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17 pages, 1320 KiB  
Article
Social and Mental Health Factors Involved in the Severity of Loneliness in Older Individuals in a Spanish Rural Area
by Mayra Alejandra Mafla-España, Silvia Corchón, Paula Jimeno-de Pedro, Vanessa Ibáñez-del Valle and Omar Cauli
Nurs. Rep. 2024, 14(4), 3737-3753; https://doi.org/10.3390/nursrep14040273 (registering DOI) - 29 Nov 2024
Abstract
Background: Loneliness in older people, especially those living in rural areas, is a phenomenon that has received little attention in research and can have detrimental effects on quality of life. The aim of this study was to evaluate loneliness and the psychosocial [...] Read more.
Background: Loneliness in older people, especially those living in rural areas, is a phenomenon that has received little attention in research and can have detrimental effects on quality of life. The aim of this study was to evaluate loneliness and the psychosocial factors associated with loneliness in rural Spain, which have been minimally studied. Methods: A cross-sectional study was carried out in a sample of permanently resident older people in the Rincón de Ademuz region (Valencia, Spain), a geographic area with very low population density. Emotional and social loneliness were assessed using the de Jong Gierveld Loneliness Scale. We also assessed whether loneliness is associated with sleep quality, depressive symptoms, and autonomy in basic and instrumental activities of daily living. Results: A total of 108 community-dwelling individuals aged 65 years and older participated in the study out of a total sample of 181. Of them, 30.6% experienced feelings of moderate loneliness, while 2.8% presented severe loneliness. A significant correlation was found between loneliness and age (Rho = 0.28, p = 0.003). Significant differences were also observed between emotional loneliness and gender (p = 0.03) but not between social loneliness and the total score on the de Jong Gierveld Scale. Men experienced more emotional loneliness than women. In the multivariate analyses, significant associations were found between the degree of loneliness and having sons/daughters (p = 0.03; odds ratio [OR] = 0.24; 95% CI 0.06–0.89) and the role of caring for a dependent person (p = 0.002; odds ratio [OR] = 0.05; 95% CI 0.009–0.36) but not living with sons/daughters or the presence of grandchildren. Conclusions: There is a high prevalence of loneliness among older people living in rural areas, which is associated with some social factors. Therefore, nursing care plans should include assessments and interventions to prevent or detect and address loneliness in older people. This study was retrospectively registered in ClinicalTrials on 24 April 2024 with registration number NCT06382181. Full article
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<p>Relationships between age and emotional (<b>A</b>), social (<b>B</b>), and total (<b>C</b>) loneliness on the de Jong Gierveld Loneliness Scale.</p>
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<p>Emotional loneliness scores in men and women. An asterisk indicates a significant difference between the two groups.</p>
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<p>Total loneliness scores in male and female caregivers of dependent people. An asterisk indicates a significant difference between the two groups.</p>
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11 pages, 860 KiB  
Article
Mortality Profile of Deaths Related to Infective Endocarditis in Brazil and Regions: A Population-Based Analysis of Death Records
by João Vitor Fazzio de Andrade Cordeiro, Letícia Martins Raposo and Paulo Henrique Godoy
Trop. Med. Infect. Dis. 2024, 9(12), 291; https://doi.org/10.3390/tropicalmed9120291 (registering DOI) - 29 Nov 2024
Abstract
Background: Studies of infective endocarditis (IE) are generally limited to institutions, underlining the need for more comprehensive epidemiological research. Objective: The aim of this study was to determine the mortality profile of IE-related deaths and related causes in Brazil at the national level [...] Read more.
Background: Studies of infective endocarditis (IE) are generally limited to institutions, underlining the need for more comprehensive epidemiological research. Objective: The aim of this study was to determine the mortality profile of IE-related deaths and related causes in Brazil at the national level and across regions. Method: We conducted a population-based study using data from the country’s mortality information system for the period 2000 to 2019. We identified IE-related deaths and related causes based on the ICD-10 codes. Cluster analysis was performed to determine the relationship between the variables. Results: There were 52,055 IE-related deaths during the study period. Deaths occurred predominantly among men and people aged between 60 and 79 years. The Southeast accounted for the largest proportion of deaths. The most frequent ICD-10 chapter mentioned in relation to IE-related deaths was diseases of the circulatory system. We identified three distinctive profiles: 1—an age of 80 years and over and women, where the most frequent chapters were endocrine, circulatory and metabolic diseases and the South and Southeast accounted for the largest proportion of deaths; 2—an age between 30 and 79 years and men, where the most frequent chapters were infectious and genitourinary diseases and the South and Southeast accounted for the largest proportion of deaths; and 3—an age between 0 and 29 years without any difference between sexes, where the most frequent chapter was diseases of the respiratory system and the North, Northeast and Midwest accounted for the largest proportion of deaths. Conclusions: The findings of the cluster analysis revealed distinctive IE-related mortality profiles, indicating regional differences. Full article
(This article belongs to the Special Issue Highlights in Infective Endocarditis)
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<p>Other causes related to IE-related deaths by ICD-10 chapter. Brazil and regions, 2000 to 2019.</p>
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<p>Mortality profile of IE-related deaths by cluster based on hierarchical clustering of the principal components detected by multiple correspondence analysis.</p>
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16 pages, 4167 KiB  
Article
Human Preferences for Dogs and Cats in China: The Current Situation and Influencing Factors of Watching Online Videos and Pet Ownership
by Xu Zhang, Yuansi He, Shuai Yang and Daiping Wang
Animals 2024, 14(23), 3458; https://doi.org/10.3390/ani14233458 (registering DOI) - 29 Nov 2024
Viewed by 59
Abstract
Dogs and cats have become the most important and successful pets through long-term domestication. People keep them for various reasons, such as their functional roles or for physical or psychological support. However, why humans are so attached to dogs and cats remains unclear. [...] Read more.
