Toxoplasma gondii: partial cross-protection among several strains of the parasite against congenital transmission in a rat model.
Rats were immunized with cysts of two Toxoplasma strains or with RH strain tachyzoites prior to pregnancy. The litters of the 13 rats that received homologous challenges with cysts during pregnancy, were all protected, whereas of 173 rats that received heterologous challenges with cysts or oocysts, only 21 protected their litters. 38.3 and 17% of rats immunized with the RH and with complete strains respectively, and 57% of control rats challenged with cysts, transmitted the infection congenitally. The percentages when similar groups were challenged with oocysts, were 33.3, 48.2, and 56.2%, respectively. Immunization with cysts did not completely protect against challenge with oocysts, even if the same strain was used. The divergence of these results from the complete protection against congenital toxoplasmosis observed in immune women and ewes, might be due to the use of excessive challenge doses in the model.


The Treatment Patterns with Brolucizumab in Germany (REALIZE) Study: A Retrospective Cohort Study Based on Longitudinal Prescription Data.
This study describes real-world treatment patterns in Germany for brolucizumab, an anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD). This single-arm retrospective cohort study used German patient-level prescription data. Patients aged ≥ 50 years, who received ≥ 1 brolucizumab prescription in one eye only (unilateral) and had a minimum of 12 months follow-up were included. Three cohorts were defined from the overall population: anti-VEGF treatment-naive patients ("treatment-naive"); anti-VEGF treatment-experienced patients ("treatment-experienced"); and of the treatment-experienced cohort, patients persistent on brolucizumab for 12 months ("treatment-experienced persistent"), i.e. who received ≥ 2 brolucizumab injections and did not discontinue or use other anti-VEGF agents in that period. Descriptive statistics were used to analyse patient characteristics and injection intervals. A total of 2089 patients with at least 12 months follow-up and one brolucizumab injection were analysed. Most were female (58.1%), aged 80+ years (54.7%). A total of 539 (25.8%) were treatment-naive, 1550 (74.2%) treatment-experienced and, of those, 787 (50.8%) were persistent. Overall, the median (interquartile range, IQR) number of brolucizumab injections during the 12 months follow-up was 5.0 (3.0-8.0). In the treatment-naive and treatment-experienced sub-cohorts it was 5.0 (3.0-8.0) and 5.0 (3.0-9.0) injections, respectively. In the treatment-experienced persistent cohort the median (IQR) number of injections was 8.0 (5.0-10.0). In this same cohort, the median (IQR) treatment interval between anti-VEGF injections before switch to brolucizumab was 5.1 (4.0-8.0) weeks, whilst the brolucizumab interval at 12 months after switch was 8.0 (6.0-11.9) weeks. Of treatment-experienced patients, 67% extended their treatment interval and those with pre-switch intervals less than 6 weeks (< q6w), in particular, had meaningful treatment interval extensions. Patients who switched to brolucizumab had a median treatment interval extension of about 3 weeks at 12 months. These results show that treatment with brolucizumab has the potential to reduce treatment burden in patients with nAMD in routine clinical practice.


Defining the impact of Peyronie's disease on the psychosocial status of gay men.
Little sexual health research has been conducted in gay men. Anecdotally, this population seems to experience more bother related to Peyronie's disease (PD). To examine the impact of PD on psychosocial factors in gay vs straight men. All PD patients who were seen in the sexual medicine clinic were included. They completed three instruments: the PD questionnaire (PDQ), Self-Esteem and Relationship (SEAR) questionnaire, and a depression questionnaire (CES-D). We described demographics and sexual variables by sexual orientation. We then compared PDQ items and summary scores by sexual orientation, using a series of independent samples t tests. 34 consecutive gay and 464 straight men were included. Age and baseline characteristics were similar between the two cohorts, with the exception that fewer gay men were partnered (56% vs 87%, P < .01), and those with a partner had a shorter relationship duration: 109 ± 9 months vs 262 ± 175 months, P < .01. For the SEAR questionnaire, gay men demonstrated a more significant psychosocial impact of PD overall with lower SEAR sums (41 vs 57, P = .01) and a lower sexual relationship subdomain score (28 vs 47, P < .01). 41% of gay men vs 26% of straight men had CES-D scores consistent with depression as defined by a score of ≥16 (P = .09). In the PDQ domains, gay men scored less favorably with regard to bother scores (7 vs 5, P = .03) and pain scores (8 vs 4, P = .04). Gay men with PD experience significantly more psychosocial impact as evidenced by less favorable SEAR sum and sexual relationship scores, CES-D scores, and PDQ pain and bother domain scores. The psychosocial impact of PD is significant in all men, but it appears to be greater in gay men.


Unravelling caramelization and Maillard reactions in glucose and glucose + leucine model cakes: Formation and degradation kinetics of precursors, α-dicarbonyl intermediates and furanic compounds during baking.
Understanding the mechanisms leading to the multitude of newly-formed compounds generated during the thermal processing of food is important for the reasoned construction of quality. Thanks to a solid food model with a structure and technological history comparable to that of a real sponge cake and containing only known amounts of precursors (glucose with or without leucine), an adapted reaction scheme unravelling Maillard and caramelization reactions was built and then compared to experimental kinetic data measured on numerous reaction markers (precursors, α-dicarbonyl intermediates and furanic compounds). For caramelization, this study showed that glucose mainly formed 1,2-enediol and then fructose rather than glucosone and glyoxal. 5-hydroxymethylfurfural started to form when there were sufficient quantities of fructose, and 3,4-dideoxyoglucosone was not generated until after this step. Furfural was mainly formed via 3-deoxyglucosone. The involvement of leucine tended to accelerate the breakdown of sugars as more degradation pathways (via enaminols) were added.


Trends of reporting of 'serious'vs. 'non-serious' adverse drug reactions over time: a study in the French PharmacoVigilance Database.
• Several factors are known to influence spontaneous reporting of adverse drug reactions (ADRs). Among them, 'seriousness' of the reaction is one of the most important. • However, evolution in the reporting of 'serious'vs.'non-serious' ADRs over time for the same drug remains unknown. • Spontaneous reports mainly involve 'non-serious' ADRs during the first years of marketing and 'serious' ADRs later, particularly for drugs with non-hospital use. To investigate trends in spontaneous reporting to the French Pharmacovigilance system of 'serious' (SADRs) and 'non-serious' (NSADRs) adverse drug reactions over time. Annual SADR : NSADR ratios were calculated for each drug and their evolution tested with linear trend tests. Among the 39 new active substances commercialized in France in 2000, 16 had sufficient data to perform linear trend tests. An increasing linear relation was found for five widely prescribed drugs, a non-significant increasing trend for eight others, i.e. drugs mostly used in hospitals. ADR reports mainly concern NSADRs during first years of marketing. Reports of SADRs are proportionally more frequent later.


Synthesis and biological evaluation of 2-(arylethynyl)quinoline derivatives as mGluR5 antagonists for the treatment of neuropathic pain.
We described here the synthesis and biological evaluation of mGluR5 antagonists containing a quinoline ring structure. Using intracellular calcium mobilization assay (FDSS assay), we identified compound 5n, showing high inhibitory activity against mGluR5. In addition, it was found that compound 5n has excellent stability profile. Finally, this compound exhibited favorable analgesic effects in spinal nerve ligation model of neuropathic pain, which is comparable to gabapentin.


CircUCK2 regulates HECTD1-mediated endothelial-mesenchymal transition inhibition by interacting with FUS and protects the blood-brain barrier in ischemic stroke.
Ischemic stroke (IS) has become a cerebrovascular disease of widespread concern. Overexpression of circUCK2 alleviates neuronal damage in IS. However, the specific regulatory mechanisms of circUCK2 are not fully understood. In this study, we found that circUCK2 and HECT domain E3 ubiquitin ligase 1 (HECTD1) were downregulated in IS models in vitro and in vivo. Overexpression of circUCK2 or HECTD1 inhibited endothelial-mesenchymal transition (EndoMT) and protected the blood-brain barrier (BBB) in transient middle cerebral artery occlusion mice from damage. It was further discovered that circUCK2 regulated HECTD1 expressions by interacting with fused in sarcoma (FUS). Moreover, FUS overexpression partially restored the effect of circUCK2 on EndoMT, and overexpression of HECTD1 weakened the effect of FUS on EndoMT. Collectively, circUCK2 upregulates the expression of HECTD1 by combining with FUS and inhibits EndoMT to alleviate BBB damage in IS both in vivo and in vitro.


Methods for studying the nuclei and chromosomes of dinoflagellates.
Dinoflagellates are unicellular eukaryotic organisms whose nuclear structure, chromosome architecture, chromatin organization, DNA composition, and mitosis show original features. It has been necessary to adapt techniques and to create innovative methods for growing cells, isolating nuclei, and studies of their chromosomes by transmission electron microscope (TEM). Among these are innovative squash and whole-mount preparations for light and TEM observations of chromosome architecture and the spatial organization of nucleofilaments. Particular attention was given to adapt high-pressure freezing (fast-freeze fixation) techniques for the best preservation of delicate antigenic sites, and good immunodetection. The study of DNA replication with or without incorporation of bromodeoxyuridine (BrdU) was also refined to use confocal laser scanning microscopy. In this chapter, we describe methods that we have invented and/or improved from existing techniques in order to better understand this fragile chromosome architecture and the mechanisms intervening during mitosis and the cell cycle. These methods allowed us to detect specific DNA-binding proteins and the distribution of B-and Z-DNA in chromosomes during the cell cycle and mitosis, and to focus on the indissoluble link between chromosome structure and function.


