Epidemiology of poliomyelitis in northwestern Ethiopia.
To determine the magnitude of poliomyelitis and assess its epidemiological features. A cross-sectional community based, house-to-house survey. Six urban and ten rural villages in Gondar Zuria district, north-western Ethiopia. Twelve thousand children aged 1-15 years residing in the randomly selected areas were enrolled in the study to identify children with walking abnormality. Paralytic poliomyelitis is considered as flaccid paralysis in one or both legs with normal sensations and acute onset without progression. Out of 12,000 children aged 1-15 years enrolled, 20 were found to have paralytic poliomyelitis. The prevalence of residual poliomyelitis was found to be 2.1 per 1000 children aged 1-15 years with the estimated annual incidence rate of 7.7 per 100,000 population. Sixty percent of the cases were from urban areas and 55% of the cases were males. The magnitude of paralytic poliomyelitis is high in the study area, thus expanding the expanded programme of immunizations with a strong surveillance system is suggested.


Host genetics and the rumen microbiome jointly associate with methane emissions in dairy cows.
Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH4) is a natural by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH4 emission is not yet well known. This study confirms individual variation in CH4 production was influenced by individual host (cow) genotype, as well as the host's rumen microbiome composition. Abundance of a small proportion of bacteria and archaea taxa were influenced to a limited extent by the host's genotype and certain taxa were associated with CH4 emissions. However, the cumulative effect of all bacteria and archaea on CH4 production was 13%, the host genetics (heritability) was 21% and the two are largely independent. This study demonstrates variation in CH4 emission is likely not modulated through cow genetic effects on the rumen microbiome. Therefore, the rumen microbiome and cow genome could be targeted independently, by breeding low methane-emitting cows and in parallel, by investigating possible strategies that target changes in the rumen microbiome to reduce CH4 emissions in the cattle industry.


Reaching rural Africans with eye care services: findings from primary eye care approaches in Rubavu District, Rwanda.
Assessment of a primary eye care programme in rural Rwanda over 2 years, with the aim of providing evidence to guide the development, training, supervision, or monitoring of primary eye care in Africa. A comprehensive eye care programme in Rubavu District including a surgical service, health promotion, diagnostic and treatment services, training of health centre nurses and village health workers, and periodic visits by eye professionals to the health centres was implemented. Monitoring systems put in place from the beginning of the programme facilitated assessment of service use over 2 years. A total of 6495 people received eye care services at eight health centres (3912 from nurses and 2583 from visiting eye professionals) and 149 Rubavu residents had surgery for cataract. Increases in service use in the first few months were not maintained over the 2-year period. The number of patients receiving surgery for cataract was less than half of the number referred for surgery. In this setting, initial increases in use of services at health centres were not maintained. Reasons varied and included the observation that VHW tend to refer patients to health centres only when there was a visiting eye professional. Reductions in visits to health centres could also be traced to changing government policies on medicines provided through insurance coverage. Increasing rates of referral and uptake of cataract surgery will require revising programme activities and adopting additional strategies.


The blocking effect of essential controller medications during aspirin challenges in patients with aspirin-exacerbated respiratory disease.
The blocking effect of controller medications for asthma could have an effect on the outcome of aspirin challenges in patients suspected of having aspirin-exacerbated respiratory disease (AERD). To evaluate whether there was any blocking effect of long-acting beta2-agonists, systemic corticosteroids, and/or inhaled corticosteroids alone or as co-therapy with leukotriene modifier drugs (LTMDs). Between 1981 and 2004, 678 patients with suspected AERD were admitted for aspirin challenge and desensitization. All patients had asthma, chronic sinusitis, nasal polyposis, and at least 1 historical reaction to a nonsteroidal anti-inflammatory drug. Asthma controller medications taken during aspirin challenge were recorded and analyzed with respect to their potential effects on 4 possible outcomes of aspirin challenge, namely, naso-ocular reaction, lower airway reaction, classic upper and lower airway reaction, or a negative challenge result. When compared with AERD patients who received no controller medications, the combined use of LTMDs, inhaled corticosteroids, and long-acting beta2-agonists led to a statistically significant change in aspirin challenge outcomes (P = .009), mainly shifting the reaction from a classic upper and lower respiratory tract reaction to naso-ocular reactions only. LTMDs appeared to have the strongest effect (P < .001) in blocking lower respiratory tract reactions. Systemic corticosteroids did not have the same effects. Blocking of both upper and lower respiratory tract reactions to aspirin as a result of taking controller medications did not occur. Controller medications are frequently needed to stabilize airways of patients with AERD. LTMDs alone or in combination with other controllers blocked lower respiratory tract reactions during aspirin challenge in some patients with AERD but did not change the overall rate of positive aspirin challenge results and did not lead to false-negative challenges.


Primary follicular lymphoma of the bladder mimicking inflammatory condition: Case report and review of the literature.
Primary lymphoma of the bladder is rare and may present with nonspecific symptoms and infection. Primary follicular lymphoma of the bladder is extremely rare with only a dozen reported cases. We present one case clinically mimicking an inflammatory process. A 79 year-old woman presents with recurrent urinary tract infections, urinary incontinence and frequency. Cystoscopic examination demonstrated a raised but flat lesion, suspicious for inflammatory lesion. Biopsy revealed a diagnosis of follicular lymphoma, grade 1-2. The presentation of primary follicular lymphoma of the bladder may be nonspecific, therefore it is important to consider this diagnosis in patients with unremitting symptoms.


Natural Course of the American Thyroid Association Response to Therapy Statuses (Dynamic Risk Stratification) in Differentiated Thyroid Cancer.
The concept of response to therapy in differentiated thyroid cancer (DTC) was introduced as a dynamic risk stratification used to assess the status of the disease at the time of the evaluation during the follow-up and the risk of recurrence in the future. Our aim in this study was to evaluate the natural course over time of different response to therapy statuses. We studied 501 nonselected DTC patients (102 males and 399 females) with a median age of 37 years (interquartile range [IQR] 29-48). All patients underwent near-total or total thyroidectomy followed by I-131 ablation (initial management). Of the 501 patients, 387 patients (77.2%) did not have any additional therapuetic interventions after the initial management. In this group, the response to therapy status at the time of the first evaluation after I-131 (median 17 months, IQR 14-22) was an excellent response in 258 (66.7%), an indeterminate response in 101 (26.1%), biochemically incomplete in 17 (4.4%), and structurally incomplete in 11 patients (2.8%). The status changed spontaneously without any intervention in many of them. At the last follow-up visit (median duration 101 months, IQR 71-126), 357 patients (92.2%) achieved an excellent response, 4 (1%) an indeterminate response, 8 (2.1%) a biochemically incomplete status, 16 (4.1%) a structurally incomplete status, and 2 (0.5%) died secondary to DTC with a structurally incomplete status. The response to therapy in the other 114 patients who underwent additional interventions changed from before intervention to the last evaluation as follows: excellent response, 0 to 60 patients (52.6%), indeterminate response, 20 (17.5%) to 1 patient (0.9%), biochemically incomplete 25 (21.9%) to 10 patients (9%), and structurally incomplete 69 (60.5%) to 43 patients (37.7%). Overall, at the last evaluation, 417 (83.2%) were in an excellent response, 5 (1%) in an indeterminate response, 18 (3.6%) in a biochemically incomplete status, 50 (10.2%) in a structurally incomplete status, and 11 (2.2%) died secondary to DTC with a structurally incomplete status. The response to therapy at the initial evaluation is predictive of the long-term outcome. Most patients with the indeterminate response and some in the biochemically incomplete statuses spontaneously regress to an excellent status. Mortality and progression of DTC occur mostly in the structurally incomplete status.


Diagnostic performance of ELISA, IFAT and Western blot for the detection of anti-Leishmania infantum antibodies in cats using a Bayesian analysis without a gold standard.
Anti-Leishmania antibodies are increasingly investigated in cats for epidemiological studies or for the diagnosis of clinical feline leishmaniosis. The immunofluorescent antibody test (IFAT), the enzyme-linked immunosorbent assay (ELISA) and western blot (WB) are the serological tests more frequently used. The aim of the present study was to assess diagnostic performance of IFAT, ELISA and WB to detect anti-L. infantum antibodies in feline serum samples obtained from endemic (n = 76) and non-endemic (n = 64) areas and from cats affected by feline leishmaniosis (n = 21) by a Bayesian approach without a gold standard. Cut-offs were set at 80 titre for IFAT and 40 ELISA units for ELISA. WB was considered positive in presence of at least a 18 KDa band. Statistical analysis was performed through a written routine with MATLAB software in the Bayesian framework. The latent data and observations from the joint posterior were simulated in the Bayesian approach by an iterative Markov Chain Monte Carlo technique using the Gibbs sampler for estimating sensitivity and specificity of the three tests. The median seroprevalence in the sample used for evaluating the performance of tests was estimated at 0.27 [credible interval (CI) = 0.20-0.34]. The median sensitivity of the three different methods was 0.97 (CI: 0.86-1.00), 0.75 (CI: 0.61-0.87) and 0.70 (CI: 0.56-0.83) for WB, IFAT and ELISA, respectively. Median specificity reached 0.99 (CI: 0.96-1.00) with WB, 0.97 (CI: 0.93-0.99) with IFAT and 0.98 (CI: 0.94-1.00) with ELISA. IFAT was more sensitive than ELISA (75 vs 70%) for the detection of subclinical infection while ELISA was better for diagnosing clinical leishmaniosis when compared with IFAT (98 vs 97%). The overall performance of all serological techniques was good and the most accurate test for anti-Leishmania antibody detection in feline serum samples was WB.


Onset of Addison Disease appeared during the first trimester of a twin pregnancy: A case report.
Addison Disease is an uncommon, life-threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced.


N-methyl serotonin analogues from the Bufo bufo toad venom interact efficiently with the α7 nicotinic acetylcholine receptors.
Two low-molecular-weight compounds were isolated from the parotid gland secret of the toad Bufo bufo, which by absorption spectra and HPLC-MS/MS chromatography data correspond to di- and trimethyl derivatives of serotonin (5-hydorxytryptamine): bufotenine (confirmed by counter synthesis) and bufotenidine (5-HTQ). In experiments on competitive radioligand binding, these compounds showed a higher affinity and selectivity for neuronal α7 nicotinic acetylcholine receptors compared with the muscular cholinergic receptors. The most efficient compound in terms of binding value was bufotenine, the efficiency of 5-HTQ was an order of magnitude lower, and the minimal activity was exhibited by serotonin.


