Abnormal Uterine Bleeding.
Abnormal uterine bleeding (AUB) is a common medical problem, with a direct influence on women's quality of life, utilization of health care resources, and costs. AUB in women older than 40 years and especially in postmenopausal women requires a prompt and efficient evaluation, mainly to exclude the presence of malignant or premalignant lesions of the endometrium. Cancer of the endometrium is the most common gynecologic malignancy, with an incidence in the United States of more than 60,000 cases and mortality estimated at 10,000 women annually. This article outlines the role of transvaginal ultrasonography in the evaluation of cases of AUB.


Normal and myopathic propagation of surface motor unit action potentials.
With the aid of a computer-assisted multichannel EMG system, the propagation of motor unit action potentials is analysed during isometric voluntary muscular contraction under normal and myopathic conditions. A linear array of 30 surface electrodes is fixed above the biceps brachii muscle, parallel to the longitudinal muscle axis and centered over the end-plate zone. The EMG is simultaneously recorded on all channels and displays the propagation of surface potentials on both sides of the innervation band. The mean muscle fibre conduction velocity is computed by a cross-correlation technique. Five adult patients in a late stage of progressive muscular dystrophy show a highly altered propagation behaviour of motor unit action potentials without a time shift between potentials of adjacent electrodes. A mathematical model is described which predicts such a behaviour and suggests that it must be due to a pathological longitudinal spread of end-plates in this patient group. In 5 boys with Duchenne muscular dystrophy and only moderate impairment of the biceps muscle the mean muscle fibre velocity was reduced (2.81 +/- 0.34 m/sec) compared to 17 healthy subjects (4.42 +/- 0.37 m/sec). Each myopathic patient examined could be separated clearly from the group of healthy subjects on the basis of the surface EMG analysis.


Modification of interface between regulatory and essential light chains hampers phosphorylation-dependent activation of smooth muscle myosin.
We examined the regulatory importance of interactions between regulatory light chain (RLC), essential light chain (ELC), and adjacent heavy chain (HC) in the regulatory domain of smooth muscle heavy meromyosin. After mutating the HC, RLC, and/or ELC to disrupt their predicted interactions (using scallop myosin coordinates), we measured basal ATPase, V(max), and K(ATPase) of actin-activated ATPase, actin-sliding velocities, rigor binding to actin, and kinetics of ATP binding and ADP release. If unphosphorylated, all mutants were similar to wild type showing turned-off behaviors. In contrast, if phosphorylated, mutation of RLC residues smM129Q and smG130C in the F-G helix linker, which interact with the ELC (Ca(2+) binding in scallop), was sufficient to abolish motility and diminish ATPase activity, without altering other parameters. ELC mutations within this interacting ELC loop (smR20M and smK25A) were normal, but smM129Q/G130C-R20M or -K25A showed a partially recovered phenotype suggesting that interaction between the RLC and ELC is important. A molecular dynamics study suggested that breaking the RLC/ELC interface leads to increased flexibility at the interface and ELC-binding site of the HC. We hypothesize that this leads to hampered activation by allowing a pre-existing equilibrium between activated and inhibited structural distributions (Vileno, B., Chamoun, J., Liang, H., Brewer, P., Haldeman, B. D., Facemyer, K. C., Salzameda, B., Song, L., Li, H. C., Cremo, C. R., and Fajer, P. G. (2011) Broad disorder and the allosteric mechanism of myosin II regulation by phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 108, 8218-8223) to be biased strongly toward the inhibited distribution even when the RLC is phosphorylated. We propose that an important structural function of RLC phosphorylation is to promote or assist in the maintenance of an intact RLC/ELC interface. If the RLC/ELC interface is broken, the off-state structures are no longer destabilized by phosphorylation.


Endothelial nitric oxide attenuates Na+/Ca2+ exchanger-mediated vasoconstriction in rat aorta.
The Na+/Ca2+ exchanger (NCX) may be an important modulator of Ca2+ entry and exit. The present study investigated whether NCX was affected by prostacyclin and nitric oxide (NO) released from the vascular endothelium, as NCX contains phosphorylation sites for PKA and PKG. Rat aortic rings were set up in organ baths. Tension was measured across the ring with a force transducer. Lowering extracellular [Na+] ([Na+]o) to 1.18 mM induced vasoconstriction in rat endothelium-denuded aortic rings. This effect was blocked by the NCX inhibitor KB-R7943 (2-2-[4-(4-nitrobenzyloxy)phenyl] ethyl isothiourea methanesulphonate; 1 microM). In endothelium-intact aortic rings, decreasing [Na+]o did not constrict the aortic rings significantly, but after treatment with the guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 1 microM) or the NOS inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester; 50 microM), a vasoconstriction that was similar in size to that in endothelium-denuded preparations was evident. The vasorelaxation induced by the NO donor sodium nitroprusside sodium nitroprusside dihydrate (30 nM) was the same in the endothelium-denuded aortic rings preconstricted with either low Na+ (1.18 mM), the thromboxane A2 agonist U46619 (9,11-dideoxy-9alpha, 11alpha-methanoepoxy prostaglandin F(2alpha); 0.1 microM) or high K+ (80 mM). The results suggest that the endothelium inhibits NCX operation via guanylate cyclase/NO. This is stronger than for other constrictors such as phenylephrine and may relate to concomitant NCX-stimulated NO release from the endothelium. This finding may be important where NCX operates in reverse mode, such as during ischaemia, and highlights a new mechanism whereby the endothelium modulates Ca2+ homoeostasis in vascular smooth muscle.


Two new species of Endocarpon (Verrucariaceae, Ascomycota) from China.
Endocarpon species are key components of biological soil crusts. Phenotypic and systematic molecular analyses were carried out to identify samples of Endocarpon collected from the southeast edge of the Tengger Desert in China. These morphological and molecular analyses revealed two previously undescribed species that form highly supported independent monophyletic clades within Endocarpon. The new taxa were named Endocarpon deserticola sp. nov. and E. unifoliatum sp. nov. Furthermore, our results indicated that the newly developed protein coding markers adenylate kinase (ADK) and ubiquitin-conjugating enzyme h (UCEH) are useful for assessing species boundaries in phylogenic analyses.


Prevalence of nocturnal enuresis, risk factors, associated familial factors and urinary pathology among school children in Iran.
To estimate the prevalence of enuresis in school-age children in Iran and determine associated factors. A total of 7562 children, aged 5-18 years, enrolled in this cross-sectional study. Using a standard questionnaire, data on demographic characteristics, and familial and physical conditions were obtained from the parents by interview. The ICD-10 definition of enuresis was used. In the case of enuretics, a detailed history was taken, and physical and ultrasonographic examinations, urinalysis and urine culture were performed. The overall prevalence of enuresis was 6.8%. A significant relationship was found between the prevalence of enuresis and age (P=0.001), educational level of parents (P=0.001), number of family members (P=0.028), positive family history of enuresis (P=0.001), parenting methods (P=0.001), and deep sleep (P=0.001). Birth weight (P=0.07), monthly income (P=0.322), employment status of parents (P=0.08), ethnic differences (P=0.09), delayed development (P=0.062), drinking (P=0.072) or urination habit before sleep (P=0.06), and stool incontinence (P=0.062) were not significantly associated with enuresis. Prevalence of urinary tract pathology was 2.9% in enuretics. This study provides a quantitative estimate of the prevalence and main risk factors for enuresis in Iranian children.


Linear alkylbenzene sulfonate threats to surface waters at the national scale: A neglected traditional pollutant.
Freshwater biodiversity and ecosystem services might decline due to exposure to chemicals. However, researchers have devoted much attention to the potential risks of emerging contaminants, while placing less effort on historical pollutants, such as the surfactant, linear-alkylbenzene-sulfonate (LAS), which is a major component of widely used synthetic detergents worldwide. In this study, a multilevel risk assessment approach was used to assess risks posed by LAS to aquatic organisms, on a wide spatial scale, based on various assessment endpoints. Additionally, bottom-up approaches were used to assess contributions of LAS source discharges to aquatic environments. Concentrations of LAS in surface waters of China ranged from less than the limit of detection to 14,200 μg/L. The predicted no effect concentration (PNEC) based on adverse effects on reproduction is 15 μg/L, which is slightly less than the PNEC based on other endpoints. 99% of surface waters in Chaohu Lake and the Hai River (Ch: Haihe) were predicted to pose a risk to growth of aquatic organisms, with a protection threshold of 5% of species (HC5). Discharges of LAS were estimated using activity data and emission factors for 280 major cities in the basin. Rural domestic sources were the main source of LAS to surface waters. These outcomes provided a process for developing comprehensive management and control approaches to help researchers and policymakers effectively manage water resources affected by increasing concentrations of LAS.


Context Matters: Posttraumatic Stress Disorder Symptom Associations With Military Sexual Trauma Event Characteristics and Dual Histories of Interpersonal Trauma.
Despite the high rates of military sexual trauma (MST) experienced by service members and veterans, little is known about how contextual features of the MST event or concurrent histories of other interpersonal traumas are associated with diverse clinical presentations. This study examined contextual factors of MST events (number of perpetrators, location of MST, relationship to perpetrator, location of MST) and dual history of interpersonal traumas (including sexual abuse or assault throughout the lifespan, repeated MST, and intimate partner violence) in relation to total symptoms and symptom clusters of Posttraumatic Stress Disorder (PTSD). MST involving multiple perpetrators was related to higher avoidance and hyperarousal. MST while combat-deployed was associated with higher hyperarousal. Veterans endorsing a history of partner violence presented with higher reexperiencing and avoidance. Recognition of phenotypic differences may assist providers in treatment planning and optimizing outcomes.


WITHDRAWN: Life-long caloric restriction counteracts apoptotic effects of aging in the brain and bolsters the action of apoptosis inhibitors.
Ahead of Print article withdrawn by publisher.


Glucose biosensor based on multi-wall carbon nanotubes and screen printed carbon electrodes.
This paper describes a disposable electrochemical biosensor for glucose monitoring. The sensor was based on multi-wall carbon nanotubes (MWCNTs) immobilized with glucose oxidase and upon screen printed carbon electrode. The effect of MWCNTs on the response of amperometric glucose oxidase electrode for glucose was examined. Results obtained, of interest for basic and applied biochemistry, represent a first step in construction of a MWCNT-enzyme electrode biosensor with potentialities for a successful application in the biosensor area.