PM2.5 contributed to pulmonary epithelial senescence and ferroptosis by regulating USP3-SIRT3-P53 axis.
Pulmonary epithelial cells act as the first line of defense against various air pollutant particles. Previous studies have reported that particulate matter 2.5 (PM2.5) could trigger pulmonary inflammation and fibrosis by inducing pulmonary epithelial senescence and ferroptosis. Sirtuin 3 (SIRT3) is one of critical the mitochondrial NAD+-dependent deacetylases, exerting antioxidant and anti-aging effects in multiple diseases. The present study aimed to explore the role of SIRT3 in PM2.5-induced lung injury as well as possible mechanisms. The role of SIRT3 in PM2.5-induced lung injury was investigated by SIRT3 genetic depletion, adenovirus-mediated overexpression in type II alveolar epithelial (AT2) cells, and pharmacological activation by melatonin. The protein level and activity of SIRT3 in lung tissues and AT2 cells were significantly downregulated after PM2.5 stimulation. SIRT3 deficiency in AT2 cells aggravated inflammatory response and collagen deposition in PM2.5-treated lung tissues. RNA-sequence and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the differentially expressed genes (DEGs) between SIRT3 flox and SIRT3 CKO mice were mainly enriched in ferroptosis and cellular longevity. Western blot further showed that SIRT3 deficiency in AT2 cells significantly upregulated the proteins associated with ferroptosis and cell senescence in PM2.5-treated lung tissues. In vitro experiments also showed that SIRT3 overexpression could decrease the levels of ferroptosis and cell senescence in PM2.5-treated AT2 cells. In addition, we found that PM2.5 could increase the acetylation of P53 via triggering DNA damage in AT2 cells. And SIRT3 could deacetylate P53 at lysines 320 (K320), thus reducing its transcriptional activity. PM2.5 decreased the protein level of SIRT3 by inducing proteasome pathway through downregulating USP3. Finally, we found that SIRT3 agonist, melatonin treatment could alleviate PM2.5-induced senescence and ferroptosis in mice. In conclusion, targeting USP3-SIRT3-P53 axis may be a novel therapeutic strategy against PM2.5-induced pulmonary inflammation and fibrosis by decreasing pulmonary epithelial senescence and ferroptosis.


Adult autoinflammatory disease frequency and our diagnostic experience in an adult autoinflammatory clinic.
Systemic autoinflammatory diseases (SAIDs) mainly include monogenic hereditary periodic fever syndromes, and NOD2-associated AID (NAID) is a polygenic SAID. Our aim was to study the disease frequency and report our diagnostic experience. A total of 266 adult patients with clinical phenotypes suspicious for SAIDs were studied at the Cleveland Clinic between November 2009 and February 2015. All patients were genotyped for NOD2 mutations or periodic fever syndrome panel. The definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. Of the 266 patients, 79 (29.7%) were diagnostic of SAIDs, including 54 cases of NAID, 13 familial Mediterranean fever (FMF), 6 tumor necrosis factor receptor-associated periodic syndrome (TRAPS), 5 cryopyrin-associated periodic disease (CAPS), and 1 hyper IgD periodic syndrome (HIDS). NOD2 genotyping had a higher concordance rate with the clinical phenotype for the diagnosis of NAID. Of 29 patients, 13 (44.8%) were clinically suspicious for FMF and had positive genetic testing. Of 66 patients, 6 (9%) were tested positive for TRAPS. Out of 23 patients, 5 (21.7%) were tested positive for CAPS. Only 1 patient tested positive for HIDS. The concordance between the working clinical diagnosis and positive genetic testing varied among the SAIDs. Our study demonstrates that NAID and FMF are relatively common in adults. TRAPS and HIDS are extremely rare, and the concordance between the working clinical diagnosis and positive genetic testing is considerably disproportional for TRAPS. Ordering of genetic testing for SAIDs should highly consider both the disease frequency and stringent phenotypes.


Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells.
Schizophrenia and major depression are associated with alterations in peripheral inflammatory markers, and anti-inflammatory therapy has been proposed as a promising add-on approach in the pharmacologic treatment of both disorders. Second-generation atypical antipsychotics are currently first-line drugs in the treatment of schizophrenia and are also used as augmentation strategies in treatment-resistant major depression. Furthermore, these drugs have been reported to exhibit distinct metabolic side effects and to influence inflammatory processes. In this study, we used ex vivo stimulation of primary human peripheral blood mononuclear cells (PBMC) from healthy blood donors with atypical antipsychotics olanzapine or aripiprazole to examine effects on cytokine production independent from metabolic side effects and disease status. Both olanzapine and aripiprazole stimulation decreased mRNA levels of IL-1β, IL-6, and TNF-α and resulted in diminished protein concentrations of IL-6 and TNF-α in conditioned medium of stimulated PBMC. A multiplex approach revealed additional downregulation of IL-2; MIP-1β and IP-10 secretion. Similarly, olanzapine and aripiprazole stimulation of the human monocytic cell line THP-1 resulted in a significant decrease in expression and secretion of IL-1β and TNF-α. Our results suggest that atypical antipsychotics directly influence immune cell function and thereby highlight the importance to factor in potential side effects of drugs routinely used in treatment of schizophrenia and major depression on inflammatory processes when considering anti-inflammatory drug therapy as an additional treatment option.


High-dose erlotinib for refractory leptomeningeal metastases after failure of standard-dose EGFR-TKIs.
After initial response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), approximately one-third of patients develop central nervous system (CNS) metastases, including leptomeningeal metastases (LM). To achieve longer survival, control of CNS metastases is important, but therapeutic options are limited for LM after failure of standard-dose EGFR-TKIs. We retrospectively evaluated the efficacy and safety of high-dose erlotinib in EGFR-mutant non-small cell lung cancer (NSCLC) patients with refractory LM after failure of standard-dose EGFR-TKIs. Survivals from diagnosis of LM to death were compared in patients with or without high-dose erlotinib. Between January 2007 and April 2013, we identified 35 patients with EGFR-mutant NSCLC, complicated with LM, and 12 underwent high-dose erlotinib, while the other 23 received only standard-dose EGFR-TKIs. In patients receiving high-dose erlotinib, magnetic resonance imaging response was confirmed in 3 (30 %) of 10 evaluable patients. Median time to CNS progression was 2.3 months (95 % confidence interval [CI] 1.8-5.5 months). Performance status and neurological symptoms improved in 4 (33 %) of 12 and 6 (50 %) of 12 patients, respectively. No severe adverse events (≥grade 3) associated with high-dose erlotinib were observed. Median survival time from diagnosis of LM in patients with high-dose erlotinib was 6.2 months (95 % CI 2.5-8.5 months), and in those without 5.9 months (95 % CI 1.3-7.8 months) (p = 0.94). High-dose erlotinib suggested its efficacy and safety in some patients with refractory LM. It represents a potential therapeutic option against LM after failure of standard-dose EGFR-TKIs, especially to palliate LM-related neurological symptoms.


Biochemical genetic analysis of formycin B action in Leishmania donovani.
Formycin B is cytotoxic toward Leishmania and is a potential chemotherapeutic agent for leishmaniasis. In order to determine the mechanism of action of formycin B, we have isolated and characterized clonal populations of formycin B-resistant Leishmania donovani. These formycin B-resistant clones are also cross-resistant to formycin A and allopurinol riboside-mediated growth inhibition. Incubation of the formycin B-resistant cells with [3H]formycin B indicates that, unlike wild type cells, the resistant populations cannot accumulate phosphorylated metabolites of exogenous [3H]formycin B. This is due to a defective transport system for formycin B in the resistant cells. However, wild type and mutant cells incorporate [3H]formycin A equally efficiently into [3H]formycin A-containing nucleotides and into RNA. These data suggest that formycin B cytotoxicity in Leishmania is not mediated by its incorporation as the adenosine analog into RNA. A plausible alternative hypothesis is proposed for the mechanism of action of the pyrazolo (4,3-d)pyrimidine C-nucleosides based upon depletion of an essential intracellular metabolite.


Relationship between the changes of positivity rate of HER2 expression and the diameter of invasive lesions in early breast cancer and its clinical significance.
The expression status of HER2 is an important factor in evaluating the prognosis of breast cancer. We found that the positivity rate of HER2 varied with the diameter of invasive lesions in early breast cancer.We aimed to explore the relationship between the change of HER2 positivity rate of early breast cancer and the diameter of the invasive foci and its clinical significance. A total of 217 patients with microinvasive breast cancer and T1a stage breast cancer were enrolled in this study. Machine learning algorithm was used to extract morphological features of invasive lesions in early breast cancer. Using Spearman to analysis the clinicopathological and morphological features related to HER2 expression McNemar test was used to analyze the consistency of HER2 expression between the carcinoma in situ area and the invasive cancer area. In early breast cancer, the diameter of the invasive foci was strongly negatively correlated with the expression status of HER2 (rho=-0.468, p < 0.001). As the diameter of the invasive foci increases, the HER2 positivity rate gradually decreases. When the diameter of the invasive foci> 2 mm, the positivity rate of HER2 was significantly reduced (from 52.6% to 16.1%, p < 0.001), which was close to the positivity rate of HER2 in ordinary invasive breast cancer. Moreover, most of the clinicopathological characteristics of breast cancer with an invasive lesion diameter of 1-2 mm and DCIS-MI were not significantly different (p > 0.05). Among 217 patients, the consistency rate of HER2 expression in carcinoma in situ and invasive foci areas was 97.7% (212/217), and there was no significant difference in HER2 expression status (p = 0.25 and p = 0.50, respectively). We recommend that breast cancer with an invasive lesion diameter of 1-2 mm should be classified as microinvasive breast cancer. In early breast cancer,the expression status of HER2 in the invasive foci area can refer to the HER2 expression status in carcinoma in situ area. However, it needs further support from a large amount of data and follow-up results.


Immunopathology of the eye: purification of canine retinal "S" antigen.
Canine retinal S antigen has been purified to study the retinal progressive atrophy of the dog. The purified antigen will be used to detect, by the ELISA technique, specific autoantibody in dogs with ocular diseases.


Diphallus associated with partial caudal duplication.
A 23-year-old man with similar pathology has presented in March 1998 for primary management of his diphallus and anorectal duplication.


CD10, estrogen and progesterone receptor expression in ovarian adenosarcoma.
: The low incidence of ovarian adenosarcomas explains the paucity of available data regarding their biologic markers. Our aim was to investigate the presence of CD10, estrogen and progesterone receptors (ER and PR) in these tumors. : Four cases of primary ovarian adenosarcoma were retrieved in our pathology databases. We assessed the immunohistochemical stainings for ER, PR and CD10 in 3 ovarian adenosarcomas without sarcomatous overgrowth (OAS), and 1 ovarian adenosarcoma with sarcomatous overgrowth (OAS-S). When considering the malignant stromal component, 2 OAS showed the presence of ER and PR, whereas the OAS-S was only ER positive. CD10 positivity was observed in the sarcomatous cells of all 3 OAS but was absent in the OAS-S. : The identification of a hormone sensitive disease is the main clinical implication of this study. Moreover, the current results add OAS to the list of CD10 positive ovarian tumors.


