DUSP10 gene polymorphism and risk of colorectal cancer in the Han Chinese population.
Dual-specificity protein phosphatases (DUSP) negatively regulate members of the mitogen-activated protein kinase superfamily, which is associated with cellular proliferation and differentiation. A recent study suggests that DUSP10 is frequently upregulated in colorectal cancer (CRC). Our study aimed to assess whether DUSP10 contributes to the risk of CRC. We analyzed nine tag single nucleotide polymorphisms (tSNPs) of DUSP10 in a case-control study of Han Chinese by the χ²-test and the SHEsis software. We found that two tSNPs (rs908858, P=0.00004; rs11118838, P=0.02510) were significantly associated with CRC using the χ²-test. Using the SHEsis software, six tSNPs (rs12041033, rs17010629, rs12724393, rs12036163, rs11118838, rs12044821) were found in the same linkage disequilibrium block. Within this linkage disequilibrium block, haplotype 'CTCAAC' showed an increased risk of CRC by 42%. By global haplotype analysis, we found that the haplotype 'ACTCAACTA' may increase the risk of CRC by ∼53%; the haplotype 'GCCCACCCA' may decrease the risk by ∼46%. Our results, combined with previous studies, suggest that certain mutations in DUSP10 correlate with the incidence of CRC. Thus, the function of the DUSP10 gene product may contribute toward CRC in the Han Chinese population.


Poisoning following exposure to chemicals stored in mislabelled or unlabelled containers: a recipe for potential disaster.
To investigate poisoning exposures to chemicals that were unlabelled, mislabelled or not in their original containers in New Zealand over the last 10 years, based on calls to the New Zealand National Poisons Centre (NZNPC). Call data from the NZNPC between 2003 and 2012 were analysed retrospectively. Parameters reviewed included patient age, route and site of exposure, product classification and recommended intervention. Of the 324,411 calls received between 2003 and 2012, 100,465 calls were associated with acute human exposure to chemicals. There were 757 inquiries related to human exposure to mislabelled or unlabelled chemicals consisting of 0.75% of chemical exposures. Adults were involved in 51% of incidents, children, <5 years 32%, 5-10 years 10%, and adolescents 5%. Child exploratory behaviour was responsible for 38% of calls and adult unintentional exposures 61%. Medical attention was advised in 26% of calls. Inadvertent exposure to toxic products stored in unlabelled or mislabelled containers is a problem for all age groups. Although it represents a small proportion of total calls to the NZNPC it remains a potential risk for serious poisoning. It is important that chemicals are stored securely, in their original containers, and never stored in drinking vessels.


Feasibility of two-dimensional speckle tracking in evaluation of arterial stiffness: Comparison with pulse wave velocity and conventional sonographic markers of atherosclerosis.
Objective Arterial stiffening is an early marker of atherosclerosis that has a prognostic value for cardiovascular morbidity and mortality. Although many markers of arterial hardening have been proposed, the search is on for newer, more user-friendly and reliable surrogates. One such potential candidate has emerged from cardiology, the speckle-tracking technique. The aim of this study was to evaluate the feasibility of the two-dimensional speckle tracking for the evaluation of arterial wall stiffness in comparison with standard stiffness parameters. Methods Carotid ultrasound and applanation tonometry were performed in 188 patients with no cardiovascular risk factors. The following parameters were then evaluated: the intima-media complex thickness, distensibility coefficient, β-stiffness index, circumferential strain/strain rate, and pulse wave velocity and augmentation index. These variables were compared with each other and with patient age, and their reliability was assessed with Bland-Altman plots. Results Strain parameters derived from two-dimensional speckle tracking and intima-media complex thickness correlated better with age and pulse wave velocity than standard makers of arterial stiffness. Moreover, the reliability of these measurements was significantly higher than conventional surrogates. Conclusions Two-dimensional speckle tracing is a reliable method for the evaluation of arterial stiffness. Therefore, together with intima-media complex thickness measurement, it offers great potential in clinical practice as an early marker of atherosclerosis.


Sp1, a CAAT-binding factor, and the adenovirus major late promoter transcription factor interact with functional regions of the gamma-fibrinogen promoter.
To study the factors which influence the coordinately and developmentally regulated expression of the three adjacent fibrinogen genes, we have defined the functional regions of the gamma-fibrinogen promoter and the proteins which bind to them. Using a series of 5' and internal deletion mutations, we found that sequences between 88 and 43 base pairs (bp) upstream of the gamma-fibrinogen transcription initiation site functioned in cis to direct properly initiated mRNA accumulation in transfected hepatocytes. The efficient function of these sequences was highly distance dependent, since transcriptional activity decreased by 92% when they were moved 32 bp upstream of the TATA box. We demonstrated that two known and one putative transcriptional factors interacted with this 47-bp sequence. The transcription factor Sp1 interacted with sequences between -51 and -46 as demonstrated by protection from DNase I digestion with the purified protein. Directly adjacent to the Sp1 site, between nucleotides -66 and -53, there was a sequence which bound a CAAT-binding factor. Finally, sequences just 5' to the CAAT factor-binding site interacted with the adenovirus major late transcriptional factor as previously demonstrated. Internal deletion mutations which disrupt these interactions diminished the activity of the promoter in vivo. One consequence of the interaction of these proteins is that a bend is placed in the DNA at or near their sites of interaction.


The yeast protein Xtc1 functions as a direct transcriptional repressor.
The yeast protein Xtc1 was identified as a protein that binds directly and specifically to the activation domains of acidic activators such as E2F-1, Gal4 and VP16. Additionally, it was shown to co-purify with the RNA polymerase II holoenzyme complex and it was suggested that Xtc1 functions as a regulator of transcription that modulates the response of RNA polymerase II to transcriptional activators. We have further analyzed the transcription function of Xtc1 and show that its fusion to a heterologous DNA binding domain can repress transcription of a reporter gene in vivo in an Srb10/11-dependent manner. We suggest that the presence of Xtc1 in the RNA polymerase II holoenzyme could help to recruit an Srb10-active form of the holoenzyme to target promoters. This same protein has also been implicated in mitochondrial DNA recombination, maintenance and repair. Determination of the subcellular localization using a GFP-Xtc1 fusion shows that it localizes to both the nucleus and the mitochondria in vivo, which is consistent with Xtc1 having a function in both cellular compartments.


Validity of the CRAFFT substance abuse screening test among adolescent clinic patients.
To determine the accuracy of the CRAFFT substance abuse screening test. Criterion standard validation study comparing the score on the 6-item CRAFFT test with screening categories determined by a concurrently administered substance-use problem scale and a structured psychiatric diagnostic interview. Screening categories were "any problem" (ie, problem use, abuse, or dependence), "any disorder" (ie, abuse or dependence), and "dependence." A large, hospital-based adolescent clinic. Patients aged 14 to 18 years arriving for routine health care. The CRAFFT receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value. Of the 538 participants, 68.4% were female, and 75.8% were from racial and ethnic minority groups. Diagnostic classifications for substance use during the past 12 months were no use (49.6%), occasional use (23.6%), problem use (10.6%), abuse (9.5%), and dependence (6.7%). Classifications were strongly correlated with the CRAFFT score (Spearman rho, 0.72; P<.001). A CRAFFT score of 2 or higher was optimal for identifying any problem (sensitivity, 0.76; specificity, 0.94; positive predictive value, 0.83; and negative predictive value, 0.91), any disorder (sensitivity, 0.80; specificity, 0.86; positive predictive value, 0.53; and negative predictive value, 0.96) and dependence (sensitivity, 0.92; specificity, 0.80; positive predictive value, 0.25; and negative predictive value 0.99). Approximately one fourth of participants had a CRAFFT score of 2 or higher. Validity was not significantly affected by age, sex, or race. The CRAFFT test is a valid means of screening adolescents for substance-related problems and disorders, which may be common in some general clinic populations.


Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes.
Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteoglycans and collagen-type-II synthesis in osteoarthritic (OA) cartilage. Human OA cartilage explants were cultured with salmon calcitonin [100 pM-100 nM]. Direct effects of calcitonin on articular cartilage were evaluated by 1) measurement of proteoglycan synthesis by incorporation of radioactive labeled 35SO4 [5 microCi] 2) quantification of collagen-type-II formation by pro-peptides of collagen type II (PIINP) ELISA, 3) QPCR expression of the calcitonin receptor in OA chondrocytes using four individual primer pairs, 4) activation of the cAMP signaling pathway by EIA and, 5) investigations of metabolic activity by AlamarBlue. QPCR analysis and subsequent sequencing confirmed expression of the calcitonin receptor in human chondrocytes. All doses of salmon calcitonin significantly elevated cAMP levels (P < 0.01 and P < 0.001). Calcitonin significantly and concentration-dependently [100 pM-100 nM] induced proteoglycan synthesis measured by radioactive 35SO4 incorporation, with a 96% maximal induction at 10 nM (P < 0.001) corresponding to an 80% induction of 100 ng/ml IGF, (P < 0.05). In alignment with calcitonin treatments [100 pM-100 nM] resulted in 35% (P < 0.01) increased PIINP levels. Calcitonin treatment increased proteoglycan and collagen synthesis in human OA cartilage. In addition to its well-established effect on subchondral bone, calcitonin may prove beneficial to the management of joint diseases through direct effects on chondrocytes.


Biomedical Applications of Self-Assembling Peptides.
Self-assembling peptides have gained increasing attention as versatile molecules to generate diverse supramolecular structures with tunable functionality. Because of the possibility to integrate a wide range of functional domains into self-assembling peptides including cell attachment sequences, signaling domains, vaccine epitopes, and even therapeutic moieties, complex nanostructures can be obtained with a wide range of applications in the biomedical field. The first part of this Review provides a concise overview of how peptide primary and secondary structure dictate the way such self-assembling peptides organize into higher ordered, supramolecular structures. Next, an overview of the literature will be given on recent studies on peptide self-assembly for application in drug delivery, vaccination, and tissue engineering.


