Laryngeal carcinoma in childhood. Report of a case and review of the literature.
A rare case of an 81/2 year old boy with a stage III well differentiated squamous cell carcinoma of the larynx, which responded to chemotherapy and irradiation, is reported. It is the 56th case in children up to 15 years of age and 20th case in children 10 years old or younger reported since 1868. Carcinoma of the larynx in children has similar clinicopathological features to those of adult laryngeal carcinoma, but markedly differs as concerning sex incidence ratio. The main differential diagnosis is juvenile papillomatosis and the principal risk factor is previous cervical irradiation. Delayed diagnosis is frequent since clinical manifestations might be attributed to the normal laryngeal maturation process or to a common respiratory infection. Treatment is problematic, for special effort must be made to preserve laryngeal anatomy and function and to avoid complications. Prognosis of childhood laryngeal cancer is unclear since the reported survival rates are not tumor stage related.


Mandibular bone structure, bone mineral density, and clinical variables as fracture predictors: a 15-year follow-up of female patients in a dental clinic.
To compare three mandibular trabeculation evaluation methods, clinical variables, and osteoporosis as fracture predictors in women. One hundred and thirty-six female dental patients (35-94 years) answered a questionnaire in 1996 and 2011. Using intra-oral radiographs from 1996, five methods were compared as fracture predictors: (1) mandibular bone structure evaluated with a visual radiographic index, (2) bone texture, (3) size and number of intertrabecular spaces calculated with Jaw-X software, (4) fracture probability calculated with a fracture risk assessment tool (FRAX), and (5) osteoporosis diagnosis based on dual-energy-X-ray absorptiometry. Differences were assessed with the Mann-Whitney test and relative risk calculated. Previous fracture, gluco-corticoid medication, and bone texture were significant indicators of future and total (previous plus future) fracture. Osteoporosis diagnosis, sparse trabeculation, Jaw-X, and FRAX were significant predictors of total but not future fracture. Clinical and oral bone variables may identify individuals at greatest risk of fracture.


Influence of growth medium, age in vitro and spontaneous bioelectric activity on the distribution of sensory ganglion-evoked activity in spinal cord explants.
The role of serum added to the culture medium and of spontaneous bioelectric activity in the development of sensory afferent connections was studied, employing fetal mouse spinal cord explants with attached dorsal root ganglia (DRG) as an in vitro model system. Afferent DRG terminals in the cord explants were localized on the basis of 'fixed-latency' DRG-evoked action potentials, which were anatomically verified in several experiments using horseradish peroxidase histology. In serum-supplemented medium (HSSM), but not in chemically defined medium (CDM), those DRG fibers which grew into the dorsal side of the cord terminated predominantly within the dorsal cord region, and remained there throughout the experimental period (18-33 days in vitro). In contrast, ventrally entering fibers terminated equally in both the dorsal and the ventral cord regions in young cultures (18-24 days in vitro) but were no longer observed after 27 days in vitro. Cultures grown in HSSM with the addition of xylocaine, in order to chronically suppress spontaneous bioelectric activity, essentially corresponded (at 25-32 days in vitro) to the picture seen in the control series at the same age. On the basis of polysynaptic DRG-evoked responses in the cord, developmental changes in local neuronal networks were inferred which resulted in less spread of DRG-evoked activity with age in HSSM, and more spread with age in CDM-grown cultures. It is concluded that for the formation of selective DRG connections in the spinal cord: (i) a serum-borne factor plays a role: and (ii) functional activity is not required.


Association of specific tyrosine phosphorylation with stages of B-cell differentiation in human lymphoid leukemias.
In vitro protein phosphorylation in various types of human fresh lymphoid leukemic cells (C-ALL, B-CLL, HCL and PCL: B-cell lineage and T-ALL, ATL and T-CLL: T-cell lineage) were studied. In cases of B-CLL and HCL, tyrosine protein kinase (TPK) activity was at least 5-fold higher than that in other cases of B- and T-cell lineages. B-cell leukemic cells at various differentiation stages had different endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. The P-tyr-containing proteins of 68K, 59K and 56K were detected commonly in all the cases of B-cell lineage. The phosphorylated protein of 32K was present only in cases of PCL. On the other hand, in T-ALL and ATL, the major substrate in tyrosine phosphorylation was 58K. These results suggest that the characterization of in vitro tyrosine phosphorylation provides a new means not only to distinguish T- and B-lymphoid leukemia, but also to differentiate stages of lymphoid development.


Specific assembly pathway of sarcoglycans is dependent on beta- and delta-sarcoglycan.
Mutations in sarcoglycans (SG) have been reported to cause autosomal-recessive limb-girdle muscular dystrophy (LGMD) and dilated cardiomyopathy. In skeletal and cardiac muscle, sarcoglycans exist as a complex of four transmembrane proteins (alpha-, beta-, gamma-, and delta-SG). In this study, the assembly of the sarcoglycan complex was examined in a heterologous expression system. Our results demonstrated that the assembly process occurs as a discrete stepwise process. We found that beta-SG appears to play an initiating role and its association with delta-SG is essential for the proper localization of the sarcoglycan complex to the cell membrane. The incorporation of alpha-SG into the sarcoglycan complex occurs at the final stage by interaction with gamma-SG. These findings were supported by chemical cross-linking of endogenous sarcoglycans in cultured myotubes. We have also provided evidence that glycosylation-defective mutations in beta-SG and a common mutation in gamma-SG (C283Y) disrupt sarcoglycan-complex formation. Our proposed model for the assembly and structure of sarcoglycans should generate important insight into their function in muscle as well as their role in muscular dystrophies and cardiomyopathies.


Systematic variation of potassium current amplitudes across the tonotopic axis of the rat medial nucleus of the trapezoid body.
Many central auditory nuclei preserve the tonotopic organization of their afferent inputs, generating a frequency "map" across the nucleus. In the medial nucleus of the trapezoid body (MNTB) the most medial neurons receive inputs corresponding to the highest frequency sounds and the most lateral neurons have the lowest characteristic frequencies. Whole-cell patch recording from MNTB principal neurons in rat brainstem slices demonstrates a corresponding tonotopic organization of voltage-gated outward potassium currents. Medial MNTB neurons had larger total outward K+ current amplitudes than lateral neurons and similar medial to-lateral gradients were observed for two K+ current subtypes distinguished by their low and high voltage activation thresholds. In contrast, a third K+ conductance with an intermediate voltage threshold and slower kinetics showed an inverse gradient (being smallest in medial MNTB). The orthogonal axes of MNTB did not exhibit potassium current gradients (dorsal-to-ventral, or rostral-to-caudal). The input resistance was unchanged across the MNTB, but a slow capacitative component was enhanced in lateral neurons. These data demonstrate that the intrinsic properties of rat MNTB neurons are tuned across the tonotopic axis so as to promote shorter action potentials, faster firing and therefore greater accuracy in transmission of auditory information in the high characteristic frequency regions.


Hydroquinone, a control agent of agglutination and adherence of Streptococcus mutans induced by sucrose.
Hydroquinone was found to alter agglutination of Streptococcus mutans induced by sucrose. The newly formed agglutination product produced by hydroquinone does not kill this cariogenic bacterium and the formation is reversible. The agglutination altering activity of hydroquinone seems to be specific for strains of S. mutans. As a result, hydroquinone inhibits sucrose-induced adherence of S. mutans.


Genotoxicity of excess thymidylate in thymidylate low-requiring Saccharomyces cerevisiae is associated with changes in phosphate metabolism.
When dTMP in concentrations greater than 100 microM is offered to growing cells of thymidylate low-requiring yeast strains it is both mutagenic and toxic. At exposure concentrations greater than 1 mM dTMP interferes significantly with the low-affinity phosphate permease even in the presence of exogenous phosphate concentrations of 6 mM. Chemical analysis and 31P NMR spectroscopy reveal that excess dTMP disturbs phosphate metabolism in thymidylate low-requiring strains but not in the wild type. The most prominent changes in phosphorus-containing molecules are found in polyphosphates of which up to 20% are broken down within a 20-min time span with a concomitant increase in orthophosphate pools.


Quantification of changes in metamorphopsia and retinal contraction in eyes with spontaneous separation of idiopathic epiretinal membrane.
To quantify changes in metamorphopsia and retinal contraction in eyes with idiopathic epiretinal membrane (ERM) before and after a spontaneous separation of ERM. Among 92 eyes of 92 patients with idiopathic ERM who were followed up at our hospital, 5 eyes of 5 patients had experienced a spontaneous separation of ERM during the follow-up period. Patient's metamorphopsia was assessed horizontally and vertically by a metamorphopsia chart developed by our group, M-CHARTS, to obtain the horizontal (MH) and vertical (MV) metamorphopsia scores. Difference in the scores before and after the membrane separation represents change in patient's metamorphopsia. Changes in retinal contraction were also evaluated horizontally and vertically with our original software for fundus image analysis. The difference between M-CHARTS scores and distances of retinal vessel movements with before and after membrane separation were measured. All five subjects showed a decrease in the retinal contraction. Improved visual acuity was observed in three subjects, and no change was seen in the other two. Four subjects obtained better metamorphopsia scores after the membrane separation, while the other one was not detected with metamorphopsia by M-CHARTS either before or after the separation. In subjects with an improved MV, horizontal retinal movement was seen larger than the vertical movement. Similarly, the subjects with an improved MH indicated a larger vertical retinal movement than the horizontal movement. The direction of patient's metamorphopsia closely associated with the direction of retinal contraction before and after a spontaneous separation of ERM.


Ingestion of a denture cleanser: did it cause gastric perforation?
Human ingestion of denture cleansers leading to gastric perforation has not previously been described. A 27-year-old male ingested three denture cleanser tablets in water over two days in an attempt to cause a false negative result on a workplace urine drug screen. Seven days later he presented to an emergency department with a perforated gastric ulcer. A literature review of cases and the chemistry of the components of his ingestion was conducted to determine the possible relationship between these events. Ingestion of intact fragments of the tablets would be likely to result in significant gastric toxicity, but ingestion of dissolved tablets would be unlikely to have caused his illness.