Anatomy of the tibial nerve in relation to the tarsal tunnel: A cadaveric study.
Tarsal tunnel syndrome (TTS) is typically caused by an anatomical variant or mechanical compression of the tibial nerve (TN) with variable success after surgical treatment. 40 lower-leg specimens were obtained. Dissections were appropriately conducted. Extremities were prepared under formaldehyde solution. The tibial nerve and branches were dissected for measurements and various characteristics. The flexor retinaculum had a denser consistency in 22.5% of the cases and the average length was 51.9 mm. The flexor retinaculum as an independent structure was absent and 77.2% of cases as an undistinguished extension of the crural fascia. The lateral plantar nerve (LPN) and abductor digiti minimi (ADM) nerve shared same origin in 80% of cases, 34.5% bifurcated proximal to the DM (Dellon-McKinnon malleolar-calcaneal line) line 31.2% distally and 34.3% at the same level. Understanding the tibial nerve anatomy will allow us to adapt our surgical technique to improve the treatment of this recurrent pathology.


Distribution of corticotropin releasing factor-like immunoreactivity in the rat brain by immunohistochemistry and radioimmunoassay: comparison and characterization of ovine and rat/human CRF antisera.
The distribution of corticotropin releasing factor (CRF)-like immunoreactivity in the rat brain has been demonstrated by immunohistochemistry and radioimmunoassay using 4 different antisera. Two antisera were directed against synthetic ovine CRF, two antisera were directed against synthetic rat/human CRF. Immunohistochemistry revealed that there are discrete regions where CRF immunoreactive cell bodies are seen with all 4 antisera (e.g., the paraventricular nucleus, the dorsolateral tegmental nucleus) whereas there are cells observed only with one rat CRF antiserum (e.g., in the cortex) or terminal fields observed only with ovine CRF antisera (e.g., the spinal trigeminal tract, the substantia gelatinosa, the spinal cord). Radioimmunoassay showed different cross reactivity of the antisera with synthetic ovine or rat/human CRF and sauvagine, however, there was no cross reactivity with a variety of other peptides. Tissue values of CRF obtained by RIA of micropunched brain nuclei with the 4 antisera were frequently dissimilar suggesting that different antisera recognize different substances. High performance liquid chromatography and radioimmunoassay of brain tissue samples, revealed that there is more than one form of CRF-like immunoreactivity present. There is indirect evidence that there exists at least one peptide in the rat brain, prominent in the medulla and the spinal cord, which cross reacts with antisera directed to ovine CRF only.


Characteristics of older adult problem gamblers calling a gambling helpline.
Few investigations have characterized groups of older adults with gambling problems, and published reports are currently limited by small samples of older adult problem gamblers. Gambling helplines represent a widespread mechanism for assisting problem gamblers to move into treatment settings. Given data from older adult problem gamblers in treatment, we hypothesized that older as compared with younger adult problem gamblers calling a gambling helpline would be less likely to report gambling-related problems. Logistic regression analyses were performed on data obtained from January 1, 2000 to December 31, 2001, inclusive, from callers with gambling problems (N = 1,084) contacting the Connecticut Council on Problem Gambling Helpline. Of the 1,018 phone calls used in the logistic regression analyses, 168 (16.5%) were from older adults and 850 (83.5%) from younger adults. Age-related differences were observed in demographic features, types and patterns of gambling reported as problematic, gambling-related problems and psychiatric symptoms, substance use problems, patterns of indebtedness, and family histories of addictive disorders. Older as compared with younger adult problem gamblers were more likely to report having lower incomes, longer durations of gambling, fewer types of problematic gambling, and problems with casino slot machine gambling and less likely to report gambling-related anxiety, family problems, illegal behaviors and arrests, drug problems, indebtedness to bookies or acquaintances, family histories of drug abuse, and problems with casino table gambling. Older as compared with younger adult problem gamblers calling a gambling helpline differ on many clinically relevant features. The findings suggest the need for improved and unique prevention and treatment strategies for older adults with gambling problems.


[Modern views on the epidemiology of legionellosis: operations procedure during epidemic outbreaks and preventive monitoring].
Key aspects of legionellosis epidemiology determining the rising role of Legionella in human infectious diseases in conditions of postindustrial community were discussed. It was shown that formation of Legionella biofilms on potentially dangerous water objects with possible further aerosol or aspiration transmission of microorganisms leads to major epidemic outbreaks and sporadic cases of infection. Main principles of actions during preventive monitoring of Legionella in the environment and epidemic outbreaks of legionellosis were described.


Fc receptors are critical for autoimmune inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis.
Multiple sclerosis (MS) is simulated by various forms of experimental autoimmune encephalomyelitis, in which T cells, antibodies, cytokines and complementary factors interact with the central nervous system (CNS) myelin proteins and lead to inflammatory damage. We investigated the role of Fc receptors (FcRs), which link the cellular and humoral branches of the immune system, in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), using two different FcRgamma knockout DBA/1 mice. The first knockout were the FcRgamma chain-deficient mice, which lack FcgammaRI, FcgammaRIII and Fc(epsilon)RI, while the second knockout mice lack only FcgammaRII. The lack of FcgammaRII enhanced the disease susceptibility with associated increased CNS demyelination. While FcRgamma+/+ DBA/1 mice also developed pronounced CNS infiltration and myelin destruction, FcRgamma-/- littermates were protected despite initial peripheral autoimmune responses to MOG. In vitro analyses revealed equivalent potentials of fluid phase phagocytosis of myelin and MOG in bone-marrow macrophages derived from both FcRgamma+/+ and FcRgamma-/- mice, while MOG-immunoglobulin (Ig)G immune complexes were only internalized by FcRgamma+/+ macrophages. This was associated with cellular activation in FcRgamma+/+ but not FcRgamma-/- macrophages, as assessed by the activation of intracellular mitogen activated protein (MAP)-kinase signalling elements. We propose that protection from EAE in FcRgamma-deficient mice is due to the inefficient antigen processing/presentation of myelin proteins during the induction of secondary immune responses locally in the CNS, which leads to demyelination. This demonstrates the importance of FcR in the promotion of autoimmune inflammation of the CNS and highlights the therapeutic possibility of treatment of MS with FcR-directed modalities.


Increased circulating endothelins are not of cardiopulmonary origin in heart failure patients.
Plasma concentrations of endothelin-1 and big-endothelin are increased in heart failure patients. However, the precise contribution of endothelin secretion from the cardiopulmonary system remains unresolved. The aim of this study was to investigate whether the cardiopulmonary system contributes to the circulating endothelin-1 and big-endothelin concentrations in heart failure patients. Blood samples were obtained at right heart catheterization from different cardiovascular regions including the coronary sinus in chronic heart failure patients (n=12) and from age-matched control subjects (n=12). The peripheral plasma concentrations of endothelin-1 were almost 3-fold higher in heart failure patients compared with the control subjects (1.25 pmol/l, 0.30-8.20 pmol/l (median, range) versus 0.46 pmol/l, 0.10-0.88 pmol/l, p<0.01). However, the endothelin-1 concentration was approximately 25% lower in plasma samples from the coronary sinus than in plasma from the inferior caval vein (p<0.05) in the heart failure patients. There were no differences in big-endothelin concentrations between any of the cardiovascular regions. In heart failure patients, increased plasma concentrations of endothelin-1 and big-endothelin mainly reflect an increased secretion from the peripheral endothelium.


Candida: an increasingly important pathogen in the nursery.
Advances in neonatal care now permit the survival of very immature infants. Although candidiasis is not a new disease, the spectrum of clinical disease has greatly widened and the rate of invasive disease has increased significantly. This article reviews the history, microbiology, and epidemiology of candidal infections, both superficial and invasive. Particular attention is paid to the pathogenesis of and risk factors associated with the development of invasive disease, as well as its clinical manifestations, diagnosis, and treatment.


MR spectroscopy in 18q(-) syndrome suggesting other than hypomyelination.
We reported a 5-year-old boy with 18q(-) syndrome who showed typical magnetic resonance imaging (MRI) findings of high signal intensity on T2-weighted imaging, and a slightly high but lower than normal signal on T1-weighted imaging of the white matter. MR spectroscopy (MRS) revealed increased concentrations of creatine, myoinositol and choline with a normal N-acetylaspartate one. The cerebral white matter lesions observed on MRI in patients with 18q(-) syndrome have been considered to reflect hypomyelination due to a decrease in myelin basic protein so far, however, MRS suggested reactive astrocytic gliosis and accelerated myelin turnover, which are compatible with recent pathological reports of 18q(-) syndrome.


The effects of muscle mass and quality on mortality of patients with acute kidney injury requiring continuous renal replacement therapy.
This study examined the effects of muscle mass on mortality in patients with acute kidney injury requiring continuous renal replacement therapy. It was conducted in eight medical centers between 2006 and 2021. The data of 2200 patients over the age of 18 years with acute kidney injury who required continuous renal replacement therapy were retrospectively collected. Skeletal muscle areas, categorized into normal and low attenuation muscle areas, were obtained from computed tomography images at the level of the third lumbar vertebra. Cox proportional hazards models were used to investigate the association between mortality within 1, 3, and 30 days and skeletal muscle index. Sixty percent of patients were male, and the 30-day mortality rate was 52%. Increased skeletal muscle areas/body mass index was associated with decreased mortality risk. We also identified a 26% decreased risk of low attenuation muscle area/body mass index on mortality. We established that muscle mass had protective effects on the mortality of patients with acute kidney injury requiring continuous renal replacement therapy. This study showed that muscle mass is a significant determinant of mortality, even if the density is low.


Knockdown of BCL2L12 leads to cisplatin resistance in MDA-MB-231 breast cancer cells.
BCL2L12, a newly identified member of Bcl-2 family, contains a BH2 domain and a putative BH3 domain. It was found to be highly expressed in normal breast tissues, and was associated with favorable prognosis in breast cancer patients. Here, we reported that the mRNA levels of BCL2L12 and its transcript variant BCL2L12A could be upregulated upon cisplatin treatment in MDA-MB-231 breast cancer cells. Knockdown of BCL2L12 and BCL2L12A dramatically inhibited cisplatin-induced apoptosis. In contrast, ectopic expressions of each of the proteins promoted cisplatin-induced apoptosis. These results indicated that decreased expressions or loss of BCL2L12 and BCL2L12A may contribute to the cisplatin resistance in breast cancer patients. Furthermore, we found that cisplatin-induced downregulation of beta-catenin was partially suppressed in BCL2L12- and BCL2L12A-knocked down MDA-MB-231 cells, which indicated that knockdown of these two proteins may stabilize beta-catenin in cisplatin-induced apoptosis. In short, we proposed that BCL2L12 and BCL2L12A may play an important role in cisplatin-induced apoptosis in MDA-MB-231 breast cancer cells.


