bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Academic Success From the Perspective of Nursing Students: A Qualitative Study
Authors: Adorno Marie , Kensler Paula A. , Tartavoulle Todd
Published: August 2021

Baccalaureate nursing education programs must focus on social transition as well as academic preparedness to maximize student success. The purpose of this qualitative research study was to identify nontraditional nursing students’ perspectives on strategies that enabled them to succeed. Focus groups were conducted with nontraditional students who graduated on time from a BSN program. Themes that emerged included resources, self-awareness, social support, and early engagement. Using findings from this study, the faculty and administration changed the new student orientation to include time management, test-taking skills, self-awareness assessments, and professional socialization.
Dose-dependent Respiratory Depression by Remifentanil in the Rabbit Parabrachial Nucleus/Kölliker–Fuse Complex and Pre-Bötzinger Complex
Authors: Palkovic Barbara , Callison Jennifer J. , Marchenko Vitaliy , Stuth Eckehard A. E. , Zuperku Edward J. , Stucke Astrid G.
Published: August 2021

Background

Recent studies showed partial reversal of opioid-induced respiratory depression in the pre-Bötzinger complex and the parabrachial nucleus/Kölliker–Fuse complex. The hypothesis for this study was that opioid antagonism in the parabrachial nucleus/Kölliker–Fuse complex plus pre-Bötzinger complex completely reverses respiratory depression from clinically relevant opioid concentrations.

Methods

Experiments were performed in 48 adult, artificially ventilated, decerebrate rabbits. The authors decreased baseline respiratory rate ~50% with intravenous, “analgesic” remifentanil infusion or produced apnea with remifentanil boluses and investigated the reversal with naloxone microinjections (1 mM, 700 nl) into the Kölliker–Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex. In another group of animals, naloxone was injected only into the pre-Bötzinger complex to determine whether prior parabrachial nucleus/Kölliker–Fuse complex injection impacted the naloxone effect. Last, the µ-opioid receptor agonist [d-Ala,2N-MePhe,4Gly-ol]-enkephalin (100 μM, 700 nl) was injected into the parabrachial nucleus/Kölliker–Fuse complex. The data are presented as medians (25 to 75%).

Results

Remifentanil infusion reduced the respiratory rate from 36 (31 to 40) to 16 (15 to 21) breaths/min. Naloxone microinjections into the bilateral Kölliker–Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex increased the rate to 17 (16 to 22, n = 19, P = 0.005), 23 (19 to 29, n = 19, P < 0.001), and 25 (22 to 28) breaths/min (n = 11, P < 0.001), respectively. Naloxone injection into the parabrachial nucleus/Kölliker–Fuse complex prevented apnea in 12 of 17 animals, increasing the respiratory rate to 10 (0 to 12) breaths/min (P < 0.001); subsequent pre-Bötzinger complex injection prevented apnea in all animals (13 [10 to 19] breaths/min, n = 12, P = 0.002). Naloxone injection into the pre-Bötzinger complex alone increased the respiratory rate to 21 (15 to 26) breaths/min during analgesic concentrations (n = 10, P = 0.008) but not during apnea (0 [0 to 0] breaths/min, n = 9, P = 0.500). [d-Ala,2N-MePhe,4Gly-ol]-enkephalin injection into the parabrachial nucleus/Kölliker–Fuse complex decreased respiratory rate to 3 (2 to 6) breaths/min.

Conclusions

Opioid reversal in the parabrachial nucleus/Kölliker–Fuse complex plus pre-Bötzinger complex only partially reversed respiratory depression from analgesic and even less from “apneic” opioid doses. The lack of recovery pointed to opioid-induced depression of respiratory drive that determines the activity of these areas.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Women's Experience of Their First Sexual Encounter After Pelvic Reconstructive Surgery
Authors: Caldwell Lauren , Halder Gabriela E. , Dunivan Gena , White Amanda B. , Ossai Uchenna , Rogers Rebecca G.
Published: August 2021

OBJECTIVE:

To describe the timing, quality and patient concerns regarding the first sexual encounter after surgery for pelvic organ prolapse (POP) or urinary incontinence (UI).

METHODS:

Women scheduled to undergo POP or UI surgery who self-identified as sexually active were recruited to this qualitative study. Routine counseling regarding the return to sexual activity was provided 4–6 weeks postoperatively. Participants completed interviews 2–4 months after their surgery. Interviews were tape recorded, de-identified, and transcribed. Transcriptions were coded for major themes by two independent researchers; disagreements were arbitrated by the research team. Analysis was performed using Dedoose software.