The Wisconsin outcomes experience: baseline outcomes of the WISCVPR Web-based Outcomes Project.
The measurement of outpatient cardiac rehabilitation (OCR) outcomes is now considered common practice. Unfortunately, because of the costs involved in purchasing outcomes tracking software, many programs are not able to participate in pooled outcomes analysis and benchmarking. The purpose of this report is to describe the current OCR outcomes data in the state of Wisconsin using a web-based model for outcomes data collection, data pooling, and benchmarking. Participating OCR programs collected individual patient outcomes according to protocols developed by the Wisconsin Society for Cardiovascular and Pulmonary Rehabilitation's Outcomes Committee. Programs analyzed their data quarterly and submitted the values to a database via an Internet web site. Aggregate outcomes data from 34 programs were collected over a 27-month period. Aggregate data representing 5235 OCR patients are presented. The mean age for the men was 64 +/- 5 years (N = 3612; 69% of the sample). The mean age for the women was 67 +/- 6 years (N = 1623; 31% of the sample). The completion rate for the group was 89% (95%CI, 86-91). The average number of OCR sessions per patient was 22 +/- 6 over 9 +/- 3 weeks. The clinical and behavioral outcomes for this sample ranged from a median value of 88% for the percentage of patients meeting the blood pressure goal (95%CI, 87-91) to less than 5% for the percentage of patients receiving formal psychosocial counseling (95%CI, 0). The major cardiovascular event rate was 0.17 per 10,000 patient-hours. This report describes the baseline OCR outcomes obtained via a state affiliate-sponsored outcomes management program. These data show that this model of OCR outcomes measurement, collection, and interprogram analysis produces data that are comparable with those of published, controlled studies. Determining baseline characteristics of OCR outcomes data will be important in the development of benchmarks and best practice guidelines.


Cataract progression in patients with atopic dermatitis.
To evaluate the possible causes of cataract progression in Japanese patients with atopic dermatitis. Department of Ophthalmology, Toyama Medical and Pharmaceutical University, Toyama, Japan. This prospective study comprised 41 patients (81 eyes) with atopic dermatitis. Cataract progression was determined by photographs and visual acuity results. Mean follow-up was 2.5 years (range 1.0 to 3.5 years). Of 41 patients, 10 (24.4%) had progression of cataract. Of 81 eyes, 10 (12.3%) had slow progression and 9 (11.1%), rapid. Cataract progression was not statistically significantly related to patient sex or severity of systemic skin lesions but was to facial skin lesions. Soft contact lens wear and eye rubbing were also correlated with cataract progression. Patients with facial atopic dermatitis, contact lenses, or both may rub their eyes more frequently than those with lesions on other body parts, increasing their risk of cataract progression.


Design, development, and evaluation of an MRI-guided SMA spring-actuated neurosurgical robot.
In this paper, we present our work on the development of a magnetic resonance imaging (MRI)-compatible Minimally Invasive Neurosurgical Intracranial Robot (MINIR) comprising of shape memory alloy (SMA) spring actuators and tendon-sheath mechanism. We present the detailed modeling and analysis along with experimental results of the characterization of SMA spring actuators. Furthermore, to demonstrate image-feedback control, we used the images obtained from a camera to control the motion of the robot so that eventually continuous MR images could be used in the future to control the robot motion. Since the image tracking algorithm may fail in some situations, we also developed a temperature feedback control scheme which served as a backup controller for the robot. Experimental results demonstrated that both image feedback and temperature feedback can be used to control the motion of MINIR. A series of MRI compatibility tests were performed on the robot and the experimental results demonstrated that the robot is MRI compatible and no significant visual image distortion was observed in the MR images during robot operation.


Idiopathic pulmonary hemosiderosis.
This article discusses an investigation of two children with idiopathic pulmonary hemosiderosis (IPH) over a long period of time that included several cycles of the disease in each patient, each cycle consisting of clinical remission, a preacute or linking phase, and acute lung bleeding. The acute phase was divided into two parts; the preacute phase takes place 5 to 10 days before the onset of the acute alveolar hemorrhage. At the beginning of the preacute phase, there was neutropenia followed by increased blood eosinophilia. The lung function test showed gas trapping. Bronchoalveolar lavage during remission showed increased numbers of neutrophils; the histologic study suggested that the neutrophils are obligatory participants in the occurrence of lung bleeding. The finding of the preacute phase and the role of the neutrophils in the acute bleeding permitted development of a new hypothesis related to the physiopathology of IPH.


Distribution, sources and ecological risk assessment of PAHs in surface sediments from the Luan River Estuary, China.
The distribution, sources and risk assessment of 16 polycyclic aromatic hydrocarbons (PAHs) of surface sediments in the Luan River Estuary, China, have been investigated in the research. The results indicated that the total concentrations of 16 PAHs in surface sediments of the Luan River Estuary ranged from 5.1 to 545.1 ng g(-1)dw with a mean value of 120.8 ng g(-1)dw, which is relatively low in comparison with other estuaries around the world. The PAHs in the study area were mainly originated from pyrogenic sources. Besides, PAHs may be contaminated by petrogenic PAHs as indicated by the selected ratios of PAHs, the 2-tailed Pearson correlation analysis and principal components analysis at different sites. The result of the ecological risk assessment shows little negative effect for most individual PAHs in surface sediments of the Luan River Estuary, China.


Ester derivatives of phyllohydroquinone effectively deliver the active form of vitamin K1 topically, owing to their non-photosensitivity.
Topical application of phylloquinone (PK) is beneficial to the skin; however, its topical use is limited in Europe owing to its photosensitive properties such as photodegradation and phototoxicity. We evaluated the suitability of ester derivatives of phyllohydroquinone (PKH), the active form of PK, for topical application to overcome the abovementioned problems of PK. We used the PKH derivatives PKH-1,4-bis-N,N-dimethylglycinate hydrochloride (PKH-DMG) and PKH-1,4-bis-hemisuccinate (PKH-SUC) for our studies. Photostability was determined by measuring the residual concentration after irradiation with artificial sunlight and multi-wavelength light. Phototoxicity after ultraviolet A (UVA) irradiation was assessed by measuring drug-induced singlet oxygen and intracellular reactive oxygen species (ROS) generation, and cell viability of a human epidermal keratinocyte cell line (HaCaT). Delivery of PKH into HaCaT cells was assessed by measuring PK epoxide (PKO) levels. The PKH derivatives showed higher photostability than PK. After UVA irradiation, PK induced high singlet oxygen levels and intracellular ROS generation, and reduced cell viability, whereas the PKH derivatives showed no effects. The PKH derivatives increased intracellular PKO levels. AUCPKO(0-72 h) values after PKH-DMG and PKH-SUC treatments were 0.741- and 22.9-fold higher than that after PK treatment, respectively. In conclusion, PKH derivatives act as PKH prodrugs and are suitable for topical application without the need for special protection from light.


The autopod: its formation during limb development.
The autopod, including the mesopodium and the acropodium, is the most distal part of the tetrapod limb, and developmental mechanisms of autopod formation serve as a model system of pattern formation during development. Cartilage rudiments of the autopod develop after proximal elements have differentiated. The autopod region is marked by a change in the expression of two homeobox genes: future autopod cells are first Hoxa11/Hoxa13-double-positive and then Hoxa13-single-positive. The change in expression of these Hox genes is controlled by upstream mechanisms, including the retinoic acid pathway, and the expression of Hoxa13 is connected to downstream mechanisms, including the autopod-specific cell surface property mediated by molecules, including cadherins and ephrins/Ephs, for cell-to-cell communication and recognition. Comparative analyses of the expression of Hox genes in fish fins and tetrapod limb buds support the notion on the origin of the autopod in vertebrates. This review will focus on the cellular and molecular regulation of the formation of the autopod during development and evolutionary developmental aspects of the origin of the autopod.


Absolute frequency metrology of buffer-gas-cooled molecular spectra at 1 kHz accuracy level.
By reducing both the internal and translational temperature of any species down to a few kelvins, the buffer-gas-cooling (BGC) technique has the potential to dramatically improve the quality of ro-vibrational molecular spectra, thus offering unique opportunities for transition frequency measurements with unprecedented accuracy. However, the difficulty in integrating metrological-grade spectroscopic tools into bulky cryogenic equipment has hitherto prevented from approaching the kHz level even in the best cases. Here, we overcome this drawback by an original opto-mechanical scheme which, effectively coupling a Lamb-dip saturated-absorption cavity ring-down spectrometer to a BGC source, allows us to determine the absolute frequency of the acetylene (ν1 + ν3) R(1)e transition at 6561.0941 cm-1 with a fractional uncertainty as low as 6 × 10-12. By improving the previous record with buffer-gas-cooled molecules by one order of magnitude, our approach paves the way for a number of ultra-precise low-temperature spectroscopic studies, aimed at both fundamental Physics tests and optimized laser cooling strategies.


[Humoral and cellular immunity and sepsis in intensive care (author's transl)].
Different parameters of humoral and cell mediated immunity were studied in 17 patients with sepsis. There is an important decrease of CH 50 (82 p. cent of patients) and variations of serum complement according with activation of alternative pathway in gram negative and gram positive septicemia. The cellular immunity is never normal: the stimulation index of lymphocyte proliferation under the influence of P. H. A. is lower than 3. There is less than 50 p. cent of T lymphocytes forming rosettes. With cure of sepsis a discrimination is observed between patients with transient decreased immunity and those with persistent lower responses.


Risk assessment, cross-resistance potential, and biochemical mechanism of resistance to emamectin benzoate in a field strain of house fly (Musca domestica Linnaeus).
Reduced sensitivity to insecticides in insect pests often results in control failures and increases in the dose and frequency of applications, ultimately polluting the environment. Reduced sensitivity to emamectin benzoate, a broad-spectrum agrochemical belonging to the avermectin group of pesticides, was reported in house flies (Musca domestica L.) collected from Punjab, Pakistan, in 2013. The aim of the present study was to investigate the risk for resistance development, biochemical mechanism, and cross-resistance potential to other insecticides in an emamectin benzoate selected (EB-SEL) strain of house flies. A field-collected strain showing reduced sensitivity to emamectin was re-selected in the laboratory for five consecutive generations and compared with a laboratory susceptible (Lab-Susceptible) reference strain, using bioassays. The field strain showed rapid development of resistance to emamectin (resistance ratio (RR) increased from 35.15 to 149.26-fold) as a result of selection experiments; however, resistance declined when the selection pressure uplifted. The EB-SEL strain showed reduction in resistance to abamectin, indoxacarb, and thiamethoxam. The results of synergism experiments using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) enzyme inhibitors and biochemical analyses revealed that the metabolic resistance mechanism was not responsible in developing emamectin resistance in the EB-SEL strain. In conclusion, the risk for the rapid development of emamectin resistance under continuous selection pressure suggests using a multifaceted integrated pest management approach for house flies. Moreover, the instable nature of emamectin resistance in the EB-SEL strain and lack of cross-resistance to other insecticides provide windows for the rotational use of insecticides with different modes of action. This will ultimately reduce emamectin selection pressure and help improving management programs for house flies without polluting the environment.