Dogs and cats have become the most important and successful pets through long-term domestication. People keep them for various reasons, such as their functional roles or for physical or psychological support. However, why humans are so attached to dogs and cats remains unclear. A comprehensive understanding of the current state of human preferences for dogs and cats and the potential influential factors behind it is required. Here, we investigate this question using two independent online datasets and anonymous questionnaires in China. We find that current human preferences for dog and cat videos are relatively higher than for most other interests, video plays ranking among the top three out of fifteen interests. We also find genetic variations, gender, age, and economic development levels notably influence human preferences for dogs and cats. Specifically, dog and cat ownership are significantly associated with parents’ pet ownership of dogs and cats (Spearman’s rank correlation coefficient is 0.43, 95% CI: 0.38–0.47), and the primary reason is to gain emotional support. Further analysis finds that women, young people, and those with higher incomes are more likely to prefer dog and cat videos. Our study provides insights into why humans become so attached to dogs and cats and establishes a foundation for developing co-evolutionary models. Full article
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<p>Box plots of the number of plays and likes, and histogram of popular videos of 15 types of human preferences. The diamond shape represents the mean value. The line inside the box shows the median. The box represents the interquartile range (IQR), containing the middle 50% of the data from the 25th percentile (Q1) to the 75th percentile (Q3). The whiskers extend to 1.5 times the interquartile range (IQR) from the 25th percentile (Q1) and the 75th percentile (Q3). Points outside the whiskers are outliers.</p>
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<p>The parental influence on dog or cat ownership: (<b>a</b>) Parents–Offspring, (<b>b</b>) Paternal grandparents–Parents, (<b>c</b>) Maternal grandparents–Parents. Here, “0” means no pets, “1” represents owning dogs or cats, and “2” represents owning both dogs and cats. Spearman’s rank correlations were used to calculate the parental influence on dog or cat ownership.</p>
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<p>The proportion of respondents (yes or no) who answered five questions about the reasons for having dogs or cats. These five options are: (1) for health improvement, (2) because of religious reasons or cultural traditions, (3) to gain emotional value (or compensation), (4) for practical uses like guarding or catching rats (treating them as tools), and (5) to follow the trend (i.e., people around them have pets).</p>
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<p>Factors influencing human preferences for dog and cat videos: (<b>a</b>) comparison between different types of videos; (<b>b</b>) comparison between different age groups; (<b>c</b>) comparison between genders; and (<b>d</b>) the relationship between the number of comments and the level of regional economic development. The whiskers in <a href="#animals-14-03458-f004" class="html-fig">Figure 4</a>a–c represent the standard error (SE) values. *** indicates <span class="html-italic">p</span> &lt; 0.001 for all comparisons.</p>
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14 pages, 679 KiB  
Article
Analysis of Immunological Memory for John Cunningham Virus in a Mexican Population of Patients with Multiple Sclerosis Under Treatment
by Silvia García, Adriana García-Martell, Sandra Quiñones-Aguilar, Sergio Sauri-Suárez, Mario Antonio Téllez González, Guillermo García-Castillo, Juan Antonio Suárez-Cuenca, Christian Gabriel Toledo-Lozano, Paul Mondragón Terán and Sofia Lizeth Alcaraz-Estrada
Biomedicines 2024, 12(12), 2737; https://doi.org/10.3390/biomedicines12122737 (registering DOI) - 29 Nov 2024
Viewed by 96
Abstract
Background/Objectives: Multiple sclerosis (MS) is a disease characterized by demyelination and axonal damage of the central nervous system. Despite the observed benefits, highly effective treatment (HET)-based therapy has adverse effects, which include an increased risk of developing progressive multifocal leukoencephalopathy (PML). Additionally, [...] Read more.
Background/Objectives: Multiple sclerosis (MS) is a disease characterized by demyelination and axonal damage of the central nervous system. Despite the observed benefits, highly effective treatment (HET)-based therapy has adverse effects, which include an increased risk of developing progressive multifocal leukoencephalopathy (PML). Additionally, the risk grows if the patient has antibodies for the John Cunningham virus (JCV). The appearance of PML is rare, and only one report has been found in Mexico. The objective of this research was to determine and analyze the immunological memory for JCV in a population of Mexican patients with MS under treatment. Methods: All participants underwent a complete medical history and neurological evaluation. Once they signed their informed consent, a blood sample was taken to determine if antibodies against JCV were present in their serum. Results: In total, 121 MS patients were analyzed, and the population consisted of 62.8% women and 37.2% men with an average age of 42.28. The three most common HETs received by the participants were natalizumab (67.76%), followed by teriflunomide and fingolimod. Conclusions: The seropositivity was 62.8%, and in this group, the average duration of disease evolution was 152.33 ± 93.37 months. Natalizumab was the most used HET, and despite this, only a positive association between a positive JCV antibody index with duration of fingolimod and history of depression was found. Also, a positive correlation of the JCV Ab index within the forms of SPMS and PPMS compared to RRMS was observed. No differences were observed between populations, type, and duration of MS. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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<p>EDSS of patients with MS. The Chi-squared test revealed a significant moderate association between EDSS and the type of multiple sclerosis, χ<sup>2</sup> = 59.18, N 121, <span class="html-italic">p</span> = 0.005, 95% CI: 3.14–4.08 RRMS, 6.3–7.2 SPMS, 3.07–9.4 PPMS, and V of Crammer = 0.495. Meanwhile, the Kruskal–Wallis test indicated a significant difference on the current EDSS across the type of multiple sclerosis, H(2) = 32.15, <span class="html-italic">p</span> = 0.005. Post hoc pairwise comparisons using the Dunn test revealed differences between RRMS and SPMS, <span class="html-italic">p</span> = *0.0001, but no significant differences were found between RRMS and PPMS, <span class="html-italic">p</span> = 0.170, and PPMS and SPMS, <span class="html-italic">p</span> = 0.626 (EDSS from 0 to 9).</p>
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<p>JCV antibody index and clinical form of MS. The Chi-squared test revealed a significant high association between JC virus index and the type of multiple sclerosis, χ<sup>2</sup> = 219.14, N 121, <span class="html-italic">p</span> = 0.007, 95% CI: 0.4–0.51 RRMS, 95% CI: 0.52–0.79 SPMS, 95% CI: −0.75–1 PPSM, and V of Crammer = 0.95. Meanwhile, the Kruskal–Wallis test indicated a significant difference on the JC virus index across the type of multiple sclerosis, H(2) = 11.32, <span class="html-italic">p</span> = 0.003. Post hoc pairwise comparisons using the Dunn test revealed differences between RRMS and SPMS, <span class="html-italic">p</span> = 0.005 *, and RRMS and PPMS, <span class="html-italic">p</span> = 0.046 **, but no significant differences between SPMS and PPMS, <span class="html-italic">p</span> = 0.314.</p>
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11 pages, 1326 KiB  
Article
Correlation Between the Pitch and Loudness of Tinnitus, Hearing Levels, and Tinnitus Handicap Inventory Scores in Patients with Chronic Subjective Tinnitus
by Panayiota Mavrogeni, András Molnár, Viktória Molnár, László Tamás and Stefani Maihoub
J. Clin. Med. 2024, 13(23), 7261; https://doi.org/10.3390/jcm13237261 (registering DOI) - 29 Nov 2024
Viewed by 95
Abstract
Objectives: The aim of this study was to investigate the relationships between tinnitus pitch and loudness, the frequency of hearing loss, hearing level, and the Tinnitus Handicap Inventory (THI) scores reported by patients. Methods: In total, 139 patients (50 men and 89 women; [...] Read more.
