Hypersomnolence and reduced activity in pan-leptin receptor knockout mice.
Excessive obesity correlates with hypersomnolence and impaired cognitive function, presumably induced by metabolic factors and cytokines. Production of the adipokine leptin correlates with the amount of adiposity, and leptin has been shown to promote sleep. To determine whether leptin plays a major role in the hypersomnolence of obesity, we measured sleep architecture in pan-leptin receptor knockout (POKO) mice that do not respond to leptin because of the production of a mutant, non-signaling receptor. The obese POKO mice had more non-rapid eye movement (NREM) sleep and less waking time than their littermate controls. This was mainly seen during the light span, although increased bouts of rapid eye movement sleep were also seen in the dark span. The increase of NREM sleep correlated with the extent of obesity. The POKO mice also had decreased locomotor activity and more immobility in the open field test, but there was no increase of forced immobility nor reduction of sucrose intake as would be seen in depression. The increased NREM sleep and reduced locomotor activity in the POKO mice suggest that it was obesity, rather than leptin signaling, that played a predominant role in altering sleep architecture and activity.


Studies with neuronal cells: From basic studies of mechanisms of neurotoxicity to the prediction of chemical toxicity.
Neurotoxicology considers that chemicals perturb neurological functions by interfering with the structure or function of neural pathways, circuits and systems. Using in vitro methods for neurotoxicity studies should include evaluation of specific targets for the functionalism of the nervous system and general cellular targets. In this review we present the neuronal characteristics of primary cultures of cortical neurons and of cerebellar granule cells and their use in neurotoxicity studies. Primary cultures of cortical neurons are constituted by around 40% of GABAergic neurons, whereas primary cultures of cerebellar granule cells are mainly constituted by glutamatergic neurons. Both cultures express functional GABAA and ionotropic glutamate receptors. We present neurotoxicity studies performed in these cell cultures, where specific neural targets related to GABA and glutamate neurotransmission are evaluated. The effects of convulsant polychlorocycloalkane pesticides on the GABAA, glycine and NMDA receptors points to the GABAA receptor as the neural target that accounts for their in vivo acute toxicity, whereas NMDA disturbance might be relevant for long-term toxicity. Several compounds from a list of reference compounds, whose severe human poisoning result in convulsions, inhibited the GABAA receptor. We also present cell proteomic studies showing that the neurotoxic contaminant methylmercury affect mitochondrial proteins. We conclude that the in vitro assays that have been developed can be useful for their inclusion in an in vitro test battery to predict human toxicity.


Navafenterol (AZD8871) in patients with mild asthma: a randomised placebo-controlled phase I study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of this novel inhaled long-acting dual-pharmacology bronchodilator.
Navafenterol (AZD8871) is an inhaled long-acting dual-pharmacology muscarinic antagonist/β2-adrenoceptor agonist (MABA) in development for the treatment of obstructive airways diseases. The safety, tolerability, pharmacodynamics, and pharmacokinetics of navafenterol were investigated in patients with mild asthma. This was a randomised, single-blind, placebo-controlled, single-ascending-dose study. Patients were randomly assigned to one of two cohorts which evaluated escalating doses of navafenterol (50-2100 μg) in an alternating manner over three treatment periods. The primary pharmacodynamic endpoint was the change from pre-dose baseline in trough forced expiratory volume in 1 s (FEV1) for each treatment period. Sixteen patients were randomised; 15 completed treatment. Data from all 16 patients were analysed. The maximum tolerated dose was not identified, and all doses of navafenterol were well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were headache (n = 10, 62.5%) and nasopharyngitis (n = 7, 43.8%). No TEAEs were serious, fatal, or led to discontinuation, and no dose dependency was identified. Navafenterol demonstrated a dose-ordered bronchodilatory response with a rapid onset of action (within 5 min post-dose). Doses ≥200 μg resulted in improvements in trough FEV1 (mean change from baseline range 0.186-0.463 L) with sustained bronchodilation for 24-36 h. Plasma concentrations increased in a dose-proportional manner, peaking ~ 1 h post-dose, with a derived terminal elimination half-life of 15.96-23.10 h. In this study navafenterol was generally well tolerated with a rapid onset of action which was sustained over 36 h. ClinicalTrials.gov; No.: NCT02573155.


The role of nitric oxide in resistance to P. aeruginosa ocular infection.
This study determined the role of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the resistance response of BALB/c mice to P. aeruginosa-induced keratitis. RT-PCR, nitrite detection, iNOS inhibition, ELISA, and immunohistochemistry were used. Early after infection, iNOS mRNA expression and nitrite levels in cornea were elevated compared to levels in the uninfected cornea. Treatment with aminoguanidine sulfate (AG), an inhibitor of iNOS, resulted in extensive corneal destruction, reduced nitrite levels, and reduced nitrotyrosine staining. Infected mice also had increased bacterial burden and elevated levels of MIP-1alpha, IL-1beta, and MIP-2 in the cornea. Dual-labeling immunohistochemistry established the macrophage as the major source of iNOS in the infected cornea. These data provide evidence that iNOS is constitutively expressed in the BALB/c cornea; that iNOS-derived NO is required for bacterial killing/stasis; and that the macrophage is the major cell source of NO.


[Number of smokers in students (results of a panel-study)].
65% of female and 45% of male enrolers score as non-smokers. This number does not change much in time of study. After studentship this number does not increase also, but the number of cigarettes smoked by the smokers is increasing. As the results of the panel-study (2000 students) show are the habits of smoking/non-smoking very stable. Smokers and non-smokers differ in various traits of personality.


Quantitative relationship between rate constants and molecular structure descriptors for the gas phase hydrogen abstraction reactions.
The abstraction of hydrogen by general radicals has a wide role in environmental and also in technological processes because it results in reactive free radicals that play a vital role in atmospheric chemistry and also in biochemical processes. In addition to experimental studies, the theoretical modelling of this elementary reaction has been important for understanding and predicting respective rate constants. In this paper, molecular descriptors in the context of a QSAR approach are used to codify the relationship between molecular structure and rate constants. Unique experimental data is collected from the literature for the reaction R(i)• + R(j)H → R(i)H + R(j)•, where R(i)• = H• and R(j)• are diverse radicals. The four-parameter QSAR model (n = 34, r(2) = 0.81, r(2)(CV) = 0.74, r(2)(scr) = 0.12, s(2) = 0.19) is presented for the bimolecular rate constants, accompanied with model diagnostics and analysis of descriptors in the model.


Mycotoxicosis produced in swine by cultural products of an isolate of Aspergillus ochraceus. I. Clinical observations and pathology.
Pigs fed a ration, 25% of which was rice culture, of Aspergillus ochraceus lost weight or failed to gain and became depressed. Some pigs died and most developed subcutaneous edema, hydrothorax, hydroperitoneum, pulmonary atelectasis, edema of the mesentery and perirenal edema. Microscopic lesions in addition to edema were primarily renal and consisted of tubular degeneration and necrosis, hyaline tubular casts, interstitial fibrosis and tubular cell regeneration. The first change found after 3 days was cytoplasmic vacuolation of the convoluted and straight segments of the proximal tubules. Necrotic proximal tubules were found after 4 days and after 9 days degeneration and necrosis involved predominantly proximal tubular segments. Pigs fed a ration, 12.5% of which was rice culture, for 8 weeks did not develop perirenal edema but had firm kidneys. Extensive interstitial fibrosis of the cortical labyrinth was the principal change. Within the fibrous connective tissue, some tubules were necrotic and others were atrophied.


Diagnostic audit of C-reactive protein in neonatal infection.
A prospective study of 250 consecutive neonatal admissions to a regional perinatal referral centre and of 10 additional consecutive cases with culture-proven neonatal septicaemia was undertaken. Quantitative C-reactive protein (CRP) determination, white cell count and differential were performed on blood samples obtained from all babies on admission, as well as 10-14 h and 22-26 h later. Using clinical signs, chest X-rays, blood cultures, tracheal aspirates obtained within 4 h of delivery and an abnormal immature/total neutrophil ratio (I/T), infected babies were defined as belonging to one of the following groups: culture-proven septicaemia (n = 19); clinical septicaemia (n = 35); congenital pneumonia (n = 28). The sensitivity, specificity, positive and negative predictive value of CRP were calculated for each sampling time and patient group. No baby had a rise in CRP (greater than 6 mg/l) before an abnormal I/T ratio was first detected. A delayed rise in CRP concentration in the majority of infected babies occurred approximately 12-24 h after the abnormal I/T ratio was first detected. The overall specificity of a CRP level of greater than or equal to 10 mg/l remained approximately constant (97%-94%) while sensitivity increased from 22%-61% with increasing time after admission. The same pattern emerged if each patient group was considered separately. The positive predictive value for a CRP level of greater than or equal to 10 mg/l 22-26 h after admission was 83% and the negative predictive value 82%. CRP had no value in the early diagnosis of neonatal infection. Its main role lies rather in the exclusion or confirmation of infection 24 h after the first clinical suspicion.


Is coagulase-negative staphylococcal bacteraemia in neonates a consequence of mechanical ventilation?
The clinical symptoms associated with coagulase-negative staphylococcal bacteraemia in infants on a Special Care Baby Unit were investigated. They were compared with those of blood culture-negative controls matched for age and weight. Infants with positive cultures were further sub-divided by judging the isolate to be a contaminant or a pathogen. There was a high incidence of respiratory symptoms in the latter patients, particularly in infants of less than 37 weeks gestation. These symptoms often responded to antimicrobial chemotherapy, particularly in infants given correct antibiotics, as demonstrated by laboratory sensitivity testing. Bacteraemia was usually detected shortly after starting mechanical ventilation, and may be its consequence in premature infants. Gentamicin-resistance occurred in over 50 per cent of blood culture isolates of coagulase-negative staphylococci. We postulate that coagulase-negative staphylococci can be a neonatal pathogen requiring appropriate antimicrobial chemotherapy.


