Cyclosporin A inhibits activation of inducible nitric oxide synthase in C6 glioma cell line.
The effects of immunosuppressant cyclosporin A (CsA) on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression in rat C6 glioma cell line were investigated. CsA applied simultaneously with iNOS activator IFN-gamma caused dose-dependent reduction of NO synthesis in confluent C6 cells, as determined by measuring accumulation of nitrite, an indicator of NO production, in 48 h culture supernatants. IFN-gamma-induced expression of iNOS, but not interferon regulatory factor-1 (IRF-1) mRNA was reduced in CsA-treated cells. The enzymatic activity of iNOS was not changed by CsA, since it failed to affect NO production in cells in which iNOS had already been induced with IFN-gamma and any further induction was blocked by protein synthesis inhibitor cycloheximide (CHX). FK506 was not able to mimic inhibitory effect of CsA on NO production in C6 cells, suggesting calcineurin-independent mechanism of CsA action.


Amino Acid Carbamates As Prodrugs Of Resveratrol.
Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene), a plant polyphenol, has important drug-like properties, but its pharmacological exploitation in vivo is hindered by its rapid transformation via phase II conjugative metabolism. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, stability and in vivo pharmacokinetic behaviour of prodrugs of resveratrol in which the OH groups are engaged in an N-monosubstituted carbamate ester (-OC(O)NHR) linkage with a natural amino acid (Leu, Ile, Phe, Thr) to prevent conjugation and modulate the physicochemical properties of the molecule. We also report a convenient, high-yield protocol to obtain derivatives of this type. The new carbamate ester derivatives are stable at pH 1, while they undergo slow hydrolysis at physiological pH and hydrolyse with kinetics suitable for use in prodrugs in whole blood. After administration to rats by oral gavage the isoleucine-containing prodrug was significantly absorbed, and was present in the bloodstream as non-metabolized unaltered or partially deprotected species, demonstrating effective shielding from first-pass metabolism. We conclude that prodrugs based on the N-monosubstituted carbamate ester bond have the appropriate stability profile for the systemic delivery of phenolic compounds.


A real-time recombinase polymerase amplification assay for fast and accurate detection of Ditylenchus destructor.
Ditylenchus destructor is a plant-parasitic nematode that seriously infests sweet potato crop in China. Thus, fast and accurate detection of D. destructor in soil and plant tissue samples is of great significance. In this study, a real-time recombinase polymerase amplification (RPA) assay was developed for the rapid and accurate detection of D. destructor in various samples. The RPA assay could be easily operated and detected as low as 1/500 individual J4 nematode DNA per reaction in 20 min at 39 °C with high specificity. The assay meets the requirements of rapid detection prior to port quarantine as well as on-site real-time detection and can be applied to detect the parasite in soil and plant samples. The modified gDNA extraction method for a single nematode established in this study significantly reduced the time of detection and improved the applicability of the real-time RPA assay for on-site detection in different environments. The real-time RPA assay to detect D. destructor will be useful for epidemiological investigations in the field as well as for quarantine processes in the sweet potato and potato trade.


Erratum: Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling.
This corrects the article DOI: 10.1038/nm.4346.


Effect of 80 kDa protein of porcine follicular fluid on gonadotropin stimulated progesterone production in rat granulosa cells in vitro.
We reported the presence of a 80 kDa polypeptide in porcine follicular fluid that inhibited the binding of 125I-radiolabelled hFSH as well as hCG to the rat ovarian gonadotropin receptors. In the present study, the biological activity of the receptor binding inhibitor is determined using an in vitro bioassay procedure. Granulosa cells isolated from PMSG primed immature rat ovaries respond to exogenously added gonadotropins in terms of progesterone production. Addition of fractions containing the gonadotropin receptor binding inhibitory activity inhibited progesterone production stimulated by the gonadotropins in a dose-dependent fashion. The receptor binding inhibitory activity was also capable of inhibiting progesterone production stimulated by PMSG, which has both FSH- and LH-like activities in rats. In contrast, progesterone production stimulated by dbcAMP was not inhibited by the receptor binding inhibitor. This result indicates that the site of action of the inhibitor is proximal to the formation of the cAMP. The above observations point out to a possible role for this factor in modulating gonadotropin activity at the ovarian level.


Primary brain tumors in children under age 3 years.
During the period from 1966 to 1996 the authors analyzed the clinicopathological characteristics of 46 cases of histologically verified primary brain tumors with symptomatic onset during the first 3 years of life. The patient group included 27 males and 19 females. There were 14 patients during the first year, 13 during the second year, and 19 during the third year. Supratentorial tumors (60.9%) were more common than infratentorial tumors. Histologically, neuroepithelial tumors predominated. The incidence of ependymal tumors, particularly malignant ones, and of neuronal/mixed neuronal-glial tumors was higher than in previous reports. Congenital brain tumors, those occurring within 2 months after birth, or tumors of dysplastic origin comprised 42.9% of the tumors that developed within 1 year of birth. At the onset, macrocephaly, failure to thrive, and seizures were prominent symptoms or signs in the younger patients. Focal neurological deficits and increased intracranial pressure predominated in the older patients. All but one patient underwent surgical treatment, and 17 patients received adjuvant therapy after surgery. The prognosis was mainly related to the histology of the malignancy. The outcome of medulloblastomas was poor. The quality of life of surviving patients was relatively good, 77.8% having better performance status (PS) than the Eastern Cooperative Oncology Group PS 2.


Several isoforms of crotoxin are present in individual venoms from the South American rattlesnake Crotalus durissus terrificus.
Crotalus durissus terrificus venoms collected either from individual snakes or from a large number of animals (more than 30) have been fractionated by high performance liquid chromatography on gel-filtration and ion exchange columns. The chromatographic patterns obtained with individual venom samples indicated that each Crotalus durissus terrificus snake synthesizes five to ten different crotoxin isoforms in widely variable relative proportions. Furthermore, the heterogeneity of venom samples collected from a large number of snakes did not appear significantly larger than that observed with venoms obtained from individual snakes. The comparison of the chromatographic patterns that we obtained with the various (individual and pooled) venoms allowed us to identify about 15 crotoxin isoforms, which may result from the expression of isogenes, since two amino acid variants have been reported to occur at several positions in the sequence of crotoxin component B. These observations confirm the existence of numerous molecular isoforms of crotoxin and suggest that an individual Crotalus durissus terrificus snake possesses several genes coding for the various crotoxin isoforms. The heterogeneity of venom samples collected from a large number of animals is explained, in a large measure, by the complexity of the venom obtained from the individual snakes.


Mitochondrial membrane permeabilization produced by PTP, Bax and apoptosis: a 1H-NMR relaxation study.
To analyze the involvement of structured water (bound to macromolecules) in apoptosis-induced mitochondrial outer-membrane permeability, we compared the dynamics of water protons from nuclear magnetic resonance (NMR) data in apoptotic liver mitochondria with that of control mitochondria incubated in vitro with free Ca(2+) (opening of the permeability transition pore, PTP) or with Bax alpha. Our results demonstrate that water molecules in apoptotic mitochondria exhibit an accelerated translational motion of structured water common with that induced by the opening of the PTP, but limited in amplitude. On the other hand, no significant quantitative change in structured water was observed in apoptotic mitochondria, a phenomenon also observed with Bax alpha-induced permeability. We conclude that the changes observed in the different water phases differ both quantitatively and qualitatively during the opening of the PTP and the Bax alpha-induced permeability, and that the apoptotic mitochondria exhibit mixed properties between these model situations.


[Treatment of humeral shaft and subcapital fractures in children. Consensus report of the child trauma section of the DGU].
The orthopedic treatment is the first choice in shaft fractures of the humerus in children. Angulations of more than 10 degrees need reduction, in that case anesthesia should be used for surgical stabilization. The preferred method is the elastic-stable intramedullary nailing (ESIN). In adolescents, even unreamed interlocking medullary nails are used. The primary paresis of the radial nerve is not an indication for nerve exploration in principle, but may be useful in special fracture situations. In subcapital fractures, more distinct angulations can be left untouched because of the highly potent epiphyseal plate. In severe displaced fractures, reduction and stabilization by ESIN is recommended in patients over the age of 10 years. The method is even applicable to pathological fractures in juvenile bone cysts. In adolescents after the start of epiphyseal plate closure, angle-stable implants are an alternative.


Prognostic implications of EGFR and HER-2 alteration assessed by immunohistochemistry and silver in situ hybridization in gastric cancer patients following curative resection.
The aim of this study was to use immunohistochemistry (IHC) and silver in situ hybridization (SISH) to evaluate alterations in EGFR and HER2 in gastric cancer in order to determine the relationship with prognosis in gastric cancer patients following curative resection. In this study, we analyzed EGFR and HER-2 status by IHC and SISH in 254 stage I-III gastric cancer patients who underwent curative surgery. Thirteen cases (2.48 %) showed EGFR alteration by IHC or SISH. EGFR alteration was associated with older age (P = 0.021), intestinal type (P = 0.040) and higher stage disease (P < 0.001). The patients with operable state gastric cancer who had EGFR alteration had an unfavorable prognosis, and multivariate analysis confirmed that EGFR alteration was an independent unfavorable prognostic factor. Twenty-seven cases (10.6 %) showed HER-2 alteration by IHC or SISH. HER-2 alteration was associated with older age (P = 0.006), well or moderately differentiated histology (P < 0.001) and intestinal type (P = 0.002). HER-2 alteration is not an independent prognostic factor for curatively resectable gastric cancer. We observed EGFR alteration in a subset of cases with operable state gastric cancer and determined that it was associated with an unfavorable prognosis.


Ringed sideroblasts with thrombocytosis: an uncommon mixed myelodysplastic/myeloproliferative disease of older adults.
Sideroblastic anaemia with ringed sideroblasts and marked thrombocytosis, hereupon referred to as ringed sideroblasts with thrombocytosis (RST), is a provisional entity in the 2001 World Health Organisation classification scheme. This retrospective study identified 16 patients with RST over a 7-year period. Proposed diagnostic criteria include a sustained platelet count > 500 x 10(9)/l, > or = 15% ringed sideroblasts, < 3% bone marrow blasts, and normal conventional cytogenetics. The median age was 76 years with eight males and eight females. With a median follow-up of 41 months, RST patients had a median overall survival of 71 months, comparable with refractory anaemia having ringed sideroblasts, but less favourable than essential thrombocythaemia. Thus far, no patients with RST are known to have died of disease-related causes. Patients with ringed sideroblasts and/or thrombocytosis need to be carefully evaluated for a variety of haematological diseases that may confer significantly different prognoses.


