Microbiology and antibiotic prophylaxis in rhinoplasty: a review of 363 consecutive cases.
A practical technique for reducing infectious complications from rhinoplasty would represent an important surgical advance. To describe the microbial flora of patients undergoing septorhinoplasty and to evaluate the role of preoperative and postoperative antibiotic prophylaxis. We performed a retrospective medical record review of 363 consecutive adult patients who underwent preoperative nasal swab testing and rhinoplasty or septorhinoplasty in a single private practice: 279 women (76.9%) and 84 men (23.1%). The average patient age was 35.9 years (age range, 17-70 years). Identification of endogenous nasal flora and pathogenic bacteria treated with culture-directed antibiotics; evaluation of comorbidities, perioperative infections, and antibiotic treatments. A total of 174 patients (47.9%) underwent primary rhinoplasty, and 189 (52%) underwent revision rhinoplasty. On preoperative nasal culture, 78.2% of patients had normal flora; 10.7% had Staphylococcus aureus; and 0.28% had methicillin-resistant S aureus (MRSA). In 7.4% of patients, fecal coliforms including Escherichia coli, Enterobacter species, and Citrobacter species were found. Age, sex, smoking, the use of oral contraceptives, or the presence of seasonal allergies did not significantly change the nasal flora or the postoperative infection rate. Patients with adult acne were found to have an increased incidence of colonization with fecal coliforms (43.8%; P < .001). Patients with diabetes were found to have an increased incidence of colonization with S aureus (66.7%; P = .002). The overall infection rate was 3.0% (11 of 363 patients), with 4.0% (7 of 174 patients) seen in primary septorhinoplasties and 2.1% (4 of 189 patients) seen in revision cases. Coliforms accounted for 5 cases (45.5%) of postoperative infections, while S aureus was responsible for 4 cases (36.4%), including 1 case of MRSA. The results of this study suggest that risk factors alone may not reliably predict the subset of patients in whom antibiotic prophylaxis is indicated. Knowledge of the endogenous nasal flora and the microbiology of common pathogens in patients undergoing septorhinoplasty will help to further reduce the incidence of infectious complications. 3.


C1QBP is upregulated in colon cancer and binds to apolipoprotein A-I.
The present study aimed to investigate the expression of complement component 1, q subcomponent-binding protein (C1QBP) in colon cancer cells, and identify proteins that interact with C1QBP. Total proteins were extracted from both the tumor and normal tissues of 22 patients with colon cancer and analyzed using liquid chromatography-mass spectrometry (LC-MS) to identify proteins that were differentially-expressed in tumor tissues. C1QBP overexpression was induced in 293T cells using a pFLAG-CMV2 expression vector. Overexpressed FLAG-tagged C1QBP protein was then immunoprecipitated using anti-FLAG antibodies and C1QBP-interacting proteins were screened using LC-MS analysis of the immunoprecipitates. The C1QBP-interacting proteins were confirmed using reverse-immunoprecipitation and the differential expression of C1QBP in tissues and cell lines was confirmed using western blot analysis. LC-MS analysis revealed that C1QBP exhibited a typical tumor expression pattern. Two immune-reactive signals (33 and 14 kDa) were detected in normal and tumor tissues from 19 patients. Furthermore, 14 kDa C1QBP protein was upregulated in the tumors of 15 patients. In total, 39 proteins were identified as candidate C1QBP-interacting proteins, and an interaction between C1QBP and apolipoprotein A-I was confirmed. The present study indicates that C1QBP is involved in colon cancer carcinogenesis, and that the mechanisms underlying the established anti-tumor properties of apolipoprotein A-I may include interacting with and inhibiting the activity of C1QBP.


RAAFT-2: Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation.
Radiofrequency ablation (RFA) for the treatment of paroxysmal Atrial Fibrillation (pAF) has a class 1 indication in patients who have not tolerated or responded to antiarrhythmic medications. Antiarrhythmic medications (AAM) are, however, limited not only by modest efficacy, but also by significant side effects. Discontinuation rates for AAM range from 11-40% in trials. The RAAFT-2 trial evaluates the use of RFA as a first line treatment for pAF compared to optimal pharmacological management (1).


Vitamin E d-α-Tocopheryl Polyethylene Glycol Succinate (TPGS) Provokes Cell Death in Human Neuroblastoma SK-N-SH Cells via a Pro-Oxidant Signaling Mechanism.
Neuroblastoma (NB) is the most common neoplasm during infancy. Unfortunately, NB is still a lethal cancer. Therefore, innovative curative therapies are immediately required. In this study, we showed the prodeath activity of TPGS in human NB SK-N-SH cancer cells. NB cells were exposed to TPGS (10-80 μM). We report for the first time that TPGS induces cell death by apoptosis in NB cells via a pro-oxidant-mediated signaling pathway. Certainly, H2O2 directly oxidizes DJ-1 cysteine106-thiolate into DJ-1 cysteine106-sulfonate, indirectly activates the transcription factors NF-kappaB, p53, and c-JUN, induces the upregulation of mitochondria regulator proteins BAX/PUMA, and provokes the loss of mitochondrial membrane potential (ΔΨm) and the activation of caspase-3/AIF, leading to nuclear disintegration, demonstrated by cellular and biochemical techniques such as fluorescence microscopy, flow cytometry, and Western blot analysis. Since TPGS is a U.S. Food and Drug Administration (FDA)-approved pharmaceutical excipient, this molecule might be used in clinical trials for NB treatment.


Current and future opportunities of autodissemination of pyriproxyfen approach for malaria vector control in urban and rural Africa.
Despite the progress made in reducing malaria burden, new ways to address the increasing challenges of insecticide resistance and the invasion and spread of exotic malaria vectors such as Anopheles stephensi in Africa are urgently needed. While African countries are adopting larviciding as a complementary intervention for malaria vector control, the autodissemination technology has the potential to overcome barriers associated with the identification and treatment of prolific habitats that impede conventional larviciding approaches in rural settings. The autodissemination technology as a "lure and release" strategy works by exploiting the resting behavior of gravid mosquitoes to transfer lethal concentration of biological or chemical insecticide such as pyriproxyfen (PPF), an insect growth regulator (IGRs) to their oviposition sites and result in adult emergence inhibition. Despite the evidence of the autodissemination approach to control other mosquito-borne diseases, there is growing and promising evidence for its use in controlling malaria vectors in Africa, which highlights the momentous research that needs to be sustained. This article reviews the evidence for efficacy of the autodissemination approach using PPF and discusses its potential as efficient and affordable complementary malaria vector control intervention in Africa. In the previous studies that were done in controlled semi-field environments, autodissemination with PPF demonstrated its potential in reducing densities of captive population of malaria vectors such as Anopheles gambiae and Anopheles arabiensis. Of importance, empirical evidence and biology-informed mathematical models to demonstrate the utility of the autodissemination approach to control wild populations of malaria vectors under field environment either alone or in combination with other tools are underway. Among others, the key determining factors for future introduction of this approach at scale is having scalable autodissemination devices, optimized PPF formulations, assess its integration/complementarity to existing conventional larviciding, and community perception and acceptance of the autodissemination approach.


Pentacarbonyl[tris[4-(methylsulfonyl)phenyl]stannyl]manganese(I): an unexpected tetragonal structure.
The title compound, [MnSn(C(7)H(7)O(2)S)(3)(CO)(5)], is asymmetric but crystallizes in the highly symmetric tetragonal space group I-4. This is achieved without the need for any disorder, either around the Sn atom or in any of the methylsulfonyl groups. The environment around the Sn atom has the following geometry: Sn-Mn = 2.6564 (7) A, mean Sn-C = 2.175 (5) A, mean C-Sn-C = 103 (2) degrees and mean C-Sn-Mn = 115 (6) degrees. The crystal packing is assisted by weak Sn.O interactions between adjacent columns of molecules, with the resulting geometry at Sn approaching highly distorted trigonal-bipyramidal.


Lapatinib in the treatment of breast cancer.
Within the past 2 years, four separate groups have reported marked improvement in relapse-free survival when trastuzumab was added to adjuvant chemotherapy in patients with HER2-overexpressing breast cancer. These results add further credence to the relevance of this receptor as a tumor target. Despite the significant benefits observed in early and advanced HER2-positive breast cancer, overexpression of the receptor is still associated with a poorer prognosis and an increased risk of disease relapse, even in patients with primary operable disease. Besides cytotoxic chemotherapy, and possibly hormonal therapy, patients whose tumors exhibit resistance to trastuzumab have few molecular-targeted options available. Recently, lapatinib, a small molecule dual inhibitor of both HER2 and EGF receptors, has been developed to expand the options for treating HER-positive breast cancer.


Plastids and stromules interact with the nucleus and cell membrane in vascular plants.
The various metabolic activities of plastids require continuous exchange of reactants and products with other organelles of the plant cell. Physical interactions between plastids and other organelles might therefore enhance the efficiency of plant metabolism. We have observed a close apposition of plastids and nuclei in various organs of Nicotiana tabacum and Arabidopsis thaliana. In hypocotyl epidermal cells, plastids and stromules, stroma-filled tubular extensions of the plastid envelope membrane, were observed to reside in grooves and infoldings of the nuclear envelope, indicating a high level of contact between the two organelle membranes. In a number of non-green tissues, including suspension-cultured cells, perinuclear plastids were frequently associated with long stromules that extended from the cell center to the cell membrane. In cotyledon petioles, cells lying adjacent to one another frequently contained stromules that met on either side of the shared cell wall, suggesting a means of intercellular communication. Our results therefore suggest that stromules have diverse roles within plant cells, perhaps serving as pathways between nuclei and more distant regions of the cell and possibly even other cells.


Driving force of metallo (Mg-H and Mg-Cl)-ene reaction mechanisms.
The potential-energy surfaces of the metallo-ene reactions of allyl-MgH and allyl-MgCl with ethylene were studied using ab initio molecular-orbital (MO) methods. The concerted path and the stepwise path of the metallo-ene reactions of allyl-MgH and allyl-MgCl with ethylene were identified and it was determined that the energy barriers on concerted paths of the metallo-ene reactions of allyl-MgH and allyl-MgCl with ethylene are lower than those on the stepwise paths. Furthermore, the concerted path of the metallo-ene reaction of allyl-MgCl with ethylene is more favorable than that of the allyl-MgH reaction system. The reaction mechanisms were analyzed using a CiLC method on the basis of CASSCF MOs. The driving force for the concerted path reactions arises from the migration process of the metal. The difference between the reactivity of allyl-MgH and allyl-MgCl can be explained with the reaction mechanism on the basis of the driving force.