CD72-mediated suppression of human naive B cell differentiation by down-regulating X-box binding protein 1.
B cells can differentiate into antibody-secreting plasma cells, however the signals that control the entry into this pathway are not clearly understood. We have investigated the role of human CD72 in mature B cell differentiation. Human CD72 is preferentially expressed in naive B cells, but marginal levels of expression can be found in switched memory B cells. CD72 cross-linking promoted an increase in B cell activation and proliferation. Interestingly, expression of CD27, whose signal induces the differentiation of B cells into plasma cells, was down-modulated by CD72 stimulation. This CD72 signaling also induced tyrosine phosphorylation of various proteins such as Blk. Plasma cell differentiation and Ig syntheses were diminished by CD72 ligation in the presence of Staphylococcus aureus Cowan strain (SAC) plus IL-2 but not in the presence of CD40 signaling or CpG oligodeoxynucleotide. Our results show that CD72 signaling reduces the expression of X-box binding protein 1 in B cells stimulated with SAC plus IL-2, but the expression of PRDI-BF1 was unaffected. Taken together, these data demonstrate that CD72 is a key molecule in regulating mature B cell differentiation, particularly in preventing the differentiation of naive B cells into plasma cells, thus blocking the production of low-affinity antibodies.


Prognostic factors associated with outcomes after giant retinal tear management using perfluorocarbon liquids.
To identify prognostic factors for visual acuity and anatomic outcomes associated with giant retinal tear management using intraoperative perfluorocarbon liquids. All patients with giant retinal tears without proliferative vitreoretinopathy (PVR) who underwent management with intraoperative perfluorocarbon liquids between 1994 and 2005 were reviewed. The study included 115 patients (117 eyes), 93 (80.9%) males and 22 (19.1%) females, with a mean age of 30.3+/-15.2 years. Mean follow-up period was 29.7+/-26.7 months. Success rate with primary procedure was 78.6%, which increased to 94% with multiple surgeries. On univariate analysis, factors significantly associated with final visual acuity better than 20/200 included phakic/clear lens at presentation (p=0.0113), partial retinal detachment (p=0.0233), absence of all postoperative complications (p=0.0122), absence of recurrent retinal detachment (p=0.0406), and absence of postoperative PVR (p=0.0062). Logistic regression analysis highlighted that phakic/clear lens at presentation, unfolded flap of the giant tear, absence of postoperative cataract, and absence of postoperative PVR were associated with final visual acuity better than 20/200. On univariate analysis, use of gas tamponade was significantly associated with recurrent retinal detachment (p=0.0190). Logistic regression analysis highlighted that placement of an encircling scleral buckle and use of silicone oil tamponade were associated with anatomic reattachment with primary procedure. Encircling scleral buckling and silicone oil tamponade decrease the risk of recurrent retinal detachment.


[Combination primary restorative surgical interventions in cancer of the rectum in women].
In the past 15 years, 136 combined operations in women with locally disseminated rectal cancer were performed. Eighty-two (60.3%) operations were primary-restorative. After them, the lethality was 2.9%, 3- and 5-year survival--64 and 40%, respectively. The performance of the combined sphincter-preserving operations is expedient, despite the spreading of the primary tumour.


Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From the INTEGRAL-ILCCO Cohort Analysis.
Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls. We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal mCAs were detected in 4.3% of subjects, in addition to ChrX mCAs in 3.6% of females and mChrY losses in 9.6% of males. Multivariable logistic regression analysis indicated that the presence of autosomal mCAs in white blood cells was associated with an increased lung cancer risk after adjusting for key confounding factors, including age, sex, smoking status, and race. This association was mainly driven by a specific type of mCAs: copy-neutral loss of heterozygosity on autosomal chromosomes. The association between autosome copy-neutral loss of heterozygosity and increased risk of lung cancer was further confirmed in two major histologic subtypes, lung adenocarcinoma and squamous cell carcinoma. In addition, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared with nonsmokers and racial differences in certain types of mCA events. Our study established a link between mCAs in white blood cells and increased risk of lung cancer.


Clinical application of 11-deoxycortisol in visualizing prolapsed vitreous body after posterior capsule rupture in cataract surgery.
To evaluate the clinical usefulness of 11-deoxycortisol, a precursor of cortisol in steroid metabolism, in visualizing the vitreous body in the anterior chamber after posterior capsule rupture during cataract surgery. Department of Ophthalmology, Tsukuba University Hospital, Ibaraki, Japan. Eight eyes had anterior vitrectomy during cataract surgery using this new technique. A suspension of 11-deoxycortisol was prepared by dilution in balanced salt solution without preservatives or emulsifying agents. After a posterior capsule rupture, the suspension was injected into the anterior chamber. The visual and anatomical outcomes of surgery were evaluated during a follow-up of 7 to 9 months. After the 11-deoxycortisol injection, the vitreous body that had prolapsed through the torn posterior capsule, with white particles entrapped on its surface, became clearly visible. Complete removal of the prolapsed vitreous body was achieved easily and safely using an anterior vitrectomy system. No postoperative complications related to the use of 11-deoxycortisol were observed. Injection of 11-deoxycortisol helped visualize the vitreous body in the anterior chamber after posterior capsule rupture. The technique minimized intraoperative and postoperative complications related to posterior capsule rupture and vitreous loss during cataract surgery [corrected]


Protection Efficacy of Recombinant HVT-ND-LT and the Live Attenuated Tissue Culture Origin Vaccines Against Infectious Laryngotracheitis Virus When Administered Individually or in Combination.
Infectious laryngotracheitis (ILT) is a respiratory disease that causes significant economic losses to the poultry industry. Control of the disease is achieved by vaccination and implementation of biosecurity measures. The use of bivalent and trivalent recombinant herpesvirus of turkey (rHVT) vaccines expressing infectious laryngotracheitis virus (ILTV) genes has increased worldwide. In the United States, vaccination programs of long-lived birds (broiler breeders and commercial layers) against ILT include immunizations with either HVT recombinant vector vaccines, in ovo or at hatch, or live attenuated vaccines administered via drinking water (chicken embryo origin [CEO]) or eye drop (tissue culture origin [TCO]). The efficacy of bivalent rHVT-LT at hatch followed by drinking water or eye-drop CEO vaccination has been shown to provide more robust protection than rHVT-LT alone. The objective of this study was to evaluate the protection efficacy of a commercial trivalent rHVT-ND-LT when administered at 1 day of age followed by TCO vaccination via eye drop at 10 wk of age. Groups vaccinated with only rHVT-ND-LT or TCO, the combination of rHVT-ND-LT + TCO, and one nonvaccinated group of chickens were challenged with a virulent ILTV strain at 15 wk of age. After challenge, mortalities were prevented only in the group of chickens vaccinated with the rHVT-ND-LT + TCO. Clinical signs of the disease and challenge virus replication in the trachea were significantly reduced for both the rHVT-ND-LT + TCO- and TCO-vaccinated groups of chickens. To assess challenge virus transmission, contact-naive chickens were introduced to all vaccinated groups immediately after challenge. At 8 days postintroduction, infection of contact-naive chickens was evidenced in those introduced to the rHVT-ND-LT and TCO group but prevented in the rHVT-ND-LT + TCO group. Overall, these results indicated that compared to rHVT-ND-LT or TCO when administered alone, the rHVT-ND-LT + TCO vaccination strategy improved protection against disease and reduced shedding of the challenge virus.


Late results of total correction of tetralogy of Fallot in adults.
Between 1966 and 1986, 30 patients underwent total correction of the tetralogy of Fallot. Preoperative presenting features were: dyspnoea on exertion, clubbing, cyanosis and polycythaemia. Twenty-six patients had one or more palliative procedures prior to definitive repair. Preoperatively, all patients had a significant gradient across the right ventricular outflow tract (mean gradient 70 +/- 46 mmHg). Peak right ventricle to left ventricle systolic pressure ratio (pRV/LV) was 0.9 +/- 0.2. A functioning Blalock Taussig shunt was ligated in 11 patients prior to the institution of cardiopulmonary bypass. All patients had a patch closure of the ventricular septal defect. An additional muscle bundle resection from the right ventricular outflow tract was performed in 15, pulmonary valvotomy in 6 and enlargement of the right ventricular outflow tract in 2 patients. There was a significant fall in pRV/LV ratio postoperatively (P less than 0.05). There were 3 early and 2 late deaths. Mild right ventricular outflow tract obstruction has persisted in all survivors. Four patients have remained on antiarrhythmic drugs. Long term results after definitive repair were satisfactory in this group of adult patients who have survived due to palliative procedures performed during childhood.


Contribution of combined colposcopy and cytology in cervical pathology.
The regular Papanicolaou (Pap) smear is the cornerstone of women's preventive healthcare. The introduction of the regular Pap smear as a screening tool for cervical cancer has markedly decreased the number of deaths from cervical cancer. During the past decade, however, the rate of death from cervical cancer has remained relatively static. This screening method is known to have a high percentage of false negative results. To improve the detection of cervical lesions using the Pap smear in screening, a number of adjunct procedures have been developed. The purpose of this study is to evaluate the utility of a magnified chemoluminescent screening examination (Colposcopy) combined with the Pap smear in detecting cervical abnormalities. We investigated a cohort of 58 subjects who have been forwarded for colposcopic evaluation due to referral cytology suggestive of persistent inflammatory process not otherwise specified, and cervical intraepithelial or invasive neoplasia, in Chania Colposcopic clinic. The higher the lesion detected by cytology, the more severe the corresponding colposcopic impression viewed. The data presented here are in harmony with previous reports and share our experience in a Regional Community Hospital Colposcopy Clinic. An integrated cytology-colposcopy program facilitates the assessment and identification of women harboring cervical pathological conditions.


Gene bookmarking: keeping the pages open.
'Gene bookmarking' is a mechanism of epigenetic memory that functions to transmit through mitosis the pattern of active genes and/or genes that can be activated to daughter cells. It is thought that, at a point before mitosis, genes that exist in an open, transcriptionally competent state are bound by proteins or marked by some kind of modification event. This is thought to facilitate the assembly of transcription complexes on the promoters in early G1, thereby ensuring that daughter cells have the same pattern of gene expression as the cell from which they derived. Little is known, however, about these 'bookmarking factors' and modifications or the mechanisms by which they mediate the transmission of transcriptional competence after mitosis is complete. Recent findings have provided new insights into the mechanisms, regulation and biological importance of gene bookmarking in eukaryotic cell function.