Ten rapid antigen tests for SARS-CoV-2 widely differ in their ability to detect Omicron-BA.4 and -BA.5.
Since late 2021, the variant landscape of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been dominated by the variant of concern (VoC) Omicron and its sublineages. We and others have shown that the detection of Omicron-BA.1 and -BA.2-positive respiratory specimens by rapid antigen tests (RATs) is impaired compared to Delta VoC-containing samples. Here, in a single-center retrospective laboratory study, we evaluated the performance of ten most commonly used RATs for the detection of Omicron-BA.4 and -BA.5 infections. We used 171 respiratory swab specimens from SARS-CoV-2 RNA-positive patients, of which 71 were classified as BA.4 and 100 as BA.5. All swabs were collected between July and September 2022. 50 SARS-CoV-2 PCR-negative samples from healthy individuals, collected in October 2022, showed high specificity in 9 out of 10 RATs. When assessing analytical sensitivity using clinical specimens, the 50% limit of detection (LoD50) ranged from 7.6 × 104 to 3.3 × 106 RNA copies subjected to the RATs for BA.4 compared to 6.8 × 104 to 3.0 × 106 for BA.5. Overall, intra-assay differences for the detection of these two Omicron subvariants were not significant for both respiratory swabs and tissue culture-expanded virus isolates. In contrast, marked heterogeneity was observed among the ten RATs: to be positive in these point-of-care tests, up to 443-fold (BA.4) and up to 56-fold (BA.5) higher viral loads were required for the worst performing RAT compared to the best performing RAT. True-positive rates for Omicron-BA.4- or -BA.5-containing specimens in the highest viral load category (Ct values < 25) ranged from 94.3 to 34.3%, dropping to 25.6 to 0% for samples with intermediate Ct values (25-30). We conclude that the high heterogeneity in the performance of commonly used RATs remains a challenge for the general public to obtain reliable results in the evolving Omicron subvariant-driven pandemic.


Efficacy of nivolumab plus ipilimumab as first-line therapy for primary tumors in patients with renal cell carcinoma.
With the emergence of several effective combination therapies, information on their effects at the primary site will be crucial for planning future cytoreductive nephrectomy (CN). The present study focused exclusively on changes in primary tumor sizes following treatment with nivolumab plus ipilimumab and investigated the clinical factors associated with a good response in primary tumors. We retrospectively assessed 27 patients diagnosed with advanced renal cell carcinoma (RCC) who started treatment with nivolumab plus ipilimumab. Changes in tumor sizes at the primary site were described using waterfall and spider plots, respectively. We analyzed the correlation of tumor shrinkage between primary and metastatic site. The parameters analyzed between responders and non-responders according to primary tumor sizes were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers, and CRP. The median age and follow-up period were 66 years and 9.3 months, respectively. The median IMDC risk score was 3 (range: 1-6). Nineteen patients were diagnosed with clear-cell RCC (ccRCC) and 8 patients with non-ccRCC. Among ccRCC patients, 9 (47.4%) achieved a significant response with a maximum reduction of 30% or more in the size of the primary tumor from baseline within 4 months, while 3 (37.5%) out of 8 patients with non-ccRCC achieved a significant response. Shrinkage of the primary tumor correlated with the metastatic tumors in both ccRCC and non-ccRCC cases. Of note, 6 patients underwent CN and no viable tumor cells were detected in the surgical specimens of 3 patients whose primary tumors shrank by approximately 50%-60% with a reduction to 4 cm or less. Among ccRCC patients, the neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were slightly lower in responders than in non-responders (P = 0.0944 and P = 0.0691). The platelet-to-lymphocyte ratio was significantly lower in responders than in non-responder (P = 0.0391). Significant responses in primary tumors to nivolumab plus ipilimumab were observed in 50% of ccRCC patients, while responses varied among non-ccRCC patients. Inflammation markers may be predictive factors of treatment responses in primary tumors. Although further studies are needed, the present results suggest the importance of considering CN from radiological and pathological viewpoints.


Predicting oral health behaviors among Iranian students by using health belief model.
The aim of this study is assessing predictors to oral health behavior in Iranian students based on the health belief model. This cross-sectional study was conducted on 416 (applying the statistical estimation) of fifth-grade female students of Tehran in 2016. Random cluster sampling method was used to recruit students. The inclusion criteria were being grade five female student (aged 10-12 years), and studying in governmental schools, and having a signed consent from the child's parent or legal guardian. Logistic regression analysis was used to identify the variables that predict oral health behaviors. Overall, 416 female students were entered into the study. Of these, only 55.3% of the students reported that they were brushing at least twice a day, 22.4% were using dental floss at least once a day, and 23.1% reported checking their teeth every 6 months. The results obtained from the logistic regression analysis indicated that perceived self-efficacy, was the significant predicting factor for brushing at least twice a day (odds ratio [OR] = 1.34, 95% confidence interval [CI] =1.06-1.69, P = 0.012) and use of dental floss at least once a day (OR = 1.61, 95% CI = 1.14-2.27, P = 0.007). Furthermore, mother's job predicted use of dental floss at least once a day by (OR = 1.83, 95% CI 1.07-3.10). Perceived benefits were the significant predicting factor for 6 months check (OR = 1.78, 95% CI = 1.14-2.77). The current study provides evidence oral health can be promoted by increasing perceived self-efficacy and enhancing perceived benefits in female students.


Role of alpha methylacyl-coenzyme A racemase in differentiating hepatocellular carcinoma from dysplastic and nondysplastic liver cell lesions.
Distinction of hepatocellular carcinoma (HCC) from liver cell dysplasia (LCD) is one of the problems faced by pathologists. In spite of various methods claimed to differentiate between these 2 lesions, no reliable marker is available until now. The aim of the study was to assess the value of alpha methylacyl-coenzyme A (COA) racemase (AMACR) in distinguishing HCC from LCD. Formalin-fixed, paraffin-embedded tissue sections from 30 HCCs and 30 nonneoplastic liver tissues (12 dysplastic and 18 nondysplastic lesions) were immunostained for AMACR. Staining intensity was interpreted as low (negative, mild) and high expressions (moderate, marked). Alpha methylacyl-COA racemase showed high expression in 21 (70%) of 30 HCCs and 7 (58.3%) of 12 LCDs. All 18 nondysplastic lesions revealed low AMACR expression. The percentage of high AMACR expression was significantly more in HCC and LCD as compared with nondysplastic lesions (P = .001 in each). There was no significant difference in AMACR expression between HCC and LCD. Furthermore, the pattern of AMACR immunostaining was coarsely granular cytoplasmic positivity in HCC as well as LCD in comparison with the weak finely granular in nondysplastic lesions. Alpha methylacyl-COA racemase cannot discriminate HCC from LCD, although it can separate HCC and LCD from nondysplastic lesions.


Neisseria meningitidis W135 pneumonia with sepicaemia in a nonogenarian.
Neisseria meningitidis infection is generally considered a disease of children or young adults, classically presenting as meningitis or sepicaemia. This infection is rare but recognised in the elderly. We present the case of a nonogenarian with meningococcal pneumonia and sinusitis with bacteraemia caused by N.meningitidis W135 a rare serogroup. We therefore thought this unusual situation of interest and worthwhile reporting.


Using soft X-ray tomography for rapid whole-cell quantitative imaging of SARS-CoV-2-infected cells.
High-resolution and rapid imaging of host cell ultrastructure can generate insights toward viral disease mechanism, for example for a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Here, we employ full-rotation soft X-ray tomography (SXT) to examine organelle remodeling induced by SARS-CoV-2 at the whole-cell level with high spatial resolution and throughput. Most of the current SXT systems suffer from a restricted field of view due to use of flat sample supports and artifacts due to missing data. In this approach using cylindrical sample holders, a full-rotation tomogram of human lung epithelial cells is performed in less than 10 min. We demonstrate the potential of SXT imaging by visualizing aggregates of SARS-CoV-2 virions and virus-induced intracellular alterations. This rapid whole-cell imaging approach allows us to visualize the spatiotemporal changes of cellular organelles upon viral infection in a quantitative manner.


Dexamethasone-induced lipolysis increases the adverse effect of adipocytes on osteoblasts using cells derived from human mesenchymal stem cells.
The increased bone marrow lipid deposition in steroid-associated bone loss diseases indicates that abnormalities in fat metabolism are associated with disease development. Recent studies have suggested that bone marrow adipocytes are secretory cells and that they may release substances that have an inhibitory effect on the differentiation and function of osteoblasts. We hypothesized that exposure of bone-marrow-derived adipocytes to corticosteroids exacerbates their deleterious effects on osteoblast metabolism and function. Adipocytes and osteoblasts derived from a human mesenchymal stem cell line (240L) were co-cultured in the absence of direct cell contact with or without dexamethasone treatment. After 6days of co-culture, osteoblasts demonstrated significantly lower levels of function based on lower mineralization, alkaline phosphatase activity and expression of osteogenic (Runx2, osteocalcin) mRNA marker. Dexamethasone treatment resulted in significantly lower levels of osteoblastic function compared with co-cultured cells without dexamethasone. Furthermore, conditioned media from dexamethasone-treated adipocytes induced a similar toxic effect and increased apoptosis involving activation of caspases 3/7 compared with conditioned media without dexamethasone treatment. Within the conditioned media, a substantial increase in the levels of leptin and two saturated fatty acids (FAs; stearate and palmitate) was observed after dexamethasone treatment. Although leptin supplementation failed to induce the inhibitory effect on osteoblasts, similar toxic results were produced with stearate and palmitate treatment, and an increase in intracellular reactive oxygen species was observed. Stearate- and palmitate-induced apoptosis was blocked by a reactive oxygen species scavenger pyrrolidine dithiocarbamate. These data show that saturated FAs secreted from adipocytes induce lipotoxic effects via mechanisms that may involve reactive oxygen species accumulation in osteoblasts. Our results suggest that inhibition of saturated FA secretion would protect osteoblasts against adipocytes in corticosteroid-associated bone loss diseases.


[Compensation of external jugular vein to the reflux of cerebral blood after bilateral ligation of the internal jugular vein].
To investigate the effects of conserving external jugular veins for compensating the back flow of intracranial veins. The rhesus monkey was underwent bilateral radical neck dissection to simulate that performed in the human. In operation, the changes of intracranial pressure (ICP) after ligating these jugular veins was observed. The results indicate that ligation of the external and internal jugular veins will increase the ICP obviously, but conserving external jugular veins will reduce the increase of ICP and shorten the recovery time from increased ICP. The conservation of the external jugular veins will compensate the back flow of intracranial veins after RND. The experiment provides a simple and effective method for the prevention of intracranial complications and preservation of the flow of facial veins.


