Abnormal maxillary sinus diagnosing on CBCT images via object detection and 'straight-forward' classification deep learning strategy.
Pathological maxillary sinus would affect implant treatment and even result in failure of maxillary sinus lift and implant surgery. However, the maxillary sinus abnormalities are challenging to be diagnosed through CBCT images, especially for young dentists or dentists in grassroots medical institutions without systematical education of general medicine. To develop a deep-learning-based screening model incorporating object detection and 'straight-forward' classification strategy to screen out maxillary sinus abnormalities on CBCT images. The large area of background noise outside maxillary sinus would affect the generalisation and prediction accuracy of the model, and the diversity and imbalanced distribution of imaging manifestations may bring challenges to intellectualization. Thus we adopted an object detection to limit model's observation zone and 'straight-forward' classification strategy with various tuning methods to adapt to dental clinical need and extract typical features of diverse manifestations so that turn the task into a 'normal-or-not' classification. We successfully constructed a deep-learning model consist of well-trained detector and diagnostor module. This model achieved ideal AUROC and AUPRC of 0.953 and 0.887, reaching more than 90% accuracy at optimal cut-off. McNemar and Kappa test verified no statistical difference and high consistency between the prediction and ground truth. Dentist-model comparison test showed the model's statistically higher diagnostic performance than dental students. Visualisation method confirmed the model's effectiveness in region recognition and feature extraction. The deep-learning model incorporating object detection and straightforward classification strategy could achieve satisfying predictive performance for screening maxillary sinus abnormalities on CBCT images.


Gene expression profile of coronary artery cells treated with nonsteroidal anti-inflammatory drugs reveals off-target effects.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have come under scrutiny because of the gastrointestinal, renal, and cardiovascular toxicity associated with prolonged use of these drugs. The purpose of this study was to identify molecular targets for NSAIDs related to cellular toxicity with a view to optimize drug efficacy in the clinic. Coronary artery smooth muscle cells and endothelial cells were treated with low (clinically achievable) and high (typically used in preclinical studies) concentrations of celecoxib, NS398, and ibuprofen for 24 hours. NSAIDs-induced gene expression changes were evaluated by microarray analysis and validated by real-time reverse-transcription polymerase chain reaction and western blotting. The functional significance of differentially expressed genes was evaluated by Ingenuity Pathway Analysis. At high concentrations, NSAIDs altered the expression of genes regulating cell proliferation and cell death. NSAIDs also altered genes associated with cardiovascular functions including inflammation, thrombosis, fibrinolysis, coronary artery disease, and hypertension. The gene expression was most impacted by ibuprofen, celecoxib, and NS398, in that order. This study revealed that NSAIDs altered expression of an array of genes associated with cardiovascular events and emphasizes the potential for fingerprinting drugs in preclinical studies to assess the potential drug toxicity and to optimize the drug efficacy in clinical settings.


Oral health status and dental needs of autistic children and young adults.
Children with autism might need more dental care than non-autistic, healthy children. The aims of this study were: (a) to describe the caries experience and treatment needs of autistic children aged 6-16 years in the United Arab Emirates; and (b) to provide baseline data at national and regional levels to enable comparisons and future planning of dental services for children with autism. All children attending a day centre in Sharjah, United Arab Emirates, for autism were selected for the study. Sixty-one autistic children aged 6-16 years (45 males and 16 females) were included in the study. Each patient received a complete oral and periodontal examination using codes and criteria as described by the World Health Organization. The overall mean for Decayed, Missing, and Filled Teeth/decayed, missing, and filled teeth was 2.4. Female autistic children had significantly higher mean Decayed, Missing, and Filled Teeth/decayed, missing, and filled teeth scores (4.4) than males (1.63). The percentage of decayed, missing, and filled teeth increased with increasing age. The restorative index and met need index for the autistic children aged 11-15 years were 0.02 and 0.10, respectively. Effective oral health promotion strategies need to be implemented to improve the oral health status of autistic children.


Gastropleural Fistula as a Rare Complication of Gastric Sleeve Surgery: A Case Report and Comprehensive Literature Review.
Gastropleural fistula (GPF) is a rare, life-threatening complication of gastric sleeve surgery. GPF is an uncommon differential diagnosis to consider in a patient presenting with a picture of pneumonia. As such, GPF should be suspected in a patient with a history of nonresolving pneumonia who recently underwent gastric sleeve surgery. To the best of our knowledge, only eight cases of gastropleural fistulas after bariatric surgery have been reported in the literature. Herein, we report a case of gastropleural fistula after gastric sleeve surgery and review the pertinent literature. A gastropleural fistula is an exceedingly rare and life-threatening complication postbariatric surgery. Nonsurgical conservative management (total parenteral nutrition, percutaneous drainage, and antibiotics with endoscopic stenting) can be considered.


Psychosocial Analysis of Cancer Survivors in Rural Australia: Focus on Demographics, Quality of Life and Financial Domains.
Cancer treatments can have long-term physical, psychological, financial, sexual and cognitive effects that may influence the quality of life. These can vary from urban to rural areas, survival period and according to the type of cancer. We here aimed to describe demographics and psychosocial analysis of cancer survivors three to five years post-treatment in rural Australia and also assess relationships with financial stress and quality of life domains. In this cross-sectional study, 65 participants visiting the outpatient oncology clinic were given a self-administered questionnaire. The inclusion criteria included three to five years post-treatment. Three domains were investigated using standardised and validated tools such as the Standard Quality of Life in Adult Cancer Survivors Scale (QLACS) and the Personal and Household Finances (HILDA) survey. Included were demographic parameters, quality of life, treatment information and well-being. There was no evidence of associations between any demographic variable and either financial stress or cancer-specific quality of life domains. Financial stress was however significantly associated with the cancer-specific quality of life domains of appearance-related concerns, family related distress, and distress related to recurrence. This unique study effectively points to psychosocial aspects of cancer survivors in rural regions of Australia. Although the majority of demographic characteristics were not been found to be associated with financial stress, this latter itself is significantly associated with distress related to family and cancer recurrence. This finding may be of assistance in future studies and also considering plans to fulfil unmet needs.


[Quantitative description of the process of radiation inactivation of cells. VII. Nature of primary radiation lesions leading to reproductive cell death].
The entity of radiation damage of viruses, bacteria and cells is defined by the organization of genetic structures. Asimmetrical chromosome exchanges have been proposed as the main reason of inactivation of di- and polyploid eukaryotic cells. If a single molecule of DNA is taken for the core of chromosome, the exchange is believed to be a consequence of cross-polymerization of two polypeptid strands of the single DNA molecule. Thus, the double strand break of DNA is necessary to produce aberration. A hypothesis is put forward on the identity of primary lesion of chromosome with the double strand break. The experimental survival curve is approximated according to the formula derived from the model. The yield of primary lesions of chromosomes is proposed to be equal to that of double strand breaks of chromosomes in order to examine the validity of the hypothesis. The optimal interaction distance of primary lesions in correspondence with parameters of the survival curve is equal to 0.8 mkm. This estimation is in good agreement with the microdosimetrical data, and the proposed hypothesis is not contradicted.


In situ forces in the anterior cruciate ligament and its bundles in response to anterior tibial loads.
The anterior cruciate ligament has a complex fiber anatomy and is not considered to be a uniform structure. Current anterior cruciate ligament reconstructions succeed in stabilizing the knee, but they neither fully restore normal knee kinematics nor reproduce normal ligament function. To improve the outcome of the reconstruction, it may be necessary to reproduce the complex function of the intact anterior cruciate ligament in the replacement graft. We examined the in situ forces in nine human anterior cruciate ligaments as well as the force distribution between the anteromedial and posterolateral bundles of the ligament in response to applied anterior tibial loads ranging from 22 to 110 N at knee flexion angles of 0-90 degrees. The analysis was performed using a robotic manipulator in conjunction with a universal force-moment sensor. The in situ forces were determined with no device attached to the ligament, while the knee was permitted to move freely in response to the applied loads. We found that the in situ forces in the anterior cruciate ligament ranged from 12.8 +/- 7.3 N under 22 N of anterior tibial load applied at 90 degrees of knee flexion to 110.6 +/- 14.8 N under 110 N of applied load at 15 degrees of flexion. The magnitude of the in situ force in the posterolateral bundle was larger than that in the anteromedial bundle at knee flexion angles between 0 and 45 degrees, reaching a maximum of 75.2 +/- 18.3 N at 15 degrees of knee flexion under an anterior tibial load of 110 N. The magnitude of the in situ force in the posterolateral bundle was significantly affected by knee flexion angle and anterior tibial load in a fashion remarkably similar to that seen in the anterior cruciate ligament. The magnitude of the in situ force in the anteromedial bundle, in contrast, remained relatively constant, not changing with flexion angle. Significant differences in the direction of the in situ force between the anteromedial bundle and the posterolateral bundle were found only at flexion angles of 0 and 60 degrees and only under applied anterior tibial loads greater than 66 N. We have demonstrated the nonuniformity of the anterior cruciate ligament under unconstrained anterior tibial loads. Our data further suggest that in order for the anterior cruciate ligament replacement graft to reproduce the in situ forces of the normal anterior cruciate ligament, reconstruction techniques should take into account the role of the posterolateral bundle in addition to that of the anteromedial bundle.


Congenital surfactant protein B (SP-B) deficiency: a case report.
The incapacity to synthesize certain components of pulmonary surfactant causes a heterogeneous group of rare respiratory diseases called genetic disorders of surfactant dysfunction. We report a female full-term infant with neonatal respiratory distress of early onset due to inherited SP-B deficiency. The infant failed oxygen weaning at multiple trials. Chest computed tomography was performed on the 29th day of life revealing ground-glass opacities, regular interlobular septal thickening and fine interlobular reticulations. Analysis of genomic DNA showed homozygosity for an extremely rare SFTPB gene variant (c.620A>G, p.Tyr207Cys). Both parents were heterozygotes for the mutation. The diagnosis of congenital SP-B deficiency should be suspected whenever an early and acute respiratory failure in a term or near-term infant does not resolve after five days of age: diagnostic confirmation can be easily and rapidly obtained with the analysis of genomic DNA.