Structural heterogeneity among unique sulfated L-galactans from different species of ascidians (tunicates).
The sulfated polysaccharides that occur in the tunic of ascidians differ markedly in molecular weight and chemical composition. A high molecular weight fraction (F-1), which has a high galactose content and a strong negative optical rotation, is present in all species. Several structural differences were observed among the F-1 fractions obtained from three species of ascidians that were studied in detail. Large numbers of alpha-L-galactopyranose residues sulfated at position 3 and linked glycosidically through position 1----4 are present in F-1 from all three ascidians. However, alpha-L-galactopyranose units, 1----3-linked and partially sulfated at position 4, comprise about half of the sugar units in the central core of F-1 from Ascidian nigra. In addition, L-galactopyranose nonreducing end units occur in F-1 from Styela plicata and A. nigra, but comprise only a minor fraction of F-1 from Clavelina sp. The combination of these various component units gives a complex structure for F-1 from S. plicata and A. nigra, whereas F-1 from Clavelina sp. possesses a simpler structure. The structures of these ascidian glycans are unique among all previously described sulfated polysaccharides, since they are highly branched (except that from Clavelina sp), sulfated at position 3, and contain large amounts of L-galactose without its D-enantiomorph. These data show unusual examples of polyanionic glycans with structural function in animal tissues.


Freedom from atrial arrhythmia and other clinical outcomes at 5 years and beyond after catheter ablation of atrial fibrillation: a systematic review and meta-analysis.
Catheter ablation of atrial fibrillation (AF) is now a mainstream procedure although long-term outcomes are uncertain. We performed a systematic review and meta-analysis of procedural outcomes at 5 years and beyond. We searched PubMed and Embase and after the screening, identified 73 studies (67 159 patients) reporting freedom from atrial arrhythmia, all-cause death, stroke, and major bleeding at ≥5 years after AF ablation. The pooled mean age was 59.7y, 71.5% male, 62.2% paroxysmal AF, and radiofrequency was used in 78.1% of studies. Pooled incidence of freedom from atrial arrhythmia at 5 years was 50.6% (95%CI 45.5-55.7%) after a single ablation and 69.7% [95%CI (confidence interval) 63.8-75.3%) after multiple procedures. The incidence was higher among patients with paroxysmal compared with non-paroxysmal AF after single (59.7% vs. 33.3%, p = 0.002) and multiple (80.8% vs. 60.6%, p < 0.001) ablations but was comparable between radiofrequency and cryoablation. Pooled incidences of other outcomes were 6.0% (95%CI 3.2-9.7%) for death, 2.4% (95%CI 1.4-3.7%) for stroke, and 1.2% (95%CI 0.8-2.0%) for major bleeding at 5 years. Beyond 5 years, freedom from arrhythmia recurrence remained largely stable (52.3% and 64.7% after single and multiple procedures at 10 years), while the risk of stroke and bleeding increased over time. Nearly 70% of patients having multiple ablations remained free from atrial arrhythmia at 5 years, with the incidence slightly decreasing beyond this period. Risk of death, stroke, and major bleeding at 5 years were low but increased over time, emphasizing the importance of long-term thromboembolism prevention and bleeding risk management.


Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers.
Multiple regulatory regions have the potential to regulate a single gene, yet how these elements combine to affect gene expression remains unclear. To uncover the combinatorial relationships between enhancers, we developed Enhancer-interference (Enhancer-i), a CRISPR interference-based approach that uses 2 different repressive domains, KRAB and SID, to prevent enhancer activation simultaneously at multiple regulatory regions. We applied Enhancer-i to promoter-distal estrogen receptor α binding sites (ERBS), which cluster around estradiol-responsive genes and therefore may collaborate to regulate gene expression. Targeting individual sites revealed predominant ERBS that are completely required for the transcriptional response, indicating a lack of redundancy. Simultaneous interference of different ERBS combinations identified supportive ERBS that contribute only when predominant sites are active. Using mathematical modeling, we find strong evidence for collaboration between predominant and supportive ERBS. Overall, our findings expose a complex functional hierarchy of enhancers, where multiple loci bound by the same transcription factor combine to fine-tune the expression of target genes.


Effect of carbonaceous components of biodiesel combustion particles on optical properties.
This paper studies the influence of carbonaceous components on the optical properties of particulate matter (PM) in biodiesel combustion by conducting a bench test on an electronically controlled high-pressure common-rail diesel engine. In addition, the PM produced by the combustion of diesel oil, soybean oil methyl ester (SME), waste edible oil methyl ester (WME), and palm oil methyl ester (PME) was collected. The carbonaceous composition and optical properties of diesel and three biodiesel particulates were then analyzed. The obtained results showed that the ratio of organic carbon (OC) to total carbon (TC) in diesel PM was 0.25 and the ratio of OC/EC was 0.33. The OC to TC ratio of biodiesel PM was significantly greater than that of diesel PM, ranging between 0.59 and 0.65, with OC/EC values in the range of 1.44-1.86. The mass absorption cross-section (MAC) values of three kinds of biodiesel particles were all higher than those of diesel particles. When the incident laser wavelength increased, the difference of MAC values among four kinds of fuel particles gradually decreased. The MAC values of all the three biodiesel particles were higher than those of the diesel particles, and the difference between the MAC values of the four fuel particles gradually decreased with the increase of the incident laser wavelength. Afterwards, the "shell-core" model of particles was developed with 80 nm EC sphere as the core. At the two refractive indices, the scattering cross section, absorption cross section, and extinction cross section of the particles decrease with the increase of the incident light wavelength, and the scattering cross section, absorption cross section, and extinction cross section of the particles increase with the increase of the OC coating thickness.


Fluctuations in Activity Demands Across Game Quarters in Professional and Semiprofessional Male Basketball.
Examination of activity demands and stoppage durations across game periods provides useful insight concerning fatigue, tactical strategies, and playing pace in team sports such as basketball. Therefore, the aims of this study were to quantify and compare game activity fluctuations across quarters in professional and semiprofessional basketball players. Video-based time-motion analyses were conducted across multiple games. Frequencies, total durations (in seconds), total distances (in meters), and mean velocities (in meters per second) were calculated for low-intensity movement (≤3 m·s), high-intensity movement (>3 m·s), shuffling, and dribbling activity. Frequencies were determined for jumping and upper-body activity; stoppage durations were also calculated. Separate repeated-measures analysis of variance and Cohen's d were used to identify significant differences and quantify the effect sizes between game quarters for all outcome measures, respectively. Pearson correlation analyses were performed to determine the relationship between stoppage duration and all activity measures. The results showed significantly (p ≤ 0.05) reduced dribbling (3.09 ± 0.03 m·s vs. 2.81 ± 0.01 m·s) and total (2.22 ± 0.04 m·s vs. 2.09 ± 0.03 m·s) activity velocities during the third compared with the first quarter in professional players. Furthermore, effect size analyses showed greater decreases in high-intensity (professional: d = 1.7-5.4; semiprofessional: d = 0.3-1.7), shuffling (professional: d = 2.3-3.2; semiprofessional: d = 1.4-2.1), and total (professional: d = 1.0-4.9; semiprofessional: d = 0.3-0.8) activity and increases in dribbling (professional: d = 1.4-4.7; semiprofessional: d = 2.5-2.8) with game progression in professional players. In semiprofessional players, stoppage duration was significantly (p ≤ 0.05) related to various low-intensity (R = 0.64-0.72), high-intensity (R = 0.65-0.72), and total (R = 0.63-0.73) activity measures. Although not directly measured, the observed game activity fluctuations were likely because of a combination of physiological (e.g., muscle glycogen depletion, dehydration), tactical (e.g., ball control, game pace), and game-related (e.g., time-outs, player fouls) factors. Basketball coaches can use the provided data to (a) develop more precise training plans and management strategies, (b) elevate semiprofessional player performance closer to the professional level, and (c) incorporate tactical strategies to maximize the benefits of stoppages.


Candida auris: Epidemiology, risk factors, virulence, resistance, and therapeutic options.
Candida auris emerged as a pathogen resistant to multiple antifungal and has been associated with nosocomial outbreaks with high transmission capacity between hospitalized individuals. C. auris was first described in 2009, after being isolated from the external ear canal discharge of a patient in Japan. The difficulty in identification, incorrect use of antifungal drugs, and treatment failure are causes of high mortality. Since then, C. auris has been increasingly reported from East Asia to North America, with substantial fatalities and misidentification. This review aims at describing the epidemiology, virulence, risk factors, resistance, and therapeutic options in C. auris infections.


Nanomolar to sub-picomolar affinity measurements of antibody-antigen interactions and protein multimerizations: fluorescence-assisted high-performance liquid chromatography.
Although several techniques exist for the measurement of high-affinity interactions, it is still challenging to determine dissociation constants around or even below 1pM. During the analysis of several human-derived monoclonal antibodies to adalimumab, we found a clone with a very high affinity that could not be measured using conventional surface plasmon resonance assays. We developed a straightforward and robust method to measure affinities in the nanomolar to sub-picomolar range. The assay is based on separation of bound and free fluorescently labeled antigen using size exclusion chromatography and quantification by in-line fluorescence detection. We describe optimal conditions and procedures that result in a very sensitive assay that can be used to reliably determine ultra-high affinities. Using the method described in this article, a dissociation constant of 0.78pM could be determined for the anti-adalimumab antibody.


Evidence of nuclear reactions in the Pd lattice.
An operating Pd//D2O, Li+, Cl(-)//Pt cell, placed in an external electrostatic field, yielded unexpected results, viz. (i) Morphological changes in the form of discrete sites exhibiting molten-like features, i.e. features that require substantial energy expenditure. (ii) Presence of elements (Al, Mg, Ca, Si, Zn, ...) that could not be extracted from cell components and deposited on discrete sites. The cell design and the experimental protocol assuring reproducibility is described in detail.