Massively parallel ionization of extended atomic systems.
Massively parallel ionization of many atoms in a cluster or biomolecule is identified as a new phenomenon of light-matter interaction which becomes feasible through short and intense FEL pulses. Almost simultaneously emitted from the illuminated target the photo-electrons can have such a high density that they interact substantially even after photoionization. This interaction results in a characteristic electron spectrum which can be interpreted as a convolution of a mean-field electron dynamics and binary electron-electron collisions. We demonstrate that this universal spectrum can be obtained analytically by summing synthetic two-body Coulomb collision events. Moreover, we propose an experiment with hydrogen clusters to observe massively parallel ionization.


Characterization of coal gasification slag-based activated carbon and its potential application in lead removal.
Highly porous activated carbons were prepared from a coal gasification slag (CGS) precursor, by KOH activation to remove Pb2+ from aqueous solution. The effects of pretreatment methods and activation parameters on the properties of the activated carbon were investigated, such as KOH/CGS mass ratio, activation temperature and activation time. The results showed that the maximum Brunauer-Emmett-Teller surface area and total pore volume with the value of 2481 m2 g-1 and of 1.711 cc g-1 were obtained at a KOH/CGS ratio of 3.0 by physical mixing, an activation temperature of 750°C and an activation time of 80 min. SEM, FTIR and EA analyses indicated that pronounced pores existed on the exterior surface of the activated samples, and the contents of H and O decreased due to the loss of surface chemical groups during activation. Experimental data for the Pb2+ adsorption were fitted well by Freundlich equation and a pseudo-second-order model with a maximum experimental adsorption capacity of 141 mg/g. All of the results indicated that CGS could be a promising material to prepare porous activated carbon for Pb2+ removal from wastewater.


Identification of major Streptococcus suis serotypes 2, 7, 8 and 9 isolated from pigs and humans in upper northeastern Thailand.
Streptococcus suis serotype 2 infections occur in many provinces of north-eastern Thailand, knowledge concerning the prevalence of the common S. suis serotypes (1, 1/2, 2, 5, 7, 8, 9, 14 and 16) among healthy and diseased pigs in upper northeastern Thailand remains limited. This study investigated S. suis isolates from pigs (healthy and diseased) and also from humans using 11 conventional biochemical tests, 16S rDNA PCR and sequence analysis and multiplex PCR genotyping of porcine cps and gdh. Thirty-three isolates were obtained between 2009 and 2012 from blood or cerebrospinal fluid of patients from northeastern Thailand previously diagnosed with S. suis infection, based on clinical symptoms and laboratory diagnosis using 11 biochemical tests and PCR detection of 16S rDNA and cps. Eleven S. suis isolates were obtained between 2006 and 2009 from diseased pigs with clinical signs and laboratory diagnoses. In addition, 43 isolates obtained from 741 nasal swab cultures of slaughtered pigs between 2011 and 2012 were included. All three methods showed similar sensitivity in detection of S. suis from clinical and diseased pig specimens, although in healthy pigs, the 11 conventional biochemical methods yielded 2.3% false positives, and the gdh PCR detection method exhibited 31% false negatives. S. suis was present among healthy pigs in 8 of 10 provinces in upper northeastern Thailand, giving an average prevalence of 5.7% (range 1%-17%) using conventional methods together with 16S rDNA PCR assay. False positives by conventional methods were due to species with similar phenotypes, such as viridian streptococci, and are not statistically different from those obtained with the 16S rDNA PCR method, and the false negatives using gdh PCR assay will require further investigation. As S. suis was recovered from both diseased and healthy pigs, raw or undercooked pork products should be considered unsafe for handling or consumption in these regions of Thailand.


Decrease of Cellular Communication Network Factor 1 (CCN1) Attenuates PTZ-Kindled Epilepsy in Mice.
To investigate the molecular mechanism of communication network factor 1 (CCN1) regulating pentylenetetrazol (PTZ)-induced epileptogenesis, deepen the understanding of epilepsy seizure pathogenesis, and provide new drug action targets for its clinical prevention and treatment. Differentially expressed genes (DEGs) on microarrays GSE47516 and GSE88992 were analyzed online using GEO2R. Pathway enrichment and protein-protein interaction network (PPI) analysis of DEGs were carried out using Metascape. Brain tissue samples of severe traumatic brain injury patients (named Healthy group) and refractory epilepsy patients (named Epilepsy group) were obtained and analyzed by qRT-PCR and immunohistochemistry (IHC) staining. A PTZ-induced epilepsy mouse model was established and verified. Morphological changes of neurons in mouse brain tissue were detected using hematoxylin and eosin (HE) staining. qRT-PCR was conducted to detect the mRNA expressions of apoptosis-associated proteins Bax, Caspase-3 and bcl2. TUNEL staining was performed to detect brain neuron apoptosis. The levels of myocardial enzymology, GSH, MDA and ROS in blood of mouse were detected by biochemical assay. CCN1 expression was increased in epilepsy brain tissue samples. CCN1 decreasing effectively prolongs seizure incubation period and decreases seizure duration. Silencing of CCN1 also reduces neuronal damage and apoptosis, decreases mRNA and protein expression of proapoptotic proteins Bax and Caspase-3, increases mRNA expression of antiapoptotic protein Bcl2. Moreover, decrease of CCN1 decreases myocardial enzymatic indexes CK and CK-MB levels, reduces myocardial tissue hemorrhage, and relieves oxidative stress response in hippocampal and myocardial tissue. CCN1 expression is increased in epileptic samples. CCN1 decreasing protects brain tissue by attenuating oxidative stress and inhibiting neuronal apoptosis triggered by PTZ injection, which probably by regulating Nrf2/HO-1 pathway.


The social support system of the Japanese elderly.
The social support system of the Japanese elderly was observed in a national representative sample of elderly community residents. Perceived availability of emotional and instrumental support from family members, children living apart, siblings and relatives, neighbors, and friends was respectively estimated. For both emotional and instrumental support, the perceived most dependable source of support was family members living together, followed by children living apart, while neighbors and friends were less dependable sources of support. The results clearly indicated family-centrality in the social support system of the Japanese elderly. However, the results also indicated differential roles of family members, children living apart, and non-kin others in the social support system of the elderly, and suggested the need to observe dyadic social relationships of Japanese elderly individuals.


Optimizing Pin-Printed and Hydrosilylated Microarray Spot Density on Porous Silicon Platforms.
Microarrays of spatially isolated chemistries on planar surfaces are powerful tools. An important factor in microarray technology is the density of chemically unique spots that can be formed per unit area. In this paper, we use contact pin-printing and evaluate how to decrease contact pin-printed spot diameters on porous silicon (pSi) platforms. Using hydrosilylation chemistry to covalently attach chemistries to the pSi surface, the variables studied included pSi porosity and surface polarity, active agent viscosity, and pin diameter. The spot characteristics were assessed by Fourier transform infrared spectroscopy (FT-IR) microscopy and X-ray photoelectron spectroscopy (XPS). Spot size decreased as pSi porosity increased in accordance with molecular kinetic theory and Darcy's law of imbibition. Increasing active agent viscosity and pin diameter (volume of printed agent) led to larger spot diameters in accordance with molecular kinetic theory and Darcy's law. Oxidizing the pSi with H2O2 increased the surface polarity but had no detectable impact on the spot size. This is consistent with formation of an oxide layer atop an unoxidized pSi sublayer.


Digital workflow for a dental prosthesis that considers lateral mandibular relation.
Most digital prosthesis designs consider only the maximal intercuspal position (MIP) and not the lateral movement. During the computer-aided design and computer-aided manufacture (CAD-CAM) prosthesis delivery process, the clinician has to adjust the prosthesis to avoid occlusal interference during lateral excursion. The novel digital workflow described in this report can be divided into 2 steps. After obtaining interocclusal records for the MIP and the lateral excursion position, the crown CAD data were designed using a general digital workflow considering only the MIP. The previous crown CAD data were then adjusted in the lateral excursion state before manufacturing the prosthesis. This process using information for 2 occlusal positions means that the definitive prosthesis design reflects not only static occlusion but also lateral mandibular relation.


Tandem ion mobility spectrometry coupled to laser excitation.
This manuscript describes a new experimental setup that allows to perform tandem ion mobility spectrometry (IMS) measurements and which is coupled to a high resolution time-of-flight mass spectrometer. It consists of two 79 cm long drift tubes connected by a dual ion funnel assembly. The setup was built to permit laser irradiation of the ions in the transfer region between the two drift tubes. This geometry allows selecting ions according to their ion mobility in the first drift tube, to irradiate selected ions, and examine the ion mobility of the product ions in the second drift tube. Activation by collision is possible in the same region (between the two tubes) and between the second tube and the time-of-flight. IMS-IMS experiments on Ubiquitin are reported. We selected a given isomer of charge state +7 and explored its structural rearrangement following collisional activation between the two drift tubes. An example of IMS-laser-IMS experiment is reported on eosin Y, where laser irradiation was used to produce radical ions by electron photodetachment starting from doubly deprotonated species. This allowed measuring the collision cross section of the radical photo-product, which cannot be directly produced with an electrospray source.


Impaired fibrinolysis in hypertension and obesity due to high plasminogen activator inhibitor-1 level in plasma.
In order to elucidate the influence of the risk factors of coronary heart disease on the fibrinolytic activity, relationships between blood pressure, body mass index (BMI), plasma lipoprotein (a) (Lp(a)) level and the plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were analyzed in the subjects with mild hypertension. Systolic blood pressure showed a positive correlation with total PAI-1 and free PAI-1. Diastolic blood pressure showed no correlation with these proteins involved in the fibrinolytic system. BMI had a positive correlation with total PAI-1, free PAI-1 and euglobulin clot lysis time (ECLT). Plasma Lp(a) level showed correlation with neither blood pressure nor fibrinolytic parameters, but it showed weak negative correlation with body mass index (BMI). These results suggest that high blood pressure and obesity tend to increase free PAI-1 which reduces fibrinolytic activity. Lp(a), however, seems not to influence directly the fibrinolytic system but may work to decrease fibrinolytic activity only in conjunction with other risk factors. The effects of daily drinking of alcohol and smoking on the fibrinolytic system were also investigated in the present study and we obtained the results that habitual drinking increased plasma levels of both tPA and PAI-1 whereas smoking did not affect fibrinolytic activity. These results suggest that risk factors for coronary heart disease such as hypertension and obesity are closely related to the impaired fibrinolysis.


