Advances in acute and chronic pancreatitis.

Acute pancreatitis (AP) and chronic pancreatitis are the third leading gastrointestinal causes for admissions and readmissions to hospitals in the United States. This review of articles published between 2019-2022 (December) from international sources identified four categories of crucial new findings: The report includes (1) New genetic pathogenic mutations (TRPV6); expected genetic outcomes in a Northern European population; (2) a new serum diagnostic marker for AP-fatty acid ethyl esters-distinguishing acute pancreatitis associated with alcohol; explanations of the impact of monocytes/macrophages on the inflammatory process that defines their future in diagnosis, staging, and treatment; (3) innovations in timing of per os low-fat, solid food intake immediately on admission; resolution of concepts of aggressive parenteral fluid intake; dramatic shifts to non-operative from operative treatment of infected pancreatic necrosis. Each modification reduced interventions, complications, and lengths-of-stay; and (4) authoritarian recommendations for medical treatment of chronic pain. These advances offer opportunities to initiate newly proven treatments to enhance outcomes, alter the natural history, and envision the future of two diseases that have no known cure.

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.

Acculturation and attitudes toward code-switching: A bidimensional framework.

AIMS AND OBJECTIVES: Code-switching, the spontaneous switching from one language to another within a single speech event, is often performed by bilinguals who have mastered a communicative competence in two languages. It is also a social strategy - using linguistic cues as a means to index social categories and group solidarity. Code-switching is, therefore, linked to attitudes, seen as a reflection of the speaker and their values and identities. Traditionally perceived negatively, attitudes toward code-switching have been shown to be acceptable in certain cases, such as in multilingual contexts. However, it has yet to be determined empirically whether attitudes toward code-switching are associated with individual social characteristics, including cultural identity and identity negotiation. Adopting the bidimensional model of acculturation, the goal of the study was to investigate the relationships among cultural identity and code-switching attitudes. Specifically, we sought to examine whether the bidimensional framework can be used to characterize and distinguish biculturals and whether such distinctions result in differences in code-switching attitudes and other related factors. DATA AND ANALYSIS: Cantonese-English bilinguals (n = 67) reported their language background and completed questionnaires relating to identity and code-switching. FINDINGS: The findings suggest the bidimensional model was successful in classifying biculturals versus non-biculturals and, additionally, that biculturals could be differentiated according to their strength of cultural identification, which we designated as strong biculturals, Canadian-oriented biculturals, Chinese-oriented biculturals, and weak biculturals. Findings also revealed significant group differences in code-switching attitudes and other factors, such as code-switching comfort and preference, among the bicultural subgroups. IMPLICATIONS: The study supports the hypothesis that code-switching is linked to bicultural identity. The results conclude that a more nuanced classification of biculturals is meaningful, as individual differences in cultural identification among biculturals are linked to significant differences in code-switching comfort, code-switching preference, code-switching attitudes, and multicultural attitudes.

Analysing nystagmus waveforms: a computational framework.

We present a new computational approach to analyse nystagmus waveforms. Our framework is designed to fully characterise the state of the nystagmus, aid clinical diagnosis and to quantify the dynamical changes in the oscillations over time. Both linear and nonlinear analyses of time series were used to determine the regularity and complexity of a specific homogenous phenotype of nystagmus. Two-dimensional binocular eye movement recordings were carried out on 5 adult subjects who exhibited a unilateral, uniplanar, vertical nystagmus secondary to a monocular late-onset severe visual loss in the oscillating eye (the Heimann-Bielschowsky Phenomenon). The non-affected eye held a central gaze in both horizontal and vertical planes (± 10 min. of arc). All affected eyes exhibited vertical oscillations, with mean amplitudes and frequencies ranging from 2.0°-4.0° to 0.25-1.5 Hz, respectively. Unstable periodic orbit analysis revealed only 1 subject exhibited a periodic oscillation. The remaining subjects were found to display quasiperiodic (n = 1) and nonperiodic (n = 3) oscillations. Phase space reconstruction allowed attractor identification and the computation of a time series complexity measure-the permutation entropy. The entropy measure was found to be able to distinguish between a periodic oscillation associated with a limit cycle attractor, a quasiperiodic oscillation associated with a torus attractor and nonperiodic oscillations associated with higher-dimensional attractors. Importantly, the permutation entropy was able to rank the oscillations, thereby providing an objective index of nystagmus complexity (range 0.15-0.21) that could not be obtained via unstable periodic orbit analysis or attractor identification alone. These results suggest that our framework provides a comprehensive methodology for characterising nystagmus, aiding differential diagnosis and also permitting investigation of the waveforms over time, thereby facilitating the quantification of future therapeutic managements. In addition, permutation entropy could provide an additional tool for future oculomotor modelling.