Possible sources of ambient PM10 inside Jadavpur University Campus, Kolkata.
High concentration of particulates in the university and research institutional campus can affect cognitive performance of students and researchers. However, studies on ambient particulate concentration in the campus of universities or research institutes are scarce. The ambient concentration of PM10 was measured in the campus of Jadavpur University, Kolkata, during two different seasons (S1: Post-monsoon; S2: Winter) to identify major sources of pollutant here. Significant seasonal variation of ambient PM10 was recorded in the campus. The average ambient PM10 concentration was recorded higher in S2 compared to S1 of the study period. Morphological characteristics of PM10 during the study period suggest that the roundness of particles was in the range of 0.66 to 0.68, whilst the mean spherical diameter suggests most of the PM10 particles were < 2.5 μ diameter. Based on factorial analysis, three factors were generated which includes factor 1: soil, building material and coal burning particles (53.76% of the variance); factor 2: particles from coal combustion (29.89% of the variance) and factor 3: particles from transport emission (16.33% of the variance). The study suggests that it is important to stop burning coal, reduce vehicular emission and reduce road dust resuspension around the campus to maintain the ambient PM10 concentration within the university campus during the post-monsoon and winter months.


Improving healthspan via changes in gut microbiota and fermentation.
Dietary resistant starch impact on intestinal microbiome and improving healthspan is the topic of this review. In the elderly population, dietary fiber intake is lower than recommended. Dietary resistant starch as a source of fiber produces a profound change in gut microbiota and fermentation in animal models of aging. Dietary resistant starch has the potential for improving healthspan in the elderly through multiple mechanisms as follows: (1) enhancing gut microbiota profile and production of short-chain fatty acids, (2) improving gut barrier function, (3) increasing gut peptides that are important in glucose homeostasis and lipid metabolism, and (4) mimicking many of the effects of caloric restriction including upregulation of genes involved in xenobiotic metabolism.


Independent mechanisms involved in suppression of the Moloney leukemia virus genome during differentiation of murine teratocarcinoma cells.
Expression and DNA methylation of the Moloney murine leukemia virus (M-MuLV) genome were investigated in murine teratocarcinoma cells after virus infection. The newly acquired viral genome was devoid of methylation, yet its expression was repressed. The integrated viral genome in undifferentiated teratocarcinoma cells was methylated within 15 days after infection. Although 5-azacytidine decreased the level of DNA methylation, it did not activate M-MuLV in undifferentiated cells. Activation by 5-azacytidine occurred only in differentiated teratocarcinoma cells. Thus two independent mechanisms seem to regulate gene expression during the course of differentiation. The first mechanism operates in undifferentiated cells to block expression of M-MuLV and other exogeneously acquired viral genes, such as SV40 and polyoma virus, and does not depend on DNA methylation. The second mechanism relates only to differentiated cells and represses expression of genes in which DNA is methylated.


Preservation of high-energy phosphates in human myocardium. A phosphorus 31-nuclear magnetic resonance study of the effect of temperature on atrial appendages.
After prolonged exposure to low temperatures (1 degree and 4 degrees C), human atrial trabeculae show poor recovery of contraction. At somewhat higher temperatures (12 degrees and 20 degrees C), recovery is much better (Keon and associates. Ann Thorac Surg 1988;46:337-41). Although better preservation of adenosine triphosphate and therefore improved contractile recovery might be expected after exposure to lower temperatures, it remained possible that, below a certain temperature, adenosine triphosphate-generating mechanisms could be slowed more than adenosine triphosphate utilization. To investigate this phenomenon further, we followed the time course of metabolic changes in human atrial appendages, harvested during cardiac bypass operations, at 1 degree, 4 degrees, 12 degrees, and 20 degrees C using high-resolution 31P and 1H nuclear magnetic resonance spectroscopy. The results are quantitated by correlation with data obtained from biochemical assays on quick-frozen tissues. Initial adenosine triphosphate levels in myocytes of human atrial appendages are 3.3 to 4.3 mumol.gm-1 tissue wet weight. At 20 degrees C, adenosine triphosphate disappears after 6 hours; at 12 degrees C, about half the initial adenosine triphosphate is still observable at this time; at 4 degrees C or 1 degree C, the decline is still slower. Only a small contribution toward adenosine triphosphate maintenance comes from creatine phosphate, since creatine phosphate, inorganic phosphate, and total creatine levels in the appendage are low (less than 2 mumol.gm-1 tissue wet weight). Glycolysis is active at all temperatures; the rate of glycolysis correlates positively with increasing temperature. Adenosine triphosphate generated by glycolysis falls just short of demand at all temperatures, but the difference is small at 1 degree and 4 degrees C. These studies lead us to conclude that the relatively poor recovery of contractile response of human atrial trabeculae, together with contracture reported previously at lower temperatures (1 degree and 4 degrees C), is not due to a failure to maintain adenosine triphosphate levels.


Potential of Inflammatory Protein Signatures for Enhanced Selection of People for Lung Cancer Screening.
Randomized trials have demonstrated a substantial reduction in lung cancer (LC) mortality by screening heavy smokers with low-dose computed tomography (LDCT). The aim of this study was to assess if and to what extent blood-based inflammatory protein biomarkers might enhance selection of those at highest risk for LC screening. Ever smoking participants were chosen from 9940 participants, aged 50-75 years, who were followed up with respect to LC incidence for 17 years in a prospective population-based cohort study conducted in Saarland, Germany. Using proximity extension assay, 92 inflammation protein biomarkers were measured in baseline plasma samples of ever smoking participants, including 172 incident LC cases and 285 randomly selected participants free of LC. Smoothly clipped absolute deviation (SCAD) penalized regression with 0.632+ bootstrap for correction of overoptimism was applied to derive an inflammation protein biomarker score (INS) and a combined INS-pack-years score in a training set, and algorithms were further evaluated in an independent validation set. Furthermore, the performances of nine LC risk prediction models individually and in combination with inflammatory plasma protein biomarkers for predicting LC incidence were comparatively evaluated. The combined INS-pack-years score predicted LC incidence with area under the curves (AUCs) of 0.811 and 0.782 in the training and the validation sets, respectively. The addition of inflammatory plasma protein biomarkers to established nine LC risk models increased the AUCs up to 0.121 and 0.070 among ever smoking participants from training and validation sets, respectively. Our results suggest that inflammatory protein biomarkers may have potential to improve the selection of people for LC screening and thereby enhance screening efficiency.


Two-carba cyclic phosphatidic acid treatment promotes phenotypic switch from M1 to M2 microglia and prevents behavioral abnormalities in a mouse model of neuropsychiatric systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the production of double-stranded DNA (dsDNA) antibodies and other antibodies that predominantly affects women with a wide range of lesions. Although neuropsychiatric lupus erythematosus (NPSLE), characterized by neuropsychiatric symptoms related to cerebrovascular diseases or depression, ranks high in severity, no specific treatment has been defined. Two-carba cyclic phosphatidic acid (2ccPA), a derivative of cyclic phosphatidic acid, was isolated from the true slime mold Physarum polycephalum in 1992. 2ccPA treatment suppresses neuroinflammation and promotes tissue repair in mouse multiple sclerosis and traumatic brain injury models. In this study, we performed behavioral tests on MRL/lpr mice as an NPSLE model. MRL/lpr mice showed increased depression-like behaviors compared with control mice, which were significantly suppressed by 2ccPA treatment. The expression of CD68, an M1 phenotypic marker of microglia, was significantly elevated in the prefrontal cortex and hippocampus of MRL/lpr mice, which was significantly suppressed by 2ccPA treatment. In contrast, the expression of Arginase1, an M2 phenotypic marker of microglia, was significantly increased by 2ccPA treatment. Compared to control mice, MRL/lpr mice showed higher plasma levels of anti-dsDNA antibodies, which are mainly involved in SLE pathogenesis. 2ccPA treatment decreased these levels in the MRL/lpr mice. These results suggest that 2ccPA treatment suppresses behavioral abnormalities by promoting a microglial phenotypic switch from M1 to M2 in MRL/lpr mice.


Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2»).
Aim To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.


Silymarin and protein kinase A inhibitor modulate glucose-mediated mouse sperm motility: An in vitro study.
Glucose is suggested to play a key role in motility hyperactivation of mammalian spermatozoa. The current study aimed to investigate the modulatory effects of silymarin and/or a protein kinase A (PKA) inhibitor (H-89) on glucose-mediated motility parameters of mouse spermatozoa. Spermatozoa were incubated in HEPES medium containing normal (NG; 5.5mM) or high (HG; 25 mM) glucose concentration. The results of computer-assisted analysis showed that samples incubated in HG resulted in a larger (p < 0.05) percentage of motile spermatozoa at 120 min (59.5 ± 14.8% vs. 34.0 ± 4.4%) compared to those incubated in NG. The average pathway velocity (VAP), curvilinear velocity (VCL), and straight-line velocity (VSL) exhibited similar patterns at 60 and 120 min when incubated in HG (p < 0.05). Treatments with silymarin (5, 10, 20 μg/mL) did not significantly affect sperm motility under NG conditions, but decreased the HG-enhanced motility, VAP, and VCL at 120 min (p < 0.05). H-89 (30 μM) reduced (p < 0.05) motility at 30 min examined in the NG or HG medium. At 90 min, H-89 also reduced (p < 0.05) the HG-enhanced motility of spermatozoa incubated with or without 20 μg/mL silymarin by 49% or 32%, respectively. In conclusion, the H-89-inhibition of glucose-mediated mouse sperm motility and certain types of velocity suggests that the glycolysis-PKA pathway is involved in the regulation of sperm motility. Silymarin may maintain sperm motility under NG conditions, but it inhibits glucose-activated sperm motility.