The GDP-switched GAF domain of DcpA modulates the concerted synthesis/hydrolysis of c-di-GMP in Mycobacterium smegmatis.
The second messenger c-di-GMP [bis-(3'-5')-cyclic dimeric guanosine monophosphate] plays a key role in bacterial growth, survival and pathogenesis, and thus its intracellular homeostasis should be finely maintained. Mycobacterium smegmatis encodes a GAF (mammalian cGMP-regulated phosphodiesterases, Anabaenaadenylyl cyclases and Escherichia coli transcription activator FhlA) domain containing bifunctional enzyme DcpA (diguanylate cyclase and phosphodiesterase A) that catalyzes the synthesis and hydrolysis of c-di-GMP. Here, we found that M. smegmatis DcpA catalyzes the hydrolysis of c-di-GMP at a higher velocity, compared with synthetic activity, resulting in a sum reaction from the ultimate substrate GTP to the final product pGpG [5'-phosphoguanylyl-(3'-5')-guanosine]. Fusion with the N-terminal GAF domain enables the GGDEF (Gly-Gly-Asp-Glu-Phe) domain of DcpA to dimerize and accordingly gain synthetic activity. Screening of putative metabolites revealed that GDP is the ligand of the GAF domain. Binding of GDP to the GAF domain down-regulates synthetic activity, but up-regulates hydrolytic activity, which, in consequence, might enable a timely response to the transient accumulation of c-di-GMP at the stationary phase or under stresses. Combined with the crystal structure of the EAL (Glu-Ala-Leu) domain and the small-angle X-ray scattering data, we propose a putative regulatory model of the GAF domain finely tuned by the intracellular GTP/GDP ratio. These findings help us to better understand the concerted control of the synthesis and hydrolysis of c-di-GMP in M. smegmatis in various microenvironments.


A new technique for combined cataract/glaucoma procedures in patients on chronic miotics.
We describe a combined cataract/glaucoma procedure for patients on chronic miotics that includes small-incision phacoemulsification to provide increased predictability of visual outcome and early visual rehabilitation, and an inferior pupilloplasty to facilitate intraoperative visualization. To date, 42 procedures have been performed with excellent results. Complications, although minimal, have included iridolenticular/iridocapsular adhesions, diplopia, rupture of 10-0 polypropylene sutures, peripheral anterior synechia, hyphema, and fibrinoid aqueous.


Vitamin D deficiency in patients with active systemic lupus erythematosus.
We investigated the effects of disease activity on bone metabolism in 36 patients with systemic lupus erythematosus (SLE). Changes in bone remodeling were not explained by corticosteroid use. A high prevalence of 25OHD deficiency in SLE patients indicates the need for vitamin D replacement, mainly during high disease activity periods. We investigated the effects of SLE disease activity on bone metabolism, their relation to inflammatory cytokines and vitamin D levels. We performed a cross-sectional analysis of 36 SLE patients classified according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in high activity (group I: 12 patients, mean age 29.6 years) or in minimal activity (group II: 24 patients, mean age 30.0 years), and compared them to normal controls (group III: 26 women, 32.8 years). Serum calcium, phosphorus, parathyroid and sex hormones, bone remodeling markers, interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), IL-1, tumor necrosis factor-alpha (TNF), 25-hydroxivitamin D (25OHD), and 1,25-dihydroxyvitamin D3 were measured, plus bone mineral density. All cytokines were significantly higher in SLE groups; IL-6 could differentiate SLE patients from controls. In group I, 25OHD levels were lower (P < 0.05), which was related to the SLEDAI (R = -0.65, P < 0.001). In multiple regression analysis, the 25OHD level was associated with SLEDAI, osteocalcin and bone-specific alkaline phosphatase. The SLEDAI score was positively correlated with all measured cytokines and especially TNF (R = 0.75, P < 0.001). SLE patients demonstrated changes in bone remodeling strongly related to disease activity. A high prevalence of 25OHD deficiency was observed in SLE patients, indicating the need for vitamin D replacement.


Osteotomies through a fusion mass in the lumbar spine.
Flat-back syndrome is one of the main causes of surgical failure after lumbar fusion and can lead to a revision surgery to correct it. Three-column pedicle subtraction osteotomy is an efficient technique to restore lumbar lordosis (LL) for fixed sagittal malalignment. The fusion mass stemming from the past surgeries makes the procedure demanding as most anatomical landmarks are missing. This review article will focus on the correction of this lack of LL through the fusion mass. We will successively review the preoperative management, the surgical specificities, and various types of clinical cases that can be encountered in flat-back syndromes. PSO in the fixed fusion mass is technically demanding. Preoperative CT-scan and preoperative navigation allow us to push the limits when anatomical landmarks disappear. Bleeding and neurologic are the two major complications feared by the surgeon. The best way to avoid these revision surgeries is to restore a proper lumbar lordosis at the time of initial surgery by considering lumbo-pelvic indexes.


Mechanisms of replication-deficient vaccinia virus/T7 RNA polymerase hybrid expression: effect of T7 RNA polymerase levels and alpha-amanitin.
Components of the eukaryotic vaccinia virus/T7 RNA polymerase hybrid expression system were assessed using recombinant and nonrecombinant forms of modified vaccinia Ankara (MVA), a replication-deficient vaccinia virus strain. Recombinant MVA virus expressing T7 RNA polymerase (Wyatt, L. S., Moss, B., and Rozenblatt, S. (1995). Virology 210, 202-205) stimulated high levels of expression from a T7 promoter-chloramphenicol acetyltransferase (CAT) reporter. Most, but not all, of the virally induced expression was T7 RNA polymerase and T7 promoter dependent, with no viral enhancement of translation of T7 transcripts. The efficacy of supplying T7 RNA polymerase expression from nonviral sources was evaluated using a self-amplifying T7 RNA polymerase autogene or an inducible T7 RNA polymerase expression vector. The latter modes yielded CAT activity dependent on T7 RNA polymerase expression; however, expression required viral factors independent of T7 RNA polymerase and did not reach that attained using the recombinant virus. In further experiments, MVA-induced T7 RNA polymerase expression was upregulated by alpha-amanitin, an inhibitor of eukaryotic polymerases. This indicates that MVA/T7 RNA polymerase hybrid expression may be rendered still more efficient by ameliorating transcriptional interference due to an alpha-amanitin-sensitive eukaryotic factor(s).


Information upper bound for McKean-Vlasov stochastic differential equations.
We develop an information-theoretic framework to quantify information upper bound for the probability distributions of the solutions to the McKean-Vlasov stochastic differential equations. More precisely, we derive the information upper bound in terms of Kullback-Leibler divergence, which characterizes the entropy of the probability distributions of the solutions to McKean-Vlasov stochastic differential equations relative to the joint distributions of mean-field particle systems. The order of information upper bound is also figured out.


Fraud and abuse provisions in the Health Insurance Portability and Accountability Act: a guide to the new act for physicians.
The Health Insurance Portability and Accountability Act, many provisions of which became effective on January 1, 1997, will have a significant impact in the area of health care fraud and abuse. This article examines the fraud and abuse provisions of the new act from the point of view of the practicing physician. The greatest impact on the health care provider will come from the increased enforcement resources which will be available as a result of the act. The act also contains some particular substantive additions to health care fraud and abuse law which will be applicable to physicians, including provisions penalizing health care fraud, wrongful disclosure of individually identifiable health information, false certification for home care, and false statement to a health benefit program.


Crystal Structure and Photocatalytic Activity of Al-Doped TiO2 Nanofibers for Methylene Blue Dye Degradation.
Al-TiO2 nanofibers were prepared using a sol-gel derived electrospinning by varying the Al/Ti molar ratio from 0 to 0.73 to investigate the effect of Al doping on the crystal structure and the photocatalytic activity of Al-TiO2 for methylene blue (MB) degradation. XRD results indicated that as the Al/Ti molar ratio rose, crystal structure of Al-TiO2 was changed from anatase/rutile (undoped), anatase (0.07-0.18), to amorphous phase (0.38-0.73), which was confirmed by XPS and Raman analysis. The degradation kinetic constant increased from 7.3 x 10(-4) min(-1) to 4.5 x 10(-3) min(-1) with the increase of Al/Ti molar ratios from 0 to 0.38, but decreased to 3.4 x 10(-3) min(-1) when the Al/Ti molar ratio reached 0.73. The Al-TiO2 catalyst doped with 0.38 Al/Ti molar ratio demonstrated the best MB degradation. Experimental results indicated that the Al doping in Al-TiO2 was mainly attributed to the crystal structure of TiO2 and the photocatalytic degradation of MB.


Bilingual deep dysphasia.
We report B.R.B., a bilingual Turkish-English speaker with deep dysphasia. B.R.B. shows the typical pattern of semantic errors in repetition with effects of lexicality and imageability on performance in both languages. The question we asked is whether language type (Turkish or English) or language status--that is, first acquired (L1) or second acquired (L2)--has a greater impact on performance. Results showed that repetition in L1 (Turkish) was better than that in L2 (English). We also observed effects of language status on oral reading, writing to dictation, and naming (spoken and written) with greater impairment to repetition than other tasks in both languages. An additional finding was that spoken-word translation in both directions was worse than written-word translation, and word class had an effect on translation from L1 to L2. We argue that interactive activation models of deep dysphasia could explain deep dysphasia in bilingual speakers and interactions between task and language, if the weighted connections that support language processing in L2 are assumed to be weaker, thus causing rapid phonological decay to have more impact on task performance in L2. Implications of the results for models of bilingual language processing are also considered.