Synthesis, Anti-Oomycete and Anti-fungal Activities of Novel Cinchona Alkaloid Derivatives Containing Sulfonate Moiety.
Using cinchona alkaloid as the lead compound, twenty-four cinchona alkaloid sulfonate derivatives (1 a-l, 2 a-c, 3 a-c, 4 a-c, and 5 a-c) were designed and prepared by modifying their C9 position, and structurally confirmed by 1 H-NMR, 13 C-NMR, HR-MS and melting points. Moreover, the stereochemical configurations of compounds 1 f and 1 l were unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, we determined the anti-oomycete and anti-fungal activities of these target compounds against Phytophthora capsici and Fusarium graminearum in vitro. The results showed that two compounds 4 b and 4 c exhibited prominent anti-oomycete activity, and the median effective concentration (EC50 ) values of 4 b and 4 c against P. capsici were 22.55 and 16.32 mg/L, respectively. This study suggested that when the C9 position of cinchona alkaloid sulfonate derivatives is in the S configuration and the 6'-position methoxy group is not present, the anti-oomycete activity is superior. In addition, five compounds 1 e, 1 f, 1 k, 3 c and 4 c displayed significant anti-fungal activity, with EC50 values of 43.64, 45.07, 80.18, 48.58 and 41.88 mg/L against F. graminearum, respectively. This result indicates that only when a specific substituent is introduced into the structural framework of the target compound, the corresponding compound exhibits significant inhibitory activity against fungi.


A case of cervical multicentric Castleman disease treated with intensity-modulated radiation therapy using helical tomotherapy.
Castleman disease (CD) is a rare lymphoproliferative disorder. Two clinical entities are described: a unicentric form with disease confined to a single lymph node region and a multicentric form characterized by generalized lymphadenopathy and systemic symptoms. Although surgery is regarded as standard therapy for the unicentric form, no consensus has been reached concerning the standard treatment for multicentric CD. We report here a case of cervical multicentric CD treated with intensity-modulated radiation therapy (IMRT), using helical tomotherapy to minimize xerostomia in comparison with conventional radiotherapy. A 29-year-old woman complained of neck swelling. Computed tomography showed lymphadenopathy in both sides of the neck. The patient was diagnosed with the plasma cell subtype of CD on biopsy. After initial treatment with prednisone, IMRT was planned to avoid normal structures, for example the parotid gland. The cervical lymphadenopathy shrank gradually during IMRT with 44 Gy in 22 fractions. Four years and 3 months after IMRT, regrowth of cervical lymph nodes has not been detected. The parotid function improved dramatically on quantitative salivary scintigraphy between 3 and 12 months after IMRT. Radiotherapy could be an option for multicentric CD, and IMRT is an effective means of minimizing xerostomia in head and neck lesions.


Effects of armagnac extracts on human platelet function in vitro and on rat arteriovenous shunt thrombosis in vivo.
The "French paradox", a low cardiovascular mortality compared to the prevalent risk factors, has been attributed to the regular use of red wine, and to the polyphenols it contains. These have among other effects an antioxidant and antithrombotic effect. The French paradox is maximal in southwest France, a region which is the region of production of armagnac, an oak cask aged spirit also rich in polyphenols. We tested the effects of a freeze-dried extract of 12-year-old armagnac (EA88) on in vitro human platelet adhesion, and on aggregation induced by collagen or ADP, in the presence or absence of hypoxanthine-xanthine oxidase (HX/XO), at concentrations ranging from 5 x 10(-9) to 5 x 10(-3) g/l, after 15-60 min incubation. We also tested the effects of 2-week oral treatment with 1, 5 and 25 mg/kg EA88 in a rat arteriovenous shunt thrombosis model. EA88 inhibited ADP-induced but not collagen-induced human platelet aggregation in vitro in a concentration- and incubation time-dependent manner, which was greater in the presence of HX/XO. In vivo, giving rats a daily oral dose of EA88 for 2 weeks inhibited thrombus formation in a dose-dependent manner, for doses consistent with the habitual human use of armagnac. Armagnac extract EA88 had an antiplatelet and antithrombotic effect that if confirmed in man could contribute to explain the intensity of the French paradox in southwest France.


Site-specific modulation of morphine and swim-induced antinociception following thyrotropin-releasing hormone in the rat periaqueductal gray.
Central administration of thyrotropin-releasing hormone (TRH) produces a short-lived antinociceptive response in rats, and also modulates opioid and non-opioid forms of antinociception. Given the presence of TRH cells, fibers and receptors in the periaqueductal gray (PAG), the present study examined the effects of TRH administered into the PAG upon antinociception following either continuous cold-water swims (CCWS, 2 degrees C for 3.5 min) or morphine (0.1-2.5 micrograms) administered into the PAG on the tail-flick and jump tests, and measured changes in core body temperatures as well. Histological examination revealed two groups in which anterior PAG placements were found rostral to the dorsal raphe nucleus, and posterior PAG placements which were at the level of this nucleus. TRH produced brief (5-15 min) but significant increases in latencies and thresholds without altering body temperature in both anterior and posterior PAG placements. Whereas TRH in anterior PAG placements dose dependently (0.1-10 micrograms) decreased CCWS antinociception on both tests, TRH in posterior PAG placements significantly increased CCWS antinociception on the jump test. TRH in both placements reduced the magnitude of CCWS hypothermia. TRH significantly potentiated the magnitude and duration of both morphine antinociception and hyperthermia in both anterior and posterior PAG placements, and shifted mesencephalic morphine's antinociceptive dose-response curve significantly to the left. These data are discussed in terms of the role of the PAG in opioid and non-opioid forms of stress-induced antinociception as well as morphine antinociception, and in terms of the roles of TRH and anterior PAG placements as potential candidates for a collateral inhibition model of antinociceptive responses.


[Experimental investigations of CO2 laser application in middle ear ossicles].
During the last few years, several laser systems have been applied for procedures in middle ear surgery. In this study, we determined the technical parameters for the dissection of the middle ear ossicles with the CO(2) laser and analyzed the histological findings. The malleus necks of 16 human temporal bones were dissected under standardized conditions using a CO(2) laser with a power output between 35 and 55 kW/cm(2). The specimens were fixed and histological probes of 50- micro m thickness were prepared. The laser outputs led to crater diameters from 0.14 to 0.55 mm. As an analogy between laser energy and thermal tissue destruction, three zones of thermal damage were differentiated: a cinder zone, a carbonization zone, and a zone of dehydration. The metrical dimensions of these zones did not show any correlation to the applied laser energy. The data of this study show that commercially available CO(2) lasers are sufficient for a safe and effective partial resection of middle ear ossicles using a power output of 35 kW/cm(2).


Metabolic engineering against the arginine microenvironment enhances CAR-T cell proliferation and therapeutic activity.
Hematological and solid cancers catabolize the semiessential amino acid arginine to drive cell proliferation. However, the resulting low arginine microenvironment also impairs chimeric antigen receptor T cells (CAR-T) cell proliferation, limiting their efficacy in clinical trials against hematological and solid malignancies. T cells are susceptible to the low arginine microenvironment because of the low expression of the arginine resynthesis enzymes argininosuccinate synthase (ASS) and ornithine transcarbamylase (OTC). We demonstrate that T cells can be reengineered to express functional ASS or OTC enzymes, in concert with different chimeric antigen receptors. Enzyme modifications increase CAR-T cell proliferation, with no loss of CAR cytotoxicity or increased exhaustion. In vivo, enzyme-modified CAR-T cells lead to enhanced clearance of leukemia or solid tumor burden, providing the first metabolic modification to enhance CAR-T cell therapies.


Enhancement of visit adherence in the national beta-blocker heart attack trial.
Efforts were made in the Beta Blocker Heart Trial (BHAT), a double-blind study of 3837 post-MI patients, to enhance visit adherence, a measure of compliance that is not subjective and can be easily monitored. Of the required visits, 93.9% were completed in the window, 3.9% of the patients were classified as dropouts and 12 persons were lost to follow-up. Methods used to enhance compliance varied with circumstances but included appointment reminders, assistance with transportation, minimal waiting times, newsletters, continuity of care, involvement of family members, and close contact with private physicians. Comparisons of the BHAT visit adherence rates to those from other clinical trials are difficult to make because there are few reports in the literature regarding follow-up in large multicenter clinical trials. However, data obtained through personal communications, as well as published reports, indicate that adherence in primary prevention trials was generally less than that of secondary prevention trials. Adherence rates in the BHAT tended to be slightly higher than those of comparable trials.


Hirudo medicinalis: a platform for investigating genes in neural repair.
We have used the nervous system of the medicinal leech as a preparation to study the molecular basis of neural repair. The leech central nervous system, unlike mammalian CNS, can regenerate to restore function, and contains identified nerve cells of known function and connectivity. We have constructed subtractive cDNA probes from whole and regenerating ganglia of the ventral nerve cord and have used these to screen a serotonergic Retzius neuron library. This identifies genes that are regulated as a result of axotomy, and are expressed by the Retzius cell. This approach identifies many genes, both novel and known. Many of the known genes identified have homologues in vertebrates, including man. For example, genes encoding thioredoxin (TRX), Rough Endoplasmic Reticulum Protein 1 (RER-1) and ATP synthase are upregulated at 24 h postinjury in leech nerve cord. To investigate the functional role of regulated genes in neuron regrowth we are using microinjection of antisense oligonucleotides in combination with horseradish peroxidase to knock down expression of a chosen gene and to assess regeneration in single neurons in 3-D ganglion culture. As an example of this approach we describe experiments to microinject antisense oligonucleotide to a leech isoform of the structural protein, Protein 4.1. Our approach thus identifies genes regulated at different times after injury that may underpin the intrinsic ability of leech neurons to survive damage, to initiate regrowth programs and to remake functional connections. It enables us to determine the time course of gene expression in the regenerating nerve cord, and to study the effects of gene knockdown in identified neurons regenerating in defined conditions in culture.


