The transcriptional regulator RbcR controls ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) genes in the cyanobacterium Synechocystis sp. PCC 6803.
Oxygenic photosynthesis evolved in cyanobacteria, primary producers of striking ecological importance. Like plants, cyanobacteria use the Calvin-Benson-Bassham cycle for CO2 fixation, fuelled by ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). In a competitive reaction this enzyme also fixes O2 which makes it rather ineffective. To mitigate this problem, cyanobacteria evolved a CO2 concentrating mechanism (CCM) to pool CO2 in the vicinity of RuBisCO. However, the regulation of these carbon (C) assimilatory systems is understood only partially. Using the model Synechocystis sp. PCC 6803 we characterized an essential LysR-type transcriptional regulator encoded by gene sll0998. Transcript profiling of a knockdown mutant revealed diminished expression of several genes involved in C acquisition, including rbcLXS, sbtA and ccmKL encoding RuBisCO and parts of the CCM, respectively. We demonstrate that the Sll0998 protein binds the rbcL promoter and acts as a RuBisCO regulator (RbcR). We propose ATTA(G/A)-N5 -(C/T)TAAT as the binding motif consensus. Our data validate RbcR as a regulator of inorganic C assimilation and define the regulon controlled by it. Biological CO2 fixation can sustain efforts to reduce its atmospheric concentrations and is fundamental for the light-driven production of chemicals directly from CO2 . Information about the involved regulatory and physiological processes is crucial to engineer cyanobacterial cell factories.


Beta-lactam allergy in Chinese patients and factors predicting genuine allergy.
Beta-lactams (BL) are the most frequently reported drug allergy, but the vast majority of patients are found not to be genuinely allergic after evaluation. Few studies have investigated the clinical predictors of genuine BL allergy, and the prevalence in hospitalized Chinese patients is unknown. Patients admitted to a tertiary hospital in Hong Kong (HK) were analyzed to identify the prevalence and factors associated with the presence of BL allergy labels among hospitalized Chinese patients. A combined cohort of patients having completed allergy investigation for suspected BL allergies in the United Kingdom (UK) and HK were analyzed to identify predictors of genuine allergy. The prevalence of BL allergy labels in hospitalized HK Chinese was 5%, which was associated with female gender and concomitant non-BL antibiotic allergy labels. The rate of genuine BL allergy patients referred for suspected allergies in the UK and HK cohort was only 14%. History of anaphylaxis and interval of less than a year since the index reaction were independent clinical predictors of genuine BL allergy. The negative predictive value of penicillin skin testing was 90%, confirming the need for drug provocation testing after negative skin testing. There was a high rate of confirmed piperacillin-tazobactam allergy. The estimated true prevalence of genuine BL allergy in hospitalized HK Chinese is around 0.5%. This high rate of BL mislabeling highlights the need for comprehensive allergy evaluation and screening. History of anaphylaxis and duration since the index reaction are important predictors of genuine allergy. Piperacillin-tazobactam allergy may pose a unique challenge in this population with a high prevalence of suspected allergies, surging antibiotic resistance, and lack of testing available.


Endothelial progenitor cell sprouting in spheroid cultures is resistant to inhibition by osteoblasts: a model for bone replacement grafts.
Survival of tissue transplants generated in vitro is strongly limited by the slow process of graft vascularization in vivo. A method to enhance graft vascularization is to establish a primitive vascular plexus within the graft prior to transplantation. Endothelial cells (EC) cultured as multicellular spheroids within a collagen matrix form sprouts resembling angiogenesis in vitro. However, osteoblasts integrated into the graft suppress EC sprouting. This inhibition depends on direct cell-cell-interactions and is characteristic of mature ECs isolated from preexisting vessels. In contrast, sprouting of human blood endothelial progenitor cells is not inhibited by osteoblasts, making these cells suitable for tissue engineering of pre-vascularized bone grafts.


cis-[(η5-C5H5)Fe(η1-CO)(μ-CO)]2, the poor relative between cis and trans tautomers. A theoretical study of the gas-phase Fe L3-edge and C and O K-edge XAS of trans-/cis-[(η5-C5H5)Fe(η1-CO)(μ-CO)]2.
The relative stability of trans-[(η5-C5H5)Fe(η1-CO)(μ-CO)]2 (trans-I) and cis-I tautomers in a vacuum and in solvents with different dielectric constants (ε) has been investigated by exploiting density functional theory (DFT). Theoretical results indicate that, in agreement with experimental evidence, trans-I is more stable than cis-I in a vacuum (∼1.5 kcal mol-1; ε = 1), while the opposite is true in media with ε > 7. Differently from solution, DFT outcomes pertaining to the vapor-phase cis-I ⇆ trans-I equilibrium at T = 368 K, the temperature at which the Fe L2,3-edges and the C and O K-edge X-ray absorption spectroscopy (XAS) data of I have been recorded, ultimately indicate the trans-I predominance (∼93%). Compositions, oscillator strengths (f) and excitation energy (EE) values of cis-I transitions substantially mirror those of trans-I; nevertheless, the weighted cis-If(EE) distributions negligibly contribute to the diverse simulated XA spectra of I.


Audit of antibiotic duration of therapy, appropriateness and outcome in patients with nosocomial pneumonia following the removal of an automatic stop-date policy.
Automatic stop-orders (ASOs) have been utilized to discourage inappropriately prolonged antibiotic therapy. An ASO policy, which required reordering of antibiotics after 7 days of therapy, had been in place at our institution prior to 2002, but was revoked after instances of compromised patient care due to inadvertent and inappropriate interruption of antimicrobial treatment. The objective of this study was to evaluate the impact of revoking the ASO policy on the duration of antibiotic therapy, infection-related outcome (cure vs failure), relapsing infection, occurrence of resistant bacteria and superinfection in patients with nosocomial pneumonia. A retrospective chart review of adult patients (≥ 18 years old) admitted to Sunnybrook Health Sciences Centre with nosocomial pneumonia requiring antibiotic therapy was conducted. Duration of antibiotic therapy, infection-related outcome (cure vs failure), rate of relapsing infection, resistant organisms and superinfection were determined for each cohort. Forty-six eligible adults with nosocomial pneumonia per cohort were included [corrected]. Duration of antibiotic therapy was not significantly different in the pre- (11.4 ± 3.8 days) compared with the post-ASO revocation cohort (10.8 ± 4.1 days; p=0.43). There were also no significant differences between the cohorts with regard to infection-related outcome (cure vs failure), relapsing infection, or the occurrence of resistant bacteria or superinfection (p>0.5). Revocation of the ASO policy for antibiotics at our institution was not associated with a longer duration of antibiotic therapy, or increased incidence of infection-related mortality, relapsing infection, resistant bacteria or superinfection for patients with nosocomial pneumonia.


Enhanced BPGM/2,3-DPG pathway activity suppresses glycolysis in hypoxic astrocytes via FIH-1 and TET2.
Bisphosphoglycerate mutase (BPGM) is expressed in human erythrocytes and responsible for the production of 2,3-bisphosphoglycerate (2,3-DPG). However, the expression and role of BPGM in other cells have not been reported. In this work, we found that BPGM was significantly upregulated in astrocytes upon acute hypoxia, and the role of this phenomenon will be clarified in the following report. The mRNA and protein expression levels of BPGM and the content of 2,3-DPG with hypoxia treatment were determined in vitro and in vivo. Furthermore, glycolysis was evaluated upon in hypoxic astrocytes with BPGM knockdown and in normoxic astrocytes with BPGM overexpression or 2,3-DPG treatment. To investigate the mechanism by which BPGM/2,3-DPG regulated glycolysis in hypoxic astrocytes, we detected the expression of HIF-1α, FIH-1 and TET2 with silencing or overexpression of BPGM and 2,3-DPG treatment. The expression of glycolytic genes and the capacity of lactate markedly increased with 6 h, 12 h, 24 h, 36 h and 48 h 1 % O2 hypoxic treatment in astrocytes. The expression of BPGM was upregulated, and the production of 2,3-DPG was accelerated upon hypoxia. Moreover, when BPGM expression was knocked down, glycolysis was promoted in HEB cells. However, overexpression of BPGM and addition of 2,3-DPG to the cellular medium in normoxic cells could downregulate glycolytic genes. Furthermore, HIF-1α and TET2 exhibited higher expression levels and FIH-1 showed a lower expression level upon BPGM silencing, while these changes were reversed under BPGM overexpression and 2,3-DPG treatment. Our study revealed that the BPGM/2,3-DPG pathway presented a suppressive effect on glycolysis in hypoxic astrocytes by negatively regulating HIF-1α and TET2.


The transmembrane protein KpOmpA anchoring the outer membrane of Klebsiella pneumoniae unfolds and refolds in response to tensile load.
In Klebsiella pneumoniae the transmembrane β-barrel forming outer membrane protein KpOmpA mediates adhesion to a wide range of immune effector cells, thereby promoting respiratory tract and urinary infections. As major transmembrane protein OmpA stabilizes Gram-negative bacteria by anchoring their outer membrane to the peptidoglycan layer. Adhesion, osmotic pressure, hydrodynamic flow, and structural deformation apply mechanical stress to the bacterium. This stress can generate tensile load to the peptidoglycan-binding domain (PGBD) of KpOmpA. To investigate how KpOmpA reacts to mechanical stress, we applied a tensile load to the PGBD and observed a detailed unfolding pathway of the transmembrane β-barrel. Each step of the unfolding pathway extended the polypeptide connecting the bacterial outer membrane to the peptidoglycan layer and absorbed mechanical energy. After relieving the tensile load, KpOmpA reversibly refolded back into the membrane. These results suggest that bacteria may reversibly unfold transmembrane proteins in response to mechanical stress.