Rates of Readmission and Emergency Department Visits of Publicly Versus Commercially Insured Patients in a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Accredited Center.
Patients with governmental insurance are known to utilize the emergency department (ER) at a higher rate and have higher readmission rates than other patients. Twenty percent of our patients are publicly insured. Our objective was to determine if there was a higher rate of readmissions and ER visits within 30 days in publicly insured patients. Data was analyzed from a single center submitted to the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Participant Use Data File from January 1, 2015 to December 31, 2018. We added insurance status and described quantitative variables using mean, and standard deviation (SD). These were reported as regression coefficients (RC) and prevalence ratio (PR), along with their 95% confidence interval (CI). P values of less than 5% were considered statistically significant. The overall rate of ER visits, readmissions, and reoperations were 3.5%, 7.4%, and 2.2% respectively. Medicaid and Medicare patients were found to have longer operative times, 62.7 minutes vs 57.5 minutes (p = 0.35). Patients on public insurance had higher adjusted risk of ER visits (PR 1.43, 95% CI: 0.41-5.3; p = 0.58) and readmissions (PR 1.64, 95% CI: 0.76-3.55; p = 0.21) than patients on commercial/self-pay insurance. Re-operations were lower in the publicly insured group (PR 0.93, 95% CI: 0.2-4.7; p = 0.92) than patients on commercial/self-pay insurance. However, these outcomes were not statistically significant. Publicly insured patients tend to have a higher adjusted risk of ER visits and readmissions but was not statistically significant. The rate of re-operation was slightly lower in publicly insured patients.


Noncontact erection is enhanced by Ginkgo biloba treatment in rats: role of neuronal NOS in the paraventricular nucleus and sacral spinal cord.
Nitric oxide (NO) is an important messenger mediating erection in the central nervous system (CNS). Paraventricular nucleus (PVN) neurons can be activated by NO and project the signals to the sacral spinal cord, which is involved in regulation of erection. Ginkgo biloba extract (EGb 761) facilitates noncontact erection (NCE) in rats; however, it is not clear whether EGb 761 increased NCE is associated with NO. The present study was designed to investigate the effects of neuronal nitric oxide synthase (nNOS) on NCE in rats following EGb 761 treatment. Adult Long-Evans male rats were treated with 50 mg/kg of EGb 761 or distilled water for 14 days. The NCE test was performed after 14 days of EGb 761 treatment and the NCE frequency was recorded. Approximately 14 h following the NCE behavioral tests, animals were sacrificed, and nNOS activity in the PVN and S6-L1 spinal cord was measured by immunohistochemistry and western blotting, respectively. Treatment with 50 mg/kg of EGb 761 for 14 days increased the NCE numbers compared to either the controls treated with distilled water on the same day or the same group on day 0. Also, EGb 761 treatment enhanced nNOS-immunoreactive cell numbers in the PVN. Furthermore, western blot analysis showed that EGb 761-treated animals displayed higher levels of nNOS expression in the S1 spinal cord than controls. Our results suggest that enhanced NCE in male rats administrated with EGb 761 may be related to the central nNOS activity in the PVN and the spinal cord.


Student participation in diabetic patient education.
As described, students who have participated in this innovative curriculum are familiar with individualized instruction. These students are thus experientially equipped to carry out the tasks of individualized patient education in the clinical setting. In the learning module the students study beginning teaching-learning principles and basic concepts of adult education in conjunction with learning to care for patients with endocrine dysfunction who require education for adaptation. Through the experience of assessing, planning, and implementing their own teaching in collaboration with the primary nurse and physician, the students learn to incorporate appropriate teaching behaviors into their concept of nursing. It is hoped that this knowledge and experience will make student nurses more effective nursing practitioners. This achievement is of utmost value to the consumer of nursing care.


Localization of natriuretic peptides in the cardiac pacemaker of Atlantic salmon (Salmo salar L.).
This study describes the location of the primary pacemaker at the sino-atrial (SA) junction and the localization of salmon cardiac peptide (sCP) and ventricular natriuretic peptide (VNP) in Atlantic salmon (Salmo salar L.). The pacemaker tissue appeared lightly stained and composed of: (1) wavy nerve bundles with oval elongated wavy appearing nuclei with pointed ends, (2) ganglion cells (12-22 μm) with granular cytoplasm and (3) wide muscle fibers with large nuclei (modified cardiomyocytes) clearly distinguishing them from the other myocardial cells. Pacemaker tissue was further evaluated using immunohistochemical staining. Immunoreactivity of natriuretic peptides (sCP and VNP) antisera showed specific staining in pacemaker ganglion cells in addition to the cardiomyocytes. Positive staining with anti-CD3ɛ antisera in the pacemaker ganglion cells is a novel finding in teleosts and is consistent with observations in mammals. In conclusion, the Atlantic salmon pacemaker was shown to be located at the SA node and to harbor sCP and VNP peptides, suggesting a possible neuromodulatory and/or neurotransmitter role for these cardiac hormones within the teleost heart.


Effect of L-fucose and fucose-rich oligo- and polysaccharides (FROP-s) on skin aging: penetration, skin tissue production and fibrillogenesis.
Skin thickness is decreasing with age. This loss concerns both dermis and epidermis, cells and extracellular matrix. We could show here that percutaneous application of an L-fucose-containing preparation produced an increase of skin thickness and a densification of collagen bundles. We also could show that 3H-L-fucose penetrates in the dermis, a prerequisite for the above mentioned favorable pharmacological activities. These results, together with the previous favorable activities on the downregulation of matrix-degrading enzymes, free radical scavenging and increased cell proliferation confirm the favorable action of fucose and fucose-rich polysaccharides (FROP-s) on the skin by slowing down its aging.


How to obtain a dermatology residency: a guide targeted to underrepresented in medicine medical students.
Efforts to increase diversity have been put forth by the Skin of Color Society (SOCS) to assist underrepresented in medicine (UIM) students during their pursuit of dermatology. Increasing diversity in dermatology relies on efforts from students and mentors established in dermatology. This article highlights and summarizes key guidelines from the SOCS.


[General practical survey of individual prostate cancer screening].
To assess the practices of general practitioners in the Auvergne region concerning individual prostate cancer screening, to compare these practices with published guidelines and to identify those points that are most difficult to perform. An anonymous postal survey using a predefined questionnaire was conducted among 1339 general practitioners in the Auvergne region identified by the URSSAF file on 1st January 2006. This was a declarative survey with no individual financial reward. The questionnaire comprised three aspects: general practitioner identification criteria, screening practices and the doctors' opinion concerning guidelines. The participation rate was 49.1: 98.3% of general practitioners declared that they proposed screening and 89.5% declared that they proposed screening to all men within certain age limits, from 50 to 75 years in 80.8% of cases. Only 4.6% of doctors provided complete preliminary information to their patients. Among the doctors,75.6% combined digital rectal examination and total PSA assay, but in the presence of an abnormality, only 10.5% referred their patients directly to an urologist without prescribing other complementary investigations (first- or second-line). Finally, 53.5% of doctors considered that published guidelines were adapted to their clinical practice. Individual prostate cancer screening is massively proposed, but differences are observed between the doctors' reported practices and official guidelines. This study emphasizes the need to provide patients with clear and complete information and to improve the general practitioners' knowledge on screening tests and patient referral in the case of positive screening tests.


Purchasing Habits, Sustainability Perceptions, and Welfare Concerns of Italian Consumers Regarding Rabbit Meat.
Several factors drive consumer behavior in buying meat, particularly rabbit meat. The consumption of rabbits has decreased in Europe, and the main causes of this trend are an increasing association with the perception of rabbits as pets, consumers' changes in lifestyle, and eating habits. Additionally, increasing attention is paid to ethical issues regarding animal welfare. Investigating consumers' knowledge, perceptions, and concerns about rabbit meat production and consumption are crucial for improving market strategies. This study investigated consumers' perspectives of rabbit meat to provide useful information to producers for promoting this sector to consumers. A mixed-methods research design was applied. Qualitative data were collected through four focus group discussions involving 32 consumers and quantitative data through a semi-structured questionnaire administered nationally and completed by 1001 consumers. The limited use of antibiotics in inbreeding and the absence of animal suffering are factors that most influence consumers' willingness to purchase rabbit meat. Rural/domestic farms were recognized as places where animal welfare measures can be applied and have a positive influence not only on organoleptic quality but also on ethical value and food safety. The cage was perceived as unsuitable for rabbit growth and was oriented to a process of fattening based on industrial feed and antibiotics. Respondents sought information on rabbit farming during purchase, and the label was the most used tool. The rabbit meat production sector should consider these results to meet consumers' demands and raise awareness among operators on the use of animal welfare-based farming systems, helping to build a more positive image of the rabbit meat industry.


Partial biochemical characterization of IgG1-inducing factor.
IgG1 induction factor elevates the IgG1 and suppresses the IgG3 and IgG2b responses in lipopolysaccharide-stimulated murine spleen cell cultures. By the use of a quantitative assay, it was found that the three activities, induction of IgG1 and reduction of IgG3 and IgG2b synthesis, were found in the same fractions after different chromatographic procedures, suggesting that the same molecule was responsible for the effects. The factor was precipitated by 60-90% saturation of ammonium sulfate and was sensitive to proteolytic cleavage and to treatment with a buffer of pH 10. It had an apparent molecular mass of 20 kDa as judged by gel filtration chromatography and was separated into two peaks after isoelectric focusing, pI 7.4-7.2 and 6.4-6.2, respectively. Finally it was weakly hydrophobic and negatively charged at pH 7.55. These characteristics indicate that the factor is different from many previously characterized lymphokines and similar or identical to the B cell stimulating factor-1 (BSF-p1). The relevance of these findings to the mechanism of the immunoglobulin class switch is discussed.


Unintentional Marijuana Exposure Presenting as Altered Mental Status in the Pediatric Emergency Department: A Case Series.
Unintentional tetrahydrocannabinol (THC) exposure in pediatric patients can present as altered mental status. Altered mental status in a pediatric patient often leads to invasive diagnostic testing. The following cases describe 3 pediatric patients in Washington state who presented to a tertiary care children's hospital emergency department (ED) with altered mental status, later found to have urine toxicology screening positive for inactive THC metabolite (positive THC toxicology screen). Case 1 is a 6-year-old boy who presented with vomiting, lethargy, and hallucinations. Case 2 is a 5-year-old girl who presented with nausea, slurred speech, ataxia, and lethargy in the setting of a minor head injury. Case 3 is a 7-month-old boy who presented with vomiting and lethargy in the setting of a minor fall the day prior to ED evaluation. All children had extensive work-ups before the diagnosis was made; 2 were discharged home and 1 was admitted to the pediatric intensive care unit. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As access to marijuana increases with growing legalization, it is important to be familiar with state marijuana legislation, to consider and ask families about access to marijuana products as a potential contributor to altered mental status, and to be aware of potential caretaker reluctance regarding disclosure of marijuana use secondary to perceived stigma. Maintaining awareness of the clinical effects of THC exposure in children may limit invasive testing in a hemodynamically stable child with altered mental status.


