The neurobiology of interoception and affect.

Scholars have argued for centuries that affective states involve interoception, or representations of the state of the body. Yet, we lack a mechanistic understanding of how signals from the body are transduced, transmitted, compressed, and integrated by the brains of humans to produce affective states. We suggest that to understand how the body contributes to affect, we first need to understand information flow through the nervous system's interoceptive pathways. We outline such a model and discuss how unique anatomical and physiological aspects of interoceptive pathways may give rise to the qualities of affective experiences in general and valence and arousal in particular. We conclude by considering implications and future directions for research on interoception, affect, emotions, and human mental experiences.

Colorectal two-week wait service and quantitative FIT: it's not just about colon cancer.

INTRODUCTION: The aim of this study was to assess faecal immunochemical test (FIT) negativity in terms of its effect on cancer risk in the local symptomatic two-week wait (2WW) population. FIT was introduced to the colorectal 2WW pathway at the start of the pandemic. This study analyses the FIT-negative (<10µg Hb/g) cohort and calculates the relative risk and odds ratio associated with a negative FIT test. METHODS: FIT tests were sent to symptomatic 2WW patients without rectal bleeding, iron-deficient anaemia or palpable mass. Where FIT was <10µg Hb/g investigations were moved to a radiology protocol. RESULTS: The test return rate was 91% with a FIT-negative (<10µg Hb/g) rate of 82%. The FIT-negative group in the symptomatic referral pathway in Cornwall have a low (1.4%) risk of colon cancer but a significant risk (6.6%) when all cancer types are considered. The impact of a negative quantitative FIT changes the odds ratio of a patient having a luminal cancer by 0.26. The odds ratio for 'all cancer' risk was affected by 0.83. CONCLUSION: A negative FIT test within the local NG12 symptomatic patient group signifies a low risk of colon cancer and identifies patients who can be initially investigated with cross-sectional imaging. However, when all cancer types are considered, cancer prevalence in this group remains above 6%. In relative risk terms a negative FIT represents a small change in overall risk and this patient group still qualify for investigation through 2WW pathways.

A Prospective, Multicenter, Pilot Trial Of A Novel Homologous Skin Construct On Deep Partial-Thickness And Full-Thickness Burns.

Split-thickness skin grafting (STSG) is the standard of care for treating deep burns. They often contract, have unpredictable cosmetic outcomes, lack dermal appendages, and result in painful, conspicuous donor sites. An autologous homologous skin construct (AHSC) has been shown to produce full-thickness skin architecture. This study examined the safety profile, engraftment, and quality of healing of a pilot group of AHSC-treated burn wounds. Following IRB approval and informed consent, patients with deep-partial/full-thickness burns requiring grafting underwent side-by-side treatment with AHSC and STSG. A 2 cm2 fullthickness harvest was processed into AHSC at an FDA-registered facility, returned within 48 hours, and applied to a 4 cm2 area alongside a STSG. AHSC donor site was closed primarily. Wounds were evaluated for healing with digital photography and investigator assessments for 90 days. All adverse events (AEs) were recorded. Eight patients with average 13.3% TBSA [range 2-58%] burn wounds were treated: 5 Caucasian and 3 African American with an average body mass index (BMI) of 26.8. Injury was due to predominantly flame burn, with additional injury from grease, scald, contact, friction and flash. Mean time between injury and AHSC treatment was 11 days [range 5-35 days]. All patients had adequate engraftment and complete epithelialization by the end of the study. Patients required one application of AHSC and no other additional surgical procedures at the application sites. The most common AEs for STSG-treated wounds included hypertrophic scarring and pruritus. One non-infected AHSC harvest site experienced a dehiscence. There were no other AEs related to AHSC treatment. AHSC treatment is feasible in deep partial and fullthickness burn wounds warranting additional investigation.

