OBJECTIVE

Nuclear receptors are involved in a wide variety of functions, including aldosteronogenesis. Nuclear receptor families NR4A [nerve growth factor-induced clone B (NGFIB), Nur-related factor 1 (NURR1) and neuron-derived orphan receptor 1 (NOR1)] and NR2F [chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), COUP-TFII and NR2F6) activate, whereas NR5A1 [steroidogenic factor 1 (SF1)] represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues.

METHODS

We collected tissues of artery (n = 9), cardiomyopathy muscle (n = 9), heart muscle (noncardiomyopathy) (n = 6), adrenal gland (n = 9) and aldosterone-producing adenoma (APA) (n = 9). 5'-rapid amplification of cDNA ends (RACE) identified transcription start sites. Multiplex reverse-transcription PCR (RT-PCR) determined use of alternative noncoding exons 1 (ANEs).

RESULTS

In adrenocortical H295R cells, angiotensin II, KCl or cAMP, all stimulated CYP11B2 transcription and NR4A was upregulated, whereas NR2F and NR5A1 were downregulated. 5'-RACE and RT-PCR revealed four ANEs of NGFIB (NR4A1), three of NURR1 (NR4A2), two of NOR1 (NR4A3) and two of SF1 (NR5A1) in cardiovascular and adrenal tissues. Quantitative multiplex RT-PCR showed NR4A and NR5A1 differentially employed multiple ANEs in a tissue-specific manner. The use of ANEs of NGFIB and NURR1 was significantly different between APA and artery. Changes in use of ANEs of NGFIB and NOR1 were observed between cardiomyopathy and noncardiomyopathy. The NR4A mRNA levels in artery were high compared with cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared with cardiovascular tissues.

CONCLUSIONS

NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland.

The reports concerning serum levels of sex hormone binding globulin (SHBG) and testosterone in women with anorexia nervosa are controversial and few in number. The aim of the study was to assess the levels of FSH, LH, PRL, unbound and bound testosterone, SHBG, estradiol, free T4, TSH in women with anorexia nervosa. The TFI (testosterone free index) used to assess SHBG ability to bind testosterone was also calculated. The studied group consisted of 29 women with anorexia nervosa: 15 women untreated hormonally and 14 women treated with estrogens and progestagens. The control group consisted of 13 women with regular menstrual cycle being in the first phase of menstrual cycle, with proper body weight and mean age comparable to the patients with anorexia nervosa. No statistically significant differences between studied groups concerning the serum concentration of FSH, LH, PRL, free testosterone, LH/FSH ratio, TSH and free T4 were found. The total testosterone concentration was statistically significantly lower in the group without hormonal therapy, contrary to SHBG concentration, which was higher in the group treated hormonally. Although there are reports about elevated SHBG and free testosterone levels in patients with anorexia nervosa, our study has shown no significant differences between women with untreated hormonally anorexia nervosa and healthy control group.

OBJECTIVE

To examine levels of fluorosis among children in two Canadian communities exposed to fluoride.

BACKGROUND

One community had discontinued fluoride, the other had maintained it. Water supplies, however, were fluoridated for all the children when their esthetically important teeth were mineralized.

METHODS

We examined 8,277 children to assess Thystrup-Fejerskov Index (TFI) scores. Multivariate Poisson regression models were used to identify the relationship between TFI and water fluoride status, age, gender, SES, and dietary and fluoride exposure histories (supplements, rinses, toothpaste amount, tooth brushing frequency, and tooth brushing starting age). Parent(s) completed questionnaires.

RESULTS

Overall, levels of fluorosis were low to mild, with residents of the fluoridation-ended communities having marginally higher TFI scores than those of the still-fluoridated community. Females had higher TFI scores than males. Children aged 10 years or more had higher TFI scores than younger children. Consuming bottled water between birth and 6 months of age was protective. Exposure to fluoridation technologies was consistently associated with fluorosis experience. Children who began brushing with fluoride toothpaste between their first and second birthdays had higher TFI scores than those who began between their second and third birthdays, regardless of daily brushing frequency. Children who regularly used supplements had higher TFI scores than those who did not. Children with a college-educated father had higher TFI scores than those whose fathers had less education.

CONCLUSIONS

Higher fluoride exposure slightly increased the likelihood that a child had a higher TFI score, especially when more fluoridation technologies were used at home.

