Comparative dynamics of four smoking withdrawal symptom scales

Aims To examine the association of person‐specific trajectories of withdrawal symptoms of urge‐to‐smoke, negative affect, physical symptoms and hunger during the first 7 days after smoking cessation with abstinence at end of treatment (EOT) and at 6 months. Design Hierarchical linear modeling (HLM) was used to model person‐specific trajectory parameters (level, slope, curvature and volatility) for withdrawal symptoms. Setting University‐based smoking cessation trials. Participants Treatment‐seeking smokers in clinical trials of transdermal nicotine versus nicotine spray (n = 514) and bupropion versus placebo (n = 421). Measurements Self‐reported withdrawal symptoms for 7 days after the planned quit date, and 7‐day point prevalence and continuous abstinence at EOT and 6 months. Findings In regressions that included trajectory parameters for one group of withdrawal symptoms, both urge‐to‐smoke and negative affect were predictive of abstinence while physical symptoms and hunger were generally not predictive. In stepwise regressions that included the complete set of trajectory parameters across withdrawal symptoms (for urge‐to‐smoke, negative affect, physical symptoms and hunger), with a single exception only the trajectory parameters for urge‐to‐smoke were predictive. Area under the receiver operator characteristic curve was 0.594 for covariates alone, and 0.670 for covariates plus urge‐to‐smoke trajectory parameters. Conclusions Among a number of different withdrawal symptoms (urge‐to‐smoke, negative affect, physical symptoms and hunger) urge‐to‐smoke trajectory parameters (level, slope and volatility) over the first 7 days of smoking cessation show the strongest prediction of both short‐ and long‐term relapse. Other withdrawal symptoms increase the predictive ability by negligible amounts.     

Management of Sphincter Dyssynergia Using the Sphincter Stent Prosthesis in Chronically Catheterized SCI Men

Abstract

This effort represents a subset analysis of the long-term Multicenter North American Trial of the UroLume sphincter stent prosthesis to determine the effect of the sphincter stent prosthesis in SCI men afflicted with detrusor-external sphincter dyssynergia (DESD) and chronically managed with an indwelling urinary catheter. Forty-one of 153 male patients in this study were evaluated urodynamically before and after placement of the sphincter stent prosthesis. Of the 41 patients, 34 (81 percent) suffered cervical-level injury while 10 patients (25 percent) had been treated previously with external sphincterotomy. Forty patients (98 percent) were troubled with recurrent urinary tract infections (UTI), with a mean of 4.6±3 episodes of UTI per year. Seven patients (17 percent) demonstrated hydronephrosis prior to stent placement.

Follow-up ranged from six to 44 months. Voiding pressures decreased from a mean of 77±23 cmH20 preoperatively to 35±18 cmH20 at 12 months (n=34) and 33±20 cmH2Û at 24 months (n=22) after stent insertion (p=0.001). Post-void residual urinary volume decreased from 202±187 ml preinsertion to 64±69 ml at 24 months (p=0.001) postinsertion. Maximum cystometric capacity remained constant at 201 ±144 ml preinsertion to 203±79 ml at 24 months (p=0.75) postinsertion. No significant changes in any of the urodynamic parameters occurred after 24 months of follow-up between patients with (n=10) and without (n=31) previous external sphincterotomy.

Neither hemorrhage requiring blood transfusion, obstructive hyperplastic epithelial overgrowth, stent encrustation or stone formation, nor soft tissue erosion occurred in any patient. No deleterious effects were observed on erectile function. Hydronephrosis resolved in four, and improved in three, of seven patients with hydronephrosis preoperatively. Eighty-two percent of the patients demonstrated complete stent epithelialization after six months, while 96 percent were epithelialized two years after stent insertion. In three patients, stent migration required repositioning or removal within the first month. In another two patients, the stent prostheses were removed one year postinsertion because of problems with condom catheter drainage.

