Human keratinocytes and monocytes release factors which regulate the synthesis of major acute phase plasma proteins in hepatic cells from man, rat, and mouse.
Human keratinocytes and activated monocytes produces factors which can stimulate the proliferation of thymocytes. The same activity has also been implicated in regulating the expression of plasma proteins in liver cells during the acute phase reaction. To assess whether factors produced by such cells can directly influence liver cells to change the production of acute phase plasma proteins, we studied in tissue culture the response pattern of hepatic cells from three species: human hepatoma cells ( HepG2 cells), and primary cultures of rat and mouse hepatocytes. Conditioned media from the squamous carcinoma COLO-16 cells, normal epidermal cells, and activated peripheral monocytes were able to stimulate the synthesis of specific acute phase plasma proteins: alpha 1-antichymotrypsin in HepG -2 cells, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, alpha 1-acute phase protein, and alpha 2-macroglobulin in rat hepatocytes, and alpha 1-acid glycoprotein, haptoglobin, and hemopexin in mouse hepatocytes. Only in rat cells, dexamethasone was found to have further enhancing effect. The increased production of plasma proteins could be explained by an elevated level of functional mRNA. Comparing thymocyte-stimulating activities with the effects on plasma protein production, we found some difference both between the conditioned media of epidermal cells and monocytes, and between the responses of the three hepatic cell systems. Furthermore, gel chromatography of conditioned media resulted in partial separation of activities regulating liver cells and thymocytes. Since there is no strict correlation between thymocyte- and hepatocyte-stimulating activities, the presence of different sets of specific factors is assumed.


An in vitro assay system for antihyperlipidemic agents by evaluating lipoprotein profiles from human intestinal epithelium-like cells.
We developed an in vitro screening system for antihyperlipidemic activity by measuring lipoprotein profiles secreted from human intestinal epithelium-like cells from the colon cancer cell line, Caco-2. Sodium (Na) butyrate at 5 mM differentiated Caco-2 cells into intestinal epithelium-like cells and numerous microvilli on the apical side of cells were observed under transmission electron microscopy. Real-time RT-PCR analysis revealed that Na butyrate stimulated expression levels of intestinal differentiation markers in Caco-2 cells in a dose-dependent manner and 5 mM Na butyrate up-regulated intestinal alkaline phosphatase, sucrase-isomaltase complex, and microsomal triglyceride transfer protein by 8.1-, 1.9-, and 2.1-fold that of non-treated cells, respectively. Lipoprotein secretions from differentiated Caco-2 cells were promoted by lysophosphatidyl choline and Na oleate, which are a stimulator of lipoprotein secretion and a substrate of triglycerides, respectively. We examined the effects of Pluronic L-81, a lipoprotein secretion inhibitor, on lipoprotein profiles of differentiated Caco-2 cells. Pluronic L-81 at 1.0 μg/ml inhibited TG contents in lipoprotein fractions from cells by 25.6 % and secretion was completely suppressed by the agent at 10 μg/ml.


Alterations in protein metabolism and amino acid concentrations in rats fed by a high-protein (casein-enriched) diet - effect of starvation.
Rats were fed with a standard laboratory diet (SLD) or a high-protein diet (HPD). After three months changes in amino acid concentration and protein metabolism were examined in fed and 24h-fasted animals. In the blood of the HPD animals sacrificed in fed state were found higher concentrations of urea, aspartate, taurine, proline, valine, isoleucine, and leucine, and lower concentrations of glycine and cysteine. The main alterations in tissues were decreased concentrations of glycine and increased concentrations of valine, isoleucine, and leucine. Differences in weight, protein concentration, protein synthesis, and proteolysis in tissues were insignificant. The exception was soleus muscle in which higher values of protein synthesis and proteolysis were found in HPD animals. The response to starvation of HPD and SLD fed animals was different. In animals fed before starvation by HPD was found more pronounced decrease in a number of individual amino acids in plasma and tissues and more pronounced decrease in protein synthesis in muscle, spleen, jejunum, and colon. It is concluded that chronic intake of HPD has not positive effect on protein balance in any tissue, results in the imbalance in aminoacidemia in extracellular and intracellular fluid, and alters the response of the organism to starvation.


Limits of 8-Tesla magnetic resonance imaging spatial resolution of the deoxygenated cerebral microvasculature.
To quantify the minimum magnetic resonance imaging (MRI) spatial resolution of the visible deoxygenated microscopic vessels of the human brain at 8 T. This study compared 8-T gradient echo (GE) images of a human cadaver brain having an in-plane resolution of 195 x 195 microm to corresponding digital photographs of 205 cryomicrotome sections of the same cadaver brain, along with summed images of 25 contiguous cryomicrotome sections. One-millimeter-thick GE images of a 1-cm-thick unfixed whole coronal brain section were acquired using techniques similar to those commonly utilized for 8-T human imaging in vivo. There was excellent MR visualization of the deoxygenated microscopic vessels within the brain down to a resolution of approximately 100 microm. By taking advantage of magnetic susceptibility-based blood oxygenation level-dependent (BOLD) contrast, deoxygenated microscopic blood vessels smaller than the pixel dimensions used for imaging can be visualized using a whole-body 8-T MRI system.


Kinetics of drug decomposition by heat conduction calorimetry.
The application of heat conduction calorimetry to the determination of decomposition mechanisms and rates for drugs is shown to be a rapid and generally useful method. The application of the method to determine the nature of the decomposition reaction, sources of systematic errors in the method, the equations relating the calorimetric signal to the kinetics of the reaction, and some examples of results are presented and discussed.


Site-specific tyrosine nitration of group 1 allergens of house dust mite Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1) in indoor dusts.
Nitration can enhance the allergenicity of proteins. The nitration status of house dust mite (HDM) allergens in indoor dusts, however, remains to be elucidated. In the study, site-specific tyrosine nitration degrees of the two important HDM allergens Der f 1 and Der p 1 in indoor dust samples were investigated by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The measured concentrations of native and nitrated allergens in the dusts were in the range of 0.86-29 μg g-1 for Der f 1 and from below the detection limit to 29 μg g-1 for Der p 1. Site-specific analysis revealed that all ten tyrosine residues in Der f 1 and Der p 1 were nitrated to different degrees in the investigated samples. The preferred nitration sites were Y56 in Der f 1 and Y37 in Der p 1 with the nitration degrees of 7.6-84% and 17-96% among the detected tyrosine residues, respectively. The measurements reveal high site-specific nitration degrees for tyrosine in Der f 1 and Der p 1 detected in the indoor dust samples. Further investigations are required to find out if the nitration really aggravates the health effects of HDM allergens and if the effects are tyrosine site-dependent.


Uptake of [14C]oxamniquine by Schistosoma mansoni.
The uptake and retention of drug-related material by Schistosoma mansoni was studied in the mouse host following a single oral or intramuscular dose (50 mg/kg) of [14C]oxamniquine. Male worms took up more labelled material than did female worms but the amount in each particular sex of worm was found to be similar after both routes of administration. Exposure of worms was therefore independent of the route of administration. Six days after drug administration, at the time of an hepatic shift, significantly more drug-related material was present in male worms than in female worms. Examination of worms recovered from mice 4 h after treatment showed that metabolites of oxamniquine constituted 70--90% of the drug-related material present in the worms. Both sexes of worms were able to take up metabolites of oxamniquine in vitro.


Synthesis and characterization of a penicillin-poly(L-lysine) which recognizes human IgE anti-penicillin antibodies.
Conjugates of poly(L-lysine) containing a penicillin or a penicilloyl residue were prepared and characterized by 1H NMR and by size-exclusion HPLC. These conjugates and conjugates with human serum albumin were used in radioallergosorbent tests (RAST) for the determination of allergy toward penicillins.


Rhinitis therapy and the prevention of hospital care for asthma: a case-control study.
Although clinical trials have demonstrated that rhinitis therapy improves subjective and objective measures of asthma, it is uncertain whether treatment of allergic rhinitis significantly affects the frequency of asthma exacerbations. The objective of this study was to determine whether treatment with intranasal corticosteroids and/or second-generation antihistamines is associated with changes in rates of asthma exacerbations resulting in emergency room visits and/or hospitalizations in patients with asthma and allergic rhinitis. This was a nested, case-control study. Treatment with either nasal corticosteroids or second-generation antihistamines was associated with a lower risk of asthma-related emergency room treatment and hospitalization (adjusted odds ratio [OR], 0.51; 95% CI, 0.34 to 0.77 and 0.34, 0.18 to 0.62, respectively). Patients who used nasal corticosteroids had a significantly lower risk of both asthma-related emergency room treatment and hospitalization (adjusted OR, 0.75; 95% CI, 0.62 to 0.91 and 0.56, 0.42 to 0.76, respectively), whereas there was a trend toward lower risk of emergency room treatment and hospitalization in patients who used second-generation antihistamines (adjusted OR, 0.88; 95% CI, 0.62 to 1.26 and 0.68, 0.40 to 1.14, respectively). Combined treatment with both medications was associated with a further lowering of the risk of both emergency room treatment and hospitalization (adjusted OR, 0.37; 95% CI, 0.19 to 0.73 and 0.22, 0.07 to 0.63). In patients with asthma, treatment of concomitant allergic rhinitis was associated with significant reductions in risk of emergency room treatment and hospitalization for asthma.


Morphological evaluation of areas of damage in blunt cardiac injury and investigation of traffic accident research.
This study investigated the relation between the cause of blunt cardiac injury and areas of damage. For the purpose of injury prevention, we also examined traffic accident cases in a micro study using engineering-based medicine. Among the 2673 patients transported to our facility within the 15-month period from February 2009 to April 2010, there were 12 cases of cardiac perforation. We studied these cases anatomically to evaluate the morphology of the damaged cardiac areas. We conducted a detailed micro-study in two cases regarding the circumstances surrounding the traffic accident and the vehicular damage. Subjects were nine men (mean age 64 years). The mean Injury Severity Score was 54.0 ± 19.6, and the probability of survival was 0.147. The actual survival rate was 16.7% (2 survivors, 10 deaths). Lesion sites in the 12 cases (21 sites in total) were the right atrium in 8 cases, superior and inferior vena cava in 5 cases, right ventricle in 4 cases, pulmonary artery and left atrium in 1 case each, and pulmonary vein in 2 cases, excluding the left ventricle and ascending aorta. In three cases, the aortic isthmus was also injured. Blunt cardiac injury was more common on the right side chamber. The survival rate was extremely close to the calculated survival probability. Proper seatbelt usage is important for the prevention of blunt cardiac injury due to traffic accidents. Increased severity of injury may be associated with accidents involving light motor vehicles.


