Acral lentiginous melanoma. A retrospective study

Background: Acral lentiginous melanoma (ALM) carries one of the worst prognoses among other subtypes. This malignant tumor is found on the distal limbs and is usually detected at late stages. Hereby, the authors present their experience on this melanoma subtype. Methods: A retrospective study was conducted. Data were extracted from patients’ medical records and from phone interviews. Results: A total of 43 patients were included in the study. The main signs and symptoms disclosed by the patients were bleeding (41.9%), size greater than 6 mm (41.9%), change in size (37.2%), change in shape (30.2%), rise above the surface of the skin (27.9%), change in color (20.9%), irregular borders (16.3%), and inflammation (16.3%). The first healthcare professional consulted was a general practitioner or a dermatologist in the majority of cases (88.3%). Only 44.2% of the patients were sent by their first physician for a biopsy, whereas 30.3% were sent by the 2nd physician. 14 patients underwent biopsy within 1 month from the first appointment with a physician, while 20 patients within 3 months and 9 patients within 6 months. Only 7 patients sought medical attention in the first 3 months; 21 patients sought medical care between 3 months and one year from the appearance of the lesion, while the remaining 15 patients waited more than a year. Conclusions: One of the major issues found in ALM is represented by the diagnostic delay; this may be due to either the patients or the physicians’ failure to recognize warning signs

Liquid biopsy in cervical cancer: Hopes and pitfalls

Cervical cancer (CC) is the fourth most common cancer in women worldwide, with about 90% of cancer-related deaths occurring in developing countries. The geographical influence on disease evolution reflects differences in the prevalence of human papilloma virus (HPV) infection, which is the main cause of CC, as well as in the access and quality of services for CC prevention and diagnosis. At present, the most diffused screening and diagnostic tools for CC are Papanicolaou test and the more sensitive HPV-DNA test, even if both methods require gynecological practices whose acceptance relies on the woman’s cultural and religious background. An alternative (or complimen-tary) tool for CC screening, diagnosis, and follow-up might be represented by liquid biopsy. Here, we summarize the main methodologies developed in this context, including circulating tumor cell detection and isolation, cell tumor DNA sequencing, coding and non-coding RNA detection, and exosomal miRNA identification. Moreover, the pros and cons of each method are discussed, and their potential applications in diagnosis and prognosis of CC, as well as their role in treatment mon-itoring, are explored. In conclusion, it is evident that despite many advances obtained in this field, further effort is needed to validate and standardize the proposed methodologies before any clinical use

DAXX mutations as potential genomic markers of malignant evolution in small nonfunctioning pancreatic neuroendocrine tumors

Management of localized well-differentiated pancreatic neuroendocrine tumors (panNETs) is controversial and primarily dependent on tumor size. Upfront surgery is usually recommended for tumors larger than 2 cm in diameter since they frequently show metastatic potential, whereas smaller panNETs are generally characterized by an indolent clinical course, with a rate of relapse or metastasis below 15%. To explore whether increased tumor size is paralleled by genomic variations, we compared the rate and the mutational patterns of putative driver genes that are recurrently altered in these tumors by investigating differential cohorts of panNET surgical specimens smaller (n = 27) or larger than 2 cm (n = 29). We found that the cumulative number of mutations detected in panNETs >2 cm was significantly higher (p = 0.03) relative to smaller tumors, while mutations of DAXX were significantly more frequent in the cohort of larger tumors (p = 0.05). Moreover, mutations of DAXX were associated with features of malignancy including increased grade, nodal involvement and lymphovascular invasion, and independently predicted both relapse after surgery (p = 0.05) and reduced DFS in multivariable analysis (p = 0.02). Our data suggest that alterations of the DAXX/ATRX molecular machinery increase the malignant potential of panNETs, and that identification of mutations of DAXX/ATRX in small, nonfunctioning tumors can predict the malignant progression observed in a minority of them

Bone Biomarkers Measured on Salivary Matrix: Study of Biological Variability in a Cohort of Young Subjects

Levels of bone turnover markers (BTM) can be measured using saliva. The aim of the present study was to determine the Biological Variability of BTM in young subjects, on serial biological salivary samples. Saliva samples of 20 apparently healthy young subjects (9 females and 11 males) have been analyzed. Samples collected using salivette with cotton swabs were obtained three times every 15 days. PTHrP; TRAcP-5b and P1NP have been assayed. The ANOVA test was used to calculate intra and interindividual variance (CVI and CVG). The individuality index (II) and reference change value (RCV) were evaluated for the clinically significant variation between two results in the same individual. CVI was highest for PTHrP and lowest for P1NP while CVG was highest for TRAcP-5b. RCV was maximum for PTHrP and minimum for P1NP. The critical difference (RCV) is of particular interest in evaluating variations in the concentrations of BMT on the salivary matrix during oral pathologies and/or dental treatments The salivary dosage of BMT during dental treatments could be fundamental to establishing establish the timing of the treatment and, in the case of orthodontic treatments, to evaluate the effectiveness of the applied forces

Alteration of the perception of cold, heat and texture of food in association with taste dysfunction in COVID-19