Hepatic microsomal metabolism of the dichloroethanes.
The binding of 1,1-dichloroethane (1,1-DCE) to the substrate binding site of hepatic microsomal cytochrome P-450, and the stimulation of hepatic microsomal CO-inhibitable NADPH oxidation by 1,1-DCE and 1,2-dichloroethane (1,2-DCE) were enhanced by induction with phenobarbital but not with beta-naphthoflavone. Incubation of the dichloroethanes with hepatic microsomes from phenobarbital-treated rats, NADPH-generating system and EDTA resulted in the conversion of 1,1-DCE to acetic acid and to a lesser extent to 2,2-dichloroethanol and probably also mono- and dichloroacetic acid and the conversion of 1,2-DCE to chloroacetaldehyde and to a lesser extent to chloroacetic acid and probably 2-chloroethanol. In addition, reaction mixtures constituted as described above resulted in slight but significant losses (ca. 13%) of hepatic microsomal cytochrome P-450. The omission of dichloroethane or the NADPH-generating system from incubation mixtures eliminated the above effects, and SKF-525A or CO diminished or eliminated the effects. Pathways for the metabolism of 1,1-DCE and 1,2-DCE are proposed.


Clinicopathological characteristics of intrahepatic cholangiocarcinoma according to gross morphologic type: cholangiolocellular differentiation traits and inflammation- and proliferation-phenotypes.
Intrahepatic cholangiocarcinoma (iCCA) is subclassified into mass-forming (MF), periductal-infiltrative (PI), and mixed types grossly; however, their clinicopathological significance remains controversial. Clinicopathological characteristics of iCCA gross types were analysed according to histopathological type (small-duct, large-duct, indeterminate) or cholangiolocellular differentiation trait (CDT) in 108 iCCAs. The expression levels of inflammation-marker (CRP, FGB) and proliferation-marker (phospho-ERK1/2, Ki-67) were evaluated by immunohistochemistry. There were 87 MF, 8 PI, and 13 mixed-gross type. Small-duct-type (39, 44.8%) and CDT (19, 21.8%) were found only in MF-gross type. The inflammation-marker expression was higher in MF-type than in PI- and mixed-gross types (P = 0.023). It was high in small-duct-type, middle in indeterminate-type, and low in large-duct-type (P = 0.015), and iCCAs with CDT showed higher inflammation-marker expression compared to those without (P < 0.001). Proliferation-marker expression did not differ according to gross type; however it was lower in iCCA with CDT compared to those without (P = 0.004). Subgrouping of the gross type according to histopathological type or CDT revealed that MF-type with small-duct-type or CDT had better overall survival compared to the others (P < 0.05). MF-type iCCA is more heterogeneous than other gross types. High inflammation-marker/low proliferation-marker expression in MF-type with CDT or small-duct-type may be related to a good outcome.


Inhibition of RUNX1 promotes cisplatin-induced apoptosis in ovarian cancer cells.
Runt-related transcription factor 1 (RUNX1), one subunit of core-binding factors in hematopoiesis and leukemia, was highly expressed in ovarian cancer (OC), but the role of RUNX1 in OC is largely unknown. Since we found that high expression of RUNX1 is correlated with poor survival in patients with OC through bioinformatic analysis of TCGA database, we developed RUNX1-knockout clones by CRISPR/Cas9 technique and discovered that RUNX1 depletion could promote cisplatin-induced apoptosis in OC cells, which was further confirmed by RUNX1 knockdown and overexpression. We also proved that RUNX1 could elevate the expression of BCL2. We then examined a total of 32 candidate miRNAs that might mediate the regulation between RUNX1 and BCL2, of which three miRNAs from the miR-17~92 cluster were found to be negatively regulated by RUNX1. Consistently, our analysis of data from TCGA database revealed the negative correlation between RUNX1 and the cluster. We further confirmed that miR-17~92 cluster could enhance cisplatin-induced apoptosis by directly targeting BCL2 3'UTR. Since rescue experiments proved that RUNX1 could repress cisplatin-induced apoptosis by up-regulating BCL2 via miR-17~92 cluster, combining RUNX1 inhibitor Ro5-3335 and cisplatin showed synergic effect in triggering OC cell apoptosis. Collectively, these findings show for the first time that combinational treatment of cisplatin and RUNX1 inhibitor could be used to potentiate apoptosis of ovarian cancer cells, and reveal the potential of targeting RUNX1 in ovarian cancer chemotherapy.


Evaluation of the effect of Papanicolaou screening in Sweden: record linkage between a central screening registry and the National Cancer Registry.
Development of in-situ or invasive carcinoma of the uterine cervix was studied among 930,127 women reported to a Swedish Central Screening Register through a record linkage between that Register and the National Cancer Registry. The relative protection against cervical cancer after one negative smear, calculated on incidence level prior to screening, is 14.5 for the first year and drops to 3.4 five years after the screening. The relative protection after two or more negative smears is considerably higher for the first three years but for the years following drops to the same level as after one negative smear.


Lost in the woods: Finding our way back to the scientific method in systematic review.
Systematic review has become the preferred approach to addressing causality and informing regulatory and other decision-making processes, including chemical risk assessments. While advocates of systematic reviews acknowledge that they hold great potential for increasing objectivity and transparency in assessments of chemicals and human health risks, standardizing and harmonizing systematic review methods have been challenging. This review provides a brief summary of the development of systematic review methods and some of the frameworks currently in use in the US and Europe. We also provide an in-depth evaluation and comparison of two "competing" US EPA systematic review frameworks, informed by the constructively critical recommendations from the US National Academies of Science, Engineering and Medicine. We conclude with suggestions for moving forward to harmonize systematic review methods, as we believe that further criticism of individual available frameworks likely will be unproductive. Specifically, we issue a call to action for an international collaboration to work toward a blueprint that embraces the most scientifically critical elements common to most systematic review frameworks, while necessarily accommodating adaptations for specific purposes. Despite the array of available systematic review methods, it is clear that there is a shared goal and desire to promote objective assessment and synthesis of scientific evidence informing globally important issues regarding disease causality and human health risk evaluation.


Evaluation of Mycobacterium tuberculosis derived cell-free DNA using pleural fluid and paired plasma samples for the diagnosis of pleural tuberculosis.
Pleural tuberculosis (pTB) is a grave clinical challenge. A novel cell-free M. tuberculosis DNA (cfM.tb-DNA) probe-based-qPCR assay was developed for the diagnosis of pTB. Total cell-free DNA was extracted from pleural fluid (PF) and paired plasma samples and cfM.tb-DNA was quantified by probe-based qPCR targeting devR (109-bp) gene of M. tuberculosis in patients with pleural effusion. Patient categorization was done using 'Composite-Reference-Standard' formulated for the study. Assay cut-offs were determined from samples in the 'Development set' (n = 17; 'Definite & Probable' pTB; n = 9 and 'Non-TB'; n = 8) by ROC-curve analysis and applied to 'Validation set' (n = 112; 'Definite' pTB; n = 8, 'Probable' pTB; n = 34, 'Possible' pTB; n = 28 and 'Non-TB'; n = 42). cfM.tb-DNA qPCR had a sensitivity of 62.5% (95%CI; 24.4,91.4) in 'Definite' pTB category and 59.5% (95%CI; 43.2,74.3) in 'Definite & Probable' pTB category with 95.2% (95%CI; 83.8,99.4) specificity using PF. In plasma (n = 85), the assay had a sub-optimal sensitivity of 7.6% (95%CI; 0.95,25.1) with 88.2% (95%CI; 72.5,96.7) specificity in 'Definite & Probable' pTB group. Xpert MTB/RIF assay detected only six-samples in the 'Validation set'. Logistic regression analysis indicated that PF-cfM.tb-DNA qPCR provided incremental advantage over existing pTB diagnostic algorithms. To the best of our knowledge, this is the first report describing the utility of cfM.tb-DNA for pTB diagnosis in India.


A functional approach to cerebral visual impairments in very preterm/very-low-birth-weight children.
Cerebral visual impairment (CVI) is a major cause of visual impairment, with very preterm birth/very low birth weight (VP/VLBW) being a major risk factor. There is no generally accepted definition of CVI. This study aims to investigate the usefulness of an empirically-based functional definition of CVI. One-hundred-five VP/VLBW children and 67 controls participated. CVI was defined after comprehensive oculomotor, visual sensory and perceptive assessment, and validated against vision problems in daily life and in terms of intellectual, behavioral, emotional and social functioning, as well as use of therapeutic services. Twenty-four per cent of the VP/VLBW children met criteria for CVI, compared to 7% of controls (P = 0.006, OR: 3.86, 95% CI: 1.40-10.70). VP/VLBW children with CVI had lower performance IQ, but not verbal IQ, than those without CVI. Visual problems in daily life were confirmed in VP/VLBW children classified with CVI. Additionally, difficulties in behavioral and social functioning were most prominent among VP/VLBW children with CVI. In VP/VLBW children, CVI defined in terms of visual function deficits is accompanied by intellectual, behavioral, and social impairments, validating our operational definition of CVI. CVI might act as a marker for developmental problems in VP/VLBW children.


[Contents and isomers distribution of vitamin E in human mature breast milk from six regions of China in 2018-2019].
The study aimed to investigate the contents and isomer composition of vitamin E in mature milk in different regions of China. Simultaneously recruited 604 lactating mothers aged(29.58±3.43) from Shanghai, Guangzhou, Tianjin, Chengdu, Lanzhou and Changchun cities. They were mainly primiparas with good education background. A total number of 604 mature milk samples was collected. The contents of α-, γ-, δ-tocopherols and the stereoisomers of α-tocopherol were determined by high performance liquid chromatography(HPLC). The M(P25, P75) concentrations of α-tocopherol, RRR-α-tocopherol, γ-tocopherol and δ-tocopherol in Chinese mature milk were 3.16(2.29, 4.16)mg/L, 2.57(1.77, 3.48)mg/L, 0.89(0.58, 1.27)mg/L and 0.17(0.09, 0.27)mg/L, respectively. The total α-TE level was 3.09(2.22, 4.10)mg/L with statistically regional differences(P<0.001). RRR-α-tocopherol was the predominated stereoisomers of α-tocopherol, accounting for 83.17%(76.36%, 88.43%). The proportion of RRR in Tianjin mature milk was significantly lower than that in Lanzhou(77.11% vs. 86.16%, P<0.001) while breast milk samples from other regions had similar RRR-α-tocopherol proportions(82.82%-85.39%). Vitamin E content in mature milk was mainly composed of α-tocopherol. Even though the contents of tocopherols have large regional differences, RRR-α-tocopherol was predominated form in all breast milk samples. It is suggested that RRR-α-tocopherol was the main active form of vitamin E in the early stage of life.