Cerebrospinal Fluid Analysis Post-COVID-19 Is Not Suggestive of Persistent Central Nervous System Infection.
This study was undertaken to assess whether SARS-CoV-2 causes a persistent central nervous system infection. SARS-CoV-2-specific antibody index and SARS-CoV-2 RNA were studied in cerebrospinal fluid following COVID-19. Cerebrospinal fluid was assessed between days 1 and 30 (n = 12), between days 31 and 90 (n = 8), or later than 90 days (post-COVID-19, n = 20) after COVID-19 diagnosis. SARS-CoV-2 RNA was absent in all patients, and in none of the 20 patients with post-COVID-19 syndrome were intrathecally produced anti-SARS-CoV-2 antibodies detected. The absence of evidence of SARS-CoV-2 in cerebrospinal fluid argues against a persistent central nervous system infection as a cause of neurological or neuropsychiatric post-COVID-19 syndrome. ANN NEUROL 2022;91:150-157.


Deletion 7q22 in uterine leiomyoma. A cytogenetic review.
The cytogenetic patterns of uterine leiomyomas have been extensively investigated, and cases characterized by specific clonal changes have been documented in detail. In these tumors one of the cytogenetic changes frequently observed has been a del(7), particularly del(7)(q22), usually as a sole anomaly. This is confirmed by our experience and by reports in the literature. The fact that del(7) is one of the most common abnormalities in leiomyoma raises the question of its role in tumor development. The main purpose of this review is to analyze the above aspect and to interpret its possible meaning. Our findings on cytogenetic abnormalities of chromosome 7 in leiomyoma, together with those reported in the literature, are reviewed and discussed. A listing of the genes located at 7q22 is also presented.


Degradation and structure change of humic acids corresponding to water decline in Zoige peatland, Qinghai-Tibet Plateau.
As the largest plateau-type wetland in the world and the largest peat storage in China, Zoige wetland faces severe water decline, and consequently accelerated peat degradation and carbon emission. Here, a variety of characterization approaches, including elemental analysis, UV-vis spectra, FT-IR spectra, and solid state (13)C NMR spectra were used to investigate the degradation and the structural shift of humic acids (HAs) in correspondence with serious water loss in Zoige peatland. Water loss derived from both natural slope and artificial drainage caused a substantial degradation of organic matter and HAs. Compared with the blocks immersed by free surface water, HAs extracted from the drier blocks had more pronounced signals of carboxyl and carbonyl groups, but carried lower content of methoxyl, carbohydrate, alcohol and ether groups. The total aliphatic carbon in HAs from natural-slope drier site decreased almost one half, but in the artificial-drained site, only slightly decreased. Correspondingly, the HA aromaticity substantially increased in the site undergoing the longer time of aerobic oxidation, whereas varied little in the site impacted by extensive water leaching.


Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.
A positive family history (FH) is a risk factor for late-onset Alzheimer's disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum. Cross-sectional analyses of data from a national biomarker study. The Alzheimer's Disease Neuroimaging Initiative national study. 257 subjects (ages 55-89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data. Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes. Univariate and multivariate analyses. In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH- subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited "pathologic signature of AD" (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH- controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH- subjects in any group. A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.


Skin Microbiome and its Interplay with the Environment.
Advances in sequencing, bioinformatics and analytics now allow the structure, function and interrelations of whole microbial communities to be studied in greater detail. Collaborative efforts and multidisciplinary studies, crossing the boundary between environmental and medical microbiology, have allowed specific environmental, animal and human microbiomes to be characterized. One of the main challenges for microbial ecology is to link the phylogenetic diversity of host-associated microbes to their functional roles within the community. Much remains to be learned on the way microbes colonize the skin of different living organisms and the way the skin microbiome reacts to the surrounding environment (air, water, etc.). In this review, we discuss examples of recent studies that have used modern technology to provide insights into microbial communities in water and on skin, such as those in natural resources (thermal spring water), large mammals (humpback whales) and humans (the skin microbiome). The results of these studies demonstrate how a greater understanding of the structure and functioning of microbiota, together with their interactions with the environment, may facilitate the discovery of new probiotics or postbiotics, provide indicators for the quality of the environment, and show how changes in lifestyle and living environment, such as urbanization, can impact on the skin microbiome and skin health and disease in humans.


Determination of carboxypeptidase A using N-acetyl-phenylalanyl-3-thiaphenylalanine as substrate: application to a direct serum assay.
N-Acetyl-L-phenylalanyl-L-3-thiaphenylalanine has been shown to be a substrate for carboxypeptidase A. Hydrolysis of the compound obeys Michaelis-Menten kinetics with a KM of 0.22 mM and a kcat of 6720 min-1 at 22 degrees C. A colorimetric assay, employing Ellman's reagent to detect the thiophenol released upon cleavage of the peptide, has been developed. The assay can be used for the direct determination of carboxypeptidase A in serum.


Validity and reliability of the Persian version of modified motivated strategies for learning questionnaire: a methodological study among medical students.
Medical undergraduates need to improve their techniques for learning in the different settings of learning in clinical rotations. Reflective learning, in which a person can learn from their experiences, is among the most well-known learning skills. In this study, we aim to translate the newly developed modified form of the motivated strategies for learning questionnaire (MSLQ) to Persian and evaluate its reliability and validity among medical students. This study was performed on medical students in clinical stages at the Shiraz University of Medical Science in 2022. The modified MSLQ questionnaire was used in this study which is a 32-item tool measuring different aspects of self-reflecting, including self-orientation, feedback-seeking, critical thinking, and self-regulation. This questionnaire was translated into Persian properly. Cronbach's alpha and confirmatory factor analysis were used to ascertain the reliability and validity of the tool. A total of 325 medical students consisting of 174 men and 151 women with an average age of 23.79 (± 2.21) were enrolled. Path diagrams of confirmatory factor analysis for both standardized regression coefficients and t-values and all the fitness indicators were in favor of the proper validation of the translated version. The overall Cronbach's alpha for the questionnaire was 0.9, and the value for each of four subscales was above 0.7. Our study showed that the Persian-translated version of the modified MSLQ is valid and reliable without taking too much time and effort to implement. We recommend that the developed tool be distributed to medical students from other Iran universities.


The obstetrician-gynecologist and reproductive health. Presidential address.
The sources of nutrition and energy on this planet are limited and already in short supply. Improvement in the health and welfare of individuals and of nations will not be possible unless man promptly and effectively decreases the numbers of children being born to numbers that can be adequately fed and provided a chance of individual development. Currently available knowledge and methodologies do provide effective means of limiting human reproduction to the number of children for whom a family unit can adequately care. Gynecologists and obstetricians might well assume a more significant role in helping to limit the numbers of children being born so that populations can be adequately fed and more individuals will have opportunity to realize health and a hope of individual achievement. Man's current needs, as well as the gynecologist-obstetrician's capabilities, suggest designation of "reproductive health" as a specialty within gynecology and obstetrics, because the management of fertility should be recognized as a major responsibility of the gynecologist and obstetrician.


Nephrotoxicity of hexachloro-1:3-butadiene in the male Hanover Wistar rat; correlation of minimal histopathological changes with biomarkers of renal injury.
Hexachloro-1:3-butadiene (HCBD) causes damage specifically to the renal proximal tubule in rats. In the present study, injury to the nephron of male Hanover Wistar rats was characterized at 24 h following dosing with HCBD in the range 5-90 mg kg⁻¹ to determine the most sensitive biomarkers of damage, that is, the biomarkers demonstrating significant changes at the lowest dose of HCBD, using a range of measurements in serum and urine, renal histopathology, and renal and hepatic gene expression. Histologically, kidney degeneration was noted at doses as low as 10 mg kg⁻¹ HCBD. Significant changes in the hepatic and renal gene expression categories of xenobiotic metabolism and oxidative stress were observed at 5 mg kg⁻¹ HCBD, and in the kidney alone, evidence of inflammation at 90 mg kg⁻¹ HCBD. Increases in the urinary excretion of α-glutathione S-transferase (α-GST) and kidney injury molecule-1 (KIM-1) were seen at 10 mg kg⁻¹ HCBD, and increases in urinary excretion of albumin and total protein were evident at 15 mg kg⁻¹ HCBD. The most sensitive, noninvasive biomarkers of HCBD-induced renal toxicity in Hanover Wistar rats were urinary α-GST and KIM-1. Urinary albumin measurement is also recommended as, although it is not the most sensitive biomarker, together with α-GST, albumin showed the largest relative increase of all the biomarkers investigated, and the protein is easily measured.


Development of inducible leucine-rich repeat kinase 2 (LRRK2) cell lines for therapeutics development in Parkinson's disease.
The pathogenic mechanism(s) contributing to loss of dopamine neurons in Parkinson's disease (PD) remain obscure. Leucine-rich repeat kinase 2 (LRRK2) mutations are linked, as a causative gene, to PD. LRRK2 mutations are estimated to account for 10% of familial and between 1 % and 3 % of sporadic PD. LRRK2 proximate single nucleotide polymorphisms have also been significantly associated with idiopathic/sporadic PD by genome-wide association studies. LRRK2 is a multidomain-containing protein and belongs to the protein kinase super-family. We constructed two inducible dopaminergic cell lines expressing either human-LRRK2-wild-type or human-LRRK2-mutant (G2019S). Phenotypes of these LRRK2 cell lines were examined with respect to cell viability, morphology, and protein function with or without induction of LRRK2 gene expression. The overexpression of G2019S gene promoted (1) low cellular metabolic activity without affecting cell viability, (2) blunted neurite extension, and (3) increased phosphorylation at S910 and S935. Our observations are consistent with reported general phenotypes in LRRK2 cell lines by other investigators. We used these cell lines to interrogate the biological function of LRRK2, to evaluate their potential as a drug-screening tool, and to investigate screening for small hairpin RNA-mediated LRRK2 G2019S gene knockdown as a potential therapeutic strategy. A proposed LRRK2 kinase inhibitor (i.e., IN-1) decreased LRRK2 S910 and S935 phosphorylation in our MN9DLRRK2 cell lines in a dose-dependent manner. Lentivirus-mediated transfer of LRRK2 G2019S allele-specific small hairpin RNA reversed the blunting of neurite extension caused by LRRK2 G2019S overexpression. Taken together, these inducible LRRK2 cell lines are suitable reagents for LRRK2 functional studies, and the screening of potential LRRK2 therapeutics.


Molecular animations in genomics education: designing for whom?
Molecular animations can be beneficial as teaching tools for genomics education; however, barriers to their effective implementation remain. This article proposes informed design guidelines from the perspective of the animator that may assist others to effectively communicate scientific concepts to their respective audiences and communities.


