AUCTORES
Globalize your Research
Review Article
*Corresponding Author: Pascal J Goldschmidt-Clermont.Alzady International LLC, Dean Emeritus, Professor of Medicine Emeritus, Miller School of Medicine University of Miami, Miami, Florida 33136.
Citation: Goldschmidt-Clermont P.J, Romet Lemonne J.P , Fontanet A, and Stevenson M. Virus Cooperation, ZIKV Viremia and In Utero Fetus Infection. J Women Health Care Issues, 2(2):Doi/10.31579/2642-9756/011
Copyright: ©2019. Pascal J Goldschmidt-Clermont. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 01 August 2019 | Accepted: 13 August 2019 | Published: 22 August 2019
Keywords: virus Cooperation; zika Virus; pregnancy; placental, fetus infection; women and child health
With growth and exponential globe trotter traveling of the human population, and many more conducive factors, the likelihood of merging and melting viruses capable of infecting humans in a cooperative fashion, has increased markedly. Hence, viruses that were limited to a particular region of the planet, or to certain population groups, have become capable of infecting humans on a pandemic scale. Some viruses not only can infect pregnant women, but also expand to the amniotic fluid and fetus. With this review, we will reflect upon some examples of known viral cooperations, as well as new ones that have the potential for compromising human health and survival of the fetus in utero.
Parnassus Avenue, a typical summer morning of 1983, the UCSF dermatology clinic is opening, there is a line of mostly young men, many of whom display one or multiple discolored (purplish) lesions of their skin or mucosa, known as Kaposi's sarcoma [1]. It was before the AIDS and Kaposi's viruses were discovered, and for patients newly diagnosed with AIDS, time from AIDS diagnosis to death was then 12 months [2]. The virus that triggers the Kaposi's lesions turned out to be of the Herpes family, Human Herpes Virus 8 (HHV8), better known today as Kaposi's Sarcoma-associated Herpes Virus (KSHV) [3]. Before the AIDS pandemic, Kaposi's sarcoma was a rare disorder, found on the skin of mostly elderly men in countries surrounding the Mediterranean Sea, Middle-Eastern Europeans, and in Africa [3]. Since the beginning of the AIDS pandemic, millions of patients have suffered from Kaposi's sarcoma, women and men almost equally. Although it has become rare again in countries where AIDS treatment is readily available and applied effectively (4), it remains the most frequent AIDS-associated cancer in sub-Saharan Africa (Figure 1).
Figure 1: As the pandemic of HIV was spreading worldwide during the last quarter of the 20th century, Kaposi Sarcoma caused by KSHV (HHV8) has expanded from an infrequent illness for elderly men in the Mediterranean Basin and Africa, to a ubiquitous cancer affecting millions of men and also women, and still is the leading cancer for AIDS patients in sub-Saharan Africa, as a result of “virus cooperation” between KSHV and HIV.
Why would two viruses like HIV-1 and KSHV expand concurrently within the human population? Both viruses can be transmitted through sexual contact, so they may naturally be more commonly found among individuals with at-risk sexual behaviors. However, there may be more to this cooperation than that, with evidence in experimental models that the replication of one virus may enhance the replication of the other, and that there is loss of T-cell proliferative response (a critical step of immune reaction) to KHSV in HIV-infected men [5].
Another virus that has expanded markedly through parenteral transmission within the human population during the past fifty years is the hepatitis C virus (HCV), with multiple cases of co-infection with HIV among injecting drug users. In this case, HCV-associated complications, and particularly hepatic fibrosis, are accelerated during co-infection with HIV, whereas the impact of HCV on HIV infection is less clear, if any ([6-8]. While in HAART-treated AIDS patients, Kaposi’s sarcoma has nearly vanished, there is only modest improvement of hepatitis C clinical progression as a result of HIV therapy, and HAART is often hepatotoxic. Hence, the net benefit from HAART on the liver condition of HCV and HIV infected patients remains controversial (6-8). Perhaps, an even more dramatic example of cooperation between viruses is the case of hepatitis delta virus (HDV), which can become infectious to humans only in the presence of hepatitis B virus infection [9].
These examples illustrate a major challenge for 21st century medicine: the cooperation between viruses. Most of the viruses that now afflict the population predated humans and have infected other animals prior to infecting humans. But what has changed drastically in recent years with the growth of the human population, the connectivity of our world, and the substantial increase in the number of world travelers, is the probability for previously distant viruses to interact, and thus possibly cooperate, to infect humans.
