Carcinogenicity of 4-methoxyphenol and 4-methylcatechol in F344 rats.
The carcinogenic potentials of 4-methoxyphenol (4-MP) and 4-methylcatechol (4-MC), phenolic compounds which are structurally similar to the known forestomach carcinogen BHA and the glandular stomach carcinogen catechol respectively, and cause considerably enhanced cell proliferation and cytotoxicities in rat forestomach and/or glandular stomach epithelium, were examined in male and female F344 rats. Groups of 30 male and female animals were administered diets containing 2% 4-MP or 2% 4-MC for 104 weeks. Histopathological findings in the 4-MP case included atypical hyperplasias (male, 67%, female, 37%), papillomas (50%, 23%) and squamous-cell carcinomas (77%, 20%) in the forestomach. 4-MC induced forestomach papillomas (70%, 93%) and squamous-cell carcinomas (53%, 37%), also glandular stomach submucosal hyperplasias (90%, 93%), adenomas (100%, 100%) and adenocarcinomas (57%, 47%), with ulceration or erosion. The degree of differentiation of the squamous-cell carcinomas induced by 4-MP was less than with 4-MC. The present study demonstrated unequivocal forestomach carcinogenicity for 4-MP and forestomach and glandular stomach carcinogenicity for 4-MC, with cytotoxicity and cell proliferation both appearing as important factors for these non-genotoxic carcinogens.


Application of air-cathode pipe reactor to simultaneously suppress sulphate reduction and accelerate COD oxidation in synthetic wastewater.
While bio-corrosion causes severe damage to sewer pipeline, removal of organics in wastewater treatment plants consume substantial energy and is costly. Accepting the electrons from degrading organics by sulphate will produce sulphide - the culprit of corrosion. In this experiment, electrodes were tested for its ability to reduce sulphide formation by transferring electrons to outside the water. Two bench-scale pipe reactors, one with and the other without electrodes were fed with acetate based synthetic wastewater (800 mg/l COD) and sulphate (39 mg/l). In all cases, electrodes were found to suppress sulphate reduction; for low sulphate feed, the average reduction was 2 compared to 4 mg/l and for high sulphate feed it was 20 compared to 68 mg/l. In addition electrodes assisted higher COD removal; the average removal during low sulphate feed was 200 compared to 300 mg/l, but during high sulphate feed they were 300 compared to 450 mg/l.


Genomic alteration profile and PD-L1 expression among different breast cancer subtypes in Chinese population and their correlations.
There were limitations existing in programmed cell-death ligand 1 (PD-L1) as predictive biomarkers for breast cancer (BC), hence exploring the correlation between PD-L1 levels and other biomarkers in BC may become a very useful therapeutic clinical tool. A total of 301 Chinese patients with different BC subtypes including 47 HR+/HER2+, 185 HR+/HER2-, 38 HR-/HER2+, and 31 triple-negative breast cancer (TNBC) were enrolled in our study. Next-generation sequencing based Yuansu450 gene panel was used for genomic alteration identification and PD-L1 expression was tested using immunohistochemistry. The most prevalent BC-related mutations were TP53 mutations, followed by mutations in PIK3CA, ERBB2, CDK12, and GATA3 in our Chinese cohort. We found that mutations DDR2 and MYCL were only mutated in HR-/HER2+ subtype, whereas H3-3A and NRAS mutations were only occurred in HR-/HER2- subtype. The percentage of patients with PD-L1-positive expression was higher in patients with HR-/HER2- mainly due to the percentage of PD-L1-high level. Mutational frequencies of TP53, MYC, FAT4, PBRM1, PREX2 were observed to have significant differences among patients with different BC subtypes based on PD-L1 levels. Moreover, a positive correlation was observed between TMB and PD-L1 level in HR+/HER2- subtype, and showed that the proportion of patients with high PD-L1 expression was higher than that of patients with low PD-L1 expression in the HR+/HER2- and HR+/HER2+ cohorts with high Ki67 expression. The genomic alterations based on PD-L1 and other biomarkers of different cohorts may provide more possibilities for the treatment of BC with different subtypes.


Toxoplasmosis lymphadenopathy-A series of 8 cases diagnosed in a 2-year timeframe: Is it a needle in a haystack?
Toxoplasmosis is a zoonosis caused by Toxoplasma gondii, an obligate intracellular parasite. Clinical presentation of infection depends on the age and immune status of the patient. In immunocompetent patient, it may present as a non-specific lymphadenopathy and self- limiting illness. In contrast, in immunocompromised patients it can be a life-threatening infection. We present a series of 8 cases of toxoplasma lymphadenitis diagnosed in our institute in last two years. Lymphadenopathy raises a suspicion of malignancy; however, diagnosis of reactive lymphadenitis often marks the end of diagnostic evaluation. Careful morphological evaluation, the classic triad, often can direct at a conclusive diagnosis. We are presenting a case series to draw attention to this entity as majority of the published literature is in the form of case report and serological surveys and very occasional study showing both the histopathology and serology in tandem.


Cost-utility and budget impact analyses of gefitinib in second-line treatment for advanced non-small cell lung cancer from Thai payer perspective.
To evaluate the cost utility and budget impact of second-line gefitinib for non-small cell lung cancer from a Thai payer perspective. A Markov model with three health states (pre-progression, post-progression and death) was constructed to estimate direct medical costs and outcomes comparing four treatment options, i.e., gefitinib, erlotinib, pemetrexed and docetaxel. The model followed patients for 2 years with discount rate of 3% annually. Clinical inputs and patients' characteristics were based on a randomized phase III trial (INTEREST). Costs were based on reference prices published by the Ministry of Public Health, Thailand, and other information related to treatment from expert opinion and presented in 2010. Deterministic and probabilistic sensitivity analyses were performed to determine the impact of model parameters on results. In the base case model, gefitinib and erlotinib yielded equal quality-adjusted life years (QALY) but 0.0140 and 0.0110 more QALY compared with docetaxel and pemetrexed, respectively. Total costs were 188 848 Baht (US$6237) for gefitinib, 196 313 Baht (US$6483) for docetaxel, 249 177 Baht (US$8229) for erlotinib and 275 303 Baht (US$9092) for pemetrexed. Drug acquisition contributed the greatest component. A series of sensitivity analyses demonstrated the robustness to various parameter variations except for docetaxel cost and duration of treatment. The budget impact analyses demonstrate the greater the percentage of substitution of gefitinib for docetaxel (ranging from 10-60%) the greater the cost saving. Gefitinib is a dominant cost saving strategy compared with docetaxel for the second-line treatment of advanced NSCLC from the Thai payer perspective.


The Current State of the Residency Match.
This article explores the current state of the residency match in 2020 with a focus on orthopedic surgery, analyzing the utility of current applicant screening methods in producing future generations of competent surgeons. Discussed are anticipated changes to the residency application process considering the COVID-19 pandemic and Step 1 becoming pass/fail in January 2022. Also explored are potential changes to improve the process for applicants and residency programs, such as identifying and using predictive factors of resident success in the applicant screening process, finding better ways to match applicants with programs, and increasing female and underrepresented minorities within orthopedics.


Inkwell pancreaticojejunal anastomosis after pancreaticoduodenectomy.
End-to-end pancreaticojejunal anastomosis after Whipple's resection poses a difficult surgical challenge because the disparity in the relative sizes of the cut pancreas and the jejunum makes it difficult to ensure a water-tight seal. Leakage exposes patients to potentially serious postoperative complications and mortality. We describe a new technique to provide accurate telescoping of the pancreas into the jejunum by dilating and inverting the jejunum over the friable pancreas. The method appears to prevent leakage of pancreatic fluid at the anastomotic site. It has been successfully performed in 5 cases. No patient showed any evidence of pancreatic leakage and all survived uneventfully. The method is easy to perform and appears to be reliable. We believe it serves to reduce morbidity and mortality from pancreatic leakage.


The effect of ambient air pollution on respiratory health of school children: a panel study.
Adverse respiratory effects of particulate air pollution have been identified by epidemiological studies. We aimed to examine the health effects of ambient particulate air pollution from wood burning on school-age students in Christchurch, New Zealand, and to explore the utility of urine and exhaled breath condensate biomarkers of exposure in this population. A panel study of 93 male students (26 with asthma) living in the boarding house of a metropolitan school was undertaken in the winter of 2004. Indoor and outdoor pollution data was continuously monitored. Longitudinal assessment of lung function (FEV1 and peak flow) and symptoms were undertaken, with event studies of high pollution on biomarkers of exposure (urinary 1-hydroxypyrene) and effect (exhaled breath condensate (EBC) pH and hydrogen peroxide concentration). Peak levels of air pollution were associated with small but statistically significant effects on lung function in the asthmatic students, but not healthy students. No significant effect of pollution could be seen either on airway inflammation and oxidative stress either in healthy students or students with asthma. Minor increases in respiratory symptoms were associated with high pollution exposure. Urinary 1-hydroxypyrene levels were raised in association with pollution events by comparison with low pollution control days. There is no significant effect of ambient wood-smoke particulate air pollution on lung function of healthy school-aged students, but a small effect on respiratory symptoms. Asthmatic students show small effects of peak pollution levels on lung function. Urinary 1-hydroxypyrene shows potential as a biomarker of exposure to wood smoke in this population; however measurement of EBC pH and hydrogen peroxide appears not to be useful for assessment of population health effects of air pollution.Some of the data presented in this paper has previously been published in Kingham and co-workers Atmospheric Environment, 2006 Jan; 40: 338-347 (details of pollution exposure), and Cavanagh and co-workers Sci Total Environ. 2007 Mar 1;374(1):51-9 (urine hydroxypyrene data).


Superficial Fungal Infections in a French Teaching Hospital in Grenoble Area: Retrospective Study on 5470 Samples from 2001 to 2011.
Superficial fungal infections are predominantly caused by dermatophytes, but the spectrum of species involved is depending on geographic areas and lifestyle. Only few studies have recently described the French epidemiology of these infections, especially dermatophytosis. To determine the epidemiological situation of superficial fungal infections and the spectrum of dermatophytes in Grenoble area. A retrospective study of mycological laboratory records from January 2001 to December 2011 was carried out among patients with suspected fungal infections in the Grenoble University Hospital. Samples (skin scrapings, nail clippings and hair specimens) were collected, and mycological analyses were carried out by conventional methods. A total of 5470 samples collected from 3740 patients were analysed. Among the 1984 (36.3 %) positive cultures, dermatophytes were identified in 1348/1984 (67.9 %) samples, non-dermatophytes in 636/1984 (32.1 %) samples (yeasts 24.4 %, moulds 7.7 %). Toenails and feet were the most frequent localizations collected (2032 samples, 37.1 %, 1181 samples, 21.5 %). These data show the predominance (more than 92.6 %) of anthropophilic dermatophytes (Trichophyton rubrum, Trichophyton interdigitale and Trichophyton tonsurans). Trichophyton rubrum was the most commonly (78.6 %) isolated dermatophyte. Among zoophilic dermatophytes, Trichophyton verrucosum and Microsporum persicolor were regularly isolated.


