Comparative effect of topical silicone gel and topical tretinoin cream for the prevention of hypertrophic scar and keloid formation and the improvement of scars.
Numerous modalities have been used to treat keloids and hypertrophic scars; however, optimal treatment has not yet been established. Therefore, prevention is the mainstay. Recently, silicone gel and tretinoin cream have been shown to be useful for the prevention of hypertrophic scars and keloids. However, there has been no comparative study of the two topical agents thus far. To determine and compare the effectiveness of silicone gel and tretinoin cream for the prevention of hypertrophic scars and keloids resulting from postoperative wounds and for scar improvement. This study included 26 patients with 44 different wounds. The postoperative wounds were divided into two treatment groups and one control group. The patients in the first and second treatment group applied silicone gel and tretinoin cream, respectively, twice a day on their wounds after their stitches were removed. In contrast, the control group patients did not apply anything. We used the Modified Vancouver Scar Scale to quantitatively examine the effectiveness of silicone gel and tretinoin cream just after stitches removal, and at 4, 8, 12 and 24 weeks after removal of the stitches. The silicone gel and tretinoin cream effectively prevented hypertrophic scars and keloids and improved scar effects in the two treatment groups compared with those in the control group. However, no significant difference was noted between the two treatment groups. To prevent hypertrophic scars and keloids and improve scars after surgery, application of a silicone gel or a tretinoin cream to the wounds is needed.


Human mobility variations in response to restriction policies during the COVID-19 pandemic: An analysis from the Virus Watch community cohort in England, UK.
Since the outbreak of COVID-19, public health and social measures to contain its transmission (e.g., social distancing and lockdowns) have dramatically changed people's lives in rural and urban areas globally. To facilitate future management of the pandemic, it is important to understand how different socio-demographic groups adhere to such demands. This study aims to evaluate the influences of restriction policies on human mobility variations associated with socio-demographic groups in England, UK. Using mobile phone global positioning system (GPS) trajectory data, we measured variations in human mobility across socio-demographic groups during different restriction periods from Oct 14, 2020 to Sep 15, 2021. The six restriction periods which varied in degree of mobility restriction policies, denoted as "Three-tier Restriction," "Second National Lockdown," "Four-tier Restriction," "Third National Lockdown," "Steps out of Lockdown," and "Post-restriction," respectively. Individual human mobility was measured with respect to the time period people stayed at home, visited places outside the home, and traveled long distances. We compared these indicators across the six restriction periods and across socio-demographic groups. All human mobility indicators significantly differed across the six restriction periods, and the influences of restriction policies on individual mobility behaviors are correlated with socio-demographic groups. In particular, influences relating to mobility behaviors are stronger in younger and low-income groups in the second and third national lockdowns. This study enhances our understanding of the influences of COVID-19 pandemic restriction policies on human mobility behaviors within different social groups in England. The findings can be usefully extended to support policy-making by investigating human mobility and differences in policy effects across not only age and income groups, but also across geographical regions.


Oral administration of sodium bicarbonate can enhance the therapeutic outcome of Doxil® via neutralizing the acidic tumor microenvironment.
The pH of the tumor microenvironment in solid tumors is reported to be more acidic than that of normal tissues. The pH is controlled by over-expression of several transporters that are associated with the progression, angiogenesis, and metastasis of solid tumors. Antitumor effects of weak-base anticancer agents, such as doxorubicin (DXR), could be reduced in an acidic environment because of increases in the ionized form of the drug under these conditions, reducing its membrane penetrability. In our previous studies, we demonstrated that oral administration of sodium bicarbonate (NaHCO3) can neutralize the acidic tumor microenvironment and enhance the effects of small molecule anticancer drugs. However, it is not known whether or not increasing the tumor pH by oral administration of NaHCO3 leads to enhanced antitumor effects of lipidic nanoparticle formulations of weak-base anticancer drugs, such as Doxil®. In this study, we investigated the antitumor efficacy of Doxil® in combination with oral administration of NaHCO3 in a Colon26 tumor-bearing mouse model. NaHCO3 clearly enhanced the tumor-growth inhibitory effect of Doxil® without exacerbating any systemic side effects. In vitro studies indicated that high levels of DXR were internalized into cells at neutral pH. These studies demonstrate that the neutralization of acidic tumor microenvironment by an oral administration of NaHCO3 could be a promising approach to enhance the therapeutic outcomes of Doxil®.


Peptide-containing nerves in the urinary bladder of the toad, Bufo marinus.
The distributions of peptide-containing nerves in the urinary bladder of the toad, Bufo marinus, were studied by means of fluorescence immunohistochemistry of whole-mount preparations. The bundles of smooth muscle in the bladder are well supplied by varicose nerve fibres displaying somatostatin-like immunoreactivity; these fibres probably arise from intrinsic perikarya. The urinary bladder also has a well-developed plexus of nerves containing substance P-like immunoreactive material; these elements probably represent sensory nerves of extrinsic origin. Nerve fibres showing immunoreactivity to vasoactive intestinal polypeptide (VIP) or enkephalin are rare within the urinary bladder of the toad. It is considered unlikely that any of these peptides directly mediates the hyoscine-resistant excitatory response of the smooth muscle to nerve stimulation in the toad bladder.


First record of the fossil snakefly genus Mesoraphidia (Insecta: Raphidioptera: Mesoraphidiidae) from the Middle Jurassic of China, with description of a new species.
Mesoraphidia daohugouensis sp. nov. is described from the Middle Jurassic Jiulongshan Formation of Inner Mongolia, China. It is diagnosed by the following character states: subquadrate pronotum, narrowly elliptical forewing, distally darkened pterostigma closed respectively by a proximal costal crossvein and a distal radial veinlet, absence of pterostigmal crossvein. The new species represents the first record of Mesoraphidiinae from the Middle Jurassic of China.


Quantification of co-, n-, and ad-lupulone in hop-based dietary supplements and phytopharmaceuticals and modulation of their contents by the extraction method.
Hop β-bitter acids (lupulones) are health-beneficial components of Humulus lupulus L. showing, for example, antidepressant-like effects in vitro. Despite of the widespread use of hops for medicinal purposes, the concentrations of lupulones in hop-based drugs have not been reported yet. The present study developed, validated, and applied a method with external calibration, which allows for the first time separate quantification of co-, n-, and ad-lupulone in hop-based drugs by UHPLC‒DAD. Concentrations between 'not detectable' and 2.7 mg/mL co-lupulone, 2.2 mg/mL nlupulone, or 0.7 mg/mL ad-lupulone were measured in nine different commercial dietary supplements and phytopharmaceuticals. Only one hop tincture contained sufficient lupulone to possibly exert potential antidepressant effects. Aiming for products with increased lupulone content, the extraction efficiency of different solvents was investigated. Complete extraction of lupulones from raw hops was achieved by organic solvents including methanol and ethanol, whereas aqueous mixtures resulted in low recovery. These results indicate that adapted extraction conditions may result in more effective hops products.


Ferrous ion enhanced Fenton-like degradation of emerging contaminants by sulfidated nanosized zero-valent iron with pH insensitivity.
In this study, the performance and mechanism of the integrated sulfidated nanosized zero-valent iron and ferrous ions (S-nZVI/Fe2+) system for oxygen activation to remove emerging contaminants (ECs) were comprehensively explored. The S-nZVI/Fe2+ system exhibited a 2.4-8.2 times of increase in the pseudo-first order kinetic rate constant for the oxidative degradation of various ECs compared to the S-nZVI system under aerobic conditions, whereas negligible removal was observed in both nZVI and nZVI/Fe2+ systems. Moreover, remarkable EC mineralization efficiency and benign detoxification capacity were also demonstrated in the S-nZVI/Fe2+ system. We revealed that dosing Fe2+ promoted the corrosion of S-nZVI by maintaining an acidic solution pH, which was conducive to O2 activation by dissolved Fe2+ and surface-absorbed Fe(II) to produce •OH. Furthermore, the generation of H* was enhanced for the further reduction of Fe(III) and H2O2 to Fe(II) and •O2-, resulting in the improvement of consecutive single-electron O2 activation for •OH production. Additionally, bisphenol A (BPA) degradation by S-nZVI/Fe2+ was positively correlated with the S-nZVI dosage, with an optimum S/Fe molar ratio of 0.15. The Fenton-like degradation process by S-nZVI/Fe2+ was pH-insensitive, indicating its robust performance over a wide pH range. This study provides valuable insights for the practical implementation of nZVI-based technology in achieving high-efficiency removal of ECs from water.


Efficacy of triclosan soap against superficial dermatomycoses: a double-blind clinical trial in 224 primary school-children in Kilombero District, Morogoro Region, Tanzania.
Superficial dermatomycoses are a common problem in tropical regions. Due to limited resources, specific antimycotic therapy is often not available. The present study was performed to assess the clinical efficacy of the antimicrobial agent Triclosan in bar soap in comparison with regular soap against selected superficial dermatomycoses in Tanzanian schoolchildren. 820 primary school children were examined for skin disorders and 224 of these were included in the soap trial. The clinical presentation of dermatomycoses was recorded using a symptom score. Samples were taken for microscopic examination and mycological culture. The study participants received either bar soap containing Triclosan or a placebo for 2 months. They were re-examined at the end of this period. The benefit achieved by the addition of Triclosan was not statistically significant. Overall cure rates for Triclosan and placebo groups taken together were 21.8% for tinea versicolor, 58.3% for tinea capitis, 55.5% for tinea corporis and 68.8% for tinea pedis. This was confirmed microscopically. For the majority of the children the dermatomycoses improved significantly. The results strongly argue for regular soap use against common dermatomycoses as a low-cost and effective treatment. This promising finding should be considered in settings where dermatophyte infections represent a public health problem and where access to appropriate treatment and financial resources are limited.