RESULTS:

Twenty patients with an average age of 52.4 years participated. Most identified themselves as White (85%), one quarter had a history of hysterectomy, and 15% had previously undergone pelvic reconstructive surgery. Nineteen (95%) patients resumed intercourse 2–4 months after surgery. Thematic saturation was reached with major themes of Outside Influences, Conflicting Emotions, Uncertainty, Sexual Changes and Stability, Normalization, and Self-Image. First sexual encounter timing was strongly influenced by partners' desires and fears and physician counseling. Fear of damage to repairs affected patients' comfort with return to sexual activity. Although uncertain of how anatomical changes or presence of mesh would affect function, women hoped that changes would be positive, regardless of preoperative sexual function. Some women found their experience unchanged, whereas others reported need for change in sexual position, use of lubrication, and sensation of foreign body. Positive changes included increase in desire, pleasure, and improvement in orgasm. Self-image generally improved after surgery, which increased women's sexual confidence.

CONCLUSION:

The return to sexual activity after surgery for POP or UI represents a great unknown for many women. Reports of initial sexual activity after surgery are often positive, and physicians strongly influence initial postoperative sexual encounter timing. Frank counseling about patient and partners' fears regarding the effect of repair on sexual activity would likely improve patients' outcomes.
Transcutaneous Electrical Nerve Stimulation for Pain Management of Aspiration Abortion up to 83 Days of Gestation
Authors: Lerma Klaira , Goldthwaite Lisa M. , Blumenthal Paul D. , Shaw Kate A.
Published: August 2021

OBJECTIVE:

To evaluate high-frequency, high-intensity transcutaneous electrical nerve stimulation (TENS) as an inexpensive, noninvasive pain management approach for first-trimester aspiration abortion.

METHODS:

We conducted a noninferiority, single-blind, randomized controlled trial of patients seeking aspiration abortion at up to 83 days of gestation. Participants received TENS (placed posteriorly, T10-L1 and S2-S4) or intravenous (IV) sedation (fentanyl, midazolam). The primary outcome was pain with aspiration, as self-reported by visual analog scale (VAS, 100 mm). To detect at least a 15 mm mean difference on the 100 mm VAS with 90% power and a significance level of .05, a total of 90 participants were required.

RESULTS:

Between January 2018 and October 2019, we enrolled 109 participants (55 TENS, 54 IV). Participant median gestation was 53 days (range 36–82) in the TENS group and 58 days (range 35–82) in the IV group (P=.65). Group demographics and clinical histories were similar. Intention-to-treat analysis (n=109) yielded noninferior results for the primary outcome (mean difference 4.8 mm, 95% CI −5.9 to 13.5 mm). In the per-protocol analysis, 9 (16%) in the TENS group were excluded after receiving IV sedation; 100 participants were included (46 TENS, 54 IV). Median (range) reported VAS for aspiration was 73 mm (13–97) and 66 mm (0–99) in the TENS and IV groups, respectively (P=.40). With a mean difference of 4.4 mm (95% CI −5.6 to 14.5 mm), we found TENS to be noninferior to IV. Physicians underestimated participant pain, perceiving pain to be 34 mm (6–91) in the TENS group and 25 mm (0–83) in the IV group (P=.003).

CONCLUSION:

We found TENS to be a noninferior alternative to IV sedation for aspiration pain during first-trimester abortion. Expanding pain management options can improve quality of and access to abortion. Transcutaneous electrical nerve stimulation could be a standalone or adjunct approach for abortion pain management for those without access to or are ineligible to receive IV sedation due to the lack of sedation practitioner, designated driver, or local restrictions.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03187002.
Relationship Between Maternal Economic Vulnerability and Childhood Neurodevelopment at 2 and 5 Years of Life
Authors: Premkumar Ashish , Mele Lisa , Casey Brian M. , Varner Michael W. , Sorokin Yoram , Wapner Ronald J. , Thorp John M. , Saade George R. , Tita Alan T.N. , Rouse Dwight J. , Sibai Baha , Costantine Maged M. , Mercer Brian M. , Tolosa Jorge E. , Caritis Steve N. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: August 2021

OBJECTIVE:

To assess the relationship between economic vulnerability during pregnancy and childhood neurodevelopment.

METHODS:

This is a secondary analysis of two parallel multicenter, randomized, controlled trials of administration of levothyroxine to pregnant individuals with subclinical hypothyroidism or hypothyroxinemia in the United States. All participants who delivered a live, nonanomalous neonate and completed the WPPSI-III (Weschler Preschool & Primary Scale of Intelligence) at 5 years of life and the Bayley-III (Bayley Scales of Infant Development) test at 2 years were included. The primary outcome is WPPSI-III score. Secondary outcome included Bayley-III subtest scores. Multivariable analyses were used to assess the relationships between economic vulnerability during the index pregnancy—defined as a household income less than 200% of the estimated federal poverty level, part-time or no employment, and use of government insurance—and the prespecified outcomes. Tests of interaction were performed to assess whether the magnitude of association differed according to whether participants were married or completed more than a high school education. A sensitivity analysis was performed to limit the income criteria for economic vulnerability to household income of less than 100% of the estimated federal poverty level.