Factors predicting change in corneal astigmatism following suture removal in post-penetrating keratoplasty patients.
To identify factors predicting corneal astigmatic change following suture removal in post-penetrating keratoplasty patients. This cross-sectional study included the data of 33 events of corneal suture removal from 27 post-penetrating keratoplasty patients. Sutures were removed from the steep axis of transplanted cornea with 16 interrupted corneal sutures. Corneal astigmatism was measured before and after suture removal using ORBSCAN II. Patients' demographic data and corneal biomechanics parameters obtaining from the Corvis ST were recorded. The changes in corneal astigmatism were calculated using vector analysis. The correlation between changes in corneal astigmatism and the potential factors was evaluated using Spearman's correlation coefficient and linear regression model. The mean corneal astigmatism before and after suture removal was 7.1±3.7 diopters (D) and 5.5±3.2D, respectively. The mean astigmatic change was 7.0±6.3D (range, 0.3-30.8D) by vector analysis at 9.7±5.5 weeks after suture removal. Change in corneal astigmatism was significantly correlated with pre-suture removal astigmatism (Rs=0.47, P=0.01). There was no correlation between the donor-recipient trephine diameter difference, the duration from corneal transplantation to suture removal, the number of removed sutures with the change in corneal astigmatism, and corneal biomechanics parameters (P>0.05). Linear regression is given by the following equation: astigmatic change (D)=1.05x pre-suture removal astigmatism (D) - 0.43. The astigmatic change after corneal suture removal in post-keratoplasty patients was significantly correlated with pre-suture removal astigmatism. These findings will permit a validated approach for reducing corneal astigmatism in post-keratoplasty patients.


Surgical Burden of Disease in Women.
Globally, an inequitable surgical burden exists. Greater than 90% of people in low- and middle-income countries (LMICs) lack access to safe, affordable surgical care. Also, patients undergoing surgery in LMICs suffer much higher rates of perioperative complications and death. In many LMICs, cesarean section is both underused and overused, and frequently performed unsafely. Obstetric fistula and women's cancers contribute to the surgical burden of women in LMICs. Surgical team nontechnical skills (eg, teamwork and communication) and use of tools such as the WHO Surgical Safety Checklist and Enhanced Recovery after Surgery program have the potential to greatly improve surgical outcomes.


Engagement in the Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine Program: Comparing the Effect of Clinic versus Community-Based Recruitment Strategies.
To determine the effectiveness of adding community-based recruitment to clinic-based recruitment to engage participants in a glaucoma detection program. Prospective cohort study. Anyone ≥ 18 years of age who does not meet exclusion criteria. The Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine (MI-SIGHT) program tests a novel way of improving glaucoma detection in communities with populations at high risk for disease, including people who identify as Black and Hispanic and those living with low socioeconomic status. The MI-SIGHT program is conducted in a free clinic (Ypsilanti, MI) and in a federally qualified health center (FQHC) (Flint, MI). Community engagement methods were used to identify outreach strategies to enhance recruitment. Participants were asked "How did you hear about the MI-SIGHT program?" and responses were summarized overall and by clinic and compared between clinic-based and community-based recruitment strategies. Proportion recruited by location, within or outside of the clinic. In total, 647 participants were recruited in the first 11 months of the study, 356 (55.0%) at the free clinic over 11 months and 291 (45.0%) at the FQHC over 6 months. Participants were on average 54.4 years old (standard deviation = 14.2); 60.9% identified as female, 45.6% identified as Black, 37.8% identified as White, 9.6% identified as Hispanic, and 10.9% had less than high school education. Participants reported hearing about the MI-SIGHT program from a clinic phone call (n = 168, 26.1%), a friend (n = 112, 17.4%), nonmedical clinic staff (n = 100, 15.5%), a clinic doctor (n = 77, 11.9%), an in-clinic brochure or flyer (n = 51, 7.9%), a community flyer (n = 44, 6.8%), the clinic website or social media (n = 28, 4.3%), or an "other" source (n = 65, 10.1%). Recruiting from the community outside the medical clinics increased participation by 265% at the free clinic and 46% at the FQHC. The Community Advisory Board recommendation to use community-based recruitment strategies in addition to clinic-based strategies for recruitment resulted in increased program participation. Proprietary or commercial disclosure may be found after the references.


Whole exome sequencing applied to 42 Han Chinese patients with posterior hypospadias.
Hypospadias, a malformation of male external genitalia, is characterized by an aberrant opening of the urethra on the ventral side of the penis. It is considered a complex disorder with both environmental and genetic factors involved in its pathogenesis. To identify the genetic abnormality involved in the pathogenesis of hypospadias, we performed whole exome sequencing (WES) analysis in 42 hypospadias patients with karyotype 46, XY in the Nanhai Meternity&Child Health Hospital of Foshan. All the likely pathogenic variants were confirmed by Sanger sequencing and assessed by Sorting Intolerant from Tolerant (SIFT), PROVEAN, PolyPhen2, ClinPred, LRT, Mutation Assessor, FATHMM, and GERP software. We discovered 27 gene mutations in 20 patients, including eight cases of the SRD5A2 gene, 4 cases of the AR gene, 3 cases of the CYP17A1 gene, 1 case of the WT1 gene, 1 case of the ANOS1 gene, 1 case of the NR5A1 gene, 1 case of the FGFR1 gene, and one case of the DHX37 gene. Our study is the first to describe six novel missense mutations, AR(c.302G > A, c.2593G > T, and c.1705G > T), CYP17A1(c.1298 T > C), FGFR1 (c.995C > T) and DHX37(c.923G > A). In summary, genetic defect detection was useful for early diagnosis of severe hypospadias in the Han Chinese population. Nevertheless, most cases remain unexplained, and the exact pathogenesis of hypospadias still needs further study.


Accuracy of death certificates in the diagnosis of alcoholic liver cirrhosis.
In 108 patients with alcoholic liver disease who died during a 10-year follow-up, the diagnoses from the liver biopsies were compared with that from the Death Certificates. Data show that the currently used ICD-9 category of cirrhosis with or without mention of alcohol has a 47.2% chance of missing the diagnosis of cirrhosis. On the other hand when the mention of liver disease in the Death Certificate is used for the diagnosis of cirrhosis, the percentage of undiagnosed cirrhosis decreases to 19.4% (p less than 0.0001).


Identification and functional validation of SRC and RAPGEF1 as new direct targets of miR-203, involved in regulation of epidermal homeostasis.
The epidermis is mostly composed of keratinocytes and forms a protecting barrier against external aggressions and dehydration. Epidermal homeostasis is maintained by a fine-tuned balance between keratinocyte proliferation and differentiation. In the regulation of this process, the keratinocyte-specific miR-203 microRNA is of the outmost importance as it promotes differentiation, notably by directly targeting and down-regulating mRNA expression of genes involved in keratinocyte proliferation, such as ΔNp63, Skp2 and Msi2. We aimed at identifying new miR-203 targets involved in the regulation of keratinocyte proliferation/differentiation balance. To this end, a transcriptome analysis of human primary keratinocytes overexpressing miR-203 was performed and revealed that miR-203 overexpression inhibited functions like proliferation, mitosis and cell cycling, and activated differentiation, apoptosis and cell death. Among the down-regulated genes, 24 putative target mRNAs were identified and 8 of them were related to proliferation. We demonstrated that SRC and RAPGEF1 were direct targets of miR-203. Moreover, both were down-regulated during epidermal morphogenesis in a 3D reconstructed skin model, while miR-203 was up-regulated. Finally silencing experiments showed that SRC or RAPGEF1 contributed to keratinocyte proliferation and regulated their differentiation. Preliminary results suggest their involvement in skin carcinoma hyperproliferation. Altogether this data indicates that RAPGEF1 and SRC could be new mediators of miR-203 in epidermal homeostasis regulation.


Human metabolic network reconstruction and its impact on drug discovery and development.
This paper describes the process for the reconstruction of a high quality human metabolic network from the genome information, the existing problems in the reconstruction and why a time-consuming literature based consolidation process is needed. The reconstructed metabolic network provides a unified platform to integrate all the biological and medical information on genes, proteins, metabolites, disease, drugs and drug targets for a system level study of the relationship between metabolism and disease. System analysis of metabolic networks will help us, not only in identifying new drug targets but also in developing a system-oriented drug design strategy.


Effects of movement duration on error compensation in periodic bimanual isometric force production.
Recent studies using bimanual force production have examined how factors influence redundancy in the nervous system. The present study examined effects of different movement durations on bimanual force control strategies. Ten healthy male participants produced periodic isometric forces such that the sum of two finger forces was a target cycling between 5 and 10 % of maximum voluntary contraction during five movement durations (500, 750, 1,000, 1,250, and 1,500 ms). Correlations between the two finger forces changed from positive to negative with an increase in duration. The polynomial regression analysis indicates that while the correlations between two finger forces were most negative at the target duration of 1,250 ms, they became more positive as the durations deviated from 1,250 ms. Similarly, while force variability was smallest at the target duration of 1,250 ms, it increased as the durations deviated from 1,250 ms. These findings suggested that while the duration of 1,250 ms might be a natural frequency of both fingers, bimanual force strategies changed from force error compensation to force coupling as the durations deviated from 1,250 ms. In addition, while the variance in the sum of two finger forces (the task-relevant variance) decreased with movement duration, the difference between both the finger forces (the task-irrelevant variance) did not change with the duration. Thus, a decrease in the task-relevant variance with movement duration resulted in the negative correlation between the two finger forces and the small force variability.


Metastatic Sertoli cell tumour in a captive giant anteater (Myrmecophaga tridactyla).
There are a few studies on diseases of anteaters, but reports on reproductive lesions and neoplasms of these animals are scarce. This is the first report of a case of metastatic Sertoli cell tumour in a giant anteater (Myrmecophaga tridactyla). The animal had renal lesions associated with impaired renal function as indicated by serum biochemistry. Histopathological and immunohistochemical examinations provided a conclusive diagnosis of Sertoli cell tumour with metastasis to the liver, kidneys and lymph nodes.


Acquiring Things: Strange Cases of Compulsive Hoarding.
Why has compulsive hoarding recently captured the American imagination? To what extent is hoarding a subtype of OCD or a discrete "disorder" in its own right? Can a cultural-studies and philosophical assessment of hoarding complement the medical model that has recently been offered by clinicians and the DSM IV? This essay tracks these and related questions in order to offer a theory of compulsive hoarding that pays particular attention to the sometimes distorted representation of hoarding in literature and the mainstream media.


Adenocarcinoma arising in a tailgut cyst: report of a case.
We report herein the unusual case of a 66-year-old woman found to have adenocarcinoma arising in a tailgut cyst. The patient had been observed for 6 months following the discovery of a presacral cystic mass measuring 10 x 9 cm for which she had refused surgery. The serum tumor marker, carcinoembryonic antigen, became slightly elevated, and diagnostic imaging distinctly revealed a tumorous lesion with papillary projection into the cyst lumen. The cystic mass was then excised through the transsacral approach. The pathological findings were compatible with moderately differentiated adenocarcinoma arising in a tailgut cyst. This entity is extremely rare, and only six cases, including our own, have been reported in the English literature. Early complete excision is advised because it is almost impossible to determine for certain whether presacral cystic masses are benign or malignant prior to surgery.


