The role of the practice order: A systematic review about contextual interference in children.
We aimed to identify and evaluate the quality and evidence of the motor learning literature about intervention studies regarding the contextual interference (CI) effect (blocked vs. random practice order) in children with brain lesions and typically developing (TD) children. Eight databases (Cinahl, Cochrane, Embase, PubMed, Pedro, PsycINFO, Scopus and Web of Knowledge) were searched systematically with predefined search terms. Controlled studies examining the CI effect in children (with brain lesions or TD) were included. Evidence level, conduct quality, and risk of bias were evaluated by two authors independently. A best evidence synthesis was performed. Twenty-five papers evaluating TD children were included. One of these studies also assessed children with cerebral palsy. Evidence levels were I, II, or III. Conduct quality was low and the risk of bias high, due to methodological issues in the study designs or poor description thereof. Best evidence synthesis showed mainly no or conflicting evidence. Single tasks showed limited to moderate evidence supporting the CI effect in TD children. There is a severe limitation of good-quality evidence about the CI effect in children who practice different tasks in one session, especially in children with brain lesions.


[The superficial circumscribed lymphangioma of the tongue].
Superficial circumscribed lymphangiomas are predominantly benign lesions occuring in the cervicofacial area. These malformations of the lymphatic vessels are frequently diagnosed in children. We report the clinical case of lymphangioma of the tongue that occurred in an old man. The differential diagnosis was made primarily with Kaposi's disease, circumscribed angiokeratoma and metastases of a solid tumor. The patient had a biopsy that confirmed the diagnosis. The decision was abstention and supervision since the patient was not embarrassed.


Variations of the Static Contact Angle of Ferrofluid Droplets on Solid Horizontal Surfaces in External Uniform Magnetic Fields.
The application of external uniform magnetic fields to ferrofluid droplets affects their magnetic order at the nanoscale as well as their shape at the macroscale, thus changing their contact angle with the surface. In this work, the effects of external uniform magnetic fields on the contact angles between different oil-based ferrofluid droplets and a handful of horizontal surfaces of varying wettability were studied. The contact angle is no longer constant around the ferrofluid droplet; rather, it varies in a rich yet predictable way. Droplets dispensed in the presence of the magnetic field on oleophobic surfaces adjust such that the contact angle increases at the front and back ends and decreases at the two perpendicular positions. The opposite behavior is reported for ferrofluid droplets on oleophilic surfaces. These direction-dependent changes in the contact angle can have a significant impact on the behavior of ferrofluid droplets on gradient surfaces where they can either diminish or enhance the surface tension gradient. Our work is fundamentally relevant to potential applications involving the controlled movement of ferrofluid droplets on surfaces like the lab-on-a-chip under the combined effects of a magnetic field and either a surface tension gradient or an electric field (i.e., electrowetting). It is important to understand how the two effects interact for the optimal utilization of these effects in future applications.


Cirrosporium novae-zelandiae, an enigmatic coelomycete with meristem arthroconidia, with ancestors in the Eurotiomycetes.
A culture of Cirrosporium novae-zelandiae, the type species of a distinctive, monotypic coelomycete genus, was isolated from a specimen collected near the holotype locality in New Zealand. Light microscopic and environmental scanning electron microscopic observations confirm the details of the unusual meristem arthric conidium ontogeny presented in the protolog. For phylogenetic analysis, a dataset of 122 species representing nine classes of euascomycetes was assembled including sequences from nuclear small and large subunits (nc18S, nc28S) and mitochondrial small subunit (mr16S) ribosomal RNA and the largest and second largest subunits of RNA polymerase II (RPB1, RPB2). A five-gene phylogeny suggests that the fungus is phylogenetically related to the Eurotiomycetes. It sits alone on a long branch as a sister to the Mycocaliciales of the Mycocaliciomycetidae. Cirrosporium exhibits several morphological characters similar to those of members of the Mycocaliciales; however, the paucity of known anamorphs in this order does not offer any further clarification on possible relationships. It is clear that the rare and broadly distributed meristem arthric ontogenetic pattern is polyphyletic, occurring in widely separate groups of anamorphs of both the Ascomycota and Basidiomycota.


Pd-Catalyzed Acetoxylation of γ-C(sp3)-H Bonds of Amines Directed by a Removable Bts-Protecting Group.
Pd-catalyzed acetoxylation of γ-C(sp3)-H bonds directed by Bts-protected amines using inexpensive PhI(OAc)2 as oxidant is reported. The Bts-protecting group is easily introduced and removed under mild conditions. This protocol provides an important strategy for the construction of γ-hydroxyl amine derivatives.


A comparison of two dental implant systems in partially edentulous patients: 1-year post-loading results from a pragmatic multicentre randomised controlled trial.
To compare the clinical effectiveness of two implant systems: Way Milano and Kentron (Geass, Pozzuolo del Friuli, UD, Italy). A total of 64 patients requiring at least two single crowns or partial fixed dental prostheses supported by a maximum of three implants had their sites randomised according to a split-mouth design to receive both implant systems at six centres. Patients were followed up for 1 year after initial loading. Outcome measures were: prosthesis/implant failures; any complication; peri-implant marginal bone level changes; and clinician preference. In total 71 Way Milano and 73 Kentron implants were placed. Six patients dropped-out before the 1-year follow-up, but all remaining patients were followed up to 1 year post-loading. No Way Milano implant failed, whereas three Kentron implants failed before loading. Two complications were reported, one for each implant type. There were no statistically significant differences for prosthesis/implant failures (difference in proportions = 0.05, P = 0.25; 95% CI -0.02 to 0.13) and complications (difference in proportions = 0, P = 1.0, 95% CI -0.07 to 0.07) between the implant systems. Three operators preferred Way Milano implants whereas the other three had no preference. At implant placement (baseline) bone levels were higher for Way Milano implants (0.27 mm) than for Kentron implants (0.41 mm). Both groups gradually lost statistically significant amounts of periimplant marginal bone at 4 months after loading and at 1 year after loading. One year after loading, Way Milano implants lost an average of 0.73 mm peri-implant bone compared with 0.84 mm of Kentron implants. Marginal bone level changes were not statistically significant different for Way Milano compared to Kentron implants at 4 months (-0.16 mm, 95% CI -0.30, 0.01; P = 0.0606) and 1 year (-0.09 mm, 95% CI -0.26, 0.09; P = 0.3407) after loading. No statistically significant differences were observed between the two implant types, although three Kentron implants failed versus none of the Way Milano type. Longer follow-up of wider patient populations are needed to better understand whether there is an effective advantage with one of the two implant designs.


[Therapeutic efficacy of benzoxazinorifamycin KRM-1648 against experimental murine tuberculosis: (1). A study on the efficacy of short course treatment with the intratracheal and intravenous infection model].
This study aims to compare in vivo activity of benzoxazinorifamycin KRM-1648 (KRM) with those rifampicin (RFP) and rifabutin (RBT) against experimental murine tuberculosis. Mice were infected with Mycobacterium tuberculosis or M. bovis by the intratracheal (i.t.) or intravenous (i.v.) routes, and treated for 10 days with various doses of each drug starting from the 9th or 11th day after the TB-infection. (A) A rapid test for in vivo evaluation of three rifamycins was conducted by examining the survival days of treated mice infected with 106 cfu of M. bovis Ravenel. Mice treated with KRM exhibited 2.13.7 times longer survival times, in comparison with those treated with RFP or RBT. (B) In the i.t.-model of M. bovis Ravenel infection, three rifamycin derivatives gave "distinctive dose-response curves" in the correlation of dose sizes with the mean survival times or "log10CFU/lungs reductions". (C) In M. tuberculosis Kurono infection models, the ranking of the anti-TB activity of the three rifamycins in each organ was as follows: i.t.-and i.v.-lungs: KRM >> RFP not equal to RBT, i.v.-spleen: KRM not equal to RBT > RFP, i.v.-liver: KRM not equal to RBT > RFP. (D) Based on the results of "log10CFU reduction" in different organs in M. tuberculosis Kurono infection models, "characteristic in vivo activity patterns of each rifamycin" were obtained. (E) The therapeutic efficacy of KRM in lungs was greater than in spleen and liver with any dose. In contrast, RBT exhibited more remarkable in vivo activity in the spleen and liver than in lungs. The prominent in vivo activity of KRM may allow small dose for effective therapy; 1/3 dose or less in comparison with those of RFP or RBT, or intermittent therapy of tuberculosis.


Efficient Expression of an Acidic Endo-polygalacturonase from Aspergillus niger and Its Application in Juice Production.
An endo-polygalacturonase gene (pga-zj5a) was cloned by reverse transcription from cDNAs synthesized from Aspergillus niger ZJ5 total RNA. The open reading frame of pga-zj5a was 1089 base pairs encoding 362 amino acids. Pga-zj5a lacking a signal peptide sequence was successfully amplified using A. niger ZJ5 cDNA as the template and was ligated into the pPIC9 vector. The resulting plasmid was transformed into competent cells of Pichia pastoris GS115 for heterologous expression. The polygalacturonase showed a maximum activity level of 10436 U/mL in the culture supernatant from a 3 L fermenter. Assays of enzymatic properties showed that the optimal pH and temperature of the recombinant PGA-ZJ5A were 4.5 and 40 °C, respectively. PGA-ZJ5A was effective in pear juice clarification, increased the volume of pear juice by 41.8%, and improved its light transmittance 3-fold.


Economic conditions during pregnancy and preterm birth: A maternal fixed-effects analysis.
Making causal inference regarding impacts of macrolevel economic conditions during pregnancy on pregnancy outcomes is hampered by the presence of unmeasured variables that may influence women's probability of giving birth under certain economic conditions (ie, exposure) as well as her pregnancy outcomes. Maternal fixed-effects (FE) analyses, in which the association between exposure and outcomes is estimated within mothers who had discordant outcomes, can control for such unmeasured variables when they are invariant across pregnancies. We utilised a maternally linked data set of all singleton births in Michigan from 1990 to 2012 (n = 2 657 272 for full sample; n = 269 943 for FE analytic sample) to examine the relationship between state-level unemployment rates during pregnancy and preterm birth (PTB, <37 weeks' gestation). Measured maternal characteristics that change across pregnancies, for example, age, marital status, education, parity, and infant sex, were included as covariates in the model. Using an FE approach, we found that each one percentage point increase in state unemployment in the first trimester of pregnancy was associated with a modest 3% increase in odds of PTB. Our results were consistent with previously published results in a national sample and held across random- versus fixed-effect models, analytic samples, and outcome measures. Our findings provide further evidence that economic downturn during early pregnancy may be associated with modest increases in PTB.