Homeostatic regulation of spontaneous and evoked synaptic transmission in two steps.
During development both Hebbian and homeostatic mechanisms regulate synaptic efficacy, usually working in opposite directions in response to neuronal activity. Homeostatic plasticity has often been investigated by assaying changes in spontaneous synaptic transmission resulting from chronic circuit inactivation. However, effects of inactivation on evoked transmission have been less frequently reported. Importantly, contributions from the effects of circuit inactivation and reactivation on synaptic efficacy have not been individuated. Here we show for developing hippocampal neurons in primary culture that chronic inactivation with TTX results in increased mean amplitude of miniature synaptic currents (mEPSCs), but not evoked synaptic currents (eEPSCs). However, changes in quantal properties of transmission, partially reflected in mEPSCs, accurately predicted higher-order statistical properties of eEPSCs. The classical prediction of homeostasis--increased strength of evoked transmission--was realized after explicit circuit reactivation, in the form of cells' pairwise connection probability. In contrast, distributions of eEPSC amplitudes for control and inactivated-then-reactivated groups matched throughout. Homeostatic up-regulation of evoked synaptic transmission in developing hippocampal neurons in primary culture requires both the inactivation and reactivation stages, leading to a net increase in functional circuit connectivity.


Crystal structure of N-[3-(benzo[d]thia-zol-2-yl)-6-bromo-2H-chromen-2-yl-idene]-4-methyl-benzenamine.
The title compound, C23H15BrN2OS, was the unexpected product in an attempted synthesis of the isomeric 3-(benzo[d]thia-zol-2-yl)-6-bromo-1-p-tolyl-quinolin-2(1H)-one. The Cchromene=N-C angle is wide [125.28 (8)°]. The benzo-thia-zole and chromene ring systems are almost coplanar, with their planes parallel to (10); the toluene ring system is rotated by ca 40° out of the chromene plane. The mol-ecular packing involves layers with π-stacking, borderline 'weak' hydrogen bonds and possible C-H⋯π contacts.


Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure.
Cardiac troponin I (cTnI), a sensitive and specific marker of myocardial cell injury, is useful in diagnosing and assessing prognosis in acute coronary syndromes. Small studies report that cTnI is elevated in severe heart failure (HF) and may predict adverse outcomes. The present study evaluated 238 patients with advanced HF referred for cardiac transplantation evaluation who had cTnI assay drawn at the time of initial presentation. Patients with acute myocardial infarction or myocarditis were excluded from analysis. cTnI was detectable (cTnI > or =0.04 ng/mL) in serum of 117 patients (49.1%). Patients with detectable cTnI levels had significantly higher B-type natriuretic peptide (BNP) levels (P<0.001) and more impaired hemodynamic profiles, including higher pulmonary wedge pressures (P=0.002) and lower cardiac indexes (P<0.0001). A significant correlation was found between detectable cTnI and progressive decline in ejection fraction over time. Furthermore, detectable cTnI was associated with increased mortality risk (RR, 2.05; 95% CI, 1.22 to 3.43). After adjustment for other factors associated with adverse prognosis including age, sex, ejection fraction, and coronary artery disease, cTnI remained a significant predictor of death. cTnI used in conjunction with BNP further improved prognostic value. cTnI is associated with impaired hemodynamics, elevated BNP levels, and progressive left ventricular dysfunction in patients with HF. cTnI may be a novel, useful tool in identifying patients with HF who are at increased risk for progressive ventricular dysfunction and death.


"Sclero-DALK": New approach for treatment of superficial corneal leukoma.
Present a new technique to perform a deep anterior lamellar keratoplasty (DALK) that could be an alternative to the "Big Bubble" or the Melles technique. The case concerns a 48 years old man who presents superficial corneal leukoma in the left eye secondary to ocular trauma 14 years ago. Sclero-DALK is performed under general anesthesia obtaining an excellent visual and refractive result. Sclero-DALK is a novelty in surgical treatment of corneal surface opacities. It offers the same advantages than conventional DALK since it is also a non-penetrating extraocular technique. Better final visual acuities are expected with this technique in comparision with PK and the conventional DALK because less residual stroma can be remained since we acces directly to the predescemetic space.


Transcervical Approach in a Thrice Recurrent Parapharyngeal Space Tumor.
Parapharyngeal space tumors are rare and account for 0.5% of all head and neck tumors. Most of them are benign (95%), of which pleomorphic adenomas of the salivary gland are the most common. Due to their anatomical location, gaining surgical access while avoiding postoperative morbidity is the main limitation. We present the case of a 35-year-old male with a history of three transcervical resections of benign pleomorphic adenomas in the parapharyngeal space within the deep lobe of the parotid gland. The patient has been followed for more than ten years and maintains an adequate quality of life.


[How "representative" are SHI (statutory health insurance) data? Demographic and social differences and similarities between an SHI-insured population, the population of Lower Saxony, and that of the Federal Republic of Germany using the example of the AOK in Lower Saxony].
Using data obtained from a statutory health insurance (AOK) in the federal state of Lower Saxony, this study examined whether there were differences between the insured population compared with that of Lower Saxony (Niedersachsen) and of Germany with respect to social structural characteristics. Data for the comparisons were provided by the statistical office of Germany, and all datasets were coded according to the same criteria. The differences in gender distribution and age distribution between the AOK, Lower Saxony, and Germany were small. The share of employed individuals among the insured compared with those of Lower Saxony and Germany did not differ for males, but it was lower in women. In the insured population a higher proportion of individuals had lower qualification levels than in Lower Saxony or in Germany; the number of individuals with higher qualifications was, however, sufficient to permit statistical analyses. There were differences in the distributions of social structural characteristics between the health insurance population on the one hand and the populations of Lower Saxony and of Germany on the other. Due to the high number of cases, it is nevertheless possible to analyze associations between social structural variables, health impairments, and patterns of health care utilization.


Three-dimensional reconstruction of paracentesis approach in transjugular intrahepatic portosystemic shunt.
To establish a digital transjugular intrahepatic portosystemic shunt (TIPS) model and provide morphological data for radiological diagnosis and interventional radiology to reduce portal vein pressure, 400 serial sectional images from the internal jugular vein superior margin to the lower edge of the liver were chosen from the Chinese Visible Human dataset. Surface and volume reconstructions were performed using 3D-DOCTOR 3.5 software on an ordinary personal computer. Volume and surface renderings were employed to perform data segmentation and image edge detection for reconstruction of the internal jugular vein, brachiocephalic vein, superior vena cava, heart, inferior vena cava, hepatic vein, and portal vein for computerized 3D reconstruction of the TIPS pathway and construction of a 3D visible model of different structures along it. The model can also display pathway and distribution characteristics and interactively show the spatial structural relationships between intrahepatic venous lines from any position and angle, plus complete data acquisition for any range and angle for 3D reconstruction with stereopsis and measurements using any visualization platform. The digital reconstruction of the TIPS pathway correctly reflected the complicated anatomic structural characteristics and spatial adjacency relationships between intrahepatic venous lines, providing a reference 3D morphology for image diagnostics and interventional TIPS therapy.


Change of TH1/TH2 cytokine equilibrium in rats with severe sepsis and therapeutic effect of recombinant interleukin-12 and Shenmai injection.
To evaluate the dynamic change of Th1/Th2 cytokines in serum, peritoneal lavage fluid (PLF) and splenic macrophages (SM) in rats with severe peritonitis, and to observe the therapeutic effects of recombinant interleukin-12 (rIL-2) and Shenmai injection (SMI), a Chinese medicinal preparation. Severe peritonitis (SP) model was induced by intraperitoneal injection of E. coli and B. frag, and mild peritonitis (MP) model was induced by cecal ligation and punching. Then the following experiments were done: (1) Survival rates of animals after every 6 hrs in the 72 hrs after modeling were recorded, serum and PLF levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-10 (IL-10), 6 hrs, 12 hrs, 24 hrs and 48 hrs after modeling were measured. (2) Model rats were treated with rIL-12 or SMI, the survival rate was recorded and serum levels of TNF-alpha, INF-gamma, and IL-10 before and after treatment were measured, and (3) amount of these cytokines produced by SM were determined 6 hrs, 12 hrs and 24 hrs after treatment. The survival rates and levels of cytokines were then compared between the groups (model group treated with rIL-12 or SMI, untreated model group, and blank group). Serum and PLF levels of IFN-gamma, TNF-alpha at all the time points in SP rats were significantly lower than those in MP rats while those of IL-10 6 hrs and 12 hrs after modeling were significantly higher in the former than that in the latter (P < 0.05). IFN-gamma secretion of SM in SP rats was significantly higher than that in MP rats 6 hrs after modeling (P < 0.05). Administration of rlL-12 or SMI given before modeling could improve the survival rate of the model rats (P < 0.05) and cause significant increase of the serum level and SM secretion of IFN-gamma. Imbalance in promoting/antagonizing inflammatory cytokines and Th2 response dominance appear in SP rats early at the initiating stage, and SM secretion of inflammation promoting factor also reduces. Administration in time of rIL-12 and SMI, may increase the survival rate, and its mechanism may be related with their immuno-stimulating action.


