Pub Date : 2025-11-26DOI: 10.3390/diseases13120384
Jael Del Rosario Eb-Rejón, José Ramón Paniagua-Sierra, Carlos Gracida-Osorno, Gloria María Molina-Salinas
Background: Acinetobacter baumannii is classified within the ESKAPE-E group of pathogens, recognized for its role in causing severe infections, and is often associated with various healthcare-related infection (HAIs) types, particularly in intensive care units. This opportunistic pathogen is distinguished by its considerable antibiotic resistance and is associated with prolonged hospital stays, high medical costs, and increased mortality rates.
Objective: This study investigated factors associated with HAIs caused by A. baumannii, versus other ESKAPE-E pathogens, to identify distinguishing intrinsic and extrinsic factors that guide the control and prevention of HAIs within our hospital.
Methods: This study included patients from a Third-Level IMSS Hospital in Mérida, Mexico, between 2018 and 2022, with 54 cases (HAIs caused by A. baumannii) and 108 matched controls (HAIs caused by other ESKAPE-E pathogens).
Results: Ventilator-associated pneumonia was the most frequent HAI in both groups, followed by catheter-related bloodstream infections. Comorbidities were more common in patients with HAIs caused by A. baumannii than in those with other ESKAPE-E pathogens. Most patients received antimicrobial treatment before HAIs development. Bivariate analysis showed that comorbidities and prior meropenem and linezolid treatment were significant risk factors, whereas multivariate analysis identified comorbidities and prior meropenem use as risk factors for A. baumannii HAIs versus other ESKAPE-E pathogens. Most A. baumannii isolates were extensively drug-resistant (90.7%), with 84% showing carbapenem resistance.
Conclusions: This study highlights the importance of optimizing antimicrobial use and measures to mitigate A. baumannii HAIs. These findings have significant implications for infection control and antimicrobial stewardship in healthcare settings.
{"title":"Hospital-Acquired Infections Caused by <i>Acinetobacter baumannii</i>: A Comparative Analysis of Risk Factors with Other ESKAPE-E Pathogens in a Third-Level IMSS Hospital in Yucatan Mexico.","authors":"Jael Del Rosario Eb-Rejón, José Ramón Paniagua-Sierra, Carlos Gracida-Osorno, Gloria María Molina-Salinas","doi":"10.3390/diseases13120384","DOIUrl":"10.3390/diseases13120384","url":null,"abstract":"<p><strong>Background: </strong><i>Acinetobacter baumannii</i> is classified within the ESKAPE-E group of pathogens, recognized for its role in causing severe infections, and is often associated with various healthcare-related infection (HAIs) types, particularly in intensive care units. This opportunistic pathogen is distinguished by its considerable antibiotic resistance and is associated with prolonged hospital stays, high medical costs, and increased mortality rates.</p><p><strong>Objective: </strong>This study investigated factors associated with HAIs caused by <i>A. baumannii</i>, versus other ESKAPE-E pathogens, to identify distinguishing intrinsic and extrinsic factors that guide the control and prevention of HAIs within our hospital.</p><p><strong>Methods: </strong>This study included patients from a Third-Level IMSS Hospital in Mérida, Mexico, between 2018 and 2022, with 54 cases (HAIs caused by <i>A. baumannii</i>) and 108 matched controls (HAIs caused by other ESKAPE-E pathogens).</p><p><strong>Results: </strong>Ventilator-associated pneumonia was the most frequent HAI in both groups, followed by catheter-related bloodstream infections. Comorbidities were more common in patients with HAIs caused by <i>A. baumannii</i> than in those with other ESKAPE-E pathogens. Most patients received antimicrobial treatment before HAIs development. Bivariate analysis showed that comorbidities and prior meropenem and linezolid treatment were significant risk factors, whereas multivariate analysis identified comorbidities and prior meropenem use as risk factors for <i>A. baumannii</i> HAIs versus other ESKAPE-E pathogens. Most <i>A. baumannii</i> isolates were extensively drug-resistant (90.7%), with 84% showing carbapenem resistance.</p><p><strong>Conclusions: </strong>This study highlights the importance of optimizing antimicrobial use and measures to mitigate <i>A. baumannii</i> HAIs. These findings have significant implications for infection control and antimicrobial stewardship in healthcare settings.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12732213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.3390/diseases13120383
Begoña Rochina-Rodríguez, Francisco Miguel Martínez-Arnau, Pilar Pérez-Ros
Background: Delirium onset is associated with increased comorbidity and mortality. Identifying reliable delirium biomarkers remains challenging. Regional cerebral oxygen saturation (rSO2) offers an objective, easily obtainable measure suitable for hospital monitoring. Objective: We aimed to analyse the relationship between regional cerebral oxygen saturation (rSO2) values obtained by near-infrared spectroscopy (NIRS) and the subsequent development of delirium. Methods: Studies eligible for inclusion in our systematic review evaluated rSO2 values obtained by NIRS or a used a similar method to study hospitalised patients aged 18 years or older, some of whom subsequently developed delirium. We searched MEDLINE, Scopus and Web of Science without restrictions to 24 March 2024. Two review authors independently assessed the methodological quality of the included studies using Joanna Briggs Institute Critical Appraisal tools. Using a random-effects model in RevMan v 5.4.0 (Cochrane Collaboration, Oxford, UK), we analysed baseline and minimum rSO2 values. Results were presented as means and mean differences (MDs) with their 95% confidence intervals (CIs). We followed PRISMA guidelines and registered our review protocol in PROSPERO (CRD42024523573). Results (or Findings): We included 22 studies (20 in the meta-analysis) published between 2009 and 2024 and involving 5757 participants. The delirium group had a lower mean baseline rSO2 value (62.47%, 95% CI 58.40 to 66.55) compared with the non-delirium group (64.24%, 95% CI 61.33 to 67.15). Meta-analysis of effect estimates confirmed this result (MD -2.92%, 95% CI -4.38 to -1.47). The MD between the delirium and non-delirium group was larger among patients assessed with the INVOS device and patients who underwent cardiac surgery. Studies that analysed baseline values according to sensor location showed a larger MD in rSO2 values obtained via a right-sided sensor. Conclusions: Our results show lower baseline and minimum rSO2 in hospitalised patients who subsequently developed delirium. The difference varies according to the type of surgery and type of NIRS monitor.