α-Solanine Isolated From Solanum Tuberosum L. cv Jayoung Abrogates LPS-Induced Inflammatory Responses Via NF-κB Inactivation in RAW 264.7 Macrophages and Endotoxin-Induced Shock Model in Mice.
α-Solanine, a trisaccharide glycoalkaloid, has been reported to possess anti-cancer effects. In this study, we investigated the anti-inflammatory effects of α-solanine isolated from "Jayoung" a dark purple-fleshed potato by examining its in vitro inhibitory effects on inducible nitric-oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines in LPS-induced RAW 264.7 macrophages and its in vivo effects on LPS-induced septic shock in a mouse model. α-Solanine suppressed the expression of iNOS and COX-2 both at protein and mRNA levels and consequently inhibited nitric oxide (NO) and prostaglandin E2 (PGE2 ) production in LPS-induced RAW 264.7 macrophages. α-Solanine also reduced the production and mRNA expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced by LPS. Furthermore, molecular mechanism studies indicated that α-solanine inhibited LPS-induced activation of nuclear factor-κB (NF-κB) by reducing nuclear translocation of p65, degradation of inhibitory κBα (IκBα), and phosphorylation of IκB kinaseα/β (IKKα/β). In an in vivo experiment of LPS-induced endotoxemia, treatment with α-solanine suppressed mRNA expressions of iNOS, COX-2, IL-6, TNF-α, and IL-1β, and the activation of NF-κB in liver. Importantly, α-solanine increased the survival rate of mice in LPS-induced endotoxemia and polymicrobial sepsis models. Taken together, our data suggest that the α-solanine may be a promising therapeutic against inflammatory diseases by inhibiting the NF-κB signaling pathway. J. Cell. Biochem. 117: 2327-2339, 2016. © 2016 Wiley Periodicals, Inc.


Effects of solution chemistry on conformation of self-aggregated tannic acid revealed by laser light scattering.
Inorganic soil solution constituents can alter the charge, size, and conformation of dissolved organic molecules, thus affecting their environmental behavior. Here, we investigated how pH, cation valence and activities induce conformational changes and aggregation-sedimentation reactions of organic polyelectrolytes. For that we determined the hydrodynamic diameter of the model compound tannic acid by laser light scattering at concentrations of 1-30 g L-1 in the pH range from 3 to 10 and with electrolyte additions of CaCl2 and hydroxyl-Al cations. Charge properties were quantified by polyelectrolyte titration and zeta potential measurements. After dispersion by sonication, aggregation was determined in time sequences up to 60 min and suspension stability was traced in sedimentation experiments. Tannic acid was present in ultrapure water in a self-aggregated state. At pH <3 as well as >7.5, its hydrodynamic diameter increased. Whereas at high pH this behavior could be assigned to unfolding of molecular conformations, at low pH it is likely that charge neutralization decreased repulsive forces and facilitated aggregation. At pH 5 and ionic strengths of up to 5 mM, CaCl2 did not affect aggregation state of tannic acid and results resembled those obtained in ultrapure water. Addition of hydroxyl-Al cations broke-up the self-aggregated tannic acid structures under formation of Al-organic coprecipitates. Strong aggregation only occurred at mixing ratios where opposite surface charges were completely balanced. Under natural conditions, self-aggregation of tannic acid can be expected only at higher solution concentrations. However, at acidic pH, hydroxyl-Al cations and tannic acid may form discrete colloidal particles already at low tannic acid concentrations, resulting in the destabilization of suspensions. Our data emphasize that the soil solution composition strongly modifies the physical state of tannic acid, and likely also of other biopolymers, and thus their interactions within environmental matrices.


Vocal Fold Insufficiency: How Effective is Injection Laryngoplasty? Short Term Clinical Outcomes.
Office based Injection Laryngoplasty has become a common and feasible method of addressing vocal fold insufficiency (VFI) resulting from a plethora of aetiologies. Contemporary to various injectates, Calcium Hydroxylapatite has met with great success across usage with various techniques. But, irrespective of the technique and injectate material, the burning question in mind of "realistic" clientele remains, "How soon will I have by voice back?". Aim of this study is to evaluate the short term (3 months postoperative) effects of Injection Laryngoplasty in cases of VFI using Calcium Hydroxylapatite via trans cricothyroid route, in terms of both objective and subjective parameters. 12 patients with mean age of 35.67 years underwent vocal fold injections (via transnasal flexible fibreoptic laryngoscopic guided trans-cricothyroid membrane approach using CaHA) for VFI. The pre injection and 1, 2- and 3-months post injection scores' changes in outcome measures in form of videostroboscopic parameters, Voice Handicap Index scores and acoustic analysis were compiled and analysed. 91.6% of patients showed statistically significant benefit after 3 months post injection. 0.1% patients showed loss of benefit of the CaHA material even 3 months post injection. Average length of benefit was 1-month post injection. No significant complication was observed in any patient. We conclude that the objective evidence of structural and functional improvement may be seen immediately post injection laryngoplasty, minimum of 3 months is required for evident improvement in patient's perception of his own voice in terms of Quality of Life parameters.


Central injection in rats of alpha-melanocyte-stimulating hormone analog: effects on food intake and brain Fos.
Lateral cerebroventricular (LCVT) administration of the alpha-MSH agonist analog Nle4DPhe7alpha-MSH (NDP-MSH) inhibited food intake in food-deprived rats, but did not inhibit water intake in water-deprived rats. When NDP-MSH was administered into the fourth ventricle (4CVT), comparable suppressions of food intake were observed. LCVT and 4CVT administration of NDP-MSH also reduced spontaneous 24 h food intake. LCVT injection of NDP-MSH greatly attenuated food intake stimulated in sated rats by acute CVT administration of neuropeptide Y (NPY). These and other data suggest that alpha-MSH is an important endogenous regulator of food intake, possibly acting downstream of NPY. In an attempt to assess further the sites of action of NDP-MSH, a qualitative mapping study of Fos-like immunoreactive (Fos-ir) neurons was performed following LCVT administration of NDP-MSH. LCVT injection of NDP-MSH induced Fos-ir in several forebrain regions including cortex, striatum, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and arcuate nucleus. The combination of NPY and NDP-MSH did not produce obvious antagonism or cancellation of effects in any region examined. Thus, the site(s) of action of NDP-MSH on food intake remain to be clarified.


Randomized double-blinded comparison of three intravenous immunoglobulin products in bone marrow transplantation.
We have used samples from the in vivo situation to compare antibody levels provided by the infusion of different IVIG products, a measure, albeit indirect, of potential therapeutic efficacy. The further correlation of in vivo antibody titers with functional activities of these antibodies (eg, opsonization and viral neutralization) would provide additive valuable information about the usefulness of this therapy.


New N-benzhydrylpiperazine/1,3,4-oxadiazoles conjugates inhibit the proliferation, migration, and induce apoptosis in HeLa cancer cells via oxidative stress-mediated mitochondrial pathway.
N-benzhydrylpiperazine and 1,3,4-oxadiazoles are pharmacologically active scaffolds which exhibits significant inhibitory growth effects against various cancer cells, however, antiproliferation effects and the underlying mechanism for inducing apoptosis for aforementioned scaffolds addressing HeLa cancer cells remains uncertain. In this study, N-benzhydrylpiperazine clubbed with 1,3,4-oxadiazoles (4a-4h) were synthesized, subsequently characterized using high resolution spectroscopic techniques and eventually evaluated for their antiproliferation potential by inducing apoptosis in HeLa cancer cells. The MTT assay screening results revealed that among all, compound 4d ( N-benzhydryl-4-((5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)methyl)piperazine) in particular, exhibited IC 50 value of 28.13 ± 0.21 μg/mL and significantly inhibited the proliferation of HeLa cancer cells in concentration-dependent manner. The in vitro anticancer assays for treated HeLa cells resulted in alterations in the cell morphology, reduction in colony formation, and inhibition of cell migration in concentration-dependent treatment. Furthermore, G2/M phase arrest, variations in the nuclear morphology, degradation of chromosomal DNA confirmed the ongoing apoptosis in treated HeLa cells. Increase in the expression of cytochrome C and caspase-3 confirmed the involvement of intrinsic mitochondrial pathway regulating the cell death. Also, elevation in reactive oxygen species level and loss of mitochondrial membrane potential signified that compound 4d induced apoptosis in HeLa cells by generating the oxidative stress. Therefore, compound 4d may act as a potent chemotherapeutic agent against human cervical cancer.


Plagiarism among nursing students: A systematic review and meta-analysis.
To summarize the findings from literature regarding the prevalence of plagiarism and its various types, knowledge, and attitudes of students toward plagiarism, factors associated with plagiarism, and the applied interventions to decrease the incidence of plagiarism. Plagiarism is a major form of academic dishonesty practiced by students at all educational levels. Academic dishonesty was defined as any unauthorized help that adds to students' formal academic performance. These dishonest behaviors can be categorized as falsifying information, hiding errors, collaborating with colleagues when not allowed, and plagiarism. Systematic search of databases was conducted in September 2021 to identify studies that discussed plagiarism in nursing studies. We included 31 studies in this systematic review and meta-analysis, with a total of 9,175 nursing students. The analysis was conducted using RevMan software. Plagiarism was the most frequent academic misconduct among nursing students (practiced by 55.3%). Paraphrasing without referencing was the most practiced form (39.53%), while submitting others' work without acknowledgment was the least one (9.61%). Most students were aware of the concept of plagiarism (80.8%) and had positive ethical attitudes toward it (88.26%). Plagiarism was negatively associated with age, parenting, and completing semester credits. However, it was positively correlated with average grades and liberal educators. Plagiarism was a significant predictor of clinical misconduct. A gap in the students' knowledge and skills were noticed. These gaps may be contributing to the high occurrence of plagiaristic acts, besides the unethical attitudes. Plagiarism is a serious academic misconduct practice that can be associated with subsequent clinical misconduct. There is a need to fill the knowledge and skills gap, and to set effective policies. In their attempts to eliminate plagiarism, nurse educators are encouraged to provide effective educational training and practical tasks, in order to fill the gaps in knowledge and skills. Additionally, implementing clear and effective punishment policies would prevent intentional plagiaristic acts. This would aid in introducing qualified nurses accountable for the health of patients.


Parkinson's disease: sensory and motor problems in arms and hands.
Fifteen undemented patients with Parkinson's disease (PD) and 15 age-matched controls were given a battery of tests to assess sensorimotor integration in the arms. PD patients made more errors (p less than 0.01) than controls, particularly in tests of proprioception. Age was not related to errors. Compared with controls, two-point discrimination thresholds were significantly higher (p less than 0.02) on the index finger of PD patients, but not on the forearm. Results confirm the sensorimotor deficits found earlier in an orofacial study, and imply that PD involves a generalized dysfunction of sensorimotor integration and proprioception, probably a result of impaired basal ganglia function in processing and integrating sensory input to organize and guide movement.