Intraductal papillary mucinous neoplasm (IPMN) with extra-pancreatic mucin: a case series and review of the literature.
Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized pancreatic neoplasm characterized by excessive mucin secretion by ductal epithelial cells resulting in a cystic dilation of the pancreatic duct. The objective of this study was to review Thomas Jefferson University's experience and the literature to determine the significance of extra-pancreatic mucin when associated with an IPMN. A retrospective analysis at our institution revealed only two cases of IPMN associated with extra-pancreatic mucin, which were classic IPMNs with rupture of the pancreatic duct and peritoneal mucin spillage. This specific finding is not previously described, although is assumed as five cases were reported in the literature with IPMN and mucin extension demonstrated by pseudomyxoma peritonei (PMP). We propose IPMN of the pancreas may be grossly compared to a mucocele of the appendix, as both are characterized by excessive secretion of mucin by ductal epithelial cells. A morbid complication of a mucocele is PMP. The presence of extra-pancreatic mucin with an IPMN could present a rare but important marker of the eventual seeding of tumor outside the primary IPMN. This has been documented with cases of iatrogenic spilling of pancreatic mucin, as well as multiple cases of IPMN associated with pseudomyxoma peritonei. At this time, there is scant reporting and consensus for the treatment of IPMN with extra-pancreatic mucin.


Use of telemedicine in the postoperative assessment of proctological patients: a case-control study.
Telemedicine is emerging as an easy way to communicate between patients and surgeons. Use of telemedicine increased during the coronavirus disease 2019 (COVID-19) pandemic. WhatsApp is one of the most common smartphone applications for user-friendly telemedicine. The aim of this study was to evaluate patient perception of health quality and positive outcomes using a diary sent by the patient to the surgeon via WhatsApp during the first post-discharge week after proctologic surgery. Ninety-eight patients discharged after proctologic surgery at the Israelite Hospital of Rome and the AOU Policlinico Umberto I of Rome in 1 January-31 December 2019 were divided into two groups: the WhatsApp group (group A), (n = 36) and the no WhatsApp group (group B) (n = 62). Group A patients received a protocol to follow for the day-by-day diary during the first post-discharge week and sending it by WhatsApp to the surgeon. Group B patients only received recommendations at discharge. The tool's usefulness was assessed by a questionnaire one month after the intervention. The two groups were homogeneous for age, sex, schooling, employment, and proctologic pathology. Group A patients had less difficulty keeping a diary (p < 0.0001). Group A patients had the perception of better follow-up post-discharge (p = 0.002). The use of the diary sent by WhatsApp significantly improved the perception of positive post-intervention outcomes (p = 0.007). WhatsApp was the only independent predictor of perception of post-surgical positive outcomes (odds ratio = 4.06; 95% CI 1.35-12.24; p = 0.01). The use of WhatsApp in the post-discharge period improves the lifestyle quality of the patients and their perception of the safety and quality of care received.


Are diabetes and its medications risk factors for the development of COVID-19? Data from a population-based study in Sicily.
Diabetes mellitus (DM) has been associated with higher incidence of severe cases of COVID-19 in hospitalized patients, but it is unknown whether DM is a risk factor for the overall COVID-19 incidence. The aim of present study was to investigate whether there is an association of DM with COVID-19 prevalence and case fatality, and between different DM medications and risk for COVID-19 infection and death. retrospective observational study on all SARS-CoV-2 positive (SARS-CoV-2+) cases and deaths in Sicily up to 2020, May 14th. No difference in COVID-19 prevalence was found between people with and without DM (RR 0.92 [0.79-1.09]). Case fatality was significantly higher in SARS-CoV-2+ with DM (RR 4.5 [3.55-5.71]). No diabetes medication was associated with differences in risk for SARS-Cov2 infection. in Sicily, DM was not a risk factor for COVID-19 infection, whereas it was associated with a higher case fatality.


The use of Anatomage table for metastases to the oral region.
The Anatomage Table is a modern device characterized by virtual reality functionality that may be used to enhance the teaching of human anatomy to medical and allied health students. The purpose of the present study was to use the virtual dissection table (3D Anatomage) as an additional tool for education and information in cases of metastases to the oral region. The hospital database of Vercelli Hospital, Vercelli, Italy, was searched for metastases to the oral region. DICOM data of Computed tomography scans were retrieved and uploaded in the Anatomage Table device. The workstation was used to obtain images of the body surface, "dissection cuts," or "vascular reconstructions," modifying the filters. The reconstructed images of three cases of metastases to the oral region from pulmonary adenocarcinoma, pulmonary sarcomatoid carcinoma, and breast ductal infiltrative adenocarcinoma were produced and presented. Different filters were used. The use of Anatomage Table, a touch interactive anatomy virtual dissection table used in anatomy education, thanks to the application of different filters, may represent a promising resource both for patients and students.


The functional effect of atorvastatin dose-dependent via inflammation factors on acute ST segment elevation myocardial infarction after emergency percutaneous coronary intervention.
To investigate the effect of different doses of atorvastatin on patients with acute ST segment elevation myocardial infarction (MI) after emergency percutaneous coronary intervention (PCI). A total of 265 patients with acute ST segment elevation MI who underwent emergency PCI were enrolled, 133 in high-dose atorvastatin administration (40 mg/day) and 132 in moderate-dose atorvastatin administration (20 mg/day). All the patients continued treatment for 1 year. The incidences of major adverse cardiovascular events (MACE) were recorded, including cardiovascular death, spontaneous MI, and unplanned revascularization. The association between clinical incidences and different doses of atorvastatin treatment was studied. Through tracking 1 year's treatment, the level of low-density lipoprotein cholesterol was lower in high-dose atorvastatin administration than in moderate treatment (1.6 ± 0.6 vs. 1.8 ± 0.6, P = 0.041). MACE significantly decreased in high-dose atorvastatin administration than in moderate treatment (9.8 vs. 18.2%, P = 0.03). Spontaneous MI was significantly more attenuated in high-dose treatment than in moderate treatment (6.8 vs. 12.8%, P = 0.03). Unplanned revascularization robustly decreased in patients with high-dose administration than those with moderate-dose treatment (5.2 vs. 8.3%, P = 0.03). There was no difference in the rate of adverse events between the two groups. For patients with acute ST segment elevation MI who underwent emergency PCI, high-dose atorvastatin could provide better performance than moderate-dose in our long-term tracking.


Extension of statutory period for compensation for certain disabilities due to undiagnosed illnesses and medically unexplained chronic multi-symptom illnesses. Interim final rule.
The Department of Veterans Affairs (VA) is issuing this interim final rule to amend its adjudication regulation regarding compensation for disabilities suffered by veterans who served in the Southwest Asia Theater of Operations during the Persian Gulf War. This amendment is necessary to extend the period during which disabilities associated with undiagnosed illnesses and medically unexplained chronic multi-symptom illnesses must become manifest in order for a veteran to be eligible for compensation.


Gut Feelings Block the Flow: Microbiota Links Stress to Vascular Disease.
Stress is linked to negative outcomes in cardiovascular diseases but exactly why is unclear. In this issue of Immunity, Xu et al. report that stress elicits glucocorticoid-induced gut permeability, in turn triggering the expansion of a population of neutrophils that can stimulate vaso-occlusive episodes.


Culturable bacteria in subglacial sediments and ice from two Southern Hemisphere glaciers.
Viable prokaryotes have been detected in basal sediments beneath the few Northern Hemisphere glaciers that have been sampled for microbial communities. However, parallel studies have not previously been conducted in the Southern Hemisphere, and subglacial environments in general are a new and underexplored niche for microbes. Unfrozen subglacial sediments and overlying glacier ice samples collected aseptically from the Fox Glacier and Franz Josef Glacier in the Southern Alps of New Zealand now have been shown to harbor viable microbial populations. Total direct counts of 2-7 x 10(6) cells g(-1) dry weight sediment were observed, whereas culturable aerobic heterotrophs ranged from 6-9 x 10(5) colony-forming units g(-1) dry weight. Viable counts in the glacier ice typically were 3-4 orders of magnitude smaller than in sediment. Nitrate-reducing and ferric iron-reducing bacteria were detected in sediment samples from both glaciers, but were few or below detection limits in the ice samples. Nitrogen-fixing bacteria were detected only in the Fox Glacier sediment. Restriction fragment analysis of 16S rDNA amplified from 37 pure cultures of aerobic heterotrophs capable of growth at 4 degrees C yielded 23 distinct groups, of which 11 were identified as beta-Proteobacteria. 16S rDNA sequences from representatives of these 11 groups were analyzed phylogenetically and shown to cluster with bacteria such as Polaromonas vacuolata and Rhodoferax antarcticus, or with clones obtained from permanently cold environments. Chemical analysis of sediment and ice samples revealed a dilute environment for microbial life. Nevertheless, both the sediment samples and one ice sample demonstrated substantial aerobic mineralization of 14C-acetate at 8 degrees C, indicating that sufficient nutrients and viable psychrotolerant microbes were present to support metabolism. Unfrozen subglacial sediments may represent a significant global reservoir of biological activity with the potential to influence glacier meltwater chemistry.


Evaluation of neurotoxicity for pesticide-related compounds in human iPS cell-derived neurons using microelectrode array.
In vivo evaluations of chemicals in neurotoxicity have certain limitations due to the considerable time and cost required, necessity of extrapolation from rodents to humans, and limited information on toxicity mechanisms. To address this issue, the development of in vitro test methods using new approach methodologies (NAMs) is important to evaluate the chemicals in neurotoxicity. Microelectrode array (MEA) allows the assessment of changes in neural network activity caused by compound administration. However, studies on compound evaluation criteria are scarce. In this study, we evaluated the impact of pesticides on neural activity using MEA measurements of human iPSC-derived neurons. A principal component analysis was performed on the electrical physiological parameters obtained by MEA measurements, and the influence of excessive neural activity due to compound addition was defined using the standard deviation of neural activity with solvent addition as the reference. By using known seizurogenic compounds as positive controls for neurotoxicity in MEA and evaluating pesticides with insufficient verification of their neurotoxicity in humans, we demonstrated that these pesticides exhibit neurotoxicity in humans. In conclusion, our data suggest that the neurotoxicity evaluation method in human iPSC neurons using MEA measurements could be one of the in vitro neurotoxicity test methods that could replace animal experiments.