Nimbolide Inhibits Nuclear Factor-КB Pathway in Intestinal Epithelial Cells and Macrophages and Alleviates Experimental Colitis in Mice.
Nimbolide is a limonoid extracted from neem tree (Azadirachta indica) that has antiinflammatory properties. The effect of nimbolide on the nuclear factor-kappa B (NF-κB) pathway in intestinal epithelial cells (IECs), macrophages and in murine colitis models was investigated. The IEC COLO 205, the murine macrophage cell line RAW 264.7, and peritoneal macrophages from interleukin-10-deficient (IL-10-/- ) mice were preconditioned with nimbolide and then stimulated with tumor necrosis factor-α (TNF-α) or lipopolysaccharide. Dextran sulfate sodium-induced acute colitis model and chronic colitis model in IL-10-/- mice were used for in vivo experiments. Nimbolide significantly suppressed the expression of inflammatory cytokines (IL-6, IL-8, IL-12, and TNF-α) and inhibited the phosphorylation of IκBα and the DNA-binding affinity of NF-κB in IECs and macrophages. Nimbolide ameliorated weight loss, colon shortening, disease activity index score, and histologic scores in dextran sulfate sodium colitis. It also improved histopathologic scores in the chronic colitis of IL-10-/- mice. Staining for phosphorylated IκBα was significantly decreased in the colon tissue after treatment with nimbolide in both models. Nimbolide inhibits NF-κB signaling in IECs and macrophages and ameliorates experimental colitis in mice. These results suggest nimbolide could be a potentially new treatment for inflammatory bowel disease. Copyright © 2016 John Wiley & Sons, Ltd.


Smoking is associated with a higher complication and failure rate in arteriovenous grafts for haemodialysis: A multi-centre experience.
Arteriovenous grafts (AVG) for haemodialysis (HD) access are recommended as a second line modality due to higher morbidity and mortality rates than arteriovenous fistulae (AVF). Smoking is already established as a risk factor in lower extremity bypass graft failure used for peripheral vascular disease, but its effect on AVGs remains unclear. We aimed to investigate the relationship of smoking on AVG outcomes. A 3 year (01/08/2015-01/08/2018) multi-centre retrospective study was carried out on patients receiving an AVG for HD. Data included patient demographics, medical history, operation, type of graft, postoperative course and primary and secondary patency rates. Statistical analyses performed were Kaplan-Meier curves and Cox's proportional hazard regression. Fifty-five AVGs were performed (1052 AVF performed) in this period. The most common complication was thrombosis (38.9%). Primary patency at 6, 12 and 24 months were 55%, 45% and 44% respectively. Secondary patency at 6, 12 and 24 months were 63%, 56% and 54% respectively. Smoking was found to be a poor prognostic factor for primary (HR 3.734 (1.818-7.668 95% CI) p < 0.001) and secondary patency (HR 6.238 (2.729-14.257) p < 0.001). Smoking was also significantly associated with graft thrombosis (HR 5.741 (2.380-13.848 95% CI) p < 0.001). Primary patency rates are lower than previous reports whilst secondary patency is equivalent. Smoking results in a greater risk of thrombosis and poorer primary and secondary patency. This is recognised in vascular surgical grafts, but has not been previously described in AVGs for HD access. Smoking is a modifiable risk factor and as AVGs are typically used for end-stage vascular access patients. Pre-operative strategies to promote smoking cessation, including patient education and prehabilitation should be employed to improve outcomes.


Portosystemic shunt is an effective treatment for complications of portal hypertension in hepatic myeloid metaplasia and improves nutritional status.
In patients affected by myelofibrosis with hepatic myeloid metaplasia (HMM), portal hypertension (PHT) complications may develop. In this case series, we analysed the efficacy and safety of transjugular portosystemic shunt (TIPS) in the treatment of PHT-related complications and its effects on the nutritional status. Six patients were evaluated and the average follow-up period after TIPS was 33 (IQR 5) months. None of the patients developed hepatic failure, nor any recurrence of variceal bleeding was recorded. No additional paracentesis or endoscopic prophylactic treatment for PHT-related complications were required. In all subjects, the average dose of diuretics was almost halved three months after TIPS. Three patients died during the follow-up, but none for liver-related causes. All patients showed an improvement in the global nutritional status. In conclusion, TIPS represent an effective and safe treatment option for patients affected by complications of PHT secondary to HMM and drives to an improvement of the nutritional status.


On the mechanism of reductive activation in the mode of action of some anticancer drugs.
Bioactivation of a number of DNA-specific antitumor drugs depends on oxidoreduction. Bleomycin, neocarzinostatin and anthracycline glycosides are the best known among such drugs in terms of reductive activation processes. Their reduction results in short-lived radical or electrophilic intermediates attacking DNA stereospecifically. The physico-chemical properties of these drugs and the nature of DNA damage are reviewed. Models for DNA-intercalation, electron-donor systems involved in drug metabolisation, and the role of oxygen in radical reactions, are discussed in the light of recent reports.


Hemodialysis morbidity and mortality: links to patient non-compliance.
Patient non-compliance with the dialysis treatment prescription has often been overlooked as an important variable that contributes to outcomes in end-stage renal disease. This review discusses evidence from a limited number of researchers that such behavior may be as important as the traditional medical indicators that predict patient survival.


Pharmacoangiographic assessment of penile arteries in patients with erectile failure.
Pudendal angiography was done before and thirty minutes after intracavernous administration of 6 mg phenoxybenzamine in 8 men in whom screening with ultrasound Doppler had revealed abnormalities of the penile blood flow. Five vessels were not visualized until phenoxybenzamine was given. Four vessels displayed marked dilatation, three had moderate and one had slight dilatation after the pharmacologic erection was provoked. The method appears to be of value to increase the quality of the angiographic examination.


Multiple ubiquitin mRNAs during Xenopus laevis development contain tandem repeats of the 76 amino acid coding sequence.
A cDNA clone, pXlgC20, was isolated from a library constructed from poly(A)+ RNA from stage 10 X. laevis gastrulae. This sequence hybridizes with up to nine different RNA species ranging in size from 1600 to 3500 nucleotides, regularly spaced at intervals of about 230 nucleotides. Clone pXlgC20 contains two complete repeats of a 228 bp sequence as well as part of a third repeat, all adjacent and in the same orientation. One possible translational reading frame in pXlgC20 completely spans the repeat sequences, coding for a protein composed of tandem 76 amino acid units. The amino acid sequence of each unit completely matches that of human ubiquitin. Ubiquitin is translated in the form of a multimeric precursor molecule containing several units. We show that genomic DNA fragments exist that contain at least 12 of these units in tandem and propose that the different mRNA size classes vary in their number of ubiquitin coding sequences.


[Intraoperative assessment of pelvic tilt and cup position in total hip arthroplasty: the relevance of navigation and robotics].
The optimal 3D positioning of the prosthesis components is of great importance for the stability and function of a total hip endoprosthesis. Pelvic tilt has a particular influence on the position of the implant. In order to use intraoperatively the knowledge on pelvic kinematics gained through preoperative imaging procedures and movement analyses, "image-based" and "image-free" robotic and navigation procedures are available. With the "image-based" procedures, a 3D CT scan serves as the surgeon's basis for operative planning. The "image-free" procedures are based on the principles of stereotaxy. In the future, information about static and dynamic pelvic tilt will be conntected with navigation and robotic systems for total hip arthroplasty. Along with intraoperative data a patientindividual optimized implant position can be achieved.


Improved production of carotenoid-free welan gum in a genetic-engineered Alcaligenes sp. ATCC31555.
To improve the production of welan gum and obtain a carotenoid-free strain while reducing the fermentation and post-treatment costs. The vitreoscilla globin (vgb) gene combined with the β-galactosidase (lacZ) promoter was inserted into the phytoene synthase (crtB) gene region of the chromosome in Alcaligenes sp. ATCC31555. When the recombinant strain was grown in a 5 l fermentor, welan gum was produced at 24 ± 0.4 g l(-1) compared to 21 g ± 0.4 g l(-1) in the wild type. Furthermore, the carotenoid-free welan gum produced using Alcaligenes sp. ATCC31555 VHb strain was less expensive with improved properties. Alcaligenes sp. ATCC31555 VHb strain was a better neutral welan-producing strain with a higher production than the wild-type strain.


pH induced damage and repair in E. coli.
Escherichia coli lost its colony-forming ability when suspended in Tris/NaOH or Tris/Mg2+ buffers of pH 10.0 and 4.0, respectively. A significant decrease in the survival of radiation-sensitive mutants recA, polA, res, rer and lexA was observed as compared to their wild-type counterpart under these conditions. The alkali-injured cells were found to recover when incubated at 37 degrees C for 2 h in 0.05 M phosphate buffer of pH 8.0, whereas no such liquid holding recovery was observed in recA and lexA mutants. Recovery in phosphate buffer was not affected by metabolic inhibitors. As a result of alkali treatment, the sensitivity of bacteria to ultraviolet light (UV) was enhanced. However, on incubation for 2 h in recovery buffer at 37 degrees C, the bacteria regained partial UV resistance. Bacteria exposed to alkaline environment exhibited an enhanced level of mutagenesis. Contrary to the treated wild-type, the mutants recA and lexA did not exhibit any increase in the mutation frequency. Alkali treatment to GC----AT transition mutants of Salmonella typhimurium, TA102 and TA104 resulted in the highest number of revertants per plate.


Anxiety, Disability, and Pain Predict Outcomes of Complex Regional Pain Syndrome: An 8-year Follow-up of a Prospective Cohort.
Factors contributing to the varied outcomes of complex regional pain syndrome (CRPS) are not well known. This study aimed to determine whether baseline psychological factors, pain, and disability influence long-term CRPS outcomes. We conducted an 8-year follow-up from a previous prospective study of CRPS outcomes. Sixty-six people diagnosed with acute CRPS were previously assessed at baseline, 6 months, and 12 months and in the current study, 45 were followed up after 8 years. At each timepoint, we measured signs and symptoms of CRPS, pain, disability, and psychological factors. Mixed-model repeated measures were used to identify baseline predictors of CRPS severity, pain, and disability at 8 years. Predictors of greater CRPS severity at 8 years were female sex, greater baseline disability, and greater baseline pain. Predictors of greater pain at 8 years were greater baseline anxiety and disability. The only predictor of greater disability at 8 years was greater baseline pain. Findings suggest CRPS is best understood from a biopsychosocial perspective, and baseline anxiety, pain, and disability may influence the trajectory of CRPS outcomes as far as 8 years later. These variables could be used to identify those at risk of poor outcomes or form targets for early interventions. PERSPECTIVE: This paper presents the findings of the first study to prospectively investigate predictors of CRPS outcomes over 8 years. Baseline anxiety, pain, and disability predicted greater CRPS severity, pain, and disability over 8 years. These factors could identify those at risk of poor outcomes or form targets for early interventions.