Objectives: The aim of this study was to investigate the relationships between tinnitus pitch and loudness, the frequency of hearing loss, hearing level, and the Tinnitus Handicap Inventory (THI) scores reported by patients. Methods: In total, 139 patients (50 men and 89 women; mean age ± SD, 60.19 ± 11.47 years) who suffered from chronic primary tinnitus associated with sensorineural hearing loss were included in the study. Participants underwent pure-tone audiometry and tinnitus pitch matching assessments. Additionally, all participants completed the Hungarian version of the THI questionnaire. Correlations were assessed using simple linear, Spearman’s, and Pearson’s correlation tests, and a linear regression model was applied. The Mann–Whitney U test was also used. Results: This study identified a significant correlation between the pitch of tinnitus and the frequency of hearing loss (p = 0.000 *; rho = 0.549). There was also a significant correlation between tinnitus noise and hearing levels (p = 0.000 *; rho = 0.375). Age was shown to significantly affect tinnitus loudness (p = 0.016 *) and hearing levels (p = 0.000 *) as determined by a linear regression model. Tinnitus duration only significantly influenced tinnitus loudness (p = 0.022). There was no significant effect of sex on tinnitus or audiometry parameters. Total THI scores were influenced solely by tinnitus loudness (p = 0.021 *). Furthermore, sex did have an effect on total THI scores, with women reporting higher scores (p = 0.000 *). Conclusions: This study concluded that there is a significant correlation between the pitch and loudness of tinnitus and hearing levels, suggesting a connection in their underlying mechanisms. The intensity of tinnitus and hearing level are primarily affected by ageing processes. Furthermore, the severity of self-perceived tinnitus is mainly related to the loudness of tinnitus. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Surgical Strategies Update on Ear Disorders)
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<p>Boxplot displaying the tinnitus frequencies and HL. The numbers above the boxes indicate the number of participants in each group. The boxes represent the middle 50% of the data, and the whiskers represent the upper and lower 25%. The black line that divides the boxes into two parts indicates the median values. HL = hearing level.</p>
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<p>Simple linear correlation analysis to explore the relationships between tinnitus pitch and the average frequency of hearing loss, as determined by pure-tone audiometry Both linear and quadratic regression analyses were applied consistently throughout the research. The <span class="html-italic">R</span><sup>2</sup>-value indicates the coefficient of determination for the linear correlation, and an <span class="html-italic">R</span><sup>2</sup>-value close to 1 indicating a perfect correlation. The lines in the figure depict the fitted lines for linear and quadratic correlations.</p>
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<p>Simple linear correlation analysis between tinnitus loudness and HL. Linear and quadratic regression analyses were utilised. The <span class="html-italic">R</span><sup>2</sup>-value indicates the coefficient of determination for the linear correlation, and an <span class="html-italic">R</span><sup>2</sup> of around 1 signifies a perfect correlation. The lines in the figure depict the fitted lines for linear and quadratic correlations. HL = hearing level.</p>
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<p>Comparison between total THI scores of male and female participants. The boxes represent the middle 50% of the data, and the whiskers represent the upper and lower 25%. The black line that divides the boxes into two parts indicates the median values. Differences were analysed using the Mann–Whitney <span class="html-italic">U</span> test (<span class="html-italic">p</span> &lt; 0.05 *). THI = Tinnitus Handicap Inventory. The asterisk (*) denotes a statistically significant difference.</p>
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14 pages, 528 KiB  
Article
Interrelation of Stress, Eating Behavior, and Body Adiposity in Women with Obesity: Do Emotions Matter?
by Irene da Silva Araújo Gonçalves, Mariana De Santis Filgueiras, Tiago Ricardo Moreira, Milena Sales Thomé, Gabrielly Luisa Diniz Paiva, Geralda Patrícia de Almeida, Rosangela Minardi Mitre Cotta, Tatiana do Nascimento Campos, Dayse Mara de Oliveira Freitas, Juliana Farias de Novaes, Alex Fabrício de Oliveira and Glauce Dias da Costa
Nutrients 2024, 16(23), 4133; https://doi.org/10.3390/nu16234133 - 29 Nov 2024
Viewed by 122
Abstract
Background/Objectives: Obesity is influenced by biological, hormonal, and social factors, contributing to chronic diseases and burdening the healthcare system. Chronic stress and emotional eating are linked to weight gain, affecting eating behaviors and metabolism. This study aimed to assess the association between stress, [...] Read more.
Background/Objectives: Obesity is influenced by biological, hormonal, and social factors, contributing to chronic diseases and burdening the healthcare system. Chronic stress and emotional eating are linked to weight gain, affecting eating behaviors and metabolism. This study aimed to assess the association between stress, eating behavior, and adiposity in obese women. Methods: This cross-sectional study included 132 obese women from Viçosa, Minas Gerais, Brazil. The participants completed the Lipp Stress Symptoms Inventory and the Dutch Eating Behavior Questionnaire. Blood samples were collected to measure plasma cortisol, and Body Mass Index (BMI) was calculated from weight and height measurements. Body fat was assessed using dual-energy X-ray absorptiometry (DXA). Associations between stress, eating behavior, and adiposity were evaluated using linear regression models, and interactions between stress and eating behavior subscales were tested. Results: Positive associations were observed between Phases I (alert), II (resistance), and III (exhaustion) of stress with emotional and external eating. A negative association was identified between dietary restraint and body fat, especially in women with lower cortisol levels (<13.7 mg/dL). Additionally, the alert phase was associated with higher android fat in these women. Conclusions: The findings support the hypothesis that stress and eating behavior are associated with body adiposity and that stress is linked to emotional and external eating. An inverse association between restrained eating and body fat was observed in women with lower cortisol levels. These results highlight the importance of an interdisciplinary approach that incorporates emotional and stress conditions in obesity treatment. Full article
(This article belongs to the Special Issue From Obesity to Eating Disorders: Scaling Up the Evidence)
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<p>Association between restraint eating and body fat stratified by serum cortisol concentration in women from Viçosa, Minas Gerais, 2022–2023. Adjusted for age, race, family income, physical activity, insufficient sleep, alcohol consumption, smoking, alertness, resistance, and exhaustion. Serum cortisol was categorized according to the 50th percentile of the sample (13.7 µg/dL).</p>
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38 pages, 1573 KiB  
Review
Sex- and Gender-Specific Considerations in Mycotoxin Screening: Assessing Differential Exposure, Health Impacts, and Mitigation Strategies
by Gayathree Thenuwara, Bilal Javed, Baljit Singh, Hugh J. Byrne and Furong Tian
Microbiol. Res. 2024, 15(4), 2455-2492; https://doi.org/10.3390/microbiolres15040165 (registering DOI) - 29 Nov 2024
Viewed by 159
Abstract
Mycotoxins, toxic secondary metabolites produced by fungi, present significant health risks through contaminated food and feed. Despite broad documentation of their general impacts, emerging research highlights the requirement of addressing both sex- and gender-specific differences in the risk of exposure, susceptibility, and health [...] Read more.