A recent "emerging infection" issue that infectious disease specialists, scientists, obstetricians and pediatricians alike are struggling with and puzzled by, is how and why does the Zika Virus (ZIKV) demonstrate such an unusual proclivity for the fetal human brain, with grave consequences for the fetus such as microcephaly and other major brain abnormalities [10-13]. In a study performed in Rio de Janeiro, Brazil, amongst pregnant women that had symptomatic, confirmed, ZIKV infection, 42% of life offspring were found to have grossly abnormal clinical features, brain imaging, or both, including 4 with microcephaly [14]. Microcephaly is the most obvious of the birth defects reported in ZIKV-infected newborns, and in Brazil, especially in the Province of Pernambuco (North-East of Brazil, on the Atlantic Ocean), cases of microcephaly have increased by 2,300% between 2014 and 2015 [15]. Microcephaly and other neurological defects of the fetus and newborn are more commonly associated with infections taking place during the first or early second trimester of the pregnancy [10], but can apparently happen during all three trimesters [14]. Other clinical symptoms include ocular lesions, congenital contractures, and hypertonia with extra-pyramidal manifestations [11].
When infected with ZIKVBR, predisposed Swiss Jim Lambert mice (SJL/J, with a splice-site mutation in the Dysferlin gene), but not wild type mice, were able to reproduce some ocular and cortical malformations reminiscent of the human fetal abnormalities seen in ZIKV infected fetus, including reduced numbers of brain cells, brain cells that often displayed a "vacuolar nuclei" appearance (consistent with accelerated cell apoptosis/necrosis), and reduced cortical layer thickness [16].
In another model, where ZIKV was injected intra-vaginally in pregnant mice, replication in the vaginal mucosa was observed, with evidence of intrauterine growth restriction and fetal brain infection [17]. Furthermore, when IFnar1-/- mice were used, the extent of virus replication in the vaginal mucosa was much stronger, viremia and placental infection ensued, and severe intrauterine fetal growth limitation and brain infection resulted, with markedly increased fetal death [17]. This model suggests that ZIKV replication in the proximity of the uterine cavity could result in more frequent placental infection and brain abnormalities in the fetus. Sexual transmission of ZIKV has been documented in Humans [10,12-14], although its impact on the fetus and role in microcephaly and other brain abnormalities will need to be established.
Pregnant non-human primates (Macaca mulatta) infected with a ZIKV isolate demonstrate prolonged maternal viremia [18]. This isolate was from Rio de Janeiro where it had been associated with high rate of fetal brain malformation, and was injected to macaques at relatively low challenge dose of a minimally passaged virus stock [18]. ZIKV could be found in the blood of pregnant macaques beyond day 7 post infection, at a time when the blood of non-pregnant macaques had become sterile after similar exposure to ZIKV. Amniotic fluid infection was also detected in nearly 50% of dams, and in utero fetal deaths were observed [18], thus reproducing many features of the ZIKV infection of pregnant women.
While the ZIKV epidemic in Latin America will result in tens of thousands of babies with neurological abnormalities [19], it is not clear why only a subgroup of women, infected with ZIKV during pregnancy, show susceptibility for having babies with brain complications. Likewise, it is not clear why the inhabitants of some regions, like the Province of Pernambuco in Brazil, displayed such strong proclivity of the infecting ZIKV for the nervous system of the unborn child. It suggests, perhaps, a role for co-factors, among which co-infection with other viruses could be one contributing factor (Figure 2). Hence, clues from existing epidemic surveys are being researched to establish plausible hypotheses that can be tested with translational and clinical research. One intriguing finding from the Brazilian epidemic was the evidence of prior infection with Dengue, confirmed in nearly 90% of pregnant women [14], and occurred at such high frequency whether the fetus presented anomalies or not.