A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy.
Altered by defects in p53, epigenetic silencing, and genomic loss, the microRNA miR-34a represents one of the most clinically relevant tumor-suppressive microRNAs. Without question, a striking number of patients with cancer would benefit from miR-34a replacement, if poor miR-34a stability, non-specific delivery, and delivery-associated toxicity could be overcome. Here, we highlight a fully modified version of miR-34a (FM-miR-34a) that overcomes these hurdles when conjugated to a synthetically simplistic ligand. FM-miR-34a is orders of magnitude more stable than a partially modified version, without compromising its activity, leading to stronger repression of a greater number of miR-34a targets. FM-miR-34a potently inhibited proliferation and invasion, and induced sustained downregulation of endogenous target genes for >120 h following in vivo delivery. In vivo targeting was achieved through conjugating FM-miR-34a to folate (FM-FolamiR-34a), which inhibited tumor growth leading to complete cures in some mice. These results have the ability to revitalize miR-34a as an anti-cancer agent, providing a strong rationale for clinical testing.


Large coalescent parenchymal nodules in pulmonary sarcoidosis: "sarcoid galaxy" sign.
The purpose of this study was to evaluate the large parenchymal nodules in pulmonary sarcoidosis and to describe a new CT sign termed the "sarcoid galaxy." The CT appearance of pulmonary sarcoidosis suggests that the large nodules arise from a coalescence of small nodules. The large nodules are surrounded by many tiny satellite nodules. These findings were considered to simulate the appearance of a galaxy. This observation was supported by radiologic-pathologic correlation. The sarcoid galaxy sign may be a useful adjunct in the diagnosis of pulmonary sarcoidosis.


[Mortality of workers employed at an asbestos cement manufacturing plant in Senigallia].
The mortality (1948-1990) was investigated in 561 workers employed in an asbestos cement plant in Senigallia (Central Italy). A significant increase in lung cancer was observed in male subjects (SMR: 276; 95% C.I.: 175.2-414.8, 23 observed). The excess mortality was a function of the induction-latency time. Five deaths were observed among women, one of which due to malignant pleural neoplasm.


A simple peak detection and label-free quantitation algorithm for chromatography-mass spectrometry.
Label-free quantitation of mass spectrometric data is one of the simplest and least expensive methods for differential expression profiling of proteins and metabolites. The need for high accuracy and performance computational label-free quantitation methods is still high in the biomarker and drug discovery research field. However, recent most advanced types of LC-MS generate huge amounts of analytical data with high scan speed, high accuracy and resolution, which is often impossible to interpret manually. Moreover, there are still issues to be improved for recent label-free methods, such as how to reduce false positive/negatives of the candidate peaks, how to expand scalability and how to enhance and automate data processing. AB3D (A simple label-free quantitation algorithm for Biomarker Discovery in Diagnostics and Drug discovery using LC-MS) has addressed these issues and has the capability to perform label-free quantitation using MS1 for proteomics study. We developed an algorithm called AB3D, a label free peak detection and quantitative algorithm using MS1 spectral data. To test our algorithm, practical applications of AB3D for LC-MS data sets were evaluated using 3 datasets. Comparisons were then carried out between widely used software tools such as MZmine 2, MSight, SuperHirn, OpenMS and our algorithm AB3D, using the same LC-MS datasets. All quantitative results were confirmed manually, and we found that AB3D could properly identify and quantify known peptides with fewer false positives and false negatives compared to four other existing software tools using either the standard peptide mixture or the real complex biological samples of Bartonella quintana (strain JK31). Moreover, AB3D showed the best reliability by comparing the variability between two technical replicates using a complex peptide mixture of HeLa and BSA samples. For performance, the AB3D algorithm is about 1.2 - 15 times faster than the four other existing software tools. AB3D is a simple and fast algorithm for label-free quantitation using MS1 mass spectrometry data for large scale LC-MS data analysis with higher true positive and reasonable false positive rates. Furthermore, AB3D demonstrated the best reproducibility and is about 1.2- 15 times faster than those of existing 4 software tools.


Transferability of short tandem repeat markers for two wild Canid species inhabiting the Brazilian Cerrado.
The maned wolf (Chrysocyon brachyurus) and the crab-eating fox (Cerdocyon thous) are two wild-canid species found in the Brazilian Cerrado. We tested cross-amplification and transferability of 29 short tandem repeat primers originally developed for cattle and domestic dogs and cats on 38 individuals of each of these two species, collected in the Emas National Park, which is the largest national park in the Cerrado region. Six of these primers were successfully transferred (CSSM-038, PEZ-05, PEZ-12, LOCO-13, LOCO-15, and PEZ-20); five of which were found to be polymorphic. Genetic parameter values (number of alleles per locus, observed and expected heterozygosities, and fixation indices) were within the expected range reported for canid populations worldwide.


Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: A randomized trial.
Clomiphene citrate is one of the effective drugs for infertility treatment due to oligo-ovulation or anovulation. Intrauterine insemination (IUI) is one of more adherent methods for treatment of infertile cases which is followed by controlled ovarian hyperstimulation (COH). the aim of this study was to evaluate Clomiphene citrate versus letrozole with gonadotropins in IUI cycles. In this prospective randomized trial, 180 infertile women who were referred to Milad Hospital were selected. The first group received 5 mg/day letrozole on day 3-7 of menstrual cycle. The second group received 100 mg/day Clomiphene in the same way as letrozole. In both groups, human menopausal gonadotropin was administered every day starting on day between 6-8 of cycle. Ovulation was triggered with urinary Human Chorionic Gonadotropin (5000 IU) when have two follicles of ≥16 mm. IUI was performed 36 hr later. The number of matured follicles, cycle cancellation, and abortion were the same in both groups. Endometrial thickness was higher at the time of human menopausal gonadotropin administration in letrozole group. Chemical and clinical pregnancy rates were much higher in letrozole group. Ovarian hyperstimulation was significantly higher in clomiphene group. Letrozole appears to be a good alternative to clomiphene citrate with fewer side effects.


Axillary recurrence rate in breast cancer patients with negative sentinel lymph node biopsy or containing micrometastases and without further lymphadenectomy: a monocentric review of 8 years and 481 cases.
Sentinel lymph node biopsy (SLNB) has almost completely replaced complete axillary lymph node dissection (CALND) as the first-line axillary procedure for clinically node-negative early stage breast cancer. We assessed the incidence of axillary relapse in patients with negative SLNB who had no additional CALND (group 1, n = 481) and in patients whose SLNB contained micrometastases and had no further CALND (group 2, n = 45). All patients were operated on between November 1997 and December 2005 and followed at the Jules Bordet Institute. The median follow-up was 48 months. A mean of 2.2 sentinel lymph nodes was removed per patient. Axillary relapse was observed in only one patient (0.2%) in group 1 and in none of the patients in group 2. This study confirms that the axillary recurrence rate after long-term follow-up of patients with a negative sentinel lymph node is very rare, provided that the selection criteria are judicious.


Thoracoscopic Radiofrequency Fragmentation of the Left Atrium as a Bridge to Decision Before Heart Transplant.
Atrial fibrillation and congestive heart failure can provoke and aggravate each other. Often the boundaries between those diseases are ambiguous, and successful diagnosis is initially elusive. However, the last stage of congestive heart failure can lead the patient to heart transplant. We suggested that restoration and stabilization of sinus rhythm could be used as a differential diagnostic criterion to distinguish dilated cardiomyopathy from atrial fibrillation. We investigated the possibility that thoracoscopic radiofrequency fragmentation of the left atrium could be a valid a bridge to decision before heart transplant in patients with the combination of atrial fibrillation and congestive heart failure with reduced left ventricular ejection fraction. The pilot study included 3 men who consecutively received thoracoscopic radiofrequency fragmentation of the left atrium from November 2021 to May 2022. All 3 patients had a combination of atrial fibrillation and congestive heart failure with a reduced ejection fraction and left ventricle dilatation (echocardiography, Simpson method: 31%, 33%, and 30%, respectively) despite receiving as highly as possible drug therapy and normalization of heart rate. The patients were 42, 38, and 55 years old, with rates of N-terminal pro-B-type natriuretic peptide of 3047, 2548, and 2542 pg/mL, respectively. The follow-up examination was performed every month. The total durations of the follow-up were 12, 9, and 7 months, respectively. By month 3 after the surgery, the left ventricular ejection fraction began to increase. By month 6 of follow-up, the left ventricular ejection fraction reached its maximum value and stabilized. All patients reported cessation of congestive heart failure symptoms. Thoracoscopic radiofrequency fragmentation of the left atrium can be considered a bridge to decision before heart transplant in patients with a combination of atrial fibrillation and congestive heart failure with reduced left ventricular ejection fraction.


[Association of genetic polymorphisms in selenoprotein GPX1 and TXNRD2 with genetic susceptibility of gastric cancer].
This study examined whether the two polymorphisms of GPX1 (198Pro--> Leu) and TXNRD2 (370Lys-->Arg) contributed alone or in combination, to the risk of gastric cancer development. A total of 361 patients with gastric cancer and 363 cancer-free controls were recruited and their genotypes of the two polymorphisms were determined by polymerase chain reaction-based restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were computed using unconditional logistic regression model. GPX1 and TXNRD2 polymorphisms individually were not associated with the risk of gastric cancer. Gene-gene interaction of GPX1 and TXNRD2 polymorphisms decreased the risk of gastric cancer. Carrying the protective genotype might decrease the risk at 62% (OR = 0.38, 95% CI = 0.26-0.55, P < 0.001) as compared with the risk genotype. The GPX1 198 Pro/Pro and TXNRD2 370Arg/Arg genotypes might be associated with the genetic susceptibility of gastric cancer.