7,12-Dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma is a well-recognized model; however, the genetic alterations during its carcinogenesis have yet to be determined. We used laser capture microdissection to specifically isolate cells from terminal end buds (TEBs), the origin of carcinoma, at 2 weeks after sesame oil treatment (control) or DMBA treatment (DMBA-TEBs), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (MC). Using an oligonucleotide microarray representing 20,600 rat probe sequences, we analyzed gene expression profiles and validated mRNA and protein levels of genes of interest by real-time quantitative PCR and immunohistochemistry. The number of differentially expressed genes dramatically increased from DMBA-TEBs (63) to DCIS (798) and MC (981). Only the expression of PEP-19, an anti-apoptotic gene, showed significant increases in DMBA-TEBs (4-fold), DCIS (10-fold) and MC (16-fold). MMP-13 expression was increased markedly in DCIS (19-fold) and MC (61-fold) while OPN expression was increased 6-fold in DCIS and 8-fold in MC. MMP-7 expression was increased 4-fold in MC. Nidogen-1; a participant in the assembly of basement membranes, TSP-2; an inhibitor of angiogenesis and COUP-TFI; a transcription repressor showed significant decreases in DCIS (4-, 9- and 17-fold, respectively) and MC (10-, 37- and 100-fold). Network analyses with IPA software revealed that the most significant network included Akt groups in DCIS and ERK groups in MC. The present findings provide us with a better understanding of the molecular alteration that occur during mammary carcinogenesis and suggest the importance of PEP-19 overexpression in the very early stage of mammary carcinogenesis.

BACKGROUND

Several studies have investigated the adhesion of glass ionomer-based restorative materials to nonfluorotic teeth, but there appears to be no information on the bond strength of these restorative materials to dentin in fluorotic teeth.

OBJECTIVE

This study investigated the effect of dental fluorosis on the bond strength of Ketac-fil conventional glass ionomer cement, Vitremer resin-modified glass ionomer cement, and Dyract polyacid modified resin to dentin.

METHODS

Ninety posterior teeth were classified according to the severity of fluorosis, by using the Thylstrup and Fejerskov index, TFI. The teeth were divided into 3 equal groups (TFI = 0,TFI = 1-3, TFI = 4+) of 30 teeth, which were again divided into 3 equal subgroups for testing each of the3 restorative materials. Occlusal surfaces of mounted teeth were ground flat to expose dentin. Cylindrical specimens (4 mm diameter and 4 mm high) of the restorative materials were bonded to the middle of the cleaned exposed dentin surfaces, according to the manufacturers' instructions. After storing the specimens in 100% humidity at 37 degrees C for 24 hours, shear bond strengths of the restorative materials were measured with an Instron testing machine at crosshead speed of 0.5 mm/min.

RESULTS

Two-way analysis of variance and Tukey-B test revealed that Dyract had significantly higher shear bond strength to dentin than Ketac-fil or Vitremer cements, regardless of severity of fluorosis (P <.05). Furthermore, there was an inverse relationship between shear bond strength and the severity of fluorosis for each of the restorative materials. Cohesive mode of failure was most prevalent in nonfluorotic teeth (TFI = 0), especially with Ketac-fil cement, whereas Dyract cement had the greatest propensity for adhesive failure.

CONCLUSIONS

Fluorosis reduces the shear bond strength of glass ionomer-based restorative materials to dentin.

Two tandem sites in the aldehyde dehydrogenase 2 promoter (designated FP330-5' and FP330-3') that bind members of the nuclear receptor superfamily were recently identified. Antibodies against apolipoprotein regulatory protein (ARP-1) altered DNA-protein interactions in electrophoretic mobility shift assays using oligonucleotides representing either promoter site and rat liver or cultured cell nuclear extracts. In vitro-translated chicken ovalbumin upstream promoter transcription factor (COUP-TFI), ARP-1, or ErbA-related protein 2 (Ear2) bound both sites. In addition, ARP-1/RXR, COUP-TFI/RXR, and ARP-1/COUP-TFI heterodimers bound the FP330-3' site. Mutagenesis of the FP330-3' site indicated that a DR-1 element was the preferred binding site for these factors. Transfected expression plasmids for these factors suppressed basal expression of reporter constructs containing the FP330-3' sites and the induction of the reporter by RXRalpha plus retinoic acid. Mutation of the two sites increased activity of a construct driven by 600 bp of the ALDH2 promoter in cell lines expressing COUP-TFs. The ALDH2 FP330-3' site appears to represent a complex nuclear receptor response element that is activated by RXRs and HNF-4 but repressed by members of the COUP-TF family.

OBJECTIVE

To evaluate the clinical and radiographic outcomes of 2-part lesser tuberosity fracture with a locked posterior dislocation.

METHODS

Retrospective case series study.

METHODS

Beijing Jishuitan Hospital ("first-level teaching hospital").

METHODS

Between April 2003 and June 2010, 29 patients received surgical treatment for 2-part lesser tuberosity fractures with an associated locked posterior shoulder dislocation. At the final follow-up, 22 of these patients were available for evaluation.

METHODS

Open reduction and internal fixation.

