The association between frailty and survival in patients with pleural disease: a retrospective cohort study.

BACKGROUND: There are currently no data on the relationship between frailty and mortality in pleural disease. Understanding the relationship between frailty and outcomes is increasingly important for clinicians to guide decisions regarding investigation and management. This study aims to explore the relationship between all-cause mortality and frailty status in patients with pleural disease. METHODS: In this retrospective analysis of a prospectively collected observational cohort study, outpatients presenting to the pleural service at a tertiary centre in Bristol, UK with a radiologically confirmed, undiagnosed pleural effusion underwent comprehensive assessment and were assigned a final diagnosis at 12 months. The modified frailty index (mFI) was calculated and participants classified as frail (mFI ≥ 0.4) or not frail (mFI ≤ 0.2). RESULTS: 676 participants were included from 3rd March 2008 to 29th December 2020. The median time to mortality was 490 days (IQR 161-1595). A positive association was found between 12-month mortality and frailty (aHR = 1.72, 95% CI 1.02-2.76, p = 0.025) and age ≥ 80 (aHR = 1.80, 95% CI 1.24-2.62, p = 0.002). Subgroup analyses found a stronger association between 12-month mortality and frailty in benign disease (aHR = 4.36, 95% CI 2.17-8.77, p < 0.0001) than in all pleural disease. Malignancy irrespective of frailty status was associated with an increase in all-cause mortality (aHR = 10.40, 95% CI 6.01-18.01, p < 0.0001). CONCLUSION: This is the first study evaluating the relationship between frailty and outcomes in pleural disease. Our data demonstrates a strong association between frailty and 12-month mortality in this cohort. A malignant diagnosis is an independent predictor of 12-month mortality, irrespective of frailty status. Frailty was also strongly associated with 12-month mortality in patients with a benign underlying cause for their pleural disease. This has clinical relevance for pleural physicians; evaluating patients' frailty status and its impact on mortality can guide clinicians in assessing suitability for invasive investigation and management. TRIAL REGISTRATION: This study is registered with the Health Research Authority (REC reference 08/H0102/11) and the NIHR Portfolio (Study ID 8960).

A multicentre survey investigating the knowledge, behaviour, and attitudes of surgical healthcare professionals to frailty assessment in emergency surgery: DEFINE(surgery).

PURPOSE: Screening for frailty in people admitted with emergency surgical pathology can initiate timely referrals to enhanced perioperative services such as intensive care and geriatric medicine. However, there has been little research exploring surgical healthcare professionals' opinions to frailty assessment, or accuracy in identification. This study aimed to assess the knowledge, behaviour, and attitudes of healthcare professionals to frailty assessment in emergency surgical admissions. METHODS: We designed a cross-sectional multicentre study developed by a multiprofessional team of surgeons, geriatricians, and supported by patients. A semi-structured survey examined attitudes and behaviours. Knowledge was assessed by comparing respondents' accuracy in scoring twenty-two surgical case vignettes using the Clinical Frailty Scale. RESULTS: Eleven hospitals across England, Wales, and Scotland participated. Two hundred and eleven clinicians responded-20.4% junior doctors, 43.6% middle grade doctors, 24.2% senior doctors, 11.4% nurses and physician associates. Respondents strongly supported perioperative frailty assessment. Most were already assessing for frailty, although frequently not using a standardised tool. There was a strong call for more frailty education. Participants scored 2175 vignettes with 55.4% accurately meeting the gold standard; accuracy improved to 87.3% when categorised into "not frail/mildly frail/severely frail" and 94% when dichotomised to "not frail/frail". CONCLUSION: Frailty assessment is well supported by healthcare professionals working in surgery. However, standardised tools are not routinely being used, and only half of respondents could accurately identify frailty. Better education around frailty assessment is needed for healthcare professionals working in surgery to improve perioperative pathway for people living with frailty.

Natural Compounds and Biomimetic Engineering to Influence Fibroblast Behavior in Wound Healing.