Leptin Receptor Mediates Bmal1 Regulation of Estrogen Synthesis in Granulosa Cells.
Chronobiology affects female fertility in mammals. Lepr is required for leptin regulation of female reproduction. The presence of E-box elements in the Lepr promoter that are recognized and bound by clock genes to initiate gene transcription suggested that circadian systems might regulate fertility through Lepr. However, it is unclear whether Bmal1, a key oscillator controlling other clock genes, is involved in leptin regulation in hormone synthesis through Lepr. In this study, serum estradiol (E2) concentration and the expressions of Bmal1, Lepr, Cyp19a1, and Cyp11a1 genes were found to display well-synchronized circadian rhythms. Knockdown of Bmal1 significantly reduced expression levels of Lepr, Fshr, and Cyp19a1 genes; protein production of Bmal1, Lepr, and Cyp19a1; and the E2 concentration in granulosa cells. Knockdown of Lepr reduced the expression levels of Cyp19a1 and Cyp11a1 genes and Cyp19a1 protein, and also reduced E2 concentration. Addition of leptin affected the expression of Cyp19a1, Cyp11a1, and Fshr genes. Bmal1 deficiency counteracted leptin-stimulated upregulation of the genes encoding E2 synthesis in granulosa cells. These results demonstrated that Bmal1 participates in the process by which leptin acts on Lepr to regulate E2 synthesis.


Tungiasis: a neglected epidermal parasitic skin disease of marginalized populations--a call for global science and policy.
Tungiasis (sand flea disease) is an ectoparasitic skin disease caused by the female sand flea/jigger flea (Tunga penetrans). As poverty is the major driving force of the disease, it can be called as a poverty-associated plague. It is one of the emerging neglected diseases in Latin America, Caribbean, sub-Saharan Africa, and India. The aim of the present scrutiny was to assess the public health impact of tungiasis, associated risk factors, and emerging opportunities to prevent and control tungiasis. Searches of PubMed, Google Scholar, and online search engines (Google, AOL, and Yahoo) using keywords "parasitic skin disease," "tungiasis," "sand flea," " tungiasis-associated risk factors," "tungiasis prevention and control," and their synonyms were used as a source of references. Searches were made without time limitations. Of 167 potential articles identified by these criteria, 51 appropriate were selected for review. Tungiasis is widespread in the resource-constrained settings of low-income economies. In the tropics, it is highly prevalent among the impoverished populations, but the associated risk factors are often poorly identified and remain uncontrolled. Though it is a self-limiting disease with considerable morbidity, the parasite may cause subsequent secondary morbidity through life-threatening complications and infections like cellulitis, tetanus, and death. However, the direct and indirect sociocultural, economic, and health impact of tungiasis is often undervalued and misunderstood. A systematic assessment on disease burden is still dearth and deficient. Over the decades, tungiasis has been largely neglected by the scientific community, policy makers, and healthcare stakeholders. In the endemic regions, even tungiasis is not listed for the disease control priorities in the regional, national, and international agenda. The majority of the epidermal parasitic skin diseases particularly tungiasis needs a sustainable global scientific research and control policy. This urges intensive efforts to develop a road map that delivers a clear vision towards zero new infection by designing low-cost prevention and control strategies. Besides, there is an urgency to develop culturally appropriate communication techniques and workable collaboration on a global scale by bringing all the stakeholders of endemic countries.


Effectiveness of collagen and gatifloxacin in improving the healing and antibacterial activities of gellan gum hydrogel films as dressing materials.
The demand for advanced wound care products is rapidly increasing nowadays. In this study, gellan gum/collagen (GG/C) hydrogel films containing gatifloxacin (GAT) were developed to investigate their properties as wound dressing materials. ATR-FTIR, swelling, water content, water vapor transmission rate (WVTR), and thermal properties were investigated. The mechanical properties of the materials were tested in dry and wet conditions to understand the performance of the materials after exposure to wound exudate. Drug release by Franz diffusion was measured with all samples showing 100 % cumulative drug release after 40 min. Strong antibacterial activities against Staphylococcus aureus and Staphylococcus epidermis were observed for Gram-positive bacteria, while Escherichia coli and Pseudomonas aeruginosa were observed for Gram-negative bacteria. The in-vivo cytotoxicity of GG/C-GAT was assessed by wound contraction in rats, which was 95 % for GG/C-GAT01. Hematoxylin and eosin and Masson's trichrome staining revealed the appearance of fresh full epidermis and granulation tissue, indicating that all wounds had passed through the proliferation phase. The results demonstrate the promising properties of the materials to be used as dressing materials.


Titers and breadth of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: A single-blinded, randomized clinical trial.
We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. HCW who had at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2 (30 μg), half-dose mRNA-1273 (50 μg), mRNA-1273 (100 μg), and MVC-COV1901 (15 μg). The primary outcomes were humoral and cellular immunogenicity and secondary outcomes assessed safety and reactogenicity at 28 days post-booster. MVC-COV1901 Three hundred and forty HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. The fold-rise of anti-spike IgG geometric mean titer was 8.4 (95% CI 6.8-10.4) for MVC-COV1901, 32.2 (27.2-38.1) for BNT162b2, 47.6 (40.8-55.6) for half-dose mRNA-1273 and 63.2 (53.6-74.6) for mRNA-1273. The live virus microneutralization assays (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron BA.1 variant were 6.4 to 13.5 times lower than those against the wild type. All booster vaccines induced a comparable T cell response. Third dose booster not only increases neutralizing antibody titer but also enhances antibody breadth against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those who received primary series of ChAdOx1 nCov-19.


Comparison of media for dissemination of information about cancer in rural communities.
A study was done in Orangeburg County, South Carolina, to compare the effectiveness of the various mass media--television, radio, and newspaper--for the dissemination of educational material about cancer. Effectiveness of these media in reaching certain subpopulations defined by race, sex, income, and population density was also examined. The newspaper was found to be generally more effective than other media. This superiority held for almost all subpopulations. Furthermore, it was found that certain subpopulations differed from others in the extent to which they were reached by a particular medium.


Chronic congestive heart failure is associated with a phenotypic shift of intramyocardial endothelial cells.
There is evidence that patients with chronic congestive heart failure have endothelial cell-related abnormalities of the peripheral circulation and the coronary microvasculature. For that reason, we have studied the phenotypic expression of endothelial cells in hearts of patients with congestive heart failure. We studied cardiac explants (n = 19) and autopsy hearts (n = 5) of patients with chronic congestive heart failure caused by either a dilated cardiomyopathy (n = 12) or ischemic heart disease (n = 12) and compared them with normal hearts (n = 12). The antigenic expression obtained with several endothelial cell markers (factor VIII-related antigen, EN-4, Ulex europaeus agglutinin-1 (UEA-1), PAL-E, endoglin, and endothelin) and adhesion molecules (intercellular adhesion molecule [ICAM], vascular cell adhesion molecule [VCAM], or E-selectin) was compared by use of immunohistochemical techniques. On the basis of the initial findings, the number of PAL-E- and EN-4-positive vessels was counted. The incidence of PAL-E-positive vessels per area was quantified and related to the percentage of heart muscle cells and the total number of vessels per area. In control hearts, endothelial cells rarely were positive for PAL-E. In hearts of patients with ischemic cardiomyopathies, there was distinct staining with this marker. Hearts of patients with dilated cardiomyopathies showed a marked increase in the number of PAL-E-positive endothelial cells. Vessels with a muscular media were PAL-E-negative. Two-sample analysis revealed a statistically significant difference between hearts with dilated cardiomyopathies and ischemic cardiomyopathies (P < .01), between hearts with dilated cardiomyopathies and control hearts (P < .01), and between hearts with ischemic cardiomyopathies and control hearts (P < .01). Endoglin and ICAM were positive but nondiscriminating. Endothelin, VCAM, and E-selectin were negative. A phenotypic shift in endothelial antigen expression of the coronary microvasculature occurs in both ischemic hearts and hearts with dilated cardiomyopathies, as revealed by PAL-E, compared with control hearts. The change may relate to compensatory mechanisms in long-standing chronic heart failure.


Heavy metals detection at chemometrics-powered electrochemical (bio)sensors.
Heavy metals represent a serious issue regarding both environmental and health status. Their monitoring is necessary and it is necessary the development of decentralized approaches that are able to enforce the risk assessment. Electrochemical sensors and biosensors, with the various architectures, represent a solid reality often involved for this type of analytical determination. Although these approaches offer easy-to-use and portable tools, some limitations are often highlighted in presence of multi-targets and/or real matrices. However, chemometrics- and artificial intelligence-based tools, both for designing and for data analyzing, display the capability in producing novel functionality towards the management of complex matrices which often contain more information than those that are visualized with sensor detection. Design of experiment, exploratory, predictive and regression analysis can push the world of electrochemical (bio)sensors beyond the state of the art, because is still too large the number of analytical chemists that do not deal with multivariate thinking. In this paper, the use of multivariate methods applied to electrochemical sensing of heavy metals is showed, and each approach is described in terms of efficacy and outputs.


Hemopericardium from right atrial laceration in a newborn.
We report the case of a newborn who suffered right atrial laceration during delivery. To our knowledge, there has been no previous report of blunt injury causing right atrial laceration with hemopericardium complicated by cardiac tamponade in the perinatal period.


Antioxidant potential of natural and synthesised polyprenylated hydroquinones.
The metabolites 2-octaprenyl-1,4-hydroquinone (1) and 2-(24-hydroxy)-octaprenyl-1,4-hydroquinone (2), isolated from the sponge Ircinia spinosula, along with a series of synthetic derivatives, were evaluated for their antioxidant capacity, in order to establish a potential relationship between structural characteristics and antioxidant activity. The antioxidant potential of both natural and synthesised compounds was evaluated in vitro by their ability: (1) to interact with the stable free 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and (2) to inhibit the peroxidation, induced by the Fe(++)/ascorbate system, of heat inactivated hepatic microsomal membrane lipids. Metabolite 1 presented a strong interaction with DPPH and had a moderate effect on lipid peroxidation, while metabolite 2 interacted extensively with DPPH and exhibited a significant effect against lipid peroxidation. All derivatives retaining the free 1,4-hydroquinone system maintained fully or partly the free radical scavenging capacity.


The alpha-helix folds more rapidly at the C-terminus than at the N-terminus.
The helix-coil dynamics of different sections of an alpha-helical model peptide were observed separately by nanosecond temperature jump experiments with IR detection on a series of isotopically labeled peptides. The results show that the helix-coil dynamics of the alpha-helical C-terminus are faster than those of the N-terminus.


