Attenuation of antigen-induced bronchospasm by fenoterol in the guinea-pig.
When guinea-pigs sensitized to ovalbumin were challenged with ovalbumin, the histamine concentrations in lung tissue decreased, whereas those in tracheal and heart tissues increased during the 15 min following challenge. Fenoterol (2.5 mg/kg, i.p.), administered 30 min prior to challenge, attenuated both the decrease and the increase in lung and tracheal histamine concentrations, respectively. The challenge-induced increase in heart histamine was also prevented. In the anaesthetized guinea-pig, a marked increase in intratracheal pressure (ITP) occurred on challenge. This was of longer latency than the increase in ITP induced by histamine and was consistent with a release process. Treatment of challenged guinea-pigs with fenoterol (2.5 mg/kg, i.v.) markedly reduced the increased ITP. However, when fenoterol was administered prior to challenge, the increase in ITP was abolished. These results indicate that there is an apparent relationship between the inhibition of histamine release in vivo by fenoterol pretreatment and the greater inhibitory effect of fenoterol on antigen-induced increases in ITP when administered prophylactically.


New cyclic glycolipids from Silene succulenta promote in vitro MCF-7 breast carcinoma cell apoptosis by cell cycle arrest and in silico mitotic Mps1/TTK inhibition.
In vitro anticancer screening of Silene succulenta Forssk. aerial parts (Caryophyllaceae) showed that the n-hexane fraction was a highly effective fraction against breast carcinoma cell lines (MCF-7) with IC50 = 15.5 μg mL-1. The bioactive-guided approach led to the isolation of two new cyclic glucolipids from the n-hexane fraction, identified as a 1,2'-cyclic ester of 11-oxy-(6'-O-acetyl-β-d-glucopyranosyl) behenic acid (1) as a C-11 epimeric mixture and 11(R)-oxy-(β-d-glucopyranosyl)-1,2'-cyclic ester of behenic acid (2). An in vitro cytotoxicity study showed the potential suppression of MCF-7 cells with IC50 values of 11.7 ± 0.04 and 6.6 ± 0.01 μg mL-1 for compounds 1 and 2, respectively, compared to doxorubicin (IC50 = 3.83 ± 0.01 μg mL-1). Accordingly, only cell cycle tracking for the most active compound (2) was assessed. The cell cycle investigation showed that compound 2 altered the cell cycle at G0/G1, S, and G2/M phases in MCF-7 treated cells. In addition, its powerful apoptotic ability resulted in a significant increase in the early and late stages of apoptosis. Moreover, molecular docking analysis, which was performed against the anticancer mitotic (or spindle assembly) checkpoint target Mps1 kinase, showed that the two new cyclic glycolipids (1 and 2) possess high binding affinity of -7.7 and - 7.6 kcal mol-1, respectively, compared to its ATP ligand. Overall, this report emphasizes that natural cyclic glycolipids can be used as potential antitumour breast cancer agents.


Perceptions de pères vivant avec un fils ou une fille adulte ayant une déficience intellectuelle sur la transition de l'après-parents.
With the increase in life expectancy, many people with intellectual disabilities (ID) are living in the family home with their parents. This research focuses on the experience of 17 fathers of adults with ID. These fathers answered a questionnaire including open and closed questions. During the individual interview, fathers described their motivations to cohabit with their son or daughter, cohabitation benefits and constraints, housing options considered and planning for the future. Results indicate that fathers chose this cohabitation. However, they experience anxiety because they do not know who will support the adult with ID when they can no longer do so. Postparental planning considerations include legal concerns and informal discussions with siblings or the extended family. These results describe a complex parental situation in which there is interaction between their emotions, their attachment to the adult with ID and their previous experiences with residential, social or rehabilitation services.


Effects of trapezoid body and superior olive lesions on choline acetyltransferase activity in the rat cochlear nucleus.
Using a microdissection and quantitative microassay approach, choline acetyltransferase activities were mapped in the cochlear nuclei of rats having either transection of the trapezoid body or destruction of the superior olivary complex on one side in the brain stem. Lateral trapezoid body transection resulted in dramatic loss of choline acetyltransferase activity in all parts of the ipsilateral cochlear nucleus, while more medial transection had little effect. Destruction of the superior olivary complex resulted in dramatic loss of choline acetyltransferase activity in the ipsilateral cochlear nucleus, and detectable loss also contralaterally. The results suggest that most of the centrifugal cholinergic projections to the rat cochlear nucleus derive from or traverse the vicinity of the superior olivary complex bilaterally and enter the cochlear nucleus ventrally from the region of the trapezoid body.


Comparative subproteomic analysis of clinically acquired fluoroquinolone resistance and ciprofloxacin stress in Salmonella Typhimurium DT104B.
Antimicrobial resistance is a worldwide public health threat and Salmonella enterica subsp. enterica serotype Typhimurium phage type DT104B multiresistant strains with additional quinolone resistance have been responsible for global outbreaks and high mortality. Quinolone resistance is known to be multifactorial but is still far from a complete understanding. To give new insights about the resistance mechanisms involved, this work aimed to evaluate subproteome changes between an S. Typhimurium DT104B clinical strain that acquired fluoroquinolone resistance after treatment (Se20) and its pretreatment parental strain (Se6), and also subproteome variations in Se20 under ciprofloxacin (CIP) stress (Se20+CIP). The proteomes were compared at the intracellular and membrane levels by a 2-DE∼LC-MS/MS and a shotgun LC-MS/MS approach, respectively. In total, 14 differentially abundant proteins were identified when comparing Se6 with Se20 and 91 were identified between Se20 and Se20+CIP. Several proteins with known and possible roles in quinolone resistance (AAC(6')-Ib-cr4, OmpD, OmpX, GlmS, GlmU, H-NS, etc.) were identified and discussed. The great number of proteins identified in this study provides important information about mechanism-related differential protein expression which supports the current knowledge and might lead to new testable hypotheses on the mechanism of action of fluoroquinolone drugs.


Transneuronal labelling of neurons in rabbit brain after injection of herpes simplex virus type 1 into the renal nerve.
We mapped the distribution of virus-labelled neurons in the brain after injection of Herpes simplex virus type 1 (HSV1) into the rabbit renal nerve. Seven days after injection, labelled neurons were observed in four brain regions, the rostral ventrolateral medulla (47 +/- 3% of neurons), the A5 area of the lower pons (38 +/- 4%), the caudal raphe nuclei and the parapyramidal area of the medulla (13 +/- 2%), and the paraventricular nucleus of the hypothalamus (1 +/- 1%). In the rostral ventrolateral medulla approximately one half of the HSV1-labelled neurons also contained tyrosine hydroxylase, characterizing them as C1 neurons. In the A5 area virtually all HSV1-labelled neurons also contained tyrosine hydroxylase. In the raphe nuclei and the parapyramidal area 47% of HSV1-positive neurons contained serotonin. The distribution of labelled neurons was similar to that observed after injection of HSV1 into the adrenal gland.


N-acyl homoserine lactonase attenuates the virulence of Salmonella typhimurium and its induction of intestinal damages in broilers.
This study aimed to investigate the potential mitigating effects of N-acyl homoserine lactonase (AHLase) on the virulence of Salmonella typhimurium and its induction of intestinal damages in broilers. In vitro study was firstly conducted to examine if AHLase treatment could attenuate the virulence of S. typhimurium. Then, an in vivo experiment was performed by allocating 240 broiler chicks at 1 d old into 3 groups (8 replicates per group): negative control (NC), positive control (PC), and PC supplemented with 10,000 U/kg AHLase. All chicks except those in NC were orally challenged by S. typhimurium from 8 to 10 d of age. Parameters were measured on d 11 and 21. The results showed that treatment with 1 U/mL AHLase suppressed the biofilm-forming ability (including biofilm biomass, extracellular DNA secretion and biofilm formation-related gene expression), together with swarming motility and adhesive capacity of S. typhimurium. Supplemental 10,000 U/kg AHLase counteracted S. typhimurium-induced impairments (P < 0.05) in broiler growth performance (including final body weight, average daily gain and average daily feed intake) during either 1-11 d or 12-21 d, and increases (P < 0.05) in the indexes of liver, spleen and bursa of Fabricius on d 11, together with reductions (P < 0.05) in ileal villus height and its ratio to crypt depth on both d 11 and 21. AHLase addition also normalized the increased (P < 0.05) mRNA expression of ileal occludin on both d 11 and 21 in S. typhimurium-challenged broilers. However, neither S. typhimurium challenge nor AHLase addition altered (P > 0.05) serum diamine oxidase activity of broilers. Noticeably, S. typhimurium challenge caused little change in the mRNA expression of ileal inflammatory cytokines except for an increase (P < 0.05) in interleukin-8 expression on d 11, whereas AHLase addition normalized (P < 0.05) this change. In conclusion, AHLase treatment could attenuate the virulence and pathogenicity of S. typhimurium, thus contributing to alleviate S. typhimurium-induced growth retardation and intestinal damages in broilers.


Evaluation of a modified Broström-Gould procedure for treatment of chronic lateral ankle instability: A retrospective study with critical analysis of outcome scoring.
Chronic lateral ankle instability accounts for 20% of the ankle injuries. This study evaluates functional outcome of the modified Broström-Gould technique using suture anchors, with 4 different clinical scores. A consecutive series of 41 patients were included with a minimum follow-up of one year. The function was assessed using 4 clinical scores including: the AOFAS for hind foot; the FAAM; the CAIT and the CAIS. Out of 41 patients; 27 patients were very satisfied, 11 satisfied and 3 were not satisfied. Ankle mobility returned to normal in 93% of patients. At follow-up the AOFAS was 89/100 (37-100), the FAAM 85/100% (35-100%), the CAIT 20/30 (5-30), and the CAIS 74/100% (27-100%). Outcome of modified Broström-Gould procedure is good with high satisfaction rate in terms of ankle mobility. The disparity in outcome of scores, signals towards the need of a standard evaluation system.


Investigation of the inclusion interaction of p-sulfonatocalix[6]arene with triamterene.
The inclusion complexation behavior of p-sulfonatocalix[6]arene (SCX6) with triamterene (TA) was investigated by fluorescence spectroscopy, UV-Vis spectroscopy, (1)H and 2D NMR, FT-IR, SEM and DSC. The results indicate that TA is able to form an inclusion complex with SCX6. The inclusion complex has a stoichiometry of 1:1 at pH 6.50. In addition, the water solubility of TA was obviously increased in the inclusion complex with SCX6.