La greffe dermo- épidermique (GDE) est le traitement de référence des brûlures profondes. La zone traitée est sujette aux brides, n'a pas d'appendices dermiques, a un aspect esthétique aléatoire et le site donneur est indéniablement douloureux. Un hybride cutané autologue- homologue (HCAH) a montré être architecturalement proche de la peau. Cette étude a pour but d'évaluer l'innocuité, la qualité de prise et la qualité cicatricielle obtenues sur un groupe pilote de brûlés profonds. Après autorisation des tutelles et consentement éclairé, les patients, nécessitant une greffe ont reçu, côte à côte, une GDE et un HCAH. Ce dernier est préparé à partir d'un prélèvement de 2 cm² de peau totale (auto- fermant), en 48 h, dans une structure approuvée par la FDA. On obtient une structure de 4 cm², installée à côté d'une GDE. Les brûlures ont été évaluées cliniquement et photographiées pendant 90 j. Tous les événements indésirables (EI) ont été répertoriés. Huit patients brûlés sur 13,3 % (2-58) de SCT ont été inclus. Il s'agissait de 5 blancs et 3 noirs (je dois traduire même ceci, qui me semble foncièrement non éthique- NDRLF) ayant un IMC de 26,8. Les brûlures étaient liées à un flamme mais aussi à de la graisse, par ébouillantement, contact, flash ou dermabrasion. Le délai moyen de mise en place de l'HCAH était de 11 jours (5-53). L'intégration de la greffe a été bonne et tous les patients étaient cicatrisés à la fin de l'étude, sans nécessité de nouvelle greffe. Les EI les plus fréquents observés sur les zones GDE étaient des cicatrices hypertrophiques et un prurit. Une zone HCAH s'est désunie (hors infection), seul EI observé dans ce groupe. L'HCAH semble utilisables sur les brûlures profondes et doit être étudié plus avant.

Analysis of polygenic risk score usage and performance in diverse human populations.

A historical tendency to use European ancestry samples hinders medical genetics research, including the use of polygenic scores, which are individual-level metrics of genetic risk. We analyze the first decade of polygenic scoring studies (2008-2017, inclusive), and find that 67% of studies included exclusively European ancestry participants and another 19% included only East Asian ancestry participants. Only 3.8% of studies were among cohorts of African, Hispanic, or Indigenous peoples. We find that predictive performance of European ancestry-derived polygenic scores is lower in non-European ancestry samples (e.g. African ancestry samples: t = -5.97, df = 24, p = 3.7 × 10-6), and we demonstrate the effects of methodological choices in polygenic score distributions for worldwide populations. These findings highlight the need for improved treatment of linkage disequilibrium and variant frequencies when applying polygenic scoring to cohorts of non-European ancestry, and bolster the rationale for large-scale GWAS in diverse human populations.

Use of cell phone type cameras to enhance focusing and magnification in optical microscopes.

Cameras with auto-focusing and zoom capability, such as those in cell phones, can simplify focusing a microscope and at the same time provide a wide range of magnification.

bHLH093/NFL and bHLH061 are required for apical meristem function in Arabidopsis thaliana.

The basic Helix-Loop-Helix (bHLH) transcription factors SCREAM/ICE1 and SCREAM2 have well-characterized roles in the terminal differentiation of stomatal guard cells in Arabidopsis thaliana. Here we report on the characterization of the functional roles of the remaining members of sub-group IIIB, bHLH093 and bHLH061. The bhlh093/bhlh061 double mutant failed to produce a primary inflorescence shoot and displayed greater phenotypic severity than bhlh093 and bhlh061 single mutants. An ultrastructural investigation revealed structural defects that develop in tissues surrounding the meristem prior to inflorescence emergence. The transition to flowering was restored in bhlh093/bhlh061 with the application of gibberellin to the apex. We also demonstrate that gibberellin application alleviates structural defects that develop in tissues surrounding the meristem and restore meristem activity. Furthermore, the bhlh093/bhlh061 double mutant was affected by delayed flowering, and the severity of the phenotype correlated with photoperiod and light intensity. Our results indicate that bHLH093 and bHLH061 function in the gibberellin-mediated establishment of functional apical meristems during the transition from vegetative to reproductive growth.

