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Abstract: Background: The association between hidradenitis suppurativa (HS) and some diseases is becoming relevant in recent years. Providing appropriate management of HS from an early stage requires to include prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat HS potentially related to the onset of a comorbidity. Objective: To provide the dermatologist with an accurate, easily used tool that will inform the diagnosis of HS comorbidity, and to facilitate decision‐making regarding the referral and treatment of patient with HS‐associated comorbidity. Methods: These recommendations have been developed by a working group composed of seven experts (three dermatologists, a cardiovascular specialist internist, a rheumatologist expert in spondyloarthritis, a gastroenterologist and a psychiatrist) and a team of three methodologist researchers. The expert group selected the HS comorbidities considered in these recommendations through a literature review. The recommendations on diagnostic criteria are based on the relevant clinical practice guidelines for each of the comorbidities and on the recommendations of the experts. The information regarding the repercussion of HS medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. Results: The comorbidities considered in this guide are as follows: cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), inflammatory bowel disease, inflammatory joint disorders and psychological disorders (anxiety and depression). In addition, the association between HS and the consumption of alcohol and tobacco is included. The tables and figures are a precise, easy‐to‐use tool to systematize the diagnosis of comorbidity in patients with HS and facilitate the decision‐making process regarding referral and treatment of patients with an associated disease. Conclusion: The application of these recommendations will facilitate the dermatologist practice and benefit HS patients’ health and quality of life. [ABSTRACT FROM AUTHOR]

Background Previous studies have not been able to correlate manometry findings with bolus perception. The aim of this study was to evaluate correlation of different variables, including traditional manometric variables (at diagnostic and extreme thresholds), esophageal shortening, bolus transit, automated impedance manometry ( AIM) metrics and mood with bolus passage perception in a large cohort of asymptomatic individuals. Methods High resolution manometry ( HRM) was performed in healthy individuals from nine centers. Perception was evaluated using a 5-point Likert scale. Anxiety was evaluated using Hospitalized Anxiety and Depression scale ( HAD). Subgroup analysis was also performed classifying studies into normal, hypotensive, vigorous, and obstructive patterns. Key Results One hundred fifteen studies were analyzed (69 using HRM and 46 using high resolution impedance manometry ( HRIM); 3.5% swallows in 9.6% of volunteers were perceived. There was no correlation of any of the traditional HRM variables, esophageal shortening, AIM metrics nor bolus transit with perception scores. There was no HRM variable showing difference in perception when comparing normal vs extreme values (percentile 1 or 99). Anxiety but not depression was correlated with perception. Among hypotensive pattern, anxiety was a strong predictor of variance in perception ( R2 up to .70). Conclusion and Inferences Bolus perception is less common than abnormal motility among healthy individuals. Neither esophageal motor function nor bolus dynamics evaluated with several techniques seems to explain differences in bolus perception. Different mechanisms seem to be relevant in different manometric patterns. Anxiety is a significant predictor of bolus perception in the context of hypotensive motility. [ABSTRACT FROM AUTHOR]

Background Multiple water swallow is increasingly used as a complementary challenge test in patients undergoing high-resolution manometry ( HRM). Our aim was to establish the range of normal pressure responses during the rapid drink challenge test in a large population of healthy subjects. Methods Pressure responses to a rapid drink challenge test (100 or 200 mL of water) were prospectively analyzed in 105 healthy subjects studied in nine different hospitals from different countries. Esophageal motility was assessed in all subjects by solid-state HRM. In 18 subjects, bolus transit was analyzed using concomitant intraluminal impedance monitoring. Key Results A virtually complete inhibition of pressure activity was observed during multiple swallow: Esophageal body pressure was above 20 mm Hg during 1 (0-8) % and above 30 mm Hg during 1 (0-5) % of the swallow period, and the pressure gradient across the esophagogastric junction was low (−1 (−7 to 4) mm Hg). At the end of multiple swallow, a postswallow contraction was evidenced in only 50% of subjects, whereas the remaining 50% had non-transmitted contractions. Bolus clearance was completed after 7 (1-30) s after the last swallow, as evidenced by multichannel intraluminal impedance. Conclusions & Inferences The range of normal pressure responses to a rapid drink challenge test in health has been established in a large multicenter study. Main responses are a virtually complete inhibition of esophageal pressures with a low-pressure gradient across esophagogastric junction. This data would allow the correct differentiation between normal and disease when using this test. [ABSTRACT FROM AUTHOR]