Risk of not being discharged home after isolated coronary artery bypass graft operations.
The age and risk profile of patients undergoing isolated coronary artery bypass grafting (CABG) is increasing, which will likely increase the proportion of CABG patients discharged to nursing homes, rehabilitation, or long-term care. Because discharge disposition can be important to a patient's treatment goals, developing and using predictive tools will improve informed treatment decision making. We examined the utility of The Society of Thoracic Surgeons (STS) risk of mortality score in predicting discharge disposition after CABG. From January 1, 2004 to October 31, 2011, 5,119 patients underwent isolated CABG at The Heart Hospital Baylor Plano or Baylor University Medical Center (Texas) and were discharged alive. The association between STS risk of mortality and discharge to nursing home, rehabilitation, or long-term care was assessed using multivariable logistic regression, adjusted for age, body surface area, marital status, site, and year of operation. At discharge, 216 patients (4.21%) went to nursing homes, 153 (2.99%) to rehabilitation, and 115 (2.25%) to long-term care. The STS risk of mortality score was significantly positively associated with discharge status (p < 0.001). Patients with 1%, 2%, 3%, 4%, and 5% STS risk of mortality had 11.25%, 22.10%, 29.45%, 35.00%, and 38.50% probability, respectively, of not being discharged home. When the STS risk of mortality was 5%, the risk of not being discharged home was 47.9% for off-pump patients and 38.10% for on-pump patients. STS risk score is strongly associated with CABG discharge status. Patients with a risk score exceeding 2 are at high risk (>22%) of not being discharged home. This risk should be discussed when treatment decisions are being made.


Apoptosis Induction by ZnFe2O4-Ag Biosynthesized by Chlorella vulgaris in MCF-7 Breast Cancer Cell Line.
The incidence and mortality of breast cancer are growing which indicates the inefficiency of the current chemotherapy drugs. Due to the anticancer potential of Zn and Ag and the magnetic feature of iron oxide, in this work, we synthesized ZnFe2O4-Ag nanocomposite using Chlorella vulgaris and investigated its anticancer effect on breast cancer cell line. Physicochemical characterization was performed by FT-IR, XRD, SEM, TEM, VSM, EDS mapping, UV, and zeta potential assays. Cell cytotoxicity and apoptosis frequency were studied by the MTT and flow cytometry assays. Also, cell cycle analysis, Hoechst staining, and measuring ROS (reactive oxygen species) level were performed. The synthesized particles were almost spherical with a size range of 14-52 nm. The FT-IR and XRD assays confirmed the proper synthesis of the particles and VSM analysis showed that particles had magnetic property and the maximum saturation magnetization was 0.8 Emu/g. Also, the EDS mapping of the nanocomposite showed the Zn, Fe, O, and Ag elements. The MTT assay showed that the 50% inhibitory concentration (IC50) of ZnFe2O4-Ag for breast cancer and normal cells were 28 and 154 µg/mL, respectively, and the nanocomposite had stronger anticancer activity than cisplatin (IC50 = 84 µg/mL). Flow cytometry analysis showed that the exposure to the nanocomposite induced cell apoptosis by 77.5% and significantly induced ROS generation. Also, treating breast cancer cells with the nanocomposite induced cell cycle arrest and apoptotic features, including chromatin condensation and fragmentation. In conclusion, ZnFe2O4-Ag nanocomposite synthesized by C. vulgaris could suppress the proliferation of breast cancer cells by the generation of oxidative stress, apoptosis induction, and cell cycle arrest.


Patient-delivered partner therapy for chlamydial infections: practices, attitudes, and knowledge of california family planning providers.
Treatment of sex partners is a core strategy for the control of chlamydia. Innovations such as patient-delivered partner therapy (PDPT) are effective in preventing repeat chlamydial infections, but providers' practice and perceptions of PDPT have not been adequately evaluated. This evaluation describes family planning providers' practices, knowledge, attitudes, and barriers regarding PDPT and assesses factors associated with routine use. A cross-sectional, self-administered, Internet-based survey of a convenience sample of family planning providers in California was conducted in 2007. Multivariate logistic regression was used to determine predictors associated with routine PDPT use. Of the 286 respondents, 73% reported routinely using PDPT for chlamydia and 77% provided medication to clients for their partner(s). Providers were more likely to offer PDPT for female versus male clients (73% vs. 53%, P < 0.0001). More than 90% agreed that PDPT helped provide better care for clients, was well-received, and protected against reinfection. Common concerns about PDPT included missed counseling opportunities (51%) and incomplete care for partners (42%). Over one-third (41%) identified lack of reimbursement for PDPT as an important barrier to routine use. Independent predictors of routine PDPT use included affiliation with an agency that received free prepackaged single-dose medication for on-site PDPT dispensing (adjusted odds ratio = 2.66, 95% confidence interval: 1.39-5.10) and support of the clinic's medical director (adjusted odds ratio = 4.85, 95% confidence interval: 1.57-14.96). A majority of providers in this sample reported routinely using PDPT for chlamydia-infected clients; provision of prepackaged medication to clinics facilitated use of PDPT.


Mycobacterium W. - An unusual side effect.
To present an interesting case of unusual side effect of Mycobacterium W. in an adult COVID 19 positive male and discuss its assessment and management. - DESIGN: Case Report. Tertiary care hospital. One. 70 years male was admitted with complaints of fever, persistent dry cough since 10-12 days and progressive breathlessness since 3-4 days. Patient was found COVID-19 RTPCR positive and is known case of Type-II Diabetes with CAD (Post PTCA). Patient was managed conservatively with Oxygen support, I/V antibiotics, I/V Steroids, oral Favipiravir and other supportive treatment. Patient was also given injection Mycobacterium W. in dose of 0.3 ml per day intradermally at 3 different sites (both deltoids) consecutively for three days. 7-8 days after administration, patient developed bright red pustules which later got converted into small punched out ulcerations on all nine local sites of administration, which were managed conservatively with oral analgesics and local steroids for 8-10 days which healed without any scar formation. Injection Mycobacterium W. is used in COVID 19 patients as an immunomodulator agent and has been proved to be safe in most of the cases but we encountered this unusual side effect of bright red pustules formation at all nine local sites of injection in our case most likely because of being administered subcutaneously instead of intradermally, making this an interesting case which is being reported to scientific fraternity.


UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor.
BiP is a major endoplasmic reticulum (ER) chaperone and is suggested to act as primary sensor in the activation of the unfolded protein response (UPR). How BiP operates as a molecular chaperone and as an ER stress sensor is unknown. Here, by reconstituting components of human UPR, ER stress and BiP chaperone systems, we discover that the interaction of BiP with the luminal domains of UPR proteins IRE1 and PERK switch BiP from its chaperone cycle into an ER stress sensor cycle by preventing the binding of its co-chaperones, with loss of ATPase stimulation. Furthermore, misfolded protein-dependent dissociation of BiP from IRE1 is primed by ATP but not ADP. Our data elucidate a previously unidentified mechanistic cycle of BiP function that explains its ability to act as an Hsp70 chaperone and ER stress sensor.


Proliferation control of mammalian cells by the tumor suppressor IRF-1.
We have attempted to establish a system in which cell proliferation is controlled by a physiological regulator. Interferon regulatory factor 1 (IRF-1) is a transcription factor that recognizes a sequence which is present in the interferon-β promoter as well as in the promoters of interferon-inducible genes. IRF-1 acts as a tumor suppressor. Constitutive overexpression of recombinant IRF-1 leads to inhibition of cell growth. The extent of this growth arrest depends on the intracellular concentration of IRF-1. In order to allow IRF-1 expression in various mammalian cells we have established two different systems for conditional IRF-1 transcription and activation, respectively. In one case, an inducible promoter, in the other case a fusion protein composed of IRF-1 and the hormone-binding domain of the human estrogen receptor was used. Both systems allow to control gradually the growth of mammalian cell lines by adjusting the intracellular concentration of IRF-1 via estradiol or tetracycline in the medium. Despite the activity of IRF-1 as an antiproliferative agent the expression of certain proteins is retained. Moreover, expression of genes which are controlled by IRF-1 responsive promoters is enhanced.


Mitochondrial DNA-targeted therapy: A novel approach to combat cancer.
Mitochondrial DNA (mtDNA) encodes proteins and RNAs that are essential for mitochondrial function and cellular homeostasis, and participates in important processes of cellular bioenergetics and metabolism. Alterations in mtDNA are associated with various diseases, especially cancers, and are considered as biomarkers for some types of tumors. Moreover, mtDNA alterations have been found to affect the proliferation, progression and metastasis of cancer cells, as well as their interactions with the immune system and the tumor microenvironment (TME). The important role of mtDNA in cancer development makes it a significant target for cancer treatment. In recent years, many novel therapeutic methods targeting mtDNA have emerged. In this study, we first discussed how cancerogenesis is triggered by mtDNA mutations, including alterations in gene copy number, aberrant gene expression and epigenetic modifications. Then, we described in detail the mechanisms underlying the interactions between mtDNA and the extramitochondrial environment, which are crucial for understanding the efficacy and safety of mtDNA-targeted therapy. Next, we provided a comprehensive overview of the recent progress in cancer therapy strategies that target mtDNA. We classified them into two categories based on their mechanisms of action: indirect and direct targeting strategies. Indirect targeting strategies aimed to induce mtDNA damage and dysfunction by modulating pathways that are involved in mtDNA stability and integrity, while direct targeting strategies utilized molecules that can selectively bind to or cleave mtDNA to achieve the therapeutic efficacy. This study highlights the importance of mtDNA-targeted therapy in cancer treatment, and will provide insights for future research and development of targeted drugs and therapeutic strategies.


56K fibroblast protein not specific for Duchenne muscular dystrophy but for skin biopsy site.
Recently, we reported the detection by two-dimensional gel electrophoresis of a 56,000 (56K)-molecular weight polypeptide that was present in cultured skin fibroblasts from normal males but was not detectable in fibroblasts from Duchenne muscular dystrophy (DMD) patients. Since then we have established that the 56K polypeptide is not present in skin fibroblasts from normal females, DMD carrier females, or in normal male fibroblasts obtained from sources other than the Repository for Mutant Human Cell Strains, Montreal. Further inquiry has led to the discovery that all the normal male fibroblast cultures obtained from the Montreal repository had been established from preputial skin. Fibroblast cultures from DMD patients, DMD carriers, as well as other normal individuals, had been derived from non-genital skin biopsies. Thus, the absence of the 56K polypeptide is not specific for DMD, but rather is related to the site of skin biopsy.