Cystic duct pressures after ligation with a novel absorbable device in an ex vivo caprine cholecystectomy model.
Laparoscopic cholecystectomy is the standard of care in human medicine for gall bladder disease. Although infrequently reported in veterinary literature, laparoscopic cholecystectomy is an option for uncomplicated gall bladder disease in canine patients. Due to the risk of cystic duct ligature slippage or clip dislodgement, we wanted to explore the use of a LigaTie; a novel absorbable medical device modeled after a cable tie. Our object was to describe the use of the LigaTie in a caprine cadaveric study of cholecystectomies as a model for canine patients and demonstrate the leak pressure of the cystic duct compared with cholecystectomies performed with 2 large endoscopic hemoclips. Samples of caprine gall bladder, liver, and cystic duct were collected. The cystic duct was ligated with either 2 large endoscopic hemoclips or a LigaTie. Maximum cystic duct pressure was recorded. Results showed that there was no statistically significant difference in the maximum cystic duct pressure achieved for cystic ducts ligated with 2 large endoscopic hemoclips or the LigaTie (P = 0.865). No leakage was observed from the cystic duct, hemoclip, or LigaTie site in either group. Supraphysiologic pressures were achieved in both groups and high pressure occlusion of the infusion pump determined the maximum intraluminal pressure achieved. Based on these results, the LigaTie may provide advantages in minimally invasive surgery, especially when considering ligation of a friable or thickened cystic duct during laparoscopic cholecystectomy. Future in vivo studies are warranted to determine minimally invasive maneuverability, tissue interaction, complications, and outcomes.


Reduced allergen-induced nasal congestion and leukotriene synthesis with an orally active 5-lipoxygenase inhibitor.
The clinical importance of leukotrienes in human allergy has not been defined, in part because there have been no selective 5-lipoxygenase inhibitors that have been effective and safe for use in humans. To address the hypothesis that stimulated leukotriene synthesis causes symptoms of immediate-hypersensitivity reactions in vivo, I investigated the effects of a new 5-lipoxygenase inhibitor, A-64077, on provoked allergic nasal symptoms and mediator release in a double-blind, randomized, placebo-controlled study. Eight subjects with allergic rhinitis underwent nasal challenge on two occasions after an oral dose of 800 mg of A-64077 or an identical-appearing placebo. Allergen-induced nasal congestion was significantly attenuated (P less than 0.02) by A-64077; peak levels of leukotriene B4 (median, 684 pg per milliliter) and 5-hydroxyeicosatetraenoic acid (median, 704 pg per milliliter) in nasal-rinse fluids were markedly reduced (to 67 and 185 pg per milliliter, respectively; P less than 0.01), whereas levels of prostaglandin D2 were not. Histamine release and sneezing were not reduced significantly by A-64077, but there was a significant correlation (P less than 0.01) between the changes in these variables within subjects. The mean (+/- SEM) stimulated synthesis of leukotriene B4 in whole blood ex vivo was markedly reduced by A-64077 (from 153 +/- 19 to 20 +/- 9 ng per milliliter, P less than 0.01), and the specificity of A-64077 for 5-lipoxygenase inhibition was verified by its lack of effect on the synthesis of serum thromboxane B2 or 12-hydroxyeicosatetraenoic acid. These results provide direct evidence of an important role for the 5-lipoxygenase products of arachidonic acid in allergic rhinitis and support the notion that further experiments in this area may lead to new therapeutic approaches to allergic disorders.


Susceptibility of lesser mealworm (Coleoptera: Tenebrionidae) adults and larvae exposed to two commercial insecticides on unpainted plywood panels.
The susceptibilities of adult and larval lesser mealworms, Alphitobius diaperinus (Panzer), to two commercially formulated insecticides, cyfluthrin and tetrachlorvinphos, were examined through exposure on treated plywood panels. Lesser mealworms were collected from four caged-layer poultry farms, three in New York and one in Maine. An additional strain was obtained from an infestation occurring in a cricket colony. In all poultry farm derived strains, a portion of the population (1.8-16.2%) survived cyfluthrin exposure. The Maine and cricket colony strains were tolerant of tetrachlorvinphos exposure as both larvae and adults, with 55-74% mortality, whereas nearly 100% mortality was observed with New York strains. The cricket colony adult beetles were highly susceptible to cyfluthrin, with 100% mortality following exposure, but larvae were considerably less susceptible (87.7%). Pesticide use histories for the poultry farms and their impact on the results are discussed. The results document that tetrachlorvinphos, an active ingredient with a long use history, may be losing its effectiveness against lesser mealworms in some poultry operations; however, it is still effective in many others.


Non-Typeable Haemophilus influenzae Infection of the Junbo Mouse.
Acute otitis media, inflammation of the middle ear bulla, is the most common bacterial infection in children. For one of the principal otopathogens, non-typeable Haemophilus influenzae (NTHi), animal models allow us to investigate host-microbial interactions relevant to the onset and progression of infection and to study treatment of middle ear disease. We have established a robust model of NTHi middle ear infection in the Junbo mouse. Intranasal inoculation with NTHi produces high rates of bulla infection and high bacterial titers in bulla fluids; bacteria can also spread down the respiratory tract to the mouse lung. An innate immune response is detected in the bulla of Junbo mice following NTHi infection, and bacteria are maintained in some ears at least up to day 56 post-inoculation. The Junbo/NTHi infection model facilitates studies on bacterial pathogenesis and antimicrobial intervention regimens and vaccines for better treatment and prevention of NTHi middle ear infection. © 2017 by John Wiley & Sons, Inc.


Concordance of peripheral blood and bone marrow measurable residual disease in adult acute lymphoblastic leukemia.
Monitoring of measurable residual disease (MRD) is essential to the management of acute lymphoblastic leukemia (ALL) and is typically performed through repeated bone marrow (BM) assessments. Using a next-generation sequencing (NGS) MRD platform, we performed a prospective observational study evaluating the correlation between peripheral blood (PB) and BM MRD in adults with ALL receiving cellular therapies (hematopoietic cell transplantation [HCT] and chimeric antigen receptor T-cell [CAR-T] therapies). Among the study cohort (N = 69 patients; 126 paired PB/BM samples), we found strong correlation between PB and BM MRD (r = 0.87; P < .001), with a sensitivity and specificity of MRD detection in the PB of 87% and 90%, respectively, relative to MRD in the BM. MRD became detectable in the PB in 100% of patients who subsequently relapsed following HCT, with median time from MRD+ to clinical relapse of 90 days, and in 85% of patients who relapsed following CAR T, with median time from MRD+ to clinical relapse of 60 days. In adult patients with ALL undergoing cellular therapies, we demonstrate strong concordance between NGS-based MRD detected in the PB and BM. Monitoring of ALL MRD in the PB appears to be an adequate alternative to frequent invasive BM evaluations in this clinical setting.


[Expression of Caspase-3 and apoptosis in interface membranes of aseptically-loose total hip replacement].
To observe expression of Caspase-3 and apoptosis around the prosthesis and explore the relationship of the expression and the apoptosis with the peri-implant osteolysis. From April 2001 to August 2006, 16 patients (10 males, 6 females) underwent the revision total hip arthroplasty surgery, who had the primary total hip arthroplasty at the ages of 45-67 years and had the revision total hip arthroplasty at the ages of 55-78 years, with the implantation duration of 7-13 years. According to their preoperative X-ray films and the findings during the operation, the patients were divided into two groups: the loose/osteolytic group (n=8) and the loose/non-osteolytic group (n=8). The interface tissues were obtained from the peri-implant region in the patients. The synovial samples were taken from another 6 patients (2 males, 4 females; age, 54-68 years; illness course, 9-15 years), who underwent the primary total hip arthroplasty for osteoarthritis. These 6 patients were used as controls. The tissues were prepared for the immunohistochemical assays to determine the expression of Caspase-3. The TUNEL assays were performed to quantify the apoptotic cells. The quantitative analysis on the positive cells and the correlation with the presence of the particulate wear debris and the severity of osteolysis were also performed. The level of the expression for Caspase-3 and the apoptosis index in the loose/osteolytic group were significantly increased when compared with those in the loose/non-osteolytic group and the control group (P<0.01). The polyethylene particles were surrounded by more positive cells than the metal particles. The positive cells were present at a higher level in the tissue sections where the high-wear status was present when compared with the areas where the low-wear status was present (P <0.05). There is a statistical correlation of the Caspase-3 expression to the apoptosis index and to the presence of the particulate wear debris and the severity of osteolysis, which may be one of the key points for the bone reconstruction inhibition and the bone resorption at the bone-implant interface under the stimulation of the wear debris. The apoptosis is involved in the pathogenesis of the Caspase-3.


Analysis of the Mutational Landscape of Osteosarcomas Identifies Genes Related to Metastasis and Prognosis and Disrupted Biological Pathways of Immune Response and Bone Development.
Osteosarcoma (OS) is the most prevalent type of bone tumor, but slow progress has been achieved in disentangling the full set of genomic events involved in its initiation and progression. We assessed by NGS the mutational spectrum of 28 primary OSs from Brazilian patients, and identified 445 potentially deleterious SNVs/indels and 1176 copy number alterations (CNAs). TP53 was the most recurrently mutated gene, with an overall rate of ~60%, considering SNVs/indels and CNAs. The most frequent CNAs (~60%) were gains at 1q21.2q21.3, 6p21.1, and 8q13.3q24.22, and losses at 10q26 and 13q14.3q21.1. Seven cases presented CNA patterns reminiscent of complex events (chromothripsis and chromoanasynthesis). Putative RB1 and TP53 germline variants were found in five samples associated with metastasis at diagnosis along with complex genomic patterns of CNAs. PTPRQ, KNL1, ZFHX4, and DMD alterations were prevalent in metastatic or deceased patients, being potentially indicative of poor prognosis. TNFRSF11B, involved in skeletal system development and maintenance, emerged as a candidate for osteosarcomagenesis due to its biological function and a high frequency of copy number gains. A protein-protein network enrichment highlighted biological pathways involved in immunity and bone development. Our findings reinforced the high genomic OS instability and heterogeneity, and led to the identification of novel disrupted genes deserving further evaluation as biomarkers due to their association with poor outcomes.