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

Retinitis pigmentosa unilateral a propósito de un caso / Unilateral retinitis pigmentosa. A case report

Caso clínico: Mujer de 27 años con historia de nictalopía y constricción de campo visual del ojo derecho. El examen oftalmológico, campo visual y electrorretinograma (ERG) fueron compatibles con una retinitis pigmentosa (RP) unilateral. Al seguimiento de un año, permanecía la afección unilateral. Discusión: La RP unilateral es un trastorno infrecuente, con una frecuencia entre el 0,2-5% de las RP. Afecta principalmente a mujeres, y en edades más avanzadas que las bilaterales. Para dar un diagnóstico definitivo tiene que haber un fondo de ojo y ERG alterados unilateralmente, y excluir causas infecciosas, inflamatorias y vasculares (AU)

Clinical case: A 27-year-old woman with a history of nyctalopia and constriction of visual field of the right eye. The ophthalmological examination showed a visual field and electroretinogram that were compatible with unilateral retinitis pigmentosa (RP). After a one year follow-up, the unilateral condition remained. Discussion: Unilateral retinitis pigmentosa is a rare condition, with a frequency between 0.2%-5% of the RP. It mainly affects women and older age groups than bilateral RP. For a definitive diagnosis, it is necessary to have a funduscopy and electroretinogram (ERG) altered unilaterally, and exclude infectious, inflammatory, and vascular causes (AU)

Characterization of non-dialyzable constituents from cranberry juice that inhibit adhesion, co-aggregation and biofilm formation by oral bacteria.

An extract prepared from cranberry juice by dialysis known as nondialyzable material (NDM) has been shown previously to possess anti-adhesion activity toward microbial species including oral bacteria, uropathogenic Escherichia coli and Helicobacter pylori. Bioassay-guided fractionation of cranberry NDM was therefore undertaken to identify the anti-adhesive constituents. An aqueous acetone-soluble fraction (NDMac) obtained from Sephadex LH-20 inhibited adhesion-linked activities by oral bacteria, including co-aggregation of oral bacteria Fusobacterium nucleatum with Streptococcus sanguinis or Porphyromonas gingivalis, and biofilm formation by Streptococcus mutans. Analysis of NDMac and subsequent subfractions by MALDI-TOF MS and 1H NMR revealed the presence of A-type proanthocyanidin oligomers (PACs) of 3-6 degrees of polymerization composed of (epi)catechin units, with some (epi)gallocatechin and anthocyanin units also present, as well as quercetin derivatives. Subfractions containing putative xyloglucans in addition to the mixed polyphenols also inhibit biofilm formation by S. mutans (MIC = 125-250 µg mL-1). These studies suggest that the anti-adhesion activities of cranberry NDM on oral bacteria may arise from a combination of mixed polyphenol and non-polyphenol constituents.

Risk of malignant progression in Barrett's esophagus indefinite for dysplasia.