Mitochondrial regulation of macrophage cholesterol homeostasis.
This review explores the relationship between mitochondrial structure and function in the regulation of macrophage cholesterol metabolism and proposes that mitochondrial dysfunction contributes to loss of the elegant homeostatic mechanisms which normally maintain cellular sterol levels within defined limits. Mitochondrial sterol 27-hydroxylase (CYP27A1) can generate oxysterol activators of liver X receptors which heterodimerise with retinoid X receptors, enhancing the transcription of ATP binding cassette transporters (ABCA1, ABCG1, and ABCG4), that can remove excess cholesterol via efflux to apolipoproteins A-1, E, and high density lipoprotein, and inhibit inflammation. The activity of CYP27A1 is regulated by the rate of supply of cholesterol substrate to the inner mitochondrial membrane, mediated by a complex of proteins. The precise identity of this dynamic complex remains controversial, even in steroidogenic tissues, but may include steroidogenic acute regulatory protein and the 18 kDa translocator protein, together with voltage-dependent anion channels, ATPase AAA domain containing protein 3A, and optic atrophy type 1 proteins. Certainly, overexpression of StAR and TSPO proteins can enhance macrophage cholesterol efflux to apoA-I and/or HDL, while perturbations in mitochondrial function, or changes in the expression of mitochondrial fusion proteins, alter the efficiency of cholesterol efflux. Molecules which can sustain or improve mitochondrial function or increase the activity of the protein complex involved in cholesterol transfer may have utility in resolving the problem of dysregulated macrophage cholesterol homeostasis, a condition which may contribute to inflammation, atherosclerosis, nonalcoholic steatohepatitis, osteoblastic bone resorption, and some disorders of the central nervous system.


Analysis of efficacy and prognostic factors of lenalidomide treatment as part of a Dutch compassionate use program.
To obtain efficacy and safety data on lenalidomide treatment outside of clinical trials, we analyzed the clinical data of 114 patients with refractory or relapsed multiple myeloma treated with lenalidomide on a compassionate use basis. The recommended treatment consisted of lenalidomide 25 mg given on days 1-21 of a 28-day cycle, in combination with dexamethasone. A median of 3 previous lines of therapy were given, including thalidomide in 91%. Most patients were treated until progression or intolerable toxicity. The median number of cycles was 7 (range, 1-21+ cycles) with a maximum response after a median of 3 cycles (range, 1-10 cycles). The overall response rate was 69%, including complete response in 6%, very good partial response in 19%, and partial response in 44%. The response rate was not influenced by previous thalidomide and/or bortezomib treatment. The median time to progression (TTP) was 9 months and the median overall survival (OS) was 22 months. A significantly longer TTP was observed in patients who previously underwent allogeneic stem cell transplantation (12.5 months vs. 8 months; P = .036). Overall survival was significantly affected by performance status (P < .0001). Lenalidomide toxicity was predominantly hematologic (37%; Common Toxicity Criteria > or = 3) and the incidence of venous thrombotic events was low (5%) using the recommended prophylaxis. This analysis confirms that, outside clinical prospective trials, treatment with lenalidomide is highly effective and feasible in heavily pretreated patients with multiple myeloma.


Increased pulmonary toxicity with bleomycin and cisplatin chemotherapy combinations.
Combination chemotherapy that included bleomycin and cisplatin was administered to 45 evaluable patients (30 with cervix carcinoma and 15 with germ cell tumors). Bleomycin was given, following cisplatin infusion, either by intravenous continuous infusion over 72 h (germ cell tumor patients) or intramuscularly every 12 h for 4 days (cervix carcinoma patients). Total bleomycin doses ranged from 156 to 360 U. Nine patients with normal renal function and no previous pulmonary disease prior to chemotherapy developed serious pulmonary toxicity. Six patients died from irreversible respiratory failure. Postmortem lung studies were performed in all six patients and revealed findings compatible with bleomycin-induced lung toxicity. Renal tubular damage was found in four kidneys available for examination. Five (71.5%) of the seven patients whose serum creatinine increased after chemotherapy was initiated developed lung injury, whereas 10.5% of those without change in the serum creatinine level presented this complication (p = 0.001). Renal damage, following cisplatin administration, with subsequent accumulation of bleomycin was the likely cause of the high lung toxicity. Extreme caution is recommended in the administration of combined bleomycin-cisplatin chemotherapy. Whenever possible, bleomycin should precede cisplatin infusion to minimize the risk of lung toxicity.


Oroantral fistula after a zygomaticomaxillary complex fracture.
Zygomaticomaxillary complex (ZMC) fractures account for a substantial proportion of trauma cases. The most frequent complications of maxillofacial fracture treatment are infections and soft tissue flap dehiscence. Postoperative infections nearly always resolve in response to oral antibiotics and local wound care. However, a significant infection can cause a permanent fistula. A 52-year-old man visited our clinic to treat an oroantral fistula (OAF), which was a late complication of a ZMC fracture. Postoperatively, the oral suture site dehisced, exposing the absorbable plate. However, he did not seek treatment. After 5 years, an OAF formed with a 2.0× 2.0 cm bony defect on the left maxilla. We completely excised the OAF, harvested a piece of corticocancellous bone from the iliac crest, inserted the harvested bone into the defect, and covered the soft tissue defect with a buccal mucosal transposition flap. Although it is necessary to excise OAFs, the failure rate is higher for large OAFs (> 5 mm in diameter) because of the extensive defect in the underlying bone that supports the overlying flap. Inappropriate management of postoperative wounds after a ZMC fracture can lead to disastrous outcomes, as in this case. Therefore, proper postoperative treatment and follow-up are essential.


Extended-therapy duration for chronic hepatitis C, genotype 1: the long and the short of it.
With pegylated interferon and ribavirin, more than half of all chronically-infected hepatitis C patients can achieve a sustained virologic response; however, patients with genotype 1 infections and those with other poor prognostic factors have relatively inferior treatment response rates. Since new therapies are still years away from approval, it is incumbent upon providers to maximize the therapeutic efficacy of today's treatment. The later the virus is undetectable in serum during treatment, the less likely it will be eradicated. Patients with a delayed or slow virologic response to therapy (at least a 2-log(10) decrease in baseline hepatitis C RNA yet detectable viremia at 12 wk of therapy and undetectable virus 12 wk subsequently) may, therefore, benefit from an extended therapy course beyond one of standard duration. Although higher rates of treatment discontinuation may plague this approach, 72 wk of treatment for genotype 1-infected slow-responders may improve response rates and diminish relapse rates relative to those of 48 wk. Based on data from both viral kinetic and clinical studies, therapy prolongation in slow responders may be a reasonable strategy to improve response rates in these treatment-refractory patients.


Postprandial decrease in LDL-cholesterol in men with metabolic syndrome.
In some epidemiological studies, blood lipids are determined at non-fasting state, which may impact cardiovascular risk estimation. The aim of this study was to evaluate postprandial LDL-C changes in men with newly diagnosed metabolic syndrome (MetSy). 36 male patients were examined: 12 men with and 24 men without MetSy. The fat tolerance test was performed before and after a three-month hypolipidemic treatment. Serum lipids were measured using routine methods, lipid peroxides (LPO) colorimetrically, apolipoproteins A-I, B, and hsCRP immunoturbidimetrically. The postprandial increase in triglycerides was associated with a decrease in LDL-C and a small decrease in apo B. In men with MetSy, the mean change in LDL-C (-19.5 ± 2.3 mg/dl) was greater than in healthy men (-5.7 ± 3.8 mg/dl). All lipid changes (ΔTG, ΔLDL-C and ΔLPO) were linearly dependent on the postprandial non-LDL-cholesterol. After three months of hypolipidemic treatment, in all men with MetSy, the apoB/apoA-I ratio remained the same as before the therapy. In men diagnosed with MetSy, postprandial decreases in LDL-cholesterol may cause underestimation of cardiovascular risk. After three months of hypolipidemic treatment, there was only a partial reduction in this risk, as the apoB/apoA-I ratio remained the same.


Tetra- versus Pentavalent Inhibitors of Cholera Toxin.
The five B-subunits (CTB5) of the Vibrio cholerae (cholera) toxin can bind to the intestinal cell surface so the entire AB5 toxin can enter the cell. Simultaneous binding can occur on more than one of the monosialotetrahexosylganglioside (GM1) units present on the cell surface. Such simultaneous binding arising from the toxins multivalency is believed to enhance its affinity. Thus, blocking the initial attachment of the toxin to the cell surface using inhibitors with GM1 subunits has the potential to stop the disease. Previously we showed that tetravalent GM1 molecules were sub-nanomolar inhibitors of CTB5. In this study, we synthesized a pentavalent version and compared the binding and potency of penta- and tetravalent cholera toxin inhibitors, based on the same scaffold, for the first time. The pentavalent geometry did not yield major benefits over the tetravalent species, but it was still a strong inhibitor, and no major steric clashes occurred when binding the toxin. Thus, systems which can adopt more geometries, such as those described here, can be equally potent, and this may possibly be due to their ability to form higher-order structures or simply due to more statistical options for binding.


Functional Properties of Natural Products and Human Health.
Natural products (NPs), broadly defined as chemicals produced by living organisms including microbes, marine organisms, animals, fungi and plants, are widely used as therapeutic agents for treating diseases and maintaining health and "wellness" [...].


[Analysis of indications for 3528 Cesarean sections based on sixteen years of clinical material (177-1992)].
Analysis was subjected on 3528 cesarean sections made in I Obstetric and Gynecology Clinic Academy of Medicine in Bytom between 1977-1992. At the drop in general number of deliveries there were noticed upward tendencies in percentage of cesarean sections but during last two years this increase was inhibited. The ratio of sudden and planned indications determined by us as index of indications (N/P) oscillated from 0.16 to 0.31. Among sudden indications imminent intrauterine fetus asphyxia was noticed most often and among planned indications state after cesarean section and loss of progress of delivery.