RESULTS:

Of 955 participants who met inclusion criteria, 406 (42.5%) were considered economically vulnerable. In bivariate analysis, the WPPSI-III score and Bayley-III subtest scores were significantly lower among children of the economically vulnerable. For the WPPSI-III, Bayley-III cognitive subtest, and Bayley-III language subtest scores, the associations between economic vulnerability and lower childhood neurodevelopmental scores were primarily seen only among those who were married or completed more than a high school education (P for interaction<.05). A similar pattern was noted when restricting the income criteria for economic vulnerability to less than 100% of the federal poverty level.

CONCLUSION:

Economic vulnerability during pregnancy is associated with an increased risk of adverse neurodevelopmental outcomes in their children at 2 and 5 years of life, particularly among those who are married or completed more than a high school education.
The Burden of Abortion Restrictions and Conservative Diagnostic Guidelines on Patient-Centered Care for Early Pregnancy Loss
Authors: Judge-Golden Colleen , Flink-Bochacki Rachel
Published: August 2021

Intrauterine pregnancies of uncertain viability are common, and guidelines for diagnosing early pregnancy loss must balance the risk of interrupting a viable pregnancy with the anxiety and medical complications resulting from delayed diagnosis. Two cases of likely early pregnancy loss presenting as intrauterine pregnancies of uncertain viability are described, with stark differences in care availability related to state reproductive health care regulations. Onerous abortion restrictions, medical and societal stigma, and inherent pronatalism in diagnostic criteria interfere with the exercise of clinical judgment and can damage patients' physical or mental health.
Pessary for Management of Cervical Varices Complicating Pregnancy
Authors: González-Bosquet Eduardo , Grau Laia , Ferrero-Martínez Sílvia , Hernandez-Saborit Alicia , Rebollo Monica , Gomez-Chiari Marta , Martínez Crespo Josep Maria , Gómez-Roig Maria Dolores
Published: August 2021

BACKGROUND:

Cervical varices complicating pregnancy are rare but can cause significant maternal and perinatal morbidity. There is limited evidence regarding the optimal management of bleeding caused by cervical varices during pregnancy.

CASE:

A 38-year-old woman was admitted to the hospital at 16 weeks of gestation due to vaginal hemorrhage in the setting of cervical varices accompanied by placenta previa. A cervical pessary was placed at 21 weeks of gestation without further bleeding. Magnetic resonance imaging demonstrated variceal reduction after pessary placement, and a cesarean delivery was performed at 36 weeks of gestation without complications.

CONCLUSION:

Cervical pessary should be considered as conservative option to control the bleeding associated with cervical varices during pregnancy.
Immune-checkpoint inhibitors in pituitary malignancies
Authors: Di Nunno Vincenzo , Franceschi Enrico , Tosoni Alicia , Gatto Lidia , Maggio Ilaria , Lodi Raffaele , Bartolini Stefania , Brandes Alba A.
Published: August 2021

To date, there are no standardized systemic treatment options for patients with metastatic pituitary carcinoma progressed to chemo and radiation therapy. Immune-checkpoint inhibitors (ICIs) have been successfully assessed in other solid malignancies and could be a concrete hope for these patients. We performed a critical review of the literature aimed to evaluate studies assessing ICIs in pituitary malignancies. We also conducted research about published translational data assessing immune-contexture in these malignancies. Some preliminary reports reported a successful administration of pembrolizumab or the combination between nivolumab and ipilimumab in patients with metastatic ACTH-secreting pituitary carcinomas. Translational data suggest that adenomas secreting growth hormone and ACTH have a suppressed immune-microenvironment, which could be more likely to benefit from ICIs. Immune-checkpoint inhibitors can be an effective treatment in patients with pituitary carcinoma and maybe also recurrent adenoma. Tumors secreting growth hormone and ACTH are more likely to benefit from ICIs due to a different immune-microenvironment.
How Shared Is Shared Decision Making? Reaching the Full Potential of Patient-Clinician Collaboration in Mental Health
Authors: Treichler Emily B. H. , Rabin Borsika A. , Cohen Amy N. , Light Gregory A.
Published: August 2021