Fc-gamma receptor polymorphisms as predictive and prognostic factors in patients receiving oncolytic adenovirus treatment.
Oncolytic viruses have shown potential as cancer therapeutics, but not all patients seem to benefit from therapy. Polymorphisms in Fc gamma receptors (FcgRs) lead to altered binding affinity of IgG between the receptor allotypes and therefore contribute to differences in immune defense mechanisms. Associations have been identified between FcgR polymorphisms and responsiveness to different immunotherapies. Taken together with the increasing understanding that immunological factors might determine the efficacy of oncolytic virotherapy we studied whether FcgR polymorphisms would have prognostic and/or predictive significance in the context of oncolytic adenovirus treatments. 235 patients with advanced solid tumors were genotyped for two FcgR polymorphisms, FcgRIIa-H131R (rs1801274) and FcgRIIIa-V158F (rs396991), using TaqMan based qPCR. The genotypes were correlated with patient survival and tumor imaging data. In patients treated with oncolytic adenoviruses, overall survival was significantly shorter if the patient had an FcgRIIIa-VV/ FcgRIIa-HR (VVHR) genotype combination (P = 0,032). In contrast, patients with FFHR and FFRR genotypes had significantly longer overall survival (P = 0,004 and P = 0,006, respectively) if they were treated with GM-CSF-armed adenovirus in comparison to other viruses. Treatment of these patients with unarmed virus correlated with shorter survival (P < 0,0005 and P = 0,016, respectively). Treating FFHH individuals with CD40L-armed virus resulted in longer survival than treatment with other viruses (P = 0,047). Our data are compatible with the hypothesis that individual differences in effector cell functions, such as NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and tumor antigen presentation by APCs caused by polymorphisms in FcgRs could play role in the effectiveness of oncolytic virotherapies. If confirmed in larger populations, FcgR polymorphisms could have potential as prognostic and predictive biomarkers for oncolytic adenovirus therapies to enable better selection of patients for clinical trials. Also, putative associations between genotypes, different viruses and survival implicate potentially important mechanistic issues.


Co-morbid pain and psychopathology in males and females admitted to treatment for opioid analgesic abuse.
The purpose of this study was to identify co-morbidity in a national sample (N=1408) of males and females entering treatment for opioid abuse. Our sample was primarily white, lived in small urban, suburban or rural locations (80%), and was well-educated. Chronic pain was a symptomatic feature in over 60% of all subjects. Furthermore, 79% of male and 85% of female prescription opioid abusers indicated that their first exposure to an opioid was a legitimate prescription for pain which subsequently led 60-70% to misuse to get high. Our data also indicate that the use of prescription opioids to get high represents the end stage on a continuum of substance abuse, beginning at a very early age. The age of first alcohol use, getting drunk, smoking, use of marijuana, stimulants and other non-opioid prescription or illicit drugs occurred very early (13-19) in prescription opioid misusers/abusers, whose first use of opioids did not occur, on average, until age 22. Finally, most of the sample had sought treatment 3 or more times for substance abuse prior to the treatment admission in which the survey was completed. Physical and mental health were very poor in both male and female prescription opioid abusers, but females were more ill and dysfunctional than males in all physical and particularly emotional domains. Our results suggest that a small number of "at risk" opioid naive pain patients, who might abuse their therapeutically appropriate opioid analgesics, can be identified by assessing pre- and co-morbid substance abuse and significant psychopathology.


Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential.
Several studies demonstrate the role of adipose mesenchymal stem cells (ASCs) in angiogenesis. The angiogenic mechanism has been ascribed to paracrine factors since these cells secrete a plenty of signal molecules and growth factors. Recently it has been suggested that besides soluble factors, extracellular vesicles (EVs) that include exosomes and microvesicles may play a major role in cell-to-cell communication. It has been shown that EVs are implicated in the angiogenic process. Herein we studied whether EVs released by ASCs may mediate the angiogenic activity of these cells. Our results demonstrated that ASC-derived EVs induced in vitro vessel-like structure formation by human microvascular endothelial cells (HMEC). EV-stimulated HMEC when injected subcutaneously within Matrigel in SCID mice formed vessels. Treatment of ASCs with platelet-derived growth factor (PDGF) stimulated the secretion of EVs, changed their protein composition and enhanced the angiogenic potential. At variance of EVs released in basal conditions, PDGF-EVs carried c-kit and SCF that played a role in angiogenesis as specific blocking antibodies inhibited in vitro vessel-like structure formation. The enhanced content of matrix metalloproteinases in PDGF-EVs may also account for their angiogenic activity. Our findings indicate that EVs released by ASCs may contribute to the ASC-induced angiogenesis and suggest that PDGF may trigger the release of EVs with an enhanced angiogenic potential.


Survival and "event-free" analysis of 785 patients with Björk-Shiley spherical-disc valves at 10 to 16 years.
Seven hundred eighty-five patients underwent Björk-Shiley spherical-disc valve replacement from 1970 to 1976. There were 268 mitral valve replacements (MVR), 227 aortic valve replacements (AVR), 65 double-valve replacements, and 225 "combined" procedures. A 97.2% follow-up (mean, 12 years) was achieved. With an operative mortality of 4.1% for MVR, 8.4% for AVR, 15.4% for double-valve replacement, and 12.4% for combined procedures, the 12-year survival was most closely related to age at valve replacement: age less than 50 years, 70%; age 50 through 59 years, 52%; and age 60 years or more, 38%. Twenty-four patients (3.1%) (6 who had MVR, 5 who had AVR, 1 who had double-valve replacement, and 12 who had combined procedures) had a thrombosed valve 1 to 134 months postoperatively; this is equal to 0.36 thrombosed valve per 100 patient-years. One hundred eighteen embolic episodes occurred in 94 (13%) of the operative survivors or 1.8 emboli per 100 patient-years. There were major bleeding complications in 0.5% of patients and minor bleeding complications, in 4.0%. Endocarditis appeared in 30 patients (4.2%) or 0.4 episode per 100 patient-years and paravalvular leaks, in 20 patients (2.8%). The event-free survival by age group and valve site at 5, 10, and 12 years is presented. Events included death, thrombosed valves, strokes, bleeding, emboli, paravalvular leaks, and endocarditis. There were 5.3 events per 100 patient-years excluding operative deaths.


Salvage replantation: free composite transfer from a non-replantable arm.
Free transfer of two undamaged fingers from a non-replantable left arm to a mutilated right hand in a 16-month-old boy is reported.


Retinal breaks secondary to vascular accidents.
Seven retinal breaks occuring after occlusion of a major retinal arterial or venous branch were found in the eyes of six patients. Five holes were in the midretina, in a nonperfused avascular area corresponding to the sector affected by the vascular accident. One was a macular hole, and one a horseshoe tear outside the area involved in the vascular occlusion caused by traction of vitreous on a tuft of neovascular tissue. Five of the holes may have been caused by a kind of sequestration of the retina secondary to vascular insufficiency.


Dynamic protein-protein interaction wiring of the human spliceosome.
More than 200 proteins copurify with spliceosomes, the compositionally dynamic RNPs catalyzing pre-mRNA splicing. To better understand protein - protein interactions governing splicing, we systematically investigated interactions between human spliceosomal proteins. A comprehensive Y2H interaction matrix screen generated a protein interaction map comprising 632 interactions between 196 proteins. Among these, 242 interactions were found between spliceosomal core proteins and largely validated by coimmunoprecipitation. To reveal dynamic changes in protein interactions, we integrated spliceosomal complex purification information with our interaction data and performed link clustering. These data, together with interaction competition experiments, suggest that during step 1 of splicing, hPRP8 interactions with SF3b proteins are replaced by hSLU7, positioning this second step factor close to the active site, and that the DEAH-box helicases hPRP2 and hPRP16 cooperate through ordered interactions with GPKOW. Our data provide extensive information about the spliceosomal protein interaction network and its dynamics.


Correction: The bZIP Transcription Factor MoAP1 Mediates the Oxidative Stress Response and is Critical for Pathogenicity of the Rice Blast Fungus Magnaporthe oryzae.
[This corrects the article DOI: 10.1371/journal.ppat.1001302.].


Role of PPAR-Allopregnanolone Signaling in Behavioral and Inflammatory Gut-Brain Axis Communications.
The gut microbiome regulates emotional behavior, stress responses, and inflammatory processes by communicating with the brain. How and which neurobiological mediators underlie this communication remain poorly understood. PPAR-α (peroxisome proliferator-activated receptor α), a transcription factor susceptible to epigenetic modifications, regulates pathophysiological functions, including metabolic syndrome, inflammation, and behavior. Mood disorders, inflammatory processes, and obesity are intertwined phenomena that are associated with low blood concentrations of the anti-inflammatory and "endogenous tranquilizer" neurosteroid allopregnanolone and poor PPAR-α function. Stress and consumption of obesogenic diets repress PPAR function in brain, enterocytes, lipocytes, and immune modulatory cells favoring inflammation, lipogenesis, and mood instability. Conversely, micronutrients and modulators of PPAR-α function improve microbiome composition, dampen systemic inflammation and lipogenesis, and improve anxiety and depression. In rodent stress models of anxiety and depression, PPAR activation normalizes both PPAR-α expression downregulation and decreased allopregnanolone content and ameliorates depressive-like behavior and fear responses. PPAR-α is known to regulate metabolic and inflammatory processes activated by short-chain fatty acids; endocannabinoids and congeners, such as N-palmitoylethanolamide, drugs that treat dyslipidemias; and micronutrients, including polyunsaturated fatty acids. Both PPAR-α and allopregnanolone are abundantly expressed in the colon, and they exert potent anti-inflammatory actions by blocking the toll-like receptor-4-nuclear factor-κB pathway in peripheral immune cells, neurons, and glia. The perspective that PPAR-α regulation in the colon by gut microbiota or metabolites influences central allopregnanolone content after trafficking to the brain, thereby serving as a mediator of gut-brain axis communications, is examined in this review.


5-hydroxytryptamine medications for the treatment of obesity.
The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15 years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2 C R as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2 C R agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2 C R modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2 C R agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.


Differential control of cardiac and vasomotor activity by neurones in nucleus paragigantocellularis lateralis in the cat.
1. In cats anaesthetized with chloralose, neuronal cell bodies were excited by micro-injection of DL-homocysteic acid (DLH). 2. Injections made into the ventrolateral medulla in the region of nucleus paragigantocellularis lateralis (p.g.l.) produced a rise in blood pressure accompanied by either an increase or decrease in heart rate according to the precise site of the injection. The tachycardia was blocked by propranolol (0.15-0.5 mg kg-1 I.V.) whilst bradycardia was abolished by vagotomy or atropine (0.2-1.5 mg kg-1 I.V.). 3. Recordings were made of blood flow to the hind-limb, renal and mesenteric vascular beds in order to study the haemodynamic changes separately in each region. 4. Vasoconstriction was seen in the renal and mesenteric beds and either vasodilatation or vasoconstriction could be evoked in hind-limb muscle. The vasodilatation in hind-limb muscle was resistant to atropine but significantly reduced by propranolol (0.15-1.5 mg kg-1 I.V.) and therefore was probably mediated mainly by circulating adrenaline. 5. The relative contribution by each vascular bed to the rise in peripheral resistance produced by micro-injection of DLH at any one site varied according to the site of the injection and there was a degree of topographical organization within p.g.l. The neuronal pools which elicit tachycardia, renal vasoconstriction and hind-limb dilatation were located at the rostral end of the nucleus whilst those which produced vasoconstriction in the hind-limb muscle and mesenteric vascular beds were represented further caudally.