背景:谵妄发作与增加的合并症和死亡率有关。确定可靠的谵妄生物标志物仍然具有挑战性。区域脑氧饱和度(rSO2)是一种客观、容易获得的指标,适用于医院监测。目的:分析近红外光谱(NIRS)测定的区域脑氧饱和度(rSO2)值与谵妄后续发展的关系。方法:有资格纳入我们系统评价的研究评估了近红外光谱获得的rSO2值,或使用类似的方法研究18岁或以上的住院患者,其中一些患者随后出现谵妄。我们检索MEDLINE、Scopus和Web of Science,检索截止日期为2024年3月24日。两位综述作者使用乔安娜布里格斯研究所关键评估工具独立评估纳入研究的方法学质量。使用RevMan v 5.4.0 (Cochrane Collaboration, Oxford, UK)中的随机效应模型,我们分析了基线和最小rSO2值。结果以均值和均值差异(MDs)及其95%置信区间(ci)表示。我们遵循PRISMA指南,并在PROSPERO注册了我们的审查方案(CRD42024523573)。结果(或发现):我们纳入了2009年至2024年间发表的22项研究(其中20项为荟萃分析),涉及5757名参与者。谵妄组的平均基线rSO2值(62.47%,95% CI 58.40 ~ 66.55)低于非谵妄组(64.24%,95% CI 61.33 ~ 67.15)。效应估计的荟萃分析证实了这一结果(MD -2.92%, 95% CI -4.38至-1.47)。在使用INVOS装置评估的患者和接受心脏手术的患者中,谵妄组和非谵妄组之间的MD更大。根据传感器位置分析基线值的研究显示,通过右侧传感器获得的rSO2值的MD较大。结论:我们的研究结果显示,住院患者随后出现谵妄的基线和最低rSO2较低。根据手术类型和近红外光谱监测仪的类型,差异有所不同。
{"title":"Regional Cerebral Oxygen Saturation and Risk of Delirium: A Systematic Review and Meta-Analysis.","authors":"Begoña Rochina-Rodríguez, Francisco Miguel Martínez-Arnau, Pilar Pérez-Ros","doi":"10.3390/diseases13120383","DOIUrl":"10.3390/diseases13120383","url":null,"abstract":"<p><p><b>Background:</b> Delirium onset is associated with increased comorbidity and mortality. Identifying reliable delirium biomarkers remains challenging. Regional cerebral oxygen saturation (rSO<sub>2</sub>) offers an objective, easily obtainable measure suitable for hospital monitoring. <b>Objective:</b> We aimed to analyse the relationship between regional cerebral oxygen saturation (rSO<sub>2</sub>) values obtained by near-infrared spectroscopy (NIRS) and the subsequent development of delirium. <b>Methods:</b> Studies eligible for inclusion in our systematic review evaluated rSO<sub>2</sub> values obtained by NIRS or a used a similar method to study hospitalised patients aged 18 years or older, some of whom subsequently developed delirium. We searched MEDLINE, Scopus and Web of Science without restrictions to 24 March 2024. Two review authors independently assessed the methodological quality of the included studies using Joanna Briggs Institute Critical Appraisal tools. Using a random-effects model in RevMan v 5.4.0 (Cochrane Collaboration, Oxford, UK), we analysed baseline and minimum rSO<sub>2</sub> values. Results were presented as means and mean differences (MDs) with their 95% confidence intervals (CIs). We followed PRISMA guidelines and registered our review protocol in PROSPERO (CRD42024523573). <b>Results (or Findings):</b> We included 22 studies (20 in the meta-analysis) published between 2009 and 2024 and involving 5757 participants. The delirium group had a lower mean baseline rSO<sub>2</sub> value (62.47%, 95% CI 58.40 to 66.55) compared with the non-delirium group (64.24%, 95% CI 61.33 to 67.15). Meta-analysis of effect estimates confirmed this result (MD -2.92%, 95% CI -4.38 to -1.47). The MD between the delirium and non-delirium group was larger among patients assessed with the INVOS device and patients who underwent cardiac surgery. Studies that analysed baseline values according to sensor location showed a larger MD in rSO<sub>2</sub> values obtained via a right-sided sensor. <b>Conclusions:</b> Our results show lower baseline and minimum rSO<sub>2</sub> in hospitalised patients who subsequently developed delirium. The difference varies according to the type of surgery and type of NIRS monitor.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12731443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.3390/diseases13120382
Wei-Hung Chang, Ting-Yu Hu, Li-Kuo Kuo
Neutropenic patients with acute myeloid leukemia (AML) are at high risk for severe, multidrug-resistant infections. Sepsis due to carbapenem-resistant Pseudomonas aeruginosa (CRPA) in this population often leads to septic shock and acute respiratory distress syndrome (ARDS), with historically poor outcomes. CytoSorb™ hemoadsorption has been proposed as an adjunctive therapy for refractory septic shock, but evidence in hematologic malignancies remains limited. This report describes a 29-year-old male with newly diagnosed AML complicated by neutropenic fever, bacteremia due to CRPA, and subsequent hospital-acquired pneumonia progressing to ARDS. Despite multiple antibiotic regimens and aggressive intensive care management, including mechanical ventilation, prone positioning, and continuous renal replacement therapy (CRRT), the patient developed refractory septic shock with persistent lactic acidosis and elevated inflammatory markers. Early adjunctive CytoSorb hemoadsorption was initiated, guided by maximal CytoScore criteria, as part of a comprehensive supportive strategy. Following CytoSorb therapy, the patient demonstrated transient hemodynamic and biochemical improvement; however, profound neutropenia and multi-organ failure persisted. Microbiological clearance of CRPA was not achieved; given confirmed colistin susceptibility and unknown carbapenemase mechanism, a salvage combination of colistin plus ceftazidime-avibactam was employed. Transient hemodynamic improvement was