Rating affective flattening from videotaped interviews.
Semistructured interviews with 28 schizophrenic patients were videotaped. The affective flattening section of the Scale for the Assessment of Negative Symptoms (SANS) was rated after each interview. At a later date, each videotape was rated by three raters as well as the interviewer. Reliability was estimated within and across rating conditions by intraclass correlation. Comparison of reliability scores across rating conditions indicated that the videotape medium had little effect on the ability of raters to rate affective flattening similarly.


Transmesenteric hernia after right nephrectomy: diagnostic and therapeutic management.
Internal abdominal hernias are a rare cause of intestinal obstruction (0.2-0.9%). Transmesenteric hernia is a rare type of internal hernia and usually in adult people is acquired. We report the case of a 44 year-old caucasian female with a small bowel occlusion after right nephrectomy for clear cell renal carcinoma caused by an acquired transmesenteric hernia. We emphasize the role of CT scanning for a prompt diagnosis and a quick surgical treatment in order to avoid intestinal gangrene.


Total and viable residual splenic volume measurement after partial splenic embolization by three-dimensional ultrasound.
We prospectively evaluated the validity of total and viable residual splenic volume after partial splenic embolization (PSE) with three-dimensional (3D) ultrasound (US) measurement. Twenty patients with splenomegaly were included. All splenic volumes were measured with transabdominal US using virtual organ computer-aided analysis (VOCAL). The viable residual splenic volume after PSE was estimated by using contrast-enhanced (CE) US with VOCAL. The agreement of the measurements from VOCAL and computed tomography (CT) was confirmed using interclass correlation coefficients (ICCs) and Bland-Altman plots. Mean volume was 503 ± 250 ml for total spleen and 209 ± 108 ml for viable residual volume. Regarding total volume, there was a high correlation and agreement (ICCs = 0.90) between 3D US and CT volumetry. Regarding viable residual volume, although there was a moderate correlation between 3D CEUS and CT volumetry, mean ICCs of 0.617 indicated poor agreement. With Bland-Altman plots, a narrow 95 % limit of agreement was observed among patients with a total volume under 1000 ml. The total splenic volume could be accurately estimated with 3D US. However, estimation of viable residual splenic volume should be limited in cases with total splenic volume under 1000 ml.


Primary osteoporosis in men: an unmet medical need.
Osteoporosis is a skeletal disease characterized by loss of bone strength and increased risk of fractures. Even though fracture prevalence is higher in women, fractures also constitute a significant public health issue in older men. Men are screened less and more frequently undertreated than female patients. It is the goal of this review, to summarize updated information about the current understanding of pathophysiology and clinical aspects of diagnosis and treatment of osteoporosis in men.


Polymorphisms of SLC30A2 and selected perinatal factors associated with low milk zinc in Chinese breastfeeding women.
The variability of breast-milk zinc concentration is high among breastfeeding women, and it is known to be independent of dietary zinc intake. As a result, transient neonatal zinc deficiency is not rare in the breastfed infants due to low milk zinc concentration in their breastfeeding mothers. Up to now, SLC30A2 has been documented the only candidate gene showing correlation with human milk zinc trait. In this study, 750 breastfeeding women were recruited and 10ml foremilk was collected on 42nd postpartum day. The milk zinc concentration was measured, and genomic DNA was isolated from breast-milk. Direct sequencing and Taqman assay were used to identify the SLC30A2 polymorphisms associated with low-milk-zinc. Subsequently, the factors associated with breast-milk zinc were investigated using regression model. The correlation study showed that SLC30A2/-697G>T and SLC30A2/1031A>G polymorphisms were associated with low-milk-zinc in our subjects. These two polymorphisms explained 3.23% of total variance in milk zinc level. For non-genetic variables, the obese breastfeeding women (BMI>25) secreted less zinc into their breast-milk. The variation of milk zinc was independent of pregnant age, birth weight, infant gender, cesarean delivery, preterm delivery and vitamin D supplementation. In conclusion, our results indicated that -697G>T and 1031A>G polymorphisms in the SLC30A2 gene may be associated with low-milk-zinc in Chinese breastfeeding women. Maternal BMI is significantly correlated with milk zinc level in negative manner. Our study demonstrated that both genetic and non-genetic factors could modulate milk zinc level.


Investigational drug available directly from CDC for the treatment of infections with free-living amebae.
Infections caused by free-living amebae (FLA) are severe and life-threatening. These infections include primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri and granulomatous amebic encephalitis caused by Balamuthia mandrillaris and Acanthamoeba species. Although several drugs have in vitro activity against FLA, mortality from these infections remains>90% despite treatment with combinations of drugs.


Ifosfamide/etoposide and mesna uroprotection in advanced breast cancer.
The object of the study was to evaluate the effectiveness of ifosfamide/etoposide and mesna therapy in advanced breast cancer. A total of 44 patients with breast cancer were included in the trial. Eligibility criteria included measurable, refractory disease; prior anthracycline therapy (or its contraindication); a life expectancy of at least 3 months; and adequate hepatic, renal, CNS and bone marrow function. All patients were less than or equal to 70 years of age and had a Karnofsky performance status of greater than or equal to 50%. There were 36 evaluable cases. Sites of metastatic disease included bone (19), skin (18), liver (9), lung (14), lymph node (19), and miscellaneous (7). Treatment consisted of 1,500 mg/m2 ifosfamide given i.v. on days 1-5, 120 mg/m2 etoposide given i.v. on days 1-3, and 400 mg i.v. mesna given with and at 4 and 8 h after ifosfamide. Cycles were repeated every 28 days. Initial doses were reduced by 25% or 50% in patients who had previously undergone both chemotherapy and radiotherapy. A median of 4 cycles (range, 2-8) were given. The myelotoxicity was marked: WHO grades 3/4 leukopenia (n = 37), grades 3/4 thrombocytopenia (n = 12), and grades 2/3 anemia (n = 13). Due to myelotoxicity, dose reduction or prolongation of treatment-free intervals was necessary in 28 cases. Alopecia was seen in 35 patients and CNS toxicity, in 8. Partial remission (PR) was obtained in five cases and complete remission (CR), in three. Sites of response included the lung (5), skin (4), lymph node (5), and peritoneum (1). The duration of response was 4 (n = 2) and 8 (n = 1) months for CR and 2 (n = 2), 6 (n = 2), and 10 (n = 1) months for PR. We conclude that the ifosfamide/etoposide and mesna regimen is effective, but its myelotoxicity is treatment-limiting.


[Long-term clinical evaluation of single tooth replacement by non-submerged implants].
To evaluate single tooth replacement by the non-submerged osseointegrated dental implants. In the time period from 1990 to 1998, 65 patients were consecutively admitted for treatment with a total of 104 ITI-implants supporting single crowns. No implant was lost during the healing phase, the 5-year cumulative survival rate was 99.1%. Prosthetic complications were loosening of screws for retention of abutment and fracture of octa-abutment. The non-submerged osseointegrated ITI dental implants can be a successful treatment in single tooth loss.


Oral health-related quality of life and masticatory function after conventional prosthetic treatment: A cohort follow-up study.
The impact of conventional prosthetic treatment on both the objective and subjective assessments of mastication as well as on well-being is unclear. The purpose of this clinical study was to compare the impact on oral health-related quality of life and masticatory function in participants treated with conventional dental prostheses. A total of 72 patients requiring prosthetic rehabilitation were enrolled by referral from the Faculty of Dentistry at the University of Granada, Spain. At baseline, demographic, behavioral, and clinical (prosthetic status, occlusal units) data were collected. In addition, the scores for quality of life, oral satisfaction, masticatory ability (Leake index), and masticatory performance (after 5, 10, and 15 cycles of bicolored chewing gum) were obtained. These records were obtained again at 6 to 8 weeks after insertion of the prostheses. The findings revealed that patients treated with fixed prostheses had better quality of life and better masticatory function than patients treated with removable prostheses. This result was even more pronounced for those treated with complete dentures. For all items, most of the treated patients improved the quality of life (average, 8.6 of the 4 items), although only between 5% and 15% of patients, especially those with a removable prosthesis, commented on functional impact after receiving treatment. Generally, masticatory performance was improved between 7% and 18% and was highly correlated not only with the number of natural teeth (r=0.61) and occlusal units (r=0.51) but also with subjective variables such as mastication satisfaction (r=0.31), impact on quality of life (r=0.30), or masticatory ability (r=0.30). Treatment with fixed prostheses achieved better results regarding quality of life, oral satisfaction, and masticatory function than treatment with removable prostheses. A moderate but significant correlation exists between the objective and subjective assessments of the masticatory functions.


Do image enhancement filters in complementary metal oxide semiconductor and photostimulable phosphor imaging systems improve the detection of fractured endodontic instruments in periapical radiography?
The aim of this study was to evaluate the influence of image enhancement filters on detection of fractured endodontic instruments and on image noise and pixel intensity. In total, 26 mandibular molars (68 root canals), divided into 4 groups (presence/absence of root canal filling, and presence/absence of a fractured endodontic instrument) were radiographed by using a complementary metal oxide semiconductor (CMOS) and a photostimulable phosphor (PSP) system. Images with 4 enhancement filters (Sharpen UM, Edges All, BC Low, and BC High) were compared with nonfiltered images. The area under the receiver operating characteristic curve (Az), sensitivity, and specificity in detection of fractured instruments were compared for each imaging condition. Means and standard deviations (SD) to measure noise and changes in pixel intensity were calculated. Analysis of variance was used to analyze the data. There were no significant differences in Az, sensitivity, and specificity values between nonfiltered and filtered images in detection of instruments in root canals without and with root canal filling (P ≥ .360). SD was reduced by filters in CMOS but not PSP radiographs. Sharpen UM caused more changes in the mean values in both systems. Filters did not improve diagnostic performance in detecting instruments. Noise and pixel intensity were affected differently.


A highly polymorphic CA repeat marker at the human interleukin 6 receptor (IL6R) locus.
A polymorphic dinucleotide (CA) sequence was isolated from a genomic clone containing the human interleukin 6 receptor (IL6R) gene. High heterozygosity (0.81) makes this polymorphism a useful marker in the genetic study of disorders affecting the inflammation process and bone resorption.


The Reverse Sural Artery Flap: A Reliable and Versatile Flap for Wound Coverage of the Distal Lower Extremity and Hindfoot.
The reverse sural artery flap is a distally based fasciocutaneous or adipofascial flap used for wound coverage of the distal one-third of the lower extremity, ankle, and posterior heel. The flap harvest can be performed without sacrificing major arteries of the lower extremity. It can be elevated and mobilized with relative ease and a short operative time. It provides a good alternative to free tissue transfer in complex lower-extremity wounds with exposed bone, tendon, or hardware. The surgeon must be familiar with the management of venous congestion to improve the success of the flap.