METHODS

The shoulder range of motion and visual analog scale pain score were recorded. The postoperative outcomes were evaluated using Score of University of California in Los Angeles (UCLA), Constant, and American Shoulder and Elbow Surgeons (ASES) Scale score. The degree of humeral head necrosis was analyzed according to plain radiographs. The effects of patients' age, dominant-side involvement, as well as time from initial injury to surgery (TFIS) on clinical outcomes and the degree of humeral head necrosis were evaluated.

RESULTS

There were 21 men and 1 woman. The average age was 41.7 years. The dominant side was involved in 12 of 22 cases (54.5%). The average TFIS was 49.5 (range, 4-148) days. The mean follow-up period was 38.1 months. The TFIS was identified as the only risk factor regarding postoperative shoulder outcome scores.

CONCLUSIONS

Acceptable outcomes can be achieved with surgical treatment for 2-part lesser tuberosity fracture with locked posterior shoulder dislocations. The TFIS has a negative impact on the final outcome.

METHODS

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Testosterone, quantitatively the most important androgen in the circulation, must enter cells to exert an androgenic effect. It is accepted that it is that fraction of the hormone not bound to the specific, binding, beta-globulin which is available for entry into the cells. By equilibrium dialysis we obtained an in vitro measurement of the unbound fraction. The product of this fraction and the total testosterone level gave us a testosterone free index (TFI). In normal men and women, our ranges were 24.6 to 93.6 and 0.8 to 3.8 ng/100 ml, respectively. Of 54 hirsute women, 24 had an elevated TFI; 4 of these had normal plasma testosterone levels. Thirteen men with hypogonadism had a decreased TFI. Nine of ten women and two men with hyperthyroidism had a normal TFI, although there was an elevated plasma testosterone level in most instances. The calculated TFI, which reflects both the extent of binding and the total testosterone level, may therefore be a better indicator of circulating androgen activity.

OBJECTIVE

To investigate the prognostic relevance of different histopathological features and local tumour extension in patients with pT3b/c N0M0 renal cell carcinoma (RCC), as recently new proposals of reclassifying tumour fat invasion in pT3b/c RCC have been made but the effect of other histopathological tumour characteristics and combinations thereof with tumour invasion has yet to be determined in these patients.

METHODS

Between 1990 and 2006, 1943 patients underwent surgical treatment for renal tumours in our institution, of which 175 patients (8.7%) had pT3b/c RCC. After exclusion of 57 patients (32.6%) with lymph node and/or distant metastases at the time of diagnosis, 118 (67.4%) remained for retrospective analysis. Different histopathological features and local tumour extension were studied for their association with cancer-specific-survival (CSS) and progression-free-survival (PFS) by univariate and multivariate analyses. Histopathology was reviewed and revised according to the 2002 Tumour-Nodes-Metastasis (TNM) classification system by one pathologist (S.B.). CSS and PFS were estimated by the Kaplan-Meier method.

RESULTS

Follow-up data were obtained from 110 patients at a median (range) of 3.2 (0.3-16.1) years. In univariate analysis, microvascular invasion (MVI) and capsular invasion increased the risk of tumour progression by 2.05- and 2.72-times (P = 0.037 and P < 0.001). Overall, tumour fat invasion (TFI) and the presence of areas composed by cells with eosinophilic cytoplasm were associated with a higher risk of progression (P = 0.001 and P = 0.011) and reduced CSS (P = 0.037 and P = 0.017). In multivariate analysis, MVI and capsular invasion were associated with a two-fold increased risk of dying from cancer (hazard risk ratio, HR 2.22, P = 0.045 and HR 2.31, P = 0.011). TFI in general (P = 0.004) and specifically coexistent perirenal fat invasion (PFI) and renal sinus fat invasion (RSFI) were associated with a three-fold increased risk of developing tumour progression (HR 3.36, P = 0.001). The 10-year CSS and PFS rates were 39% and 36% for all patients, 47% and 45% for pT3b/c RCC with no PFI or RSFI, and 25% and 10% for PFI + RSFI.

CONCLUSIONS

Patients with pT3b/c RCC with MVI, capsular invasion, TFI and especially PFI + RSFI, have a markedly reduced prognosis compared with patients with pT3b/c RCC without these features. When these results are corroborated by additional studies and external validation, modification of the TNM classification system would be a sensible consequence.

OBJECTIVE

Tinnitus affects more than 40 million people in the Unites States, and cognitive difficulties are among the most commonly associated symptoms.

OBJECTIVE

To test the feasibility and preliminarily the effectiveness of using a putative neuroplasticity-enhancing drug, D-cycloserine, to facilitate a computer-assisted CT program for improving tinnitus bother and related cognitive difficulties.

METHODS

Double-blind, randomized clinical trial at an outpatient academic medical center of 34 participants aged 35 to 65 years with subjective, unilateral or bilateral, nonpulsatile tinnitus of at least 6 months' duration.