Ionotropic receptors mediate olfactory learning and memory in Drosophila.
Phenylacetaldehyde (PAH), an aromatic compound, is present in a diverse range of fruits including overripe bananas and prickly pear cactus, the two major host fruits for Drosophila melanogaster. PAH acts as a potent ligand for the ionotropic receptor 84a (IR84a) in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex. Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance. In D. melanogaster, two distinct kinds of olfactory receptors, that is, odorant receptors (ORs) and ionotropic receptors (IRs), perceive the odorant stimuli. They display unique structural, molecular, and functional characteristics in addition to having different evolutionary origins. Traditionally, olfactory cues detected by the ORs such as ethyl acetate, 1-butanol, isoamyl acetate, 1-octanol, 4-methylcyclohexanol, etc. classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies. This underlines the participation of OR-activated olfactory pathways in learning and memory formation. Our study elucidates that likewise ethyl acetate (EA) (an OR-responsive odorant), PAH (an IR-responsive aromatic compound) too can form learning and memory when associated with an appetitive gustatory reinforcer. The association of PAH with sucrose (PAH/SUC) led to learning and formation of the long-term memory (LTM). Additionally, the Orco1 , Ir84aMI00501 , and Ir8a1 mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning. These results highlight the involvement of IRs via an IR-activated pathway in facilitating robust olfactory behavior.


Workplace cafeteria and other multicomponent interventions to promote healthy eating among adults: A systematic review.
The objective of this review is to evaluate evidence for the effectiveness of workplace cafeteria and other supporting multicomponent interventions to promote healthy eating and reductions in health risks among adults. We conducted an electronic search in EMBASE, CINAHL, EconLit, Ovid, Cochrane, Web of Science and PubMed for English-language articles published from 1985 to July 2019. Studies were original articles reporting the results of workplace cafeteria interventions to promote healthy eating and reduction in health risks. Outcomes were classified as changes in fruit and vegetable intake, health risk indicators, dietary intake, and food sales. Interventions were categorized as interventions targeting food quality or quantity, targeting price, targeting food choice at point of purchase, targeting improved supply, targeting client's information, education or motivation and targeting organization policies. Behavioral change conditions used in interventions were identified using the COM-B system of behavioral change. Results were presented in a narrative summary. A total of 55 studies out of 6285 articles were identified for this review. Several studies used multicomponent interventions and the most featured interventions included interventions targeting food quality or quantity, targeting client's information, education or motivation and targeting food choice at point of purchase. There is evidence that workplace cafeteria and other supporting multicomponent interventions resulted in higher intake of fruit and vegetables, improved dietary intake, improved health outcomes and healthy food sales. The findings of this review have the potential to inform future cafeteria-based and other supporting multicomponent workplace health interventions. The review protocol was not registered in a repository.


Model of intraabdominal abscess in mice.
Intraperitoneal inoculation of sterile mouse feces into mice produced intraabdominal abscesses. The addition of Bacteroides fragilis increased the incidence and the number of abscesses.


Effects of slag-based cementitious material on the mechanical behavior and heavy metal immobilization of mine tailings based cemented paste backfill.
Slag-based cementitious material was synthesized from blast furnace slag, clinker, gypsum, and activator to replace cement in cemented paste backfill (CPB). We researched the influence of slag-based cementitious material dosages and curing times on the properties of CPB, including unconfined compressive strength tests, leachate toxicity and chemical speciation of heavy metal as well as microstructural tests and analyses. The results indicated that the addition of slag-based cementitious material improved the compressive strength of the CPB, which attained the compressive strength requirements (≥1.0 MPa) at 28 days. The leachate concentrations of Pb, Cr, Cu, and Cd in CPB decreased as the slag-based cementitious material dosage and curing period increased, which met the standard (GB 5085.3-2007). The dosage of 10% slag-based cementitious material could effectively immobilize the heavy metals in the tailings, and the immobilization performance was similar to that of 20% cement, which indicated the amount of slag-based cementitious material was only half the quantity of cement in CPB. Microstructural analysis showed the hydration products included calcium silicate hydrate, ettringite, and portlandite, which could enhance the bonding force between the tailing grains.


Basic fibroblast growth factor regulates proliferation and motility of human hepatoma cells by an autocrine mechanism.
Basic fibroblast growth factor has mitogenic and angiogenic properties. In this study, we aimed to evaluate the role of fibroblast growth factor in the development and progression of human hepatocellular carcinoma. The expression of basic fibroblast growth factor, fibroblast growth factor receptor-1, and a receptor isoform was investigated by in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction, Western blot analysis and confocal laser-scanning microscopy. The influence of exogenous basic fibroblast growth factor on DNA synthesis and motility of human hepatoma cells were also evaluated. Basic fibroblast growth factor and fibroblast growth factor receptor-1 messenger RNAs were present mainly in tumor cells and less so in hepatocytes from noncancerous liver tissue. Immunoreactive products of basic fibroblast growth factor and fibroblast growth factor receptor-1 were observed in tumor cells. The isoform IIIc was expressed in hepatocellular carcinoma tissue and hepatoma cell lines. Exogenous basic fibroblast growth factor stimulated DNA synthesis and motility of hepatoma cells. The effect was more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. Fibroblast growth factor-1 expression on hepatoma cells was also more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. The stimulated motility on basic fibroblast growth factor was suppressed by an anti-fibroblast growth factor receptor-1 antibody. Basic fibroblast growth factor may play an important role in the development and progression of hepatocellular carcinoma via an autocrine mechanism involving fibroblast growth factor and its receptor.


Going home: identifying and overcoming barriers to nursing home discharge.
This article describes barriers to nursing home discharge encountered in an intervention designed to transition nursing home residents to the community. Staff in the intervention ("Project Home") provided intensive case management and discharge planning services to nursing home residents who expressed a desire to return to community-based living arrangements. Sixty program participants took part in the program evaluation that informs this article. With the exception of Medicaid status, no differences were found between the social, demographic, and health characteristics of individuals who remained in the nursing home and those who were discharged. A qualitative analysis was conducted to describe barriers to discharge and strategies intervention staff used to leverage each client's strengths and work around obstacles. Three main barriers to discharge were found: having an unstable or complex medical condition, lacking family or social support, and being unable to obtain suitable housing. Intervention staff advocated on the behalf of clients, encouraged clients to build skills toward independent living. and contributed extensive knowledge of local resources to advance client goals. Cases of successful transition suggest that a person-centered approach from intervention staff combined with a flexible organizational structure is a promising model for future interventions.


Complement-mediated antibody-dependent enhancement of HIV-1 infection requires CD4 and complement receptors.
In this study it is demonstrated that complement-mediated antibody-dependent enhancement (C'-ADE) of HIV-1 infection in vitro is blocked by murine monoclonal antibodies to CD4 and complement receptor type 2 (CR2) while HIV-1 infection in the absence of C'-ADE is blocked by anti-CD4 but not anti-CR2 monoclonal antibodies. The anti-CR2 murine monoclonal antibody, OKB7, blocked C'-ADE of HIV-1 infection at concentrations greater than 1 microgram/ml. The anti-CD4 monoclonal antibody, OKT4a, but not OKT4f blocked C'-ADE at concentrations greater than 0.06 microgram/ml. HIV-1 infections were quantitated by cytopathic effect, indirect immunofluorescence, and reverse transcriptase release. It appears from these in vitro studies that C'-ADE of HIV-1 infection requires both CD4 and complement receptors while HIV-1 infection in the absence of antibody and complement requires only CD4.


Characteristics of infections caused by extended-spectrum β-lactamase-producing Escherichia coli from community hospitals in South Africa.
A study was designed to characterize 22 nonrepeat extended-spectrum β-lactamase (ESBL)-producing Escherichia coli clinical isolates recovered from specimens originating from doctor's consultation rooms and several private and a state hospital in the Cape Town metropolitan area during 2008-2009. Characterization was done by using isoelectric focusing, PCR, sequencing of bla(CTX-M), bla(TEM), bla(SHV), and bla(OXA) as well as PCR for plasmid-mediated quinolone resistance determinants, ST131, phylogenetic groups, and plasmid replicon typing. Genetic relatedness was determined with pulsed-field gel electrophoresis using XbaI and multilocus sequencing typing. The majority of patients (17/22 [77%]) presented with urinary tract infections (UTIs) originating from the hospital setting. Thirteen (59%) of the isolates produced CTX-M-15, 7 produced CTX-M-14, and 1 isolate each produced CTX-M-3 and SHV-2, respectively. Sixteen (73%) isolates were nonsusceptible to ciprofloxacin and 8 (36%) were positive for aac(6')-Ib-cr. Overall, 10/22 (45%) of ESBL producers belonged to clonal complex ST131 that produced CTX-M-15 or CTX-M-14. Molecular characteristics of ST131 showed that this clone belonged to phylogenetic group B2. Our study illustrated that clonal complex ST131 isolates producing CTX-M-15 and CTX-M-14 had emerged as an important cause of UTIs due to ESBL-producing E. coli in the Cape Town area. This is the first report to identify ST131 in ESBL-producing E. coli from Southern Africa.


Effects of global postural alignment on posture-stabilizing synergy and intermuscular coherence in bipedal standing.
Clinicians frequently assess and intervene on postural alignment; however, notions of what constitutes good postural alignment are variable. Furthermore, the majority of current evidence appeals either to population norms or defines good postural alignment as the negation of what has been observed to correlate with pathology. The purpose of this study was to identify affirmative indicators of good postural alignment in reference to motor control theory. Electromyography (anterior leg, posterior leg, and trunk muscles) and motion capture data were acquired from 13 participants during 4 min bipedal standing trials in 4 conditions: control, - 10%, + 30%, and + 60% of subject-specific anterior limits of stability. Synergistic kinematic coordination was quantified via the uncontrolled manifold framework, and correlated neural drive was quantified in posture-relevant muscle groups (anterior, posterior, and trunk) via intermuscular coherence. Multilevel models assessed the effects of sagittal plane alignment on both outcomes. We observed a within-subjects fixed effect in which kinematic synergistic coordination decreased as subjects became more misaligned. We also observed within-subjects fixed effects for middle- and high-frequency intermuscular coherence in the posterior group (increased coherence with increased misalignment) and for trunk intermuscular coherence across all frequency bands (decreased coherence with increased misalignment). Our findings indicate that it may be possible to describe healthy postural alignment in light of referent control theory. Greater misalignment with respect to vertical is associated with compromises in synergistic control of posture and increased corticospinal drive to specific muscle groups. These results suggest that postural alignment may not simply be an empirical phenomenon.