Monoclonal antibodies to the synthetic adjuvant muramyl dipeptide: characterization of the specificity.
Monoclonal antibodies to MDP were prepared by hybridization of NSO myeloma cells with spleen cells of BALB/c mice immunized with MDP conjugated to methyl-BSA. Hybridomas secreting anti-MDP antibodies were selected by the binding activity of their supernates to MDP-A--L using a radioimmunoassay. After cloning in soft agar, the specificities of monoclonal anti-MDP antibodies were assayed by an inhibition of ELISA with various derivatives of MDP. Fine structural analysis of specificity for one such clone (2-4) is reported. This antibody recognizes the N-acetyl-muramic acid (N-Ac-Mur) linked to the dipeptide but not N-Ac-Mur or/and dipeptide alone. The N-Ac group on muramic acid is an important antigenic determinant and the glycopeptide linkage seems to be crucial in presenting the sugar moiety. Conservative substitution of L-Ala (i.e. by L-Ser or L-Val) had no effect on the binding ability to the antibody whereas a radical change, i.e. replacement of L-Ala by L-Pro or N-methyl-L-Ala completely abolished the antigenicity of the molecule. There was no clear correlation between biological activities of various derivatives of MDP and their ability to react with this antibody. Some possible hypotheses explaining this lack of correlation are presented.


Autism and attention-deficit/hyperactivity disorder in children with cerebral palsy: high prevalence rates in a population-based study.
To assess a total population of school-age children with cerebral palsy (CP) for autism and attention-deficit/hyperactivity disorder (ADHD) with a view to determining their prevalence and to relate findings to motor function, intellectual disability, and other associated impairments. Of 264 children, born between 1999 and 2006, from the CP register of western Sweden, 200 children (109 males, 91 females, median age at assessment 14y, range 7-18y) completed comprehensive screening and further neuropsychiatric clinical assessments. Ninety children (45%) were diagnosed with autism, ADHD, or both, 59 (30%) were diagnosed with autism, and 60 (30%) were diagnosed with ADHD. Intellectual disability was present in 51%. Two-thirds had autism, ADHD, and/or intellectual disability. In regression models, autism was mainly predicted by intellectual disability (odds ratio [OR]=4.1) and ADHD (OR=3.2), and ADHD was predicted by intellectual disability (OR=2.3) and autism (OR=3.0). Autism was more common in children born preterm (OR=2.0). Gross motor function was not associated with autism. ADHD prevalence was low in children with severe motor impairment, possibly due to diagnostic limitations. Autism and ADHD were common in this population of children with CP and were mainlyindependent of motor severity and CP type. The strongest predictor of autism/ADHD was intellectual disability. Assessment for autism and ADHD is warranted as part of the evaluation in CP. Forty-five percent of the children with cerebral palsy also had autism, attention-deficit/hyperactivity disorder (ADHD), or both. Autism and ADHD were predicted mainly by intellectual disability. Established diagnostic instruments worked well for all but the most disabled group of children.


[Clinical and anthropologic aspects of form and size of the child's head].
The author recommends the classic direct cephalometry for measurements in clinical anthropology during childhood. It is referred a trend of debrachycephalization in the Czech child population. The presented results prove a decreasing cephalic index from birth up to 3 years of life and a relationship between positioning of the child and the shape and size of the child's neurocranium.


Biplanar plating of mandibular fractures: a new concept with in vitro testing and comparison with the traditional plate-and-screw technique.
To introduce the concept of biplanar plating of mandibular fractures and to present an in vitro comparison of this method with traditional use of a single mandibular plate. A device for the delivery of repetitive simulated masticatory stress to mandibular models was developed. Using the device, we compared biplanar with single-plate fixation of vertical mandibular body fractures by determining cycles to failure. Tertiary care academic medical center. A simulated masticatory force was delivered vertically to the anterior end of polymer hemimandibles as used for in vitro teaching of plating methods. Mobility at the fracture site was tested at intervals corresponding to 6000 chewing cycles each. Of 5 specimens plated with a mandibular fixation plate, 4 developed greater than 0.010 cm of vertical mobility at the fracture site after 12 000 cycles. Only 1 of the 5 specimens fixed with biplanar plating developed this degree of mobility. Single-plate fixation of mandibular fractures is greatly enhanced by a miniplate spanning the fracture along the inferior border. We used this technique on 15 patients with unfavorable fractures and found it simple, secure, and reliable. We had no complications. An inferior marginal plate serves the same function as a tension band, and can be placed on mandibles through the same incision as the main fixation plate without additional dissection. We prefer this to a traditional tension band when the percutaneous route of access to a mandibular fracture site is used.


Increased production of bacterial cellulose as starting point for scaled-up applications.
Bacterial cellulose is composed of an ultrafine nanofiber network and well-ordered structure; therefore, it offers several advantages when used as native polymer or in composite systems.In this study, a pool of 34 acetic acid bacteria strains belonging to Komagataeibacter xylinus were screened for their ability to produce bacterial cellulose. Bacterial cellulose layers of different thickness were observed for all the culture strains. A high-producing strain, which secreted more than 23 g/L of bacterial cellulose on the isolation broth during 10 days of static cultivation, was selected and tested in optimized culture conditions. In static conditions, the increase of cellulose yield and the reduction of by-products such as gluconic acid were observed. Dried bacterial cellulose obtained in the optimized broth was characterized to determine its microstructural, thermal, and mechanical properties. All the findings of this study support the use of bacterial cellulose produced by the selected strain for biomedical and food applications.


Upregulation of synapsin IIa and IIb mRNAs in the paraventricular and supraoptic nuclei in chronic salt loaded and lactating rats.
The effects of chronic salt loading (2% saline to drink for 5 and 10 days), gestation, lactation and adrenalectomy on the expression of synapsin IIa and IIb genes were examined in the rat paraventricular (PVN) and supraoptic nuclei (SON), using in situ hybridization histochemistry. In each control, synapsin IIa and IIb genes were moderately expressed in the magnocellular division of the PVN and SON, while few transcripts of synapsin IIa and IIb were observed in the parvocellular division of the PVN. Chronic salt loading, gestation on day 21 and lactation on day 10 caused significant increases in synapsin IIa and IIb transcripts in the magnocellular division of the PVN and SON, compared to each control. Although corticotropin-releasing hormone transcripts in the parvocellular division of the PVN were significantly increased in the adrenalectomized rats, no changes in the transcripts of synapsin IIa and IIb were observed throughout the PVN. These results suggest that physiological stimuli such as osmotic challenge and lactation potently increase synapsin IIa and IIb mRNAs in the magnocellular neurons of the PVN and SON.


Highly sensitive and selective detection of phosphate using novel highly photoluminescent water-soluble Mn-doped ZnTe/ZnSe quantum dots.
Herein, the facile method with high selectivity for phosphate ion (Pi) sensing using novel Type-II core/shell Mn: ZnTe/ZnSe quantum dots (QDs) was reported. This was the first time that Mn: ZnTe/ZnSe QDs with highlighted optical properties were used for sensing. The water-soluble Mn: ZnTe/ZnSe QDs with a high quantum yield of 7% were synthesized by aqueous synthetic method. Compared with traditional ZnSe QDs or Mn: ZnSe QDs, the smaller effective band gap, longer wavelength and lower ionization potential (high valence band edge) for effective hole localization made Type-II core/shell Mn: ZnTe/ZnSe QDs to be stable and had high photoluminescence (PL). Only Mg(2+) was found to be able to enhance Mn: ZnTe/ZnSe QDs PL selectively. The mechanism of fluorescence enhancement was attributed to the passivated surface nonradiative relaxation centers of Mn: ZnTe/ZnSe QDs. In the presence of Pi anion, the PL intensity got quenched due to the aggregation species of QDs via electrostatic attraction between Pi and Mg(2+) on the surface of Mn: ZnTe/ZnSe QDs. Therefore, the quenching effect can be used to detect Pi selectively. The PL was observed to be linearly proportional to the Pi analyte concentration in the range from 0.67 to 50.0 μmol/L, with a detection limit of 0.2μ mol/L (S/N=3). The novel "on-off" fluorescence nanosensor for Pi detection was sensitive and convenient in the real analysis application. The reported analytical method of Mn: ZnTe/ZnSe QDs is highly sensitive and selective, which can corroborate the extension of its usages in chemo/ biosensing and bioimaging.


Middle fossa approach for a facial nerve schwannoma: how I do it.
Facial nerve schwannomas can extend to the middle fossa or the cerebellopontine angle through the labyrinthine and cisternal segments of the facial nerve. The middle fossa approach (MFA) and its extensions provide a wide approach to deal with a large variety of lesions located in the middle and posterior cranial fossa junction. We describe the MFA along with its advantages and limitations to treat a facial nerve schwannoma involving the middle and posterior cranial fossa. The MFA is a well-established route to surgically deal with tumors located in and around the proximal four segments of the facial nerve.


Evaluation of the acceptability of Peer Physical Examination (PPE) in medical and osteopathic students: a cross sectional survey.
Peer physical examination (PPE) is a method of training in medical and osteopathic curricula. The aim of this study was to compare the acceptability of PPE in two classes of medical and osteopathic students after their first experience, to obtain comparative information useful for an understanding of the different professional approaches. The leading hypothesis was that osteopathic students enter the curriculum with a more positive attitude to bodily contact.As a secondary aim, this study validated the new version of a questionnaire to assess the acceptability of PPE. A new version of a previously validated questionnaire and an instrument from the literature (the Examining Fellow Student [EFS] questionnaire) were used for a cross-sectional survey in a class of 129 3rd year medical students and in two parallel classes of 1st year osteopathic students (total of 112 students). The mean score of the new questionnaire was significantly higher for the osteopathic students than for the medical students (53.4 ± 6.3 vs. 43.4 ± 8.9; p < 0.01). The only independent variables that were significantly predictive of the score in a linear regression analysis were gender and the condition of medical or osteopathic student. The EFS mean score also showed a significant difference between the osteopathic and medical students (30.76 ± 2.9 vs. 27.85 ± 4.3; p < 0.01).Factor analysis of the new questionnaire identified three factors (appropriateness and usefulness, sexual implications and passive role) accounting for 62.8% of the variance. Criterion validity was assessed by correlation with the EFS (Pearson's r coefficient = 0.61). Reliability was expressed in terms of Cronbach's alpha coefficient, which equals 0.86. These quantitative results are consistent with previous qualitative research on the process of embodiment both in medicine and osteopathy. The new questionnaire proved to be valid and reliable. The objective assessment of the acceptability of PPE is a way to determine differences in students' attitudes towards contact with the body and can be used for counselling students regarding career choice. This study can also highlight differences between students from different professions and serve as a basis for reflection for improved mutual interprofessional understanding and future interprofessional education.