METHODS

Five weeks of twice-weekly computer-based CT with either 250 mg D-cycloserine or placebo orally prior to computer CT sessions.

METHODS

Difference in the change in Tinnitus Functional Index (TFI) score between the 2 groups.

RESULTS

After excluding 1 participant lost to follow-up, 1 who withdrew, 1 who did not complete 90% of sessions, and 1 outlier, 30 participants were included in the analysis. The D-cycloserine plus CT group showed a significant improvement in median TFI score (-5.8 [95% CI, -9.4 to -1.1]) and self-reported cognitive deficits (-4.5 [95% CI, -11.5 to -1.0]), but the placebo group did not (-1.0 [95% CI, -11.7 to 4.9] and -2.0 [95% CI, -5.1 to 2.0], respectively). After controlling for age and duration of tinnitus, there was no significant difference in TFI score change between the 2 groups (P = .41). After confounders were controlled for, the D-cycloserine group demonstrated a significantly greater improvement in self-reported cognitive deficits as compared with the placebo group (P = .03). No serious adverse events were reported.

CONCLUSIONS

Use of a computer-based CT program with a putative neuroplasticity-sensitizing drug, D-cycloserine, was feasible and well tolerated. With the limited sample size, the adjuvant use of D-cycloserine was no more effective than placebo at improving tinnitus bother. The finding that D-cycloserine use was more effective than placebo at improving self-reported cognitive difficulties could be important given the high rate of concern for cognitive deficits in patients with tinnitus. D-cycloserine and other putative neuroplasticity-facilitating agents could be investigated in the future as a strategy to enhance neuroplasticity-based tinnitus treatments.

BACKGROUND

clinicaltrials.gov Identifier: NCT01550796.

Alterations in body composition during extracorporeal hemodialysis (HD) were investigated in 12 hemodialysis patients (9 males and 3 females, mean age 50 +/- 15 years) with a mean ultrafiltration of 2.6 +/- 1.0 L. Analysis was performed using a dual-energy x-ray absorptiometry technique (DXA), which measures 3 principal components of the body: fat mass (FM): lean body mass (LBM), i.e., all soft tissues excluding fat; and bone mineral content (BMC). These 3 components were calculated for the whole body and for different body regions (namely, the thorax, trunk, lower limbs, and upper limbs). The thoracic cage region could be defined manually, separately from the trunk, and its tissue composition was calculated. DXA analysis was performed concomitant with a measurement of the basal thoracic impedance (TFI) by bioimpedance cardiography prior to and 1 h after dialysis. We found a significant decrease in the total LBM, from 55.8 +/- 8.8 to 53.3 +/- 9.3 kg (p < 0.05), but no change in either the FM or BMC. Moreover, there was a disproportional reduction in the LBM in different regions, being significantly greater in the thorax (7.47 +/- 3.7%) than in the other body regions (trunk 4.3 +/- 2.0%, lower limbs 5.4 +/- 2.1%, and upper limbs 4.7 +/- 1.5%). Regarding bioimpedance, a stronger significant correlation was detected between the percentage changes in the TFI and the changes in thoracic fluid (r = 0.80, p < 0.01) than between the changes in the TFI and the changes in the total body fluid (r = 0.63, p < 0.01). The absolute values of the TFI were also significantly and negatively correlated to the thoracic lean mass to fat mass ratio, both before and after HD (r = 0.82, p < 0.001 and r = 0.86, p < 0.001, respectively). In conclusion, DXA is a very sensitive technique to detect fluid changes during HD in the thorax when the thoracic cavity is defined as a region of interest as well as for the whole body. The data also indicate an extracellular compartmental imbalance between different regions with a significantly greater change in the thoracic region. Transthoracic bioimpedance is a useful technique for evaluating the HD induced changes in the thoracic fluid, rather than total body fluid.

The "cloaked" bacterial pathogen that is Chlamydia trachomatis continues to cause sexually transmitted infections (STIs) that adversely affect the health and well-being of children, adolescents and adults globally. The reproductive disease sequelae follow unresolved or untreated chronic or recurrent asymptomatic C.trachomatis infections of the lower female genital tract (FGT) and can include pelvic pain, pelvic inflammatory disease (PID) and ectopic pregnancy. Tubal Factor Infertility (TFI) can also occur since protective and long-term natural immunity to chlamydial infection is incomplete, allowing for ascension of the organism to the upper FGT. Developing countries including the WHO African (8.3 million cases) and South-East Asian regions (7.2 million cases) bear the highest burden of chlamydial STIs. Areas covered: Genetic advances for Chlamydia have provided tools for transformation (including dendrimer-enabled transformation), lateral gene transfer and chemical mutagenesis. Recent progress in these areas is reviewed with a focus on vaccine development for Chlamydia infections of the female genital tract. Expert commentary: A vaccine that can elicit immuno-protective responses whilst avoiding adverse immuno-pathologic host responses is required. The current technological advances in chlamydial genetics and proteomics, as well as novel and improved adjuvants and delivery systems, provide new hope that the elusive chlamydial vaccine is an imminent and realistic goal.