Local pulmonary blood flow: control and gas exchange.
We studied the local response of the pulmonary vasculature to combined changes in alveolar PO2 and PCO2 in the right apical lobe (RAL) of six conscious sheep. That lobe inspired an O2-CO2-N2 mixture adjusted to produce one of 12 alveolar gas compositions: end-tidal PCO2 (PETCO2) of 40, 50, and 60 Torr, each coupled with end-tidal PO2 (PETO2) of 100, 75, 50, and 25 Torr. In addition, at each of the four PETO2, the inspired CO2 was set to 0 and PETCO2 was allowed to vary as RAL perfusion changed. The remainder of the lung, which served as control (CL) inspired air. Fraction of the total pulmonary blood flow going to the RAL (%QRAL) was obtained by comparing the methane elimination from the RAL to that of the whole lung, and expressed as a percentage of that fraction at PETCO2 = 40, PETO2 = 100. Cardiac output, pulmonary vascular pressures, and CL gas tensions were unaffected or only minimally affected by changes in RAL gas composition. A drop in PO2 from 100 to 50 Torr decreased local blood flow by 60% in normocapnia and by 66% at a PCO2 of 60. At all levels of oxygenation, an increase in PCO2 from 40 to 60 reduced QRAL by nearly 50%. With these stimulus-response data, we developed a model of gas exchange, which takes into account the effects of test segment size on blood flow diversion. This model predicts that: (1) when the ventilation to one compartment of a two compartment lung is progressively decreased, PAO2 remains above 60 Torr for up to 60% reductions in alveolar ventilation, irrespective of compartment size; (2) the decrease in PAO2 that occurs at altitude is accompanied by a drop in PACO2 that limits the decrease in conductance and minimizes the pulmonary hypertension; and (3) as we stand, local blood flow control by the alveolar gas tensions halves the alveolar-arterial PO2 and PCO2 differences imposed by gravity.


Expeditious microwave-assisted thionation with the system PSCl3/H2O/Et3N under solvent-free condition.
A novel thionation protocol for carbonyl compounds, with the system PSCl3/H2O/Et3N has been discovered. Clean, rapid, and efficient synthesis of a variety of thiocarbonyl compounds such as thioamides, thiolactams, thioketones, thioxanthones, and thioacridone can be achieved through this simple and convenient method under solventless condition with microwave irradiation.


Dietary Plukenetia conophora seed alters muscle cholesterol, antioxidant enzymes, and fatty acids in growing rabbits.
The influence of dietary inclusion of Plukenetia conophora seed (PCS) on growth, carcass, muscle antioxidant enzymes, fatty acids, meat quality, and sensory attributes of Longissimus thoracis et lumburum muscle in rabbits was examined. Seventy-two, 28 d old male New Zealand rabbits (750 ± 20 g) were randomly allotted to diets containing either no PCS (PCS-0), 2.5% PCS (PCS-2.5) or 5% PCS (PCS-5) for eight weeks, and euthanized. PCS-5 rabbits had higher (P < 0.05) body and carcass weights than the PCS-0 rabbits. Dietary PCS improved feed efficiency in rabbits. Muscle antioxidant enzymes activities and total phenols were higher while muscle cholesterol was lower (P < 0.05) in supplemented meat than the PCS-0 meat. The concentration of C22:6n-3, C20:5n-3 and C18:3n-3 was higher (P < 0.05) in the supplemented meat than the PCS-0 meat. Sensory attributes, carbonyl, and TBARS values and physicochemical properties of meat did not differ among diets. Supplementation of PCS-5 enhances muscle n-3 fatty acids without impairing the sensory properties, and oxidative stability of rabbit meat.


Pharmacological consequences of oxidative stress in ocular tissues.
The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma, cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior uvea, both H2O2 and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior uvea especially on the sympathetic nerves and smooth muscles of the iris-ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H2O2 and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [3H] D-aspartate, in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers such as nitric oxide, prostaglandins and isoprostanes. The ability of H2O2 to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma.


Clinical Outcomes of Rate vs Rhythm Control for Atrial Fibrillation in Older People: A Systematic Review and Meta-Analysis.
Atrial fibrillation (AF) is highly prevalent in older adults and has been associated with increased morbidity and mortality. To reduce this AF-related morbidity in older adults, antiarrhythmic drugs (AADs) are regularly used for rhythm control, assuming that increasing time in sinus rhythm reduces AF-related morbidity. However, whether AADs can improve clinical outcomes in older adults remains unclear because of the increased risk for adverse drug events compared with rate control. The aim of this study was to determine the impact of rhythm control versus rate control on clinical outcomes in older adults with AF. We conducted a systematic review and meta-analysis targeting patients aged ≥65 years with AF and using drugs to control rate or rhythm. Articles that met the following criteria were included: enrolled older patients (sample mean ≥75 years) with AF, compared pharmacological rate versus rhythm control, and reported all-cause mortality, cardiovascular mortality, or ischemic stroke. Five observational studies were included. In total, 86,926 patients with AF with a mean age ranging from 75 to 92 years were studied. No differences were found between rhythm and rate control for all-cause mortality (odds ratio [OR] 1.11; 95% confidence interval [CI] 0.78-1.59; I2 = 79.6%; n = 28,526; four studies) and cardiovascular mortality (OR 1.09; 95% CI 0.81-1.47; I2 = 0%; n = 2292; two studies). Rhythm control resulted in fewer strokes (OR 0.86; 95% CI 0.80-0.93; I2 = 0%; n = 59,496), although this was mainly determined by one study. All collected data were observational, which precluded making strong recommendations. Furthermore, all CIs were wide, increasing the uncertainty of the observed effects. As such, evidence was insufficient to recommend rhythm or rate control as the first-line therapy for AF in older adults. As AF is particularly prevalent in older people, more randomized controlled trials are needed in this population.


Proteomics study reveals that the dysregulation of focal adhesion and ribosome contribute to early pregnancy loss.
Early pregnancy loss (EPL) affects 50-70% pregnant women in first trimester. The precise molecular mechanisms underlying EPL are far from being fully understood. Therefore, we aim to identify the molecular signaling pathways relating to EPL. We performed proteomics and bioinformatics analysis of the placental villi in women who have undergone EPL and in normal pregnant women. The proteomics data were validated by Western blot analysis. We identified a total of 5952 proteins in placental villi, of which 588 proteins were differentially expressed in the EPL women. Bioinformatics analysis revealed that these differentially expressed proteins participated in a variety of signaling pathways, including the focal adhesion pathway and ribosome pathway. Moreover, results of the Western blot confirmed that Desmin, Lamin A/C, MMP-9, and histone H4 were upregulated in EPL and the Lamin C/ Lamin A ratio decreased obviously in EPL. These proteins could be associated with the pathophysiology of EPL. The data have been deposited to the ProteomeXchange with identifier PXD002391. Our study demonstrated that the focal adhesion pathway and ribosome pathway are involved in EPL, and these findings might contribute to unveil the pathophysiology of EPL.


Boron concentration prediction from Compton camera image for boron neutron capture therapy based on generative adversarial network.
Prompt gamma monitoring for the prediction of boron concentration is valuable for the dose calculation of boron neutron capture therapy (BNCT). This work proposes to use generative adversarial network (GAN) to predict the boron distribution based on Compton camera (CC) imaging quickly and provide a scientific basis for its application in BNCT. The BNCT and Compton imaging process was simulated, then the image reconstructed from the simulation and the contour of skin from CT are used as input, and the distribution of boron concentration from PET data is set as the output to train the network. The structural similarity, peak signal-to-noise ratio, and root mean square error of the images generated by the trained network are improved significantly, and the ratio of the boron concentration between the tumor area and the normal tissue is improved from 1.55 to 3.85, which is much closer to the true value of 3.52. The trained network can optimize the original image within 0.83 s, which is much faster than iterative optimization. The proposed method could help to ease the current online monitoring problem of boron concentration on a computational level, thereby promoting the clinical development of BNCT technology.


Antimyoclonic efficacy of piracetam in idiopathic generalized epilepsy.
Piracetam, a derivative of gamma-aminobutyric acid (GABA), has been used extensively for treatment of myoclonus in a variety of conditions, but not in patients with idiopathic generalized epilepsy (IGE). We have treated a patient with juvenile myoclonic epilepsy who had frequent and inconvenient morning myoclonus with 3,200 mg of piracetam daily. She had had only two generalized tonic-clonic seizures, with the last seizure 10 years earlier. Her obesity precluded the use of sodium valproate. She had a dramatic response to piracetam with sustained cessation of myoclonus and no side effects during 1.5 years' follow-up. Further trials of piracetam for control of myoclonus in patients with IGE are justified.


An automated method for the analysis of nicotinic acid in serum.
Rational antihyperlipemic therapy based on the use of nicotinic acid and its derivatives and/or combinations demands a rapid and reliable method for monitoring nicotinic acid blood levels. To this end, an automated colorimetric method for the analysis of nicotinic acid in serum has been elaborated. For serum from rats, dogs and man given p.o. nicotinic acid or 3-pyridine methanol, the method is greater than 90% specific for nicotinic acid. The limit detection for nicotinic acid is 2 microgram/ml based on 0.15 ml of serum or 0.3 microgram/ml based on 1.5 ml of serum.


