Bidirectional effects of estradiol on the control of water intake in female rats.

The inhibitory effect of estradiol (E2) on water intake has been recognized for 50 years. Despite a rich literature describing this phenomenon, we report here a previously unidentified dipsogenic effect of E2 during states of low fluid intake. Our initial goal was to test the hypothesis that the anti-dipsogenic effect of E2 on unstimulated water intake is independent of its anorexigenic effect in female rats. In support of this hypothesis, water intake was reduced during estrus, compared to diestrus, when food was present or absent. Water intake was reduced by E2 in ovariectomized rats when food was available, demonstrating a causative role of E2. Surprisingly, however, when food was removed, resulting in a significant reduction in baseline water intake, E2 enhanced drinking. Accordingly, we next tested the effect of E2 on water intake after an acute suppression of intake induced by exendin-4. The initial rebound drinking was greater in E2-treated, compared to Oil-treated, rats. Finally, to reconcile conflicting reports regarding the effect of ovariectomy on water intake, we measured daily water and food intake, and body weight in ovariectomized and sham-operated rats. Predictably, ovariectomy significantly increased food intake and body weight, but only transiently increased water intake. Together these results provide further support for independent effects of E2 on the controls of water and food intake. More importantly, this report of bidirectional effects of E2 on water intake may lead to a paradigm shift, as it challenges the prevailing view that E2 effects on fluid intake are exclusively inhibitory.

Quality of life, shoulder range of motion, and spinal accessory nerve status in 5-year survivors of head and neck cancer.

OBJECTIVE: To determine the association of neck dissection and radiation treatment for head and neck cancer (HNC) with subsequent shoulder range of motion (ROM) and quality of life (QOL) in 5-year survivors. DESIGN: A cross-sectional convenience sample. SETTING: Otolaryngology clinics at tertiary care hospital and Veterans Affairs medical center. PATIENTS: Five-year, disease-free survivors of HNC. METHODS: Demographic and cancer treatment information was collected, including type of neck dissection (none, spinal accessory "nerve sparing," and "nerve sacrificing") and radiation. QOL questionnaires were administered, and shoulder ROM was measured. MAIN OUTCOME MEASUREMENTS: University of Washington Quality of Life (UWQOL), Functional Assessment of Cancer Therapy (FACT) Head and Neck, and Performance Status Scale for Head and Neck. Shoulder ROM measurements included abduction, adduction, flexion, extension, internal and external rotation. RESULTS: One hundred and five survivors completed QOL surveys; 85 survivors underwent additional shoulder ROM evaluations. The nerve sacrifice group exhibited significantly poorer scores for UWQOL measures of disfigurement, level of activity, recreation and/or entertainment, speech and shoulder disability, and willingness to eat in public, FACT functional well-being, and FACT Head and Neck (P < .05). Shoulder ROM for flexion and abduction was poorest in the nerve sacrifice group (P < .05). Radiation was associated with significantly worse UWQOL swallowing (P < .05), but no other differences were found for QOL or ROM measurements. Decreased QOL scores were associated with decreased shoulder flexion and abduction (P < .05). Survivors with decreased shoulder abduction had significantly (P < .05) worse scores in disfigurement, recreation and/or entertainment, employment, shoulder disability, and FACT emotional well-being. CONCLUSIONS: Sparing the spinal accessory nerve during neck dissection is associated with significantly less long-term shoulder disability in 5-year survivors of HNC. QOL measures demonstrated the highest level of function in the no dissection group, an intermediate level of functioning with nerve sparing, and poorest function when the nerve is sacrificed. Decreased shoulder flexion and abduction is associated with reduced QOL in long-term survivors of HNC.

Survivorship care plans for patients with head and neck cancer.

OBJECTIVE: To determine the perceived value of survivorship care plans (SCPs) (cancer treatment summaries and follow-up recommendations). DESIGN: Survey of patients and their physicians between 3 and 4 years after receipt of the SCP. SETTING: Ambulatory, tertiary care medical center. PATIENTS: A convenience sample of head and neck cancer survivors living 3 years after each had been mailed a personal SCP shortly after completion of cancer treatment. Twenty survivors were contacted, and all agreed to participate. INTERVENTIONS: Institutional review board-approved, scripted telephone survey to determine whether patients and their primary care physicians still had their SCPs and found them useful. MAIN OUTCOME MEASURES: Survey responses. RESULTS: Only 2 of 20 survivors and 11 of 21 physicians or dentists were able to locate or remember having received the SCPs 3 years later. Eighteen of 20 survivors were unsure of the value of SCPs. CONCLUSIONS: Despite a widely held belief that patients benefit from receiving SCPs, our initial attempt found little awareness of these documents by either the head and neck cancer survivors or their primary care physicians.