Essential Role for an Isoform of Escherichia coli Translation Initiation Factor IF2 in Repair of Two-Ended DNA Double-Strand Breaks.
In Escherichia coli, three isoforms of the essential translation initiation factor IF2 (IF2-1, IF2-2, and IF2-3) are generated from separate in-frame initiation codons in infB. The isoforms have earlier been suggested to additionally participate in DNA damage repair and replication restart. It is also known that the proteins RecA and RecBCD are needed for repair of DNA double-strand breaks (DSBs) in E. coli. Here, we show that strains lacking IF2-1 are profoundly sensitive to two-ended DSBs in DNA generated by radiomimetic agents phleomycin or bleomycin, or by endonuclease I-SceI. However, these strains remained tolerant to other DSB-generating genotoxic agents or perturbations to which recA and recBC mutants remained sensitive, such as to mitomycin C, type-2 DNA topoisomerase inhibitors, or DSB caused by palindrome cleavage behind a replication fork. Data from genome-wide copy number analyses following I-SceI cleavage at a single chromosomal locus suggested that, in a strain lacking IF2-1, the magnitude of recombination-dependent replication through replication restart mechanisms is largely preserved but the extent of DNA resection around the DSB site is reduced. We propose that in the absence of IF2-1 it is the synapsis of a RecA nucleoprotein filament to its homologous target that is weakened, which in turn leads to a specific failure in assembly of Ter-to-oriC directed replisomes needed for consummation of two-ended DSB repair. IMPORTANCE Double-strand breaks (DSBs) in DNA are major threats to genome integrity. In Escherichia coli, DSBs are repaired by RecA- and RecBCD-mediated homologous recombination (HR). This study demonstrates a critical role for an isoform (IF2-1) of the translation initiation factor IF2 in the repair of two-ended DSBs in E. coli (that can be generated by ionizing radiation, certain DNA-damaging chemicals, or endonuclease action). It is proposed that IF2-1 acts to facilitate the function of RecA in the synapsis between a pair of DNA molecules during HR.


ABCG2 Q141K polymorphism is associated with chemotherapy-induced diarrhea in patients with diffuse large B-cell lymphoma who received frontline rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone chemotherapy.
ATP-binding cassette transporter G2 (ABCG2) is the most recently described transporter of the multidrug-resistance pump and it promotes resistance to anticancer drugs such as doxorubicin, mitoxantrone, topotecan, and SN-38. Of the ABCG2 polymorphisms, V12M and Q141K alter the functional activity of the ABCG2 transporter and influence the drug response and various toxicities to chemotherapeutic agents. We therefore evaluated the impact of the ABCG2 V12M and Q141K polymorphisms on the therapeutic outcomes and toxicities of primary rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in 145 Korean patients with diffuse large B-cell lymphoma (DLBCL). ABCG2 V12M and Q141K genotyping was carried out by pyrosequencing of polymerase chain reaction products. The clinical characteristics, treatment outcomes, toxicities of the patients, and the predictive value of the polymorphisms on response, survival, and adverse events to R-CHOP for 145 patients were analyzed according to the ABCG2 V12M and Q141K polymorphisms. No differences were observed according to ABCG2 Q141K and V12M genotype in patient characteristics, disease characteristics, response, survival, or hematology toxicity profiles in patients with DLBCL who received frontline R-CHOP chemotherapy. On multivariate analysis, grade I-IV diarrhea was statistically significant according to ABCG2 Q141K polymorphism (the QQ genotype vs the QK or KK genotypes; hazard ratio 2.835; 95% confidence interval 1.432-5.613; P = 0.003). This study demonstrates that the ABCG2 Q141K polymorphism may correlate with chemotherapy-induced diarrhea in patients with DLBCL who have received frontline R-CHOP chemotherapy, and this has implications for optimizing treatment with such agents.


Coexpression Network Analysis of Benign and Malignant Phenotypes of SIV-Infected Sooty Mangabey and Rhesus Macaque.
To explore the differences between the extreme SIV infection phenotypes, nonprogression (BEN: benign) to AIDS in sooty mangabeys (SMs) and progression to AIDS (MAL: malignant) in rhesus macaques (RMs), we performed an integrated dual positive-negative connectivity (DPNC) analysis of gene coexpression networks (GCN) based on publicly available big data sets in the GEO database of NCBI. The microarray-based gene expression data sets were generated, respectively, from the peripheral blood of SMs and RMs at several time points of SIV infection. Significant differences of GCN changes in DPNC values were observed in SIV-infected SMs and RMs. There are three groups of enriched genes or pathways (EGPs) that are associated with three SIV infection phenotypes (BEN+, MAL+ and mixed BEN+/MAL+). The MAL+ phenotype in SIV-infected RMs is specifically associated with eight EGPs, including the protein ubiquitin proteasome system, p53, granzyme A, gramzyme B, polo-like kinase, Glucocorticoid receptor, oxidative phosyphorylation and mitochondrial signaling. Mitochondrial (endosymbiotic) dysfunction is solely present in RMs. Specific BEN+ pattern changes in four EGPs are identified in SIV-infected SMs, including the pathways contributing to interferon signaling, BRCA1/DNA damage response, PKR/INF induction and LGALS8. There are three enriched pathways (PRR-activated IRF signaling, RIG1-like receptor and PRR pathway) contributing to the mixed (BEN+/MAL+) phenotypes of SIV infections in RMs and SMs, suggesting that these pathways play a dual role in the host defense against viral infections. Further analysis of Hub genes in these GCNs revealed that the genes LGALS8 and IL-17RA, which positively regulate the barrier function of the gut mucosa and the immune homeostasis with the gut microbiota (exosymbiosis), were significantly differentially expressed in RMs and SMs. Our data suggest that there exists an exo- (dysbiosis of the gut microbiota) and endo- (mitochondrial dysfunction) symbiotic imbalance (EESI) in HIV/SIV infections. Dissecting the mechanisms of the exo-endo symbiotic balance (EESB) that maintains immune homeostasis and the EESI problems in HIV/SIV infections may lead to a better understanding of the pathogenesis of AIDS and the development of novel interventions for the rational control of this disease.


Outcomes for women in a flexible sigmoidoscopy-based colorectal cancer screening programme.
There are concerns that technical and anatomical factors can reduce the potential benefit of flexible sigmoidoscopy (FS) as a colorectal cancer (CRC) screening tool in women compared with men. Our aim was to review the outcomes for female participants in a community-based CRC screening project using FS. In 1995, a programme of unsedated FS-based screening of asymptomatic average-risk individuals aged 55-64 years was established at Fremantle Hospital, Western Australia. Insertion depths, pathological findings and site of adenomas and subject-rated pain scores have been prospectively recorded. Later diagnoses of malignancy were determined by linkage of the cohort with the West Australian Cancer Registry. Between 1995 and 2005, 3402 primary screening FS examinations had been carried out (women 41%). Mean age of participants was 59.6 years. Women were more likely to undergo a FS with insertion depth less than 40 cm (17 vs 6%, P < 0.0001). Mean pain score was 2.9 for men and 4.0 for women (P < 0.0001). Women were less likely to have any neoplasia detected, independent of pain score or insertion depth (odds ratio 0.5, 95% confidence interval 0.4-0.6). Increasing insertion depth from 50 to 60 cm in a woman would only have a 0.4% chance of detecting any additional neoplasia. An insignificant trend to higher incidence of later interval CRC was observed in women with normal sigmoidoscopy. Women probably undergo FS with more discomfort and lesser insertion depth than men. It is unlikely that moderate increases in insertion depth would have a substantial benefit.


Gender stereotype endorsement differentially predicts girls' and boys' trait-state discrepancy in math anxiety.
Mathematics is associated with anxiety for many students; an emotion linked to lower well-being and poorer learning outcomes. While findings typically show females to report higher trait math anxiety than males, no gender differences have to date been found in state (i.e., momentary) math anxiety. The present diary study aimed to replicate previous findings in investigating whether levels of academic self-concept was related to this discrepancy in trait vs. state anxiety measures. Additionally, mathematics-related gender stereotype endorsement (mathematics is a male domain) was investigated as an additional predictor of the trait-state discrepancy. The sample included 755 German 9th and 10th graders who completed self-report measures of trait math anxiety, math self-concept, and gender stereotype endorsement, in addition to state measures of anxiety after math classes by use of a standardized diary for 2-3 weeks (N within = 6207). As expected, females reported higher trait math anxiety but no gender differences were found for state math anxiety. Also in line with our assumptions, multilevel analyses showed the discrepancy between trait and state anxiety to be negatively related to students' self-concept (i.e., a lower discrepancy for students with higher self-concepts). Furthermore, gender stereotype endorsement differentially predicted the trait-state discrepancy: When controlling for self-concept in mathematics, females who endorsed the gender stereotype of math being a male domain more strongly overestimated their trait math anxiety as compared to their state anxiety whereas this effect was not significant for males. The present findings suggest that gender stereotype endorsement plays an important role in explaining gender differences in math anxiety above and beyond academic self-concept. Implications for future research and educational practice are discussed.


Embryology in the medical curriculum.
Embryology as a field is in a period of unprecedented change in its knowledge base. Similarly, this is a period of great change in medical curricular planning. One of the most significant questions in embryology education for medical students is how much of the "new" molecular embryology to mix with the "old" developmental anatomy approach. The other question is the most effective venue for instruction in medical embryology. Not all medical curricula have the same objectives; nor do they use the same educational approach. With that in mind, this review outlines several ways in which medical embryology can be offered and how it can be integrated into the medical curriculum. It also lays out topics that are worthy of inclusion in a modern embryology course or sequence.


"Keeping Them Warm"-A Randomized Controlled Trial of Two Passive Perioperative Warming Methods.
Inadvertent perioperative hypothermia is a common problem for patients undergoing surgery. Heat redistribution from the body's core to the periphery after induction of anesthesia is the major contributor. A prospective randomized controlled trial was conducted to determine if reflective blankets are more effective than cotton blankets in reducing the core-peripheral temperature gradient and increasing peripheral compartment heat content during the preoperative phase among adult patients undergoing elective surgery of less than 1 hour. About 328 adult patients undergoing general anesthesia were randomly allocated into two groups. Data were analyzed using independent t tests for continuous variables and chi-square tests for categorical variables. There was a significantly smaller reduction in temporal artery/foot temperature gradient (1.13 vs 1.64°C, P < .001) and a significant increase in foot temperature (0.64 vs 0.11°C, P < .001) in the reflective blanket group. Reflective blankets are more effective than cotton blankets in warming patients' periphery and reducing core-peripheral temperature gradient preoperatively. ACTRN12614000931673 (retrospective registration).


