Nutritional screening in a cancer prehabilitation programme: A cohort study.

BACKGROUND: Cancer patients are often malnourished pre-operatively. The present study aimed to establish whether current screening was appropriate for use in prehabilitation and investigate any association between nutritional risk, functionality and quality of life (QoL). METHODS: This cohort study used routinely collected data from September 2020 to August 2021 from patients in a Prehab4cancer programme. Included patients were aged ≥ 18 years, had colorectal, lung or oesophago-gastric cancer and were scheduled for surgery. Nutritional assessment included Patient-Generated Subjective Global Assessment (PG-SGA) Short-Form and QoL with a sit-to-stand test. Association between nutritional risk and outcomes was analysed using adjusted logistic regression. RESULTS: From 928 patients referred to Prehab4Cancer service over 12 months, data on nutritional risk were collected from 526 patients. Pre-operatively, 233 out of 526 (44%) patients were at nutritional risk (score ≥ 2). During prehabilitation, 31% of patients improved their PG-SGA and 74% of patients maintained or improved their weight. Odds ratios (OR) with confidence intervals (CI) showed that patients with better QoL using EuroQol-5 Dimensions (OR = 0.05, 95% CI = 0.01, 0.45, p = 0.01), EuroQol Visual Analogue Scale (OR = 0.96, 95% CI = 0.93, 1.00, p = 0.04) or sit-to-stand (OR = 0.96, 95% 0.93, 1.00, p = 0.04) were less likely to be nutritional at risk. CONCLUSIONS: Almost half of patients in Prehab4Cancer programme assessed using PG-SGA were at risk of malnutrition. However, almost half of the sample did not have their risk assessed. Patients at risk of malnutrition were more likely to have a poorer QoL and sit-to-stand test than those who were not at risk.

Examination of Intramuscular and Skin Temperature Decreases Produced by the PowerPlay Intermittent Compression Cryotherapy.

CONTEXT: Previous research has found ice bags are more effective at lowering intramuscular temperature than gel packs. Recent studies have evaluated intramuscular temperature cooling decreases with ice bag versus Game Ready and with the PowerPlay system wetted ice bag inserts; however, intramuscular temperature decreases elicited by PowerPlay with the standard frozen gel pack inserts have not been examined. OBJECTIVE: Evaluate the rate and magnitude of cooling using PowerPlay with frozen gel pack (PP-gel) option, PowerPlay with wetted ice bag (PP-ice) option, and control (no treatment) on skin and intramuscular temperature (2 cm subadipose). DESIGN: Repeated-measures counterbalanced study. SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twelve healthy college-aged participants (4 men and 8 women; age = 23.08 (1.93) y, height = 171.66 (9.47) cm, mass = 73.67 (13.46) kg, and subcutaneous thickness = 0.90 (0.35) cm). INTERVENTION(S): PowerPlay (70 mm Hg) with either wetted ice bag or frozen gel pack was applied to posterior aspect of nondominant calf for 30 minutes; control lay prone for 30 minutes. Participants underwent each treatment in counterbalanced order (minimum 4 d, maximum 10 d between). MAIN OUTCOME MEASURE(S): Muscle temperature was measured via 21-gauge catheter thermocouple (IT-21; Physitemp Instruments, Inc). Skin temperature was measured via surface thermocouple (SST-1; Physitemp Instruments, Inc). RESULTS: Significant treatment-by-time interaction for muscle cooling (F10,80 = 11.262, P = .01, [Formula: see text], observed ß = 0.905) was observed. PP-ice cooled faster than both PP-gel and control from minutes 12 to 30 (all Ps < .05); PP-gel cooled faster than control from minutes 18 to 30 (all Ps < .05). Mean decreases from baseline: PP-ice = 4.8°C (2.8°C), PP-gel = 2.3°C (0.8°C), and control = 1.1°C (0.4°C). Significant treatment-by-time interaction for skin cooling (F10,80 = 23.920, P = .001, [Formula: see text], observed ß = 0.998) was observed. PP-ice cooled faster than both PP-gel and control from minutes 6 to 30 (all Ps < .05); PP-gel cooled faster than control from minutes 12 to 30 (all Ps < .05). Mean decreases from baseline: PP-ice = 14.6°C (4.8°C), PP-gel = 4.0°C (0.9°C), and control = 1.0°C (1.0°C). CONCLUSIONS: PP-ice produces clinically and statistically greater muscle and skin cooling compared with PP-gel and control.

A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome.