Throughout history, natural products have played a significant role in wound healing. Fibroblasts, acting as primary cellular mediators in skin wound healing, exhibit behavioral responses to natural compounds that can enhance the wound healing process. Identifying bioactive natural compounds and understanding their impact on fibroblast behavior offers crucial translational opportunities in the realm of wound healing. Modern scientific techniques have enabled a detailed understanding of how naturally derived compounds modulate wound healing by influencing fibroblast behavior. Specific compounds known for their wound healing properties have been identified. Engineered biomimetic compounds replicating the natural wound microenvironment are designed to facilitate normal healing. Advanced delivery methods operating at micro- and nano-scales have been developed to effectively deliver these novel compounds through the stratum corneum. This review provides a comprehensive summary of the efficacy of natural compounds in influencing fibroblast behavior for promoting wound regeneration and repair. Additionally, it explores biomimetic engineering, where researchers draw inspiration from nature to create materials and devices mimicking physiological cues crucial for effective wound healing. The review concludes by describing novel delivery mechanisms aimed at enhancing the bioavailability of natural compounds. Innovative future strategies involve exploring fibroblast-influencing pathways, responsive biomaterials, smart dressings with real-time monitoring, and applications of stem cells. However, translating these findings to clinical settings faces challenges such as the limited validation of biomaterials in large animal models and logistical obstacles in industrial production. The integration of ancient remedies with modern approaches holds promise for achieving effective and scar-free wound healing.

Pharmacological and cell-based treatments to increase local skin flap viability in animal models.

Local skin flaps are frequently employed for wound closure to address surgical, traumatic, congenital, or oncologic defects. (1) Despite their clinical utility, skin flaps may fail due to inadequate perfusion, ischemia/reperfusion injury (IRI), excessive cell death, and associated inflammatory response. (2) All of these factors contribute to skin flap necrosis in 10-15% of cases and represent a significant surgical challenge. (3, 4) Once flap necrosis occurs, it may require additional surgeries to remove the entire flap or repair the damage and secondary treatments for infection and disfiguration, which can be costly and painful. (5) In addition to employing appropriate surgical techniques and identifying healthy, well-vascularized tissue to mitigate the occurrence of these complications, there is growing interest in exploring cell-based and pharmacologic augmentation options. (6) These agents typically focus on preventing thrombosis and increasing vasodilation and angiogenesis while reducing inflammation and oxidative stress. Agents that modulate cell death pathways such as apoptosis and autophagy have also been investigated. (7) Implementation of drugs and cell lines with potentially beneficial properties have been proposed through various delivery techniques including systemic treatment, direct wound bed or flap injection, and topical application. This review summarizes pharmacologic- and cell-based interventions to augment skin flap viability in animal models, and discusses both translatability challenges facing these therapies and future directions in the field of skin flap augmentation.

Unlocking the 'ova'-coming power: immunotherapy's role in shaping the future of ovarian cancer treatment.

Ovarian cancer is a prominent cancer worldwide with a relatively low survival rate for women diagnosed. Many individuals are diagnosed in the late stage of the disease and are prescribed a wide variety of treatment options. Current treatment options are primarily a combination of surgery and chemotherapy as well as a new but promising treatment involving immunotherapy. Nevertheless, contemporary therapeutic modalities exhibit a discernible lag in advancement when compared with the strides achieved in recent years in the context of other malignancies. Moreover, many surgery and chemotherapy options have a high risk for recurrence due to the late-stage diagnosis. Therefore, there is a necessity to further treatment options. There have been many new advancements in the field of immunotherapy. Immunotherapy has been approved for 16 various types of cancers and has shown significant treatment potential in many other cancers as well. Researchers have also found many promising outlooks for immunotherapy as a treatment for ovarian cancer. This review summarizes many of the new advancements in immunotherapy treatment options and could potentially offer valuable insights to gynecologists aimed at enhancing the efficacy of their treatment approaches for patients diagnosed with ovarian cancer.

Adapting to Visual Noise Alleviates Visual Snow.

Purpose: Visual snow syndrome-characterized by flickering specks throughout the visual field and accompanied by other symptoms-can disrupt daily life and affects roughly 2% of the population. However, its neural bases remain mysterious, and treatments are lacking. Here, we report the first intervention that can temporarily eliminate the visual snow symptom, allowing many observers to see the world without snow for the first time since symptom onset. Prolonged viewing of a visual stimulus strongly reduces the responsiveness of the visual pathways to subsequent stimuli, and we tested whether such adaptation could affect visual snow. Methods: Participants with visual snow (total n = 27) viewed high-contrast dynamic noise patterns, resembling television static, and then judged the strength of the symptom. Results: Visual snow was temporarily reduced in strength to the point that it was invisible at longer adaptation durations for most observers. The effect followed typical trends of adaptation for physical stimuli in normally sighted observers: Effect duration increased monotonically with duration of exposure to the adapter and was specific to dynamic noise. Conclusions: These results establish that spontaneous neural activity in the visual system is causally related to the visual snow percept. Because they perceive this activity, people with visual snow may provide a unique window into the generation and suppression of noise in the visual system. Adaptation allows reliable experimental control over visual snow, and so is a strong candidate for diagnostic testing and a promising tool for further understanding its neural origins, which could in turn aid the development of treatments.