Equilibrium gel permeation: measurement of solute partitioning by direct fluorescence scanning.
The feasibility fo using fluorescence detection in quantitative gel permeation measurements has been explored. It is shown that the effect of scattering by the gel matrix can be evaluated in terms of pathlength-dependent turbidity functions for excitation and emission wavelengths. Experimental studies were carried out to evaluate these funcitons in cross-linked dextran gels (Sephadexes) and in agarose gels (Sepharoses). Empirical turbidity functions derived for these gels have a simple form, leading to accurate simplifying approximations for the scattering correction required in a fluorescence gel permeation measurement. Using this approach...


Field-flow fractionation of macromolecules.
Field-flow fractionation (FFF) is a versatile family of techniques, applicable to macromolecules, colloids, and cell-sized particles. This paper focuses specifically on the applicability of FFF to macromolecules. Following a brief description of the principles of FFF, the characteristics of FFF that bear on its efficacy in separating macromolecules are summarized. The basis of selectivity is established. The general applicability of FFF to macromolecules is then surveyed. For this purpose macromolecular substances are divided into four classes, distinguished by a molecular weight cutoff of 10(6) and by aqueous versus organic solubility. The capabilities of different FFF subtechniques in fractionating these classes of macromolecules is then discussed.


Structure and activity dependence of recombinant human insulin-like growth factor II on disulfide bond pairing.
The complete peptide map of purified folded recombinant human insulin-like growth factor II (rhIGF-II) was determined to verify its sequence and disulfide bonding scheme. Each peptide generated by digestion with pepsin was purified and characterized by amino acid analysis, amino acid sequence analysis, and fast atom bombardment/mass spectrometry. Some peptides were also sequenced using tandem mass spectrometry. The rhIGF-II peptide map was compared to that of rat insulin-like growth factor II and to that of a disulfide-bonded isomer of rhIGF-II. The data obtained in these studies are consistent with the conclusion that the rhIGF-II obtained from Escherichia coli has the correct amino acid composition, sequence, and the native disulfide-bonded structure. The binding affinities of these forms of recombinant IGF-II for IGF carrier proteins were measured in an IGF binding protein assay. The disulfide isomer of rhIGF-II was 160-fold less potent than native rhIGF-II in the competitive protein binding assay. These studies illustrate the need to characterize recombinant polypeptides containing disulfide bonds to allow the native structure to be verified before characterizing the biological properties of such molecules in hopes of elucidating their physiologic functions.


[Experimental emphysema following intravenous injection of trypsin].
The injection of trypsin provokes a decrease of the circulating antiproteases. Its effect on an elastase-induced emphysema is negligible. Paradoxically, emphysema is quantitatively demonstrated in rats treated with trypsin alone: an influx of polymorphonuclear leucocytes into the lung is observed during the acute phase of experiment.


Sonographic findings in a case of cloverleaf skull deformity and prune belly.
A rare case of cloverleaf skull is reported that was not diagnosed in utero. The case is more unusual because it was not associated with hydrocephalus and was associated with prune belly.


Correction: Lochbaum et al. The Profile of Moods States and Athletic Performance: A Meta-Analysis of Published Studies. Eur. J. Investig. Health Psychol. Educ. 2021, 11, 50-70.
Error in Section 2.6 [...].


Epidemiological characteristics of hand, foot, and mouth disease clusters during 2016-2020 in Beijing, China.
Hand, foot, and mouth disease (HFMD) is an infectious disease that usually occurs in children under 5 years and is caused by a group of enteroviruses. This study aimed to investigate the epidemiological characteristics of HFMD clusters from 2016 to 2020 in Tongzhou, Beijing, and explored the genetic evolution of CV-A6. The HFMD case information came from the Information System of China Center for Disease Control and Prevention (CDC), as well as the clusters information verification and on-site investigation by Tongzhou CDC. ARIMA model was applied to forecast HFMD clusters in 2020. Totally 440 HFMD clusters were reported during 2016-2020. The large peak of the clusters occurred in April-July, followed by a smaller peak in October-November during 2016-2019. However, in 2020, the two peaks disappeared. The main site of HFMD clusters was childcare facilities (65.0%) and mostly occurred in urban areas (46.1%). The detection rate of CV-A6 was the highest (36.1%), and cases with CV-A6 infection had the highest proportion of fever. The phylogenetic analysis based on CV-A6 VP1 gene showed that the predominant strains mainly located in Group F during 2016-2017, while changed into Group A during 2018-2020. HFMD clusters presented seasonality, mainly located in childcare facilities and urban areas, and CV-A6 was the major causative agent. Targeted prevention and control measures should be taken to reduce HFMD clusters.


Diagnostic testing and treatment of pediatric headache in the emergency department.
To describe the variability in diagnostic testing and treatment of headaches in children presenting to the emergency department (ED) with use of a nationally representative sample. This was a retrospective cohort study using the National Hospital Ambulatory Medical Care Survey during 2005-2009. To assess the use of evidence-based treatment, we analyzed all patients <18 years old in 2 groups: (1) primary discharge diagnosis of headache and (2) discharge diagnosis of migraine. Four hundred forty-eight sampled ED visits from 2005-2009 represented a national estimate of 1.7 million visits with a discharge diagnosis of headache. A total of 95 visits represented a national estimate of 340 000 visits with a discharge diagnosis of migraine. Median age was 13.1 years and 60% were female with a primary diagnosis of headache. In this group, neuroimaging was performed in 37% of patients and 39% underwent blood tests. Nonsteroidal anti-inflammatory drugs and opioids were most commonly used for treatment. For children with a discharge diagnosis of migraine, approximately 40% of patients received non-evidence-based treatment, most commonly with opioid medications, and >20% of patients underwent computed tomography scanning. There is significant variability in the evaluation and treatment of pediatric headache in the ED. Despite evidence-based clinical guidelines for migraine headache, a large number of children continue to receive opioids and ionizing radiation in the ED.


A novel resource utilization method using wet magnesia flue gas desulfurization residue for simultaneous removal of ammonium nitrogen and heavy metal pollutants from vanadium containing industrial wastewater.
In the present study, a novel resource utilization method using wet magnesia flue gas desulfurization (FGD) residue for the simultaneous removal of ammonium nitrogen (NH4-N) and heavy metal pollutants from vanadium (V) industrial wastewater was proven to be viable and effective. In this process, the wet magnesia FGD residue could not only act as a reductant of hexavalent chromium [Cr(vi)] and pentavalent vanadium [V(v)], but also offered plenty of low cost magnesium ions to remove NH4-N using struvite crystallization. The optimum experimental conditions for Cr(vi) and V(v) reduction are as follows: the reduction pH = 2.5, the wet magnesia FGD residue dose is 42.5 g L-1, t = 15.0 min. The optimum experimental conditions for NH4-N and heavy metal pollutants removal are as follows: the precipitate pH = 9.5, the n(Mg2+) : n(NH4 +) : n(PO4 3-) = 0.3 : 1.0 : 1.0, t = 20.0 min. Finally the NH4-N, V and Cr were separated from the vanadium containing industrial wastewater by forming the difficult to obtain, soluble coprecipitate containing struvite and heavy metal hydroxides. The residual pollutant concentrations in the wastewater were as follows: Cr(vi) was 0.047 mg L-1, total Cr was 0.1 mg L-1, V was 0.14 mg L-1, NH4-N was 176.2 mg L-1 (removal efficiency was about 94.5%) and phosphorus was 14.7 mg L-1.


Effective models of periodically driven networks.
Circadian rhythms are governed by a highly coupled, complex network of genes. Due to feedback within the network, any modification of the system's state requires coherent changes in several nodes. A model of the underlying network is necessary to compute these modifications. We use an effective modeling approach for this task. Rather than inferred biochemical interactions, our method utilizes microarray data from a group of mutants for its construction. With simulated data, we develop an effective model for a circadian network in a peripheral tissue, subject to driving by the suprachiasmatic nucleus, the mammalian pacemaker. The effective network can predict time-dependent gene expression levels in other mutants.


Ambient particulate matter exposure causes visual dysfunction and retinal neuronal degeneration.
PM2.5 pollution is related to neurotoxic and vascular effects in eye diseases such as glaucoma. This study investigates the adverse effects of PM2.5 exposure on visual function and retinal neurons. A versatile aerosol concentration enrichment system was used to expose mice to either control air or PM2.5 polluted air. Six months after PM2.5 exposure, visual function was measured by electroretinography (ERG). Hematoxylin and eosin staining and immunofluorescence staining were used for histopathological analysis. Protein markers of apoptosis, astrocytic reactivity, inflammatory cytokines, lipid peroxidation, protein nitration and DNA damage response were quantified with ELISA, western blot or detected using immunofluorescence and immunohistochemistry. After six months of exposure, PM2.5-exposed mice responded poorly to light stimuli compared with those exposed to the control air. PM2.5 exposure caused retinal thinning and reduction in the expression of retinal ganglion cell-selective marker RNA-binding protein with multiple splicing (RBPMS). Further, positive TUNEL staining was observed in the inner nucleus and outer nuclear layers of the retinae after exposure to PM2.5, which was accompanied by the activation of apoptosis signaling molecules p53, caspase-3 and Bax. PM2.5 induced the release of inflammatory cytokines including tumor necrosis factor-α and cleaved interleukin-1β. Furthermore, increased levels of 8-OHdG and γ-H2AX in the mouse retinea were indicative of DNA single and double strand breaks by PM2.5 exposure, which activated PARP-1 mediated DNA damage and repair. In conclusion, this study demonstrates sub-chronic systemic exposure to concentrated PM2.5 causes visual dysfunction and retinal neuronal degeneration. DATA AVAILABILITY: The datasets during and/or analyzed during the current study available from the corresponding author on reasonable request.