The sphincter stent prosthesis is an attractive, potentially reversible treatment option for DESD in men managed with an indwelling catheter, even if external sphincterotomy has been performed previously. (J Spinal Cord Med;] 8:88–94)     

Musicians show general enhancement of complex sound encoding and better inhibition of irrelevant auditory change in music: an ERP study

Using electrophysiology, we have examined two questions in relation to musical training – namely, whether it enhances sensory encoding of the human voice and whether it improves the ability to ignore irrelevant auditory change. Participants performed an auditory distraction task, in which they identified each sound as either short (350 ms) or long (550 ms) and ignored a change in timbre of the sounds. Sounds consisted of a male and a female voice saying a neutral sound [a], and of a cello and a French Horn playing an F3 note. In some blocks, musical sounds occurred on 80% of trials, while voice sounds on 20% of trials. In other blocks, the reverse was true. Participants heard naturally recorded sounds in half of experimental blocks and their spectrally‐rotated versions in the other half. Regarding voice perception, we found that musicians had a larger N1 event‐related potential component not only to vocal sounds but also to their never before heard spectrally‐rotated versions. We therefore conclude that musical training is associated with a general improvement in the early neural encoding of complex sounds. Regarding the ability to ignore irrelevant auditory change, musicians' accuracy tended to suffer less from the change in timbre of the sounds, especially when deviants were musical notes. This behavioral finding was accompanied by a marginally larger re‐orienting negativity in musicians, suggesting that their advantage may lie in a more efficient disengagement of attention from the distracting auditory dimension.     

Morphology assessment and fluorescence in situ hybridization of the same spermatozoon using a computerized cell-scanning system

BACKGROUND: Poor sperm morphology is statistically associated with an increase in the incidence of chromosome abnormalities. Our aim was to examine the possible correlation between chromosomal aberrations and sperm morphology in the same cell. METHODS: 12349 spermatozoa from 7 teratozoospermic and one globozoospermic patients, and from 3 fertile donors were analyzed using a system which scans for cell morphology and chromosomal ploidy in the same cell using digital technology. RESULTS: Chromosomal aberrations were detected in 5.3% of teratozoospermic cases and in 6.7% in the globozoospermic patient compared with 1.6% in donors (P < 0.0001). Chromosomal aberrations were more common in abnormally formed sperm compared with normal spermatozoa: 4.5% vs 1.3% in the teratozoospermic group and 2.0% vs 0.3% in the control group (NS), especially frequent among sperm with two heads or two tails (52.1-77.2%) or extreme head deformations (10.6-11.1%) irrespective of grouping, and in mild amorphous heads in the globozoospermic patients (20.2%). The frequency of chromosomal aberrations in morphologically normal sperm was comparable whether derived from teratozoospermic or normospermic patients. CONCLUSIONS: The computerized cell-scanning system demonstrated the relationship between chromosomal aberrations and sperm morphology in the same spermatozoon. The incidence of chromosomal aberrations was positively linked to abnormal sperm morphology, the more severe the abnormality, the higher the incidence of aneuploidy.     

Activity of Indatuximab Ravtansine against Triple-Negative Breast Cancer in Preclinical Tumor Models

Purpose

Triple-negative breast cancer (TNBC) is related with a poor prognosis as patients do hardly benefit from approved therapies. CD138 (Syndecan-1) is upregulated on human breast cancers. Indatuximab ravtansine (BT062) is an antibody-drug-conjugate that specifically targets CD138-expressing cells and has previously shown clinical activity in multiple myeloma. Here we show indatuximab ravtansine as a potential mono- and combination therapy for TNBC.

Methods

The effects of indatuximab ravtansine were assessed in vitro in SK-BR-3 and T47D breast cancer cell lines. The in vivo effects of indatuximab ravtansine alone and in combination with docetaxel or paclitaxel were assessed in MAXF401, MAXF1384 and MAXF1322 xenograft TNBC models.