We investigated the genome of a 5-year-old male who presented with global developmental delay (motor, cognitive, and speech), hypotonia, possibly ataxia, and cerebellar hypoplasia of unknown origin. Whole genome sequencing (WGS) and mRNA sequencing (RNA-seq) were performed on a family having an affected proband, his unaffected parents, and maternal grandfather. To explore the molecular and functional consequences of the variant, we performed cell proliferation assays, quantitative real-time PCR (qRT-PCR) array, immunoblotting, calcium imaging, and neurite outgrowth experiments in SH-SY5Y neuroblastoma cells to compare the properties of the wild-type TATA-box-binding protein factor 1 (TAF1), deletion of TAF1, and TAF1 variant p.Ser1600Gly samples. The whole genome data identified several gene variants. However, the genome sequence data failed to implicate a candidate gene as many of the variants were of unknown significance. By combining genome sequence data with transcriptomic data, a probable candidate variant, p.Ser1600Gly, emerged in TAF1. Moreover, the RNA-seq data revealed a 90:10 extremely skewed X-chromosome inactivation (XCI) in the mother. Our results showed that neuronal ion channel genes were differentially expressed between TAF1 deletion and TAF1 variant p.Ser1600Gly cells, when compared with their respective controls, and that the TAF1 variant may impair neuronal differentiation and cell proliferation. Taken together, our data suggest that this novel variant in TAF1 plays a key role in the development of a recently described X-linked syndrome, TAF1 intellectual disability syndrome, and further extends our knowledge of a potential link between TAF1 deficiency and defects in neuronal cell function.

Infants at familial risk for depression show a distinct pattern of cortisol response to experimental challenge.

BACKGROUND: The aim of the study was to examine the link between maternal depression and the infant's HPA axis functioning in relation to a sequence of emotional challenges at 12 months postpartum, while controlling for maternal anxiety disorder and general sociodemographic risk. METHOD: Two hundred and fifty-seven infants whose mothers had been interviewed in pregnancy, as part of a prospective longitudinal study of a nationally representative sample of U.K. families, were individually tested in the laboratory and then observed during a simulated birthday party scenario. Three cortisol samples were taken over the course of 1½ h of afternoon testing. RESULTS: The cortisol levels of infants whose mothers had no history of depression decreased significantly after individual testing, and rose again significantly in response to the birthday party challenge. In contrast, infants whose mothers had been diagnosed with depression before conception, during pregnancy or in the first 6 months postpartum showed no decrease from the initially elevated levels at entry to the laboratory and a less marked increase in response to the party. LIMITATIONS: The study does not employ a traditional stress paradigm; instead it introduces a novel design to assess HPA axis functioning in relation to everyday emotional challenges. CONCLUSIONS: The findings suggest that altered responses to mildly challenging events in infancy may be a marker for infants' familial risk for depressive illness.

Antibody-linked spherical nucleic acids for cellular targeting.

Spherical nucleic acid (SNA) constructs are promising new single entity gene regulation materials capable of both cellular transfection and gene knockdown, but thus far are promiscuous structures, exhibiting excellent genetic but little cellular selectivity. In this communication, we describe a strategy to impart targeting capabilities to these constructs through noncovalent functionalization with a complementary antibody-DNA conjugate. As a proof-of-concept, we designed HER2-targeting SNAs and demonstrated that such structures exhibit cell type selectivity in terms of their uptake, and significantly greater gene knockdown in cells overexpressing the target antigen as compared to the analogous antibody-free and off-target materials.

A Photoconductive, Thiophene-Fullerene Double-Cable Polymer, Nanorod Device.

Gold/double-cable copolymer/gold multisegmented nanorods were prepared electrochemically via a template-based method. These "bulk heterojunction" nanorods showed photoconductivity providing us with a platform to study photoinduced charge separation/transport at the nanointerface and begin to think about the rational design of nanoscale solar cells based on such structures.

Biomedical nanotechnology.

This chapter summarizes the roles of nanomaterials in biomedical applications, focusing on those highlighted in this volume. A brief history of nanoscience and technology and a general introduction to the field are presented. Then, the chemical and physical properties of nanostructures that make them ideal for use in biomedical applications are highlighted. Examples of common applications, including sensing, imaging, and therapeutics, are given. Finally, the challenges associated with translating this field from the research laboratory to the clinic setting, in terms of the larger societal implications, are discussed.

mRNA expression of canine ATP10C, a P4-type ATPase, is positively associated with body condition score.