Effectiveness of glass ionomer cements in the restorative treatment of radiation-related caries - a systematic review.
The aim of this systematic review was to investigate the clinical effectiveness of glass ionomer cements (GICs) compared to other restorative materials in the treatment of radiation-related caries. Two independent researchers searched literature databases (PubMed, Scopus, Web of Science, Cochrane Library, Lilacs/BBO) and the grey literature to identify clinical trials that compared GICs with other restorative materials for the treatment of radiation-related caries. The clinical criteria considered for the performance of the restorations were based on the parameters of marginal adaptation/anatomical form, secondary caries, retention, and cumulative failures of the restorations. The methodological quality and risk of bias were evaluated using the Cochrane Collaboration tool. From a total of 511, only four articles fulfilled the inclusion criteria. Conventional GIC restorations presented higher marginal adaptation failures than the resin-modified glass ionomer cements (RM-GICs) and composite restorations in all of the follow-up periods. Secondary caries was not observed in conventional GIC restorations throughout the follow-up periods, in three out of four of the included studies. RM-GICs and composite restorations showed significantly lower cumulative failure rates than conventional GICs at 6-, 12-, and 18-month follow-ups. Due to insufficient scientific evidence, it was not possible to conclude that GICs are more effective than other restorative materials for the treatment of radiation-related caries.


A rare case of self-healing giant condyloma acuminatum.
Giant condyloma acuminatum (GCA) which is also called Buschke-Lowenstein tumor. It is a rare tumor of the anorectal area and external genitalia associated with low-risk HPV types 6 or 11. GCA has a high-rate of recurrence (66%) and malignant transformation (56%). The clinical features of GCA are progression of exophytic, ulcerative, and cauliflower-shaped tumors, it has significant dimensions and may undergo malignant transformation such as squamous cell carcinoma or cervical cancer. It is difficult to treat GCA, and it may be impossible for GCA to self-healing, but we herein report a rare case of a 19-year-old female with self-healing GCA.


Magnetic resonance imaging reveals distinct bone marrow patterns in indolent and advanced systemic mastocytosis.
Systemic mastocytosis (SM) is broadly subcategorized according to mast cell (MC) burden and organ involvement into indolent (ISM), smoldering (SSM), and advanced SM (AdvSM). However, the pattern and extent of bone involvement remains controversial. In this institutional review board (IRB)-approved study, 115 patients with different forms of SM (ISM (n = 37, 32%), SSM (n = 9, 8%), and AdvSM (n = 69, 60%)) underwent a whole-body magnetic resonance imaging including sagittal and coronal T1 and turbo inversion recovery magnitude (TIRM) sequences of the spine. The evaluation included the pattern and extent of pathologic bone marrow (BM) signals in the spine and extremities, osteolytic lesions, and vertebral fractures. A pathologic BM pattern was observed in 4/37 (11%), 8/9 (89%), and 66/69 (96%); affection of the appendicular skeleton in 3/37 (8%), 8/9 (89%), and 67/69 (97%); and vertebral fractures in 7/37 (19%), 0/9, and 13/69 (19%) patients with ISM, SSM, and AdvSM, respectively. In AdvSM, pathologic BM pattern included activated (62%), diffuse sclerotic (25%), and small-spotted BM (9%), respectively. Only activated/sclerotic BM was associated with significantly higher MC burden, organ damage, and inferior median survival (2.9 years, p = 0.04). Vertebral fractures resembled classical multi-segmental osteoporotic fractures in ISM but not in AdvSM in which they were only found in activated/sclerotic BM. Only one patient with AdvSM had a focal osteolytic lesion in the femur. Activated/sclerotic BM changes of the spine and affection of the appendicular skeleton are indicative for SSM or AdvSM. Osteolytic lesions, which are very rare, and osteoporotic fractures are ineligible for the diagnosis of AdvSM.


Low curcumin concentrations combined with blue light inhibits cutibacterium acnes biofilm-induced inflammatory response through suppressing MAPK and NF-κB in keratinocytes.
Curcumin has been employed as a photosensitizer agent during photodynamic therapy (PDT). Cutibacterium acnes (C. acnes) can cause an inflammatory response in human keratinocytes; however, no research has been conducted to determine whether curcumin and its photodynamic properties can prevent this inflammatory reaction. We hypothesized that curcumin may control the C. acnes biofilm-induced inflammatory response in keratinocytes, either alone or in combination with blue light photodynamic therapy. Following C. acnes biofilm stimulation, human primary keratinocytes were treated with 20 μM curcumin solution alone or 5 μM curcumin with combined blue light irradiation. The amount of secreted protein was measured using an ELISA kit. The expression levels of Toll-like receptor 2 (TLR2) and its downstream proteins were determined using western blot. Treatment with 20 μM curcumin, but not 5 μM curcumin, reduced the inflammatory response to C. acnes biofilms in keratinocytes by blocking the TLR2/MAPK/NF-κB pathway. Interestingly, 5 μM curcumin combined with blue light also reduced the C. acnes biofilm-induced inflammation indicated above by blocking the TLR2/MAPK/NF-κB pathway. Curcumin alone, in sufficient concentrations, or low-concentration curcumin with blue light had anti-inflammatory activity on keratinocytes stimulated by C. acnes biofilms through inhibition of MAPK and NF-κB signaling pathways by downregulating TLR2 expression.


Recommendations for post-implementation adaptations to optimize family navigation in pediatric primary care: a qualitative study with parents and navigators.
Family Navigation (FN) is an evidence-based care management intervention designed to reduce disparities in access to care by providing families with individually tailored support and care coordination. Early data suggest FN is effective, but effectiveness is significantly influenced by both contextual (e.g. setting) and individual (e.g., ethnicity) variables. To better understand how FN could be tailored to address this variability in effectiveness, we set forth to explore proposed adaptations to FN by both navigators and families who received FN. This study was a nested qualitative study set within a larger randomized clinical trial of FN to improve access to autism diagnostic services in urban pediatric primary care practices in Massachusetts, Pennsylvania, and Connecticut serving low-income, racial and ethnic minority families. Following FN implementation, key informant interviews were conducted based on the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) with a purposeful sample of parents of children who received FN (n = 21) and navigators (n = 7). Interviews were transcribed verbatim and were coded using framework-guided rapid analysis to categorize proposed adaptations to FN. Parents and navigators proposed 38 adaptations in four domains: 1) content of the intervention (n = 18), 2) context of the intervention (n = 10), 3) training and evaluation (n = 6), and 4) implementation and scale-up (n = 4). The most frequently endorsed adaptation recommendations focused on content (e.g., lengthening FN, providing parents with additional education on autism and parenting children with autism) and implementation (e.g., increasing access to navigation). Although probes targeted critical feedback, parents and navigators were overwhelmingly positive about FN. This study builds upon prior FN effectiveness and implementation research by providing concrete areas for adaptation and refinement of the intervention. Recommendations by parents and navigators have the potential to inform improvement of existing navigation programs and development of new programs in similarly underserved populations. These findings are critical as adaptation (cultural and otherwise) is an important principle in the field of health equity. Ultimately, adaptations will need to be tested to determine clinical and implementation effectiveness. ClinicalTrials.gov, registration number NCT02359084, February 9, 2015.


SLC25A12 and CMYA3 gene variants are not associated with autism in the IMGSAC multiplex family sample.
Autism is a severe neurodevelopmental disorder with a complex genetic predisposition. Linkage findings from several genome scans suggest the presence of an autism susceptibility locus on chromosome 2q24-q33, making this region the focus of candidate gene and association studies. Recently, significant association with autism has been reported for single-nucleotide polymorphisms (SNPs) in the SLC25A12 and CMYA3 genes on chromosome 2q. We attempted to replicate these findings in the collection of families from the International Molecular Genetic Study of Autism Consortium (IMGSAC), using the transmission disequilibrium test and case-control comparison. Our study failed to reveal any significant association for the SNPs tested at either locus, suggesting that these variants are unlikely to play a major role in genetic susceptibility to autism in our sample.


Effects of temperature on survival, infectivity and in vitro encystment of the cercariae of Echinostoma caproni.
The effects of temperature on survival, infectivity and in vitro encystment of Echinostoma caproni cercariae in artificial spring water (ASW) were studied. Effects of aging cercariae in ASW at various temperatures showed that at 23 degrees C cercariae achieved 50% survival in 24 h, compared to 92 h at 12 degrees C. Cercariae aged in ASW at 28 and 37.5 degrees C showed 50% survival at 16 and 10 h, respectively. Cercariae aged at different temperatures for various times were used to infect juvenile Helisoma trivolvis (Colorado strain) snails maintained in ASW at 23 degrees C. Index of infectivity was based on counting encysted metacercariae in the snails at 8 to 12 h post-infection. Cercariae aged at 23, 28 and 37.5 degrees C showed 50% encystment at 6, 8 and 4 h, respectively. Cercariae aged at 4 degrees C showed 50% encystment in 10 h and cercariae aged at 12 degrees C showed 50% encystment beyond 16 h. Cercariae showed maximal longevity and infectivity in snails when aged at 12 degrees C in ASW. For E. caproni, as in other digeneans, the infective period of cercariae is markedly shorter than the maximal life-span at any given temperature. Studies on in vitro encystment of E. caproni cercariae in Locke's solution:ASW (1:1) showed that encystment was optimal at 23 degrees C (78% encystment) and that it declined to 44% at 28 degrees C and became almost nil (0.02%) at 12 or 37.5 degrees C.


Perceived-Benefit-of-Drinking Scale: approach to screening for adolescent alcohol abuse.
An index that measures adolescents' perceived benefits of drinking, the self-administered Perceived-Benefit-of-Drinking Scale, has been tested on a high school population. Results indicate that the instrument is practical and that it generates a scalable, reliable, and valid measure of reasons for drinking. The scale's strong relationship with other drinking behavior indicators makes it a potentially useful clinical screening device because it can serve as a proxy measure to assess the drinking behaviors of adolescents.


Novel Risk Factors for Type 2 Diabetes in African-Americans.
In the USA, compared to whites, African-Americans are disproportionately impacted by the diabetes epidemic. Traditional diabetes risk factors, such as obesity, are more common among African-Americans, but these traditional risk factors do not explain all of the disparity in diabetes risk. Recent research has identified novel environmental, lifestyle, physiologic, and genetic risk factors for diabetes, some of which appear to impact African-Americans more than whites. This manuscript reviews the recent literature to highlight some of these novel risk factors that may be contributing to the racial disparity in diabetes risk. Further study is needed of the modifiable risk factors for development of interventions to reduce the risk of diabetes in African-Americans, as well as other high-risk populations.


