"It's Important to Work with People that Look Like Me": Black Patients' Preferences for Patient-Provider Race Concordance.
A compelling body of research supports the race concordance hypothesis, which asserts that racially minoritized patients who share the same race and ethnicity with their provider have improved communication, better perceptions of care, and better health outcomes. Using a mixed methods approach, this study examined (1) the association between racial identity and patients' preference for race-concordant patient-provider dyads and (2) Black patients' subjective experiences of race concordance. Data were gathered from 47 Black caregivers who completed both a survey and participated in a focus group. Quantitative analyses revealed that the majority (83%) of caregivers reported that it is important to have a mental health provider of the same race and ethnicity. Greater racial centrality, but not private or public regard, was associated with a stronger race concordance preference. Thematic analysis of qualitative data revealed six themes related to race-concordant preferences: aspects related to the patient care experience, cultural humility, relatability, diversity in cultural experiences, role models for children, and intersecting identities. Patients with a race concordance preference felt more comfortable with their provider, perceived that it was easier to build a rapport with their provider, and emphasized the value of representation for themselves and their children. Patients who were neutral in their race concordance preference emphasized professionalism over race, valued diverse perspectives, and appreciated their providers' cultural awareness and willingness to self-educate. The integration of these findings will help to elucidate a more nuanced understanding of the factors that build the therapeutic relationship and cultivate a framework of comfort and understanding in the clinical setting.


Cocaine- and amphetamine-regulated transcript and calcium binding proteins immunoreactivity in the subicular complex of the guinea pig.
In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S. In the PrS and PaS, single CART-IR perikarya were dispersed, however with a tendency to be found only in superficial layers. CART-IR fibers were observed throughout the entire guinea pig subicular neuropil. Double-labeling immunofluorescence showed that CART-IR perikarya, as well as fibers, did not stain positively for any of the three CaBPs. CART-IR fibers were only located near the CB-, CR-, PV-IR perikarya, whereas CART-IR fibers occasionally intersected fibers containing one of the three CaBPs. The distribution pattern of CART was more similar to that of CB and CR than to that of PV. In the PrS, the CART, CB and CR immunoreactivity showed a laminar distribution pattern. In the case of the PV, this distribution pattern in the PrS was much less prominent than that of CART, CB and CR. We conclude that a heterogeneous distribution of the CART and CaBPs in the guinea pig SC is in keeping with findings from other mammals, however species specific differences have been observed.


Dietary manganese source does not affect Mn, Zn and Cu tissue deposition and the activity of manganese-containing enzymes in lambs.
Manganese (Mn) is a trace element required for normal physiological processes in animals and humans. Organic forms of trace elements are expected to have higher bioavailability in comparison with inorganic sources. The effect of feeding a diet supplemented with different sources of manganese to lambs was studied in a 112-d feeding trial. The aim of this study was to investigate the deposition of Mn in relation to activities of superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD) and arginase in the tissues of lambs fed the diet supplemented with an inorganic or an organic source of manganese up to the maximum total Mn content allowed in the European Union (150mg Mn/kg). A total of eighteen female lambs of the improved Valachian breed were randomly allocated to three dietary treatments and fed an unsupplemented basal diet (Control, 31mg Mn/kg) or the identical diet supplemented with manganese sulphate (MnSO4) or manganese chelate of glycine hydrate (Mn-Gly) with a total Mn content up to 150mg/kg. Regardless of the source, feed supplementation with manganese increased Mn concentrations in plasma (P˂0.05) and the liver (P˂0.001) as well as the activity of liver MnSOD (P˂0.05) and arginase (P˂0.001) compared with the control lambs. In the kidney cortex, the concentration of Mn was greatest in lambs fed the diet supplemented with the chelated Mn source compared with animals receiving the inorganic Mn source (P˂0.05) and the unsupplemented diet (P˂0.001). The 112-d intake of feed enriched with manganese did not result in any change in Mn levels, SOD or MnSOD activity in pancreas and kidney tissues. Plasma Cu concentration was depressed in both supplemented treatments. No analyzed tissue showed a change in zinc and copper levels, except the greater Cu concentration in the liver of lambs fed the diet with Mn-Gly. The presented results did not indicate any differences between dietary Mn sources either in Mn tissue deposition or activity of SOD, MnSOD and arginase in lamb tissues; however, it seems that manganese intake of up to 150mg/kg in feed may decrease plasma Cu concentration in lambs.


Phenylarsine oxide (PAO) blocks antigen receptor-induced calcium response and tyrosine phosphorylation of a distinct group of proteins.
Antigen receptor (AgR) crosslinking by antigens or AgR-specific antibodies induces a cascade of enzymatic events in lymphocytes which involves activation of several non-receptor tyrosine- and serine/threonine kinases, phosphatases, phospholipases, etc. Here we show data demonstrating that a thiol group-reactive protein tyrosine phosphatase (PTP) inhibitor, phenylarsine oxide (PAO), uncouples a crucial part of the signaling events induced by anti-IgM or anti-Leu-4 (CD3) in human tonsil B lymphocytes, BL41 and Daudi B cell lines and Jurkat T lymphoma cells. PAO treatment (10 microM) resulting in distinct modification of AgR-induced tyrosine phosphorylation pattern inhibited the AgR-mediated calcium response (Ca++ release and influx) of all of these cells completely. Since this treatment did not alter the cell viability and the binding capacity of the AgR crosslinking antibodies, alteration of the tyrosine phosphorylation pattern and blockage of the calcium response indicate prompt inactivation of essential signal transduction element(s).


Further studies on bilitranslocase, a plasma membrane protein involved in hepatic organic anion uptake.
Bilitranslocase, a plasma membrane protein involved in bilirubin and other organic anion uptake by the liver, exhibits a high molecular weight (170 000) when isolated in the presence of deoxycholate. This value is decreased to approx. 100 000 if deoxycholate is not included in the isolation medium. Both preparations can be resolved into two kinds of subunit, alpha and beta , of 37 000 and 35 500, respectively, by reduction with 2-mercaptoethanol and addition of sodium dodecyl sulfate. Under these conditions the two subunits are still capable of high-affinity sulfobromophthalein binding and, despite the presence of the detergent, may be isolated by preparative polyacrylamide gel electrophoresis still associated with the dye. It may be suggested that the physiological subunit composition of bilitranslocase is alpha 2-beta.


Simple gene transfer technique based on I-SceI meganuclease and cytoplasmic injection in IVF bovine embryos.
Although transgenic methods in mammals are inefficient, an easy and highly efficient transgenesis system using I-SceI meganuclease (intron-encoded endonuclease from S. cerevisiae) was recently described in Xenopus. The method consisted of injection into fertilized eggs of an I-SceI reaction mixture with a plasmid DNA carrying the transgene, flanked by the meganuclease recognition sites (pIS). In the present study, the effects of I-SceI on gene transfer were tested apparently for the first time in mammals, in particular, in cattle. Various conditions were evaluated, including three concentrations of the plasmid pIS Pax6egfp, carrying I-SceI recognition sites flanking egfp under Pax6 promoter and two injection times (before IVM and after IVF) of pIS CAGegfp, carrying I-SceI sites fanking egfp under CAG promoter. In addition, the quantity of transgene was measured using quantitative polymerase chain reaction, and presence of transgene signals was evaluated using fluorescence in situ hybridization analysis. Transgene expression rates were higher (P < 0.05) for groups treated after IVF (79.1%, 91/115 and 63.0%, 75/119) than before IVM (32.6%, 31/95 and 34.7%, 33/95), with and without I-SceI, respectively. Interestingly, injection with pIS plus I-SceI after IVF increased frequency (P < 0.05) of nonmosaic transgene-expressing embryos (58.3%, 42/72 vs. 29.7%, 25/84) for pIS plus I-SceI and pIS alone. Based on fluorescence in situ hybridization analysis, injection with I-SceI increased (P < 0.05) the proportion of embryos with transgene signals in all blastomeres compared with pIS alone (44.0%, 11/25 vs. 6.9%, 2/29) for pIS plus I-SceI and pIS alone. In addition, transgene copy number was numerically higher for the group treated with pIS plus I-SceI compared with pIS alone. In conclusion, I-SceI gene transfer increased transgene signals in bovine embryos.


Long-Read Sequencing Reveals a GC Pressure during the Evolution of Porcine Endogenous Retrovirus.
Here, we present the complete genome sequence of a porcine endogenous retrovirus determined by Pacific Biosciences sequencing. A comparison of the genome of this isolate with those of other strains revealed the operation of a mechanism resulting in the selective accumulation of G and C bases in the viral DNA.


Gc (vitamin D binding protein) subtypes in rheumatoid arthritis.
Two hundred and six patients with rheumatoid arthritis were examined for their association with the subtypes of Gc (vitamin D binding protein). In patient groups there is 11% excess of individuals with Gc*2 allele compared to the control group, giving a relative risk of 1.55. This risk increases with the humoral status of the individual. A possible physiological basis between the association of vitamin D binding protein and rheumatoid arthritis is discussed.


An Unusual Presentation of Extramedullary Plasmacytoma in the Orbit in a Middle-Aged Woman.
Orbital location for an extramedullary plasmacytoma is very rare. We report a case of 48 years old woman with swelling in the upper medial aspect of Right eye for 1 year. Histopathological evaluation was consistent with Plasmacytoma and IHC was strongly positive for CD 138. Her thorough evaluation for Multiple myeloma was negative.


A molecular material based on electropolymerized cobalt macrocycles for electrocatalytic hydrogen evolution.
An electrocatalytic material for the H2 evolution reaction (HER) in acidic aqueous solution has been prepared by electropolymerization of Co(ii) dibenzotetraaza[14] annulene (CoTAA). Chemical analysis by X-ray photoelectron spectroscopy (XPS) confirms that the structural integrity of the [Co(II)-N4] motif is preserved in the poly-CoTAA film. In acetate buffer solution at pH 4.6, an overpotential η = -0.57 V is required to attain a catalytic current density -ik = 1 mA cmgeom(-2). The faradaic efficiency of poly-CoTAA for the HER is 90% over a period of one hour of electrolysis, but there is a decrease of the apparent concentration of Co sites after prolonged H2 production, which we ascribe to partial demetallation of the poly-CoTAA film at negative potentials.