LncRNA GAS5-hnRNPK axis inhibited ovarian cancer progression via inhibition of AKT signaling in ovarian cancer cells.
The incidence of ovarian cancer ranks third among gynecologic malignancies, but the mortality rate ranks first. The expression of GAS5 is low in ovarian cancer and is associated with the low survival of ovarian cancer patients according to public ovarian cancer databases. GAS5 overexpression inhibited ovarian malignancy by affecting the proliferation and migratory abilities in OVCAR3 and A2780 cells. GAS5 overexpression increased the rate of cell apoptosis, and the cells were blocked in the G1 phase as assessed by flow cytometry. We found that hnRNPK was a potential target gene, which was regulated negatively by GAS5 based on RNA-pulldown and mass spectrometry analysis. Mechanistically, GAS5 affected the inhibition of the PI3K/AKT/mTOR pathways and bound the protein of hnRNPK, which influenced hnRNPK stability. Furthermore, rescue assays demonstrated hnRNPK was significantly involved in the progression of ovarian cancer. Our study showed one of the mechanisms that GAS5 inhibited ovarian cancer metastasis by down-regulating hnRNPK expression, and GAS5 can be used to predict the prognosis of ovarian cancer patients.


Metabolic dysfunctions in Nigerian pre-eclamptics.
The patho-physiology of pre-eclampsia is not fully understood. This study determined the plasma levels of markers of oxidative stress, thyroid hormones, nitric oxide, C-reactive protein, and nutritional profiles in pre-eclamptic patients. Thirty-two pregnant women with pre-eclampsia and 40 women with normal pregnancy (controls) participated in this study. The pre-eclamptics were recruited after 20 weeks of gestation. They presented with hypertension (systolic pressure = 169 ± 26.0 mmHg, diastolic pressure = 102 ± 11.0 mmHg), significant proteinuria (368 ± 39 mg/24 h), severe headache, abdominal pain and vomiting. The plasma levels of total antioxidant potential (TAP), total plasma peroxides (TPP), total cholesterol (TC), total protein (TP), albumin, globulin, nitric oxide (NO), C-reactive protein (CRP), total tri-iodotyronine (TT3) and thyroid stimulating hormone (TSH) were determined in them using spectrophotometry, radial immunodiffusion and enzyme linked immunosorbent assay (ELISA) methods, respectively. Oxidative stress index (OSI) was calculated as the percent ratio of TPP and TAP. The weight and body mass index of pre-eclamptics increased significantly (p < 0.05) when compared with the controls. The mean systolic and diastolic blood pressure increased significantly (p < 0.001) in pre-eclamptics when compared with the controls. Plasma mean values of TAP, NO, albumin, TP and TT3 decreased significantly (p < 0.05) in pre-eclamptics when compared with the controls. The plasma mean values of TSH, TPP, OSI, CRP, and TC increased significantly (p < 0.05) in pre-eclamptics when compared with the controls. There was no significant change in the plasma value of globulin when compared with the controls. TT3 correlated positively with plasma TP and globulin in the pre-eclamptics. It could be concluded that hypothyroidism, hypercholesterolemia, oxidative stress and deranged inflammatory responses are possible features of pre-eclampsia.


A Randomized, Controlled Trial Comparing the Impact of a Low-Calorie Ketogenic vs a Standard Low-Calorie Diet on Fat-Free Mass in Patients Receiving an Elipse™ Intragastric Balloon Treatment.
The Elipse™ intragastric balloon (EIGB) is a new swallowable balloon for weight loss (WL). Preserving metabolically active fat-free mass (FFM) and resting metabolic rate (RMR) during WL are crucial to maximize fat mass (FM) loss. After EIGB placement, a standard low-calorie diet (LCD) is generally prescribed. A low-calorie ketogenic diet (LCKD) has proven to be safe and effective in reducing FM while preserving FFM and RMR. To prospectively compare the effects on WL, FM, FFM, and RMR in two groups of patients who were randomized to two different diets: LCKD and a standard LCD after EIGB placement. WL, FM, FFM, and RMR were measured before EIGB and at 4 months in 48 patients who received either a LCKD (n = 24) or a standard LCD (n = 24). Compliance in following the prescribed diet was determined with food frequency questionnaires in all patients. The impact of LCKD and LCD on renal function was also evaluated. The LCKD group showed a significantly lower decrease in FFM and RMR when compared with the LCD group (3.55 vs 14.3%, p < 0.001; 9.79 vs 11.4%, p < 0.001, respectively). FM decreased more significantly with LCKD compared to LCD (41.6 vs 33.1%, p = 0.0606). Compliance in following the prescribed diets, without negative impact on renal function, was found. Based on our findings, despite the small sample size, we were able to support the hypothesis that LCKD is associated with an increased FM loss while reducing the FFM loss and the RMR, without interfering with renal function after EIGB.


External validation of subclassification system and progression pattern analysis in hepatocelluar carcinoma with macroscopic vascular invasion.
The present study aimed to validate the performance of a previously proposed subclassification model to predict prognosis after combined transarterial chemoembolization (TACE) and external beam radiotherapy (RT) for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) in an independent cohort that received the same first-line treatment for the patients with the similar disease extent characteristics, and analyzed the progression patterns as well as progression-free survival (PFS). This study was conducted using prospectively collected data from the XXXXX HCC registry for newly diagnosed, previously untreated HCC between 2005 and 2018. Finally, 417 patients who satisfied the eligibility criteria were included and analyzed. The median PFS and overall survival (OS) were 5.2 and 13.9 months, respectively. Similar to a previous study, subclassification of patients into very low-, low-, intermediate-, and high-risk groups showed a median OS of 98.4, 18.3, 9.7, and 5.8 months, respectively (P < 0.001). Additionally, subclassification of patients into the very low-, low-, intermediate-, and high-risk groups showed median PFS of 18.7, 6.7, 3.3, and 2.3 months, respectively (p < 0.001). Overall, intrahepatic progression was the most common pattern of progression; however, extrahepatic progression was more common in the intermediate- and high-risk groups. The previously proposed subclassification model was successfully validated in an independent cohort. Treatment modification should be considered in the intermediate- and high-risk patient groups because of their frequent extrahepatic as well as intrahepatic progressions after combined TACE and RT.


Clonogenic survival of human keratinocytes and rodent fibroblasts after irradiation with 25 kV x-rays.
Low energy x-rays (E(ph) </=50 keV) are widely used in diagnostic radiology and radiotherapy. However, data on their relative biological effectiveness (RBE) are scarce. Of particular importance for risk estimation are the RBE values of x-rays in the range which is commonly used in mammography (10-30 keV). We have determined clonogenic survival after low-energy x-ray irradiation for three cell lines: primary human epidermal keratinocytes (HEKn), mouse fibroblasts (NIH/3T3) and Chinese hamster fibroblasts (V79). Experiments were performed with a 25 kV x-ray tube and compared to 200 kV x-rays as a reference. Compared to the effect of 200 kV x-rays, irradiation with 25 kV x-rays resulted in a decreased survival rate in the murine fibroblasts, but not in the human epithelial cell line. The RBE value was calculated for 10% surviving fraction. For HEKn cells, RBE was 1.33+/-0.27, for NIH/3T3 cells 1.25+/-0.07 and for V79 cells 1.10+/-0.09, respectively. No consistently increased RBE was observed in the various cell lines. Nevertheless, a potential of increased cytogenetic changes has to be considered for risk estimation of low-energy x-rays.


Adult human aortic cells in primary culture: heterogeneity in shape.
Adult human aortic cells have different shapes in situ. To determine whether populations of cultured aortic cells are also polymorphic, a technique for separation of cells from the intimal and medial layers of the human aorta by enzymatic dispersion of the vascular tissue was employed. It was established that aortic cells are polymorphic in primary culture, at least within the first 7 days after seeding. Four main morphological cell types were identified--elongated, asymmetric, polygonal, and stellate. Polygonal and stellate cells are found only in cultures of grossly normal intima. Elongated and asymmetric cells are present in practically all cultures. The ratio of elongated to asymmetric cells in cultures obtained from healthy aortas and atherosclerotic plaques is more or less the same and is approximately 3:1. In cultures of fatty streaks, the portion of asymmetric cells exceeds 50%. With immunofluorescent staining and ultra-structural analysis, cells of all four types were identified as smooth muscle. Possible reasons for the cells polymorphism in primary culture and the prospects of utilizing this culture method in the investigation of cellular aspects of atherogenesis are discussed.


Injuries in mountain bike racing: frequency of injuries in endurance versus cross country mountain bike races.
To determine the frequency of injuries requiring medical attention among mountain bike racers at endurance races (6 hours or greater in duration) versus traditional cross country races (less than 6 hours duration) and to determine the medical support available at races. A survey was developed to determine participants' experience level, previous injuries, and demographic information. An additional survey was completed by injured riders to determine injuries and treatment received. The number of medical providers, their level of training, and the supplies available was determined. The endurance riders had more years of mountain biking experience, averaged more hours of riding per week, and had fewer injuries requiring medical attention in the past year than the riders in the races. Of the cross-country riders, 7.2% were injured during the race, and 4.7% of endurance racers were injured. There was no increased risk of being injured in a race over an endurance race (odds ratio 1.6, 95% CI [0.50, 2.92]). Lacerations and abrasions were the most common injuries in both events. Head injuries, eye injuries, and blisters were only reported in the endurance events. Endurance events were more likely to have medical assistance available. There was a greater percentage of riders reporting injuries in the cross-country races. It is possible that many of the endurance racers did not report injuries, continuing to ride or taking care of their own injuries quickly. Both events tended to have similar types of injuries and, therefore, both events most likely need similar medical support.


