature from the Medline, Embase and Cochrane Central databases was performed. From 1970 to 2017, all articles meeting specific inclusion criteria were included by at least one specialist physician for each field. We included 95 articles, mostly dealing with genetics or management of VHL associated tumors in one organ system. There were no papers discussing the manifestations of VHL altogether, which was the aim of our paper. VHL requires a multidisciplinary management to provide the highest quality of care. Coordination and communication between patients and caregivers is enhanced when knowledge is shared. Gathering together specialists in different domains around the production and reading of a comprehensive document such as the one hereby may contribute to this purpose.


[A Korean national survey for colorectal cancer screening and polyp diagnosis methods using web-based survey].
There is a paucity of national guideline for colorectal cancer screening and polyp diagnosis in Korea. Thus, we investigated the present state of colorectal cancer screening and polyp diagnosis methods using web-based survey to use as reference data for developing a guideline. A multiple choice questionnaires of screening recommendations was sent via e-mail to members of the Korean Association for the Study of Intestinal Diseases and primary care physicians who participated in the national colonoscopy surveillance program. Among 425 colonoscopists, a total 263 colonoscopists replied (response rate, 61.9%). The most commonly recommended starting age for colorectal cancer screening and polyp diagnosis was 50 years old in the average risk group, and 40 years old in groups who had a family history of colon cancer (64.3% and 65.0% respectively). Surgeons had a tendency to recommend screening in younger people than internist do. Ninety-eight percent of physicians recommended screening colonoscopy to asymptomatic, average-risk patients as a first choice. Only 2% of physicians chose sigmoidoscopy as a screening tool. When the initial colonoscopy showed a negative finding, over 60% of internists repeated the exam 5 years later, whereas 62% of surgeons did so within 3 years. The starting age of colorectal cancer screening and the interval of the colorectal polyp examination are not uniform in various medical environments, and there is a discrepancy between the practical recommendations and western guidelines. Thus, a new evidence-based national practice guideline for colorectal cancer screening and polyp diagnosis should be developed.


A systematic approach to hepatic complications in hematopoietic stem cell transplantation.
Hepatic injury is a common complication of hematopoietic stem cell transplantation (HSCT) and carries a high risk of early morbidity and mortality. Evaluation of the patient for hepatic complications should begin in the pretransplant period with the identification of pretransplant risk factors, such as hepatitis status, that may predict severe liver complications and continue through the early and late transplant periods. Early hepatic complications include drug toxicity, hepatic veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), infection, and cholestatic disorders. With increased survival of HSCT recipients, long-term liver complications from chronic viral hepatitis, chronic GVHD, and iron overload are being reported. The diagnosis and management of hepatic disorders in transplant can be complex, because one must decide whether a given symptom is due to one or a combination of diverse causes. Making the diagnosis can be crucial, because specific therapies can improve one condition but worsen another. This review describes a systematic approach to the evaluation of HSCT patients with hepatic complications with an emphasis on the need to intervene early with radiologic imaging and liver biopsy. Updated treatment options are also discussed. It is hoped that a standard approach will help to streamline clinical management of these very complex patients.


Burst suppression on processed electroencephalography as a predictor of postcoma delirium in mechanically ventilated ICU patients.
Many patients, due to a combination of illness and sedatives, spend a considerable amount of time in a comatose state that can include time in burst suppression. We sought to determine if burst suppression measured by processed electroencephalography during coma in sedative-exposed patients is a predictor of post-coma delirium during critical illness. Observational convenience sample cohort. Medical and surgical ICUs in a tertiary care medical center. Cohort of 124 mechanically ventilated ICU patients. None. Depth of sedation was monitored twice daily using the Richmond Agitation-Sedation Scale and continuously monitored by processed electroencephalography. When noncomatose, patients were assessed for delirium twice daily using Confusion Assessment Method for the ICU. Multiple logistic regression and Cox proportional hazards regression were used to assess associations between time in burst suppression and both prevalence and time to resolution of delirium, respectively, adjusting for time in deep sedation and a principal component score consisting of Acute Physiology and Chronic Health Evaluation II score and cumulative doses of sedatives while comatose. Of the 124 patients enrolled and monitored, 55 patients either never had coma or never emerged from coma, yielding 69 patients for whom we performed these analyses; 42 of these 69 (61%) had post-coma delirium. Most patients had burst suppression during coma, although often short-lived (median [interquartile range] time in burst suppression, 6.4 [1-58] min). After adjusting for covariates, even this short time in burst suppression independently predicted a higher prevalence of post-coma delirium (odds ratio, 4.16; 95% CI, 1.27-13.62; p = 0.02) and a lower likelihood (delayed) resolution of delirium (hazard ratio, 0.78; 95% CI, 0.53-0.98; p = 0.04). Time in burst suppression during coma, as measured by processed electroencephalography, was an independent predictor of prevalence and time to resolution of postcoma/post-deep sedation delirium. These findings of this single-center investigation support lighter sedation strategies.


[Clinico-psychopathologic analysis of so-called juvenile asthenic incompetence].
On the material of 72 young students, the author describes psychopathological manifestations of atypical juvenile subdepressions defined in the literature as "asthenic juvenile deficiency". It has been shown that the syndrome has a polymorphic structure, is usually endogenic but does not posses nosological specificity. Cognitive dicturbances due to vital asthenia and a vital change of affectiveness are predominant manifestations which lead to social disadaptation. Early diagnosis and adequate therapy makes it possible in most cases to compensate for the pathological condition in the outpatient setting, preventing thereby social disadaptation. The necessity of inclusion of psychiatric service into the general somatic polyclinic network to provide specialized psychiatric help for such patients is demonstrated.


Naked-eye sensing of phytic acid at sub-nanomolar levels in 100% water medium by a charge transfer complex derived from off-the-shelf ingredients.
Naked-eye sensing of phytic acid, one of the most abundant antinutrients, was achieved in 100% water medium using a charge transfer complex, composed of pyranine and methyl viologen. Since both the ingredients are commercially available, the design of such sensory systems needs zero synthetic effort, which essentially makes it economically viable. Only the physical mixture of both of these compounds showed a color-changing response from brown to yellow in the presence of phytic acid with a turn-on fluorescence response (LOD: 0.56 nM). The electrostatic interaction leads to charge pairing between phytic acid and methyl viologen, which releases free pyranine in solution. Considering its high sensitivity, low-cost test strips were developed for the on-site detection of phytic acid, even in remote locations. Additionally, estimation of phytic acid was achieved in grain samples with a sufficiently high accuracy, as evident from a sufficiently low relative standard deviation (<5%).


[The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 3. The morphological and ultrastructural changes in the lungs of rats].
The morphological and ultrastructural changes revealed in the lungs of rats kept within the Chernobyl accident zone during the period of 6 to 24 months were shown to be uniform and multicomponent. The changes were found both in the respiratory and the vascular connective tissue. The inflammatory processes occurred with formation of pneumonic foci, hypo- and disatelectasis, emphysematous changes, impairment of interalveolar septa, and connective tissue cell proliferation. In the lung tissue, focal and diffuse lymphoid proliferates and, at later stages, lymphomatous changes were revealed.