An insertion deletion polymorphism in the signal peptide of the human apolipoprotein B gene.
In this communication we report the genetic properties of an insertion/deletion polymorphism in the signal peptide of the human apolipoprotein B (apo b) gene. There are two alleles of the apo B signal peptide; one codes for a peptide 27 amino acids in length and the other a peptide only 24 amino acids in length. Using the polymerase chain reaction the difference of nine nucleotides between the two alleles is readily detectable after electrophoresis of the amplification products. The relative frequencies of the Ins and Del alleles are 0.655 and 0.345, respectively. The apo B signal peptide genotypes are transmitted in a manner consistent with an autosomal codominant mode of inheritance with two alleles.


The frequency of HLA class I alleles in Japanese patients with bone marrow failure.
The frequencies of the HLA-B*4002 and HLA-A*0206 alleles in patients with aplastic anemia (AA) (n=32; 21.9%) and paroxysmal nocturanl hemoglobinuria (PNH) (n=24; 22.9%), respectively, were significantly different from those in controls (n=371; 8.6%, p<0.002 and 7.7%, p<0.001, respectively), suggesting that each specific allele in AA or PNH may be related to the immunologic pathophysiology of these disorders.


Quantitation of the renal effect of calcitonin in the hypercalcaemia of malignancy.
The renal effect of calcitonin (independent of changes due to variations in sodium excretion) was quantitated in malignancy associated hypercalcaemia. There was considerable inter- and intra-patient variability in response but this was unaffected by tumour type. Humoral hypercalcaemia tended to be resistant to control. In responsive patients the renal effects of calcitonin unlike those described in bone did not diminish with time.


Six just-noticeable differences in retinal image quality in 1 line of visual acuity: toward quantification of happy versus unhappy patients with 20/20 acuity.
To determine the number of just-noticeable differences in wavefront blur necessary to induce a 1-line loss of corrected distance visual acuity (CDVA). Visual Optics Institute, College of Optometry, University of Houston, Houston, Texas, USA. Evidence-based manuscript. The 3.0 mm wavefront error of a well-corrected average eye was scaled to yield 9 small steps of blur quantified in units of log visual Strehl (logVS). For each logVS value, 10 unique 3-line acuity charts were generated. Using a temporal forced-choice paradigm, subjects compared each test chart to a reference acuity chart and indicated which chart was blurrier. The difference between 80% and 50% on the psychometric function defined a just-noticeable difference. The CDVA was measured up to fifth-letter miss for several aberrated logMAR charts for 6 logVS values. The number of just-noticeable differences necessary to lose 1 line of acuity was defined as the change in logVS necessary to lose 1 line of acuity divided by the 1 just-noticeable difference in logVS. Linear regression showed that logVS = -2.98 × (logMAR acuity) - 0.31 (R(2) = 0.961). The mean just-noticeable difference was 0.049 logVS ± 0.012 (SD), resulting in a mean of 6.1 just-noticeable differences per line of logMAR acuity. The retinal image quality metric logVS was highly correlated with logMAR acuity. The 6 just-noticeable differences in logVS before 1 line of acuity was lost may provide an objective explanation for the distinction between patients with 20/20 CDVA who are happy and patients with 20/20 CDVA who are unhappy and other aberration-related clinical complaints when acuity is near normal.


[The reconstructive use of bipedicled chest flap in cancer surgery of the neck (author's transl)].
The reconstructive use of bipedicled chest flap in cancer surgery of the neck is described. This flaps have been found extremely useful in cases of surgical treatment of postlaryngectomy tracheal stomal recurrences.


The effect of nitric oxide, growth factors, and estrogen on gastric cell migration.
To study gastric epithelial cell migration during nitric oxide (NO) and growth factor treatment, simulating inflammation and infection. Also, the effects of estrogen on migration of different malignant and nonmalignant gastric epithelial cell lines were explored. Isolated primary cultured rabbit gastric epithelial cells, rat gastric mucosal cells, human gastric adenocarcinoma cells, and human colon adenocarcinoma cells (WiDr) were cultured to confluency in appropriate media (5% CO2, 37 degrees C). The cells were treated by hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-alpha) and keratinocyte growth factor (KGF), with and without sodium nitroprusside (SNP, NO donor) or 17beta-estradiol. Caspase-3 activity and cell viability and migration speed after wounding were measured. HGF was the most potent growth factor to stimulate migration. SNP dose-dependently decreased the speed of migration. HGF and TGF-alpha were able to overcome the SNP-induced inhibition of migration, whereas KGF was not. SNP also induced caspase-3 activity, which was inhibited by HGF and TGF-alpha. 17beta-estradiol decreased migration in all epithelial cells, but the decrease was more profound in malignant cell lines. HGF could overcome the estrogen retarded migration. Growth factors can overcome NO-induced retardation of cell migration and inhibit NO-induced caspase-3 activity, which altogether might also have physiological significance in in vivo inflammation and in gastric cancer. The more profound decrease in migration speed of gastric adenocarcinoma cell line may suggest that estrogen might be one of the protective factor against female gastric adenocarcinoma before menopausal age.


Lifting polarization degeneracy of modes by fiber design: a platform for polarization-insensitive microbend fiber gratings.
Polarization dependence in microbend gratings is an inherent problem, even in perfectly circular fibers, since antisymmetric modes are almost degenerate linear combinations of four distinct, polarization-sensitive modes. We demonstrate a novel fiber design that lifts polarization degeneracies of the antisymmetric modes to solve this problem. By intentionally exacerbating the polarization splittings, we achieve coupling to only the polarization-insensitive doublet, over wavelength ranges exceeding 100 nm, thus demonstrating a device with practical usable bandwidths. This allows all previous applications envisaged with UV-induced long-period gratings to be realized with the significantly lower-cost microbend technology platform.


Glycopolymer vesicles with an asymmetric membrane.
Direct dissolution of glycosylated polybutadiene-poly(ethylene oxide) block copolymers can lead to the spontaneous formation of vesicles or membranes, which on the outside are coated with glucose and on the inside with poly(ethylene oxide).


Flexible Ureteroscopy as a Major Ambulatory Surgery Procedure. Single Center Experience and Analysis of Variables Related to Hospital Readmission.
To assess our experience in flexible ureteroscopy (fURS) in major ambulatory surgery (MAS) and to detect variables related to unplanned medical assistance after surgery. We conducted a retrospective study among patients with renal stones undergoing a fURS from 2014 to 2019 in MAS at our hospital. Age, gender, ASA physical status, type of anesthetic technique performed, stone characteristics, influence of double J stent before or after surgery, and postoperative complications according to the Clavien-Dindo modified classification. We evaluated variables related to hospital readmission or visit to the emergency room after surgery. A total of 222 consecutive fURS for stone disease were performed in MAS. Patients' average age was 52.9 ± 13.91 years old. The mean operating time was 57.86 ± 21.11 minutes. The mean stone size was 1.92 ± 1.43 with a diameter of 10.01 ± 4.24 mm. 47.3% of patients had a double J stent before fURS, and in 35.14% of cases, a stent was placed after surgery. 7.65% of patients required unplanned hospitalization. 14.86% of patients presented to the emergency room in the following month after surgery. Among them, one-third consulted for symptoms related to the double J. Patients who carried a double J stent before the fURS had 64% less risk of visiting the emergency department in the following month after surgery [OR = 0,363; IC95% (0.153-0.798)]. All other variables (age, gender, operating time...) did not modify the risk of unplanned medical assistance. The low complication rate following flexible ureteroscopy allows its performance as an ambulatory surgery. Patients who carry double J stent before the procedure have less risk of requiring unplanned medical assistance after the surgery.


Sequence-based identification of 3D structural modules in RNA with RMDetect.
Structural RNA modules, sets of ordered non-Watson-Crick base pairs embedded between Watson-Crick pairs, have central roles as architectural organizers and sites of ligand binding in RNA molecules, and are recurrently observed in RNA families throughout the phylogeny. Here we describe a computational tool, RNA three-dimensional (3D) modules detection, or RMDetect, for identifying known 3D structural modules in single and multiple RNA sequences in the absence of any other information. Currently, four modules can be searched for: G-bulge loop, kink-turn, C-loop and tandem-GA loop. In control test sequences we found all of the known modules with a false discovery rate of 0.23. Scanning through 1,444 publicly available alignments, we identified 21 yet unreported modules and 141 known modules. RMDetect can be used to refine RNA 2D structure, assemble RNA 3D models, and search and annotate structured RNAs in genomic data.


Trophic transfer and toxicity of heavy metals from dengue mosquito Aedes aegypti to predator dragonfly Tramea cophysa.
Heavy metal pollution in aquatic habitats can be detrimental to both prey and predators in a food web. To investigate the potential for bio-transfer and bioaccumulation of heavy metals between specific trophic levels, 3rd instar larvae of Aedes aegypti were exposed to mercury (Hg), lead (Pb), cadmium (Cd), copper (Cu), and zinc (Zn) for three consecutive generations and fed to dragonfly (Tramea cophysa) nymphs. Exposure to Hg caused the highest mortality in A. aegypti larvae and T. cophysa nymphs. Bioaccumulation and life-history parameters of A. aegypti, including egg hatching time, larval and pupal duration, male and female life span, and fecundity, were also evaluated after metals exposure. All life-history parameters except larval duration were significantly affected by heavy metal treatments. Bioaccumulation of metals in A. aegypti larvae and adults gradually and significantly increased from 1st to 3rd generation. To the best of our knowledge, this is the first study describing the acute toxicity of heavy metals to mosquitoes. Our study shows that heavy metals cause dietary toxicity to an aquatic predator, dragonfly, via trophic transfer, which could have considerable consequences on aquatic ecosystems.