Barrett's esophagus is a well-recognized risk factor for esophageal adenocarcinoma. The natural history of Barrett's esophagus classified as 'indefinite for dysplasia' (IND) is poorly characterized. The aim of this study is to characterize the natural history of IND by determining the rate of neoplastic progression and identifying risk factors for progression. Patients from the University of Pennsylvania Health System pathology database and Barrett's esophagus registry with a diagnosis of IND between 2000 and 2014 were identified. Exclusion criteria included: (1) prior diagnosis of low-grade dysplasia (LGD), high-grade dysplasia (HGD), or esophageal adenocarcinoma (EAC); (2) presence of LGD, HGD, or EAC at the time of diagnosis of IND; and (3) lack of follow-up endoscopy after diagnosis. Patients with neoplastic progression were classified as having either prevalent disease (LGD, HGD, or EAC on surveillance biopsy within 12 months of IND diagnosis) or incident disease (LGD, HGD, or EAC on surveillance biopsy >12 months after IND diagnosis). One hundred six patients were eligible for analysis. Of 87 patients with follow-up endoscopy and biopsies within 1 year of IND diagnosis, 7 (8%) had prevalent disease (2 LGD, 4 HGD, 1 EAC). The prevalence of LGD was 2.3%, HGD was 4.6%, and EAC was 1.1%. Importantly, four of the seven prevalent (2 LGD, 2 HGD) cases were found to have dysplasia within 6 months of IND diagnosis. No demographic or endoscopic characteristics studied were associated with prevalent disease. Of the 106 IND patients, there were 66 patients without prevalent dysplasia with >1-year follow-up. Three (4.5%) progressed (1 to LGD after 12 months, 2 to HGD after 16.5 and 28 months), yielding an incidence rate for any dysplasia of 1.4 cases/100 person-years and HGD/EAC of 0.9/100 person-years. Risk factors for incident disease were smoking (p = 0.02) and Barrett's esophagus segment length (p = 0.03). IND is associated with considerable risk of prevalent dysplasia, especially within the first 6 months after diagnosis. However, the incidence of HGD/EAC is low and similar to previous studies of IND. These data suggest that IND patients should have repeat endoscopy within 6 months with careful surveillance protocols. Longer BE length and smoking history may help predict which patients are more likely to develop dysplasia, and therefore identify patients who may warrant even closer monitoring.

Tracking and predicting hand, foot, and mouth disease (HFMD) epidemics in China by Baidu queries.

Hand, foot, and mouth disease (HFMD) is highly prevalent in China, and more efficient methods of epidemic detection and early warning need to be developed to augment traditional surveillance systems. In this paper, a method that uses Baidu search queries to track and predict HFMD epidemics is presented, and the outbreaks of HFMD in China during the 60-month period from January 2011 to December 2015 are predicted. The Pearson correlation coefficient (R) of the predictive model and the mean absolute percentage errors between observed HFMD case counts and the predicted number show that our predictive model gives excellent fit to the data. This implies that Baidu search queries can be used in China to track and reliably predict HFMD epidemics, and can serve as a supplement to official systems for HFMD epidemic surveillance.

Unilateral retinitis pigmentosa. A case report. / Retinitis pigmentosa unilateral a propósito de un caso.

CLINICAL CASE: A 27-year-old woman with a history of nyctalopia and constriction of visual field of the right eye. The ophthalmological examination showed a visual field and electroretinogram that were compatible with unilateral retinitis pigmentosa (RP). After a one year follow-up, the unilateral condition remained. DISCUSSION: Unilateral retinitis pigmentosa is a rare condition, with a frequency between 0.2%-5% of the RP. It mainly affects women and older age groups than bilateral RP. For a definitive diagnosis, it is necessary to have a funduscopy and electroretinogram (ERG) altered unilaterally, and exclude infectious, inflammatory, and vascular causes.

Entomological surveillance following a long-lasting insecticidal net universal coverage campaign in Midwestern Uganda.