Age changes in Alcian blue staining of glycosaminoglycans in sheep articular cartilage.
Alcian blue staining of glycosaminoglycans in sheep articular cartilage is described and discussed. Chodrocytes contain mainly low molecular weight chondroitin sulphate in the outer layers but keratan sulphate increases with depth. Protein-polysaccharide interaction increases with age but the cellular staining decreases in intensity with age. Lacunar capsules contain material of higher molecular weight, much of which is chondroitin sulphate, but no protein-polysaccharide interaction occurs. The matrix of the outer layers is deeply stained while that of the inner layer is pale and consists mainly of keratan sulphate. When stained in high salt concentrations (greater than 0-7 M) the matrix of the middle layer shows two zones; hyaluronidase treatment allows these zones to be differentiated at lower salt concentrations.


Clinical and imaging findings in three patients with advanced inflammatory demyelinating polyradiculoneuropathy associated with nerve root hypertrophy.
Chronic inflammatory demyelinating polyradiculoneuropathy is a treatable neuropathy that is challenging to diagnose and has a broad spectrum of presentations. We report the clinical, electrodiagnostic, and radiographic presentations in three patients whose workup revealed hypertrophic nerve roots. We retrospectively reviewed the clinical, electrodiagnostic, and imaging data for patients diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy over a 3-year period. All patients had features of proximal and distal neuropathy with progressive or recurrent courses. Diagnosis and management were significantly altered by the concomitant clinical findings and/or radiographic findings. Our cases highlight the use of magnetic resonance imaging to evaluate for nerve root hypertrophy as an additional tool to electrodiagnostic testing in the setting of refractory or atypical neuropathy condition. Awareness of the radiographic features will assist in confirmation of the diagnosis, institution of the appropriate therapy, and prevention of inadequate or delay of treatment.


Abnormalities in cardiac and inflammatory biomarkers in ambulatory subjects after COVID-19 infection.
Coronavirus-2019 (COVID-19) is known to affect the heart and is associated with a pro-inflammatory state. Most studies to date have focused on clinically sick subjects. Here, we report cardiac and proinflammatory biomarkers levels in ambulatory young adults with asymptomatic or mild COVID-19 infection compared to those without infection 4-8 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) testing. 131 asymptomatic or mildly symptomatic subjects were enrolled following testing for SARS-COV-2. Fifty subjects tested negative, and 81 subjects tested positive. Serum samples were collected for measurement of C-reactive protein, ferritin, interleukin-6, NT-pro-B-type natriuretic peptide, and cardiac troponin 28-55 days after SARS-COV-2 RT-PCR testing. Biomarker levels trended higher in SARS-COV-2-positive vs negative subjects, but differences in biomarker levels or proportion of subjects with elevated biomarkers were not statistically significant with respect to SARS-COV-2 status. Among individuals with ≥ 1 comorbidity, odds of elevated CRP were greater compared to individuals without any comorbidities (odds ratio [OR] = 2.90); this effect size was increased 1.4-fold among SARS-COV-2-positive subjects (OR = 4.03). Similarly, NT-pro-BNP was associated with CVD, with the strongest association in COVID-positive individuals (OR = 16.9). In a relatively young, healthy adult population, mild COVID-19 infection was associated with mild elevations in cardiac and proinflammatory biomarkers within 4-8 weeks of mild or asymptomatic COVID-19 infection in individuals with preexisting comorbidities, but not among individuals without comorbidities. For the general population of young adults, we did not find evidence of elevation of cardiac or proinflammatory biomarkers 4-8 weeks after COVID-19 infection.Clinical Perspective: This is a characterization of cardiac and proinflammatory biomarkers in ambulatory subjects following asymptomatic or mild COVID-19 infection. Young, ambulatory individuals did not have cardiac and proinflammatory biomarker elevation 4-8 weeks after mild COVID-19 infection. However, COVID-19 infection was associated with biomarker elevations in select individuals with comorbidities.Clinical study number: H-47423.


Inhibition of cellular cholesterol esterification can decrease low density lipoprotein receptor number in human fibroblasts.
In fibroblasts deprived of exogenous cholesterol to induce low density lipoprotein receptors there is a continuing flux of cholesterol esterification. The structurally unrelated inhibitors of acyl-CoA; cholesterol acyl-transferase, progesterone, trimethylcyclohexanyl mandelate and 3-[decyldimethylsilyl]-N-[2-(4-methylphenyl)-1-phenylethyl] propanamide, (58035), could all inhibit this basal rate of esterification within 1h of addition. Exposure of cholesterol-deprived fibroblasts for 17h to progesterone or trimethylcyclohexanyl mandelate caused decreased specific binding and metabolism of low density lipoprotein. The effect was not a direct inhibition of lipoprotein binding; it was time dependent and followed from the reversible inhibition of cholesterol esterification by these two compounds. The irreversible inhibition of esterification by 58035 left the receptor number unaffected. The results indicate that down regulation of low density lipoprotein receptors is initiated by accumulation of cholesterol in a specific intracellular pool. Inhibition of cholesterol esterification by progesterone and trimethylcyclohexanyl mandelate causes accumulation of cholesterol in this pool but 58035 does not.


Androstenedione production by biotransformation of phytosterols.
Androstenedione is a key intermediate of microbial steroid metabolism. It belongs to the 17-keto steroid family and is used as starting material for the preparation of different steroids. Androstenedione can be produced by microbial side chain cleavage of phytosterol, which is an alternative to multi-step chemical synthesis. In this review, various methods of biotransformation of sterols to androstenedione are surveyed. It begins with the history and current research status in this field. The existing methods of chemical and biochemical synthesis are examined. Various issues related to these methods and how researchers have addressed them is presented. Among these, the low solubility of sterols in aqueous systems is a critical problem since it limits the product yield. The main content of this review focuses on new methods of biotransformation that are being investigated. Recent biotechnological advances in this field are presented. The review ends with a note on future perspectives.


Some questions of identity: late miscarriage, stillbirth and perinatal loss.
This paper examines some of the attitudes and procedures which de-construct the identities of a mother and baby when loss occurs through late miscarriage, stillbirth and perinatal loss. Various factors which play a part in a woman's acceptance of her loss are explored, such as contact with the dead baby, formal and 'informal' ritual and early hospital discharge. Ways in which hospitals deal with and define these losses are looked at. It is suggested that all-too-often there seems to be no physical or psychological space for a maternity case without a baby. Is she a mother or is she a patient? The findings suggest that both roles may be lost simultaneously. The dead baby is usually whisked away and the bereaved woman sent back to the community with what feels like indecent haste. Birth and death seem to cancel out. Definitional ambiguities and anomalies about the status of the baby are examined and common sense views about 'hierarchies of sadness' are discussed. This study challenges existing assumptions about the way in which some babies are seen by the professionals as 'lesser' losses, and looks at the implications of these perceptions. The findings are based upon interviews with health professionals in four London hospitals; and a series of in-depth interviews with bereaved parents.


Geriatric 8 and Vulnerable Elders Survey-13 predict length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery.
The Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are established screening tools for assessing vulnerability in older patients. Here we investigated their usefulness as predictors of length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery. This study included 643 patients who underwent urological surgery (74% were for malignancy) at our institute from 2017 to 2020. G8 and VES-13 scores were routinely recorded upon admission. These indices and other clinical data were obtained through chart review. The correlation between G8 group (high, >14; intermediate, 11-14; low, <11) or VES-13 group (normal, <3; high, ≥3) and length of total hospital stay (LOS), postoperative hospital stay (pLOS), and postoperative complications including delirium were analyzed. The median patient age was 69 years. A total of 44%, 45%, and 11% of patients were classified into high, intermediate, and low G8 groups, respectively, while 77% and 23% were classified into normal and high VES-13 groups, respectively. Univariate analyses revealed that low G8 scores were associated with prolonged LOS (vs. intermediate, odds ratio [OR] 2.87, P < 0.001; vs. high, OR 3.87, P < 0.001), prolonged pLOS (vs. intermediate, OR 2.37, P = 0.005; vs. high, OR 3.06, P < 0.001), and delirium (vs. intermediate, OR 3.23, P = 0.007; vs. high, OR 5.38, P < 0.001), and high VES-13 scores were associated with prolonged LOS (OR 2.85, P < 0.001), prolonged pLOS (OR 2.97, P < 0.001), and Clavien-Dindo grade ≥ 2 complications (OR 1.74, P = 0.044), and delirium (OR 3.18, P = 0.001). Furthermore, multivariate analyses revealed that low G8 and high VES-13 scores were independent factors which predicted prolonged LOS (low G8; vs. intermediate, OR 2.96, P < 0.001; vs. high, OR 3.94, P < 0.001; high VES-13; OR 2.98, P < 0.001) and prolonged pLOS (low G8; vs. intermediate, OR 2.41, P = 0.008; vs. high, OR 3.18, P = 0.002; high VES-13; OR 3.47, P < 0.001), respectively. The G8 and VES-13 may be effective tools for predicting prolonged LOS/pLOS and postoperative complications in Japanese patients who undergo urological surgery.


Factors regulating the elongation of palmitic and stearic acid by rat liver microsomes.
Analysis of the rates of overall chain elongation and condensation of malonyl-CoA with palmitoyl-CoA and stearoyl-CoA as primers demonstrated that for each primer, the rate of the overall metabolic process was similar to the initial condensation. The specific activity for condensation with palmitoyl-CoA was eleven times greater than for stearoyl-CoA. The specific activities of both the beta-hydroxyacyl-CoA dehydrase and 2-trans-enoyl-CoA reductase reactions were much higher than for either condensation or chain elongation, although these rates were somewhat greater with the intermediates required in chain elongating palmitoyl-CoA than for stearoyl-CoA. Both substrates were incorporated into phospholipids at low rates and there was a time-dependent hydrolytic cleavage of the acyl-CoA primers which was partially prevented by bovine serum albumin. These findings demonstrate that there was no selective removal of either primer which could result in specific substrate depletion and an apparent reduction in the rate of condensation. These combined results firmly establish the rate-limiting nature and high degree of substrate specificity exhibited during the initial condensation step in fatty acid elongation.


Ankle kinematics of individuals with chronic ankle instability while walking and jogging on a treadmill in shoes.
To evaluate frontal and sagittal plane ankle kinematics between subjects with chronic ankle instability (CAI) and healthy controls while walking and jogging shod on a treadmill. Cross-sectional study. Motion analysis laboratory. Fifteen subjects with self-reported CAI and 13 healthy subjects volunteered. Sagittal and frontal plane ankle kinematics were calculated throughout the gait cycle. For each speed, the means and associated 90% confidence intervals (CIs) were calculated in each plane across the entire gait cycle and increments in which the CI bands for the groups did not cross each other for at least 3 consecutive percentage points of the gait cycle were identified. At various increments while both walking and jogging, CAI subjects were found to be more plantar flexed compared to controls. In the frontal plane, CAI subjects were found to be more inverted at three different increments while jogging only. While shod, kinematic differences were observed between groups. The alterations may indicate that while shod, CAI subjects may adjust their gait in order to successfully accomplish the given task.