Controlling the electrodeposition, morphology and structure of hydroxyapatite coating on 316L stainless steel.
Hydroxyapatite (HAp) coatings were prepared on 316L stainless steel (316LSS) substrates by electrochemical deposition in the solutions containing Ca(NO3)2·4H2O and NH4H2PO4 at different electrolyte concentrations. Along with the effect of precursor concentration, the influence of temperature and H2O2 content on the morphology, structure and composition of the coating was thoroughly discussed with the help of X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectra. The in vitro tests in simulated body fluids (SBF) were carried out and then the morphological and structural changes were estimated by SEM and electrochemical techniques (open circuit potential, polarization curves, Nyquist and Bode spectra measurements). Being simple and cost-effective, this method is advantageous for producing HAp implant materials with good properties/characteristics, aiming towards in vivo biomedical applications.


S-adenosyl-L-methionine: its effect on aminolevulinate dehydratase and glutathione in acute ethanol intoxication.
The effect of disulfiram and S-adenosyl-L-methionine (SAM) administration to acute ethanol intoxicated mice on the hepatic glutathione (GSH) concentration and aminolevulinic and dehydratase (ALA-D) activity was investigated. It was found that both GSH levels and ALA-D activity were decreased, and evidence suggested that the toxic action of ethanol was due to its conversion into acetaldehyde. Administration of SAM reverses the effects of acute alcohol abuse by increasing liver GSH availability. In vitro, hepatic ALA-D activity was not modified by ethanol; instead it was non-competitively inhibited by acetaldehyde. This inhibition was efficiently reversed by GSH and cysteine (CySH). Therefore, a mechanism for the action of ethanol on ALA-D, based on the inhibitory effect of acetaldehyde, is proposed.


Replication and Meta-Analysis of Common Gene Mutations in TTF1 and TTF2 with Papillary Thyroid Cancer.
Papillary thyroid cancer (PTC), one of the most common malignant thyroid tumors, exits widely in the thyroid of adolescents. Thyroid transcription factor 1 (TTF1) and 2 (TTF2) were thyroid-specific transcription factors, and regulated expression of the thyroid-specific genes. Hence, the aim of the present study was to evaluate the correlation between gene variants of TTF1 and TTF2 and the risk of PTC in Chinese population.Two tagging single-nucleotide polymorphisms (tSNPs) on TTF1 and TTF2 were selected and genotyped by matrix-assisted laser desorption/ionization time-of-flight (MALDITOF) mass spectrometry in a hospital-based case-control study of 297 PTC patients and 594 healthy controls. Furthermore, a meta-analysis of the association between TTF1 and TTF2 and PTC risk was also performed.We found that the rs944289 on the TTF1 was significantly associated with increased PTC risk (TT vs CC, OR = 1.53, 95% CI = 1.05-2.24; CT + TT vs TT, OR = 1.34, 95% CI = 1.00-1.79; T vs C, OR = 1.27, 95% CI = 1.04-1.55). Similarly, the rs965513 on the TTF2 can also elevate the risk of PTC significantly (GA vs GG, OR = 1.67, 95% CI = 1.07-2.59; AA+GA vs AA, OR = 1.37, 95% CI = 1.09-1.82; A vs G, OR = 1.29, 95% CI = 1.05-1.59). Furthermore, results of stratified analysis revealed that the risk effects of rs944289 and rs965513 were more overpowering in the subgroups of patients with MNG, as well as subjects without metastasis. Results of meta-analysis from the previous study and our new data indicated that variants of rs944289 and rs965513 might be the genetic susceptible factors both in Asians and Caucasians.We get the conclusion that mutations of TTF1 and TTF2 are significantly associated with an increasing risk of PTC in Chinese. However, more detailed investigations and further large-scale studies on genetic functions to provide more conclusive and accurate evidence are required in the future.


Failing Performance Validity Cutoffs on the Boston Naming Test (BNT) Is Specific, but Insensitive to Non-Credible Responding.
This study was designed to examine alternative validity cutoffs on the Boston Naming Test (BNT).Archival data were collected from 206 adults assessed in a medicolegal setting following a motor vehicle collision. Classification accuracy was evaluated against three criterion PVTs.The first cutoff to achieve minimum specificity (.87-.88) was T ≤ 35, at .33-.45 sensitivity. T ≤ 33 improved specificity (.92-.93) at .24-.34 sensitivity. BNT validity cutoffs correctly classified 67-85% of the sample. Failing the BNT was unrelated to self-reported emotional distress. Although constrained by its low sensitivity, the BNT remains a useful embedded PVT.


The effects of grating area and spatial frequency on contrast sensitivity as a function of light level.
Contrast sensitivity was measured as a function of retinal illuminance (I) for vertical cosine gratings of various circular areas (A) and spatial frequencies (f < or = 4 c/deg). Spatial frequency and grating diameter varied in inverse proportion to each other in order to keep the relative grating area (A x f2) constant at either 3.14, 12.6, 50.3, or 201 square cycles. At all grating areas and spatial frequencies contrast sensitivity in dim light first increased in proportion to the square root of retinal illuminance. Then the increase saturated and contrast sensitivity became independent of luminance level in bright light. For gratings with constant relative area contrast sensitivity functions were similar in shape and had the same maximum sensitivity but were shifted horizontally towards lower illuminances with decreasing spatial frequency. However, when replotted as a function of retinal illuminance divided by spatial frequency squared, contrast sensitivity functions fell on a common curve at all levels of relative retinal illuminance (I/f2).


Tolerance to orally induced anaphylactic sensitisation to cow's milk proteins and patency of the intestinal mucosa in the neonatal guinea pig.
Guinea pigs fed cow's milk within 2 days of birth may acquire tolerance to anaphylactic sensitisation to cow's milk proteins. Appreciable amounts of beta-lactoglobulin may be detected in their blood, in contrast with animals receiving cow's milk later than this age. Uptake of beta-lactoglobulin from the gut to circulation ceases after the 6th postnatal day. These findings could be relevant to cot death in the human infant should the anaphylactic hypothesis be substantiated.


Cyclosporin A reduces expression of adhesion molecules in the kidney of rats with chronic serum sickness.
Treatment with cyclosporin A (CsA) improves proteinuria and reduces renal cellular infiltration in chronic serum sickness (CSS). We examined if these effects were associated with a reduced renal expression of CD54 and its ligands, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and MHC class II molecules. We studied two groups of rats in which CSS was induced by daily injections of ovalbumin (OVA): a group treated with CsA (OVA.CsA group, n = 11) and a group that received no treatment (OVA.CSS group, n = 11). An additional group of five rats (control group) received only phosphate buffer. Immunostaining techniques were used to follow CSS and to study the expression of CD54, CD18, CD11b/c, IFN-gamma, TNF-alpha and MHC class molecules. Proteinuria (mg/24 h) was reduced from 248.2 +/- 73.1 (OVA.CCS group) to 14.5 +/- 13.1 with CsA treatment (P < 0.0001). The renal expression of CD54 and its ligands (CD18 and CD11b/c) was reduced by 50% to 75%. Correspondingly, there was a 60% to 85% reduction in the number of infiltrating leucocytes. The number of cells expressing TNF-alpha, IFN-gamma and MHC II molecules was also reduced. CsA reduces expression of CD54 and its ligands. This effect is associated with a reduction of cellular infiltration, IFN-gamma, TNF-alpha-producing cells and with MHC II expression in the kidney. These findings suggest that expression of adhesion molecules plays a critical role in CSS and underline the importance of cellular immunity in this experimental model.


Gene expression studies of plastic and evolutionary responses to global warming.
Phenotypic plasticity can be a rapid response for coping with global warming, yet may be insufficient to protect species from extinction. Evolutionary adaptation may reinforce adaptive or oppose maladaptive plastic responses. With advances in technology whole transcriptomes can provide us with an unprecedented overview of genes and functional processes underlying the interplay between plasticity and evolution. We advocate that insects provide ideal opportunities to study plasticity in non-adapted and thermally adapted populations to infer reaction norms across the whole transcriptome ('reactionomes'). This can advance our understanding of how the interplay between plasticity and evolution shapes responses to warming. So far, a limited number of studies suggest predominantly maladaptive plastic responses to novel environments that are reduced with time, but much more research is needed to infer general patterns.


Life cycle assessment of a printed circuit board manufacturing plant in Turkey.
The objective of this study is to investigate the environmental impacts of a printed circuit board (PCB) manufacturing plant through streamlined life cycle assessment approach. As a result, the most effective recommendations on minimizing the environmental impacts for the mentioned sector are revealed and first steps towards establishing a country specific database are taken. The whole PCB production consists of two consecutive stages: namely board fabrication followed by the manufacturing of PCB. Manufacturing of PCB contributes the highest shares to freshwater aquatic ecotoxicity potential (FAETP) and ozone layer depletion potential (ODP). Eighty-nine percent of FAETP is found to be generated from the manufacturing of PCB. Almost all of this contribution can be attributed to the disposal of copper containing wastewater treatment sludge from etching operations to incineration. On the other hand, PCB manufacturing has 73% share in total ODP. Within the manufacturing of PCB, as etching operations are found to be of importance for all the impact categories except eutrophication potential (EP), it is recommended to focus further studies on in-plant control of etching.