Beneficial effects of CCL8 inhibition at lipopolysaccharide-induced lung injury.
CCL8 (MCP-2) is a chemoattractive cytokine associated with various immune-related pathologies. Recent studies show that CCL8 is significantly stimulated during acute respiratory distress syndrome in severely ill patients with COVID-19, making the inhibition of CCL8 activity a promising treatment. Lipopolysaccharide (LPS)-induced lung injury was evaluated in mice using a neutralizing antibody (1G3E5) against human CCL8. Pharmacokinetic studies indicated that following IP administration, 1G3E5 was sustained at higher levels and for a longer period compared to IV administration. CCL8 expression in the lungs was not enhanced by LPS, but CCR2 and CCR5 receptors were significantly stimulated. 1G3E5-mediated inhibition of CCL8 was associated with the reduction of pulmonary inflammation and suppression of various pro-inflammatory cytokines. These results point to a previously unrecognized, permissive role for CCL8 in mediating cytokine induction and ultimately sustaining inflammation. Disruption of CCL8 activity may provide a strategy for mitigating pulmonary inflammation during lung injury when related to abnormal cytokine induction.


Dynamics of the vesicles composed of fatty acids and other amphiphile mixtures: unveiling the role of fatty acids as a model protocell membrane.
Fundamental research at the interface of chemistry and biology has the potential to shine light on the question of how living cells can be synthesized from inanimate matter thereby providing plausible pathways for the emergence of cellular life. Compartmentalization of different biochemical reactions within a membrane bound water environment is considered an essential first step in any origin of life pathway. It has been suggested that fatty acid-based vesicles can be considered a model protocell having the potential for change via Darwinian evolution. As such, protocell models have the potential to assist in furthering our understanding of the origin of life in the laboratory. Fatty acids, both by themselves and in mixtures with other amphiphiles, can form different self-assembled structures depending on their surroundings. Recent studies of fatty acid-based membranes have suggested likely pathways of protocell growth, division and membrane permeabilisation for the transport of different nutrients, such as nucleotides across the membrane. In this review, different dynamic processes related to the growth and division of the protocell membrane are discussed and possible pathways for transition of the protocell to the modern cell are explored. These areas of research may lead to a better understanding of the synthesis of artificial cell-like entities and thus herald the possibility of creating new form of life distinct from existing biology. Graphical Abstract Table of Content (TOC) only.


Isolated congenital asplenia: a French nationwide retrospective survey of 20 cases.
To better describe the natural history, mode of inheritance, and the epidemiological and clinical features of isolated congenital asplenia, a rare and poorly understood primary immunodeficiency. A French national retrospective survey was conducted in hospital pediatric departments. A definitive diagnosis of ICA was based on the presence of Howell-Jolly bodies, a lack of detectable spleen, and no detectable cardiovascular malformation. The study included 20 patients (12 males and 8 females) from 10 kindreds neither related to each other nor consanguineous. The diagnosis of ICA was certain in 13 cases (65%) and probable in 7 cases (35%). Ten index cases led to diagnosis of 10 additional cases in relatives. Five cases were sporadic and 15 were familial, suggesting autosomal dominant inheritance. Median age was 12 months at first infection (range, 2-516 months), 11 months at diagnosis of asplenia (range, 0-510 months), and 9.9 years at last follow-up (range, 0.7-52 years). Fifteen patients sustained 18 episodes of invasive bacterial infection, caused mainly by Streptococcus pneumoniae (61%). Outcomes were poor, with 9 patients (45%) dying from fulminant infection. ICA is more common than was previously thought, with an autosomal dominant inheritance in at least some kindreds. Relatives of cases of ICA should be evaluated for ICA, as should children and young adults with invasive infection.


Michelob_x is the missing inhibitor of apoptosis protein antagonist in mosquito genomes.
Apoptosis is implicated in the life cycle of the malaria parasite in mosquitoes. The genome project for the primary malaria vector Anopheles gambiae showed a significant expansion of the inhibitor of apoptosis protein (IAP) and caspase gene families in comparison with Drosophila. However, because of extensive sequence divergence, no orthologue was identified for the reaper/grim-like IAP antagonist genes that have a pivotal role in cell death regulation in Drosophila. Using a customized searching strategy, we identified michelob_x(mx), a gene not predicted by the genome project, as the missing IAP antagonist in the An. gambiae and other mosquito genomes. Mx has a highly conserved amino-terminal IAP-binding motif. Expression of Mx induces rapid cell death in insect cell lines and is a potent tissue ablator in vivo. Its proapoptotic activity is totally dependent on the IAP-binding motif. Like reaper in Drosophila, mx is transcriptionally induced by ultraviolet irradiation to mediate cell death.


The effect of caffeine on ambulatory blood pressure in hypertensive patients.
Because the potential impact of habitual caffeine intake on blood pressure is a controversial issue, a study was carried out to explore the relationship between caffeine and various humoral factors that could account for a coffee-induced rise in blood pressure. Twenty-three hypertensive patients who refrained from caffeine for 2 to 3 weeks were given 250 mg oral caffeine powder dissolved in water. Blood pressure was recorded every 15 min by blood pressure monitor. Caffeine blood level, renin and endothelin were measured before and 1, 2, 3, and 6 h after caffeine intake. Urinary electrolytes and catecholamines were measured under caffeine influence (period I), and for the next 6 h (period II). A significant increase in systolic (P = .017) and diastolic blood pressure (P = .023) occurred in 13 subjects who were 58 +/- 10.4 years old. Nonresponders were younger (44.5 +/- 15.8 years). A statistically significant decrease in heart rate was seen during the first hour after caffeine intake in both responders (P = .008) and nonresponders (P = .004). Marked diuresis and natriuresis were observed during period I in both groups. Renin and endothelin levels were unchanged. Although chronic studies point to development of tolerance to long-term caffeine ingestion, acute studies like the one described are essential to obtain data on the immediate effects that can be of practical importance, especially in the elderly.


Expression of Fos protein in brainstem after application of l-menthol to the rat nasal mucosa.
There are two functional pathways for the nasotrigeminal reflex: the spinal nucleus of trigeminal nerve (SPV) to the Kölliker-Fuse (KF) nucleus and the nucleus of solitary tract (NTS) to the lateral parabrachial nucleus (PBl). Although stimulation of the nasal mucosa by cool temperature induces respiratory depression, it is still unknown whether these nuclei are activated. In the present study, we examined the expression of Fos protein in rat brainstem neurons after nasal application of l-menthol, which is known to activate cold-sensitive nasal receptors. Application of l-menthol, but not paraffin oil, decreased the respiratory rate from 99.7+/-15.6 to 78.5+/-7.3 min(-1). Furthermore, a significantly higher density of Fos-immunoreactive cells was observed in the SPV and KF in the l-menthol rats than in the controls. In the SPV, the density of Fos-immunoreactive cells was highest at approximately 0.5mm rostral to the obex in both the l-menthol (48.5+/-11.5 cells/section) and paraffin oil (26.0+/-9.6 cells/section) groups. In the KF, the mean density of Fos-immunoreactive cells was highest at approximately 5.0mm rostral to the obex in both groups (l-menthol: 67.8+/-14.0 cells/section, control: 41.0+/-12.7 cells/section). The present study suggests that the SPV-KF pathway is important for the cold-induced respiratory depression.


Development of a candidate multi-epitope vaccine against Sphingobacterium spiritivorum : Reverse vaccinology and immunoinformatics approach.
To develop a candidate vaccine aginst the Sphingobacterium spiritivorum. Since there is currently no vaccine against this pathogen, we employed in-silico methods to extensively explore the outer membrane toxin-producing proteins found specifically in S. spiritivorum to forecast a multi-epitope chimeric vaccine design. This computational study was conducted in Saudi Arabia in 2022 (study design: computational; ethical approval not applicable). TThe vaccine peptide comprises multiple linear and conformational B-cell epitopes, which have the potential to elicit humoral immunity. Projected B-cell- derived T-cell epitopes for outer membrane proteins are present in the produced protein. The docking and molecular dynamic simulation results indicating that the chimeric vaccine had adequate binding stability with TLR-4. Following the immunological simulation, significant levels of immune cell expression were observed as immunoglobulin (Ig) M and IgG, IgM, IgM1, and IgM2, and independently IgG1 and IgG2. The developed vaccine candidate is suitable for further testing and can assist experimental vaccinologists in developing an effective vaccine against S. spiritivorum.


Relaxation of large coronary artery by verapamil, D600, and nifedipine is constrictor selective: comparison with glyceryl trinitrate.
We compared the vasodilator potencies of a number of Ca2+-entry blockers with glyceryl trinitrate (GTN) in isolated ring segments of dog coronary arteries contracted by a variety of substances. Rings were contracted to 80% of maximum by serotonin, phenylephrine (PE), noradrenaline (NA), K+ (KCl), or U46619 (stable thromboxane A2 analogue). Cumulative additions of a vasodilator then relaxed the ring towards basal tone. GTN had a similar IC50 value (0.1 - 0.3 microM) regardless of the substance used to contract the ring. In contrast, nifedipine and verapamil were weak relaxant drugs against arteries contracted by U46619. Nifedipine was most potent in rings contracted by K+, whereas verapamil was similarly effective towards K+ and serotonin, but threefold less potent against PE or NA. The (-)enantiomers of verapamil and D600 were more potent (seven-to 26-fold) than the (+)enantiomers in arteries contracted by K+ or serotonin, but not for PE or NA. A combination of (-)verapamil and GTN showed additive effects without a change in the IC50 for GTN. We conclude that, in contrast with GTN, the effectiveness of Ca2+-entry blockers in the treatment of coronary vasospasm may be dependent on the nature of the constrictor signal.


Cyanidin-3-O-β-glucoside regulates fatty acid metabolism via an AMP-activated protein kinase-dependent signaling pathway in human HepG2 cells.
Hepatic metabolic derangements are key components in the development of fatty liver disease. AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and carnitine palmitoyl transferase 1 (CPT-1) pathway. In this study, cyanidin-3-O-β-glucoside (Cy-3-g), a typical anthocyanin pigment was used to examine its effects on AMPK activation and fatty acid metabolism in human HepG2 hepatocytes. Anthocyanin Cy-3-g increased cellular AMPK activity in a calmodulin kinase kinase dependent manner. Furthermore, Cy-3-g substantially induced AMPK downstream target ACC phosphorylation and inactivation, and then decreased malonyl CoA contents, leading to stimulation of CPT-1 expression and significant increase of fatty acid oxidation in HepG2 cells. These effects of Cy-3-g are largely abolished by pharmacological and genetic inhibition of AMPK. This study demonstrates that Cy-3-g regulates hepatic lipid homeostasis via an AMPK-dependent signaling pathway. Targeting AMPK activation by anthocyanin may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease.