Shared decision making in mental health is a priority for stakeholders, but faces significant implementation barriers, particularly in settings intended to serve people with serious mental illnesses (SMI). As a result, current levels of shared decision making are low. We highlight these barriers and propose that a novel paradigm, collaborative decision making, will offer conceptual and practical solutions at the systemic and patient/clinician level. Collaborative decision making is tailored for populations like people with SMI and other groups who experience chronic and complex symptoms, along with power imbalances within health systems. Advancing from shared decision making to collaborative decision making clarifies the mission of the model: to facilitate an empowering and recovery-oriented decision-making process that assigns equal power and responsibility to patients and clinicians; to improve alignment of treatment decisions with patient values and priorities; to increase patient trust and confidence in clinicians and the treatment process; and, in the end, to improve treatment engagement, satisfaction, and outcomes. The primary purpose of collaborative decision making is to increase values-aligned care, therefore prioritizing inclusion of patient values, including cultural values and quality of life–related outcomes. Given the broad and constantly changing context of treatment and care for many people with SMI (and also other groups), this model is dynamic and continuously evolving, ready for use across diverse contexts. Implementation of collaborative decision making includes increasing patient knowledge but also patient power, comfort, and confidence. It is one tool to reshape patient-clinician and patient-system relationships and to increase access to value-aligned care for people with SMI and other groups.
CAPRL Scoring System for Prediction of 30-day Mortality in 949 Patients with Coronavirus Disease 2019 in Wuhan, China: A Retrospective, Observational Study
Authors: Chen Hui-Long , Yan Wei-Ming , Chen Guang , Zhang Xiao-Yun , Zeng Zhi-Lin , Wang Xiao-Jing , Qi Wei-Peng , Wang Min , Li Wei-Na , Ma Ke , Xu Dong , Ni Ming , Huang Jia-Quan , Zhu Lin , Zhang Shen , Chen Liang , Wang Hong-Wu , Ding Chen , Zhang Xiao-Ping , Chen Jia , Yu Hai-Jing , Ding Hong-Fang , Wu Liang , Xing Ming-You , Song Jian-Xin , Chen Tao , Luo Xiao-Ping , Guo Wei , Han Mei-Fang , Wu Di , Ning Qin
Published: August 2021

Background:

Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces.

Methods:

In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality.

Results:

The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than10 × 109/L, neutrophil count of more than 7 × 109/L, lymphocyte count of less than 0.8 × 109/L, platelet count of less than 100 × 109/L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively.

Conclusions:

We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.
The COVID-19 Vaccine in Clinical Trials: Where Are We Now?
Authors: Jiang Hu-Dachuan , Li Jing-Xin , Zhang Peng , Huo Xiang , Zhu Feng-Cai
Published: August 2021

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to scale up around the world, costing severe health and economic losses. The development of an effective COVID-19 vaccine is of utmost importance. Most vaccine designs can be classified into three camps: protein based (inactivated vaccines, protein subunit, VLP and T-cell based vaccines), gene based (DNA or RNA vaccines, replicating or non-replicating viral/bacterial vectored vaccines), and a combination of both protein-based and gene-based (live-attenuated virus vaccines). Up to now, 237 candidate vaccines against SARS-CoV-2 are in development worldwide, of which 63 have been approved for clinical trials and 27 are evaluated in phase 3 clinical trials. Six candidate vaccines have been authorized for emergency use or conditional licensed, based on their efficacy data in phase 3 trials. This review summarizes the strengths and weaknesses of the candidate COVID-19 vaccines from various platforms, compares, and discusses their protective efficacy, safety, and immunogenicity according to the published clinical trials results.
ACE2 and TMPRSS2 Expression in Hepatocytes of Chronic HBV Infection Patients
Authors: Hu Xiao-Xiao , Ma Yan-Xiu , Lin Yao-Xiang , Wu Xiang-Ji , Wu Jing , Ma Hui , Lin Sheng-Zhang , Chen Gong-Yin , Pan Xiao-Ben
Published: August 2021

Background:

Pre-existing liver disease is a risk factor for the worse prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate whether chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) affect the expression of viral receptor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the liver.

Methods:

Twelve pairs of matched liver tissues of HCC and para-carcinoma were collected from the First Affiliated Hospital of Zhejiang University School of Medicine. And 20 liver biopsies from CHB patients were collected from Peking University People's Hospital. The expression of ACE2 and TMRPSS2 were detected using immunofluorescence staining, western blot, and RT-qPCR. The effects of hepatitis B virus (HBV) replication or interferon on ACE2 and TMPRSS2 expression were tested in hepatic cell lines.

Results:

The mRNA expression of TMPRSS2 in HCC tissues was six-fold higher than that of para-carcinoma tissues (P = 0.002), whereas that of ACE2 was not statistically different between HCC and para-carcinoma tissues. Hepatocellular ACE2 expression was detected in 35% (7/20) of CHB patients and mostly distributed in the inflammatory areas. However, there was no difference in TMPRSS2 expression between areas with or without inflammation. IFN-α2b slightly induced ACE2 expression (2.4-fold, P = 0.033) in HepG2 cells but not in Huh-7, QSG-7701, and L-02 cells. IFN-α2b did not affect TMPRSS2 expression in these cell lines. In addition, HBV replication did not alter ACE2 expression in HepAD38 cells.

Conclusions:

Although HBV replication does not directly affect the expression of ACE2 and TMPRSS2, intrahepatic inflammation and carcinogenesis may increase their expression in some patients, which, in turn, may facilitate SARS-CoV-2 infection in hepatocytes.
Systematic Discovery and Pathway Analyses of Metabolic Disturbance in COVID-19
Authors: Li Bo-Wen , Fan Xing , Cao Wen-Jing , Tian He , Wang Si-Yu , Zhang Ji-Yuan , Lam Sin Man , Song Jin-Wen , Zhang Chao , Zhang Shao-Hua , Xu Zhe , Xu Ruo-Nan , Fu Jun-Liang , Huang Lei , Jiang Tian-Jun , Shi Ming , Wang Fu-Sheng , Shui Guang-Hou
Published: August 2021

Background:

The ongoing global coronavirus disease 2019 (COVID-19) pandemic is posing a serious public health threat to nations worldwide. Understanding the pathogenesis of the disease and host immune responses will facilitate the discovery of therapeutic targets and better management of infected patients. Metabolomics technology can provide an unbiased tool to explore metabolic perturbation.