Semen quality in Schistosoma haematobium infected men in Madagascar.
The seminal vesicles and the prostate are frequently affected by egg-induced inflammation in Schistosoma haematobium infected men. The objective of this study was to assess the semen quality in men with male genital schistosomiasis (MGS). The examination of the semen samples was performed in men aged 15 to 49 years living an S. haematobium endemic area in Madagascar prior to anti-schistosoma treatment with praziquantel and five months later. Men from the high endemic Sirama sugarcane plantation with positive egg excretion in the urine and circulating anodic antigen (CAA) present in serum (n=85) were compared to men (without egg excretion and no CAA) from the neighbouring low-endemic Mataipako village (n=57). The proportion of men with egg excretion in semen was significantly higher in Sirama than in Mataipako (53% versus 4%), whereas the median ejaculate volume was significantly lower in Sirama (1.8 ml versus 2.4 ml). There was no statistical difference in median spermatocyte counts and in the proportions of men detected with azoospermia. The mean apoptotic rate was 7.8% in a subgroup of 30 men from Sirama. A positive correlation was found between apoptotic rate and seminal eosinophil cationic protein (ECP) level (rho=0.560; P<0.001). At follow up, egg excretion and ECP level in semen declined significantly and were paralleled by a significant reduction in the apoptotic rate. The study suggests that S. haematobium infection is associated with sperm apoptosis and a reduced production of seminal fluid. Egg induced inflammation in the seminal vesicles and the prostate could be underlying mechanism for both observations.


Pain management trend of vaso-occulsive crisis (VOC) at a community hospital emergency department (ED) for patients with sickle cell disease.
Pain management at the emergency department (ED) for vaso-occulsive crisis (VOC) for patients with sickle cell disease has not been optimum, with a long delay in giving the initial analgesic. We conducted a retrospective survey over a 7-year period to determine our ED's timing in giving pain medication to patients with VOC as a quality improvement project. We compared different periods, children vs adults, and the influence of gender in the analgesic administration timing. This is a retrospective chart review of three different periods: (1) years 2007-2008, (2) years 2011-2012, and (3) year 2013. We extracted relevant information from ED records. Data were analyzed using Student t test, chi-square analysis, and the Kruskal-Wallis test. There was a progressive improvement in the time interval to the 1st analgesic over these three periods. Children received analgesics more quickly than adults in all periods. Male adult patients received pain medication faster than female adult patients, although initial pain scores were higher in female than in male patients. Progressively fewer pediatric patients utilized ED over these three periods, but no difference for adult patients was observed. The proportion of pediatric patients admitted to the hospital increased with each period. The progressive decrease in both the number of patients and the number of visits to the ED by children suggested that the collective number of VOC in children has decreased, possibly secondary to the dissemination of hydroxyurea use. We failed to observe the same trend in adult patients. The need for IV access, and ordering laboratory tests or imaging studies tends to delay analgesic administration. Delay in administration of the first analgesic was more pronounced for female adult patients than male adult patients in spite of their higher pain score. Health care providers working in ED should make conscious efforts to respect pain in women as well as pain in men. Though not proven from this study, we believe that a significantly wider use of hydroxyurea by adult patients most likely would reduce their utilization of ED for the purpose of relief of pain, and further pediatric hematologists may be better positioned to increase hydroxyurea adherence by young adult patients, since they have had established rapport with them before transitioning to adult care.


Learning curve for sonographic examination of the fetal nasal bone at 11-14 weeks.
To determine the number of ultrasound examinations necessary for training sonographers to examine accurately the fetal nasal bone at 11-14 weeks' gestation. Fifteen sonographers with experience in measuring nuchal translucency were asked to examine the nasal bone during the routine 11-14-week scan. The supervising doctor recorded if the sonographer succeeded in obtaining the correct image. Each sonographer performed a total of 140 examinations, and the data were analyzed in seven groups of 20 examinations. In a second study, two sonographers with extensive experience in examining the nasal bone examined independently 100 consecutive patients at a median fetal crown-rump length of 65 (45-84) mm and median gestational age of 12 (11-14) weeks and recorded whether the nasal bone was absent or present. In the first group of 20 examinations, there was failure to obtain the correct image of the fetal profile in 1-5 (median, 4) cases. In the subsequent three groups, there was failure to obtain the correct image in 0-3 (median, 1) cases. In the fifth and sixth groups failure occurred in 0-2 (median, 0) cases and in the seventh group all sonographers obtained successful images of the fetal profile in all cases. One sonographer obtained successful images of all cases after the first 40 scans, four after the first 60 scans, six after the first 80 and two each after the first 100 and 120 scans. In the second study, there was agreement between the two sonographers that the nasal bone was absent in two and present in 98 of the 100 consecutive patients examined. The minimum number of scans required for an experienced sonographer to become competent in examining the fetal nasal bone is on average 80, with a range of 40-120.


Mutant CYP3A4/5 Correlated with Clinical Outcomes by Affecting Rivaroxaban Pharmacokinetics and Pharmacodynamics in Patients with Atrial Fibrillation.
This study was designed to investigate the impact of single-nucleotide polymorphism-encoded cytochrome P450 enzymes (CYP3A4/5) on clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) based on pharmacokinetics and pharmacodynamics (PK/PD) aspects. A prospective study enrolling 165 rivaroxaban-treated patients with NVAF was conducted. Genotyping of CYP3A4 (rs2242480, rs2246709, rs3735451, and rs4646440) and CYP3A5 (rs776746) was performed to explore their impact on the trough plasma concentrations (Ctrough) of rivaroxaban, coagulation indicators at the Ctrough including activated partial thromboplastin time (APTT) and prothrombin time (PT), and clinical outcomes. Patients with mutant genotype CYP3A4 (rs2242480, rs2246709, and rs3735451) and CYP3A5 (rs776746) had higher levels of rivaroxaban Ctrough, PT values than that of wild-type. Furthermore, a positive relationship was revealed between Ctrough and PT (r = 0.212, p = 0.007), while no significant correlation was found between Ctrough and APTT. Regarding the clinical outcomes, the minor allele carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were associated with higher incidence of minor bleeding (p = 0.028 and p = 0.038, respectively) and were identified as the independent risk factors of minor bleeding treated with rivaroxaban (p = 0.024 and p = 0.036, respectively), with the receiver operating characteristic (ROC) curve validated (AUC = 0.8956, 95% CI: 0.829-0.962). The CYP3A4 polymorphisms (rs2242480, rs2246709, and rs3735451) and CYP3A5 rs776746 were associated with variations in rivaroxaban PK/PD. The minor allele (C) carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were correlated with clinical outcomes.


The synthetic flavonoid WYC02-9 inhibits colorectal cancer cell growth through ROS-mediated activation of MAPK14 pathway.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In this study, we explored the anti-cancer activity of WYC02-9, a synthetic protoapigenone, on human HCT116 CRC cells. The anti-cancer activity of WYC02-9 and its underlying mechanisms were analyzed using XTT cell proliferation assays, colony formation assays, FACS analysis, annexin V staining, immunoblotting analysis, reactive oxygen species (ROS) generation assays, soft agar assays, a nude mice xenograft study and immunohistochemistry assays. Data showed that WYC02-9 suppressed CRC cell growth by arresting cells at G2/M and inducing cell death via apoptotic pathways. Further analysis demonstrated that WYC02-9-induced apoptosis was mediated by the activation of a ROS-mediated MAPK14 pathway. An in vivo xenograft study revealed that WYC02-9 enhanced MAP2K3/6 and MAPK14 phosphorylation, induced apoptosis, and suppressed CRC tumor growth. WYC02-9 exerts its anti-tumor effect via ROS/MAPK14-induced apoptosis and has the potential to be developed as a chemotherapeutic agent for CRC.


Effect of mild cognitive impairment and APOE genotype on resting cerebral blood flow and its association with cognition.
Using whole-brain pulsed arterial spin labeling magnetic resonance imaging, resting cerebral blood flow (CBF) was measured in 20 mild cognitive impairment (MCI; 11 ɛ3 and 9 ɛ4) and 40 demographically matched cognitively normal (CN; 27 ɛ3 and 13 ɛ4) participants. An interaction of apolipoprotein (APOE) genotype (ɛ3 and ɛ4) and cognitive status (CN and MCI) on quantified gray-matter CBF corrected for partial volume effects was found in the left parahippocampal and fusiform gyri (PHG/FG), right middle frontal gyrus, and left medial frontal gyrus. In the PHG/FG, CBF was elevated for CN ɛ4 carriers but decreased for MCI ɛ4 carriers. The opposite pattern was seen in frontal regions: CBF was decreased for CN ɛ4 carriers but increased for MCI ɛ4 carriers. Cerebral blood flow in the PHG/FG was positively correlated with verbal memory for CN ɛ4 adults (r=0.67, P=0.01). Cerebral blood flow in the left medial frontal gyrus was positively correlated with verbal memory for MCI ɛ4 adults (r=0.70, P=0.05). Findings support dynamic pathophysiologic processes in the brain associated with Alzheimer's disease risk and indicate that cognitive status and APOE genotype have interactive effects on CBF. Correlations between CBF and verbal memory suggest a differential neurovascular compensatory response in posterior and anterior cortices with cognitive decline in ɛ4 adults.


Breakthrough Candida krusei fungemia during fluconazole prophylaxis followed by breakthrough zygomycosis during caspofungin therapy in a patient with severe aplastic anemia who underwent stem cell transplantation.
We report a case of breakthrough invasive zygomycosis in a stem cell transplant recipient who was receiving caspofungin for treatment of a breakthrough Candida krusei fungemia that occurred during fluconazole prophylaxis. Also, patients receiving the echinocandin caspofungin remain at risk for pathogens, such as zygomycetes, that are intrinsically resistant to this agent.


Effect of pressure on the release of radioactive glycine and gamma-aminobutyric acid from spinal cord synaptosomes.
Exposure to high hydrostatic pressure produces neurological changes referred to as the high-pressure nervous syndrome (HPNS). Manifestations of HPNS include tremor, EEG changes, and convulsions. These symptoms suggest an alteration in synaptic transmission, particularly with inhibitory neural pathways. Because spinal cord transmission has been implicated in HPNS, this study investigated inhibitory neurotransmitter function in the cord at high pressure. Guinea pig spinal cord synaptosome preparations were used to study the effect of compression to 67.7 atmospheres absolute on [3H]glycine and [3H]gamma-aminobutyric acid ([3H]GABA) release. Pressure was found to exert a significant suppressive effect on the depolarization-induced calcium-dependent release of glycine and GABA by these spinal cord presynaptic nerve terminals. This study suggests that decreased tonic inhibitory regulation at the level of the spinal cord contributes to the hyperexcitability observed in animals with compression to high pressure.