Cardiac mechanoenergetics for understanding isoproterenol-induced rat heart failure.
Considering from clinical implication, it is often complained that short-term experimental diseased heart models do not mimic long-term diseased hearts that one often clinically encountered. The left ventricle (LV) function in rat cardiac hypertrophy models treated with isoproterenol (ISO) up to 16 weeks was followed up with a non-invasive echocardiography. Infusion of either ISO (1.2mgkg(-1)day(-1) for 3 days-16 weeks) or vehicle (saline 24μlday(-1) for 3 days-16 weeks; SA group) was performed by subcutaneously implanting osmotic minipump. LV and right ventricle (RV) weight ratios to body weight (mgg(-1)) in SA, ISO3d, ISO7d and ISO4w were: 1.94±0.10 and 0.54±0.04 (n=7), 2.56±0.10 and 0.66±0.05 (n=7), 2.50±0.25 and 0.64±0.07 (n=10) and 2.40±0.08 and 0.59±0.08 (n=9), respectively. From echocardiography, the LV function of the hypertrophy models at 3 days, 1 and 2 weeks was unchanged but the model at the longer-term than 4 weeks resulted in prolonged systolic failure. These results indicated that only 3-day ISO infusion induced the hypertrophy model similar in shape and function to that induced by 2-week ISO infusion; the 3-day model sufficiently represents the effects of 2-week ISO infusion. In this review, left ventricular (LV) function was compared between rat cardiac hypertrophy models treated with ISO for 3 days (ISO3d) and 7 days (ISO7d) by analyzing LV mechanical work and energetics. The LV mechanical work and energetics was unchanged in SA, ISO3d and ISO7d groups. The LV relaxation rate at 240bpm in ISO3d and ISO7d groups was significantly slower than that in SA group with unchanged contraction rate. The amounts of expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a), phospholamban (PLB), phosphorylated-Ser(16) PLB (p-PLB), phospholemman (PLM) and Na(+)-K(+)-ATPase (NKA) are significantly decreased in ISO3d and ISO7d groups. Furthermore, the marked collagen production (types I and III) was observed in ISO3d and ISO7d groups. These results suggested the possibility that physiological LV function is compensated, although molecular changes have been generated even in the short-term hypertrophy model. Although a novel histone deacetylase (HDAC) inhibitor, has some beneficial effects on hemodynamics, it has no effects of anti-hypertrophic modalities in ISO3d model. However, a selective sodium proton exchanger-1 (NHE-1) inhibitor normalized ISO-induced down-regulation of SERCA2a without changes in pPLB/PLB expression in the ISO7d model and ameliorates cardiac Ca(2+) handling impairment and prevents the development of cardiac dysfunction. This result indicated that SERCA2a is a key molecule in the ISO7d model. Slow LV relaxation rate in ISO7d model may be due to down-regulation of SERCA2a. In conclusion, lowering the heart rate make it possible to rescue the impairment of LV mechanical work and energetics in the ISO-induced compensatory hypertrophied rat hearts, providing basic evidence for clinical therapy for patients with some types of cardiac failure.


SARS-CoV-2 antibody seroprevalence after the first wave among workers at a community healthcare system in the Greater Boston area.
SARS-CoV-2 antibody seroprevalence among health-care workers (HCW) can assess past exposure and possible immunity, which varies across different regions, populations and times. We investigated the seroprevalence among HCW in Massachusetts (a region suffering high COVID-19 mortality) at the end of first wave of the SARS-CoV-2 pandemic. All HCW at Cambridge Health Alliance were invited to participate in this cross-sectional survey in June 2020. Those who volunteered, consented and provided a blood sample were included. Dried blood specimens from finger-prick sampling collected either at home by each HCW or onsite by the study team were analyzed for anti-SARS-CoV-2 IgM and IgG to the virus' receptor binding domain, using an enzyme-linked immunosorbent assay. IgM and IgG antibody abundance were categorized based on the number of standard deviations above the cross-reacting levels found in existing, pre-pandemic blood samples previously obtained by the Ragon Institute and analyzed by the Broad Institute (Cambridge, MA). Seroprevalence estimates were made based on 'positive' IgM or IgG using 'low' (>6 SD), 'medium' (>4.5 SD), and 'high' prevalence cutoffs (>3 SD).A total of 433 out of 5,204 eligible HCWs consented and provided samples. Participating HCWs had a lower cumulative incidence (from the start of the pandemic up to the bloodspot collections) of SARS-CoV-2 RT-PCR positivity (1.85%) compared to non-participants (3.29%). The low, medium, and high seroprevalence estimates were 8.1%, 11.3%, and 14.5%, respectively. The weighted estimates based on past PCR positivity were 13.9%, 19.4%, and 24.9%, respectively, for the entire healthcare system population after accounting for participation bias.


From experiments to ecosystems? Reviewing public participation, scientific governance and the systemic turn.
The article discusses a recent systemic turn in public participation in science studies. It reviews the main lines of criticism brought forward in science, technology and society towards public participation in science discourse and argues that much of it refers to the field's preoccupation with isolated, stage-managed minipublics. It then discusses a series of efforts in science, technology and society, and other fields to study public participation in a more systemic or holistic perspective. The article advances the argument that there are different ways of conceptualizing such a perspective, not all of which are well equipped to account for contestation, conflict and power. We distinguish between an aggregative approach, deliberative systems theory, an eco-systemic and a decentred governance approach and argue that the latter allows us to study the complexities of public participation without relying on a normative concept of system and account for power relations that may structure the field of public participation.


Estimation of muscle fatigue by ratio of mean frequency to average rectified value from surface electromyography.
A new method to estimate muscle fatigue quantitatively from surface electromyography (EMG) is proposed. The ratio of mean frequency (MNF) to average rectified value (ARV) is used as the index of muscle fatigue, and muscle fatigue is detected when MNF/ARV falls below a pre-determined or pre-calculated baseline. MNF/ARV gives larger distinction between fatigued muscle and non-fatigued muscle. Experiment results show the effectiveness of our method in estimating muscle fatigue more correctly compared to conventional methods. An early evaluation based on the initial value of MNF/ARV and the subjective time when the subjects start feeling the fatigue also indicates the possibility of calculating baseline from the initial value of MNF/ARV.


The alpha, but not the beta, isoform of the human thromboxane A2 receptor is a target for nitric oxide-mediated desensitization. Independent modulation of Tp alpha signaling by nitric oxide and prostacyclin.
In humans, thromboxane A2 signals through two thromboxane A2 receptor (TP) isoforms termed TP alpha and TP beta. Signaling by TP alpha, but not TP beta, is subject to prostacyclin-induced desensitization mediated by direct protein kinase (PK) A phosphorylation where Ser329 represents the phosphotarget (Walsh, M. T., Foley, J. F., and Kinsella, B. T. (2000) J. Biol. Chem. 275, 20412-20423). In the current study, the effect of the vasodilator nitric oxide (NO) on intracellular signaling by the TP isoforms was investigated. The NO donor 3-morpholinosydnonimine, HCl (SIN-1) and 8-bromo-guanosine 3',5'-cyclic monophosphate (8-Br-cGMP) functionally desensitized U46619-mediated calcium mobilization and inositol 1,4,5-trisphosphate generation by TP alpha whereas signaling by TP beta was unaffected by either agent. NO-mediated desensitization of TP alpha signaling occurred through a PKG-dependent, PKA- and PKC-independent mechanism. TP alpha, but not TP beta, was efficiently phosphorylated by PKG in vitro and underwent NO/PKG-mediated phosphorylation in whole cells. Deletion/site-directed mutagenesis and metabolic labeling studies identified Ser331 as the target residue of NO-induced PKG phosphorylation of TP alpha. Although TP alpha S331A was insensitive to NO/PKG-desensitization, similar to wild type TP alpha its signaling was fully desensitized by the prostacyclin receptor agonist cicaprost occurring through a PKA-dependent mechanism. Conversely, signaling by TP alpha S329A was insensitive to cicaprost stimulation whereas it was fully desensitized by NO/PKG signaling. In conclusion, TP alpha undergoes both NO- and prostacyclin-mediated desensitization that occur through entirely independent mechanisms involving direct PKG phosphorylation of Ser331, in response to NO, and PKA phosphorylation of Ser329, in response to prostacyclin, within the unique carboxyl-terminal tail domain of TP alpha. On the other hand, signaling by TP beta is unaffected by either NO or prostacyclin.


UvrA expression of Lactococcus lactis NZ9000 improve multiple stresses tolerance and fermentation of lactic acid against salt stress.
Lactococcus lactis is subjected to several stressful conditions during industrial fermentation including oxidation, heating and cooling, acid, high osmolarity/dehydration and starvation. DNA lesion is a major cause of genetic instability in L. lactis that usually occurs at a low frequency, but it is greatly enhanced by environmental stresses. DNA damages produced by these environmental stresses are thought to induce DNA double-strand breaks, leading to illegitimate recombination. Nucleotide excision repair (NER) protein UvrA suppresses multiple stresses-induced illegitimate recombination. UvrA protein can survive a coincident condition of environmental harsh conditions, multiple stress factors supposedly encountered in the host and inducing UvrA in L. lactis. In this study the expression of UvrA and growth performance and viability of control strain L. lactisVector and recombinant strain L. lactisUvrA under multiple stress conditions were determined. The recombinants strain had 30.70 and 52.67% higher growth performances when subjected to acidic and osmotic stresses conditions. In addition, the L. lactisUvrA strain showed 1.85-, 1.65-, and 2.40-fold higher biomass, lactate production, and lactate productivity, compared with the corresponding values for L. lactisVector strain during the osmotic stress. Results demonstrated NER system is involved in adaptation to various stress conditions and suggested that cells with a compromised UvrA as DNA repair system have an enhanced protection behavior in L. lactis NZ9000 against DNA damage.


Ultrathin CoOx-modified hematite with low onset potential for solar water oxidation.
Photoelectrochemical water splitting holds great potential for solar energy conversion and storage with zero greenhouse gas emission. Integration of a suitable co-catalyst with an absorber material enables the realization of highly efficient photocleavage of water. Herein, nanostructured hematite film was coated with an ultrathin and conformal CoOx overlayer through atomic layer deposition (ALD). The best performing hybrid hematite with a 2-3 nm ALD CoOx overlayer yielded a remarkable turn on potential of 0.6 VRHE for the water oxidation reaction. Moreover, material analyses revealed that the surface amorphous CoOx/Co(OH)2 component exhibited good optical transparency and hydrophilic properties, which were beneficial for the formation of an ideal hematite/electrolyte interface. In addition to the presence of the CoOx overlayer, a negative shift of flat band potential (VFB) as well as suppression of surface recombination helped to significantly promote the charge separation and collection properties, contributing to the overall solar conversion efficiency. As a result, the external quantum efficiency (IPCE) obtained on hematite increases by 66% at 1.23 VRHE.