Methods:

Twenty-six healthy controls and 50 COVID-19 patients with mild, moderate, and severe symptoms in the Fifth Medical Center of PLA General Hospital from January 22 to February 16, 2020 were recruited into the study. Fasting blood samples were collected and subject to metabolomics analysis by liquid chromatography–mass spectrometry. Metabolite abundance was measured by peak area and was log-transformed before statistical analysis. The principal component analysis, different expression analysis, and metabolic pathway analysis were performed using R package. Co-regulated metabolites and their associations with clinical indices were identified by the weighted correlation network analysis and Spearman correlation coefficients. The potential metabolite biomarkers were analyzed using a random forest model.

Results:

We uncovered over 100 metabolites that were associated with COVID-19 disease and many of them correlated with disease severity. Sets of highly correlated metabolites were identified and their correlations with clinical indices were presented. Further analyses linked the differential metabolites with biochemical reactions, metabolic pathways, and biomedical MeSH terms, offering contextual insights into disease pathogenesis and host responses. Finally, a panel of metabolites was discovered to be able to discriminate COVID-19 patients from healthy controls, and also another list for mild against more severe cases. Our findings showed that in COVID-19 patients, citrate cycle, sphingosine 1-phosphate in sphingolipid metabolism, and steroid hormone biosynthesis were downregulated, while purine metabolism and tryptophan metabolism were disturbed.

Conclusion:

This study discovered key metabolites as well as their related biological and medical concepts pertaining to COVID-19 pathogenesis and host immune response, which will facilitate the selection of potential biomarkers for prognosis and discovery of therapeutic targets.
Keep Eyes on COVID-19: Ophthalmic Symptoms and Potential Transmission of SARS-CoV-2 through the Oculus
Authors: Ran Hong Li , Zhou Xiang Tian , Liu William J. , Gao George F.
Published: August 2021

In December 2019, a new coronavirus disease 2019 (COVID-19) emerged and rapidly spread globally, posing a worldwide health emergency. The pathogen causing this pandemic was identified as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is well known that SARS-CoV-2 transmits via respiratory droplets and close contact with infected individuals or contaminated items. In addition to these two major transmission routes, other modes of transmission have not been confirmed. Considering that some COVID-19 patients have presented with ocular discomforts and positive SARS-CoV-2 RNA in ocular surfaces, as well as the discovery of the SARS-CoV-2 receptors, angiotensin-converting enzyme 2, and transmembrane protease, serine 2, in the oculus, the ocular surface is now thought to be a possible alternative route of SARS-CoV-2 transmission and a replication site. This review summarizes the evidence connecting COVID-19 with ocular tissues, ocular symptoms during SARS-CoV-2 infection, the potential role of the conjunctiva in SARS-CoV-2 transmission, and the physiopathological mechanisms. Appropriate precautions in ophthalmology departments, including innovative complete and effective patient management plans, protective personal equipment, hand hygiene, and strict personal distance intervals, are essential to effectively minimize the spread of SARS-CoV-2 and control the pandemic.
HIV Compartmentalization in Male Genital Tract: Relevance for Viral Eradication
Authors: Peng Xiaorong , Isnard Stéphane , Lin John , Fombuena Brandon , Royston Lena , Routy Jean-Pierre
Published: August 2021

Human immunodeficiency virus (HIV) has been shown to evolve independently in different anatomical compartments. Characterizing HIV genetic evolution in different tissues and cells provides insights into the mechanisms that maintain the viral reservoir. HIV compartmentalization has been well documented in the semen but rarely in male genital tract (MGT) organs. The precise mechanisms that result in the development of HIV compartmentalization in multiple genitourinary sites have been poorly explored due to the difficulty in accessing these tissues. Based on evidence from lymph nodes and gut tissues, mechanisms that may influence compartmentalization include immune pressures, local concentrations of antiviral drugs, clonal expansion of different cell types and inflammation that alters the cellular microenvironment. We reviewed phylogenetic evidences supporting viral compartmentalization between the blood and multiple genitourinary sites in HIV-infected people. Characterizing distinct viral sub-populations enhances our overall understanding of the HIV reservoir in MGT and could ultimately lead to the development of novel therapies to eradicate the virus in tissues.
Combination of Tripterygium Wilfordii Hook F With Antiretroviral Therapy Delayed Viral Rebound in A Patient of Acute HIV-1 Infection
Authors: Cao Wei , Cui Yizhi , Weng Huiling , Yue Yongsong , Mai Zhibiao , Han Yang , Qiu Zhifeng , Song Xiaojing , Xie Jing , Lyu Wei , Zhang Gong , Wang Jianhua , Routy Jean-Pierre , Wang Tong , Li Taisheng
Published: August 2021