Effect of acute levodopa on brain catecholamines after selective MAO and COMT inhibition in male rats.
Interactions between a selective catechol-O-methyltransferase (COMT) inhibitor OR-462 and a monoamine oxidase (MAO)-A inhibitor clorgyline were studied measuring concentrations of L-dopa, dopamine and their metabolites in the rat hypothalamus and striatum after administration of levodopa/carbidopa (15/30 mg/kg i.p.). Part of the experiments were performed in rats pretreated with 6-OH-dopamine (6-OHDA) intracerebroventricularly (i.c.v.) to determine whether changes in dopamine metabolism occurred inside or outside catecholaminergic neurons. OR-462 was an effective COMT inhibitor at the doses 3 and 30 mg/kg i.p. Inhibition of 3-O-methyldopa (3-OMD) formation from L-dopa was reflected in the hypothalamus (45-81% decrease) and striatum (87-88% decrease), since 3-OMD penetrates the blood-brain barrier. Homovanillic acid (HVA) was decreased only in the striatum at 30 mg/kg of OR-462. Clorgyline (8 and 32 mg/kg i.p.) decreased 3,4-dihydroxyphenylacetic acid (DOPAC) formation in the hypothalamus and striatum by 61-91%. When given together, OR-462 and clorgyline elevated hypothalamic dopamine levels 3.2-4.6-fold, but striatal dopamine only 1.3-1.9-fold. The formation of 3-OMD and DOPAC remained suppressed and even brain HVA levels were decreased by 51-97%. 6-OHDA treatment decreased striatal and hypothalamic dopamine by 50% and noradrenaline by 75%. In these animals levodopa/carbidopa increased brain L-dopa 2.4-4-fold, those of 3-OMD 1.2-1.7-fold compared to intact animals, but the synthesis and metabolism of dopamine and the effects of COMT and MAO inhibitors were not significantly changed. Levodopa/carbidopa treatment decreased significantly prolactin and thyrotropin levels in serum but none of the additional treatments changed this action.


Lipid composition of serum lipoproteins in patients with primary type IIb and type IV hyperlipoproteinemia.
Cholesterol, triglyceride and phospholipid concentrations of VLDL, LDL and HDL were studied in 20 patients with primary type IIb, 25 patients with primary type IV and in 18 controls. Both types are not only characterized by different concentrations of lipoprotein lipids, but also by their different lipid composition. Type IIb had more triglycerides in the LDL, type IV in the LDL and HDL. The HDL cholesterol content of type IV was decreased. The percent phospholipid concentration of HDL was identical in the 3 groups, demonstrating the constant role of this lipid fraction. The lipid relationships between the lipoproteins showed that the LDL/HDL lipid ratio of type IIb exceeded type IV ratio in spite of normal HDL lipid concentration in type IIb.


Heat flux from the fetal scalp during labor and fetal outcome.
In 40 deliveries a new variable, heat flux from the fetal scalp, was recorded and correlated with fetal outcome. The heat flux from the fetus, which reflects the temperature gradient between the warmer fetus and the mother was measured by a transducer attached to the fetal scalp after rupture of the membranes. In the last 20 min before delivery we found a statistically significant correlation (p less than 0.05) between heat flux from the fetus and pH of umbilical artery blood. Heat flux in the group with higher pH differed significantly from those with lower pH. We conclude that heat flux measurements could be developed and used for fetal monitoring.


Relationship of the internal carotid artery to the anterior aspect of the C1 vertebra: implications for C1-C2 transarticular and C1 lateral mass fixation.
Anatomic study of the internal carotid artery (ICA) location with respect to C1 based on computed tomography (CT) scans with contrast medium. To measure the location of the ICA relative to the anterior aspect of C1 to assess the risk of placing C1-C2 transarticular or C1 lateral mass screws. Vertebral artery injury is a known risk from placement of screws in C1. A previous case report revealed an ideally placed C1-C2 transarticular screw abutting and narrowing the ICA. The risk of ICA injury from C1 screws is unknown. Fifty random head and neck CT scans with contrast medium were retrospectively analyzed. Measurements were taken bilaterally including the closest distance from the ICA lumen to C1 and the distance from the medial edge of the ICA to a line drawn along the medial border of the foramen transversarium. The risk of inserting bicortical C1-C2 transarticular and C1 lateral mass screws was estimated based on these measurements. The mean distance from the ICA to C1 was 2.88 mm on the left and 2.89 mm on the right. The ICA lumen was medial to the foramen transversarium in 42 (84%) of 50 cases (mean: 2.78 mm on the left and 3.00 mm on the right). The proximity of the ICA to C1 posed moderate risk in 46% of cases and high risk in 12% (on at least one side). Because of the risk of ICA injury from a drill bit or the tip of a bicortical screw, we recommend preoperative CT scan with contrast medium in all cases in which a screw is to be placed into C1. If the ICA is in close proximity to the anterior border of C1, unicortical fixation or a different fusion technique should be considered.


Endodontic and post-endodontic management of a fused molar.
Treatment of fused teeth needs special care and attention to the bizarre anatomy. This paper describes root canal treatment of a fused carious tooth presenting with apical periodontitis. It is a rare case of fusion of the mandibular second molar with a paramolar. There is no literature regarding placement of crown over endodontically treated fused teeth. In this case, the fused teeth were endodontically treated and restored by a porcelain fused to metal crown.


Epigenetic Age Acceleration and Hearing: Observations From the Baltimore Longitudinal Study of Aging.
Objectives: Age-related hearing loss (ARHL) is highly prevalent among older adults, but the potential mechanisms and predictive markers for ARHL are lacking. Epigenetic age acceleration has been shown to be predictive of many age-associated diseases and mortality. However, the association between epigenetic age acceleration and hearing remains unknown. Our study aims to investigate the relationship between epigenetic age acceleration and audiometric hearing in the Baltimore Longitudinal Study of Aging (BLSA). Methods: Participants with both DNA methylation and audiometric hearing measurements were included. The main independent variables are epigenetic age acceleration measures, including intrinsic epigenetic age acceleration-"IEAA," Hannum age acceleration-"AgeAccelerationResidualHannum," PhenoAge acceleration-"AgeAccelPheno," GrimAge acceleration-"AgeAccelGrim," and methylation-based pace of aging estimation-"DunedinPoAm." The main dependent variable is speech-frequency pure tone average. Linear regression was used to assess the association between epigenetic age acceleration and hearing. Results: Among the 236 participants (52.5% female), after adjusting for age, sex, race, time difference between measurements, cardiovascular factors, and smoking history, the effect sizes were 0.11 995% CI: (-0.00, 0.23), p = 0.054] for Hannum's clock, 0.08 [95% CI: (-0.03, 0.19), p = 0.143] for Horvath's clock, 0.10 [95% CI: (-0.01, 0.21), p = 0.089] for PhenoAge, 0.20 [95% CI: (0.06, 0.33), p = 0.004] for GrimAge, and 0.21 [95% CI: (0.09, 0.33), p = 0.001] for DunedinPoAm. Discussion: The present study suggests that some epigenetic age acceleration measurements are associated with hearing. Future research is needed to study the potential subclinical cardiovascular causes of hearing and to investigate the longitudinal relationship between DNA methylation and hearing.


Association between SGK1 and α-synuclein in skeletal muscle in an MPTP-induced Parkinson's disease model.
Parkinson's disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the substantia nigra and it is known to involve the accumulation of α-synuclein (α-syn), which is a neuroprotein that promotes degeneration of dopaminergic neurons. Serum/glucocorticoid-related kinase 1 (SGK1) is involved in the physiological and pathological processes in neurons. The aim of this study was to examine the relationship between SGK1 and α-syn expression in muscle tissue of a PD model and in C2C12 cells. Western blotting, immunohistochemistry, and immunofluorescence microscopy confirmed reduced SGK1 and increased α-syn expression in skeletal muscle of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice compared to the control group. To determine the relationship between SGK1 and α-syn, SGK1 small interfering RNA (siRNA) knockdown was performed in C2C12 cells, which showed that suppression of SGK1 levels resulted in increased α-syn expression. The main finding of our study is that reduction of SGK1 expression contributes to the pathogenesis of PD by increasing the expression of α-syn in skeletal muscle of MPTP-treated mice and C2C12 cells. This study confirms that decreased SGK1 induces increased α-syn expression in skeletal muscle, which suggests that maintaining SGK1 expression may improve PD symptoms.


An incarcerated appendix and the ileocecum within a left inguinal hernia in an infant.
An 8-month-old boy with a left-sided incarcerated inguinal hernia involving the appendix, cecum, and terminal ileum was successfully managed via an inguinal approach during an emergency operation. A mobile cecum seemed to have contributed to the left-sided incarceration. Only 13 similar cases with the left-sided Amyand's hernia have been reported in the literature.


Survival in patients with poorly compressible leg arteries.
This study sought to compare survival of patients with poorly compressible arteries (PCA) to those with a normal ankle-brachial index (ABI) and those with peripheral arterial disease (PAD). Limited data are available regarding survival in patients with PCA identified in the clinical setting by noninvasive lower extremity arterial evaluation. We conducted a historical cohort study of consecutive patients who underwent outpatient, noninvasive lower extremity arterial evaluation at the Mayo Clinic, Rochester, Minnesota, from January 1998 through December 2007, and who were followed for a mean duration of 5.8 ± 3.1 years. An ABI 1.00 to 1.30 was considered normal, PAD was defined as a resting or post-exercise ABI ≤0.90, and PCA defined as an ABI ≥1.4 and/or an ankle systolic blood pressure >255 mm Hg. Patients were followed for all-cause mortality through September 30, 2009. Of 16,493 individuals (mean age 67.8 ± 13.0 years, 59% male); 29% had normal ABI, 54% had PAD, and 17% had PCA. During follow-up (mean duration 5.8 ± 3.1 years), 4,365 patients (26%) died. The percent alive at the end of the study period was 88%, 70%, and 60% for normal ABI, PAD, and PCA, respectively. After adjustment for age, sex, cardiovascular risk factors, comorbid conditions, and medication use, the hazard ratios (95% confidence intervals) of death associated with PCA were 2.0 (1.8 to 2.2) and 1.3 (1.2 to 1.4) compared with the normal ABI and PAD groups, respectively. Patients identified by noninvasive vascular testing to have poorly compressible leg arteries have poor survival, worse than those with a normal ABI or those with PAD.