An optical and visual multi-mode sensing platform base on nitrogen, sulfur, boron co-doped carbon dots for rapid and simple determination of ferric ions in water.
Abnormal iron ions levels may lead to some diseases and serious environmental pollution. Herein, optical and visual detection strategies of Fe3+ in water based on co-doped carbon dots (CDs) were established in the present study. Firstly, a one-pot synthetic strategy for the preparation of the N, S, B co-doped CDs with a home microwave oven was developed. Secondly, the optical properties, chemical structures, and morphology of CDs were further characterized by fluorescence spectroscopy, Uv-vis absorption spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscope. Finally, the results indicated that the fluorescence of the co-doped CDs was quenched by ferric ions via the static mechanism and the aggregation of CDs, accompanied by the increased red color. The multi-mode sensing strategies of Fe3+ with fluorescence photometer, UV-visible spectrophotometer, portable colorimeter and smartphone had the advantages of good selectivity, excellent stability and high sensitivity. Fluorophotometry based on co-doped CDs was a powerful probe platform for measuring lower concentrations of Fe3+ due to its higher sensitivity, better linear relationship, lower limit of detection (0.27 μM) and limit of quantitation (0.91 μM). In addition, the visual detection methods with a portable colorimeter and smartphone had been proven to be very suitable for rapid and simple sensing of higher concentrations of Fe3+. Moreover, the co-doped CDs utilized for Fe3+ probes in tap water and boiler water obtained satisfactory results. Consequently, the efficient, versatile optical and visual multi-mode sensing platform could be extended to apply such a visual analysis of ferric ions in the biological, chemical and other fields.


Studies on liver specific antigens--partial purification, characterization, and immunization.
Seven liver specific antigens, liver protein-I, liver protein-II, liver specific antigen (Espinosa), F-antigen, hepato-renal antigen, liver cell membrane antigen (Ray) and Tamm-Horsfall glycoprotein were partially purified from human liver and urine. Anti-sera against these antigens were raised in rabbits. Anti-sera against liver protein-I, liver protein-II, liver specific antigen (Espinosa) and liver cell membrane antigen (Ray) were absorbed by human serum, kidney, lung and spleen while anti-sera against hepato-renal antigen and Tamm-Horsfall glycoprotein were absorbed by human serum, lung and spleen to remove antibodies against non-specific antigens. There were no cross reactivities among these antibodies.


The PE multigene family: a 'molecular mantra' for mycobacteria.
The PE multigene family of Mycobacterium tuberculosis is remarkable in that it is composed of approximately 100 highly homologous genes that are found only in mycobacteria. Early evidence suggests that proteins encoded by certain members of this gene family could be present in the mycobacterial cell wall, impact antigen-presentation pathways and the ensuing host immune responses, and also provide a mechanism for generating antigenic diversity in mycobacteria.


A gene prioritization method based on a swine multi-omics knowledgebase and a deep learning model.
The analyses of multi-omics data have revealed candidate genes for objective traits. However, they are integrated poorly, especially in non-model organisms, and they pose a great challenge for prioritizing candidate genes for follow-up experimental verification. Here, we present a general convolutional neural network model that integrates multi-omics information to prioritize the candidate genes of objective traits. By applying this model to Sus scrofa, which is a non-model organism, but one of the most important livestock animals, the model precision was 72.9%, recall 73.5%, and F1-Measure 73.4%, demonstrating a good prediction performance compared with previous studies in Arabidopsis thaliana and Oryza sativa. Additionally, to facilitate the use of the model, we present ISwine ( http://iswine.iomics.pro/ ), which is an online comprehensive knowledgebase in which we incorporated almost all the published swine multi-omics data. Overall, the results suggest that the deep learning strategy will greatly facilitate analyses of multi-omics integration in the future.


Molecular analysis of archived blood slides reveals an atypical human Trypanosoma infection.
In 2003, a 10-month-old Ghanaian boy recovered from a Trypanosoma brucei infection, although the patient was not treated with antitrypanosomal drugs. Only T. brucei gambiense and T. brucei rhodesiense are able to infect humans, causing human African trypanosomiasis. The disease is considered 100% fatal if left untreated. The identity of the trypanosome was determined by DNA extraction from the archived stained blood slides followed by sequential application of polymerase chain reactions (PCRs) that are specific for the order, subgenus, species and subspecies, followed by genotyping with microsatellite PCR. Molecular analysis indicated that the parasites observed in the patient's blood in 2003 belong to the T. brucei subspecies brucei, which is normally not infectious to humans. Next to the clinical message, this article provides technical information to extract successfully DNA from archived blood slides for subsequent molecular analysis and to identify a trypanosome by taxon-specific PCRs and microsatellite genotyping.


When physician-industry interactions go awry.
Financial connections between members of the profession and professional organizations and the pharmaceutical, device, and biotechnology industries are increasingly common and can lead to biased medical decision making, higher costs of care, and decline in the public's trust of the profession. To preserve its reputation and its autonomy over medical decisions, the profession must begin to police itself.


Executive Summary of the Lower Anogenital Tract Cancer Evidence Review Conference.
The Centers for Disease Control and Prevention sponsored a project conducted by the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. For this final module, focusing on the cancers of the lower anogenital tract (vulva, vagina, and anus), a panel of experts in evidence assessment from the Society for Academic Specialists in General Obstetrics and Gynecology, ASCCP, and the Society of Gynecologic Oncology reviewed relevant literature and current guidelines. Panel members conducted structured literature reviews, which were then reviewed by other panel members. Representatives from stakeholder professional and patient advocacy organizations met virtually in September 2022 to review and provide comment. This article is the executive summary of the review. It covers prevention, early diagnosis, and special considerations of lower anogenital tract cancer. Knowledge gaps are summarized to provide guidance for future research.


Approach-avoidance of facial affect is moderated by the presence of an observer-irrelevant trigger.
This study examined whether approach-avoidance related behaviour elicited by facial affect is moderated by the presence of an observer-irrelevant trigger that may influence the observer's attributions of the actor's emotion. Participants were shown happy, disgusted, and neutral facial expressions. Half of these were presented with a plausible trigger of the expression (a drink). Approach-avoidance related behaviour was indexed explicitly through a questionnaire (measuring intentions) and implicitly through a manikin version of the affective Simon task (measuring automatic behavioural tendencies). In the absence of an observer-irrelevant trigger, participants expressed the intention to avoid disgusted and approach happy facial expressions. Participants also showed a stronger approach tendency towards happy than towards disgusted facial expressions. The presence of the observer-irrelevant trigger had a moderating effect, decreasing the intention to approach happy and to avoid disgusted expressions. The trigger had no moderating effect on the approach-avoidance tendencies. Thus the influence of an observer-irrelevant trigger appears to reflect more of a controlled than automatic process.


Conservative hepatectomy for tumors involving the middle hepatic vein and segment 1: the liver tunnel.
For lesions invading the middle hepatic vein (MHV) at caval confluence (CC) the mini-mesohepatectomy(MMH) was proposed.1 If the lesion is extended to the paracaval portion of segment 1(S1) in contact or invading the MHV a new procedure is proposed. Case-1: mass forming cholangiocarcinoma (MFCCC) 4cm in size invading the MHV and in contact with right (RHV) and left hepatic vein (LHV) at the CC. In Case-2, two colorectal liver metastases (CLM) both 2cm in size occupied S1 (T1) and S8 (T2): T1 was located between RHV and the inferior vena cava (IVC), T2 was in contact with MHV at CC. According to tumor-vessel intraoperative-ultrasound classification2 and color-flow analysis3 parenchyma-sparing procedure was performed. In Case-1 a communicating vein (CV) between RHV and MHV was detected at color-flow-IOUS. Contacts between MFCCC with RHV and LHV were confirmed at IOUS as detachable. In Case-2 contact between T1 with MHV was confirmed at IOUS as detachable. Liver-tunnel with IVC and main portal vein bifurcation exposure was performed resecting the MHV in Case-1 and preserving it in Case-2. Both patients had ad an uneventful postoperative course and were discharged on the 8th postoperative day. For tumors involving S1, S4s and/or S8 and infiltrating or in contact with the MHV at the CC, can be removed in a conservative manner by means of the herein described ''Liver Tunnel'' approach. The latter introduces a further step in favour of parenchyma-sparing policy for centrally located lesions with complex tumor-vessel relationship.


Betacellulin drives therapy resistance in glioblastoma.
The transcription factor signal transducer and activator of transcription 3 (STAT3) drives progression in glioblastoma (GBM), suggesting STAT3 as a therapeutic target. Surprisingly however, GBM cells generally show primary resistance to STAT3 blockade. Human glioblastoma cell lines LN229, U87, SF767, and U373, and patient-derived xenografts (PDXs) GBM8 and GBM43 were used to evaluate epidermal growth factor receptor (EGFR) activation during STAT3 inhibition. Protein and gene expression experiments, protein stability assays, cytokine arrays, phospho-tyrosine arrays and EGFR-ligand protein arrays were performed on STAT3 inhibitor-treated cells. To evaluate antitumor activity, we administered a betacellulin (BTC)-neutralizing antibody alone and in combination with STAT3 inhibition. BTC is an EGFR ligand. We therefore treated mice with orthotopic xenografts using the third-generation EGFR inhibitor osimertinib, with or without STAT3 knockdown. We demonstrate that both small-molecule inhibitors and knockdown of STAT3 led to expression and secretion of the EGFR ligand BTC, resulting in activation of EGFR and subsequent downstream phosphorylation of nuclear factor-kappaB (NF-κB). Neutralizing antibody against BTC abrogated activation of both EGFR and NF-κB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in GBM cells. Blocking EGFR and STAT3 together inhibited tumor growth, improving survival in mice bearing orthotopic GBM PDXs in vivo. These data reveal a feedback loop among STAT3, EGFR, and NF-κB that mediates primary resistance to STAT3 blockade and suggest strategies for therapeutic intervention.


A public mental health approach to the postdisaster treatment of children and adolescents.
This article describes the implementation of mental health intervention programs for children, adolescents,and their families exposed to natural disaster and violence. Recommendations are made regarding needed levels of organization, methods of screening and triage, training and supervision of mental health staff, design and implementation of treatment approaches, and longitudinal monitoring of course of recovery and intervention outcome.