Initial Evidence for the Efficacy of an Everyday Memory and Metacognitive Intervention.
The objective of this paper is to demonstrate the efficacy of an Everyday Memory and Metacognitive Intervention (EMMI) designed to improve everyday functioning of older adults. The EMMI emphasizes self-regulation as a behavioral approach to take priority over habitual behaviors that often impede everyday functioning. This study used a quasi-experimental design (intervention vs waitlist control) to test whether the EMMI improved several aspects of everyday cognition. Thirty-three EMMI participants (M age = 70.24) were compared to 20 control participants (M age = 71.70 years). The 2 groups were compared on everyday memory failures and successes, measures of well-being, subjective memory, and a prospective memory task. Participants who received the EMMI reported more memory successes and fewer memory failures over a 10-day measurement period postintervention. In addition, EMMI participants reported significantly higher life satisfaction and better subjective memory at posttest than the control group. Critically, the EMMI participants performed better on a laboratory contact prospective memory task. The results from this study suggest that the EMMI is a promising approach that has potential to improve everyday memory functioning and perhaps help extend functional independence. Future studies will include randomized controlled trials as well as electronic measurement of memory incidents.


Localization and mobility of bacterial proteins by confocal microscopy and fluorescence recovery after photobleaching.
This chapter describes the use of laser-scanning confocal fluorescence microscopy for determining the localization of fluorescently tagged proteins within bacterial cells, discussing the problems caused by the limited resolution of an optical microscope. It also explains a relatively simple method for using fluorescence recovery after photobleaching (FRAP) to observe and quantify the diffusion of fluorescently tagged proteins in bacterial cells. The techniques are illustrated with reference to measurements on green fluorescent protein (GFP)-tagged proteins in Escherichia coli.


Subacromial corticosteroid injection for poststroke shoulder pain: an exploratory prospective case series.
To assess the effectiveness of subacromial corticosteroid injections for poststroke shoulder pain. Exploratory, prospective case series. Ambulatory setting, university-affiliated hospital. Stroke survivors (N=10) with pain in the hemiparetic shoulder. Consecutive stroke survivors with evidence of supraspinatus impingement, supraspinatus tendonitis, or subacromial bursitis received subacromial corticosteroid injections. The primary outcome measure was the Brief Pain Inventory (BPI) question 12 (BPI 12), which assesses "worst pain" in the previous 7 days. Secondary measures included BPI question 15, which assesses present pain and BPI question 23 (BPI 23), which assesses pain interference with 7 daily activities. Outcomes were assessed at baseline, weekly for the first 4 weeks and then at 8 and 12 weeks postinjection. Repeated measure analysis of variance revealed significant within group time effect for BPI 12 (F=7.7, P<.001). Based on absolute means, the largest therapeutic benefit was seen by the second week postinjection with partial loss of effect thereafter. There were significant within group time effects for the general activity (F=3.2, P=.009), sleep (F=3.9, P=.003), and enjoyment of life (F=2.3, P=.044) domains of BPI 23. Subacromial corticosteroid injection is associated with significant reduction in poststroke shoulder pain in patients with evidence of supraspinatus impingement, supraspinatus tendonitis, or subacromial bursitis. However, there is a gradual loss of effect with time. Controlled trials are needed to show a cause and effect relationship.


Novel mutations in factor IX gene from western India with reference to their phenotypic and haplotypic attributes.
Hemophilia B (HB) is an X-linked recessively inherited bleeding disorder caused by heterogeneous mutations in the factor IX gene. We screened for mutations in HB patients using a combination of multiplex polymerase chain reaction, conformation sensitive gel electrophoresis, and DNA sequencing. Phenotypic analysis was performed using 1 stage assay for factor IX: C activity and enzyme-linked immunosorbent assay for factor IX: Ag. Haplotype analysis was performed using the common polymorphic markers of the factor IX gene. Seventeen novel mutations comprising of missense mutations, nonsense mutations, and small deletions were detected. Haplotype analysis indicated that some of the patients had a common haplotype background but had different molecular defects thereby suggesting that all the mutations arose de novo. Phenotypic data suggested that about one-fourth of the patients (23%) had antigen-activity discordance. Furthermore, it was observed that a majority of the molecular defects (71%) were located in exon H of the factor IX gene. The mutation screening strategy was thus modified wherein exon H was screened first followed by screening of other exons. The present findings suggest that there is a wide phenotypic and genotypic heterogeneity in HB. Presence of more than 70% of mutations in exon H of the factor IX gene allows us to adopt a cost effective screening strategy in offering genetic diagnosis to the affected families.


The peroxisomes of the hepatopancreas in two species of chitons
. This paper presents the first description of peroxisomes in polyplacophorans. As in other molluscs, the hepatopancreas of chitons is composed of basophilic and digestive cells. In the basophilic cells, the endoplasmic reticulum is abundant and several Golgi stacks can be observed. These cells also possess secretion granules and vacuoles with spherites. The digestive cells are mainly characterized by the presence of many food vacuoles. Several peroxisomes were observed in the basophilic cells of Acanthochiton crinita, most of them almost spherical. The matrix is filled with tubular structures and a crystalline nucleoid is also present in these organelles. In the digestive cells of A. crinita, peroxisomes are also almost spherical and possess two kinds of nucleoids. One of them presents a diamond shape and a bundle of tubular structures forms a second kind of nucleoid, which shows an elongated form. In Lepidochitona cinerea, the peroxisomes of basophilic cells are spherical or oval. Within the matrix, a cluster of dense rods and a prismatic nucleoid were observed. In the digestive cells of this species, almost spherical or oval peroxisomes are common, but they are smaller than the peroxisomes of the preceding cells. Nucleoids were not detected, but a few dense rods could be observed in the matrix. In both cell types of the two species, catalase activity was detected in the peroxisomal matrix. In addition, the elongated nucleoid of A. crinita digestive-cell peroxisomes and the nucleoid of L. cinerea basophilic-cell peroxisomes also present catalase activity.


Gut microbiome can be restored without adverse events after Helicobacter pylori eradication therapy in teenagers.
The effect of Helicobacter pylori eradication on the gut microbiota of teenagers is unknown; hence, this study aimed to assess changes in the gut microbiome after H. pylori eradication therapy in teenagers. Changes in gut microbiota before and after H. pylori eradication were prospectively investigated in eight students without any underlying diseases, via next-generation sequencing of 16S rDNA. Twenty-four stool samples were collected, and operational taxonomic unit analysis was performed. As secondary analyses, alpha and beta diversity were evaluated. Furthermore, pre-treatment microbiome compositions were compared with those 1 week and 2 months after treatment. Alpha diversity analysis revealed that both species richness and evenness were recovered to pre-treatment levels at 2 months after eradication therapy. Slight but non-significant differences were observed in bacterial species abundance between pre- and post-treatment samples, upon beta diversity analysis. Although the relative abundance of Bacteroidetes tended to increase and that of Actinobacteria significantly decreased immediately after eradication therapy, the taxonomic composition was similar to that before treatment and at 2 months post-eradication. However, two students showed significant changes in the gut microbiota in relative abundances at the level of the phylum, class, and order. Although H. pylori eradication therapy caused short-term dysbiosis, microbial diversity was restored in healthy teenagers. However, as the relative abundance of gut microbiota in some cases remained altered, the effect of H. pylori eradication therapy on the gut microbiome should be continuously monitored.


Chronic kidney disease-associated pruritus significantly impacts on quality of life of patients on haemodialysis and associates with increased levels of serum calcium and phosphorus.
Chronic kidney disease-associated pruritus (CKD-aP) is common among patients on maintenance haemodialysis (HD). We performed a study to explore the clinical features of patients with CKD-aP and evaluate the impact of CKD-aP on the quality of life of HD patients. Patients who were receiving regular HD over 3 months were recruited. Quality of life was quantified by the Short Form-12 (SF-12) questionnaire. Pruritus was evaluated by the 5D-Itch Scale. Demographic characteristics and biochemical indicators were obtained from the medical record system. Multiple linear regression was used to assess the association between pruritus and targeting factors. The relationship between the scores on the 5D-Itch Scale and SF-12 was analysed using multiple linear regression, adjusted for other factors, to demonstrate the impact of CKD-aP on the quality of life of HD patients. In total, 269 out of 301 (89.4%) patients accomplished all investigations. The prevalence of CKD-aP in our cohort was 40.9%. Age (B=0.339, p=0.042), treatment with haemoperfusion (B=1.853, p=0.018), and serum level of calcium (B=3.566, p=0.008) and phosphorus (B=1.543, p=0.002) were independently associated with pruritus. Score on the 5D-Itch Scale negatively impacted on physical component summary (B=-0.778, p<0.001) and mental component summary (B=-0.675, p<0.001). Pruritus significantly aggravates the quality of life of HD patients. Irregularity in the metabolism of calcium and phosphorus may partially explain the mechanism of CKD-aP. More effective treatment of CKD-MBD may help to prevent pruritus and improve patients' mental and physical health conditions.


Trichinella spiralis and laryngeal carcinoma: a case report.
An uncommon presentation of Trichinella spiralis with squamous cell carcinoma of the larynx is reported. The possible carcinogenic potential of trichinosis and its management are discussed.


An in vivo reporter for tracking lipid droplet dynamics in transparent zebrafish.
Lipid droplets are lipid storage organelles found in nearly all cell types from adipocytes to cancer cells. Although increasingly implicated in disease, current methods to study lipid droplets in vertebrate models rely on static imaging or the use of fluorescent dyes, limiting investigation of their rapid in vivo dynamics. To address this, we created a lipid droplet transgenic reporter in whole animals and cell culture by fusing tdTOMATO to Perilipin-2 (PLIN2), a lipid droplet structural protein. Expression of this transgene in transparent casper zebrafish enabled in vivo imaging of adipose depots responsive to nutrient deprivation and high-fat diet. Simultaneously, we performed a large-scale in vitro chemical screen of 1280 compounds and identified several novel regulators of lipolysis in adipocytes. Using our Tg(-3.5ubb:plin2-tdTomato) zebrafish line, we validated several of these novel regulators and revealed an unexpected role for nitric oxide in modulating adipocyte lipid droplets. Similarly, we expressed the PLIN2-tdTOMATO transgene in melanoma cells and found that the nitric oxide pathway also regulated lipid droplets in cancer. This model offers a tractable imaging platform to study lipid droplets across cell types and disease contexts using chemical, dietary, or genetic perturbations.