Outcomes in 144 patients with colorectal cancer treated in a phase I clinic: the MD Anderson Cancer Center experience.
Patients with advanced colorectal cancer have a poor prognosis once standard therapies fail. This retrospective study presents the characteristics and outcomes in 144 patients treated in phase I clinical trials. We retrospectively reviewed the clinical outcomes in 144 consecutive patients with colorectal cancer referred to the phase I clinic at MD Anderson. Median age was 60 years (range, 35-86 years). The median number of previous systemic therapies was 4 (range, 1-7). The median PFS with the last line of conventional systemic treatment was 12.3 weeks (95% confidence interval [CI], 11.0-14.4); the median PFS of the best phase I treatment was shorter at 8.1 weeks (95% CI, 7.9-8.7 weeks; log-rank test, P < .0001). In the multivariate analysis that included the RMH score, sex (male vs. female, P = .02; hazard ratio [HR], 1.57), hemoglobin (< 10.5 vs. ≥ 10.5 g/dL; P = .03; HR 1.79), and the RMH score (2-3 vs. 0-1; P < .003; HR, 1.85) were significant predictors of poor survival. The PFS of patients with colorectal cancer in phase I treatment was shorter than it was on their last line of conventional systemic treatment. Multivariate analysis confirmed the value of the RMH score for predicting overall survival in patients with colorectal cancer enrolled in phase I studies.


Diabetes mortality: new light on an underestimated public health problem.
Mortality from diabetes is underestimated four- to fivefold by methods of analysis of death certification data which use only underlying cause of death. This problem is partially overcome by coding all conditions mentioned on death certificates. For a sample of deaths in England and Wales over the years 1972-1977, the observed proportion of certificates with specific underlying causes of death for certificates mentioning diabetes was compared with the expected proportion for all certificates. These observed/expected ratios were significantly increased in each sex for circulatory diseases and were significantly reduced for neoplasms. For 'nephritis' they were also increased, especially below 45 years of age. These results were confirmed by an analysis of underlying cause of death in a cohort of nearly 6,000 members of the British Diabetic Association. Of the 2,134 deaths in this cohort, diabetes was not mentioned on 33% of the death certificates. For the period 1972-1977, death rates for circulatory diseases associated with diabetes increased by 6% for males but remained constant for females.


Inhalable pH-responsive DNA tetrahedron nanoplatform for boosting anti-tumor immune responses against metastatic lung cancer.
Despite advancements in the treatment of pulmonary cancer, the existence of mucosal barriers in lung still hampered the penetration and diffusion of therapeutic agents and greatly limited the therapeutic benefits. In this work, we reported a novel inhalable pH-responsive tetrahedral DNA nanomachines with simultaneous delivery of immunomodulatory CpG oligonucleotide and PD-L1-targeting antagonistic DNA aptamer (CP@TDN) for efficient treatment of pulmonary metastatic cancer. By precisely controlling the ratios of CpG and PD-L1 aptamer, the obtained CP@TDN could specifically release PD-L1 aptamer to block PD-1/PD-L1 immune checkpoint axis in acidic tumor microenvironment, followed by endocytosis by antigen-presenting cells to generate anti-tumor immune activation and secretion of anti-tumor cytokines. Moreover, inhalation delivery of CP@TDN showed highly-efficient lung deposition with greatly enhanced intratumoral accumulation, ascribing to the DNA tetrahedron-mediated penetration of pulmonary mucosa. Resultantly, CP@TDN could significantly inhibit the growth of metastatic orthotopic lung tumors via the induction of robust antitumor responses. Therefore, our work presents an attractive approach by virtue of biocompatible DNA tetrahedron as the inhalation delivery system for effective treatment of metastatic lung cancer.


Expression of TGF-β and MMP-2 in hereditary gingival fibromatosis epithelial cells. A possible contribution of the epithelium to its pathogenesis.
Although the molecular mechanisms that cause the development of hereditary gingival fibromatosis are not fully understood, multiple theories have been suggested to clarify its pathogenesis. However, the overlying keratinocytes' function is poorly comprehended. This work aimed to investigate the expression of TGF-β and MMP-2 in hereditary gingival fibromatosis epithelial cells compared to the normal gingival epithelium to give an insight into the mechanism of the development of this condition. Biopsies were obtained from 20 hereditary gingival fibromatosis patients and 20 healthy controls. Biopsies were stained immunohistochemically and statistically analyzed for MMP-2 and TGF-β expression. Regarding MMP-2, The hereditary gingival fibromatosis group recorded a higher mean value compared to the normal gingiva, with a mean difference of 3.29 ± 0.34. This difference was statistically significant (p = 0.00). Regarding TGF-β, a higher mean value was recorded in the HGF group compared to the normal gingiva, with a mean difference of 15.88 ± 1.05 The difference was statistically significant (p = 0.00). A strong positive correlation was detected between MMP-2 and TGF-β (R = 0.534, p = 0.015). In hereditary gingival fibromatosis, the epithelium expresses higher levels of TGF-β and MMP-2 than normal gingival tissue. There was an evident positive correlation between MMP-2 and TGF-β. Our data suggest that the expression of TGF-β and MMP2 by epithelial cells of HGF may play a role in the epithelial-mesenchymal transition pathogenic pathway.


Reproductive isolation among cryptic species in the ectomycorrhizal genus Strobilomyces: population-level CAPS marker-based genetic analysis.
Among the higher fungi, reproductively isolated cryptic species exist that are morphologically difficult to distinguish owing to a lack of taxonomically useful morphological characters. Mating tests are helpful for detecting reproductive isolation between cryptic species, but are often difficult to perform for higher fungi, especially ectomycorrhizal fungi. In order to identify cryptic species of the ectomycorrhizal genus Strobilomyces more efficiently, lineages were defined based on the nucleotide sequence of two mitochondrial genes. Then the gene flow among lineages was measured using cleaved amplified polymorphic sequences (CAPS) markers designed for single copy nuclear genes. No heterozygosity was observed between different lineages, but within the same lineage heterozygosity was present at the ratio expected given Hardy Weinberg equilibrium. These results show that the mtDNA lineages are separate Mendelian populations, possibly cryptic species that are reproductively isolated from each other.


How can patient registries facilitate guideline-based healthcare? A retrospective analysis of the CEDATA-GPGE registry for pediatric inflammatory bowel disease.
Early diagnosis is mandatory for the medical care of children and adolescents with pediatric-onset inflammatory bowel disease (PIBD). International guidelines ('Porto criteria') of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommend medical diagnostic procedures in PIBD. Since 2004, German and Austrian pediatric gastroenterologists document diagnostic and treatment data in the patient registry CEDATA-GPGE on a voluntary basis. The aim of this retrospective study was to analyze whether the registry CEDATA-GPGE reflects the Porto criteria and to what extent diagnostic measures of PIBD according to the Porto criteria are documented. Data of CEDATA-GPGE were analyzed for the period January 2014 to December 2018. Variables representing the Porto criteria for initial diagnostic were identified and categorized. The average of the number of measures documented in each category was calculated for the diagnoses CD, UC, and IBD-U. Differences between the diagnoses were tested by Chi-square test. Data on possible differences between data documented in the registry and diagnostic procedures that were actually performed were obtained via a sample survey. There were 547 patients included in the analysis. The median age of patients with incident CD (n = 289) was 13.6 years (IQR: 11.2-15.2), of patients with UC (n = 212) 13.1 years (IQR: 10.4-14.8) and of patients with IBD-U (n = 46) 12.2 years (IQR: 8.6-14.7). The variables identified in the registry fully reflect the recommendations by the Porto criteria. Only the disease activity indices PUCAI and PCDAI were not directly provided by participants but calculated from obtained data. The category 'Case history' were documented for the largest part (78.0%), the category 'Imaging of the small bowel' were documented least frequently (39.1%). In patients with CD, the categories 'Imaging of the small bowel' (χ2 = 20.7, Cramer-V = 0.2, p < 0.001) and 'Puberty stage' (χ2 = 9.8, Cramer-V = 0.1, p < 0.05) were documented more often than in patients with UC and IBD-U. The registry fully reproduces the guideline's recommendations for the initial diagnosis of PIBD. The proportion of documented diagnostic examinations varied within the diagnostic categories and between the diagnoses. Despite technological innovations, time and personnel capacities at participating centers and study center are necessary to ensure reliable data entry and to enable researchers to derive important insights into guideline-based care.


A simple animal model of hyperammonemia.
Rats were fed a standard diet or the standard diet supplemented with ammonium acetate (20% w/w) for up to 100 days. The effect of the ingestion of the high-ammonium diet on some aspects of nitrogen metabolism in rats was studied. Ammonia levels in blood increased approximately 3-fold; in brain, liver and muscle the increases were 36, 34 and 50%, respectively. Urea levels in blood and urea excretion increased approximately 2-fold. There was no increase of carbamyl phosphate synthase. Liver glutamine synthase activity increased by 58% and glutamate dehydrogenase by 40%, whereas glutaminase was not affected. Glutamine content in brain was twice that of controls. This new animal model to study hyperammonemia offers several advantages over others: it is simpler, is bloodless, requires no animal manipulation and permits long-term studies.


The impact of hand movement velocity on cognitive conflict processing in a 3D object selection task in virtual reality.
Detecting and correcting incorrect body movements is an essential part of everyday interaction with one's environment. The human brain provides a monitoring system that constantly controls and adjusts our actions according to our surroundings. However, when our brain's predictions about a planned action do not match the sensory inputs resulting from that action, cognitive conflict occurs. Much is known about cognitive conflict in 1D/2D environments; however, less is known about the role of movement characteristics associated with cognitive conflict in 3D environment. Hence, we devised an object selection task in a virtual reality (VR) environment to test how the velocity of hand movements impacts human brain responses. From a series of analyses of EEG recordings synchronized with motion capture, we found that the velocity of the participants' hand movements modulated the brain's response to proprioceptive feedback during the task and induced a prediction error negativity (PEN). Additionally, the PEN originates in the anterior cingulate cortex and is itself modulated by the ballistic phase of the hand's movement. These findings suggest that velocity is an essential component of integrating hand movements with visual and proprioceptive information during interactions with real and virtual objects.