COVID-19 Outcomes Among People With HIV and COVID-19 in New York City.
Literature on the impact of human immunodeficiency virus (HIV) on coronavirus disease 2019 (COVID-19)-related outcomes remains mixed. Few studies have evaluated COVID-19 outcomes by HIV status using population-based data. Using data from New York City COVID-19 surveillance and HIV surveillance systems prior to the widespread availability of COVID-19 vaccines, we conducted a retrospective cohort study comparing the risk of COVID-19 hospitalization and mortality by HIV status among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnoses from 29 February to 17 October 2020. Risk of hospitalization and death among people with HIV (PWH) withCOVID-19 were both nearly 30% higher compared with people without HIV. In crude models, incidence of adverse COVID-19 outcomes among PWH compared to people without HIV was elevated in certain groups, including women, and black, Hispanic/Latino, Native American, and multiracial people. CD4 cell count at SARS-CoV-2 diagnosis and presence of an underlying, non-HIV-related condition were independently and strongly associated with risk for COVID-19 hospitalization and death among PWH. New Yorkers with HIV experienced elevated risk for poor COVID-19 outcomes compared to those without HIV during 2020. PWH, particularly those with low CD4 counts or underlying conditions, should be an ongoing focus for COVID-19 vaccination and rigorous identification and treatment of SARS-CoV-2 infections to prevent adverse outcomes.


Nonneurogenic voiding disorders in children and adolescents: clinical and videourodynamic findings in 4 specific conditions.
We determined if there were any unique findings regarding specific clinical manifestations and videourodynamics among our patients with nonneurogenic voiding disorders. A cohort of 237 normal children with lower urinary tract symptoms were evaluated by videourodynamics and uroflow/electromyogram, and divided into 4 groups based on the specific urodynamic findings 1) dysfunctional voiding (active electromyogram during voiding with or without detrusor overactivity), 2) idiopathic detrusor overactivity disorder (detrusor overactivity on urodynamics but quiet electromyogram during voiding), 3) detrusor underutilization disorder (willful infrequent but otherwise normal voiding) and 4) primary bladder neck dysfunction. Association of lower urinary tract symptoms, urinary tract infection, vesicoureteral reflux and abnormal urodynamic parameters within each condition was compared. The only strong correlation between a particular symptom and a specific condition was between hesitancy and primary bladder neck dysfunction. Urgency was reported to some degree with all 4 conditions. The most common abnormal urodynamic finding was detrusor overactivity, which was seen in 91% of patients with dysfunctional voiding. The highest detrusor pressures were seen in dysfunctional voiding during voiding and in idiopathic detrusor overactivity disorder during detrusor overactivity. Vesicoureteral reflux was seen in a third of children with dysfunctional voiding or idiopathic detrusor overactivity disorder, in all 8 boys with a history of urinary tract infection and in 51% of patients with febrile or recurrent urinary tract infections with lower urinary tract symptoms when not infected. Bilateral vesicoureteral reflux and bowel dysfunction were most common in dysfunctional voiding. On objective urodynamic assessment pediatric nonneurogenic voiding dysfunction can essentially be divided into 4 specific conditions. These conditions have distinct urodynamic features that distinguish them from each other, as opposed to their clinical features (particularly lower urinary tract symptoms), which frequently overlap and are not as defining as they are often presumed to be.


Crude extracts of metabolites from co-cultures of lactic acid bacteria are highly antagonists of Listeria monocytogenes.
Listeria monocytogenes is a pathogen difficult to control, due to its resistance to extreme conditions. The antimicrobial activity of a mixture of metabolites produced by lactic acid bacteria was evaluated against L. monocytogenes. Bacterial combined cultures in 1:1 ratio of Lactobacillus plantarum and Weissella cibaria (treatment LP + WC) and mixtures in ratio 1:1:1 of Lactobacillus brevis, L. plantarum, and W. cibaria, (treatment (LB + LP + WC) were grown by discontinuous fermentation, at 32 °C for 48 h. At 1, 2, 6, 12, 24 and 48 h of fermentation, samples were taken, the biomass was separated from the metabolites, and the antimicrobial activity of the metabolites was measured in vitro against L. monocytogenes. For comparison, experimental data published in the literature corresponding to monocultures of L. brevis (L.B), L. plantarum (LP) and W. cibaria (WC) were used. The antimicrobial activity was measured by a surface diffusion technique using absorbent paper discs impregnated with 60 μl from each metabolite and placed on the TSA agar surface (36 °C, 24 h). The metabolites from the microbial mixtures showed statistical differences with respect to their respective monocultures. With the treatment (LP + WC) an inhibition diameter of 2.54 cm was obtained at 12 h of fermentation, this value was higher than those obtained in the monoculture LP (2.19 cm), and WC (2.44 cm), during the same period. In the mixture (LB + LP + WC) during the first 12 h of fermentation, the antimicrobial activity was higher (2.12-2.28 cm) than the antimicrobial activity of the monoculture LB (1.66-2.23 cm). The use of metabolites from the co-culture of L brevis, L. plantarum and W. cibaria under the evaluated conditions, potentiate the antimicrobial activity of L. brevis against L. monocytogenes, therefore, they are promising in bio-preservation.


Comparison of low and high doses of carvedilol on restoration of cardiac function and calcium-handling proteins in rat failing heart.
1. The beta-adrenoceptor antagonist carvedilol reverses cardiac dysfunction in the failing heart. A recent study showed that beta-adrenoceptor antagonists indirectly normalize Ca(2+)-regulatory proteins. The relationship between these two phenomena and the suitable dosage of carvedilol remains unclear. 2. We investigated the change in left ventricular (LV) remodelling and function in a rat model of heart failure due to myocardial infarction (MI) with or without carvedilol (30 or 2 mg/kg per day) treatment for 6 weeks. The expression of mRNA and proteins of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLB) in cardiomyocytes was also measured. 3. There was significant LV remodelling and cardiac contractile dysfunction in MI rats. The expression of SERCA mRNA and protein were downregulated (P < 0.01), but the expression of PLB mRNA and protein were upregulated (P < 0.01) in MI rats compared with sham-operated rats. After treatment with carvedilol, LV remodelling and cardiac contractile dysfunction were clearly improved. Low-dose carvedilol was better at improving some parameters of LV remodelling and function than the high dose. Carvedilol partially restored the low expression of SERCA (P < 0.05), but had no effect on PLB expression (P > 0.05). Moreover, low-dose carvedilol induced a more significant improvement in SERCA expression than did the high dose (P < 0.05). 4. The results of the present study suggest that carvedilol is effective in improving LV remodelling and cardiac contractile dysfunction after MI. This may be related to the normalization of SERCA expression.


Pilates exercise improves the clinical and immunological profiles of patients with human T-cell lymphotropic virus 1 associated myelopathy: A pilot study.
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an infectious chronic-inflammatory disease, which can lead to lower limb motions. The study evaluated the effects of serial Pilates exercises on the clinical and immunological profiles of patients with HAM/TSP. Eight patients with ages ranging from 39 to 70 years old (2 males and 6 females), 2 wheelchair users and 6 with compromised gait, were evaluated. The patients were submitted to 20 Pilates sessions for 10 weeks. Data were collected at 3 time points (beginning of the study, after Pilates sessions and after 10 weeks without Pilates) and consisted of evaluations of the pain level, spasticity, motor strength, balance, mobility, functional capacity, quality of life and quantification of IFN-γ, IL-10 and IL-9 cytokines levels. After the Pilates sessions, significant improvements in pain level, static and dynamic balance, trunk control, mobility and quality of life were observed, with simultaneous and significant reductions in the serum levels of the cytokines IFN-γ and IL-10. However, after 10 weeks without Pilates, there were significant changes in terms of increasing pain and regression of mobility, with no changes in strength, spasticity, functional capacity in any of the periods of the study. The results suggest that Pilates may be a promising auxiliary physical therapy for patients with HAM/TSP.


Percutaneous biopsy of adrenal and extra-adrenal retroperitoneal lesions: beware of catecholamine secreting tumours!
Many patients undergo abdominal imaging for non-specific symptoms. An increasing number of these patients are discovered to have incidental adrenal or retroperitoneal tumours. Approximately 5% of all incidentally detected adrenal lesions are phaeochromocytomas and 25% of phaeochromocytomas are discovered during imaging studies for unrelated disorders. 10% of phaeochromocytomas are extra-adrenal. Retrospective case notes review of three patients with adrenal/retroperitoneal lesions who had percutaneous biopsy before biochemical testing and tertiary referral. Adrenal/retroperitoneal lesions are still being biopsied without prior biochemical testing. One patient with phaeochromocytoma had a critical event. The others were found to have a phaeochromocytoma and a ganglioneuroma. The possibility of a catecholamine secreting tumour should be considered in adrenal and extra-adrenal retroperitoneal lesions. If a biopsy is planned, rarely required in adrenal lesions, phaeochromocytoma must be excluded by biochemical testing prior to the biopsy to avoid potential life threatening complications.


Characterization of W-Cr Metal Matrix Composite Coatings Reinforced with WC Particles Produced on Low-Carbon Steel Using Laser Processing of Precoat.
The paper presents the study results of laser processing of precoat applied on C30 steel. The precoat consisted of powder mixtures with a binder in the form of water glass. Tungsten powder, chromium, and tungsten carbide (WC) were used to produce the precoat. The laser processing was carried out using a Yb:YAG disc laser with a rated power of 1 kW. Constant producing parameters (power of laser beam, 600 W; laser beam scanning rate, 400 mm/min) were applied. Chemical composition of the precoat was a variable parameter in coating production. A mixture consisting of 50% W and 50% Cr as a metal matrix was prepared. Subsequently, WC particles in weight ratios of 25%, 50%, and 75% were added to matrix. As a result, W-Cr metal matrix composite coatings reinforced with WC particles were formed. This study focused on investigation of microstructure, microhardness, phase, and chemical composition as well as corrosion and wear resistance, of the newly formed W-Cr/WC coatings. An instrumented nanoindentation test was also used in this study. As a result of laser beam action, the newly formed coatings had an interesting microstructure and good properties which were improved in comparison to substrate material. It is anticipated that the resulting coatings, depending on the treatment parameters (e.g., W-Cr/WC powder mixture) used, can be successfully applied to metal forming or foundry tools.