The Effect of Sarcopenia on Postoperative Outcomes Following Emergency Laparotomy: A Systematic Review and Meta-Analysis.

Emergency laparotomy procedures have high rates of postoperative mortality and morbidity in older patient. Sarcopenia is associated with poor postoperative outcomes in elective surgeries and there is growing evidence for its use as a risk predictor in the emergency setting. The study aimed to evaluate the effect of sarcopenia on postoperative mortality and morbidity following emergency laparotomy. Five electronic databases were systematically searched (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science) from conception until the 14th February 2022. All prospective cohort studies were included. Risk of bias was assessed with the Newcastle-Ottawa score. Pooled meta-analyses were estimated using the Mantel-Haenszel and inverse-generic variance method for mortality and morbidity outcomes. Eleven retrospective cohort studies were included, of which ten were included in the meta-analysis comprising of 3492 patients (1027 sarcopenic, 2465 non-sarcopenic). The study level incidence of sarcopenia ranged from 24.6 to 50.3% with a median rate of 25.1%. Sarcopenia was associated with increased 30-day mortality (OR 2.36, 95% CI, 1.66, 3.37, I2 = 43%), 90-day mortality (OR 2.51, 95% CI, 1.79, 3.52, I2 = 0%), and length of hospital stay (in days) (MD 1.18, 95% CI, 0.42, 1.94, I2 = 0%, P=0.002), but not incidence of postoperative major complications (OR 1.49, 95% CI, 0.86, 2.56, I2 = 70%, P = 0.15). Sarcopenia predicts poor outcomes following emergency laparotomy. We suggest assessment of sarcopenia should be incorporated into acute surgical assessment to identify high risk patients and inform clinical decision-making prior to an emergency laparotomy.

Effects of supplementing milk replacer with essential amino acids on blood metabolites, immune response, and nitrogen metabolism of Holstein calves exposed to an endotoxin.

This study evaluated the effects of supplementing calf milk replacer with essential AA on immune responses, blood metabolites, and nitrogen metabolism of 32 Holstein bull calves [28 d of age, 44 ± 0.8 kg of body weight (BW)] exposed to lipopolysaccharide (LPS). Calves were bottle-fed a commercial milk replacer (20% crude protein and 20% fat, dry matter basis) twice daily along with a calf starter (19% crude protein, dry matter basis) for 45 d. The experiment was a randomized complete block design and treatments were a 2 × 2 factorial arrangement. Treatments were milk replacer (fed twice daily at 0.5 kg/d of powder) supplemented with or without 10 essential AA (+AA vs. -AA), and subcutaneous injection of sterile saline with or without LPS (+LPS vs. -LPS) at 3 h after the morning feeding on d 15 (4 µg LPS per kg of BW) and 17 (2 µg LPS per kg of BW). Calves also received a 2-mL subcutaneous injection of ovalbumin (6 mg of ovalbumin/mL) on d 16 and 30. Rectal temperature and blood samples were collected on d 15 before LPS injection and at h 4, 8, 12, and 24 thereafter. From d 15 to 19, total fecal and urinary output were collected, and feed refusals were documented. Rectal temperature was greater in +LPS than -LPS calves at h 4, 8, and 12 after LPS injection. Serum cortisol was greater for +LPS than -LPS at h 4 after LPS exposure. At d 28, serum antiovalbumin IgG level was greater in +LPS +AA calves compared with +LPS -AA. Serum glucose was lower for +LPS than -LPS at h 4 and 8. Serum insulin was greater in +LPS than -LPS calves. Plasma concentrations of Thr, Gly, Asn, Ser, and hydroxyproline were lower for +LPS versus -LPS calves. Plasma concentrations of Met, Leu, Phe, His, Ile, Trp, Thr, and Orn were greater in +AA calves than -AA calves. Plasma urea N and N retention were not different among LPS and AA treatments. The lower concentrations of AA in +LPS than -LPS calves indicate higher demand for AA in immuno-compromised calves fed milk replacer. Additionally, higher concentration of ovalbumin-specific IgG level in +LPS calves supplemented with +AA compared with +LPS calves with -AA suggests that supplementing AA to immune-compromised calves might improve immune status.