Anterior cruciate ligament fascia lata allograft reconstruction: progressive histologic changes toward maturity.
Biopsy samples were obtained arthroscopically from 21 patients who had undergone anterior cruciate ligament (ACL) reconstruction using rolled, freeze-dried fascia lata allograft in order to evaluate progressive histologic changes toward maturation. The study period was 3-20 months postoperation. The mean age (+/- SEM) was 31.9 +/- 10.3. Histomorphometry was used for quantitative evaluation. Arthroscopic examination showed fully synovialized allografts in all patients. Varying degrees of degenerative tissues were observed histologically. There was a significant, direct correlation between the percentage of polarized tissue and the maturity of the biopsy specimen (r = 0.9; p < 0.04). The mean area of polarization in the postrehabilitation period (10-20 months) was significantly higher (p < 0.01) than in the rehabilitation period (3-20 months). Overall, there was a progressive decrease in cellularity and vascularity as the allograft matured. Compared with the biopsy samples of normal ACLs, the allograft was still undergoing maturation 20 months postoperatively.


Oligometastatic Pancreatic Cancer to the Liver in the Era of Neoadjuvant Chemotherapy: Which Role for Conversion Surgery? A Systematic Review and Meta-Analysis.
Background: the improved survival rates achieved using new polychemotherapy regimens in patients with metastatic pancreatic cancer (mPDAC) have suggested a potential role for surgery following a favorable response to initial chemotherapy (IC). The purpose of this systematic review is to summarize the available evidence on the role of surgery following IC in mPDAC, focusing on oligometastatic disease to the liver (lmPDAC). Methods: studies reporting on patients with lmPDAC undergoing surgery after IC were included. The main outcome was overall survival (OS). Results: six observational retrospective studies were included in the qualitative analysis. Data were retrieved on 2087 patients. The most common IC regimen in patients undergoing surgery was FOLFIRINOX (N 84, 73%). Only three studies reported survival comparison among patients treated with IC+surgery vs. IC alone. Median OS varied from 23 to 56 months after conversion surgery vs. 11 to 16.4 months after IC alone. Conclusions: despite wide heterogeneity of chemotherapy regimens, different downstaging criteria and potential selection biases, patients with oligometastatic lmPDAC undergoing surgery after IC have significantly higher survival rates compared to patients treated with IC alone. Future trials are needed for definition of univocal criteria of downstaging, oligometastatic definition and indications for surgery.


Relationships that compulsive buying has with addiction, obsessive-compulsiveness, hoarding, and depression.
Compulsive buying has been associated with addiction, depression, and obsessive-compulsive disorder, as well as hoarding. The present study investigated the relationship that compulsive buying (CB) has with 'addictive' (i.e., sensitivity to reward), obsessive-compulsive, and depressive phenomena, after controlling for hoarding, substance dependence, manic, and Borderline Personality Disorder symptoms. 87 participants from a community population completed the online questionnaires for the study, however 70 participants (M=29.19, SD=10.45; 70% were female) were used in the analyses because of exclusion criteria. As expected, CB measures correlated with hoarding, depression, sensitivity to reward, and, but less so, obsessive-compulsive measures. Sensitivity to reward was the most important predictor of CB severity, compared to obsessive-compulsive and depression symptoms. Hoarding was also an important predictor of CB severity. Small sample size meant gender comparisons could not be made, and the use of a novel, communicated questionnaire meant that interpretation should be considered conservatively. Overall, findings suggest that CB may be most closely related to the phenomena associated with addiction (an increased sensitivity to reward), rather than obsessive-compulsive or depression symptoms. Hoarding and reward sensitivity perhaps might separate compulsive buying from ordinary and recreational shopping.


Discovery of a new strain of murine rotavirus that is consistently shed in large quantities after oral inoculation of adult mice.
In 1990, we developed the adult mouse model for studies on active immunity against shedding of the EDIM strain of murine rotavirus. Low and inconsistent levels of EDIM shedding in some strains of adult mice, particularly those on C57BL/6 backgrounds, established the need for an alternative murine rotavirus strain for these studies. Fortuitously, such a rotavirus strain was obtained from mice housed within the conventional colony at Children's Hospital. This strain, named EMcN, was clearly distinguishable from EDIM based on electropherotype. Furthermore, sequence analyses of VP4 and VP7 genes of EMcN revealed non-identities in 5% of the amino acids of both proteins relative to EDIM but established EMcN as another G3P[16] strain of murine rotavirus. Subgroup analysis showed EMcN belonged to SG1 while EDIM was found to be non-SG1/SG2. Similarly, unlike EDIM, the EMcN strain was identified as serotype G3 based on neutralization by hyperimmune antisera developed against prototype human and simian G3 rotavirus strains. Although EDIM produced more days of diarrhea and was shed in greater quantities in neonatal BALB/c mice, EMcN was shed in much greater quantities in adult BALB/c mice. More importantly, in contrast to the EDIM strain, EMcN was shown to be consistently shed in large quantities in adult C57BL/6 mice and ko mice on this background. Therefore, it is recommended that the EMcN strain be used for future challenge studies with mice on this background.


Pharmacological treatments for SSc-ILD: Systematic review and critical appraisal of the evidence.
Many therapies have been investigated for systemic sclerosis-associated interstitial lung disease (SSc-ILD), including immunosuppressive therapies, antifibrotic agents, immunomodulators and monoclonal antibodies. There is a high unmet medical need to better understand the current evidence for treatment efficacy and safety. This systematic review aims to present the existing literature on different drug treatments investigated for SSc-ILD and to critically assess the level of evidence for these drugs. A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A structured literature search was performed for clinical trials and observational studies on the treatment of SSc-ILD with pharmaceutical interventions from 1 January 1990 to 15 December 2020. The quality of each reference was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. A total of 77 references were reviewed and 13 different treatments were identified. We found high-quality evidence for the use of cyclophosphamide, nintedanib, mycophenolate and tocilizumab. Therefore, we would posit that the clinical community has four valid options for treatment of SSc-ILD. Further research is mandatory to provide more evidence for the optimal treatment strategy in SSc-ILD, including the optimal time to initiate treatment, selection of patients for treatment and upfront combination therapy.


Phylogeny and systematics of the Proterodiplostomidae Dubois, 1936 (Digenea: Diplostomoidea) reflect the complex evolutionary history of the ancient digenean group.
The Proterodiplostomidae Dubois, 1936 is a relatively small family of diplostomoidean digeneans parasitising the intestines of reptilian hosts associated with freshwater environments in tropical and subtropical regions. The greatest diversity of proterodiplostomids is found in crocodilians, although some parasitise snakes and turtles. According to the most recent revision, the Proterodiplostomidae included 17 genera within 5 subfamilies. Despite the complex taxonomic structure of the family, availability of testable morphology-based phylogenetic hypotheses and ancient hosts, molecular phylogenetic analyses of the group were practically lacking. Herein, we use novel DNA sequence data of the nuclear lsrRNA gene and mitochondrial cox1 gene from a broad range of proterodiplostomid taxa obtained from crocodilian, fish, and snake hosts on four continents to test the monophyly of the family and evaluate the present morphology-based classification system of the Proterodiplostomidae in comparison with the molecular phylogeny. This first detailed phylogeny for the Proterodiplostomidae challenges the current systematic framework. Combination of molecular phylogenetic data with examination of freshly collected quality specimens and re-evaluation of morphological criteria resulted in a number of systematic and nomenclatural changes along with a new phylogeny-based classification of the Proterodiplostomidae. As the result of our molecular and morphological analyses: (i) the current subfamily structure of the Proterodiplostomidae is abolished; (ii) three new genera, Paraproterodiplostomum n. g., Neocrocodilicola n. g. and Proteroduboisia n. g., are described and Pseudoneodiplostomoides Yamaguti, 1954 is restored and elevated from subgenus to genus level; (iii) two new species, Paraproterodiplostomum currani n. g., n. sp. and Archaeodiplostomum overstreeti n. sp., are described from the American alligator in Mississippi, USA. Comparison of the structure of terminal ducts of the reproductive system in all proterodiplostomid genera did not support the use of these structures for differentiation among subfamilies (or major clades) within the family, although they proved to be useful for distinguishing among genera and species. Our study includes the first report of proterodiplostomids from Australia and the first evidence of a snake acting as a paratenic host for a proterodiplostomid. A key to proterodiplostomid genera is provided. Questions of proterodiplostomid-host associations parasitic in crocodilians are discussed in connection with their historical biogeography. Our molecular phylogeny of the Proterodiplostomidae closely matches the current molecular phylogeny of crocodilians. Directions for future studies of the Proterodiplostomidae are outlined.


Cardiovascular disease and related risk factors in adults with cerebral palsy: a systematic review.
To summarize the literature on the prevalence of cardiovascular disease (CVD), risk factors of CVD, and CVD-related mortality in adults with cerebral palsy (CP). A systematic review was conducted by searching the PubMed, Embase, MEDLINE (Ovid), Cochrane, and CINAHL databases. Selection criteria included adults with CP aged 18 years or over. Methodological quality was assessed using the Newcastle-Ottawa scale for observational studies. Data were reported descriptively. Nineteen studies met the inclusion criteria. Only one study reported directly on the presence of CVD in adults with CP, which found adults with CP reported greater CVD conditions than adults without CP (15.1 vs 9.1%, p<0.001). The most commonly reported risk factor of CVD in adults with CP was overweight/obesity. Five studies included data on CVD-related mortality in persons with CP, where CVD-related and circulatory system-related deaths were elevated and more common at a younger age in adults with CP than in the general population. The prevalence of CVD and the risk of death because of CVD in this population seems increased, though the knowledge base is fragmented by studies that are small in size and geographically isolated. Further research is required to understand prevalence of risk factors among adults with CP, in particular overweight/obesity. Overweight and obesity are risk factors of cardiovascular disease (CVD) that are commonly reported in adults with cerebral palsy (CP). CVD-related and circulatory system-related deaths are elevated in individuals with CP compared to the general population.


Loss of intercellular substance antigens in oral hyperkeratosis, epithelial dysplasia, and squamous cell carcinoma.
Tissues from 20 oral squamous cell carcinomas and 32 leukoplakic lesions were investigated for the presence of intercellular substance antigens by the indirect immunofluorescent technique using sera from patients with proven pemphigus vulgaris. The leukoplakic lesions included 19 hyperkeratoses without histologic evidence of dysplasia and 13 hyperkeratoses with varying degrees of epithelial dysplasia. Oral tissues from 20 healthy subjects were included as a control group. The great majority of squamous cell carcinomas (95%) showed partial or complete loss of the intercellular substance antigen reactivity. Similarly, hyperkeratoses with dysplasia demonstrated, in 92% of the cases, decreased or complete absence of intercellular substance antigen reactivity. Furthermore, the degree of antigenic loss seemed to be directly related to the degree of cellular anaplasia. On the other hand, in the hyperkeratosis group without histologic signs of epithelial dysplasia, retention of normal intercellular substance antigenic pattern was observed in 73.7% of the cases as compared to the control specimens. The authors suggest that further studies are necessary to assess what value lies in determining the loss of epithelial antigens in predicting the malignant potential of dysplastic oral epithelium.