Objective measurement of knee laxity and stiffness with reference to knee injury diagnosis. Part 2: Results.
Equipment capable of objective knee analysis has been used to obtain data from 85 'normal' healthy knees, 47 patients suffering with knee disorders, and three cadaveric knee joints. Among the 'normals' it was found that there was a correlation between body weight and stiffness and laxity. A lower stiffness and higher laxity was recorded at 20 degrees of knee flexion than at 90 degrees. Using relative-paired difference analysis the variables affected by different injuries in patients were identified and are presented. In a separate analysis a multi-variate technique is used to interpret the data. The technique could be used to predict or diagnose knee injury, and as such may be highly useful to clinicians.


Malignancy in Guillain-Barré syndrome: A twelve-year single-center study.
The relationship between Guillain-Barré syndrome (GBS) and malignancy is uncertain. We retrospectively analyzed data of 118 consecutive patients admitted with GBS from Birmingham, U.K. (2001-2012). We calculated relative cancer risk using different definitions and determined characteristics of malignancy-associated GBS. Malignancy was globally commoner in our GBS cohort compared to the general population (odds ratio: 2.08; CI: 1.06-3.71; p=0.036). However, this was unconfirmed if paraneoplastic criteria were applied. GBS patients with cancer were significantly more likely to be older (p=0.043), hyponatremic (p=0.037) and demonstrate more axonal loss (p<0.05). Cerebrospinal fluid (CSF) protein levels were lower in the malignancy group (p=0.002) and neurological improvement less likely (p=0.023). In-patient mortality was significantly higher in patients with malignancy (p<0.01). We conclude global cancer risk is higher in GBS than in the general population, although definition-dependent. Malignancy requires consideration in elderly, hyponatremic subjects with normal CSF protein, severe axonal loss, who fail to improve post-treatment.


[Relationship between psychiatric diagnosis and social or medical data in a child mental health center (author's transl)].
The aim of the present study is to point out the most significant sociodemographic and medical parameters related to psychiatric diagnoses, such as registered at the Alfred-Binet Child Mental Health Center (Paris). Statistical analysis shows the specific tendencies of each diagnosis and their similarities. Some diagnoses are particularly associated to negative aspects of the investigated parameters. This is true for psychotic disorders whereas normal variations are linked to positive aspects. Between these two extremes, neurotic disorders, the most numerous, are located in a middle position for all the investigated variables.


Omentum support for cardiac regeneration in ischaemic cardiomyopathy models: a systematic scoping review.
Preclinical in vivo studies using omental tissue as a biomaterial for myocardial regeneration are promising and have not previously been collated. We aimed to evaluate the effects of the omentum as a support for bioengineered tissue therapy for cardiac regeneration in vivo. A systematic scoping review was performed. Only English-language studies that used bioengineered cardio-regenerative tissue, omentum and ischaemic cardiomyopathy in vivo models were included. We initially screened 1926 studies of which 17 were included in the final qualitative analysis. Among these, 11 were methodologically comparable and 6 were non-comparable. The use of the omentum improved the engraftment of bioengineered tissue by improving cell retention and reducing infarct size. Vascularization was also improved by the induction of angiogenesis in the transplanted tissue. Omentum-supported bioengineered grafts were associated with enhanced host reverse remodelling and improved haemodynamic measurements. The omentum is a promising support for myocardial regenerative bioengineering in vivo. Future studies would benefit from more homogenous methodologies and reporting of outcomes to allow for direct comparison.


Outcome of paediatric cataract surgery with primary posterior capsulotomy and anterior vitrectomy using intra-operative preservative-free triamcinolone acetonide.
To evaluate the intra-operative and postoperative outcome of paediatric cataract surgery with primary posterior capsulotomy (PPC) and anterior vitrectomy using intra-operative preservative-free triamcinolone acetonide. In this prospective, interventional case-control study, 20 Children who underwent cataract surgery for both eyes were enrolled and their eyes were randomized into two groups. Group A consists of 20 eyes in which standard phacoaspiration with PPC with intracameral triamcinolone was used, and Group B consists of 20 eyes in which triamcinolone were not used. Intra-operative complications and postoperative outcome like intraocular pressure (IOP), posterior synechiae, pigment deposits and posterior capsule opacification (PCO) were studied. In both groups, age range varied between 2-8 years comprising 18 males and two females. The mean postoperative IOP did not show any significant variation during 6-month follow-up. In study group, all the 20 eyes were quiet at 2 weeks, while there was cellular reaction 1+ in four eyes (20%) and nil in 16 eyes (80%) at 2 week in the control group (p = 0.035). Pigment deposits on IOL optic was seen in two eyes (10%) of the study group while in control group, IOL deposits were present in 14 eyes (70%) (p = 0.001). Posterior capsule opacification was seen in two eyes (10%) in control group at 3 months while none occurred in study group. Intra-operative use of preservative-free triamcinolone acetonide led to less anterior chamber inflammation and pigment deposits on IOL optic postoperatively compared to those eyes where it was not used.


Trace metals in different socioeconomic indoor residential settings, implications for human health via dust exposure.
In this study a number of heavy metals namely chromium (Cr), cadmium (Cd), zinc (Zn), barium (Ba), copper (Cu), manganese (Mn), cobalt (Co), rubidium (Rb), selenium (Se) are studied in the floor and air condition (AC) filter dust collected from urban and rural households of Saudi Arabia. To the best of our knowledge, many of these heavy metals are reported for the very first time in the indoor dust of Saudi Arabia. Studied metals were higher in urban dust than rural except Mn and Rb which were significantly higher (P < 0.05) in rural dust. All metals, except Cd, Zn, and Ba in urban settings, were detected at higher (P < 0.05) levels in AC filter dust than household floor dust from both rural and urban residential settings. Levels of the two dominant metals i.e., Zn and Mn were up to 1600 and 700 μg/g, respectively in studied dust samples. Also associations between heavy metals and a number of different socio-economic parameters were studied which was significant for some trace metals. In literature exposure to many of trace metals are associated with various health problems, therefore health risk assessment for the Saudi population was calculated by incremental lifetime cancer risk (ILCR) and hazardous index (HI) via dust ingestion, inhalation, and dermal contact. The ILCR for all metals was within the tolerable range of reference values of USEPA (1 × 10- 11 to 1 × 10- 4). However, calculated HI for Mn, Cu, Ni, and Zn was more than 1 via dust exposure, which signifies the non-carcinogenic risk. The study highlights the occurrence of toxic metals in the indoor environments of Saudi Arabia and provides baseline data for future studies on these toxic metals in the region.


Genomic analysis of cyclic-di-GMP-related genes in rhizobial type strains and functional analysis in Rhizobium etli.
Rhizobia are soil bacteria that can fix nitrogen in symbiosis with leguminous plants or exist free living in the rhizosphere. Crucial to their complex lifestyle is the ability to sense and respond to diverse environmental stimuli, requiring elaborate signaling pathways. In the majority of bacteria, the nucleotide-based second messenger cyclic diguanosine monophosphate (c-di-GMP) is involved in signal transduction. Surprisingly, little is known about the importance of c-di-GMP signaling in rhizobia. We have analyzed the genome sequences of six well-studied type species (Bradyrhizobium japonicum, Mesorhizobium loti, Rhizobium etli, Rhizobium leguminosarum, Sinorhizobium fredii, and Sinorhizobium meliloti) for proteins possibly involved in c-di-GMP signaling based on the presence of four domains: GGDEF (diguanylate cyclase), EAL and HD-GYP (phosphodiesterase), and PilZ (c-di-GMP sensor). We find that rhizobia possess a high number of these proteins. Conservation analysis suggests that c-di-GMP signaling proteins modulate species-specific pathways rather than ancient rhizobia-specific processes. Two hybrid GGDEF-EAL proteins were selected for functional analysis, R. etli RHE_PD00105 (CdgA) and RHE_PD00137 (CdgB). Expression of cdgA and cdgB is repressed by the alarmone (p)ppGpp. cdgB is significantly expressed on plant roots and free living. Mutation of cdgA, cdgB, or both does not affect plant root colonization, nitrogen fixation capacity, biofilm formation, motility, and exopolysaccharide production. However, heterologous expression of the individual GGDEF and EAL domains of each protein in Escherichia coli strongly suggests that CdgA and CdgB are bifunctional proteins, possessing both diguanylate cyclase and phosphodiesterase activities. Taken together, our results provide a platform for future studies of c-di-GMP signaling in rhizobia.


Revisional Roux-en-Y gastric bypass after failed gastric banding: a case-matched study.
Revisional surgery is technically demanding and is usually associated with higher intraoperative and perioperative risks than primary procedures. The objective of this study is to compare outcomes of patients who had gastric bypass procedures performed as a rescue procedure for failed gastric banding, with those who had a primary gastric bypass. The group of patients undergoing revisional gastric bypass for failed gastric band was matched in a 1:2 ratio with control patients who underwent a primary RYGB, based on gender, score, preoperative body mass index, and comorbidities. Data were retrospectively retrieved. Thirty one (33.3%) patients underwent band removal and gastric bypass (group A) and 62 (66.6%) only primary gastric bypass (group B). Nonsignificant differences were seen in operative time, operative bleeding, or length of stay. Complications were more frequent in group A. Postoperative weight at 12-month follow-up was greater in group A, however, not statistically significant. Changes in weight, both absolute, and percentage were not different between groups. This observation was also true for BMI, in which no significant differences were seen. Overall, mean follow-up was 16 ± 3.2 months. Gastric bypass can be performed as revisional bariatric surgery, with low complication rates and acceptable outcomes, though not with the same safety as a primary procedure. Gastric bypass is a satisfactory option for patients with a failed gastric band.


Cronkhite-Canada syndrome. A case of sustained partial-remission.
A case of Cronkhite-Canada syndrome is described. Few cases have been published and in most patients the prognosis is poor. A variety of medical measures have been attempted in those in whom remission has been reported. In the patient presented here, a sustained partial-remission has been achieved with steroids.