Mycotoxins, toxic secondary metabolites produced by fungi, present significant health risks through contaminated food and feed. Despite broad documentation of their general impacts, emerging research highlights the requirement of addressing both sex- and gender-specific differences in the risk of exposure, susceptibility, and health outcomes in mycotoxin screening and mitigation strategies. Distinct biological (sex-based) and sociocultural (gender-based) factors can influence the risk of mycotoxin exposure and subsequent health impacts; women may for example exhibit specific exposures to certain mycotoxins due to physiological and hormonal differences, with increased risks during critical life stages such as pregnancy and lactation. Conversely, men may demonstrate distinct metabolic and immune responses to these toxins. Socioeconomic and cultural factors also contribute to gender-specific exposure risks, including occupational exposures, dietary habits, and healthcare access. Current mycotoxin screening methodologies and regulatory frameworks often disregard these sex and gender disparities, resulting in incomplete risk assessments and suboptimal public health interventions. This review addresses the incorporation of sex- and gender-specific data into mycotoxin research, the development of advanced screening techniques, and the implementation of targeted mitigation strategies. Addressing these sex and gender differences is crucial for enhancing the efficacy of mycotoxin management policies and safeguarding public health. Future research directions and policy recommendations are discussed to promote a more comprehensive and practical approach to mycotoxin risk assessment and control. Full article
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<p>Sex-specific reproductive toxicity of mycotoxins: impact on male hormonal balance, sperm health, and fertility, and female sexual maturation, reproductive disorders, and pregnancy outcomes (created with BioRender).</p>
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<p>Sex-based cancer risks associated with exposure to major mycotoxins: AFB1, FB1, ZEN, and OTA (created with BioRender).</p>
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16 pages, 1094 KiB  
Article
Prevalence of Abnormalities at Tandem Endoscopy in Patients Referred for Colorectal Cancer Screening/Surveillance Colonoscopy
by George Triadafilopoulos
Cancers 2024, 16(23), 3998; https://doi.org/10.3390/cancers16233998 - 29 Nov 2024
Viewed by 144
Abstract
Introduction: Performing a tandem endoscopy and colonoscopy in selected individuals has advantages, such as the early detection of benign and/or precancerous foregut diseases; it is efficient, and it may allow added therapies. It may also have disadvantages, such as generating anxiety from false-positive [...] Read more.
Introduction: Performing a tandem endoscopy and colonoscopy in selected individuals has advantages, such as the early detection of benign and/or precancerous foregut diseases; it is efficient, and it may allow added therapies. It may also have disadvantages, such as generating anxiety from false-positive screening, possible harm from further testing, and unproven cost-effectiveness. Aims: We aimed to examine the prevalence of foregut endoscopic and histologic abnormalities in subjects referred for screening/surveillance colonoscopy who also underwent a tandem endoscopy. We wanted to (1) assess implications for cancer detection, intervention, and surveillance of precancerous foregut abnormalities, (2) identify benign foregut lesions, and (3) generate data on the utilities of this tandem approach. Patients and Methods: A retrospective cohort study of consecutive subjects referred for screening or surveillance colonoscopy who also underwent an endoscopy. Based on national screening guidelines, responses to prompting questions, personal or family history, or other risk factors, subjects were assigned to tandem endoscopy with biopsies (modified Seattle and Sydney protocols), under one anesthesia. Results: Of the 1004 patients referred for colonoscopy, 317 (32%) underwent tandem endoscopy. There were 214 women and 103 men. There were 237 Whites, 16 Asians, 40 Blacks, and 24 Hispanics. Median age was 59 (range 19–85). At endoscopy, we identified actionable benign (45%) peptic, inflammatory, and H. pylori-related abnormalities, and premalignant findings (i.e., intestinal metaplasia, 27%, dysplasia, 2%, and cancer 0.9%), comparable to the premalignant (40.3%) and malignant (0.6%) colonoscopy yield. Conclusions: When implemented based on national screening guidelines, tandem EGD and colonoscopy combines Barrett’s esophagus and gastric cancer screening in one examination, and it has a high yield in a diverse US population. Full article
(This article belongs to the Collection Oncology: State-of-the-Art Research in the USA)
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<p>Study flow diagram.</p>
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<p>Need for action depending on endoscopic and histologic findings at endoscopy in the 317 subjects of the dual EGD/colonoscopy cohort.</p>
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<p>Point % prevalence of key benign and malignant endoscopic abnormalities at tandem EGD and colonoscopy in 317 subjects. PD: Peptic duodenitis; PS: Pyloric Stenosis; G: Gastritis; AN: Antral Nodule; FP: Fundic Polyp; Cancer; HH: Hiatal Hernia; SR: Schatzki’s Ring; EE: Erosive Esophagitis; BE: Barrett’s Esophagus; EoE: Eosinophilic Esophagitis; Polyps; CRC: Colorectal Cancer.</p>
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<p>Point % prevalence of key histologic abnormalities at tandem EGD and colonoscopy in 317 subjects. DL: Duodenal lymphocytosis; HP+: Active <span class="html-italic">H. pylori</span> infection; GIM: Gastric Intestinal Metaplasia; SCJ-IM: Squamocolumnar Junction–Intestinal Metaplasia; PAM: Pancreatic Acinar Metaplasia; Cancer; PE: Peptic esophagitis; EoE: Eosinophilic esophagitis; TA: Tubular Adenoma (including serrated polyps); HP: Hyperplastic polyps; CRC: Colorectal cancer.</p>
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19 pages, 873 KiB  
Article
Association of IDH1 Mutation and MGMT Promoter Methylation with Clinicopathological Parameters in an Ethnically Diverse Population of Adults with Gliomas in England
by Hiba A. Wanis, Henrik Møller, Keyoumars Ashkan and Elizabeth A. Davies
Biomedicines 2024, 12(12), 2732; https://doi.org/10.3390/biomedicines12122732 - 29 Nov 2024
Viewed by 155
Abstract
Background: Molecular profiles can predict which patients will respond to current standard treatment and new targeted therapy regimens. Using data from a highly diverse population of approximately three million in Southeast London and Kent, this study aims to evaluate the prevalence of IDH1 [...] Read more.