Comparison of micro-CT and cone beam CT on the feasibility of assessing trabecular structures in mandibular condyle.
To evaluate the accuracy of CBCT in assessing trabecular structures. Two human mandibles were scanned by micro-CT (Skyscan 1173 high-energy spiral scan micro-CT; Skyscan NV, Kontich, Belgium) and CBCT (3D Accuitomo 170; Morita, Japan). The CBCT images were reconstructed with 0.5 and 1 mm thicknesses. The condylar images were selected for registration. A parallel algorithm for histogram computation was introduced to perform the registration. A mutual information (MI) value was used to evaluate the match between the images obtained from micro-CT and CBCT. In comparison with the micro-CT image for the two samples, the CBCT image with 0.5 mm thickness has a MI value of 0.873 and 0.903 while that with 1.0 mm thickness has a MI value of 0.741 and 0.752. The CBCT images with 0.5 mm thickness were better matched with micro-CT images. CBCT shows comparable accuracy with high-resolution micro-CT in assessing trabecular structures. CBCT can be a feasible tool to evaluate osseous changes of jaw bones.


Electrochemical nano biosensors for the detection of extracellular vesicles exosomes: From the benchtop to everywhere?
Detection of extracellular vesicles (EVs) exosomes is a challenge to address the need for better diagnostic tests and to create a point-of-care (POC) platform that can detect, monitor and treat health conditions early to allow personalized therapies. A multidisciplinary approach is needed to address these health-related technical issues. Over the past decade, materials scientists and engineers have worked on the same platform to develop flexible, lightweight, miniaturized, and integrated POC devices for exosome detection. Therefore, exosome detection based on various nanomaterials is of particular interest. In this paper, we describe the current state of knowledge on 0D-3D nanostructured materials and present a POC-based technique for exosome detection. Finally, the challenges that need to be solved to expand their clinical application are discussed.


Analyzing long-term impacts of ungulate herbivory on forest-recruitment dynamics at community and species level contrasting tree densities versus maximum heights.
Herbivores are constitutive elements of most terrestrial ecosystems. Understanding effects of herbivory on ecosystem dynamics is thus a major, albeit challenging task in community ecology. Effects of mammals on plant communities are typically explored by comparing plant densities or diversity in exclosure experiments. This might over-estimate long-term herbivore effects at community levels as early life stage mortality is driven by a multitude of factors. Addressing these challenges, we established a set of 100 pairs of ungulate exclosures and unfenced control plots (25 m2) in mixed montane forests in the Alps in 1989 covering a forest area of 90 km2. Investigations ran until 2013. Analogous to the gap-maker-gap-filler approach, dynamically recording the height of the largest trees per tree species in paired plots with and without exclosures might allow for assessing herbivore impacts on those individuals with a high probability of attaining reproductive stages. We thus tested if recording maximum heights of regenerating trees would better reflect effects of ungulate herbivory on long-term dynamics of tree regeneration than recording of stem density, and if species dominance patterns would shift over time. For quantifying the effects of ungulate herbivory simultaneously at community and species level we used principle response curves (PRC). PRCs yielded traceable results both at community and species level. Trajectories of maximum heights yielded significant results contrary to trajectories of total stem density. Response patterns of tree species were not uniform over time: e.g., both Norway spruce and European larch switched in their response to fencing. Fencing explained about 3% of the variance of maximum tree heights after nine years but increased to about 10% after 24 years thus confirming the importance of long-term surveys. Maximum height dynamics of tree species, addressed in our study, can thus reflect local dominance of tree species via asymmetric plant competition. Such effects, both within and among forest patches, can accrue over time shaping forest structure and composition.


Molecular discrimination of enterotoxin C subtype in clinical isolates of Staphylococcus aureus.
The subtype of staphylococcal enterotoxin C (SEC) of 33 S. aureus clinical isolates was determined by polymerase chain reaction and direct DNA sequencing of a portion of the SEC gene encoding the SEC subtype-specific region. With the exception of a single strain with the SEC2 gene, all other strains showing different biologic and genetic properties were proved to possess the SEC3 gene.


Assembly of the endoplasmic reticulum phospholipid bilayer: the phosphatidylcholine transporter.
Phospholipids are synthesized and concomitantly inserted on the cytoplasmic surface of the endoplasmic reticulum. Assembly of the phospholipid bilayer requires translocation to the lumenal monolayer. The hypothesis that rat liver microsomes contain a protein transporter, or "flippase," for phosphatidylcholine was tested by measuring the transport of sn-1,2,-dibutyroylphosphatidylcholine (diC4PC). This homolog retains the polar head group, the portion of the phospholipid unable to undergo spontaneous transmembrane movement in vesicles, and its water solubility permits application of standard transport methods. DiC4PC entered the lumenal compartment of microsomal vesicles. Transport was saturable and was dependent on time, amount of microsomes, and an intact permeability barrier. DiC4PC transport was inhibited by structural analogs (but not by sn-2,3-diC4PC) and by treatment of microsomes with proteases, N-ethylmaleimide, and trinitrobenzenesulfonic acid. These data suggest that the transmicrosomal movement of diC4PC is protein mediated. DiC4PC was not transported across PC vesicles or red cell membranes, where PC translocation is slow.


Control of neurosecretory vasopressin cells by noradrenergic projections of the caudal ventrolateral medulla.
Activation of noradrenergic afferents arising from the A1 cell group of the caudal VLM excites neurosecretory AVP cells of both the supraoptic and paraventricular nuclei, thus stimulating the release of this potent vasoconstrictor into the circulation. Although this effect is mimicked by application of alpha 1-adrenoreceptor agonists to AVP cells, the excitatory effects of A1 afferents may not be mediated by activation of post-synaptic alpha 1-receptors. Evidence has also been obtained that the actions of A1 afferents are not dependent upon the release of excitatory amino acids or NPY, although the latter is co-stored with NA in A1 cells and potentiates the actions of low concentrations of NA on AVP cells. Although a projection to AVP and OXY neurosecretory cells from the A2 NA cell group of the NTS has been established, this projection does not appear to contribute directly to the control of SON AVP cell activity. Rather, NTS stimulation excites SON AVP cells via a relay projection through the A1 cell group. This pathway is likely to correspond to that involved in the stimulatory effects of haemorrhage and caval constriction on AVP secretion, although it is uncertain whether the effects of these particular stimuli are contingent upon unloading of arterial baroreceptors and atrial stretch receptors, as commonly presumed, or upon the activation of other receptors such as ventricular mechanoreceptors or chemoreceptors. On balance, current evidence suggests that the A1 projection is unlikely to be critically involved in mediating the effects of arterial baroreceptor, arterial chemoreceptor, or atrial stretch receptor activation on AVP cells.


[Parenteral nutrition using branched-chain amino acids (Nutramin VLI Spofa) in the early postoperative period in patients with intra-abdominal inflammatory diseases].
In 19 patients with intraabdominal septic conditions hospitalized at the Surgical Clinic of the Medical Faculty of Hygiene, Charles University, Prague 10 in 1987-1988, the effect of the gradually increasing ratio of branched amino acids administered in parenteral nutrition was investigated. The administration of branched amino acids (Nutramin VLI Spofa) was started already on the first day after operation. By increasing the ratio to 43% of branched amino acids gradual normalization of metabolic changes occurred, incl. normalization of free amino acid plasma levels.


Cell cycle protein profile of the hepatic stellate cells(HSCs)in dimethylnitrosamine-induced rat hepatic fibrosis.
Cell cycle regulating proteins are known to have close relation with the proliferation of the mammalian cells. In injured liver, the number of HSCs is increased from proliferation. However, the expression of cell cycle proteins of HSCs during proliferation remains unevaluated. Therefore, cell cycle protein profiles of HSCs were studied in dimethyl-nitrosamine (DMN)-induced rat liver fibrosis model. Sprague-Dawley rats were intraperitoneally injected of DMN and the animals were sacrificed every week up to 4 weeks. HSCs were separated and the number of the cells in S phase was counted to evaluate the cell proliferation by flow cytometry. The expression of cyclin A, cyclin B, cyclin D1, cdk2, cdk4, cdc2, proliferating cell nuclear antigen (PCNA), p21(Cip/WAF1), and p27 was examined with immunoblotting analysis. Portion of S-phase cells peaked 7days after DMN injection. At that time, cyclin A, and PCNA showed significant increase in HSCs compared to untreated HSCs (114% and 116%, respectively, P<0.001). p21(Cip/WAF1) was decreased significantly in DMN-treated HSCs compared to control cells (88%, P<0.001). The increase of cyclin A, and PCNA and the decrease of p21(Cip/WAF1) seem to play important roles in the proliferation of HSCs during the early period of DMN treatment.


