Tobacco smoking and alcohol consumption are well‐established risk factors for head and neck cancer. The prognostic role of smoking and alcohol intake at diagnosis have been less well studied. We analysed 1,393 people prospectively enrolled into the Head and Neck 5000 study (oral cavity cancer, n=403; oropharyngeal cancer, n=660; laryngeal cancer, n=330) and followed up for a median of 3.5 years. The primary outcome was all‐cause mortality. We used Cox proportional hazard models to derive minimally adjusted (age and gender) and fully adjusted (age, gender, ethnicity, stage, comorbidity, body mass index, HPV status, treatment, education, deprivation index, income, marital status, and either smoking or alcohol use) mortality hazard ratios (HR) for the effects of smoking status and alcohol intake at diagnosis. Models were stratified by cancer site, stage and HPV status. The fully‐adjusted HR for current versus never‐smokers was 1.7 overall (95% confidence interval [CI] 1.1, 2.6). In stratified analyses, associations of smoking with mortality were observed for oropharyngeal and laryngeal cancers (fully adjusted HRs for current smokers: 1.8 (95% CI=0.9, 3.40 and 2.3 (95% CI=0.8, 6.4)). We found no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non‐drinkers (HR=1.2 (95% CI=0.9, 1.6)). There was no strong evidence that HPV status or tumour stage modified the association of smoking with survival. Smoking status at the time of a head and neck cancer diagnosis influenced all‐cause mortality in models adjusted for important prognostic factors.

Host nutrition can affect the outcome of parasitic diseases through metabolic effects on host immunity and/or the parasite. Here we show that modulation of mouse immunometabolism through brief restriction of food intake (dietary restriction, DR) prevents neuropathology in experimental cerebral malaria (ECM). While no effects are detected on parasite growth, DR reduces parasite accumulation in peripheral tissues including brain, and increases clearance in the spleen. Leptin, a host-derived adipokine linking appetite, energy balance and immune function, is required for ECM pathology and its levels are reduced upon DR. Recombinant leptin abrogates DR benefits, while pharmacological or genetic inhibition of leptin signaling protects against ECM. DR reduces mTORC1 activity in T cells, and this effect is abrogated upon leptin administration. Furthermore, mTORC1 inhibition with rapamycin prevents ECM pathology. Our results suggest that leptin and mTORC1 provide a novel mechanistic link between nutrition, immunometabolism and ECM pathology, with potential therapeutic implications for cerebral malaria.

.Th e da ta obtain ed in the in vestigation of t he phase equilibria in the systems ber~' llia a lumina, ber yllia-titania, and a lumina-titan ia suggest that the published equilibrium diagrams of these systems n eed to be revised : the system BeO-Ti02 shows no compounds, an eutectic at about 85 weight per cent of Ti02 and 1,670° ± 3° C, and an area of Ti02 solid-solu tion . The system BeO-A120 3 has three eu tectics: (1) at 1,890° ± 10° C a nd abo u t mole r atio 1BeO: 4Ah03 (94. 2% AI,03); (2) at 1,850° ± 10° C a nd abou t mol e ratio 2BcO : 3AI,03 (85.9% Ah03); and (3) at 1,835° ± 10° C and about 75 weight percen t of A1,03, an d t wo co ngru ently melt ing co mpounds, Be O.3 A1,03 (92.4% A1,03) at 1,9 10° ± 10° C and chr,vsobery l (B eO.-AI,03-80. 3% A1,03) at 1,870° ± 10° C. The system Al, 0 3-TiOz has two eutect ics: ( 1) at 1,705° ± 5° C and about 20 weight percen t of A1,03; a nd (2) at 1,840° ± 10 0 C and about mo le rat io 5AJ,03:4TiO, (6 1.5% AI,03), and a hig h-and low-temperat ure form (a lpha a nd beta) of aluminum t itanate (AIz03.TiOz-56. 1% AI,03); t he a lpha form is stable from t he alpha-beta inversion te mperat ure of 1,820° ± 10° C and melts co ngruently at 1,860° ± 10° C, and t he beta form seems to be stable for p eriods up to 100 hours from room temperature to abo ut 750° C and from abo u t 1,300° C to its inversion te mperature. The eq uilibria for t he system BeO-AL,03-Ti02 was found to contain four invarient points : (1) at 1,572° ± 5° C and abou t mole ratio ZBeO: 1A120 3: 2Ti02 (16.1% BeO, 32.7% A1,03, 51.2 % TiO,); (2) at 1,577° ± 5° C and abou t mole ratio 2BeO: l A1,03: 4Ti02 (10.6% Be O, 21.6 % A.120 3, 67.8% TiO,); (3) a t 1,580° ± 5° C and about mole ratio IBeO:lAI20 3 :1Ti02 (12.1% B eO, 49.3% A1,03 38.6 % TiO,); and (4) probabl y at abo ut 1,755° ± 10° C and abo ut mole mlio 2Beo': 5AI,03: 2Ti02 (7.0 % B eO, 79. 8% AI, 0 3, 22.2 % TiO,). No ternary co mpounds were foun d in t his system.The genera l physical propert ies of practically imper vious porcelai ns of t hi s syste m were found to be : maturing range, usua lly 1,525° to 1,575° C, bu t with some of t he higha lumina-con tain ing bodies maturing between 1,600° and 1,700° C ; apparent d ensity. 3.3 to 3.7 g/ cm3 ; shrinkage, 11 to 19 percent ; Toom-temperature co mpressive strength , 187,000 to 280000 Ib/in.2; room-te mpera t ure transverse strengt h, 13,700 t o 25,000 Ib/ in . 2 ; Young's modulus at room temperature, 42,000,000 to 47,000,000 Ib/in .2; tran sverse strength a t 1,800° F (982° C), 10,500 to 17,000 Ib/ in.2; approximate Young's modulus at 1,800° F , 22,000,000 to 41 ,000,000 Ib/ in.2; relative the rmal-shock Tesistance, pOol' ; and the lin ear t her mal expansion of a few selected bodies, in t he range 25° to 950° C, usua lly was regular and ranged from 0 .81 to 0. 89 per cent.