Results

CD138⁺ SK-BR-3 and T47D cells were highly sensitive to indatuximab ravtansine. The high CD138-expressing MAXF401 xenograft model demonstrated strong inhibition of tumor growth with 4 mg/kg indatuximab ravtansine. High doses of indatuximab ravtansine (8 mg/kg), docetaxel and the combination of both led to complete remission. In the low CD138-expressing MAXF1384 xenograft model, only combination of indatuximab ravtansine and docetaxel demonstrated a significant efficacy. In the MAXF1322 xenograft model, indatuximab ravtansine alone and in combination with paclitaxel elicited complete remission.

Conclusions

These data demonstrate potential use of indatuximab ravtansine in combination with docetaxel or paclitaxel for CD138-positive TNBC.

     

The Role of Social Context in Racial Disparities in Self-Rated Health

Race disparities in self-rated health in the USA are well-documented, such that African Americans rate their health more poorly than whites. However, after adjusting for health status, socioeconomic status (SES), and health behaviors, residual race differences are observed. This suggests the importance of unmeasured variables. Because African Americans and whites tend to live in differing social contexts, it is possible that accounting for social and environmental conditions may reduce racial disparities in self-rated health. Differences in self-rated health among whites and African Americans were assessed in a low-income, urban integrated community (Exploring Health Disparities in Integrated Communities (EHDIC)) and compared with a national sample (National Health Interview Survey (NHIS)). Controlling for demographics, SES, health insurance, status, and behaviors, African Americans in NHIS had higher odds of reporting fair or poor health (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.18–1.66) than whites. In EHDIC, there was no race difference in self-rated health (OR = 0.83, 95% CI = 0.63–1.11). These results demonstrate the importance of social context in understanding race disparities in self-rated health.     

Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord

Urotensin II (UII) is a cyclic peptide initially isolated from the caudal neurosecretory system of teleost fish. Subsequently, UII has been characterized from a frog brain extract, indicating that a gene encoding a UII precursor is also present in the genome of a tetrapod. Here, we report the characterization of the cDNAs encoding frog and human UII precursors and the localization of the corresponding mRNAs. In both frog and human, the UII sequence is located at the C-terminal position of the precursor. Human UII is composed of only 11 amino acid residues, while fish and frog UII possess 12 and 13 amino acid residues, respectively. The cyclic region of UII, which is responsible for the biological activity of the peptide, has been fully conserved from fish to human. Northern blot and dot blot analysis revealed that UII precursor mRNAs are found predominantly in the frog and human spinal cord. In situ hybridization studies showed that the UII precursor gene is actively expressed in motoneurons. The present study demonstrates that UII, which has long been regarded as a peptide exclusively produced by the urophysis of teleost fish, is actually present in the brain of amphibians and mammals. The fact that evolutionary pressure has acted to conserve fully the biologically active sequence of UII suggests that the peptide may exert important physiological functions in humans.     

Growth of normal mouse vaginal epithelial cells in and on collagen gels.

Sustained growth in primary culture of vaginal epithelial cells from ovariectomized adult BALB/cCrgl mice embedded within or seeded on collagen gel matrix was achieved in a serum-free medium composed of Ham's F-12 medium/Dulbecco's modified Eagle's medium, 1:1 (vol/vol), supplemented with insulin, bovine serum albumin fraction V, epidermal growth factor, cholera toxin, and transferrin. Three-dimensional growth of vaginal epithelial cells occurred inside the collagen gel matrix. Cell numbers increased 4- to 8-fold in collagen gel and about 4-fold on collagen gel after 9-10 days in culture. The effect of 17 beta-estradiol (0.00018-180 nM in gel or 0.018-180 nM on gel) and diethylstilbestrol (DES; 0.0186-186 nM in gel) on the growth of vaginal epithelial cells was examined. The addition of estrogen did not enhance the growth of vaginal epithelial cells during this time period either in the complete medium or in a suboptimal medium. Cultures on floating collagen gels in the serum-free medium are composed of 1-3 cell layers with superficial cornification. Estrogen does not appear to be a direct mitogen for vaginal epithelial cells, at least in this system.