Y-chromosomal STR haplotypes in a Romanian population sample.
A set of seven STR-loci mapping on the male-specific region of the human Y chromosome (DYS19, DYS385, DYS389 I/II, DYS390, DYS391, DYS392, DYS393) were typed by means of two multiplex PCR reactions and capillary electrophoresis in a Romanian population sample of 104 unrelated males. Among the 97 different haplotypes observed, 92 were unique, while 5 occurred more than once. The observed haplotype diversity was 0.989.


Chemotactic cell movement during development.
Chemotaxis is an important mechanism controlling cell migration over either short or long distances during different developmental processes. Small rapid diffusing chemo-attractants are detected through serpentine, G protein coupled receptors through graded activation of receptors along the length of the cell. Internal amplification results in polarisation of the actin and myosin cytoskeletal dynamics along the gradient and directed movement. The dynamics of these processes can now be studied in individual cells in developing organisms. Slow diffusing chemo-attractants such as growth factors, providing short-range guidance information, often signal through tyrosine kinase receptors. Detection of these signals may involve the active extension of very long cellular process up growth factor gradients, followed by translocation of the cell in the direction of the gradient.


When are two qualitative taxonomic characters compatible?
A proof is given of a procedure that has previously appeared claiming to determine when two amino acid positions on a protein could both possibly be divergent taxonomic characters. An algorithm for executing this procedure is described.


Towards an integrated approach in surveillance of vector-borne diseases in Europe.
Vector borne disease (VBD) emergence is a complex and dynamic process. Interactions between multiple disciplines and responsible health and environmental authorities are often needed for an effective early warning, surveillance and control of vectors and the diseases they transmit. To fully appreciate this complexity, integrated knowledge about the human and the vector population is desirable. In the current paper, important parameters and terms of both public health and medical entomology are defined in order to establish a common language that facilitates collaboration between the two disciplines. Special focus is put on the different VBD contexts with respect to the current presence or absence of the disease, the pathogen and the vector in a given location. Depending on the context, whether a VBD is endemic or not, surveillance activities are required to assess disease burden or threat, respectively. Following a decision for action, surveillance activities continue to assess trends.


The relationship between sociocultural pressure to be thin and body dissatisfaction in preadolescent girls.
This study investigates the relationships among sociocultural pressures to be thin, internalisation of the thin ideal, social comparison, body mass index, and body dissatisfaction in young girls. One hundred and fifty-three 10-13 year old girls completed measures assessing sociocultural pressure to be thin, media exposure, body dissatisfaction, social comparison, and internalisation of the thin ideal. Although sociocultural factors, as a group, were significantly associated with internalisation of the thin ideal, perceived media pressure was the only sociocultural influence uniquely related to internalisation of the thin ideal. Perceived pressure to be thin delivered by the media was found to be associated with body dissatisfaction via internalisation of the thin ideal. The relationship between internalisation of the thin ideal and body dissatisfaction was also partially influenced by social comparison. Body mass was found to have a direct association with body dissatisfaction. A model incorporating the relationships among media pressure, internalisation of the thin ideal, social comparison, and body dissatisfaction is proposed.


Quality of Otology and Neurotology Research in Otolaryngology Journals.
To identify trends in the quality of otology studies published in general otolaryngology journals over a 20-year period. Retrospective analysis. Otologic and neurotologic papers from 1997, 2007, and 2017 were identified in the three general otolaryngology journals with the highest Eigenfactor scores: the Laryngoscope, European Archives of Otorhinolaryngology, and Otolaryngology-Head and Neck Surgery. The studies were reviewed and assigned level of evidence (LoE) based on standards set by the Centres for Evidence Based Medicine (CEBM). One-way analysis of variance were calculated with a 95% bootstrap sensitivity analysis performed. A total of 786 otology articles were reviewed for level of evidence, of which 557 (70.8%) were original, clinical research, eligible for LoE assignation. Total publications increased for each year in all three journals. Both the absolute number and proportion of high evidence studies (level of evidence 1 and 2) increased with respect to time in all three journals. Lower evidence studies (level of evidence 3, 4, or 5) made up 66.8% of total publications in 2017. There was a reduction in average level of evidence (towards higher quality evidence) by 0.431 units from 1997 to 2017 (Diff = -0.431 between 1997 and 2017, p < 0.001). There was no significant difference in rate of change of level of evidence between 1997 and 2007 and 2007 and 2017 (0.033, p = 0.864). Over a 20-year period the number of total publications increased with time. The majority of otology publications in 2017 were lower evidence studies, though significant increases in the number and proportion of high evidence studies in general otolaryngology journals were observed throughout the study period.


Diminutions of acceleration and deceleration output during professional football match play.
This study examined distances covered at low (1-2 ms(-2)), moderate (2-3 ms(-2)) and high (>3 ms(-2)) acceleration (L(ACC), M(ACC) and H(ACC) respectively) and deceleration (L(DEC), M(DEC), and H(DEC) respectively) during competitive football games. Temporal and transient patterns of acceleration and deceleration were also examined. Observational, repeated measures. Thirty-six professional male professional footballers were monitored using a 10 Hz non-differential global positioning system (NdGPS). Match data was organised into six 15 min periods (P1: 1-15 min, P2: 16-30 min, P3: 31-45 min, P4: 46-60 min, P5: 61-75 min, and P6: 76-90 min) for analysis of temporal patterns, and into eighteen 5 min periods for analysis of transient patterns. ANOVA with Bonferroni post hoc tests were used to identify significant (p<0.05) differences between periods. Distance covered at L(ACC), M(ACC), H(ACC), L(DEC), M(DEC), and H(DEC) was 424±75 m, 242±25 m, 178±38 m, 365±54 m, 210±23 m and 162±29 m respectively. Between period decrements ranged from 8.0% to 13.2% from P1 to P3, 9.2% to 16.3% from P4 to P6, and from 14.9% to 21.0% from P1 to P6. Following PEAK H(ACC) (148% of mean 5 min H(ACC)), H(ACC) at 5POST was 10.4% lower than mean (p<0.01). Time-dependent reductions in distances covered suggest that acceleration and deceleration capability are acutely compromised during match play. Further, the occurrence of transient fatigue may be supported by the findings that HACC and HDEC performance following PEAK was approximately 10% lower than mean values.


Process integration possibilities for biodiesel production from palm oil using ethanol obtained from lignocellulosic residues of oil palm industry.
In this paper, integration possibilities for production of biodiesel and bioethanol using a single source of biomass as a feedstock (oil palm) were explored through process simulation. The oil extracted from Fresh Fruit Bunches was considered as the feedstock for biodiesel production. An extractive reaction process is proposed for transesterification reaction using in situ produced ethanol, which is obtained from two types of lignocellulosic residues of palm industry (Empty Fruit Bunches and Palm Press Fiber). Several ways of integration were analyzed. The integration of material flows between ethanol and biodiesel production lines allowed a reduction in unit energy costs down to 3.4%, whereas the material and energy integration leaded to 39.8% decrease of those costs. The proposed integrated configuration is an important option when the technology for ethanol production from biomass reaches such a degree of maturity that its production costs be comparable with those of grain or cane ethanol.


BsmI polymorphisms in vitamin D receptor gene are associated with diabetic nephropathy in type 2 diabetes in the Han Chinese population.
We investigated the relationship between BsmI/ApaI polymorphisms in vitamin D receptor gene and diabetic nephropathy in a Han Chinese population. PCR-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI and ApaI polymorphisms in 304 patients with type 2 diabetes mellitus (DM group) and 100 control individuals (ND group). The DM group was further divided into DN0 (no diabetic nephropathy), DN1 (diabetes with small amount of albuminuria), DN2 (diabetes with large amount of albuminuria), L/NDN (late-onset DN after 5 years/no DN over the whole follow-up period of 5 years) and EDN (early-onset diabetic nephropathy occurring within first year) subgroup. We found that (1) genotype and allele frequency of BsmI polymorphism had significant difference between DM and ND group; BB+Bb genotype and B allele frequency were significantly higher in DN2 group than in ND and DN0 group; the ApaI polymorphism and allele frequency did not show any difference between DM and ND group; (2) BsmI BB+Bb genotype and B allele frequency were significantly higher in EDN group than in L/NDN group; (3) among patients with nephropathy, albumin excretion rate (AER) in 24-hour urine was significantly higher in those with BB+Bb phenotype than in those with bb phenotype (P<0.01), (4) unconditional logistic regression analysis showed that BsmI BB+Bb genotype was not only correlated with type 2 diabetic nephropathy, but also correlated with early-onset type 2 diabetic nephropathy. We conclude that the allele B (BB or Bb genotype) in vitamin D receptor gene is correlated with large amount albuminuria in the Han Chinese population with type 2 diabetes, and is probably a risk factor for early-onset diabetic nephropathy.


Polar localization of the ATPase ClpV-5 occurs independent of type VI secretion system apparatus proteins in Burkholderia thailandensis.
ClpV, the ATPase of the type VI secretion system (T6SS) recycles cytoplasmic T6SS proteins following effector translocation. Fluorescent protein fusions to ClpV showed that it localizes to discrete and dynamic foci. ClpV-1-sfGFP of the bacterial cell targeting T6SS-1 of Burkholderia thailandensis exhibits a virtually random localization, whereas ClpV-5-sfGFP of the T6SS-5 targeting host cells is located at one or both poles. The mechanisms underlying the differential localization pattern are not known. Previous analysis of T6SSs, which target bacterial cells revealed that ClpV foci formation is dependent on components of the T6SS. Here, we investigated if the T6SS-5 apparatus confers polar localization of ClpV-5. ClpV-5-sfGFP foci formation and localization was examined in a B. thailandensis mutant harboring a deletion of the entire T6SS-5 gene cluster. We found that ClpV-5-sfGFP localization to discrete foci was not abolished in the absence of the T6SS-5 apparatus. Furthermore, the number of ClpV-5-sfGFP foci displaying a polar localization was not significantly different from that of ClpV-5-sfGFP expressed in the wild type genetic background. These findings suggest the presence of a T6SS-independent localization mechanism for ClpV-5 of the T6SS-5 targeting host cells.


Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model.
Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV.


Aneurysm of the pulmonary trunk in association with minimal pulmonary stenosis.
We report a rare instance of aneurysm of the pulmonary trunk (maximum diameter 6.8 cm) in association with trivial valvar pulmonary stenosis (peak gradient 18 mm Hg). The relevant literature is briefly reviewed.