Association of peptidyl prolyl cis/trans isomerase Rrd1 with C terminal domain of RNA polymerase II.
The largest subunit of RNAPII extends as the conserved unstructured heptapeptide consensus repeats Y1S2P3T4S5P6S7 and their posttranslational modification, especially the phosphorylation state at Ser2, Ser5 and Ser7 of CTD recruits different transcription factors involved in transcription. In the current study, fluorescence anisotropy, pull down assay and molecular dynamics simulation studies employed to conclude that peptidyl-prolyl cis/trans-isomerase Rrd1 has strong affinity for unphosphorylated CTD rather than phosphorylated CTD for mRNA transcription. Rrd1 preferentially interacts with unphosphorylated GST-CTD in comparison to hyperphosphorylated GST-CTD in vitro. Fluorescence anisotropy revealed that recombinant Rrd1 prefers to bind unphosphorylated CTD peptide in comparison to phosphorylated CTD peptide. In computational studies, the RMSD of Rrd1-unphosphorylated CTD complex was greater than the RMSD of Rrd1-pCTD complex. During 50 ns MD simulation run Rrd1-pCTD complex get dissociated twice viz. 20 ns to 30 ns and 40 ns to 50 ns, while Rrd1-unpCTD complex remain stable throughout the process. Additionally, the Rrd1-unphosphorylated CTD complexes acquire comparatively higher number of H-bonds, water bridges and hydrophobic interactions occupancy than Rrd1-pCTD complex, concludes that the Rrd1 interacts more strongly with the unphosphorylated CTD than the pCTD.


Influence of hydrological parameters on hydroxylated tetraether lipids in a deep Lake Fuxian, China: Implications for their use as environmental proxies.
Hydroxylated isoprenoid glycerol dialkyl glycerol tetraethers (OH-GDGTs) have shown their potential in environmental reconstructions. However, the unclear underlying mechanism challenges their application. To elucidate the effects of water parameters on OH-GDGT-derived indices and understand their environmental implications, we investigated the core OH-GDGTs of suspended particulate matter (SPM) from water columns in a year cycle and surface sediments at different water depths along a nearshore-offshore transect in Lake Fuxian, a deep and large lake in southwestern China. OH-GDGTs were primarily found in the hypolimnion and were produced in situ by Group I.1a Thaumarchaeota. The relative abundance of OH-GDGTs (%OH-GDGTs) and ring indices (RI-OH and RI-OH') in the hypolimnion were significantly influenced by dissolved oxygen (DO) and pH, particularly DO, which regulated the inverse physiological functions of the hydroxyl and cyclopentane moieties of archaea. %OH-GDGTs values in SPM were positively correlated with DO and negatively correlated with pH levels, while RI-OH values exhibited an inverse relationship with DO and positive correlation with pH levels. OH-GDGTs in surface sediments appeared to be homologous to that of water columns, indicating that their inferred proxies could be regulated by the configuration of water parameters. The sedimentary %OH-GDGTs values increased as the RI-OH values decreased with water depth along the transect from the lakeshore to the lake center, suggesting their potential as lake-level proxies.


Behavioral and biochemical investigations of bupropion metabolites.
The stimulus effects of bupropion metabolites were examined in a drug discrimination procedure using (-)nicotine- and (+)amphetamine-trained rats. (+)- and (-)threohydrobupropion partially substituted in each group. R,R-hydroxybupropion produced vehicle-appropriate responding in (-)nicotine animals but, when given in combination with the training dose of (-)nicotine, resulted in an attenuated effect. S,S-Hydroxybupropion partially (66%) substituted for (-)nicotine. In (+)amphetamine-trained animals, S,S-hydroxybupropion (ED50=4.4 mg/kg) generalized completely and was similar in potency to bupropion (ED50=5.4 mg/kg). Bupropion and its metabolites lacked affinity for nicotinic acetylcholinergic receptors, but all antagonized (-)nicotine-induced 86Rb+ efflux in cells expressing alpha3beta4 nicotinic cholinergic receptors. S,S-Hydroxybupropion possessed affinity at the dopamine transporter comparable to bupropion, and was also found to bind at the norepinephrine transporter. Although it is unlikely that any metabolite isomer is chiefly responsible for the stimulus actions of bupropion, some probably play a role in the complex actions of this agent.


The ionic strength dependence of the cooperativity factor for DNA melting.
The melting temperature for the d(AT)24.d(AT)24 stretch, located inside the DNA helix and terminally, have been determined in a wide range of ionic strength values (0.01 - 1 M Na+). The cooperativity factor was calculated from the shifts in the melting temperature of the stretch due to its different boundary conditions. With the sodium concentration decreasing from 1 M to 0.01 M the cooperativity factor dropped by three orders of magnitude, its change being less marked at high than at low ionic strength.


Proteolytic activation of proapoptotic kinase protein kinase Cδ by tumor necrosis factor α death receptor signaling in dopaminergic neurons during neuroinflammation.
The mechanisms of progressive dopaminergic neuronal loss in Parkinson's disease (PD) remain poorly understood, largely due to the complex etiology and multifactorial nature of disease pathogenesis. Several lines of evidence from human studies and experimental models over the last decade have identified neuroinflammation as a potential pathophysiological mechanism contributing to disease progression. Tumor necrosis factor α (TNF) has recently emerged as the primary neuroinflammatory mediator that can elicit dopaminergic cell death in PD. However, the signaling pathways by which TNF mediates dopaminergic cell death have not been completely elucidated. In this study we used a dopaminergic neuronal cell model and recombinant TNF to characterize intracellular signaling pathways activated during TNF-induced dopaminergic neurotoxicity. Etanercept and neutralizing antibodies to tumor necrosis factor receptor 1 (TNFR1) were used to block TNF signaling. We confirmed the results from our mechanistic studies in primary embryonic mesencephalic cultures and in vivo using the stereotaxic lipopolysaccharide (LPS) model of nigral dopaminergic degeneration. TNF signaling in dopaminergic neuronal cells triggered the activation of protein kinase Cδ (PKCδ), an isoform of the novel PKC family, by caspase-3 and caspase-8 dependent proteolytic cleavage. Both TNFR1 neutralizing antibodies and the soluble TNF receptor Etanercept blocked TNF-induced PKCδ proteolytic activation. Proteolytic activation of PKCδ was accompanied by translocation of the kinase to the nucleus. Notably, inhibition of PKCδ signaling by small interfering (si)RNA or overexpression of a PKCδ cleavage-resistant mutant protected against TNF-induced dopaminergic neuronal cell death. Further, primary dopaminergic neurons obtained from PKCδ knockout (-/-) mice were resistant to TNF toxicity. The proteolytic activation of PKCδ in the mouse substantia nigra in the neuroinflammatory LPS model was also observed. Collectively, these results identify proteolytic activation of PKCδ proapoptotic signaling as a key downstream effector of dopaminergic cell death induced by TNF. These findings also provide a rationale for therapeutically targeting PKCδ to mitigate progressive dopaminergic degeneration resulting from chronic neuroinflammatory processes.


The SMC family: from chromosome condensation to dosage compensation.
Recent genetic analyses in yeasts and biochemical studies in vertebrate cells have led to the discovery of a family of putative ATPases that play a fundamental role in chromosome condensation and segregation in mitosis. One of the members was also found to be involved in dosage compensation in Caenorhabditis elegans, providing a new link between global regulation of gene expression and chromosome structure. This unique family of proteins may control higher-order chromosome dynamics by regulated self-assembly or mechanochemical activity.


Regional cerebral blood flow of acute carbon monoxide poisoning in cats.
The mechanism of selective vulnerability of the cerebral white matter and pallidum in acute carbon monoxide (CO) poisoning was experimentally investigated by measuring regional cerebral blood flow (rCBF) with the iodo-[14C]antipyrine method. A CO group consisting of five cats was exposed to 0.2%-0.3% CO gas and the rCBF was measured when moderate systemic hypotension (70-80 mm Hg) occurred; because systemic hypotension of this level during exposing to 0.2%-0.3% CO gas induces typical cerebral lesions of acute CO poisoning in almost all cats [Okeda et al. Acta Neuropathol (Berl) 54:1-10 (1981)]. Controls were a hypotension group of three cats with moderate systemic hypotension induced for 1 h without CO exposure, and a control group of five cats which inhaled only air for 2 h. The rCBF of each structure in the CO and hypotension groups was evaluated as a percentage of that of the control group. The rCBF of the CO group exhibited a wide range (68%-127%) according to the structures examined, and the mean (94.6%) was large compared with that (range: 53%-82%, mean: 67.4%) of the hypotension group. In the CO group, the examined brain structures where divided in two groups according to the rCBF values; low-value structures and high-value structures. There was significant (P less than 0.05) difference between rCBFs of both the structure groups. The cerebral white matter and pallidum belonged to low-value structures, and these rCBFs did not show any significant difference from those of other structures in this structure group.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of biologically effective spectra for erythema and pre-vitamin D3 synthesis.
The short wavelength cut-off (lambdac), the wavelength of the maximum spectral UV (lambdaMax) of spectral pre-vitamin D3 effective solar UV irradiance (UVD3), and the spectral erythemal UV (UVEry) were compared at 5-min intervals over a 6-month period at solar zenith angles (SZA) ranging from 4.7 degrees to 80 degrees. Averaged over the entire period, lambdac for UVD3 is higher by 1.05 nm than that for UVEry. The lambdaMax is higher for UVD3 compared to UVEry for SZA<approximately 50 degrees. For higher SZA (>55 degrees), the ratio of lambdaMax for UVD3 to that for UVEry is less than 1. As the erythemal action spectrum extends into the UVA, the ratio of UVD3 to UVEry irradiances decreases with increasing SZA, along with a decrease in the ratio of lambdaMax for UVD3 compared to UVEry. The changes in lambdac and lambdaMax influence both personal UVD3 and UVEry exposure and, to take this into account, a dual calibration technique for polysulphone dosimeters has been developed to simultaneously provide measurements of both types of exposure.


Stereospecificity of hydrogen transfer in the saccharopine dehydrogenase reaction.
The stereospecificity of hydrogen transfer in the synthesis of saccharopine from alpha-ketoglutarate and L-lysine catalyzed by saccharopine dehydrogenase (N5-(1,3-dicarboxypropyl)-L-lysine: NAD oxidoreductase (L-lysine-forming), EC 22.214.171.124) was examined by using [4A-3H]- and [4B-3H]NADH. The enzyme showed the A-stereospecificity. The NMR analysis of the saccharopine prepared with [4"A-2H]NADH revealed that the label was incorporated into the C-2 of the glutaryl moiety.