Pure mini-laparoscopic transperitoneal pyeloplasty in an adult population: feasibility, safety, and functional results after one year of follow-up.
To report the results of mini-laparoscopic pyeloplasty (mLP) in an adult population. The feasibility of pure mLP has been previously reported in children. From April 2009 to February 2010, 10 patients with ureteropelvic junction obstruction (UPJO) were enrolled in this prospective study and underwent pure mLP (using only 3-mm instruments) according to the Anderson-Hynes technique. Inclusion criteria were: age >18 years, body mass index <25, primary UPJO, and no previous surgery on the affected kidney or a history of major abdominal surgery. Demographic and perioperative data, as well as 1-, 3-, 6-, and 12-month follow-up data were collected. The mean operative time was 134 minutes, and blood loss was negligible. All procedures but one were completed using only 3.9-mm ports and 3-mm instruments. No perioperative complications occurred, and no patients had computed tomography evidence of hydronephrosis at 6 months after surgery. No functional obstructions were visualized with renal scintigraphy at 12 months after surgery. All patients were satisfied with the intervention and with their cosmetic results, as assessed by the Patient Scar Assessment Questionnaire and Scoring System. The results of our study suggest that pure mLP in an adult population is feasible and seems to be safe and effective in the treatment of UPJO. Furthermore, the patients tolerated the procedure well and appreciated its excellent cosmetic results. Further studies are required to determine the true advantages of mLP over standard laparoscopy.


Latitudinal Variation in Circadian Rhythmicity in Nasonia vitripennis.
Many physiological processes of living organisms show circadian rhythms, governed by an endogenous clock. This clock has a genetic basis and is entrained by external cues, such as light and temperature. Other physiological processes exhibit seasonal rhythms, that are also responsive to light and temperature. We previously reported a natural latitudinal cline of photoperiodic diapause induction in the parasitic wasp Nasonia vitripennis in Europe and a correlated haplotype frequency for the circadian clock gene period (per). To evaluate if this correlation is reflected in circadian behaviour, we investigated the circadian locomotor activity of seven populations from the cline. We found that the proportion of rhythmic males was higher than females in constant darkness, and that mating decreased rhythmicity of both sexes. Only for virgin females, the free running period (τ) increased weakly with latitude. Wasps from the most southern locality had an overall shorter free running rhythm and earlier onset, peak, and offset of activity during the 24 h period, than wasps from the northernmost locality. We evaluated this variation in rhythmicity as a function of period haplotype frequencies in the populations and discussed its functional significance in the context of local adaptation.


Osmotic potential and turgor maintenance in Spartina alterniflora Loisel.
The dependence of leaf water potential (Ψ), osmotic potential (π) and turgor pressure (P) on relative water content (RWC) was determined for leaves of tall and short growth forms of Spartina alterniflora Loisel. from a site on Canary Creek marsh in Lewes, Delaware. Tall plants (ca. 1.5 m) occured along a drainage ditch where interstitial water salinity was approximately 20‰, and short plants (ca. 0.2 m) were 13 m away near a pan and exposed to 80‰ salinity during the most stressful period. Leaves were collected at dawn and pressure-volume measurements were made as they desiccated in the laboratory. Pressure equilibrium was used to measure Ψ, RWC was determined from weight loss and dry weight, π was determined from the pressure volume curve, and P was calculated as the difference between Ψ and π. Physical properties of the bulk leaf tissue that have a role in regulating water balance of the two growth forms were estimated: relative water content of apoplastic water (RWCa) relative water content at zero turgor (RWC0), the bulk modulus of elasticity (E), and water capacity (C w). There were no detectable temporal trends in any of the parameters measured from Nune through September and no significant differences between the two growth forms when compared on the basis of RWCa, RWC0, E, and C w. There was a clear difference between the two growth forms with respect to π; at RWC0, π was-4.5±0.40 MPa for short form plants and-3.3±0.40 MPa for tall form.Turgor pressure of plants in the field (P') was lower in leaves from short form than for the tall form plants with average difference of about 0.4 MPa. In July, P' in short form leaves dropped to zero by mid-morning as expected for leaves experiencing water stress.These results show that S. alterniflora is capable of reducing osmotic potential in response to increased salinity and that turgor pressure was lower in short growth form than in tall forms.


[Angiofollicular lymph node hyperplasia. About an exceptional meso-sigmoid localization (author's transl)].
The authors report the first angiofollicular Lymph-Node Hyperplasia (Castleman'tumor) case with a meso-sigmoid location. They carry out a general review of the literature on 315 observations and insist on the anatomic and evolutive aspects allowing a better understanding of the histogenesis of the lesion. The inflammatory theory, actually acknowledge by most of the authors, also seems to them the most plausible.


Polarization modulation with optical lock-in detection reveals universal fluorescence anisotropy of subcellular structures in live cells.
The orientation of fluorophores can reveal crucial information about the structure and dynamics of their associated subcellular organelles. Despite significant progress in super-resolution, fluorescence polarization microscopy remains limited to unique samples with relatively strong polarization modulation and not applicable to the weak polarization signals in samples due to the excessive background noise. Here we apply optical lock-in detection to amplify the weak polarization modulation with super-resolution. This novel technique, termed optical lock-in detection super-resolution dipole orientation mapping (OLID-SDOM), could achieve a maximum of 100 frames per second and rapid extraction of 2D orientation, and distinguish distance up to 50 nm, making it suitable for monitoring structural dynamics concerning orientation changes in vivo. OLID-SDOM was employed to explore the universal anisotropy of a large variety of GFP-tagged subcellular organelles, including mitochondria, lysosome, Golgi, endosome, etc. We found that OUF (Orientation Uniformity Factor) of OLID-SDOM can be specific for different subcellular organelles, indicating that the anisotropy was related to the function of the organelles, and OUF can potentially be an indicator to distinguish normal and abnormal cells (even cancer cells). Furthermore, dual-color super-resolution OLID-SDOM imaging of lysosomes and actins demonstrates its potential in studying dynamic molecular interactions. The subtle anisotropy changes of expanding and shrinking dendritic spines in live neurons were observed with real-time OLID-SDOM. Revealing previously unobservable fluorescence anisotropy in various samples and indicating their underlying dynamic molecular structural changes, OLID-SDOM expands the toolkit for live cell research.


Management of high-flow priapism in paediatric patients: a case report and review of the literature.
Priapism is rare in the paediatric population and hence there is little consensus as to appropriate management strategies. This is a report of a case of high-flow priapism in a 9-year-old boy managed expectantly. A review of the literature found 52 previously published cases. This report highlights the diagnostic problems and examines the safety and effectiveness of expectant management in the paediatric population.


Coronary heart disease risk factors and menopause: a study in 1980 Tehranian women, the Tehran Lipid and Glucose Study.
The menopause is associated with an increased incidence of coronary heart disease (CHD). Assessing CHD risk factors in menopausal women can shed more light on the pathogenesis of accelerated atherosclerosis after the cessation of ovarian function. In this study, 1980 women aged 44-69 years were selected from among 15 005 participants in the Tehran Lipid and Glucose Study (TLGS) and assessed for CHD risk factors. They were classified into three groups: premenopausal women (n = 483), aged between 44 and 50 years, without any history of menstrual irregularities; menopausal women (n = 310), with permanent cessation of menses for at least 12 months and a duration of less than 3 years; and postmenopausal women (n = 1187), with at least a 3-year history of cessation of menses. Demographic information including waist size, height, weight and systolic and diastolic blood pressures was recorded, and body mass index, low-density lipoprotein/high-density lipoprotein ratio (LDL/HDL) and waist/hip ratio were calculated. Serum total cholesterol, triglycerides and HDL were measured and an oral glucose tolerance test was performed. The LDL level was calculated using the Friedwald formula. Mean systolic blood pressures were 121 +/- 18, 125 +/- 20 and 136 +/- 23 mmHg (p< 0.001) and mean diastolic blood pressures were 80 +/- 10, 81 +/- 11 and 82 +/- 11 mmHg (p< 0.001) in premenopausal, menopausal and postmenopausal women, respectively. For premenopausal, menopausal and postmenopausal women, mean cholesterol levels were 215 +/- 42, 238 +/- 45 and 245 +/- 46 mg/dl (p< 0.001), respectively. HDL and LDL levels were 44 +/- 11, 48 +/- 12 and 47 +/- 11 mg/dl and 138 +/- 38, 156 +/- 41 and 161 +/- 42 mg/dl (p< 0.001) for premenopausal, menopausal and postmenopausal women, respectively. Mean LDL/HDL ratios were 3.4 +/- 1.4, 3.5 +/- 1.3 and 3.6 +/- 1.2 (p< 0.01) and mean waist measurements were 92 +/- 11, 93 +/- 12 and 95 +/- 12 cm (p< 0.001) for the same groups of women, respectively. However, body mass index, waist/hip ratio and triglycerides showed no significant differences between the three groups. These data demonstrate an increase in CHD risk factors in a group of Tehranian women after the menopause.


Effects of microRNA-195 on the Prognosis of Glioma Patients and the Proliferation and Apoptosis of Human Glioma Cells.
Glioma is the most common and aggressive intracranial malignant tumor with poor prognosis. Acts as a tumor suppressor, microRNA-195 (miR-195) plays important roles in a variety of cancers. However, the expression of miR-195 and role of miR-195 in glioma are still not well understood. 186 patients with glioma were enrolled and the follow-up period ranges from 1 to 69 months. MiR-195 was exogenously transfected into human glioma U87 cell line. The cell proliferation assay (CCK-8), colony formation assay, cell cycle analysis and cell apoptosis analysis were examined to investigate miR-195 effect on U87 cells. MiR-195 levels were reversely correlated with pathological grades (r = -0.487, p = 0.003). For patients with low miR-195 levels, their median survival time was 15 months, whereas the median survival time in patients with high miR-195 levels was 56.53 months. Multi-factor Cox regression analysis showed that high level of miR-195 (Odds ratio (OR): 0.347, 95% CI: 0.121-0.992) was associated with decreased mortality risk of patients. Moreover, overexpression of miR-195 inhibits proliferation and colony formation, and induces apoptosis of U87 cells. MiR-195 could block the glioma cells in G0/G1 phase, reducing S phase cells and regulating apoptosis related proteins (Caspase-3, Caspase-8, Caspase-9 and Bcl-2). Downregulation of miR-195 was associated with poor prognosis in human glioma. MiR-195 acted as tumor suppressor through inhibiting cell proliferation and promoting cell apoptosis via blockade of cell cycle and regulation of apoptosis related proteins.


Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib.
Observational studies have shown reduced risk of Alzheimer dementia in users of nonsteroidal anti-inflammatory drugs. To evaluate the effects of naproxen sodium and celecoxib on cognitive function in older adults. Randomized, double-masked chemoprevention trial. Six US memory clinics. Men and women aged 70 years and older with a family history of Alzheimer disease; 2117 of 2528 enrolled had follow-up cognitive assessment. Celecoxib (200 mg twice daily), naproxen sodium (220 mg twice daily), or placebo, randomly allocated in a ratio of 1:1:1.5, respectively. Seven tests of cognitive function and a global summary score measured annually. Longitudinal analyses showed lower global summary scores over time for naproxen compared with placebo (- 0.05 SDs; P = .02) and lower scores on the Modified Mini-Mental State Examination over time for both treatment groups compared with placebo (- 0.33 points for celecoxib [P = .04] and - 0.36 points for naproxen [P = .02]). Restriction of analyses to measures collected from persons without dementia attenuated the treatment group differences. Analyses limited to measures obtained while participants were being issued study drugs produced results similar to the intention-to-treat analyses. Use of naproxen or celecoxib did not improve cognitive function. There was weak evidence for a detrimental effect of naproxen.


Efficacy and safety of Guhong injection for coronary heart disease: A protocol for systematic review and meta-analysis.
Coronary heart disease (CHD) is considered one of the major causes of morbidity and mortality worldwide, posing a serious threat to public health. Current therapeutic approaches for CHD mainly focus on drug therapy, coronary artery bypass grafting, and percutaneous coronary intervention. However, there still exist some problems including drug side effects, adverse cardiac events after percutaneous coronary intervention. Guhong injection is a compound preparation of traditional Chinese medicine and western medicine. Several clinical studies have shown that Guhong injection can effectively relieve the clinical symptoms of CHD patients and improve clinical efficacy. However, there is no systematic review to evaluate the effectiveness and safety of Guhong injection in treating CHD. Therefore, in this study we will plan to systematic review to evaluate the effectiveness and safety of Guhong injection for CHD, providing a strong evidence-based medical reference for clinical use. The database search includes EMBASE, PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang Database, Chinese Biomedical Database, Chinese Scientific Journal Database. The retrieval time was from their inception to November 30, 2021. The main outcome indicators include the frequency, severity, and duration of angina pectoris attacks, electrocardiogram changes, and dose of nitroglycerin. The analysis software uses RevMan 5.3. By collecting the existing evidence, the results of this study will systematically evaluate the effects of Guhong injection in the treatment of CHD. The results of this study will provide evidence for the efficacy and safety of Guhong injection in the treatment of CHD. INPLASY2021120032.


Microbiology of chronic suppurative otitis media in a tertiary care setup of uttarakhand state, India.
Chronic suppurative otitis media (CSOM) is a notorious infection and a major health problem in developing countries causing serious local damage and threatening complications. Early and effective treatment based on the knowledge of causative micro-organisms and their antimicrobial sensitivity ensures prompt clinical recovery and possible complications can thus be avoided. The aim of this study was to isolate the organisms associated with CSOM and to detect the antibiogram of the aerobic isolates. A total of 204 patients clinically diagnosed of CSOM were enrolled in the study and the samples were obtained from each patient using sterile cotton swabs and cultured for microbial flora. Drug susceptibility testing for aerobic isolates was conducted using Kirby-Bauer disc diffusion method. The most common causative organisms isolated were Staphylococcus aureus (48.69%) and Pseudomonas aeruginosa (19.89%) amongst the 191 aerobic isolates. Anaerobes accounted for 29.41% of the isolates while 12.25% were fungi. Antimicrobial profile of aerobic isolates revealed maximum sensitivity to amikacin (95.5%), ceftriaxone (83.4%) and gentamicin (82.7%). Knowing the etiological agents of CSOM and their antimicrobial susceptibility is of essential importance for an efficient treatment, prevention of both complications and development of antibiotic resistance and finally, the reduction of the treatment costs.


Studies of formation and efflux of methotrexate polyglutamates with cultured hepatic cells.
Methotrexate polyglutamates are extensively synthesized when cultured hepatocytes and H35 hepatoma cells are exposed to micromolar concentrations of methotrexate. The predominant species found within the cell have from two to four additional gamma-linked glutamate residues. When either cell type containing a mixture of methotrexate and its polyglutamate derivatives is exposed to medium lacking methotrexate, there is a rapid release of methotrexate. This release has a T1/2 of 2 to 4 min and is apparently complete within 30 to 60 min. Methotrexate polyglutamates leave the cells much more slowly and appear to do so by two mechanisms. Although cleavage to methotrexate and subsequent efflux appears to be quantitatively the more important pathway, there is also a slow, finite loss of intact methotrexate polyglutamates from cells which exclude trypan blue. The T1/2 for the loss of methotrexate polyglutamates by both cell types, when placed in medium lacking methotrexate, is approximately 6 to 8 hr. These results, together with those of an earlier study (Galivan, J. (1980) Mol. Pharmacol. 17:105-110), suggest that the polyglutamate derivatives are forms of methotrexate which are as cytotoxic as methotrexate but which offer a potentially greater capacity for cellular destruction because they are retained longer in the tissue.


An 8-year-old boy with altered mental status.
Management of an acutely ill pediatric patient with undifferentiated altered mental status is a common challenge facing air medical crewmembers. The transport team is often the vital link between the referring agency and a tertiary care center; it is incumbent upon the team to be able to meet the challenges of patient management including airway management, providing hemodynamic support, and addressing presenting symptoms. This case presents a child with altered mental status and seizure activity requiring advanced interventions and support. His hospital course is described and reveals an encephalopathy caused by the Bartonella henselae bacterium also known as cat-scratch disease. This case shows the pathology, symptomology, and management along with the importance of proper management and interventions by air medical crewmembers to maximize outcomes.


What factors should we modify to promote high functioning and prevent functional decline in people with schizophrenia?
Since research in schizophrenia mainly focuses on deficits and risk factors, we need studies searching for high-functioning protective factors. Thus, our objective was to identify protective (PFs) and risk factors (RFs) separately associated with high (HF) and low functioning (LF) in patients with schizophrenia. We collected information (sociodemographic, clinical, psychopathological, cognitive, and functional) from 212 outpatients with schizophrenia. Patients were classified according to their functional level (PSP) as HF (PSP > 70, n = 30) and LF (PSP ≤ 50, n = 95). Statistical analysis consisted of Chi-square test, Student's t-test, and logistic regression. HF model: variance explained: 38.4-68.8%; PF: years of education (OR = 1.227). RFs: receiving a mental disability benefit (OR = 0.062) and scores on positive (OR = 0.719), negative-expression (OR = 0.711), and negative-experiential symptoms (OR = 0.822), and verbal learning (OR = 0.866). LF model: variance explained: 42.0-56.2%; PF: none; RFs: not working (OR = 6.900), number of antipsychotics (OR = 1.910), and scores on depressive (OR = 1.212) and negative-experiential symptoms (OR = 1.167). We identified specific protective and risk factors for high and low functioning in patients with schizophrenia and confirmed that high functioning factors are not necessarily the opposite of those associated with low functioning. Only negative experiential symptoms are a shared and inverse factor for high and low functioning. Mental health teams must be aware of protective and risk factors and try to enhance or reduce them, respectively, to help their patients improve or maintain their level of functioning.


Percutaneous cholecystostomy treatment of acute cholecystitis in pregnancy.
Medical treatment of acute cholecystitis in pregnancy may lead to prolonged management and recurrent hospitalizations, whereas surgical management predisposes the mother and fetus to the inherent risks of surgery and general anesthesia. Although percutaneous cholecystostomy has been proven to be an efficacious treatment in critically ill and general surgery patients who are at high risk for surgery, this technique has not been used routinely as a treatment for acute cholecystitis in pregnancy. We report two women (at 30 and 32 weeks' gestation, respectively) who presented with acute calculus cholecystitis. The first patient was a 33-year-old female who failed endoscopic retrograde cholangiopancreatography and papillotomy and had multiple return visits for nausea and vomiting. The second patient was a 23-year-old female with three previous admissions for cholecystitis during the pregnancy. These two patients underwent emergency ultrasound-guided percutaneous transhepatic cholecystostomy. Percutaneous cholecystostomy provided adequate biliary decompression for the remainder of the pregnancy; the patients delivered healthy infants and underwent successful uncomplicated elective laparoscopic cholecystectomy within 3 months of delivery. Percutaneous cholecystostomy may provide a safe and effective alternative for the palliation of acute cholecystitis in pregnancy until a postpartum cholecystectomy can be performed.


A new enzymatic method for the determination of glycollate in urine and plasma.
An enzymatic assay for the measurement of glycollate in urine and plasma is described. Gycollic acid oxidase (glycollate:oxygen oxidoreductase, EC 1.1.3), extracted from spinach leaves, is used in the enzymatic oxidation of glycollate to produce glyoxylate and hydrogen peroxide. In the presence of peroxidase, the hydrogen peroxide oxidatively couples sulphonated 2,4-dichlorophenol and 4-aminophenazone to form a soluble purple quinoneimine dye. Interfering substances are removed from plasma by deproteinisation and from urine by adsorption onto activated charcoal before analysis. Glycollic acid oxidase also catalyses the oxidation of lactic acid which therefore has to be determined separately. The mean normal urinary glycollate for adults is 0.19 mmol/24 h with no difference between males and females. The mean normal plasma glycollate for adults is 0.17 mmol/l, but higher in males than in females.


Dexamethasone suppression and energy balance: a study of anorexic patients.
The performance of the dexamethasone suppression test (DST) was investigated in 45 female anorexic out-patients (cross-sectional study) and in nine female anorexic in-patients (longitudinal study). DST non-suppression was strongly associated with negative energy balance (low body weight and low Ponderal Index) but there was no significant association with the presence of affective or neurotic disturbance in these patients. These findings cast doubt on the value of the DST in the management of depressive illness.


[VESTIBULAR FUNCTION AFTER REPEATED SPACE FLIGHTS].
Results of the vestibular function testing of 32 cosmonauts on return from repeated 125- to 215-day space flights (SF) on the International space station are presented. The cosmonauts were tested twice before flight (baseline data collection) and on days 1-2, 4-5 and 8-9 after landing. Electro- and video-oculography were used to register simultaneously eye and head movements. It was found that deadaptation following a repeated stay in long-duration SF takes statistically much shorter time. Most often, atypical vestibular disorders and changed patterns of the otolith-semicircular canal interaction are observed in cosmonauts who have made their maiden flights to microgravity.