Using text messaging to prevent relapse to smoking: intervention development, practicability and client reactions.

AIMS: The NHS Stop Smoking Service (NHS-SSS) helps approximately half its clients to quit for 4 weeks. However, most initially successful quitters relapse within 6 months. Short message service (SMS) texting has been shown to facilitate stopping smoking. We describe the development, implementation and subsequent evaluation, in terms of practicability and client response, of an SMS text-based relapse prevention intervention (RPI) delivered within routine community and specialist National Health Service (NHS) Stop Smoking Service (SSS) provision in four Primary Care Trusts. DESIGN: Text messages aimed at motivation to remain abstinent, preventing careless lapses and continuing the full course of medicine for smoking cessation were developed and sent weekly to clients' mobile phones for 12 weeks and fortnightly for 6 months. They were asked to respond to some of the texts and contact the NHS SSS if they lapsed. They were also offered free nicotine mini lozenges to be sent via the mail on three occasions. SETTING: NHS SSS. PARTICIPANTS: 202 clients who had been abstinent for 4 weeks. MEASUREMENTS: Feasibility of introducing RPI into routine care; response to interactive messages and requests for the medication; rating of the helpfulness of RPI; self-reported and carbon monoxide (CO)-validated smoking status for up to 26 weeks. FINDINGS: A text-based RPI was easy to implement within the NHS SSS provided by specialist advisers, but enrollment of clients from services provided by a network of pharmacists was difficult because client contact details were often lacking. Where records of the number of people invited to RPI were available, 94% of eligible participants enrolled. The RPI was well received by both SSS clients and staff, with 70% (n = 63) of clients who completed follow-up considering the intervention helpful. Eighty-five per cent (n = 172) of clients responded to at least one of the nine interactive text messages. Sixty-four clients (32% of the total, 47% of those we managed to contact) reported continuous abstinence at 6 months. Eighteen (9%) clients who relapsed to smoking used the RPI to re-engage with the NHS SSS and 10 (5%) successfully re-established abstinence. CONCLUSIONS: In smokers attending National Health Service Stop Smoking Services who are abstinent 4 weeks after their quit date, a relapse prevention intervention based on SMS text messaging was well received, and can be implemented economically and rapidly. A controlled trial is needed to establish whether it has a significant impact on relapse.

The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy.

There is growing evidence that macroautophagic cargo is not limited to bulk cytosol in response to starvation and can occur selectively for substrates, including aggregated proteins. It remains unclear, however, whether starvation-induced and selective macroautophagy share identical adaptor molecules to capture their cargo. Here, we report that Alfy, a phosphatidylinositol 3-phosphate-binding protein, is central to the selective elimination of aggregated proteins. We report that the loss of Alfy inhibits the clearance of inclusions, with little to no effect on the starvation response. Alfy is recruited to intracellular inclusions and scaffolds a complex between p62(SQSTM1)-positive proteins and the autophagic effectors Atg5, Atg12, Atg16L, and LC3. Alfy overexpression leads to elimination of aggregates in an Atg5-dependent manner and, likewise, to protection in a neuronal and Drosophila model of polyglutamine toxicity. We propose that Alfy plays a key role in selective macroautophagy by bridging cargo to the molecular machinery that builds autophagosomes.

Potent inhibitors of Huntingtin protein aggregation in a cell-based assay.

A quinazoline that decreases polyglutamine aggregate burden in a cell-based assay was identified from a high-throughput screen of a chemical-compound library, provided by the NIH Molecular Libraries Small Molecule Repository (MLSMR). A structure and activity study yielded leads with submicromolar potency.

Clinical results using bioabsorbable staple line reinforcement for circular staplers.