Slow-fast control of eye movements: an instance of Zeeman's model for an action.

The rapid eye movements (saccades) used to transfer gaze between targets are examples of an action. The behaviour of saccades matches that of the slow-fast model of actions originally proposed by Zeeman. Here, we extend Zeeman's model by incorporating an accumulator that represents the increase in certainty of the presence of a target, together with an integrator that converts a velocity command to a position command. The saccadic behaviour of several foveate species, including human, rhesus monkey and mouse, is replicated by the augmented model. Predictions of the linear stability of the saccadic system close to equilibrium are made, and it is shown that these could be tested by applying state-space reconstruction techniques to neurophysiological recordings. Moreover, each model equation describes behaviour that can be matched to specific classes of neurons found throughout the oculomotor system, and the implication of the model is that build-up, burst and omnipause neurons are found throughout the oculomotor pathway because they constitute the simplest circuit that can produce the motor commands required to specify the trajectories of motor actions.

Colorectal Cancer in Persons Under Age 50: Seeking Causes and Solutions.

Early onset colorectal cancer (EOCRC) refers to colorectal cancer (CRC) in individuals under age 50. Although the incidence and mortality due to later onset CRC (≥50 years) has been declining over several decades, both are increasing in those under 50. EOCRC is more likely to occur in the distal colon and rectum. There are some unique pathologic and genetic features to these tumors; they are not usually associated with a germline mutation in a gene that predisposes to cancer, and at least some may have a distinct pathogenesis. Initiating CRC screening at an earlier age (40-45 years of age) would presumably detect more early stage and asymptomatic EOCRCs, but this would imply a major additional health care burden. The understanding of EOCRC and the optimal management approach to this problem are unsolved problems.

An inconclusive study comparing the effect of concrete and abstract descriptions of belief-inconsistent information.

Linguistic bias is the differential use of linguistic abstraction (as defined by the Linguistic Category Model) to describe the same behaviour for members of different groups. Essentially, it is the tendency to use concrete language for belief-inconsistent behaviours and abstract language for belief-consistent behaviours. Having found that linguistic bias is produced without intention or awareness in many contexts, researchers argue that linguistic bias reflects, reinforces, and transmits pre-existing beliefs, thus playing a role in belief maintenance. Based on the Linguistic Category Model, this assumes that concrete descriptions reduce the impact of belief-inconsistent behaviours while abstract descriptions maximize the impact of belief-consistent behaviours. However, a key study by Geschke, Sassenberg, Ruhrmann, and Sommer [2007] found that concrete descriptions of belief-inconsistent behaviours actually had a greater impact than abstract descriptions, a finding that does not fit easily within the linguistic bias paradigm. Abstract descriptions (e.g. the elderly woman is athletic) are, by definition, more open to interpretation than concrete descriptions (e.g. the elderly woman works out regularly). It is thus possible that abstract descriptions are (1) perceived as having less evidentiary strength than concrete descriptions, and (2) understood in context (i.e. athletic for an elderly woman). In this study, the design of Geschke et al. [2007] was modified to address this possibility. We expected that the differences in the impact of concrete and abstract descriptions would be reduced or reversed, but instead we found that differences were largely absent. This study did not support the findings of Geschke et al. [2007] or the linguistic bias paradigm. We encourage further attempts to understand the strong effect of concrete descriptions for belief-inconsistent behaviour.

Blood lactate thresholds and walking/running economy are determinants of backpack-running performance in trained soldiers.