Electron beam irradiation induced degradation of antidepressant drug fluoxetine in water matrices.
With the development of psychiatric disorder in the current society, abuse of antidepressant drug fluoxetine (FLX) has made such compound an emerging contaminant in natural waters, and causes endocrine systems disturbance on some aquatic species. Herein, an efficient advanced oxidation process (AOP), electron beam irradiation was carried out to investigate the decomposition characteristics of such novel environmental pollutant, including the effects of initial concentration, pH, radical scavengers and anions. The results showed that FLX degradation followed pseudo-first-order kinetics. The degradation rate and dose constant decreased with increasing initial FLX concentration; and G-values elevated with the increase of initial concentration but reduced with increase of absorbed dose. Acidic condition was more conducive to FLX destruction than neutral and alkaline. The radical scavenger experiments indicated OH was the main reactive species for the decomposition of FLX, while the reductive species e-aq and H played an adjuvant role. The presence of anions slightly decreased or even no impact on FLX degradation rate. Various water matrices influenced degradation processes of FLX. Experimental results suggested radiolytic degradation showed the best performance in pure water rather than natural water no matter with filtration or not. Moreover, with the occurrence of defluorination and dealkylation during degradation process, some organic and inorganic intermediates were detected, and the possible degradation mechanisms and pathways of FLX were proposed.


Survival of bacterial pathogens during the thermophilic anaerobic digestion of biowaste: laboratory experiments and in situ validation.
Anaerobic digestion is continually gaining importance for the processing of the organic fraction of municipal solid wastes. Although methods for studying the survival of pathogen exist, these methods often need adaptations, are expensive, time consuming or generally not well suited for the harsh conditions within an anaerobic digestion system. In the present study we investigated the applicability of commercially available, mechanically stable and inexpensive pathogen carriers to validate in situ pathogen inhibition within a 750,000l thermophilic, bio-waste treating anaerobic digester. None of the pathogens investigated (Listeria monocytogenes, Salmonella enterica, Escherichia coli, and Campylobacter jejuni) was capable of survival under the conditions of the biogas reactor for more than 24 h indicating that the temperature and physico-chemical properties of the sludge of the fermenter were effective in inhibiting the survival of these microorganisms.


Comparative characteristics of DNA loop domains rearrangement in glioblastoma multiforme T98G and glioblastoma astrocytoma U373 cell lines under different culture conditions.
The loop domain organization of chromatin, which plays an important role in transcription regulation, may depend on the cell functional state. The aim of this work was to investigate DNA loop reorganization upon functional transitions in two cell lines ‒ glioblastoma multiforme T98G and glioblastoma astrocytoma U373. Single cell gel electrophoresis (the comet assay) was used to analyze the kinetics of the DNA loop migration from the nucleoids obtained from the lysed cells. The DNA fraction in the surface loops and the size of these loops were found to be similar in two glioblastoma cell lines. When synthetic processes were inhibited, the migration of a small portion of inner loops was observed in T98G but not U373 cells. In T98G cells, stimulation of cell proliferation and transcription was accompanied by an increase in DNA fraction in the inner loops and an essential increase in the size of these loops. The effect of stimulation was practically absent in U373 cells. However, the linear density of the loops resolved by the comet assay was found to decrease upon stimulation of proliferation in both cell lines. A decrease in the loop density appears to be associated with an intensification of the synthetic processes in cells upon their stimulation.


Computational Fluid Dynamics Support for Fontan Planning in Minutes, Not Hours: The Next Step in Clinical Pre-Interventional Simulations.
Computational fluid dynamics (CFD) modeling may aid in planning of invasive interventions in Fontan patients. Clinical application of current CFD techniques is however limited by complexity and long computation times. Therefore, we validated a "lean" CFD method to magnetic resonance imaging (MRI) and an "established" CFD method, ultimately aiming to reduce complexity to enable predictive CFD during ongoing interventions. Fifteen Fontan patients underwent MRI for CFD modeling. The differences between lean and established approach, in hepatic and total flow percentage to the left pulmonary artery (%LPA), power loss and relative wall shear stress area were 1.5 ± 4.0%, -0.17 ± 1.1%, -0.055 ± 0.092 mW and 1.1 ± 1.4%. Compared with MRI, the lean and established method showed a bias in %LPA of -1.9 ± 3.4% and -1.8 ± 3.1%. Computation time was for the lean and established approach 3.0 ± 2.0 min and 7.0 ± 3.4 h, respectively. We conclude that the proposed lean method provides fast and reliable results for future CFD support during interventions.


[Continuous glucose monitoring in type 2 diabetes with gastroparesis].
To observe the glucose profile in type 2 diabetic gastroparesis. 31 patients diagnosed with type 2 diabetes were enrolled into this study for measurement of gastric emptying of solids and continuous glucose monitoring to observe blood glucose levels for 72 hours on a balanced diet; the results were compared with 7 subjects with normal glucose regulation. 58.1% of 31 type 2 diabetic patients were found to have delayed gastric emptying of solids. The average glucose level was lower after breakfast [(7.82 +/- 1.42) mmol/L vs (9.35 +/- 2.28) mmol/L, P < 0.01] in the patients with gastroparesis than in those without. Maximal blood glucose level after breakfast [(10.21 +/- 2.17) mmol/L vs (12.24 +/- 2.82) mmol/L, P < 0.01] was lower in the patients with gastroparesis but it reached the peak at a similar time. Two hour AUC was also lower after breakfast in the patients with gastroparesis [(877.62 +/- 272.78) min x mmol x L(-1) vs (1028.40 +/- 283.98) min x mmol x L(-1), P < 0.05]. Post-prandial glucose level in type 2 diabetic patients with gastroparesis tends to be lower than those without.


Does the grading of chondromalacia patellae influence anterior knee pain following total knee arthroplasty without patellar resurfacing?
The influence of chondromalacia patellae (CMP) on post-operative anterior knee pain (AKP) following total knee arthroplasty (TKA) remains controversial, and few studies have focused on the relationship between them. The purpose of this study was to determine whether different CMP grades affect the incidence of AKP after TKA without patellar resurfacing. We performed a retrospective analysis of prospectively collected data on 290 TKAs with the use of the low contact stress mobile-bearing prosthesis, without patellar resurfacing in 290 patients from February 2009 to January 2013. Patients were assessed by the Outerbridge classification for CMP, visual analog scale for AKP, the Knee Society clinical scoring system of knee score (KS), function score (FS), the patellar score (PS) for clinical function, and patients' satisfaction. The intra-operative grading of CMP: grade I in 30 patients, grade II in 68 patients, grade III in 97 patients, and grade IV in 95 patients. The incidence of AKP at 36-month follow-up was 10.3% (30/290). No statistical difference was detected among the different CMP grades in terms of the incidence of AKP (p = 0.995), patients' satisfaction (p = 0.832), KS (p = 0.228), FS (p = 0.713), and PS (p = 0.119) at 36-month follow-up. The findings may suggest no relevant influence of CMP grading on the incidence of AKP after TKA without patellar resurfacing.


Determination of the in vivo Km and Vmax of a drug with tracer studies.
A method is described for determining the in vivo Km and Vmax values for a drug, utilizing a variant of the Michaelis-Menten equation and the elimination-rate constants of tracer doses of the drug administered at two different serum concentration values. The new method is the most accurate yet devised; unlike older methods, it is dependent on assumptions that generally are true and can be validated empirically. Application of the method is demonstrated by a study of phenytoin in humans.


Erratum: Influence of GLP-1 receptor agonist on insulin dosage and blood glucose control of patients with type 2 diabetes mellitus.
[This corrects the article on p. 11814 in vol. 13, PMID: 34786110.].


Financing Diabetes Care in the U.S. Health System: Payment Innovations for Addressing the Medical and Social Determinants of Health.
Review innovations in health care financing promoting health system investments in addressing medical and social determinants of health (SDH) for patients with diabetes. Particular payment models implemented in the public and private sectors increasingly offer flexibility in health care organizations (HCOs) to allocate resources towards helping patients with diabetes overcome the medical and socio-economic problems driving poor population and individual health. The barriers imposed by the traditional fee-for-service (FFS) payment model to incorporating SDH into health care delivery across the health system are being overcome with new payment approaches rewarding the quality of care provided rather than strictly the volume of health services rendered. Evidence suggests health care financing changes will facilitate the realization of health reform goals to provide the right care to the right people at the right time through the expansion of the role of integrated care teams that can address patients' medical and health-related social needs.


Campylobacter jejuni gene expression in the chick cecum: evidence for adaptation to a low-oxygen environment.
Transcriptional profiling of Campylobacter jejuni during colonization of the chick cecum identified 59 genes that were differentially expressed in vivo compared with the genes in vitro. The data suggest that C. jejuni regulates electron transport and central metabolic pathways to alter its physiological state during establishment in the chick cecum.


Chloroquine removal of HLA antigens from platelets for the platelet immunofluorescence test.
Chloroquine-treated platelets did not react with HLA antisera in a platelet suspension immunofluorescence test (PSIFT), while the reactions with platelet-specific antibodies (P1A1, Baka) seemed even stronger after treatment. The method might be useful in discerning HLA and platelet-specific antibodies without absorption procedures. The treatment causes death of a proportion of the cells, with nonspecific fluorescence making the reading difficult. This may be circumvented by using special phase-contrast lenses.


Characterization of a novel mitovirus isolated from the phytopathogenic fungus Fusarium pseudograminearum.
Mycoviruses are widespread in all major groups of plant-pathogenic fungi. So far, only one mycovirus has been reported to be associated with Fusarium pseudograminearum, the causal agent of Fusarium crown rot of wheat. In this study, a double-stranded RNA (dsRNA) segment was isolated from F. pseudograminearum strain JW2-1, and the sequence of its full-length cDNA (3077 nucleotides) was determined. Sequence analysis using the fungal mitochondrial genetic code (UGA coding for tryptophan) indicated that a single large open reading frame (ORF) is present on the positive strand of this dsRNA segment. The ORF encodes a putative RNA-dependent RNA polymerase (RdRp) of 748 amino acids (aa) with a molecular mass of 83.46 kDa. BLASTp analysis revealed that its aa sequence was 28.49-44.03% identical to those of viruses of the family Mitoviridae, with the most similarity to the corresponding RdRp sequences of Ophiostoma mitovirus 1c (44.03% identity) and Ophiostoma mitovirus 1b (40.33% identity). Phylogenetic analysis showed that this mycovirus, designated as "Fusarium pseudograminearum mitovirus 1" (FpgMV1), should be classified as a member of a new species in the earlier proposed genus "Duamitovirus" within the family Mitoviridae. To our best of our knowledge, this is the first report of a mitovirus infecting F. pseudograminearum.