Prolonged antiretroviral therapy (ART)-free remission post-treatment has been observed and reported in human immunodeficiency virus-1 (HIV-1) infection. The primary factors for such achievement have been linked to the transcriptional inactivation of HIV-1 DNA and immune recovery. Here, we reported a patient with acute HIV-1 infection who immediately received intensified quadruple ART. At month 9 (M9), an old CFDA-approved immuno-suppressive herbal medicine, Tripterygium Wilfordii Hook F (TwHF), was used in addition to ART. The patient was closely monitored. Virological and immunological tests as well as transcriptome analysis were carried out at each visit. The results showed that TwHF reduced serum IP-10 level and inhibited T cell activation. Both ART and TwHF were discontinued in M24, and levels of peripheral blood HIV-1 RNA and DNA remained suppressed for consecutive 12 months. With transcriptome analysis, we found pattern changes linking immuno-activation and amino acid metabolism with viral suppression and rebound. This indicates that the intentional suppression of immuno-activation is a promising approach for a functional cure of HIV-1 infection.
Gender differences in long-term mortality after spontaneous intracerebral hemorrhage in southern Portugal
Authors: Teles Joana , Martinez Joana , Mouzinho Maria , Guilherme Patrícia , Marreiros Ana , Nzwalo Hipólito
Published: August 2021

Introduction:

the prognosis of spontaneous intracerebral hemorrhage (SICH) remains poor. Understanding gender differences can clarify the clinico-epidemiological and process of care related factors that influence SICH prognosis. We analyzed the long-term gender differences of mortality after SICH in Algarve, southern Portugal.

Patients and Methods:

analysis of consecutive community representative of SICH survivors (2009–2015). Logistic regression analysis and Kaplan–Meier method was used to assess gender differences on 1-year mortality and survival. We further analyzed if differences exist between 4 age and gender based subgroups (women <75 years, women ≥75 years, men <75 years, men ≥75 years).

Results:

a total of 285 survivors were analyzed; majority men (66.3%). Women were 2 years older on average. Overall case fatality was 11.6% [CI: 8.3–15.8]. A non-statistically significant (P = .094) higher case-fatality rate was observed in women; men were more frequently admitted to stroke unit; women had more often poor functional outcome or modified Rankin scale (mRS) ≥3. Predictors of death were: being women with ≥ 75 years, in-hospital pneumonia and hospital discharge mRS ≥3. The likelihood of death was higher in women ≥75 years (OR = 2.91 [1.23–8.1], P = .035) in comparison to women <75 years and men ≥75 years. Women <75 years had the longest survivor time, whereas women ≥75 years the shortest survivor time (P < .001).

Conclusion:

gender and age interact to influence long-term mortality after SICH. Women ≥75 years are at increased risk of death and have reduced survival after SICH in southern Portugal. Further studies are needed to clarify the biological or social factors contributing for the poor prognosis in the very old women in the region.
Prognostic value of platelet-to-lymphocyte ratio in neoadjuvant chemotherapy for solid tumors
Authors: Long Yuming , Zhang Yingtian , Ni Liwei , Yuan Xuya , Liu Yuanliang , Tao Jialong , Zhang Yusong
Published: August 2021

Introduction:

Previous research indicates that the platelet-to-lymphocyte ratio (PLR) may be an indicator of poor prognosis in many tumor types. However, the PLR is rarely described in patients undergoing neoadjuvant chemotherapy (NAC) for solid tumors. Thus, we performed a meta-analysis to investigate the prognostic value of this ratio for patients with solid tumors treated by NAC.

Methods:

A comprehensive search of the literature was conducted using the PubMed, EMBASE, Cochrane Library, and Web of Science databases, followed by a manual search of references from the retrieved articles. Pooled hazard ratios (HRs) with 95% confidence interval (CIs) were used to evaluate the association between PLR and 3 outcomes, namely, overall survival, disease-free survival, and pathological complete response rate after NAC.

Results:

Eighteen studies published no earlier than 2014 were included in our study. A lower PLR was associated with better overall survival (HR = 1.46, 95% CI, 1.11–1.92) and favorable disease-free survival (HR = 1.81, 95% CI, 1.27–2.59). A PLR that was higher than a certain cutoff was associated with a lower pathological complete response rate in patients with cancer who received NAC (Odds ratio = 1.93, 95% CI, 1.40–2.87).