Circadian photoperiod alters TREK-1 channel function and expression in dorsal raphe serotonergic neurons via melatonin receptor 1 signaling.
Seasonal day length has been linked to the prevalence of mood disorders, and however, the mechanisms underlying this relationship remain unknown. Previous work in our laboratory has shown that developmental exposure to seasonal photoperiods has enduring effects on the activity of mouse dorsal raphe serotonergic neurons, their intrinsic electrical properties, as well as on depression and anxiety-related behaviors. Here we focus on the possible ionic mechanisms that underlie the observed programming of the electrophysiological properties of serotonin neurons, focusing on the twin-pore K + channels TREK-1 and TASK-1 that set resting membrane potential and regulate excitability. Pharmacological inhibition of TREK-1 significantly increased spike frequency in Short and Equinox photoperiods, but did not further elevate the firing rate in slices from Long photoperiod mice, suggesting that TREK-1 function is reduced in Long photoperiods. In contrast, inhibition of TASK-1 resulted in increases in firing rates across all photoperiods, suggesting that it contributes to setting excitability, but is not regulated by photoperiod. We then quantified Kcnk2 mRNA levels specifically in dorsal raphe 5-HT neurons using triple-label RNAscope. We found that Long photoperiod significantly reduced levels of Kcnk2 in serotonin neurons co-expressing Tph2, and Pet-1. Photoperiodic effects on the function and expression of TREK-1 were blocked in melatonin 1 receptor knockout (MT-1KO) mice, consistent with previous findings that MT-1 signaling is necessary for photoperiodic programming of dorsal raphe 5-HT neurons. Taken together these results indicate that photoperiodic regulation of TREK-1 expression and function plays a key role in photoperiodic programming the excitability of dorsal raphe 5-HT neurons.


Comparison of the five 2011 guidelines for the treatment of carotid stenosis.
In 2011, five independent, international guideline committees reported their recommendations for the management of symptomatic and asymptomatic carotid artery stenosis. These included the American College of Cardiology/American Heart Association, the Society for Vascular Surgery, the European Society of Cardiology, the Australasian, and the UK National Institute of Health and Clinical Excellence. As the recommendations of these five guideline committees were based on the same published literature, it would be expected that they are similar, at least to a large extent. Surprisingly, there were considerable differences between the five guidelines regarding the management of both symptomatic and asymptomatic carotid patients. The differences in the recommendations between the five Guideline Committees are analyzed and discussed.


Porous POSS-PANI nanofibre from interfacial polymerization and hydrothermal approach.
Nowadays, novel applications for polyaniline (PANI) make new demands on its morphology controlling, and designing novel PANI or PANI composite polymeric materials has been more and more attractive. In this work, octaaminophenyl polyhedral oligomeric silsesquioxane (POSS) was employed to prepare nanostructured PANI composites via controlled fabrication. By interfacial copolymerization, fibrous nanostructure was obtained. The size and morphology of this structure was adjusted by changing POSS to OAPS ratio: the size increased from about 20 to 200 nm when the molar ratio of POSS in the composites increased from 0.5 to 2.0 mol %. More importantly, further hydrothermal treatment for the samples with higher POSS concentration resulted in mesoporous structure on a more microscopic scale, which helps to improve the thermal stability. In the total synthesis, POSS played an important role in the morphology controlling of the composites.


[RENAL TUBULAR DYSGENESIS SECONDARY TO MUTATIONS IN GENES ENCODING THE RENIN-ANGIOTENSIN SYSTEM].
Autosomal recessive renal tubular dysgenesis (RTD;OMIM: 267430) is a rare kidney disease secondary to mutations in genes encoding the renin-angiotensin system which have a role in renal tissue development during fetal life and in the maintenance of blood pressure and electrolyte balance. The disease is characterized by oligohydramnios, prematurity, neonatal renal failure, hypotension and abnormalities in cranial bone development. Nearly all affected individuals die either in-utero or within the first few days of life, although a few long term survivors were reported during the last decade. We describe the management of 5 newborns diagnosed with RTD in pregnancy who survived the neonatal period, four of them belong to an extended Bedouin family. In 4/5 patients we identified a mutation in angiotensin converting enzyme (ACE) gene. Variable presentation was noticed in the patients, starting with peritoneal dialysis and extreme low blood pressure treated with vasopressors and plasma infusions and ending with no symptoms. Currently, the patients are 5-20 years old with variable stages of chronic kidney disease. In conclusion, the spectrum of RTD is wider than previously reported. Prompt diagnosis is necessary for optimal decision-making by families and physicians. Intensive treatment of low blood pressure in the postnatal period is critical for their survival and better prognosis.


Usefulness of contrast kinetics for predicting and monitoring tissue changes in muscle following thermal therapy in long survival studies.
To investigate Gd-DTPA kinetics as indicators of subacute and subchronic histopathological changes following focused ultrasound (FUS) thermal therapy for improved evaluation. A total of 18 FUS lesions were created in the thigh muscle of five rabbits under magnetic resonance (MR) guidance at 1.5 Tesla. The rabbits were killed at different times: 40 hours, three days, and seven days. All lesions were analyzed histologically. An analysis of the uptake kinetics of Gd-DTPA, injected within two hours postheating and before sacrifice, was performed. The resulting kinetic maps, permeability (K(trans)) and leakage space (v(e)), were correlated to T(2)-weighted MR and histology. Images of K(trans) and v(e) better differentiate subacute and subchronic changes not visible on conventional MR in the days following therapy and are consistent with the histopathology observed. In particular, the border between nonviable and viable tissue is well demarcated. The extent of damage is best indicated on v(e), whereas the borders of inflammation are shown on K(trans). The total lesion extent is relatively stable over the 7 days posttherapy and can be predicted by v(e) or T(2)-weighted MR at early times after heating. Our results suggest that Gd-DTPA kinetics can complement conventional MR for improved evaluation of FUS thermal therapy by providing finer differentiation of necrotic states, inflammation, and repair processes.


Comparative genomics of closely related salmonellae.
As the number of completed genome sequences increases, there is increasing emphasis on comparative genomic analysis of closely related organisms. Comparison of the similarities and differences between the five publicly available Salmonella genome sequences reveals extensive sequence conservation among the Salmonella serovars. However, horizontal gene transfer has provided each genome with between 10% and 12% of unique DNA. Genome comparisons of the closely related salmonellae emphasize the insights that can be gleaned from sequencing genomes of a single species.


RPC technical report #18: information that should be included in every patient's radiotherapy treatment record (external beam).
The Radiological Physics Center (RPC) has frequently been asked to develop a model daily treatment record. It became obvious that there was some minimum information that must be in patient records. However, equally obvious was the fact that practices at institutions could be very different, so organization of information in records was different. We have compiled a list of data that must be in a patient's treatment record to assure that the radiation treatment can be reconstructed at a later date. The ordering of this information in forms and records is left to the discretion of the institution.


Profiling of lipophilic and phenolic phytochemicals of four cultivars from cherimoya (Annona cherimola Mill.).
The lipophilic and phenolic extractives of the ripe mesocarp of four cherimoya cultivars ('Perry Vidal', 'Mateus I', 'Mateus III' and 'Funchal') from Madeira Island, were studied for the first time. The predominant lipophilic compounds are kaurene diterpenes (42.2-59.6%), fatty acids (18.0-35.6%) and sterols (9.6-23.7%). Kaur-16-en-19-oic acid is the major lipophilic component of all cultivars accounting between 554 and 1350mgkg(-1) of dry material. The studied fruits also contain a high variety of flavan-3-ols, including galloylated and non-galloylated compounds. Five phenolic compounds were identified for the first time: catechin, (epi)catechin-(epi)gallocatechin, (epi)gallocatechin, (epi)afzelechin-(epi)catechin and procyanidin tetramer. 'Mateus I' and 'Mateus III' cultivars present the highest content of phenolic compounds (6299 and 9603mgkg(-1) of dry weight, respectively). These results support the use of this fruit as a rich source of health-promoting components, with the capacity to prevent or delay the progress of oxidative-stress related disorders.


[Basaliomas].
Basal cell carcinoma is the most frequent skin tumor in humans. It is mostly located in the face and its incidence is steadily rising. The tumor develops from basal, undifferentiated epithelial cells of the skin and its appendices and shows locally destroying growth, but generally without metastatic outspread typical of carcinomas of other origin. The tumor does not occur on the vermilion border of the lips and in the mucosa. Surgery is the most widespread and accepted treatment of basaliomas. It gives the possibility of histologic diagnosis of the whole specimen including margins of resection and allows immediate closure of the defect by means of plastic surgical methods. Regarding aesthetic and functional demands of the region, maxillofacial surgeons have the best prerequisites for this treatment. Recent research results clearly demonstrate the role of UVB light in the etiology, which is modified or promoted by genetic factors. Because of its typical malignant properties, such as progressive growth and infiltration, the term "basalioma", which is mostly used in German, should be replaced by "basal cell carcinoma" as it is known in the international literature.


The Holocaust after 70 years: Holocaust survivors in the United States(.).
Over 70 years, there have been different narratives of the Holocaust survivors coming to the United States. Survivors' stories begin with an event of major historical significance. Difficulties in conceptualizing historical trauma, along with common distortions and myths about Holocaust survivors and their children are examined. This article proposes that it is impossible to discuss the consequences of extreme suffering without consideration of historical meaning and social context with which they are entwined. The evolution of the social representation of the Holocaust and the contradictions in clinical attributions to survivors and their children with consideration of the future is described. Attributions to survivors and their children with consideration of the future is described.