Antipsychotic-like effects of a novel phosphodiesterase 10A inhibitor MT-3014 in rats.
Phosphodiesterase (PDE) 10A is an attractive therapeutic target for schizophrenia. Here, we investigated the antipsychotic-like effects of a novel PDE10A inhibitor, 1-({2-(7-fluoro-3-methylquinoxalin-2-yl)-5-[(3R)-3-fluoropyrrolidin-1-yl]pyrazolo[1,5-α]pyrimidin-7-yl}amino)-2-methylpropan-2-ol hydrochloride (MT-3014) in rats. MT-3014 showed a potent and selective inhibitory effect against PDE10A (IC50 = 0.357 nmol/L). Oral administration of MT-3014 (1.0-10 mg/kg) significantly increased the levels of cAMP, cGMP and cAMP response element-binding protein (CREB) phosphorylation in the rat striatum. MT-3014 decreased MK-801 (0.075 mg/kg)-induced hyperactivity (ED50 = 0.30 mg/kg) in a dose-dependent manner, although it decreased spontaneous locomotion in control rats (ED50 = 0.48 mg/kg); its effects were equivalent to those of risperidone. MT-3014 (0.3-3.0 mg/kg and 0.2 mg/kg) attenuated MK-801-induced prepulse inhibition deficits and cognitive deficits in rats, respectively, whereas risperidone attenuated MK-801-induced prepulse inhibition at only a high dose and failed to improve MK-801-induced cognitive deficits. Similar to risperidone (ID50 = 0.63 mg/kg), MT-3014 suppressed the conditioned avoidance response (ID50 = 0.32 mg/kg). Interestingly, MT-3014 did not elicit catalepsy and plasma prolactin increases at high doses. Furthermore, it also did not affect body weight. A positron emission tomography study using [11C]IMA107 showed a plasma concentration-dependent increase in brain PDE10A occupancy after oral administration of MT-3014 within the pharmacological dose range in rats. Brain PDE10A occupancy corresponding to the ID50 value in the conditioned avoidance response was approximately 60%, predicting the target occupancy in patients with schizophrenia. These results suggest that MT-3014 may be a novel antipsychotic drug, which is expected to have additional effects on cognitive impairment, without the prominent side effects associated with current atypical antipsychotics.


Early or delayed palatoplasty in complete unilateral cleft lip and palate patients? A systematic review of the effects on maxillary growth.
The aim of this study was to review the effects of early and late hard palate repair on maxillary growth. PubMed, Scopus, Web of Science, LILACS, Cochrane Library CENTRAL databases, OpenGrey, Google Scholar, and Clinical Trials were searched using a PICO strategy, with terms related to unilateral cleft lip and palate (UCLP) and timing of repair. Methodological quality evaluation was carried out using the Fowkes and Fulton guidelines, and quality (or certainty) of evidence and strength of recommendations were evaluated using GRADE (grading of recommendations, assessment, development and evaluation). Five retrospective and non-randomized studies were included in the study. Folkes and Fulton assessment showed a high risk of bias in all articles and very low levels of certainty (GRADE). The results showed conflicting findings for comparisons of the effects of timing of repair of hard palate in UCLP. Two studies presented better maxillary growth in a group operated on later (18 months after birth), two presented no differences between the results, and another presented better results in the group operated on earlier than 18 months of age. At this point, it cannot be proven or refuted that postponing hard palate surgery brings benefits for maxillary growth. Studies included in this review did not show similar conclusions. Randomized clinical trials present some ethical issues that make them difficult to perform.


Comparison of the pharmacokinetics and pharmacodynamics of unformulated and formulated 4-hydroxyandrostenedione taken orally by healthy men.
A study of the aromatase inhibitor 4-hydroxy-androstenedione (4-OHA) was conducted in normal healthy men to compare the oral administration of two preparations of the drug: an unformulated, micronized powder and a formulated microcrystalline material (CGP 32349). The formulated material achieved a significantly higher mean peak concentration (88% greater than that obtained using the unformulated powder) and a higher mean AUC (not significant). The median time to peak was 1.5 h for both preparations and the elimination rate constants were similar (0.31 for micronized 4-OHA and 0.36 h-1 for formulated 4-OHA). Plasma concentrations of 4-OHA in this group were markedly lower than those previously observed in postmenopausal breast cancer patients. Significant biological activity was demonstrated with the formulated material in its suppression of plasma oestradiol levels, whereas no significant suppression was obtained using the micronized powder. An increase in androgen levels was observed that may have been due to competitive inhibition of enzymes involved in metabolic clearance of androgens and/or to decreased feedback inhibition of gonadotrophin secretion by oestradiol.


Expression and copy number analysis of TRPS1, EIF3S3 and MYC genes in breast and prostate cancer.
The long arm of chromosome 8 is one of the most common regions of amplification in cancers of several organs, especially carcinomas of the breast and prostate. TRPS1, MYC and EIF3S3 genes are located in one of the minimal regions of amplification, 8q23-q24, and have been suggested to be the target genes of the amplification. Here, our goal was to study copy number and expression of the three genes in order to investigate the significance of the genes in breast and prostate cancer. By using fluorescence in situ hybridisation (FISH), we first found that TRPS1 and EIF3S3 were amplified together in about one-third of hormone-refractory prostate carcinomas. Next, we analysed the mRNA expression of the three genes by real-time quantitative RT-PCR and the gene copy number by FISH in six breast and five prostate cancer cell lines. Breast cancer cell line, SK-Br-3, which contained the highest copy number of all three genes, showed overexpression of only EIF3S3. Finally, the expression levels of TRPS1, EIF3S3 and MYC were measured in freshly frozen clinical samples of benign prostate hyperplasia (BPH), as well as untreated and hormone-refractory prostate carcinoma. The TRPS1 and MYC expression levels were similar in all prostate tumour groups, whereas EIF3S3 expression was higher (P=0.029) in prostate carcinomas compared to BPH. The data suggest that the expression of EIF3S3 is increased in prostate cancer, and that one of the mechanisms underlying the overexpression is the amplification of the gene.


Trauma Prevalence and Resource Utilization During 4 COVID-19 "Surges": A National Analysis of Trauma Patients From 92 Trauma Centers.
We aim to assess the trends in trauma patient volume, injury characteristics, and facility resource utilization that occurred during four surges in COVID-19 cases. A retrospective cohort study of 92 American College of Surgeons (ACS)-verified trauma centers (TCs) in a national hospital system during 4 COVID-19 case surges was performed. Patients who were directly transported to the TC and were an activation or consultation from the emergency department (ED) were included. Trends in injury characteristics, patient demographics & outcomes, and hospital resource utilization were assessed during four COVID-19 case surges and compared to the same dates in 2019. The majority of TCs were within a metropolitan or micropolitan division. During the pandemic, trauma admissions decreased overall, but displayed variable trends during Surges 1-4 and across U.S. regions and TC levels. Patients requiring surgery or blood transfusion increased significantly during Surges 1-3, whereas the proportion of patients requiring plasma and/or platelets increased significantly during Surges 1-2. Patients admitted to the hospital had significantly higher Injury Severity Score (ISS) and mortality as compared to pre-pandemic during Surge 1 and 2. Patients with Medicaid or uninsured increased significantly during the pandemic. Hospital length of stay (LOS) decreased significantly during the pandemic and more trauma patients were discharged home. Trauma admissions decreased during Surge 1, but increased during Surge 2, 3 and 4. Penetrating injuries and firearm-related injuries increased significantly during the pandemic, patients requiring surgery or packed red blood cells (PRBCs) transfusion increased significantly during Surges 1-3. The number of patients discharged home increased during the pandemic and was accompanied by a decreased hospital length of stay (LOS).


Purification and characterization of cannabichromenic acid synthase from Cannabis sativa.
Cannabichromenic acid synthase was purified to apparent homogeneity by sequential column chromatography including DEAE-cellulose, phenyl-Sepharose CL-4B, and hydroxylapatite. The enzyme catalysed the oxidocyclization of cannabigerolic acid and cannabinerolic acid to cannabichromenic acid. The K(m) values for both substrates were in the same order of magnitude although the Vmax value for the former was higher than that for the latter. These results suggested that cannabichromenic acid is predominantly formed from cannabigerolic acid rather than cannabinerolic acid. The enzyme required neither molecular oxygen nor hydrogen peroxide, indicating that the cannabichromenic acid synthase reaction proceeds through direct dehydrogenation without hydroxylation.


Relationship between perineal muscle contractions, penile tumescence, and penile rigidity during nocturnal erections.
The mechanism of penile erection and erectile dysfunction is still unclear and widely debated. The role of the perineal muscles in the erectile process, especially in changes in intracavernous pressure, is increasingly being studied on the hypothesis that perineal muscular contractions are essential to full penile rigidity. In a previous investigation we studied the correlation between voluntary perineal muscle contractions and intracavernous pressure during artificially induced erections. The purpose of the current study was to examine whether under normal conditions of nocturnal erection a similar relationship exists between the electromyographic activities of perineal muscles and changes in penile rigidity. Nocturnal penile recordings were made of seven volunteers with psychogenic erectile dysfunctions. During nocturnal erections simultaneous computerized recordings were made of penile tumescence, penile rigidity, and electromyographic activities of perineal muscles. The peaks for the three variables were reached simultaneously. The results of this study suggest the existence of two different physiologic phases: a vascular phase and a muscular phase. Furthermore, in cases of dysfunctions, specific diagnostic assessment and therapeutic management will be required for both penile tumescence and penile rigidity.


Ageing modifies the effects of beetroot juice supplementation on 24-hour blood pressure variability: An individual participant meta-analysis.
Abnormal circadian oscillations of blood pressure (BP) and nocturnal-diurnal BP differences (i.e., dipping) increase cardiovascular risk. Whether inorganic nitrate supplementation influences 24-hr BP variability is currently unknown. We studied the effects of high-nitrate beetroot juice supplementation on BP variability measured by 24-hr ambulatory BP monitoring (24-hr ABPM) in older subjects. Data from four independent randomised clinical trials were collated. Eighty-five older participants (age range: 55-76 years) were included in the final database. Two trials had an open-label, parallel design and two trials had a cross-over, double-blind design. Participants were randomised to either beetroot juice or placebo. Changes in 24-hr ABPM (daily, diurnal, nocturnal), variability (weighted-SDs), night-dipping, morning surge for systolic and diastolic BP were measured. Meta-analysis was conducted to obtain pooled estimates of the effect size for each BP outcome. Sub-group analyses were conducted to evaluate the influence of age, BMI, gender, BP status and changes in nitrite concentrations on the effect size. The pooled effect of beetroot juice on all BP outcomes was not significant. Beetroot juice ingestion determined a significant decrease in nocturnal systolic BP variability in subjects aged less than 65 y (2.8 mmHg, -4.5 -1.0, p = 0.002) compared to the older group (≥ 65 y; 1.0 mmHg, -2.2 4.2, p = 0.54). A greater change in NO2(-) concentrations after beetroot supplementation was associated with significant differences for nocturnal mean (-3.4 mmHg, -0.6 -2.4, p = 0.02) and variability (-0.8 mmHg, -1.5 -0.06, p = 0.03) of systolic BP. The vascular responsiveness to inorganic nitrate may be modified by mechanisms of vascular ageing influencing the reducing capacity to convert inorganic nitrate into nitrite and tissue-specific responses to dietary nitrate supplementation.