Background: Molecular profiles can predict which patients will respond to current standard treatment and new targeted therapy regimens. Using data from a highly diverse population of approximately three million in Southeast London and Kent, this study aims to evaluate the prevalence of IDH1 mutation and MGMT promoter methylation in the gliomas diagnosed in adult patients and to explore correlations with patients’ demographic and clinicopathological characteristics. Methods: Anonymised data on 749 adult patients diagnosed with a glioma in 2015–2019 at King’s College Hospital were extracted. Univariable and multivariable logistic regressions were used to estimate odds ratios (ORs) for expressing IDH1 mutation and MGMT promoter methylation, based on each patient’s age, sex, ethnicity, histology, tumour location and extent of resection. The Kaplan–Meier method was used to estimate the overall survival functions. Results: A total of 19.5% of cases were IDH1-mutated. Being 39 years and younger (OR 5.48, 95% CI 3.17–9.47), from Asian/Asian British background (OR 3.68, 95% CI 1.05–12.97), having MGMT methylation (OR 15.92, 95% CI 7.30–34.75), an oligodendroglioma diagnosis (OR 7.45, 95% CI 2.90–19.13) and receiving a gross total/total microscopic resection (OR 1.95, 95% CI 1.24–3.08) were each univariately correlated with IDH1 mutation. MGMT methylation association persisted on adjustment (OR 14.13, 95% CI 3.88–51.43). MGMT promoter methylation was seen in 54.3% of gliomas. In the univariate adjusted ORs, being younger than 39 years (OR 2.56, 95% CI 1.48–4.43), female (OR 1.52, 95% CI 1.11–2.08), having IDH1 mutation (OR 15.92, 95% CI 7.30–34.75) and an oligodendroglioma diagnosis (OR 6.20, 95% CI 1.33–28.88) were associated with MGMT methylation. Being female (OR 1.75, 95% CI 1.22–2.51) and having an IDH1 mutation (OR 15.54, 95% CI 4.73–51.05) persisted after adjustment for age, sex, ethnicity, histology, tumour location and extent of resection. IDH1 mutant and MGMT methylated gliomas were associated with frontal lobe location. Survival analysis showed that patients with both IDH1 mutation and MGMT methylation had significantly better survival than those with either molecular marker alone. Over a 3-year period, women with unmethylated MGMT promoters generally had better survival than men with unmethylated MGMT. Conclusion: This study showed that the molecular markers of IDH1 mutation and MGMT promoter methylation were associated with age, sex, Asian/Asian British ethnic group, tumour histology, anatomical location and extent of resection. This study has demonstrated the importance of assessing glioma molecular markers in the clinical setting and the need to stratify patients according to their clinicopathological characteristics. Full article
(This article belongs to the Special Issue Diagnosis, Pathogenesis and Treatment of CNS Tumors)
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<p>Kaplan–Meier survival curves of 749 King’s College Hospital glioma patients comparing IDH1 wild-type and unmethylated MGMT promoter (wtIDH/unmethMGMT); IDH1 wild-type and methylated MGMT promoter (wtIDH/methMGMT); IDH1 mutation and unmethylated MGMT promoter (mIDH/unmethMGMT); IDH1 mutation and methylated MGMT promoter (mIDH/methMGMT) (<span class="html-italic">p</span> &lt; 0.001). <span class="html-italic">p</span>-values were calculated by the log-rank test.</p>
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<p>Kaplan–Meier survival curves of the King’s College Hospital glioma patient cohort (<b>a</b>) for males (n = 453) vs. females (n = 296) (<span class="html-italic">p</span> = 0.521). (<b>b</b>) according to MGMT promoter methylation status for males (methMGMT = 171; unmethMGMT = 94) vs. females (methMGMT = 236; unmethMGMT = 197) (<span class="html-italic">p</span> &lt; 0.001). <span class="html-italic">p</span>-values were calculated by the log-rank test.</p>
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12 pages, 2818 KiB  
Article
Modulation of C. albicans-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid
by Samuele Sabbatini, Linda Zatini, Eleonora Narducci, Lucrezia Rosati, Andrea Ardizzoni, Antonella Mencacci, Mario Rende, Eva Pericolini, Francesco Galli, Desirée Bartolini and Claudia Monari
Microorganisms 2024, 12(12), 2455; https://doi.org/10.3390/microorganisms12122455 - 29 Nov 2024
Viewed by 147
Abstract
Vulvovaginal candidiasis (VVC) is a prevalent women’s infection characterized by excessive inflammation and damage of the vaginal epithelium that, in its recurrent form (RVVC), causes more than three symptomatic episodes per year, impacting nearly 8% of women globally. Current antifungal treatments alleviate symptoms [...] Read more.
Vulvovaginal candidiasis (VVC) is a prevalent women’s infection characterized by excessive inflammation and damage of the vaginal epithelium that, in its recurrent form (RVVC), causes more than three symptomatic episodes per year, impacting nearly 8% of women globally. Current antifungal treatments alleviate symptoms but often fail to restore the inflammatory homeostasis of mucosal tissue and prevent recurrences. α-Tocopherol (α-TOH) and garcinoic acid (GA), a vitamin E metabolite, with immunomodulatory properties, were investigated for the first time in vaginal epithelial cells exposed to C. albicans infection to assess their effects on inflammatory signaling parameters important to restore cellular homeostasis. For this purpose, the protein kinases MKK3/6, p38 stress kinase (SAPK), and ERK1/2 were studied together with c-Fos transcription factor and IL-6, IL-1α, and IL-1β secretion in A-431 vaginal epithelial cells pre-treated with GA or with α-TOH and then infected with C. albicans. GA, differently from α-TOH, significantly reduced the C. albicans-induced activation of p38-SAPK while increasing pro-survival MAPK ERK1/2 activity. This resulted in a significant reduction in the secretion levels of the inflammatory cytokines IL-6 and IL-1α, as well as IL-1β. Overall, our data indicate that GA holds potential for restoring the immuno-metabolic properties of the vaginal epithelium exposed to C. albicans infection, which may help to treat inflammatory symptoms in VVC/RVVC. Full article
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<p>Effects of GA and α-TOH treatments on vaginal cell viability. A-431 cells were exposed to increasing levels of GA (<b>A</b>) or α-TOH (<b>B</b>) between 1 and 100 µM for 48 h and then assessed for viability by the MTT test. Data are the means ± SDs of triplicate determinations. * <span class="html-italic">p</span> &lt; 0.05 (Ctr vs. all treatments). Ctr = uninfected cells.</p>