COVID19 is characterized by alteration of smell and taste perception. It was investigated the presence of alteration for cold, heat, and food consistency perception in COVID-19 patients and the possible correlation with the most commonly used biomarkers in a routine way (CRP, IL-6, IL-1, PSP, PCT) to show if the local inflammatory process may induce alteration of cold, heat, and food consistency perception in COVID-19. From March 2020 to April 2021, a survey about taste and oral tactile/thermal sensitivity dysfunction was carried out on 1155 patients with mild or moderate COVID-19, while patients admitted to intensive care were excluded because they could not answer questions from health professionals. Positive RT-PCR confirmed all diagnoses. CRP, IL-6, IL-1, PSP, and PCT were detected for each patient. Taste and Smell Questionnaire Section of the US NHANES 2011−2014 protocol (CDC 2013b) was used for gustatory function assessment. The study was approved by the Ethics committee of AOU Policlinico Consorziale di Bari (No. 6388 COVID19 DOM-protocol number 0034687/12-05-2020), and written informed consent was obtained. A total of 208 patients referred only to alteration to taste (208/821). 75/208 ageusia, 71/208 ipoageusia, 21/208 fantageusia, 19/208 dysgeusia, 22/208 parageusia. Significant correlations between CRP, IL-6, IL-1, PSP, PCT levels and type of dysfunctions about the perception of heat, cold and food consistency have not been found (P>0.05). Loss of taste can be due to the action of inflammatory mediators on gustatory buds, while alteration of cold, heat and food consistency perception may be due to direct damage of filiform papillae, allowing virus binding through the spike protein to ACE2 receptors of filiform papillae cells

Retrospective analysis of risk factors and gaps in prevention strategies for mother-to-child HIV transmission in Rio de Janeiro, Brazil

Background Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15–24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. Methods We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. Results We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). Conclusions While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis

Cognitive Control Reflects Context Monitoring, Not Motoric Stopping, in Response Inhibition

The inhibition of unwanted behaviors is considered an effortful and controlled ability. However, inhibition also requires the detection of contexts indicating that old behaviors may be inappropriate – in other words, inhibition requires the ability to monitor context in the service of goals, which we refer to as context-monitoring. Using behavioral, neuroimaging, electrophysiological and computational approaches, we tested whether motoric stopping per se is the cognitively-controlled process supporting response inhibition, or whether context-monitoring may fill this role. Our results demonstrate that inhibition does not require control mechanisms beyond those involved in context-monitoring, and that such control mechanisms are the same regardless of stopping demands. These results challenge dominant accounts of inhibitory control, which posit that motoric stopping is the cognitively-controlled process of response inhibition, and clarify emerging debates on the frontal substrates of response inhibition by replacing the centrality of controlled mechanisms for motoric stopping with context-monitoring

Validation of brief screening instruments for internalizing and externalizing disorders in Mozambican adolescents

Background Mental disorders are the leading cause of disability for youth worldwide. However, there is a dearth of validated, brief instruments to assess mental health in low- and middle-income countries (LMIC). We aimed to facilitate identification of mental disorders in LMIC contexts by adapting and validating measures of internalizing and externalizing disorders for adolescents in Mozambique, an LMIC in southeastern Africa. Methods We selected instruments with good support for validity in high-income and other LMIC settings: the Patient Health Questionnaire Adolescent (PHQ-A), Generalized Anxiety Disorders 7 (GAD-7), and Strengths and Difficulties Questionnaire (SDQ). Instruments were adapted by local and international mental health specialists followed by cognitive interviews (n = 48) with Mozambican adolescents. We administered the instruments along with the Miniature International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)to 485 adolescents aged 12–19 years attending two secondary schools in Maputo City, Mozambique. One week later, we re-administered instruments to a randomly selected sample of 49 adolescents. Results Participants were 66.2% (n = 321) female and the average age was 15.9 (S.D = 1.7).Internal consistency (alpha = 0.80, PHQ-A; 0.84, GAD-7; 0.80, SDQ) and test–retest reliabilty (ICC = 0.74, PHQ-A; 0.70, GAD-7; 0.77, SDQ) were acceptabe for the PHQ-A, GAD-7, and the full SDQ. The SDQ internalizing subscale showed poor test–retest reliability (ICC = 0.63) and the SDQ externalizing subscale showed poor internal consistency (alpha = 0.65). All instruments demonstrated good sensitivity and specificity (> 0.70). Youden’s index identified optimal cutoff scores of 8 for the PHQ-A, 5 for the GAD-7, 10 for the SDQ internalizing and 9 for the SDQ externalizing subscales, though a range of scores provided acceptable sensitivity and specificity. Conclusions Our data supports reliability and validity of the PHQ-A, GAD-7, and SDQ instruments for rapidly assessing mental health problems in Mozambican adolescents. Use of these tools in other contexts with limited specialists may asist with expanding mental health assessment. Specific instrument and cutoff selection should be based on screening goals, treatment resources, and program objectives

Subjecting Elite Athletes to Inspiratory Breathing Load Reveals Behavioral and Neural Signatures of Optimal Performers in Extreme Environments

Background: It is unclear whether and how elite athletes process physiological or psychological challenges differently than healthy comparison subjects. In general, individuals optimize exercise level as it relates to differences between expected and experienced exertion, which can be conceptualized as a body prediction error. The process of computing a body prediction error involves the insular cortex, which is important for interoception, i.e. the sense of the physiological condition of the body. Thus, optimal performance may be related to efficient minimization of the body prediction error. We examined the hypothesis that elite athletes, compared to control subjects, show attenuated insular cortex activation during an aversive interoceptive challenge. Methodology/Principal Findings: Elite adventure racers (n = 10) and healthy volunteers (n = 11) performed a continuous performance task with varying degrees of a non-hypercapnic breathing load while undergoing functional magnetic resonance imaging. The results indicate that (1) non-hypercapnic inspiratory breathing load is an aversive experience associated with a profound activation of a distributed set of brain areas including bilateral insula, dorsolateral prefrontal cortex and anterior cingulated; (2) adventure racers relative to comparison subjects show greater accuracy on the continuous performance task during the aversive interoceptive condition; and (3) adventure racers show an attenuated right insula cortex response during and following the aversive interoceptive condition of non-hypercapnic inspirator