Conclusion:

Elevated PLR is associated with poor prognosis in various solid tumors. PLR may be a useful biomarker in delineating those patients with poorer prognoses who may benefit from neoadjuvant therapies.
Refractory hyponatremia in neuromyelitis optica in a pediatric patient
Authors: Lin Tai-Han , Hsu Po-Chang , Sung Chia-Cheng , Fang Hung-Hsiang , Tien Chiung-Hsi , Hu Chih-Fen , Wu Po-Wei , Yu Chia-Hsiang , Ding Jhao-Jhuang , Ho Sheng-Yuan , Chen Shyi-Jou
Published: August 2021

Rationale:

Neuromyelitis optica spectrum disorders (NMOSD) is a rare autoimmune disease predominantly involving optic nerves and spinal cord, and possible comorbidities including syndrome of inappropriate antidiuretic hormone secretion or urinary complication. We reported a young girl diagnosed with NMOSD presented with refractory hyponatremia, acute urine retention, and general weakness. Clinical symptoms improved gradually after receiving intravenous immunoglobulin, high-dose methylprednisolone, and plasmapheresis. NMOSD should be kept in mind in adolescence with acute urine retention, intermittent fever, and hyponatremia.

Patient concerns:

A 15-year-old girl admitted to our hospital due to no urination for 2 days.

Diagnosis:

Aquaporin-4 antibodies were detected showing positive both in serum and cerebrospinal fluid. Long transverse myelitis in cervical and thoracic spinal cord and optic neuritis was revealed in magnetic resonance imaging.

Interventions:

Intravenous immunoglobulin 2 g/kg was infused totally in 4 days, and methylprednisolone pulse therapy was subsequently followed in 5 days; followed by 5 courses of plasmapheresis a week later.

Outcomes:

Her muscle power, syndrome of inappropriate antidiuretic hormone secretion condition, and urinary function were all improved after immune-modulated treatment course; NMOSD relapsed twice within the first year after diagnosis, however no relapse of NMOSD in the subsequent 1 year.

Lessons:

To the best of our knowledge, this was the first childhood case of NMO accompanied by refractory hyponatremia in the reported literature. In childhood cases presenting with refractory hyponatremia and limb weakness, NMO or NMOSD should be considered possible diagnoses despite their rarity in pediatric cases.
Safety and feasibility of symptom-limited cardiopulmonary exercise test using the modified Naughton protocol in children with cerebral palsy
Authors: Kim Ah-Ran , Suk Min-Hwa , Kwon Jeong-Yi
Published: August 2021

Variables derived from the cardiopulmonary exercise test (CPX) provide objective information regarding the exercise capacity of children with cerebral palsy (CP), which can be used as the basis for exercise recommendations. Performing maximal CPX might not be appropriate, safe, or practical for children with CP. In the present study, the safety and feasibility of symptom-limited CPX using the modified Naughton protocol, a submaximal protocol, were investigated in children with CP, Gross Motor Function Classification System (GMFCS) level I or II. The present study included 40 children aged 6 to 12 years with CP who underwent symptom-limited CPX. CPX was performed to measure cardiopulmonary fitness using a treadmill with a modified Naughton protocol. Motor capacity was assessed using the Gross Motor Function Measure (GMFM), Pediatric Balance Scale (PBS), Timed Up and Go (TUG) test, and 6-minute walk test. Thirty-seven children with CP successfully completed testing without any adverse events during or immediately after CPX (dropout rate 7.5%). The reason for test termination was dyspnea (51.4%) or leg fatigue (48.6%). Based on the respiratory exchange ratio (RER), 21 of 37 (56.8%) children chose premature termination. The relationship between the reason for test termination and RER was not statistically significant (Spearman rho = 0.082, P = .631). CPX exercise time was strongly correlated with GMFM (Spearman rho = 0.714) and moderate correlation with PBS (Spearman rho = 0.690) and TUG (Spearman rho = 0.537). Peak oxygen uptake during CPX showed a weak correlation with GMFM and a moderate correlation with PBS. This study revealed that symptom-limited CPX using the modified Naughton protocol was safe and feasible for children with CP and GMFCS level I or II.
Associations of serum estradiol level, serum estrogen receptor-alpha level, and estrogen receptor-alpha polymorphism with male infertility
Authors: Luo Hongcheng , Huang Yanxin , Han Mengran , Pang Yanfang , Yu Pei , Tang Yujin , Yuan Huixiong , Li Jie , Chen Wencheng
Published: August 2021

Estradiol regulates spermatogenesis partly via estrogen receptor-alpha (ESRα). This study aimed to analyze the associations of serum estradiol level, serum ESRα level, and ESRα gene polymorphisms with sperm quality.

This retrospective study included infertile men attending the Reproductive Center, Affiliated Hospital of Youjiang Medical University for Nationalities, and a control group without a history of fertility (October, 2016 to March, 2017). Data regarding sperm quality, serum levels of estradiol and ESRα, and rs2234693C/T genotype were extracted from the medical records. Pearson/Spearman correlations (as appropriate) between estradiol level, ESRα level, and sperm quality parameters were evaluated.