Short-Term Effects of Temperature and Thyrotropin-Releasing Hormone Stimulation on Adrenocorticotropin Stability in Horses.
Pituitary pars intermedia dysfunction (PPID) is diagnosed by increased basal or post thyrotropin-releasing hormone (TRH) stimulation ACTH concentrations. ACTH is known to be unstable; however, the effect of different temperatures and TRH stimulation on equine ACTH stability is poorly described. In total, 15 horses, including 8 PPID positive (ACTH > 35 pg/mL at baseline or >65 pg/mL 30 min after TRH stimulation), were divided into 2 groups: 9, including 5 PPID positive, with basal ACTH concentrations and 6, including 3 PPID positive, with post TRH stimulation ACTH concentrations. Whole blood was stored for 1 h at 4, 20, 30, 40, or 70 °C. After centrifugation, immunoreactive ACTH concentrations were determined using a chemiluminescent assay. Linear mixed effect models were used to detect the effects of temperature, PPID status, and TRH stimulation on the immunoreactive ACTH concentration. Temperature had a significant effect (p = 0.003) on immunoreactive ACTH concentrations, and this effect was greater in PPID-negative horses (p = 0.01), with the changes in immunoreactive ACTH concentrations being slightly unpredictably higher or lower than samples stored at 4 °C. Even at 20 °C, mean immunoreactive ACTH concentrations minimally changed by 5% in PPID horses and 12% in non-PPID horses after 1 h. No significant effect of TRH stimulation was identified. Although ACTH concentrations should ideally be determined from samples kept at 4 °C, samples inadvertently left at temperatures of up to 40 °C can provide valid results if analyzed within 1 h; however, this increases the risks of altered ACTH concentrations, occasionally influencing the diagnosis of PPID.


Multi-strategy engineering unusual sugar TDP-l-mycarose biosynthesis to improve the production of 3-O-α-mycarosylerythronolide B in Escherichia coli.
The insufficient supply of sugar units is the key limitation for the biosynthesis of glycosylated products. The unusual sugar TDP-l-mycarose is initially attached to the C3 of the polyketide erythronolide B, resulting in 3-O-α-mycarosylerythronolide B (MEB). Here, we present the de novo biosynthesis of MEB in Escherichia coli and improve its production using multi-strategy metabolic engineering. Firstly, by blocking precursor glucose-1-phosphate competing pathways, the MEB titer of triple knockout strain QC13 was significantly enhanced to 41.2 mg/L, 9.8-fold to that produced by parental strain BAP230. Subsequently, the MEB production was further increased to 48.3 mg/L through overexpression of rfbA and rfbB. Moreover, the CRISPRi was implemented to promote the TDP-l-mycarose biosynthesis via repressing the glycolysis and TDP-l-rhamnose pathway. Our study paves the way for efficient production of erythromycins in E. coli and provides a promising platform that can be applied for biosynthesis of other glycosylated products with unusual sugars.


Design and testing of a 750MHz CW-EPR digital console for small animal imaging.
This paper describes the development of a digital console for three-dimensional (3D) continuous wave electron paramagnetic resonance (CW-EPR) imaging of a small animal to improve the signal-to-noise ratio and lower the cost of the EPR imaging system. A RF generation board, an RF acquisition board and a digital signal processing (DSP) & control board were built for the digital EPR detection. Direct sampling of the reflected RF signal from a resonator (approximately 750MHz), which contains the EPR signal, was carried out using a band-pass subsampling method. A direct automatic control system to reduce the reflection from the resonator was proposed and implemented in the digital EPR detection scheme. All DSP tasks were carried out in field programmable gate array ICs. In vivo 3D imaging of nitroxyl radicals in a mouse's head was successfully performed.


Role of the small GTPase Rho1 in cell wall integrity, stress response, and pathogenesis of Aspergillus fumigatus.
Aspergillus fumigatus is a major pathogen of invasive pulmonary aspergillosis. The small GTPase, Rho1, of A. fumigatus is reported to comprise a potential regulatory subunit of β-1,3-glucan synthase and is indispensable for fungal viability; however, the role of AfRho1 on the growth, cell wall integrity, and pathogenesis of A. fumigatus is still poorly understood. We constructed A. fumigatus mutants with conditional- and overexpression of Rho1 and found that defects of AfRho1 expression led to the reduction of β-1,3-glucan and glucosamine moieties on the cell wall, with down-regulated transcription of genes in the cell wall integrity signaling pathway and a decrease of calcofluor white (CFW)-stimulated mitogen-activated protein kinase (MpkA) phosphorylation and cytoplasmic leakage compared to those of the wild-type strain (WT). In addition, down-regulation of AfRho1 expression caused much higher sensitivity of A. fumigatus to H2O2 and alkaline pH compared to that of WT. Decrease of AfRho1 expression also attenuated the A. fumigatus pathogenicity in Galleria mellonella and inhibited conidial internalization into lung epithelial cells and inflammatory factor release. In contrast, overexpression of Rho1 did not alter A. fumigatus morphology, susceptibility to cell wall stresses, or pathogenicity relative to its parental strain. Taken together, our findings support AfRho1 as an essential regulator of the cell wall integrity, stress response, and pathogenesis of A. fumigatus.


Oromucosal delivery of macromolecules: Challenges and recent developments to improve bioavailability.
Owing to their biological diversity, high potency, good tolerability, low immunogenicity, site-specific activity, and great efficacy, macromolecular drugs (i.e., proteins and peptides, antibodies, hormones, nucleic acids, vaccines, etc.) are extensively used as diagnostics, prophylactics, and therapeutics in various diseases. To overcome drawbacks associated with parenteral (invasive) delivery of macromolecules as well as to preserve their therapeutic integrity, oromucosal route (sublingual and buccal) has been proven efficient alternate port of delivery. This review aims to summarize challenges associated with oromucosal route and overtime developments in conventional delivery systems with special emphasis on most recent delivery strategies. Over the past few decades, significant efforts have been made for improving the oromucosal absorption of macromolecules by employing chemical penetration enhancers (CPE), enzyme inhibitors, chemical modification of drug structure (i.e., lipidation, PEGylation, etc.), and mucoadhesive materials in the form of buccal tablets, films (or patches), sprays, fast disintegrating tablets, and microneedles. Adaptation of adjunct strategies (e.g., iontophoresis in conjunction with CPE) has shown significant improvement in oromucosal absorption of macromolecules; however, these approaches were also associated with many drawbacks. To overcome these shortcomings and to further improve therapeutic outcomes, specialized delivery devices called "hybrid nanosystems" have been designed in recent times. This newer intervention showed promising potential for promoting oromucosal absorption and absolute bioavailability of macromolecules along with improved thermostability (cold chain free storage), enabling self-administration, site-specific activity, improving therapeutic efficacy and patient compliance. We anticipate that tailoring of hybrid nanosystems to clinical trials as well as establishing their short- and long-term safety profile would substantiate their therapeutic value as pharmaceutical devices for oromucosal delivery of macromolecules.


Xenobiotic-sensing nuclear receptors as targets for phthalates-induced lung injury and antagonism of lycopene.
Phthalates are extensively used in the production of plastics products and have been verified to induce lung injury. Lycopene (LYC) has proved an effective preventive and can be utilized to prevent phthalates-induced toxicity. However, the role of phthalate in pathogenesis of lung injury remain poorly researched, and little work has been devoted whether LYC could alleviate phthalate-induced lung toxicity via modulating nuclear xenobiotic receptors (NXRs) response. Here, di (2-ethylhexyl) phthalate (DEHP) is used as the representative of phthalates for further studies on toxicity of phthalates and the antagonistic role of LYC in phthalates-induced lung injury. We found that DEHP exposure caused alveoli destruction and alveolar epithelial cells type II damage. Mechanistically, DEHP exposure increased nuclear accumulation of aryl hydrocarbon receptor (AHR) and its downstream genes level, including cytochrome P450-dependent monooxygenase (CYP) 1A1 and CYP1B1. Constitutive androstane receptor (CAR) and their downstream gene level, including CYP2E1 are also increased after phthalates exposure. Significantly, LYC supplementation relieves lung injury from DEHP exposure by inhibiting the activation of NXRs. We confirm that NXRs plays a key role in phthalates-induced lung injury. Our study showed that LYC may have a positive role in alleviating the toxicity effects of phthalates, which provides an effective strategy for revising phthalates-induced injury.


An acoustic-speech study of patients who received orthognathic surgery.
Several reports have suggested that orthognathic surgery may influence speech patterns. The purpose of this study was to examine the formant frequency changes of speech following orthognathic surgery in patients whose speech was considered perceptually normal preoperatively and postoperatively. Speech samples were obtained from five patients (three patients with Class II, Division 1 malocclusions and two patients with Class III malocclusions). Significant second-formant frequency shifts were found for the vowel 'e' (as in 'seat'); however, only minor second-formant frequency variations were found for the vowels 'a' (as in 'sat') and 'u' (as in 'suit'). The pattern of formant frequencies before and after surgical treatment suggested that the speakers adjusted their articulation to accommodate the orthognathic surgery. Overall, the data from this study indicate that speech patterns may be reorganized after orthognathic surgery even though speech remains perceptually "normal."


Aberrant accumulation of interleukin-10-secreting neutrophils in TRAF2-deficient mice.
Highly coordinated expression of inflammatory and anti-inflammatory cytokines is crucial for maintaining homeostasis of the gut that is constantly exposed to large amounts of commensal bacteria. We have previously reported that tumor necrosis factor (TNF) receptor-associated factor (Traf)2(-/-) mice spontaneously develop severe colitis and that the development of colitis largely depends on TNFα-dependent apoptosis of colonic epithelial cells. However, the detailed molecular mechanisms underlying the immunological disorders of Traf2(-/-) mice are not fully understood. Here we show that interleukin (IL)-10-secreting neutrophils accumulated in peripheral blood and bone marrow (BM) cells from Traf2(-/-) mice compared with those from wild-type mice. Treatment of Traf2(-/-) mice with neutralizing antibody against TNFα or crossing Traf2(-/-) mice with Tnfr1(-/-) mice reduced the percentages of IL-10-secreting neutrophils, suggesting that the development of IL-10-secreting neutrophils largely depended on TNFα signals. Moreover, stimulation of BM cells from wild-type mice with lipopolysaccharide and Pam3CS(K)4, a ligand for Toll-like receptor 4 and 2, respectively, induced differentiation of BM cells into IL-10-secreting neutrophils. These results suggest that the development of IL-10-secreting neutrophils is not restricted to Traf2(-/-) mice, but could be generalized to wild-type mice under certain conditions such as inflammation. Finally, combined treatment of Traf2(-/-) mice with neutralizing antibodies against TNFα and IL-10, but not each antibody alone, substantially ameliorated colitis and prolonged survival. Together, abrogation of immunosuppressive conditions mediated by IL-10-secreting neutrophils might be an alternative strategy to treat chronic inflammatory diseases at least under certain conditions.