Auxin requirements for a meristematic state in roots depend on a dual brassinosteroid function.
Root meristem organization is maintained by an interplay between hormone signaling pathways that both interpret and determine their accumulation and distribution. The interacting hormones Brassinosteroids (BR) and auxin control the number of meristematic cells in the Arabidopsis root. BR was reported both to promote auxin signaling input and to repress auxin signaling output. Whether these contradicting molecular outcomes co-occur and what their significance in meristem function is remain unclear. Here, we established a dual effect of BR on auxin, with BR simultaneously promoting auxin biosynthesis and repressing auxin transcriptional output, which is essential for meristem maintenance. Blocking BR-induced auxin synthesis resulted in rapid BR-mediated meristem loss. Conversely, plants with reduced BR levels were resistant to a critical loss of auxin biosynthesis, maintaining their meristem morphology. In agreement, injured root meristems, which rely solely on local auxin synthesis, regenerated when both auxin and BR synthesis were inhibited. Use of BIN2 as a tool to selectively inhibit BR signaling yielded meristems with distinct phenotypes depending on the perturbed tissue: meristem reminiscent either of BR-deficient mutants or of high BR exposure. This enabled mapping of the BR-auxin interaction that maintains the meristem to the outer epidermis and lateral root cap tissues and demonstrated the essentiality of BR signaling in these tissues for meristem response to BR. BR activity in internal tissues however, proved necessary to control BR levels. Together, we demonstrate a basis for inter-tissue coordination and how a critical ratio between these hormones determines the meristematic state.


Dietary macronutrient composition influences tissue trace element accumulation in diabetic Sprague-Dawley rats.
The purpose of the present investigation was to study the role of two potential contributory factors, hyperphagia and alterations in fuel metabolism, on the development of tissue trace element accumulation in the experimentally induced diabetic rat. The role of increased mineral intake associated with diabetic hyperphagia on tissue trace element accumulation was evaluated by feeding control and diabetic rats high-carbohydrate (HC) diets which varied in Zn, Cu, Mn, and Mg concentrations. Diabetic rats were hyperphagic and had lower plasma Mg, and higher liver Zn, Cu, and Mn concentrations than control rats, regardless of dietary mineral intake. In a second study, diabetic hyperphagia was reduced by feeding control and diabetic rats a HC, high-fat (HF), or high-protein (HP) diet; the effects of altering diabetic metabolism on trace element status was studied. Liver Mn and Zn concentrations of diabetic rats fed the HF diet were lower than diabetic rats fed the HC diet and HP diet, and were similar to control rats. Liver Cu concentrations of diabetic rats fed the HF and HP diets were lower than diabetic rats fed the HC diet and were similar to control rats. While diabetic rats, in general, had higher plasma glucagon concentrations and lower percent body fat than control rats, diabetic rats fed the HF diet had similar plasma glucagon and percent body fat to control rats. These data suggest that tissue-specific biochemical needs, such as the need for metals as cofactors for enzymes, rather than hyperphagia per se, may drive the accumulation of trace elements in the diabetic animal.


Growth hormone-releasing hormone antagonist MZ-4-71 inhibits in vivo proliferation of Caki-I renal adenocarcinoma.
In view of evidence that growth hormone (GH) and insulin-like growth factors (IGF) may play a role in the development of renal cell carcinoma (RCC), we investigated the effects of growth hormone-releasing hormone (GH-RH) antagonist MZ-4-71 on the proliferation of the human renal adenocarcinoma cell line Caki-I in vitro and in vivo. Male nude mice bearing xenografts of human Caki-I RCC were treated for 4 weeks with MZ-4-71 injected s.c. twice daily at a dose of 20 microg per animal. Tumor growth, serum, liver, and tumor IGF levels and IGF-I receptor concentrations in Caki-I cell membranes were measured. After 4 weeks of therapy, the final volume of Caki-I tumors in nude mice treated with MZ-4-71 was significantly (P < 0.01) decreased to 52.6 +/- 12.3 mm3 as compared with controls that measured 504.2 +/- 104.1 mm3. Treatment with GH-RH antagonist also significantly reduced tumor weight, serum levels of GH and IGF-I, liver concentrations of IGF-I, and tumor levels of IGF-I and IGF-II. High-affinity binding sites for IGF-I were detected in the cell membranes of Caki-I tumors. IGF-I and IGF-II stimulated the proliferation of Caki-I cells in tissue cultures. Antagonist MZ-4-71 could inhibit in vitro growth of Caki-I cells, but only at high concentrations. Our findings demonstrate that GH-RH antagonist MZ-4-71 can significantly inhibit the growth of Caki-I RCC. MZ-4-71 may exert its suppressive effect on tumor growth through a reduction in GH release from the pituitary and the subsequent decrease in the production of IGF-I in the liver and IGF-I and II by the tumors. The efficacy of MZ-4-71 suggests that this compound could be considered for the therapy of recurrent or metastatic RCC.


Automatic tube compensation (ATC).
Automatic tube compensation (ATC) is a new option to compensate for the non-linearly flow-dependent pressure drop across an endotracheal or tracheostomy tube (ETT) during inspiration and expiration. ATC is based on a closed-loop working principle. ATC is not a true ventilatory mode but rather a new option which can be combined with all conventional ventilatory modes. ATC compensates for the tube-related additional work of breathing. As of yet, ATC has been associated with certain benefits for the tracheally intubated spontaneously breathing patient. Among these, reduced work of breathing, preservation of the natural "noisy" breathing pattern, enhanced synchronization between the patient and the ventilator, and improvement of respiratory comfort seem to be most important. Moreover, sufficient spontaneous breathing with ATC alone, i.e. without any additional ventilatory assist, might help to predict more accurately readiness for extubation in the last phase of weaning from mechanical ventilation. Furthermore, it has been shown in patients with acute lung injury that ATC unloaded the inspiratory muscles and increased alveolar ventilation without adversely affecting cardiorespiratory function. It is the purpose of this article to describe the working principle of ATC and to give a review of the actual scientific discussion concerning ATC.


Statin therapy improves survival in patients with severe pulmonary hypertension: a propensity score matching study.
Inflammation is an increasingly recognized hallmark of pulmonary hypertension (PH). Statins have been shown to attenuate key pathologic mechanisms via pleiotropic effects in animal models. However, clinical benefit of statins in patients with PH is unknown and their effect on mortality has not been studied. We performed a retrospective analysis of patients between January 2002 to January 2012, with severe PH (pulmonary artery systolic pressure ≥60 mmHg) and preserved left ventricular function (ejection fraction ≥50%), defined by transthoracic echocardiograms. Patients were divided into two groups based on statin therapy for 12 consecutive months after diagnosis of PH. Propensity score matching was performed. Subgroup analysis was done based on COPD status. Study endpoint was 1-year all-cause mortality and hospitalization. 2363 patients (age 71 ± 16; 31% male) were included; 140 (6%) were on statin therapy. Overall 1-year mortality was 34%. Following propensity score matching, 138 patients were included in the statin group and 624 patients in the no-statin group; all-cause mortality was significantly lower in the statin group compared with the no-statin group [15.2 vs. 33.8%, HR 0.42 (95% CI 0.27, 0.66), p < 0.001], but hospitalization was comparable between two groups. After stratifying patients based on COPD status, patients with COPD showed a marginally significant survival benefit from statins [HR 0.53 (95% CI 0.26, 1.10), p = 0.09]; and statins significantly reduced 1-year all-cause mortality in patients without COPD [HR 0.36 (95% CI 0.19, 0.67), p = 0.001]. We found no significant difference in the effect of statins on patients with COPD compared to those without (p = 0.16). Statin therapy is associated with reduced mortality risk in patients with severe PH and preserved left ventricular function. This beneficial effect was not found to be dependent on COPD status. These novel findings should be confirmed in large randomized trials.


Plumbagin prevents osteoarthritis in human chondrocytes through Nrf-2 activation.
Osteoarthritis (OA) is an inflammatory disorder dealing with the focal degradation of articular cartilage. Oxidative stress and inflammation are the major events in OA. The present study aimed at identifying the mechanism of the potent antioxidant, plumbagin, in protecting against hydrogen peroxide (H2O2)‑induced chondrocyte oxidative stress and inflammatory signaling. Oxidative stress was determined by measuring reactive oxygen species, lipid peroxidation, non‑enzymic (glutathione; GSH) and enzymic antioxidant activities (GSH, glutathione S‑transferase, glutathione peroxidase, superoxide dismutase, catalase). Expression levels of nuclear factor (erythroid‑derived 2)‑like 2 (Nrf‑2), heme oxygenase 1 (HO‑1), NAD(P)H:quinone oxidoreductase 1 (NQO‑1), nuclear factor‑κB (NF‑κB), cyclooxygenase‑2 (COX‑2) and inducible NO synthase (iNOS) were determined by western blot analysis. Pro‑inflammatory cytokine expression levels were assessed using ELISA. Results from reactive oxygen species generation, lipid peroxidation content and antioxidant enzyme activities demonstrated that plumbagin significantly inhibited oxidative stress status in H2O2‑induced chondrocytes. In addition, plumbagin modulated transcription factors involved in redox and inflammation regulation, including NF‑κB and Nrf‑2, by nuclear expression. plumbagin enhanced antioxidant status by increasing the expression levels of Nrf‑2 target genes, including HO‑1 and NQO‑1. An anti‑inflammatory effect against chondrocyte‑induced inflammation was demonstrated by downregulating COX‑2, iNOS and pro‑inflammatory cytokine expression levels (tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑8). The present study identified strong evidence for a protective role of plumbagin against H2O2-induced oxidative stress and inflammation in chondrocytes by modulating redox signaling transcription factors.