Follicular dendritic cell sarcoma of the uterine cervix: a case report.
Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal tumor that mostly occurs in systemic lymph nodes. FDCS in the uterine cervix has not yet been reported. A 49-year-old woman was referred to our department with a cervical tumor, which was histologically suspected to be undifferentiated carcinoma. She underwent hysterectomy, salpingo-oophorectomy, and pelvic lymphadenectomy after neoadjuvant chemotherapy with paclitaxel and carboplatin. The resected specimen contained high numbers of spindle cells and was immunohistochemically confirmed to be FDCS. The tumor was completely resected and recurrence was not detected at a 16-month follow-up. FDCS is an extremely rare malignant tumor in the uterine cervix, and an accurate diagnosis and complete resection are essential for a good prognosis.


Wound healing in sarcoma-bearing rats: tumor effects on cutaneous and deep wounds.
Many surgeons think that cancer causes a higher incidence of wound complications. Wound healing was examined in a cutaneous and deep model in control and sarcoma-bearing rats to evaluate this concept. In a dorsal incisional wound, a significant decrease in wound breaking strength was observed from 19 days after tumor implantation onward. The amount of the breaking strength deficit increased with the size of tumor and the day post-tumor implant. In a deeper wound chamber, hydroxyproline levels, 3H-thymidine incorporation into DNA, histology, and collagen types were examined, and tumor produced no significant change in any parameter. The presence of tumor appeared to inhibit wound healing in cutaneous wounds but had no apparent effect on deeper wounds. This difference in healing in the two wound models is important to surgical oncologists. Because there is no demonstrable tumor-induced healing deficit in deep wounds, cancer-bearing organisms probably still heal these wounds normally.


Code Red in the Supply Center: The Impact of Immune Activation on Hematopoiesis.
This Special Issue entitled "The Impact of Immune Activation on Hematopoiesis" aims to bring together review and primary articles focused on distinct types of immune activation that impact hematopoiesis [...].


Increased risk of transurethral and suprapubic catheter self-extraction in COVID-19 patients: real-life experience.
This study evaluated the prevalence of transurethral catheter self-removal in critically-ill COVID-19 non-sedated adult patients compared with non-COVID-19 controls. COVID-19 patients who self-extracted transurethral or suprapubic catheters needing a urological intervention were prospectively included (group A). Demographic data, medical and nursing records, comorbidities and nervous system symptoms were evaluated. Agitation, anxiety and delirium were assessed by the Richmond Agitation and Sedation Scale (RASS). The control group B were non-COVID-19 patients who self-extracted transurethral/suprapubic catheter in a urology unit (subgroup B1) and geriatric unit (subgroup B2), requiring a urological intervention in the same period. 37 men and 11 women were enrolled in group A. Mean RASS score was 3.1 ± 1.8. There were 5 patients in subgroup B1 and 11 in subgroup B2. Chronic comorbidities were more frequent in group B than the COVID-19 group (P<0.01). COVID-19 patients had a significant difference in RASS score (P<0.006) and catheter self-extraction events (P<0.001). Complications caused by traumatic catheter extractions (severe urethrorrhagia, longer hospital stay) were greater in COVID-19 patients. This is the first study focusing on the prevalence and complications of catheter self-removal in COVID-19 patients. An increased prevalence of urological complications due to agitation and delirium related to COVID-19 has been demonstrated-the neurological sequelae of COVID-19 must be considered during hospitalisation.


Prostacyclin-dependent cyclic AMP formation in endothelial cells.
The effect of the stable prostacyclin (PGI2) mimetic iloprost on cyclic AMP levels was investigated in cultured porcine aortic endothelial cells. Iloprost (10(-10)-10(-5) mol/l) did not change cyclic AMP levels at passage 1 when endothelial cells were untreated but did so after inhibition of endogenous PGI2 formation by 48 or 72 h treatment with indomethacin or diclofenac (10(-5) mol/l). Iloprost increased cyclic AMP in a concentration-dependent manner and up to 6-fold above control when cells from passage 6 were used. In these cells, basal PGI2 generation was reduced to 20% of that at passage 1. Cyclic AMP stimulation by iloprost (10(-5) mol/l) in passage 6 cells was enhanced, reaching up to 11-fold the control level, when cells were cultured for 48 h in the presence of indomethacin or diclofenac (10(-5) mol/l). Cyclic AMP formation in LLC-PK1 cells, a kidney epithelial cell line without endogenous PGI2 biosynthesis, was markedly (25-fold above basal) stimulated by iloprost and unchanged by pretreatment with indomethacin and diclofenac. The data demonstrate that a continuous basal PGI2 generation occurs in porcine aortic endothelial cells that may be sufficient to completely desensitize PGI2-dependent adenylate cyclase activation, presumably at the receptor or GTP-binding protein level.


Development of a 3D functional assay and identification of biomarkers, predictive for response of high-grade serous ovarian cancer (HGSOC) patients to poly-ADP ribose polymerase inhibitors (PARPis): targeted therapy.
Poly(ADP-ribose) polymerase inhibitors (PARPis) specifically target homologous recombination deficiency (HRD) cells and display good therapeutic effect in women with advanced-stage BRCA1/2-mutated breast and epithelial ovarian cancer (EOC). However, about 50% of high grade serous ovarian cancers (HGSOC) present with HRD due to epigenetic BRCA1 inactivation, as well as genetic/epigenetic inactivation(s) of other HR genes, a feature known as "BRCAness". Therefore, there is a potential for extending the use of PARPis to these patients if HR status can be identified. We have developed a 3D (spheroid) functional assay to assess the sensitivity of two PARPis (niraparib and olaparib) in ascites-derived primary cell cultures (AsPCs) from HGSOC patients. A method for AsPCs preparation was established based on a matrix (agarose), allowing for easy isolation and successive propagation of monolayer and 3D AsPCs. Based on this method, we performed cytotoxicity assays on 42 AsPCs grown both as monolayers and spheroids. The response to PARPis treatment in monolayer AsPCs, was significantly higher, compared to 3D AsPCs, as 88% and 52% of the monolayer AsPCs displayed sensitivity to niraparib and olaparib respectively, while 66% of the 3D AsPCs were sensitive to niraparib and 38% to olaparib, the latter being more consistent with previous estimates of HRD (40%-60%) in EOC. Moreover, niraparib displayed a significantly stronger cytotoxic effect in both in 3D and monolayer AsPCs, which was confirmed by consecutive analyses of the HR pathway activity (γH2AX foci formation) in PARPis-sensitive and resistant AsPCs. Global gene expression comparison of 6 PARPi-resistant and 6 PARPi-sensitive 3D AsPCs was indicative for the predominant downregulation of numerous genes and networks with previously demonstrated roles in EOC chemoresistance, suggesting that the PARPis-sensitive AsPCs could display enhanced sensitivity to other chemotherapeutic drugs, commonly applied in cancer management. Microarray data validation identified 24 potential gene biomarkers associated with PARPis sensitivity. The differential expression of 7 selected biomarkers was consecutively confirmed by immunohistochemistry in matched EOC tumor samples. The application of this assay and the potential biomarkers with possible predictive significance to PARPis therapy of EOC patients now need testing in the setting of a clinical trial.


Effect of bariatric surgery versus medical therapy on long-term cardiovascular risk in low BMI Chinese patients with type 2 diabetes: a propensity score-matched analysis.
Reducing the risk of death due to cardiovascular disease (CVD) is an important direction for diabetes prevention and treatment. The Chinese population with type 2 diabetes (T2D) has a high risk of developing CVD at relatively low body mass index (BMI) levels. Currently, no studies have evaluated the effect of bariatric surgery versus medical therapy on long-term CVD risk in patients with T2D and low BMI. To compare bariatric surgery versus medical therapy for long-term CVD risk in Chinese patients with T2D and low BMI by using the China Prediction for ASCVD Risk equations and the United Kingdom Prospective Diabetes Study risk engine. University hospital, China. Medical records of patients with T2D with a BMI <35 kg/m2 undergoing bariatric surgery or medical therapy from May 2010 to December 2018 were reviewed. A 1:1 propensity score matching was performed by using 7 preoperative characteristics. Variables for calculating CVD risk scores over the 5-year follow-up were assessed. A total of 684 patients with T2D underwent bariatric surgery (n = 75) or medical therapy (n = 609), and 52 pairs of matched subjects were selected from both groups after propensity score matching. The 10-year and lifetime atherosclerotic CVD risk by using the China Prediction for ASCVD Risk equation at 5 years follow-up period in the bariatric surgery group improved significantly compared with the medical therapy group. In the fifth year of follow-up, the 10-year risk of coronary heart disease, fatal coronary heart disease, stroke, and fatal stroke by using the United Kingdom Prospective Diabetes Study risk engine were much lower in the bariatric surgery group than in the medical therapy group (10.37 ± 5.64% versus 27.25 ± 7.28%, P = .004; 6.3 ± 4.5% versus 22.3 ± 7.35%, P = .002; 4.97 ± 3.73% versus 15.05 ± 3.63%, P = .001; .59 ± .45% versus 1.52 ± .14%, P < .001. respectively). The use of glucose-lowering medications, including insulin, was reduced from baseline in both groups, and patients in the bariatric surgery group required significantly fewer of these medications than those in the medical therapy group. Bariatric surgery in patients with T2D and low BMI conferred a lower calculated risk of CVD compared with medical therapy over 5 years of follow-up.


Drug resistance in melanoma: mechanisms, apoptosis, and new potential therapeutic targets.
Melanoma is the most aggressive form of skin cancer. Patients with advanced disease, such as lymph node involvement and distant metastases, have 5-year survival rates of 50% and 10-20%, respectively. This poor prognosis largely results from resistance to conventional chemotherapy, namely cytotoxic drugs. The basis for drug resistance in melanoma is most likely dysregulation of apoptosis, although other mechanisms including drug transport, detoxification, and enhanced DNA repair may also play a role. Defects at multiple levels and in both major apoptotic pathways have been described in melanoma. Our laboratory has identified an inhibitor of apoptosis, termed survivin, that is expressed in melanoma and required for maintenance of melanoma cell viability. Targeting of survivin and other apoptotic regulators increases the sensitivity of melanoma cells to cytotoxic drugs, and may provide a promising new therapeutic approach to cancer.