The impact of diagnostic disclosure in dementia: a qualitative case analysis.
The aim of this study was to give an in-depth description of the impact of disclosure of the diagnosis of dementia on a patient and the patient's partner. Grounded theory interview study. Analysis of the interviews revealed that disclosure had an impact on three key domains: awareness of dementia, interpersonal relationship and social relationships. Disclosure was perceived as a confirmation of the pre-test ideas of both patient and carer. Formal disclosure of dementia was especially relevant for the carer in reconsidering her response to the patient's changed behavior. Receiving the diagnosis of dementia can be considered as a crucial moment in the process of becoming aware of the changes in one's life. Moreover, disclosure marks a new phase in the process of caring by the caregiver.


Effect of the Common Fat Mass and Obesity Associated Gene Variants on Obesity in Pakistani Population: A Case-Control Study.
Obesity has become a global epidemic due to an increase in the number of obese individuals worldwide. There is little research in the field of obesity genetics in Pakistan. The aim of the current study was to analyze the association of common variants in Fat Mass and Obesity associated (FTO) gene with obesity in Pakistan, to find out the effect of the selected SNPs on anthropometric and biochemical traits, and to observe whether these variants act synergistically. Samples from 631 subjects were taken after informed consent and were used for serum parameters and genetic analysis. Lipid profile was determined, tetra-ARMS PCR was used for genotyping, and allele/genotype frequencies and genescore were calculated. All FTO variants were associated with obesity, and some biochemical and anthropometric measures and had higher minor allele frequencies than those reported for Asian populations previously. The risk allele of each single nucleotide polymorphism resulted in an increase in BMI in a quantitative manner. Common forms of obesity are due to a combined net effect of many variants presented in same or different genes. The more the number of risk alleles present, the higher the risk and severity of obesity resulting from an increase in BMI.


RCAI-61 and related 6'-modified analogs of KRN7000: their synthesis and bioactivity for mouse lymphocytes to produce interferon-γ in vivo.
We synthesized ten new analogs of 6'-modified KRN7000 (A): RCAI-58, 61, 64, 83, 85-87, 113, 119, and 125. They could be synthesized by α-selective galactosylation of ceramide 9 with the 6-modified D-galactopyranosyl fluorides (8a-8f) or L-arabinopyranosyl fluoride (17), or by etherification of the known alcohol 19. Bioassay of the ten analogs demonstrated that RCAI-61 (1, 6'-O-methylated analog of A) was the most potent immunostimulant among them, and could induce the production of a large amount of IFN-γ even at a low concentration in mice in vivo.


Suspect screening of large numbers of emerging contaminants in environmental waters using artificial neural networks for chromatographic retention time prediction and high resolution mass spectrometry data analysis.
The recent development of broad-scope high resolution mass spectrometry (HRMS) screening methods has resulted in a much improved capability for new compound identification in environmental samples. However, positive identifications at the ng/L concentration level rely on analytical reference standards for chromatographic retention time (tR) and mass spectral comparisons. Chromatographic tR prediction can play a role in increasing confidence in suspect screening efforts for new compounds in the environment, especially when standards are not available, but reliable methods are lacking. The current work focuses on the development of artificial neural networks (ANNs) for tR prediction in gradient reversed-phase liquid chromatography and applied along with HRMS data to suspect screening of wastewater and environmental surface water samples. Based on a compound tR dataset of >500 compounds, an optimized 4-layer back-propagation multi-layer perceptron model enabled predictions for 85% of all compounds to within 2min of their measured tR for training (n=344) and verification (n=100) datasets. To evaluate the ANN ability for generalization to new data, the model was further tested using 100 randomly selected compounds and revealed 95% prediction accuracy within the 2-minute elution interval. Given the increasing concern on the presence of drug metabolites and other transformation products (TPs) in the aquatic environment, the model was applied along with HRMS data for preliminary identification of pharmaceutically-related compounds in real samples. Examples of compounds where reference standards were subsequently acquired and later confirmed are also presented. To our knowledge, this work presents for the first time, the successful application of an accurate retention time predictor and HRMS data-mining using the largest number of compounds to preliminarily identify new or emerging contaminants in wastewater and surface waters.


Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and effect.
The efficacy of fine-needle aspiration (FNA) biopsy and its role in the management of a nodular goiter are clearly established. The accuracy of cytologic diagnosis approaches 95%. FNA biopsy is a reasonable approach to thyroid nodules; it has decreased costs substantially because it facilitates selection of patients who need to undergo surgical excision. Selecting patients for operation on the basis of results of FNA biopsy has more than doubled the yield of carcinoma. The limitations of cytologic examination, nondiagnostic results, and cellular follicular neoplasms should be remembered but need not negate continued use of FNA biopsy. Negative (benign) and positive (malignant) cytologic results are conclusive; careful clinical follow-up of benign nodules and surgical excision of malignant nodules are recommended. Nondiagnostic results are inconclusive; further evaluation by repeated FNA biopsy, ultrasound-guided biopsy, or radionuclide scanning is necessary. Suspicious cytologic results are also inconclusive and are associated with a 20% chance of malignant involvement; surgical treatment is necessary for clarification. The role of levothyroxine therapy remains uncertain and is not recommended until compelling data are available. FNA biopsy is a safe, simple, reliable, and cost-effective means of detecting benign nodules. FNA biopsy, not thyroid scanning or ultrasonography, is the preferred initial diagnostic test in all patients with thyroid nodules.


Diminished quality of two-dimensional (2-D) gel electrophoresis after freezing of the first-dimension gels.
Two-dimensional (2-D) gels were compared before and after freezing mini isoelectric focusing (IEF) gels in their glass tubes at -20 degrees C. Overnight storage of mini IEF gels significantly reduced the separation, resolution and number of proteins in 2-D gels.


Mass spectrometry based phospholipidomics of mammalian thymus and leukemia patients: implication for function of iNKT cells.
In previous studies phospholipids have been proved to be involved in biochemical, physiological, and pathological processes. As a special class of phospholipids, peroxisome-derived lipids (PDLs) have been proved to be potential ligands of invariant natural killer T (iNKT) cells in recent studies. Here, on the basis of phospholipidomics, we focused on the relative quantity of PDLs extracted from mammalian thymus or bone marrow using electrospray ionization mass spectrometry (MS). In phospholipid analysis, we identified 12 classes of phospholipids and accounted for their relative quantities by comparing their relative abundances in the MS(1) map. Our results show that PDLs are present in mammalian thymus as well as mouse spleen and liver. Interestingly, the relative quantity of PDLs extracted from human acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) bone marrows is higher than that extracted from bone marrow of healthy donors. Our results may help to explain the close correlation between PDLs and iNKT cell function in thymus, spleen, liver, and especially in leukemia patients. We think that our phospholipidomics work may reveal a function of iNKT cells.


Patient-selection algorithm for outpatient shoulder arthroplasty in ambulatory surgery center: a retrospective update.
Outpatient total shoulder arthroplasty (TSA) presents a safe alternative to inpatient arthroplasty, while helping meet the rapidly rising volume of shoulder arthroplasty needs and minimizing health care costs. Identifying the correct patient for outpatient surgery is critical to maintaining the safety standards with TSA. This study sought to update an ambulatory surgery center (ASC) TSA patient-selection algorithm previously published by our institution. A retrospective chart review of TSAs was performed in an ASC at a single institution to collect patient demographics, perioperative risk factors, and postoperative outcomes with regard to reoperations, hospital admissions, and complications. The existing ASC algorithm for outpatient TSA was altered based on collected perioperative information, review of pertinent literature, and anesthesiology recommendations. A total of 319 TSAs were performed in an ASC in 298 patients over 7 years. Medically related complications occurred in 3 patients (0.9%) within 90 days of surgery, 2 of whom required hospital admission (0.6%) for acute kidney injury and pulmonary embolus. There were no instances of major cardiac events. Orthopedic-related complications occurred in 11 patients (3.4%), with hematoma development requiring evacuation and instability requiring revision being the most common causes. There was a low rate of perioperative complications and hospital admissions, confirming the safety of TSAs in an ASC setting. Based on prior literature and the population included, a pre-existing patient-selection algorithm was updated to better reflect increased comfort, knowledge, and data regarding safe patient selection for TSA in an ASC.


Study on novel hydrogels based on thermosensitive PNIPAAm with pH sensitive PDMAEMA grafts.
A series of novel hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm) with pendant poly(N-(2-(dimethylamino) ethyl)-methacrylamide) (PDMAEMA) grafts were designed and synthesized. The influence of the pendant PDMAEMA grafts on the properties of the resulted hydrogels was examined in terms of morphology observed by scanning electron microscopy (SEM), thermal property characterized by differential scanning calorimetry (DSC) and shrinking/swelling kinetics upon external temperature changes. In comparison with the conventional PNIPAAm hydrogels, resulting hydrogels presented favorable pH sensitivity as well as improved thermosensitive properties, including enlarged water containing capability at room temperature and faster shrinking/swelling rate upon heating. In addition, fish DNA, used as a model drug, was loaded into the hydrogels, and the controlled release behavior of the drug-loaded hydrogels at different temperatures (22 and 37 degrees C) was further studied.


Retracted: Optimization of Online Course Platform for Piano Preschool Education Based on Internet Cloud Computing System.
[This retracts the article DOI: 10.1155/2022/6525866.].


Substrate balances across skeletal muscle tissue in severe sepsis.
Substrate metabolism of skeletal muscle was studied by the forearm technique in eight patients with severe sepsis. The data were compared to those of 13 patients after elective surgery. In the septic group forearm blood flow was increased, but muscular utilisation of oxygen was diminished. Arterial concentrations of free fatty acids and ketone bodies were low. Thus, both only played a minor role in the supply of skeletal muscle with substrates. From the decreased production of lactate and alanine and the comparable utilisation of glucose we conclude that in the septic patients energy expenditure of skeletal muscle was mainly met by oxidation of glucose. In contrast to reduced lipolysis of adipose tissue intramuscular lipolysis may still be working since muscular production of lactate and glycerol was correlated. These findings suggest a changing pattern of arterial supply of substrates and utilisation of substrates by skeletal muscle during deterioration of clinical condition in the course of sepsis.