Cross-regulation between type I and type II NKT cells in regulating tumor immunity: a new immunoregulatory axis.
Negative immunoregulation is a major barrier to successful cancer immunotherapy. The NKT cell is known to be one such regulator. In this study we explored the roles of and interaction between the classical type I NKT cell and the poorly understood type II NKT cell in the regulation of tumor immunity. Selective stimulation of type II NKT cells suppressed immunosurveillance, whereas stimulation of type I NKT cells protected against tumor growth even when responses were relatively skewed toward Th2 cytokines. When both were stimulated simultaneously, type II NKT cells appeared to suppress the activation in vitro and protective effect in vivo of type I NKT cells. In the absence of type I, suppression by type II NKT cells increased, suggesting that type I cells reduce the suppressive effect of type II NKT cells. Thus, in tumor immunity type I and type II NKT cells have opposite and counteractive roles and define a new immunoregulatory axis. Alteration of the balance between the protective type I and the suppressive type II NKT cell may be exploited for therapeutic intervention in cancer.


sd(2) Graphene: Kagome band in a hexagonal lattice.
Graphene, made of sp^{2} hybridized carbon, is characterized with a Dirac band, representative of its underlying 2D hexagonal lattice. The fundamental understanding of graphene has recently spurred a surge in the search for 2D topological quantum phases in solid-state materials. Here, we propose a new form of 2D material, consisting of sd^{2} hybridized transition metal atoms in hexagonal lattice, called sd^{2} "graphene." The sd^{2} graphene is characterized by bond-centered electronic hopping, which transforms the apparent atomic hexagonal lattice into the physics of a kagome lattice that may exhibit a wide range of topological quantum phases. Based on first-principles calculations, room-temperature quantum anomalous Hall states with an energy gap of ∼0.1 eV are demonstrated for one such lattice made of W, which can be epitaxially grown on a semiconductor surface of 1/3 monolayer Cl-covered Si(111), with high thermodynamic and kinetic stability.


Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia.
We treated 45 adult patients with T-lymphoblastic lymphoma (T-LBL) (age range 15-61 years) with 2 protocols designed for adult acute lymphoblastic leukemia (ALL). An encouraging cure rate of 90% was recently reported for T-LBL in children treated with a similar approach. In our study, an 8-drug standard induction was administered over 8 weeks including prophylactic cranial (24 Gy) and mediastinal irradiation (24 Gy) followed by consolidation and reinduction therapy. At diagnosis, 91% of the 45 patients showed a mediastinal tumor and 40% had pleural/pericardial effusions; 73% of the patients had stage III/IV disease. Overall, 42 patients (93%) achieved a complete remission (CR), 2 patients (4%) achieved a partial remission, and 1 patient (2%) died during induction. In patients with stage I-III disease (n = 18) the CR rate was 100% compared with 89% in stage IV (n = 27). There were 15 patients who relapsed (36%) within 12 months. The majority of relapses (47%) occurred in the mediastinum (n = 7) despite mediastinal irradiation with 24 Gy in 6 out of 7 patients. The estimates for overall survival, continuous CR, and disease-free survival at 7 years are 51%, 65%, and 62%, respectively. Stage, age, lactate dehydrogenase, and all other parameters had no influence on achievement of CR or outcome. This study demonstrates in a large cohort of patients with adult T-LBL that a high CR rate and a favorable outcome can be achieved with an ALL-type regimen. Mediastinal recurrence was the major obstacle and further improvement by intensification of chemotherapy, increased dose of mediastinal irradiation (36 Gy), and extended indications for stem cell transplantation seem to be required.


Comparison of gene expression profiles among papilla, medulla and cortex in rat kidney.
The aim of this study was to compare gene expression profiles in the different kidney regions as the basis for toxicogenomics. Rat kidney was separated into papilla, medulla and cortex, and total RNA was isolated from these and from the whole slice. Gene expression profiling was performed using Affymetrix Rat Genome 230 2.0 Array. When global normalization was applied, the expression of beta-actin or GAPDH varied among the regions. It was considered that such a comparison could not be made, especially between papilla and other portions, since the production of total mRNA in the former was relatively low. In fact, ANOVA was performed on the gene expression values with global normalization in papilla, medulla, cortex, and whole slice, and the numbers of genes appeared to be the highest in papilla. It was also observed that many genes showed their maximum or minimum in the whole slice, which was theoretically impossible. To overcome the problems associated with global normalization, the "percellome" normalization (a way to obtain the values directly related to the copies of mRNA per cell) was employed to compare the regions. In applying this procedure, probe sets with regional difference in expression were efficiently extracted by ANOVA. When they were sorted by the fold difference to other regions, the higher rank was occupied by genes characteristic of the functions of kidney, i.e., channels, transporters and metabolic enzymes. Some of them were consistent with the literature and were related to pathophysiological phenomena. Comprehensive comparison of data of gene expression in the renal anatomical area will greatly enhance studies of the physiological function and mechanism of toxicity in kidney.


Automated analysis of the American College of Radiology mammographic accreditation phantom images.
A significant metric in federal mammography quality standards is the phantom image quality assessment. The present work seeks to demonstrate that automated image analyses for American College of Radiology (ACR) mammographic accreditation phantom (MAP) images may be performed by a computer with objectivity, once a human acceptance level has been established. Twelve MAP images were generated with different x-ray techniques and digitized. Nineteen medical physicists in diagnostic roles (five of which were specially trained in mammography) viewed the original film images under similar conditions and provided individual scores for each test object (fibrils, microcalcifications, and nodules). Fourier domain template matching, used for low-level processing, combined with derivative filters, for intermediate-level processing, provided translation and rotation-independent localization of the test objects in the MAP images. The visibility classification decision was modeled by a Bayesian classifer using threshold contrast. The 50% visibility contrast threshold established by the trained observers' responses were: fibrils 1.010, microcalcifications 1.156, and nodules 1.016. Using these values as an estimate of human observer performance and given the automated localization of test objects, six images were graded with the computer algorithm. In all but one instance, the algorithm scored the images the same as the diagnostic physicists. In the case where it did not, the margin of disagreement was 10% due to the fact that the human scoring did not allow for half-visible fibrils (agreement occurred for the other test objects). The implication from this is that an operator-independent, machine-based scoring of MAP images is feasible and could be used as a tool to help eliminate the effect of observer variability within the current system, given proper, consistent digitization is performed.


Non-Debye response for the structural relaxation in glass-forming liquids: test of the Avramov model.
The experimentally observed characteristic features of the alpha-relaxation process in glass-forming liquids are the non-Arrhenius behavior of the structural relaxation times and the non-Debye character of the macroscopic relaxation function. The Avramov model in which relaxation is considered as an energy activation process of surmounting random barriers in liquid energy landscape was successfully applied to describe the temperature and pressure dependences of the macroscopic relaxation times or viscosity. In this paper, we consider the dielectric spectrum associated with Avramov model. The asymmetrical broadening of the loss spectra was found to be related directly to dispersion of the energy barrier distribution. However, it turns out that temperature dependence of the spectrum broadening as predicted by the Avromov model is at odds to experimental observation in glass-forming liquids.


Hypocretin role in posttraumatic stress disorder-like behaviors induced by a novel stress protocol in mice.
Posttraumatic stress disorder (PTSD) is a psychiatric disorder developed in individuals who expose to traumatic events. These patients may experience symptoms, such as recurrent unwanted memory of the traumatic event, avoidance of reminders of the trauma, increased arousal, and cognitive difficulty. The hypocretinergic system originates from the lateral hypothalamic area (LHA) and projects diffusely to the whole brain, and hypocretin may be involved in the features of stress-related disorder, PTSD. Our study aimed to investigate the role of basolateral amygdala (BLA) hypocretin signals in the pathophysiology of PTSD-like symptoms induced by the modified multiple-prolonged stress (MPS) protocol. The BLA, a brain region involved in fear-related behaviors, receives the hypocretin projections. In this study, TCS1102, a dual hypocretin receptor antagonist, was used to block the hypocretin signal in BLA. Our data indicated that the MPS protocol is a potential PTSD-like paradigm in mice. Meanwhile, the blockade of hypocretin signaling in the BLA relieved the MPS-induced fear response, and partially reduced PTSD-like anxiety behaviors performed by the open field test (OFT) and elevated plus maze (EPM) task. Our findings suggest that the hypocretinergic system is a potential therapeutic approach for PTSD treatment. With further research, the hypocretin-based medication can be a candidate for human PTSD treatment.


Hemoplasma infection in HIV-positive patient, Brazil.
Hemotrophic mycoplasmas infect a variety of mammals. Although infection in humans is rarely reported, an association with an immunocompromised state has been suggested. We report a case of a Mycoplasma haemofelis-like infection in an HIV-positive patient co-infected with Bartonella henselae.


Contrast-carrying liposomes. Current status.
The goal of recent research has been to encapsulate standard, water-soluble radiographic contrast media (RCM) into liposomes, in order to direct them to reticuloendothelial tissues. Toward this end several varieties of contrast-carrying liposomes (CCLs) have been prepared. Each of these has proven effective in opacifying the liver and spleen of animals on computed tomography (CT). The suitability of two new encapsulation techniques: (1) Microemulsification (MELs), and (2) Dehydration Rehydration Vesicles (DRVs), for CCL production has been explored recently. Each of these two new preparative techniques were valuable in the effort to "scale-up" the CCL production process, leading to "pharmaceutically acceptable" preparation.


LncRNA FTO-IT1 promotes glycolysis and progression of hepatocellular carcinoma through modulating FTO-mediated N6-methyladenosine modification on GLUT1 and PKM2.
Long non-coding RNAs (LncRNAs) have been extensively studied to play essential roles in tumor progression. However, more in-depth studies are waiting to be solved on how lncRNAs regulate the progression of hepatocellular carcinoma (HCC). Different expression levels of lncRNAs in HCC cells were compared by analysis of Gene Expression Omnibus and The Cancer Genome Atlas databases. The effects of lncRNA FTO Intronic Transcript 1 (FTO-IT1) on HCC cells were assessed by gain- and loss-of-function experiments. Colony formation assay, Edu assay, glucose uptake and lactic acid production assay were performed to evaluate the regulation of proliferation and glycolysis of HCC cells by FTO-IT1. The binding between protein interleukin enhancer binding factor 2/3 (ILF2/ILF3) and FTO-IT1 was determined by RNA pull-down, mass spectroscopy and RNA immunoprecipitation experiments. RNA stability assay, quantitative reverse transcription PCR and Western blot were employed to determine the regulatory mechanisms of FTO-IT1 on fat mass and obesity-associated (FTO). Methylated RNA immunoprecipitation assay was used to assessed the regulation of key enzymes of glycolysis by FTO. The role of FTO-IT1/FTO in vivo was confirmed via xenograft tumor model. LncRNA FTO-IT1, an intronic region transcript of FTO gene, was highly expressed in HCC and associated with poor prognosis of patients with HCC. FTO-IT1 was related to proliferation and glycolysis of HCC cells, and contributed to the malignant progression of HCC by promoting glycolysis. Mechanistically, FTO-IT1 induced stabilization of FTO mRNA by recruiting ILF2/ILF3 protein complex to 3'UTR of FTO mRNA. As a demethylase for N6-methyladenosine (m6A), FTO decreased m6A modification on mRNAs of glycolysis associated genes including GLUT1, PKM2, and c-Myc which alleviated the YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated mRNA degradation. Therefore, the upregulated expression of FTO-IT1 leaded to overexpression of GLUT1, PKM2, and c-Myc by which enhanced glycolysis of HCC. Meanwhile, it was found that c-Myc transcriptional regulated expression of FTO-IT1 by binding to its promoter area under hypo-glucose condition, forming a reciprocal loop between c-Myc and FTO-IT1. This study identified an important role of the FTO-IT1/FTO axis mediated m6A modification of glycolytic genes contributed to glycolysis and tumorigenesis of HCC, and FTO-IT1 might be served as a new therapeutic target for HCC.