The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies.
Over the last 20 years, iron oxide nanoparticles (IONPs) have been the subject of increasing investigation due to their potential use as theranostic agents. Their unique physical properties (physical identity), ample possibilities for surface modifications (synthetic identity), and the complex dynamics of their interaction with biological systems (biological identity) make IONPs a unique and fruitful resource for developing magnetic field-based therapeutic and diagnostic approaches to the treatment of diseases such as cancer. Like all nanomaterials, IONPs also interact with different cell types in vivo, a characteristic that ultimately determines their activity over the short and long term. Cells of the mononuclear phagocytic system (macrophages), dendritic cells (DCs), and endothelial cells (ECs) are engaged in the bulk of IONP encounters in the organism, and also determine IONP biodistribution. Therefore, the biological effects that IONPs trigger in these cells (biological identity) are of utmost importance to better understand and refine the efficacy of IONP-based theranostics. In the present review, which is focused on anti-cancer therapy, we discuss recent findings on the biological identities of IONPs, particularly as concerns their interactions with myeloid, endothelial, and tumor cells. Furthermore, we thoroughly discuss current understandings of the basic molecular mechanisms and complex interactions that govern IONP biological identity, and how these traits could be used as a stepping stone for future research.


[Metastatic breast cancer in the uterine cervix: two cases of a rare occurrence].
Authors report on the recurrence of breast cancer to the uterine cervix in two patients. In the first patient the tumor recurrence was suspected by cytology 43 months after she was cured for breast cancer. An ultrasound examination revealed the recurrence in the second patient who have been cured for the breast cancer for 53 months. The final diagnoses was proved by cervical conisation in the first patient and by hysterectomy in the second one. Authors call attention for the possibility of the rare site of symptom free recurrence.


Absence of glucagon and insulin action reveals a role for the GLP-1 receptor in endogenous glucose production.
The absence of insulin results in oscillating hyperglycemia and ketoacidosis in type 1 diabetes. Remarkably, mice genetically deficient in the glucagon receptor (Gcgr) are refractory to the pathophysiological symptoms of insulin deficiency, and therefore, studies interrogating this unique model may uncover metabolic regulatory mechanisms that are independent of insulin. A significant feature of Gcgr-null mice is the high circulating concentrations of GLP-1. Hence, the objective of this report was to investigate potential noninsulinotropic roles of GLP-1 in mice where GCGR signaling is inactivated. For these studies, pancreatic β-cells were chemically destroyed by streptozotocin (STZ) in Gcgr(-/-):Glp-1r(-/-) mice and in Glp-1r(-/-) animals that were subsequently treated with a high-affinity GCGR antagonist antibody that recapitulates the physiological state of Gcgr ablation. Loss of GLP-1 action substantially worsened nonfasting glucose concentrations and glucose tolerance in mice deficient in, and undergoing pharmacological inhibition of, the GCGR. Further, lack of the Glp-1r in STZ-treated Gcgr(-/-) mice elevated rates of endogenous glucose production, likely accounting for the differences in glucose homeostasis. These results support the emerging hypothesis that non-β-cell actions of GLP-1 analogs may improve metabolic control in patients with insulinopenic diabetes.


Mechanics of membrane fusion.
Diverse membrane fusion reactions in biology involve close contact between two lipid bilayers, followed by the local distortion of the individual bilayers and reformation into a single, merged membrane. We consider the structures and energies of the fusion intermediates identified in experimental and theoretical work on protein-free lipid bilayers. On the basis of this analysis, we then discuss the conserved fusion-through-hemifusion pathway of merger between biological membranes and propose that the entire progression, from the close juxtaposition of membrane bilayers to the expansion of a fusion pore, is controlled by protein-generated membrane stresses.


Barriers of West African women scientists in their research and academic careers: A qualitative research.
This study aims to identify barriers to the professional advancement of women researchers in West Africa. This was a descriptive, observational, cross-sectional qualitative study conducted between June and September 2020 in five West African countries (Ghana, Senegal, Burkina Faso, Niger and Mali). Interviews were conducted with 21 female and 9 male health researchers by video call. After transcription, the data was thematically analysed using an inductive process. Four themes associated with barriers to women's careers development were identified. First. was family- and environmental-related barriers. Gender norms that assign domestic tasks and responsibilities to women reduced the time they were able to dedicate to research. Second was gender insensitive organisational culture and institutional policies that deepened gender disparities and made it more difficult for women to attain leadership positions. Third was the need for women in research to undergo emancipation programs to strengthen their resilience and ability to make critical decisions as strategic approaches to address the challenges faced by women in the academia were a lot more focused on addressing their relationship with their spouse. Forth, was the individual intermediate perception of professional and personal success which for many women, they perceive themselves as competent as their male counterparts and should not be subject to the gender discrimination they experience. The web created between work-life and home-life for West African women researchers mainly as a result of the gender inequalities in the social structure will require more medium- and long-term strategic planning by institutional authorities to reduce gender disparities in research and academia. This work has highlighted the influence of family and social life on the professional lives of West African women researchers. The study could help contribute to the development of gender equality interventions for the career development of women researchers in West Africa.


Impact of stepwise ablation on the biatrial substrate in patients with persistent atrial fibrillation and heart failure.
Ablation of persistent atrial fibrillation can be challenging, often involving not only pulmonary vein isolation (PVI) but also additional linear lesions and ablation of complex fractionated electrograms (CFE). We examined the impact of stepwise ablation on a human model of advanced atrial substrate of persistent atrial fibrillation in heart failure. In 30 patients with persistent atrial fibrillation and left ventricular ejection fraction ≤35%, high-density CFE maps were recorded biatrially at baseline, in the left atrium (LA) after PVI and linear lesions (roof and mitral isthmus), and biatrially after LA CFE ablation. Surface area of CFE (mean cycle length ≤120 ms) remote to PVI and linear lesions, defined as CFE area, was reduced after PVI (18.3±12.03 to 10.2±7.1 cm(2); P<0.001) and again after linear lesions (7.7±6.5 cm(2); P=0.006). Complete mitral isthmus block predicted greater CFE reduction (P=0.02). Right atrial CFE area was reduced by LA ablation, from 25.9±14.1 to 12.9±11.8 cm(2) (P<0.001). Estimated 1-year arrhythmia-free survival was 72% after a single procedure. Incomplete linear lesion block was an independent predictor of arrhythmia recurrence (hazard ratio, 4.69; 95% confidence interval, 1.05-21.06; P=0.04). Remote LA CFE area was progressively reduced following PVI and linear lesions, and LA ablation reduced right atrial CFE area. Reduction of CFE area at sites remote from ablation would suggest either regression of the advanced atrial substrate or that these CFE were functional phenomena. Nevertheless, in an advanced atrial fibrillation substrate, linear lesions after PVI diminished the target area for CFE ablation, and complete lesions resulted in a favorable clinical outcome.


A Patient-Centered Approach to Guide Follow-Up and Adjunctive Testing and Treatment after First Rib Resection for Venous Thoracic Outlet Syndrome Is Safe and Effective.
Controversies in the treatment of venous thoracic outlet syndrome (VTOS) have been discussed for decades, but still persist. Calls for more objective reporting standards have pushed practice towards comprehensive venous evaluations and interventions after first rib resection (FRR) for all patients. In our practice, we have relied on patient-centered, patient-reported outcomes to guide adjunctive treatment and measure success. Thus, we sought to investigate the use of thrombolysis versus anticoagulation alone, timing of FRR following thrombolysis, post-FRR venous intervention, and FRR for McCleery syndrome (MCS) and their impact on patient symptoms and return to function. All patients undergoing FRR for VTOS at our institution from 4 April 2000 through 31 December 2013 were reviewed. Demographics, symptoms, diagnostic and treatment details, and outcomes were collected. Per "Reporting Standards of the Society for Vascular Surgery for Thoracic Outlet Syndrome", symptoms were described as swelling/discoloration/heaviness, collaterals, concomitant neurogenic symptoms, and functional impairment. Patient-reported response to treatment was defined as complete (no residual symptoms and return to function), partial (any residual symptoms present but no functional impairment), temporary (initial improvement but subsequent recurrence of any symptoms or functional impairment), or none (persistent symptoms or functional impairment). Sixty FRR were performed on 59 patients. 54.2% were female with a mean age of 34.3 years. Swelling/discoloration/heaviness was present in all but one patient, deep vein thrombosis in 80%, and visible collaterals in 41.7%. Four patients had pulmonary embolus while 65% had concomitant neurogenic symptoms. In addition, 74.6% of patients were anticoagulated and 44.1% also underwent thrombolysis prior to FRR. Complete or partial response occurred in 93.4%. Of the four patients with temporary or no response, further diagnostics revealed residual venous disease in two and occult alternative diagnoses in two. Use of thrombolysis was not related to FRR outcomes (p = 0.600). Performance of FRR less than or greater than six weeks after the initiation of anticoagulation or treatment with thrombolysis was not related to FRR outcomes (p = 1). Whether patients had DVT or MCS was not related to FRR outcomes (p = 1). No patient had recurrent DVT. From a patient-centered, patient-reported standpoint, VTOS is equally effectively treated with FRR regardless of preoperative thrombolysis or timing of surgery after thrombolysis. A conservative approach to venous interrogation and intervention after FRR is safe and effective for symptom control and return to function. Additionally, patients with MCS are effectively treated with FRR.