Nutritional status, intestinal parasitic infections, and socio-environmental conditions in Mbyá-guaraní children: The current situation in communities in central Misiones, Argentina.
Our previous research in Mbyá-guaraní communities of central Misiones showed high levels of growth stunting and intestinal parasites in children, as well as associations between these variables and deficient sanitary conditions. New studies were necessary to update the present health status of the previously studied Mbyá populations after around two decades. Therefore, we evaluated the current nutritional status, intestinal parasites, and socio-environmental conditions among Mbyá-guaraní children from these communities. Body weight and height of 102 individuals (aged 2-14) were measured and nutritional status was estimated according to the World Health Organization criteria. Serial fecal samples and anal swabs were analyzed from 75 children (aged 1-14). Socio-environmental data were obtained from questionnaires. The prevalence of undernutrition was 31.4% and excess of weight was 10.8%. The prevalence of stunting and of overweight reached 30.4% and 8.8%, respectively. About 85% of the children were infected with at least one of the 14 species identified, and around 44% had multiple parasite infections. The most prevalent species were Enterobius vermicularis and hookworms. Among undernourished children, 88.2% were parasitized by at least one of the potentially pathogenic species detected. Most of the families lived in overcrowded conditions in precarious houses, defecated in latrines, and consumed well water. A higher risk of parasitosis was associated with the source of drinking water. Although the prevalence of undernutrition and intestinal parasites decreased compared with our previous studies, we still observed the coexistence of stunting, excess weight, and parasitic infections, in a context of socio-environmental vulnerability.


Effect of vidarabine and related compounds on corneal endothelium.
The endothelial surface of rabbit corneas was perfused with vidarabine monophosphate (with and without adenosine deaminase inhibitor), vidarabine (with and without adenosine deaminase inhibitor), and ara-Hx. In concentrations 10 times to 1,500 times higher than those that have been obtained in the aqueous humor following topical, subconjunctival, or systemic administration, none of the compounds had any effect on corneal endothelial cell function or ultrastructure for the duration of the experimental model.


Reagent-less and sub-minute quantification of sulfite in food samples using substrate-integrated hollow waveguide gas sensors coupled to deep-UV LED.
The increasing consumption of processed foods demands the usage of chemical preservatives to ensure freshness and extended shelf life. For this purpose, sodium sulfite and its derivatives have been widely used in a variety of food products to inhibit microbial spoilage and for mitigating oxidative decay. However, the excessive consumption of sulfite may cause health problems, thus requiring rapid and accurate analytical methods for the rapid identification of threshold levels. Conventionally, sulfite is volatilized from food samples by acidification followed by trapping of the gaseous SO2 and determination using a suitable analytical technique. Herein, we propose a yet unprecedented reagent-less approach via direct absorbance measurements of gaseous SO2 at 280 nm after sample acidification. The detection system combines a deep-UV LED and a SiC photodiode with a substrate-integrated hollow waveguide (iHWG) gas cell. Absorbance measurements were performed using a log-ratio amplifier circuitry, resulting in noise levels <0.7 mAU. This innovative concept enabled the determination of sulfite in beverages in the range of 25-1000 mg L-1 with suitable linearity (r2 > 0.99) and an analysis time <30 s. The limit of detection (LOD) was calculated at 14.3 mg L-1 (3σ) with an iHWG providing an optical path length of 75 mm. As a proof of concept, this innovative analytical platform was employed for sulfite quantification in concentrated grape juice, coconut water and beer, with suitable accuracy in terms of recovery (83-117%) and favorable comparison with the official Monier-Williams method. Given the inherent modularity and adaptability of the device concept, we anticipate the application of the proposed analytical platform for the in-situ studies addressing sulfite and other volatilized preservatives in a wide variety of food products with tailorable detectability.


miR-34a inhibits the in vitro cell proliferation and migration in human esophageal cancer.
Increasing studies demonstrate that reduced expression of miR-34a is involved in the initiation and progression of cancers, and it has been characterized as a tumor suppressor in various types of cancers. In present study, we investigated the expression and role of miR-34a in esophageal cancer. qRT-PCR assays were performed to analyze the expression of miR-34a in human esophageal cancer tissues and adjacent esophageal tissues. CCK8 assay, flow cytometry analysis and in vitro migration assays were performed to analyze the role of miR-34a in human esophageal cancer cell. MSP assay was performed to analyze the DNA methylation of the miR-34a promoter. The expression of miR-34a was down-regulated in human esophageal cancer tissues. miR-34a ectopic expression affected esophageal cancer cells survival, proliferation and capabilities of migration in vitro. p53 status was not correlated with miR-34a. Subsequently, aberrant DNA methylation of the miR-34a promoter was found in human esophageal cancer, and 5-AZA-dC inhibited DNA methylation of the miR-34a promoter. our data showed that miR-34a acted as a tumor suppressor in human esophageal cancer.


Complications of central venous catheter in patients transplanted with hematopoietic stem cells in a specialized service.
to identify the model, average length of stay on site and complications of central venous catheter in patients undergoing transplant of hematopoietic stem cells and verify the corresponding relationship between the variables: age, gender, medical diagnosis, type of transplant, implanted catheter and insertion site. a retrospective and quantitative study with a sample of 188 patients transplanted records between 2007 and 2011. the majority of patients used Hickman catheter with an average length of stay on site of 47.6 days. The complication fever/bacteremia was significant in young males with non-Hodgkin's lymphoma undergoing autologous transplant, which remained with the device for a long period in the subclavian vein. nurses should plan with their team the minimum waiting time, recommended between the catheter insertion and start of the conditioning regimen, as well as not to extend the length of time that catheter should be on site and undertake their continuing education, focusing on the prevention of complications.


Up-regulation of Toll-like receptor 4 was suppressed by emodin and baicalin in the setting of acute pancreatitis.
Acute pancreatitis (AP) activates the systemic inflammatory response and is potentially lethal. Recent studies demonstrated that pancreatic enzymes could induce cytokine expression via Toll-like receptor 4 (TLR4) signal pathway, indicating a possible role of TLR4 in local pancreatic injury and systemic inflammatory response. Emodin, an anthraquinone derivative from Radix et Rhizoma Rhei, and baicalin, a flavone from Scutellaria baicalensis Georgi, both have been reported to possess anti-inflammatory activities. In present study, we investigated the combined effect of emodin and baicalin on pancreatic damage and pancreatitis associated lung injury, as well as tissue TLR4 expression in the setting of AP. The results showed that combination of emodin and baicalin significantly reduced serum amylase, tumor necrosis factor-alpha and interleukin-6, attenuated pancreatic and pulmonary damage, also suppressed TLR4 expression in pancreas and lung. It could be speculated that amelioration of pancreatic and pulmonary damage by emodin and baicalin might contribute, in part at least, to the suppression of TLR4 expression. The present study provides beneficial evidence as to simultaneous treatment for AP, and also suggests an important role of TLR4 in pathophysiology of AP.


Exploration of 100 commonly used drugs and supplements on cognition in older adults.
There are conflicting reports and a lack of evidence-based data regarding effects of medications on cognition in cognitively normal older adults. We explored whether use of 100 common medications taken by older adults is associated with longitudinal cognitive performance. A longitudinal observational cohort was used with analysis of data collected from September 2005 through May 2011 and maintained in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set. Participants were aged 50 years or older and cognitively normal (N = 4414). Composite scores were constructed from 10 psychometric tests. Scores for each participant reflecting change in the psychometric composite score from the baseline clinical assessment to the next assessment were calculated. General linear models were used to test whether the mean composite change score differed for participants who reported starting, stopping, continuing, or not taking each of the 100 most frequently used medications in the NACC sample. The average time between assessments was 1.2 years (SD = 0.42). Nine medications showed a difference (P < .05) across the four participant groups in mean psychometric change scores from the first to the second assessment. Medications associated with improved psychometric performance were naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline. Medications associated with declining psychometric performance were bupropion, oxybutynin, and furosemide. Reported use of common medications is associated with cognitive performance in older adults, but studies are needed to investigate the mechanisms underlying these effects.


A split NanoLuc complementation-based human norovirus-like particle entry assay facilitates evaluation of anti-norovirus antibodies in live cells.
Human noroviruses (NoVs) are the most common cause of acute gastroenteritis worldwide. One major obstacle in developing NoV vaccines is the lack of robust cell culture for efficacy evaluation. In this study, we successfully developed a NoV virus-like particle (VLP) entry assay based on split NanoLuc luciferase (LgBiT and HiBiT) complementation. HiBiT-tagged NoV GII.4 VLP (VLP-HiBiT) can be efficiently produced in Pichia pastoris and retain binding activity towards NoV receptor histo-blood group antigens (HBGAs). A 293T-FUT2-LgBiT cell line was established and was shown to stably express cell surface HBGAs and intracellular LgBiT. GII.4 VLP-HiBiT can bind and enter into the 293-FUT2-LgBiT cells, producing strong luminescence signals in live cells. Anti-GII.4 sera can inhibit VLP-HiBiT entry into the 293-FUT2-LgBiT cells in a dose-dependent manner, and neutralizing titers well correlate with their blocking titers measured by HBGAs-binding blockade assay. Moreover, such a surrogate infection/neutralization assay can be applied to other NoV genotypes such as GI.1 and GII.17. Together, the VLP-HiBiT entry assay can mimic both NoV attachment and internalization in live cells and thus facilitate reliable and comprehensive evaluation of NoV vaccine and antibodies.


CTRP3 attenuates hepatic stellate cell activation through transforming growth factor-β/Smad signaling pathway.
Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of liver fibrosis. C1q/tumor necrosis factor-related protein 3 (CTRP3), a member of CTRPs, was involved in fibrosis. However, little is known about the role of CTRP3 in liver fibrosis. This study aimed to determine its role in liver fibrosis and explore the possible mechanism. Our results demonstrated that CTRP3 was lowly expressed in liver fibrosis tissues and activated HSCs. Overexpression of CTRP3 inhibited the proliferation and migration of HSCs, as well as suppressed the expression of extracellular matrix (ECM) in transforming growth factor-β1 (TGF-β1)-stimulated HSC-T6 cells. Furthermore, CTRP3 overexpression greatly inhibited the expression level of phosphorylation of Smad3 in TGF-β1-stimulated HSC-T6 cells. In conclusion, the present study demonstrated that CTRP3 inhibited the proliferation and migration of TGF-β1-induced HSC-T6 cells and attenuated liver fibrosis, at least in part, through inhibiting the Smad signaling pathway. These findings suggest that CTRP3 may be a promising therapeutic target for the treatment of liver fibrosis.