A cluster randomised, 16-week, parallel-group multicentre trial to compare the effectiveness of a digital school-based cognitive behavioural resilience/wellbeing-building intervention targeting emotional and behavioural problems in vulnerable Year 4 primary school children in whole classes, to the usual school curriculum: a study protocol to the "CUES for Schools" trial.

BACKGROUND: Around 10% of school-aged children experience mental health difficulties. Many more are 'vulnerable': experiencing emotional and/or behavioural problems reaching clinical levels, and thus at greatest risk of future mental illness. The trial aim is to evaluate the effectiveness of the CUES for schools programme in reducing emotional and behavioural problems in vulnerable children. METHODS: The "CUES for Schools" study is a multicentre cluster randomised controlled trial in primary schools in south east England. Schools will be randomised to receive the usual school curriculum, or the CUES programme (1:1). We aim to enrol 74 schools (5550 children including 2220 vulnerable children). CUES is a whole-class teacher-facilitated interactive digital cognitive-behavioural intervention, delivered as 24 short (20-min) modules over 12 weeks, targeting emotional/behavioural regulation skills. Children self-report emotional/behavioural problems at baseline, 8, and 16 weeks, and wellbeing and cognitive vulnerability at 0 and 16 weeks. Adverse events are assessed at 8 and 16 weeks. Teachers rate classroom behaviour at baseline and 16 weeks. School senior leadership teams and individual teachers consent to involvement in the study; parents can opt their child out of CUES sessions, assessments, or research. Children can similarly opt out and assent to research participation. The primary objective of this trial is to evaluate the effectiveness of CUES for schools compared to the usual school curriculum in improving emotional/behavioural problems for vulnerable Year 4 (8-9 years old) children at 16 weeks post-randomisation, as measured using a standardised questionnaire designed for primary schools. The secondary objective is to investigate the impact of the CUES for schools programme on both vulnerable and non-vulnerable children on wellbeing and teacher-rated classroom behaviour. DISCUSSION: The study will show whether CUES for schools is more effective than the usual curriculum in reducing emotional and behavioural problems in vulnerable Year 4 children, and thus reducing the risk of mental health difficulties in later adolescent and adult life. As a digital, teacher-facilitated intervention, CUES for schools can be readily implemented, at minimal cost. If effective, CUES for schools therefore has the potential to reduce the impact of emotional/behavioural difficulties on children's learning, behaviour, and relationships and the burden of future mental health morbidity. TRIAL REGISTRATION: Trial Registration ISRCTN11445338. Registered on September 12, 2022.

The effect of flash vacuum cooling on the flavor of ultrapasteurized milk.

Ultrapasteurization (UP) extends the shelf life of milk. Direct steam injection (DSI) is commonly used for UP because milk is quickly heated and cooled. During this process, steam is directly injected into milk and removed by a vacuum cooler. Consumers do not prefer the flavor of DSI-UP milk compared with traditional high temperature short time (HTST) milk due to the higher cooked and eggy flavors of DSI-UP milk. The objective of this research was to characterize the effect of the vacuum cooler on the flavor of DSI-UP milk. Raw skim milk was pasteurized at 140°C for 2.3 s by DSI and homogenized at 20.7 MPa. By using a liquid sample port, steam-infused pasteurized milk was sampled after heating but before reaching the vacuum chamber. A septum was installed in the vacuum chamber to allow sampling of the removed volatiles by solid-phase microextraction (SPME) fiber followed by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) combined with a sulfur-selective flame photometric detector. Steam-infused milk and vacuum-cooled milk diluted to the same solids contents were evaluated by descriptive sensory analysis and volatile compound analysis. The entire experiment was replicated 3 times. Milks cooled by the vacuum cooler were lower in sweet aromatic, sulfur/eggy, and cooked flavors than milk sampled before the vacuum cooler. Volatile compounds removed by the vacuum cooler included the sweet aromatic flavor contributors furaneol, maltol, furfural, sotolon, 2-heptanone, γ-dodecalactone, γ-decalactone, and δ-decalactone, as well as the cooked and sulfur/eggy contributors hydrogen sulfide and dimethyl sulfide. The vacuum cooler applied during DSI-UP of milk is effective at removing steam and cooling UP milk, but this process may also remove important flavor compounds from fluid milk.