Methodological characteristics and quality of alcohol treatment outcome studies, 1970-98: an expanded evaluation.
To examine the methodological quality of the research literature examining treatment for alcohol use disorders. In total, 701 studies first reported between 1970 and 1998 were evaluated with a scoring system covering 19 areas of research quality. Methodological quality improved from a score of 8.2 out of a possible 28.5 in the 1970s, to 10.6 in the 1990s. Strengths included reporting the initial number of participants and conducting follow-ups of 12 months or longer. Although the percentage of studies with adequate power also increased overall, the average statistical power of comparative studies to detect a medium-sized treatment effect was low (0.54). Areas with room for improvement include: ensuring that follow-up data are collected when respondents are not under the influence of alcohol, testing for differential dropout among treatment groups with respect to participant background characteristics, reporting the number of individuals being treated in the programs from which samples are drawn, noting the reliability and validity of measures used and conducting process analyses to examine potential mechanisms underlying treatment effects.


Safety and Efficacy of Pitavastatin in Patients With Impaired Fasting Glucose and Hyperlipidemia: A Randomized, Open-labeled, Multicentered, Phase IV Study.
Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG). In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels. Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P < 0.01). The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.


Cytogenetic findings in clear cell chondrosarcoma.
Clear cell chondrosarcoma is a rare cartilaginous tumor of low-grade malignancy that most often arises in the epiphysis of long bones in the third and fourth decades of life. Cytogenetic studies of clear cell chondrosarcoma are few. In this study, the cytogenetic findings of 4 cases of clear cell chondrosarcoma are presented. Clonal chromosomal abnormalities were detected in 3 cases. A tumor specific anomaly was not identified, however, extra copies of chromosome 20 and loss or rearrangements of 9p appear to be recurrent.


Study on the effects of nitrilotriproprionic acid and 4,5-dihydroxy-1,3-benzene disulphonate on the fractionation of beryllium in human serum using graphite furnace atomic absorption spectrometry.
Occupational exposure to beryllium may cause Chronic Beryllium Disease (CBD), a lung disorder initiated by an electrostatic interaction with the MHC class II human leukocyte antigen (HLA). Molecular studies have found a significant correlation between the electrostatic potential at the HLA-DP surface and disease susceptibility. CBD can therefore be treated by chelation therapy. In this work, we studied the effect of two complexing agents, nitrilotriproprionic acid (NTP) and 4,5-dihydroxy-1,3-benzene disulphonate (Tiron), on the fractionation of beryllium in human serum analysed by graphite furnace atomic absorption spectrometry (GFAAS). We found the average serum beryllium concentration of fourteen non-exposed individuals to be 0.53 (+/- 0.14) microg l(-1), with 21 (+/- 3)% of the beryllium mass bound to the low molecular weight fraction (LMW), and 79 (+/- 3)% bound to the high molecular weight fraction (HMW). The addition of Tiron increased the beryllium mass in the HMW fraction, while NTP was not seen to have any influence on the fractionation of beryllium between the two fractions. NTP was, however, shown to complex 94.5% of the Be mass in the LMW fraction. The beryllium GFAAS detection limit, calculated as three times the standard deviation of 10 replicates of the lowest standard (0.05 microg L(-1)), was 6.0 (+/- 0.2) ng L(-1). The concentration of beryllium or its fractionation in human serum was not affected by sex or smoking habit. On average, three quarters of the beryllium in serum were found in the HMW fraction. Of the two ligands tested, only Tiron was effective in mobilising beryllium under physiological conditions, thus increasing the Be content in the HMW fraction.


Lifetime prevalence of non-suicidal self-injury in patients with eating disorders: a systematic review and meta-analysis.
Against a backdrop of increasing research, clinical and taxonomic attention in non-suicidal self-injury (NSSI), evidence suggests a link between NSSI and eating disorders (ED). The frequency estimates of NSSI in ED vary widely. Little is known about the sources of this variation, and no meta-analysis has quantified the association between ED and NSSI. Using random-effects meta-analyses, meta-regression analyses, and 1816-6466 unique participants with various ED, we estimated the weighted average percentage of individuals with ED, those with anorexia nervosa (AN) and those with bulimia nervosa (BN) who are reported to have a lifetime history of NSSI across studies. We further examined predictors of NSSI in ED. The weighted average percentage of patients with a lifetime history of NSSI was 27.3% [95% confidence interval (CI) 23.8-31.0%] for ED, 21.8% (95% CI 18.5-25.6%) for AN, and 32.7% (95% CI 26.9-39.1%) for BN. The difference between BN and AN was statistically significant [odds ratio (OR) 1.77, 95% CI 1.14-2.77, p = 0.013]. The odds of NSSI increased by 24% for every 10% increase in the percentage of participants with histories of suicide attempts (OR 1.24, 95% CI 1.04-1.48, p = 0.020) and decreased by 26% for every 10% increase in the percentage of participants with histories of substance abuse (OR 0.74, 95% CI 0.58-0.95, p = 0.023). In the specific context of ED, NSSI is highly prevalent and correlates positively with attempted suicide, urging for NSSI-focused treatments. A novel finding is that NSSI is potentially antagonized by substance abuse.


Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease.
The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.


Distal upper limb involvement in myasthenia-myositis association.
Myasthenia gravis-inflammatory myopathy (MG-IM) association has been rarely reported as specific clinical entity characterized by variable myositis manifestations, ranging from subclinical to diffuse muscle involvement with characteristic distal upper limb weakness. Although, in view of this, it has been hypothesized that distal muscle weakness in MG-IM could be due to the muscle inflammation instead of a pure neuromuscular transmission impairment, a biopsy-proven myositis process of distal muscles of upper limbs has not yet been provided. We report on clinical, immunological, and myopathological characterization of a novel case affected by MG-IM association showing the typical distal upper limb weakness, including muscle biopsy of a weak forearm muscle. Histological and immunohistochemical studies showed a marked inflammatory process on muscle biopsy of extensor digitorum communis. The patient, a 47-year-old man with 10-year history of anti-acetylcholine receptor (AChR) and anti-titin antibody-positive MG with thymoma, developed a progressive, diffuse, and non-fatigable weakness predominant in distal upper limb muscles, unresponsive to acetylcholinesterase inhibitors associated to myalgia and creatine kinase (CK) elevation. We provide the histopathological evidence of a prominent inflammatory process responsible of distal upper limb weakness in MG-IM association. Muscle biopsy does not reveal any typical histopathological feature of other nosologically definite inflammatory myopathy, leading MG-IM association to come close to the group of overlap-myositis (OM) with the myopathological features of non-specific myositis (NSM).


Giant sacral meningeal diverticulum containing a thickened filum with lipoma in an adult with spinal cord tethering. Case report and review of the literature.
An unusual case of a patient with a giant intrasacral meningeal diverticulum and spinal cord tethering with a thickened filum is presented. Instead of being empty as is typical, the meningeal diverticulum in this case contained a segment of the thickened tethering filum, which entered from the thecal sac through an ostium. A search of the literature revealed no prior description of a meningeal diverticulum containing a portion of tethered filum or any other structure. Only 2 previous cases of intrasacral meningeal cyst and spinal cord tethering with a thickened filum were found, both in the non-English literature.


Triglycerides revisited: is hypertriglyceridaemia a necessary therapeutic target in cardiovascular disease?
Despite the atherosclerotic cardiovascular disease (ASCVD) risk reduction achieved by low-density lipoprotein cholesterol (LDL-C) lowering therapy, residual ASCVD risk still exists. Previous epidemiological studies have suggested high plasma triglyceride (TG) levels as a risk factor or risk marker for ASCVD independent of LDL-C levels. In this review, we highlighted the underlying pathophysiology of hypertriglyceridaemia, the mechanistic action of therapeutic agents, the interpretation of conflicting results on recent clinical trials, and the present options for primary and secondary prevention. The benefits of fibrates-induced reduction in TG and increase in high-density lipoprotein cholesterol might outweigh the disadvantages of increasing LDL-C levels in primary prevention. In secondary CVD prevention, using eicosapentaenoic acid without docosahexaenoic acid, in addition to statins, will be beneficial. This comprehensive review may prove useful for the development of novel approaches that target hypertriglyceridaemia in future.


Studies on the Nonalkaloidal Secondary Metabolites of Hippeastrum vittatum (L'Her.) Herb. Bulbs.
Sixteen chemically varied metabolites were isolated from the bulbs of Hippeastrum vittatum (L'Her.) Herb., including eight flavonoids [3'-methyl isoliquiritigenin (2), 7-hydroxyflavan (8), 7-hydroxyflavanone (9), 7-hydroxyflavan-3-ol (10), 7-methoxy-3',4'-methylenedioxyflavan-3-ol (11), 7-hydroxy-3',4'-methylenedioxy flavan (12), 2',4'-dihydroxy-3'-methyl-3,4-methylenedioxychalcone (13), and isoliquiritigenin (14)], four acetophenones [2,6-dimethoxy-4-hydroxyacetophenone (3), 2,4-dihydroxyacetophenone (4), 2,4-dihydroxy-6-methoxy-3-methylacetophenone (6), and 2,4,6-trimethoxyacetophenone (7)], two alkaloids [lycorine (1) and narciprimine (15)], one phenol derivative [p-nitrophenol (5)], and one steroid [β-sitosterol 3-O-β-glucopyranoside (16)]. Their structures were elucidated by combining one- and two-dimensional NMR and ESI-MS techniques and by comparison with the reported literature data and some authentic samples. Except for lycorine (1), the isolated metabolites were obtained herein for the first time from Hippeastrum plants, among which compound 13 was identified as a new chalcone derivative. Additionally, the total phenolic and flavonoid contents of the total ethanol extract and different fractions of the bulbs were determined by the Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively, whereas their antioxidant potential was compared using the phosphomolybdenum and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. Finally, the binding affinities of compounds 1-16 to some key target proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), were screened and compared using molecular docking analysis. The possible chemotaxonomic significance of the identified metabolites was also discussed.