Inhibitory effect of a fava bean component on the in vitro development of Plasmodium falciparum in normal and glucose-6-phosphate dehydrogenase deficient erythrocytes.
We examined the hypothesis that G-6-PD deficiency associated with fava bean ingestion confers resistance to malaria by studying the in vitro interactions between malaria parasites (Plasmodium falciparum), human erythrocytes with varying degrees of G-6-PD deficiency, and isouramil (IU), a fava bean extract that is known to cause oxidant stress and hemolysis of G-6-PD-deficient erythrocytes. Untreated G-6-PD-deficient and normal erythrocytes supported the in vitro growth of P. falciparum equally well. However, after pretreatment with IU, G-6-PD-deficient erythrocytes did not support parasite growth in vitro, whereas growth remained high in normal erythrocytes. Parasite growth was proportional to the G-6-PD activity of the IU-treated erythrocytes. In contrast, when parasitized erythrocytes were exposed to IU, parasites even in normal erythrocytes were destroyed. Ring forms were much less sensitive than late trophozoites and schizonts. The results suggest that there are two modes by which IU affects the development of P. falciparum and demonstrate in vitro that G-6-PD deficiency confers resistance against malaria under conditions of fava-bean-associated oxidant stress.


Sinophobic Stigma Going Viral: Addressing the Social Impact of COVID-19 in a Globalized World.
This article critically examines the recent literature on stigma that addresses the overspread association among the COVID-19 pandemic and racial and ethnic groups (i.e., mainland Chinese and East Asian populations) assumed to be the source of the virus.The analysis begins by reviewing the way in which infectious diseases have historically been associated with developing countries and their citizens, which, in turn, are supposed to become prime vectors of contagion. The latter extends to the current labeling of COVID-19 as the "Chinese virus," that-along with a number of other terms-has fueled race-based stigma against Asian groups in the United States and overseas. This review further discusses the limitations of current COVID-19 antistigma initiatives that mostly focus on individual-based education campaigns as opposed to multisectorial programs informed by human rights and intersectional perspectives.Finally, the article ends with a call to the international public health community toward addressing the most recent outbreak of stigma, one that has revealed the enormous impact of words in amplifying racial bias against particular minority populations in the developed world.


Design and Clinical Considerations for Endovascular Stent Grafts.
Endovascular treatment for aortic abnormality is an excellent alternative option for patients who are not good candidates for conventional open surgery. Although the technique of placing endovascular stent grafts has evolved since the first grafts, the basic principles remain the same. Use of endografts is limited by anatomic criteria, and advances in graft design have allowed for more widespread use for a broader patient range. The most important limitations to overcome are achieving high-quality aortic neck "healthy" landing zone, smaller-diameter delivery systems, and endografts that allow for more angled aortic necks.


[Caudal regeneration in Nicodrilus giardi (Ribaucourt) (Oligocheta, Lumbricidae): worms amputated at the end of summer diapause].
N. giardi collected at the end of the summer diapause were amputated at two levels of the posterior part of the body: After amputation of the 100 posterior segments (nearly half the body), the regeneration processes appear quickly. An amputation removing only the 30 posterior segments is followed by a reorganization in the injured area, but the worms are incapable of regeneration.


Effect of omega-3 fatty acids on plasma level of 8-isoprostane in kidney transplant patients.
It has been shown previously that the serum level of F2-isoprostanes acts as an indicator of oxidative stress, which is a risk factor for vascular disease especially in end-stage renal disease. It is not known whether n-3 polyunsaturated fatty acids can decrease oxidative stress in renal recipient patients. In this single blind, randomized, placebo-controlled study, the effect of 3 and 6 months of fish oil administration on 8-isoprostane levels in renal transplant recipients was evaluated. Twenty-two renal transplant patients who fulfilled inclusion and exclusion criteria randomly received either fish oil dietary supplementation, 6 g/day (720 mg of DHA and 1,080 mg of EPA) or placebo for 6 months. Serum 8-isoprostane concentration was measured as markers of oxidative stress. A significant decrease in 8-isoprostane levels was observed only in the placebo group after transplantation compared to baseline (P < 0.05). However, the group receiving fish oil had a significantly lower cholesterol level than that of the placebo group (P < 0.05). On the basis of our results, omega-3 fatty acids supplementation decreased the beneficial effects of kidney transplantation on oxidative stress.


Diseases related to Notch glycosylation.
The Notch receptors are a family of transmembrane proteins that mediate direct cell-cell interactions and control numerous cell-fate specifications in humans. The extracellular domains of mammalian Notch proteins contain 29-36 tandem epidermal growth factor-like (EGF) repeats, most of which have O-linked glycan modifications: O-glucose added by POGLUT1, O-fucose added by POFUT1 and elongated by Fringe enzymes, and O-GlcNAc added by EOGT. The extracellular domain is also N-glycosylated. Mutations in the glycosyltransferases modifying Notch have been identified in several diseases, including Dowling-Degos Disease (haploinsufficiency of POFUT1 or POGLUT1), a form of limb-girdle muscular dystrophy (autosomal recessive mutations in POGLUT1), Spondylocostal Dysostosis 3 (autosomal recessive mutations in LFNG), Adams-Oliver syndrome (autosomal recessive mutations in EOGT), and some cancers (amplification, gain or loss-of-function of POFUT1, Fringe enzymes, POGLUT1, MGAT3). Here we review the characteristics of these diseases and potential molecular mechanisms.


Study protocol for a randomized controlled trial of the effectiveness of adding motivational interviewing or stratified vocational advice intervention to usual case management on return to work for people with musculoskeletal disorders. The MI-NAV study.
Little research exists on the effectiveness of motivational interviewing (MI) on return to work (RTW) in workers on long term sick leave. The objectives of this study protocol is to describe a randomized controlled trial (RCT) with the objectives to compare the effectiveness and cost-effectiveness of usual case management alone with usual case management plus MI or usual case management plus stratified vocational advice intervention (SVAI), on RTW among people on sick leave due to musculoskeletal (MSK) disorders. A multi-arm RCT with economic evaluation will be conducted in Norway with recruitment of 450 participants aged 18-67 years on 50-100% sick leave for > 7 weeks due to MSK disorders. Participants will be randomized to either usual case management by the Norwegian Labour and Welfare Administration (NAV) alone, usual case management by NAV plus MI, or usual case management by NAV plus SVAI. Trained caseworkers in NAV will give two MI sessions, and physiotherapists will give 1-4 SVAI sessions depending upon risk of long-term sick leave. The primary outcome is the number of sick leave days from randomization to 6 months follow-up. Secondary outcomes are number of sick leave days at 12 months follow-up, time until sustainable RTW (≥4 weeks of at least 50% of their usual working hours) at 12 months, proportions of participants receiving sick leave benefits during 12 months of follow-up, and MSK symptoms influencing health at 12 months. Cost-utility evaluated by the EuroQoL 5D-5L and cost-benefit analyses will be performed. Fidelity of the interventions will be assessed through audio-recordings of approximately 10% of the intervention sessions. The results from this RCT will inform stakeholders involved in supporting RTW due to MSK disorders such as staff within NAV and primary health care. ClinicalTrials.gov ID: NCT03871712 registered March 12th 2020.


Strong coupling in a single quantum dot-semiconductor microcavity system.
Cavity quantum electrodynamics, a central research field in optics and solid-state physics, addresses properties of atom-like emitters in cavities and can be divided into a weak and a strong coupling regime. For weak coupling, the spontaneous emission can be enhanced or reduced compared with its vacuum level by tuning discrete cavity modes in and out of resonance with the emitter. However, the most striking change of emission properties occurs when the conditions for strong coupling are fulfilled. In this case there is a change from the usual irreversible spontaneous emission to a reversible exchange of energy between the emitter and the cavity mode. This coherent coupling may provide a basis for future applications in quantum information processing or schemes for coherent control. Until now, strong coupling of individual two-level systems has been observed only for atoms in large cavities. Here we report the observation of strong coupling of a single two-level solid-state system with a photon, as realized by a single quantum dot in a semiconductor microcavity. The strong coupling is manifest in photoluminescence data that display anti-crossings between the quantum dot exciton and cavity-mode dispersion relations, characterized by a vacuum Rabi splitting of about 140 microeV.


Intravenous butyrate and healing of colonic anastomoses in the rat.
Intracolonic infusions of short chain fatty acids promote healing of colonic anastomoses. Because the intravenous route may have wider clinical application, we studied the effect of intravenous n-butyrate on the mechanical strength of colonic anastomoses in the rat. After placement of an indwelling intravenous catheter, the descending colon was transected and an anastomosis was performed. Rats were then randomized to receive total parenteral nutrition (TPN group; n = 15) or total parenteral nutrition plus 130 mM/l of n-butyrate (TPN+BUT group; n = 13). On the fifth postoperative day, bursting pressure and bowel wall tension of the anastomoses were measured in situ. Anastomotic tissues were analyzed for hydroxyproline. The TPN+BUT group had a significantly higher bursting pressure (107.5 +/- 30.3 vs. 83 +/- 41.0 mmHg; P = 0.04) and bowel wall tension (20.7 +/- 7.6 vs. 14.1 +/- 9.9 Newton; P = 0.03). Tissue hydroxyproline was not different between the two groups (TPN, 45.8 +/- 9.2, and TPN+BUT, 47.9 +/- 2.9 microg/mg tissue nitrogen). We conclude that intravenous butyrate improves mechanical strength of a colonic anastomosis without a detectable change in total collagen content.


The hamster papovavirus: evolutionary relationships with other polyomaviruses.
The hamster papovavirus (HaPV) is a polyoma virus with a restricted tumor spectrum. It is actively replicated in hair follicle tumors arising spontaneously in young Syrian hamsters. It can also induce lymphomas and leukemias in newborn hamsters. The complete nucleotide sequence of a cloned HaPV has been established recently. This report presents a comparison of this sequence with other polyomavirus genomes (polyoma, SV40, BKV, LPV) by matrix dot analysis and electron microscopy heteroduplex mapping. The results demonstrate a close relationship between the HaPV and the murine polyoma virus and designate the LPV as the closest relative among the primate polyomaviruses.