Effects of micellar casein concentrate purity and milk fat on sulfur/eggy flavor in ultrapasteurized milk-based beverages.

Our objectives were to determine the level of milk-derived whey protein (MDWP) removal necessary to achieve no detectable sulfur/eggy flavor in ultrapasteurized fat-free micellar casein concentrate (MCC) beverages (6.5% protein) and in the same beverages containing 1 and 2% milk fat. Micellar casein concentrate with 95% MDWP removal was produced from skim milk (50°C) with a 3×, 3-stage ceramic microfiltration (MF) process using 0.1-µm pore size graded permeability membranes (n = 3). In experiment 1, MCC-based beverages at about 6.5% (wt/wt) true protein were formulated at a fat content of 0.15% fat (wt/wt) at 4 different levels of MDWP removal percentages (95.2%, 91.0%, 83.2%, and 69.3%). In experiment 2, a similar series of beverages at 3 MDWP removal percentages (95.2%, 83.2%, and 69.3%) with 0.1, 1, and 2% fat content were produced. The purity (or completeness of removal of whey protein by MF) of MCC was determined by the Kjeldahl method and sodium dodecyl sulfate (SDS)-PAGE. Sensory properties of beverages were documented by descriptive sensory analysis, and volatile sulfur compounds were evaluated using solid-phase microextraction followed by gas chromatography-triple quadrupole mass spectrometry. The purity of MCC measured by the Kjeldahl method (casein as a percentage of true protein) was higher after thermal treatment than before, whereas MCC purity evaluated by SDS-PAGE was unchanged by heat treatment. The purity of MCC had an effect on the flavor profile of thermally processed beverages at 6.5% protein made with fresh liquid MCC. No sulfur/eggy flavor was detected in MCC beverages when 95% of the MDWP was removed (MCC purity about 93 to 94%) from skim milk by microfiltration at 0.1, 1, and 2% fat. As the fat content of 6.5% protein beverages produced with MCC increased, sulfur/eggy flavor intensity and hydrogen sulfide concentration decreased. However, the effect of increasing milk fat on reducing sulfur/eggy flavor in MCC-based beverages at 6.5% protein was less than that of increasing MDWP removal from MCC. Sulfur off-flavors in neutral-pH dairy protein beverages can be mitigated by use of high-purity MCC or by incorporation of fat in the beverage, or both.

Children's perceptions of fluid milk with varying levels of milkfat.

Schools participating in federal meal programs are limited to serving skim or low-fat (≤1%) flavored and unflavored milk. Few studies have directly addressed child perceptions and preferences for milk containing different amounts of milkfat. The objective of this study was to determine whether children can differentiate between flavored and unflavored fluid milk containing varying levels of milkfat and whether preferences for certain levels of milkfat exist. Flavored and unflavored milks containing 4 different percentages of milkfat (≤0.5, 1, 2, and 3.25%) were high-temperature, short-time processed, filled into half-gallon light-shielded milk jugs, and stored at 4°C in the dark. Milks were evaluated by children (ages 8-13 yr) following 7 d at 4°C. Acceptance testing and tetrad difference testing were conducted on flavored and unflavored milks with and without visual cues to determine if differences were driven by visual or flavor or mouthfeel cues. Child acceptance testing (n = 138 unflavored; n = 123 flavored) was conducted to evaluate liking and perception of selected attributes. Tetrad testing (n = 127 unflavored; n = 129 flavored) was conducted to determine if children could differentiate between different fat levels even in the absence of a difference in acceptance. The experiment was replicated twice. When visual cues were present, children had higher overall liking for 1% and 2% milks than skim for unflavored milk and higher liking for chocolate milks containing at least 1% milk fat than for skim. Differences in liking were driven by appearance, viscosity, and flavor. In the absence of visual cues, no differences were observed in liking or flavor or mouthfeel attributes for unflavored milk but higher liking for at least 1% milk fat in chocolate milk compared with skim was consistent with the presence of visual cues. From tetrad testing, children could visually tell a difference between all unflavored pairs except 2% versus whole milk and could not detect consistent differences between milkfat pairs in the absence of visual cues. For chocolate milk, children could tell a difference between all milk fat pairs with visual cues and could tell a difference between skim versus 2% and skim versus whole milk without visual cues. These results demonstrate that in the absence of package-related flavors, school-age children like unflavored skim milk as well as milk with higher fat content in the absence of visual cues. In contrast, appearance as well as flavor and mouthfeel attributes play a role in children's liking as well as their ability to discriminate between chocolate milks containing different amounts of fat, with chocolate milk containing at least 1% fat preferred. The sensory quality of school lunch milk is vital to child preference, and processing efforts are needed to maximize school milk sensory quality.