Respiratory symptoms, lung function, and nasal cellularity in Indonesian wood workers: a dose-response analysis.
It was hypothesised that inflammation plays a dominant part in the respiratory effects of exposure to wood dust. The purpose of this study was to relate the nasal inflammatory responses of workers exposed to meranti wood dust to (a) levels of exposure, (b) respiratory symptoms and (c) respiratory function. A cross sectional study was carried out in 1997 in a woodworking plant that used mainly meranti, among 982 workers exposed to different concentrations of wood dust. Personal sampling (n=243) of inhalable dust measurements indicated mean exposure in specific jobs, and enabled classification of 930 workers in three exposure classes (<2, 2-5, and >5 mg/m(3)) based on job title. Questionnaires were used to screen respiratory symptoms in the entire population. Lung function was measured with two different techniques, conventional flow-volume curves and the forced oscillation technique. Nasal lavage was done to assess inflammation in the upper respiratory tract. A negative trend between years of employment and most flow-volume variables was found in men, but not in women workers. Current exposure, however, was not related to spirometric outcomes, respiratory symptoms, or nasal cellularity. Some impedance variables were related to current exposure but also with better function at higher exposure. Exposure to meranti wood dust did not cause an inflammation in the upper respiratory tract nor an increase of respiratory symptoms or decrease of lung function. These data do not corroborate the hypothesis that inflammation plays a part in airway obstruction induced by wood dust.


Female submissiveness, nonverbal behavior, and body boundary definition.
Previous studies in the United States have suggested that submissive women may be more vulnerable to criminal victimization because they present certain cues of vulnerability. Richards, Rollerson, and Phillips (1991) observed that submissive women exhibited more controlled body movements and more body-concealing clothing than did dominant women. Our purpose here was to determine whether such variability might be due to differences in body boundary definition. The results revealed no significant difference in the body boundary indicators of dominant and submissive subjects but did suggest that highly feminine women are more likely to have weak body boundaries than are more androgynous women.


Polyoma middle T-induced vascular tumor formation: the role of the plasminogen activator/plasmin system.
The middle T antigen of murine Polyomavirus (PymT) rapidly transforms endothelial cells, leading to the formation of vascular tumors in newborn mice. Transformed endothelial (End.) cell lines established from such tumors exhibit altered proteolytic activity as a result of increased expression of urokinase-type plasminogen activator (uPA) and are capable of inducing vascular tumors efficiently when injected into adult mice. In this study we have used mice lacking components of the PA/plasmin system to analyze the role of this system in the transformation process and in tumor growth. We found that the proteolytic status of the host is not a critical determinant for PymT-induced vascular tumor formation. In addition, the lack of either uPA or tissue-type PA (tPA) activity is not limiting for the establishment and proliferation of End. cells in vitro, although the combined loss of both PA activities leads to a marked reduction in proliferation rates. Furthermore, the in vitro morphogenetic properties of mutant End. cells in fibrin gels could only be correlated with an altered proteolytic status in cells lacking both uPA and tPA. However, in contrast with tumors induced by PymT itself, the tumorigenic potential of mutant and wild-type End. cell lines was found to be highly dependent on the proteolytic status of both the tumor cells and the host. Thus, genetic alterations in the PA/plasmin system affect vascular tumor development, indicating that this system is a causal component in PymTmediated oncogenesis.


Optimal regulation of tumour-associated neutrophils in cancer progression.
In a tumour microenvironment, tumour-associated neutrophils could display two opposing differential phenotypes: anti-tumour (N1) and pro-tumour (N2) effector cells. Converting N2 to N1 neutrophils provides innovative therapies for cancer treatment. In this study, a mathematical model for N1-N2 dynamics describing the cancer survival and immune inhibition in response to TGF-β and IFN-β is considered. The effects of exogenous intervention of TGF-β inhibitor and IFN-β are examined in order to enhance N1 recruitment to combat tumour progression. Our approach employs optimal control theory to determine drug infusion protocols that could minimize tumour volume with least administration cost possible. Four optimal control scenarios corresponding to different therapeutic strategies are explored, namely, TGF-β inhibitor control only, IFN-β control only, concomitant TGF-β inhibitor and IFN-β controls, and alternating TGF-β inhibitor and IFN-β controls. For each scheme, different initial conditions are varied to depict different pathophysiological condition of a cancer patient, leading to adaptive treatment schedule. TGF-β inhibitor and IFN-β drug dosages, total drug amount, infusion times and relative cost of drug administrations are obtained under various circumstances. The control strategies achieved could guide in designing individualized therapeutic protocols.


Influence of aggregation and relative humidity on longevity of unfed bush tick, Haemaphysalis longicornis Neumann (Acari: Ixodidae).
The survival of all stages of Haemaphysalis longicornis was investigated at different densities and at 3 levels of relative humidity. Larvae survived longer when the density was higher, or the size of a cluster was larger, or both. However, in nymphs and adults, there was no significant relationship between the density and the survival period. Moreover, in nymphs and adults, there was no positive relationship between the size of the aggregation and tick longevity, except for 2 nymphs/vial in high humidity. These results suggest that the advantage gained from a higher density, or from taking part in a cluster, or both, differed between stages. Furthermore, the fact that the survival period of larvae and nymphs was influenced by cohort suggests that a maternal effect, as well as aggregation, influences the survival of immature ticks.


[Nitrogen metabolism of Streptomyces antibioticus on media with various glucose contents].
The dynamics of the glutamine synthetase and glutamate dehydrogenase activity was studied during cultivation of Str. antibioticus on media with different contents of glucose and ammonium sulfate. No correlation between the enzymes activity and the levels of oleandomycin production by the mycelium was observed. It was shown that the levels of oleandomycin biosynthesis repression by glucose did not depend on ammonium sulfate concentration in the medium.


Interaction-induced shift of the cyclotron resonance of graphene using infrared spectroscopy.
We report a study of the cyclotron resonance (CR) transitions to and from the unusual n=0 Landau level (LL) in monolayer graphene. Unexpectedly, we find the CR transition energy exhibits large (up to 10%) and nonmonotonic shifts as a function of the LL filling factor, with the energy being largest at half filling of the n=0 level. The magnitude of these shifts, and their magnetic field dependence, suggests that an interaction-enhanced energy gap opens in the n=0 level at high magnetic fields. Such interaction effects normally have a limited impact on the CR due to Kohn's theorem [W. Kohn, Phys. Rev. 123, 1242 (1961)], which does not apply in graphene as a consequence of the underlying linear band structure.


Frequency of cross-fertilization in the human malaria parasite Plasmodium falciparum.
Two clones of the human malaria parasite Plasmodium falciparum, denoted 3D7 and HB3, were grown in vitro under conditions permitting the development of gametocytes. The two clones differ in their allelic forms of two antigen genes MSP1 and MSP2. The alleles can be distinguished as size differences of polymerase chain reaction (PCR) amplified fragments of repetitive regions of each gene. Mosquitoes (Anopheles stephensi) were fed on a mixture of these gametocytes. A total of 128 oocysts was isolated from the midguts of infected mosquitoes from 9 crossing experiments between the clones. DNA extracted from these oocysts was amplified by PCR. Oocysts which contained both alleles of each gene (MSP1 and MSP2) had developed from heterozygotes produced by cross-fertilization events between 3D7 and HB3 gametes. The remaining oocysts contained single alleles of each gene, in parent clone combinations, and these had developed from homozygotes formed by self-fertilizations. The results suggest that gametes in the original mixture fed to mosquitoes had undergone random mating.


Continuous Ligand-Free Catalysis Using a Hybrid Polymer Network Support.
Although the pharmaceutical and fine chemical industries primarily utilize batch homogeneous reactions to carry out chemical transformations, emerging platforms seek to improve existing shortcomings by designing effective heterogeneous catalysis systems in continuous flow reactors. In this work, we present a versatile network-supported palladium (Pd) catalyst using a hybrid polymer of poly(methylvinylether-alt-maleic anhydride) and branched polyethyleneimine for intensified continuous flow synthesis of complex organic compounds via heterogeneous Suzuki-Miyaura cross-coupling and nitroarene hydrogenation reactions. The hydrophilicity of the hybrid polymer network facilitates the reagent mass transfer throughout the bulk of the catalyst particles. Through rapid automated exploration of the continuous and discrete parameters, as well as substrate scope screening, we identified optimal hybrid network-supported Pd catalyst composition and process parameters for Suzuki-Miyaura cross-coupling reactions of aryl bromides with steady-state yields up to 92% with a nominal residence time of 20 min. The developed heterogeneous catalytic system exhibits high activity and mechanical stability with no detectable Pd leaching at reaction temperatures up to 95 °C. Additionally, the versatility of the hybrid network-supported Pd catalyst is demonstrated by successfully performing continuous nitroarene hydrogenation with short residence times (<5 min) at room temperature. Room temperature hydrogenation yields of >99% were achieved in under 2 min nominal residence times with no leaching and catalyst deactivation for more than 20 h continuous time on stream. This catalytic system shows its industrial utility with significantly improved reaction yields of challenging substrates and its utility of environmentally-friendly solvent mixtures, high reusability, scalable and cost-effective synthesis, and multi-reaction successes.


Modelling Pathological Narcissism Using the Brief PNI in Terms of Structure and Convergent and Divergent Validity: A New Perspective.
The Pathological Narcissism Inventory (PNI) is a popular measure and the first to attempt to tap into both grandiose and vulnerable narcissism (GN/VN). However, data have raised questions as to whether it appropriately formulates GN and differentiates it from VN. In this study, we examined the Brief-PNI's structure and construct validity, by using a novel model based on the theoretical notion of GN and VN sharing core features. Participants (N = 1,061) completed the Brief-PNI, and psychological distress and social avoidance questionnaires. Results showed a better fit and differentiation of GN and VN for a model with cross-loading of shared first-order factors on GN and VN, compared with the traditional PNI structure. We concluded that the Brief-PNI can offer an appropriate formulation and differentiation of VN and GN, provided that their shared variance is considered.