Bonding glass-ionomer cements to chemomechanically-prepared dentin.
The aim of this investigation was to compare the shear bond strengths of two commercially available glass-ionomer cement base materials to remaining dentin: (1) after conventional caries removal and polyacrylic acid conditioning; (2) after chemomechanical caries removal (Caridex); and (3) after chemomechanical caries removal and polyacrylic acid conditioning. Ninety freshly extracted carious teeth were randomly assigned for caries removal with either the chemomechanical technique (N = 60), or with conventional mechanical drilling (N = 30). Caries removal was continued until the remaining dentin surfaces were judged sound. The remaining dentin in 30 of the teeth prepared with the chemomechanical technique, and in all of the teeth prepared with mechanical drilling, was treated with 10% aqueous polyacrylic acid for 10 seconds. Groups of 15 teeth were assigned for bonding with either Ketac-Bond or Shofu Glasionomer Base Cement. All bonded specimens were stored in a humidor at 37 degrees C for 24 hr. Shear bond strength was tested by means of a mechanical testing machine at a cross-head speed of 0.05 cm/min. Analysis of variance indicated no significant difference (p greater than 0.05) in the mean bond strength among the groups.


Avulsion fracture of the pelvis: separation of the secondary ossification center in the superior margin of the acetabulum.
A 13-year-old female sustained a rare avulsion fracture of the secondary ossification center in the superior margin of the acetabulum as the result of contraction of the reflected head of the rectus femoris muscle. Diagnosis was made from plain films and CT scans with 3D image reconstruction. The patient was treated non-operatively by bed rest with semiflexion of the hip and knee, and appropriate analgesia.


Nanobodies: a tool to open new horizons in diagnosis and treatment of prostate cancer.
Prostate cancer is one of the most common cancers in men and its incidence has increased dramatically in the last decade. This increase in the detection of this type of cancer is based more on the detection of PSA or PSMA antigens as the most important specific antigens of this cancer, and this early detection has greatly helped in the more optimal treatment of patients. Many methods have been proposed by researchers for early detection of prostate cancer, but most of the methods used today to detect this type of cancer have been using classical antibodies. Although classical antibodies are able to detect tumor cell markers, but instability, large size, costly and laborious production, and random immobility characteristics, causes many problems. Nanobodies or VHHs, which are derived from camel heavy chain antibodies, have special advantages and have eliminated the disadvantages of classical antibodies which makes them attractive to use in biosensors and cancer diagnostic kits. The research that has been done so far shows that the introduced nanobodies are created for the purpose of targeting, detecting and sensing prostate cancer cells with two main purposes. The first is the efficient identification of prostate cancer and the second is the elimination of cancer cells. Research shows the use of specific nanobodies against prostate cancer antigens in the design of biosensors and target therapy will be very interesting. In this review article, these nanobodies are introduced and categorized based on their performance.


Long-term outcomes of internal limiting membrane peeling with and without indocyanine green in macular hole surgery.
To compare the long-term anatomic closure rate and visual outcome in patients who underwent internal limiting membrane (ILM) peeling with and without indocyanine green (ICG) dye staining for idiopathic macular hole repair. Retrospective, nonrandomized, comparative study of consecutive case series. A total of 190 eyes of 182 patients with idiopathic macular holes underwent macular hole repair between March 1998 and June 2003. Surgery consisted of pars plana vitrectomy, lensectomy if phakic, ILM peeling, intravitreal gas tamponade, and 1 week's face-down positioning. In the initial 94 consecutive eyes, ILM peeling was performed without adjuvants (non-ICG group). The subsequent 96 eyes underwent surgery with ICG-stained ILM peeling (ICG group), in which the ILM was stained with intravitreal application of 0.1 to 0.2 mL of 0.1% ICG solution. Two groups of patients had comparable clinical backgrounds preoperatively. Mean follow-up time was 30.7 months in non-ICG group and 26.2 months in ICG group. Anatomic closure of the macular hole was achieved in 99% of the cases in both groups, with both groups showing statistically significant visual improvement. There was no statistically significant difference in visual acuity between the two groups at each follow-up visit. There were also no intraoperative or postoperative complications attributed to the use of ICG. Long-term follow-up of patients undergoing ILM peeling for idiopathic macular hole repair shows equivalent anatomic and visual outcomes with and without the use of ICG.


Nitric oxide and metalloproteinases in canine articular ligaments: a comparison between the cranial cruciate, the medial genual collateral and the femoral head ligament.
Osteoarthritis due to cranial cruciate ligament (CCL) rupture or hip dysplasia is one of the most important causes of chronic lameness in dogs. This study aimed at comparing nitric oxide (NO) production by the CCL with that of the femoral head ligament (FHL) and the medial collateral ligament (MCL), and investigating the pathway of NO production and the concomitant metalloproteinase (MMP) activity in the presence or absence of an inflammatory stimulus. Ligaments of normal dogs were subjected to different stimuli, and NO and MMP activity from explant culture supernatants were compared. The results showed that in explant cultures of the canine CCL more NO was produced than in those of the other two ligaments. A higher level of NO was produced when CCLs were exposed to the inducible nitric oxide synthase (iNOS)-inducing cocktail TNF/IL-1/LPS, and NO synthesis could be inhibited by both l-NMMA, a general nitric oxide synthase (NOS) inhibitor and l-NIL, a specific iNOS inhibitor. However, a correlation between NO synthesis and iNOS expression levels as determined by immunohistochemistry was not observed. In contrast to CCL, no evidence for iNOS-dependent NO synthesis was observed for MCL and FHL. The CCL produced less MMP than MCL and FHL, and no correlation between MMP and NO could be demonstrated. MMP activity in the CCL increased significantly after 48 h of incubation with the inflammatory stimulus. The results suggest that in canine osteoarthritis NO synthesized by canine CCL plays a more important role in the pathogenesis of osteoarthritis of the stifle than that synthesized by FHL and MCL.


Speed-dependent Voigt lineshape parameter database from dual frequency comb measurements at temperatures up to 1305 K. Part II: Argon-broadened H2O absorption, 6801-7188 cm-1.
We report argon-broadened water vapor transition parameters and their temperature dependence based on measured spectra spanning 6801-7188 cm-1 from a broad-bandwidth, high-resolution dual frequency comb spectrometer. The 25 collected spectra of 2% water vapor in argon ranged from 296 K to 1305 K with total pressure spanning 100 Torr to 600 Torr. A multispectrum fitting routine was used in conjunction with a quadratic speed-dependent Voigt profile to extract broadening and shift parameters, and a power-law temperature-dependence exponent for both. The measurements represent the first broad bandwidth, argon-broadened water vapor absorption study, and are an important step toward a foreign-gas-perturbed, high-temperature database developed using advanced lineshape profiles.


Real-Time Monitoring of Pharmacokinetics of Mitochondria-Targeting Molecules in Live Cells with Bioorthogonal Hyperspectral Stimulated Raman Scattering Microscopy.
The dynamics of mitochondria in live cells play a pivotal role in biological events such as cell metabolism, early stage apoptosis, and cell differentiation. Triphenylphosphonium (TPP) is a commonly used mitochondria-targeting agent for mitochondrial studies. However, there has been a lack of understanding in intracellular behaviors of TPP in the course of targeting mitochondria due to the difficulty in tracking and quantifying small molecules in a biological environment. Here, we report the utility of hyperspectral stimulated Raman scattering (SRS) microscopy associated with a Raman tag synthesized for real-time visualization and quantitation of TPP dynamics within live cells at the subcellular level. With the myriad of merits offered by a synthesized aryl-diyne-based Raman tag such as excellent photostability, negligible background interferences, and a linear dependence of the SRS signal on the TPP concentration, we successfully establish a quantitative model to associate the mitochondrial membrane potential with the key pharmacokinetic parameters of TPP inside the live cells. The model reveals that reduction in the mitochondrial membrane potential leads to significant decreases in both the uptake rate and intracellular concentrations of TPP. Further, on the basis of the multiplexed SRS images concurrently highlighting the cellular proteins and lipids without further labeling, we find that the TPP uptake causes little cytotoxicity to the host cells. The bioorthogonal hyperspectral SRS microscopy imaging reveals that TPP can maintain stable affinity to mitochondria during the restructuring of mitochondrial networking, demonstrating its great potential for real-time monitoring of pharmacokinetics of small molecules associated with live biological hosts, thereby promoting the development of mitochondria-targeting imaging probes and therapies in the near future.


Airway Evaluation with Multidetector Computed Tomography Post-Processing Methods in Asthmatic Patients.
Asthma is a chronic inflammatory obstructive airways disease. The disease occurs regardless of age and manifests with cough, attacks of breathlessness, and tightness in the chest. The pathophysiology of asthma is complex and still not fully understood. It is essential to find answers concerning the role of each part of the bronchial tree in asthma, especially the role of small bronchioles. With the development of newer generations of multidetector computed tomography (MDCT) and advanced post-processing methods it is possible to obtain more detailed images and gain insight into further aspects of asthma. MDCT post-processing methods can be divided into two-dimensional (2D) and three-dimensional (3D). In 2D projections, visualized hypodense regions correspond to the airway flow limitations. With the more advanced methods, such as multi planar reconstructions (MPR), images in different planes (axial, coronal, or sagittal) can be created. In the MPR technique only the voxels which are adjacent to each other in the predetermined plane can be extracted from the data set. Using the minimal/maximal intensity projections and shaded surface display, the volume of interest (VOI) can be extracted. High resolution CT scans can be used to create a more advanced imaging tool - the virtual bronchoscopy (VB). Using the VB makes it possible to visualize regions of obturation in the bronchi of up to the 5-8th generation. The MDCT with advanced post-processing methods is likely to assume an important role in the differential diagnosis of asthma, particularly when the diagnosis is dubious or hard to settle due to accompanying other lung diseases.


Separation and identification of phase I and phase II [14C]antipyrine metabolites in rat and dog urine.
A simple and accurate HPLC procedure was developed to quantify, in a single run, all phase I and phase II [14C]antipyrine metabolites that occur in rat and dog urine. All metabolites were subjected to thermospray-LC-MS and EI-MS in order to establish their structure. The rat metabolizes antipyrine to eight major metabolites, six of which are conjugated; 1.4% of the dose was excreted unchanged, 18.9% in a free form, 30.6% as sulfates and 21.1% as glucuronides. The dog metabolizes antipyrine to four metabolites, all as sulfate (61.0% of the dose) or glucuronide conjugates (16.2% of the dose).