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<p>Microscopic analysis of VECs infected for 3 h with <span class="html-italic">C. albicans</span> SC5314. The representative images, observed by optical microscopy, show the fungal cells in the transition to the hyphal form. The pictures were taken at magnifications of 200× (<b>A</b>,<b>B</b>) and 400× (<b>C</b>,<b>D</b>).</p>
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<p>Effects of GA and α-TOH pre-treatments on phospho (P)-p38 and c-Fos levels in VECs infected with <span class="html-italic">C. albicans</span>. A-431 cells were pre-treated with 10 and 25 µM GA (<b>A</b>,<b>B</b>) or with 25 and 50 µM α-TOH (<b>C</b>,<b>D</b>) for 48 h and then infected for 3 h with <span class="html-italic">C. albicans</span>. P-p38 and c-Fos activation were determined by using Western blot analysis. The immunoblot images are representative of three independent experiments with similar results. The densitometric data depicted in the histograms are the means ± SDs of three independent experiments. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.001 (UCV vs. <span class="html-italic">C. albicans</span>-infected cells); ** <span class="html-italic">p</span> &lt; 0.001 (<span class="html-italic">C. albicans</span>-infected cells vs. <span class="html-italic">C. albicans</span>-infected cells + GA). Ctr = uninfected cells; UCV = uninfected cells + vehicle.</p>
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<p>Effects of GA pre-treatment on phospho (P)-MKK3/6 and P-ERK1/2 levels of VECs infected with <span class="html-italic">C. albicans</span>. A-431 cells were pre-treated with 10 and 25 µM GA for 48 h and then exposed for 3 h to <span class="html-italic">C. albicans</span>. P-MKK3/6 and P-ERK1/2 activation was determined by using Western blot analysis. The immunoblot images are representative of three independent experiments with similar results (<b>A</b>). The densitometric data in the histograms depict the means ± SDs of three independent experiments (<b>B</b>). ** <span class="html-italic">p</span> &lt; 0.001 (UCV vs. <span class="html-italic">C. albicans</span>-infected cells); * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.001 (<span class="html-italic">C. albicans</span>-infected cells vs. <span class="html-italic">C. albicans</span>-infected cells + GA). Ctr = uninfected cells; UCV = uninfected cells + vehicle.</p>
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<p>Proposed model of mechanistic aspects of GA immuno-modulatory effects in vaginal epithelial cells exposed to <span class="html-italic">C. albicans</span> infection. The MKK3/6-p38/SAPK pathway and its regulatory interplay with pro-survival MAPK ERK1/2 are molecular targets of GA, with modulating activity on IL-6, IL-1 α, and IL-1β levels secreted by the infected vaginal epithelium. The effect of GA on these cytokines may preserve the immune-metabolic properties of the vaginal epithelium and support post-infection recovery and the restoration of cellular homeostasis. (<b>A</b>) Mechanism of action of <span class="html-italic">C. albicans</span> on vaginal epithelial cells. (<b>B</b>) Effect of pre-treatment with GA on vaginal cells infected with <span class="html-italic">C. albicans.</span> The dotted line in the arrows indicates that there is a trend toward a non-significant reduction in the proposed event; the solid line indicates a significant reduction/inhibition; red arrows indicate increased production; blue arrows indicate decreased secretion. The image was produced by using BioRender software (<a href="https://www.biorender.com" target="_blank">https://www.biorender.com</a>; license number: C81D6A59-0002).</p>
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12 pages, 561 KiB  
Article
An Exploratory Study on the Correlation Between Reactive Agility and Downhill Trail Running Performance in Amateur Trail Runners
by Juan Pablo García Muñoz, Francisco García-Muro San José, Ángel Luis Rodríguez Fernández, Ella Jayne Neale and Arturo Pérez Gosálvez
Appl. Sci. 2024, 14(23), 11128; https://doi.org/10.3390/app142311128 - 29 Nov 2024
Viewed by 229
Abstract
Agility appears to be an important skill in the downhill sections of trail running; however, its actual role in the performance of this sport is unknown. The aim of the study was to evaluate the correlation of reactive agility (RA) and certain biomechanical [...] Read more.
Agility appears to be an important skill in the downhill sections of trail running; however, its actual role in the performance of this sport is unknown. The aim of the study was to evaluate the correlation of reactive agility (RA) and certain biomechanical parameters with the performance of runners when performing trail running descents. Nine amateur trail runners (four women and five men) performed a session of change of direction, RA, and 15 m linear sprint tests. In a second session, they performed a trail running race of 400 m with a negative elevation gain of 40 m. The relationship between the variables obtained in both sessions was evaluated using Pearson’s correlation coefficient. The results revealed significant correlations of performance during the trail running descent, with the time of the 15 m linear sprint (r = 0.77, ρ ≤ 0.05.), 5 m linear sprint (r = 0.79, ρ ≤ 0.05.), and with the reaction time in the reactive agility test with a sport-specific stimulus (r = 0.82, ρ ≤ 0.05.). The correlations found in the tests suggest that reactive agility skills and acceleration abilities have a significant relationship with performance on downhill sections in trail running. Full article
(This article belongs to the Special Issue Motor Control and Movement Biomechanics)
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<p>(<b>a</b>) The 45° change of direction test design; (<b>b</b>) design of the reactive agility test in response to a generic stimulus displayed on the screen, RAge. (<b>c</b>) Design of the reactive agility tests with sport-specific stimulus, RAsp.</p>
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18 pages, 943 KiB  
Article
Open-Access 12 Minute MRI Screening for Acute Appendicitis: A Five-Year Retrospective Observational Study of Diagnostic Accuracy
by Andrew Owen Jones and James Nol
J. Clin. Med. 2024, 13(23), 7257; https://doi.org/10.3390/jcm13237257 (registering DOI) - 28 Nov 2024
Viewed by 260
Abstract
Objective: This retrospective observational diagnostic accuracy study aims to demonstrate that open-access rapid-sequence non-contrast magnetic resonance imaging (MRI) is accurate for exclusion or confirmation of acute appendicitis (AA). Methods: In 2017, a locally designed 12 min MRI protocol was made available [...] Read more.