Quantitation of IgM, IgA and IgG rheumatoid factors by ELISA in rheumatoid arthritis and other rheumatic disorders.
We describe the evaluation of an enzyme-linked immunosorbent-assay (ELISA) for the measurement of IgM, IgA and IgG rheumatoid factor (RF). Results were obtained from sera of normal controls and patients with different rheumatic disorders in a cross-sectional study. Both human and rabbit IgG could be used as antigen in the assays. IgA-RF and IgG-RF were measured after pepsin digestion. The WHO reference preparation was used to standardise IgM-RF, but could not be used in the IgA- and IgG-RF assay, because neither IgA- nor IgG-RF could be detected in this standard serum. The ELISA for detection of RF is a highly sensitive and reproducible method and quantitation of results can be standardised. It yields good discriminative values for RA versus controls, in particular when more RF-isotypes are determined. In RA patients a correlation between IgM-, IgA- and IgG-RF concentrations does exist, although a wide variation was found in the ratio of these concentrations.


Investigation of Immunostimulatory Effects of IFN-γ Cytokine and CD40 Ligand Costimulatory Molecule for Development of HIV-1 Therapeutic Vaccine Candidate.
The most crucial disadvantage of DNA-based vaccines is their low immunogenicity; therefore, finding an effectual adjuvant is essential for their development. Herein, immunostimulatory effects of IFNγ cytokine and a CD40 ligand (CD40L) costimulatory molecule are evaluated as combined with an antigen, and also linked to an antigen in mice. For this purpose, after preparation of the HIV-1 Nef, IFNγ, and CD40L DNA constructs, and also their recombinant protein in an Escherichia coli expression system, nine groups of female BALB/c mice are immunized with different regimens of DNA constructs. About 3 weeks and also 3 months after the last injection, humoral and cellular immune responses are assessed in mice sera and splenocytes. Additionally, mice splenocytes are exposed to single-cycle replicable (SCR) HIV-1 virions for evaluating their potency in the secretion of cytokines in vitro. The data indicate that the linkage of IFNγ and CD40L to Nef antigen can significantly induce the Th-1 pathway and activate cytotoxic T lymphocytes compared to other regimens. Moreover, groups receiving the IFNγ-Nef and CD40L-Nef fusion DNA constructs show higher secretion of IFNγ and TNF-α from virion-infected lymphocytes than other groups. Therefore, the IFNγ-Nef and CD40L-Nef fusion DNA constructs are suggested to be a potential option for development of an efficient HIV-1 vaccine.


Variable region of betanodavirus RNA2 is sufficient to determine host specificity.
Betanodaviruses, the causative agents of viral nervous necrosis in marine fish, have bipartite positive-sense RNA genomes. The viruses have been classified into 4 distinct types based on nucleotide sequence similarities in the variable region (the so-called T4 region) of the smaller genomic segment RNA2 (1.4 kb). Betanodaviruses have marked host specificity, although the primary structures of the viral RNAs and encoded proteins are similar among the viruses. We have previously demonstrated, using reassortants between striped jack nervous necrosis virus (SJNNV) and redspotted grouper nervous necrosis virus (RGNNV), that RNA2, which encodes the coat protein, strictly controls host specificity. However, because RNA2 is large, we were unable to propose a mechanism underlying this RNA2-based host specificity. To identify the RNA2 region that controls host specificity, we constructed RNA2 chimeric viruses from SJNNV and RGNNV and tested their infectivity in the original host fish, striped jack Pseudocaranx dentex and sevenband grouper Epinephelus septemfasciatus. Among these chimeric viruses, SJNNV mutants containing the variable region of RGNNV RNA2 infected sevenband grouper larvae in a manner similar to RGNNV, while RGNNV mutants containing the variable region of SJNNV RNA2 infected striped jack larvae in a manner similar to SJNNV. Immunofluorescence microscopic studies using anti-SJNNV polyclonal antibodies revealed that these chimeric viruses multiplied in the brains, spinal cords and retinas of the infected fish, as in infections by the parental viruses. These results indicate that the variable region of RNA2 is sufficient to control host specificity in SJNNV and RGNNV.


Expression of myosin heavy chain isoforms in the human supraspinatus muscle: variations related to age and sex.
The contractile function of skeletal muscles is primarily regulated by the expression of myosin heavy chain (MHC) isoforms. Adult human skeletal muscles express three MHC isoforms (MHC-I, MHC-IIa and MHC-IIx). The muscles mainly expressing MHC-I are slow but resistant to fatigue, while those with major expression of MHC-IIa and MHC-IIx are fast and powerful but less resistant to fatigue. In this study, mRNA levels of the MHC isoforms were assessed in 24 human supraspinatus muscles by reverse-transcription polymerase chain reaction. The average expression of the MHC-I isoform was 36.72%, that of the MHC-IIa isoform was 33.52%, and the average expression of the MHC-IIx isoform was 29.76%. The higher average expression of the two MHC-II isoforms taken together (63.28%) indicates that the human supraspinatus muscle is a powerful, fast muscle with relatively low resistance to fatigue, in accordance with its role in the elevation of the upper extremity. In women, and more markedly in older women, the trend towards upregulation of the fast MHC-II isoforms and downregulation of the slow MHC-I isoform, which is absent in males, may improve our understanding of possible causes of the subacromial impingement syndrome.


[In vitro antibacterial activity of a new macrolide: miokamycin. Comparison with erythromycin and josamycin].
Minimal inhibitory concentrations (MIC) of miokamycin (M) were evaluated by agar dilution, comparatively with erythromycin (E) and josamycin (J) for 81 bacterial strains chosen as a function of susceptibility and resistance to Macrolides-Lincosamides-Streptogramins group (MLS). On Gram positive cocci, mode MIC of E, J, and M for strains sensitive to MLS were respectively (micrograms/ml): Staphylococci: 0.25; 1; 2-Streptococci and Pneumococci: 0.016; 0.03-0.12; 0.06-0.25-Enterococci: 0.5; 0.5-1; 1-2. Activity of the three antibiotics was similar against Staphylococci resistant to lincomycin and streptogramin A, those resistant to streptogramins A and B, on Staphylococci and Streptococci only resistant to lincosamides by inactivation. M, as J, was active on coagulase negative (Staphylococci resistant to E by inactivation and on MLBB inducible Staphylococci; on these strains, M is a resistance non-inducible macrolide. Activity of E, J and M was reduced on MLSB inducible Streptococci. The three antibiotics were inactive on Staphylococci Streptococci and Enterococci MLSB resistant constitutive. On Haemophilus, E (2-8 micrograms/ml) was more active than J (2-16) and M (8-32). Thus, M, as J, was shown to be among macrolide antibiotics of resistance non-inducing type on MLSB inducible resistant Staphylococci; its activity was slightly inferior to that of J, but very similar to that of spiramycin, other macrolide of this group.


Ultrastructural features of phagocytosis and intracellular killing of Candida albicans by mouse polymorphonuclear phagocyte monolayers.
Phagocyte monolayers provided a simple method of following ultrastructural events associated with phagocytosis and intracellular killing of Candida albicans. Preformed monolayers of mouse polymorphonuclear (PMN) phagocytes attached to glass coverslips were incubated with blastospore phase C. albicans and then examined by scanning and transmission electron microscopy. Scanning electron microscopy revealed phagocytosis of C. albicans by mouse phagocytes. Ingestion of the organism was facilitated by the production of lamellipodia by the phagocytes. Transmission electron microscopy revealed complete phagocytosis of C. albicans and the fusion of lysosomal granules with loose and tight phagosomes. Ingested C. albicans remained structurally intact after 2 hr incubation in blastospore-free medium. However, cytoplasmic alterations were clearly evident, with a patchy loss of electron density. Alterations of the blastospore cell wall were also observed, with complete disruption of the plasma membrane but the wall remaining morphologically intact.


Microbiological quality of drinking rainwater in the inland region of Pajeú, Pernambuco, Northeast Brazil.
Despite all efforts to store and reduce its consumption, water is becoming less inexhaustible and its quality is falling faster. Considering that water is essential to animal life, it is necessary to adopt measures to ensure its sanitary conditions in order to be fit for consumption. The aim of this study was to analyze the microbiological quality of drinking rainwater used by rural communities of Tuparetama, a small town located in Northeast Brazil. The study covered seven rural communities, totaling 66 households. In each household two samples were collected, one from a tank and the other from a clay pot located inside the home, resulting in 132 samples (tank plus clay pot). Approximately 90% of samples were below the standard recommended by the current legislation, being considered unfit for human consumption. Part of this high microbiological contamination of drinking rainwater could be related to the lack of sanitary education and of an adequate sewerage sanitation system.


Brain dynamic mechanisms of scale effect in visual spatial attention.
The dynamic mechanisms of the early event-related potential scale effect of different attentive regions in the brain was studied. The paradigm of this experiment is the precue-target visual search paradigm by event-related potential technique. The results showed that the reaction time was shortened with the reduction of cue scale, a cue to how big the search area would be, and fixed target stimulus, while the amplitudes of P1 and N1 components of event-related potentials increased. These results not only provided the electrophysiological evidences that supported the zoom-lens theory, but also indicated that the zoom-lens effect happened at the early selected attention period. The results also showed that there existed two kinds of separation in the P2 effect.