The analysis included 215 men with infertility and 83 healthy controls. The infertile group had higher serum levels of estradiol (147.57 ± 35.3 vs 129.62 ± 49.11 pg/mL, P < .05) and ESRα (3.02 ± 2.62 vs 1.33 ± 0.56 pg/mL, P < .05) than the control group. For the infertile group, serum estradiol level was negatively correlated with sperm concentration, percentage of progressively motile sperm, and percentage of sperm with normal morphology (r = 0.309, 0.211, and 0.246, respectively; all P < .05). Serum estradiol and ESRα levels were lower in infertile men with normozoospermia than in those with azoospermia, oligozoospermia, mild azoospermia, or malformed spermatozoa (all P < .05). Sperm concentration, percentage of progressively motile sperm, serum ESRα level, and serum estradiol level did not differ significantly among the rs2234693 CC, CT, and TT genotypes.

Elevated serum levels of estradiol and possibly ESRα might have a negative impact on sperm quality and fertility, whereas single nucleotide polymorphisms at rs2234693 of the ESRα gene had little or no effect.
Distribution of alleles, genotypes and haplotypes of the CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) genes in the Malian population
Authors: Kassogue Yaya , Diakite Brehima , Kassogue Oumar , Konate Issa , Tamboura Kadidiatou , Diarra Zoumana , Maiga Mamoudou , Dehbi Hind , Nadifi Sellama , Traore Cheick Bougadari , Kamate Bakarou , Dao Sounkalo , Doumbia Seydou , Dolo Guimogo
Published: August 2021

Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D’ = 0.91 and r2 = 0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.
Exploring diagnostic and prognostic predictive values of microRNAs for acute myocardial infarction
Authors: Lee Gien-Kuo , Hsieh Yen-Ping , Hsu Shang-Wei , Lan Shou-Jen
Published: August 2021

Objective:

Previous investigations yielded inconsistent results for diagnostic and prognostic predictive values of MicroRNAs (miRNAs) for acute myocardial infarction (AMI).

Methods and results:

We systematically searched on PubMed and Web of Science for articles explored association of miRNAs and AMI published from January 1989 to March 2019. For diagnostic studies, a summary of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR), which indicated the accuracy of microRNAs in the differentiation of AMI and no AMI, were calculated from the true positive (TP), true negative (TN), false positive (FP), and false negative (FN) of each study. In addition, the summary receive-operating characteristics (SROC) curve was constructed to summarize the TP and FP rates. For follow-up study, we computed hazard ratios (HRs) and 95% confidence intervals (CIs) for individual clinical outcomes. The meta-analysis showed a sensitivity [0.72 (95% CI: 0.61--0.81)] and specificity [0.88 (95% CI: 0.79--0.94)] of miR-1 for AMI. In addition, miR-133 showed a sensitivity [0.73 (95% CI: 0.55--0.85)] and specificity [0.88 (95% CI: 0.74--0.95)] for AMI. Moreover, the present study showed a sensitivity [0.83 (95% CI: 0.74--0.89)] and specificity [0.96 (95% CI: 0.82--0.99)] of miR-208 for AMI. A significant association was found between miR-208 and mortality after AMI (HR 1.09, 95% CI 1.01--1.18). It also indicated a sensitivity [0.84 (95% CI: 0.70--0.92)] and specificity [0.97 (95% CI: 0.87--0.99)] of miR-499 for AMI.

Conclusions:

Circulating miR-1, miR-133, miR-208, and miR-499 showed diagnostic values in AMI.
A seven-m6A regulator-related CpG site-based prognostic signature for endometrial carcinoma
Authors: Zhang Xiang , Pang Xuecheng , Huang Yue , Qian Sumin
Published: August 2021

Background

Endometrial carcinoma (EC) has become a common gynecologic malignancy with a high mortality. The m6A regulators have been identified to be closely associated with multiple human cancers including EC. However, the CpG methylation signature related to m6A regulators in EC remains unclear.

Method

The methylation profiles of EC patients including cancer samples and adjacent normal samples were obtained from The Cancer Genome Atlas (TCGA) database. The CpG sites in 20 m6A regulators were identified. Univariate Cox regression and LASSO Cox regression analysis were used to screen key CpG sites which were located at m6A regulators and significantly related to the prognosis of EC. The predictive model for EC prognosis was constructed, and multivariate Cox regression analysis was applied to explore whether the risk score derived from the model could function as an independent signature for EC prognosis. Meanwhile, a nomogram model was constructed by combing the independent prognostic signatures for prediction of the long-term survival in EC patients.

Results

A total of 396 CpG sites located at 20 m6A regulators were identified. A specific predictive model for EC prognosis based on 7 optimal CpG sites was constructed, which presented good performance in prognosis prediction of EC patients. Moreover, risk score was determined to be an independent signature both in the training set and validation set. By bringing in three independent prognostic factors (age, risk score, and TNM stage), the nomogram was constructed and could effectively predict the 3- and 5-year survival rates of EC patients.

Conclusion

Our study suggested that the CpG sites located at m6A regulators might be considered as potential prognostic signatures for EC patients.