Protective effect of passive immunization on herpetic retinitis of newborn rabbits.
We studied the protective effects of passive immunization with virus specific antibody in newborn rabbits inoculated subcutaneously with type 2 herpes simplex virus (HSV-2). Newborn rabbits given anti-HSV-2 antibody intraperitoneally (IP) on days 0, 2 and 4 post infection had smaller herpetic skin lesions and reduced mortality when compared to controls. In addition, the IP treatment using this schedule reduced virus growth in the skin lesions and virus dissemination, so that it decreased the frequency of herpetic retinitis. When the IP antibody administration was started at 24 hours post virus inoculation, according to the schedule days 1, 3 and 5, there was less protection; larger skin lesions, higher mortality, and greater evidence of virus dissemination. Also HSV-infected mononuclear cells (MNCs) treated with anti-HSV serum resulted in a significant reduction in the number of infected MNCs. The results of these studies suggest that anti-HSV-2 antibody contributes to protection against HSV-2 infection of skin as well as eyes, probably by inactivation of the virus locally at the skin inoculation site, and by combating the hematogenous spread of HSV-infected MNCs as well as free virus to various organs including the eye.


Hapten antibody production and the relevance of allogeneic reactions to elimination of the carrier effect.
Lewis (LEW) rats immunized 3 weeks before by injection of DNP-KLH together with Bordetella pertussis showed high levels of DNP antibody as judged by serum binding of 10(-7) M 3H-DNP-lysine 10 days after secondary immunization with DNP-KLH. Sera obtained from LEW rats following secondary immunization with DNP-BGG showed reduced DNP hapten binding. However, injection of 10(8) F1 hybrid Lewis X Brown Norway spleen cells into DNP-primed LEW rats 2 days before secondary immunization with DNP-BGG significantly increased the level of serum binding of 3H-DNP-lysine. These results provide evidence that the allogeneic cellular reaction associated with a host-versus-graft response induced by injection of F1 hybrid lymphoid cells into DNP-primed parental strain recipients partially obviates the requirement for carrier-specific T cells in the secondary anti-DNP response thereby providing a stimulus for triggering primed host B cells to produce antibody.


The adult respiratory distress syndrome bronchogenic pulmonary tuberculosis.
In three cases of pulmonary tuberculosis associated with the adult respiratory distress syndrome the clinical features, which were similar to those of patients with miliary tuberculosis and adult respiratory distress syndrome, included a history of cough, fever, and dyspnoea on effort, and the physical signs of fever, tachypnoea, pulmonary adventitious sounds, tachycardia, and hepatomegaly. In these cases the radiological features, though suggestive of diffuse pulmonary oedema, were more prominent on the side in which the cavitatory lesion appeared. The diagnosis of tuberculosis was made easily from direct examination of sputum. Despite early ventilatory support and antituberculous therapy, two of the three patients died. Postmortem examination of the lungs in these cases showed evidence of acute alveolar damage (loss of type 1 pneumocytes and the presence of hyaline membranes within alveolar ducts) and of chronic alveolar damage (interstitial and alveolar fibrosis).


Adjuvant treatment for post-operative head and neck squamous cell carcinoma.
One of the mainstays of treatment for locally advanced head and neck squamous cell carcinoma is surgery. However, for post-operative patients with high-risk factors for recurrence, surgery alone is insufficient and improving survival requires adjuvant treatment after surgery. Unlike with most other malignancies, the standard adjuvant treatment for post-operative head and neck cancer patients with high-risk factors for recurrence is radiotherapy concurrent with chemotherapy. This review article focuses on the history and future perspectives of adjuvant treatment for post-operative head and neck squamous cell carcinoma.


Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis.
Intraperitoneal chemotherapy and cytoreductive surgery have been combined to reach treatment objectives in patients with peritoneal carcinomatosis or sarcomatosis that neither modality by itself can achieve. These treatments must be combined with the proper selection of patients in order to observe "high value" results from therapy. There are three principles of management to support treatments for peritoneal carcinomatosis and sarcomatosis. First, the clinician must select patients who have isolated disease distributed on the surfaces of abdominal and pelvic structures. Patients treated for peritoneal implants who have persistent disease at other sites will profit little or not at all. Second, this disease must be reduced to its lowest possible mass by peritonectomy procedures and resections of viscera. Third, maximal intraperitoneal and systemic chemotherapy are utilized to eradicate the disease on peritoneal surfaces as well as control the primary or recurrent tumor. These principles of management and a presentation of the results achieved to date are reviewed.


Painless photodynamic therapy for facial actinic keratoses: A retrospective cohort study of the post-treatment inflammatory response.
Photodynamic therapy (PDT) is a safe, non-mutagenic, and non-scarring treatment for actinic keratoses (AK). 'Painless' photodynamic therapy (p-PDT) is a regimen for AK that employs simultaneous aminolevulinate incubation and blue light illumination. The efficacy of p-PDT resembles that of traditional PDT, but detailed mechanisms of action for p-PDT are not well understood. To characterize the inflammatory effects of the p-PDT procedure 48 h following treatment and determine the association of inflammation with precancer burden, we performed a retrospective cohort study of 104 patients with AK of face or scalp treated with p-PDT between 2017 and 2019. Patients self-reported their side effects 48 h following p-PDT and took photographs of their face and scalp. Photographs were edited to define seven anatomic regions, and erythema was scored by four investigators. Ninety-eight patients provided photographs suitable for erythema evaluation. Most patients experienced 2 or more side effects and some pain 48 h post-procedure. Females experienced more pain (p = 0.01) and side effects (p = 0.002) compared to males. AK burden was positively associated with post p-PDT erythema response (p < 0.0001) at all sites, but particularly in the temples (p = 0.002) and supralabial area (p = 0.009). This study confirms a strong clinical inflammatory response after p-PDT. Severity of inflammation is positively associated with AK tumor burden, suggesting that post-treatment inflammation may be a pre-requisite for p-PDT efficacy. Interestingly, the results also identify certain gender-related differences in the severity of side effects experienced by patients post-PDT.


P. acnes-Driven Disease Pathology: Current Knowledge and Future Directions.
This review discusses the biology and behavior of Propionibacterium acnes (P. acnes), a dominant bacterium species of the skin biogeography thought to be associated with transmission, recurrence and severity of disease. More specifically, we discuss the ability of P. acnes to invade and persist in epithelial cells and circulating macrophages to subsequently induce bouts of sarcoidosis, low-grade inflammation and metastatic cell growth in the prostate gland. Finally, we discuss the possibility of P. acnes infiltrating the brain parenchyma to indirectly contribute to pathogenic processes in neurodegenerative disorders such as those observed in Parkinson's disease (PD).


An unusual presentation of spontaneous spinal epidural hematoma.
We report a rare case of spontaneous spinal epidural hematoma. Various presentations may occur, most commonly including neck pain, interscapular pain, radicular pain, and paralysis. This condition is frequently associated with paralysis and long-term disability. This case is unique because it presented with right hand cyanosis, in addition to pain. A 69-year-old Caucasian female presented with cyanosis of the right hand, and severe right upper extremity pain which awakened her approximately 11 hours earlier. The pain was exacerbated on extending her head. The patient further reported bilateral shoulder pain and interscapular pain. She reported no motor weakness or paralysis. She denied any history of trauma. The patient was taking aspirin 81 mg/d for the past 2 months. Physical examination revealed cyanosis of the digits of the right hand as well as mildly diminished right biceps reflex and right grip strength. No edema or rashes were noted. Skin was warm and dry. Pulses were +2 in all extremities. Vital signs were within normal limits. The remainder of the physical examination was unremarkable. Magnetic resonance imaging of the cervical/thoracic spine revealed a right posterior-lateral epidural hematoma extending from the 3rd cervical level to the 1st thoracic level of the spinal cord. There was also evidence of cord compression at the 4th-5th and 5th-6th cervical levels. Given the potential for significant complications, clinicians should maintain a high index of suspicion for spinal epidural hematoma, particularly in those patients taking anticoagulation. Symptoms, including extremity cyanosis, pain, and paralysis all are suggestive of the diagnosis.


Selling digital art in bulk through prepaid URLs.
Suppose a major donor anywhere in the world could sponsor tens of thousands (or any number) of copies of a song, video, or any other digital "content"--letting tens of thousands of people in social networks just click to download free, with no registration ever, instantly paying the artists or a cause by the act of free downloading itself. And each sponsor can deliver a message to the thousands of anonymous end users who download from his or her contribution. We show how independent artists could market globally at no expense if people care about their work--offering an alternative to corporate monoculture. Or they could donate their digital art to an organization that sells it this way to raise funds.


Transabdominal Ultrasonography-Defined Optimal and Definitive Bladder-Filling Protocol With Time Trends During Pelvic Radiation for Cervical Cancer.
Advanced radiotherapy techniques have emphasized on the importance of accurate target volume localization and delineation. The aim of this study was to determine time taken to achieve moderate bladder volume under physiological conditions, using transabdominal ultrasound. Patients with cervical cancer undergoing radical radiation with or without concomitant chemotherapy underwent serial ultrasound to estimate bladder filling. With a strict bladder protocol of consuming 1000 mL of water orally over 30 minutes after emptying the bladder, ultrasound was done after 45 minutes from bladder emptying time and repeated at 15-minute interval till 300 (25) mL filling was achieved and repeated every week. Forty-six patients with weekly ultrasound for bladder-filling documentation were evaluated. The mean (standard deviation) bladder volume measured at 45 minutes was 220 (93), 210 (95), 195 (91), 195 (96), and 190 (85) mL (average: 200; median: 195 mL) for the first to fifth week, respectively, and the mean (standard deviation) volume at 75 minutes was 300 (95), 310 (80), 290 (80), 295 (80), and 285 (70) mL (average: 295; median: 300 mL). The mean (standard deviation) time for bladder filling to 300 mL in the first, second, third, fourth, and fifth week was 57 ( 13.5), 67 (16.6), 66 (16.7), 66 (15.5), and 69 (17.1) minutes, respectively. Bladder filling to a definitive moderate volume at a reasonably fixed time period in each week of radiation is well tolerated, feasible, and measurable by weekly transabdominal ultrasound measurements.