A lineage tree-based hidden Markov model quantifies cellular heterogeneity and plasticity.
Individual cells can assume a variety of molecular and phenotypic states and recent studies indicate that cells can rapidly adapt in response to therapeutic stress. Such phenotypic plasticity may confer resistance, but also presents opportunities to identify molecular programs that could be targeted for therapeutic benefit. Approaches to quantify tumor-drug responses typically focus on snapshot, population-level measurements. While informative, these methods lack lineage and temporal information, which are particularly critical for understanding dynamic processes such as cell state switching. As new technologies have become available to measure lineage relationships, modeling approaches will be needed to identify the forms of cell-to-cell heterogeneity present in these data. Here we apply a lineage tree-based adaptation of a hidden Markov model that employs single cell lineages as input to learn the characteristic patterns of phenotypic heterogeneity and state transitions. In benchmarking studies, we demonstrated that the model successfully classifies cells within experimentally-tractable dataset sizes. As an application, we analyzed experimental measurements in cancer and non-cancer cell populations under various treatments. We find evidence of multiple phenotypically distinct states, with considerable heterogeneity and unique drug responses. In total, this framework allows for the flexible modeling of single cell heterogeneity across lineages to quantify, understand, and control cell state switching.


Immunohistochemical localization of (neuro)peptide hormones in endocrine cells and nerves of the gut of a stomachless teleost fish, Barbus conchonius (Cyprinidae).
Enteroendocrine cells containing glucagon-, substance P-, neurotensin- and VIP-like substances have been demonstrated immunocytochemically in the gut of Barbus conchonius. Mainly based on the distribution of the immunoreactive endocrine cells in this and a previous study, at least eight different enteroendocrine cell types appear to be present in this stomachless fish: C-terminal-gastrin-immunoreactive cells, predominantly present in the upper parts of the folds of the proximal part of the intestinal bulb. Metenkephalin-immunoreactive cells, basally located in the folds of the first segment. Pancreatic polypeptide (PP)-immunoreactive cells, mainly present in the first half of the first segment. Glucagon-like-immunoreactive (GLI) cells that are basally located in the folds of the first segment and that contain a different polypeptide (possibly glicentin) than pancreatic glucagon cells. Substance P-immunoreactive cells, present in the upper parts of the folds throughout the gut. C-terminal-neurotensin-immunoreactive cells, basally located in the folds throughout the first segment. Vasoactive intestinal polypeptide (VIP)-immunoreactive cells, present in small numbers in the proximal part of the intestinal bulb. Nonspecifically-immunoreactive cells, found throughout the intestinal bulb. Many VIP-immunoreactive nerves have been demonstrated in the smooth muscle layer and myenteric plexus of the gut; furthermore some of them are peptide histidine-isoleucine (PHI)-immunoreactive. Substance P-, somatostatin-, neurotensin- and met-enkephalin-immunoreactive nerves are also found. Thus, at least partial sequences of four different mammalian neuropeptide hormones (VIP, substance P, neurotensin, met-enkephalin) occur both in endocrine cells and enteric nerves of the gut of B. conchonius.


Patient-individualized CD8⁺ cytolytic T-cell therapy effectively combats minimal residual leukemia in immunodeficient mice.
Adoptive transfer of donor-derived cytolytic T-lymphocytes (CTL) has evolved as a promising strategy to improve graft-versus-leukemia (GvL) effects in allogeneic hematopoietic stem-cell transplantation. However, durable clinical responses are often hampered by limited capability of transferred T cells to establish effective and sustained antitumor immunity in vivo. We therefore analyzed GvL responses of acute myeloid leukemia (AML)-reactive CD8(+) CTL with central and effector memory phenotype in a new allogeneic donor-patient specific humanized mouse model. CTL lines and clones obtained upon stimulation of naive CD45RA(+) donor CD8(+) T cells with either single HLA antigen-mismatched or HLA-matched primary AML blasts, respectively, elicited strong leukemia reactivity during cytokine-optimized short to intermediate (i.e., 2-8 weeks) culture periods. Single doses of CTL were intravenously infused into NOD/scidIL2Rcg(null) mice when engraftment with patient AML reached bone marrow infiltration of 1-5%, clinically defining minimal residual disease status. This treatment resulted in complete regression of HLA-mismatched and strong reduction of HLA-matched AML infiltration, respectively. Most importantly, mice receiving AML-reactive CTL showed significantly prolonged survival. Transferred CTL were detectable in murine bone marrow and spleen and demonstrated sustained AML-reactivity ex vivo. Moreover, injections with human IL-15 clearly promoted CTL persistence. In summary, we show that naive donor-derived CD8(+) CTL effectively combat patient AML blasts in immunodeficient mice. The donor-patient specific humanized mouse model appears suitable to evaluate therapeutic efficacy of AML-reactive CTL before adoptive transfer into patients. It may further help to identify powerful leukemia rejection antigens and T-cell receptors for redirecting immunity to leukemias even in a patient-individualized manner.


Closed-class immanence in sentence production.
The closed-class hypothesis asserts that function words play a privileged role in syntactic processes. In language production, the claim is that such words are intrinsic to, identified with, or immanent in phrasal skeletons. Two experiments tested this hypothesis with a syntactic priming procedure. In both, subjects tended to produce utterances in the same syntactic forms as priming sentences, with the structures of the self-generated sentences varying as a function of differences in the structures of the primes. Changes in the closed-class elements of the priming sentences had no effect on this tendency over and above the impact of the structural changes. These results suggest that free-standing closed-class morphemes are not inherent components of the structural frames of English sentences.


Mutations in surface and polymerase gene of chronic hepatitis B patients with coexisting HBsAg and anti-HBs.
To investigate the clinical significance and presence of mutations in the surface (S) and overlapping polymerase gene of hepatitis B patients with coexisting HBsAg and anti-HBs. Twenty-three patients with chronic hepatitis B were studied. Of the 23 patients, 11 were both positive for hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBV surface antigen (anti-HBs), 12 were negative for anti-HBs while positive for HBsAg. DNA was extracted from 200 muL serum of the patients. Nucleotide of the surface and overlapping polymerase gene from HBV-infected patients was amplified by PCR, and the PCR products were sequenced. Forty-one mutations were found within the surface gene protein of HBV in 15 patients (10 with coexisting HBsAg and anti-HBs). Six (14.6%) out of 41 mutations were located at "alpha " determinant region in 5 patients (4 positive for HBsAg and anti-HBs). Eleven mutations (26.8%) occurred in the downstream or upstream of "alpha " determinant region. Lamivudine (LMV)-selected mutations were found in three patients who developed anti-HBs, which occurred in amino acid positions (196, 198, 199) of the surface protein and in YMDD motif (M204I/V) of the polymerase protein simultaneously. Presence of these mutations did not relate to changes in ALT and HBV DNA levels. Besides mutations in the "alpha " deter-minant region, mutations at downstream or upstream of the "alpha " determinant region may contribute to the development of anti-HBs. These mutations do not block the replicating competency of HBV in the presence of high titer of anti-HBs.


Critical analysis of sensors for physiological responsive pacing.
Physiological responsive pacing includes the application of sensors to measure physiologic variables, which in turn are used to control pacemaker rate. Six such systems are evaluated based on a comparison of (1) speed of response, (2) sensor reliability, and (3) system specificity. Although there is not a clear-cut solution, and every system has some weaknesses, several sensors seem more feasible than others. Much research remains to be done, and the indications and patient benefits must be established.


Primary diagnosis of gynecological tumors by ultrasonography and computed tomography.
In 33 patients with a pelvic mass or otherwise suspected to have gynecological malignancy, ultrasonography and computed tomography of the abdomen were performed. The results were compared afterward with the findings at operation. With both methods the nature of the tumor had been predicted correctly in the majority of cases. Localization and metastases were more frequently detected by computed tomography. Both tests appeared, in a way, to be complementary. There were no false-negative findings in both sonography and computed tomography. In three cases false-positive results were seen with both techniques.


Dietary administration of mangosteen, Garcinia mangostana, peel extract enhances the growth, and physiological and immunoendocrinological regulation of prawn, Macrobrachiumrosenbergii.
In this study, we investigated the potential immunostimulatory effects of mangosteen (Garcinia mangostana) peel extract on Macrobrachium rosenbergii, specifically in enhancing immunity and resistance against Lactococcus garvieae. We employed a dietary administration approach to assess the impact of different extract preparations from mangosteen peel, namely mangosteen peel powder (MPP), boiled mangosteen peel powder (MPB), and mangosteen peel extract (MPE). Following the administration of mangosteen peel extract, we evaluated growth performance, innate immune parameters, and disease resistance in the prawns. The results revealed a significant increase in total haemocyte count (THC), differential haemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), as well as phagocytic activity and clearance efficiency against L. garvieae. Based on these findings, we suggest that mangosteen peel extract can be utilized as an immunostimulant for prawns through dietary administration, regulating immune responses and enhancing resistance against pathogens by modulating carbohydrate metabolism.


Expression of lncRNAs in response to bacterial infections of goat mammary epithelial cells reveals insights into mammary gland diseases.
Mastitis or inflammation of the mammary gland is a highly economic and deadly alarming disease for the dairy sector as well as policymakers caused by microbial infection. Transcriptomic and proteomic approaches have been widely employed to identify the underlying molecular mechanisms of bacterial infections in the mammary gland. Numerous differentially expressed mRNAs, miRNAs, and proteins together with their associated signaling pathways have been identified during bacterial infection, paving the way for analysis of their biological functions. Long noncoding RNAs (lncRNAs) are important regulators of multiple biological processes. However, little is known regarding their role in bacterial infection in mammary epithelial cells. Hence, RNA-sequencing was performed by infecting primary mammary epithelial cells (pMECs) with both gram-negative (E. coli) and gram-positive bacteria (S. aureus). Using stringent pipeline, a set of 1957 known and 1175 novel lncRNAs were identified, among which, 112 lncRNAs were found differentially expressed in bacteria challenged PMECs compared with the control. Additionally, potential targets of the lncRNAs were predicted in cis- and trans-configuration. KEGG analysis revealed that DE lncRNAs were associated with at least 15 immune-related pathways. Therefore, our study revealed that bacterial challenge triggers the expression of lncRNAs associated with immune response and defense mechanisms in goat mammary epithelial cells.