We developed a standardized laboratory treadmill protocol for assessing physiological responses to a simulated backpack load-carriage task in trained soldiers, and assessed the efficacy of blood lactate thresholds (LTs) and economy in predicting future backpack running success over an 8-mile course in field conditions. LTs and corresponding physiological responses were determined in 17 elite British soldiers who completed an incremental treadmill walk/run protocol to exhaustion carrying 20 kg backpack load. Treadmill velocity at the breakpoint (r = -0.85) and Δ 1 mmol l(-1) (r = -0.80) LTs, and relative V˙O2 at 4 mmol l(-1) (r = 0.76) and treadmill walk/run velocities of 6.4 (r = 0.76), 7.4 (r = 0.80), 11.4 (r = 0.66) and 12.4 (r = 0.65) km h(-1) were significantly associated with field test completion time. We report for the first time that LTs and backpack walk/run economy are major determinants of backpack load-carriage performance in trained soldiers.

Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome.

Background. Lynch Syndrome (LS) is characterized by germline mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC) and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC), and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del) and c.1852_1853delinsGC (p.K618A) in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs) in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel.

The Effects of Outgroup Threat and Opportunity to Derogate on Salivary Cortisol Levels.

Perceptions of intergroup threat have been related to both experiences of physiological stress responses and derogation of the outgroup. In this study, a neuroscience perspective was used to investigate the relationship between stress and opportunity to derogate the outgroup, in a threatening intergroup context. Research from a social identity perspective suggests that engaging in outgroup derogation alleviates stress when perceiving an intergroup threat. However, in line with the model of intergroup anxiety, opportunity to derogate could exacerbate the negative connotations of a threatening situation, resulting in more stress. Canadian participants (N = 110) were exposed to text describing either discriminatory or favorable comments expressed by Chinese individuals towards Canadians. Half of the participants were given the opportunity to derogate via a bias task. Salivary cortisol was used as a measure of stress and was collected at baseline, post-threat, and post-derogation. As expected, threatening identity led to more stress as evidenced by increased cortisol concentrations. Furthermore, threatened participants who had an opportunity to derogate showed greater cortisol concentrations than those who did not. These results demonstrate a link between stress and the opportunity to derogate, and highlights the value of using biological markers within the intergroup context. Rewrite abstract to remove all the references (they are meaningless because the abstracting services will use the abstract as is but will not provide the references so their presence is useless.

Classification of infantile nystagmus waveforms.

Classification of infantile nystagmus waveforms is an important problem because the characteristic waveforms can be used to distinguish between infantile and acquired nystagmus. A clear description of the nystagmus is also a necessary first stage in understanding its origin. Currently infantile nystagmus waveforms are classified into at least 12 different types. In this study we analyse a database of nystagmus recordings in order to investigate if this classification can be simplified. Application of principal components analysis revealed that 96.9% of the variance of the waveforms is described by a linear sum of two component waveforms. The components consist of sawtooth and pseudocycloid waveforms that account for 78.7% and 18.2% of the variance respectively for the most common single cycle waveforms. This simplified description of infantile nystagmus highlights the importance of identifying the origin of the jerk component and its synchronisation with the pseudocycloid component for the characterisation and treatment of the nystagmus.

Situational variations in ethnic identity across immigration generations: Implications for acculturative change and cross-cultural adaptation.

This study examined whether the acculturation of ethnic identity is first evident in more public situations with greater opportunity for intercultural interaction and eventually penetrates more intimate situations. It also investigated whether situational variations in identity are associated with cross-cultural adaptation. First-generation (G1), second-generation (G2) and mixed-parentage second-generation (G2.5) young adult Canadians (n = 137, n = 169, and n = 91, respectively) completed a questionnaire assessing their heritage and Canadian identities across four situational domains (family, friends, university and community), global heritage identity and cross-cultural adaptation. Consistent with the acculturation penetration hypothesis, the results showed Canadian identity was stronger than heritage identity in public domains, but the converse was true in the family domain; moreover, the difference between the identities in the family domain was attenuated in later generations. Situational variability indicated better adaptation for the G1 cohort, but poorer adaptation for the G2.5 cohort. For the G2 cohort, facets of global identity moderated the relation, such that those with a weaker global identity experienced greater difficulties and hassles with greater identity variability but those with a stronger identity did not. These results are interpreted in light of potential interpersonal issues implied by situational variation for each generation cohort.

Prevalence of somatic mutl homolog 1 promoter hypermethylation in Lynch syndrome colorectal cancer.