Regulatory proteins alter nucleotide binding to acto-myosin of sliding filaments in motility assays.
The sliding speed of unregulated thin filaments in motility assays is only about half that of the unloaded shortening velocity of muscle fibers. The addition of regulatory proteins, troponin and tropomyosin, is known to increase the sliding speed of thin filaments in the in vitro motility assay. To learn if this effect is related to the rate of MgADP dissociation from the acto-S1 cross-bridge head, the effects of regulatory proteins on nucleotide binding and release in motility assays were measured in the presence and absence of regulatory proteins. The apparent affinity of acto-heavy meromyosin (acto-HMM) for MgATP was reduced by the presence of regulatory proteins. Similarly, the regulatory proteins increase the concentration of MgADP required to inhibit sliding. These results suggest that regulatory proteins either accelerate the rate of MgADP release from acto-HMM-MgADP or slow its binding to acto-HMM. The reduction of temperature also altered the relationship between thin filament sliding speed and the regulatory proteins. At lower temperatures, the regulatory proteins lost their ability to increase thin filament sliding speed above that of unregulated thin filaments. It is hypothesized that structural changes in the actin portion of the acto-myosin interface are induced by regulatory protein binding to actin.


The effect of eel calcitonin on calcium influx and plasma ion levels in axolotls, Ambystoma mexicanum.
Plasma total calcium and calcium influx, measured during 4-h 45Ca influx experiments, were lower in control axolotls, Ambystoma mexicanum, during August when compared to those in July. A single intraperitoneal injection of 10 micrograms of synthetic eel calcitonin significantly reduced the calcium influx rates during both months but the effect was greater in July (P less than 0.001) than in August (P less than 0.05). Plasma levels of calcium, sodium, potassium, and magnesium were not affected. In neotonous wholly aquatic amphibians, eel calcitonin may work in the same way as it does in fish by reducing the uptake of dissolved calcium from the ambient medium.


High glucose impairs insulin signaling via activation of PKR pathway in L6 muscle cells.
Double stranded RNA (dsRNA) activated protein kinase R (PKR), a ubiquitously expressed serine/threonine kinase is a key inducer of inflammation, insulin resistance and glucose homeostasis in obesity. Recent studies have demonstrated that PKR can respond to metabolic stress in mice as well as in humans. However the underlying molecular mechanism is not fully understood. The aim of the present study was to examine the effect of high glucose on cultured rat L6 muscle cells and to investigate whether inhibition of PKR could prevent any deleterious effects of high glucose in these cells. PKR expression was determined by immunofluorescence and immunoblotting. The expression of different insulin signaling gene markers were measured by RT-PCR. Oxidative stress and apoptosis were determined by flow cytometry. High glucose treated L6 muscle cells developed a significant increase in PKR expression. Impaired insulin signaling as well as reduced insulin stimulated glucose uptake was observed in high glucose treated L6 muscle cells. A significant increase in reactive oxygen species generation and apoptosis formation was also observed in high glucose treated cultured L6 muscle cells. All these effects of high glucose were attenuated by a selective PKR inhibitor imoxin. Our study demonstrates PKR may have an additive role against the deleterious effects of high glucose in diabetes. Prevention of PKR activation, by safer and specific inhibitors is a therapeutic option in metabolic disorders that needs to be explored further.


The role of synapse elimination in the establishment of neuromuscular compartments.
To investigate the specificity of development of initial neuromuscular connections, we examined the compartmental distribution of synapses in neonatal rat lateral gastrocnemius (LG) muscle. Initial neuromuscular connections might be restricted to the compartmental territories present in adults; alternatively, synapse elimination could establish the compartments from a less precise pattern of innervation. We examined 46 pups of ages 0 to 14 postnatal days using a variety of techniques. The principle method was evoked electromyographic (EMG) activity in response to nerve stimulation. The nerve branch to one neuromuscular compartment was cut and the remainder of the nerve was stimulated. The presence of EMG activity was used to identify the areas of muscle contracting in response to nerve stimulation. After cutting a particular branch, EMG activity generally could not be recorded from the denervated compartment. These results indicate that the pattern of innervation at birth is essentially compartment-specific, and that neuromuscular compartments are not shaped from some less precise pattern by postnatal synapse elimination. The factors which operate prenatally to determine this high degree of specificity in neuromuscular connectivity seen at the time of birth, however, remain unknown.


Vanishing contrast-enhancing peri-lead oedema following deep brain stimulation surgery: A case report.
Idiopathic peri-lead oedema (IPLE) after deep brain stimulation (DBS) surgery is still a poorly understood phenomenon. It is usually asymptomatic and does not present contrast enhancement at the post-operative Magnetic Resonance Imaging (MRI). Here we present the rare case of contrast-enhancing IPLE occurring in a completely asymptomatic patient vanishing spontaneously at the radiological follow-up at one month. The radiological picture raised the concerns of peri-lead abscess, but the absence of clinical and laboratory signs of infection and the benefit of DBS over the patient's dystonic symptoms prompted a more conservative approach. To our knowledge, this is the first reported case of asymptomatic contrast-enhancing IPLE conservatively managed.


The effects of a caries-removing gel (Carisolv) on FM3A cell-line in vitro.
The aim of this study was to examine the cytotoxic effects of Carisolv on mouse mammary carcinoma cell line (FM3A) at different application times. The FM3A cell line obtained from the European Collection of Animal Cell Cultures was used in the cell culture assays. Exponentially growing cells were seeded in 5x10(5)cells/well in 5 ml of RPMI 1640 medium supplemented with 10(%) fetal calf serum and antibiotics in each well of a six-well plate. Carisolv gel was applied onto the cell culture medium for 1, 5 and 20 min and incubated for 24 h at 37 degrees C in a humidified atmosphere of 5(%) carbon dioxide (CO(2)). After 24 h incubation, the cells were collected by trypsinisation and counted with a hemocytometer. The cytotoxicity of the Carisolv was determined by evaluation of cell growth and viability in comparison to untreated controls (cell growth=100%). For cell viability, the trypane blue exclusion assay was used. Dunnett's t-test was used for statistical analysis. Cell growth was significantly reduced after 20 min application of Carisolv in comparison to the control (p < 0.001) and 1 min treatment groups (p < 0.05) No significant differences were found in cell viability between the study groups. It can be concluded that prolonged application of Carisolv did not affect cell viability, but had a reducing effect on cell growth in the FM3A cell line.


Serial D-dimer levels in the assessment of tumor mass and clinical outcome in ovarian cancer.
D-dimer (DD)--an end product of fibrinolysis--was measured in serum by enzyme immunoassay using a monoclonal antibody to the gamma gamma crosslink in patients with ovarian cancer, before primary surgery and during chemotherapy for 12 months or more. Serial DD levels were found to have a high sensitivity for the detection of tumor in patients with subclinical disease (91%) as well as for predicting progression of disease (100%). As determined by a careful second-look laparotomy in patients with complete clinical remission the DD marker was highly predictive of tumors less than 1 cm. The negative predictive value (82%) was higher than the positive predictive value (69%). However, there were 31% of the patients who showed a false-positive result; a close examination of the clinical data of these 9 patients failed to reveal an explanation for the positive DD levels. Despite the lack of specificity (50% in the present series), the findings support the use of DD in the assessment of patients with ovarian cancer, especially those with subclinical disease.


The Relationship between Hope and Self-Esteem in Patients with Leukemia.
Patients with hematologic malignancies often experience many emotional reactions which are different based on patient's culture. Indeed culture determines the different ways that patients understand cancer. Accordingly, the aim of this study was to determine the relationship of self-esteem and hope among Iranian cancer patients. This descriptive-correlational study was undertaken among 85 leukemic patients admitted to Shahid Ghazi hospital in East-Azerbaijan province, Iran. They were selected using consecutive sampling method. Persian form of Hearth Hope Index and Coppersmith Self-Esteem Inventory were used to identify patients' hope and self-esteem. The data were analyzed using SPSS version 13.0. The overall scores of hope and self-esteem were 33.05 (5.24) and 94.61 (11.51), respectively. There was a positive correlation between hope and self-esteem (rs = 0.73, n = 85, P < 0.001). Although culture determines the different ways that patients understand cancer, but it seems that the self-esteem and hope relationship could be similar in different cultures. The findings of this study indicate that nurses could be helpful through designing and implementing appropriate educational programs in order to enhance hope and self-esteem of leukemia patients.


Presacral myelolipoma in a patient with rectal cancer: diagnosis by magnetic resonance imaging and aspiration cytology.
State-of-the-art magnetic resonance imaging (MRI) protocol for the evaluation of rectal cancer suggests only T2-weighted fast spin-echo sequences. We present a case of rectal cancer with a simultaneous presacral myelolipoma that could have been misdiagnosed on MRI as a metastasis if a T1-weighted sequence had not also been used in the evaluation.


Skin biopsy for assessment of autonomic denervation in Parkinson's disease.
Autonomic dysfunction in Parkinson's disease (PD) is considered a late complication of the disease or an adverse effect of anti-parkinsonian medications. Morphological changes are demonstrated only by postmortem examination. The study objective was to evaluate peripheral autonomic neural involvement in PD using punch skin biopsy. The study sample included 22 patients (mean age 50 +/- 7.7 years, mean disease duration 5.3 +/- 3.8 years) and 19 controls. Four-millimeter skin biopsies were immunohistochemically stained with anti-PGP 9.5 antibody. Autonomic innervation of the blood vessels, sweat glands, and erector pili muscles was assessed and rated from 0 (normal) to 2 (severe). Cutaneous autonomic innervation was decreased in patients compared to controls. Semi quantitative analysis demonstrated reduced autonomic innervation of the blood vessels (1.0 +/- 0.8 vs. 0.42 +/- 0.8 in controls; p < 0.02), of sweat glands (0.95 +/- 0.67 vs. 0.47 +/- 0.61; p < 0.02) and of the erector pili muscles (1.06 +/- 0.55 vs 0.21 +/- 0.42; p < 0.001). This method demonstrates that the peripheral autonomic system is affected in PD at early stage of the disease and that autonomic involvement in PD may be more prevalent than previously thought.