OBJECTIVE

To report total fluid intake (TFI) and the intake of different fluid types in adults (≥ 18 years old) from Mexico, Argentina, Brazil and Uruguay. To compare intakes between countries and with recommended adequate intake (AI) of water from fluids.

METHODS

Cross-sectional data were collected using a validated liquid intake 7-day record (Liq.In 7 ) in populations from Argentina (n = 1089), Brazil (n = 477), Mexico (n = 1677) and Uruguay (n = 554). Population characteristics, including age, gender, body mass index and socioeconomic level were recorded. Mean TFI was compared with the AI of water from fluids set by the USA Institute of Medicine.

RESULTS

The lowest TFI was recorded in Mexican women (1748 mL/day) and the highest in Argentinean men (2318 mL/day). Median daily TFI was significantly different between countries; Uruguay and Argentina had higher values than Mexico and Brazil. In the former, plain water contributed to only 25% of TFI, the remainder being predominantly from hot beverages. Approximately, a third of adults did not drink enough fluid to meet the recommended AI. High SSB consumption was reported, which was significantly different between countries (p < 0.05), the highest being in Mexico (median 25-75th percentiles): 531 (300-895 mL/day.

CONCLUSIONS

This survey highlights the need to increase water consumption and reduce SSB intake in this region to avoid potential associated health risks. These findings may be useful information in monitoring public health policy strategies.

BACKGROUND

Managing chronic tinnitus is challenging, and innovative ways to address the resulting health-care burden are required. Internet-based cognitive behavioral therapy (iCBT) for tinnitus shows promise as a cost-effective treatment option. The feasibility and effectiveness of iCBT in the United Kingdom are yet to be explored. Furthermore, it is not known if iCBT can be supported by an audiologist rather than a psychologist.

OBJECTIVE

This study aimed to determine the feasibility of guided iCBT using audiological support on tinnitus distress and tinnitus-related comorbidities. Furthermore, it aimed to establish the feasibility of iCBT for tinnitus distress in the United Kingdom, by determining recruitment, attrition, and compliance rates. Finally, it aimed to identify which aspects of the protocol require refinement for subsequent clinical trials.

METHODS

A single-group open trial design was implemented. This study would serve as a prerequisite study, to identify barriers, before undertaking effectiveness trials.

METHODS

Participants consisted of 37 adults (18 males, 19 females), with an age range of between 50 and 59 yr. The mean preintervention tinnitus severity rating was 56.15 (standard deviation = 18.35), which is categorized as "severe tinnitus" as measured by the Tinnitus Functional Index (TFI). Five participants withdrew during the study, and 29 of the remaining participants completed the postintervention questionnaire.

METHODS

The guided iCBT intervention ran over an eight-week period and consisted of 16 obligatory modules and five optional modules. The intervention was designed to be interactive, interesting, and stimulating. A key element was the provision of support from an audiologist throughout the program.

METHODS

Online questionnaires were used throughout the study. These were administered at baseline and postintervention to determine attrition and compliance rates and to facilitate sample size estimates for further clinical trials. Outcome measures for tinnitus severity, hearing handicap, insomnia, cognitive functioning, hyperacusis, anxiety, depression, and life satisfaction were used to investigate the effects of iCBT with audiological support. In addition, a weekly questionnaire was incorporated to monitor change in tinnitus distress while undertaking the intervention.

RESULTS

Feasibility was established using an audiologist to support this guided iCBT intervention, as a significant change postintervention was found for tinnitus severity, as measured by the TFI and the Tinnitus Handicap Inventory, Screening version. The attrition rate was 22% and compliance was variable. Although these results were based on a small sample, they provide encouraging evidence for the feasibility of delivering iCBT treatment for tinnitus symptoms with audiology support in the United Kingdom.

CONCLUSIONS

An Internet-based intervention of tinnitus appears to be feasible in the United Kingdom when using audiological support. Randomized controlled trials to further investigate the effectiveness of iCBT for tinnitus in the United Kingdom are required.

Background: Internet-based cognitive behavioral therapy (ICBT) for tinnitus is an evidence-based intervention. The components of ICBT for tinnitus have, however, not been dismantled and thus the effectiveness of the different therapeutic components is unknown. It is, furthermore, not known if heterogeneous tinnitus subgroups respond differently to ICBT.