observed after CytoSorb initiation; however, cytokine assays were not performed, and microbiological clearance was not achieved, precluding any mechanistic attribution to CytoSorb. This case highlights the complexity of managing CRPA sepsis and ARDS in neutropenic AML patients, and the challenges in attributing observed clinical improvement to CytoSorb therapy in the context of multiple simultaneous interventions. The absence of cytokine assays (e.g., IL-6, TNF-α) precludes any mechanistic attribution of observed changes to cytokine adsorption, and interpretation should remain descriptive rather than causal. Observed transient changes occurred amid simultaneous interventions (broad-spectrum antibiotics, CRRT, prone ventilation, corticosteroids, and filgrastim), precluding attribution to any single therapy, including CytoSorb. Given the fatal outcome and persistent CRPA positivity, the clinical impact of this observation is limited, and the generalizability of a single-case report is restricted. Cautious interpretation is warranted, and CytoSorb may be considered as part of a comprehensive care bundle rather than as a standalone solution. Alternative tetracycline-based combinations were reviewed but not adopted under our center's salvage protocol for this XDR presentation. Future studies are warranted to clarify its clinical benefit and optimal timing in this population.
{"title":"Early CytoSorb Hemoadsorption in a Neutropenic Acute Myeloid Leukemia Patient with Carbapenem-Resistant <i>Pseudomonas</i> Septic Shock and ARDS.","authors":"Wei-Hung Chang, Ting-Yu Hu, Li-Kuo Kuo","doi":"10.3390/diseases13120382","DOIUrl":"10.3390/diseases13120382","url":null,"abstract":"<p><p>Neutropenic patients with acute myeloid leukemia (AML) are at high risk for severe, multidrug-resistant infections. Sepsis due to carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) in this population often leads to septic shock and acute respiratory distress syndrome (ARDS), with historically poor outcomes. CytoSorb™ hemoadsorption has been proposed as an adjunctive therapy for refractory septic shock, but evidence in hematologic malignancies remains limited. This report describes a 29-year-old male with newly diagnosed AML complicated by neutropenic fever, bacteremia due to CRPA, and subsequent hospital-acquired pneumonia progressing to ARDS. Despite multiple antibiotic regimens and aggressive intensive care management, including mechanical ventilation, prone positioning, and continuous renal replacement therapy (CRRT), the patient developed refractory septic shock with persistent lactic acidosis and elevated inflammatory markers. Early adjunctive CytoSorb hemoadsorption was initiated, guided by maximal CytoScore criteria, as part of a comprehensive supportive strategy. Following CytoSorb therapy, the patient demonstrated transient hemodynamic and biochemical improvement; however, profound neutropenia and multi-organ failure persisted. Microbiological clearance of CRPA was not achieved; given confirmed colistin susceptibility and unknown carbapenemase mechanism, a salvage combination of colistin plus ceftazidime-avibactam was employed. Transient hemodynamic improvement was observed after CytoSorb initiation; however, cytokine assays were not performed, and microbiological clearance was not achieved, precluding any mechanistic attribution to CytoSorb. This case highlights the complexity of managing CRPA sepsis and ARDS in neutropenic AML patients, and the challenges in attributing observed clinical improvement to CytoSorb therapy in the context of multiple simultaneous interventions. The absence of cytokine assays (e.g., IL-6, TNF-α) precludes any mechanistic attribution of observed changes to cytokine adsorption, and interpretation should remain descriptive rather than causal. Observed transient changes occurred amid simultaneous interventions (broad-spectrum antibiotics, CRRT, prone ventilation, corticosteroids, and filgrastim), precluding attribution to any single therapy, including CytoSorb. Given the fatal outcome and persistent CRPA positivity, the clinical impact of this observation is limited, and the generalizability of a single-case report is restricted. Cautious interpretation is warranted, and CytoSorb may be considered as part of a comprehensive care bundle rather than as a standalone solution. Alternative tetracycline-based combinations were reviewed but not adopted under our center's salvage protocol for this XDR presentation. Future studies are warranted to clarify its clinical benefit and optimal timing in this population.