[Questionable procedures in environmental medicine using an example of "multiple chemical sensitivity"].
"Multiple Chemical Sensitivity" (MCS) has to be regarded as a merely subjective concept without etiological and pathological background or objective criteria for diagnosis. Most of the "MCS" patients suffer from various psychiatric disorders; in a small minority somatic diseases can be found. The data recently won in the German multicenter study on MCS underline this point of view. The informal German "MCS network" consisting of patients' self-help groups, "therapists" with or without medical background and law firms specialised in compensation claims nevertheless strictly denies any psychogenic model. They do, however, propose a whole range of diagnostic and therapeutic procedures based on different theoretical concepts. Some of the procedures are derived from scientifically based medicine, others have an unconventional and esoteric background. Most of them are logically incompatible; however, they are applied in a polypragmatic manner. None of these so-called diagnostic or therapeutic procedures or health technologies can be regarded as evidence-based. Some of them, however, are extremely expensive and/or pose significant risks for patients' health. In any case, wrong subjective disease concepts are perpetuated iatrogenically. Additionally, those procedures make effective help for the real underlying medical and/or psychiatric conditions impossible.


Quantum mechanical models of the resting state of the vanadium-dependent haloperoxidase.
Density functional theory has been used to investigate structural and electronic properties of complexes related to the resting form of the active site of vanadium haloperoxidase as a function of environment and protonation state. Results obtained by studying models of varying size and complexity highlight the influence of environment and protonation state on the structure and stability of the metal cofactor. The study shows that, in the trigonal bipyramidal active site, where one axial position is occupied by a key histidine, the trans position cannot contain a terminal oxo group. Further, a highly negatively charged vanadate unit is not stable. Protonation of at least one equatorial oxo ligand appears necessary to stabilize the metal cofactor. The study also indicates that, while at rest within the protein, the vanadate unit is most likely an anion with an axial hydroxide and an equatorial plane containing two oxos and a hydroxide. For the neutral, protonated state of the vanadate unit, there were two minima found. The first structure is characterized by an axial water with two oxo and one hydroxo group in the equatorial plane. The second structure contains an axial hydroxo group and an equatorial plane composed of one oxo and two hydroxo oxygen atoms. These two species are not significantly different in energy, indicating that either form may be important during the catalytic cycle. These data support the initial crystallographic assignment of an axially bound hydroxide, but an axial water is also a possibility. This study also shows that the protonation state of the vanadate ion is most likely greater than previously proposed.


Mycobacterium tuberculosis may escape helper T cell recognition by infecting human fibroblasts.
The host immune response can limit Mycobacterium tuberculosis (Mtb) spreading in primary tuberculosis (TB) without eradicating all bacilli, which can persist causing latent TB infection and are responsible for reactivation TB. Persistent Mtb is confined to granulomas within phagocytes, but it is also found in other non-immune cells. We focused on fibroblasts since these cells participate to the granuloma formation and were shown to be infected in latent TB infections. We show that in vitro both Mtb and Bacille Calmette-Guérin actively replicate in human fibroblasts. Mycobacterial infection of fibroblasts causes a significant inhibition of interferon (IFN)-γ induced membrane expression of major histocompatibility complex class II molecules in these cells. The functional consequence of in vitro infection is a significant reduction of the fibroblast capacity to present peptides and soluble proteins to autologous specific CD4(+) T cell clones. Moreover, fibroblasts are capable of presenting antigen derived from the processing of heat-killed Mtb, but not from viable Mtb. Data indicate that IFN-γ treated fibroblasts are capable of presenting antigens derived from the processing of whole bacteria in addition to the capacity to present peptides and isolated proteins. Interestingly, Mtb infected fibroblasts lose this capacity, suggesting that Mtb may evade T helper immune surveillance by infecting fibroblasts.


Immediate versus delayed free TRAM breast reconstruction: an analysis of perioperative factors and complications.
Immediate breast reconstruction provides superior psychological benefit to the patient compared with delayed reconstruction, and has a financial advantage. Smokers undergoing immediate free TRAM breast reconstruction have a higher incidence of flap necrosis than smokers undergoing delayed free TRAM reconstruction. Whereas the differences in psychological benefit, effects of smoking and cost are well addressed in the literature, the differences in morbidity between immediate and delayed free TRAM breast reconstruction are still unknown. Knowledge of any differences would help to determine the best timing for reconstruction, and would support surgical decision making and preoperative patient advice. We present a retrospective review of 105 consecutive free TRAM breast reconstructions performed in 97 patients (89 unilateral and eight bilateral reconstructions). There were 48 immediate reconstructions and 57 delayed reconstructions. In the immediate-reconstruction group six flaps required revision of the anastomosis, and three flaps (6%) were lost. In the delayed-reconstruction group five flaps required revision of the anastomosis, and only one flap (2%) could not be salvaged. Delayed healing of the chest-wall skin flaps only occurred in immediate reconstructions (16%, P = 0.017).


Adsorptive Behavior and Voltammetric Determination of Hydralazine Hydrochloride at A Glassy Carbon Electrode Modified with Multiwalled Carbon Nanotubes.
An electroanalytical method has been introduced for highly sensitive determination of hydralazine hydrochloride (Hy-HCl) based on its oxidation at a glassy carbon electrode modified with multiwalled carbon nanotubes (MWCNT/GCE). Studies showed that the electrochemical oxidation of Hy-HCl was accompanied by adsorption and highly sensitive responses could be achieved by adsorptive stripping voltammetry. The electrooxidation of Hy-HCl at MWCNT/GCE occurred at ~32 mV which was lower than that observed at bare GCE (~52 mV). The optimum working conditions for determination of the drug using differential-pulse adsorptive stripping voltammetry (DPAdSV) were established. The method exhibited linear responses to Hy-HCl in the concentration range 10-220 nM with a detection limit of 2.7 nM. The proposed method was successfully applied to the determination of this compound in pharmaceutical dosage forms.


Spatial heterogeneity in biofilm metabolism elicited by local control of phenazine methylation.
Within biofilms, gradients of electron acceptors such as oxygen stimulate the formation of physiological subpopulations. This heterogeneity can enable cross-feeding and promote drug resilience, features of the multicellular lifestyle that make biofilm-based infections difficult to treat. The pathogenic bacterium Pseudomonas aeruginosa produces pigments called phenazines that can support metabolic activity in hypoxic/anoxic biofilm subzones, but these compounds also include methylated derivatives that are toxic to their producer under some conditions. In this study, we uncover roles for the global regulators RpoS and Hfq/Crc in controlling the beneficial and detrimental effects of methylated phenazines in biofilms. Our results indicate that RpoS controls phenazine methylation by modulating activity of the carbon catabolite repression pathway, in which the Hfq/Crc complex inhibits translation of the phenazine methyltransferase PhzM. We find that RpoS indirectly inhibits expression of CrcZ, a small RNA that binds to and sequesters Hfq/Crc, specifically in the oxic subzone of P. aeruginosa biofilms. Deletion of rpoS or crc therefore leads to overproduction of methylated phenazines, which we show leads to increased metabolic activity-an apparent beneficial effect-in hypoxic/anoxic subpopulations within biofilms. However, we also find that under specific conditions, biofilms lacking RpoS and/or Crc show increased sensitivity to phenazines indicating that the increased metabolic activity in these mutants comes at a cost. Together, these results suggest that complex regulation of PhzM allows P. aeruginosa to simultaneously exploit the benefits and limit the toxic effects of methylated phenazines.


Transcatheter Interventions for Mitral Regurgitation: Multimodality Imaging for Patient Selection and Procedural Guidance.
Transcatheter therapies to treat mitral regurgitation are rapidly developing. Currently, there are several devices commercially available to treat mitral regurgitation. The underlying cause of mitral regurgitation and specific anatomical aspects of the mitral valve and surrounding structures are considered when patients with symptomatic severe mitral regurgitation for transcatheter mitral valve therapies are selected. Multimodality imaging plays an important central role in the selection of patients, providing information about the mechanism of mitral regurgitation, the anatomy of the mitral valve and spatial relationships with the coronary sinus, the circumflex coronary artery and left ventricular outflow tract and to predict the procedural outcomes. During the transcatheter procedure, transesophageal echocardiography and fluoroscopy are key for monitoring the procedural steps to maximize the outcomes and minimize the complications. This paper provides a comprehensive review of the most important aspects to visualize in order to appropriately select patients for transcatheter mitral valve repair and replacement and to guide the procedure for the different transcatheter devices.


BILATERAL PNEUMOTHORAX AS A COMPLICATION OF PERCUTANEOUS TRACHEOSTOMY: CASE REPORT.
Percutaneous dilatational tracheostomy is a common surgical procedure that is becoming the method of choice in critically ill patients whenever prolonged airway secure and/or ventilation support is needed. Although adverse events are relatively uncommon, serious life threatening complications can arise from this bedside procedure. We report a case of a 70-year-old female who developed extensive subcutaneous emphysema and bilateral pneumothorax immediately after a percutaneous dilatational tracheostomy procedure. Different mechanisms, such as damage to posterior or anterior tracheal wall, false passage or paratracheal placement or dislocation of the cannula are considered to be responsible for the development of pneumothorax and subcutaneous emphysema. Although bronchoscopic control after the tracheostomy procedure did not reveal any tracheal injury, we believe that subcutaneous emphysema and bilateral pneumothorax are most likely caused by procedure induced injuries of the trachea in addition to the applied high airway pressure induced by excessive or inappropriate ventilation. In our case report, we would like to emphasize that continuous bronchoscopic guidance during percutaneous tracheostomy is invaluable in decreasing the incidence of its overall complications, especially during enhancing the team experience.


Acute respiratory failure in COVID-19: is it "typical" ARDS?
In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China. The World Health Organization (WHO) declared this outbreak a significant threat to international health. COVID-19 is highly infectious and can lead to fatal comorbidities especially acute respiratory distress syndrome (ARDS). Thus, fully understanding the characteristics of COVID-19-related ARDS is conducive to early identification and precise treatment. We aimed to describe the characteristics of COVID-19-related ARDS and to elucidate the differences from ARDS caused by other factors. COVID-19 mainly affected the respiratory system with minor damage to other organs. Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation. The clinical manifestations were relatively mild in some COVID-19 patients, which was inconsistent with the severity of laboratory and imaging findings. The onset time of COVID-19-related ARDS was 8-12 days, which was inconsistent with ARDS Berlin criteria, which defined a 1-week onset limit. Some of these patients might have a relatively normal lung compliance. The severity was redefined into three stages according to its specificity: mild, mild-moderate, and moderate-severe. HFNO can be safe in COVID-19-related ARDS patients, even in some moderate-severe patients. The more likely cause of death is severe respiratory failure. Thus, the timing of invasive mechanical ventilation is very important. The effects of corticosteroids in COVID-19-related ARDS patients were uncertain. We hope to help improve the prognosis of severe cases and reduce the mortality.