[The microsurgical treatment of the so-called tuberculum-sellae-meningiomas (author's transl)].
Experience from five cases operated on within one year (among 50 microsurgical operations at the base of the brain) persuades us to discuss the topical relations of the meningiomas of the tuberculum sellae and the modifications in operating techniques necessary. For the two contrasting types of tumour found, which are:-- 1. Tumours en plaque with osseous reactions, particularly of the sphenoidal ridge, in which the exact predetermination of the positions of the optic nerve and of the carotid artery is facilitated by means of measurement and by fronto-temporal approach (which does not preclude a frontal or a bifrontal approach). 2. Suprasellar tumours whose topical relationships to the posterior surface of the chiasma, the pituitary stalk, the big vessels, and the perforating arteries increase the risk of operation. Radical operations for tumours near the pituitary stalk are not always advisable. Pre- and postoperative analysis of the anatomical characteristics of the individual case is essential before microsurgical intervention.


Endoscopic balloon dilatation for congenital membranous stenosis in the jejunum in an infant.
As endoscopic equipment and instruments have improved, the indications for endoscopic treatment have also been extended. This report presents an applicable procedure of endoscopic balloon dilatation for an infant patient with congenital membranous stenosis in the jejunum. We used a 9-mm flexible endoscope and a through-the-scope multidiameter balloon catheter in the endoscopic treatment. Dilatation was performed for dilatation diameters 10, 12, and 15 mm each for 2 min. After carrying out balloon dilatation, the endoscope could be smoothly inserted through the opening. In upper jejunal stenosis, endoscopic balloon dilatation was minimally invasive and effective as a treatment modality.


Advances and insights in the diagnosis of viral infections.
Viral infections are the most common among diseases that globally require around 60 percent of medical care. However, in the heat of the pandemic, there was a lack of medical equipment and inpatient facilities to provide all patients with viral infections. The detection of viral infections is possible in three general ways such as (i) direct virus detection, which is performed immediately 1-3 days after the infection, (ii) determination of antibodies against some virus proteins mainly observed during/after virus incubation period, (iii) detection of virus-induced disease when specific tissue changes in the organism. This review surveys some global pandemics from 1889 to 2020, virus types, which induced these pandemics, and symptoms of some viral diseases. Non-analytical methods such as radiology and microscopy also are overviewed. This review overlooks molecular analysis methods such as nucleic acid amplification, antibody-antigen complex determination, CRISPR-Cas system-based viral genome determination methods. Methods widely used in the certificated diagnostic laboratory for SARS-CoV-2, Influenza A, B, C, HIV, and other viruses during a viral pandemic are outlined. A comprehensive overview of molecular analytical methods has shown that the assay's sensitivity, accuracy, and suitability for virus detection depends on the choice of the number of regions in the viral open reading frame (ORF) genome sequence and the validity of the selected analytical method.


The response of rice grain quality to ozone exposure during growth depends on ozone level and genotype.
The effects of ozone exposure during the cropping season on rice grain quality were investigated in chamber experiments employing four ozone treatments (charcoal filtered air, ambient, 2× ambient, and 2.5× ambient concentration) and six genotypes. The concentrations of protein and lipids in brown rice increased significantly in response to ozone, while starch concentration and thousand kernel mass decreased. Other parameters, including the concentrations of iron, zinc, phenolics, stickiness and geometrical traits did not exhibit significant treatment effects. Total brown rice yield, protein yield, and iron yield were negatively affected by ozone. Numerous genotypic differences occurred in the response to ozone, indicating the possibility of optimizing the grain quality in high ozone environments by breeding. It is concluded that although the concentrations of two important macronutrients, proteins and lipids, increased in ozone treated grains, the implications for human nutrition are negative due to losses in total grain, protein and iron yield.


Adsorptive removal of organic dyes via porous materials for wastewater treatment in recent decades: A review on species, mechanisms and perspectives.
Organic dyes, a type of high toxic and carcinogenic chemicals that present severe threats to human and aquatic life, are the most commonly seen organic pollutants in wastewater of industries such as textile, rubber, cosmetic industry etc. Various techniques for the removal of dyes are compared in this review. Adsorption has proven to be a facile and promising approach for the removal of dyes in wastewater. This work focuses on the latest development of various porous materials for the adsorption of organic dyes. The characteristics, functionalization and modification of different porous materials are also presented. Furthermore, adsorption behaviors and mechanism of these adsorbents in the adsorption of organic dyes are critically reviewed. Finally, challenges and opportunities for future research in the development of novel materials for the highly efficient removal of dyes are proposed.


DNA microarray profiling of genes differentially regulated by three heterochromatin protein 1 (HP1) homologs in Drosophila.
Heterochromatin protein 1 (HP1) is an epigenetic gene silencing protein that is regulated by lysine 9 methylation of histone H3. Most eukaryotes have at least three HP1 homologs with similar domain structures but with different localization patterns and functions in heterochromatin and euchromatin. However, little is known about the genome-wide effects of the three main HP1 homologs on gene expression. Here, to gain insight into the different gene expression effects of the three HP1 homologs, we performed a comprehensive and comparative microarray analysis of Drosophila HP1 homologs. Bioinformatic analysis of the microarray profiling revealed significant similarity and uniqueness in the genes altered in HP1-knockdown S2 cells in Drosophila. Although global changes of these transcripts were surprisingly subtle (4-6%), there were ~582 common target genes for the three HP1s that showed transcript levels either reduced or induced >1.5-fold. Depletion of HP1 resulted in up-regulated and down-regulated gene profiles, indicating that HP1 mediates both repression and activation of gene expression. This study is the first to systematically analyze the bioinformatics of HP1 paralogs and provide basic clues to the molecular mechanism by which HP1 might control gene expression in a homolog-specific manner.


iCOPE With COVID-19: A Brief Telemental Health Intervention for Children and Adolescents During the COVID-19 Pandemic.
The COVID-19 pandemic has prompted extensive disruptions to the daily lives of children and adolescents worldwide, which has been associated with an increase in anxiety and depressive symptoms in youth. However, due to public health measures, in-person psychosocial care was initially reduced, causing barriers to mental health care access. This study investigated the feasibility, acceptability and preliminary effectiveness of iCOPE with COVID-19, a brief telemental health intervention for children and adolescents to address anxiety symptoms. Sessions were provided exclusively using videoconferencing technology. Feasibility and acceptability were measured with client satisfaction data. The main outcome measure for effectiveness was anxiety symptom severity measured using the Screen for Child Anxiety and Related Disorders (SCARED). Results indicated that the treatment was well accepted by participants. Significant reductions in anxiety were noted for social anxiety, and were observed to be trending towards a mean decrease for total anxiety. The findings suggest that this brief telemental health intervention focused on reducing anxiety related to COVID-19 is acceptable and feasible to children and adolescents. Future research using a large sample and with a longer follow-up period could inform whether symptom decreases are sustained over time.


Short-term effects of fine particulate matter on acute myocardial infraction mortality and years of life lost: A time series study in Hong Kong.
Previous studies have applied years of life lost (YLL) as a complementary indicator to assess the short-term effect of the air pollution on the health burden from all-cause mortality, but sparsely focused on individual diseases such as acute myocardial infraction (AMI). In this study, we aimed to conduct a time-series analysis to evaluate short-term effects of fine particulate matter (PM2.5) on mortality and YLL from AMI in Hong Kong from 2011 to 2015, and explore the potential effect modifiers including sex and age by subgroup analysis. We applied generalized additive Poisson and Gaussian regression model for daily death count and YLL, respectively. We found that 10μg/m3 increment in concentration of PM2.5 lasting for two days (lag01) was associated with a 2.35% (95% CI 0.38% to 4.36%) increase in daily mortality count and a 1.69 (95% CI 0.01 to 3.37) years increase in YLL from AMI. The association between PM2.5 and AMI mortality count was stronger among women and older people than men and young people, respectively. We concluded that acute exposure to PM2.5 may increase the risk of mortality and YLL from AMI in Hong Kong and this effect can be modified by age and gender. These findings add to the evidence base for public health policy formulation and resource allocation.


Isolation and partial characterization of the major glycoprotein from the plasma membranes of AH-66 hepatoma cells.
A major glycoprotein of the plasma membranes of AH-66 hepatoma ascites cells was isolated in essentially pure form and in milligram amounts. The plasma membranes were solubilized with a solution containing both 0.3 M lithium diiodosalycylate and 0.2% cetylpyridinium chloride, and further extracted with 50% phenol, followed by gel filtration on Sepharose 6B in the presence of 0.1% Ammonyx-LO at pH 8.0. The apparent molecular weight of the purified glycoprotein was estimated to be 165 000 in 5.6% polyacrylamide gels, of which 54% was carbohydrate and 46% was protein. The chemical composition of the glycoprotein resembles glycophorin A from human erythrocyte membranes in that it has a high content of N-acetylgalactosamine, N-acetylglucosamine, galactose and sialic acid and a particularly large proportion of serine, threonine, aspartic acid and glutamic acid.


Structural investigations of the lipopolysaccharide isolated from Vibrio cholera, Inaba 569 B.
On hydrolysis, the purified lipopolysaccharide (LPS) isolated from Vibrio cholera, Inaba 569 B, yielded glucose, mannose, a heptose behaving like D-glycero-L-manno-heptose and one behaving like D-glycero-L-gluco-heptose, 2-amino-2-deoxyglucose, and glucuronic acid in the molar ratios of approximately 9:4:5:1:2:5. Studies on the LPS, the polysaccharide (PS), and carboxyl-reduced LPS showed that the PS has a branched structure, with (1 leads to 2)-linked mannopyranosyl and a heptopyranosyl, and (1 leads to 4)-linked glucopyranosyluronic and 2-amino-2-deoxyglucopyranosyl residues in the interior part of the molecule, and glucopyranosyl and heptopyranosyl residues as nonreducing end-groups.