Stimulation of CD107 affects LPS-induced cytokine secretion and cellular adhesion through the ERK signaling pathway in the human macrophage-like cell line, THP-1.
Lysosome-associated membrane proteins (LAMPs), a family of highly glycosylated transmembrane proteins, are well known lysosomal markers. Recent investigations revealed the cell surface expression of LAMPs, especially after activation in various cell types. Although their role in lysosome function is under intense investigation, little is known about the function of this cell surface form of LAMPs. To investigate the role of cell surface LAMPs in macrophage activities, the human macrophage-like cell line THP-1 was stimulated with monoclonal antibodies specific to CD107a (LAMP-1) or CD107b (LAMP-2). Stimulation of CD107 enhanced LPS-induced IL-8 secretion and induced adhesion of THP-1 cells to culture plates coated with extracellular matrix proteins such as collagen, fibronectin, and laminin. Utilization of specific inhibitors of signaling adapters and Western blot analysis revealed that extracellular signal-regulated kinase (ERK) mediates the regulatory action of CD107. These results suggest that stimulation of THP-1 cells through CD107 affects macrophage-associated functions such as cytokine secretion and cellular adhesion through activation of ERK.


More than a Genetic Code: Epigenetics of Lung Fibrosis.
At the end of the last century, genetic studies reported that genetic information is not transmitted solely by DNA, but is also transmitted by other mechanisms, named as epigenetics. The well-described epigenetic mechanisms include DNA methylation, biochemical modifications of histones, and microRNAs. The role of altered epigenetics in the biology of various fibrotic diseases is well-established, and recent advances demonstrate its importance in the pathogenesis of pulmonary fibrosis-predominantly referring to idiopathic pulmonary fibrosis, the most lethal of the interstitial lung diseases. The deficiency in effective medications suggests an urgent need to better understand the underlying pathobiology. This review summarizes the current knowledge concerning epigenetic changes in pulmonary fibrosis and associations of these changes with several cellular pathways of known significance in its pathogenesis. It also designates the most promising substances for further research that may bring us closer to new therapeutic options.


A new synthetic ultrasound-assisted method for dibenzoepines.
In this study, we have developed a new ultrasonic synthesis method of dibenzoepines using olanzapine and quetiapine, which are well-known drugs for the treatment of schizophrenia and bipolar disorder. The method is based on the N-alkylation reaction of the piperazine fragment in tricyclic compounds with methyl iodide or 2-(2-chloroethoxy)ethanol as the alkylating agent, respectively. The synthesis reactions were carried out in an ultrasonic bath with solvents such as acetonitrile or dimethylformamide in the presence of potassium or sodium carbonate or sodium hydroxide and metal-free, ecological phase transfer catalyst at a temperature of 40-50 °C. This allowed us to obtain olanzapine in 1 h (Y = 67%), and quetiapine in 3 h (Y = 72%). An ultrasonic reactor (Qsonica Q700) was used in the synthesis of olanzapine and made it possible to shorten the reaction time to 10 min and obtain 90% yield with very high purity. The developed method allows obtaining compounds in mild conditions and in a short time, thanks to which the process is more ecological than others described in the literature.


Radioimmunoassay of some hormones simultaneously measured in serum and breast cyst fluid.
Blood and breast cyst fluid were drawn simultaneously for hormonal determination. There was no difference between serum and cyst fluid values of PRL and TSH. A significant difference was noted for LH (p less than 0.01) and FSH (p less than 0.05), serum concentrations being higher than cyst fluid concentrations.


Predictors of Clostridium difficile infection and predictive impact of probiotic use in a diverse hospital-wide cohort.
Hospital-based predictive models for Clostridium difficile infection (CDI) may aid with surveillance efforts. A retrospective cohort of adult hospitalized patients who were tested for CDI between May 1, 2011, and August 31, 2016, was formed. Proposed clinical and sociodemographic predictors of CDI were evaluated using multivariable predictive logistic regression modeling. In a cohort of 5,209 patients, including 1,092 CDI cases, emergency department location (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.51, 2.41; compared with an intensive care unit reference category, which had the lowest observed odds in the study) and prior exposure to a statin (aOR, 1.26, 95% CI, 1.06, 1.51), probiotic (aOR, 1.39; 95% CI, 1.08, 1.80), or high-risk antibiotic (aOR, 1.54; 95% CI, 1.29, 1.84), such as a cephalosporin, a quinolone, or clindamycin, were independent predictors of CDI. Probiotic use did not appear to attenuate the odds of CDI in patients exposed to high-risk antibiotics, but moderate-risk antibiotics appeared to significantly attenuate the odds of CDI in patients who received probiotics. Emergency department location, high-risk antibiotics, probiotics, and statins were independently predictive of CDI. Further exploration of the relationship between probiotics and CDI, especially in diverse patient populations, is warranted.


Atrial natriuretic peptide increases human capillary filtration and venous distensibility.
The main aim of this study was to examine whether atrial natriuretic peptide (ANP) alters capillary filtration and venous distensibility. The study was designed to examine the local effects of i.a. infusion of ANP upon capillary filtration and venous distensibility in human forearms of eight healthy volunteers. Using a water plethysmograph, we measured venous distensibility and capillary filtration from changes in forearm volume when transmural venous pressure was increased in a stepwise manner and held constant during i.a. infusion of saline, ANP and sodium nitroprusside (SNP). The doses of ANP and SNP were chosen to double baseline forearm blood flow obtained during saline infusion. ANP and SNP infusion both increased venous distensibility to the same extent compared with saline infusion. Capillary filtration was greater during ANP than during saline or SNP infusion. Small vein pressure was comparable during infusion of the two drugs. Our results suggest that ANP increases venous distensibility and capillary filtration in human forearms.


Withholding of resuscitation for adult traumatic cardiopulmonary arrest.
The National Association of EMS Physicians (NAEMSP) and the American College of Surgeons Committee on Trauma (ACS-COT) believe that it is appropriate to withhold resuscitation for certain trauma patients for whom death is the predictable outcome. This paper is the official statement on the withholding of resuscitation that has jointly been passed by the NAEMSP and ACS-COT.


Thrombectomy after in-house stroke in the transfer population.
Patients with large-vessel occlusion (LVO) who initially present to a non-thrombectomy-capable center ("spoke") have worse outcomes than those presenting directly to a thrombectomy-capable center ("hub"). Furthermore, patients who suffer in-hospital strokes (IHS) suffer worse outcomes than those suffering strokes in the community. Data on patients who suffer IHS at a spoke hospital is lacking. We aim to characterize this particularly vulnerable population, define their outcomes, and compare them to patients who develop IHS at a hub institution. We retrospectively reviewed prospectively collected data from patients suffering an IHS at a spoke hospital who were then transferred to the hub hospital for endovascular therapy (EVT). We then compared outcomes of these patients under EVT after developing IHS at the hub institution. A total of 108 IHS patients met inclusion criteria: 91 (84%) at a spoke facility and 17 (16%) at the hub facility. Baseline characteristics and reason for hospital admission were comparable between the two groups. Time from imaging to IV-tPA administration (17 vs. 70 min, p = 0.01) and time to EVT (120 vs. 247 min, p = 0.001) were significantly shorter in the hub group. More patients had a 90 day-mRS of 0-3 in the hub group than the spoke group (57% vs 22%, p < 0.05). Patients undergoing EVT after suffering IHS at a spoke hospital have significantly higher rates of poor outcomes compared to patients who suffer IHS at a hub hospital. Prolonged time delays in the initiation of IV-tPA and EVT represent areas of improvement.


A stereological ultrastructural study of stimulated peritoneal macrophages in the germ-free mouse.
Peritoneal macrophage ultrastructure was analysed stereologically in germ-free mice given a single intraperitoneal injection of sterile, pyrogen-free saline. Thus the stimulant was non-particulate, non-antigenic and inorganic, and effects of immune reactions were minimal. Macrophages were recovered 1, 6, 24 and 72 h after stimulation. A sequence of structural alterations is reported which may be fundamental to macrophage activation. The plasma membrane and nuclear envelope increased in area within only 1 h of saline injection. During the next 5 h loss of plasma membrane, probably by pinocytosis, caused cellular "rounding" and clear-cut alteration in surface configuration. At the same time lysosome-like granules enlarged but decreased in number. By 24 h most cellular structures and compartments (including the plasma membrane) were enlarged. Morphological evidence of nuclear activation accompanied a rather modest enlargement of the nucleus at this stage. The RER hypertrophied last and must, therefore, be judged sufficient in resident macrophages to support the initial growth response which results after stimulation. Thus hypertrophy was observed eventually in every structure examined. Even the minimally activated macrophages resident in the peritoneum of germ-free mice respond readily to stimulation.


Creating a Learning Health System for Improving Diagnostic Safety: Pragmatic Insights from US Health Care Organizations.
To identify challenges and pragmatic strategies for improving diagnostic safety at an organizational level using concepts from learning health systems METHODS: We interviewed 32 safety leaders across the USA on how their organizations approach diagnostic safety. Participants were recruited through email and represented geographically diverse academic and non-academic settings. The interview included questions on culture of reporting and learning from diagnostic errors; data gathering and analysis activities; diagnostic training and educational activities; and engagement of clinical leadership, staff, patients, and families in diagnostic safety activities. We conducted an inductive content analysis of interview transcripts and two reviewers coded all data. Of 32 participants, 12 reported having a specific program to address diagnostic errors. Multiple barriers to implement diagnostic safety activities emerged: serious concerns about psychological safety associated with diagnostic error; lack of infrastructure for measurement, monitoring, and improvement activities related to diagnosis; lack of leadership investment, which was often diverted to competing priorities related to publicly reported measures or other incentives; and lack of dedicated teams to work on diagnostic safety. Participants provided several strategies to overcome barriers including adapting trigger tools to identify safety events, engaging patients in diagnostic safety, and appointing dedicated diagnostic safety champions. Several foundational building blocks related to learning health systems could inform organizational efforts to reduce diagnostic error. Promoting an organizational culture specific to diagnostic safety, using science and informatics to improve measurement and analysis, leadership incentives to build institutional capacity to address diagnostic errors, and patient engagement in diagnostic safety activities can enable progress.