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12732260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Head and neck carcinomas represent a heterogeneous group of aggressive malignancies with often poor prognosis and high recurrence rates. In recent years, the identification and characterization of cancer stem cells (CSCs) within these tumors have profoundly reshaped our understanding of tumorigenesis, resistance mechanisms, and metastatic potential in this anatomical district. Cancer stem cells (CSCs) play a central role in therapeutic resistance, recurrence, and metastatic progression in head and neck squamous cell carcinoma (HNSCC), particularly within the anatomically complex maxillofacial region. This review has synthesized recent advances in CSC biology, including marker heterogeneity, stemness-associated pathways, and interactions with the tumor microenvironment. Methods: A narrative review of the available literature was conducted, focusing on studies dealing with cancer stem cells in head and neck carcinoma and their implications for maxillofacial surgery. Results: We have critically examined emerging systemic and locoregional CSC-targeted therapies, highlighting inhibitors of Notch, Wnt/β-catenin, Hedgehog, and Hippo/YAP pathways, ALDH and ABC transporter inhibitors, autophagy modulators, nanoparticle-based delivery systems, and CSC-directed immunotherapies. The implications of these approaches for surgical planning, resection margins, and postoperative disease control in maxillofacial oncology have been discussed. To enhance clarity and analytical value, we have incorporated two comprehensive tables summarizing CSC markers and therapeutic strategies. Collectively, the evidence indicates that integrating CSC-oriented diagnostics and therapeutics into multimodal management may improve long-term outcomes for patients with maxillofacial HNSCC. Conclusions: This review highlights the critical need for integrating CSC-focused research into clinical practice to develop more effective, personalized, and durable treatment strategies. Such an approach could enhance oncologic control, reduce recurrence, and improve functional outcomes for patients undergoing complex oncologic procedures in the maxillofacial region.
{"title":"Biological and Therapeutic Roles of Stem Cells in Head and Neck Carcinoma: Implications for Maxillofacial Surgery.","authors":"Luca Michelutti, Alessandro Tel, Marco Zeppieri, Chiara Martinazzo, Massimo Robiony, Caterina Gagliano, Fabiana D'Esposito, Matteo Capobianco, Marieme Khouyyi","doi":"10.3390/diseases13120381","DOIUrl":"10.3390/diseases13120381","url":null,"abstract":"<p><p><b>Background</b>: Head and neck carcinomas represent a heterogeneous group of aggressive malignancies with often poor prognosis and high recurrence rates. In recent years, the identification and characterization of cancer stem cells (CSCs) within these tumors have profoundly reshaped our understanding of tumorigenesis, resistance mechanisms, and metastatic potential in this anatomical district. Cancer stem cells (CSCs) play a central role in therapeutic resistance, recurrence, and metastatic progression in head and neck squamous cell carcinoma (HNSCC), particularly within the anatomically complex maxillofacial region. This review has synthesized recent advances in CSC biology, including marker heterogeneity, stemness-associated pathways, and interactions with the tumor microenvironment. <b>Methods</b>: A narrative review of the available literature was conducted, focusing on studies dealing with cancer stem cells in head and neck carcinoma and their implications for maxillofacial surgery. <b>Results</b>: We have critically examined emerging systemic and locoregional CSC-targeted therapies, highlighting inhibitors of Notch, Wnt/β-catenin, Hedgehog, and Hippo/YAP pathways, ALDH and ABC transporter inhibitors, autophagy modulators, nanoparticle-based delivery systems, and CSC-directed immunotherapies. The implications of these approaches for surgical planning, resection margins, and postoperative disease control in maxillofacial oncology have been discussed. To enhance clarity and analytical value, we have incorporated two comprehensive tables summarizing CSC markers and therapeutic strategies. Collectively, the evidence indicates that integrating CSC-oriented diagnostics and therapeutics into multimodal management may improve long-term outcomes for patients with maxillofacial HNSCC. <b>Conclusions</b>: This review highlights the critical need for integrating CSC-focused research into clinical practice to develop more effective, personalized, and durable treatment strategies. Such an approach could enhance oncologic control, reduce recurrence, and improve functional outcomes for patients undergoing complex oncologic procedures in the maxillofacial region.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12731832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.3390/diseases13110380
Sehar Iqbal, Zoha Imtiaz Malik, Maher Al Dabbas, Ishmal Akhtar, Aya Hussein
Background: Zinc deficiency is a major global health issue and appears to be responsible for risk of diarrhea and death, particularly in children under 5 years. This review therefore aimed to summarize the existing literature related to zinc supplementation and fortification for the prevention of diarrhea.