BACKGROUND: A universal coverage campaign (UCC) with long-lasting insecticidal nets (LLINs) was implemented in four districts in Midwestern Uganda in 2009-2010. Entomological surveys were carried out to monitor changes in vector density, behaviour and malaria transmission following this intervention. METHODS: Anopheles mosquitoes were collected using CDC light traps quarterly and human landing catch twice a year in four sites. Collections were done at baseline before the campaign and over a three-year period following the campaign. Plasmodium falciparum circumsporozoite enzyme-linked immunosorbent assays were performed. A subset of anophelines were molecularly identified to species, and kdr L1014S frequencies were determined. RESULTS: The prevailing malaria vector in three sites was Anopheles gambiae s.l. (>97 %), with An. funestus s.l. being present in low numbers only. An. gambiae s.s. dominated (> 95 %) over An. arabiensis within A. gambiae s.l. In the remaining site, all three vector species were observed, although their relative densities varied among seasons and years. Vector densities were low in the year following the UCC but increased over time. Vector infectivity was 3.2 % at baseline and 1.8 % three years post-distribution (p = 0.001). The daily entomological inoculation rate (EIR) in 2012 varied between 0.0-0.98 for the different sites compared to a baseline EIR that was between 0.0-5.8 in 2009. There was no indication of a change in indoor feeding times, and both An. gambiae s.l. and An. funestus s.l. continued to feed primarily after midnight with vectors being active until the early morning. Kdr L1014S frequencies were already high at baseline (53-85 %) but increased significantly in all sites over time. CONCLUSIONS: The entomological surveys indicate that there was a reduction in transmission intensity coinciding with an increase in use of LLINs and other antimalarial interventions in areas of high malaria transmission. There was no change in feeding behaviour, and human-vector contact occurred indoors and primarily after midnight constantly throughout the study. Although the study was not designed to evaluate the effectiveness of the intervention compared to areas with no such intervention, the reduction in transmission occurred in an area with previously stable malaria, which seems to indicate a substantial contribution of the increased LLIN coverage.

Family structure and quality of life of elders in rural China: the role of the new rural social pension.

Using data from a survey in Ankang district of Shaanxi province of China in 2011, this article examines the protective effect of the New Rural Social Pension (NRSP) on quality of life of rural elders, as well the moderating effect on association between family structure and quality of life. An instrumental variable approach is used. NRSP is shown to significantly improve the quality of life of rural elders, and a robustness check shows that this effect is consistent across different sets of subgroups. Compared with the elders who have at least one son, the quality of life of those who are childless or have only one child is significantly lower. The NRSP is more likely to significantly improve the quality of life of one-child elders. In addition, the associations between the NRSP and the different facets of quality of life of the elders are significant except for the facet of sensory abilities.

Paracetamol treatment of patent ductus arteriosus in preterm infants.

OBJECTIVE: To determine the effectiveness of paracetamol in closing patent ductus arteriosus (PDA) in preterm infants of our population. STUDY DESIGN: Infants with symptomatic PDA who failed or could not get ibuprofen treatment, and who were candidates for surgical ligation, were administered oral paracetamol 15 mg kg⁻¹ every 6h, for up to 7 days and were monitored for clinical, echocardiographic and laboratorial courses. RESULT: Seven infants, between 24-27 weeks' gestation, were included. In four the DA was closed while treated by paracetamol-in one of them the DA reopened, treated with paracetamol again, and closed. In one infant, the DA almost closed, symptoms disappeared, and the DA subsequently closed spontaneously later. Two needed surgical ligation. There were no hematologic or biochemical abnormalities. CONCLUSION: Although there is the possibility that PDA may have closed spontaneously, it is proposed that paracetamol could contribute to the closure of PDA in preterm infants.

Note: folded optical system for narrow forward looking probe.

An optical system is described in which a laser beam makes three passes through a single graded index lens, forming a focus along the optic axis. It has important applications in endoscopic probes, where the forward looking characteristic permits the avoidance of obstacles and the narrow structure makes it minimally invasive.

Where are persons with intellectual disabilities in medical research? A survey of published clinical trials.