Communicable diseases in the immigrant population attended to in a tropical medicine unit: epidemiological aspects and public health issues.
For geographical and historical reasons, Spain is receiving an increasing number of immigrants. The aim of this study was to evaluate some epidemiological aspects and the main public health issues of communicable diseases in Barcelona's immigrant population. From 2001 to 2004, a population of immigrants from tropical, subtropical regions and Eastern Europe was attended to in our centre. Each patient was offered a complete screening for tropical and common diseases. The prevalence and demographical characteristics of eight diseases with a potential risk of transmission in our setting were studied: latent and active tuberculosis, syphilis, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), Chagas disease, Giardia intestinalis and Entamoeba histolytica/Entamoeba dispar. In all, 2464 immigrants mainly from sub-Saharan Africa were seen. Among the patients who underwent the screening, 46.5% had a positive tuberculin skin test (>or=10 mm), incidence of active tuberculosis was 324.7/100,000 immigrants in the period of the study, 6.4% had a positive syphilis serology, 7.7% had a positive HBsAg, 3.1% had a positive serology for HCV and 2.8% were HIV positive, 41 patients from Latin America with risk factors for American Trypanosomiasis were screened for Chagas disease by immunofluorescence assay and 34% had a positive result; 5.4% of stools parasitological tests were positive for G. intestinalis; 4.2% for E. histolytica/E. dispar. Communicable diseases in immigrant population could lead to emerging and re-emerging infections in the European Union with important issues for public health. European countries may have to establish guidelines for screening of infectious diseases in immigrants from low-income countries.


Temporal generalization and diffusion in forgetting.
Two processes may contribute to the decrement in discriminability with increasing temporal distance between the occasioning event and later choice. One is the length of the interval and the other is generalization decrement. In the model described by White and Wixted [J. Exp. Anal. Behav. 71 (1999) 91-113], choice was predicted by the relative payoff for correct delayed matching responses, conditional on the current value of the stimulus sampled from Thurstone-like probability distributions of the effect of the sample stimuli. In the model, discriminability decreased with increasing temporal distance because the variance of the distributions increased with time. However, White and Wixted did not specify the function relating variance to temporal distance. If a diffusion process is assumed, and if diffusion increases exponentially with time, the resulting forgetting function is a negative exponential. An additional process involves exponential generalization of remembering from one time to other times. Alternative diffusion functions result in hyperbolic or power forgetting functions. The combination of two exponential processes yields forgetting functions that are double exponential in form and which appear consistent with a wide range of data.


Ginsenoside Rb1 promotes neurotransmitter release by modulating phosphorylation of synapsins through a cAMP-dependent protein kinase pathway.
Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), has been extensively used in traditional oriental medicine for the prevention and treatment of aging-related disorders for over 2000 years. Accumulating evidence suggests that ginsenosides such as Rg1 and Rb1, which are the pharmacologically active ingredients of ginseng, modulate neurotransmission. Synapsins are abundant phosphoproteins essential for regulating neurotransmitter release. All synapsins contain a short amino-terminal domain A that is highly conserved and phosphorylated by cAMP-dependent protein kinase (PKA), which plays a key role in regulating neurotransmitter release. In the present study, we demonstrated that both Rg1 and Rb1 increased neurotransmitter release in undifferentiated and differentiated PC12 cells. However, in the presence of the PKA inhibitor H89, Rg1, but not Rb1, still induced neurotransmitter release. Moreover, Rb1, but not Rg1, enhanced the phosphorylation of synapsins via PKA pathway. In summary, Rb1 promotes neurotransmitter release by increasing the phosphorylation of synapsins through the PKA pathway, whereas the similar effects observed with Rg1 are independent of the phosphorylation of synapsins.


The Cardiac Genetics Clinic: a model for multidisciplinary genomic medicine.
To describe patient characteristics, standard operating procedure, and uptake of genetic testing at the multidisciplinary Cardiac Genetics Clinic (CGC) at the Royal Melbourne Hospital during its first 6 years. Database exploration of referral diagnoses, sex, number of clinic visits and incidence of genetic testing in a population of individuals attending the CGC. Tertiary referral hospital (Royal Melbourne Hospital) providing cardiac genetics services to the state of Victoria. All individuals initially attending the clinic between July 2007 and July 2013, either as the proband or as an at-risk family member. Classification of patients into diagnostic categories, number of probands and at-risk relatives assessed, incidence and outcomes of genetic testing. 1170 individuals were seen for the first time over the 6-year period; 57.5% made only one visit. The median age was 39 years. Most were encompassed within four broad diagnostic categories: cardiomyopathy (315 patients), aortopathy (303 patients), arrhythmia disorders (203 patients) and resuscitated cardiac arrest and/or family history of sudden cardiac death (341 patients); eight patients had "other" diagnoses. Genetic testing (mutation detection or predictive testing) was undertaken in 381 individuals (32.6%), and a pathogenic mutation was identified in 47.6% of tests, representing 15.3% of the total population. The CGC fulfils an important role in assisting clinicians and patients by reviewing genetic cardiac diagnoses. Clinical practice during the study period moved from a selected candidate gene approach to broader gene panel-based testing. This move to next-generation sequencing may increase the detection of mutations and variants of unknown significance. A major contribution by the clinic to the care of these individuals and their families is the provision (or negating) of a diagnosis, and of a plan for managing risks of predictable cardiac disease.


Rapid diagnostic methods in sexually transmitted infections.
Sexually transmitted infections (STIs) are common infections throughout the developed and the developing world. It is estimated that worldwide there are 1 million new cases per day of curable bacterial STIs. As part of the World Health Organization 2001 Sexually Transmitted Diseases Diagnostics Initiative, the organization explored the need for simple, affordable, point-of-care STI testing for curable bacterial STIs. This article reviews the evidence supporting the implementation of currently available rapid tests for five common STIs: syphilis, gonorrhea, chlamydia, HIV, and herpes.


Do family physicians know the costs of medical care? Survey in British Columbia.
To determine the cost of 46 commonly used investigations and therapies and to assess British Columbia family doctors' awareness of these costs. Mailed survey asking about costs of 23 investigations and 23 therapies relevant to family practice. A random sample of 600 doctors was asked to report their awareness of costs and to estimate costs of the 46 items. British Columbia. Six hundred family physicians. Estimates within 25% of actual cost were considered correct. Associations between cost awareness and respondents'characteristics (eg, sex, practice location) were sought. Degree of error in estimates was also assessed. Overall, 283 (47.2%) surveys were returned and 259 analyzed. Few respondents estimated costs within 25% of true cost, and estimates were highly variable. Physicians underestimated costs of expensive drugs and laboratory investigations and overestimated costs of inexpensive drugs. Cost awareness did not correlate with sex, practice location, College certification, faculty appointment, or years in practice. Family doctors in British Columbia have little awareness of the costs of medical care.


N-Heterocyclic Carbene/Lewis Acid Dual Catalysis for the Divergent Construction of Enantiopure Bridged Lactones and Fused Indenes.
The chiral triazole carbene and Ti(OPr-i)4 cocatalyzed reaction between α,β-unsaturated aldehydes and 2-(aroylvinyl)benzaldehydes was systematically studied. A divergence in reaction pathways was observed under different reaction conditions. In benzene solvent and at ambient temperature, the reaction produced 4,5-dihydro-1,4-methanobenzo[c]oxepin-3-ones, the bridged caprolactones, as the major products in moderate yields with excellent enantioselectivity. The same reaction in dichloroethane and at 50 °C, however, gave 2,8-dihydrocyclopenta[a]indenes as the major products in most cases. The application of the method developed was demonstrated by the transformation of the bridged lactone products into enantiopure 4-hydroxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic acids.


Pre-treatment of real pharmaceutical wastewater by heterogeneous Fenton and persulfate oxidation processes.
This study compares the pre-oxidation of pharmaceutical wastewater by hydroxyl radical based advanced oxidation (HR-AOP) and a sulfate radical based advanced oxidation process (SR-AOP). The heterogeneous Fenton process is chosen as a model HR-AOP and persulfate (PS) activation as a model SR-AOP. The pre-treatment efficacy of both processes in terms of TOC, and COD removals using Fe3O4-rGO catalyst were considered. Under the investigated experimental conditions, both processes yielded fluctuating COD values with time. The heterogeneous Fenton process discovered to be the most efficient to remove 68.7% TOC in 180 min of treatment, when Fe3O4-rGO: H2O2 = 300 mg L-1:150 mM H2O2 was used at pH 3. Notably, the heterogeneous Fenton system was not considerably inhibited at the natural pH of pharmaceutical wastewater (6.75), as the process successfully removed 64.6% TOC. On the other hand, in persulfate activation studies, Fe3O4-rGO: PS = 400 mg L-1: 5 mM was the ideal condition for removing 59.5% TOC in 180 min at pH 3. Whereas the natural pH condition significantly inhibited the TOC removal, as only 20.8% TOC removal was feasible. The wastewater characterisation before and after Fenton treatment reveals that Fenton oxidation leads to an increase in inorganics (chlorides: 160 ± 15 mg L-1, nitrates: 63.14 ± 3.08 mg L-1, sulfates: 266.31 ± 31.39 mg L-1) necessitating an additional treatment step to reduce COD and inorganics further.


Small molecules with anti-inflammatory properties in clinical development.
Inflammation is a crucial physiological response of our body to any kind of noxa be it an infection or tissue injury. However, this physiological process can be detrimental if dysregulated, and when the acute inflammatory response fails to resolve the cause of inflammation, there can be a switch to chronification. According to ICD 10 (WHO) over 3.000 diseases exist with the suffix "-itis" which terms an inflammatory disease. For the treatment of inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widespread drugs while glucocorticoids are among our strongest weapons against inflammation, making them emergency treatments for acute episodes of chronic inflammation. For the treatment of many inflammatory disorders, both are not satisfying. Consequently, industrial and academic research on anti-inflammatory drugs is very intensive. In this review, we evaluate current treatments and unmet needs of chronic inflammatory diseases with high prevalence (rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disease, inflammatory bowel disease, and psoriasis), and systematically review small molecules with anti-inflammatory properties presently in clinical trials for the aforementioned diseases. As the pathophysiological knowledge of diseases increased over the last decades, a more specific intervention of inflammatory pathways becomes possible. After one hundred years of NSAIDs and over fifty years of glucocorticoids, more specific drugs for anti-inflammatory therapy such as roflumilast or fingolimod are rising. The aim of this article is to critically review the literature on small anti-inflammatory molecules in clinical trials to generate an idea of what we can expect in the future.