Methods: In this literature review, we discussed the zinc-related biochemistry and pathophysiology of diarrhea and role of zinc in reducing the risk of diarrhea in children. Moreover, this literature review particularly analyzed studies published between 2014 and 2025, including systematic reviews, meta-analyses, and randomized controlled trials focusing on zinc fortification and supplementation for the prevention of childhood diarrhea. The studies covered a range of zinc dosing regimens (5-20 mg daily), preventive and therapeutic approaches, and combined interventions in children. Main outcomes such as diarrhea duration, severity, recurrence, growth, and side effects were assessed across diverse low- and middle-income populations.
Results: Routine zinc supplementation helps to reduce all-cause diarrhea and respiratory infections. Zinc supplementation consistently reduced both the duration and severity of diarrhea in children. Also, diarrhea episodes and frequency were reduced in children taking zinc supplementation. Lower doses (5-10 mg) were mostly recommended to reduce vomiting. Combined zinc and vitamin A supplementation further improved outcomes, while long-term low-dose zinc supplementation prevented diarrhea and infections.
Conclusion: This review confirms that zinc supplementation and fortification are effective, affordable strategies for reducing childhood diarrhea. Supplementation during diarrheal episodes reliably shortens duration and severity, with long-term benefits lasting for months. Continued research and integrated approaches for dosing and delivery are needed for both low- and middle-income countries.
{"title":"Zinc Fortification and Supplementation to Reduce Diarrhea in Children: A Literature Review.","authors":"Sehar Iqbal, Zoha Imtiaz Malik, Maher Al Dabbas, Ishmal Akhtar, Aya Hussein","doi":"10.3390/diseases13110380","DOIUrl":"10.3390/diseases13110380","url":null,"abstract":"<p><strong>Background: </strong>Zinc deficiency is a major global health issue and appears to be responsible for risk of diarrhea and death, particularly in children under 5 years. This review therefore aimed to summarize the existing literature related to zinc supplementation and fortification for the prevention of diarrhea.</p><p><strong>Methods: </strong>In this literature review, we discussed the zinc-related biochemistry and pathophysiology of diarrhea and role of zinc in reducing the risk of diarrhea in children. Moreover, this literature review particularly analyzed studies published between 2014 and 2025, including systematic reviews, meta-analyses, and randomized controlled trials focusing on zinc fortification and supplementation for the prevention of childhood diarrhea. The studies covered a range of zinc dosing regimens (5-20 mg daily), preventive and therapeutic approaches, and combined interventions in children. Main outcomes such as diarrhea duration, severity, recurrence, growth, and side effects were assessed across diverse low- and middle-income populations.</p><p><strong>Results: </strong>Routine zinc supplementation helps to reduce all-cause diarrhea and respiratory infections. Zinc supplementation consistently reduced both the duration and severity of diarrhea in children. Also, diarrhea episodes and frequency were reduced in children taking zinc supplementation. Lower doses (5-10 mg) were mostly recommended to reduce vomiting. Combined zinc and vitamin A supplementation further improved outcomes, while long-term low-dose zinc supplementation prevented diarrhea and infections.</p><p><strong>Conclusion: </strong>This review confirms that zinc supplementation and fortification are effective, affordable strategies for reducing childhood diarrhea. Supplementation during diarrheal episodes reliably shortens duration and severity, with long-term benefits lasting for months. Continued research and integrated approaches for dosing and delivery are needed for both low- and middle-income countries.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12651211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/objectives: A decrease in serum AMH is generally associated with low ovarian response in assisted reproductive procedures, whether or not in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is performed.
Methods: We report a case involving a 31-year-old woman who had never been pregnant and with irregular menstrual cycles. An ultrasound scan performed on the second day of the cycle showed several annular follicles, a high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio suggesting polycystic ovary syndrome (PCOS), and an undetectable serum level of AMH.
Results: Despite these observations, she exhibited an unpredictable hyperresponse during controlled ovarian stimulation, followed by a failed pregnancy despite successful in vitro fertilization with ICSI and a good-quality thawed embryo transfer (4AA).
Conclusions: This case highlights the challenges of relying solely on AMH as a predictive marker of ovarian response. Although AMH is widely used for assessing ovarian reserve and stimulation outcomes, its limitations become evident in atypical cases. The paradoxical hyperresponse observed here may result from alternative regulatory mechanisms influenced by elevated LH levels, enhanced gonadotropin receptor sensitivity, or local ovarian factors. This report underscores the need for a personalized, multidimensional approach combining hormonal profiles, ultrasound assessments, and clinical history to optimize stimulation protocols and mitigate risks such as ovarian hyperstimulation syndrome (OHSS). Such tailored protocols are essential for managing patients with complex profiles, particularly those with undetectable AMH levels. Further research is needed to explore the mechanisms behind these atypical ovarian responses, including the roles of genetic polymorphisms, inflammatory markers, and environmental factors. This case demonstrates the importance of cautious interpretation of AMH results and emphasizes the value of comprehensive evaluations in assisted reproductive technologies.