Although linear surgical staple line reinforcement has been shown to increase anastomotic tensile strength in animal models and reduce the incidence of staple line bleeding and anastomotic leaks in colorectal surgery, the benefits of staple line reinforcement on circular stapled anastomoses in bariatric surgery remain unreported in the literature. The purpose if this study was to compare the incidence of anastomotic bleeding, leak, and stricture in patients undergoing laparoscopic gastric bypass with circular staple line reinforcements with those with no circular staple line reinforcements. Since May 2006, 138 consecutive patients (Group B) have undergone laparoscopic Roux-en-Y divided gastric bypass with a 25-mm circular stapled gastrojejunal anastomosis using GORE SEAMGUARD bioabsorbable circular staple line reinforcement (CBSG) with a mean follow up of 9 months. The incidence of anastomotic bleeding, leak, and stricture was compared with 255 similar patients (Group A) who underwent surgery before May 2006 without gastrojejunal reinforcement with a mean follow up of 22 months. The rates of anastomotic bleeding, leak, and stricture for Group B versus Group A were 0.7 per cent versus 1.1 per cent (P = 0.64); 0.7 per cent versus 1.9 per cent (P = 0.34); and 0.7 per cent versus 9.3 per cent (P = 0.0005), respectively. The use of CBSG reduced the incidence of anastomotic stricture by 93 per cent and the incidence of a composite end point of all anastomotic complications by 85 per cent. Our results indicate that the use of circular staple line reinforcement at the gastrojejunal anastomosis in patients undergoing laparoscopic gastric bypass significantly decreases the incidence of anastomotic stricture and a composite end point of all anastomotic complications. On this basis, strong consideration should be given to the routine use of CBSG staple line reinforcement in patients undergoing laparoscopic divided gastric bypass with a circular stapled gastrojejunal anastomosis.

Dental status and quality of life in long-term head and neck cancer survivors.

OBJECTIVES: To analyze how the dental status of long-term head and neck cancer survivors affects their subjective quality of life. STUDY DESIGN: Observational case series. METHODS: A convenience sample of 5-year head and neck cancer survivors underwent the following battery of tests: 1) targeted head and neck examination, 2) updated medical history, 3) dental evaluation, 4) standardized quality of life questionnaires. RESULTS: Eighty-six survivors were included in the study. The following associations were identified: 1) those who became edentulous secondary to cancer treatment and those without occlusion at time of the study demonstrated worse Pain, Activity, Recreation/Entertainment, Chewing, Swallowing, Speech, Eating in Public, Normalcy of Diet, Physical Well-Being, Social/Family Well-Being, Functional Well-Being, and Additional Concerns scores; 2) higher Decayed/Missing/Filled scores were associated with worse Pain, Disfigurement, Activity, Recreation/Entertainment, Employment, Chewing, Swallowing, Speech, Eating in Public, Understandability of Speech, Normalcy of Diet, Physical Well-Being, Additional Concerns scores, and weight loss; 3) decreased oral opening measurements were associated with worse Chewing, Swallowing, Eating in Public, Normalcy of Diet, Additional Concerns scores, and weight loss; 4) edentulous survivors who did not use dentures had worse Pain, Activity, Recreation/Entertainment, Understandability of Speech, and Eating in Public scores. CONCLUSIONS: Although previous studies have shown that many of the effects of cancer treatment disappear between 1 and 3 years, this study shows that the dental status has a persistent impact on subjective quality of life.

Psychosocial effects in long-term head and neck cancer survivors.

BACKGROUND: To identify and rate the importance of several psychosocial and physiologic influences on quality of life (QOL) among a cohort of 5-year head and neck cancer survivors, we conducted a cross-sectional study of a convenience sample that used both questionnaires and physiologic evaluations. METHODS: QOL was assessed by the Functional Assessment of Cancer Therapy (FACT) and the FACT Head and Neck additional concerns (FACT-H&N) questionnaires. Psychosocial characteristics (or risk factors) potentially influencing QOL were measured by the Millon Behavioral Health Inventory (MBHI) and the Social Support Questionnaire (SSQSR). Physiologic risk factors were measured in examinations that included shoulder and neck range of motion, whole and stimulated saliva measurements, and oropharyngeal swallowing efficiency. We evaluated the association of selected QOL measures with three groups of potential risk factors: psychosocial factors, consisting of selected MBHI and SSQSR scales; physiologic factors, consisting of selected physical ability measures; and a combination of psychosocial/physiologic factors. RESULTS: The entire study population of 105 subjects completed the FACT and FACT-H&N questionnaires; 86 of these completed the physiologic tests as well. Combined psychosocial/physiologic models best predicted all QOL measures considered. Psychosocial models alone, compared with physiologic models alone, better predicted FACT physical and social/family well-being measures. Physiologic models alone, compared with psychosocial models alone, better predicted FACT-H&N additional concerns measures. Premorbid pessimism (MBHI) was consistently the best predictor of QOL measures. CONCLUSIONS: Both psychosocial and physiologic factors influence QOL in patients with head and neck cancer, but many QOL measures are most strongly influenced by psychosocial considerations. Physicians and surgeons caring for long-term head and neck cancer survivors should be cognizant of the importance of psychosocial risk factors in the QOL of their patients.