Autologous transplantation of mobilized peripheral blood CD34+ cells selected by immunomagnetic procedures in patients with multiple myeloma.
In the use of autologous PBPC transplantation in patients with multiple myeloma, contamination of PBPC with myeloma cells is commonly observed. Enrichment for CD34+ cells has been employed as a method of reducing this contamination. In this study the reduction of myeloma cells in PBPC was accomplished by the positive selection of CD34+ cells using immunomagnetic bead separation (Isolex 300 system). PBPC were mobilized from 18 patients using cyclophosphamide (4.5 g/m2) and G-CSF (10 microg/kg/day). A median of two leukaphereses and one selection was performed per patient. The median number of mononuclear cells processed was 3.50 x 10(10) with a recovery of 1.11 x 10(8) cells after selection. The median recovery of CD34+ cells was 48% (range 17-78) and purity was 90% (29-99). The median log depletion of CD19+ cells was 3.0. IgH rearrangement, assessed by PCR, was undetectable in 13 of 24 evaluable CD34+ enriched products. Patients received 200 mg/m2 of melphalan followed by the infusion of a median of 2.91 x 10(6)/kg CD34+ cells (1.00-16.30). The median time to absolute neutrophil count >0.5 x 10(9)/l was 11 days, and sustained platelet recovery of >20 x 10(9)/l was 14 days. We conclude that immunomagnetic-based enrichment of CD34+ cells results in a marked reduction in myeloma cells without affecting engraftment kinetics.


Nucleophosmin is required for chromosome congression, proper mitotic spindle formation, and kinetochore-microtubule attachment in HeLa cells.
Nucleophosmin (NPM) is an abundantly expressed multifunctional nucleolar phosphoprotein. Here we show that depletion of NPM by RNA interference causes defects in cell division, followed by an arrest of DNA synthesis due to activation of a p53-dependent checkpoint response in HeLa cells. Depletion of NPM leads to mitotic arrest due to spindle checkpoint activation. The mitotic cells arrested by NPM depletion have defects in chromosome congression, proper mitotic spindle and centrosome formation, as well as defects in kinetochore-microtubule attachments. Loss of NPM thus causes severe mitotic defects and delayed mitotic progression. These findings indicate that NPM is essential for mitotic progression and cell proliferation.


Author Correction: The structure of a red-shifted photosystem I reveals a red site in the core antenna.
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-19953-w.


Prevalence and molecular identification of Balantioides coli isolates from pet guinea pigs in Central China.
Balantioides coli is the only known zoonotic ciliate that can infect humans and is usually acquired from swine. It has, however, been reported in other mammals, including guinea pigs, where infection prevalence and molecular characterization are relatively unknown. In the present study, 32 guinea pigs from two different pet markets in Luoyang city of the Henan province in China were evaluated for ciliate-like trophozoites or cysts by direct fecal smear microscopy. Positive samples were further characterized using 18S rDNA and ITS1-5.8S rDNA-ITS2 sequence analysis. Microscopy indicated that ciliate-like cysts were observed in the fecal samples of several guinea pigs, were spherical in shape, and exhibited sizes of 40-65 μm in diameter. The average cyst-positive prevalence in guinea pigs was 62.5%. Sequence analysis indicated that the guinea pig-derived ciliate isolates belonged to B. coli and included two genetic variants (A and B), of which genetic variant A was more dominant among the guinea pig samples. To the best of our knowledge, the present study is the first molecular identification of B. coli in guinea pigs and provides some important information for investigating the molecular epidemiology of B. coli.


Human cornea: superior and central oxygen demands.
Corneal oxygen demands, expressed as ratios of uptake rate relative to baseline rates derived from unstressed corneas, were determined with a micropolarographic system for central (closed eye) and superior (open eye) locations of one cornea of each of seven human subjects. The closed-eye central corneal measurements were repeated during two additional experimental sessions. Intrasubject variability of the three mean closed-eye central corneal rate ratios ranged as high as 23%, possibly representing effects of homeostatic mechanisms on the palpebral conjunctival capillaries of some subjects. For the open-eye superior cornea, which was covered by the upper eyelid of every subject prior to measurement, oxygen demand was found to have a greater intersubject range, but was diminished in magnitude relative to the demand associated with the closed-eye central cornea. Superior corneal oxygen demand was not found to be predictable from closed-eye central corneal oxygen demand or extent of eyelid overlap onto the cornea and thus indicated localized open-eye superior corneal environments that were significantly different from those of the corresponding closed-eye central corneas. Such localized environments may be critically important when gauging the susceptibility of particular eyes to superior corneal pathology during contact lens wear.


Ki67 expression in different epithelial types in columnar lined oesophagus indicates varying levels of expanded and aberrant proliferative patterns.
To evaluate proliferative patterns in metaplastic columnar epithelia of the oesophagus, classified as oxynto-cardiac (n = 43), cardiac (n = 45) intestinal without dysplasia (n = 41), dysplastic intestinal epithelium (n = 25), and adenocarcinoma (n = 15) by Ki67 immunohistochemistry. Abnormal patterns of Ki67 immunoreactivity were classified into (i) expanded proliferation, characterized by increased levels of Ki67 expression in the deep and mid third of the foveolar pit; and (ii) aberrant proliferation, characterized by positive staining in the surface epithelium and superficial third of the foveolar pit. A significant step-wise increase in the frequency of expanded proliferation was seen in oxynto-cardiac, cardiac, intestinal and dysplastic intestinal epithelium indicative of increasing levels of damage. Aberrant proliferation was absent in oxynto-cardiac mucosa, present at a low and similar level in cardiac, intestinal and low-grade dysplastic epithelia and at a significantly increased frequency in high-grade dysplasia. These findings suggest that oxynto-cardiac mucosa occurs in a low damage environment and intestinal metaplasia in a high damage environment along the length of the columnar lined oesophageal segment. Aberrant proliferative patterns with Ki67 staining are not useful in differentiating reactive epithelia from low-grade dysplasia, but may prove useful in the diagnosis of high-grade dysplasia.


Transcriptomics of the Carotid Body.
The carotid body (CB) has emerged as a potential therapeutic target for treating sympathetically mediated cardiovascular, respiratory, and metabolic diseases. In adjunct to its classical role as an arterial O2 sensor, the CB is a multimodal sensor activated by a range of stimuli in the circulation. However, consensus on how CB multimodality is achieved is lacking; even the best studied O2-sensing appears to involve multiple convergent mechanisms. A strategy to understand multimodal sensing is to adopt a hypothesis-free, high-throughput transcriptomic approach. This has proven instrumental for understanding fundamental mechanisms of CB response to hypoxia and other stimulants, its developmental niche, cellular heterogeneity, laterality, and pathophysiological remodeling in disease states. Herein, we review this published work that reveals novel molecular mechanisms underpinning multimodal sensing and reveals numerous gaps in knowledge that require experimental testing.


Inter-muscular coordination during running on grass, concrete and treadmill.
Running is an exercise that can be performed in different environments that imposes distinct foot-floor interactions. For instance, running on grass may help reducing instantaneous vertical impact loading, while compromising natural speed. Inter-muscular coordination during running is an important factor to understand motor performance, but little is known regarding the impact of running surface hardness on inter-muscular coordination. Therefore, we investigated whether inter-muscular coordination during running is influenced by running surface. Surface electromyography (EMG) from 12 lower limb muscles were recorded from young male individuals (n = 9) while running on grass, concrete, and on a treadmill. Motor modules consisting of weighting coefficients and activation signals were extracted from the multi-muscle EMG datasets representing 50 consecutive running cycles using non-negative matrix factorization. We found that four motor modules were sufficient to represent the EMG from all running surfaces. The inter-subject similarity across muscle weightings was the lowest for running on grass (r = 0.76 ± 0.11) compared to concrete (r = 0.81 ± 0.07) and treadmill (r = 0.78 ± 0.05), but no differences in weighting coefficients were found when analyzing the number of significantly active muscles and residual muscle weightings (p > 0.05). Statistical parametric mapping showed no temporal differences between activation signals across running surfaces (p > 0.05). However, the activation duration (% time above 15% peak activation) was significantly shorter for treadmill running compared to grass and concrete (p < 0.05). These results suggest predominantly similar neuromuscular strategies to control multiple muscles across different running surfaces. However, individual adjustments in inter-muscular coordination are required when coping with softer surfaces or the treadmill's moving belt.


Cutaneous immune-related adverse events and photodamaged skin in patients with metastatic melanoma: could nicotinamide be useful?
Cutaneous immune-related adverse events (irAEs) occur in more than one-third of patients treated with immune checkpoint inhibitors; they are often the first clinical manifestation, although they may occur months after initiation of therapy. We noticed that our patients usually have these cutaneous AEs on photodamaged skin. In fact, out of 19 patients being treated for metastatic melanoma, 8 (42%), all of whom had significant cutaneous actinic damage, developed cutaneous irAEs earlier and in a more serious form than those without such damage. Thus, we gave a high oral dose of nicotinamide (500 mg twice daily) to the patients with metastatic melanoma who had photodamaged skin, and continued this for the entire duration of the immunotherapy. The appearance of the first signs of cutaneous irAEs was 180 days after starting therapy in nicotinamide-treated patients, compared with 65 days for patients not treated with nicotinamide.


Capsaicin-induced reflex fall in rat blood pressure is mediated by afferent substance P-containing neurones via a reflex centre in the brain stem.
Injection of 0.03 micrograms capsaicin into one femoral artery elicited a fall in blood pressure in the rat. This effect was completely and reversibly abolished following intrathecal injection of 1 nmol of the specific substance P antagonist, [D-Pro2,D-Trp7,9] substance P. The capsaicin-evoked depressor reflex is therefore exclusively mediated by substance P-containing primary afferent fibres. Using spinal rats or decerebration experiments, the centre of the capsaicin-evoked reflex fall in blood pressure could be localized in the brain stem.