Sexual dimorphism in the Chinese femur.
In the last decade, there has been renewed interest in contemporary and ancient Chinese skeletal populations. The purpose of this research is the osteometric assessment of sexual dimorphism in recent mainland Chinese cemetery populations and the development of discriminant function standards to determine sex from the femur. The sample for this project was composed of 87 adult skeletons from cemeteries in Chang Chun City (Liaoning) and Qingdao (Shandong). A total of six femoral measurements was taken and subjected to SPSS discriminant function analysis. Three dimensions were selected by the stepwise analysis in the following order: distal epiphyseal breadth, maximum length, and anteroposterior diameter of the midshaft. This function produced 92.3% classification accuracy. Direct analysis revealed that distal epiphyseal breadth alone provided an even better separation (94.9%). The remaining functions were less discriminating. In conclusion, distal epiphyseal breadth is the most dimorphic part of the Chinese femur. This contrasts with earlier findings on American Whites and Blacks in which head diameter is the most dimorphic. This and other significant differences underscore the necessity of obtaining population-specific values for metric analysis of sex. These findings also support previous studies indicating that linear dimensions such as length are often less discriminating than breadth and circumference measurements in long bones. Finally, the fact that maximum dimorphism was found at a major weight-bearing joint suggests that the size differentials between Chinese males and females may be in large part functional in nature, perhaps arising from sex-specific physical activities.


Clinical utility of self- and informant-reported memory, attention, and spatial navigation in detecting biomarkers associated with Alzheimer disease in clinically normal adults.
Preclinical Alzheimer disease (AD) has been associated with subtle changes in memory, attention, and spatial navigation abilities. The current study examined whether self- and informant-reported domain-specific cognitive changes are sensitive to AD-associated biomarkers. Clinically normal adults aged 56-93 and their informants completed the memory, divided attention, and visuospatial abilities (which assesses spatial navigation) subsections of the Everyday Cognition Scale (ECog). Reliability and validity of these subsections were examined using Cronbach's alpha and confirmatory factor analysis. Logistic regression was used to examine the ability of ECog subsections to predict AD-related biomarkers (cerebrospinal fluid (CSF) ptau181/Aβ42 ratio (N = 371) or hippocampal volume (N = 313)). Hierarchical logistic regression was used to examine whether the self-reported subsections continued to predict biomarkers when controlling for depressive symptomatology if available (N = 197). Additionally, logistic regression was used to examine the ability of neuropsychological composites assessing the same or similar cognitive domains as the subsections (memory, executive function, and visuospatial abilities) to predict biomarkers to allow for comparison of the predictive ability of subjective and objective measures. All subsections demonstrated appropriate reliability and validity. Self-reported memory (with outliers removed) was the only significant predictor of AD biomarker positivity (i.e., CSF ptau181/Aβ42 ratio; p = .018) but was not significant when examined in the subsample with depressive symptomatology available (p = .517). Self-reported memory (with outliers removed) was a significant predictor of CSF ptau181/Aβ42 ratio biomarker positivity when the objective memory composite was included in the model. ECog subsections were not robust predictors of AD biomarker positivity.


Management of pediatric patients with pseudotumor cerebri.
The care of patients with pseudotumor cerebri (idiopathic intracranial hypertension) involves ophthalmologists, neurologists and neurosurgeons. Its clinical characteristics in the pediatric population are distinct from those in adult patients. Fifty-nine patients diagnosed with pseudotumor cerebri were identified from the neurosurgery and neurology databases at Children's Hospital, Birmingham, AL, USA. Clinical data were collected from the ophthalmology, neurology and neurosurgery departments. The average age of patients at diagnosis was 11.4 years (range 3-17). The average opening pressure of lumbar puncture (LP) was 37 cm of water. Most of the patients responded well to therapeutic LPs and medical management. Neurosurgical interventions included intracranial pressure monitoring and shunt insertion in nine patients. In three patients who presented with acute visual decline, two recovered and one remains legally blind. The care of patients with pseudotumor cerebri requires a multiple-disciplinary approach. Neurosurgical interventions are sometimes needed for diagnostic and treatment purpose. Prompt and accurate communication among specialists is necessary to ensure timely treatment and optimal outcomes.


Localization of atherosclerotic lesions in the bifurcation of the main left coronary artery.
The detailed distribution of atherosclerotic lesions in the branching region of the left main coronary artery in man was studied. Tissue cubes of the hearts, containing the left coronary arteries, were removed, and 1.5-mm-thick parallel and consecutive slices were cut perpendicular to the main coronary artery. Histological sections of the slices were stained and photographed. Drawings of the cross-sections of the arteries, including information about thickness of the intima and borders of the atherosclerotic lesions, were fed into a computer, scaled and analyzed. Casts were made of the left main coronary bifurcation from additional hearts. The curvature of the arteries and the angles of the bifurcation were measured. Atherosclerotic lesions have a distinct pattern with a high frequency on the outer walls of the bifurcation and at the inner curvature downstream from the bifurcation. The extent of intimal thickening and the occurrence of atherosclerotic lesions were mostly in agreement.


Synthesis of a robust, water-stable, and biodegradable pulp foam by poly-lactic acid coating towards a zero-plastic earth.
Biodegradable cellulosic pulp foams with robustness and water resistance are urgently needed in nowadays to replace petroleum-based plastic foams for environmental sustainability. In this work, a facile protocol to fabricate robust poly-lactic acid (PLA) coated cellulose foams (PCCF) was developed through a combined water-based foaming and PLA melt-coating process using pulp as the raw material. In the synthesis, the so-called PLA coating was realized through melting PLA powders dispersed between fibers by an in-situ heating and post cooling process. Performance tests revealed that the incorporation of PLA coating significantly enhances mechanical strength, water stability, and biodegradability of the synthesized PCCF samples compared with conventional cellulosic foams. Specifically, the low-density PCCF were observed with mechanical strength up to 81.24 kPa, high water stability, and more than 95% degradation in 56 days. As the fabrication process is simple and pulp is highly cost competitive, our proposed synthesis strategy makes the PCCF a promising substitute for petroleum-based plastic foams at large-scale production.


Examining key sociodemographic characteristics of adolescents and young adults with cancer: A post hoc analysis of the Promoting Resilience in Stress Management randomized clinical trial.
The "Promoting Resilience in Stress Management" intervention is a skills-based, early palliative care intervention with demonstrated efficacy in adolescents and young adults with cancer. Utilizing data from a randomized clinical trial of Promoting Resilience in Stress Management versus Usual Care, we examined whether response to Promoting Resilience in Stress Management differed across key sociodemographic characteristics. Adolescents and young adults with cancer completed patient-reported outcome measures of resilience, hope, benefit-finding, quality of life, and distress at enrollment and 6 months. Participants were stratified by sex, age, race, and neighborhood socioeconomic disadvantage based on home address (Area Deprivation Index scores with 8-10 = most disadvantaged). Differences in the magnitude of effect sizes between stratification subgroups were noted using a conservative cutoff of d > 0.5. Participants were 12 to 25 years old, English-speaking, and receiving cancer care at Seattle Children's Hospital. In total, 92 adolescents and young adults (48 Promoting Resilience in Stress Management, 44 Usual Care) completed baseline measures. They were 43% female, 73% 12 to 17 years old, 64% White, and 24% most disadvantaged. Effect sizes stratified by sex, age, and race were in an expected positive direction and of similar magnitude for the majority of outcomes with some exceptions in magnitude of treatment effect. Those who lived in less disadvantaged neighborhoods benefited more from Promoting Resilience in Stress Management, and those living in most disadvantaged neighborhoods benefited less. The "Promoting Resilience in Stress Management" intervention demonstrated a positive effect for the majority of outcomes regardless of sex, age, and race. It may not be as helpful for adolescents and young adults living in disadvantaged neighborhoods. Future studies must confirm its generalizability and integrate opportunities for improvement by targeting individual needs.


Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.
The ability to couple with multiple G protein subtypes, such as Gs, Gi/o, or Gq/11, by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with Gs protein, have been determined. However, no structure of class B GPCRs with Gq/11 has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G11 and Go. We compare these structures with the structure of CRF2R in complex with Gs to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.


Vaginal prostaglandin E2 for missed abortion and intrauterine fetal death.
Vaginal suppositories containing 20 mg. of prostaglandin E2 (PGE2) were given to 50 patients with a diagnosis of either missed abortion or fetal death. A total of 94 percent of the patients (47/50) expelled products of conception, and 84 percent of these expulsions (42/50) were complete. The mean time to expulsion of the fetus was 11.3 hours with a mean dose of 3.6 suppositiries. A total 60 per cent of the patients experienced vomiting, diarrhea, and pyrexia. Four patients had a blood loss in excess of 500 ml., and two of these patients required blood transfusion. Vaginal administration of PGE2 suppositories appeared to be a rapid, safe, and reliable means of managing missed abortion and intrauterine fetal death.


Effect of dietary docosahexaenoic acid on biosynthesis of docosahexaenoic acid from alpha-linolenic acid in young rats.
Docosahexaenoic acid (DHA), a crucial nervous system n-3 PUFA, may be obtained in the diet or synthesized in vivo from dietary alpha-linolenic acid (LNA). We addressed whether DHA synthesis is regulated by the availability of dietary DHA in artificially reared rat pups, during p8 to p28 development. Over 20 days, one group of rat pups was continuously fed deuterium-labeled LNA (d5-LNA) and no other n-3 PUFA (d5-LNA diet), and a second group of rat pups was fed a d5-LNA diet with unlabeled DHA (d5-LNA + DHA diet). The rat pups were then euthanized, and the total amount of deuterium-labeled docosahexaenoic acid (d5-DHA) (synthesized DHA) as well as other n-3 fatty acids present in various body tissues, was quantified. In the d5-LNA + DHA group, the presence of dietary DHA led to a marked decrease (3- to 5-fold) in the total amount of d5-DHA that accumulated in all tissues that we examined, except in adipose. Overall, DHA accretion from d5-DHA was generally diminished by availability of dietary preformed DHA, inasmuch as this was found to be the predominant source of tissue DHA. When preformed DHA was unavailable, d5-DHA and unlabeled DHA were preferentially accreted in some tissues along with a net loss of unlabeled DHA from other organs.