Cation exchange chromatography on a monodisperse 3 µm particle enables extensive analytical similarity assessment of biosimilars.
Biosimilarity assessment requires extensive characterization and comparability exercises to investigate product quality attributes of an originator product and its potential biosimilar(s) and to highlight any differences between them. Performing a thorough comparison allows a shortened approval path, which also eliminates lengthy and expensive clinical trials, ensuring comparable product quality and efficacy but at lower drug prices. The wide variety of analytical methods available for biosimilar assessment ranges from biological to analytical assays, each providing orthogonal information to fully characterize biosimilar candidates. Intact native mass spectrometry (MS) has been shown to be an excellent tool for detection and monitoring of important quality attributes such as N-glycosylation, deamidation, sequence truncation and higher order structures. When combined with efficient upfront separation methods, simplification of the proteoform heterogeneity and associated complexity prior to MS analysis can be achieved. Native mass spectrometry can provide robust and accurate results within short analysis times and requires minimal sample preparation. In this study we report the use of a monodisperse strong cation exchange chromatography phase hyphenated with Orbitrap mass spectrometry (SCX-MS) to compare the best-selling biopharmaceutical product Humira® with 7 commercially approved biosimilar products. SCX-MS analysis allowed for the identification of previously described as well as so far unreported proteoforms and their relative quantitation across all samples, revealing differences in N-glycosylation and lysine truncation, as well as unique features for some products such as sialylation and N-terminal clipping. SCX-MS analysis, powered by a highly efficient separation column, enabled deep and efficient analytical comparison of biosimilar products.


Electrochemical improvement of the performance of PO2 electrodes.
Rotating ring-disc electrode studies have indicated that relatively large quantities of hydrogen peroxide ion, HO2-, are produced when oxygen is reduced at a platinum or gold polarographic electrode surface. The electrochemical reduction processes are improved and the quantity of HO2- is reduced by using alkaline buffer electrolytes (pH 10 to 11) and by polarising the electrode at voltages more negative than -0.9 V. The presence of HO2- in the electrolyte has been shown to be the cause of excessively long time response in both blood-gas and respiratory polarographic PO2 electrodes; electrode alinearity on micro-blood-gas PO2 electrodes has also been shown to be due to the absence of a plateau on the polarogram of electrodes when used with conventional electrolytes. The use of a high pH buffer and high negative voltage results in a long, flat plateau and a marked improvement in both electrode linearity and response time. This two-fold improvement in electrode performance holds true for both platinum and gold polarographic respiratory gas and blood-gas PO2 electrodes.


What are the holistic experiences of adults living long-term with the consequences of cancer and its treatment? A qualitative evidence synthesis.
The number of people living with and beyond cancer is increasing; a significant number of these people will experience the long-term and late effects of cancer and its treatment. Research into this group has been identified as a priority to better understand healthcare needs. This review identified and synthesised qualitative research data relating to the lived experience of the consequences of cancer and its treatment. A systematic search via electronic databases was conducted in July 2019. Literature was identified that explored the experience of adults living beyond cancer from their own perspective. Thematic synthesis was used to extract and analyse data. Six articles were reviewed. Three main themes were identified with four subthemes:1. Living with an altered sense of self; 2. Things are never going to be quite the same again (2.1. The unexpected. 2.2 The uncertain.); 3. Ways of coping with the unexpected and the uncertain. (3.1. Drawing on internal resilience. 3.2. The influence and impact of external relationships.). The findings showed that the participants' world-view changed after cancer and this affected everyday lives both positively and negatively. The experience of having had cancer remains significant long after diagnosis and treatment, yet effective preparation and ongoing support for living beyond cancer is lacking. The experience of living long-term after cancer is characterised by an altered sense of self and has implications for long-term wellbeing. Further research should explore healthcare needs and services required to adequately meet the needs of this growing group of people.


Low testosterone level predicts prostate cancer in re-biopsy in patients with high grade prostatic intraepithelial neoplasia.
What's known on the subject? and What does the study add? High grade prostatic intraepithelial neoplasia (HGPIN) is a risk factor for prostate cancer (PCa), but only multifocality is an indication for early rebiopsy. Other risk factors for PCa development from HGPIN remain unknown. PCa is related to testosterone. Testosterone has been proven to be linked to PCa detection and poor prognosis PCa. This study shows that low free and bioavailable testosterone levels are associated with an increased risk of PCa in a rebiopsy after HGPIN diagnosis. Men with low testosterone levels and HGPIN could therefore be considered a high-risk cohort for developing PCa. To determine the relevance of the hormonal profile of patients with high grade prostatic intraepithelial neoplasia (HGPIN) and its relationship to prostate cancer (PCa) in rebiopsy. We prospectively analysed 82 consecutive patients with a diagnosis of HGPIN without PCa in a prostate biopsy between September 2007 and December 2009. Of these 82 patients, 45 underwent rebiopsy and their hormonal profile was determined (testosterone and sex hormone-binding globulin [SHBG]) as part of our clinical protocol. Patient age, PSA level, prostate volume, PSA density, testosterone, free testosterone, bioavailable testosterone and SHBG were recorded prospectively. A comparative study between those patients with a positive rebiopsy and those with a negative rebiopsy was performed. We found that free testosterone (P = 0.04), bioavailable testosterone (P = 0.04) and SHBG (P = 0.02) were significantly associated with a positive rebiopsy. Other variables such as age (P = 0.745), PSA level (P = 0.630), prostate volume (P = 0.690), PSA density (P = 0.950), testosterone (P = 0.981) and prostatic intraepithelial neoplasia multifocality (P = 0.777) were not associated with the presence of adenocarcinoma in the rebiopsy. Patients with adenocarcinoma of the prostate after a diagnosis of HGPIN have higher SHBG levels and lower calculated free testosterone levels than patients with a negative rebiopsy. Testosterone levels might be a useful indication for rebiopsy after HGPIN diagnosis.


Identifying biomarkers of drug use recurrence using wearable device technologies and phone applications.
Identifying predictors of drug use recurrence (DUR) is critical to combat the addiction epidemic. Wearable devices and phone-based applications for obtaining self-reported assessments in the patient's natural environment (e.g., ecological momentary assessment; EMA) have been used in various healthcare settings. However, the utility of combining these technologies to predict DUR in substance use disorder (SUD) has not yet been explored. This study investigates the combined use of wearable technologies and EMA as a potential mechanism for identifying physiological/behavioral biomarkers of DUR. Participants, recruited from an SUD treatment program, were provided with a commercially available wearable device that continuously monitors biometric signals (e.g., heart rate/variability [HR/HRV], sleep characteristics). They were also prompted daily to complete an EMA via phone-based application (EMA-APP) that included questionnaires regarding mood, pain, and craving. Seventy-seven participants are included in this pilot study (34 participants experienced a DUR during enrollment). Wearable technologies revealed that physiological markers were significantly elevated in the week prior to DUR relative to periods of sustained abstinence (p<0.001). Results from the EMA-APP revealed that those who experienced a DUR reported greater difficulty concentrating, exposure to triggers associated with substance use, and increased isolation the day prior to DUR (p<0.001). Compliance with study procedures during the DUR week was lower than any other period of measurement (p<0.001). These results suggest that data acquired via wearable technologies and the EMA-APP may serve as a method of predicting near-term DUR, thereby potentially prompting intervention before drug use occurs.


Extraction of a vascular function for a fully automated dynamic contrast-enhanced magnetic resonance brain image processing pipeline.
To develop a deep-learning model that leverages the spatial and temporal information from dynamic contrast-enhanced magnetic resonance (DCE MR) brain imaging in order to automatically estimate a vascular function (VF) for quantitative pharmacokinetic (PK) modeling. Patients with glioblastoma multiforme were scanned post-resection approximately every 2 months using a high spatial and temporal resolution DCE MR imaging sequence ( ≈5 s and ≈2 cm3 ). A region over the transverse sinus was manually drawn in the dynamic T1-weighted images to provide a ground truth VF. The manual regions and their resulting VF curves were used to train a deep-learning model based on a 3D U-net architecture. The model concurrently utilized the spatial and temporal information in DCE MR images to predict the VF. In order to analyze the contribution of the spatial and temporal terms, different weighted combinations were examined. The manual and deep-learning predicted regions and VF curves were compared. Forty-three patients were enrolled in this study and 155 DCE MR scans were processed. The 3D U-net was trained using a loss function that combined the spatial and temporal information with different weightings. The best VF curves were obtained when both spatial and temporal information were considered. The predicted VF curve was similar to the manual ground truth VF curves. The use of spatial and temporal information improved VF curve prediction relative to when only the spatial information is used. The method generalized well for unseen data and can be used to automatically estimate a VF curve suitable for quantitative PK modeling. This method allows for a more efficient clinical pipeline and may improve automation of permeability mapping.


Shall we play together? Game-based learning for engagement and classroom climate in Spanish socially deprived communities.
The purpose of this study is to analyze the effects of a game-based learning (GBL) program on the classroom climate and engagement of high schools in socially deprived communities in Spain. The study included 277 students from two secondary schools located in Southern Spain, situated in Zones in Need of Social Transformation. Sampling was non-probabilistic and accidental, based on the accessibility of the school and the willingness of the management and teaching staff to participate in the GBL program. The study employed a control group and two experimental groups (cooperative games group only and cooperative and competitive games group) to compare pre-test and post-test data in both groups. The Brief Class Climate Scale and Engagement Inventory, validated in academic literature, were used as assessment instruments. The study used a series of ANOVA tests to compare the experimental groups with the control group. The results indicated statistically significant changes in all study variables. In all cases, the experimental groups demonstrated greater benefits than the control group. The study findings reveal that games can provide significant benefits to students, regardless of whether they are cooperative or competitive. The study provides evidence of the benefits of GBL in high schools located in socially deprived communities in Spain.