Background Multiple rapid swallow has been proposed as a challenge test that can help diagnosis and management of patients with esophageal motility disorders. Our aim was to characterize specific pressure patterns in response to a rapid drink challenge test in patients with esophageal motility disorders, and to determine the potential of these patterns in the diagnosis of patients with esophageal symptoms but normal single swallow manometry. Methods Pressure responses to a rapid drink challenge test (rapid swallow of 200 mL water) were prospectively analyzed in 30 healthy controls and 285 patients with esophageal symptoms: 33 achalasia, 68 hypocontractile motility, 27 hypercontractile motility and 160 patients with normal manometry. Key Results Three different patterns of responses were characterized: (i) hypopressive or normal pattern that was shared by healthy subjects and patients with hypocontractile peristalsis, and discriminated patients with non-obstructive hypercontractile motility or achalasia ( p < 0.001; sensitivity 80% and specificity 93%), (ii) brief hyperpressive pattern observed in patients with non-obstructive hypercontractile disorders (distal spasm and hypercontractile esophagus), and (iii) prolonged hyperpressive pattern, that discriminated achalasia from patients with non-obstructive hypercontractile disorders ( p < 0.001; sensitivity 70% and specificity 85%). Seventeen percent of patients with esophageal symptoms but normal single swallow manometry had abnormal responses to the drink challenge test: 14% a brief hyperpressive pattern, and 3% a prolonged hyperpressive pattern. Conclusions & Inferences Specific patterns of responses to a rapid drink challenge test could help identification of motility disorders in patients with esophageal symptoms but unclear or normal esophageal manometry. [ABSTRACT FROM AUTHOR]

Developmental reading disorder (RD) affects 5-10% of school aged children, with a heritability of approximately 60%. Genetic association studies have identified several candidate RD susceptibility genes, including DCDC2; however, a direct connection between the function of these genes and cognitive or learning impairments remains unclear. Variants in DCDC2, a member of the doublecortin family of genes, have been associated in humans with RD and ADHD and Dcdc2 may play a role in neuronal migration in rats. In this study, we examined the effect of Dcdc2 mutation on cognitive abilities in mice using a visual attention and visuo-spatial learning and memory task. We show that both heterozygous and homozygous mutations of Dcdc2 result in persistent visuo-spatial memory deficits, as well as visual discrimination and long-term memory deficits. These behavioral deficits occur in the absence of neuronal migration disruption in the mutant mice, and may be comorbid with an anxiety phenotype. These are the first results to suggest a direct relationship between induced mutation in Dcdc2 and changes in behavioral measures. Dcdc2 mutant mice should prove useful in future studies designed to further dissect the underlying neural mechanisms that are impaired following Dcdc2 mutation. [ABSTRACT FROM AUTHOR]

Although severe infectious complications are rare, it is important to properly screen patients for predisposing conditions before beginning treatment with infliximab. We assessed immunity markers that might provide prognostic value for the development of infection in Crohn's disease patients after treatment with infliximab. In a prospective study, 34 fistulizing Crohn's disease patients (mean age 37 years) were studied. Patients were scheduled to receive three infusions of infliximab (5 mg/kg) at weeks 0, 2, and 6. Immunologic studies: Serum immunoglobulin (IgG, IgA, IgM), IgG-subclasses, and complement (C3, C4, factor B) determined by nephelometry; CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD56+CD3– lymphocyte subsets performed by flow cytometry. During a mean follow-up of 56 months, 1 patient had disseminated tuberculosis and 2 patients had severe bacterial infections. The presence of infection was associated with significantly higher IgM (246 vs. 121 mg/dL; Mann-Whitney test, P= 0.01), lower C3 (64 vs. 118, P= 0.02), lower C4 concentrations (12 vs. 25, P= 0.02), and with decreased levels of CD19 B cells (47 vs. 290, P= 0.03) in the baseline study. Further prospective studies in a larger number of patients are suggested to examine whether early monitoring of immunocompetence might help to identify the risk of infection in patients treated with infliximab. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To compare the clinical and microbiological outcome of non-surgical periodontal therapy after 6 months with data obtained after hygienic phase or 6 weeks after completion of non-surgical therapy, in order to evaluate the value of clinical and microbiological parameters to predict treatment success. MATERIAL AND METHODS: Clinical and microbiological data were available from 271 sites in 10 systemically healthy non-smokers with moderate-to-advanced chronic periodontal disease (24-32 sites per individual). Subgingival plaque samples were tested for the presence of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Tannerella forsythensis and Treponema denticola using RNA probes. RESULTS: Stepwise multiple linear regression analysis revealed a significant impact of the number of sites with visible plaque index >1 after hygienic phase on the bleeding tendency of a subject at month 6 (p<0.01). Furthermore, an association could be demonstrated between the number of residual pockets (PD>3 mm) 6 months after therapy and the number of bleeding sites and suppurating sites after hygienic phase (p=0.016). Six weeks after therapy, the mean total bacterial loads had a significant impact on the bleeding tendency of a subject at month 6 (p<0.01). Although the average numbers of sites with persisting P. gingivalis, A. actinomycetemcomitans, T. forsythensis and T. denticola seemed to be very similar 6 weeks and 6 months after therapy, large variations were noted between subjects, and therefore the microbiological status of a subject at week 6 could not predict the status at month 6. CONCLUSIONS: The present study showed a limited potential of microbiological tests, performed after hygienic phase or shortly after non-surgical periodontal therapy, to predict the clinical outcome 6 months later, but confirmed the importance of an establishment of perfect oral hygiene before non-surgical therapy. [ABSTRACT FROM AUTHOR]