Thoracic Duct Narrowing-Innovative Technique Restraining Weight Gain in Rats.
The lymphatic system is responsible for the absorption of fats from the digestive system, conveying 60-70 % of ingested fat to the blood stream. From the anatomical point of view, all the lymphatic drainage from the lower half of the body converges in the abdomen to enter the thoracic duct. This experimental study aim was to study the result of thoracic duct narrowing (TDN), an innovative surgical technique, on weight gain restrain in high-fat diet-fed rats. Forty-seven rats were allocated into three groups: thoracic duct narrowing ("S"-surgery), sham operation ("CS"-control surgery), and no surgery ("C"-control). All rats were fed with high-fat, cholesterol-rich diet. Food consumption and metabolic syndrome parameters including weight gain, plasma lipids and glucose, blood pressure, and viscera weight and histopathology were analyzed. Thoracic duct narrowing was proved simple and safe surgical procedure in the rat model. TDN induced weight gain restrain, associated with mild hepatic steatosis compared to moderate-severe hepatic steatosis in control groups. Splenomegaly and splenic fatty histiocytes were shown in the treated animals. TDN improved several parameters of the metabolic syndrome in high-fat diet-fed rats. TDN carries the potential of innovative obesity treatment using the lymphatic route of lipid absorption.


Gentamicin-induced bilateral vestibulopathy in rabbits: vestibular dysfunction and histopathology.
Bilateral vestibulopathy (BV) is a mostly persistent and disabling disorder causing dizziness, oscillopsia, and imbalance during locomotion. The animal model is a prerequisite for experimental investigation on prevention and treatment of this disorder. The aim of this study was to determine the vestibular dysfunction and histopathology in rabbits with gentamicin-induced BV. Prospective animal study in rabbits. We performed intratympanic gentamicin (ITGM) injections in 12 Lionhead rabbits. The injection was applied to each ear with a 3-day interval. The control group received injections of 0.9% normal saline. The animals were subjected to sinusoidal harmonic accelerations and open field tests for evaluation of the vestibular function before and after the procedures. We also determined histologic changes in the vestibular labyrinth 30 days after the first injection. One day after unilateral ITGM injection, the rabbits mostly showed ipsiversive head tilt, contralesional spontaneous nystagmus, ipsiversive circling behavior, and decreased gain of the vestibulo-ocular reflex (VOR) during ipsiversive rotation. The second injection to the contralateral ear improved the head tilt but induced marked reduction in the activities and the VOR gains in both directions. These changes persisted until the histologic study confirmed the loss of the hair and supporting cells, diminished nerve fibers, and thinning of the sensory epithelium of the cristae ampullaris and otolith organs in the ITGM group 1 month later. ITGM injection securely induced BV in rabbits without side effects such as nephrotoxicity. This rabbit model may be utilized for experiments on the prevention and treatment of BV.


Use of oral prazosin hydrochloride in congestive failure following acute myocardial infarction.
The hemodynamic effects of the new oral vasocilator prazosin were evaluated in 11 patients with congestive failure following myocardial infarction. Prazosin decreased pulmonary trunk, pulmonary capillary, and right atrial pressures, systemic blood pressure, systemic vascular and total pulmonary resistances, and the heart rate X systolic blood pressure product (P less than 0.001). Cardiac and stroke indexes increased (P less than 0.001 and P less than 0.02, respectively). Heart rate, myocardial perfusion gradient, and stroke work index remained unchanged (P less than 0.05). Prazosin effect began in most patients 30 minutes after an oral administration of 2.5 to 7 mg; the maximum effect occurred from one to three hours later. The action is sustained for at least 6 hours in most patients and sometimes is present even 12 hours after a single dose administration. We conclude that prazosin, with a nitroprusside-like effect, improves left ventricular performance and myocardial O2 supply-demand relationship in patients with acute myocardial infarction, but optimal doses vary significantly, and the hazard of severe and sustained hypotension, or decline in cardiac output in patients with normal blood pressure or slightly elevated filling pressure, is present.


In Vivo and Explant Electroporation of Morpholinos in the Developing Mouse Retina.
Neonatal in vivo electroporations and retinal explant electroporations have been widely employed in understanding the effects of loss or gain of function of protein-coding genes in retinal development. Here, we describe a rapid and efficient delivery of morpholinos to add another tool to perturb gene expression during mouse retinal development.


Short-term stability of anterior open bite treatment with clear aligners in adults.
This study aimed to examine the stability of anterior open bite (AOB) treatment with clear aligners. This retrospective cohort study included 52 adult AOB patients (aged >18 years; 15 males, 37 females) who underwent nonextraction clear aligner treatment and were at least 1 year posttreatment. Eleven cephalometric measurements were evaluated at pretreatment, end of active treatment, and at least 1-year posttreatment. Overbite change, the primary outcome variable, and other cephalometric changes during treatment and retention were calculated, and repeated measures analysis of variance were performed. Stepwise multiple regression was used to make a prediction equation for open bite relapse. The mean retention period was 2.1 ± 1.1 years. The mean change in overbite during treatment was 3.3 ± 1.5 mm; 6% of patients presented relapse at least 1 year after treatment completion. The mean change of overbite (0.2 ± 0.5 mm) during the retention period was not statistically significant (P = 0.59). None of the 11 cephalometric measurements showed significant change during the retention period. The prediction model showed that only the coefficient for a tongue posture issue at the initial examination was statistically significant. AOB was successfully corrected in all 52 patients using only clear aligners with no additional adjunctive aids such as microimplants. When retained with maxillary and mandibular fixed retainers and maxillary and mandibular vacuum-formed retainers, there was no significant change in cephalometric measurements during the short-term retention period.


Eosinophil leukocyte degranulation in response to serum-opsonized beads: C5a and platelet-activating factor enhance ECP release, with roles for protein kinases A and C.
Eosinophils have a typical content of granule-bound, cytotoxic, cationic proteins which may, when released to the external milieu, play roles in diseases such as asthma and parasitic infestation. Therefore, we have investigated possible mechanisms by which their release is regulated in eosinophils. The enzyme-linked immunosorbent assay (ELISA) was used to detect released eosinophil cationic protein (ECP). Release of ECP was induced by serum-opsonized, nonphagocytosable Sephadex beads (SOS). The complement fragment C5a and platelet-activating factor (PAF) were found to enhance ECP release in response to SOS in a dose-dependent fashion, and, contrary to previous reports, they were not found to act as secretagogues themselves on eosinophils in suspension. The role of protein kinase C (PKC) in eosinophil degranulation has been controversial. We found that ECP release induced by SOS was inhibited by the PKC inhibitors staurosporine and calphostin C. Activation of protein kinase A (PKA), by raising cAMP, also inhibited ECP release. Furthermore, pertussis toxin decreased ECP release on opsonized beads, indicating the involvement of pertussis-toxin-sensitive G proteins. C5a, and PAF enhance granule release, rather than acting as secretagogues themselves. PKC and PKA have opposing roles in the regulation of ECP release in response to SOS.


Midwife-led pandemic telemedicine services for maternal health and gender-based violence screening in Bangladesh: an implementation research case study.
The COVID-19 pandemic disrupted maternal and newborn health services in Bangladesh, exacerbating the large gaps in service utilization that existed prior to the pandemic. As part of its response, Bangladesh initiated remote antenatal and postnatal care telemedicine services led by midwives in 36 sub-district hospitals across five of Bangladesh's 64 districts. Gender-based violence screening and referral were integrated into the service to address a reported rise in violence following the country's pandemic lockdown. Mixed-methods implementation research was used to develop an intrinsic case study describing the design and implementation of the telemedicine program. Qualitative analysis comprised document review, key informant interviews, and focus group discussions. Quantitative analysis employed an interrupted time series analysis with segmented multi-variate regression to compare maternity care service use trends before and after implementation. Poisson regression analysis was used to examine the trend in number of gender-based violence remote screenings, sessions held, and cases identified. A statistically significant change in trend for onsite antenatal and postpartum care as well as women seeking care at the hospital as a result of postpartum hemorrhage arising in the community was observed following the introduction of telemedicine. Facility births and cases of eclampsia appropriately identified and managed also had significant increases. In addition, over 6917 women were screened for GBV, 223 received counseling and 34 referrals were made, showing a statistically significant increase in frequency over time following the implementation of the telemedicine program. Challenges included that not all midwives adopted GBV screening, some women were reluctant to discuss GBV, there was an unanticipated need to introduce a patient visit scheduling system in all intervention hospitals, and many women were not reachable by phone due to lack of access or network coverage. Maternal health and gender-based violence telemedicine led by midwives was an effective, low-cost intervention in Bangladesh for addressing pandemic and pre-pandemic gaps in service use. Other low and middle-income countries planning to implement remote maternal health interventions via midwives should consider whether a patient visit scheduling system needs to be introduced, as well as limitations around mobile phone access and connectivity. Future research should include care quality oversight and improvement, and a more well-informed strategy for facilitating effective GBV screening.


Three-dimensional analysis of the structure and ecology of a novel, ultra-small archaeon.
Fully understanding the biology of acid mine drainage (AMD) is central to our ability to control and manipulate its environmental impact. Although genomics and biogeochemical methods are relatively well established in the field, their combination with high-resolution imaging of intact members of microbial biofilm communities has not yet reached its full potential. Here, we used three-dimensional (3D) cryogenic electron tomography to determine the size and ultrastructure of intact ARMAN cells, a novel ultra-small archaeon, and sought evidence for their interactions with other members of its community. Within acid mine drainage biofilms, apparently free-living ARMAN cells from a deeply branched archaeal lineage have volumes of 0.009-0.04 microm(3) (mean approximately 0.03+/-0.01 microm(3)), only approximately 92 ribosomes, yet are frequent hosts for replicating viruses. Organization within the periplasm and partitioning of ribosomes to the inner surface of the cytoplasmic membrane may be factors in size minimization. Most cells contain enigmatic tubular structures of unknown function. The low ribosome copy number per unit volume, indicative of slow growth rates and targeting of cells by diverse viruses may account for the low abundance of ARMAN cells compared with other biofilm community members. Our results provide the first 3D analysis of structural features of these novel and enigmatic cells and their interactions with at least two types of viruses. Our findings also emphasize that new biological phenomena remain to be discovered among lower abundance organisms from novel uncultivated lineages.