Objective: This retrospective observational diagnostic accuracy study aims to demonstrate that open-access rapid-sequence non-contrast magnetic resonance imaging (MRI) is accurate for exclusion or confirmation of acute appendicitis (AA). Methods: In 2017, a locally designed 12 min MRI protocol was made available as a new open-access option (no booking needed) for any emergency department (ED) or acute surgical patient with any clinical presentation at the authors’ sites. Uninterrupted single-radiologist reporting availability was provided. A 5-year consecutive report list from 1 January 2019 to 31 December 2023 was recorded in an activity log, from which 3478 eligible reports were identified as ED-based referrals assessing for possible AA. There was “appendicitis possibility” in 581/3478 (17%) reports and “no evidence of appendicitis” in 2897/3478 (83%). These were retrospectively compared with the medical record findings of 557/3478 proven cases of AA (16%). Report availability and reliability metrics have been assessed. Results: Overall, 2583/3478 reports (74%) were finalized within 2 h of MRI study completion, 3254/3478 (94%) within 4 h. The 3478 reports combined had 98% sensitivity, 98% specificity, 98% accuracy, 94% positive predictive value, and 99% negative predictive value for AA (φ = 0.95). The largest 5-year subgroup, females 15–19 years old, 66/440 with proven AA, had 98% report accuracy. Pregnant women, 21/171 with proven AA, had 99% report accuracy. Conclusions: The described MRI protocol is accurate for appendicitis assessment and is a suitable first-imaging choice for children, young adults, and pregnant women. It does not require intravenous contrast and poses no radiation risk. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
11 pages, 838 KiB  
Article
Hemodynamic and Genetic Associations with the Risk of Idiopathic Pulmonary Arterial Hypertension Development in an Ethnic Cohort of Kazakhs
by Dana Taizhanova, Togzhan Nurpissova, Gulshara Abildinova, Tamilla Martynyuk, Nazgul Kulmyrzayeva and Elena Zholdybayeva
Diagnostics 2024, 14(23), 2687; https://doi.org/10.3390/diagnostics14232687 - 28 Nov 2024
Viewed by 137
Abstract
Introduction: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease. The aim of this study was to evaluate the association of polymorphism of the type 2 bone morphogenetic protein receptor gene (BMPR2) with the risk of IPAH development in an ethnic [...] Read more.
Introduction: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease. The aim of this study was to evaluate the association of polymorphism of the type 2 bone morphogenetic protein receptor gene (BMPR2) with the risk of IPAH development in an ethnic group of Kazakhs. We also describe the clinical and hemodynamic characteristics and outcomes of patients with and without carriers of BMPR2 gene mutations in IPAH. No available research highlights this problem in an ethnic group of Kazakhs. Materials and methods: A total of 53 patients of only Kazakh nationality with IPAH participated in the study. Clinical, functional, and hemodynamic characteristics, as well as the outcome of the disease, were compared among carriers and non-carriers of the BMPR2 mutation. Results: When receiving IPAH diagnosis, the average age of patients was 40.0 (32.0–48.0) years. Women predominated among the patients (86.8%). Of these, 17 (32.0%) were carriers of the gene mutation, and 36 (68.0%) did not have this mutation. The results of our research demonstrate that the Rs17199249 variant in BMPR2 contributed to increased susceptibility to IPAH. The T allele was associated with an increased risk of IPAH, with T = 75 (70.75%), G = 31 (29.24%), MAF—0.2925, x2—0.001, and HWE p—0.975. Carriers of the BMPR2 mutation were predominantly women (80.0%), and they had higher pulmonary vascular resistance (8.7–14.9 vs. 5.9–12.6 WU; p = 0.038), a low cardiac index (1.9–2.6 vs. 2.3–3.1 L/min per m2; p = 0.027), and a shorter time to death (p = 0.022). Conclusions: This is the first study of the genetic causes of IPAH that demonstrates the genetic polymorphism of BMPR2 is associated with an increased risk of IPAH developing with worse hemodynamic parameters and clinical outcomes. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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<p>Kaplan–Meier survival curves according to BMPR2 mutation status. Total patients.</p>
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<p>Kaplan–Meier survival curves according to BMPR2 mutation status among female patients.</p>
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12 pages, 6329 KiB  
Article
Pilot Data Suggest That Obesity and Presence of Malignancy Are Associated with Altered Immune Cell Infiltration in Endometrial Biopsies
by Eline Jacques, Anouk van den Bosch, Peggy de Vos van Steenwijk, Loes Kooreman, Bert Delvoux, Andrea Romano and Henrica Werner
J. Clin. Med. 2024, 13(23), 7248; https://doi.org/10.3390/jcm13237248 (registering DOI) - 28 Nov 2024
Viewed by 357
Abstract
(1) Background: The worldwide endometrial cancer (EC) incidence is rising, amongst others linked to obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome, possibly due to low-grade adipose tissue inflammation. We studied immune cell infiltration in the endometrium in relation to diagnosis [...] Read more.
(1) Background: The worldwide endometrial cancer (EC) incidence is rising, amongst others linked to obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome, possibly due to low-grade adipose tissue inflammation. We studied immune cell infiltration in the endometrium in relation to diagnosis and obesity. (2) Methods: A cohort was created (n = 44) from postmenopausal women, lean (n = 15) and obese (n = 29), with bleeding complaints due to EC (n = 18) or benign pathology (n = 26). Endometrial biopsies were used to study the immune microenvironment and stained for macrophages (CD68 and CD163), T-cells (CD3 and CD8), and NK-cells (CD56). (3) Results: Malignant samples showed reduced intraepithelial CD3+ and CD8+ T-cells and increased stromal CD3+ T-cells. In obese patients, increased intraepithelial CD3+ and CD8+ T-cells were detected, especially in obese patients with T2DM. Epithelial CD56+ NK-cells were depleted in EC; however, no effect of obesity on NK-cell infiltration was observed. Stromal CD68+ cells were reduced in EC patients, whereas the CD163+ cells were increased. (4) Conclusions: Obesity and malignancy are associated with differences in immune cell presence. The alterations in immune cell infiltration seen in obese EC patients with and without diabetes suggest a complex interaction where obesity-related low-grade inflammation plays a central role. Full article
(This article belongs to the Special Issue Endometrial Cancer: State-of-the-Art and Clinical Perspective)
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<p><b>Flowchart of patient inclusion</b>. Patients with postmenopausal blood loss divided by benign or malignant result on pathological examination of pipelle or biopsy and BMI groups in 2020. Because of a too-small sample size, four slender patients with a malignancy diagnosed before 2020 were added. ET, endometrial thickness; BMI, body mass index (kg/m<sup>2</sup>); MMR, mismatch repair. Multiple exclusion criteria are applicable to some patients.</p>
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<p>(<b>A</b>) Immune cell presence in endometrial epithelium and stroma. Example of immunohistochemical staining of CD3, CD8, CD68, CD56, and CD163 in an endometrioid adenocarcinoma. (<b>B</b>) QuPath analysis of immune cell presence and distribution. The identification of immune cells and recognition of stroma and epithelium by QuPath software (Version 0.3.2 QuPath, Northern Ireland, UK ) is shown. Stromal cells are green, and epithelial cells are purple. Immune cells located in the stroma and epithelium are dark green and dark purple, respectively (indicated by the arrows). Scale bars = 100 µm.</p>
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<p><b>Epithelial immune cell infiltration by diagnosis, BMI, and presence of diabetes.</b> Number of CD3-, CD8-, CD56-, CD68-, and CD163-positive immune cells per mm<sup>2</sup> epithelium in (<b>A</b>) patients with a benign vs. malignant cause of postmenopausal blood loss, (<b>B</b>) patients with a normal BMI or obesity and benign or malignant cause of postmenopausal blood loss, and (<b>C</b>) lean vs. obese patients with a malignancy with and without the presence of diabetes type 2. BMI, body mass index (kg/m<sup>2</sup>); T2DM, type 2 diabetes mellitus. * <span class="html-italic">p</span> &lt; 0.05. Mild (1.5 × interquartile range) and extreme outliers (3.0 × interquartile range) are represented respectively by solid and hollow dots.</p>
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16 pages, 2884 KiB  
Systematic Review
Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis
by Ting-Jui Hsu, Rong-Hong Hsieh, Chin-Huan Huang, Chih-Shou Chen, Wei-Yu Lin, Yun-Ching Huang, Jian-Hui Lin, Kuo-Tsai Huang, Yu-Liang Liu, Hui-Ming Tsai and Dong-Ru Ho
Nutrients 2024, 16(23), 4116; https://doi.org/10.3390/nu16234116 - 28 Nov 2024
Viewed by 208
Abstract
Background/Objectives: Primary dysmenorrhea (PD) is a common condition affecting up to 90% of menstruating women, which often results in significant pain without an underlying pathology. Zinc, recognized for its anti-inflammatory and antioxidant effects through inhibiting prostaglandin production and superoxide dismutase 1 (SOD1) upregulation, [...] Read more.