Bladder pressure monitoring significantly enhances care of infants with abdominal wall defects: a prospective clinical study.
Increased intraabdominal pressure (IAP) has been demonstrated to cause intestinal and renal ischemia in both animals and humans. Neonates undergoing closure of anterior abdominal wall defects are at risk for these complications from markedly increased IAP, which are putatively responsible for a 13% to 20% mortality. In an effort to decrease morbidity and mortality we performed a 4-year prospective clinical study to determine if monitoring IAP using bladder pressure (BdP) measurements would significantly improve perioperative care in infants with abdominal wall defects. Forty-two consecutive infants with gastroschisis (28) and omphalocele (14) were prospectively studied. Intraoperative and serial postoperative measurements of BdP were obtained from an indwelling bladder catheter using a standard pressure transducer. Methods of initial closure, as well as manipulations in sedation, paralysis, and silo reduction, were selected to keep BdP < 20 mm Hg. Bladder pressure monitoring significantly altered the management of 64% of our patients, particularly those with gastroschisis (74%). Thirteen patients with gastroschisis underwent staged closure; in 7 (54%) this decision was based on high BdP even though bowel reduction was mechanically possible. Elevated BdP influenced the closure method and timing of silo reductions in 5 of 14 (42%) infants with omphalocele. There were no episodes of renal failure or refractory oliguria. There were three patients in a single cluster who developed uncomplicated, nonsurgical necrotizing enterocolitis late in their respective courses. One patient whose bowel was placed in a silo had severe hypotension associated with group B streptococcal sepsis and subsequently developed necrotic bowel despite low BdP.(ABSTRACT TRUNCATED AT 250 WORDS)


MicroRNA-29b is involved in the Src-ID1 signaling pathway and is dysregulated in human lung adenocarcinoma.
The c-Src kinase regulates cancer cell invasion through inhibitor of DNA binding/differentiation 1 (ID1). Src and ID1 are frequently overexpressed in human lung adenocarcinoma. The current study aimed at identifying microRNAs (miRNAs) involved in the Src-ID1 signaling in lung cancer. Incubation of lung cancer cells with the Src inhibitor saracatinib led to the upregulation of several miRNAs including miR-29b, which was the most highly upregulated miRNA with predicted binding to the ID1 3'-untranslated region (UTR). Luciferase reporter assays confirmed direct binding of miR-29b to the ID1 3'-UTR. Expression of miR-29b suppressed ID1 levels and significantly reduced migration and invasion. Expression of antisense-miR-29b (anti-miR-29b), on the other hand, enhanced ID1 mRNA and protein levels, and significantly increased lung cancer cell migration and invasion, a hallmark of the Src-ID1 pathway. The ectopic expression of ID1 in miR-29b-overexpressing cells was able to rescue the migratory potential of these cells. Both, anti-miR-29b and ID1 overexpression diminished the effects of the Src inhibitors saracatinib and dasatinib on migration and invasion. Saracatinib and dasatinib decreased c-Myc transcriptional repression on miR-29b and led to increased ID1 protein levels, whereas forced expression of c-Myc repressed miR-29b and induced ID1. In agreement, we showed direct recruitment of c-Myc to the miR-29b promoter. miR-29b was significantly downregulated in primary lung adenocarcinoma samples compared with matched alveolar lung tissue, and miR-29b expression was a significant prognostic factor for patient outcome. These results suggest that miR-29b is involved in the Src-ID1 signaling pathway, is dysregulated in lung adenocarcinoma and is a potential predictive marker for Src kinase inhibitors.


Surgeon-industry conflict of interest: survey of North Americans' opinions regarding surgeons consulting with industry.
Surgeon-industry conflict of interest (COI) has become a source of considerable interest. Professional medical societies, industry, and policy makers have attempted to regulate potential COI without consideration for public opinion. The objective of this study was to report on the opinions of individuals representing the general public regarding surgeon-industry consulting relationships. Web-based survey. Survey was administered using a "spine Web site," and opinions are collected on surgeon-industry consulting and regulation. Associations among responses to similar questions were assessed to ensure validity and subgroup analysis performed for respondent age, sex, education, insurance, employment, and patient status. Six hundred ten of 642 surveys had complete data. The sample population comprised more females and was older and more educated than the American population. About 80% of respondents felt it was ethical and either beneficial or of no influence to the quality of health care if surgeons were consultants for surgical device companies. Most felt disclosure of an industry relationship was important and paying surgeons royalties for devices, other than those they directly implant, would not affect quality of care. Respondents support multidisciplinary surgeon-industry COI regulation and trust doctors and their professional societies to head this effort. Despite the known potential negative impact of surgeon-industry COI on patient care, this study revealed that this does not seem to be reflected in the opinion of the general public. The respondents felt that disclosure is deemed one of the most important means of self-regulation and COI management, which is in agreement with current trends of most spine societies and journals that are increasing the stringency of disclosure policies.


The natural history of carcinoma in situ involving bronchial resection margins.
Microscopic residual disease in the bronchial resection margins after surgical resection of lung cancer is rare, and its clinical significance remains unsettled. We studied the natural history of patients with carcinoma in situ (CIS) at their bronchial resection margins to focus on the issue of stump recurrence. Eleven individuals who had undergone radical surgery for N0M0 lung tumors were found to have CIS at the bronchial resection margins. All of the resection specimens were reviewed with respect to the pattern of CIS extension and reclassified as follows: superficial CIS, involving surface epithelium only (CIS-S), CIS extending into the submucosal gland ducts but not deeper (CIS-D), and CIS extending into submucosal gland acini (CIS-A). Patients were followed using autofluorescence bronchoscopy and high-resolution computer tomography. Clinical parameters and the local extent of CIS at histology review were correlated with outcome. Median follow-up was 35 months (range, 15 to 89). Histology review showed two CIS-S cases, six CIS-D cases, and three CIS-A cases. All of the patients with CIS-A developed stump recurrences in contrast with those with only CIS-S. Three patients with CIS-D have developed metachronous primaries in the contralateral lung, whereas the stump region remained free of tumor. The presence of CIS in the bronchial resection margin after resection of lung cancers is associated with stump recurrences. Although absolute numbers are too small for firm conclusions, our data suggest that those with deep glandular extension of CIS bear the highest risk of early recurrence. However, the development of new primaries away from the stump region and the possible development of distant disease are equally relevant considerations with respect to the choice of additional therapy.


Epithelial-Mesenchymal Transition-Based Gene Signature and Distinct Molecular Subtypes for Predicting Clinical Outcomes in Breast Cancer.
Regulation of inducers and transcription factor families influence epithelial-mesenchymal transition (EMT), a contributing factor to breast cancer invasion and progression. Molecular subtypes were classified based on EMT-related mRNAs using ConsensusClusterPlus package. Differences in tumor immune microenvironment and prognosis were assessed among subtypes. Based on EMT genes, a gene signature for prognosis was built using TCGA training set by performing multivariate and univariate Cox regression analyses. Prediction accuracy of the signature was validated by receiver operating characteristic (ROC) curves and overall survival analysis on internal and external datasets. By conducting univariate and multivariate Cox regression analyses, the risk signature as an independent prognostic indicator was assessed. A nomogram was constructed and validated by calibration analysis and decision curve analysis (DCA). Five molecular subtypes were characterized based on EMT genes. Patients in Cluster 2 exhibited an activated immune state and a better prognosis. An 11-EMT gene-signature was built to predict breast cancer prognosis. After validation, the signature showed independence and robustness in predicting clinical outcomes of patients. A nomogram combining the RiskScore and pTNM_stage accurately predicted 1-, 2-, 3-, and 5-year survival chance. In comparison with published model, the current model showed a higher area under the curve (AUC). We characterized five breast cancer subtypes with distinct clinical outcomes and immune status. The study developed an 11-EMT gene-signature as an independent prognostic factor for predicting clinical outcomes of breast cancer.


[Variation and Distribution of the Eelpout Species of the Genus Zoarces (Pisces: Zoarcidae) of the Sea of Okhotsk].
Complex molecular genetic, karyological, and comparative morphological analyses of eelpouts of the genus Zoarces from the Sea of Okhotsk were carried out. Genetic heterogeneity of Z. elongatus and the existence of a considerably diverged form probably deserving of species status was discovered. The eelpouts caught near Shantar Islands were identified as Z. fedorovi and Z. andriashevi. The new data point to a wider distribution of these species, from Western Kamchatka to the Shantar Islands.


Association of Aspirin with Dementia or Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Randomized Trials.
At present, the effect of aspirin in preventing dementia or mild cognitive impairment (MCI) is controversial. Clarifying their association is of interest for subsequent relevant clinical trials. Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched from inception to May 12, 2023, for randomized controlled trials (RCTs) that explored the effects between aspirin and dementia or MCI. Two reviewers independently extracted and analyzed data using Stata software. Discrepancy was resolved by a third reviewer. The primary outcomes were dementia and MCI. The secondary outcomes were cognitive decline and changes in cognitive scores. Five RCTs with 46,804 participants at randomization were included. For the primary outcomes, low-certainty evidence showed that aspirin was not associated with dementia (odds ratio [OR] = 0.93, 95% confidence interval [CI]: [0.85, 1.03], p > 0.05, I2 = 0%) or MCI (OR = 1.00, 95% CI: [0.88, 1.14], p > 0.05, I2 = 3.3%). For the secondary outcomes, moderate-certainty evidence showed that aspirin was not associated with cognitive decline (OR = 1.02, 95% CI: [0.93, 1.11], p > 0.05, I2 = 0%) and a change in global cognitive score (standard mean difference [SMD] = -0.01, 95% CI: [-0.03, 0.02], p > 0.05, I2 = 0%). Low-certainty evidence showed that aspirin was not associated with a change in verbal learning memory score (SMD = -0.04, 95% CI: [-0.09, 0.01], p > 0.05; I2 = 72.5%). Low- and moderate-certainty evidence showed that aspirin was not associated with dementia, MCI, cognitive decline, or better cognitive scores. Future research may need to focus more on subtypes of dementia, mainly vascular dementia or other vascular neurocognitive diseases, and assess whether aspirin has long-term clinical benefits in a large sample of patients with dementia or MCI.


Characteristic biochemical differences in human T and B lymphocytes separated on nylon wool.
T and B lymphocytes from human tonsils were separated on a nylon wool column. T. cells are enriched in the nonadherent, B cells in the adherent fraction. Several enzymes and other markers were tested in separated and non separated lymphocyte populations. Certain enzymes and other properties can be used as T or B lymphocyte markers because of their preferential occurrence and because of the advantages of their estimation (simple, quick methods, objective evaluation). The following characteristics were considered as markers on the basis of our results: (I) acid phosphatase, Na+-K+-activated ATPase, BAEE-peptidase and chromium labeling in T lymphocytes; (II) 5'-nucleotidase, FITC-IgG binding, N-acetyl-D-glucosaminidase, thymidine and valine incorporation in B lymphocytes.


Use of Real-World Evidence for Drug Regulatory Decisions in China: Current Status and Future Directions.
Real-world data (RWD) and real-world evidence (RWE) have garnered great interest for supporting drug research and development (R&D) by medical researchers and regulators in recent years. The application and development of RWD/E in drug regulatory decision-making have been vigorously promoted in China. This study seeks to provide a broad overview of how RWE has been contributing to drug regulatory decisions in China. In this paper, we review the development of RWD and RWE, summarize key elements that promote application of RWE, introduce relevant methods and guidelines, elaborate on the opportunities and challenges of RWE in regulatory decision-making in China, and put forward suggestions to promote the application of RWE in China's regulatory decision-making and to further facilitate innovative drug evaluation and regulation.