High rate of complications after corrective midfoot/subtalar arthrodesis and Achilles tendon lengthening in Charcot arthropathy type Sanders 2 and 3.
Corrective midfoot resection arthrodesis is the standard treatment of Charcot arthropathy type Sanders 2 and 3 with severe dislocation. In order to critically evaluate the effect of surgical correction, a retrospective analysis of our patient cohort was performed. Hereby, special emphasis was set on the analysis of the pre- and post-operative equinus position of the hindfoot. Retrospectively, all patients (n = 82) after midfoot resection arthrodesis in Charcot type Sanders 2 or 3 were included. Complications were recorded, and the mean complication-free interval was calculated. Additionally, the calcaneal pitch as well as Meary's angle were measured pre- and post-operatively and in case of complications. Overall complication rate was 89%. Revision surgery was necessary in 46% of all patients. The mean complication-free interval was 285 days (0-1560 days). Calcaneal pitch and Meary's angle significantly improved after operation but returned to pre-operative values after onset of complications. Achilles tendon lengthening showed no significant effects on the mean complication-free interval. Operative treatment of Charcot arthropathy remains a surgical challenge with high complication rates. Surgical correction of equinus position has been highlighted for successful treatment but was not able to prevent complications in this study, which is demonstrated by the recurrent decrease of the calcaneal pitch in cases of reoperation. Therefore, as a conclusion of our results, our treatment algorithm changed towards primarily addressing the equinus malpositioning of the hindfoot by corrective arthrodesis of the hindfoot.


Matrix metalloproteinases in dog brains exhibiting Alzheimer-like characteristics.
We have previously reported that the amount of the neuronal matrix metalloproteinase (MMP) MMP-9, capable of cleaving beta-amyloid,-40 predominantly at Leu34-Met35, is increased in a latent form in hippocampal specimens from AD patients and have suggested that the lack of activation of this enzyme may contribute to the deposition of beta-amyloid in plaques. The current study addresses whether similar matrix proteinases are detectable in amyloid-positive and -negative brain specimens of aged beagles. Using quantitative zymography, three major neutral proteinases with molecular masses of 60, 95, and 280 kDa were readily detected. These enzymes have the characteristics of MMPs because they were inhibited by EDTA and 1, 10-phenanthroline, and their activities were restored by addition of both Ca2+ and Zn2+. The 95- and 280-kDa proteinases cross-reacted with specific monoclonal antibodies to human MMP-9 (gelatinase B; EC 3.4. 24.35). Canine MMP-9 was latent because activation by organomercurial treatment resulted in a characteristic decrease in molecular mass. Statistical analysis revealed no difference in the 60-kDa proteinase activity in amyloid-positive and -negative brain specimens. However, significantly increased amounts of latent MMP-9 were observed in amyloid-positive brain specimens (p < or = 0.05) compared with amyloid-negative brain specimens. The observations document that changes in MMP-9 expression in amyloid-positive beagle brains are similar to those reported in the human Alzheimer's disease hippocampus and suggest the possibility that insufficient activation of MMP-9 may contribute to beta-amyloid accumulation, a hypothesis that needs to be further investigated.


Microbiota of the first-pass meconium and subsequent atopic and allergic disorders in children.
Some cohort studies have suggested that gut microbiota composition is associated with allergic diseases in children. The microbiota of the first-pass meconium, which forms before birth, represents the first gut microbiota that is easily available for research and little is known about any relationship with allergic disease development. We investigated whether the bacterial composition of the first-pass meconium is associated with the development of allergic diseases before 4 years of age. Prospective birth cohort study. Bacterial composition of first-pass meconium was analysed using bacterial 16S rRNA gene amplicon sequencing. Atopic and allergic diseases were evaluated via online survey or telephone to age 4 years, based on the International Study of Asthma and Allergies in Childhood questionnaire. During a 6-week period in 2014, 312 children were born at the Central Finland Central Hospital. Meconium was collected from 212 at a mean of 8-hour age. Outcome data at 4 years were available for 177 (83%) children, and 159 of these had sufficient amplification of bacterial DNA in meconium. Meconium microbiota composition, including diversity indices and relative abundances of the main phyla and genera, was not associated with subsequent atopic eczema, wheezing or cow's milk allergy. Principal components analysis did not identify any clustering of the meconium microbiomes of children with respect to wheezing or cow's milk allergy. We found no evidence that gut microbiota composition of first-pass meconium is associated with atopic manifestations to age 4 years. However, larger studies are needed to fully exclude a relationship.


Organic dust disease of airways.
Exposure to aerosols of organic dusts such as coffee, tea, spices, soy, fur, and animal food in an occupational setting can affect the respiratory health of industrial workers. Based on our experience with workers from many small industries processing organic materials, we discuss the clinical features and possible mechanisms responsible for the respiratory impairment associated with these types of dust exposure. Significantly higher prevalences for most chronic respiratory symptoms were found among exposed workers than among control workers. Smoking appears to aggravate these symptoms. A large number of exposed workers complained of acute symptoms which developed during the work shift. In exposed workers, significant across-shift reductions in lung function were recorded for all spirometric tests, but particularly for the flow rates at 50% and 25% of vital capacity on maximum expiratory flow-volume curves. Comparison of preshift measured ventilatory capacity tests with predicted normal values indicates that these workers demonstrate obstructive changes affecting primarily flow rate at low lung volumes. The data suggest that exposure to organic aerosols in industrial settings, particularly in conjunction with smoking, may be associated with the development of chronic obstructive lung disease.


Super-selective transcatheter arterial embolization of a traumatic splenic arteriovenous fistula.
We report a 61-year-old woman with arteriovenous fistula (AVF) of a splenic artery caused by traumatic injury, which was successfully occluded by percutaneous transcatheter arterial embolization (TAE). We embolized the AVF with a coaxial system using six microcoils. This case suggests that super-selective TAE for traumatic AVF of a splenic artery is an effective and primary choice of first treatment. The use of a microcatheter and microcoils is an alternative to surgery.


Bis(4-acetyl-anilinium) hexa-chlorido-stannate(IV).
In the title compound, (C(8)H(10)NO)(2)[SnCl(6)], the Sn(IV) atom exists in an octa-hedral coordination environment. In the crystal, inter-molecular N-H⋯O and N-H⋯Cl hydrogen bonds link the cations and anions into a three-dimensional framework.


Clinical characteristics of hospitalized patients with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results.
To determine clinical characteristics associated with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results to help inform coronavirus disease 2019 (COVID-19) testing practices in the inpatient setting. A retrospective observational cohort study. Tertiary-care facility. All patients 2 years of age and older tested for SARS-CoV-2 between March 14, 2020, and April 30, 2020, who had at least 2 SARS-CoV-2 reverse-transcriptase polymerase chain reaction tests within 7 days. The primary outcome measure was a false-negative testing episode, which we defined as an initial negative test followed by a positive test within the subsequent 7 days. Data collected included symptoms, demographics, comorbidities, vital signs, labs, and imaging studies. Logistic regression was used to model associations between clinical variables and false-negative SARS-CoV-2 test results. Of the 1,009 SARS-CoV-2 test results included in the analysis, 4.0% were false-negative results. In multivariable regression analysis, compared with true-negative test results, false-negative test results were associated with anosmia or ageusia (adjusted odds ratio [aOR], 8.4; 95% confidence interval [CI], 1.4-50.5; P = .02), having had a COVID-19-positive contact (aOR, 10.5; 95% CI, 4.3-25.4; P < .0001), and having an elevated lactate dehydrogenase level (aOR, 3.3; 95% CI, 1.2-9.3; P = .03). Demographics, symptom duration, other laboratory values, and abnormal chest imaging were not significantly associated with false-negative test results in our multivariable analysis. Clinical features can help predict which patients are more likely to have false-negative SARS-CoV-2 test results.


DNA hairpins containing the cytidine analog pyrrolo-dC: structural, thermodynamic, and spectroscopic studies.
Structures formed by single-strand DNA have become increasingly interesting because of their roles in a number of biological processes, particularly transcription and its regulation. Of particular importance is the fact that antitumor drugs such as Actinomycin D can selectively bind DNA hairpins over fully paired, double-strand DNA. A new fluorescent base analog, pyrrolo-deoxycytidine (PdC), can now be routinely incorporated into single-strand DNA. The fluorescence of PdC is particularly useful for studying the formation of single-strand DNA in regions of double-strand DNA. The fluorescence is quenched when PdC is paired with a complementary guanine residue, and thus is greatly enhanced upon formation of single-strand DNA. Hence, any process that results in melting or opening of DNA strands produces an increase in the fluorescence intensity of this base analog. In this study we measured the structural effects of incorporating PdC into DNA hairpins, and the effect of this incorporation on the binding of the hairpins by a fluorescent analog of the drug Actinomycin D. Two hairpin DNAs were used: one with PdC in the stem (basepaired) and one with PdC in the loop (unpaired). The thermal stability, 7-aminoactinomycin D binding, and three-dimensional structures of PdC incorporated into these DNA hairpins were all quite similar as compared to the hairpins containing an unmodified dC residue. Fluorescence lifetime measurements indicate that two lifetimes are present in PdC, and that the increase in fluorescence of the unpaired PdC residue compared to the basepaired PdC is due to an increase in the contribution of the longer lifetime to the average fluorescence lifetime. Our data indicate that PdC can be used effectively to differentiate paired and unpaired bases in DNA hairpin secondary structures, and should be similarly applicable for related structures such as cruciforms and quadruplexes. Further, our data indicate that PdC can act as a fluorescence resonance energy transfer donor for the fluorescent drug 7-aminoactinomycin D.


Design of new dopamine D2 receptor ligands: biosynthesis and pharmacological evaluation of the hydroxylated metabolite of LASSBio-581.
LASSBio-581 is a N-phenylpiperazine derivative designed for the treatment of schizophrenia. In this study, four strains of filamentous fungi were screened for their capabilities to biotransform LASSBio-581. Cunninghamella echinulata ATCC 9244 was chosen to scale up the biosynthesis of the p-hydroxylated metabolite of LASSBio-581. The chemical structure of the metabolite was confirmed by NMR, LC-MS and X-ray crystallography. Binding studies performed on brain homogenate indicated that the p-hydroxylated metabolite can be considered more selective for dopamine receptors than LASSBio-581, and, therefore, can be used to design new selective dopamine inhibitors.