ANALYSIS OF GENOTYPIC DIFFERENCES IN DEVELOPMENTAL STABILITY IN ANNONA CHERIMOLA.
The genetic basis of developmental stability, measured as asymmetry (fluctuating asymmetry in leaves), was analyzed in leaves and flowers of cherimoya (Annona cherimola Mill) and atemoya (A. cherimola × A. squamosa). The individuals analyzed belonged to a controlled collection of cultivars (clones) that had previously been characterized by means of isozymes. We used a nested design to analyze the differences in asymmetry at several sampling levels: individual leaves and flowers, individual trees, and genotypes. The clonal repeatability of developmental stability was not significantly different from zero, thus suggesting the absence of heritability of the asymmetry for leaves and flowers under these environmental conditions. No relationship between asymmetry and individual heterozygosity was found, but leaf fluctuating asymmetry was significantly related to particular isozymic genes. Petal and leaf size showed a phenotypically plastic response to the exposure zone of the tree (mainly due to light). Leaf fluctuating asymmetry also showed such a plastic response. No significant correlation was found between asymmetry and any pomological characters (some of these being fitness related). Finally, the hybrid species (atemoya) did not show larger developmental instability than did the parental species (cherimoya). All these data show that cherimoya asymmetry reveals the random nature of developmental noise, with developmental stability for leaves being possibly related to specific chromosome regions, but with weak evidence for genotypic differences in developmental stability.


Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives.
Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease characterized by the progressive death of motor neurons, leading to paralysis and death. It is a rare disease characterized by high patient-to-patient heterogeneity, which makes its study arduous and complex. Extracellular vesicles (EVs) have emerged as important players in the development of ALS. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargo through the secretion of EVs, even in distant tissues. Importantly, owing to their nature and composition, EVs' formation and cargo can be exploited for better comprehension of this elusive disease and identification of novel biomarkers, as well as for potential therapeutic applications, such as those based on stem cell-derived exosomes. This review highlights recent advances in the identification of the role of EVs in ALS etiopathology and how EVs can be promising new therapeutic strategies.


Absolute ethanol embolotherapy for hemangioma with Kasabach-Merritt syndrome.
This report describes a female baby having a hemangioma over the right thigh that had appeared as an irregular bruise since two days old. Severe thrombocytopenia, consumptive coagulopathy, anemia, and heart failure developed at three months old. With a diagnosis of Kasabach-Merritt syndrome, systemic corticosteroid, vincristine, subcutaneous alpha-interferon, and massive plate transfusion were given. However, the platelet count remained low and the skin lesion enlarged gradually. Trans-feeding-arterial embolotherapy with a 5 ml pure ethanol (1 ml/kg) injection was performed at four months of age. Thirty days later, her platelet count recovered and the hemangioma shrunk in size. This case illustrates that absolute ethanol embolotherapy is an effective treatment for hemangioma with Kasabach-Merritt syndrome and may be life-saving for those with lesions refractory to medical therapy.


Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide.
The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn(2+), suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn(2+)-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn(2+)-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn(2+)-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.


Effect of calcium hydroxide-treated Prevotella nigrescens on the gene expression of matrix metalloproteinase and its inhibitor in MG63 cells.
The purpose of this study was to monitor the expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) produced by an osteoblastic cell line MG63 stimulated with Prevotella nigrescens lipopolysaccharides (LPS), and to compare the level of secretion before and after the P. nigrescens LPS was treated with calcium hydroxide [Ca(OH)2]. The underlying hypothesis is that the balance between MMP and TIMP secretion is the key to an understanding of the host degradative pathways involved in the pathogenesis of bacterial derived pulpal and periapical diseases. Confluent monolayers of MG63 human osteosarcoma cells were exposed to varying concentrations of P. nigrescens or Escherichia coli LPS. Alternately, confluent cultures were exposed to 10 microg/ml of bacterial LPS pretreated with Ca(OH)2 (12.5 mg/ml) for 72 hours. At the end of the experimental period, total RNA was extracted and real-time quantitative polymerase chain reaction (PCR) was performed for MMP-1, TIMP-1, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The results showed that the expression of MMP-1 mRNA was low and invariant for the experimental period in the negative controls. However, exposure to P. nigrescens LPS increased expression after 48 hours. Expression of TIMP-1 mRNA was highly increased at 24 and 48 hours with lower concentrations of LPS in contrast to a suppression with a concentration of 10 microg/ml. Treatment of P. nigrescens LPS with Ca(OH)2 resulted in a down-regulation of MMP-1, whereas pretreated E. coli LPS demonstrated no stimulatory activity for MMP-1 gene expression. Both types of LPS when pretreated with Ca(OH)2 induced slightly up-regulated expression of TIMP-1.


Next-generation sequencing virulome analysis of a Yersinia enterocolitica subsp. palearctica bioserotype 4/O:3 ST18 isolated from human blood in Brazil.
Yersinia enterocolitica is a widespread Gram-negative bacterium that causes gastrointestinal disease and other clinical manifestations in humans. Potentially pathogenic Y. enterocolitica has been isolated in Brazil, from human, environmental, food, and animal sources. Herein we report a genome sequence of Y. enterocolitica subsp. palearctica strain YE 19, serotype O:3, biotype 4, sequence type 18, with virulence determinants isolated from human blood in Rio de Janeiro in 2005. The results corroborate other findings that this strain harbors a set of virulence determinants that could play a role in host pathoadaptation and may also justify the successful dissemination of bioserotype 4/O:3 in Brazil. The presence of strains harboring all of these virulence genes in Brazil is a potential threat to young children and immunocompromised individuals, for whom yersiniosis are a significant source of morbidity and mortality. The results of a genomic data analysis will help understand the virulence of Brazilian strains and provide data for Y. enterocolitica studies worldwide.


[Clinical research of electroacupuncture at acupoints of qijie area combined with spine balance-regulating massage on posterior circulation ischemia].
To compare the clinical efficacy difference between electroacupuncture (EA) at qijie area combined with spine balance-regulating massage and medication for posterior circulation ischemia (PCI). One hundred cases of PCI were randomly divided into a treatment group (50 cases) and a medication group (50 cases). The treatment group was treated with EA at Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Shenshu (BL 23), Danzhong (CV 17), etc. in qijie area combined with spine muscle-relieving massage and comprehensive chiropractic. The medication group was treated with oral administration of nimodipine (30 mg per time, three treatments per day) and vinpocetine injection with 500 mL of glucose injection or intravenous drip of 500 mL 0.9% sodium chloride injection, once a day. Ten treatments were taken as one course in both groups, and two courses were given. The symptom score, mean resistance index (RI) of vertebral artery (VA) and basilar artery (BA), mean velocity of blood flow (Vm) and comprehensive clinical efficacy were compared before and after treatment in two groups. The cured and markedly effective rate was 79.6% (39/49) in the treatment group, which was superior to 54.7% (23/42) in the medication group (P<0.05). The symptom score was both significantly improved after treatment in two groups (both P<0.05), which was more obvious in the treatment group (P<0.05). The RI of VA and BA, Vm of VA and BA were significantly improved after treatment in two groups (all P<0.05), which were more obvious in the treatment group (all P<0.05). The electroacupuncture combined with spine balance-regulating massage has superior effect on improving mean velocity of blood flow and resistance index of vertebral artery and basilar artery as well as symptom score to medication, and is believed to be a safe and effective treatment for posterior circulation ischemia.


Comparison of Machine-Learning Algorithms for the Prediction of Current Procedural Terminology (CPT) Codes from Pathology Reports.
Pathology reports serve as an auditable trial of a patient's clinical narrative, containing text pertaining to diagnosis, prognosis, and specimen processing. Recent works have utilized natural language processing (NLP) pipelines, which include rule-based or machine-learning analytics, to uncover textual patterns that inform clinical endpoints and biomarker information. Although deep learning methods have come to the forefront of NLP, there have been limited comparisons with the performance of other machine-learning methods in extracting key insights for the prediction of medical procedure information, which is used to inform reimbursement for pathology departments. In addition, the utility of combining and ranking information from multiple report subfields as compared with exclusively using the diagnostic field for the prediction of Current Procedural Terminology (CPT) codes and signing pathologists remains unclear. After preprocessing pathology reports, we utilized advanced topic modeling to identify topics that characterize a cohort of 93,039 pathology reports at the Dartmouth-Hitchcock Department of Pathology and Laboratory Medicine (DPLM). We separately compared XGBoost, SVM, and BERT (Bidirectional Encoder Representation from Transformers) methodologies for the prediction of primary CPT codes (CPT 88302, 88304, 88305, 88307, 88309) as well as 38 ancillary CPT codes, using both the diagnostic text alone and text from all subfields. We performed similar analyses for characterizing text from a group of the 20 pathologists with the most pathology report sign-outs. Finally, we uncovered important report subcomponents by using model explanation techniques. We identified 20 topics that pertained to diagnostic and procedural information. Operating on diagnostic text alone, BERT outperformed XGBoost for the prediction of primary CPT codes. When utilizing all report subfields, XGBoost outperformed BERT for the prediction of primary CPT codes. Utilizing additional subfields of the pathology report increased prediction accuracy across ancillary CPT codes, and performance gains for using additional report subfields were high for the XGBoost model for primary CPT codes. Misclassifications of CPT codes were between codes of a similar complexity, and misclassifications between pathologists were subspecialty related. Our approach generated CPT code predictions with an accuracy that was higher than previously reported. Although diagnostic text is an important source of information, additional insights may be extracted from other report subfields. Although BERT approaches performed comparably to the XGBoost approaches, they may lend valuable information to pipelines that combine image, text, and -omics information. Future resource-saving opportunities exist to help hospitals detect mis-billing, standardize report text, and estimate productivity metrics that pertain to pathologist compensation (RVUs).