Aims: This dismantling study aimed to explore the contribution of applied relaxation within ICBT for reducing tinnitus distress and comorbidities associated with tinnitus. A secondary aim was to assess whether outcomes varied for three tinnitus subgroups, namely those with significant tinnitus severity, those with low tinnitus severity, and those with significant depression.

Methods: A parallel randomized controlled trial design (n = 126) was used to compare audiologist-guided applied relaxation with the full ICBT intervention. Recruitment was online and via the intervention platform. Assessments were completed at four-time points including a 2-month follow-up period. The primary outcome was tinnitus severity as measured by the Tinnitus Functional Index. Secondary outcomes were included for anxiety, depression, insomnia, negative tinnitus cognitions, health-related quality of life, hearing disability, and hyperacusis. Treatment engagement variables including the number of logins, number of modules opened, and the number of messages sent. Both an intention-to-treat analysis and completer's only analysis were undertaken.

Results: Engagement was low which compromised results as the full intervention was undertaken by few participants. Both the ICBT and applied relaxation resulted in large reduction of tinnitus severity (within-group effect sizes d = 0.87 and 0.68, respectively for completers only analysis), which were maintained, or further improved at follow-up. These reductions in tinnitus distress were greater for the ICBT group, with a small effect size differences (between-group d = 0.15 in favor of ICBT for completers only analysis). Tinnitus distress decreased the most at post-intervention for those with significant depression at baseline. Both ICBT and applied relaxation contributed to significant reductions on most secondary outcome measures, with no group differences, except for a greater reduction of hyperacusis in the ICBT group.

Conclusion: Due to poor compliance partly attributed to the COVID-19 pandemic results were compromised. Further studies employing strategies to improve compliance and engagement are required. The intervention's effectiveness increased with initial level of tinnitus distress; those with the highest scores at intake experienced the most substantial changes on the outcome measures. This may suggest tailoring of interventions according to tinnitus severity. Larger samples are needed to confirm this.

Keywords: Applied relaxation; CBT, Cognitive Behavioral Therapy; CONSORT, Consolidated Standards of Reporting Trials; Cognitive behavioral therapy; Digital therapeutics; GAD-7, Generalized Anxiety Disorder; HHIA-S, Hearing Handicap Inventory for Adults - Screening; ICBT, Internet-based Cognitive Behavioral Therapy Intervention; ISI, Insomnia Severity Index; Internet intervention; PHQ-9, Patient Health Questionnaire; RCI, Reliable Change Index; TFI, Tinnitus Functional Index; Telehealth; Tinnitus; US, United States.

BACKGROUND

The aim of the present study was to evaluate the efficacy of tertiary and quaternary cytoreduction in recurrent ovarian cancer patients.

METHODS

Between January 1997 and December 2014, 53 patients were submitted to cytoreductive surgery for second and third ovarian cancer recurrence at our Unit.

RESULTS

Median age at first diagnosis was 48 years (range=20-69). Forty-six patients (86.8%) underwent tertiary cytoreduction. At the time of surgery, isolated and diffuse disease was observed in 48 (90.6%) and 5 (9.4%) patients, respectively. Complete and optimal cytoreduction was obtained in 41 (77.5%) and in 1 (1.9%) patients, respectively. We did not observe any statistically significant survival differences according to residual tumor. Patients with TFI >12 months showed longer PFS (38 vs. 7 months, p<0.002) than those with TFI <12 months. In 18 of these patients a third recurrence was observed. In 12 patients (66.7%) a complete quaternary cytoreduction was performed. Longer PFS (16 vs. 21 months; p=0.032) and OS (152 vs. 116 months; p=0.015) in patients submitted to cytoreduction with respect to those treated with chemotherapy were observed.

CONCLUSIONS

Our data suggest that selected ovarian cancer patients who develop a secondary and tertiary recurrence may benefit from additional cytoreductive attempts. The benefit seems to be greater in patients with TFI >12 months showing a single-site recurrence disease, in which complete cytoreduction is achievable. Further studies are required to better-define the role of tertiary and quaternary cytoreduction in recurrent ovarian cancer patients.