BACKGROUND: Colorectal cancers (CRCs) that have microsatellite instability (MSI) and mutL homolog 1 (MLH1) immunoloss are observed in 3 clinical scenarios: Lynch syndrome (LS), sporadic MSI CRC, and Lynch-like syndrome (LLS). v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational analysis is used to differentiate LS from sporadic MSI CRC. The role of MLH1 promoter methylation status for the differential diagnosis of these clinical forms is not well established. The objectives of this study were: 1) to analyze MLH1 promoter methylation in MLH1-deficient CRCs by pyrosequencing, and 2) to assess its role in the differential diagnosis of MLH1-deficient CRCs. METHODS: In total, 165 CRCs were analyzed, including LS (n = 19), MSI BRAF-mutated CRC (n = 37), MSI BRAF wild-type CRC (n = 60), and a control group of CRCs without MSI (microsatellite stable [MSS] CRC; n = 49). MLH1 promoter methylation status was analyzed by pyrosequencing, and the ability of different strategies to identify LS was assessed. RESULTS: The average ± standard deviation methylation in LS (9% ± 7%) was significantly lower than that in MSI BRAF-mutated CRC (42% ± 17%; P < .001) and in MSI BRAF wild-type CRC (25% ± 19%; P = .002). Somatic MLH1 hypermethylation was detected in 3 patients (15.8%) with LS, in 34 patients (91.9%) with MSI BRAF-mutated CRC, and in 37 patients (61.7%) with MSI BRAF wild-type tumors. Patients with MSI BRAF wild-type, unmethylated tumors (ie, LLS) had a stronger family history of CRC than those who had tumors with MLH1 methylation (P < .05). The sensitivity for ruling out LS was 100% for BRAF analysis, 84.2% for MLH1 methylation analysis, and 84.2% for the combination of both analyses. CONCLUSIONS: Somatic MLH1 promoter methylation occurs in up to 15% of LS CRCs. Somatic BRAF analysis is the most sensitive strategy for ruling out LS. Patients who have CRCs with loss of MLH1 protein expression and neither BRAF mutation nor MLH1 methylation resemble patients with LS.

The development of infantile nystagmus.

PURPOSE: To obtain quantitative measurements of the development of infantile nystagmus in children. This task is challenging because the eye movement recording requires some cooperation. METHOD: The oscillations in short duration eye movement recordings were identified by the method of close returns and the characteristics of the saccadic main sequence were used to calibrate the oscillations. These techniques were applied to 11 subjects, aged 0-4 years, who were all tested on more than one occasion. RESULTS: The range of waveforms could be described by a sum of asymmetric pendular and pseudocycloid components. The amplitude of the nystagmus decreased from 0 to 1.5 years and then increased again. The foveation associated with the nystagmus increased up to 1.5 years and then remained approximately constant. The average visual acuity of the subjects increased steadily from 0 to 4 years. CONCLUSIONS: These findings imply that developmental waveform changes are associated with improved visual acuity but only until 1.5-2 years of age.

Components of the neural signal underlying congenital nystagmus.

Congenital nystagmus is an involuntary bilateral horizontal oscillation of the eyes that develops soon after birth. In this study, the time constants of each of the components of the neural signal underlying congenital nystagmus were obtained by time series analysis and interpreted by comparison with those of the normal oculomotor system. In the neighbourhood of the fixation position, the system generating the neural signal is approximately linear with 3 degrees of freedom. The shortest time constant was in the range of 7-9 ms and corresponds to a normal saccadic burst signal. The other stable time constant was in the range of 22-70 ms and corresponds to the slide signal. The final time constant characterises the unidentified neural mechanism underlying the unstable drift component of the oscillation cycle and ranges between 31 and 32 ms across waveforms. The characterisation of this unstable time constant poses a challenge for the modelling of both the normal and abnormal oculomotor control system. We tentatively identify the unstable component with the eye position signal supplied to the superior colliculus in the normal eye movement system and explore some of the implications of this hypothesis.

Perceived exertion and heart rate models for estimating metabolic workload in elite British soldiers performing a backpack load-carriage task.