Background: To cope with the daily increments of gastric gas, the stomach can propel gas to the small bowel or trigger the belching reflex. Our aim was to evaluate transit of free gastric gas in healthy humans, and its relationship with abdominal symptoms. Methods: In 24 healthy volunteers a gas mixture was infused into the stomach at 0 mL/min (sham infusion), 25 mL/min, 50 mL/min, and 100 mL/min (n = 6 each) up to 1500 mL. Belching, rectal gas evacuation, and abdominal perception were continuously recorded for 90 min. Key Results: Sham infusion was associated to low rectal gas evacuation (187 ± 94 mL after 90 min), and belching (0 ± 0). In contrast, gastric gas infusion increased rectal gas evacuation (1198 ± 176 mL; P = .025) and belching (4 ± 1 belches; P = .0520) without differences between the infusion rates tested. Overall, there was a negative correlation between rectal gas evacuation and belching (r = −.72; P < .0001): 6 subjects had frequent belching (14 ± 2 belches) and minor rectal gas evacuation (330 ± 112 mL), whereas 12 subjects had virtually no belches (1 ± 1 belches) and greater rectal gas evacuation (1630 ± 147 mL; P < .001 vs belchers for both). Gas infusion induced lower abdominal symptoms in belchers (score increment 0.7 ± 0.3) than in rectal gas evacuators (score increment 1.7 ± 0.5; P = .033). Conclusions and Inferences: An excellent balance between belching and distal gastric empting allows the stomach to adapt to great variations in gas intake. In general, most gastric gas is emptied to distal intestinal segments, but in some circumstances gastric gas induces belching, a mechanism that may improve gas tolerance. Large amounts of gas enter into the stomach daily, mainly during meals, but the mechanisms for clearance of free gastric gas in humans, and the relation with abdominal symptoms have not been explored. An original methodology to determine transit and evacuation of free gastric gas was developed, and the mechanisms involved in clearance of free gastric gas, and its relation with gas‐related abdominal symptoms were studied. In healthy subjects, an excellent balance between belching and distal gastric empting allows the stomach to adapt to great variations in gas intake preventing gas‐related abdominal symptoms. [ABSTRACT FROM AUTHOR]

Senescent cells accumulate in tissues over time, favoring the onset and progression of multiple age-related diseases. Senescent cells present a remarkable increase in lysosomal mass and elevated autophagic activity. Here, we report that two main autophagic pathways macroautophagy (MA) and chaperone-mediated autophagy (CMA) are constitutively upregulated in senescent cells. Proteomic analyses of the subpopulations of lysosomes preferentially engaged in each of these types of autophagy revealed profound quantitative and qualitative changes in senescent cells, affecting both lysosomal resident proteins and cargo proteins delivered to lysosomes for degradation. These studies have led us to identify resident lysosomal proteins that are highly augmented in senescent cells and can be used as novel markers of senescence, such as arylsulfatase ARSA. The abundant secretome of senescent cells, known as SASP, is considered their main pathological mediator; however, little is known about the mechanisms of SASP secretion. Some secretory cells, including melanocytes, use the small GTPase RAB27A to perform lysosomal secretion. We found that this process is exacerbated in the case of senescent melanoma cells, as revealed by the exposure of lysosomal membrane integral proteins LAMP1 and LAMP2 in their plasma membrane. Interestingly, a subset of SASP components, including cytokines CCL2, CCL3, CXCL12, cathepsin CTSD, or the protease inhibitor SERPINE1, are secreted in a RAB27A-dependent manner in senescent melanoma cells. Finally, proteins previously identified as plasma biomarkers of aging are highly enriched in the lysosomes of senescent cells, including CTSD. We conclude that the lysosomal proteome of senescent cells is profoundly reconfigured, and that some senescent cells can be highly active in lysosomal exocytosis., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)