Speech intelligibility and quality of life in head and neck cancer survivors.

OBJECTIVE: Poor speech intelligibility adversely affects quality of life self-assessment in long term survivors of head and neck cancer treatment. STUDY DESIGN: Observational case series including both objective clinical speech testing and subjective quality of life questionnaire administration. METHODS: Five-year head and neck cancer survivors were recruited to study the association between speech intelligibility and quality of life. Survivors were analyzed as an entire group, and also subdivided into laryngectomees and non-laryngectomees. Objective testing included sentence and word intelligibility. Subjective testing included quality of life questionnaires (UWQOL, FACT, FACT-head and neck, and PSS-HN) and a locally prepared "cancer concern" question. Associations were sought between intelligibility, quality of life and demographics. RESULTS: Sixty-two survivors underwent testing. Lower sentence intelligibility and word intelligibility scores were associated with diminished self-perceived UWQOL Speech (P = .0001 and P = .0001, respectively) and PSS-HN Understandability of Speech (P = .009 and P = .005). Decreased word intelligibility was additionally associated with decreased UWQOL Chewing (P = .003), UWQOL Swallowing (P = .02), UWQOL Recreation (P = .05), PSS-HN Willingness to Eat in Public (P = .03), and PSS-HN Normalcy of Diet (P = .0001). The associations continued even after patients who had undergone laryngectomy were excluded. CONCLUSIONS: Long-term survivors of head and neck cancer continue to have both objective and subjective deficits in speech parameters five years after treatment. Objective deficits are associated with subjective concerns about speech, eating, and recreation. Understanding how communication deficits affect quality of life in long-term head and neck cancer survivors may allow more effective therapies to modulate these concerns in the recovery period.

Aspiration, weight loss, and quality of life in head and neck cancer survivors.

OBJECTIVE: To determine associations between objective assessments (swallowing function and weight change) and subjective quality-of-life (QOL) measures. DESIGN: Observational case series using clinical testing and questionnaires. SETTING: University hospital-based tertiary clinical practice. PATIENTS: Convenience sample of 5-year survivors of head and neck cancer (62 nonlaryngectomy survivors were studied). INTERVENTIONS: Objective testing included examination, weight history, videofluoroscopic swallow studies (VFSS), and oropharyngeal swallowing efficiency (OPSE). Subjective testing included QOL questionnaires (University of Washington Quality-of-Life [UWQOL] Scale, Performance Status Scale for Head and Neck Cancer Patients [PSS-HN], Functional Assessment of Cancer Treatment-General [FACT-G] Scales, and Functional Assessment of Cancer Therapy-Head and Neck [FACT-H&N] Scale). MAIN OUTCOME MEASURES: Aspiration (identified by VFSS), weight change, and QOL measures. RESULTS: Aspiration was associated with the decreased QOL scores in chewing, swallowing, normalcy of diet, and additional concerns of the FACT-H&N Scale. No association was found between aspiration and willingness to eat in public, subjective understandability, or any of the FACT-G scales. Of the nonlaryngectomy survivors, 27 (44%) demonstrated some degree of aspiration during VFSS. Associations were found between aspiration, primary tumor T stage, weight change, and OPSE. Aspirators lost a mean of 10.0 kg from precancer treatment weight, while nonaspirators gained a mean of 2.3 kg (P<.001). Mean OPSE scores were 69 for nonaspirators and 53 for aspirators (P =.01). CONCLUSIONS: Almost half of long-term nonlaryngectomy head and neck cancer survivors demonstrated at least some degree of aspiration. The presence of aspiration is associated with substantial weight loss, advanced initial tumor stage, diminished oropharyngeal swallowing efficiency, and lower scores on a variety of QOL scales.