Predictive Genomic Biomarkers of Hormonal Therapy Versus Chemotherapy Benefit in Metastatic Castration-resistant Prostate Cancer.
Biomarkers predicting second-generation novel hormonal therapy (NHT) benefit relative to taxanes are critical for optimized treatment decisions for metastatic castration-resistant prostate cancer (mCRPC) patients. These associations have not been reported simultaneously for common mCRPC genomic biomarkers. To evaluate predictive associations of common genomic aberrations in mCRPC using an established comprehensive genomic profiling (CGP) system. A retrospective cohort study used data from a deidentified US-based clinicogenomic database comprising patients treated in routine clinical practice between 2011 and 2020, evaluated with Foundation Medicine CGP in tissue biopsies obtained around the time of treatment decision. The main cohort included 180 NHT and 179 taxane lines of therapy (LOTs) from 308 unique patients. The sequential cohort comprised a subset of the main cohort NHT LOTs immediately followed by taxane from 55 unique patients. Prostate-specific antigen (PSA) response, time to next treatment (TTNT), and overall survival (OS) were assessed. Main cohort analyses were adjusted for known treatment assignment biases via inverse probability of treatment weighting (IPTW) in treatment interaction models. In the main cohort, patients with AR amplification (ARamp) or PTEN aberrations (PTENalt) had worse relative PSA response on NHT versus taxanes compared with patients without. Patients with ARamp, PTENalt, or RB1 aberrations (RB1alt) also had worse relative TTNT and OS on NHT but not on taxanes. In multivariable models for TTNT and OS adjusted via IPTW, ARamp, PTENalt, and RB1alt were shown as poor prognostic factors overall and demonstrated significant treatment interactions, indicating reduced hazards of therapy switch and death on taxanes versus NHT. Consistent associations favoring increased benefit from subsequent taxane despite prior NHT treatment line were observed only for ARamp in the sequential cohort, in which very few patients had RB1alt for assessment. ARamp status is a candidate biomarker to predict poor effectiveness of NHT relative to taxanes in mCRPC in scenarios where both options are considered. Specific alterations in the DNA of tumors may assist in choosing between novel oral hormonal therapies and standard chemotherapy in advanced prostate cancer patients.


Cytokeratins in normal lung and lung carcinomas. I. Adenocarcinomas, squamous cell carcinomas and cultured cell lines.
The various epithelial cells of the lower respiratory tract and the carcinomas derived from them differ markedly in their differentiation characteristics. Using immunofluorescence microscopy and two-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissues we have considered whether cytokeratin polypeptides can serve as markers of cell differentiation in epithelia from various parts of the human and bovine lower respiratory tract. In addition , we have compared these protein patterns with those found in the two commonest types of human lung carcinoma and in several cultured lung carcinoma cell lines. By immunofluorescence microscopy, broad spectrum antibodies to cytokeratins stain all epithelial cells of the respiratory tract, including basal, ciliated, goblet, and alveolar cells as well as all tumor cells of adenocarcinomas and squamous cell carcinomas. However, in contrast, selective cytokeratin antibodies reveal cell type-related differences. Basal cells of the bronchial epithelium react with antibodies raised against a specific epidermal keratin polypeptide but not with antibodies derived from cytokeratins characteristic of simple epithelia. When examined by two-dimensional gel electrophoresis, the alveolar cells of human lung show cytokeratin polypeptides typical of simple epithelia (nos. 7, 8, 18 and 19) whereas the bronchial epithelium expresses, in addition, basic cytokeratins (no. 5, small amounts of no. 6) as well as the acidic polypeptides nos. 15 and 17. Bovine alveolar cells also differ from cells of the tracheal epithelium by the absence of a basic cytokeratin polypeptide. All adenocarcinomas of the lung reveal a "simple-epithelium-type" cytokeratin pattern (nos. 7, 8, 18 and 19). In contrast, squamous cell carcinomas of the lung contain an unusual complexity of cytokeratins. We have consistently found polypeptides nos. 5, 6, 8, 13, 17, 18 and 19 and, in some cases, variable amounts of cytokeratins nos. 4, 14 and 15. Several established cell lines derived from human lung carcinomas (SK-LU-1, Calu -1, SK-MES-1 and A-549) show a uniform pattern of cytokeratin polypeptides (nos. 7, 8, 18 and 19), similar to that found in adenocarcinomas. In addition, vimentin filaments are produced in all the cell lines examined, except for SK-LU-1.(ABSTRACT TRUNCATED AT 400 WORDS)


Autoantibodies to synapsin I sequestrate synapsin I and alter synaptic function.
Synapsin I is a phosphoprotein that coats the cytoplasmic side of synaptic vesicles and regulates their trafficking within nerve terminals. Autoantibodies against Syn I have been described in sera and cerebrospinal fluids of patients with numerous neurological diseases, including limbic encephalitis and clinically isolated syndrome; however, the effects and fate of autoantibodies in neurons are still unexplored. We found that in vitro exposure of primary hippocampal neurons to patient's autoantibodies to SynI decreased the density of excitatory and inhibitory synapses and impaired both glutamatergic and GABAergic synaptic transmission. These effects were reproduced with a purified SynI antibody and completely absent in SynI knockout neurons. Autoantibodies to SynI are internalized by FcγII/III-mediated endocytosis, interact with endogenous SynI, and promote its sequestration and intracellular aggregation. Neurons exposed to human autoantibodies to SynI display a reduced density of SVs, mimicking the SynI loss-of-function phenotype. Our data indicate that autoantibodies to intracellular antigens such as SynI can reach and inactivate their targets and suggest that an antibody-mediated synaptic dysfunction may contribute to the evolution and progression of autoimmune-mediated neurological diseases positive for SynI autoantibodies.


Oral Anticoagulation After Successful Atrial Fibrillation Ablation Operations: Is It Necessary?
This study analyzed the results of atrial fibrillation (AF) ablation concomitant to open heart operations using continuous monitoring. We investigated 70 consecutive patients (mean age, 72.1 ± 6 years; European System for Cardiac Operative Risk Evaluation II: 9.7% ± 8.2%) who underwent AF ablation concomitant to cardiac operations in our institution between February 2012 and February 2013. For precise rhythm analysis we implanted Reveal XT devices (Medtronic Inc, Minneapolis, MN) in all patients at the end of operations. Twenty-two patients had paroxysmal (31.4%), 20 persistent (28.6%) and 28 longstanding-persistent AF (40%). AF duration time was at a median 18 months. Cardiac rhythm data were obtained by telemonitoring at 1-month intervals, and the AF burden was calculated at 3, 6, and 9 months and at 1 year postoperatively (ablation procedure success was defined as a burden of ≤ 0.5%). Further, a neurologic follow-up was performed at 1 year postoperatively. Overall survival was 95.7% at 30 days and 84.3% at 1 year. At 1 year, 66.7% of patients were in stable sinus rhythm, and AF burden was significantly reduced even in nonresponders: 88.2% of patients were off antiarrhythmic drugs, and oral anticoagulation had been stopped in 92.1%. No late neurologic events had occurred. Sinus rhythm at discharge and paroxysmal type of AF were predictive for later sinus rhythm (p = 0.04 and p = 0.048, respectively). Considering the long AF duration and the high proportion of longstanding-persistent AF, the overall success of ablation procedures was satisfactory. Even though oral anticoagulation was stopped in most patients, no neurologic events were detected.


In vivo somatic mutations in Werner's syndrome.
The frequencies of mutant erythrocytes with loss of heterozygosity at the glycophorin A (GPA) locus and mutant CD4+ T cells lacking surface expression of the T-cell receptor alphabeta (TCR)/CD3 complex were measured by flow cytometry for Japanese Werner's syndrome (WRN) patients. The hemizygous and homozygous GPA mutant frequencies (GPA Mfs) and the TCR/CD3-defective mutant frequency (TCR Mf) in WRN patients were found to be significantly higher than those in normal controls in the same age range. However, because these Mfs in the patients are only about twice those in controls, it is difficult to conclude that the WRN gene mutations cause instability of somatic genes. This contrasts markedly with Bloom's syndrome (BLM) patients, whose GPA and TCR Mfs were previously reported to increase about 50- and 15-fold, respectively. The difference in Mfs is one aspect of the large variation in the phenotype observed between WRN and BLM patients, suggesting a different role of the responsible genes, both of which belong to the RecQ DNA helicase gene family, in the control of somatic mutagenesis.


Cooperative reaction chemistry derived from a borata-diene framework.
The bifunctional frustrated BH(-)/B hydridoborate nucleophile/borane Lewis acid pair 6 is prepared starting from the borata-diene 3 by a sequence of sequential protonation/hydride attachment, followed by hydroboration with Piers' borane [HB(C6F5)2]. The trans-1,2-bifunctional system 6 reduced carbon monoxide eventually to the aldehyde product 10.


Plate tectonics of the Mediterranean region.
The seismicity and fault plane solutions in the Mediterranean area show that two small rapidly moving plates exist in the Eastern Mediterranean, and such plates may be a common feature of contracting ocean basins. The results show that the concepts of plate tectonics apply to instantaneous motions across continental plate boundaries.


The Prostacyclin Analog Iloprost Promotes Cementum Formation and Collagen Reattachment of Replanted Molars and Up-regulates Mineralization by Human Periodontal Ligament Cells.
This study evaluated the use of the prostacyclin analog iloprost as a root surface treatment agent in promoting acellular cementum (AC) formation and collagen reattachment after tooth replantation in vivo. In addition, its effect on human periodontal ligament cell (hPDLC) mineralization was assessed in vitro. First molars of 8-week-old Wistar rats were extracted. In 1 group, the root surfaces were treated with Hank's balanced salt solution (HBSS), and the other group's root surfaces were treated with 10-6 mol/L iloprost before replantation. At day 30, maxillae were prepared for micro-computed tomographic imaging and histomorphometric analysis. The effect of iloprost on mineralization by hPDLCs was analyzed by mineralized nodule formation and quantitative polymerase chain reaction at 7 and 14 days. Micro-computed tomographic imaging demonstrated a significant higher bone volume in the iloprost groups, whereas the HBSS groups had extensive bone and root resorption. Histologic analysis revealed deposition of a thick AC layer along the root in the iloprost group with well-organized periodontal ligament fibers inserted into the cementum. The HBSS group demonstrated more osteoclasts than the iloprost group. In vitro, iloprost-treated hPDLCs had a significantly increased RUNX2, OSX, BSP, and ALP gene expression that coincided with an increased deposition of mineralized nodules. These effects were abrogated by a PGI2 receptor inhibitor. Our results revealed that iloprost promoted PDL regeneration in replanted molars. Furthermore, resorption of the roots was decreased, whereas AC deposition was stimulated. Iloprost-treatment increased hPDLC mineralization and was mediated by PGI2 receptor activation. These observations indicate that iloprost may be a promising root surface treatment agent.