[Minimal effective dose of spinal hyperbaric bupivacaine for adult anorectal surgery: a double-blind, randomized study].
The aim of the study was to find minimal effective dose of spinal hyperbaric bupivacaine for adult anorectal surgery. The study included 93 adult consecutive patients admitted for anorectal operations. Dural puncture was made before surgery in the sitting position at L3-L4 or L4-L5 with 25-26G Tamanho spinal needle (BBraun, Germany) and different volumes of hyperbaric bupivacaine (Marcaine Spinal Heavy 0.5%, AstraZeneca) were injected over 2 minutes: group 1 (n=17) 1.5 ml, group 2 (n=38) 1.0 ml, group 3 (n=38) 0.8 ml. After sitting for 10 minutes patients were asked to lie down and surgery was started. Following variables were assessed: rate of success, level and duration of sensory and motor block, time to voiding and ambulation, complications, consumption of analgesics, quality of anesthesia according to the patient and medical staff. Groups were comparable in demographics. No case of failure was registered but 4 patients (10.5%) in the group 3 received supplemental i/v fentanyl to treat tension in the abdomen intraoperatively. Level of sensory block in groups 1, 2, 3 was 10.4+/-1.7, 7.013+/-2.2, 6.7+/-1.9 dermatomes, respectively (p<0.0001 ANOVA; p<0.0001 group 1 vs 2, group 1 vs 3, p=1.0 group 2 vs 3, Bonferroni). Extent of motor block was 2-3 scores according to the Bromage scale in 70.5% of group 1 cases, compared to 0-1 score in 97.3% of group 2 and 92.1% of group 3 cases. Median (range) duration of motor block in groups 1, 2, 3 was 90 (0-120), 0 (0-90), and 0 (0-60) min, respectively (p<0.0001 ANOVA; p<0.0001 group 1 vs 2, group 1 vs 3, p=0.13 group 2 vs 3, Bonferroni). Time of ambulation was 181.5+/-41.5, 136.6+/-32.2 and 123.0+/-45.9 min, respectively (p<0.0001 ANOVA; p<0.001 group 1 vs 2, p<0.00001 group 1 vs 3, p=0.43 group 2 vs 3, Bonferroni). There was no significant intergroup difference in time to urinate; retention developed in 20.4% of total cases. No difference was found in morphine consumption, 64.5% of cases did not require rescue analgesics. Quality of anesthesia was stated as excellent by the anesthesiologist and surgeon in all groups. However, quality was rated as excellent by patient in the operating room in groups 1, 2, 3: 58.8, 94.7, and 86.8%, respectively (p=0.003), on day 1 postoperatively: 76.5, 92.1, and 97.4%, respectively (p=0.023); by nursing staff: 82.4, 100, and 97.4%, respectively (p=0.019). Lower rates in group 1 were due to extensive motor block. In conclusion, a minimal recommended dose of spinal hyperbaric bupivacaine for anorectal surgery is 4-5 mg; a dose of 7.5 mg is excessive due to prolonged sensory and motor block.


Prenatal diagnosis of cystic neuroblastoma.
Cystic adrenal masses are unusual in the fetus. The most common diagnosis for adrenal cyst is hemorrhage. We report 2 cases of cystic neuroblastoma diagnosed prenatally by ultrasound. In each case, diagnosis was confirmed in the neonatal period first by scintigraphy, then by histology. Differential diagnosis and management after delivery are discussed.


Polymorphisms of -800G/A and +915G/C in TGF-β1 gene and lung cancer susceptibility.
We studied the relationship between the polymorphisms of -800G/A and +915G/C in transforming growth factor-β1 (TGF-β1) gene and lung cancer susceptibility. The sequence-specific primer polymerase chain reaction (PCR-SSP) technique was used to test 156 non-small cell lung cancer (NSCLC) patients that were selected as the observation group and 156 patients with pneumonia and tuberculosis that were selected as the control group (age and gender 1:1 proximal matching principle) and the polymorphisms of the first exon -800G/A and +915G/C TGF-β1 genes. The expression of TGF-β1 levels in peripheral blood was detected using ELISA. The proportion of -800G/A gene AA subtype and A allelic gene in the observation group was significantly higher than that in the control group, while the proportion of +915G/C gene CC subtype and C allelic gene was also significantly higher than that in the control group (P<0.05). The cancer risk [odds ratio (OR)] of patients with A allelic gene in -800G/A gene was 4.8 (95% CI=2.563-6.537, P<0.05), while the cancer risk (OR) of patients with C allelic gene in +915G/C gene was 4.7 (95% CI=2.317-5.864, P<0.05). The serum TGF-β1 expression levels of -800G/A gene AA subtype in the observation group was significantly higher than the GG type, GA type and the control group, while the TGF-β1 level of +915G/C gene CC subtype was significantly higher than the GG type, GC type and the control group (P<0.05). Therefore, the polymorphisms of -800G/A and +915G/C in TGF-β1 gene are closely related to the lung cancer susceptibility.


Replenishment of pituitary estrogen receptor in chronically estrogenized rats.
Replenishment of pituitary estrogen receptor (ER) following a single injection of estradiol-17 beta (E2) was examined in chronically estrogenized ovariectomized rats. Subcutaneous implantation of E2-pellet in castrated rats for 7 days caused a shift of ER distribution in the pituitary (39.9 +/- 5.7 fmol/10 mg tissue in the cytosol vs 24.8 +/- 1.9 fmol/10 mg tissue in the nucleus). An intraperitoneal injection of 5 micrograms E2 in the E2-implanted rats resulted in a significant decrease in cytosol ER with a concomitant significant increase in nuclear ER (16.6 +/- 1.2 fmol in the cytosol vs. 36.7 +/- 4.1 fmol in the nucleus at 1 h). However, cytosol ER was rapidly replenished, which was accompanied by nuclear ER reduction, and both values returned to the pre-injection levels at 4 h. An administration of 150 micrograms cycloheximide, that effectively blocked protein synthesis in the E2-implanted and 5 micrograms E2 injected rats, completely inhibited the replenishment of ER. These findings suggest that replenishment of ER following E2 administration in the pituitary of chronically estrogenized rats is entirely dependent on protein synthesis.


Lack of lamins A and C in mammalian hemopoietic cell lines devoid of intermediate filament proteins.
Using immunofluorescence microscopy and immunoblot analysis, we have examined the composition of the nuclear lamina in several murine and human cell lines. Whereas it was shown that intermediate filament-positive Ehrlich ascites tumor and HeLa-S3 cells contain the three major mammalian lamin subspecies, only lamin B could be detected in several myeloid- and lymphoid-derived cell lines representative of distinct stages in hemopoietic differentiation but all devoid of cytoplasmic intermediate filament proteins. These included the murine plasmacytoma cell types MPC-11 and MOPC-31C, murine myeloma cells X63-Ag126.96.36.199 and human promyelocytic leukemia cells HL-60. Our results provide the first evidence that mammalian somatic cells capable of normal proliferation may lack both cytoplasmic intermediate filament proteins and a normal complement of nuclear lamins.


Estimating the costs and cost-effectiveness of promoting mammography screening among US-based Latinas.
We characterize the costs and cost-effectiveness of a community health worker (CHW)-based intervention to promote screening mammography among US-based non-adherent Latinas. The parent study was a randomized controlled trial for 536 Latinas aged 42-74 years old who had sought care within a safety net health center in Western Washington. Participants were block-randomized within clinic to the control arm (usual care) or intervention arm (CHW-led motivational interviewing intervention). We used the perspective of the organization implementing promotional activities to characterize costs and cost-effectiveness. Cost data were categorized as program set-up and maintenance (initial training, booster/annual training) program implementation (administrative activities, intervention delivery); and, overhead/miscellaneous expenses. Cost-effectiveness was calculated as the incremental cost of screening for each additional woman screened between the intervention and control arms. The respective costs per participant for standard care and the intervention arm were $69.96 and $300.99. There were no study arm differences in 1-year QALYs were small among women who completed a 12-month follow-up survey (intervention= 0.8827, standard care = 0.8841). Most costs pertained to program implementation and administrative activities specifically. The incremental cost per additional woman screened was $2,595.32. Our findings are within the ranges of costs and cost-effectiveness for other CHW programs to promote screening mammography among underserved populations. Our strong study design and focus on non-adherent women provides important strengths to this body of work, especially give implementation and dissemination science efforts regarding CHW-based health promotion for health disparity populations.


Vaccines and cardiovascular outcomes: lessons learned from influenza epidemics.
Cardiovascular disease (CVD) is the leading cause of death in the world and is largely preventable. An increasing amount of evidence suggests that annual influenza vaccination reduces CVD-related morbidity and mortality. Despite various clinical guidelines recommending annual influenza vaccination for the general population for influenza-like illness risk reduction, with a particular emphasis on people with CVD, vaccination rates fall consistently below the goal established by the World Health Organization. This review outlines the importance of influenza vaccination, mechanisms of cardiovascular events in influenza, summarizing the available literature on the effects of influenza vaccine in CVD and the benefits of influenza vaccine during the COVID-19 pandemic.


Endocrine and metabolic effects of labetalol in man.
The effects of intravenous infusion of the alpha- and beta-adrenoceptor blocking drug labetalol (100 mg over 10 min) on heart rate, blood pressure, and several endocrine and metabolic variables have been evaluated in 12 hypertensive patients (6 men and 6 women). Drug administration was associated with significant lowering of heart rate and systolic and diastolic blood pressure in comparison with a control study performed with saline infusion. Plasma glucose was significantly increased, while no changes were observed in serum-free fatty acids, insulin, C-peptide, and growth hormone levels. Serum prolactin concentration was significantly increased in the whole group, a marked rise occurred in females, while only a trend upward was observed in males. The acute lowering of blood pressure suggests a predominant activity on alpha-adrenoceptors following intravenous labetalol infusion, although the reduction in heart rate is consistent with the beta-adrenoceptor blocking effect of the drug. Although the reason for the increase in plasma glucose is not apparent, it might depend on the rise in norepinephrine levels observed after labetalol. Stimulation of prolactin release by intravenous labetalol is not easily attributable to interference with adrenergic receptors. The mechanism of this action of the drug is presently obscure, although a possible antidopaminergic activity of labetalol might be involved.