Background/Objectives: Primary dysmenorrhea (PD) is a common condition affecting up to 90% of menstruating women, which often results in significant pain without an underlying pathology. Zinc, recognized for its anti-inflammatory and antioxidant effects through inhibiting prostaglandin production and superoxide dismutase 1 (SOD1) upregulation, alleviates menstrual pain by preventing uterine spasms and enhancing microcirculation in the endometrium, suggesting its potential as an alternative treatment for primary dysmenorrhea. The goal of this systematic review and meta-analysis was to assess the efficacy and safety of zinc supplementation in reducing pain severity among women with PD and to explore the influence of dosage and treatment duration. Methods: Following the PRISMA 2020 guidelines, we conducted an extensive search across databases such as PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar, up to May 2024. Randomized controlled trials assessing the effects of zinc supplementation on pain severity in women with PD were included. Pain severity was evaluated with established tools, such as the Visual Analog Scale (VAS). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool. Two reviewers independently performed the data extraction, and a random-effects model was used for meta-analysis. Meta-regressions were conducted to examine the influence of zinc dosage and treatment duration on pain reduction. Adverse events were also analyzed. Results: Six RCTs involving 739 participants met the inclusion criteria. Zinc supplementation significantly reduced pain severity compared to placebo (Hedges’s g = −1.541; 95% CI: −2.268 to −0.814; p < 0.001), representing a clinically meaningful reduction in pain. Meta-regression indicated that longer treatment durations (≥8 weeks) were associated with greater pain reduction (p = 0.003). While higher zinc doses provided additional pain relief, the incremental benefit per additional milligram was modest (regression coefficient = −0.02 per mg; p = 0.005). Adverse event rates did not differ significantly between the zinc and placebo groups (odds ratio = 2.54; 95% CI: 0.78 to 8.26; p = 0.122), suggesting good tolerability. Conclusions: Zinc supplementation is an effective and well-tolerated option for reducing pain severity in women with primary dysmenorrhea. Doses as low as 7 mg/day of elemental zinc are sufficient to achieve significant pain relief, with longer durations (≥8 weeks) enhancing efficacy. The favorable safety profile and ease of use support the consideration of zinc supplementation as a practical approach to managing primary dysmenorrhea. Full article
(This article belongs to the Special Issue Nutritional Effects on Women’s Reproductive Health and Disease)
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<p>PRISMA 2020 diagram summarizing the study selection process for this meta-analysis.</p>
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<p>Quality assessment summary for studies included in the meta-analysis, evaluated using the Cochrane Risk of Bias 2 tool.</p>
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<p>Forest plot showing the overall effect of zinc supplementation on pain severity using the longest follow-up data [<a href="#B12-nutrients-16-04116" class="html-bibr">12</a>,<a href="#B13-nutrients-16-04116" class="html-bibr">13</a>,<a href="#B23-nutrients-16-04116" class="html-bibr">23</a>,<a href="#B24-nutrients-16-04116" class="html-bibr">24</a>,<a href="#B25-nutrients-16-04116" class="html-bibr">25</a>,<a href="#B26-nutrients-16-04116" class="html-bibr">26</a>].</p>
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<p>Forest plot for the subgroup analysis using the follow-up duration as the moderator, including one, two, and three months. The directions of association between zinc supplementation and pain scale assessment were consistent across all follow-up durations, with overlapping 95% confidence intervals (CIs), indicating similar trends in pain reduction over time despite varying levels of statistical significance and heterogeneity [<a href="#B12-nutrients-16-04116" class="html-bibr">12</a>,<a href="#B13-nutrients-16-04116" class="html-bibr">13</a>,<a href="#B23-nutrients-16-04116" class="html-bibr">23</a>,<a href="#B24-nutrients-16-04116" class="html-bibr">24</a>,<a href="#B25-nutrients-16-04116" class="html-bibr">25</a>,<a href="#B26-nutrients-16-04116" class="html-bibr">26</a>].</p>
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<p>Meta-regression of Hedges’s g versus treatment duration (month). The coefficient was −0.452 with a <span class="html-italic">p</span> value &lt; 0.001.</p>
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<p>Meta-regression of Hedges’s g against daily dose (mg/day). Coefficient = −0.02; <span class="html-italic">p</span> = 0.005.</p>
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<p>Sensitivity analysis using the one-study removal method. The primary outcome remained consistent after excluding each individual trial. Zinc supplementation consistently showed significant pain reduction [<a href="#B12-nutrients-16-04116" class="html-bibr">12</a>,<a href="#B13-nutrients-16-04116" class="html-bibr">13</a>,<a href="#B23-nutrients-16-04116" class="html-bibr">23</a>,<a href="#B24-nutrients-16-04116" class="html-bibr">24</a>,<a href="#B25-nutrients-16-04116" class="html-bibr">25</a>,<a href="#B26-nutrients-16-04116" class="html-bibr">26</a>].</p>
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<p>Funnel plot of included studies displaying asymmetrical distribution, suggesting potential publication bias.</p>
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<p>Forest plot of adverse event rates associated with treatment. No significant difference was observed between the two groups (<span class="html-italic">p</span> = 0.122) [<a href="#B12-nutrients-16-04116" class="html-bibr">12</a>,<a href="#B13-nutrients-16-04116" class="html-bibr">13</a>,<a href="#B23-nutrients-16-04116" class="html-bibr">23</a>].</p>
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