Internet Use by First-Time Mothers for Infant Feeding Support.
Optimal nutrition during infancy has benefits to individuals and to society. Australian women actively seek health and nutrition information from a wide variety of sources and have extensive access to the Internet, but its efficacy in supporting recommendation-consistent infant feeding is unknown. The objectives of this study were to evaluate sources of infant feeding information used by first-time mothers and to describe breast and formula feeding patterns 6 months post birth associated with successful use of the Internet for breastfeeding support. Healthy women between 18 and 40 years of age in their first pregnancy were recruited to the Feeding Queensland Babies Study by convenience sampling in Brisbane, Australia, between June 2010 and March 2011. Participants completed a questionnaire online when their infants were 6 months of age and a demographic questionnaire. Health care providers, books, general Internet searches, family, and friends were common sources of breastfeeding information for women during infants' first 6 months. Information sources for infant formula were less often accessed. Of mothers who sought breastfeeding assistance on the Internet, those who found it unhelpful had lower odds of giving breast milk at 6 months (odds ratio [OR] = 0.3; 95% confidence interval [CI], 0.1-0.5) and higher odds of giving formula (OR = 3.3; 95% CI, 1.7-6.5) compared with those who found the help they needed, adjusted for age and socioeconomic status. Professional, print, and interpersonal information resources for infant feeding are widely accessed by mothers. Online breastfeeding information and support may help women to meet their breastfeeding intentions and to minimize formula use.


Clinical approach to a child with poikiloderma: A case report.
There are various causes of childhood poikiloderma. A proper history and clinical examination may help to get conclusion and narrow down the differentials for the causes of poikiloderma.


Language of transducer manipulation 2.0: continuing to codify terms for effective teaching.
Accurate communication is an integral component of ultrasound education. In light of the recent global pandemic, this has become even more crucial as many have moved to virtual education out of necessity. Several studies and publications have sought to establish common terminology for cardinal ultrasound probe motions. To date, no studies have been performed to determine which of these terms have been adopted by the ultrasound community at large. A survey was developed which asked respondents to describe videos of six common probe motions in addition to providing basic demographic and training data. The survey was disseminated electronically across various academic listservs and open access resources. Data were collected over a 6-week period and yielded 418 unique responses. Responses demonstrated significant variation in terminology related to all 6 cardinal probe motions. While some degree of difference in response can be accounted for by discipline of training, inter-group variation still exists in terminology to describe common probe motions. Of the survey respondents, 57.5% felt that inconsistent probe motion terminology made teaching ultrasound more difficult. The results demonstrate that despite efforts to codify probe motions, variation still exists between ultrasound practitioners and educators in the description of cardinal probe motions. This lack of consensus can contribute to challenges in both virtual and in-person ultrasound education.


LIFU-responsive nanomedicine enables acoustic droplet vaporization-induced apoptosis of macrophages for stabilizing vulnerable atherosclerotic plaques.
Due to the high risk of tearing and rupture, vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases. Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event, but the efficiency is still low and undesirable. Herein, we rationally design and engineer the low-intensity focused ultrasound (LIFU)-responsive FPD@CD nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane (PFH) into biocompatible PLGA-PEG-PLGA nanoparticles (PPP NPs) and then attaching dextran sulphate (DS) onto the surface of PPP NPs for targeting delivery. DS, as a typical macrophages-targeted molecule, can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization (ADV) effect. In addition, the introduction of DiR and Fe3O4 endows nanomedicine with near-infrared fluorescence (NIRF) and magnetic resonance (MR) imaging capabilities. The engineered FPD@CD nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on in vivo and in vitro evaluation outcomes. A reduction of 49.4% of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period. This specific, efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns.


CD8(+) T cell differentiation: choosing a path through T-bet.
Activated CD8(+) T cells can differentiate into transient effector cells or long-lived memory cells. In this issue of Immunity, Joshi et al. (2007) suggest that inflammatory cytokines dictate this balance by regulating the expression of the transcription factor T-bet.


Reduction of antibiotic-resistant-E. coli, -K. pneumoniae, -A. baumannii in aged-sludge of membrane bioreactor treating hospital wastewater.
A pilot-scale of membrane bioreactor (MBR) had functioned without sludge withdrawal for six months, proposed to minimize antibiotic-resistant bacteria (ARB) dissemination from hospital wastewater. With this proposal, an aging sludge in MBR has concerned as preserved-severe multidrug-resistant microorganisms. Thus, this study aims to investigate resistance alteration of ARB in the aging-sludge compared to that in the wastewater. Escherichia coli (EC), Klebsiella pneumoniae (KP), and Acinetobacter baumannii (AB) were antimicrobial-resistant indicators. In wastewater, AB showed the highest concentration followed by KP and EC, respectively, while an inverse order of those species showed in MBR-aging sludge. 60-isolates of each species per sample were tested on 8-antibiotics (AMAB) and 19-antibiotics (AMEC&AMKP) to evaluate antimicrobial resistance (AM) potency. The results show that high ARB variation of 0 to 100% population among those ARB had shown in the wastewater, while a significant reduction of those ARB population in MBR-aged-sludge had appeared surprisingly (P < 0.05). For example, the AMEC population of sludge to influent was <0.5 as of ESBL, Cefoperazone, Cefquinome, Imipenem, Gentamicin, Enrofloxacin, and Marbofloxacin. Among the three species studied, AB showed the highest antibiotic-resistant reduction of 8 antibiotics (100%), followed by KP (17 antibiotics, 99.44%) and EC (16 antibiotics, 88.89%), respectively. High dissolved oxygen levels and prolonged sludge age were possibly contributing to the reduction of those ARB in the MBR. This study gives a new point of view on potential ARB population reduction via the appropriate MBR operation.


Observation of superconducting diode effect.
Nonlinear optical and electrical effects associated with a lack of spatial inversion symmetry allow direction-selective propagation and transport of quantum particles, such as photons1 and electrons2-9. The most common example of such nonreciprocal phenomena is a semiconductor diode with a p-n junction, with a low resistance in one direction and a high resistance in the other. Although the diode effect forms the basis of numerous electronic components, such as rectifiers, alternating-direct-current converters and photodetectors, it introduces an inevitable energy loss due to the finite resistance. Therefore, a worthwhile goal is to realize a superconducting diode that has zero resistance in only one direction. Here we demonstrate a magnetically controllable superconducting diode in an artificial superlattice [Nb/V/Ta]n without a centre of inversion. The nonreciprocal resistance versus current curve at the superconducting-to-normal transition was clearly observed by a direct-current measurement, and the difference of the critical current is considered to be related to the magnetochiral anisotropy caused by breaking of the spatial-inversion and time-reversal symmetries10-13. Owing to the nonreciprocal critical current, the [Nb/V/Ta]n superlattice exhibits zero resistance in only one direction. This superconducting diode effect enables phase-coherent and direction-selective charge transport, paving the way for the construction of non-dissipative electronic circuits.


Distribution and cellular localization of preproenkephalin mRNA in the ovine brain and pituitary.
In this study in situ hybridization histochemistry was used to determine the regional and cellular localization of preproenkephalin (PPE) mRNA in the sheep brain and pituitary. Coronal brain sections were hybridized with an 35S-labelled synthetic 45-mer deoxyribonucleotide probe complementary to a portion of the bovine PPE gene. The specificity of the probe was confirmed by Northern blot analysis. The highest density of labelled cell bodies was found in the nucleus accumbens, caudate-putamen, olfactory tubercle, the central nucleus of the amygdala, the paraventricular nucleus of the hypothalamus, the suprachiasmatic nucleus and in the gigantocellular division of the medullary reticular formation. Labelled cells were also found in the olfactory bulb, prefrontal cortex, piriform cortex and cerebral cortex and in the vicinity of the locus coeruleus, parabrachial nucleus and the nucleus of the solitary tract. In the pituitary a dense PPE mRNA signal was observed in the intermediate lobe; cells in the anterior or neural lobe did not express PPE mRNA. The widespread distribution of cells containing PPE mRNA transcripts within the ovine brain agrees with a similar distribution in the rat. The data suggest that PPE neurons may be involved in diverse physiological functions including the processing of sensory and nociceptive information and in the regulation of endocrine and motor responses.


Masses in the membranes.
A 24-year-old woman with systemic lupus erythematosus presented with a 1-year history of painless vision loss in the right eye. Examination was notable for a bitemporal hemianopia. Brain imaging revealed multiple contrast enhancing dural masses, including one along the planum sphenoidale. She underwent excisional biopsy for a presumed diagnosis of multiple meningiomas. Five years later, she developed worsening vision in the left eye, hypesthesia in the V1 distribution, and oculomotor nerve palsy. Repeat imaging showed an enhancing mass in the cavernous sinus and orbital apex. Biopsy demonstrated a lymphoplasmacyte rich infiltrate in dense extracellular material. She was diagnosed with lupus-induced hypertrophic pachymeningitis and started on immunosuppressive therapy. On further worsening of symptoms, her initial biopsy was reexamined and revealed a kappa light chain restricted B-cell and plasmacyte population. This led to the final diagnosis of central nervous system extranodal marginal zone lymphoma.


The use of anti-cartilage antisera in the study of human spleen.
Antisera against human hyaline cartilage, particularly antisera against collagenase-treated residue obtained after extraction of cartilage homogenate with 3.4 mol dm-3 NaCl and extraction with 0.05 mol dm-3 sodium citrate buffer at pH = 3.2, reacted with different fibrillary and membraneous structures of the human spleen. Very intensive immunofluorescence was observed in special spongiform structures at the end of the arterial system, referred to as spongy arterial terminals. Fibrillary and membraneous structures situated perivascularly, in lymphatic sheaths and the periphery of follicles displayed similar reactions. The discontinuous walls of sinuses and reticular fibrils in pulp cords reacted less intensively. The given antisera are used to advantage as immunohistologic reagents since they clearly visualize the basic structure, and particularly the spongy arterial terminals, otherwise inconspicuous. In the hyaline cartilage of the rib and knee, the cartilage channels yielded the most intensive reaction. Of the other organs studied the marked reaction in the mesangium of the renal glomerulus was the most remarkable.