Aminopyrine metabolism in the presence of hyperbilirubinemia due to cholestasis or hepatocellular disease. Combined use of laboratory tests to study disease-induced alterations in drug disposition.
Hepatocellular diseases, such as hepatitis, cirrhosis, or hepatic neoplasm, are associated with impaired metabolism of certain drugs, including aminopyrine, whereas cholestasis produced variable effects on aminopyrine metabolism. Reasons for the variable effects of cholestasis on hepatic aminopyrine metabolism were sought by performing in patients with hyperbilirubinemia the aminopyrine breath test (ABT), which consists of measurements of 14CO2 in breath 2 hr after oral administration of [14C]aminopyrine. Hyperbilirubinemia (total serum bilirubin less than 1.2 mg/100 ml) in these patients was due to hepatocellular disease or cholestasis. The ABT, defined as the percentage of the administered dose of 14C excreted in breath for 2 hr after [14C]aminopyrine administration, was 6.2 +/- 0.8% (mean +/- SD) in 107 control patients with normal total serum bilirubin. The ABT was severely abnormal (less than 3.1%) in 54 of 77 hyperbilirubinemic patients (70%) with hepatocellular disease and normal (greater than 4.5%) in only 5 of these patients (6%). In contrast, the ABT was severely abnormal in only 1 of 40 cases of cholestasis with hyperbilirubinemia and normal in 70% of these patients. Thus, aminopyrine metabolism is normal in most cases of hyperbilirubinemia due to cholestasis and is only rarely severely abnormal in these patients. On the other hand, severe abnormality in aminopyrine metabolism occurs in the majority of patients with hyperbilirubinemia due to hepatocellular disease. It therefore appears that the ABT may be useful in hyperbilirubinemia to distinguish patients with hyperbilirubinemia due to cholestasis form most patients with hyperbilirubinemia due to hepatocellular disease.


Is the national nutrition survey in Japan representative of the entire Japanese population?
We examined the representativeness of the sample used in the National Nutrition Survey in Japan (J-NNS). The distribution of the J-NNS sample from 1995 to 2000 was compared with that of the national census with respect to gender, age group, place of residence, and number of household members. In the survey sample, as compared with the national census distributions, the proportion of females was 1% to 2% larger, the proportion of individuals who were 20 to 39 y of age was a few percentages smaller, and a slight bias toward rural areas was seen. Among individuals who were 20 to 59 y of age, the proportion of individuals who lived in single-person households was 50% to 66% of that found in the national census. Observed disparities between the sample and the population were minimal except in the case of the proportion of individuals who lived alone. The sample used in the J-NNS is generally representative of the entire Japanese population with the exception of individuals in single-person households.


TLR3 and MDA5 Knockout DF-1 cells Enhance Replication of Avian Orthoavulavirus 1.
Despite the essential role of innate immunity in defining the outcome of viral infections, the roles played by different components of the avian innate immune system are poorly delineated. Here, we investigated the potential implication of avian toll-like receptor (TLR) 3 (TLR3) and melanoma differentiation-associated (MDA) gene 5 (MDA5) receptors of double-stranded RNA (dsRNA) in induction of the interferon pathway and avian orthoavulavirus 1 (AOAV-1) replication in chicken-origin DF-1 fibroblast cells. TLR3 and MDA5 knockout (KO) DF-1 cells were generated using our avian-specific CRISPR/Cas9 system and stimulated with a synthetic dsRNA ligand polyinosinic:polycytidylic acid [poly(I:C)] or infected with AOAV-1 (previously known as Newcastle disease virus). Poly(I:C) treatment in cell culture media resulted in significant upregulation of interferon (IFN)α, IFNβ, and Mx1 gene expression in wild type (WT) DF-1 cells but not in TLR3-MDA5 double KO cells. Interestingly, poly(I:C) treatment induced rapid cell degeneration in WT and MDA5 KO cells, but not in TLR3 knockout or TRL3-MDA5 double knockout (DKO) cells, directly linking poly(I:C)-induced cell degeneration to TLR3-mediated host response. The double knockout cells supported significantly higher replication of AOAV-1 virus than did the WT cells. However, no correlation between the level of virus replication and type I IFN response was observed. Our study suggests that innate immune response is host- and pathogen specific, and further investigation is needed to understand the relevance of dsRNA receptor-mediated immune responses in viral replication and pathogenesis in avian species.


[Hypothermic effect on mice of a 1-10 kD fraction of the small intestine of the hibernating suslik Citellus undulatus during hypoxia and hypercapnia].
Studies have been made on a possibility of inducing a prolonged hypothermia by injections to albino mice of a fraction with a molecular mass 1-10 KD isolated from the small intestine of hibernating ground squirrels. Specific conditions for the onset of hibernation (hypoxia, hypercapnia, temperature) were simulated. Exposure of mice to hypoxia and hypercapnia for 2 hours in combination with injection of the mentioned fraction extended hypothermic condition in animals up to 24-36 hours as compared to 2-3 hours after sole injection of the fraction. After the injection of 5-OT under the same conditions, the prolonged hypothermia was less stable.


[Pemetrexed as second-line treatment and beyond for elderly patients with advanced non-small-cell lung cancer].
In Japan, the standard first-line therapy for elderly patients with advanced non-small lung cancer(NSCLC)is docetaxel(DOC)monotherapy. However, there is very limited information about second-line and beyond chemotherapy regimens for elderly patients with advanced NSCLC. Pemetrexed(PEM)monotherapy has been recognized as a standard regimen for advanced NSCLC in second-line settings, just as DOC monotherapy has been. The objective of this study was to examine the efficacy and safety of PEM as second-line therapy and beyond for elderly patients. The records of previously -treated elderly patients with advanced NSCLC, who had been treated with PEM as second-line therapy and beyond between July 2009 and December 2010, were retrospectively reviewed. median age: 73 years old(range 70-79 years old); gender: male/female, 11/8; PS 0-1/≥2, 19/0; clinical stage: III B/IV/postoperative recurrence, 4/10/5; pathology: adeno/LCNEC/other, 17/1/1 patient. The objective response-rate and disease control-rate were 15. 8% and 57. 9%, respectively. Median progression-free survival time was 3. 2 months. There were no treatment-related deaths, and most of the toxicities of the treatment regimen were mild and acceptable. PEM monotherapy exhibits activity in previously treated elderly NSCLC patients and has an acceptably low toxicity. Further study is warranted to confirm our results.


Eosinophilic variant of chromophobe renal cell carcinoma metastasizing to the liver: Diagnostic pitfall.
An 82-year-old man developed a hypervascular renal tumor, 2 cm in size, and multiple liver tumors. Liver tumors had obscured tumor margins on ultrasonography. Positron emission tomography/computed tomography (PET/CT) showed no areas of avid radiotracer uptake in the liver. Routine pathological examination failed to demonstrate tumor cells in 9 tissue samples obtained from repeated core needle biopsies. Even a frozen section of the liver segment 8 tumor further failed to prove malignant cells, and an additive frozen section of the liver section 2 tumor finally proved atypical cells growing in tubular and solid fashions with eosinophilic cytoplasm. Tumors showed expansive growth patterns, were in direct contact with normal liver cells, had abundant micro-vessels, had only sparse hyalinized septa, and had no pale cells. Immunostaining revealed the tumor cells to be positive for CD10, CD117, and E-cadherin and negative for CK7, and PAX8, leading to the diagnosis of metastatic chromophobe renal cell carcinoma (chRCC) in the liver. Arginase-1 immunostaining clearly demarcated the boundary between the chRCC cells and normal hepatic cells. Diagnostic physicians should note that chRCCs are of low-grade malignancy despite their abundant intra-tumoral blood flow and can often pose imaging and pathologic diagnostic difficulties.


The economic burden of overweight and obesity in Brazil: perspectives for the Brazilian Unified Health System.
Parallel to rising obesity prevalence in Brazil, there is expected to be increased direct health care costs related to non-communicable diseases (NCDs). In this study, we estimated the economic burden of NCDs attributable to overweight and obesity in the Brazilian Unified Health System (SUS). We used self-reported body mass index of 85,715 adults from the 2019 Brazilian National Health Survey. Annual costs (1 US$ = 2.281 Reais) with inpatient and outpatient procedures were obtained from the Hospital and Ambulatory Information Systems of the Brazilian SUS. Relative risks for cardiovascular disease, chronic respiratory disease, neoplasm, digestive disease, musculoskeletal disorders, diabetes and kidney diseases, sense organ diseases, and neurological disorders were retrieved from the Global Burden of Disease study. Annually, US$ 654 million (95% uncertainty interval: US$ 418.4 to US$ 893.2) direct health care costs related to NCDs were attributable to overweight and obesity. Attributable costs were higher in women than men. Cardiovascular diseases had the highest attributable costs (US$ 289 million), followed by chronic respiratory diseases (US$ 110 million), neoplasms (US$ 96 million), digestive diseases (US$ 60 million), musculoskeletal disorders (US$ 44 million), diabetes and kidney disease (US$ 31 million), sense organ diseases (US$ 22 million) and neurological disorders (US$ 11 million). Overweight and obesity account for US$ 654 million direct costs of NCDs annually. Effective policies to promote healthy body weight may have economic benefits.


Toxicological Analysis by Assessment of Vascularization and Cell Viability Using the Chicken's Chorioallantoic Membrane (CAM Assay).
The chorioallantoic membrane (CAM) assay is an increasingly popular method using a hen's egg as an experimental organism. Animal models have been established in scientific research for centuries. Yet, awareness of animal welfare in society rises, and the transferability of findings obtained in rodent models to human physiology is challenged. Thus, using fertilized eggs as an alternative platform for animal experimentation might be a promising alternative. The CAM assay is utilized for toxicological analysis by determination of CAM irritation as well as analysis of organ damage and ultimately death of the embryo. Furthermore the CAM provides a micromilieu suited for the implantation of xenografts. Xenogene tissues and tumors grow on the CAM due to a lack of rejection by the immune system and a dense vascular network providing oxygen and nutrients. Multiple analytical methods including in vivo microscopy and various imaging techniques are applicable to this model. Additionally, ethical aspects, a comparatively low financial burden, and low bureaucratic hurdles legitimize the CAM assay.We here describe an in ovo model utilized for xenotransplantation of a human tumor. The model can be used to evaluate the efficacy as well as the toxicity of different therapeutic agents after intravascular injection. Additionally, we present the evaluation of vascularization and viability by intravital microscopy, ultrasonography, and immunohistochemistry.