The myokine irisin increases cortical bone mass.
It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 µg kg(-1). We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 µg kg(-1) per week) cause browning of adipose tissue; this was not seen with low-dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes, Opn and Sost, but not Ucp1 or Pparγ expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulated Atf4, Runx2, Osx, Lrp5, β-catenin, Alp, and Col1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursor Fndc5 was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressed Fndc5, albeit at low levels. Furthermore, muscle fibers from r-irisin-injected mice displayed enhanced Fndc5 positivity, and irisin induced Fdnc5 mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle-bone connectivity.


Molecular origin of the weak susceptibility of kinesin velocity to loads and its relation to the collective behavior of kinesins.
Motor proteins are active enzymatic molecules that support important cellular processes by transforming chemical energy into mechanical work. Although the structures and chemomechanical cycles of motor proteins have been extensively investigated, the sensitivity of a motor's velocity in response to a force is not well-understood. For kinesin, velocity is weakly influenced by a small to midrange external force (weak susceptibility) but is steeply reduced by a large force. Here, we utilize a structure-based molecular dynamic simulation to study the molecular origin of the weak susceptibility for a single kinesin. We show that the key step in controlling the velocity of a single kinesin under an external force is the ATP release from the microtubule-bound head. Only under large loading forces can the motor head release ATP at a fast rate, which significantly reduces the velocity of kinesin. It underpins the weak susceptibility that the velocity will not change at small to midrange forces. The molecular origin of this velocity reduction is that the neck linker of a kinesin only detaches from the motor head when pulled by a large force. This prompts the ATP binding site to adopt an open state, favoring ATP release and reducing the velocity. Furthermore, we show that two load-bearing kinesins are incapable of equally sharing the load unless they are very close to each other. As a consequence of the weak susceptibility, the trailing kinesin faces the challenge of catching up to the leading one, which accounts for experimentally observed weak cooperativity of kinesins motors.


Gag-dependent enrichment of HIV-1 RNA near the uropod membrane of polarized T cells.
The enrichment of HIV-1 macromolecules at the uropod of polarized T cells can significantly promote virus assembly and cell-mediated infection. Using live-cell fluorescence microscopy, we demonstrate that full-length HIV-1 RNA is enriched at the uropod membrane; furthermore, the presence of HIV-1 Gag containing a functional nucleocapsid domain is necessary for this HIV-1 RNA enrichment. The results from these studies provide novel insights into the mechanism of HIV-1 replication in polarized T cells.


[A case of asymptomatic urachal cyst in autopsy--histopathological study of urachal cyst and review of the literature of 99 cases during a 10 year period in Japan].
Disorders of urachal remnants are common. While urachal cysts are usually asymptomatic, infection may mimic a variety of acute abdomen. Here we report a very rare case of urachal cyst that protruded in the urinary bladder cavity and among 99 accumulated cases, only 4 cases have been reported similar to this case characterized by intravesical development from 1990 to 1999. An uninfected urachal cyst was found in a 79-year-old male who had died of bile duct carcinoma. The cyst showed ovoid protrusion into urinary bladder cavity from the dome (3.5 x 2.0 x 2.0 cm in size). Histopathologically, the cyst wall was thin and consisted of fibrous connective tissue with muscular tissue and peripheral nerve, and lined by cuboidal epithelium but no inflammatory cells could be seen. Urachal cysts occur in both sexes are affected with equal frequency, and frequently occur in a younger population. In clinical symptoms the umbilical manifestations are predominant in patients younger than 30 years old, while the bladder manifestations are predominant in those older than 30.


Membrane Trafficking in Neuronal Development: Ins and Outs of Neural Connectivity.
During development, neurons progress through rapid yet stereotypical shape changes to achieve proper neuronal connectivity. This morphological progression requires carefully orchestrated plasma membrane expansion, insertion of membrane components including receptors for extracellular cues into the plasma membrane and removal and trafficking of membrane materials and proteins to specific locations. This review outlines the cellular machinery of membrane trafficking that play an integral role in neuronal cell shape change and function from initial neurite formation to pathway navigation and synaptogenesis.


Temporal accumulation of salicylic acid activates the defense response against Colletotrichum in strawberry.
Many authors have reported interactions between strawberry cultivars and pathogenic microorganisms, yet little is known about the mechanisms triggered in the plant. In this paper we examine the participation of the salicylic acid (SA) signaling pathway involved in the response of Fragaria x ananassa cv. Pájaro plants to pathogens. Strawberry plants were challenged with the virulent strain M11 of Colletotrichum acutatum, or with the avirulent strain M23 of Colletotrichum fragariae which confers resistance to the former. Our study showed that the isolate M23 induced a temporal SA accumulation that was accompanied with the induction of PR-1 gene expression in strawberry plants. Such events occured after the oxidative burst, evaluated as the accumulation of hydrogen peroxide and superoxide anion, and many hours before the protection could be detected. Similar results were obtained with exogenously applied SA. Results obtained supports the hypothesis that strawberry plants activate a SA mediated defense mechanisms that is effective against a causal agent of anthracnose. In contrast, plants inoculated with M11 did not show oxidative burst, SA accumulation or PR1 gene induction. This is the first report about a defense response signaling pathway studied in strawberry plants.


Alginate-based bipolymeric-nanobioceramic composite matrices for sustained drug release.
Alginate-based bipolymeric-nanobioceramic composite matrices for sustained drug release were developed through incorporation of nano-hydroxyapatite [nHAp] powders within ionotropically-gelled calcium ion-induced alginate-poly (vinyl pyrrolidone) blends polymeric systems. nHAp powders were synthesized by precipitation technique using calcium hydroxide [Ca(OH)2] and orthophosphoric acid [H3PO4] as raw materials. The average particle size of these was synthesized. nHAp powders was found as 19.04 nm and used to prepare nHAp-alginate-PVP beads containing DS. These beads exhibited drug entrapment efficiency (%) of 65.82±1.88 to 94.45±3.72% and average bead sizes of 0.98±0.07 to 1.23±0.15 mm. These beads were characterized by scanning electron microscopy (SEM) and Fourier transform-infra red (FTIR) spectroscopy analyses. Various nHAp-alginate-PVP beads containing DS exhibited prolonged sustained drug release and followed the Koresmeyer-Peppas model of drug release (R2=0.9908-0.9978) with non-Fickian release (anomalous transport) mechanism (n=0.73-0.84) for drug release over 8 h.


[Urethral cytology and diagnosis of the term of pregnancy. Various cytological aspects].
607 urethral smears were obtained from 330 women at the end of pregnancy. The cells of the stratified columnar epithelium were observed only in smears with at-term or post-term patterns : the presence of separated columnar cells is not significant ; in contrast small clusters of basal columnar cells or separated parabasal squamous cells characterize smears with post-term patterns. The significance of these observations is discussed.


Prevalence and mortality among children with anorectal malformation: A multi-country analysis.
We examined the total prevalence, trends in prevalence, and age-specific mortality among individuals with anorectal malformation (ARM) METHODS: We conducted a retrospective cohort study using data from 24 population- and hospital-based birth defects surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) from 18 countries and for births from 1974 to 2014. We estimated pooled and program-specific total prevalence per 10,000 total births. Poisson regression was used to assess time trends in prevalence from 2001 to 2012 when most programs contributed data. We calculated selected age-specific proportions of deaths, stratified by case status RESULTS: The pooled total prevalence of ARM was 3.26 per 10,000 total births (95% Confidence Interval = 3.19, 3.32) for birth years 1974-2014. About 60% of cases were multiple or syndromic. Prevalence of multiple, syndromic, and stillborn cases decreased from 2001 to 2012. The first week mortality proportion was 12.5%, 3.2%, 28.3%, and 18.2% among all, isolated, multiple, and syndromic cases, respectively CONCLUSIONS: ARM is relatively rare, with multiple and syndromic cases showing decreasing prevalence during the study period. Mortality is a concern during the first week of life, and especially among multiple and syndromic cases. Our descriptive epidemiological findings increase our understanding of geographic variation in the prevalence of ARM and can be used to plan needed clinical services. Exploring factors influencing prevalence and mortality among individuals with ARM could inform future studies.


Collagen VI deposition mediates stromal T cell trapping through inhibition of T cell motility in the prostate tumor microenvironment.
The tumor extracellular matrix (ECM) is a barrier to anti-tumor immunity in solid tumors by disrupting T cell-tumor cell interaction underlying the need for elucidating mechanisms by which specific ECM proteins impact T cell motility and activity within the desmoplastic stroma of solid tumors. Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. We found that CD4+ T cells largely lack expression of integrin α1 in the prostate tumor microenvironment and that blockade of α1β1 integrin heterodimers inhibited CD8+ T cell motility on prostate fibroblast-derived matrix, while re-expression of ITGA1 improved motility. Taken together, we show that the Col VI-rich microenvironment in prostate cancer reduces the motility of CD4+ T cells lacking integrin α1, leading to their accumulation in the stroma, thus putatively inhibiting anti-tumor T cell responses.


Variation in life-history characteristics over a clinal gradient in three populations of a communal orb-weaving spider.
Adult size and fecundity, total reproductive biomass, egg size, and spiderling size and resistance to desiccation were compared in three populations of the communal orb-weaving spider,Metepeira spinipes, in Mexico. In a desert population and in one from a moist tropical forest adult size, fecundity, and total reproductive biomass were similar, but were markedly smaller than in a climatologically intermediate agricultural habitat. Egg size and protein content were greater in the desert and agricultural habitats than in the moist forest, but spiderling size increased from desert to agricultural to moist forest populations. Desert spiderlings survived significantly longer than moist forest spiderlings at all humidity treatments over a 10% to 100% range. An explanation for these results is proposed based on apparent differences in energy allocation and expenditure which arise from the distinct climate, colony structure, and prey and space availability in the three habitats.