[Perindopril and losartan attenuate bleomycin A5-induced pulmonary fibrosis in rats].
To evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor (AT-1 receptor) blocker on the progression of rat pulmonary fibrosis induced by bleomycin A5. Twenty-four male Wistar rats were randomized into pulmonary fibrosis model, perindopril treatment, losartan treatment and control groups. In the former 3 groups, pulmonary fibrosis was induced via intratracheal injection of bleomycin A5 (5 mg/kg), after which the rats in the perindopril and losartan groups received intragastric administration of the corresponding agents at the daily dose of 2 mg/kg and 10 m/kg, respectively. The rats in the control group had intratracheal injection of normal saline only. In the 4th week, the histological changes of the lung tissues were examined microscopically with Masson staining. Hydroxyproline content in the lungs was measured, and the protein expressions of AT-1 receptor, TGF-beta1 and IkappaBalpha were examined using Western blotting. DNA binding activity of NF-kappaB was analyzed with electrophoretic gel mobility shift assay (EMSA), and zymography was used to assess the activity of matrix metalloproteinase-2 and 9 (MMP-2, 9). Both perindopril and losartan treatment significantly reduced the pulmonary fibrosis score, content of hydroxyproline, protein expression of TGF-beta1, DNA binding activity of NF-kappaB and MMP-2, 9 activity, and increased cytoplasmic protein expression of IkappaBalpha. Perindopril treatment lowered the protein level of AT-1 receptor. Perindopril and losartan may inhibit bleomycin A5-induced pulmonary fibrosis in rats by reducing the protein expression of TGF-beta1 and suppressing the DNA binding activity of NF-kappaB and MMP-2, 9 activity.


[Exosomes derived from PMN-MDSCs preconditioned by hypoxia attenuate arthropathy of collagen-induced arthritis mice].
Objective To investigate the role of the exosomes (EX) derived from polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) preconditioned by hypoxia in the treatment of the collagen-induced arthritis (CIA) mouse model. Methods CIA mouse model was induced by bovine type II collagen(Col2) and Freund's adjuvant. PMN-MDSCs were isolated from CIA mouse spleen by magnetic beads. PMN-MDSC-derived exosomes (PMN-MDSC-EXs) were extracted from the supernatant of PMN-MDSCs under normal (210 mL/L O2) and hypoxia (10 mL/L O2) conditions. PMN-MDSC-EXs were identified by transmission electron microscopy and flow cytometry. The surface-specific markers of PMN-MDSC-EXs were detected by Western blotting, including CD9, CD63, heat shock protein 70 (HSP70), and calnexin. PMN-MDSC-EXs were added to the CD4+ T cell proliferation system in vitro to detect immunosuppressive ability. PMN-MDSC-EXs were injected into the CIA mouse model through the tail vein. The clinic scores of joints were recorded every three days, and the joint structures were observed by HE staining. The levels of total IgG, Col2 antibody, interferon γ (IFN-γ), interleukin 17 (IL-17) in the serum were detected by ELISA. The content of miR-29a-3p and miR-93-5p in PMN-MDSC-EXs under normal and hypoxia conditions was detected by real-time quantitative PCR. Results PMN-MDSCs were successfully isolated from the spleens of CIA mice and PMN-MDSC-EXs was prepared under normal and hypoxia conditions. Compared with normal PMN-MDSC-EXs, hypoxia-treated PMN-MDSC-EXs could inhibit the proliferation of CD4+ T cells more effectively. The swelling degree of toes, clinical scores, and joint damage in the group of hypoxia-treated PMN-MDSC-EXs were significantly reduced. The levels of total IgG, Col2 antibody, IFN-γ and IL-17 in the serum decreased after the treatment with hypoxia-treated PMN-MDSC-EXs. The content of miR-29a-3p and miR-93-5p in hypoxia-treated PMN-MDSC-EXs was much higher than that in normal PMN-MDSC-EXs. Conclusion Under hypoxia condition, the immunosuppressive ability of PMN-MDSC-EXs is stronger, which can alleviate the arthropathy of CIA mice more effectively.


Changes in plasma progesterone, estradiol, follicle-stimulating hormone and luteinizing hormone during diestrus and ovulation in rats with 5-day estrous cycles: effect of antibody against progesterone.
Progesterone secretion remained significantly higher during diestrus in the 5-day cyclic rat than in the 4-day cyclic animal. Injection of a sufficient amount of antiprogesterone serum (APS) at 2300 h on metestrus in a 5-day cycle advances ovulation and completion of the cycle by 1 day in the majority of animals (75 and 80%, respectively). Progesterone (250 micrograms) administered with APS eliminated the effect of the antiserum. Within 2 h after administration of APS, levels of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) elevated significantly, while a significant elevation of plasma estradiol above the control value followed as late as 36 h after the treatment. None of the 5-day cyclic rats treated with APS showed ovulatory increases of FSH and LH at 1700 h on the second day of diestrus, although 3 of the 4 animals receiving the same treatment ovulated by 1100 h on the following day. The onset of ovulatory release of gonadotropins might have been delayed for several hours in these animals. These results indicate that recurrence of the 5-day cycle is due to an elevated progesterone secretion on the morning of diestrus, and suggest that a prolongation of luteal progesterone secretion in an estrous cycle suppresses gonadotropin secretion. Rather than directly blocking the estrogen triggering of ovulatory LH surge, the prolonged secretion of luteal progesterone may delay the estrogen secretion itself, which decreases the threshold of the neural and/or hypophyseal structures for ovulatory LH release.


Association Between Nutritional Knowledge, Dietary Regimen, and Excess Body Weight in Primary School Teachers.
Peru is one of the developing countries with the highest prevalence of overweight and obesity in Latin America and Caribbean region. Primary school teachers are identified as a high-risk group for overweight and obesity. However, studies conducted in this population group are limited. This study evaluated the association between nutritional knowledge, dietary regimen, and excess body weight in primary school teachers. This was a cross-sectional study that included 151 teachers from two state schools in the eastern region of Lima, Peru. The level of nutritional knowledge was assessed using a validated questionnaire. Dietary regimen was also determined. The body mass index (BMI) was determined through self-reported weight and height. Logistic regression analysis was used to assess the association between possible risk factors with excess body weight among teachers. Inadequate nutritional knowledge level (AOR = 5.21, 95% CI: 1.31-20.93), being male teachers (AOR = 2.25, 95% CI: 1.13-4.45), and being married (AOR = 2.49, 95% CI: 1.17-5.30) were the significant predictors of excess body weight. In contrast, vegetarian teachers were less likely to have excess body weight (AOR = 0.35, 95% CI: 0.47-0.97). Future intervention programs should include improving nutritional knowledge with greater attention to male and married teachers to decrease the risk of excess body weight.


Oxidative stress and cardiomyocyte necrosis with elevated serum troponins: pathophysiologic mechanisms.
The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.


Minimum Resistance Anisotropy of Epitaxial Graphene on SiC.
We report on electronic transport measurements in rotational square probe configuration in combination with scanning tunneling potentiometry of epitaxial graphene monolayers which were fabricated by polymer-assisted sublimation growth on SiC substrates. The absence of bilayer graphene on the ultralow step edges of below 0.75 nm scrutinized by atomic force microscopy and scanning tunneling microscopy result in a not yet observed resistance isotropy of graphene on 4H- and 6H-SiC(0001) substrates as low as 2%. We combine microscopic electronic properties with nanoscale transport experiments and thereby disentangle the underlying microscopic scattering mechanism to explain the remaining resistance anisotropy. Eventually, this can be entirely attributed to the resistance and the number of substrate steps which induce local scattering. Thereby, our data represent the ultimate limit for resistance isotropy of epitaxial graphene on SiC for the given miscut of the substrate.


Modulation of the voltage-dependent anion channel (VDAC) by glutamate.
The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is a large channel permeable to anions, cations, ATP, and other metabolites. VDAC was purified from sheep brain synaptosomes or rat liver mitochondria using a reactive red-agarose column, in addition to the hydroxyapatitate column. The red-agarose column allowed further purification (over 98%), concentration of the protein over ten-fold, decreasing Triton X-100 concentration, and/or replacing Triton X-100 with other detergents, such as Nonidet P-40 or octylglucoside. This purified VDAC reconstituted into planar-lipid bilayer, had a unitary maximal conductance of 3.7 +/- 0.1 nS in 1 M NaCl, at 10 mV and was permeable to both large cations and anions. In the maximal conducting state, the permeability ratios for Na(+), acetylcholine(+), dopamine,(+) and glutamate(-), relative to Cl(-), were estimated to be 0.73, 0.6, 0.44, and 0.4, respectively. In contrast, in the subconducting state, glutamate(-) was impermeable, while the relative permeability to acetylcholine(+) increased and to dopamine(+) remained unchanged. At the high concentrations (0.1-0.5 M) used in the permeability experiments, glutamate eliminated the bell shape of the voltage dependence of VDAC channel conductance. Glutamate at concentrations of 1 to 20 mM, in the presence of 1 M NaCl, was found to modulate the VDAC channel activity. In single-channel experiments, at low voltages (+/-10 mV), glutamate induced rapid fluctuations of the channel between the fully open state and long-lived low-conducting states or short-lived closed state. Glutamate modification of the channel activity, at low voltages, is dependent on voltage, requiring short-time (20-60 sec) exposure of the channel to high membrane potentials. The effect of glutamate is specific, since it was observed in the presence of 1 M NaCl and it was not obtained with aspartate or GABA. These results suggest that VDAC possesses a specific glutamate-binding site that modulates its activity.


Open access fundholding endoscopy in the private sector.
We conducted a comparative study of 150 patients referred for endoscopy to an NHS hospital and 150 patients referred to an open access scheme in the private sector for fundholding GPs. The concept of consultoscopy, whereby a consultant gastroenterologist gives an opinion at the same visit as the endoscopy is performed, is introduced. Results showed a similar number of normal studies (about 40%) were performed in each group, although the number of examinations showing serious pathology was significantly higher in the fundholding group (p < 0.01). Patients seen in the fundholding scheme had less sedation, required fewer outpatient appointments, and the GPs were given more advice on further management than those seen in the non-fundholding group. We conclude that open access endoscopy in the private sector is a workable option and may result in work being transferred from NHS hospitals to the private sector unless NHS hospitals review their working practices. The concept of consultoscopy is a useful development on traditional open access systems.