Comparison of two-dimensional orthoradially reformatted computed tomography and panoramic radiography for dental implant treatment planning.
The widespread use of dental implants in partially and completely edentulous patients has brought about a need to preoperatively depict and quantify accurate bone height and contour. A number of conventional intraoral and extraoral radiographic techniques have been used, including the relatively new modality of two-dimensional orthoradially reformatted computed tomography. Despite rapid advances in imaging technology, many clinicians continue to rely on techniques such as panoramic radiography that produce images that distort the jaws nonuniformly. This study compared bone height measurements of jaws made with these two imaging modalities. Nineteen sites in 10 patients were imaged with both techniques and mean bone height was determined for each imaging technique and site. Significant differences were found between mean bone heights measured with the two imaging modalities (p < 0.0005). Situations in which the use of dental implants would be particularly advantageous demonstrated the largest discrepancies, that is, when bone height measurements were less than 15 mm.


Tumor microenvironment-initiated lipid redox cycling for efficient triple-negative breast cancer therapy.
The use of overwhelming reactive oxygen species (ROS) attack has shown great potential for treating aggressive malignancies; however, targeting this process for further applications is greatly hindered by inefficiency and low selectivity. Here, a novel strategy for ROS explosion induced by tumor microenvironment-initiated lipid redox cycling was proposed, which was developed by using soybean phosphatidylcholine (SPC) to encapsulate lactate oxidase (LOX) and sorafenib (SRF) self-assembled nanoparticles (NPs), named LOX/SRF@Lip. SPC is not only the delivery carrier but an unsaturated lipid supplement for ROS explosion. And LOX catalyzes excessive intratumoral lactate to promote the accumulation of large amounts of H2O2. Then, H2O2 reacts with excessive endogenous iron ions to generate amounts of hydroxyl radical for the initiation of SPC peroxidation. Once started, the reaction will proceed via propagation to form new lipid peroxides (LPO), resulting to devastating LPO explosion and widespread oxidative damage in tumor cells. Furthermore, SRF makes contribution to mass LPO accumulation by inhibiting LPO elimination. Compared to normal tissue, tumor tissue has higher levels of lactate and iron ions. Therefore, LOX/SRF@Lip shows low toxicity in normal tissues, but generates efficient inhibition on tumor proliferation and metastasis, enabling excellent and safe tumor-specific therapy. This work offers new ideas on how to magnify anticancer effect of ROS through rational nanosystem design and tumor-specific microenvironment utilization.


Effect of flumetsulam alone and coexistence with polyethylene microplastics on soil microbial carbon and nitrogen cycles: Elucidation of bacterial community structure, functional gene expression, and enzyme activity.
Flumetsulam (FLU) is a new class of broad-spectrum herbicides. With the widespread use of plastic products, polyethylene (PE) microplastics (MPs) may remain in the soil. It is possible for these two novel contaminants to co-exist in the soil environment. In the present study, we used brown soil as the test soil and determined the toxicity of FLU at 0.05, 0.5 and 2.5 mg kg-1 alone and in combination with PE MPs (1%) on soil microorganisms. The obtained results demonstrated that the exposure of FLU and FLU+MPs had an inhibitory effect on the numbers of bacteria and fungi. In addition, FLU and FLU+MPs caused changes in the relevant functional bacterial genera, favored nitrogen fixation and denitrification, and promoted soil carbon fixation, but inhibited nitrification. Compared to FLU exposure alone, exposure to FLU+MPs gave rise to significant differences in soil bacterial community composition, but did not affect carbon and nitrogen cycling. The integrated biomarker response results indicated that the toxicity of FLU and FLU+MPs to soil microorganisms increased with increasing concentrations of FLU. The present experiment clarified the toxicological effects of co-exposure of FLU and MPs on microorganisms and filled the toxicological data gap of FLU.


In vitro inhibitory effects of ethanol extract of Danshen (Salvia miltiorrhiza) and its components on the catalytic activity of soluble epoxide hydrolase.
Soluble epoxide hydrolase (sEH) has been demonstrated to be a key enzyme involved in the pathologic development of several cardiovascular diseases and inflammation, and inhibition of sEH is therefore very helpful or crucial for the treatment of ischemia-reperfusion injury, cardiac hypertrophy, hypertension and inflammation. Danshen, the dried root of Salvia miltiorrhiza (Fam. Labiatae), has been used for the treatment of cardiovascular and cerebrovascular diseases in China and other countries for hundreds of years. Recent studies indicated that Danshen and its preparations also have potential for the management of inflammation. However, little information is available about the possibility of Danshen and its components on sEH inhibition. Danshen extracts and its constituents were tested for sEH inhibition using its physiological substrate, 8,9-EET, based on a LC-MS/MS assay in this study. Among the tested 15 compounds, tanshinone IIA and cryptotanshinone were found to be the potent (Ki = 0.87 μM) and medium (Ki = 6.7 μM) mixed-type inhibitors of sEH, respectively. Salvianolic acid C (Ki = 8.6 μM) was proved to be a moderate noncompetitive sEH inhibitor. In consistent with the inhibition results of the pure compounds, the 75% ethanol extract of Danshen (EE, IC50 = 86.5 μg/ml) which contained more tanshinone IIA and cryptotanshinone exhibited more potent inhibition on sEH than the water extract (WE, IC50 > 200 μg/ml) or 1 M NaHCO3 (BE, IC50 > 200 μg/ml) extract. These data indicated that using the ethanol fraction of Danshen and increasing the amounts of tanshinone IIA, cryptotanshinone and salvianolic acid C, especially the contents of tanshinone IIA in Danshen extract or preparations to enhance the inhibitory effects on sEH might be efficient ways to improve its cardiovascular protective and anti-inflammatory effects, and that herbal medicines could be an untapped reservoir for sEH-inhibition agents and developing sEH inhibitors from the cardiovascular protective and anti-inflammatory herbs is a promising approach.


Brain chondroitin/dermatan sulfate, from cerebral tissue to fine structure: extraction, preparation, and fully automated chip-electrospray mass spectrometric analysis.
Chondroitin sulfate (CS) and dermatan sulfate (DS) glycosaminoglycans (GAGs) are covalently linked to proteins, building up a wide range of proteoglycans, with a prevalent expression in the extracellular matrix (ECM). In mammalian tissues, these GAG species are often found as hybrid CS/DS chains. Their structural diversity during chain elongation is produced by variability of sulfation in the repeating disaccharide units. In central nervous system, a large proportion of the ECM is composed of proteoglycans; therefore, CS/DS play a significant role in the functional diversity of neurons, brain development, and some brain diseases. A requirement for collecting consistent data on brain proteoglycan glycosylation is the development of adequate protocols for CS/DS extraction and detailed compositional and structure analysis. This chapter will present a strategy, which combines biochemical tools for brain CS/DS extraction, purification, and fractionation, with a modern analytical platform based on chip-nanoelectrospray multistage mass spectrometry (MS) able to provide information on the essential structural elements such as epimerization, chain length, sulfate content, and sulfation sites.


[Dynamics of neurospecific protein S-100 accumulation in the brain of AKR/J and DBA/2J strain mice in the process of postnatal development].
The content of total S-100 protein and its water-soluble fraction was determined in the brain of DBA/2J and AKR/J mice during postnatal development. Reliable differences between the two strains were found in the content of total S-100 protein (from the 27th day after birth on) and its water-soluble fraction (from the 35th day).


Better success rate for root canal therapy when treatment includes obturation short of the apex.
Medline and reference lists of identified articles in English only. Initial screening identified studies on humans with radiographic information on the terminal point of obturation. Subsequently studies with (a) a minimum follow-up of at least 2 years; (b) data on termination of obturation/instrumentation; (c) failures of treatment defined adequately (with a minimum radiographic evaluation for failure outlined and defined); (d) data available on success/failure of root canal therapy in relationship to the obturation/instrumentation length; and (e) presence or absence of rarefaction included. This meta-analysis considered three categories of obturation length from the radiographic apex: (a) 0-1 mm (group A), (b) >1 mm but <3 mm (group B), (c) obturated past the radiographic apex, including sealer (group C). The studies were independently assessed for quality with readers blinded to the names of the authors and their institutions, names of the journals, sources of funding, and acknowledgements. Statistical analyses were done using the DerSimonian and Laird estimates. Four studies met the inclusion criteria. In terms of percentage rates of success, the meta-analysis showed that obturation 0-1 mm short of the apex (group A) was better than obturation 1-3 mm short of the apex (group B); both were superior to obturation beyond the apex (group C). The success rate in group A was 28.9% better than group C and 5.9% better than group B (95% CI=-3.8%, 61.5%), P=0.08 and (95% CI=-1.3%, 13.1%), P=0.11, respectively. After adjustment for quality, the results remained unchanged. The results demonstrate that obturating materials extruding beyond the radiographic apex correlated with a poorer prognosis. In addition, we realised that standardised protocols are necessary in endodontic procedures and in dental research. If studies are to be compared and the information used clinically, the design of the studies must be similar and repeatable. The results of prospective studies will then be comparable and the data can be combined statistically, thereby creating a more powerful, clinically useful meta-analysis.


Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis.
To discuss the expression of long noncoding RNA TUG1 (lncRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of lncRNA-TUG1 in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between lncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using lncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA-transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after lncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western-blot test. The expression level of lncRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P < 0.05) and the high expression level of lncRNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (P < 0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by lncRNA-TUG1 specific siRNA (P < 0.05). The results of qRT-PCR and western-blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after lncRNA-TUG1 was silenced (P < 0.05). lncRNA-TUG1 shows an up-regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. lncRNA-TUG1 can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met.


Basosquamous papilloma. A benign epithelial skin tumor with multiple cytogenetic clones.
Cytogenetic analysis of short-term cultures from a basosquamous papilloma revealed the following mosaic karyotype: 46,XX,t(2;5)(q31;q31),t(8;15)(p21;q21)/46,XX,t(7;17)(p13;p13)/47,XX, t(3;20)(q12;p13),+7/46,XX,t(1:12)(p12;q13). The finding of four abnormal, cytogenetically unrelated clones suggests a multicellular origin of this benign skin tumor. None of the structural rearrangements encountered have previously been associated with neoplasia.


Medical journals and advertiser tracking-Consequences for patients, clinicians, and editors.
Medical journal websites frequently contain tracking code that transfers data about journal readers to third parties. These data give drug, device, and other medical product companies a potentially powerful resource for targeting advertisements and other marketing materials to journal readers based on unique attributes and medical interests that can be inferred from the articles they read. Thus, while editors may strictly regulate the content of advertisements that such companies place in their journals' pages, they simultaneously provide those companies with the means to target readers in other forums, possibly in ways that subvert editorial guidelines. We examine the implications of third-party tracking on medical journal webpages, and recommend actions that publishers, editors, and academic societies can take to curb it.