Prevalence of urologic sequelae and bladder and bowel dysfunctions in patients with congenital Zika syndrome: A multicenter evaluation of the Zika virus bladder and bowel sequelae assistance network.
Neurogenic bladder was first confirmed as a urological sequela of Congenital Zika Syndrome (CZS) in 2018. Further clinical-epidemiological evidence also confirmed neurogenic bowel dysfunction and cryptorchidism. To strengthen the care for these children, the Congenital Zika Virus Bladder and Bowel Sequelae Network (RASZ in Brazilian) was created, including six integrated centers in Brazil. This article represents the initial outcome of the efforts by RASZ. To evaluate the prevalence of bladder and bowel dysfunction, cryptorchidism and other urological sequelae related to CZS in cohorts attended in six Brazilian states. Observational, prospective, multicenter study including children with CZS assisted in one of six RASZ collaborative centers between June 2016 and February 2023. Data were collected from patient's first assessment using the same protocols for urological and bowel evaluation. Categorical variables were analyzed by frequency of occurrence and numerical variables by mean, median, and standard deviation. The study was approved by the Research Ethics Committees of each center, all parents/caregivers provided written informed consent. The study included 414 children aged 2 months to 7 years (mean 2.77 years, SD 1.73), 227 (54.8 %) were male and 140 (33,8 %) referred urological and bowel symptoms on arrival. Prevalence of both urological and bowel sequelae was 66.7 %, 51 % of children aged 4 years and older had urinary incontinence (UI). UTI was confirmed in 23.4 % (two presented toxemia) and among males, 18.1 % had cryptorchidism. Renal ultrasonography, performed in 186 children, was abnormal in 25 (13.4 %), 7 had hydronephrosis. Among the 287 children who performed urodynamics, 283 (98.6 %) were altered: 232 had a lower bladder capacity, 144 a maximum bladder pressure of ≥40 cm H2O, and 127 did not satisfactorily empty their bladder. A higher prevalence of NLUTD, neurogenic bowel and cryptorchidism was confirmed in children with CZS. Early diagnosis and appropriate treatment, including a multidisciplinary approach, may reduce the risk of UTIs, UI and kidney damage. A limitation of the study was the inability of children to complete the protocol, specifically urodynamic evaluation, and ultrasonography. In both exams, the percentage of abnormal cases was higher than that expected in the normal population. A 66,7 % prevalence of combined urological sequelae and bladder-bowel dysfunction related to CZS was confirmed in patients evaluated in six Brazilian cohorts. The most frequent changes were related to NLUTD, neurogenic bowel, and cryptorchidism. Prevalence may be underestimated due to access restrictions to diagnostic tests.


Genome-wide association study of anthropometric traits in Korcula Island, Croatia.
To identify genetic variants underlying six anthropometric traits: body height, body weight, body mass index, brachial circumference, waist circumference, and hip circumference, using a genome-wide association study. The study was carried out in the isolated population of the island of Korcula, Croatia, with 898 adult examinees who participated in the larger DNA-based genetic epidemiological study in 2007. Anthropometric measurements followed standard internationally accepted procedures. Examinees were genotyped using HumanHap 370CNV chip by Illumina, with a genome-wide scan containing 316730 single nucleotide polymorphisms (SNP). A total of 11 SNPs were associated with the investigated traits at the level of P<10(-5), with one SNP (rs7792939 in gene zinc finger protein 498, ZNF498) associated with body weight, hip circumference, and brachial circumference (P=3.59-5.73 x 10(-6)), and another one (rs157350 in gene delta-sarcoglycan, SGCD) with both brachial and hip circumference (P=3.70-6.08 x 10(-6). Variants in CRIM1, a gene regulating delivery of bone morphogenetic proteins to the cell surface, and ITGA1, involved in the regulation of mesenchymal stem cell proliferation and cartilage production, were also associated with brachial circumference (P=7.82 and 9.68 x 10(-6), respectively) and represent interesting functional candidates. Other associations involved those between genes SEZ6L2 and MAX and waist circumference, XTP6 and brachial circumference, and AMPA1/GRIA1 and height. Although the study was underpowered for the reported associations to reach formal threshold of genome-wide significance under the assumption of independent multiple testing, the consistency of association between the 2 variants and a set of anthropometric traits makes CRIM1 and ITGA1 highly interesting for further replication and functional follow-up. Increased linkage disequilibrium between the used markers in an isolated population makes the formal significance threshold overly stringent, and changed allele frequencies in isolate population may contribute to identifying variants that would not be easily identified in large outbred populations.


Dendritic plasticity in mouse barrel cortex following postnatal vibrissa follicle damage.
Neonatal damage to a row of mystacial vibrissae in the mouse causes cytoarchitectonic alterations in the contralateral SmI barrel Cortex. The region for the appropriate row of barrels develops as a smaller homogeneous zone while barrels in adjacent rows are expanded. To investigate the effects of this phenomenon on the morphology of individual neurons, adult mice in which Row-C vibrissae (the middle row) had been cauterized on days 1--5 following birth were processes by the Golgi-Cox method. All neurons in layer IV of the Row-C zones, of the Row-C barrels of a control hemisphere, and some neurons in the adjacent enlarged Row-B barrels were measured with a computer-assisted microscope. Their location with respect to cytoarchitectonic boundaries was determined from a Nissl counterstain. Data from 239 cells are presented. For each cell, measures of dendritic length and branching were obtained. The orientation of the dendritic trees with respect to the barrel sides was also measured. The measures of dendritic lengths and branching did not show any differences between control and experimental animals or between animals damaged on different days. Measures of orientation did show changes related to the age at the time of damage. In animals damaged on postnatal day (PND)-3 or earlier, many cells in the Row-C zone were observed with dendrites orienting toward the adjacent Rows-B or -D. "Putative" Row-C cells in the expanded parts of Rows-B and -D were strongly oriented toward barrels in those rows. These results suggest that dendritic length and branching may be determined intrinsically but that the orientation of the dendritic trees appears to be strongly influenced by the pattern of extrinsic afferent inputs from the thalamus. In the case of the whisker-damaged animals, the orientation of the Row-C neuron dendritic trees toward the "functional" thalamocortical inputs in Rows-B and -D contributes strongly to the resultant cytoarchitectonic changes. The implications of these results for normal developmental processes and their relationship to functional studies of the cortex are considered.


Ocular expression of cyclin-dependent kinase 5 in patients with proliferative diabetic retinopathy.
Inhibition of peroxisome proliferator-activated receptor gamma (PPARγ) phosphorylation mediated by cyclin-dependent kinase 5 (Cdk5) is one of the main mechanisms of action of antidiabetic drugs. In this study, we analyzed the ocular expression and activation of Cdk5 in patients with proliferative diabetic retinopathy (PDR). The concentrations of PPARγ, Cdk5 and its activating subunit (p35) were determined in the vitreous body of 24 PDR and 63 control eyes by enzyme-linked immunosorbent assay. In addition, the messenger ribonucleic acid and protein expression levels of PPARγ, Cdk5 and p35 were measured in proliferative neovascular membranes from seven PDR eyes and non-neovascular epiretinal membranes from five control eyes by quantitative real-time polymerase chain reaction and immunohistochemical analysis. PPARγ, Cdk5 and p35 concentrations in the vitreous body were significantly higher in the PDR group compared with the control group. There was also a positive significant correlation of Cdk5 with PPARγ and p35 in the PDR group. Furthermore, the messenger ribonucleic acid expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes were significantly higher in the PDR group compared with the control group. Immunostaining showed increased protein expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes in the PDR group compared with the control group. Cdk5 activation is involved in PDR pathogenesis through PPARγ expression, and inhibition of Cdk5-mediated PPARγ phosphorylation might be a new therapeutic target for treatment of PDR.


An alternative one layer inverting suture technique for intestinal anastomosis.
An alternative method of anastomosis using a suture one layer inverting was proposed in which the sutures are placed the serosa, proper muscle layer, submucosal layer and muscularis mucosae, but not mucosa. An experimental study using canine intestine revealed that tensile strength as well as bursting pressure at the anastomotic site is significantly superior in our method to the end-on method.


Electrophilicity parameters for sigma-complexation by uncharged electron-deficient aromatic and heteroaromatic structures.
Using appropriate sets of reference nucleophiles, the reactivity of neutral electrophiles of widely different reactivity and structure has been ranked on the comprehensive electrophilicity scale of Mayr (Acc. Chem. Res., 2003, 36, 66), holding promise of a general rationalization of sigma-complexation processes and related SNAr substitutions.


Hepatitis B surface antigen produced by a human hepatoma cell line.
The human hepatoma cell line, PLC/PRF/5, was shown to produce hepatitis B surface antigen (HBsAg). Immunologically reactive material was present in the supernatant tissue culture medium in significant amounts, and was associated with spherical particles approximately 20 nm in diameter. The rate of antigen production by the cells was estimated at 500 ng/day/10(6) cells by reference to a purified HBsAg standard. All immunological activity was neutralized by specific antibody and the subtype was ad. The studies reported here broaden the scope of investigations on both the in vitro production of HBsAg and the association between this antigen and primary liver cancer.


Development of mental transformation abilities.
Mental representation and transformation of spatial information is often examined with mental rotation (MR) tasks, which require deciding whether a rotated image is the same as or the mirror version of an upright image. Recent research with infants shows early discrimination of objects from mirror-image versions. However, even at the age of 4 years, many children perform at near chance level on more standard measures. Similar age discrepancies can be observed in other domains, including perspective taking, theory of mind, and intuitive physics. These paradoxical results raise the questions of how performance relates to competence and how to conceptualize developmental change. There may be a common underlying mechanism: the development of the ability to imagine things and mentally transform them in a prospective fashion.


Comparative analysis of junctions in the myelin sheath of central and peripheral axons of fish, amphibians and mammals: a freeze-fracture study using complementary replicas.
Tight junction-like structures are found in freeze-fractured myelin of the peripheral and central nervous system of the electric eel and trout, but not in the electric ray, Torpedo californicus. Myelin junctions are more difficult to find in the peripheral myelin of Xenopus frogs and of mice and rats, except in the myelinating fibres of young animals. Junctions are most frequently seen at the outer mesaxons, but are also observed at the inner mesaxons, paranodal loops, incisures of Schmidt-Lanterman and in compact myelin. The junctional strands vary considerably in appearance; instead of displaying the extensive strands and grooves of typical tight junctions, they are usually particulate with single or fused particles, short strands, and corresponding pits and grooves. After fixation, elements of the junctions partition between P- and E-faces with the majority of particles remaining with the P-face. In unfixed fish myelin, strands often remain with the E-face but fixation does not greatly alter the appearance of rat myelin. Complementary replicas show that junctions are often discontinuous. The significance of the distribution and morphology of junctions among the different specimens examined is discussed with regard to the possible functions and maintenance of myelin junctions.