ZIKV is a member of the genus Flavivirus of the Flaviviridae family, classified as an arbovirus (arthropod-born), which includes Dengue (DENV), Japanese Encephalitis (JEV) viruses, West Nile (WNV), Yellow Fever (YFV), and are closely related to, and share symptoms with, the Chikungunya virus (CHICV) which is a member of the Togaviridae family (19-21). Hence, it has been speculated that prior or concurrent infection with another one of these viruses could somehow facilitate placental infection by ZIKV and brain defects. One reported mechanism could involve antibody-dependent enhancement (ADE) of virus infection by ZIKV (21). But so far, no such acute co-infection involving ZIKV and another virus of the arbovirus group seems to account for fetal susceptibility, and for ZIKV proclivity for their nervous system (14). While the concept of general immune suppression (as in patients post-organ transplant) during pregnancy has been effectively rejected as overly simplistic, [22], the prolonged ZIKV viremia observed in infected pregnant primates [18] could be secondary to a specific situation of immune “tolerance” relative to this particular virus during pregnancy. Such prolonged viremia could be a major factor involved in secondary amniotic fluid and fetus infection [18]. In situations where ZIKV-infected mosquito bites are more frequent, the prolongation of viremia in pregnancy may lead to cumulative rise ZIKV viremia over time, to a point of overwhelming the natural defense of the placenta and consequent infection of the fetus brain (autologous cooperation) (Figure 2).
Figure 2: Virus cooperation hypothesis for ZIKV infection of the placenta and the fetus brain.
A. The prolonged viremia of ZIKV seen in non-human primates (18) might allow for accumulation of the virus load resulting from consecutive exposures to bites from Ae. Aegypti mosquito (carrier of ZIKV). The resulting viremia overwhelms the placental defense against the virus (autologous cooperation). Alternatively, a prior or concurrent infection (reactivation) of a pregnant woman with a Human Herpes Virus (HHVn) capable of infecting the placenta, might weaken placental resistance to ZIKV, thus creating an opportunity for ZIKV to invade placenta and fetus even in the presence of lower ZIKV viremia (heterologous cooperation).
In both cases, ZIKV ends up infecting the brain (the proclivity of ZIKV for the brain of the unborn fetus results in microcephaly as shown), and other fetal tissues. In the absence of such viral cooperation, the placenta is readily capable of blocking ZIKV and thus protecting the fetus1.
B. Theoretical graph showing successive mosquito bites (red dots) in a non-pregnant woman (left panel) resulting in limited viremia, versus successive bites in a pregnant woman (right panel), showing the impact on viremia. The challenge created by pregnancy to eliminate ZIKV from the mother’s blood results in a cumulative viremia that exceeds the threshold (dotted line) for infection of the placenta and fetus.
1Artist rendering of virus capsids for figures 1 and 2 were inspired by the image reconstruction of the viral capsids as defined by electron cryomicroscopy work: (a) KSHV: Trus BL, Heymann B, Nealon K, Cheng N, Newcomb WW, Brown JC, Kedes DH, Steven AC. Capsid structure of Kaposi’s sarcoma-associated herpersvirus, a gammaherpesvirus, compared to those of an alphaherpesvirus, herpes simplex virus type 1, and a betaherpesvirus, cytomegalovirus. J Virology 75:2879-2890, 2001. (b) HIV: Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497:643-646, 2013. (c) ZIKV: Sirohi D, Chen Z, Sun L, Klose T, Pierson TC, Rossmann MG, Kuhn RJ. The 3.8 Å resolution cryo-EM structure of Zika virus. Science 10.1126/science.aaf5316, 2016. (d) HCMV: Butcher SJ, Aitken J, Mitchell J, Gowen B, Dargan DJ. Structure of the human cytomegalovirus B capsid by electron cryomicroscopy and image reconstruction. J Structural Biology 124:70-76, 1998
The mechanism for immune tolerance to ZIKV in pregnancy is unknown, but infection of the placenta and fetus could be secondary to virus cooperation, autologous or heterologous cooperation. Indeed, concurrent infections of the human fetal brain with ZIKV and HHV have also been reported [23].
Before the Brazilian ZIKV epidemic, another ubiquitous virus, Cytomegalovirus (CMV, HHV5) [24], which, like KSHV (HHV8) and Epstein Barr (HHV4) virus, is a member of Human Herpes Virus family (Herpesviridae), was well known for infecting the placenta of pregnant women and causing nervous system damage, although not with the prevalence and severity of ZIKV [14,25]. Among newly infected women, the rate of transmission in utero of CMV is very high (between 30 and 40%), and fetal abnormalities occur mainly with infections that occur during the first trimester [24]. Intriguingly, other members of the Herpes Virus family can also infect the human placenta, although less frequently than CMV. Human Herpes Virus 1, 2, 6, Epstein Barr Virus (EBV), and even KSHV, all have been shown, as with CMV, to infect the placenta [23,26].