Prevalence of fibromyalgia and co-morbid bipolar disorder: A systematic review and meta-analysis.
Fibromyalgia (FM) is a chronic disorder with high morbidity and significant health service utilization costs. Few studies have reported on the phenotypic overlap of FM and bipolar disorder (BD). The aim of this review is to qualitatively and quantitatively summarize the results and clinical implications of the extant literature on the co-occurrence of FM and BD. A systematic search of PubMed/Medline, Cochrane, PsycINFO, CINAHL and Embase was conducted to search for relevant articles. Articles were included if incidence and/or prevalence of BD was determined in the FM sample. Results of prevalence were pooled from all studies. Pooled odds ratio (OR) was calculated based on case-control studies using standard meta-analytic methods. A total of nine studies were included. The pooled rate of BD comorbidity in samples of FM patients was 21% (n=678); however, results varied greatly as a function of study methodology. Case-controlled studies revealed a pooled OR of 7.55 of BD co-morbidity in samples of FM patients [95% Confidence Interval (CI)=3.9-14.62, FM n=268, controls n=413] with low heterogeneity (I(2)=0%). The current study was limited by the low number of available studies and heterogeneity of study methods and results. These data strongly suggest an association between BD and FM. Future studies employing a validated diagnostic screen are needed in order to more accurately determine the prevalence of BD in FM. An adequate psychiatric assessment is recommended in FM patients with suspected symptoms consistent with BD prior to administration of antidepressants in the treatment of FM.


Bonding properties and dimensional stability of hydrocolloid impression systems in fixed prosthodontics.
Four hydrocolloid impression systems for fixed prosthodontics and one conventional alginate were tested for bonding properties between the syringe and the tray materials of the systems. Their dimensional stability was tested also after the impressions were kept in a humidor for 1, 3, and 24 hours before casts were poured. Findings showed that there was a true bond between the syringe and the tray materials for all combinations. The precision tests gave a mean percent difference between the master model and the cast of less than 0.15 for all material combinations at both the 1- and 3-hours observations. The same was true at the 24-hours observation, except for one combination. From a clinical point of view, all the materials can be used for fixed prosthodontic impressions even if kept for 1 and 3 hours in 100% humidity before pouring the casts; however one material was unsuitable if kept for 24 hours before pouring.


An exploratory qualitative study of women's perceptions of risk management options for familial ovarian cancer: implications for informed decision making.
Women who are at increased risk of familial ovarian cancer face complex decisions about strategies for managing their risk due to a lack of evidence regarding the benefits of ovarian cancer screening (OCS) and prophylactic surgery. At present, there is a limited understanding of women's attitudes towards these options. In-depth interviews were conducted to explore perceptions of ovarian cancer screening and prophylactic oophorectomy (PO) in 10 women who were newly identified as being at increased risk of familial ovarian cancer. The study findings highlight the gaps in women's knowledge about risk management options. Although most women derived considerable reassurance from ovarian screening, many were not aware of the limitations of the screening process or the likelihood of receiving false positive results. Areas in which women's knowledge about prophylactic oophorectomy could be improved include the practicalities of surgery, the risks and benefits of HRT given postsurgically, the limitations of surgery in removing risk, and the absence of concrete information on which to base surgical decisions. In particular, women who were not previously aware of their increased risk may need additional psychological support and preparation. The present study raises serious questions about the extent to which women are making informed decisions about familial ovarian cancer risk management strategies. Suggestions are made for improving the information and support provided to women and for large-scale prospective research.


Pro-inflammation and pro-atherosclerotic responses to short-term air pollution exposure associated with alterations in sphingolipid ceramides and neutrophil extracellular traps.
Air pollution has been associated with the development of atherosclerosis; however, the pathophysiological mechanisms underlying pro-atherosclerotic effects of air pollution exposure remain unclear. We conducted a prospective panel study in Beijing and recruited 152 participants with four monthly visits from September 2019 to January 2020. Linear mixed-effect models were applied to estimate the associations linking short-term air pollution exposure to biomarkers relevant to ceramide metabolism, pro-inflammation (neutrophil extracellular traps formation and systemic inflammation) and pro-atherosclerotic responses (endothelial stimulation, plaque instability, coagulation activation, and elevated blood pressure). We further explored whether ceramides and inflammatory indicators could mediate the alterations in the profiles of pro-atherosclerotic responses. We found that significant increases in levels of circulating ceramides of 9.7% (95% CIs: 0.7, 19.5) to 96.9% (95% CIs: 23.1, 214.9) were associated with interquartile range increases in moving averages of ambient air pollutant metrics, including fine particulate matter (PM2.5), black carbon, particles in size fractions of 100-560 nm, nitrogen dioxide, carbon monoxide and sulfur dioxide at prior up to 7 days. Higher air pollution levels were also associated with activated neutrophils (increases in citrullinated histone H3, neutrophil elastase, double-stranded DNA, and myeloperoxidase) and exacerbation of pro-atherosclerotic responses (e.g., increases in vascular endothelial growth factor, lipoprotein-associated phospholipase A2, matrix metalloproteinase-8, P-selectin, and blood pressure). Mediation analyses further showed that dysregulated ceramide metabolism and potentiated inflammation could mediate PM2.5-associated pro-atherosclerotic responses. Our findings extend the understanding on potential mechanisms of air pollution-associated atherosclerosis, and suggest the significance of reducing air pollution as priority in urban environments.


Polyethylene glycol protects primary hepatocytes during supercooling preservation.
Cold storage (at 4°C) offers a compromise between the benefits and disadvantages of cooling. It allows storage of organs or cells for later use that would otherwise quickly succumb to warm ischemia, but comprises cold ischemia that, when not controlled properly, can result in severe damage as well by both similar and unique mechanisms. We hypothesized that polyethylene glycol (PEG) 35 kDa would ameliorate these injury pathways and improve cold primary hepatocyte preservation. We show that reduction of the storage temperature to below zero by means of supercooling, or subzero non-freezing, together with PEG supplementation increases the viable storage time of primary rat hepatocytes in University of Wisconsin (UW) solution from 1 day to 4 days. We find that the addition of 5% PEG 35 kDa to the storage medium prevents cold-induced lipid peroxidation and maintains hepatocyte viability and functionality during storage. These results suggest that PEG supplementation in combination with supercooling may enable a more optimized cell and organ preservation.


Pivot Superior Capsular Reconstruction of the Shoulder.
Massive rotator cuff tears involving the posterosuperior rotator cuff remain difficult to treat, particularly in the younger population. Fatty infiltration of the muscle, excessive chronic tendon retraction, and degeneration are the main irreversible factors predisposing to high failure rates of direct repair. Many techniques exist for superior capsular reconstruction (SCR), mainly using allograft. However, the higher costs of dermal grafts and morbidity of fascia lata autograft led us to find another option for SCR of the shoulder using the semitendinosus autograft as a pivot in a better biomechanical configuration. The pivot SCR technique has shown good functional and biomechanical results. We have found this technique to be a reliable and less expensive option for irreparable lesions of the rotator cuff.


Effect of Insulin and Metformin Combination Treatment on Colon Adenoma and Advanced Adenoma Among DM II.
The risk for colorectal adenoma and advanced adenoma among diabetes mellitus II (DM II) has been debated to differ with the type of anti-diabetic therapy. Insulin increases whereas metformin decreases the risk for colon adenoma (Ad) and advanced Ad (AAd). There have been no studies to evaluate the effect of combination treatment with insulin and metformin on colon Ad and AAd. The retrospective study included DM II patients undergoing screening colonoscopy. Subjects with incomplete colonoscopy, poor bowel preparation, personal history of colorectal cancer (CRC)/inflammatory bowel disease/hereditary nonpolyposis colorectal cancer/familial adenomatosis polyposis/colectomy or family history of CRC were excluded. Subjects were categorized into group 1 (insulin only), group 2 (metformin only), group 3 (combination of insulin and metformin) and group 4 (miscellaneous). Group 4 was excluded from data analysis. Ad detection rate (ADR) and advanced ADR (AADR) were calculated for each group. Three hundred thirty-nine subjects composed the study group, with a mean age of 60.0 years and male to female ratio of 1:1.4. Composite ADR and AADR for study population was 35.1 and 15.3 %, respectively. Groups 1, 2 and 3 were composed of 88 (26.0 %), 211 (62.2 %) and 40 (11.8 %) subjects, respectively. ADR for groups 1, 2 and 3 was 40.9, 33.2 and 32.5 %, respectively (p value = 0.413). AADR for groups 1, 2 and 3 was 18.2, 15.2 and 10.0 %, respectively (p value = 0.489). A decremental trend was observed in ADR and AADR across group 1, group 2 and group 3 (p value >0.05).


Mitochondrial electron transport chain deficiency, cardiomyopathy, and long-term cardiac transplant outcome.
Organ transplantation in multisystemic mitochondrial cytopathies is usually not performed because of perceived untoward complications. We report three patients with demonstrated oxidative phosphorylation defects and dilated cardiomyopathy who underwent cardiac transplant. All three patients tolerated immunosuppression medications and have had an excellent long-term outcome. Our results suggest that with proper patient selection in this population, cardiac transplantation is feasible and can have good outcomes.


Evolving epidemiologic characteristics of invasive group a streptococcal disease in Utah, 2002-2010.
Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity and mortality. Recent national surveillance data report stable rates of invasive GAS disease, although these may not capture geographic variation. We performed a population-based, retrospective laboratory surveillance study of invasive GAS disease among Utah residents from 2002-2010. We used Intermountain Healthcare's electronic medical records and data warehouse to identify patients from whom GAS was isolated by culture. We defined clinical syndromes of invasive GAS disease on the basis of International Classification of Diseases, Ninth Revision codes. We abstracted demographic information, comorbidities, and microbiologic and laboratory findings. From 2002-2010, we identified 1514 cases of invasive GAS disease among Utah residents. The estimated mean annual incidence rate was 6.3 cases/100,000 persons, which was higher than the national rate of 3.6 cases/100,000 (P < .01). The incidence of invasive GAS disease in Utah rose from 3.5 cases/100,000 persons in 2002 to 9.8 cases/100,000 persons in 2010 (P = .01). Among children aged <18 years, the incidence of invasive GAS increased from 3.0 cases/100,000 children in 2002 to 14.1 cases/100,000 children in 2010 (P < .01). The increase in the pediatric population was due, in part, to an increase in GAS pneumonia (P = .047). The rate of invasive GAS disease in adults aged 18-64 years increased from 3.4 cases/100 000 persons in 2002 to 7.6 cases/100,000 persons in 2010 (P = .02). Rates among those aged ≥65 years were stable. The incidence of acute rheumatic fever declined from 6.1 to 3.7 cases/100,000 (P = .04). The epidemiologic characteristics of invasive GAS disease in Utah has changed substantially over the past decade, including a significant increase in the overall incidence of invasive disease-driven primarily by increasing disease in younger persons-that coincided temporally with a decrease in the incidence of acute rheumatic fever.