Exploring the young demographic profile of COVID-19 cases in Hong Kong: Evidence from migration and travel history data.
This paper investigates the profile of COVID-19 cases in Hong Kong, highlighting the unique age structure of confirmed cases compared to other territories. While the majority of cases in most territories around the world have fitted an older age profile, our analysis shows that positive cases in Hong Kong have been concentrated among younger age groups, with the largest incidence of cases reported in the 15-24 age group. This is despite the population's rapidly aging structure and extremely high levels of population density. Using detailed case data from Hong Kong's Centre for Health Department and Immigration Department, we analyze the sex and age distribution of the confirmed cases along with their recent travel histories and immigration flows for the period January to April 2020. Our analysis highlights Hong Kong's high proportion of imported cases and large overseas student population in developing COVID-19 hotspot areas such as the United Kingdom. Combined with community action and targeted and aggressive early policy measures taken to contain the virus, these factors may have contributed to the uniquely younger age structure of COVID-19 cases in the city. Consequently, this young profile of confirmed cases may have prevented fatalities in the territory. Recent research has highlighted the importance of a demographic approach to understanding COVID-19 transmission and fatality rates. The experience in Hong Kong shows that while an older population age structure may be important for understanding COVID-19 fatality, it is not a given. From a social science perspective at least, there is 'no easy answer' to why one area should experience COVID-19 differently from another.


Optimal time-jerk trajectory planning for the landing and walking integration mechanism using adaptive genetic algorithm method.
Because the current research on the lander mostly has focused on the traditional lander, the Soft Landing and Walking Integration (SLWI) lunar lander has yet not been studied. To solve the problem, first, a novel type of mobile landing mechanism is proposed and its kinematics is deduced. Second, in order to ensure the motion stability of the mechanism, the cubic spline curve is used to scheme the key points of the SLWI, and based on the weighted coefficient method, an optimal time-jerk pedestal trajectory planning model is established. Finally, the adaptive genetic algorithm (AGA) is used to search the global optimal solution of time-jerk trajectory planning model. Simulation shows that the motion performance of the mechanism is continuous and stable, which proves the rationality and effectiveness of the foot trajectory planning method. At the same time, the AGA converges to the optimal solution. Thus, the blindness of the initial optimization can be greatly reduced and the amount of computation can be saved. It also laid a theoretical foundation for the follow-up research of SLWI lunar lander.


Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.
Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.


Coronavirus disease 2019 (COVID-19) in a patient with ankylosing spondylitis treated with secukinumab: a case-based review.
Severe acute respiratory syndrome coranovirus-2 (SARS-CoV-2) infection has become an important health-care issue worldwide. The coronavirus disease 2019 (COVID-19) has also raised concerns among patients with inflammatory rheumatic conditions and their treating physicians. There are emerging data regarding the potential risks of SARS-CoV-2 for this particular patient group. However, less is known with regard to the course of COVID-19 among patients receiving IL-17 inhibitors. The aim of the current article is to review the growing body of knowledge on the course/management of COVID-19 in patients with inflammatory rheumatic diseases by presenting a SARS-CoV-2 infected case with ankylosing spondylitis under secukinumab therapy. A 61-year old patient with ankylosing spondylitis who was on secukinumab therapy for 5 months admitted with newly onset fever and gastrointestinal complaints. After being hospitalized, she developed respiratory manifestations with focal pulmonary ground-glass opacities and multiple nodular densities in both lungs. The patient was tested positive for SARS-CoV-2 infection. Substantial clinical improvement was obtained following a management plan, which included tocilizumab, hydroxychloroquine, prednisolone and enoxaparin sodium. PubMed/MEDLINE and Scopus databases were searched by using relevant keywords and their combinations. The literature search revealed four articles reporting the clinical course of COVID-19 in seven rheumatic patients on secukinumab. The clinical course of SARS-CoV-2 infection was mild in most of these patients, while one of them experienced severe COVID-19. Interleukin-17 has been related to the hyperinflammatory state in COVID-19 and IL-17 inhibitors were presented as promising targets for the prevention of aberrant inflammation and acute respiratory distress in COVID-19. However, this hypothesis still remains to be proved. Further studies are warranted in order to test the benefits and risks of IL-inhibitors in SARS-CoV-2 infected individuals.


TASK-1 induces gefitinib resistance by promoting cancer initiating cell formation and epithelial-mesenchymal transition in lung cancer.
Cancer initiating cell (CIC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in lung cancer cell invasion and metastasis. They have been shown to occur in gefitinib resistance. Studying the molecular mechanisms of CICs, EMT and acquired gefitinib resistance will enhance the understanding of the pathogenesis and progression of the disease and offer novel targets for effective therapies. TWIK-related acid-sensitive K(+) (TASK-1) is expressed in a subset of non-small-cell lung cancer (NSCLC) cell lines, where it promotes cell proliferation while inhibiting apoptosis. In the present study, TASK-1 was demonstrated to induce gefitinib resistance in the A549 NSCLC cell line. Overexpression of TASK-1 promoted the acquisition of CIC-like traits by A549 cells. CD133, octamer-binding transcription factor 4 (OCT-4) and Nanog have been suggested to be markers of CICs in lung cancer. It was demonstrated that overexpression of TASK-1 promoted CD133, OCT-4 and Nanog protein expression in A549 cells. Increased formation of stem cell-like populations results in EMT of cancer cells. The present study found that overexpression of TASK-1 promoted EMT of A549 cells. Thus, downregulation of TASK-1 may represent a novel strategy for EMT reversal, decreasing CIC-like traits and increasing gefitinib sensitivity of NSCLCs.


Palmitic acid analogues exhibiting antinociceptive activity in mice.
Three palmitic acid derivatives were synthesized and evaluated as a potential platform for antinociceptive drug development. Female Swiss Webster mice were given N-(4-Methoxy-2-nitrophenyl)hexadecanamide (1), 2-amino-3-(palmitoylamino)benzoic acid (2) or 4-amino-3-(palmi-toylamino)benzoic acid (3) orally in doses of 10-100 mg/kg. The animals were tested for nociception using the hot plate and abdominal constriction response (writhing) tests. Compound 1 generated a dose-dependent antinociceptive effect, reflected by longer latencies (paw-lick and escape responses) and a decrease in writhing. Morphine (1.5-6 mg/kg, p.o.) and diclofenac (10-100 mg/kg, p.o.) were used as positive controls, respectively. Compounds 2 and 3 were less active in both nociceptive tests. The antinociception provoked by compound 1 was partially blocked by naloxone (1 mg/kg, i.p.) suggesting that this pharmacological effect could be due to the activation of micro-opioid receptors. N-(4-Methoxy-2-nitrophenyl)hexadecanamide showed antinociceptive effects in both nociceptive tests suggesting the possibility that this compound may define a new type of antinociceptive.


Repeated testing of basal FSH levels has no predictive value for IVF outcome in women with elevated basal FSH.
It is a common practice to repeatedly test the level of basal FSH early in the cycle and to start IVF treatment only when the FSH level is below a certain threshold value. This is based on the idea that these women will respond better to ovarian stimulation when the basal FSH level is lower at the start of the cycle. The aim of this study is to assess the value of this practice. Between January 1995 and January 2003, 39 women were identified. These women underwent two IVF treatment cycles within a 12 month period. The basal FSH level prior to each of these cycles was known to have changed. The treatment cycles were divided into cycles with a high basal FSH (> or =10 IU/l) and cycles with a low basal FSH (<10 IU/l). The 39 women underwent a total of 78 treatment cycles (in the first cycle 20 had elevated level of FSH and 19 had low FSH and vice versa in the second cycle). Therefore, there were 39 cycles with high FSH and 39 cycles with low FSH. There was obviously no live birth in the first treatment cycle, hence the reason for the patient undergoing another treatment cycle within 12 months of the first one. In the high FSH group, six became pregnant [pregnancy rate (PR) = 15.4%] and five delivered [live birth rate (LBR) = 12.8%]. In the low FSH group, three became pregnant (PR = 7.7%) and two delivered (LBR = 5.1%). The difference in PR and LBR, however, was not significant. Neither were there significant differences between the two groups with regard to the number of oocytes collected, oocytes fertilized, embryos transferred or miscarriage rate. The results of this study reveal that women who are poor responders or with reduced ovarian reserve have a poor outcome and repeatedly testing them will add no value. Cycling women with a history of elevated FSH should be offered treatment without further delay. Delaying treatment for these women could be counterproductive, as they may have to wait for many months, during which time they are getting older and closer to their menopause.


Screening for Information Environments: A Role for Health Systems to Address the Misinformation Crisis.
Misinformation about health topics is a public health issue. We are bombarded with information from many sources, across many digital means of communication, affecting the ways in which we are born, grow, work, live, and age. This makes information environments a social determinant of health (SDoH), but one not currently adequately addressed by clinical or public health practitioners. Since health systems are already screening for social determinants of health, existing mechanisms can additionally screen for unhealthy information environments. Then, for those patients who screen positive, we can apply best practices learned from initiatives addressing vaccine hesitancy: providing a non-judgmental environment in which to discuss health beliefs, using motivational interviewing techniques to gage patient perspectives and readiness for change, and taking a harm-reduction approach in recognizing that behavior change evolves over time. Displacing misinformation is a process, not an event. As such, we need to address the underlying psychological and sociological reasons that people maintain unscientific beliefs as we would hope to do with any other SDoH. Furthermore, as information environments are the product of both individual choices and structural factors, clinicians should approach patients immersed in unhealthy information environments without blame or ostracism, much as we would approach any patient adversely impacted by social determinants of health.