The molecular characteristics of gastric cancer patients living in Qinghai-Tibetan Plateau.
Gastric cancer, or stomach cancer, that originates in the inner lining of the stomach, was the fifth most common cancer and the fourth mortality globally, with over one million new cases in 2020 and an estimated 769,000 deaths. The molecular characteristics of gastric cancer has been complicated by histological and intratumor heterogeneity. The incidence of gastric cancer shows wide geographical variation. As the largest and highest region in China, Qinghai-Tibetan Plateau is one of the important global biodiversity hotspots. Here, we collect tumour and paired normal bio-samples from 31 primary gastric cancer patients from Qinghai Provincial People's Hospital, and discuss the molecular characteristics for gastric cancer patients living in plateau. They have more single nucleotide polymorphisms (SNP) located in chromosome 7 with C → T and G → A as the most common alteration types, barely share the cancer driver genes with western patients, and have no significant differences in various Chinese nation. These characteristics offers a great opportunity to further understanding the divergent mechanism of gastric cancer, increase the efficacy for diagnosis and prognosis, finally lead the optimal targeted therapeutics.


Isotherm data for adsorption of amoxicillin, ampicillin, and doripenem onto bentonite.
The dataset reported in this article describes the adsorption isotherms of amoxicillin, ampicillin, and doripenem onto bentonite. Batch adsorption experiments were carried out on single antibiotic solutions with various dosage of bentonite across temperatures from 30 to 50 °C. The adsorbent loading dataset was later obtained by measuring the concentration of antibiotic solution at adsorption equilibrium via UV-Vis spectrophotometer. The dataset was also fitted using various isotherm models including Freundlich, Langmuir, Toth, Hill, and Dubinin-Radushkevich models to further analyze the adsorption behavior. On top of that, orthogonal regression was applied to avoid fitting biasness, whereby the fitting results revealed the highest adsorption capacities of 82.259 mg g-1 for amoxicillin, 78.851 mg g-1 for ampicillin, and 93.278 mg g-1 for doripenem using Langmuir model, which gave an accurate representation of the adsorption isotherm dataset that was consistent with the results of Toth and Hill model.


The utility of SARS-CoV-2 nucleocapsid protein in laboratory diagnosis.
The Coronavirus Disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has now become a global pandemic owing to its high transmissibility. The SARS-CoV-2 nucleocapsid protein tests are playing an important role in screening and diagnosing patients with COVID-19, and studies about the utility of SARS-CoV-2 nucleocapsid protein tests are increasing now. In this review, all the relevant original studies were assessed by searching in electronic databases including Scopus, Pubmed, Embase, and Web of Science. "SARS-CoV-2", "COVID-19", "nucleocapsid protein", and "antigen detection" were used as keywords. In this review, we summarized the utility of SARS-CoV-2 nucleocapsid protein in laboratory diagnosis. Among the representative researches, this review analyzed, the sensitivity of SARS-CoV-2 nucleocapsid protein detection varies from 13% to 87.9%, while the specificity could almost reach 100% in most studies. As a matter of fact, the sensitivity is around 50% and could be higher or lower due to the influential factors. It is well suggested that SARS-CoV-2 nucleocapsid protein is a convenient method with a short turnaround time of about half an hour, and the presence of N antigen is positively related to viral transmissibility, indicating that SARS-CoV-2 N protein immunoassays contribute to finding out those infected people rapidly and segregating them from the uninfected people.


Nasopharynx is well-suited for core temperature measurement during hypothermia therapy.
Rectal temperature is commonly used as the core temperature during therapeutic hypothermia therapy in neonates with hypoxic-ischemic encephalopathy (HIE). The purpose of this study was to examine whether nasopharyngeal temperature could serve as a substitute for rectal temperature. We prospectively investigated 40 neonates with HIE who underwent therapeutic hypothermia by selective head cooling, which involved cooling the body to 34°C for 72 h. During this period, nasopharyngeal temperature was measured and compared with rectal temperature every hour. For 40 neonates included in this study, the mean rectal and nasopharyngeal temperatures were 34.3 ± 0.4°C (n = 2920) and 34.3 ± 0.4°C (n = 2920), respectively. Nasopharyngeal temperature strongly correlated with rectal temperature (R2 = 0.623, P < 0.0001) and magnitude of the mean difference between nasopharyngeal and rectal temperature varied little during the 72 h of therapeutic hypothermia. Nasopharyngeal temperature in neonates with perinatal HIE undergoing therapeutic hypothermia may be a suitable substitute for rectal temperature.


Randomized, controlled trial of dexamethasone in neonatal chronic lung disease: 13- to 17-year follow-up study: II. Respiratory status, growth, and blood pressure.
To study the growth, health status, and respiratory outcomes at 13 to 17 years of infants enrolled in a double-blind, randomized, controlled trial of dexamethasone for the treatment of neonatal chronic lung disease. A total of 287 infants who were chronically dependent on supplementary oxygen between 2 and 12 weeks of age were recruited from 31 centers in 6 countries to a double-blind, randomized, controlled trial of dexamethasone base (0.5 mg/kg per day for 1 week) or placebo, and survivors were evaluated at 3 years. Children from the 25 British and Irish centers were traced for reassessment at 13 to 17 years of age. Respiratory symptoms, lung-function testing, height, weight, head circumference, blood pressure, health resource usage, and school absences. There was no significant difference in respiratory outcomes between the dexamethasone and placebo groups. Lung function was impaired but with no difference between the 2 groups. Growth was also impaired in both groups, with height z score of -0.7, weight z score of -0.4, and head circumference z score of -1.1. Systolic blood pressure was >95th percentile for age and height for 15% of children, but with no difference between the 2 groups. There was no difference in the numbers of hospital admissions for respiratory causes or other causes. Despite a shorter duration of neonatal assisted ventilation, there is no evidence that dexamethasone use is associated with long-term improvement in lung function. Impaired growth and poor health status are long-term consequences of neonatal chronic lung disease, irrespective of exposure to neonatal dexamethasone.


Human tissue ownership and use in research: what laboratorians and researchers should know.
The use of human blood and tissue is critical to biomedical research. A number of treaties, laws, and regulations help to guide the ethical collection of these specimens. However, there are no clearly defined regulations regarding the ownership of human tissue specimens and who can control their fate. This review discusses the existing regulations governing human studies and the necessary components of patient consent. Legal cases that have addressed the issue of ownership of human tissue are reviewed, including recent settlements that have led to the destruction of millions of specimens of patient tissue. The unique regulations that guide the use of tissues collected postmortem are also examined. Potential changes in the future of biomedical research that uses human tissue, including genetic material, are also discussed. The use of human tissue is directed by numerous laws and regulations. Awareness of these rules and of how and when to obtain meaningful informed consent from patients is essential for laboratorians and researchers, who should also be familiar with situations that have led to lawsuits and in some cases the destruction of valuable human tissue specimens.


Spatial variation in inversion-focused vs 24-h integrated samples of PM2.5 and black carbon across Pittsburgh, PA.
A growing literature explores intra-urban variation in pollution concentrations. Few studies, however, have examined spatial variation during "peak" hours of the day (e.g., rush hours, inversion conditions), which may have strong bearing for source identification and epidemiological analyses. We aimed to capture "peak" spatial variation across a region of complex terrain, legacy industry, and frequent atmospheric inversions. We hypothesized stronger spatial contrast in concentrations during hours prone to atmospheric inversions and heavy traffic, and designed a 2-year monitoring campaign to capture spatial variation in fine particles (PM2.5) and black carbon (BC). Inversion-focused integrated monitoring (0600-1100 hours) was performed during year 1 (2011-2012) and compared with 1-week 24-h integrated results from year 2 (2012-2013). To allocate sampling sites, we explored spatial distributions in key sources (i.e., traffic, industry) and potential modifiers (i.e., elevation) in geographic information systems (GIS), and allocated 37 sites for spatial and source variability across the metropolitan domain (~388 km(2)). Land use regression (LUR) models were developed and compared by pollutant, season, and sampling method. As expected, we found stronger spatial contrasts in PM2.5 and BC using inversion-focused sampling, suggesting greater differences in peak exposures across urban areas than is captured by most integrated saturation campaigns. Temporal variability, commercial and industrial land use, PM2.5 emissions, and elevation were significant predictors, but did not more strongly predict concentrations during peak hours.


Comparison of the antioxidant properties of HYAFF-11p75, AQUACEL and hyaluronan towards reactive oxygen species in vitro.
In chronic wounds, a number of host factors are released which perpetuate the inflammatory process, including polymorphonuclear leukocyte (PMN)-derived reactive oxygen species (ROS), such as superoxide radical (O2*-) and hydroxyl radical (*OH) species. The glycosaminoglycan. hyaluronan, has been shown to act as an antioxidant towards ROS, although the potential for biomaterials, such as HYAFF -11p75 (the 75% benzyl ester of hyaluronan) and AQUACEL (carboxymethylcellulose), to act in this manner has yet to be elucidated. This study compared the antioxidant properties of high and low molecular weight hyaluronan (HMWT HA and LMWT HA), HYAFF -11p75, AQUACEL and an AQUACEL /hyaluronan composite (AQUACEL /HA) against O2*- and *OH. The antioxidant capacities of each material were assessed by their ability to inhibit cytochrome C reduction by O2*- fluxes, generated via the oxidation of hypoxanthine by xanthine oxidase, and their inhibition of 2-deoxy-D-ribose degradation by *OH fluxes, generated by the reaction of hydrogen peroxide (H2O2) and iron (Fe2+). All materials studied possessed dose dependent antioxidant properties towards O2*-, with HYAFF 11p75 having the greatest antioxidant potential towards these species, followed by AQUACEL, HMWT HA, AQUACEL /HA and LMWT HA. Only HMWT HA exhibited dose dependent antioxidant properties towards *OH at the fluxes examined. Gas chromatography/mass spectrometry analysis implied that ester bonds between the hyaluronan backbone and benzyl groups of HYAFF -11p75 are highly susceptible to O2*- hydrolysis, with the de-esterified benzyl alcohol being rapidly degraded in the presence of *OH. This data supports the hypothesis that HYAFF -11p75 has greater antioxidant capacity towards O2*-, due to the esterified benzyl groups providing alternative sites for O2*- attack other than the hyaluronan backbone of HYAFF -11p75 itself and explains the inability of HYAFF -11p75 to scavenge *OH, due to benzyl alcohol degradation by *OH. The antioxidant activities of these biomaterials, particularly HYAFF -11p75 and AQUACEL, towards O2*- could be beneficial, as the scavenging of PMN-derived O2*- may remove initial sources of O2*- and further prevent the secondary formation of *OH. These ROS are thought to be a primary causal factor for the extensive degradation and metabolic alterations observed in chronic wounds.