A new cluster-based oversampling method for improving survival prediction of hepatocellular carcinoma patients.
Liver cancer is the sixth most frequently diagnosed cancer and, particularly, Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers. Clinicians assess each patient's treatment on the basis of evidence-based medicine, which may not always apply to a specific patient, given the biological variability among individuals. Over the years, and for the particular case of Hepatocellular Carcinoma, some research studies have been developing strategies for assisting clinicians in decision making, using computational methods (e.g. machine learning techniques) to extract knowledge from the clinical data. However, these studies have some limitations that have not yet been addressed: some do not focus entirely on Hepatocellular Carcinoma patients, others have strict application boundaries, and none considers the heterogeneity between patients nor the presence of missing data, a common drawback in healthcare contexts. In this work, a real complex Hepatocellular Carcinoma database composed of heterogeneous clinical features is studied. We propose a new cluster-based oversampling approach robust to small and imbalanced datasets, which accounts for the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing procedures of this work are based on data imputation considering appropriate distance metrics for both heterogeneous and missing data (HEOM) and clustering studies to assess the underlying patient groups in the studied dataset (K-means). The final approach is applied in order to diminish the impact of underlying patient profiles with reduced sizes on survival prediction. It is based on K-means clustering and the SMOTE algorithm to build a representative dataset and use it as training example for different machine learning procedures (logistic regression and neural networks). The results are evaluated in terms of survival prediction and compared across baseline approaches that do not consider clustering and/or oversampling using the Friedman rank test. Our proposed methodology coupled with neural networks outperformed all others, suggesting an improvement over the classical approaches currently used in Hepatocellular Carcinoma prediction models.


Mini-review: Enteric glial cell reactions to inflammation and potential therapeutic implications for GI diseases, motility disorders, and abdominal pain.
Enteric glial cells are emerging as critical players in the regulation of intestinal motility, secretion, epithelial barrier function, and gut homeostasis in health and disease. Enteric glia react to intestinal inflammation by converting to a 'reactive glial phenotype' and enteric gliosis, contributing to neuroinflammation, enteric neuropathy, bowel motor dysfunction and dysmotility, diarrhea or constipation, 'leaky gut', and visceral pain. The focus of the minireview is on the impact of inflammation on enteric glia reactivity in response to diverse insults such as intestinal surgery, ischemia, infections (C. difficile infection, HIV-Tat-induced diarrhea, endotoxemia and paralytic ileus), GI diseases (inflammatory bowel diseases, diverticular disease, necrotizing enterocolitis, colorectal cancer) and functional GI disorders (postoperative ileus, chronic intestinal pseudo-obstruction, constipation, irritable bowel syndrome). Significant progress has been made in recent years on molecular pathogenic mechanisms of glial reactivity and enteric gliosis, resulting in enteric neuropathy, disruption of motility, diarrhea, visceral hypersensitivity and abdominal pain. There is a growing number of glial molecular targets with therapeutic implications that includes receptors for interleukin-1 (IL-1R), purines (P2X2R, A2BR), PPARα, lysophosphatidic acid (LPAR1), Toll-like receptor 4 (TLR4R), estrogen-β receptor (ERβ) adrenergic α-2 (α-2R) and endothelin B (ETBR), connexin-43 / Colony-stimulating factor 1 signaling (Cx43/CSF1) and the S100β/RAGE signaling pathway. These exciting new developments are the subject of the minireview. Some of the findings in pre-clinical models may be translatable to humans, raising the possibility of designing future clinical trials to test therapeutic application(s). Overall, research on enteric glia has resulted in significant advances in our understanding of GI pathophysiology.


Combined orthodontic and surgical correction of an adolescent patient with thin palatal cortex and vertical maxillary excess.
This paper describes the treatment of a male patient aged 14 years who presented with a skeletal class I, vertical maxillary excess, marked increase in overjet, thin palatal cortex and a gummy smile. Considering the severity of his malocclusion and its impact severity on his psychosocial well being, he was managed with a combined approach of Fixed Orthodontic therapy and Orthognathic surgery, even though his growth was not complete. Records of Pre treatment, Post treatment and three years in retention were analyzed and the functional and esthetic results were found to be fairly stable.


Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase.
The focal adhesion kinase (FAK) has been implicated in signal transduction pathways initiated by cell adhesion receptor integrins and by neuropeptide growth factors. To gain insight into FAK function, we examined the potential interaction of FAK with intracellular signaling molecules containing the Src homology 2 domains. We report here the stable association of FAK with phosphatidylinositol 3-kinase (PI3-kinase; EC 22.214.171.124) in NIH 3T3 mouse fibroblasts. This interaction was stimulated by cell adhesion concomitant with FAK activation. We also found that recombinant FAK bound to the p85 subunit of PI 3-kinase directly in vitro and that autophosphorylation of recombinant FAK in vitro increased its binding to PI 3-kinase. We detected increased tyrosine phosphorylation of the p85 subunit of PI 3-kinase during cell adhesion and observed direct phosphorylation of p85 by FAK in vitro. Together, these results suggest that PI 3-kinase may be a FAK substrate in vivo and serve as an effector of FAK.


[Effect of anticancer drugs on in vitro survival of cell lines derived from various gynecologic tumors (author's transl)].
Effect of various anticancer drugs on in vitro survival of gynecologic tumor cells were investigated by using established cell lines derived from human ovarian adenocarcinoma (HOC-21), endometrial adenocarcinoma (HEC-1B), and cervical squamous cell carcinoma (SKG-1). As compared with other established cell lines, 1) HOC-21 cells were more sensitive to Cis-platinum, Adriamycin, and actinomycin-D. 2) HEC-1B cells were more sensitive to progesterone. 3) SKG-1 cells were more sensitive to bleomycin and mitomycin-C. These results are consistent with the clinical effects of various anticancer drugs, and established cell lines derived from various human gynecologic tumors are useful to select effective anticancer drugs in vitro.


Designing of Combined Nano and Microfiber Network by Immobilization of Oxidized Cellulose Nanofiber on Polycaprolactone Fibrous Scaffold.
In this study, the immobilization of oxidized cellulose nanofiber (OCNF) network on the polycaprolactone (PCL) fibrous scaffold was performed by the aminolysis procedure through electrospinning and layer by layer (LBL) techniques. The morphology of the fibrous scaffold was examined by field emission scanning electron microscopy (FE-SEM), and it indicated that after immobilization of OCNF on PCL, the unique nanofiber and nano network was created. Moreover, the physical and chemical properties of samples were examined using X-ray photoelectron spectroscopy (XPS), Fourier transform spectroscopy (FT-IR), thermogravimetric analysis (TGA), water contact angle measurement, and BSA adsorption properties. Furthermore, the cellular responses to PCL scaffold with and without modification by OCNF were examined by seeding rat bone marrow stem cells (RBMSCs) on the fibrous scaffold for assessing cell attachment, cell viability, and proliferation. Thus, the present study focused on preparation and characterization of a membrane and tubular scaffold with a unique nanostructure, which is an excellent candidate for use as a blood vessel scaffold graft.


Evaluation of cosmetic appearance of herniotomy wound scars in African children: Comparison of tissue glue and subcuticular suturing.
To evaluate the cosmetic appearance of herniotomy wound scars closed using either the tissue glue or subcuticular suturing technique. Prospective randomised control study; randomisation into tissue glue and suturing groups. Ethical clearance obtained. Cosmetic outcome were based on visual analogue scale by parents and Hollander wound evaluation scale by a Plastic Surgeon blinded to the wound closure method. Fifty one wounds were evaluated, 26 in the tissue glue group and 25 in the suturing group. Parents' evaluation using Visual Analogue scale (VAS) showed that in the suturing group, 17 parents (68%) gave a VAS of 8cm while six parents (24%) gave a score of 7cm. Two parents (8%) gave a score of 9cm. In the tissue glue group, 22 parents (84.6%) scored the scar of their children as 8 or 9cm on the VAS while four parents (15.4%) gave a score of 7cm. The median VAS was 8cm for both groups with a range of 7 to 9cm. The Chi- square test showed that the parents preferred tissue glue compared with subcuticular suturing (X2 = 7.90, P < 0.05). The Hollander Wound Evaluation Scale (HWES) used by Plastic Surgeon showed 21 herniotomy wounds (84%) had a score of 6 in the suturing group while four wounds (16%) had a score of 5. In the tissue glue group, 19 wounds (73%) had a score of 6, six wounds (23.1%) had a score of 5 and a patient (3.8%) had a score of 4. The median score is 6 for both groups. There was no statistically significant difference between both groups (X(2) = 1.481, P = 0.393). This study has shown that the cosmetic outcome of wound closure using the tissue glue technique and subcuticular suturing technique are similar.


Family Structure, Residential Mobility, and Environmental Inequality.
This study combines micro-level data on families with children from the Panel Study of Income Dynamics with neighborhood-level industrial hazard data from the Environmental Protection Agency and neighborhood-level U.S. census data to examine both the association between family structure and residential proximity to neighborhood pollution and the micro-level, residential mobility processes that contribute to differential pollution proximity across family types. Results indicate the existence of significant family structure differences in household proximity to industrial pollution in U.S. metropolitan areas between 1990 and 1999, with single-mother and single-father families experiencing neighborhood pollution levels that are on average 46% and 26% greater, respectively, than those experienced by two-parent families. Moreover, the pollution gap between single-mother and two-parent families persists with controls for household and neighborhood socioeconomic, sociodemographic, and race/ethnic characteristics. Examination of underlying migration patterns reveals that single-mother, single-father, and two-parent families are equally likely to move in response to pollution. However, mobile single-parent families move into neighborhoods with significantly higher pollution levels than do mobile two-parent families. Thus, family structure differences in pollution proximity are maintained more by these destination neighborhood differences than by family structure variations in the likelihood of moving out of polluted neighborhoods.