Caffeine's neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity shows no tolerance to chronic caffeine administration in mice.
We investigated the effect of chronic daily caffeine treatment on caffeine's neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic toxicity. Mice received either caffeine (20 mg/kg) or saline daily for 9 days. Caffeine-induced locomotion tolerance developed within 3 days of treatment and persisted for the duration of the experiment. On day 10, mice were treated with MPTP (20 mg/kg, x4). Caffeine (20 mg/kg) or saline was administered 10 min before each MPTP dose. Acute pretreatment with caffeine attenuated MPTP-induced loss of striatal dopamine and dopamine transporter binding sites, and this attenuation was identical in mice pretreated chronically with caffeine or with saline. Thus, in contrast to the locomotor stimulant effect of caffeine, its neuroprotectant effect did not show tolerance to prior caffeine exposure. These data raise the possibility that caffeine may induce neuroprotection and locomotion by distinct mechanisms.


Adenocarcinoma in an intrapancreatic accessory spleen: report of a case.
We report a case of adenocarcinoma in an intrapancreatic accessory spleen (IPAS). A 78-year-old woman presented with abdominal discomfort, and investigations revealed an elevated serum carbohydrate antigen 19-9 level, to 161.8 U/ml (normal, <37 U/ml). Ultrasonography showed a heterogeneous echogenic tumor with a vascular hilum. Computed tomography showed a heterogeneously enhanced tumor, 8 cm in diameter, adjacent to the pancreatic body, accompanying a feeding artery arising from the splenic artery, and a drainage vein flowing into the splenic vein. We performed a distal pancreaticosplenectomy. The tumor was surrounded by a fibrous capsule and was in contact with the pancreatic body. Histological examinations revealed invasive growth of adenocarcinoma in a structure identical to the spleen. The results of both radiological and histological examinations suggested that the tumor originated from an intrapancreatic accessory spleen. Extensive examinations revealed no other malignancy, based on which we concluded that the adenocarcinoma was primary. Surgical intervention is strongly recommended when a malignancy in an IPAS cannot be ruled out.


Naja haje (Egyptian cobra) venom. Purification, some properties and the amino acid sequences of four toxins (CM-7, CM-8, CM-9, and CM-10b).
Four toxins (CM-7, CM-8, CM-9 and CM-10b) were purified from Naja haje haje (Egyptian cobra) venom by gel filtration on Sephadex G-50 followed by ion-exchange chromatography on CM-cellulose. They each contain 60 amino acid residues and are cross-linked by four intrachain disulphide bridges. The complete primary structure of the four toxins have been elucidated. The toxicities, the immunochemical properties, the sequences and invariant amino acid residues opf toxins CM-7, CM-8, CM-9 and CM-10b resemble the corresponding properties of the cytotoxin group.


[Specific anosmia to isovaleric acid in the peripheral portion of the olfactory analyzer of the laboratory mouse].
The olfactory mucosa of laboratory male mice of lines C57BL/6 and AKR was stimulated by vapours of isovaleric acid and isoamylacetate of various concentrations. Study of electro-olfactography has demonstrated that mice of line C57BL/6 were insensitive to isovaleric acid of concentrations from 10(-5) to 10(-3) mol/l and remained normally sensitive to isoamylacetate. The mice of line AKR were sensitive to isovaleric acid of the same concentrations. The authors suggest using mice of these line as a model for investigations of the olfactory reception mechanisms.


[Treatment of the neurological complications of kyphosis and kyphoscoliosis by spinal cord transposition].
The authors report their experience of radiculomedullary transposition for the treatment of neurological complications by kyphosis or kyphoscoliosis. They use a posterolateral approach by transversoarthropediculectomy. They underline the necessity to treat all etiopathological aspects.


A rare human variation: a major branch of the ulnar artery found in the carpal tunnel.
During a routine anatomic dissection of a 60-year-old female cadaver, a large branch of the ulnar artery in the carpal tunnel was found in the left forearm. This branch crossed the median nerve anteriorly. Guyon's canal contained another branch of the ulnar artery and the ulnar nerve. There was no superficial palmar arch in the left hand. The right forearm was without any vascular anomalies. This anomaly has considerable consequences for surgeons considering endoscopic carpal release, because there is a significant risk of injury to the ulnar artery branch.


Promises and Remaining Challenges for Further Integration of Basophil Activation Test in Allergy-Related Research and Clinical Practice.
More than 20 years after having been initially proposed, the relevance and usefulness of basophil activation test (BAT) for the field of allergy research and testing were demonstrated on many occasions. Leveraging the fully open format of a flexible, whole blood-based functional assay, BAT has been shown to be equally important for fundamental research, clinical research, and diagnosis. Regardless of whether the focus of a study is on the characterization of the allergenic moiety, on the patient side, or on the study of the fundamental processes involved in the allergic disease or its treatment, BAT enables the gathering of very important insights. In spite of this, its full capabilities have yet to be leveraged. Various bottlenecks, including but not limited to assay logistics, robustness, flow cytometry access, and/or expertise, have indeed been limiting its development beyond experts and long-term users. Now, various initiatives, aiming at resolving these bottlenecks, have been launched. If successful, a broader use of BAT could then be contemplated. In such a situation, its more thorough integration in clinical practice has the potential to significantly change the allergic patient's journey.


Optical immunosensor using carbon nanotubes coated with a photovoltaic polymer.
In this work, an on-chip optical immunosensor using an individually assembled carbon nanotube (CNT) coated with a photovoltaic polymer has been proposed, developed, characterized, and applied for the detection of cardiac biomarkers. An individual CNT was self-assembled on a nickel (Ni)-patterned electrode by magnetically attracting the residual iron catalyst at one end of the CNT. After the CNT self-assembled electrode was prepared, it was coated with a photovoltaic polymer to implement a CNT photodetector. Under an incident light, the photovoltaic polymer generated electrons that changed the conductivity of the CNT. The CNT photodetector was finally insulated with parylene to prevent interruptions of charged molecules in a sample solution, such as non-specifically bound proteins and various ions. Chemiluminescent immunoassay was directly performed on the CNT photodetector for an on-chip detection of cardiac troponin T (cTnT) with a detection limit of 12 pg/mL. High sensitivity and reliable selectivity have been achieved through the use of on-chip measurement of chemiluminescent light by the CNT photodetector. As a result, the developed device is envisaged as a new platform for optical immunosensing using the individually self-assembled CNT for point-of-care (POC) clinical diagnostics.


Health issues for aboriginal youth: social and cultural factors associated with resilience.
Research into Aboriginal health has tended to focus on the morbidity of babies and young children, or on the chronic illnesses of adults. Adolescent Aborigines are rarely the target of health research. While health services for Aboriginal people, even in remote areas, have improved enormously over the last few years with the provision of Aboriginal-controlled organizations, health services alone do not prevent the major causes of morbidity. In any case, young people, particularly adolescent boys, are poor users of these facilities. The major causes of adolescent Aboriginal morbidity and mortality are preventable: they have to do with ways of living, with the social, cultural and physical environments which surround adolescents. The paper draws on anthropological fieldwork which pays close attention to these issues. The paper examines the concept of 'adolescence' among Aboriginal groups, and explores the reasons for the resilience of some populations to a particular health problem, that of petrol sniffing among the young.


Palpitation was associated with clinical outcomes in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease with diversified clinical presentation and it is important to identify new predictors of clinical outcomes and survival in HCM patients. In our study, 206 HCM patients were compared with respect to major adverse cardiovascular and cerebrovascular events. By multivariable logistic analysis, we determined that palpitation, together with chronic heart failure (CHF) > 1 year, was an independent predictor of major adverse cardiovascular and cerebral events (MACCE) in HCM patients (OR 3.24, 95% CI 1.60-6.57, P = 0.001). Specially, palpitation was related to higher prevalence of rehospitalization (OR 3.86, 95% CI 2.08-7.08, P < 0.001), cardiac death (OR 2.96, 95% CI 1.05-8.32, P = 0.04) and heart failure exacerbation (OR 4.07, 95% CI 2.04-8.13, P < 0.001). However, patients presented with palpitation did not show a significantly different cardiac phenotype and function. Finally, palpitation predicted a poor prognosis in HCM patients without atrial fibrillation by utilizing Kaplan-Meier analysis (P = 0.041). In conclusion, palpitation could be a new predictor of clinical outcomes and overall survival in HCM patients.


Efficacy of Transcranial Direct Current Stimulation Combined with Conventional Swallowing Rehabilitation Training on Post-stroke Dysphagia.
To observe the clinical effects of transcranial direct current stimulation (tDCS) combined with conventional swallowing rehabilitation training on post-stroke dysphagia and explore its long-term efficacy. A total of 40 patients with dysphagia after the first stroke were randomly divided into a treatment group (n = 20) and a conventional group (n = 20). The treatment group received tDCS combined with conventional swallowing rehabilitation training, while the conventional group only received conventional swallowing rehabilitation training. The Standardized Swallowing Assessment (SSA) Scale and the Penetration-Aspiration Scale (PAS) were used to assess dysphagia before and after treatment, at the end of 10 treatments, and at the 3-month follow-up. The changes in infection indicators [the white blood cell (WBC), C-reactive protein (CRP) and procalcitonin (PCT)], the oxygenation indicator [arterial partial pressure of oxygen (PaO2)] and nutrition-related indicators [hemoglobin (Hb) and serum prealbumin (PAB)] were compared before and after treatment. The SSA and PAS scores were lower in both groups after treatment than before treatment, and the difference was statistically significant (P < 0.01). The SSA and PAS scores of the treatment group were lower than those of the conventional group before and after treatment and during follow-up, and the difference was statistically significant (P < 0.05, P < 0.01). A within-group comparison showed that WBC, CRP and PCT after treatment were lower than those before treatment, and the difference was statistically significant (P < 0.05). The PaO2, Hb and serum PAB were higher after treatment than before treatment, with a statistically significant difference (P < 0.05). The WBC, CRP and PCT of the tDCS group were lower than those of the conventional group, and PaO2, Hb and serum PAB were higher in the treatment group than in the conventional group, with a statistically significant difference (P < 0.01). The tDCS combined with conventional swallowing rehabilitation training can improve dysphagia with a better effect than conventional swallowing rehabilitation training and has a certain long-term efficacy. In addition, tDCS combined with conventional swallowing rehabilitation training can improve nutrition and oxygenation and reduce infection levels.