Effect of nitric oxide synthase modulation on resuscitation success in a swine ventricular fibrillation cardiac arrest model.
We have demonstrated previously that the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NNA) decreases free radical generation and nitrosative injury via peroxynitrite formation after epicardial dc shocks. Our purpose was to explore the effects of NOS inhibition and NOS donation on cardiopulmonary resuscitation (CPR) success after cardiac arrest of variable duration. We used the non-selective NOS inhibitor L-NNA and the selective neuronal NOS inhibitor ARR-17477, the NOS donor S-nitroso-N-acetylpenicillamine (SNAP) and the vasodilator Enalaprilat, which lowers arterial pressure via a non-NO mechanism. Part I: 17 pigs undergoing 4 min supported (i.e. with closed-chest compression and ventilation) ventricular fibrillation (VF) were divided into two groups: a no-L-NNA group (n=8) receiving IV saline and an L-NNA group (n=9) receiving IV L-NNA (5 mg/kg) for 8 min before VF was induced. Part II: 35 pigs undergoing 6-8 min VF were randomized to three groups: a no-L-NNA group (n=13) receiving IV saline, an L-NNA group (n=11) receiving IV L-NNA (5 mg/kg) and an ARR17477 group (n=11) receiving IV ARR17477 (5 mg/kg) before VF. All animals in Part II underwent unsupported VF (no chest compression or ventilation) for 6 min (n=13) or 8 min (n=22); closed-chest compression, ventilation and epinephrine (adrenaline) were employed after defibrillation. Part III: 12 swine were divided into two groups: control (n=6) receiving saline and an LNNA group (n=6) receiving IV LNNA (5 mg/kg). Swine underwent 6 min unsupported VF and 2 min supported VF before defibrillation. Part IV: 25 animals were studied to determine the effect of the NO donor SNAP and the angiotensin-converting enzyme inhibitor Enalaprilat on coronary perfusion pressure (CPP). In Part I, after defibrillation, with continued ventilation, chest compression and epinephrine, 8/9 L-NNA pigs achieved ROSC versus 4/8 control pigs (p=0.11). After 60 s of CPR, 7/9 pigs in the L-NNA group achieved ROSC versus 2/8 pigs in the no-L-NNA group (p<0.05). Only 2/9 pigs receiving L-NNA required epinephrine (1 mg) after defibrillation, compared to 6/8 pigs requiring at least one dose of epinephrine in the no-L-NNA group (p<0.05). In Part II, there was no significant difference between L-NNA, ARR17477 and control pigs in ROSC. However, control pigs required 6.8+/-1.4S.E. mg epinephrine; L-NNA pigs and ARR17477 pigs required less epinephrine (3.7+/-0.7 and 3.0+/-0.3 mg, both p=0.01). Shorter chest compression was required in the L-NNA group (252+/-38 s, p<0.05) and in ARR17477 group (222+/-15 s, p<0.05) compared to the control group (405+/-77 s). In Part III, L-NNA infusion caused a significant increase in mean blood pressure at baseline, but did not change CPP throughout the experiment. In Part IV, there were no significant differences in the changes of mean blood pressure and CPP between SNAP and Enalaprilat group in all animals throughout the experiment. NOS inhibition pre-arrest did not improve survival, but did reduce requirements for epinephrine and closed-chest compression in a swine resuscitation model.


Investigation of peripheral neuropathy.
Much exciting work has been carried out on the peripheral nervous system during the past 20 years and has led to a greater understanding of peripheral nerve disorders and to improved diagnosis and treatment. This article sets out a systematic approach to the diagnosis of the patient with peripheral neuropathy.


A new scanning electron microscope (SEM) method for the determination of particle size in parenteral fat emulsions.
Fat droplets larger than 6 micron given intravenously constitute a health hazard. To characterize the droplet size and thus emulsion stability, a fixation procedure capable of fixing high lipid concentrations was developed. Osmium tetroxide as fixative and Nucleopore filter membranes as carrier medium gave the best results. The fat droplets were well defined.


Erratum to acute exacerbation of interstitial lung diseases secondary to systemic rheumatic diseases: a prospective study and review of the literature.
[This corrects the article DOI: 10.21037/jtd.2019.03.28.].


A competency framework for Ph.D. programs in health information management.
The job expectations and professional competencies required by health information management (HIM) students/graduates are constantly changing and workforce development requires curricula in line with new emerging competencies. Although there are some competency frameworks in this field, there is no one specifically for Ph.D. educational programs in HIM. We aimed to develop a competency framework for Ph.D. programs in HIM in Iran. We firstly developed a list of competencies based on those published in the literature or by related associations in nine domains and 51 sub-domains. We used the modified Delphi technique and invited Ph.D. students/graduates in HIM and related faculty members throughout the country to participate. Competencies with more than 75% agreement were considered as high priority competencies and those with 50% to 75% agreement as a medium priority. Competencies with less than 50% agreement were dropped. After two rounds, the competency framework was finalized. All suggested competencies were considered a high priority in the first round. Based on suggestions, two new domains (health knowledge management and information technology) and 20 new sub-competencies were added and then accepted in the second round. The final framework includes these competency domains: health data and information management; health data analytics; information technology; teaching competencies; research competencies; health information technology and digital health; health information classifications, terminologies, and ontologies; health information systems governance; managerial competencies; health knowledge management; and digital health entrepreneurship. This framework suggests a list of competencies in 11 domains and 71 sub-domains for Ph.D. students/graduates in HIM that should be considered for the development of future curricula for these educational programs.


Dietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate airway hyperreactivity.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential nutrients that can affect inflammatory responses. While n-3 PUFAs are generally considered beneficial for cardiovascular disease and obesity, the effects on asthma, the most common inflammatory lung disease are unclear. While prenatal dietary n-3 PUFAs decrease the risk for childhood wheezing, postnatal dietary n-3 PUFAs can worsen allergic airway inflammation. Sphingolipid metabolism is also affected by dietary n-3 PUFAs. Decreased sphingolipid synthesis leads to airway hyperreactivity, besides inflammation, a cardinal feature of asthma, and common genetic asthma risk alleles lead to lower sphingolipid synthesis. We investigated the effect of dietary n-3 PUFAs on sphingolipid metabolism and airway reactivity. Comparing a fish-oil diet with a high n-3 PUFA content (FO) to an isocaloric coconut oil-enriched diet (CO), we found an n-3 PUFA-dependent effect on increased airway reactivity, that was not accompanied by inflammation. Lung and whole blood content of dihydroceramides, ceramides, sphingomyelins, and glucosylceramides were lower in mice fed the n-3 PUFA enriched diet consistent with lower sphingolipid synthesis. In contrast, phosphorylated long chain bases such as sphingosine 1-phosphate were increased. These findings suggest that dietary n-3 PUFAs affect pulmonary sphingolipid composition to favor innate airway hyperreactivity, independent of inflammation, and point to an important role of n-3 PUFAs in sphingolipid metabolism.


Levetiracetam.
[Symbol: see text] Levetiracetam is an ethyl analogue of the nootropic agent piracetam.[Symbol: see text] Results from rodent studies indicate that the drug may offer protection against absence, generalised and partial seizures.[Symbol: see text] Levetiracetam exhibits linear pharmacokinetics and has a wide therapeutic index. Its potential to interact with other anticonvulsants appears to be low.[Symbol: see text] Initial findings from a total of 29 patients with treatment-refractory epilepsy suggest that levetiracetam may be beneficial in patients with partial seizures. These results require confirmation.[Symbol: see text] Somnolence and asthenia were the most common adverse events reported in patients receiving levetiracetam 1000 to 4000 mg/day; these appeared to be dose-related.


A structure-activity profile of substance P and some of its fragments on supraspinal neurones in the rat.
Responses of neurones in the cingulate cortex to iontophoretically applied substance P (SP) were compared to its various C-terminal fragments. Fragments as short as the hexapeptide sequence were at least as active in increasing neuronal firing as the parent molecule. The pentapeptide sequence was much less active and the tripeptide sequence inactive. Compared on a current basis the octa-, hepta- and hexapeptides all evoked larger responses than the full sequence SP. In addition, the nonapeptide N-terminal sequence of SP had no effect on any neurone on which it was tested.


Modified vestibuloplasty of the zygomaticoalveolar crest to gain intradefect support for an obturator prosthesis.
This clinical report details a novel surgical modification at the time of maxillectomy to improve obturator function. A vestibuloplasty and split thickness skin graft of the zygomaticoalveolar crest created a denture-bearing surface that, when engaged, provided support and stability for the obturator prosthesis. This report outlines the surgical and prosthodontic procedures and the results achieved.


Ultrastructural observations on neuronal lipofuscin (age pigment) and dense bodies induced by a proteinase inhibitor, leupeptin, in rat hippocampus.
The ultrastructure of lipofuscin (age pigment) and dense bodies induced by intraventricular administration of leupeptin, a cysteine proteinase inhibitor, were investigated in the neurons of rat hippocampal dentate gyrus. Four-day treatment with leupeptin (0.5 mg/day) rapidly caused a considerable accumulation of intracytoplasmic dense bodies and swelling of neuronal processes. We demonstrated, as inner structures of the pigments, that penta-laminar structure with a thickness of 12-13 nm and finely granular matrix were exactly common to the leupeptin-induced dense bodies and lipofuscin granules. Furthermore, the transitional stages from lysosomes into the dense granules were observed in the neurons of the leupeptin-treated rats. On the other hand, some morphological differences between the leupeptin-induced dense bodies and lipofuscin granules have been shown: (1) distribution in different cell types, (2) intracytoplasmic location, (3) tendencies to associate with vacuoles, and (4) electron density. The present findings suggested that the decline of the lysosomal protein degradation could play a role in lipofuscinogenesis, especially in the genesis of their electron-dense portion, but some other mechanisms might participate in the formation and accumulation of lipofuscin with aging.


Implementing Physical Activity Recommendations in Clinical Practice: A Survey of Oncology Nurses' Perspectives.
Better understanding of oncology nurses' perspectives about how interventions should be designed can promote physical activity (PA) in clinical settings. 75 oncology nurses completed online surveys. A published survey, guided by the Consolidated Framework for Implementation Research, was used to assess multilevel factors that influence implementation of evidence-based interventions. Descriptive statistics were applied to quantitative data; directed content analyses were applied to qualitative data. Participants believed it was important to discuss PA with patients; however, they had limited self-efficacy and resources to provide PA counseling. Barriers to providing counseling included competing clinical demands and a lack of education about PA for cancer survivors and resources. Findings inform how interventions can be designed for implementation and sustained practice change in clinical settings. Integration of PA education in routine clinical practice will lead to increased PA and, ultimately, improved quality of life among cancer survivors.


Mitochondrial dysfunctions during aging: vitamin E deficiency or caloric restriction--two different ways of modulating stress.
Caloric restriction (CR), which has been demonstrated to offset the age-associated accrual of oxidative injury, involves a reduction in calory intake while maintaining adequate nutrition, preserves the activities of antioxidant enzymes in postmitotic tissues, maintains organ function, opposes the development of spontaneous diseases, and prolongs maximum life span in laboratory rodents. It has been proposed that reductions in Reactive Oxygen Species (ROS) production and cellular oxidative injury are central to the positive effects of CR. In the present investigation we studied the effect of CR and of a vitamin E deprived diet on mitochondrial structure and features in the liver of rats during aging, in order to ascertain the extent of modifications induced by these experimental conditions. CR rats displayed structural and functional mitochondrial properties (fatty acid pattern, respiratory chain activities, antioxidant levels, and hydroperoxide contents) similar to those of younger rats whilst vitamin E deficient rats appeared older than their own age. The mitochondria of the former, together with those of young rats, possessed the lowest Coenzyme Q9, hydroperoxide, and cytochrome contents as well as a suitable fatty acid membrane composition. Our study confirms that CR is a valuable tool in limiting aging-related free-radical damage also at mitochondrial liver level.