Co-digestion of primary sewage sludge and industrial wastewater under anaerobic sulphate reducing conditions: enzymatic profiles in a recycling sludge bed reactor.
The first stage in the degradation and recycling of primary sewage sludge and particulate organic matter is the solubilisation and enhanced hydrolysis of complex polymeric organic carbon structures associated with the anaerobic sulphidogenic environment. Solubilization of complex carbon substrates provides the primary reaction in the BioSURE Process, and is effected in the recycling sludge bed reactor (RSBR). During the process of anaerobic digestion, macromolecules are broken down into simpler low molecular weight compounds in the presence of extracellular enzymes. Though hydrolysis of the complex carbon sources was enhanced under biosulphidogenic conditions, no studies have examined the role of enzymes and the enzymatic profiles in the RSBR. To investigate the overall enzymology in the RSBR variations in COD, pH, sulphate, sulphite and sulphide concentrations, carbohydrates, protein and activities of glucosidases, proteases and lipases were studied over 50 days in the reactor at three different depths: 0-16 cm; 16-32 cm; 32-50 cm. While the pH profile remained fairly constant between 6.9 and 7.3 the sulphate and sulphide levels, as expected, changed dramatically as sulphate reduction took place. Proteases, lipases and glucosidases all showed enhanced activity with depth in the bioreactor. It is suggested that the increased sulphide concentration generated during the sulphate reduction process stimulates the enzymes, leading to enhanced solubilisation of primary sewage sludge.


Inclusion of a core patient-reported outcomes battery in adolescent and young adult cancer clinical trials.
Disparities in care, treatment-related toxicity and health-related quality of life (HRQoL) for adolescents and young adults (AYAs, aged 15-39 years) with cancer are under-addressed partly because of limited collection of patient-reported outcomes (PROs) in cancer clinical trials (CCTs). The AYA years include key developmental milestones distinct from younger and older patients, and cancer interrupts attainment of critical life goals. Lack of consensus on a standardized approach to assess HRQoL and treatment-related toxicity in AYA CCTs has limited the ability to improve patient outcomes. The National Cancer Institute's Clinical Trials Network AYA PRO Task Force was assembled to reach consensus on a core set of PROs and foster its integration into AYA CCTs. Eight key considerations for selecting the core PRO AYA battery components were identified: relevance to AYAs; importance of constructs across the age continuum; prioritization of validated measures; availability of measures without licensing fees; availability in multiple languages; applicability to different cancer types and treatments; ability to measure different HRQoL domains and toxicities; and minimized burden on patients and sites. The Task Force used a modified Delphi approach to identify key components of the PRO battery. The Patient-Reported Outcomes Measurement Information System (PROMIS) and the PRO Common Terminology Criteria for Adverse Events Measurement System met all criteria and were selected to assess HRQoL and treatment toxicity, respectively. Investigators are rapidly incorporating the recommendations of the Task Force into AYA trials. Inclusion of a standardized assessment of HRQoL and treatment toxicities in AYA CCTs is a vital first step to develop interventions to improve health outcomes for AYAs diagnosed with cancer.


Activation of gene expression by histone deubiquitinase OTLD1.
One of the main mechanisms of epigenetic control is post translational modification of histones, and one of the relatively less characterized, yet functionally important histone modifications is monoubiquitylation, which is reversed by histone deubiquitinases. In Arabidopsis, only two of such enzymes are known to date. One of them, OTLD1, deubiquitylates histone 2B and functions as a transcriptional repressor. But, could the same deubiquitinase act both as a repressor and an activator? Here, we addressed this question. Using gain-of-function and loss-of-function Arabidopsis alleles, we showed that OTLD1 can promote expression of a target gene. This transcriptional activation activity of OTLD1 involves occupation of the target chromatin by this enzyme, deubiquitination of monoubiquitylated H2B within the occupied regions, and formation of the euchromatic histone acetylation and methylation marks. Thus, OTLD1 can play a dual role in transcriptional repression and activation of its target genes. In these reactions, H2B ubiquitylation acts as both a repressive and an active mark whereas OTLD1 association with and deubiquitylation of the target chromatin may represent the key juncture between two opposing effects of this enzyme on gene expression.


Levels of IL-1 beta control stimulatory/inhibitory growth of cancer cells.
Different cellular signaling pathways operate in response to varying levels of IL-1 beta leading to genotoxic damage, cell apoptosis or cell growth. At high levels of IL-1 beta, cells receiving genotoxic insults engage apoptotic pathways. The IL-1 beta over expressing stable MCF7 cell secreting high level of IL-1 beta peptides undergo cell apoptosis. Cotreatment with an inhibitor of IL-1 beta and TNF-alpha synthesis prevented stilbene estrogen-induced lesions. In addition to direct effect of 17 beta-estradiol (E2) on mitochondria and redox cycling of catechol estrogens, E2-induced overexpression of IL-1 beta can produce an increase in the level of ROS. Our recent data showed that MCF7 cell growth and cyclin D1 expression are suppressed by antioxidants and mitochondrial blockers. Stably IL-1 beta transfected cells secreting moderate level of IL-1 beta peptides stimulated the clonal expansion of MCF7 cells. These studies support that in addition to ovarian estrogens, mitogenic signals may also come from TNF-alpha and IL-1 beta-generated O2*- and hydrogen peroxide. Further validation of this concept that the concentrations of the peptide interleukin-1 beta within the cells determine its stimulatory or inhibitory signals regulating the growth of estrogen-dependent tumors might result in novel preventive strategies.


Effects of nerve growth factor on neuronal nitric oxide production after spinal cord injury in rats.
To explore the protective effects of nerve growth factor (NGF) on injured spinal cord. The spinal cord injury (SCI) model of Wistar rats was established by a 10 gx2.5 cm impact force on the T(8) spinal cord. NGF (60 microg/20 microl) was given to the rats of the treatment group immediately and at 2, 4, 8, 12, 24 hours after SCI. The level of neuronal constitutive nitric oxide synthase (ncNOS) and the expression of ncNOS mRNA in the spinal cord were detected by the immunohistochemistry assay and in situ hybridization method. Abnormal expression of ncNOS was detected in the spinal ventral horn motorneuron in injured rats. The levels of ncNOS protein in the NGF group were significantly lower than those in the normal saline group (P<0.05 ). The ncNOS mRNA expression was found in the spinal ventral horn motorneuron in injured rats and the expression in the NGF group was significantly decreased compared with that in the normal saline group (P<<0.01). NGF can protect the injured tissue of the spinal cord by prohibiting abnormal expression of nitric oxide synthase and the neurotoxicity of nitric oxide.


Individuals with agenesis of the corpus callosum show sensory processing differences as measured by the sensory profile.
Given reports of high pain thresholds and reduced auditory response in individuals with agenesis of the corpus callosum (AgCC), this study investigated whether affected participants report atypical experiences and behaviors on a well-established sensory processing measure. Fourteen participants with AgCC (ages 11-59) completed the Adolescent/Adult Sensory Profile (Brown & Dunn, 2001). Sensory profile scales were classified as "Atypical" if they were more than 1 standard deviation from the mean. Fifty-seven percent of participants with AgCC reported reduced sensory registration as compared to an expected 16% of the normative sample. Similarly, 50% of the AgCC participants reported atypically increased auditory processing difficulties. Using a well-established sensory processing questionnaire, participants with AgCC reported measurable differences in multiple aspects of sensory processing. The most notable difference was in the quadrant of low sensory registration, suggesting that individuals with AgCC may require sensory information to be presented more slowly or at a higher intensity for adequate processing. The sensory modality that was most affected was the auditory system, which is consistent with increased rates of language disorders and autism spectrum disorders in this population. Understanding sensory processing in individuals with AgCC can both elucidate the role of interhemispheric transfer in the development of intact sensory processing as well as contribute to our knowledge of the role of the corpus callosum in a range of disorders in which sensory processes are impacted. (PsycINFO Database Record


Immunohistochemical diagnosis of disseminated intravascular coagulation in newborns.
Disseminated intravascular coagulation (DIC) and other clotting abnormalities are common in sick newborn infants who have a variety of conditions. To document evidence of DIC at autopsy, immunoperoxidase staining of fibrin-related antigens (FRA) was used to detect intravascular microthrombi in liver, kidney, and lung from 127 newborns. Patients were selected from seven major disease groups: hyaline membrane disease/bronchopulmonary dysplasia, infection, meconium aspiration, necrotizing enterocolitis, congenital heart disease, other congenital anomalies, and extreme prematurity. Staining for FRA in intravascular microthrombi was seen in 40% of cases studied. The liver showed the highest frequency of intravascular microthrombi, located predominantly in the sinusoids. Unlike the adult kidney, the newborn kidney seldom had evidence of intravascular coagulation. Extravascular staining of FRA was observed in the renal distal tubular epithelium in 48 cases, many of which also had evidence of intravascular FRA staining. No significant differences in FRA staining patterns were seen among the disease groups except for cases of extreme prematurity in which all tissues showed minimal staining. Control tissues from SIDS patients also showed minimal FRA staining. Hepatic sinusoidal staining was the only tissue finding that correlated with thrombocytopenia, a clinical indicator of DIC. Despite the use of this immunohistochemical staining method, discrepancies between the clinical and autopsy diagnosis of DIC remain.


Combining mutations in HIV-1 protease to understand mechanisms of resistance.
HIV-1 develops resistance to protease inhibitors predominantly by selecting mutations in the protease gene. Studies of resistant mutants of HIV-1 protease with single amino acid substitutions have shown a range of independent effects on specificity, inhibition, and stability. Four double mutants, K45I/L90M, K45I/V82S, D30N/V82S, and N88D/L90M were selected for analysis on the basis of observations of increased or decreased stability or enzymatic activity for the respective single mutants. The double mutants were assayed for catalysis, inhibition, and stability. Crystal structures were analyzed for the double mutants at resolutions of 2.2-1.2 A to determine the associated molecular changes. Sequence-dependent changes in protease-inhibitor interactions were observed in the crystal structures. Mutations D30N, K45I, and V82S showed altered interactions with inhibitor residues at P2/P2', P3/P3'/P4/P4', and P1/P1', respectively. One of the conformations of Met90 in K45I/L90M has an unfavorably close contact with the carbonyl oxygen of Asp25, as observed previously in the L90M single mutant. The observed catalytic efficiency and inhibition for the double mutants depended on the specific substrate or inhibitor. In particular, large variation in cleavage of p6(pol)-PR substrate was observed, which is likely to result in defects in the maturation of the protease from the Gag-Pol precursor and hence viral replication. Three of the double mutants showed values for stability that were intermediate between the values observed for the respective single mutants. D30N/V82S mutant showed lower stability than either of the two individual mutations, which is possibly due to concerted changes in the central P2-P2' and S2-S2' sites. The complex effects of combining mutations are discussed.