Identifying field measures to estimate backpack load-carriage work intensity in elite soldiers is of interest to the military. This study developed rating of perceived exertion (RPE) and heart rate models to define metabolic workload for a backpack load-carriage task valid for a population of elite soldiers using serial data. Male soldiers (n = 18) from the British Parachute or Special Air Service Regiment completed an incremental treadmill walking and (or) running protocol while carrying a 20-kg backpack. Heart rate, RPE, and oxygen uptake were recorded at each incremental stage of the protocol. Linear mixed models were used to model the RPE and heart rate data in the metric of measured peak oxygen uptake. Workload was accurately estimated using RPE alone (SE = 6.03), percentage of estimated maximum heart rate (%E-MHR) (SE = 6.9), and percentage of measured maximum heart rate (%M-MHR) (SE = 4.9). Combining RPE and %E-MHR resulted in a field measure with an accuracy (SE = 4.9) equivalent to the %M-MHR model. We conclude that RPE, %E-MHR, and %M-MHR provide accurate field-based proxy measures of metabolic workload in elite British soldiers performing a backpack load-carriage task. The model is accurate for the metabolic range measured by these serial data for the backpack load-carriage task.

Recent insights into the pathogenesis of colorectal cancer.

PURPOSE OF REVIEW: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the Western world, but our understanding of this disease is incomplete. The recent advent of new technologies has provided novel insights into the pathogenesis of CRC. RECENT FINDINGS: Genome-wide association studies have recently linked CRC to 10 common genetic variants or single-nucleotide polymorphisms that map to chromosomes 8q23, 8q24, 10p14, 11q23, 14q22, 15q13, 16q22, 18q21, 19q13 and 20p1. However, the causal significance of these variants is not understood, and some are located in poorly characterized genomic regions or gene deserts. Recent studies indicate that the single-nucleotide polymorphism rs6983267, which maps to 8q24, serves as an enhancer of MYC expression by binding T cell factor 4 (TCF4) and influencing Wnt signaling. In addition, several microRNAs interact with genes such as K-RAS, APC, p53, PTEN, TCF4, COX-2, DNMT3a and DNMT3b. Germline hypermethylation of the DNA mismatch repair genes MLH1 and MSH2 may serve as predisposing events in some CRC patients. SUMMARY: Recent studies have elucidated novel mechanisms involved in CRC, including the involvement of single-nucleotide polymorphisms not located within traditional genes, the role of microRNAs and epimutations in DNA mismatch repair genes. Interestingly, most of this progress has been made by understanding DNA that does not encode genes.

Promoter methylation in the genesis of gastrointestinal cancer.

Colorectal cancers (CRC)--and probably all cancers--are caused by alterations in genes. This includes activation of oncogenes and inactivation of tumor suppressor genes (TSGs). There are many ways to achieve these alterations. Oncogenes are frequently activated by point mutation, gene amplification, or changes in the promoter (typically caused by chromosomal rearrangements). TSGs are typically inactivated by mutation, deletion, or promoter methylation, which silences gene expression. About 15% of CRC is associated with loss of the DNA mismatch repair system, and the resulting CRCs have a unique phenotype that is called microsatellite instability, or MSI. This paper reviews the types of genetic alterations that can be found in CRCs and hepatocellular carcinoma (HCC), and focuses upon the epigenetic alterations that result in promoter methylation and the CpG island methylator phenotype (CIMP). The challenge facing CRC research and clinical care at this time is to deal with the heterogeneity and complexity of these genetic and epigenetic alterations, and to use this information to direct rational prevention and treatment strategies.

Promoter Methylation in the Genesis of Gastrointestinal Cancer

Colorectal cancers (CRC)-and probably all cancers-are caused by alterations in genes. This includes activation of oncogenes and inactivation of tumor suppressor genes (TSGs). There are many ways to achieve these alterations. Oncogenes are frequently activated by point mutation, gene amplification, or changes in the promoter (typically caused by chromosomal rearrangements). TSGs are typically inactivated by mutation, deletion, or promoter methylation, which silences gene expression. About 15% of CRC is associated with loss of the DNA mismatch repair system, and the resulting CRCs have a unique phenotype that is called microsatellite instability, or MSI. This paper reviews the types of genetic alterations that can be found in CRCs and hepatocellular carcinoma (HCC), and focuses upon the epigenetic alterations that result in promoter methylation and the CpG island methylator phenotype (CIMP). The challenge facing CRC research and clinical care at this time is to deal with the heterogeneity and complexity of these genetic and epigenetic alterations, and to use this information to direct rational prevention and treatment strategies.