The Impact of First UK-Wide Lockdown (March-June 2020) on Sexual Behaviors in Men and Gender Diverse People Who Have Sex with Men During the COVID-19 Pandemic: A Cross-Sectional Survey.
The global COVID-19 pandemic resulted in strict social distancing measures restricting close physical contact. Men (cis and trans) and other gender diverse people who have sex with men (MGDSM) are at higher risk of sexually transmitted infections (STIs) and may have experienced changes in sexual behavior during government restrictions on social and sexual contact. We aimed to examine self-reported sexual behavior of MGDSM during the first UK-wide lockdown to identify the characteristics of the individuals who might most require sexual health promotion and clinical support. In April-May 2020, we conducted an online survey of MGDSM, promoted on social media and Grindr. Our exploratory approach used descriptive analysis to identify self-reported changes in sexual behavior and performed regression analyses to identify correlates of casual sex during the lockdown. A total of 1429 respondents completed the survey: mean age 36 years, 84% White, 97% male or trans male, 98% assigned male sex at birth, 2% female or non-binary, 65% degree educated or higher. During the lockdown, 76% reported not having any casual sex partners. While the majority reported reduced casual sex, 3% reported an increase in casual sex with one person and 2% with three or more people (group sex). About 12% of the sample engaged in casual sex with only one person and 5% with four or more sexual partners during the lockdown. Reporting casual sex during lockdown was associated with: lower level of education OR = 2.37 [95% CI 1.40-4.01]; identifying as a member of an ethnic minority OR = 2.27[1.40-3.53]; daily usage of sexual networking apps OR = 2.24[1.54-3.25]; being less anxious about contracting SARS-CoV-2 through sex OR = 1.66[1.12-2.44]; using PrEP before lockdown OR = 1.75[1.20-2.56]; continuing to use PrEP OR = 2.79[1.76-4.57]; and testing for STIs during lockdown OR = 2.65[1.76-3.99]. A quarter of respondents remained sexually active with casual partners, indicating a need to provide STI screening services and health promotion targeted to groups most likely to have need over this period. Future research is required to better understand how to support sexual and gender minorities to manage sexual risk in the context of pandemic public health initiatives.


[Evolution of the incidence and results at 12 months of parathyroidectomy: 40 years of experience in a dialysis center with two successive surgical departments].
Secondary hyperparathyroidism remains the main complication of mineral and bone metabolism in patients with chronic kidney disease. In case of resistance to medical treatment (native and active vitamin D, calcium and calcimimetics), surgical parathyroidectomy is indicated. The aim of this retrospective study is to show the evolution of the incidence and results of surgical parathyroidectomy in our center between 1980 and 2020 as patient characteristics, diagnostic and therapeutic strategies have changed. We collected data from dialysis patients who had a first surgical parathyroidectomy between 2000 and 2020 (period 2) in the same surgical department and compared them with historical data between 1980 and 1999 (period 1) operated in one other center. In period 1, 53 surgical parathyroidectomy were performed (2.78/year, 0 to 5, 8.5/1000 patients-year) vs.56 surgical parathyroidectomy in period 2 (2.8/year, 0 to 9, 8/1000 patients-year). The patients of the 2 periods were comparable except for the higher dialysis vintage in period 1 (149±170 vs.89±94 months; P=0.02). In comparison with dialysis patients not requiring surgical parathyroidectomy during the same period, patients who had surgical parathyroidectomy were younger, had higher dialysis vintage and lower diabetes prevalence, but more frequently carriers of glomerulopathy or polycystosis. Systematically performed in period 2, cervical ultrasound identified at least one visible gland in 78.6% of cases while the scintigraphy, performed only in 66% of cases, found at least one gland in 81% of cases. Twelve months after surgery, PTH > 300 pg/mL (marker of secondary hyperparathyroidism recurrence or surgery failure) was present in 30% of patients in period 1 vs. 5.3% in period 2. Hypoparathyroidism was also more frequently observed in period 2 (35.7 vs. 18.8%). Surgical complications were also higher in period 1. Despite therapeutic and strategic advances, severe secondary hyperparathyroidism is still as common as ever. It is favored by excessively high PTH targets, by suboptimal prevention before dialysis and poor tolerance of calcimimetics. The surgical parathyroidectomy is effective and safe in the hands of a specialized team with an ultrasound and scintigraphic preoperative assessment.


Laying-up of sterile instruments in the operating theatre: equal or superior protection by using a horizontal unidirectional air flow system.
A system for the preparation of sterilized instruments with unidirectional horizontal air flow (UDHF) has several advantages over a unidirectional down flow system (UDDF). The advantages are based on the installation of the system being more flexible and easier to use, no cooling of the air flow being necessary and less air being needed for circulation, resulting in reduced energy use. The objective of this study was to determine whether a system with UDHF performs equal or superior to a system with UDDF in terms of prevention of contamination of the air (the presence of particles and micro-organisms) during the laying-up process. The degree of protection (DP) offered by two UDHF system variants and two UDDF system variants was determined for several static set-ups and a dynamic simulation of the process. In addition to determining the level of protection for several categories of particle size, colony-forming units (CFU) were also measured during process simulations. When maximum protection (no particles present) is considered, the UDHF systems performed significantly better than the UDDF systems for particles ≥2.5μm. When particles were present, there was no significant difference between systems for particles ≥0.3 and ≥0.5μm. However, the performance of the UDHF system was superior to that of the UDDF system (DP) for particles ≥1.0μm representing the bacteria-carrying particles. During the process measurements, no CFU were found with the UDDF system in 64% of the measurements, compared with 90% for the UDHF system (P = 0.012). The UDHF system offers equal or superior protection to the UDDF system against contamination of the clean area within which the laying up takes place. Despite our finding that the differences did not always reach statistical significance (due to low background concentrations), there is a clear trend, from the small-sized particles (≥1.0μm) up to the largest sizes considered, including bacteria-carrying particles, that demonstrates the superiority of the horizontal flow system. The UDHF system offers a more robust solution than the UDDF system, provided that good work instructions are given and the height of the table and height of the plenum are properly adjusted.


Seasonality and daily weather conditions in relation to myocardial infarction and sudden cardiac death in Olmsted County, Minnesota, 1979 to 2002.
We assessed the relationship of season and weather types with myocardial infarction (MI) and sudden cardiac death (SCD) in a geographically defined population, and tested the hypothesis that the increased risk in winter was related to weather. Winter peaks in coronary heart disease (CHD) have been documented. Yet, it is uncertain if seasonality exists for both incident events and deaths, and the role of weather conditions is not clear. The daily occurrence of incident MI and SCD in Olmsted County was examined with data from the National Weather Service. Poisson regression models were used to assess the relative risks (RRs) associated with season and climatic variables. Subsequent analysis stratified SCD into those with and without antecedent CHD (unexpected SCD). Between 1979 and 2002, 2,676 MI and 2,066 SCD occurred. The age-, gender-, and year-adjusted RR of SCD, but not of MI, was increased in winter versus summer (1.17, 95% confidence interval [CI] 1.03 to 1.32) and in low temperatures (1.20, 95% CI 1.07 to 1.35, for temperatures below 0 degrees C vs. 18 degrees C to 30 degrees C). These associations were stronger for unexpected SCD than for SCD with prior CHD (p < 0.05). After adjustment for all climatic variables, low temperature was associated with a large increase in the risk of unexpected SCD (RR = 1.38, 95% CI 1.10 to 1.73), while the association with winter declined (RR = 1.06, 95% CI 0.83 to 1.35). These data suggest that the winter peak in SCD can be accounted for by daily weather.


Hepatic radiofrequency ablation: markedly reduced systemic effects by modulating periablational inflammation via cyclooxygenase-2 inhibition.
To determine whether celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can potentiate hepatic radiofrequency ablation (RFA)-induced local cellular infiltration and distant tumour growth. First, COX-2 expression was evaluated using immunohistochemistry in the local periablational rim 24 h after hepatic RFA without/with intraperitoneal celecoxib in normal Fisher 344 rat liver. Next, local cellular infiltration of macrophages, stellate cells, and hepatocyte proliferation were quantified in C57BL6 mice 3-7d after RFA without/with celecoxib. c-Met, HGF, and VEGF levels after RFA were also measured. Finally, distant tumour growth and proliferation (Ki67 and CD34) were observed in subcutaneous R3230 tumours after hepatic RFA with/without celecoxib. Hepatic RFA-induced local activation of COX-2 was significantly suppressed using celecoxib. Celecoxib also reduced RFA-associated a) increased c-Met expression at 24 h, b) HGF and VEGF levels at 72 h, c) periablational macrophage and stellate cells at 3d, and d) hepatocyte proliferation at 7d. Similarly, celecoxib with RFA reduced distant tumour growth, tumour cell proliferation, and tumour microvascular density to sham levels, compared to increases observed with hepatic RFA alone. Increased activation of COX-2 after hepatic RFA contributes to periablational cellular infiltration and inflammation-mediated distant tumour growth, which can be successfully suppressed with a COX-2 inhibitor. • Thermal ablation of liver tissue can increase local inflammation and COX-2 expression. • Ablation-induced local inflammation can contribute to stimulation of distant tumour growth. • Local COX-2 inhibition with celecoxib can block ablation-induced distant tumour growth.


Frequency and types of partner violence among Mexican American college women.
The authors studied the prevalence of partner violence, by type, among Mexican American college women aged 18 to 35 years (N = 149; response rate = 85%). Twelve percent of women who reported a dating partner in the past year were physically or sexually assaulted, 12.1% were stalked, and 9.1% scored as psychologically abused. Among those experiencing partner violence, almost half experienced stalking and 89% reported psychological abuse. Few women (25%) who experienced physical violence believed violence was a problem in their relationship. Partner violence was prevalent in this population, and participants experienced many forms of violence. Because few women experiencing physical violence report that violence is a problem in their relationship, interventions must address perceptions of violence and its impact on women's mental and physical health in college populations.