The impact of longitudinal anthropometric changes during adjuvant chemotherapy on long-term survival in non-metastatic colon cancer is unclear. Herein, we analyzed the prognostic significance of computed tomography (CT)-measured body composition changes in colon cancer patients who underwent surgery followed by adjuvant FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) chemotherapy. Data of 167 patients with stage III or high-risk stage II colon cancer were analyzed. Skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral fat index (VFI), subcutaneous fat index (SFI), and total fat index (TFI) changes during chemotherapy were calculated using preoperative and postchemotherapy CT image data. The Cox proportional hazard model was used to determine the correlation between changes in anthropometric values and overall survival (OS). The median changes (%) in SMI, SMR, VFI, SFI, and TFI over 210 days during chemotherapy were 8.7% (p < 0.001), 3.4% (p = 0.001), -19% (p < 0.001), -3.4% (p = 0.936), and -11.9% (p < 0.001), respectively. Cut-off values of changes in SMI (skeletal muscle index change, SMIC) and SMR (skeletal muscle radiodensity change, SMRC) were defined at -2% and -2 Hounsfield units (HU) respectively, whereas those of changes in VFI (visceral fat index change, VFIC), SFI (subcutaneous fat index change, SFIC), and TFI (total fat index change, TFIC) were based on values that provided the largest χ2 on the Mantel-Cox test. Multivariable analysis revealed that low SMR measured on a postchemotherapy CT scan (hazard ratio, HR: 0.32, 95% confidence interval, CI: 0.15-0.70, p = 0.004) and visceral fat loss of at least 46.57% (HR: 0.31, 95% CI: 0.14-0.69, p = 0.004) were independent poor prognostic factors for OS. Severe visceral fat loss during FOLFOX chemotherapy and low skeletal muscle radiodensity measured on postchemotherapy CT scans are associated with poor OS in stage III and high-risk stage II colon cancer patients.

OBJECTIVE

Compared with trans-femoral percutaneous coronary intervention (TFI), trans-radial PCI (TRI) has a lower risk of bleeding, access site complications and hospital costs, and is preferred by patients. However, TRI accounts for a minority of PCIs in the US, and there is currently little research that explores why.

UNASSIGNED

We conducted a national survey in February 2013 to assess perceptions of TRI vs. TFI, and barriers to TRI adoption and implementation among interventional cardiologists employed by the US Veterans Health Administration (VHA), and linked these data to site-level TRI annual rates for 2013.

RESULTS

We received 78 completed surveys (32% response rate). Respondents at sites that perform few or no TRIs identified increased radiation exposure as the greatest barrier while at sites that perform a high percentage of TRIs respondents identified the steep learning curve as the greatest barrier. Majorities of survey respondents at all sites rated TRI as superior on 5 of 7 criteria, including patient comfort and bleeding complications, but rated TFI as superior on procedure time and procedure success.

CONCLUSIONS

Even interventional cardiologists at sites that perform few or any TRIs recognized the superiority of TRI for patient comfort and safety, but rated it inferior to TFI on procedure time and technical results. Interventional cardiologists at high-TRI labs rated TRI as equivalent on procedure time and technical results. Efforts to increase TRI adoption and implementation may be more successful if they emphasize that procedure times and technical results depend on achieving proficiency.

BACKGROUND

We hypothesized that overnight fasting after a short dietary period, especially with carbohydrates, could allow performing breath-hold diving with no restraint for diaphragm excursion and blood shift and without any increase of metabolism, and in turn improve the diving response.

METHODS

During two separate sessions, 8 divers carried out two trials: (A) a 30-m depth dive, three hours after a normal breakfast and (B) a dive to the same depth, but after following a diet and fasting overnight. Each test consisted of 3 apnea phases: descent, static and ascent whose durations were measured by a standard chronometer. An impedance cardiograph, housed in an underwater torch, provided data on trans-thoracic fluid index (TFI), stroke volume (SV), heart rate (HR) and cardiac output (CO). Mean blood pressure (MBP), arterial O2 saturation (SaO2), blood glucose (Glu) and blood lactate (BLa) were also collected.

RESULTS

In condition B, duration of the static phase of the dive was longer than A (37.8 ± 7.4 vs. 27.3 ± 8.4 s respectively, P < 0.05). In static phases, mean ∆ SV value (difference between basal and nadir values) during fasting was lower than breakfast one (-2.6 ± 5.1 vs. 5.7 ± 7.6 ml, P < 0.05). As a consequence, since mean ∆ HR values were equally decreased in both metabolic conditions, mean ∆ CO value during static after fasting was lower than the same phase after breakfast (-0.4 ± 0.5 vs. 0.4 ± 0.5 L · min(-1) respectively, P < 0.05). At emersion, despite the greater duration of dives during fasting, SaO2 was higher than A (92.0 ± 2.7 vs. 89.4 ± 2.9 % respectively, P < 0.05) and BLa was lower in the same comparison (4.2 ± 0.7 vs. 5.3 ± 1.1 mmol∙L(-1), P < 0.05).

CONCLUSIONS

An adequate balance between metabolic and splancnic status may improve the diving response during a dive at a depth of 30 m, in safe conditions for the athlete's health.