Carotid duplex and transcranial color-coded sonography in evaluation of carotid-cavernous sinus fistulas.
We performed carotid duplex and transcranial color-coded sonography in three patients with traumatic and one patient with spontaneous carotid-cavernous fistulas. High flow and low resistance were detected by carotid Doppler imaging in the extracranial internal carotid artery in three cases and in the external carotid artery in one case. The fistula could be demonstrated directly as heterogenous color flashes with turbulent flow by transcranial color-coded sonography through the orbital or temporal window. The transorbital approach showed that the ophthalmic venous flow was normal or to-and-fro bidirectional in patients without proptosis and was retrograde, away from the cavernous sinus with arteriolization in patients with proptosis. Combination of carotid duplex and transcranial color-coded sonography provides a noninvasive method for more accurate hemodynamic study of cerebral circulation and direct imaging of CCF.


Membrane lipid patterns typify distinct anaerobic methanotrophic consortia.
The anaerobic oxidation of methane (AOM) is one of the major sinks of this substantial greenhouse gas in marine environments. Recent investigations have shown that diverse communities of anaerobic archaea and sulfate-reducing bacteria are involved in AOM. Most of the relevant archaea are assigned to two distinct phylogenetic clusters, ANME-1 and ANME-2. A suite of specific (13)C-depleted lipids demonstrating the presence of consortia mediating AOM in fossil and recent environments has been established. Here we report on substantial differences in the lipid composition of microbial consortia sampled from distinct compartments of AOM-driven carbonate reefs growing in the northwestern Black Sea. Communities in which the dominant archaea are from the ANME-1 cluster yield internally cyclized tetraether lipids typical of thermophiles. Those in which ANME-2 archaea are dominant yield sn-2-hydroxyarchaeol accompanied by crocetane and crocetenes. The bacterial lipids from these communities are also distinct even though the sulfate-reducing bacteria all belong to the Desulfosarcina/Desulfococcus group. Nonisoprenoidal glycerol diethers are predominantly associated with ANME-1-dominated communities. Communities with ANME-2 yield mainly conventional, ester-linked diglycerides. ANME-1 archaea and associated sulfate-reducing bacteria seem to be enabled to use low concentrations of methane and to grow within a broad range of temperatures. Our results offer a tool for the study of recent and especially of fossil methane environments.


Combined EXAFS Spectroscopic and Quantum Chemical Study on the Complex Formation of Am(III) with Formate.
The complexation of Am(III) with formate in aqueous solution is studied as a function of the pH value using a combination of extended X-ray absorption fine structure (EXAFS) spectroscopy, iterative transformation factor analysis (ITFA), and quantum chemical calculations. The Am LIII-edge EXAFS spectra are analyzed to determine the molecular structure (coordination numbers; Am-O and Am-C distances) of the formed Am(III)-formate species and to track the shift of the Am(III) speciation with increasing pH. The experimental data are compared to predictions from density functional calculations. The results indicate that formate binds to Am(III) in a monodentate fashion, in agreement with crystal structures of lanthanide formates. Furthermore, the investigations are complemented by thermodynamic speciation calculations to verify further the results obtained.


Blood component therapy.
Blood loss in orthopaedic injuries or procedures may be substantial, and more than 23 million units of blood components are transfused each year. The most frequent components used include whole blood, packed red blood cells, platelets, plasma derivatives, leukocytes, and clotting factors. This article will discuss blood classification systems, transfusion components, administration and potential complications of transfusion therapy, and nursing implications.


Vitamin D can help stave off respiratory tract infections.
Vitamin D supplements can help prevent acute respiratory tract infections, particularly among people deficient in vitamin D, new study results suggest.


Relationship between vertebral fracture prevalence and abdominal aortic calcification in men.
To study the relationship between the prevalence of vertebral fractures (VFs) using VF assessment (VFA) in asymptomatic men and the prevalence and severity of abdominal aortic calcification (AAC). We enrolled 709 men with mean (s.d.) age 62.4 (8.6) (range 45-89) years. Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of the Genant semi-quantitative (SQ) approach and morphometry. VFA images were scored for AAC using a validated 24-point scale. VFA images showed that 68 (14.2%) of the participants had at least one grade 2/3 VF, 82% did not have any detectable AAC, whereas the prevalence of significant atherosclerotic burden, defined as an AAC score of ≥5, was 2.8%. The group of men with grade 2/3 VFs had a statistically significant higher AAC score and higher proportion of subjects with extended AAC, and lower weight, height and lumbar spine and hip BMD and T-scores than those without a VFA-identified VF. Multiple regression analysis showed that the presence of grade 2/3 VFs was significantly associated with BMI [odds ratio (OR 0.915; 95% CI 0.589, 0.975; P = 0.006], AAC score ≥5 (OR 4.509; 95% CI 1.505, 13.504; P = 0.007) and osteoporosis in any site (OR 5.159; 95% CI 3.116, 8.540; P ≤ 0.0001). In elderly men, extended AAC is an indicator of the increased risk for prevalent VFs regardless of age, BMI, history of fractures, smoking and BMD.


Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential.
Curcumin, isolated from Curcuma longa L., is a fat-soluble natural compound that can be obtained from ginger plant tuber roots, which accumulative evidences have demonstrated that it can resist viral and microbial infection and has anti-tumor, reduction of blood lipid and blood glucose, antioxidant and removal of free radicals, and is active against numerous disorders various chronic diseases including cardiovascular, pulmonary, neurological and autoimmune diseases. In this article is highlighted the recent evidence of curcuminoids applied in sevral aspects of medical problem particular in COVID-19 pandemics. We have searched several literature databases including MEDLINE (PubMed), EMBASE, the Web of Science, Cochrane Library, Google Scholar, and the ClinicalTrials.gov website via using curcumin and medicinal properties as a keyword. All studies published from the time when the database was established to May 2021 was retrieved. This review article summarizes the growing confirmation for the mechanisms related to curcumin's physiological and pharmacological effects with related target proteins interaction via molecular docking. The purpose is to provide deeper insight and understandings of curcumin's medicinal value in the discovery and development of new drugs. Curcumin could be used in the prevention or therapy of cardiovascular disease, respiratory diseases, cancer, neurodegeneration, infection, and inflammation based on cellular biochemical, physiological regulation, infection suppression and immunomodulation.


Antigenicity and immunogenicity of peptide analogues of a low affinity peptide of the human telomerase reverse transcriptase tumor antigen.
Human telomerase reverse transcriptase (hTRT) is a potential target for therapeutic vaccination against cancer. Therefore, it is critically important to identify T cell epitopes useful to induce cytotoxic T cell responses. Here we used a positional scanning combinatorial peptide library to identify peptide analogues for a previously characterized low affinity hTRT peptide (p572). From an initial library containing over 300 billion different peptides and through successive rounds of selection, we retained 72 candidate peptide analogues for further assessment of antigenicity and in vivo immunogenicity in HLA A2.1-transgenic mice. While antigenically cross-reactive with p572, only a fraction of these peptides was immunogenic in mice. Immunogenicity appeared to correlate with the stability of binding to the MHC molecule and the presence of HLA A2.1 anchor residues in position 2 and 9. Two peptides differing by five residues from the reference p572 (p49 and p50) were more effective than p572 in inducing CTL cross-reacting with p572 in HLA A2.1-transgenic mice. Both peptides also expanded specific CTL in peripheral blood lymphocytes of normal human volunteers ex vivo. The present study shows that positional scanning combinatorial peptide libraries can be used to identify hTRT peptide analogues for inclusion in a cancer vaccine.


Changes of plasma norepinephrine and serum N-terminal pro-brain natriuretic peptide after exercise training predict survival in patients with heart failure.
Short-term changes of neurohormones can give important prognostic information in heart failure (HF) patients. In this study, we evaluate whether changes in plasma Norepinephrine (NE) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) after exercise training predict cardiac mortality in HF patients. We enrolled 221 HF patients (mean age 72.5 ± 10.2 year) followed-up for a mean period of 27.64 ± 10.7 months. All pts underwent a 3-month exercise training. Before training, clinical examination, echocardiography, peak VO2 determination, and blood draw for NT-proBNP and NE measurements were performed. Primary end-point was cardiac related mortality. Eighty-six-nine percent of patients were in NYHA class III, mean left ventricular ejection fraction (LVEF) was 32.5 ± 10.4%, and mean peak VO2 was 12.36 ± 1.45 ml/kg/min. At baseline, mean NT-proBNP was 2111.4 ± 1145.6 pg/ml and mean NE was 641.8 ± 215.3 pg/ml. One hundred-one subjects died for cardiac causes. Training was associated with a significant increase of peak VO2 and LVEF, whereas NE, NT-proBNP, and heart rate decreased. Multiple Cox proportional hazards regression analysis was performed using delta% values (post vs pre-training) of LVEF, heart rate, NE, and NT-proBNP along with baseline covariates, revealing delta value of NE as the strongest predictor of cardiac mortality. Noteworthy, training reduced NT-proBNP in both survivor and non-survivor patients, while a lack of reduction of NE was observed in non survivors. In our HF population, short-term changes of NE after exercise training independently predicted long-term cardiac mortality.


Structure of the shell from eggs of the tuatara, Sphenodon punctatus.
Shells from eggs of the tuatara (Sphenodon punctatus) are 0.2 mm thick and are composed of a layer of calcite and a multi-layered, fibrous shell membrane. Most of the calcareous layer is composed of roughly circular columns of crystalline material that extend deep into the shell membrane. The crystalline matrix of the columns is interwoven with fibers of the shell membrane except near the outer surface of the eggshell, where the calcareous material is more compact. Overlying the columns is a granular layer composed of blocks of crystalline material of random size, shape, and orientation. Disruption of this granular layer, perhaps through swelling of the eggs or as a result of environmental factors, gives the outer surface of the eggshell a coarse, weathered appearance. Removal of the calcareous material with a decalcifying agent shows that the outer surface of the shell membrane is composed of a meshwork of small fibers bound together by an amorphous matrix. No matrix was observed in inner layers of the shell membrane, and the fibers of these inner layers are arranged somewhat more regularly than the outer fibers. No structure comparable to the central cores of avian and certain chelonian eggs was observed in eggshells of the tuatara.


Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis.
In human osteoarthritis (OA), various forms of pathology are observed. Besides cartilage damage and fibrosis, neogenesis of bone, osteophyte formation, also occurs. Osteophytes are thought to limit joint movement and cause pain. The objective of this study was to investigate whether synovial macrophages are involved in osteophyte formation in experimental OA, and if they are, to study which mechanism may be involved. Experimental OA was induced by two intra-articular injections of collagenase on alternate days into murine knee joints. The role of synovial lining macrophages in this model was studied by selective removal of these cells prior to OA induction using clodronate liposomes. After 1 and 2 weeks, knee joints were dissected and examined (immuno)histologically. At days 7 and 14 after induction of OA, osteophyte formation and fibrosis were observed. Depletion of synovial macrophages resulted in spectacular reduction of osteophyte formation, 84% and 66%, respectively, at days 7 and 14. Fibrosis and synovial activation, measured by MRP8/14 expression, were also ameliorated (40-60%). In addition, production of growth factors (TGFbeta, BMP-2 and BMP-4) in the lining was largely prevented but production of these growth factors in deeper layers of the synovium and the periosteum did not differ from controls. These results indicate the synovial macrophage to be a pivotal cell in the synovium mediating osteophyte formation and other OA-related pathology, like fibrosis, during experimental OA. Production of growth factors and induction of synovial activation by these cells may play a crucial role in this event.


Oscillating bubbles at the tips of optical fibers in liquid nitrogen.
We report that a bubble with a radius of a few micrometers may be created at a precise location on a metal-coated optical fiber tip immersed in liquid nitrogen by microsecond optical pulses with peak powers of less than 20 mW. Dynamic optical measurements reveal that after termination of the optical pulse the bubble exhibits stable oscillations for several tens of microseconds, at frequencies up to several megahertz, as it slowly collapses.


Interpretation of laboratory values in older adults.
This article describes age-related physiologic changes in the older adult and the effect of these changes, if any, on commonly ordered laboratory tests. As reported in selected research studies and literature reviews, some laboratory parameters change minimally or not at all with age, still remaining within recommended reference ranges, while others are altered with age. Misinterpretation of an abnormal laboratory value as an aging change can lead to underdiagnosis and undertreatment in some instances (such as anemia). Failure to appreciate age-related changes can lead to overdiagnosis and overtreatment in others (such as hyperglycemia). The results from ongoing national studies are needed to establish uniform older adult reference intervals.


Structure of Chorismate Mutase-like Domain of DAHPS from Bacillus subtilis Complexed with Novel Inhibitor Reveals Conformational Plasticity of Active Site.
3-deoxy-D-arabino-heptulosonate-7-phosphate-synthase (DAHPS) is the first enzyme of the shikimate pathway and is responsible for the synthesis of aromatic amino acids in microorganisms. This pathway is an attractive target for antimicrobial drugs. In Bacillus subtilis, the N-terminal domain of the bifunctional DAHPS enzyme belongs to an AroQ class of chorismate mutase and is functionally homologous to the downstream AroH class chorismate mutase. This is the first structure of chorismate mutase, AroQ (BsCM_2) enzyme from Bacillus subtilis in complex with citrate and chlorogenic acid at 1.9 Å and 1.8 Å resolution, respectively. This work provides the structural basis of ligand binding into the active site of AroQ class of chorismate mutase, while accompanied by the conformational flexibility of active site loop. Molecular dynamics results showed that helix H2' undergoes uncoiling at the first turn and increases the mobility of loop L1'. The side chains of Arg45, Phe46, Arg52 and Lys76 undergo conformational changes, which may play an important role in DAHPS regulation by the formation of the domain-domain interface. Additionally, binding studies showed that the chlorogenic acid binds to BsCM_2 with a higher affinity than chorismate. These biochemical and structural findings could lead to the development of novel antimicrobial drugs.


Mammary gland carcinoma in a dog with peripheral blood and bone marrow involvement associated with disseminated intravascular coagulation.
A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC.


Study of the time-course of cis/trans (Z/E) isomerization of lycopene, phytoene, and phytofluene from tomato.
In this study we investigated the formation of isomers of lycopene, phytoene, and phytofluene from tomato and their theoretical energy. The results indicated that certain (Z)-isomers are favored thermodynamically and/or kinetically over their (all-E)-counterparts. The relative percentages of (5Z)-lycopene in either thermodynamic or kinetic equilibria were approximately 33%, and those of (all-E)-lycopene were only approximately 22%. Most strikingly (15Z)-phytoene was the major isomer (>90%) when the thermodynamic or the kinetic equilibria were reached. These observations can explain the high levels of lycopene (Z)-isomers found in humans and their rapid formations upon additions of oil to tomato products. In addition, the results can be useful to predict the isomeric forms of lycopene, phytoene, and phytofluene expected in foods as well as in plasma and tissues upon ingestion. In light of the data in the present study, the use of certain geometrical isomers of phytoene, phytofluene and lycopene on their own or as mixtures is recommended in future studies aimed at assessing their possible bioactivity.


Reinforcement of Aluminum Oxide Filler on the Flexural Strength of Different Types of Denture Base Resins: An In vitro Study.
Acrylic resins have been used extensively for the fabrication of denture bases because of their aesthetic qualities, ease of manipulation and repairability. Flexural fatigue of the denture base has been shown to be a factor in the clinical failure of polymethyl methacrylate resin dentures. Also, the fracture can result from impact, fatigue or degradation of the base material. Hence, there is a need to increase the strength of denture base resins. To evaluate the effect of reinforcing alumina oxide filler on the flexural strength of different acrylic resins. A total of 180 acrylic specimens were fabricated, which were divided into three groups self cure acrylic resin (SC), conventional heat cure resin (HC) and high strength heat cure resin (HI). Each group was divided into four subgroups i.e., control group and the specimens of the remaining three groups were reinforced with aluminum oxide (Al2O3) powder by 5%, 10% and 15% by weight. Specimens were stored in distilled water for one week; flexural strength was tested by universal testing machine. Results were analysed by one-way analysis of variance and post-hoc Tukey paired group comparison tests. Flexural strength of SC increased by 9%, 13% and 19%, Flexural strength of HC increased by 8%, 15% and 19% and that of HI increased by 21%, 26% and 29% compared to control group by adding 5%,10% and 15% of alumina filler (p-value <0.001). Addition of 15% of alumina powder to SC showed high flexure strength compared to control group of HC (p-value <0.001). Addition of 10% and 15% of alumina powder to HC showed high flexural strength compared to control group of HI (p-value <0.001). Addition of alumina to self cure acrylic resin, conventional heat cure acrylic resin and high strength heat cure acrylic resin increased the flexural strength. Increasing the flexural strength of the acrylic resin base material could lead to more clinical success.


Antimicrobial susceptibility testing of Clostridium difficile using EUCAST epidemiological cut-off values and disk diffusion correlates.
With the emergence of reduced susceptibility of Clostridium difficile to metronidazole and vancomycin the value of antimicrobial susceptibility testing has increased. The aim of our study was to evaluate disk diffusion for susceptibility testing of C. difficile by comparing disk diffusion results with MICs from gradient tests and to propose zone diameter breakpoint correlates for the EUCAST epidemiological cut-off values (ECOFFs) recently published. We tested 211 clinical isolates of C. difficile, from patients with diarrhoea hospitalized at Aarhus and Odense University Hospitals, Denmark. Furthermore, ten clinical isolates of C. difficile from the Anaerobe Reference Laboratory, University Hospital of Wales, with known reduced susceptibility to either metronidazole or vancomycin, were included. Isolates were tested with Etest gradient strips and disk diffusion towards metronidazole, vancomycin and moxifloxacin on Brucella Blood Agar supplemented with hemin and vitamin K. We found an excellent agreement between inhibition zone diameter and MICs. For each MIC value, the inhibition zones varied from 0 to 8 mm, with 93% of values within 6 mm for metronidazole, 95% of values within 4 mm for vancomycin, and 98% of values within 4 mm for moxifloxacin. With proposed zone diameter breakpoints for metronidazole, vancomycin and moxifloxacin of WT ≥ 23 mm, WT ≥ 19 and WT ≥ 20 mm, respectively, we found no very major errors and only major errors below 2%. In conclusion, we suggest that disk diffusion is an option for antimicrobial susceptibility testing of C. difficile.


Long-term quality of life outcome after treatment for Helicobacter pylori gastric infection.
Helicobacter pylori has been associated with a number of upper gastrointestinal diseases. Treatment directed toward H. pylori promotes ulcer healing and decreases ulcer recurrence. This study reports a longer-term quality of life follow-up in a group of patients treated for H. pylori. Thirty patients who were treated for upper gastrointestinal symptoms at least 2 years (median 32 months) prior to the initiation of this study had the Gastrointestinal Symptom Rating Scale questionnaire mailed to them. 19 patients responded. This scale measures abdominal pain, heartburn, acid regurgitation, sucking sensations in the upper abdomen, nausea and vomiting, borborygmus, abdominal distention, and belching. Three groups of patients were studied: symptomatic patients without H. pylori infection, symptomatic patients with H. pylori infection and successful eradication, and symptomatic patients with H. pylori infections without eradication. The median symptom scores for each group were no more than 1.5. However, there were no statistically significant differences among these three groups in any of the eight items measured by the Gastrointestinal Symptom Rating Scale. The sample size of this study was sufficient to detect a difference between groups of 1.6. Patients treated for H. pylori have no to occasional upper gastrointestinal symptoms in more than 2 years' follow-up. There appears to be no difference in patients treated for the infection and those without the infection.


Conjecture on the role of dry charges in radiosensitization.
A model of cellular radiation damage that involves dry electrons and holes is proposed and the implications of this model to hypoxic radiosenstization are discussed. The transport and reaction properties of dry charges in the structured water surrounding polar biomolecules are considered and a solvation time of 600 picoseconds in this medium is derived. Pre-solvation charge migration, attachment and recombination and the relevance of these processes to sensitization are discussed. DNA damage by physico-chemical interactions with dry holes is proposed and is shown to be modified by oxygen and other electron affinic sensitizers.