{"title":"Undetectable Serum Level of Anti-Müllerian Hormone (AMH) in a Woman with an Unpredictable Hyper-Response During Controlled Ovarian Stimulation for an IVF-ICSI Program: Case Report.","authors":"Omar Sefrioui, Modou Mamoune Mbaye, Ismail Kaarouch, Smahane Aboulmaouahib, Latifa Ahbbas, Omar Touzani, Noureddine Louanjli, Bouchra Ghazi","doi":"10.3390/diseases13110379","DOIUrl":"10.3390/diseases13110379","url":null,"abstract":"<p><strong>Background/objectives: </strong>A decrease in serum AMH is generally associated with low ovarian response in assisted reproductive procedures, whether or not in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is performed.</p><p><strong>Methods: </strong>We report a case involving a 31-year-old woman who had never been pregnant and with irregular menstrual cycles. An ultrasound scan performed on the second day of the cycle showed several annular follicles, a high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio suggesting polycystic ovary syndrome (PCOS), and an undetectable serum level of AMH.</p><p><strong>Results: </strong>Despite these observations, she exhibited an unpredictable hyperresponse during controlled ovarian stimulation, followed by a failed pregnancy despite successful in vitro fertilization with ICSI and a good-quality thawed embryo transfer (4AA).</p><p><strong>Conclusions: </strong>This case highlights the challenges of relying solely on AMH as a predictive marker of ovarian response. Although AMH is widely used for assessing ovarian reserve and stimulation outcomes, its limitations become evident in atypical cases. The paradoxical hyperresponse observed here may result from alternative regulatory mechanisms influenced by elevated LH levels, enhanced gonadotropin receptor sensitivity, or local ovarian factors. This report underscores the need for a personalized, multidimensional approach combining hormonal profiles, ultrasound assessments, and clinical history to optimize stimulation protocols and mitigate risks such as ovarian hyperstimulation syndrome (OHSS). Such tailored protocols are essential for managing patients with complex profiles, particularly those with undetectable AMH levels. Further research is needed to explore the mechanisms behind these atypical ovarian responses, including the roles of genetic polymorphisms, inflammatory markers, and environmental factors. This case demonstrates the importance of cautious interpretation of AMH results and emphasizes the value of comprehensive evaluations in assisted reproductive technologies.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12651738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.3390/diseases13110378
Luigi Citrigno, Annamaria Cerantonio, Ludovico Neri, Pierluigi Sebastiani, Alessia Colanardi, Gabriele Turacchio, Tiziana Del Beato, Beatrice Marziani, Anna Aureli
Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently accompanied by behavioral dysregulation. While genetic factors involving monoaminergic systems have been implicated, emerging evidence suggests a role for mitochondrial dysfunction in ADHD pathophysiology. Mitochondrial DNA copy number (mtDNA-cn), a surrogate marker of mitochondrial biogenesis and cellular energy demand, may reflect underlying neurobiological alterations and oxidative stress-related mechanisms relevant to ADHD.
Methods: We assessed mtDNA-cn in the peripheral blood of 56 Italian children and adolescents with ADHD and 27 age- and sex-matched healthy controls. ADHD symptoms and aggressive behavior were evaluated using DSM-5 criteria and the Conners' 3 Rating Scales. Genotyping was performed for MAOA (rs6323, rs1137070) and 5-HTT (rs4795541) polymorphisms.
Results: ADHD patients showed significantly higher mtDNA-cn than controls (p = 0.002), supporting mitochondrial dysregulation. Comparing the ADHD patient subgroups with aggressive behavior and those without, a non-significant reduction in mtDNA-cn was observed in the first subgroup. Notably, individuals with the TT genotype (rs6323) or CC genotype (rs1137070) had significantly higher mtDNA-cn compared to controls with the same genotypes (p = 0.031). Similar increases were seen across all 5-HTT rs4795541 genotypes in ADHD patients.
Conclusions: Our findings suggest that mitochondrial alterations may contribute to ADHD pathophysiology. The association between mtDNA-cn and monoaminergic gene variants highlights a potential link between neurotransmitter metabolism, oxidative stress, and mitochondrial function. Thus, mtDNA-cn may serve as a peripheral biomarker and therapeutic target in ADHD.
{"title":"Exploring Mitochondrial DNA Copy Number in Italian Children with ADHD: Implications for Neurobiological Mechanisms.","authors":"Luigi Citrigno, Annamaria Cerantonio, Ludovico Neri, Pierluigi Sebastiani, Alessia Colanardi, Gabriele Turacchio, Tiziana Del Beato, Beatrice Marziani, Anna Aureli","doi":"10.3390/diseases13110378","DOIUrl":"10.3390/diseases13110378","url":null,"abstract":"<p><strong>Background: </strong>Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently accompanied by behavioral dysregulation. While genetic factors involving monoaminergic systems have been implicated, emerging evidence suggests a role for mitochondrial dysfunction in ADHD pathophysiology. Mitochondrial DNA copy number (mtDNA-cn), a surrogate marker of mitochondrial biogenesis and cellular energy demand, may reflect underlying neurobiological alterations and oxidative stress-related mechanisms relevant to ADHD.</p><p><strong>Methods: </strong>We assessed mtDNA-cn in the peripheral blood of 56 Italian children and adolescents with ADHD and 27 age- and sex-matched healthy controls. ADHD symptoms and aggressive behavior were evaluated using DSM-5 criteria and the Conners' 3 Rating Scales. Genotyping was performed for <i>MAOA</i> (rs6323, rs1137070) and 5-HTT (rs4795541) polymorphisms.