Clostridium acidurici electron-bifurcating formate dehydrogenase.
Cell extracts of uric acid-grown Clostridium acidurici catalyzed the coupled reduction of NAD(+) and ferredoxin with formate at a specific activity of 1.3 U/mg. The enzyme complex catalyzing the electron-bifurcating reaction was purified 130-fold and found to be composed of four subunits encoded by the gene cluster hylCBA-fdhF2.


Association of plasma vitamin C concentration to total and cause-specific mortality: a 16-year prospective study in China.
Vitamin C insufficiency occurs across many countries and has been hypothesised to increase risk of various diseases. Few prospective studies with measured circulating vitamin C have related deficiency to disease mortality, particularly in low-income and middle-income countries. We randomly selected 948 subjects (473 males and 475 females) aged 53-84 years from a Chinese cohort and measured meta-phosphoric acid-preserved vitamin C concentrations in plasma samples collected in 1999-2000. A total of 551 deaths were accrued from sample collection through 2016, including 141 from cancer, 170 from stroke and 174 from heart diseases. Vitamin C was analysed using season-specific quartiles, as a continuous variable and as a dichotomous variable based on sufficiency status (normal >28 µmol/L vs low ≤28 µmol/L). HRs and 95% CIs were estimated using Cox proportional hazards models. We found significant inverse associations between higher plasma vitamin C concentrations and total mortality in quartile (HRQ4 vs Q10.75, 95% CI 0.59 to 0.95), continuous (HRq20umol/L0.90, 95% CI 0.82 to 0.99) and dichotomous analyses (HRnormal-vs-low0.77, 95% CI 0.63 to 0.95). We observed significant lower risks of heart disease (ptrend-by-quantile=0.03) and cancer deaths (pglobal-across-quantile=0.04) for higher vitamin C, whereas the association was attenuated for stroke in adjusted models. Similar inverse associations were found when comparing normal versus low vitamin C for heart disease (HRnormal-vs-low0.62, 95% CI 0.42 to 0.89). In this long-term prospective Chinese cohort study, higher plasma vitamin C concentration was associated with lower total mortality, heart disease mortality and cancer mortality. Our results corroborate the importance of adequate vitamin C to human health.


Toroidal rotation driven by the polarization drift.
Starting from a phase space conserving gyrokinetic formulation, a systematic derivation of parallel momentum conservation uncovers a novel mechanism by which microturbulence may drive intrinsic rotation. This mechanism, which appears in the gyrokinetic formulation through the parallel nonlinearity, emerges due to charge separation induced by the polarization drift. The derivation and physical discussion of this mechanism will be pursued throughout this Letter.


[Changes of soil enzyme activities in heavy metals polluted region: a case study in a wastewater-irrigated agricultural area near a smelter in Xinluo District of Longyan City, Fujian Province].
Surface soil samples were collected from a wastewater-irrigated agricultural area near a smelter in the Xinluo District of Longyan City, Pujian Province, and their basic physical and chemical properties, activities of urease, cellulase, alkaline phosphomonoesterase, polyphenol oxidase and catalase, and contents of Cu, Cd, Pb and Zn were determined, aimed to approach the effects of heavy metals pollution and soil properties on the activities of soil enzymes. Correlation analysis showed that the total and available contents of soil Cu, Cd, Pb and Zn had significant positive correlations with the activities of soil urease, cellulase, alkaline phosphomonoesterase and polyphenol oxidase, but significant negative correlation with the activity of soil catalase. Soil pH had significant positive correlation with the activity of soil alkaline phosphomonoesterase, and soil silt content had significant negative correlation with the activity of soil catalase. Path analysis showed that Cu, Cd, Pb and Zn pollution promoted the activities of soil urease, cellulase and polyphenol oxidase, but had less effects on the activity of soil alkaline phosphomonoesterase. Soil available Cu, Cd, Pb and Zn didn't directly affect the activity of soil catalase, but indirectly inhibited it significantly. Soil physical and chemical properties had greater effects on soil enzyme activities, e.g., alkaline-hydrolyzable N directly inhibited the activity of soil urease, total P directly stimulated the activities of soil alkaline phosphomonoesterase and catalase and indirectly stimulated the activity of soil cellulase via available P, available P directly promoted the activity of soil cellulase but inhibited the activities of soil alkaline phosphomonoesterase and catalase, total K directly inhibited the activities of soil alkaline phosphomonoesterase and polyphenol oxidase, available K stimulated the activity of soil catalase via available P, and particle composition had significant effects on the activities of soil polyphenol oxidase and catalase. The above results demonstrated that because of the complicated and uncertain relationships between the contents of soil Cd, Pb, Zn and Cu and the activities of the five soil enzymes, it should be cautious to use the test enzyme activities to indicate soil heavy metals pollution.


Changing profile of couples seeking genetic counseling for consanguinity in Australia.
Consanguineous marriage is rare in most Western countries and, for example, in the USA it may be subject to regulation by both civil legislation and religious prescription. This is not the case in many regions of Asia and Africa where marriage within the family is strongly favored. Since the 1970s there has been widespread migration to North America, Western Europe, and Australasia from communities which encourage consanguineous marriage. To assess the effect of this trend on a genetic counseling program, the records of 302 couples referred to Genetic Services of Western Australia for consanguinity counseling were abstracted for the period 1975-2001. Overall, a family history of genetic disease or a previously affected child was reported in 28.8% of cases. Premarital or prepregnancy counseling on grounds of consanguinity was sought by 41.0% of couples, and a further 18.2% of consanguineous couples had been referred because of a consanguineous pregnancy. In 7.6% of cases a relationship closer than first cousin was involved. Through time there was a significant increase in the numbers of consanguineous consultants, and their patterns of religious affiliation and ethnic origin widened markedly. Although effectively excluded from entry to Australia prior to 1975, couples of Asian origin accounted for 25.5% of all consanguineous consultants. With ongoing migration, changes in the ethnic profiles and the specific counseling requirements of consanguineous couples can be expected to continue and probably accelerate.


Safer Conception Methods and Counseling: Psychometric Evaluation of New Measures of Attitudes and Beliefs Among HIV Clients and Providers.
With data from 400 HIV clients with fertility intentions and 57 HIV providers in Uganda, we evaluated the psychometrics of new client and provider scales measuring constructs related to safer conception methods (SCM) and safer conception counselling (SCC). Several forms of validity (i.e., content, face, and construct validity) were examined using standard methods including exploratory and confirmatory factor analysis. Internal consistency was established using Cronbach's alpha correlation coefficient. The final scales consisted of measures of attitudes towards use of SCM and delivery of SCC, including measures of self-efficacy and motivation to use SCM, and perceived community stigma towards childbearing. Most client and all provider measures had moderate to high internal consistency (alphas 0.60-0.94), most had convergent validity (associations with other SCM or SCC-related measures), and client measures had divergent validity (poor associations with depression). These findings establish preliminary psychometric properties of these scales and should facilitate future studies of SCM and SCC.


Back pain in a large Canadian police force.
A survey of a random sample of 1002 members of the Royal Canadian Mounted Police to determine their experience with low back pain. To determine the prevalence of low back pain among Royal Canadian Mounted Police members and to assess the validity of the perception that the patrol car seat and the duty belt are causing a higher rate of low back pain among members of the Royal Canadian Mounted Police than in the general population. Low back pain is a common problem throughout the industrialized world, with reported 1-year prevalence rates between 25% and 62%. Prevalence of low back pain among people who drive motor vehicles for a significant part of the day appears higher than in the general population. Among police officers, 1-year prevalence rates of between 44% and 62% have been reported. A computerized database of 14,897 serving regular members was used to identify a sample of officers on active duty. A low back pain questionnaire was mailed to each selected member, eliciting information regarding their experience with low back pain, their exposure to known and putative risk factors, and their opinions about the contribution of these potential risk factors. The respondents to the questionnaire remained anonymous. The response rate was 80%. The prevalence of "chronic or recurring low back pain since joining the force" was 54.9%, which is comparable with the lifetime prevalence reported for the general population. Of those who reported having back problems, only 8.5% had such problems before joining the force. Seventy-six percent who had low back pain reported having a problem within the last year, giving an overall 1-year prevalence of 41.8%, which is comparable with that for the general population. The a priori assumption that driving or wearing a duty belt contributed to the problem was shared by most police officers surveyed. However, only about half of the members who replied drove for more than half the working day or wore the duty belt. These members had the same prevalence of low back pain as those who did not drive or wear the duty belt. The prevalence of low back pain in this police force is comparable with that in the general population, and driving a patrol car or wearing the duty belt does not appear to influence the prevalence rate in this population.


Smad3 controls β-1,3-glucuronosyltransferase 1 expression in rat nucleus pulposus cells: implications of dysregulated expression in disc disease.
To study the regulation of expression of β-1,3-glucuronosyltransferase 1 (GlcAT-1), an important regulator of glycosaminoglycan (GAG) synthesis, by Smad3 in nucleus pulposus (NP) cells. GlcAT-1 expression was examined in rat NP and anulus fibrosus (AF) cells treated with transforming growth factor β (TGFβ). The effects of Smad signaling and Smad suppression on GlcAT-1 were examined in rat NP cells. GlcAT-1 expression was analyzed in the discs of Smad3-null mice and in degenerated human NP tissue. TGFβ increased the expression of GlcAT-1 in rat NP but not rat AF cells. Suppression of GlcAT-1 promoter activity was evident with dominant-negative ALK-5 (DN-ALK-5). Cotransfection with Smad3 strongly induced promoter activity independent of TGFβ. Bioinformatics analysis indicated the presence of several Smad binding sites in the promoter; deletion analysis showed that the region between -274 and -123 bp was required for Smad3 response. DN-Smad3, Smad 3 small interfering RNA, and Smad7 strongly suppressed basal as well as TGFβ-induced promoter activity. Induction of promoter activity by Smad3 was significantly blocked by DN-Smad3; Smad7 had a very small effect. Lentiviral transduction of NP cells with short hairpin RNA Smad3 resulted in a decrease in GlcAT-1 expression and accumulation of GAG. Compared to wild-type mice, significantly lower expression of GlcAT-1 was seen in the discs of Smad3-null mice. Analysis of degenerated human NP tissue specimens showed no positive correlation between GlcAT-1 and TGFβ expression. Moreover, isolated cells from degenerated human tissue showed a lack of induction of GlcAT-1 expression following TGFβ treatment, suggesting an altered response. Our findings demonstrate that in healthy NP cells, the TGFβ-Smad3 axis serves as a regulator of GlcAT-1 expression. However, an altered responsiveness to TGFβ during disc degeneration may compromise GAG synthesis.