Mouse and human Atp10c genes are strong candidates for changes in bodyweight and glucose homeostasis. Using comparative genomic analysis, a novel canine P4-type ATPase, ATP10C, was identified. Expression of ATP10C was compared between sex-matched lean (body condition score, BCS<8; n=7) and obese (BCS⩾8, n=8) client-owned dogs of comparable ages. Canine ATP10C is highly expressed in visceral and subcutaneous fat at approximately 3-fold levels compared to the omental adipose depot. There was a 5-fold significant increase (P<0.0001) in mRNA expression of ATP10C in dogs with a BCS⩾8.

Infants' Use of Force to Defend Toys: The Origins of Instrumental Aggression.

The two aims of the study were (a) to determine when infants begin to use force intentionally to defend objects to which they might have a claim and (b) to examine the relationship between toddlers' instrumental use of force and their tendencies to make possession claims. Infants' and toddlers' reactions to peers' attempts to take their toys were assessed in three independent data sets in which the same observational coding system had been used (N = 200). To ensure that infants' use of force was goal-directed and not a simple physical reaction, we recorded infants' reactions when peers picked up toys that the focal infants had just put down, or were nearby or in the focal infants' mothers' laps. The use of force in response to peers' taking over toys was evident before the first birthday, but more common thereafter, although only a minority of children in each sample used force. Analysis of a combined data set revealed that force was deployed more often by 2-year-olds than younger infants, and was significantly associated with verbal references to people's possession of objects. These observations show that toddlers do deploy force intentionally to defend their possessions.

Delivering Child Community Psychology Services in the Community: Experiences from the NIPPERS Project.

BACKGROUND: The NIPPERS (Nursery Intervention Project for Parents & Education Related Services) was a novel community psychology service based in nursery settings in socio-economically disadvantaged, inner-city areas in London. METHOD: The service included consultation work with nursery staff, structured parenting groups and individual sessions for parents. RESULTS: The delivery of the clinical service and research evaluation underwent several changes in the first phase of the project, in particular to ensure that the service was acceptable and accessible to families and staff. Although take-up of community services was higher than in the local clinic-based services, it was not taken up by some 40% of parents. Due to the allocation design, it was not possible to measure the effectiveness of the intervention. CONCLUSIONS: The NIPPERS service was successful in delivering a community child psychology service to families with high levels of early child behavioural problems at high risk for continuing difficulties.

Colloidal gold and silver triangular nanoprisms.

It is now well-known that the size, shape, and composition of nanomaterials can dramatically affect their physical and chemical properties, and that technologies based on nanoscale materials have the potential to revolutionize fields ranging from catalysis to medicine. Among these materials, anisotropic particles are particularly interesting because the decreased symmetry of such particles often leads to new and unusual chemical and physical behavior. Within this class of particles, triangular Au and Ag nanoprisms stand out due to their structure- and environment-dependent optical features, their anisotropic surface energetics, and the emergence of reliable synthetic methods for producing them in bulk quantities with control over their edge lengths and thickness. This Review will describe a variety of solution-based methods for synthesizing Au and Ag triangular prismatic structures, and will address and discuss proposed mechanisms for their formation.

Curvature-induced base pair "slipping" effects in DNA-nanoparticle hybridization.

Experiments are presented that suggest DNA strands chemically immobilized on gold nanoparticle surfaces can engage in two types of hybridization: one that involves complementary strands and normal base pairing interactions and a second one assigned as a "slipping" interaction, which can additionally stabilize the aggregate structures through non-Watson-Crick type base pairing or interactions less complementary than the primary interaction. The curvature of the particles appears to be a major factor that contributes to the formation of these slipping interactions as evidenced by the observation that flat gold triangular nanoprism conjugates of the same sequence do not support them. Finally, these slipping interactions significantly stabilize nanoparticle aggregate structures, leading to large increases in T(m)'s and effective association constants as compared with free DNA and particles that do not have the appropriate sequence to maximize their contribution.

"Three-dimensional hybridization" with polyvalent DNA-gold nanoparticle conjugates.