Maternal outcome after abdominal packing for uncontrolled postpartum hemorrhage despite peripartum hysterectomy.
Intra-abdominal packing is a possible option for persistent bleeding following hysterectomy for postpartum hemorrhage. However, to date, only very limited data about maternal outcome after intra-abdominal packing for surgically uncontrolled hemorrhage following hysterectomy are available. The objective of the current study was to estimate maternal outcome after intra-abdominal packing following unsuccessful peripartum hysterectomy for postpartum hemorrhage. A questionnaire was mailed to all maternity units performing more than 850 deliveries per year. Inclusion criteria were: all cases of abdominal packing performed following unsuccessful peripartum hysterectomy for postpartum hemorrhage between 2003 and 2013. The primary outcome was success of intra-abdominal packing, defined as the arrest of hemorrhage with no need of additional procedure. The total number of deliveries during the study period that occurred in the 51 participating centers was 1,430,142. The centers reported a total of 718 (1 per 2000 deliveries) peripartum hysterectomies for PPH and 53 abdominal packings performed after unsuccessful peripartum hysterectomy (about 1 per 14 hysterectomies). A median of 5 [IQR 3-7] pads were used for packing. Abdominal packing was removed after a median of 39.5 hours [IQR 24-48]. The success rate of abdominal packing was 62% (33/53). Among the 20 (38%) women in whom bleeding did not stop following the use of abdominal packing, 6 required a second surgical intervention, 6 a pelvic artery embolization and the 8 other women had "only" further intensive resuscitation and pharmacological treatments. Finally, mortality rate was 24% (13/53). Our results suggest that abdominal packing, used for duration of 24 to 48 hours, seems to be an option as an ultimate procedure to control persistent life-threatening postpartum hemorrhage following peripartum hysterectomy.


Cost-effectiveness of denosumab compared with zoledronic acid in patients with breast cancer and bone metastases.
Results from a phase III clinical trial showed that denosumab significantly reduced the risk of first on-study and subsequent skeletal-related events (SREs) compared with zoledronic acid. This study aims to assess the cost-effectiveness of denosumab vs. zoledronic acid in the prevention of SREs in patients with advanced breast cancer and bone metastases. A Markov model was developed with 4-week model cycles and a 1-year time horizon. The health states were defined by SRE status (no SRE, first on-study SRE, subsequent SRE, no SRE but history of SRE) and SRE type (pathologic fracture, radiation to the bone, surgery to the bone, spinal cord compression). Costs (in 2011 US dollars) included drug, SRE treatment, and adverse event (AE) costs and were assessed from a third-party payer perspective. The primary outcome was incremental total cost per SRE avoided; the secondary outcome was incremental total cost per pathologic fracture avoided. One-way and probabilistic sensitivity analyses were used to assess the robustness of the model. During the 1-year treatment period, denosumab incurred $7522 higher costs ($30,033 for denosumab and $23,511 for zoledronic acid), 0.06 fewer SREs, and 0.02 fewer pathologic fractures per patient, which led to an incremental total cost per SRE and pathologic fracture avoided of $114,628 and $290,136, respectively, compared with zoledronic acid. Results were robust to 1-way and probabilistic sensitivity analyses. Although denosumab demonstrated superiority in preventing SREs in the phase III trial, it may not be cost-effective compared with zoledronic acid because of its high cost.


Massive retroperitoneal dedifferentiated liposarcoma in a young patient.
Liposarcomas are rare malignant tumors that mostly develop in the retroperitoneum. They have a broad behavioral spectrum, from small masses of tissue to highly aggressive tumors. The dedifferentiation process occurs in up to 10% and it's most likely to occur in the retroperitoneum, a process that not only changes its components but also its prognosis. These tumors can grow to a massive size since most of them do not give any symptoms until they invade the adjacent structures. Timely detection and surgery could avoid all these potentially lethal scenarios. We present a case of a 34-year-old patient, who reported a growing mass in her abdomen that reached massive proportions but remained untreated due to lack of sufficient access to healthcare facilities in her geographic location. After complete removal of the mass the patient underwent complete recovery, dedifferentiated liposarcoma was the final diagnosis.


[The role of the constitutional features and rearrangement of the H-ras 1 oncogene in the development of human lung cancer].
Length polymorphism of restriction fragments of oncogene HRASI was studied in 52 patients with lung cancer as compared with corresponding normal tissues and leukocytes of these patients and of healthy volunteers. Enhanced frequency of one of main alleles of HRASI A4 was found to correlate with development of the disease aggressive symptoms. Alterations in the HRASI locus of tumoral DNA appear to correlate distinctly with the elevate frequency of the allele (P less than 0.01). Relationship between the allele A4 and active metastases spreading in lung cancer of the III-IV stages as well as specific rearrangements as a result of which allele A4 maintained unaltered or even amplified in carcinomas enabled to suggest that the allele A4 of HRASI oncogene serves as an endogenous risk factor in impairment with non-small cellular lung cancer in addition to typical exogenous factors such as smoking.


Drug resistance and associated genetic mutations among patients with suspected MDR-TB in Uttar Pradesh, India.
Programmatic Management of Drug-Resistant Tuberculosis (PMDT) programme in 32 districts of Uttar Pradesh (UP), India. To provide epidemiological status of multidrug-resistant tuberculosis (MDR-TB) and associated microbial genetic mutations among suspected cases in UP. We retrospectively studied and tested using line-probe assay (LPA) 4895 retreatment patients with suspected MDR-TB who were enrolled for PMDT during 2012-2015. The demographic characteristics of cases, LPA-determined drug resistance, the genetic mutation profile, trends in drug resistance over the study period as well as the comparative performance of LPA and phenotypic drug susceptibility testing (DST) were analysed. MDR-TB and rifampicin-resistant TB (RR-TB) were confirmed in respectively 34.5% and 40.3% cases. The RR-TB detection rate (a valid proxy for MDR-TB) initially declined during the study period. Age ⩿30 years and implemented MDR-TB suspicion criteria were independent predictors for RR-TB (P < 0.01). LPA indicated predominant distribution of S531L (1483/1970, 75.3%) and S315T1 (1981/2116, 93.6%) mutations in the rpoB and katG genes, respectively, and had >94.0% agreement with phenotypic DST in determining rifampicin/isoniazid resistance. MDR-TB prevalence in retreatment cases is very high, highlighting the need to reduce the development and transmission of drug-resistant TB.


The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer.
Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. GH/Insulin/insulin-like growth factor-1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases lifespan in nematodes, fruit flies and mice. The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both lifespan extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore, metformin seems to decrease the risk for cancer in diabetic patients.


Electron microscopy of cells infected with Semliki forest virus temperature-sensitive mutants: correlation of ultrastructural and physiological observations.
Cells infected at the permissive temperature with three temperature-sensitive mutants of Semliki Forest virus were not significantly different in appearance from cells infected, at either the permissive or nonpermissive temperature, with wild-type virus. Virus particles, nucleocapsids, spherules, and tubules were seen in the cytoplasm. But replication of the mutants was inhibited in cells infected at the nonpermissive temperature. This was evidenced by the absence of virus particles and nucleocapsids (except in one case) and the absence or limited production of spherules and tubules. These observations are discussed with reference to the physiological defects of the mutants.


Further studies to quantify the dose of natural aerosols of foot-and-mouth disease virus for pigs.
Foot-and-mouth disease virus (FMDV) can be spread by a variety of mechanisms, including wind. Simulation models, developed to predict the risk of airborne spread, have played an important part in decision making in some outbreaks. The amount of airborne virus excreted as well as the minimal infectious dose (MID) of FMDV for different species are important determinants of airborne spread. The objective of this study was to obtain data for the O1 Lausanne, O SKR 2000 and O UKG 2001 strains of FMDV to enhance the capability of such models. Pigs were exposed to naturally generated aerosols of the three strains using an experimental design which delivered high doses of the two strains O1 Lausanne and O SKR 2000 over a short period, or of the O UKG 2001 strain over an extended period. The average excretion of the O1 Lausanne strain was 10(6.4) TCID50 per pig per hour. The excretion of the O SKR 2000 strain averaged 10(5.8) and the O UKG 2001 strain 10(6.1) TCID per pig per 24 h. The results show that the previous estimate of 'above' 800 TCID50 as the MID50 for the O1 Lausanne strain is a considerable under-estimate and that the real dose may be as high as 6000 TCID50. A dose of around 650 TCID50 of the O SKR 2000 strain failed to infect any pigs. Thus, the aerosol MID50 for pigs for this isolate is at least 1000 TCID50 and likely to be as high or higher than the O1 Lausanne strain. The exposure of pairs of recipient pigs kept physically separated from donor pigs in a series of rooms to aerosol exposure doses of the O UKG 2001 strain of around 50 TCID50 per min for 24-48 h failed to infect any of eight pigs. Thus, the present experiment confirms our previous findings that pigs, compared to cattle and sheep, are relatively resistant to infection with airborne FMDV.


Selected anthropometric variables and aerobic fitness as predictors of cardiovascular disease risk in children.
The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children.


Discussion on Improvement of the Incidence of Complications After the Application of Self-Management and Continuous Nursing in Children with Primary Nephrotic Syndrome.
To analyze the effects of self-management and continuous nursing on improving the incidence of complications in children with primary nephrotic syndrome. A retrospective analysis of 80 cases of children with primary nephrotic syndrome treated in our hospital from January 2019 to October 2022 was conducted. The patients were divided into a control group and an observation group, with 40 cases in each group. The control group received routine nursing, while the observation group received self-management and continuous nursing. After different nursing measures were taken in the two groups, the incidence of complications, the total satisfaction rate of patients' parents, quality of life scores, and the urinary albumin excretion rate before and after nursing between the two groups were analyzed. (1) In comparison to the control group, the observation group had a lower incidence of complications (gastrointestinal discomfort, hypoglycemia, and abnormal liver function) (P < .05). (2) In comparison to the control group, the observation group had a higher total satisfaction rate of the patients' parents after nursing (P < .05). (3) Compared to the control group, the observation group reported higher quality of life scores (psychological function, spiritual vitality, and somatic function) after nursing (P < .05). (4) Compared to the control group, the observation group revealed higher self-management ability scores after nursing (P < .05). (5) After nursing, the urinary albumin excretion rate in the observation group was lower than that in the control group (P < .05). (6) In terms of disease recurrence rate after 1 month and 2 months of nursing, the observation group reported was lower rate of disease recurrence compared to the control group (P < .05). The application values of self-management and continuous nursing in children with primary nephrotic syndrome are significant.


Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study.
Previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of alternating combination chemotherapy, including vincristine, doxorubicin, alkylating agents, and prednisone (160 patients) was more effective than conventional chemotherapy with melphalan and prednisone (77 patients), and whether the addition of the immunomodulating agent levamisole to maintenance chemotherapy enhanced the survival of patients achieving remission. The treatment groups were well matched for all major factors. The more aggressive chemotherapy was more effective at inducing remission, with a significantly higher proportion of patients achieving at least 75% tumor mass regression (53% with alternating combinations versus 32% with melphalan-prednisone, p = 0.002). Furthermore, the median survival was increased to 43 months with alternating combination chemotherapy as compared to 23 months with melphalan-prednisone (p = 0.004). After six to 12 months of induction therapy, 84 patients achieving remission were rerandomized to receive maintenance chemotherapy alone or with the addition of levamisole. The survival from the start of maintenance therapy was longer in patients receiving the added levamisole than with chemotherapy alone (p = 0.01). These findings support the use of aggressive multiagent chemotherapy for remission induction in patients with advanced-stage multiple myeloma.


[Advances of using antibody against B cell activating factor for treatment of autoimmune diseases].
In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.


Dilemma of diagnosing thoracic sarcoidosis in tuberculosis-endemic regions: An imaging-based approach. Part 2.
The second part of the review discusses the role of different existing imaging modalities in the evaluation of thoracic sarcoidosis, including chest radiograph, computed tomography, magnetic resonance imaging, endobronchial ultrasound, and positron emission tomography. While summarizing the advantages and pitfalls of each imaging modality, the authors propose imaging recommendations and an algorithm to be followed in the evaluation of clinically suspected case of sarcoidosis in tuberculosis-endemic regions.


Leukaemia inhibitory factor in endometrium during the oestrous cycle, early pregnancy and in ovariectomized steroid-treated ewes.
Leukaemia inhibitory factor (LIF), a pleiotropic cytokine, is essential for blastocyst implantation in mice and maintains the development of ovine embryos in culture. The expression of LIF was examined by northern blot analysis in endometrial tissue from cyclic (days 4-16) and pregnant (days 4-20) ewes, and the corresponding protein was immunolocalized. Expression of mRNA encoding LIF remained relatively constant throughout the oestrous cycle and was present during early pregnancy. A decrease in mRNA encoding LIF was observed during early pregnancy (on days 12-14) and expression was highest on days 16-20. Immunoreactive LIF was present in the cellular compartments of the endometrium throughout the oestrous cycle and early pregnancy, with maximal immunostaining in the caruncular and intercaruncular luminal epithelium, and moderate staining in the glandular epithelium and intercaruncular stroma. Immunoreactive LIF was also detected in the trophoblast cells of day 17 blastocysts. Separately cultured endometrial epithelial and stromal cells from pregnant animals both expressed mRNA encoding LIF. Ovariectomized steroid-treated ewes were studied to establish whether steroid hormones had a role in regulating endometrial LIF. Ewes treated with oestradiol alone showed lower concentrations of immunoreactive LIF in the endometrium in comparison to ovariectomized, control animals, while treatment of ovariectomized animals with both oestradiol and progesterone had a greater inhibitory effect on LIF immunolocalization. These studies demonstrate the presence of mRNA encoding LIF and protein throughout the oestrous cycle and early pregnancy and suggest that steroid hormones may be involved in their regulation.


Combined Wharton's jelly derived mesenchymal stem cells and nerve guidance conduit: A potential promising therapy for peripheral nerve injuries.
Peripheral nerve injuries represent a clinical problem with insufficient or unsatisfactory treatment options. Functional outcome with nerve guidance conduits was unsatisfactory in nerve defects with increased gap size. So, cell therapy may benefit as a tool for optimizing the regeneration process. The aim of the present study was to evaluate the impact of combination of cell therapy and nerve guidance conduits on the nerve regeneration and on the expression of the factors aiding the regeneration in a rat model of sciatic nerve injury. Sixty Wistar rats were randomly divided into four groups: Group I: normal control group; Group II: sciatic nerve injury (SNI) with a 10mm long sciatic nerve gap; Group III: SNI with using a nerve conduit (NC) for nerve gap bridging; and Group IV: SNI with using a NC associated with Wharton's jelly derived mesenchymal stem cells (WJ-MSCs). The results showed that the combination therapy NC+WJ-MSCs caused much better beneficial effects than NC alone evidenced by increasing sciatic nerve index and pin-prick score. The histopathological analysis found that the use of the NC combined with WJ[HYPHEN]MSCs resulted in a structure of the sciatic nerve comparable to the normal one with better nerve regeneration when compared with NC only. There was no differentiation of WJ-MSCs into nerve structure. Lastly, there was an upregulation of expression for netrin-1, ninjurin, BDNF, GDNF, VEGF and angiopoitin-1 rat genes in NC+WJ-MSCs group than NC alone. The addition of WJ-MSCs to the nerve guidance conduits seems to bring significant advantage for nerve regeneration, basically by increasing the expression of neurotrophic and angiogenic factors establishing more favorable environment for nerve regeneration.


Meta-analysis of the results of haploidentical transplantation in the treatment of aplastic anemia.
This meta-analysis was to evaluate the outcome of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) for aplastic anemia (AA) compared with matched related donor (MRD)-HSCT, matched unrelated donor (MUD)-HSCT, and immunosuppressive therapy (IST). Pubmed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases were searched for relevant studies from inception to 22 June 2022. Relative risk (RR) was used to indicate the effect indicator, with a 95% confidence interval (CI) being applied to express the effect size. A subgroup analysis based on the literature quality (low, fair, and high) was applied. Totally, 25 studies were included in this study, comprising 2252 patients. Our findings demonstrated no difference between Haplo-HSCT and MRD-HSCT in 1-, 2-, and 3-year overall survival (OS), failure-free survival (FFS), and engraftment. However, Haplo-HSCT had higher incidences of II-IV acute graft-versus-host disease (aGVHD), chronic GVHD (cGVHD), and cytomegalovirus infection. There were no differences in 3- and 5-year OS, 3-year FFS, platelet engraftment, graft failure (GF), II-IV grade of aGVHD, and complication between Haplo-HSCT and MUD-HSCT; however, Haplo-HSCT had a lower incidence of cGVHD. Compared with IST, Haplo-HSCT had a higher 3-year FFS and 3- and 6-month response rate. However, there were no differences in 3- and 5-year OS, and 12-month response rate between Haplo-HSCT and IST. This study suggests that Haplo-HSCT may be a realistic therapeutic option for AA, which may provide a reference for decision-making.


[Activity of the sympathetic nervous system and the levels of prostaglandins and intracellular electrolytes in patients with arterial hypertension and low plasma renin activity].
Differential-diagnosis tests for low-renin hypertension viz essential hypertension and arterial hypertension due to Conn's syndrome (adrenocortical adenoma or hyperplasia) have been assessed. The examined patients showed considerable humoral and metabolic differences, as compared to patients with high and normal plasma renin activity (PRA). For example, patients with essential hypertension and low PRA showed depressed noradrenalin and PGE2 secretion, increased PGF2 alpha secretion, low triglyceride level, and elevated erythrocyte sodium content. Patients with adrenocortical adenoma exhibited increased secretion of adrenalin, dopamine and PGF2 alpha, and a higher erythrocyte sodium level. Enhanced dopamine synthesis in patients with Conn's syndrome may be an adaptive response to a high aldosterone level.


Therapeutic efficacy of caffeic acid phenethyl ester in cancer therapy: An updated review.
Nowadays, there is a lot of public and scientific interest in using phytochemicals to treat human ailments. Existing cancer medicines still run across obstacles, despite significant advancements in the field. For instance, chemotherapy may result in severe adverse effects, increased drug resistance, and treatment failure. Natural substances that are phytochemically derived provide innovative approaches as potent therapeutic molecules for the treatment of cancer. Bioactive natural compounds may enhance chemotherapy for cancer by increasing the sensitivity of cancer cells to medicines. Propolis has been found to interfere with the viability of cancer cells, among other phytochemicals. Of all the components that make up propolis, caffeic acid phenethyl ester (CAPE) (a flavonoid) has been the subject of the most research. It demonstrates a broad spectrum of therapeutic uses, including antitumor, antimicrobial, antiviral, anti-inflammatory, immunomodulatory, hepatoprotective, neuroprotective, and cardioprotective effects. Studies conducted in vitro and in vivo have demonstrated that CAPE specifically targets genes involved in cell death, cell cycle regulation, angiogenesis, and metastasis. By altering specific signaling cascades, such as the NF-κB signaling pathway, CAPE can limit the proliferation of human cancer cells. This review highlights the research findings demonstrating the anticancer potential of CAPE with a focus on multitargeted molecular and biological implications in various cancer models.


Blood pressure and urinary sodium in black American adolescents.
For 56 black American adolescents ranging in age from 13 to 19 years, 24-hour urinary sodium excretion was compared with blood pressure. The volunteers came from families of middle to low economic levels. Their body weight varied from 70 to 129 percent of ideal body weight. The average systolic pressure of all the subjects was 112.1 mmHg with a standard deviation of 9.5 mmHg; mean diastolic pressure was 69.6 mmHg with a SD of 8 mmHg. The average 24-hour urinary sodium excretion of the total population was 131.5 mEq/24 h with a SD of 59 mEq. For the 29 male subjects, the mean value was 137 mEq/24 h (range, 30 to 309 mEq) and for 27 female subjects, 126.3 mEq/24 h (range, 40 to 197 mEq). The average urinary excretion among these groups was not significantly different (P > .05) and the urinary Na/K ratio of the total group was 4.3 with a SD of 2.0. This ratio among various age and sex subgroups was not significantly different (P > .05). Urinary sodium excretion values were taken as a reflection of dietary salt intake among these volunteers. The data suggest that the black adolescents studied do not consume excess sodium and contradict the belief that blacks eat excess sodium. Further, these baseline data must be considered among the factors responsible for the development of hypertension.