</p><p><strong>Results: </strong>ADHD patients showed significantly higher mtDNA-cn than controls (<i>p</i> = 0.002), supporting mitochondrial dysregulation. Comparing the ADHD patient subgroups with aggressive behavior and those without, a non-significant reduction in mtDNA-cn was observed in the first subgroup. Notably, individuals with the TT genotype (rs6323) or CC genotype (rs1137070) had significantly higher mtDNA-cn compared to controls with the same genotypes (<i>p</i> = 0.031). Similar increases were seen across all 5-HTT rs4795541 genotypes in ADHD patients.</p><p><strong>Conclusions: </strong>Our findings suggest that mitochondrial alterations may contribute to ADHD pathophysiology. The association between mtDNA-cn and monoaminergic gene variants highlights a potential link between neurotransmitter metabolism, oxidative stress, and mitochondrial function. Thus, mtDNA-cn may serve as a peripheral biomarker and therapeutic target in ADHD.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12651835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.3390/diseases13110377
Dorina Stan, Dragoș Voicu, Pușica Zainea, Alexandra Toma, Anamaria Ciubară
Dental phobia is a disabling yet underdiagnosed condition that prevents many patients from seeking essential oral healthcare, leading to avoidable pain, disease progression, and reduced quality of life. Cognitive Behavioral Therapy (CBT) is the most widely supported psychological intervention for specific phobias and has demonstrated significant efficacy in reducing dental anxiety and avoidance. This narrative review synthesizes recent evidence on CBT applications for phobia management, with particular emphasis on dental settings. In addition to reviewing established mechanisms of CBT, this paper highlights emerging adjunctive approaches such as virtual reality, eye movement desensitization and reprocessing (EMDR), and hypnosis. Special attention is given to pediatric populations, trauma-exposed individuals, and patients with neurodevelopmental disorders, who are often underrepresented in clinical research. The findings underscore the central role of CBT in addressing dental phobia while identifying gaps in standardized protocols, long-term outcomes, and accessibility across diverse healthcare contexts. Future research should prioritize controlled trials, cultural adaptations, and the integration of psychological training into dental curricula to enhance the translation of evidence into everyday practice.
{"title":"Reframing Dental Anxiety: Cognitive Behavioral Therapy and Its Role in Phobia Treatment-A Narrative Review.","authors":"Dorina Stan, Dragoș Voicu, Pușica Zainea, Alexandra Toma, Anamaria Ciubară","doi":"10.3390/diseases13110377","DOIUrl":"10.3390/diseases13110377","url":null,"abstract":"<p><p>Dental phobia is a disabling yet underdiagnosed condition that prevents many patients from seeking essential oral healthcare, leading to avoidable pain, disease progression, and reduced quality of life. Cognitive Behavioral Therapy (CBT) is the most widely supported psychological intervention for specific phobias and has demonstrated significant efficacy in reducing dental anxiety and avoidance. This narrative review synthesizes recent evidence on CBT applications for phobia management, with particular emphasis on dental settings. In addition to reviewing established mechanisms of CBT, this paper highlights emerging adjunctive approaches such as virtual reality, eye movement desensitization and reprocessing (EMDR), and hypnosis. Special attention is given to pediatric populations, trauma-exposed individuals, and patients with neurodevelopmental disorders, who are often underrepresented in clinical research. The findings underscore the central role of CBT in addressing dental phobia while identifying gaps in standardized protocols, long-term outcomes, and accessibility across diverse healthcare contexts. Future research should prioritize controlled trials, cultural adaptations, and the integration of psychological training into dental curricula to enhance the translation of evidence into everyday practice.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12651226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-16DOI: 10.3390/diseases13110376
Tina Zavidić, Ema Dejhalla, David Zahirović
Background: Toxic shock syndrome (TSS) is a rare but potentially fatal condition most often caused by Staphylococcus aureus or Streptococcus pyogenes. However, other streptococcal species, including Streptococcus agalactiae (group B Streptococcus (GBS)), can also cause TSS, sometimes leading to severe complications, such as multiorgan failure.
Case description: We report the case of a 45-year-old woman who developed TSS associated with tampon use. She presented with fever, chills, hypotension, and leg pain, progressing rapidly to septic shock and multiorgan failure. Blood and urine cultures revealed S. agalactiae group B, while a gynecological examination identified Ureaplasma urealyticum and S. agalactiae. Imaging demonstrated bilateral pneumonic infiltrates and pleural effusion. The patient required intensive care, vasopressor support, and broad-spectrum antibiotic therapy, leading to full clinical recovery.
Discussion: Despite advances in tampon design, menstrual TSS remains a significant clinical concern. Early symptoms may be nonspecific, but rapid progression highlights the need for timely recognition and intervention. Although S. agalactiae is an uncommon cause of TSS, it should be considered in relevant clinical scenarios. Prompt empirical antibiotic therapy, followed by targeted treatment based on culture results, along with supportive intensive care, is essential to improve outcomes.
Conclusions: Menstrual TSS continues to pose a serious health risk. Physicians should maintain a high index of suspicion in tampon users presenting with fever, rash, and shock. Early diagnosis and rapid initiation of appropriate therapy are crucial to reducing morbidity and mortality.