We have determined the minimum number of base pairings necessary to stabilize DNA-Au NP aggregates as a function of salt concentration for particles between 15 and 150 nm in diameter. Significantly, we find that sequences containing a single base pair interaction are capable of effecting hybridization between 150 nm DNA-Au NPs. While traditional DNA hybridization involves two strands interacting in one dimension (1D, Z), we propose that hybridization in the context of an aggregate of polyvalent DNA-Au NP conjugates occurs in three dimensions (many oligonucleotides oriented perpendicular to the X, Y plane engage in base pairing), making nanoparticle assembly possible with three or fewer base pairings per DNA strand. These studies enabled us to compare the stability of duplex DNA free in solution and bound to the nanoparticle surface. We estimate that 4-8, 6-19, or 8-33 additional DNA bases must be added to free duplex DNA to achieve melting temperatures equivalent to hybridized systems formed from 15, 60, or 150 nm DNA-Au NPs, respectively. In addition, we estimate that the equilibrium binding constant (K(eq)) for 15 nm DNA-Au NPs (3 base pairs) is approximately 3 orders of magnitude higher than the K(eq) for the corresponding nanoparticle free system.

Screening the sequence selectivity of DNA-binding molecules using a gold nanoparticle-based colorimetric approach.

We have developed a novel competition assay that uses a gold nanoparticle (Au NP)-based, high-throughput colorimetric approach to screen the sequence selectivity of DNA-binding molecules. This assay hinges on the observation that the melting behavior of DNA-functionalized Au NP aggregates is sensitive to the concentration of the DNA-binding molecule in solution. When short, oligomeric hairpin DNA sequences were added to a reaction solution consisting of DNA-functionalized Au NP aggregates and DNA-binding molecules, these molecules may either bind to the Au NP aggregate interconnects or the hairpin stems based on their relative affinity for each. This relative affinity can be measured as a change in the melting temperature (Tm) of the DNA-modified Au NP aggregates in solution. As a proof of concept, we evaluated the selectivity of 4',6-diamidino-2-phenylindone (an AT-specific binder), ethidium bromide (a nonspecific binder), and chromomycin A (a GC-specific binder) for six sequences of hairpin DNA having different numbers of AT pairs in a five-base pair variable stem region. Our assay accurately and easily confirmed the known trends in selectivity for the DNA binders in question without the use of complicated instrumentation. This novel assay will be useful in assessing large libraries of potential drug candidates that work by binding DNA to form a drug/DNA complex.

Silver nanoparticle-oligonucleotide conjugates based on DNA with triple cyclic disulfide moieties.

We report a new strategy for preparing silver nanoparticle-oligonucleotide conjugates that are based upon DNA with cyclic disulfide-anchoring groups. These particles are extremely stable and can withstand NaCl concentrations up to 1.0 M. When silver nanoparticles functionalized with complementary sequences are combined, they assemble to form DNA-linked nanoparticle networks. This assembly process is reversible with heating and is associated with a red shifting of the particle surface plasmon resonance and a concomitant color change from yellow to pale red. Analogous to the oligonucleotide-functionalized gold nanoparticles, these particles also exhibit highly cooperative binding properties with extremely sharp melting transitions. This work is an important step toward using silver nanoparticle-oligonucleotide conjugates for a variety of purposes, including molecular diagnostic labels, synthons in programmable materials synthesis approaches, and functional components for nanoelectronic and plasmonic devices.

Maximizing DNA loading on a range of gold nanoparticle sizes.

We have investigated the variables that influence DNA coverage on gold nanoparticles. The effects of salt concentration, spacer composition, nanoparticle size, and degree of sonication have been evaluated. Maximum loading was obtained by salt aging the nanoparticles to approximately 0.7 M NaCl in the presence of DNA containing a poly(ethylene glycol) spacer. In addition, DNA loading was substantially increased by sonicating the nanoparticles during the surface loading process. Last, nanoparticles up to 250 nm in diameter were found have approximately 2 orders of magnitude higher DNA loading than smaller (13-30 nm) nanoparticles, a consequence of their larger surface area. Stable large particles are attractive for a variety of biodiagnostic assays.

Multisegmented one-dimensional nanorods prepared by hard-template synthetic methods.

In the science and engineering communities, the nanoscience revolution is intensifying. As many types of nanomaterials are becoming more reliably synthesized, they are being used for novel applications in all branches of nanoscience and nanotechnology. Since it is sometimes desirable for single nanomaterials to perform multiple functions simultaneously, multicomponent nanomaterials, such as core-shell, alloyed, and striped nanoparticles, are being more extensively researched. Nanoscientists hope to design multicomponent nanostructures and exploit their inherent multiple functionalities for use in many novel applications. This review highlights recent advances in the synthesis of multisegmented one-dimensional nanorods and nanowires with metal, semiconductor, polymer, molecular, and even gapped components. It also discusses the applications of these multicomponent nanomaterials in magnetism, self-assembly, electronics, biology, catalysis, and optics. Particular emphasis is placed on the new materials and devices achievable using these multicomponent, rather than single-component, nanowire structures.