The effect of the burial environment on adipocere formation.
Adipocere is a decomposition product comprising predominantly of saturated fatty acids which results from the hydrolysis and hydrogenation of neutral fats in the body. Adipocere formation may occur in various decomposition environments but is chiefly dependent on the surrounding conditions. In a soil burial environment these conditions may include such factors as soil pH, temperature, moisture and the oxygen content within the grave site. This study was conducted to investigate the effect of these particular burial factors on the rate and extent of adipocere formation. Controlled laboratory experiments were conducted in an attempt to form adipocere from pig adipose tissue in model burial environments. Infrared spectroscopy, inductively coupled plasma-mass spectrometry, and gas chromatography-mass spectrometry were employed to determine the lipid profile and fatty acid composition of the adipocere product which formed in the burial environments. The results suggest that adipocere can form under a variety of burial conditions. Several burial factors were identified as enhancing adipocere formation whilst others clearly inhibited its formation. This study acts as a preliminary investigation into the effect of the burial environment on the resultant preservation of decomposing tissue via adipocere formation.


Exosome miR-223-3p in the bone marrow-derived mesenchymal stem cells alleviates the inflammation and airway remodeling through NLRP3-induced ASC/Caspase-1/GSDMD signaling pathway.
Asthma is one of the most common chronic respiratory diseases in the world. Exploration and understanding of the pathogenesis of epithelial-mesenchymal transition in airway epithelial cells, and the development of new molecular drugs targeted at airway inflammation and remodeling have become the key and hot points in the prevention and treatment of asthma. Emerging evidence has proven that miRNAs are strongly associated with numerous chronic respiratory diseases including asthma, but the involved molecular mechanisms have not been revealed. In the present study, we successfully isolated exosomes from BMMSCs and found that the derived exosomes could improve airway inflammation and remodeling in ovalbumin-induced asthma rats. Furthermore, we found that the highly expressed miR-223-3p in exosomes might play a key pivotal role in the protective effects on airway remodeling and asthma by regulating the NLRP3-induced ASC/Caspase-1/GSDMD signaling pathway. These results provided a promising molecule candidate and target for the therapy of asthma.


[Clinical and muscle istochemical observations in secondary hypokalaemia (author's transl)].
A case of hypokalaemia due to chronic administration of Clortalydone is reported. The histochemistry of muscle biopsy showed the morphologic changes which are usually found in the muscle fibers of periodic familial paralysis (necrotic fibers, accumulation of PAS positive substance, inflammatory cells, intermyofibrillar network degeneration, increase of lipids content). Such findings suggest some clues to the pathophysiology of the essential hypokalaemic paralysis and the possible practical importance of these histopathologic muscular findings in the diagnosis of secondary hypokalaemia.


Erratum: A rare intracranial tumor consisting of malignant anaplastic and papillary meningioma subtypes.
[This corrects the article on p. 21 in vol. 7, PMID: 26981322.].


Enzyme-linked immunosorbent assay for the detection of antibodies to the alcelaphine herpesvirus of malignant catarrhal fever in exotic ruminants.
An ELISA for antibodies to the alcelaphine herpesvirus-1 of malignant catarrhal fever was developed. Of sera that represented 42 exotic ruminant species, 216 were evaluated by the ELISA and a virus-neutralization test. A significant correlation (r = 0.564, P less than 0.001, n = 216) between the ELISA and virus-neutralization test results was found. Of the sera having positive test results by virus neutralization, 86.1% also had positive results by the ELISA, and of the sera having negative test results by virus neutralization, 83.9% also had negative results by the ELISA. The presence of antibody, as measured by the ELISA, correlated with clinical signs of malignant catarrhal fever and the isolation of herpesvirus.


Dietary polyunsaturated fatty acids and the Pro12Ala polymorphisms of PPARG regulate serum lipids through divergent pathways: a randomized crossover clinical trial.
Human and animal studies suggest an interaction between the Pro12Ala polymorphism of PPARG and dietary fat. In this randomized crossover clinical trial, we investigated whether subjects with the Pro12Pro and Ala12Ala genotypes of PPARG respond differently to a diet supplemented with high saturated (SAFA) or polyunsaturated fatty acid (PUFA).We recruited non-diabetic men from a population-based METSIM study (including 10,197 men) to obtain men with the Ala12Ala and the Pro12Pro genotypes matched for age and body mass index. Seventeen men with the Pro12Pro genotype and 14 with the Ala12Ala genotype were randomized to both a PUFA diet and a SAFA diet for 8 weeks in a crossover setting. Serum lipids and adipose tissue mRNA expression were measured during the diet intervention. At baseline, subjects with the Ala12Ala genotype had higher levels of HDL cholesterol and lower levels of LDL cholesterol, total triglycerides, and apolipoprotein B compared to those subjects with the Pro12Pro genotype (P < 0.05, FDR < 0.1). The Ala12Ala genotype also associated with higher mRNA expression of PPARG2, LPIN1, and SREBP-1c compared to participants with the Pro12Pro genotype (FDR < 0.001). On the other hand, PUFA diet resulted in lower levels of fasting glucose, total cholesterol, total triglycerides, and apolipoprotein B (P < 0.05, FDR < 0.1) but did not affect PPARG2 mRNA expression in adipose tissue. We conclude that individuals with the Pro12Pro genotype, with higher triglyceride levels at baseline, are more likely to benefit from the PUFA diet. However, the beneficial effects of dietary PUFA and the Ala12Ala genotype of PPARG on serum lipids are mediated through divergent mechanisms.


Serum Interleukin-33 as a Biomarker in Predicting Neonatal Sepsis in Premature Infants.
Neonatal sepsis is considered as the most frequent cause of death in newborns. Early diagnosis is important to reduce mortality and morbidity. The rapid progression of the disease requires proper use of biomarkers specific for prompt diagnosis and intervention. We aimed to evaluate the benefit of interleukin-33 serum levels in the diagnosis and treatment of neonatal sepsis. We included 51 infants with neonatal sepsis as the main study group and 50 neonates without sepsis as the control group. Serum levels of interleukin-6, interleukin-33 and C-reactive protein were measured on the 1st, 3rd and 7th days of sepsis in the study group and on the 3rd postpartum day in the control group, respectively. Serum levels of interleukin-6, interleukin-33 and C-reactive protein were significantly higher in the first day of sepsis. Serum levels of interleukin-6, interleukin-33 and C-reactive protein decreased significantly on the 3rd and the 7th days of antibiotic treatment. We found a significant relationship between interleukin-33 and C-reactive protein and between interleukin-6 and C-reactive protein on the first day of sepsis. Serum interleukin-33 level is up-regulated in neonatal sepsis, which might be used as a novel diagnostic marker and also a useful tool to predict prognosis in early neonatal sepsis.


Effects of the Magnetic Orientation of M13 Bacteriophage on Phage Display Selection.
Although phage display selection using a library of M13 bacteriophage has become a powerful tool for finding peptides that bind to target materials on demand, a remaining concern of this method is the interference by the M13 main body, which is a huge filament >103 times larger than the displayed peptide, and therefore would nonspecifically adhere to the target or sterically inhibit the binding of the displayed peptide. Meanwhile, filamentous phages are known to be orientable by an external magnetic field. If M13 filaments are magnetically oriented during the library selection, their angular arrangement relative to the target surface would be changed, being expected to control the interference by the M13 main body. This study reports that the magnetic orientation of M13 filaments vertical to the target surface significantly affects the selection. When the target surface was affinitive to the M13 main body, this orientation notably suppressed the nonspecific adhesion. Furthermore, when the target surface was less affinitive to the M13 main body and intrinsically free from the nonspecific adhesion, this orientation drastically changed the population of M13 clones obtained through library selection. The method of using no chemicals but only a physical stimulus is simple, clean, and expected to expand the scope of phage display selection.


Ureteroscopy for treatment of ureteral stones in children: factors influencing the outcome.
To evaluate the factors that affect the success and complication rate of ureteroscopy for ureteral stone treatment in children. We retrospectively reviewed the records of children who were treated for ureteral stones at our institution from 2009 to 2011. The demographic data, stone size, stone location, number of stones, intraoperative complications, stone-free status, postoperative complications, and conversion to an open procedure were recorded. A total of 54 ureteroscopic procedures were performed in 32 children. The mean age was 5.91 ± 4.98 years. Conversion to an open surgical procedure was required in 6 patients (18.75%). A significant relationship was found between conversion to an open procedure and patient age. Although the initial complete clearance rate was 57% after the first session, overall, the stone-free rate was 92.68%. A significant relationship was found between stone-free status and patient age and stone composition. Our overall complication rate was 9.7%. Only 1 major complication (2.4%) occurred. A significant relationship was found between the occurrence of complications and patient age. Ureteroscopy is an effective method to treat ureteral stones in children. Cystine stones and lower patient age carry a risk of not achieving a stone-free status. The complication rate and conversion to an open procedure were greater in patients <5 years old. Parents should be informed before treatment that their children might require multiple treatment sessions.


Skeletal disease in primary hyperparathyroidism.
Most patients with primary hyperparathyroidism in the 1980s do not have evidence of bone disease when they are evaluated by conventional radiography. We sought to determine whether skeletal involvement can be appreciated when more sensitive techniques, such as bone densitometry and bone biopsy, are utilized. We investigated 52 patients with primary hyperparathyroidism. They had mild hypercalcemia, 2.8 +/- 0.03 mmol/liter (11.1 +/- 0.1 mg/dl), low normal phosphorus, 0.9 +/- 0.03 mmol/liter (2.8 +/- 0.1 mg/dl), and no symptoms or specific radiological signs of skeletal involvement. The greatest reduction in bone mineral density was found at the site of predominantly cortical bone, the radius (0.54 +/- 0.1 g/cm; 79 +/- 2% of expected), whereas the site of predominantly cancellous bone, the lumbar spine (1.07 +/- 0.03 g/cm2), was normal (95 +/- 3% of expected). The site of mixed composition, the femoral neck (0.78 +/- 0.14 g/cm2), gave an intermediate value (89 +/- 2% of expected). Preferential involvement of cortical bone with apparent preservation of cancellous bone in primary hyperparathyroidism was confirmed by percutaneous bone biopsy. Over 80% of patients had a mean cortical width below the expected mean, whereas cancellous bone volume in over 80% of patients was above the expected mean. The results indicate that the majority of patients with asymptomatic primary hyperparathyroidism have evidence by bone densitometry and bone biopsy for cortical bone disease. The results also indicate that the mild hyperparathyroid state may be protective of cancellous bone. The therapeutic implications of these observations await further longitudinal experience with this study population.