Direct proteomic quantification of the secretome of activated immune cells.
Protein secretion allows communication of distant cells in an organism and controls a broad range of physiological functions. We describe a quantitative, high-resolution mass spectrometric workflow to detect and quantify proteins that are released from immune cells upon receptor ligation. We quantified the time-resolved release of 775 proteins, including 52 annotated cytokines from only 150,000 primary Toll-like receptor 4-activated macrophages per condition. Achieving low picogram sensitivity, we detected secreted proteins whose abundance increased by a factor of more than 10,000 upon stimulation. Secretome to transcriptome comparisons revealed the transcriptionally decoupled release of lysosomal proteins. From genetic models, we defined secretory profiles that depended on distinct intracellular signaling adaptors and showed that secretion of many proinflammatory proteins is safeguarded by redundant mechanisms, whereas signaling adaptor synergy promoted the release of anti-inflammatory proteins.


Stonefly nymphs use hydrodynamic cues to discriminate between prey.
Playback experiments conducted in a Rocky Mountain, USA, stream determined whether predatory stonefly nymphs (Kogotus modestus; Plecoptera: PerlodiMae) used hydrodynamic cues to discriminate prey species from nonprey species. In the laboratory we recorded pressure wave patterns associated with swimming escape behavior of Baetis bicaudatus (Baetidae), the favored mayfly prey species, and those of a nonprey mayfly, Ephemerella infrequens (Ephemerellidae). We video taped the responses of 24-h starved Kogotus to Baetis playbacks, Ephemerella playbacks or no playbacks made by oscillating (or not) live mayflies (Ephemerella) or clear plastic models placed within in situ flow-through observation boxes. The probability of attacks per encounter with Baetis playbacks was highest and independent of the model type used, but Kogotus also showed an unexpected high probability of attacks per encounter when Ephemerella playbacks were made through live Ephemerella. Thus, Kogotus discriminated between Baetis and Ephemerella swimming patterns but only when playbacks were made through the plastic model. Kogotus never attacked motionless mayflies or motionless plastic models. We allowed some Kogotus to successfully capture one small Baetis immediately before playbacks, which resulted in a much higher probability of attacks per encounter with Baetis playbacks on either model and a heightened discrimination of prey versus nonprey playbacks. The probability of attacks per encounter by Kogotus with live Baetis swimming under similar experimental conditions was strikingly similar to its response to Baetis playbacks made by oscillating the plastic model after a successful capture. Order of playback presentation (Baetis first or Ephemerella first) did not influence predatory responses to mayfly swimming patterns. This study is the first to document the use of hydrodynamic cues by stream-dwelling predators for discrimination of prey from nonprey and provides a mechanism to explain selective predation by stoneflies on Baetis in nature.


Peripheral T-Cell Lymphomas: Therapeutic Approaches.
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare neoplasms of mature T cells or natural killer (NK) cell. PTCLs usually have an aggressive course and a poor outcome. In recent years, significant progress has been made in the knowledge of the molecular lymphomagenesis of PTCLs, and through the development of new, more specific therapeutic molecules, one can hope in the coming years for more personalized medicine and improved patient prognosis. This review aims to provide an up-to-date overview of the current therapeutic approaches in nodal PTCLs.


Carcinoma of the oropharynx: factors affecting outcome.
To assess the value of both patient- and tumor-related factors of oropharyngeal squamous cell carcinoma in predicting patient outcome, with respect to the three primary subsites of the disease. It was hypothesized that the subsite has a significant impact on outcome. Historical cohort study. A chart review was conducted of 126 patients diagnosed with squamous cell carcinoma of the oropharynx over a 10-year period. The oropharynx was divided into the following subsites: 1) base of tongue, 2) tonsil and pillars, and 3) uvula, soft palate, and posterior pharyngeal wall. Patient-related factors included age and gender. Tumor-related factors included American Joint Committee on Cancer stage, T stage, N stage, and grade. These factors were compared using the end points of disease-free survival and treatment response (complete response or partial response/no response). Tumor-related factors such as American Joint Committee on Cancer stage (P = .016) and T stage (P = .008) had a significant impact on treatment response. The American Joint Committee on Cancer stage (P = .030) and the T stage (P = .005) were also significant predictors of disease-free survival. Base-of-tongue lesions responded significantly worse to treatment than did tonsil and pillar or uvula, soft palate, and posterior pharyngeal wall lesions (P = .014). The disease-free survival for base-of-tongue cancer was significantly worse than for tonsil and pillar or for uvula, soft palate, and posterior pharyngeal wall cancer (P = .010). Patient-related factors such as age and gender were not significant in predicting disease-specific outcome. Important tumor-related factors were the American Joint Committee on Cancer stage and the T stage. Among the oropharyngeal subsites, squamous cell carcinoma of the base of tongue was associated with the worst outcome.


Novel protective properties of auranofin: inhibition of human astrocyte cytotoxic secretions and direct neuroprotection.
Steroidal and non-steroidal anti-inflammatory drugs are used for treatment of peripheral inflammation, but they are not effective in neurodegenerative disorders. Gold compounds are also used to treat peripheral inflammation, but their effects on neuroimmune reactions are unknown. This study investigated the effects of gold compounds on astrocytic cell functions and assessed in vivo distribution of auranofin after its oral administration in mice. Auranofin and three other gold compounds were investigated for their ability to reduce the secretion of pro-inflammatory cytokines and cytotoxins produced by activated human astrocytic cells. Ability of the gold compounds to protect neuronal cells from glial cytotoxins and from oxidative damage induced by hydrogen peroxide was also studied. The in vivo distribution of auranofin was investigated using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Auranofin (0.1-5 μM) inhibited the toxicity of stimulated primary human astrocytes and U-373 MG astrocytic cells towards human neuronal cells, but did not inhibit secretion of cytokines. Treatment of neuronal cells with high nanomolar to low micromolar concentrations of auranofin protected them from toxicity induced by hydrogen peroxide and supernatants of stimulated astrocytic cells through the upregulation of heme-oxygenase (HOX)-1. Aurothiomalate, aurothioglucose, and aurothiosulphate were ineffective in the assays used. Auranofin reached low micromolar concentrations in mouse brains following daily oral administration for one week. Since auranofin may protect neurons by inhibiting astrocyte toxicity and is also directly neuroprotective, it could be useful in neurodegenerative diseases where activation of astrocytes contributes to the neuronal loss.


C1q and mobility score in predicting sarcopenia in an Australian cohort of cancer surgery patients.
Sarcopenia has been shown to have significant adverse health outcomes in a range of patient populations. Particularly, sarcopenic patients having cancer surgery are a unique group who demonstrate poorer post-operative outcomes. Currently, the gold standard in diagnosing sarcopenia is through the use of computed tomography. However, the widespread use of imaging to diagnose patients with sarcopenia is neither cost-effective nor practical. Identifying a serum biomarker or a simple mobility scoring system as an alternative diagnostic tool may aid in identifying more patients at risk of sarcopenia. C1q, a novel biomarker, has previously been shown to correlate with sarcopenia. Similarly, we sought to explore whether mobility scores may provide a useful surrogate marker for sarcopenia. This was a prospective cohort study of patients who presented for colorectal cancer surgery between the dates of 6/10/2016 and 4/10/2017 at John Hunter Hospital. Computed tomography was utilized to calculate the psoas area at the L3 spinal level. Pre-operative blood samples were obtained for C1q analysis and de Morton Mobility Index (DEMMI) was also performed. A total of 51 patients were included in the study. The median age of the patients were 69 years old. We did not demonstrate a correlation between serum C1q and DEMMI scores with psoas area. Our findings suggest that neither C1q nor DEMMI scores are correlated with psoas area in a colorectal cancer population.


Determination of jasmonic acid in Lemna minor (L.) by liquid chromatography with fluorescence detection.
A new method is described for the determination of endogenous jasmonic acid (JA) in Lemna minor plant extracts using liquid chromatography (LC) with fluorescence detection. Plant tissues were extracted and derivatised using 9-anthryldiazomethane (ADAM reagent) prepared in situ. Accuracy and precision were improved by using the internal standard dihydrojasmonic acid (dh-JA) for the correction of JA losses during sample preparation steps. Liquid chromatography-mass spectrometry (LC/MS) analysis of ADAM derivatives of JA and dh-JA confirmed that a single molecule of JA and dh-JA was coupled with one molecule of reagent. Derivatives of JA and dh-JA were separated with gradient elution on a C18 reversed-phase column using acetonitrile/water as a mobile phase and detected by a fluorescence detector at excitation and emission wavelengths of 254 and 412 nm, respectively. The detection limits of JA and dh-JA were 2.9 ng mL(-1) and 3.7 ng mL(-1) per 50-microL injection. The method is reproducible and selective and yields single peaks for each compound regardless of isomer. The specificity and accuracy of the proposed LC/FD method was confirmed by liquid chromatography-TurboIon Spray tandem mass spectrometric (LC/MS/MS) analysis of free JA in Lemna minor samples under multiple reaction monitoring conditions.


Outcome of pediatric epilepsies in adulthood.
A good understanding of the long-term outcome of epileptic disorders that have begun in infancy or childhood allows the practitioner to choose the best medical management and to adjust it throughout the life of the patient. The identification of risk factors of poor outcome is crucial, the issue being to prevent or minimize their impacts by appropriate interventions. However, knowledge on the natural course and long-term outcome of pediatric epilepsies is fragmentary for a lot of them for reasons that the authors discuss in this chapter. After reviewing general considerations on outcome for the epilepsies persisting throughout life, the authors will discuss the present state of knowledge on specific aspects concerning some pediatric epilepsy syndromes. These disorders have been chosen because they are representative of the wide range of potential outcomes that can be observed in adults.


Prealbumin as a hapten carrier protein in certain varieties of dermatitis.
A significant decrease of serum prealbumin levels and an increased proportion of prealbumin bearing lymphocytes in peripheral blood have been found in patients of hapten-induced diseases. Prealbumin deposition in the vessel walls, and/or prealbumin positive cells (granulocytes, lymphocytes, macrophages) in the dermis have been observed in patients with proved drug allergy as well as allergic contact dermatitis using immunofluorescence technique. The eluates from membrane of lymphocytes of patients with drug allergy contained a mitogenic substance, probably antigen and sometimes prealbumin as well. These results also support the earlier suggested hypothesis that the prealbumin may act as a hapten carrier protein.


A protective device for performing cranial autopsies.
An effective device for performing cranial autopsies is described. This device prevents the aerosolization of potentially infectious particulate material while opening the cranial vault.