Systemic Mitochondrial Oxidative Phosphorylation Protein Levels Correlate with Neuroimaging Measures in Chronically HIV-Infected Individuals.
Few studies have examined systemic mitochondrial function in conjunction with brain imaging in human immunodeficiency virus (HIV) disease. Oxidative phosphorylation enzyme protein levels of peripheral blood mononuclear cells were measured in association with neuroimaging indices in 28 HIV+ individuals. T1-weighted magnetic resonance imaging yielded volumes of seven brain regions of interest; diffusion tensor imaging determined fractional anisotropy (FA) and mean diffusivity (MD) in the corpus callosum (CC). Higher nicotinamide adenine dinucleotide dehydrogenase levels correlated with lower volumes of thalamus (p = .005) and cerebral white matter (p = .049) and, in the CC, with lower FA (p = .011, body; p = .005, genu; p = .009, total CC) and higher MD (p = .023, body; p = .035, genu; p = .019, splenium; p = .014, total CC). Greater cytochrome c oxidase levels correlated with lower thalamic (p = .034) and cerebellar gray matter (p = .021) volumes. The results indicate that systemic mitochondrial cellular bioenergetics are associated with brain health in HIV.


Real-time polymerase chain reaction analysis of MDM2 and CDK4 expression using total RNA from core-needle biopsies is useful for diagnosing adipocytic tumors.
Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL. A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage. In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P < 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P < 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test). Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.


Enhanced cytokinin degradation in leaf primordia of transgenic Arabidopsis plants reduces leaf size and shoot organ primordia formation.
The plant hormone cytokinin is a key morphogenic factor controlling cell division and differentiation, and thus the formation and growth rate of organs during a plant's life cycle. In order to explore the relevance of cytokinin during the initial phase of leaf primordia formation and its impact on subsequent leaf development, we increased cytokinin degradation in young shoot organ primordia of Arabidopsis thaliana by expressing a cytokinin oxidase/dehydrogenase (CKX) gene under control of the AINTEGUMENTA (ANT) promoter. The final leaf size in ANT:CKX3 plants was reduced to ∼27% of the wild-type size and the number of epidermal cells was reduced to ∼12% of the wild type. Kinematic analysis revealed that cell proliferation ceased earlier and cell expansion was accelerated in ANT:CKX3 leaves, demonstrating that cytokinin controls the duration of the proliferation phase by delaying the onset of cell differentiation. The reduction of the cell number was partially compensated by an increased cell expansion. Interestingly, ANT:CKX3 leaf cells became about 60% larger than those of 35S:CKX3 leaves, indicating that cytokinin has an important function during cell expansion as well. Furthermore, ANT:CKX3 expression significantly reduced the capacity of both the vegetative as well as the generative shoot apical meristem to initiate the formation of new leaves and flowers, respectively. We therefore hypothesize that the cytokinin content in organ primordia is important for regulating the activity of the shoot meristem in a non-autonomous fashion.


Two novel brain-specific splice variants of the murine Cbeta gene of cAMP-dependent protein kinase.
We have previously characterized two murine cAMP-dependent protein kinase catalytic subunit genes, Calpha and Cbeta1. Targeted disruption of the Cbeta1 promoter revealed two splice variants of the Cbeta catalytic subunit gene (designated Cbeta2 and Cbeta3) that continue to be expressed. These variants arise from unique promoters and are brain-specific. Cbeta2 is expressed in several discrete areas in the limbic system. These include the lateral septum, the bed nucleus of the stria terminalis, the ventral medial hypothalamus, and the amygdala. In the neocortex, expression is highest in cortical areas such as the prefrontal and insular cortex that are associated limbic structures. By contrast, Cbeta1 is most highly expressed in the cortex and hippocampus and is also present in all non-neuronal tissues examined. Cbeta3 is expressed at very low levels with wide distribution throughout the brain. Both the Cbeta2 and Cbeta3 variants are enzymatically active and induce gene expression in transient transfections with a cAMP response element-reporter construct. This activity is inhibited by protein kinase A regulatory subunits, the protein kinase inhibitor, and the chemical inhibitor H-89. We also demonstrate that Cbeta1 is myristoylated at the amino terminus like the Calpha isoform, but neither Cbeta2 nor Cbeta3 is myristoylated. The discrete expression of Cbeta variants in the brain suggests specific functional roles in neuronal signaling.


Disrupted Resting-State Functional Connectivity between the Dorsal Attention, Default Mode, and Frontoparietal Networks in Nonorganic Gastrointestinal Disorder Patients with Spleen Deficiency Syndrome.
Spleen deficiency syndrome (SDS), a common clinical syndrome of traditional Chinese medicine, is manifested with digestive symptoms and cognitive impairments. However, the cognitive neural mechanism in brain networks of SDS still remained unclear. Our aim was to investigate the changes between the default mode, dorsal attention, and frontoparietal networks in SDS. Twenty nonorganic gastrointestinal disorder (NOGD) patients with SDS and eighteen healthy controls were enrolled to attend functional magnetic resonance imaging scan and participated a continuous performance test (CPT) before scanning. Compared with healthy controls, NOGD patients with SDS showed the significantly increased functional connectivity (FC) between dorsal attention network (DAN) and left frontal-parietal control network (LFPN) and significantly decreased FC between LFPN and default mode network (DMN). The functional network connectivity analysis showed positive correlation coefficients between the DAN and LFPN and DAN and DMN as well as negative correlation between LFPN and DMN in NOGD patients with SDS compared with healthy controls. Correlation analysis revealed that the increased FC between LFPN and DAN was positively correlated with 4-digitnumber reaction time mean (RTM) and 3-digitnumber RTM. Our study may provide novel insights into the relationship among the DMN, DAN, and FPN in NOGD patients with SDS to deepen our understanding of the neuropsychological mechanisms of SDS.


Modified norcyanines enable ratiometric pH imaging beyond 1000 nm.
Activatable fluorophores with emission beyond 1000 nm have the potential to enable high contrast imaging in complex in vivo settings. However, there are few scaffolds that can be applied to this challenge. Here we detail the synthesis and evaluation of benzo[c,d]indole-substituted norcyanines that enable pH responsive fluorescence imaging in the long wavelength (>1150 nm) range. A key component of our molecular design is the installation of a hydrophilic substituted quaternary amine in the central dihydropyridine ring system. A compound with a C4'-phenyl substituent, but not the C4'-protio homologue, exhibits absorbance maxima of 740 nm and 1130 nm in basic and acidic media, respectively, with evidence of J-aggregate-like properties. These two distinct absorbances enabled ratiometric imaging of probe internalization in a tumor model. Overall, these studies provide a new class of activatable long-wavelength responsive fluorophores with promising photophysical properties.


Tricalysiosides A-G: rearranged ent-kauranoid glycosides from the leaves of Tricalysia dubia.
Seven rearranged ent-kaurane glycosides, named tricalysiosides A-G (1-7), were isolated from the leaves of Tricalysia dubia collected on Okinawa Island. Their C-18 and 19 methyls were found to have rearranged to form an alpha,beta-unsaturated gamma-lactone ring, with other functional groups remotely located only on C-15, -16, and -17 of the five-membered ring. Information available from various kinds of two-dimensional NMR spectra was limited and insufficient to allow total characterization of the structures. Finally, using X-ray crystallographic analysis, the structure of tricalysioside A (1) was determined to be 4-nor-18-homo-ent-kauran-4(18)-en-15beta,16beta,17-triol-3beta,19-olide 16-O-beta-D-glucopyranoside (1). On the basis of the crystal structure of 1, the structures of the other tricalysiosides (2-7) were also established.


The role of alpha-2 adrenoceptors in the anticonvulsant effects of adenosine on pentylenetetrazole-induced seizure threshold in mice.
Adenosine has anticonvulsant effects in various models of seizures. Alpha-2 adrenoceptors have also demonstrated different effects in different models of epilepsy. In this study, the role of alpha-2 adrenoceptors in the anticonvulsant effects of adenosine in mice was determined according to the method of intravenous pentylenetetrazole-induced seizure. In this study, N(6)-cyclohexyladenosine (CHA) (a selective A1 receptor agonist), clonidine (an alpha-2 adrenoceptors agonist), yohimbine (an alpha-2 adrenoceptors antagonist) and 8-cyclopentyl-1,3-dimethylxanthine (8-CPT) (a selective A1 receptor antagonist) were used. CHA at doses of 0.5, 1 and 2mg/kg significantly increased seizure threshold with the maximum anticonvulsant effect at 2mg/kg. Yohimbine (0.1, 1 and 10mg/kg), clonidine (0.1, 0.5, 1 and 2mg/kg) and 8-CPT (0.5, 1, 2 and 4mg/kg) had no effect on seizure by itself. Combination of yohimbine (10mg/kg) and CHA (0.25mg/kg) increased clonic seizure latency showing that yohimbine and CHA have an additive effect. Increasing the seizure threshold created by combining ineffective doses of yohimbine (10mg/kg) and CHA (0.25mg/kg) was completely inhibited by 8-CPT (4mg/kg) or clonidine (1 and 2mg/kg). Clonidine (0.5, 1 and 2mg/kg) inhibited the anticonvulsant effects of CHA (2mg/kg). Combination of 8-CPT (1mg/kg) and clonidine (0.5mg/kg) which completely inhibited the anticonvulsant effect of CHA (2mg/kg) indicates that 8-CPT and clonidine have an additive effect. In conclusion, adenosine and yohimbine exhibit an additive effect on the enhancement of the pentylenetetrazole-induced seizure threshold in mice, indicating the interaction of alpha-2 adrenoceptors and A1 adenosine receptors.


A test for the assessment of disinfectant/sanitizers used for napkin storage.
A test is described for assessing the effect of hypochlorites in reducing the bacterial load on soiled napkins during storage, between removal from the infant and laundering.