The frequency of malignancy and the relationship between malignancy and ultrasonographic features of thyroid nodules with indeterminate cytology.
Various approaches are available for the management of nodules that are evaluated to be indeterminate according to the results of thyroid fine needle aspiration biopsy. The present study aimed to determine the rate of malignancy and the ultrasonographic features that could be used as predictor of malignant pathologies at the nodules with indeterminate cytology. A total of 201 patients who underwent total thyroidectomy and whose fine needle aspiration biopsy results were evaluated to be Hurthle cell lesion (n = 99), follicular neoplasm (n = 61) and [corrected] suspicious for malignancy (n = 41) were enrolled in this study. Of these patients, 178 were females (88.6 %) and 23 were males (11.4 %). The rates of malignancy were found to be 33.3 % in the Hurthle cell lesion group, 23.0 % in the follicular neoplasm group and 53.7 % in the suspicious for malignancy group (p = 0.006). The comparison of the ultrasonographic characteristics of the malignant and benign nodules revealed hypoechogenicity and microcalcification to be more common in malignant nodules (34.3 vs. 16.9 %, p = 0.005; 27.1 vs. 13.1 %, p = 0.014; respectively). While 92.3 % of the malignant nodules were ≥1 cm, 82.9 % of the benign nodules were ≥1 cm (p = 0.042). We believe that as the patients at Hurthle cell lesion group have higher risk of malignancy than the patients with Follicular Neoplasia so total thyroidectomy will be suitable for these patients. [corrected]. In addition, microcalcification and hypoechoic nodules at patients with indeterminate cytology can be related with increased risk of malignancy. [corrected].


Microbiota and adipocyte mitochondrial damage in type 2 diabetes are linked by Mmp12+ macrophages.
Microbiota contribute to the induction of type 2 diabetes by high-fat/high-sugar (HFHS) diet, but which organs/pathways are impacted by microbiota remain unknown. Using multiorgan network and transkingdom analyses, we found that microbiota-dependent impairment of OXPHOS/mitochondria in white adipose tissue (WAT) plays a primary role in regulating systemic glucose metabolism. The follow-up analysis established that Mmp12+ macrophages link microbiota-dependent inflammation and OXPHOS damage in WAT. Moreover, the molecular signature of Mmp12+ macrophages in WAT was associated with insulin resistance in obese patients. Next, we tested the functional effects of MMP12 and found that Mmp12 genetic deficiency or MMP12 inhibition improved glucose metabolism in conventional, but not in germ-free mice. MMP12 treatment induced insulin resistance in adipocytes. TLR2-ligands present in Oscillibacter valericigenes bacteria, which are expanded by HFHS, induce Mmp12 in WAT macrophages in a MYD88-ATF3-dependent manner. Thus, HFHS induces Mmp12+ macrophages and MMP12, representing a microbiota-dependent bridge between inflammation and mitochondrial damage in WAT and causing insulin resistance.


Informed Consent for Pediatric Endoscopy.
Informed consent and refusal for pediatric procedures involves a process in which the provider, child, and parents/guardians participate. In pediatric gastroenterology, many procedures are considered elective and the process generally begins with an office visit and ends with the signing of the consent document. If the process is emergent then this occurs more expeditiously and a formal consent may not be required. Information about the procedure should be shared in a way that allows a decision-making process to occur for both the parent/guardian and the child, if of assenting age.


Behavioral Disorders in Mares with Ovarian Disorders, Outcome after Laparoscopic Ovariectomy: A Case Series.
Owner complaints of estrus-related behavior in mares are a common cause of referral for laparoscopic ovariectomy. Granulosa cell tumors are a common neoplastic condition affecting the equine ovary, causing behavioral changes at rest and reduced performance. The reported success rate of ovariectomy in treating behavioral disorders is 64-86%. The aim of this study was to retrospectively evaluate the long-term follow-up of laparoscopic ovariectomy in mares in our case series, focusing on the owner's perspective of the behavior of the mares after surgery. In addition, the histopathological features of the removed ovaries were investigated. The clinical records of mares that underwent laparoscopic ovariectomy between 2015 and 2022 were retrospectively reviewed. Owners complaining of poor behavior were interviewed about the main behavioral problem leading to referral and its eventual resolution after surgery. Eleven mares were included. The most common complaints were increased sensitivity on both flanks (10/11, 91%) and general riding problems (9/11, 82%). In 5/11 cases (45%), both ovaries were removed by laparoscopic ovariectomy. Histopathologic findings consistent with GCT/GTCT were found in five out of six examined ovaries (five granulosa theca cell tumors, GTCT). According to owner interviews, the scores assigned to each behavior improved significantly after surgery, regardless of histological findings. Although many factors can influence the behavior of horses, granulosa cell tumors (GCTs) proved to be a common cause and, as reported by the owners, ovariectomy resulted in improvement or complete resolution of the abnormal behavior.


Canine perinatal mortality: a cohort study of 224 breeds.
Canine perinatal mortality is known to be relatively high. However, the literature on perinatal mortality in dogs is still sparse and often refers to a single or only a few breeds. The aim of this large-scale observational study was to describe the perinatal mortality in purebred dogs of various breeds at both puppy and litter level. In addition, the influence of breed, breed size, litter size, age of the bitch, litter number and season for whelping on the risk of perinatal mortality at litter level was studied and the mean litter size at eight days and eight wks after birth was calculated. A retrospective cohort study was performed by studying 10,810 litters of 224 breeds registered in the Norwegian Kennel Club in 2006 and 2007. Perinatal mortality was defined as the sum of stillborn puppies and puppies that died during the first wk after birth (early neonatal mortality) and was present in 24.6% of the litters. Eight percent of the puppies died before eight days after birth, with 4.3% as stillbirth and 3.7% as early neonatal mortality. For most breeds the perinatal mortality was low, but for some breeds a higher perinatal mortality was found. The mean litter size at eight days and eight wks after birth was 4.97 (±0.02) and 4.92 (±0.02) puppies, respectively. Of all puppies born, only 1% died during the period from eight days to eight wks after birth. Random effects logistic regression analysis indicated that increasing litter size and age of the bitch were associated with an increased risk of stillbirth, early neonatal mortality and total perinatal mortality at the litter level (P < 0.001). The random breed effect was significant for all outcomes. Litter number also had a significant effect on stillbirth, early neonatal mortality and total perinatal mortality at the litter level, with the highest risk of perinatal mortality found in the first litter (P < 0.001). Further, the risk of early neonatal mortality was doubled in litters with stillborn puppies. No significant effect of whelping season on perinatal mortality at litter level was found. An interaction existed between the age of the bitch and litter number and the risk of stillbirth was three times as high (odds ratio = 3.00) in litters from bitches having their first litter after the age of six y. Breed was a more important determinant of perinatal mortality in litters than breed size. However, more than 90% of the variation in perinatal mortality was found at the individual litter level and efforts to minimize puppy mortality should be targeted at the management of the individual litter rather than at the breed level.


Olfactory bulb responses telemetered during an odor discrimination task in rats.
Electrodes were chronically implanted in eight rats to record multiple-unit activity during the acquisition and performance of an isoamyl acetate (10(-3) concentration)/air discrimination task in order to obtain a water reward. Localized stimulus choice points permitted each rat to regulate its time of exposure to the two positive reinforcing stimuli. Each rat had stimulus sampling times of much less than 1 s while performing at an 80% or more correct choice level. Whereas four of the rats exhibited only occasional neural activity, probably due to electrode position, the other four developed individual neural burst patterns, after learning, which were different for the two stimuli. Changes in the neural patterns during testing, when they occurred in two of the four responsive animals, appeared to correlate with changes in stimulus sampling. These results confirm that much less than 1 s is needed for odor identification and demonstrate that multiunit activity can show differential response patterns. The results have possible implications for future studies.


Can Trait Mindfulness Improve Job Satisfaction? The Relationship Between Trait Mindfulness and Job Satisfaction of Preschool Teachers: The Sequential Mediating Effect of Basic Psychological Needs and Positive Emotions.
Objective: This study aims to explore the relationship between basic psychological needs and positive emotions of preschool teachers between trait mindfulness and job satisfaction. Methods: Three hundred and ninety-eight preschool teachers were tested with mindfulness attention awareness scale, basic psychological needs scale, positive emotion scale, and job satisfaction scale. Results: Preschool teachers trait mindfulness can predict job satisfaction (β = 0.265, p < 0. 001). Preschool teachers trait mindfulness has an indirect impact on job satisfaction through basic psychological needs (β = 0.059, p = 0.002), and preschool teachers trait mindfulness has an indirect impact on job satisfaction through positive emotions (β = 0.123, p < 0. 001). In addition, basic psychological needs and positive emotions play a sequential intermediary role between preschool teachers trait mindfulness and job satisfaction (β = 0.017, p < 0. 001). Conclusion: Basic psychological needs and positive emotions play a sequential mediating role between preschool teachers trait mindfulness and job satisfaction, and this sequential mediating effect accounts for a high proportion of the total effect.


Functional role for suppression of the insular-striatal circuit in modulating interoceptive effects of alcohol.
The insular cortex (IC) is a region proposed to modulate, in part, interoceptive states and motivated behavior. Interestingly, IC dysfunction and deficits in interoceptive processing are often found among individuals with substance-use disorders. Furthermore, the IC projects to the nucleus accumbens core (AcbC), a region known to modulate the discriminative stimulus/interoceptive effects of alcohol and other drug-related behaviors. Therefore, the goal of the present work was to investigate the possible role of the IC ➔ AcbC circuit in modulating the interoceptive effects of alcohol. Thus, we utilized a chemogenetic technique (hM4Di designer receptor activation by designer drugs) to silence neuronal activity in the IC of rats trained to discriminate alcohol (1 g/kg, IG) versus water using an operant or Pavlovian alcohol discrimination procedure. Chemogenetic silencing of the IC or IC ➔ AcbC neuronal projections resulted in potentiated sensitivity to the interoceptive effects of alcohol in both the operant and Pavlovian tasks. Together, these data provide critical evidence for the nature of the complex IC circuitry and, specifically, suppression of the insular-striatal circuit in modulating behavior under a drug stimulus control.


Streptococcus uberis: In vitro biofilm production in response to carbohydrates and skim milk.
Streptococcus uberis has become one of the most important environmental pathogens associated with clinical and subclinical bovine mastitis. Biofilm confers to bacteria more resistance to physical and chemical agents as well as to different mechanisms of the innate immune system. The aim of this work was to evaluate the ability of in vitro biofilm production in 32 S. uberis isolates from bovine mastitis and identified by biochemical tests and subsequently confirmed by the amplification of the pauA gene. The isolates were cultivated in TMP broth and TMP broth with the addition of 0.5% glucose, 1% sucrose, 1% lactose or 0.5% skim milk in microtiter plates stained with crystal violet. We demonstrated that S. uberis isolated from bovine mastitis are able to produce biofilms in TMP broth and, also that biofilm formation by S. uberis can be significantly enhanced by the addition of 0.5% glucose or 1% sucrose to TMP broth. This may suggest that the carbohydrates in milk or within the ruminant gut might affect the growth mode of S. uberis. In addition, our results showed that in vitro biofilm production under different conditions of supplementation displays variation among the isolates and that each isolate shows a particular profile of biofilm production. This phenotypic heterogeneity in biofilm production exhibited by S. uberis could at least partly explain why this bacterium has the ability to adapt to different niches facilitating survival to diverse and stressful conditions.