BACKGROUND: Persons with intellectual disabilities (ID) are exposed to the same medical interventions as everyone else. Given the unique health profiles of many persons with ID, it cannot be assumed that they will react to medical treatments the same as persons without ID. It is not clear if medical clinical trials routinely include persons with ID. The purpose of this research survey was to examine the inclusion of persons with ID in medical research trials, and to determine whether accommodations and/or study modifications could have been made to promote greater inclusion in medical research. METHOD: Three hundred randomised control and clinical trials published between 2007 and 2011 in the six highest impact medical journals were randomly selected. Each study was reviewed for inclusion of persons with ID, and possible accommodations that could have been put in place without compromising research integrity. Corresponding authors received a follow-up survey to determine whether persons with ID were included, but were not mentioned in the article. RESULTS: Only 6 (2%) of 300 randomly chosen studies clearly included persons with ID. Over 90% of studies were designed in ways that would automatically exclude persons with ID from participating. The author survey revealed three additional studies including persons with ID. Most persons with ID could have participated in at least 70% of the studies with simple accommodations and/or minor procedural modifications. DISCUSSION: The findings highlight the exclusion of persons with ID in medical research. Efforts are needed to increase inclusion through research policy initiatives and education.

Phylogenetic resolution power of microsatellites and various single-nucleotide polymorphism types assessed in 10 divergent chicken populations.

There has been some debate over the question of which types of DNA variation are most appropriate to accurately reconstruct evolutionary events. We compared the capacity of microsatellites (STRs) and various types of single-nucleotide polymorphism (SNP) loci in the chicken genome. The SNP types differ in their location: in exons, introns and promoters. Genetic distances between all possible pairs of 10 populations were calculated for each marker type. STR loci, which are much more polymorphic than are SNPs, are considered to have occurred at recent time compared with old evolutionary events of SNPs. Using structure software, STR loci assigned individuals to their population much more correctly than did any other marker types, whereas SNPs at promoter regions gave the poorest ascription. Furthermore, 29 STR markers were even better than all 152 SNPs together. Ancient evolutionary events that produced genetic differences between the most distant populations such as Red Jungle Fowl and domestic chicken were detected better by exons and introns than by STR loci and promoters. The significant interactions found between marker types and populations suggest that marker types had different phylogenetic histories, possibly related to a different timescale.

The role of cultural transmission in human demographic change: an age-structured model.

Human populations vary demographically with population sizes ranging from small groups of hunter-gatherers with less than fifty individuals to vast cities containing many millions. Here we investigate how the cultural transmission of traits affecting survival, fertility, or both can influence the birth rate, age structure, and asymptotic growth rate of a population. We show that the strong spread of such a trait can lead to a demographic transition, similar to that experienced in Europe in the late 19th and early 20th centuries, without using ecological or economic optimizing models. We also show that the spread of a cultural trait that increases fertility, but not survival, can cause demographic change similar to the 'Neolithic demographic transition': a period of increased population growth that is thought to have accompanied the transition from hunter-gatherer to agricultural lifestyles. We investigate the roles of vertical, oblique, and horizontal learning of such a trait in this transition and find that compared to vertical learning alone, horizontal and oblique learning can accelerate the trait's spread, lead to faster population growth, and increase its equilibrium frequency.

The coevolution of long-term pair bonds and cooperation.

The evolution of social traits may not only depend on but also change the social structure of the population. In particular, the evolution of pairwise cooperation, such as biparental care, depends on the pair-matching distribution of the population, and the latter often emerges as a collective outcome of individual pair-bonding traits, which are also under selection. Here, we develop an analytical model and individual-based simulations to study the coevolution of long-term pair bonds and cooperation in parental care, where partners play a Snowdrift game in each breeding season. We illustrate that long-term pair bonds may coevolve with cooperation when bonding cost is below a threshold. As long-term pair bonds lead to assortative interactions through pair-matching dynamics, they may promote the prevalence of cooperation. In addition to the pay-off matrix of a single game, the evolutionarily stable equilibrium also depends on bonding cost and accidental divorce rate, and it is determined by a form of balancing selection because the benefit from pair-bond maintenance diminishes as the frequency of cooperators increases. Our findings highlight the importance of ecological factors affecting social bonding cost and stability in understanding the coevolution of social behaviour and social structures, which may lead to the diversity of biological social systems.