Does the Prosperity of a Country Play a Role in COVID-19 Outcomes?

OBJECTIVE: This study aims to clarify the association between prosperity and the coronavirus disease (COVID-19) outcomes and its impact on the future management of pandemics. METHODS: This is an observational study using information from 2 online registries. The numbers of infected individuals and deaths and the prosperity rank of each country were obtained from worldometer.info and the Legatum Institute's Prosperity Index, respectively. RESULTS: There is a combination of countries with high and low prosperity on the list of COVID-19-infected countries. The risk of the virus pandemic seems to be more extensive in countries with high prosperity. A Spearman's rho test confirmed a significant correlation between prosperity, the number of COVID-19 cases, and the number of deaths at the 99% level. CONCLUSION: New emerging pandemics affect all nations. In order to increase the likelihood of successfully managing future events, it is important to consider preexisting health security, valid population-based management approaches, medical decision-making, communication, continuous assessment, triage, treatment, early and complete physical distancing strategies, and logistics. These elements cannot be taught on-site and on occasion. There is a need for innovative and regular educational activities for all stakeholders committed to safeguarding our future defense systems concerning diagnostic, protection, treatment, and rehabilitation in pandemics, as well as other emergencies.

Post-immunotherapy imaging in lung cancer.

By boosting the immune system, immunotherapy with immune checkpoint inhibitors (ICIs) has altered the management of patients with various cancers including those with metastatic non-small cell lung cancer (NSCLC). As a result of immune system activation, ICIs are associated with unique response patterns (that are not addressed by traditional response criteria) and inflammatory side effects termed immune-related adverse events. In this article, we will review the role of immunotherapy in cancer treatment, specifically ICIs used in NSCLC treatment, radiological response criteria of immunotherapy, and the imaging spectrum of immune-related adverse events.

Post-chemotherapy and targeted therapy imaging of the chest in lung cancer.

Non-small-cell lung cancer (NSCLC) is frequently diagnosed when it is not amenable to local therapies; therefore, systemic agents are the mainstay of therapy for many patients. In recent years, treatment of advanced NSCLC has evolved from a general approach primarily involving chemotherapy to a more personalised strategy in which biomarkers such as the presence of genomic tumour aberrations and the expression of immune proteins such as programmed death-ligand 1 (PD-L1), in combination with other elements of clinical information such as histology and clinical stage, guide management. For instance, pathways resulting in uncontrolled growth and proliferation of tumour cells due to epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements may be targeted by tyrosine kinase inhibitors (TKIs). In this article, we review the current state of medical oncology, imaging characteristics of mutations, pitfalls in response assessments and the imaging of complications.

Ready-to-drink protein beverages: Effects of milk protein concentration and type on flavor.

This study evaluated the role of protein concentration and milk protein ingredient [serum protein isolate (SPI), micellar casein concentrate (MCC), or milk protein concentrate (MPC)] on sensory properties of vanilla ready-to-drink (RTD) protein beverages. The RTD beverages were manufactured from 5 different liquid milk protein blends: 100% MCC, 100% MPC, 18:82 SPI:MCC, 50:50 SPI:MCC, and 50:50 SPI:MPC, at 2 different protein concentrations: 6.3% and 10.5% (wt/wt) protein (15 or 25 g of protein per 237 mL) with 0.5% (wt/wt) fat and 0.7% (wt/wt) lactose. Dipotassium phosphate, carrageenan, cellulose gum, sucralose, and vanilla flavor were included. Blended beverages were preheated to 60°C, homogenized (20.7 MPa), and cooled to 8°C. The beverages were then preheated to 90°C and ultrapasteurized (141°C, 3 s) by direct steam injection followed by vacuum cooling to 86°C and homogenized again (17.2 MPa first stage, 3.5 MPa second stage). Beverages were cooled to 8°C, filled into sanitized bottles, and stored at 4°C. Initial testing of RTD beverages included proximate analyses and aerobic plate count and coliform count. Volatile sulfur compounds and sensory properties were evaluated through 8-wk storage at 4°C. Astringency and sensory viscosity were higher and vanillin flavor was lower in beverages containing 10.5% protein compared with 6.3% protein, and sulfur/eggy flavor, astringency, and viscosity were higher, and sweet aromatic/vanillin flavor was lower in beverages with higher serum protein as a percentage of true protein within each protein content. Volatile compound analysis of headspace vanillin and sulfur compounds was consistent with sensory results: beverages with 50% serum protein as a percentage of true protein and 10.5% protein had the highest concentrations of sulfur volatiles and lower vanillin compared with other beverages. Sulfur volatiles and vanillin, as well as sulfur/eggy and sweet aromatic/vanillin flavors, decreased in all beverages with storage time. These results will enable manufacturers to select or optimize protein blends to better formulate RTD beverages to provide consumers with a protein beverage with high protein content and desired flavor and functional properties.