Reduced expression of BTBD10, an Akt activator, leads to motor neuron death.
BTBD10, an Akt interactor, activates Akt by decreasing the protein phosphatase 2A-mediated dephosphorylation and inactivation of Akt. Overexpression of BTBD10 suppresses motor neuron death that is induced by a familial amyotrophic lateral sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutant, G93A-SOD1 in vitro. In this study, we further investigated the BTBD10-mediated suppression of motor neuron death. We found that the small interfering RNA-mediated inhibition of BTBD10 expression led to the death of cultured motor neurons. In Caenorhabditis elegans (C. elegans), disruption of the btbd-10 gene caused not only loss of neurons, including both motor and touch-receptor neurons, but also a locomotion defect. In addition, we found that the expression of BTBD10 was generally decreased in the motor neurons from patients of sporadic ALS and transgenic mice overexpressing G93A-SOD1 (G93A-SOD1-transgenic mice). Collectively, these results suggest that the reduced expression of BTBD10 leads to motor neuron death both in vitro and in vivo.


Predictive and protective factors for allogenic blood transfusion in total knee arthroplasty. A retrospective cohort study.
This study aimed to identify the predictive and protective factors of blood transfusion in patients undergoing total knee arthroplasty (TKA) and therefore determine the profile of patients with low and high risk of blood transfusion after arthroplasty. We conducted a retrospective study with all patients who underwent primary TKA between January 2017 and December 2019 (n = 1.028 patients) in our institution. Information about allogenic transfusion was collected from medical records to determine the incidence, the predictive and protective factors of blood transfusion. All cases of blood transfusions were documented as well the number of units and the moment of each transfusion. We performed univariate and multivariate logistic regression analyses to identify the independent risk and protective factors. The total transfusion rate was 11%, 1.1% at intraoperative and 9,9% at postoperative period. The independent risk factors for transfusion were female gender (OR 1.64), older age (>55yo, OR > 2) higher surgical risk (ASA III, OR 3.07), lower preoperative hemoglobin levels (p = 0.024), post-traumatic arthritis (OR 4.11) and use of postoperative drains (OR 1.81) The protective factors for transfusion were male gender (OR 0.60), obesity (IMC >30, OR 0.60) and use of intravenous tranexamic acid intraoperatively (OR 0.40). We conclude that in addition to the well-established risk factors for blood transfusion such as advanced age, low hemoglobin levels and high surgical risk, we can add post-fracture arthroplasty, non-use of tranexamic acid and the use of postoperative joint drain.


American Society for Reproductive Medicine position statement on uterus transplantation: a committee opinion.
Following the birth of the first child from a transplanted uterus in Gothenburg, Sweden, in 2014, other centers worldwide have produced scientific reports of successful uterus transplantation, as well as more recent media reports of successful births. The American Society for Reproductive Medicine recognizes uterus transplantation as the first successful medical treatment of absolute uterus factor infertility, while cautioning health professionals, patient advocacy groups, and the public about its highly experimental nature.


Patterns of vestibular function in patients with dizziness after COVID-19 vaccination; dual tertiary referral center study.
Although dizziness is a common symptom after vaccination, the mechanism, and prognosis are not well understood. This study aimed to investigate patients with dizziness after COVID-19 vaccination by analyzing objective information. A retrospective study of patients who visited the outpatient clinics of two institutes with a complaint of dizziness occurring within 72 h after a COVID-19 vaccination. In most cases, patients experienced only a single event of dizziness, and the subjective symptom was relieved after a few weeks. All patients decreased gain of vestibular ocular reflex (VOR). The vestibular function test results showed signs of central vestibulopathy in some cases. We separated patients into two groups; the direction-fixed nystagmus (DFN) group and the direction-changing nystagmus (DCN) group. All patients showed decreased gain on the rotational chair test (RCT). The DFN group showed an 80% decrease in video head impulse test (vHIT) gain, whereas the DCN group only showed a decrease of 25%. In RCT, 66% of the DFN group showed asymmetry compared to 20% showing asymmetry in the DCN group. The patients who suffered from dizziness after the COVID-19 vaccination exhibited decreased VOR gain and in some cases signs of central vestibulopathy.


The efficacy of combining a vascularized biogenic conduit and a decellularized nerve graft in the treatment of peripheral nerve defects: An experimental study using the rat sciatic nerve defect model.
Although decellularized nerve grafts are often used as a bridging material in nerve defect repair, the lack of perfusion support in this procedure limits the regeneration capacity. To address this, we applied vascularized biogenic conduits, which are fibrous membranes prefabricated around the silicone rod that contain rich vascularity and macrophages, to nerve defect repair procedures using decellularized nerve grafts. The purpose of this study is to investigate the capacity of combining a vascularized biogenic conduit and a decellularized nerve graft for peripheral nerve regeneration using a 10-mm nerve defect model in rats. Sixteen adult male rats (F344 rats, 10-12 weeks, 200-250 g) were used in this study. For the prefabrication of vascularized biogenic conduits, a silicone rod was transplanted next to the sciatic nerve. After 8 weeks, this silicone rod was enveloped in connective tissue, called a vascularized biogenic conduit. The first rat was used to investigate the histological characteristics of vascularized biogenic conduits through immunofluorescence studies. The remaining 15 rats were divided into three groups to evaluate the efficacy of the combination of a decellularized nerve graft and a vascularized biogenic conduit: a decellularized nerve graft (DNG) group, a decellularized nerve graft with a vascularized biogenic conduit (DNG-w-VBC) group, and an autologous nerve graft (ANG) group. Eight weeks after nerve graft surgery, the assessment results of both functional recovery (electrophysical studies and target muscle atrophy) and morphological recovery (total number, diameter, and myelin thickness of the regenerated axons) of the regenerated nerves were examined. Immunofluorescence studies revealed that the VBC contains extracellular matrix, vascular tissue, and macrophages. The results of the DNG-w-VBC group were superior to the DNG group in electrophysiological studies (CMAP; 6.29 ± 0.80% vs. 4.02 ± 3.35%, MNCV; 50.6 ± 8.4% vs. 25.7 ± 15.6%, p < .05, respectively), regenerated axon number (11,348 ± 812 vs. 7697 ± 2197, p < .05), and mean axon diameter (2.72 ± 0.33 μm vs. 1.64 ± 0.12 μm, p < .05). Our study confirms that vascularized biogenic conduits supply vascularity and macrophages to nerve defect sites. Combining vascularized biogenic conduits with decellularized nerve grafts to treat nerve defects offers superior functional and morphological recovery of regenerated axons.


Detection and analysis of DNA mixtures with the MiSeq FGx®.
Recognizing and interpreting mixtures are challenges that occur frequently in forensic casework. Therefore, any new analysis methods that are implemented must handle the challenges of mixed forensic samples. Next generation sequencing offers advantages over capillary electrophoresis in amplicon multiplexing and degraded sample analysis; however, advantages with mixed samples rely heavily on the advancement of user-friendly analysis software. This research analyzed samples with the ForenSeq™ DNA Signature Prep Kit on the MiSeq FGx® and compared them with the GlobalFiler™ STR Kit for capillary electrophoresis. Metrics tested for both chemistries included concordance, limits of detection, and mixture analysis. Data analysis for mixture samples was completed with the MixtureAce™ plug-in and ArmedXpert™ software. Next generation sequencing offered distinct advantages in limits of detection and isoallele heterozygosity but suffered from increased variability in stutter and allele count ratios compared to capillary electrophoresis.


The uptake of platelets, fibrinogen and leucocytes in ePTFE vascular grafts in relation to blood flow--an experimental study in sheep.
The uptake of platelets, fibrinogen and leucocytes in relation to blood flow was studied in ePTFE arterial grafts inserted in both common carotid arteries of 10 adult sheep. Autologous platelets labelled with In-111, autologous leucocytes labelled with Tc-99m and homologous fibrinogen labelled with I-125 were used. The leucocyte uptake was studied in five of the animals. The uptake was measured with a gamma scintillation technique. The blood flow in the graft on one side was restricted to 25 ml/mm, and in the other graft the blood flow was unrestricted (median 170 ml/min). One out of 10 grafts in the reduced flow group occluded but none of the grafts in the unrestricted flow group. The mean thrombus weight was significantly higher in the reduced unrestricted flow (0.28 vs. 0.19 g). At the proximal anastomosis the uptake of platelets, fibrinogen and leucocytes was higher in the reduced than unrestricted flow. The differences were significantly higher for fibrinogen for the whole duration of the experiments and for platelets and leucocytes during the last 48 min. Distally the platelet and fibrinogen uptake were higher in the reduced than in unrestricted flow. The leucocyte uptake did not differ distally. The differences were significant for fibrinogen for the whole duration of the experiments and for platelets during the last 120 min. A comparison between the proximal and distal anastomosis showed a higher uptake distally.


Curcumin inhibits superoxide anion-induced pain-like behavior and leukocyte recruitment by increasing Nrf2 expression and reducing NF-κB activation.
This study aimed at evaluating the activity of curcumin in superoxide anion-induced pain-like behavior and leukocyte recruitment in mice. Administration of curcumin 10 mg/kg subcutaneously 1 h before stimulus. KO2 was used as superoxide anion donor. Overt pain-like behaviors were determined by the number of abdominal writhings, paw flinches and time spent licking the paw. Mechanical and thermal hyperalgesia were determined using an electronic anesthesiometer and hot plate, respectively. Cytokine concentration and NF-κB activity were determined by ELISA, antioxidant effect by nitrobluetretrazolium assay and ABTS radical scavenging ability. Myeloperoxidase activity was measured by colorimetric assay. The Nrf2, heme oxygenase-1 (HO-1) and gp91phox mRNA expression was determined by quantitative PCR. Data were analyzed by ANOVA followed by Tukey's post hoc and considered significant when p<0.05. Curcumin inhibited superoxide anion-induced overt pain-like behaviors as well as mechanical and thermal hyperalgesia. Curcumin also inhibited superoxide anion-induced leukocyte recruitment in the peritoneal cavity and in the paw skin inhibited myeloperoxidase activity, oxidative stress, IL-1β and TNF-α production and NF-κB activation as well as enhanced IL-10 production, and HO-1 and Nrf2 mRNA expression. Curcumin inhibits superoxide anion-induced inflammatory pain-like behaviors and leukocyte recruitment by targeting inflammatory molecules and oxidative stress; and inducing antioxidant and anti-inflammatory pathways.