Background People with head and neck cancer (HNC) have higher comorbidity levels but it remains unclear if pre-treatment comorbidity is an independent prognosticator in HNC. Methods Survival analyses were performed using data from participants in a UK multicentre cohort study with cancers of the oral cavity (n = 668), oropharynx (n = 1,074) and larynx (n = 530). Survival analyses were incrementally adjusted for age, gender, marital status, income, education, stage, alcohol and smoking. Results After adjusting for demographic, clinical and behavioural confounders, higher baseline comorbidity was associated with reduced overall survival (mild comorbidity HR 1.4, 95% CI 1.1, 1.7; moderate comorbidity HR 1.7, 95% CI 1.3, 2.2; severe comorbidity HR 2.8, 95% CI 1.9, 4.; p-trend<.001). Conclusions Our findings suggest that comorbidity is an independent prognosticator for overall survival in HNC. Comorbid illnesses should be considered in the assessment and treatment planning of people with HNC.

The motivation in different demographic subgroups to participate in living liver transplantation is described. Differences in donation readiness resulting from the situation of every donor and recipient are thoroughly outlined. The acceptance for a living liver donation was found to be high - and comparable to that of living kidney donation.

Living with end-stage organ failure is associated with an accumulation of traumatic medical events, and despite recovery after solid-organ transplantation (SOT), many children continue to exhibit lower quality of life (QOL). Few studies have examined the relationship between post-traumatic stress disorder (PTSD) and QOL among pediatric SOT recipients. We conducted a retrospective, cross-sectional review of 61 pediatric SOT recipients (12 heart, 30 kidney, and 19 liver) to evaluate the association of PTSD with self-reported QOL. PTSD was measured by the Child Trauma Screening Questionnaire (CTSQ), and QOL was measured using the PedsQL and PedsQL Transplant Module (PedsQL-TM) surveys. Demographics, baseline, and contemporaneous factors were tested for independent association. SOT recipients were 15.2 (12.1-17.6) years old at survey completion. Median CTSQ score was 2 (1-3), highest in kidney recipients, and 13% were identified as high risk for PTSD. Median PedsQL score was 83 (70-91) and significantly associated with the CTSQ score (r = −.68, p < .001). Median PedsQL Transplant Module score was 89 (83-95) and similarly associated with the CTSQ score (r = −.64, p < .001). Age at time of surveys and presence of any disability were also independently associated with PedsQL and PedsQL-TM, respectively. When adjusted for Emotional Functioning, CTSQ remained associated with PedsQL subscores (r = −.65, p < .001). Trauma symptoms are a major modifiable risk factor for lower self-perceived QOL and represent a potentially important target for post-transplant rehabilitation. Additional research is needed to understand the root contributors to PTSD and potential treatments in this population.

Reveromycin A (RM-A), a small natural product isolated from Streptomyces bacteria, is a potential osteoporosis therapeutic in that it specifically induces apoptosis in osteoclasts but not osteoblasts. The purpose of the study presented here was to further elucidate the intracellular mechanisms of RM-A death effects in mature osteoclasts. A specific clone of RAW264.7 murine macrophages that was previously characterized for its ability to acquire an osteoclast nature on differentiation was differentiated in the presence of receptor activator of nuclear factor kappa B ligand (RANKL). Subsequent staining was performed for tartrate-resistant acid phosphatase to confirm their osteoclast character. These osteoclasts were treated with ten micromolar RM-A for 2, 4, 6, 24, and 48 h at a pH of 5.5. Peak apoptosis induction occurred at 4-6 h as measured by caspase 3 activity. Lactate dehydrogenase release assay revealed no significant RM-A-induced necrosis. Western blot analysis of cytoplasmic extracts demonstrated activation of caspase 9 (2.3-fold at 2 h and 2.6-fold at 4 h, each P < 0.05) and no significant changes in Bcl-XL . In nuclear extracts, NFκB levels significantly increased on differentiation with RANKL but then remained constant through RM-A treatment. Over the extended time course studied, RM-A-induced apoptosis in osteoclasts was not accompanied by necrosis, suggesting that RM-A would likely have limited effects on immediate, neighboring bone cell types. This specific cell death profile is promising for potential clinical investigations of RM-A as a bone antiresorptive.

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