Design, characterization, and adsorption properties of Padina gymnospora/zeolite nanocomposite for Congo red dye removal from wastewater.
A comprehensive study combined experimental, computational and field experiments was conducted to find out the most appropriate adsorbent system for industrial elimination of congo red (CR) dye from simulated industrial wastewater. Modification of the zeolite (Z) by the Padina gymnospora algae (PG) (Egyptian marine algae) was evaluated in terms of the adsorption capability of the zeolite (Z) to remove CR dye from aqueous solutions. The zeolite/algae composite (ZPG) was fabricated using the wet impregnation technique. Various techniques were used to characterize the PG, Z, and the produced ZPG nanocomposite. Batch experiments were performed to study the influence of various practical variables on adsorption processes. The isotherms and kinetics of dye adsorption were also studied. The newly synthesized ZPG nanocomposite exhibits much higher adsorption capacity, especially at low CR concentrations than that of Z. The computational calculations have shown that owing to the presence of intermolecular interactions, the adsorption of the CR molecule on zeolite surfaces is exothermic, energetically favorable, and spontaneous. For all configurations, increasing the zeolite size does not have a noticeable impact on the adsorption energies. The experimental results revealed that the ZPG nanocomposite can be applied as an economical nanoadsorbent to eliminate anionic dyes from simulated industrial wastewater at low CR dye concentrations. The adsorption isotherm of dye onto Z, PG, and ZPG almost agreed with Langmuir isotherm and pseudo-second-order kinetics. The sorption mechanism was also evaluated using Weber's intra-particle diffusion module. Finally, the field experiments revealed optimistic results for the newly synthesized adsorbent in removing dyes from industrial wastewater with 82.1% efficiency, which in turn confirmed the foundation of new eco-friendly materials that aid in the reuse of industrial wastewater.


In-situ immuno-gold nanoparticle network ELISA biosensors for pathogen detection.
Food poisoning microorganisms that contaminate food products and compromise food safety and security have been considered a major health threat and a serious concern for food producers and processors. Developing sensor technologies that are rapid for sensitive and selective detection and quantification of pathogens is a high priority for scientists in academia, state and federal research institutes, and industries. In this work we propose an in-situ immuno-AuNP network-based ELISA biosensor integrated with a sample concentration step based on immuno-magnetic separation to detect pathogenic microorganisms with high sensitivity. The sensor system was optimized by the specific formation of immuno-AuNP network onto the antigenic site present at the outer membrane surface of bacteria and the analytical concept was validated by a microtiter immunoassay. The in-situ network biosensor was able to detect pathogens at extremely low numbers: 3 cells/mL of Escherichia coli O157:H7 and Salmonella typhimurium in buffer and 3 CFU/mL of E. coli O157:H7 and 15CFU/mL of S. typhimurium in real sample conditions within 2h of inoculation. The ability to monitor target bacteria with improved analytical sensitivity compared to the current techniques presents a unique opportunity for routine monitoring to improve the safety of foods.


Anterior cranial base glioneuronal heterotopia.
Cranial base glioneuronal heterotopia is a nest or linear array of glioneuronal tissue within the basal meninges. It is thought to arise from aberrant migration of embryonic neuroepithelial tissues into the subarachnoid space. It frequently mimics tumors and may extend through basal skull bones into extracranial soft tissues. We describe a case of intracranial anterior skull base leptomeningeal glioneuronal heterotopia in a newborn female who was diagnosed in the prenatal period by ultrasound examination to have an intracranial space-occupying lesion at 35 weeks of gestation. There was no evidence of increased intracranial pressure at birth. Magnetic resonance imaging showed a large, predominantly solid, minimally enhancing tumor in the anterior cranial fossa extending into the suprasellar region as well as into the right and left middle fossae. The gross tumor was totally resected through bifrontal craniotomy. Although uncommon, diagnosis of intracranial extracerebral glioneuronal heterotopia should be strongly ascertained while evaluating intracranial space-occupying lesions during the prenatal period and infancy. It needs to be distinguished histologically from teratoma and primary central nervous system tumors. Prenatal screening for early diagnosis of the lesion is vital. The location of the lesion and its relationship to the surrounding structures should lead to an accurate diagnosis in the majority of cases. Complete resection is curative and should be the goal. Long-term prognosis is excellent in view of the benign nature and extraaxial origin of the lesion.


A brain network model explaining tremor in Parkinson's disease.
This paper presents a novel model of tremor in Parkinson's disease (PD) based on extensive literature review as well as novel results stemming from functional stereotactic neurosurgery for the alleviation of tremor in PD. Specifically, evidence that suggests the basal ganglia induces PD tremor via excessive inhibitory output to the thalamus and altered firing patterns which in turn generate rhythmic bursting activity of thalamic cells is presented. Then, evidence that the thalamus generates PD tremor by facilitating the generation and consolidation of rhythmic bursting activity of neurons within its nuclei is also offered. Finally, evidence that the cerebellum may modulate characteristics of PD tremor by treating it as if it was a voluntary motor behavior is presented. Accordingly, the current paper proposes that PD tremor is induced by abnormal basal ganglia activity; it is generated by the thalamus, and modulated or reinforced by the cerebellum.


Laparoscopic intragastric approach for stromal tumours located at the posterior gastric wall.
Surgical resection is indicated for gastrointestinal stromal tumour (GIST). Laparoscopic resection with clear margins is effective in gastric GIST. However, GIST located in the posterior gastric wall with close proximity to the oesophagogastric junction poses special challenges. Laparoscopic intragastric resection offers a new approach to the management of these tumours. The surgical technique, our experience and a summary of the literature are presented.


The essence of care in health vulnerability: a Heideggerian construction.
Reflect on the essence of care in health vulnerability from the phenomenological perspective of Martin Heidegger. Theoretical-reflexive study, anchored in three essential parts: 1) Care in Heidegger; 2) The essence of care in health vulnerability; And 3) Nursing care actions on health vulnerability. Vulnerability must be recognized as an indelible trait of the human condition and has its constituents in the human being, co-presence and care. Caring is an interactive process that reveals itself in the relationship with the other. Respecting the integrity of the Being in vulnerability must be a priority in nursing care, through behaviors that privilege the Being. Understanding ontological care and its relation to vulnerability under Heidegger's phenomenological view allowed us to uncover the facets of care in health vulnerability by adding to the nursing knowledge body a comprehensive and reflective perspective. Refletir sobre a essência do cuidado na vulnerabilidade em saúde sob a perspectiva fenomenológica de Martin Heidegger. Estudo teórico-reflexivo, ancorado em três partes essenciais: 1) O cuidado em Heidegger; 2) A essência do cuidado na vulnerabilidade em saúde; e 3) As ações do cuidar em enfermagem na vulnerabilidade em saúde. A vulnerabilidade deve ser reconhecida como traço indelével da condição humana e tem seus constituintes na pessoa humana, co-presenças e cuidado. O cuidar é um processo interativo que se desvela na relação com o outro. Respeitar a integridade do Ser em vulnerabilidade deve ser prioridade no cuidar em enfermagem, por meio de comportamentos que privilegiem o Ser. Compreender ontologicamente o cuidado e a sua relação com a vulnerabilidade sob o olhar fenomenológico de Heidegger permitiu desvelar as facetas do cuidado na vulnerabilidade em saúde, agregando ao corpo de conhecimento da Enfermagem uma perspectiva compreensiva e reflexiva.


Novel negative-definiteness conditions on the quadratic polynomial function with application to stability analysis of continuous time-varying delay systems.
When analyzing the stability of time-varying delay systems in view of the Lyapunov-Krasovskii functional, a quadratic polynomial function with regard to time-varying delay is always generated. And it is particularly crucial to determine the negativeness of the matrix of such a quadratic form function for obtaining an analysis result expressed in linear matrix inequalities. This paper proposes a method of tangent intersection in the delay interval segmentation, producing the generalized quadratic convex conditions by further utilizing the cross point between every two tangent lines. It reduces the conservatism of the existing conditions remarkably without requiring unexplainable adjustable parameters and additional decision variables. Benefiting from the newly proposed quadratic convex conditions, the novel stability conditions are derived, the superiority of which is demonstrated through several widely used numerical instances and single area power system PI control example.


ASSESSMENT OF RADIATION DOSE AND EXCESSIVE LIFE-TIME CANCER RISK FROM THE BUNAIR GRANITE, NORTHERN PAKISTAN.
Natural radioactivity was measured in Bunair Granite using high purity germanium gamma-ray spectrometer and compared to world's granites and building materials to access its suitability for the construction purpose. Average gamma-activities of 226Ra, 232Th and 40K were found to be 52.41, 58.41 and 1130.12 Bq kg-1, respectively. The Indoor and outdoor radiation indices including excessive life-time cancer risk (ELCR) were calculated. The average indoor ELCR was estimated as 3.49 × 10-3. The average outdoor ELCR was assessed as 0.46 × 10-3. As a basic building material Bunair Granite should be on low propriety. For flooring, facing the buildings and as Table tops, in kitchens and other utilities it is safe.


The impact of racial discrimination on the health of Asian Americans during the COVID-19 pandemic: a scoping review.
ABSTRACTObjective: Cases of discrimination and hate crimes against Asian Americans have surged ever since the beginning of the COVID-19 pandemic, with deleterious effects. This scoping review synthesizes the literature on how pandemic-related discrimination is associated with the health of Asian Americans.Design: First, application search terms were entered into selected databases. Next, using a set of inclusion criteria, the articles were screened and assessed for eligibility. Data from the selected articles were extracted and summarized to answer the research questions.Results: Thirty-five studies were included. Almost all the studies examined psychological well-being. The remaining studies examined physical and workplace well-being. All the studies found that discrimination was associated with poorer health outcomes.Conclusion: Further research is needed to address the gaps in knowledge about how pandemic-related discrimination is associated with various domains of health among Asian Americans.


[Endovascular treatment of arteriovenous vertebro-vertebral fistula].
Vertebral arteriovenous fistulae are relatively rare, with limited experience in most centers. We report our experience in the treatment of a vertebral arteriovenous fistula treated by interventional method. A review of the literature is made and the etiology, presentation and treatment of this unusual lesion are discussed. The endovascular occlusion is now the treatment of choice of vertebral fistulae.