{"title":"Toxic Shock Syndrome in a 45-Year-Old Woman Possibly Associated with Tampon Use: A Case Report of Multiorgan Failure Due to <i>Streptococcus agalactiae</i>.","authors":"Tina Zavidić, Ema Dejhalla, David Zahirović","doi":"10.3390/diseases13110376","DOIUrl":"10.3390/diseases13110376","url":null,"abstract":"<p><strong>Background: </strong>Toxic shock syndrome (TSS) is a rare but potentially fatal condition most often caused by <i>Staphylococcus aureus</i> or <i>Streptococcus pyogenes</i>. However, other streptococcal species, including <i>Streptococcus agalactiae (group B Streptococcus (GBS))</i>, can also cause TSS, sometimes leading to severe complications, such as multiorgan failure.</p><p><strong>Case description: </strong>We report the case of a 45-year-old woman who developed TSS associated with tampon use. She presented with fever, chills, hypotension, and leg pain, progressing rapidly to septic shock and multiorgan failure. Blood and urine cultures revealed <i>S. agalactiae group B</i>, while a gynecological examination identified <i>Ureaplasma urealyticum</i> and <i>S. agalactiae</i>. Imaging demonstrated bilateral pneumonic infiltrates and pleural effusion. The patient required intensive care, vasopressor support, and broad-spectrum antibiotic therapy, leading to full clinical recovery.</p><p><strong>Discussion: </strong>Despite advances in tampon design, menstrual TSS remains a significant clinical concern. Early symptoms may be nonspecific, but rapid progression highlights the need for timely recognition and intervention. Although <i>S. agalactiae</i> is an uncommon cause of TSS, it should be considered in relevant clinical scenarios. Prompt empirical antibiotic therapy, followed by targeted treatment based on culture results, along with supportive intensive care, is essential to improve outcomes.</p><p><strong>Conclusions: </strong>Menstrual TSS continues to pose a serious health risk. Physicians should maintain a high index of suspicion in tampon users presenting with fever, rash, and shock. Early diagnosis and rapid initiation of appropriate therapy are crucial to reducing morbidity and mortality.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12650958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-15DOI: 10.3390/diseases13110375
Maricela García-Avalos, Juana Canul-Reich, Lil María Xibai Rodríguez-Henríquez, Erick Natividad De la Cruz-Hernández
Background: This study developed a Causal Graphical Model (CGM) to analyze Bacterial Vaginosis (BV), a condition caused by an imbalance in the vaginal microbiota, whose bacterial composition varies among women. While previous studies used variable selection, clustering, and association rules to identify BV-associated bacteria, these approaches lack visual tools to explore causal relationships and determine which are the most relevant. In contrast, the CGM generated in this study allows visualization of associated bacteria and their causal links, thereby identifying those most influential.
Methods: Path Analysis (PA), a statistical structural equation modeling method, was used to construct the CGM, with emphasis on observable variables and to assess direct and indirect effects through correlations and covariances. PA was applied to an already-collected third-party dataset related to BV diagnosis, consisting of data from 132 pregnant women between 4 and 24 weeks of gestation.
Results: The CGM, built using a theoretical model based on the Spearman correlation matrix, was validated through statistical metrics and by a clinical-biological expert. The resultant model highlights bacteria influencing BV diagnosis, specifically Mycoplasma hominis (Mh), Atopobium vaginae (Av), Gardnerella vaginalis (Gv), Megasphaera Type 1 (MT1), and Bacteria Associated with Bacterial Vaginosis Type 2 (BVAB2). Among them, MT1 and BVAB2 showed the strongest association with BV.
Conclusions: The CGM effectively identifies causal associations among bacteria related to BV.
{"title":"Causal Graphical Model of Bacterial Vaginosis in Pregnant Women.","authors":"Maricela García-Avalos, Juana Canul-Reich, Lil María Xibai Rodríguez-Henríquez, Erick Natividad De la Cruz-Hernández","doi":"10.3390/diseases13110375","DOIUrl":"10.3390/diseases13110375","url":null,"abstract":"<p><strong>Background: </strong>This study developed a Causal Graphical Model (CGM) to analyze Bacterial Vaginosis (BV), a condition caused by an imbalance in the vaginal microbiota, whose bacterial composition varies among women. While previous studies used variable selection, clustering, and association rules to identify BV-associated bacteria, these approaches lack visual tools to explore causal relationships and determine which are the most relevant. In contrast, the CGM generated in this study allows visualization of associated bacteria and their causal links, thereby identifying those most influential.</p><p><strong>Methods: </strong>Path Analysis (PA), a statistical structural equation modeling method, was used to construct the CGM, with emphasis on observable variables and to assess direct and indirect effects through correlations and covariances. PA was applied to an already-collected third-party dataset related to BV diagnosis, consisting of data from 132 pregnant women between 4 and 24 weeks of gestation.</p><p><strong>Results: </strong>The CGM, built using a theoretical model based on the Spearman correlation matrix, was validated through statistical metrics and by a clinical-biological expert. The resultant model highlights bacteria influencing BV diagnosis, specifically <i>Mycoplasma hominis</i> (Mh), <i>Atopobium vaginae</i> (Av), <i>Gardnerella vaginalis</i> (Gv), <i>Megasphaera Type 1</i> (MT1), and <i>Bacteria Associated with Bacterial Vaginosis Type 2</i> (BVAB2). Among them, MT1 and BVAB2 showed the strongest association with BV.</p><p><strong>Conclusions: </strong>The CGM effectively identifies causal associations among bacteria related to BV.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12651228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}