Long-term medical management and complications of 'resistant' ascites.
This paper reports the experience of treating patients with hepatic cirrhosis and ascites with an aldosterone inhibitor in addition to conventional therapy. Good results are demonstrated in 13 patients previously resistant to treatment.


Fibroblast growth factor signalling in osteoarthritis and cartilage repair.
Regulated fibroblast growth factor (FGF) signalling is a prerequisite for the correct development and homeostasis of articular cartilage, as evidenced by the fact that aberrant FGF signalling contributes to the maldevelopment of joints and to the onset and progression of osteoarthritis. Of the four FGF receptors (FGFRs 1-4), FGFR1 and FGFR3 are strongly implicated in osteoarthritis, and FGFR1 antagonists, as well as agonists of FGFR3, have shown therapeutic efficacy in mouse models of spontaneous and surgically induced osteoarthritis. FGF18, a high affinity ligand for FGFR3, is the only FGF-based drug currently in clinical trials for osteoarthritis. This Review covers the latest advances in our understanding of the molecular mechanisms that regulate FGF signalling during normal joint development and in the pathogenesis of osteoarthritis. Strategies for FGF signalling-based treatment of osteoarthritis and for cartilage repair in animal models and clinical trials are also introduced. An improved understanding of FGF signalling from a structural biology perspective, and of its roles in skeletal development and diseases, could unlock new avenues for discovery of modulators of FGF signalling that can slow or stop the progression of osteoarthritis.


Genomic Epidemiology of Major Extraintestinal Pathogenic Escherichia coli Lineages Causing Urinary Tract Infections in Young Women Across Canada.
A few extraintestinal pathogenic Escherichia coli (ExPEC) multilocus sequence types (STs) cause the majority of community-acquired urinary tract infections (UTIs). We examine the genomic epidemiology of major ExPEC lineages, specifically factors associated with intestinal acquisition. A total of 385 women with UTI caused by E. coli across Canada were asked about their diet, travel, and other exposures. Genome sequencing was used to determine both ST and genomic similarity. Logistic regression was used to identify factors associated with the acquisition of and infection with major ExPEC STs relative to minor ExPEC STs. ST131, ST69, ST73, ST127, and ST95 were responsible for 54% of all UTIs. Seven UTI clusters were identified, but genomes from the ST95, ST127, and ST420 clusters exhibited as few as 3 single nucleotide variations across the entire genome, suggesting recent acquisition. Furthermore, we identified a cluster of UTIs caused by 6 genetically-related ST1193 isolates carrying mutations in gyrA and parC. The acquisition of and infection with ST69, ST95, ST127, and ST131 were all associated with increased travel. The consumption of high-risk foods such as raw meat or vegetables, undercooked eggs, and seafood was associated with acquisition of and infection with ST69, ST127, and ST131, respectively. Reservoirs may aid in the dissemination of pandemic ExPEC lineages in the community. Identifying ExPEC reservoirs may help prevent future emergence and dissemination of high-risk lineages within the community setting.


A multicenter study of the clinical, laboratory characteristics, and potential prognostic factors in patients with amyloid A amyloidosis on hemodialysis.
While light chain (AL) amyloidosis is more common in western countries, the most common type of amyloidosis is amyloid A (AA) amyloidosis in Eastern Mediterranean Region, including Turkey. Although worse prognosis has been attributed to the AL amyloidosis, AA amyloidosis can be related to higher mortality under renal replacement therapies. However, there are no sufficient data regarding etiology, clinical presentation, and prognostic factors of AA amyloidosis. The objective of our study is to evaluate the clinical, laboratory characteristics, and possible predictive factors related to mortality in patients with AA amyloidosis undergoing hemodialysis (HD). This multicenter, cross-sectional study was a retrospective analysis of 2100 patients on HD. It was carried out in 14 selected HD centers throughout Turkey. Thirty-two patients with biopsy-proven AA amyloidosis and thirty-two control patients without AA amyloidosis undergoing HD were included between October 2018 and October 2019. There was no significant difference between the groups in terms of age and dialysis vintage. Causes of AA amyloidosis, treatment (colchicine and/or anti-interleukin 1 [IL] treatment), and the number of familial Mediterranean fever (FMF) attacks in the last year in case of FMF, systolic and diastolic blood pressures, biochemical values such as mean CRP, hemoglobin, serum albumin, phosphorus, calcium, PTH, ferritin, transferrin saturation, total cholesterol levels, EPO dose, erythropoietin-stimulating agents resistance index, interdialytic fluid intake, body mass indexes, heparin dosage, UF volume, and Kt/V data in the last year were collected by retrospective review of medical records. Prevalence of AA amyloidosis was found to be 1.87% in HD centers. In amyloidosis and control groups, 56% and 53% were male, mean age was 54 ± 11 and 53 ± 11 years, and mean dialysis vintage was 104 ± 94 and 107 ± 95 months, respectively. FMF was the most common cause of AA amyloidosis (59.5%). All FMF patients received colchicine and the mean colchicine dose was 0.70 ± 0.30 mg/day. 26.3% of FMF patients were unresponsive to colchicine and anti-IL-1 treatment was used in these patients. In AA amyloid and control groups, erythropoietin-stimulating agents resistance index were 7.88 ± 3.78 and 5.41 ± 3.06 IU/kg/week/g/dl, respectively (p = 0.008). Additionally, higher CRP values (18.78 ± 18.74 and 10.61 ± 10.47 mg/L, p = 0.037), lower phosphorus (4.68 ± 0.73 vs. 5.25 ± 1.04 mg/dl, p = 0.014), total cholesterol (135 ± 42 vs. 174 ± 39 mg/dl, p < 0.01), and serum albumin (3.67 ± 0.49 mg/dl, 4.03 ± 0.22, p < 0.01) were observed in patients with AA amyloidosis compared to the control group. In this study, we found that long-term prognostic factors including higher inflammation, malnutritional parameters, and higher erythropoietin-stimulating agents resistance index were more frequent in AA amyloidosis patients under HD treatment.


Evaluation of toxicity and mutagenicity of oxaliplatin on germ cells in an alternative in vivo model Caenorhabditis elegans.
The platinum compound oxaliplatin is a widely used chemotherapeutic drug that shows a broad spectrum of activity in various human tumors. While the treatment-related side effects of oxaliplatin on directly treated individuals have been well-documented, little is known about the influence of oxaliplatin on germ cells and non-exposed progenies. Here we investigated the reproductive toxicity of oxaliplatin in a 3R-compliant in vivo model Caenorhabditis elegans, and evaluated the germ cell mutagenicity of oxaliplatin by using whole genome sequencing. Our results indicated that oxaliplatin treatment significantly disrupts development of spermatids and oocytes. By treating parental worms with oxaliplatin for three successive generations, sequencing data unveiled the mutagenic effects of oxaliplatin on germ cells. Analysis of genome-wide mutation spectra showed the preferentially induction of indels by oxaliplatin. In addition, we uncovered the involvement of translesion synthesis polymerase ζ in modulating mutagenic effects of oxaliplatin. These findings suggest that germ cell mutagenicity is worthy of consideration for the health risk assessment of chemotherapeutic drugs, while the combined use of alternative in vivo models and next generation sequencing technology appears to be a promising way for the preliminary safety assessment of various drugs.


FCGRs Polymorphisms and Response to Trastuzumab in Patients With HER2-Positive Breast Cancer: Far From Predictive Value?
The aim of the study was to validate the association between the Arg166His polymorphisms of the Fc immunoglobulin receptor 2A (FCGR2A) and the Val212Phe of FCGR3A and pathological clinical response (pCR) to trastuzumab in HER2-positive breast cancer patients. Polymorphisms were characterized by pyrosequencing in 26 patients with ductal histotype breast cancer in a neoadjuvant setting and genotype association with pCR was analyzed. No association was found between the FCGR3A Val212Phe polymorphisms and pCR. In contrast, the FCGR2A GG genotype (Arg allele) was found to be positively associated with pCR (P = 0.012). Our results do not support previously reported data on the effect of polymorphisms in immunoglobulin Fc receptors upon response to trastuzumab therapy.


Internal phosphorus loading and its driving factors in the dry period of Brazilian semiarid reservoirs.
This study investigated the relationships between physical, limnological and climatic drivers with the internal total phosphorus (TP) loading produced over the dry period in 30 water supply reservoirs of the Brazilian semiarid. Improvements in the understanding of sedimentary TP fluxes in reservoirs of dryland regions are pressing as they usually have serious water quality related issues, remaining mostly eutrophic especially under frequent drought events. Gross daily fluxes and net seasonal average release rates were calculated from mass balance and regression equations considering water and sediment TP concentrations, anoxic duration, water temperature and fish contribution. Additionally, the ratio of wind speed to reservoir volume was proposed as a new surrogate and then applied as explanatory variable to predictive models. The results indicated TP release rates higher than reported for non-semiarid lakes/reservoirs with average gross fluxes ranging from 17.64 to 35.99 mg m-2 day-1. This may be attributed to the enriched sediments (1029.49 ± 552.49 mg kg-1) allied with warmer water temperature, high trophic state, and prolonged anoxic periods (average duration of about 60 days). The average release rates were negatively correlated with water transparency and water depth, and positively correlated with Chl-a, wind speed and trophic state. The release rates increased across the trophic gradient (p < 0.05), about 10-fold higher under hypertrophic conditions than in oligotrophic ones. As anoxia is linked with eutrophication, phosphorus release is more likely in eutrophic ecosystems. Regarding the new surrogate, a strong predictive ability for TP release (R2: 0.26-0.93) was observed. Similarly, the proposed models presented a physically consistent behavior with a stabilizing releasing pattern suggesting the achievement of equilibrium in nutrient exchange between sediment-water interface. This research advanced by combining and proposing methods to assess and quantify sedimentary fluxes in data-scarce regions balancing accuracy and transferability, in order to be replicable to other dryland environments globally.