Nurses' perception of solutions proposed by nurse leaders in face of COVID-19 pandemic: A cross-sectional study.
To evaluate the perception of bedside nurses regarding the implementation of solutions proposed by nurse leaders for patient and employee care during the COVID-19 pandemic. Nurse leaders have proposed solutions to better manage the challenges of the pandemic. However, multiple factors influence the transposal of actions from the tactical to the operational levels. This cross-sectional study was carried out in a 620-bed non-profit institution. Participants were bedside nurses who completed an online survey. One hundred sixty-eight nurses participated in the study. Most of the proposed solutions were very effective and easily identified by the nurses. These solutions included adaptations of the physical structure, availability of medical supplies and adequacy of institutional protocols. The actions that stood out with low perception were adequate integration of new employees and the availability of remote work, hotel accommodations for frontline health care workers and day care for children whose parents worked at the hospital. Bedside nurses were able to recognize most of the solutions proposed by their nurse leaders during the COVID-19 pandemic. Tactical-level nurse leaders need constant proximity to bedside nurses and continuous elucidation of the objectives to be achieved by the strategies adopted.


Unusual primary prostatic malignancies.
Atypical prostatic cancer is defined as any malignancy of prostatic origin, excluding the common acinar prostatic adenocarcinoma. These atypical prostate cancers account for less than 5 percent of all prostatic malignancies. Because atypical prostatic malignancies occur rarely, little is known about their biologic behavior. To date, no large series of patients have been reported, and specific treatment protocols have yet to be defined. Herein we describe 5 new cases of atypical prostatic cancer. By reporting the occurrence of new cases, we believe a better understanding of the natural history of these lesions will emerge.


Stanniocalcin2 inhibits the epithelial-mesenchymal transition and invasion of trophoblasts via activation of autophagy under high-glucose conditions.
Maternal pregnancy hyperglycemia is often accompanied by placental dysfunction. During placental development, epithelial-mesenchymal transition (EMT) contributes to the transformation of relatively noninvasive trophoblasts into highly invasive extravillous trophoblasts (EVTs). However, the specific role of EMT in placentas under hyperglycemia environments remains relatively unexplored. Stanniocalcin2 (STC2) regulates EMT in many cancers. In this study, we first demonstrated that STC2 expression was upregulated in GDM placenta. We found that STC2 activated autophagy and suppressed EMT in high-glucose-treated EVTs and was associated with a lack of invasiveness. Specifically, STC2 inhibited the interactions between p62/SQSTM1 (p62) and EMT transcription factors to promote the degradation of Twist1 and Snail via a proteasome-dependent pathway. Furthermore, the PI3K/AKT/AMPK signaling pathway was involved in the regulation of autophagy and EMT by STC2. Taken together, our results reveal that STC2 may serve as a potential prognostic biomarker in GDM and sheds light on the regulatory mechanisms of trophoblast invasion.


Correction to: Carfentanil: a narrative review of its pharmacology and public health concerns.
In the article entitled: "Carfentanil: a narrative review of its pharmacology and public health concerns" published online and in the April 2019 issue of the Journal, Can J Anesth 2019; DOI: https://doi.org/10.1007/s12630-019-01294-y , the Figure showed the wrong structures for remifentanil and carfentanil. This is now corrected in the accompanying revised figure and legend.


Assessment of GH releasing hormone activity in sephadex-separated fractions of porcine hypothalamic extracts by hypophyseal portal vessel infusion in the rat.
Growth hormone-releasing hormone (GH-RH) activity in Sephadex G-25 fractions of porcine stalk median eminence (SME) extracts was examined in vivo by infusing these samples into a rat hypophyseal portal vessel. The increment of immunoreactive GH levels in the serum was used as the index for GH-RH activity. The GH-RH activities were found in two different locations: in the early fractions Nos. 3-4, and in somewhat retarded fraction No. 7. These GH-RH activities were not due to TRH, vasopressin, or potassium. The location of LH releasing hormone (LH-RH) and prolactin release-inhibiting hormone (PR-IH) determined in this in vivo system was in agreement with those found in other in vivo and in vitro assay systems for LH-RH and PR-IH, respectively. These results help validate this assay system.


Molecular characterization of MET fusions from a large real-world Chinese population: A multicenter study.
MET is a notable driver gene in the diversity of aberrations with clinical relevance, including exon 14 skipping, copy number gain, point mutations, and gene fusions. Compared with the former two, MET fusions are severely under-reported, leaving a series of unanswered questions. In this study, we addressed this gap by characterizing MET fusions in a large, real-world Chinese cancer population. We retrospectively included patients with solid tumors who had DNA-based genome profiles acquired through targeted sequencing from August 2015 to May 2021. MET fusion-positive (MET+) patients were subsequently selected for clinical and molecular characterization. We screened 79,803 patients across 27 tumor types and detected 155 putative MET fusions from 122 patients, resulting in an overall prevalence of 0.15%. Lung cancer comprised the majority of MET+ patients (92, 75.4%). Prevalence was markedly higher in liver cancer, biliary tract cancer, and renal cancer (range 0.52%-0.60%). It was lower in ovarian cancer (0.06%). A substantial proportion (48/58, 82.8%) of unique partners were reported for the first time. High heterogeneity was observed for partners, with ST7, HLA-DRB1, and KIF5B as the three most common partners. Mutational landscape analysis of lung adenocarcinoma (n = 32) revealed a high prevalence of TP53 in MET+ alterations, EGFR L858R, EGFR L861Q, and MET amplification. To our knowledge, this is currently the largest study in characterizing MET fusions. Our findings warrant that further clinical validation and mechanistic study may translate into therapeutic avenues for MET+ cancer patients.


Expression of caveolin-1 is correlated with Akt-1 in colorectal cancer tissues.
Caveolin is a major component of caveolae which is a plasma membrane microdomain. The emerging role of caveolin in tumorigenesis was based mainly on in vitro experiments with cancer cell lines. We performed semi-quantitative RT-PCR for caveolin, Akt and EGFR to understand the role of caveolins in colorectal tumor biology. Cancer tissue samples and the neighboring normal colon mucosa were obtained from 95 colorectal cancer patients who underwent operations at Ewha Womans University Mokdong Hospital. With these fresh tissues, semi-quantitative RT-PCR was performed by coamplification of the gene for caveolin-1, EGFR and Akt-1 with beta-actin. The average age was 60.21+/-13.33 years old, and sex ratio was 1.44:1. Caveolin-1 is more expressed in tumors than normal mucosa (P=0.025). The expression of caveolin-1 and Akt-1 had a definitive positive relationship (P=0.002). But, the expression of caveolin-1 and EGFR was not significantly related. We could not find correlations between caveolin-1 expression and clinical factors. In conclusion, caveolin-1 is more expressed in cancer tissues than normal colon and related with Akt-1, not with EGFR expression in colorectal cancer tissues, which suggests that signaling for caveolin-1 affects Akt-1 activation, but this reaction is not initiated by EGFR stimulation in colon cancer.


Oncogene amplification in transforming myelodysplasia.
The MLL gene, located within band 11q23, has been shown to be involved in translocations with a large variety of reciprocal sites in both lymphoid and myeloid leukemia and has also been shown to undergo submicroscopic self-fusion/partial duplication. We report 29 patients with cytogenetic evidence of 11q23 alteration, all of which demonstrate molecular cytogenetic evidence of amplification of the MLL gene by fluorescence in situ hybridization (FISH). In all MLL cases, the patients were clinically classified as having transforming myelodysplasia (RAEB/RAEBT) or AML. An additional patient with AML was found by 24-color and gene-specific FISH to have AML1 oncogene amplification. Four patients had been previously diagnosed with cancer and had received topoisomerase II targeted drug therapy which is known to be associated with fusion transcripts involving the MLL and AML1 genes. MLL amplification appeared in various forms: an atypical banded region that bridges from 11q23 into a dicentric chromosome, expanded regions emanating from band 11q23, chromosome 11 paint-positive rings with "spoke-like" MLL amplification, and expansion at sites other than chromosome 11 (including extra markers) in the absence of one of the 11 homologues. The fluorescence pattern in most cases suggests palindromic duplication with neighboring sequences in the long arm of chromosome 11. As opposed to MYCN amplification in hsrs (homogeneously staining regions) and double minutes in neuroblastoma, amplification of MLL in most cases occurred at the site of the gene. All of our patients rapidly developed refractory AML. The frequency and clinical correlations of MLL gene amplification in leukemia will need careful follow-up, since the frequently cryptic amplification described in these cases may not generally provoke confirmatory FISH studies. The reported MLL cases represented about 1% of the total abnormal MDS/AML cases over 8 years. A common cytogenetic profile of 5 q-, -17/17 p-, -18/18 q-, and a missing or abnormal chromosome 11, may help direct appropriate follow-up studies. The MLL and the AML1 oncogenes appear to be the only oncogenes amplified at the natural site of the gene. Both genes also show a high degree of diversity of pathogenic mechanisms of leukemia evolution, including numerous reciprocal fusion genes in transformation to either AML or ALL and gain of function amplification.


Finding specific 10-joint Juvenile Arthritis Disease Activity Score (JADAS10) and clinical JADAS10 cut-off values for disease activity levels in non-systemic juvenile idiopathic arthritis: a Finnish multicentre study.
To establish the cut-off values for inactive disease, as well as low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) in non-systemic JIA based on the Juvenile Arthritis Disease Activity Score (JADAS) and assessed with the 10-joint JADAS (JADAS10) and clinical JADAS10 (cJADAS10). In a multicentre cross-sectional study consisting of ∼20% of all patients with JIA in Finland (n = 509), we obtained data on their most recent registered visits between January 2013 and January 2014. We calculated the JADAS10 and cJADAS10 and established the cut-off values of both of these scores using two different receiver operating characteristics-based statistical methods. Of the 509 patients studied, 65.8% were females and 53.8% had polyarticular disease. The most suitable method for determining cut-off values was the Youden index. In oligoarticular patients, a JADAS10 score of 0-0.5 represented inactive disease, 0.6-2.7 LDA and ≥2.8 MDA. In polyarticular disease, a JADAS10 score of 0-0.7 represented inactive disease, 0.8-3.9 LDA and ≥4.0 MDA. The cut-off values for HDA were not possible to establish because only two visits fulfilled HDA criteria. We established cut-off values for LDA and MDA. A reliable definition for HDA will require more patients. In the clinical setting, both the cJADAS10 and JADAS10 serve equally well both for research and quality control purposes. In the future, uniform clinical disease activity levels should be established. We also suggest revising and validating the criteria for HDA. Valid and robust cut-off values for disease activity levels can guide both clinicians and researchers and equip them for quality control.