Mechanism of chromyl chloride epoxidation.
Modern electronic structure methods including complete active space perturbation theory to second order (CASPT2), and a range of density functional (DFT) methods are used to characterize the intermediates and transition states associated with ethylene epoxidation by chromyl chloride. A novel zwitterionic direct addition pathway is characterized which, when coupled with a dinuclear complex, exothermically produces epoxide through a pathway with a small kinetic barrier.


Patterns of disease in patients at a tertiary referral centre requiring reoperative parathyroidectomy.
Reoperative parathyroidectomy is required when there is persistent or recurrent hyperparathyroidism following the initial surgery (at least 5% of parathyroidectomies nationally). By convention, 'persistent disease' is defined as the situation where the patient has not been cured by the first operation. The term 'recurrent hyperparathyroidism' is used when the patient was confirmed to be biochemically cured for six months from the first operation but has hyperparathyroidism after this date. Reoperative surgery is associated with higher rates of postoperative complications as well as a greater rate of failure to cure. The aim of our study was to review our departmental experience of reoperative parathyroidectomy, with a view to identify patterns of disease persistence and recurrence. Using a departmental database, patients were identified who had undergone reoperative parathyroidectomy between 2006 and 2014. All the pre, intra and postoperative information was documented including the operative note so as to record the location of the abnormal parathyroid gland found at reoperation. Almost two-thirds (63%) of patients had negative, equivocal or discordant conventional imaging so secondary investigative tools were required frequently. The majority of abnormal glands were found in eutopic locations. The most common locations for ectopic glands were intrathyroidal, mediastinal and intrathymic. A third (33%) of the patients had multigland disease and over a quarter (28%) had coexisting thyroid disease. Persistent hyperparathyroidism represents a challenging patient subgroup for which access to all radiological modalities and intraoperative parathyroid hormone monitoring are required. Patient selection for reintervention is a key determinant in the reoperation cure rate.


Forced-flow electrophoresis of proteins and viruses.
This article describes a model for forced-flow electrophoresis (FFE), considering the desired species fraction removal, other fraction removals, and outlet concentrations of all species in the system. The model predicts the necessary inlet flow rate of the retentate chamber and the rate of filtration and the voltage gradient and also provides an appropriate heat balance permitting consideration of possible heat denaturation of the species. The equipment consists of two membranes and a filter, the electric field being imposed by means of external electrodes, and two fractions are obtainable. The main discriminating factor is not the pore sizes of the filter but the relative solute ionization, which depends on the pH and the ionic strength of the buffer solution. Serum proteins (albumin, gamma-globulin) and bacteriophages (M13, MS2, phiX174) have been used to characterize the separation process.


In vitro expression of cytokeratin 18, 19 and tube formation of adipose-derived stem cells induced by the breast epithelial cell line HBL-100.
Fat transplantation is increasingly used in breast augmentation; and recently, the issue of safety concerns from a cellular and molecular point of view has been raised. In this study, attentions were paid to the interaction between adipose-derived stem cells (ADSC) and mammary epithelial cells: human breast cancer cell line - 100 (HBL - 100) cells were used to simulate the normal microenvironment in breast tissue, ADSCs were harvest from human and co-cultured with HBL-100 cells. It was found that ADSCs formed tube-like structures in the co-culture with HBL-100 cells in contrast to the normal morphology of ADSCs in the control group. In addition, the immunofluorescence imaging showed that cytokeratin 18 and 19 (CK18 and 19) were significantly expressed in ADSCs after the co-culture with HBL-100 cells. The ultrastructure of those ADSCs also showed epithelial changes. In conclusion, ADSCs are not biological stable when co-cultured with HBL-100 cells. They differentiate into epithelial-like cells with the expression of epithelial surface marks (CK 18, 19) and form tube-like structures. This may offer an important evidence for the further study of clinical application of transplanting ADSCs rich adipose tissue into the breast in the future.


Antibody response to herpes simplex virus glycoprotein D: effects of acyclovir and relation to recurrence.
We developed an enzyme-linked immunosorbent assay (ELISA) for measuring the antibody response to herpes simplex virus (HSV) glycoprotein D (gD). The ELISA was specific and more sensitive than immunoblotting techniques. Antibody to HSV gD was detected in 10 of 12 sera (geometric mean titer, 36.3) obtained from HSV-2-infected guinea pigs 14 days after intravaginal inoculation, and the titer increased to greater than or equal to 5,120 on day 60. Therapy with acyclovir delayed and diminished the antibody response to gD, although by day 60 the titers of antibody to gD in acyclovir-treated animals were not significantly different from those in controls. An increased titer of antibody to gD seemed to be associated with a reduced number of recurrent episodes and to a reduced number of days with recurrent lesions.


Are interleukin-1 gene polymorphisms risk factors or disease modifiers in AD?
Polymorphisms in the interleukin-1 genes, IL-1A and IL-1B, have been associated with AD, but not in all studies. The authors genotyped the IL-1A(-889) and IL-1B(-511) polymorphisms in large independent cohorts of 503 control individuals and 395 patients with AD, and a further 100 with brain Abeta load. No evidence was found of risk for AD with these variants, nor of an effect on age at onset. However, an impact of IL-1B(-511) on Abeta(40) load (p < 0.05) was detected.


Formal loss of an H radical by a cobalt complex via metal-ligand cooperation.
A (PNP)Co(I)methyl diamagnetic complex formally loses an H atom from the pincer ligand, exhibiting a long-range metal-ligand cooperation in what may be considered as an unusual example of 'C-H cleavage'. Spectroscopic data indicate that the product is a neutral Co(I) complex with a radical delocalized in the ligand backbone.


A woman in her 20s with delusions, hallucinations and dystonic eye movements.
A woman in her early 20s with a rare neurogenetic syndrome was admitted to the Psychiatric Department on suspicion of a psychotic disorder. During the course of her illness, the patient suffered episodes with involuntary eye movements, behavioural changes and psychotic symptoms that were difficult to treat.


Spatial shift of lattice soliton scattering in the Fermi-Pasta-Ulam model.
Spatial shift produced in scattering process of lattice soliton is studied in the Fermi-Pasta-Ulam model with anharmonic-limit potential. Kink-shaped and antikink-shaped lattice solitons are excited by kicking one single particle. Different behaviors are discovered in two types of head-on collision: kink-kink-shaped collision and kink-antikink-shaped collision. In both cases, the spatial shift not only depends on the scattering pair of lattice solitons but also depends on their collision configuration, i.e., their phase difference. To make a comparison between integrable and nonintegrable lattices, and also to check our method, the Toda model is revisited.


Abscisic acid and jasmonic acid activate wound-inducible genes in potato through separate, organ-specific signal transduction pathways.
Mechanical damage to leaf tissue causes an increase in abscisic acid (ABA) which in turn activates the biosynthesis of jasmonic acid (JA). The resulting higher endogenous JA levels subsequently activate the expression of wound-inducible genes. This study shows that JA induces the expression of different sets of genes in roots and leaves of potato plants. When roots of intact plants were treated with JA, high levels of proteinase inhibitor II (pin2), cathepsin D inhibitor, leucine aminopeptidase and threonine deaminase mRNAs accumulated in the systemic leaves. However, in the treated roots, very low, if any, expression of these genes could be detected. In contrast, a novel, root-specific pin2 homologue accumulated in the JA-treated root tissue which could not be detected in leaves, either systemic or those directly treated with JA. Application of okadaic acid and staurosporine revealed that a protein phosphorylation step is involved in the regulation of this differential response. In leaves, a protein phosphatase is required for the JA-induced expression of pin2 and the other genes analysed. This phosphatase activity is not necessary for the JA-induced expression of a pin2 homologue in roots, suggesting the existence of different transduction pathways for the JA signal in these organs. The requirement of a protein phosphatase activity for JA-mediated gene induction has enabled identification of a JA-independent pathway for ABA induction of pin2 and the other wound-inducible genes. This alternative pathway involves a protein kinase, and appears to be selective for wound-inducible genes. Our data suggest the presence of a complex, organ-specific transduction network for regulating the effects of the plant hormones ABA and JA on gene expression upon wounding.


Hereditary hemorrhagic telangiectasia patient presenting with brain abscess due to silent pulmonary arteriovenous malformation.
Hereditary hemorrhagic telangiectasia is a rare autosomal dominant inherited disease that is usually complicated by visceral vascular malformations. Patients harboring such malformations are at increased risk of brain abscess formation, which despite advances in diagnostic and surgical methods remains a life threatening medical emergency with high mortality and morbidity rates. In the present report we describe a case of cerebral abscess due to silent pulmonary arteriovenous malformation (AVM) in a young patient previously undiagnosed for hereditary hemorrhagic telangiectasia syndrome (HHT).


Effect of Fiber Misalignment and Environmental Temperature on the Compressive Behavior of Fiber Composites.
This experimental study investigated how defects, in particular fiber misalignment, affect the mechanical behavior of glass fiber composites (GFRP) under compressive loading. GFRP cross-plies with three different types of fiber misalignment, namely a fold, a wave, and an in-plane undulation, were fabricated using the resin transfer molding process. The compressive tests were performed at four different temperatures, in order to investigate the role of a change in the matrix properties on the strength of the composite. The experiments showed that the defects, especially at lower temperatures, had a significant impact on the mechanical properties of the composite, exceeding the proportion of the defects inside the composite. With increasing temperature, the damage mechanism changed from fiber-dominated to matrix-dominated and, in doing so, decreased the significance of fiber misalignment for the mechanical behavior.


Update on global climate change.
Global climate change brings new challenges to the control of infectious diseases. Since many waterborne and vector-borne pathogens are highly sensitive to temperature and rainfall, health risks resulting from a warming and more variable climate are potentially huge. Global climate change involves the entire world, but the poorest countries will suffer the most. Nations are coming together to address what can be done to reduce greenhouse gas emissions and cope with inevitable temperature increases. A key component of any comprehensive mitigation and adaptation plan is a strong public health infrastructure across the world. Nothing less than global public health security is at stake.