MAP kinase phosphatase-1--a new player at the nexus between sarcopenia and metabolic disease.
Sarcopenia, which is defined by the loss of skeletal muscle mass, predisposes skeletal muscle to metabolic dysfunction which can precipitate metabolic disease. Similarly, overnutrition, which is a major health problem in modern society, also causes metabolic dysfunction in skeletal muscle and predisposition to metabolic disease. It is now the prevailing view that both aging and overnutrition negatively impact skeletal muscle metabolic homeostasis through deleterious effects on the mitochondria. Accordingly, interplay between the molecular pathways implicated in aging and overnutrition that induce mitochondrial dysfunction are apparent. Recent work from our laboratory has uncovered the stress-responsive mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) as a new player in the regulation of metabolic homeostasis in skeletal muscle and mitochondrial dysfunction caused by overnutrition. These observations raise the intriguing possibility that MKP-1 may function as a common target in the convergence between sarcopenia and overnutrition in a pathophysiological pathway that leads to a loss of skeletal muscle mitochondrial function. With the increasing aging population it will become more important to understand how MKP-1, and possibly other phosphatases, operate at the nexus between sarcopenia and metabolic disease.


Diagnosis of Alzheimer's disease with Electroencephalography in a differential framework.
This study addresses the problem of Alzheimer's disease (AD) diagnosis with Electroencephalography (EEG). The use of EEG as a tool for AD diagnosis has been widely studied by comparing EEG signals of AD patients only to those of healthy subjects. By contrast, we perform automated EEG diagnosis in a differential diagnosis context using a new database, acquired in clinical conditions, which contains EEG data of 169 patients: subjective cognitive impairment (SCI) patients, mild cognitive impairment (MCI) patients, possible Alzheimer's disease (AD) patients, and patients with other pathologies. We show that two EEG features, namely epoch-based entropy (a measure of signal complexity) and bump modeling (a measure of synchrony) are sufficient for efficient discrimination between these groups. We studied the performance of our methodology for the automatic discrimination of possible AD patients from SCI patients and from patients with MCI or other pathologies. A classification accuracy of 91.6% (specificity = 100%, sensitivity = 87.8%) was obtained when discriminating SCI patients from possible AD patients and 81.8% to 88.8% accuracy was obtained for the 3-class classification of SCI, possible AD and other patients.


Female genital mutilation and childbirth.
The practice of female genital mutilation sadly remains to this day, part of the life of many women worldwide. In the Middle East and Africa, it is hard to practice obstetrics and gynecology without some knowledge of the condition. This review is an attempt to discuss the salient points as regards to management of these women during pregnancy and labor.


Gluten content of medications.
The establishment of a database for the identification of the presence of gluten in excipients of prescription medications is described. While resources are available to ascertain the gluten content of a given medication, these resources are incomplete and often do not contain a source and date of contact. The drug information service (DIS) at Robert Wood Johnson University Hospital (RWJUH) determined that directly contacting the manufacturer of a product is the best method to determine the gluten content of medications. The DIS sought to establish a resource for use within the institution and create directions for obtaining this information from manufacturers to ensure uniformity of the data collected. To determine the gluten content of a medication, the DIS analyzed the manufacturer's package insert to identify any statement indicating that the product contained gluten or inactive ingredients from known sources of gluten. If there was any question about the source of an inactive ingredient or if no information about gluten content appeared in the package insert, the manufacturer of the particular formulation of the queried medication was contacted to provide clarification. Manufacturers' responses were collected, and medications were categorized as "gluten free," "contains gluten," or "possibly contains gluten." To date, the DIS at RWJUH has received queries about 84 medications and has cataloged their gluten content. The DIS at RWJUH developed a database that categorizes the gluten status of medications, allowing clinicians to easily identify drugs that are safe for patients with celiac disease.


The force control and path planning of electromagnetic induction-based massage robot.
Massage robot is considered as an effective physiological treatment to relieve fatigue, improve blood circulation, relax muscle tone, etc. The simple massage equipment quickly spread into market due to low cost, but they are not widely accepted due to restricted massage function. Complicated structure and high cost caused difficulties for developing multi-function massage equipment. This paper presents a novel massage robot which can achieve tapping, rolling, kneading and other massage operations, and proposes an improved reciprocating path planning algorithm to improve massage effect. The number of coil turns, the coil current and the distance between massage head and yoke were chosen to investigate the influence on massage force by finite element method. The control system model of the wheeled massage robot was established, including control subsystem of the motor, path algorithm control subsystem, parameter module of the massage robot and virtual reality interface module. The improved reciprocating path planning algorithm was proposed to improve regional coverage rate and massage effect. The influence caused by coil current, the number of coil turns and the distance between massage head and yoke were simulated in Maxwell. It indicated that coil current has more important influence compared to the other two factors. The path planning simulation of the massage robot was completed in Matlab, and the results show that the improved reciprocating path planning algorithm achieved higher coverage rate than the traditional algorithm. With the analysis of simulation results, it can be concluded that the number of coil turns and the distance between the moving iron core and the yoke could be determined prior to coil current, and the force can be controllable by optimizing structure parameters of massage head and adjusting coil current. Meanwhile, it demonstrates that the proposed algorithm could effectively improve path coverage rate during massage operations, therefore the massage effect can be improved.


Temporal alterations of immunohistochemical findings in polymyositis.
To investigate the pathological mechanisms of polymyositis, we performed immunohistochemical analyses with biopsied muscles. Comparative studies using specimens obtained from the same patient enabled us to analyze the pathological alterations at different sequential clinical phases without taking into account each immunogenetic difference. Expression of MHC (major histocompatibility complex) antigens, especially ectopic MHC-class-II antigens, in muscle fibers and infiltrating T-cells were shown to increase concomitantly with the clinically observed exacerbation. Moreover, other observations seem to support the possibilities that 1) administration of steroids lowers the number of invading CD8-positive cells, 2) induction of MHC-class-I antigens in muscle fibers precedes the inflammatory cell infiltration and that 3) remaining MHC-class-I antigens in muscle fibers may explain the recurrence of myositis often observed in the follow up period.


Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder.
Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P < 0.05) was significantly enriched for candidates previously studied in ADHD or treatment outcome. We prioritised the nominally significant SNPs by functional annotation and expression quantitative trait loci (eQTL) analysis in human brain, and we identified 33 SNPs tagging cis-eQTL in 32 different loci (referred to as eSNPs and eGenes, respectively). Pathway enrichment analyses revealed an over-representation of genes involved in nervous system development and function among the eGenes. Categories related to neurological diseases, psychological disorders and behaviour were also significantly enriched. We subsequently meta-analysed the association with clinical outcome for the 33 eSNPs across the discovery sample and an independent cohort of 189 ADHD adult patients (target sample) and we detected 15 suggestive signals. Following this comprehensive strategy, our results provide a better understanding of the molecular mechanisms implicated in MPH treatment effects and suggest promising candidates that may encourage future studies.


Clinical application of a new cone-beam computerized tomography system to assess multiple two-dimensional images for the preoperative treatment planning of maxillary implants: case reports.
Accurate assessment of the location of the maxillary sinuses, incisive canal, and nasal cavity, as well as the height, width, and angulation of bone is essential for implant treatment planning. The purpose of this study was to introduce the clinical application of a cone-beam computerized tomography system (Ortho-CT) to assess multiple two-dimensional (2D) images for the preoperative treatment planning of maxillary implants. To evaluate the multiple 2D images scanned using the Ortho-CT system the maxillary region placed with radiopaque template in the maxilla. Ortho-CT images provided useful information for evaluating the morphology of the maxilla, for locating the incisive canal, maxillary sinuses, nasal cavity, and for showing the relationship of the template to the bone. It is concluded that the Ortho-CT system is a useful aid for diagnosis and treatment planning for maxillary implant treatment.


Factors Affecting Survival and Future Foaling Rates in Thoroughbred Mares with Hydrops.
Prognosis for life and future fertility in broodmares following hydrops is reportedly good, but evidence to support these reports is limited. The objective of this case series was to describe the prognosis for survival and fertility in mares presented to a referral hospital following diagnosis of hydrops. Medical records were reviewed to identify mares diagnosed with hydrops. Data collected included history (gestation, sire of the foal), clinical findings at presentation and throughout hospitalization (complications, treatments, survival to discharge) and future foaling rates. Thirty mares were presented for hydrops between 2009 and 2019. Ninety percent (27/30) of mares survived (94.7% [18/19] hydrallantois, 75% [6/8] hydramnios) and 95% (20/21) of mares successfully had a future foal, of which 75% (15/21) had a foal the following year. There was no reoccurrence of hydrops. Mares managed with transcervical gradual fluid drainage demonstrated higher survival rate compared to those not managed with transcervical drainage (100% with vs. 78.6% without). The most frequent complications observed in mares that did not survive included hypovolemic shock (n = 7), hemorrhage (n = 4) and laminitis (n = 3). Complications observed in mares not returning to breeding included hypovolemic shock and hemorrhage. Causes of non-survival included peritonitis secondary to abdominal wall rupture or uterine tear, and tibial fracture. These results suggest that prognosis for survival and future fertility following a diagnosis of hydrops is good, provided the hydrops is diagnosed and treated appropriately with no damage to the reproductive tract or abdominal wall.


Improved convergence in block copolymer self-consistent field theory by Anderson mixing.
A modification to real space polymeric self-consistent field theory algorithms that greatly improves the convergence properties is presented. The method is based on Anderson mixing [D. G. Anderson, J. Assoc. Comput. Mach. 12, 547 (1965)], and each iteration computed takes negligibly longer to perform than with other methods, but the number of iterations required to reach a high accuracy solution is greatly reduced. No a priori knowledge of possible phases is required to apply this method. We apply our approach to a standard diblock copolymer melt, and demonstrate iteration reductions of more than a factor of 5 in some cases.