The Use of Kits in the Analysis of Tissue Lipids Requires Validation.
The ready availability and ease of use of kits for the measurement of serum lipids has greatly facilitated these measurements. In many cases it would be convenient to use these kits in the determination of lipid concentrations in tissues. The successful application of serum kits in tissue analysis requires that two important issues be considered. First, the solvent system for the extraction of the lipids and the solvent used for analysis by the kit must be compatible with the reactions in the kit. Second, the concentration range in the analyzed solution must be within the range for which the kit is used. We report here that lipids in liver and adipose tissues may be significantly underestimated by the use of some kits. We recommend that the use of kits for tissue analysis of lipids be validated for the specific analysis.


[Paravasal sclerotherapy: experimental study on the effect of sclerosing agents (author's transl)].
Sclerosing and side effects of three solutions mostly used for paravasal sclerotherapy were studied by subcutaneous injections in lower legs of rats. The results demonstrate that of the three examined sclerosing agents 5 p.c. phenol in almond oil has the lowest toxocity in tissue besides a sufficient production of collagen fibres.


Calcium dynamics at a plastic synapse in Aplysia.
Because certain primitive behavioral responses in the large sea snail Aplysia have recently been linked to neurophysiological events at a synaptic level, special interest attaches to the role played by calcium ions at such synapses. Using an extended version of the model applied earlier to trace the flow of energy and information through a ganglion of the medicinal leech (Triffet & Green, 1980), the authors investigate the electropotential effects of small transient localized changes in the calcium concentration near the inner membrane surface of a neuron in the resting state. When this state is well below the firing threshold, changes in Ca2+ concentration less than 10(-8)M are shown to result only in low-level harmonic background oscillations. When the potential of the neurons is closer to threshold, however, and/or the Ca2+ concentration is of the order of 10(-8)M, easily recognizable graded potentials appear, and these grow into firing peaks when the calcium concentration is increased still further. Though no attempt is made to deal with the amplification effects dependent on calcium-vesicle interactions and the related release of transmitter molecules, a unified mechanism for the underlying calcium ion dynamics is proposed. Graded potentials of increasing size are associated with a progressive localized thickening of the inner and outer Debye layers. Moreover, the transverse and longitudinal calcium currents set up in such regions prove adequate to account for both the depletion of Ca2+ ions necessary to achieve habituation, and the increase in their concentration required for sensitization.


Cost-Effectiveness of Surgical Weight-Loss Interventions for Patients With Knee Osteoarthritis and Class III Obesity.
Class III obesity (body mass index [BMI] ≥40 kg/m2 ) is associated with worse knee pain and total knee replacement (TKR) outcomes. Because bariatric surgery yields sustainable weight loss for individuals with BMI ≥40 kg/m2 , our objective was to establish the value of Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) in conjunction with usual care for knee osteoarthritis (OA) patients with BMI ≥40 kg/m2 . We used the Osteoarthritis Policy model to assess long-term clinical benefits, costs, and cost-effectiveness of RYGB and LSG. We derived model inputs for efficacy, costs, and complications associated with these treatments from published data. Primary outcomes included quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs), all discounted at 3%/year. This analysis was conducted from a health care sector perspective. We performed sensitivity analyses to evaluate uncertainty in input parameters. The usual care + RYGB strategy increased the quality-adjusted life expectancy by 1.35 years and lifetime costs by $7,209, compared to usual care alone (ICER = $5,300/QALY). The usual care + LSG strategy yielded less benefit than usual care + RYGB and was dominated. Relative to usual care alone, both usual care + RYGB and usual care + LSG reduced opioid use from 13% to 4%, and increased TKR usage from 30% to 50% and 41%, respectively. For cohorts with BMI between 38 and 41 kg/m2 , usual care + LSG dominated usual care + RYGB. In the probabilistic sensitivity analysis, at a willingness-to-pay threshold of $50,000/QALY, usual care + RYGB and usual care + LSG were cost-effective in 70% and 30% of iterations, respectively. RYGB offers good value among knee OA patients with BMI ≥40 kg/m2 , while LSG may provide good value among those with BMI between 35 and 41 kg/m2 .


Fabrication of ATP/PEG/MnO2NWs composite for solar steam generation with high conversion efficiency.
Solar steam generation is widely used in seawater desalination because of its high efficiency and environmental protection. However, using low-cost materials to produce efficient solar evaporators is a severe challenge. In this study, a porous carbon material was prepared by combining Attapulgite (ATP), Polyethylene glycol (PEG) and Manganese dioxide nanowires (MnO2NWs) composite, through freeze-drying and high-temperature carbonization. The prepared CAPM aerogel shows a three-dimensional porous structure, which has high evaporation properties in pure water and simulated seawater. Under 1 sun simulated illumination, the pure water evaporation is 1.4574 kg m-2h-1 and the corresponding energy conversion efficiency is 85.94%. The prepared CAPM aerogel showed excellent durability and salt tolerance in 20%Nacl solution, indicating that the CAPM has excellent desalinization performance. In addition, CAPM aerogel has and exhibits super hydrophilic properties, which can transfer water molecules quickly. Due to the advantages of low cost, simple preparation method, and high solar energy conversion efficiency, the CAPM has excellent potential as a photothermal material for solar energy generation.


Effect of bovine oocyte vitrification with EGTA and post-warming recovery with resveratrol on meiotic spindle, mitochondrial function, reactive oxygen species, and developmental competence.
The present study aimed to determine the effects of the addition of EGTA to vitrification solutions and a post-warming recovery period supplemented with 1 μM resveratrol on meiotic spindle integrity, mitochondrial activity, ATP content, reactive oxygen species (ROS) levels, and developmental potential of partially denuded, vitrified-warmed bovine oocytes. Results of microtubule distribution and chromosomal arrangement indicated that resveratrol supplementation, irrespective to EGTA addition, reduced the incidence of abnormal meiotic spindles to similar levels of the control group. Mitochondrial membrane potential was similar in all groups, but ATP content was negatively affected by the vitrification-warming procedure and failed to recover after 4 h of post-warming culture. Resveratrol caused the reduction of ROS to lower levels of the control group, and showed the lowest ROS levels when combined with EGTA treatment. Oocytes in all vitrification groups presented lower developmental potential when compared to fresh oocytes. However, oocytes that underwent vitrification supplemented with EGTA and post-warming culture along with resveratrol showed higher developmental competence compared with vitrified-warmed oocytes not supplemented with resveratrol. The results of our study indicate that submitting vitrified-warmed, partially denuded bovine oocytes to a post-warming recovery period supplemented with 1 μM resveratrol improves vitrification outcomes. However, the benefits of EGTA on vitrification and warming of bovine oocytes need to be further investigated.


Antigen recognition by an antibody light chain.
A monoclonal antibody to vasoactive intestinal polypeptide (VIP) was reduced and alkylated and its light and heavy chains were purified by denaturing gel filtration. Following renaturation, the light chain displayed sequence-specific binding of VIP. The specific VIP binding activity of several fractions spanning the light chain peak recovered from the gel filtration column was constant, the light chain was electrophoretically homogeneous, the VIP binding activity was precipitated by anti-light chain antibody but not anti-heavy chain antibody and the activity remained associated with a light chain fraction recovered by resolutive chromatography on a hydroxylapatite column. N-terminal amino acid sequencing of the light and heavy chain fractions confirmed the purity of these proteins and suggested that the VL and VH regions belonged to kappa-family II and gamma-family III, respectively. The VIP-binding affinity of the light chain was only 5-fold lower than that of the parent antibody and the light chain did not bind unrelated peptides. These observations suggest that light chains display structural characteristics necessary for high affinity antigen binding.


Study of a temperature-sensitive mutant of the ras-related YPT1 gene product in yeast suggests a role in the regulation of intracellular calcium.
Intragenic mutations were isolated that suppressed the dominant-lethal phenotype of the YPT1ile121 mutant gene in a temperature-dependent fashion. Among different amino acid substitutions resulting from single point mutations, two, Ala161----Val (A161V) and Met165----Ile (M165I), restored the function of the YPT1ile121 mutant protein. Mutants expressing the YPT1ile121/val161 allele (ypt1ts) only, grew normally at temperatures up to 30 degrees C but were arrested at 37 degrees C. At the restrictive temperature, ypt1ts mutants accumulated ER membranes, small vesicles, and unprocessed invertase, and they exhibited cytoskeletal defects and an enhanced 45Ca2+ uptake. Similar alterations were seen in YPT1-depleted cells. The ypt1ts mutant cells could be rescued from growth arrest by increasing extracellular Ca2+, and, even at the permissive temperature, they displayed increased trifluoperazine sensitivity.


Minimally invasive posterior stabilization for treating spinal tuberculosis.
We describe a case of dorsal-lumbar vertebral tuberculosis (Pott's disease) first treated with antibiotic therapy, bed rest, and cast. After 2 months of treatment patient's symptoms worsened. Minimally invasive posterior vertebral stabilization was carried out, with excellent clinic and radiographic results.


Biceps brachii muscle hardness assessed by a push-in meter in comparison to ultrasound strain elastography.
This study investigated the relationship between push-in meter (PM) and ultrasound strain elastography (USE) for biceps brachii (BB) muscle hardness. BB hardness of 21 young men was assessed by PM and USE during rest and isometric contractions of six different intensities (15, 30, 45, 60, 75, 90% of maximal voluntary contraction: MVC) at 30°, 60° and 90° elbow flexion. Muscle hardness (E) was calculated from the force-displacement relationship in PM, and strain ratio (SR) between an acoustic coupler (elastic modulus: 22.6 kPa) and different regions of interest (ROIs) in BB was calculated and converted to Young's modulus (YM) in USE. In resting muscle, E was 26.1 ± 6.4 kPa, and SR and YM for the whole BB was 0.88 ± 0.4 and 30.8 ± 12.8 kPa, respectively. A significant (p < 0.01) correlation was evident between E and logarithmical transformed SR (LTSR) for the ROI of whole BB (r = - 0.626), and E and converted YM (r = 0.615). E increased approximately ninefold from resting to 90% MVC, and E and LTSR (r = - 0.732 to - 0.880), and E and converted YM for the SR above 0.1 were correlated (r = 0.599-0.768, p < 0.01). These results suggest that muscle hardness values obtained by PM and USE are comparable.