It is tempting to speculate, and readily testable, that co-infection with ZIKV and one of the Human Herpes Viruses could potentiate the likelihood of placental transmission of ZIKV, and perhaps aggravate consequential infection of the fetal brain. This hypothesis has been tested clinically already for CMV, and results so far do not support cooperation between acute CMV infection and ZIKV, but it has not been tested for other Human Herpes Viruses that are known to infect the placenta [23,26]. Furthermore, a prior CMV infection may cause diminished bystander activation of natural killer (NK) cells [27], thereby reducing resistance to other infecting viruses such ZIKV, even in the absence of acute CMV infection.
Upon co-infection of ZIKV with HHV-2 (HSV-2) in mice, HHV-2 enhanced placental sensitivity to ZIKV, and allowed ZIKV to breach the placental barrier and access the fetus [28]. If such a hypothesis and animal experiments were to be confirmed in humans, pregnant women infected with ZIKV could be treated with available drugs that control Human Herpes Virus infections. For sure, more work needs to focus on how the placental barrier can be broken so effectively for some pregnant women infected with ZIKV [29].
Viruses display an exquisite disposition for frequent mutations, which they rely upon to assure their survival in adverse conditions, as well as their ability to adapt to new hosts in the case of zoonotic infections. At times, they even engage in a process of "hypermutation", whenever surrounding conditions are changing or challenging. For example, when its transmission amongst humans is facilitated, it is known that a virus can become more aggressive and proliferates faster. A recent study on ZIKV has suggested that a single mutation that occurred in 2013 could explain the heightened proclivity of ZIKV for mouse and human brains [30].
Alternatively, if transmission is a challenge, the virus can adopt a more chronic, benign gestalt. Hypermutation may also explain why KSHV became so much more virulent and contagious than it was before the onset of the AIDS epidemic, and why it was able to infect equally men and women, rather than having greater infectivity for men [31,32]. Hence, viruses adapt to their environment through phenotypic changes that are the result of genetic mutations. In some cases, genetic changes result in creation of new genes. In order to infect humans, the ancestors of the lentiviruses evolved genes that neutralize antiviral proteins of the host that themselves evolved to oppose threats from exogenous pathogens [33]. At the gene level, alterations in viral envelope genes could lead to altered host cell tropism and allow the virus to take up residence in immune-privileged sites such as the CNS.
The human genome does not undergo much mutation, and certainly never to the extent observed in viruses (even within tumor tissues). Without such mutational plasticity and rapid phenotypic adaptation, human resilience and adaptability instead rely on individual and collective inventiveness and creativity (human “hyperideation” as a corollary for viral “hypermutation”) to adapt to environmental challenges, such as antimicrobial drugs/vaccination campaigns used to combat pandemic infections. Human endeavors in science and research are our best solution to adapt to the changing battlefield involving microbes and their cooperation that will continue to impact human health, starting in utero, throughout the 21st century.
Clinical Implications
For women, ZIKV infection is a dreadful health issue because of the risk of infection of the placenta, the fetus and consequent condition of their children. ZIKV is transmitted to humans mostly through the bite of Aedes aegypti mosquitoes. This mosquito feeds mainly at dusk and dawn, but can bite at any time of the day, hence bed nets at night are not sufficiently protective. For pregnant women (from first trimester to delivery), the safest protection is to stay, or move, away from endemic area, where the chance of getting bitten by Ae. Aegypti carrying ZIKV multiple times is high (Figure 2). If “away” is not an option, then getting rid of stagnant water (especially inside the house, toilets, showers etc.), long sleeve clothing, screens and bed nets, use of insect repellants containing DEET (N, N-diethylmetatoluamide, 20%-30%) or p-menthane-3,8-diol (from lemon eucalyptus), all were shown effective in reducing bites of Ae. Aegypti mosquito, and hopefully below the threshold of viremia required for placenta and fetus infection.
Acknowledgement
The authors want to thank the University of Miami’s Institute of AIDS and Emerging Infectious Diseases for its funding support of this work.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