Matrix metalloproteinases and their tissue inhibitors in the developing neonatal mouse uterus.
Postnatal development of the mouse uterus involves differentiation and development of the endometrial glands as well as the myometrium. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in extracellular matrix breakdown and morphogenesis of many epitheliomesenchymal organs. As a first step to understanding their roles in postnatal mouse uterine development, MMPs and TIMPs found to be expressed in the neonatal mouse uterus by microarray analysis were localized by in situ hybridization. The MMP-2 mRNA was detected only in the uterine stroma, whereas the MMP-10 mRNA was present only in the uterine epithelium from Postnatal Day (PND) 3 to PND 9. All other MMPs (MMP-11, MMP-14, and MMP-23) as well as TIMP-1, TIMP-2, and TIMP-3 were detected in both epithelial and stromal cells of the endometrium, but not in the myometrium. Uterine extracts were then analyzed by gelatin and casein gel zymography to detect active gelatinases and stromelysins, respectively. Five major gelatinase bands of activity were detected and inhibited by the MMP inhibitors, EDTA or 1,10-phenanthroline, but not by PMSF, a serine protease inhibitor. Western blot analysis confirmed the presence of MMP-2 and MMP-9 proteins in the uterus. Immunoreactive MMP-9 protein was detected only in the endometrial stroma, whereas immunoreactive MMP-2 protein was detected in both the stroma and epithelium of the uterus. Casein zymography detected three major bands of activity ( approximately 54, 63, and 80 kDa) that were inhibited by the serine protease inhibitor, PMSF, but not by the MMP inhibitors, EDTA or 1,10-phenanthroline, suggesting that they were serine proteases. These results support the hypothesis that MMPs and TIMPs regulate postnatal development of the mouse uterus.


Clinical utility of a computed tomography-based receiver operating characteristic curve model for the diagnosis of COVID-19.
The outbreak of COVID-19 poses a major and urgent threat to global public health. CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. This study aimed to retrospectively analyze abnormal lung changes following initial computed tomography (CT) among patients with coronavirus disease 2019 (COVID-19) in Yunnan, and to evaluate the effectiveness of a chest CT-based model for the diagnosis of COVID-19. One hundred and nine patients with COVID-19 pneumonia confirmed with the positive new coronavirus nucleic acid antibody who exhibited abnormal findings on initial CT were retrospectively analyzed. Thereafter, changes in the number, distribution, shape, and density of the lesions were observed. Further, the epidemiological, clinical, and CT imaging findings (+/-) were correlated. Following univariate and multivariate logistic regression analysis, receiver operating characteristic (ROC) curves were generated for significant factors, and models were established to evaluate the diagnostic ability of CT for COVID-19. Our results showed significant differences between patients with COVID-19 in epidemiological history (first, second, and third generation), clinical type (moderate, severe, and critical), and abnormal CT imaging characteristics (+/-) (P<0.05). Moreover, significant differences in abnormal CT imaging characteristics, including region, extent, and focus, were observed between the first generation and the other generations (P<0.05). For the diagnosis of COVID-19, the areas under the ROC curves for logistic regression models 1, 2, and 3 were 0.8016 (95% CI: 0.6759-0.9274), 0.9132 (95% CI: 0.8571-0.9693), and 0.9758 (95% CI: 0.9466-1), respectively. The ROC curve regression model based on chest CT signs displayed a high diagnostic value for COVID-19.


Viruses with Circular Single-Stranded DNA Genomes Are Everywhere!
Circular single-stranded DNA viruses infect archaea, bacteria, and eukaryotic organisms. The relatively recent emergence of single-stranded DNA viruses, such as chicken anemia virus (CAV) and porcine circovirus 2 (PCV2), as serious pathogens of eukaryotes is due more to growing awareness than to the appearance of new pathogens or alteration of existing pathogens. In the case of the ubiquitous human circular single-stranded DNA virus family Anelloviridae, there is still no convincing direct causal relation to any specific disease. However, infections may play a role in autoimmunity by changing the homeostatic balance of proinflammatory cytokines and the human immune system, indirectly affecting the severity of diseases caused by other pathogens. Infections with CAV (family Anelloviridae, genus Gyrovirus) and PCV2 (family Circoviridae, genus Circovirus) are presented here because they are immunosuppressive and affect health in domesticated animals. CAV shares genomic organization, genomic orientation, and common features of major proteins with human anelloviruses, and PCV2 DNA may be present in human food and vaccines.


Short-term ascorbic acid deficiency does not impair antioxidant status in lens of guinea pigs.
We examined whether short-term ascorbic acid deficiency impairs antioxidant status in the lens of guinea pigs. Male guinea pigs aged 4 wk were given a scorbutic diet (20 g/animal per day) with and without ascorbic acid (400 mg/animal per day) in drinking water for 3 wk. The ascorbic acid-deficient group showed no lens opacity. The ascorbic acid-deficient group had 14% of serum ascorbic acid concentration, 6% of aqueous humor ascorbic acid concentration, and 18% of lens ascorbic acid content in the ascorbic acid-adequate group. There were no differences in the contents of lens reduced glutathione and thiobarbituric acid reactive substances, an index of lipid peroxidation, between the ascorbic acid-deficient and adequate groups, while the deficient group had higher lens vitamin E content than the adequate group. The ascorbic acid-deficient group had higher serum vitamin E concentration than the ascorbic acid adequate group, while there were no differences in the concentrations of serum reduced glutathione and tiobarbituric acid reactive substances between the deficient and adequate groups. These results indicate that short-term ascorbic acid deficiency does not impair antioxidant status in the lens of guinea pigs despite induction of severe ascorbic acid depletion in the tissue, which may result in no cataract formation.


Risk of diabetes with fibrates and statins: a pharmacoepidemiological study in VigiBase®.
In contrast to statins, the risk of diabetes with fibrates was not clearly studied. This study investigates a putative signal of diabetes associated with the use of fibrates using the World Health Organization (WHO) global individual case safety reports database, VigiBase® . We included all reports registered until the 31st December 2017 in VigiBase® to measure the risk of reporting 'hyperglycemia or new onset of diabetes' (SMQ term) compared with all other reports [as a reporting odds ratio (ROR 95% CI)] for fibrates, statins, and the combination fibrates + statins. The likelihood that diabetes resulted from statin-fibrate interaction was also estimated. According to the interaction additive model, a ROR value for coexposure exceeding the sum of the RORs estimated for each individual class of drug supports a potential drug-drug interaction (DDI). To assess the stability of our results, we performed several sensitivity analyses, according to outcome definition and after exclusion of putative competitive (hyperglycemic) drugs. We included 19 149 patients exposed to fibrates (without statins), 177 323 to statins (without fibrates) and 3 247 to statins plus fibrates. In contrast to statins (ROR = 1.75, 95% CI 1.72-1.78), no association was found for fibrates (ROR = 0.76, 95% CI 0.71-0.82). The ROR value was lower for the combination statins plus fibrates (ROR = 1.46, 95% CI 1.28-1.67). Similar trends were found in sensitivity analyses. This study, performed in the real conditions of use, failed to find a signal of diabetes with fibrates. It strengths the association previously described with statin without any evidence for a statin-fibrate DDI.


Resilience as a Mediator of the Association Between Perceived Stigma and Quality of Life Among People With Inflammatory Bowel Disease.
Background: Improving Quality of Life (QOL) is an essential objective in the management of inflammatory bowel disease. An accumulating body of research has been conducted to explore the association between perceived stigma and QOL among patients with chronic illness. Still, underlying mechanisms behind this pathway have not been thoroughly examined. Objective: To investigate (a) the effect of perceived stigma on QOL among patients with inflammatory bowel disease; and (b) the mediating role of resilience in the association between perceived stigma and QOL. Methods: This cross-sectional study included a convenient sample of patients diagnosed with inflammatory bowel disease from four tertiary hospitals in Jiangsu Province, China. Patients completed the Perceived Stigma Scale in Inflammatory Bowel Disease (PSS-IBD), the Resilience Scale for Patients with Inflammatory Bowel Disease (RS-IBD), and the Inflammatory Bowel Disease Questionnaire (IBDQ). A bootstrapping analysis was implemented using the SPSS macro PROCESS. Results: A total of 311 patients with Cohn's disease and ulcerative colitis participated in this study, and 57.6% were men. The mean disease duration was 3.51 ± 1.04 years. Approximately 40% of the sample exceeded the criterion score for moderate stigma. Patients who perceived moderate or severe stigma reported lower QOL compared with those with mild stigma. After controlling for sociodemographic and clinical variables, we observed that perceived stigma was negatively associated with resilience. Moreover, resilience was found to mediate the relationship between perceived stigma and all aspects of QOL. Conclusions: These findings suggested that QOL of patients with inflammatory bowel disease was associated with perceived stigma and resilience and identified the mediating effects of resilience in the relationship between perceived stigma and QOL. Furthermore, this suggests that integrating intervention techniques to target resilience into the QOL improvement program of individuals with perceived stigma is possible.


[Aortic disease in Marfan syndrome: current role of surgery and thoracic endovascular aortic repair].
Aortic disease is the most life-threatening complication of Marfan syndrome. Over the last decades, improved medical management and surgical results of prophylactic aortic interventions on the aortic root have dramatically increased expectancy of life in Marfan syndrome patients. As a result, the number of Marfan syndrome patients requiring secondary interventions on the thoracic or thoraco-abdominal aorta due to development of aortic disease or new type B dissection, has substantially increased. In this setting, open surgical interventions represent the treatment of choice. Nevertheless, the available literature, although restricted to small case series, indicates that endovascular repair is a feasible treatment option leading to satisfactory short-term results and may provide a bridging role to definitive open reconstruction. The aim of this paper was to review surgical and endovascular outcomes of aortic disease in Marfan syndrome.