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.

PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.

Ataxia and mobility in children following surgical resection of posterior fossa tumour: A longitudinal cohort study.

PURPOSE: To report the course of ataxia in children up to 2 years post-operatively, following surgical resection of a posterior fossa tumour (PFT). METHODS: Thirty-five children, (median age 9 years, range 4-15) having resection of PFT, were assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Brief Ataxia Rating Scale (BARS) and the mobility domain of the Paediatric Evaluation of Disability Index (PEDI-m) at initial post-operative period (baseline), 3 months, 1 year and 2 years post-operatively. RESULTS: Baseline median scores of the SARA and BARS were 8.5 (range 0-35.5), and 7 (0-25) respectively. Ataxia improved at 3 months (median SARA and BARS reduction 3.5 and 4, respectively). Additional gradual improvements in SARA were recorded at 1 (median reduction 2) and 2 years post-operatively (median reduction 0.5). Median baseline PEDI-m was 54.75 (range 15.2-100) with improvement at 3 months (median increase 36.95) and small improvement at 1 year (median increase 2.5) and 2 years (median increase 5.8). Children with medulloblastoma and midline tumours (median baseline SARA 10 and 11, respectively) demonstrated more severe ataxia than children with low-grade gliomas and unilateral tumours (median baseline SARA 7.5 and 6.5, respectively). CONCLUSION: The largest improvement in ataxia scores and functional mobility scores is demonstrated within the first 3 months post-operatively, but ongoing gradual improvement is observed at 2 years. Children with medulloblastoma and midline tumour demonstrated higher ataxia scores long term.

Non-steroidal anti-inflammatory agents and anastomotic leak rates across colorectal cancer operations and anastomotic sites: A systematic review and meta-analysis of anastomosis specific leak rate and confounding factors.

BACKGROUND: Surgical intervention presents a fundamental therapeutic choice in the management of colorectal malignancies. Complications, the most serious one being anastomotic leak (AL), still have detrimental effects upon patients' morbidity and mortality. We aimed to assess whether NSAIDs, and their sub-categories, increase AL in colonic anastomoses and to identify whether this affects specific anastomotic sites. MATERIALS AND METHODS: A systematic search of MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, Science Direct, Google Scholar was conducted between January 1, 1999 till the October 30, 2020. Cohort studies and randomized control trials examining AL events in NSAID-exposed, colorectal cancer patients were included. NSAIDs were grouped according to the 2019 NICE guidelines in non-specific (NS-NSAIDs) and specific COX-2 inhibitors. The primary outcome was AL events in NSAID-exposed patients undergoing operations with either ileocolic, colocolic or colorectal anastomoses. Secondary outcomes included NSAID category-specific AL events and demographic confounding factors increasing AL risk in this patient population. RESULTS: Fifteen studies involving 25,395 patients were included in the systematic review and meta-analysis. Of all anastomoses, colocolic anastomoses were found to be statistically more prone to AL events in the NS-NSAID-exposed population [OR 3.24 (95% CI 0.98-10.72), p = 0.054]. Male gender was an independent confounder increasing AL rate regardless of NSAID exposure. CONCLUSION: The association between NSAID exposure and AL in oncology patients remains undetermined. Whilst in present work, colocolic anastomoses appear to be more sensitive to AL events, the observed association may be anastomotic site and NSAID-category dependent.