Percutaneous coronary intervention (PCI) in the elderly is a major hospital burden since this group of patients exhibits high mortality rates and many comorbidities. The aim of this study was to analyze the impact of a transradial intervention (TRI) approach for PCI on bleeding complications in octogenarians. We retrospectively analyzed a consecutive cohort of 2530 patients who underwent PCI at a tertiary care center in Japan. Octogenarians constituted 12 % (291 cases) of the total PCI cases during the study period. Bleeding complications and all-cause mortality were observed at 30 days after PCI. Average age was 83 ± 3 years and female gender was 32 %. Stable coronary artery disease was 59 %. TRI was performed in 218 patients (75 %) and transfemoral intervention (TFI) in 73 (25 %). Bleeding Academic Research Consortium (BARC) major bleeding unrelated to bypass surgery were observed in 7.6 %, which were significantly lower in TRI than TFI (5.1 vs. 15.1 %, P = 0.005). The 30-day mortality rate was significantly low in patients without bleeding (4.9 vs. 31 %, p < 0.0001). In octogenarians, major bleeding complication was significant at 30 days after PCI. TRI had lower bleeding complication rate than TFI in this population. Octogenarians may be a subgroup of patients who derive benefits from TRI.

OBJECTIVE

To estimate the prevalence of frailty using five different instruments in a cohort of older adults and explore the association between frailty and various risk factors.

METHODS

1,867 participants aged 65 years and above were included in the current retrospective cross-sectional study. Frailty was operationalized according to the Fried definition, the FRAIL Scale, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI), and the Groningen Frailty Index (GFI). We explored the role of various frailty risk factors using logistic regression analyses.

RESULTS

The prevalence of frailty varied depending on the definition used (Fried definition = 4.1%, FRAIL Scale = 1.5%, FI = 19.7%, TFI = 24.5%, and GFI = 30.2%). The only risk factors consistently associated with frailty irrespectively of definition were education and age.

CONCLUSIONS

The frailty prevalence reported in our study is similar or lower to that reported in other population studies. Qualitative differences between frailty definitions were observed.

This study examined the factor structure and validity of the Therapeutic Factors Inventory-Short Form (TFI-S), a measure originally developed to assess Yalom's eleven conceptually derived therapeutic factors. Patients in a group-oriented day treatment program (n = 174) completed the TFI-S and other measures to assess concurrent and predictive validity. Four broad therapeutic factors were identified: Instillation of Hope, Secure Emotional Expression, Awareness of Interpersonal Impact, and Social Learning. Alpha coefficients ranged from .71 to .91. Significant correlations between the TFI-S factors and Group Climate Questionnaire subscales provided preliminary evidence for the concurrent validity of the TFI S. Significant relationships were also identified between the TFI-S factors and improvement in symptoms, quality of life, and interpersonal distress at the end of treatment, suggesting that the TFI-S may have predictive validity.

The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of COUP-TFI mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function.

BACKGROUND

Chronic tinnitus (phantom perception of sound) significantly disrupts quality of life in 15-20% of those who experience it. Understanding how certain personality traits impact tinnitus perception and distress can be beneficial for the development of interventions to improve the lives of tinnitus sufferers.

OBJECTIVE

Four key self-reported personality traits (social closeness, stress reaction, alienation, and self-control) were identified from previous research as being associated with tinnitus. These were compared between tinnitus and age-, gender-, and hearing level-matched nontinnitus controls to see whether underlying profile differences exist, and if personality traits levels correlate with various tinnitus characteristics assessed in typical clinical questionnaires.

METHODS

A Web-based personality survey was administered comprising of self-control, stress reaction, alienation, and social closeness subscale questions of the Multidimensional Personality Questionnaire, the Hearing Handicap Inventory-Screening Version, TFI, and the Tinnitus Case History Questionnaire.

METHODS

A total of 154 participants with tinnitus (81 males, 73 females, mean age = 62.6 yr) and 61 control (32 males, 29 females, mean age = 59.62 yr) participants were recruited via e-mail invitations to a tinnitus research clinic database, poster, and social media Web site advertising.

METHODS

Statistical analysis was conducted using parametric statistics and IBM SPSS® Version 22 software.

RESULTS

Tinnitus sufferers displayed higher levels of stress reaction, lower social closeness, lower self-control, and higher alienation than the control group (p < 0.05). Alienation was related to tinnitus pitch and self-reported hyperacusis measured using the Tinnitus Case History Questionnaire (p < 0.05). Stress reaction correlated with self-reported hyperacusis, whether tinnitus sufferers had sought other treatments, and whether loud sounds make the tinnitus worse (p < 0.05).

CONCLUSIONS

The four personality traits examined in this study exhibited a consistent association with tinnitus perception and distress, and differentiated tinnitus sufferers from nontinnitus control. Some of the traits also correlated significantly with certain characteristics measured in tinnitus history questionnaires. Personality traits are described in relation to "maladaptive" residuals under the Adaptation Level Theory model of tinnitus. The results of the study suggest that certain personality traits correlate with the clinical presentation of tinnitus.