scholarly journals Update on the Molecular Genetics of Timothy Syndrome

2021 ◽  
Vol 9 ◽  
Author(s):  
Rosemary Bauer ◽  
Katherine W. Timothy ◽  
Andy Golden
Keyword(s):  
Case Reports ◽  
Clinical Findings ◽  
Future Research ◽  
Timothy Syndrome ◽  
Genetic Changes ◽  
Neurodevelopmental Delay ◽  
Future Research Directions ◽  
Prolonged Qt Interval ◽  
Biophysical Changes

Timothy Syndrome (TS) (OMIM #601005) is a rare autosomal dominant syndrome caused by variants in CACNA1C, which encodes the α1C subunit of the voltage-gated calcium channel Cav1.2. TS is classically caused by only a few different genetic changes and characterized by prolonged QT interval, syndactyly, and neurodevelopmental delay; however, the number of identified TS-causing variants is growing, and the resulting symptom profiles are incredibly complex and variable. Here, we aim to review the genetic and clinical findings of all published case reports of TS to date. We discuss multiple possible mechanisms for the variability seen in clinical features across these cases, including mosaicism, genetic background, isoform complexity of CACNA1C and differential expression of transcripts, and biophysical changes in mutant CACNA1C channels. Finally, we propose future research directions such as variant validation, in vivo modeling, and natural history characterization.

scholarly journals Coronavirus disease 2019 infection and pituitary apoplexy: A causal relation or just a coincidence? A case report and review of the literature

2021 ◽  
Vol 12 ◽  
pp. 317
Author(s):  
Walaa A. Kamel ◽  
Mustafa Najibullah ◽  
Mamdouh S. Saleh ◽  
Waleed A. Azab
Keyword(s):  
Mr Imaging ◽  
Causal Relation ◽  
Histopathological Examination ◽  
Case Reports ◽  
English Literature ◽  
Clinical Findings ◽  
Oculomotor Nerve Palsy ◽  
Future Research ◽  
Endoscopic Endonasal ◽  
Transsphenoidal Resection

Background: Pituitary tumor apoplexy (PA) is an emergency condition caused by hemorrhage or infarction of the preexisting adenoma. Many factors are currently well-known to predispose to PA. However, during the period of coronavirus disease 2019 (COVID-19) pandemic, case reports of PA associated with COVID-19 infection have been sequentially published. To the best of our knowledge, four cases have been reported so far in the English literature. We herein report the fifth case of this association and review the pertinent literature. Case Description: A 55-year-old male patient with confirmed COVID-19 infection presented by progressive decrease in visual acuity and oculomotor nerve palsy. His medical history is notable for diabetes mellitus, hypertension, and pituitary macroadenoma resection 11 years ago. He was on hormonal replacement therapy for panhypopituitarism that complicated the surgery. Previous magnetic resonance (MR) imaging studies were consistent with enlarging residual pituitary adenoma. During the current hospitalization, computed tomography revealed hyperdensity of the sellar and suprasellar areas. MR imaging revealed PA in a recurrent large adenoma. Endoscopic endonasal transsphenoidal resection was uneventfully undertaken with near total excision of the adenoma and partial improvement of visual loss and oculomotor palsy. Histopathological examination demonstrated classic features of PA. However, his chest condition progressed and he had to be transferred to COVID-19 intensive care unit in the referring hospital where he was intubated and put on mechanical ventilation. One week later, the patient unfortunately passed away due to complications of severe COVID-19 pneumonia. Conclusion: We report the fifth case of PA associated with COVID-19 infection. Based on our patient’s clinical findings, review of the other reported cases, as well as the available literature, we put forth a multitude of pathophysiological mechanisms induced by COVID-19 that can possibly lead to the development of PA. In our opinion, the association between both conditions is not just a mere coincidence. Although the histopathological features of PA associated with COVID-19 are similar to PA induced by other etiologies, future research may disclose unique pathological fingerprints of COVID-19 virus that explains its capability of inducing PA.

Using Prolonged Exposure With an Older Male U.S. Veteran With Childhood Sexual Abuse-Related PTSD

2018 ◽  
Vol 18 (2) ◽  
pp. 115-127 ◽  
Author(s):  
Elissa McCarthy ◽  
Joan M. Cook
Keyword(s):  
Sexual Abuse ◽  
Childhood Sexual Abuse ◽  
Randomized Clinical Trials ◽  
Prolonged Exposure ◽  
Case Reports ◽  
Future Research ◽  
Sexual Assaults ◽  
Meaningful Improvement ◽  
Chronic Ptsd

Older adults have generally not been included in randomized clinical trials of psychotherapy for posttraumatic stress disorder (PTSD). Of the case reports and treatment outcome studies that have included those aged 55 and older, most did not include men with sexual abuse-related PTSD. This case report presents the successful application of Prolonged Exposure (PE) to a 58-year-old single, Caucasian noncombat U.S. Army veteran with severe, chronic PTSD related to several sexual assaults, including childhood sexual abuse. PE is a manualized, short-term, evidence-based psychotherapy for the treatment of PTSD which involves psychoeducation, breathing retraining, in vivo exposure, and imaginal exposure. PTSD and depressive symptoms demonstrated clinically meaningful improvement during the course of treatment. In addition, he experienced significant improvement in quality of life as well as meaning and purpose from baseline to posttreatment. Implications for clinically working with older men with untreated childhood sexual abuse-related PTSD later in life are presented. Future research directions are discussed.

Blood vessel remodeling and physical inactivity in humans

2011 ◽  
Vol 111 (6) ◽  
pp. 1836-1845 ◽  
Author(s):  
Dick H. J. Thijssen ◽  
Daniel J. Green ◽  
Maria T. E. Hopman
Keyword(s):  
Vascular Function ◽  
Physical Inactivity ◽  
Future Research ◽  
Vessel Remodeling ◽  
Resistance Vessels ◽  
Future Research Directions ◽  
Response To Exercise ◽  
The Impact

Physical inactivity is associated with an increase in cardiovascular risk that cannot be fully explained by traditional or novel risk factors. Inactivity is also associated with changes in hemodynamic stimuli, which exert direct effects on the vasculature leading to remodeling and a proatherogenic phenotype. In this review, we synthesize and summarize in vivo evidence relating to the impact of local and systemic models of physical inactivity on conduit arteries, resistance vessels, and the microcirculation in humans. Taken together, the literature suggests that a rapid inward structural remodeling of vessels occurs in response to physical inactivity. The magnitude of this response is dependent on the “dose” of inactivity. Moreover, changes in vascular function are found at resistance and microvessel levels in humans. In conduit arteries, a strong interaction between vascular function and structure is present, which results in conflicting data regarding the impact of inactivity on conduit artery function. While much of the cardioprotective effect of exercise is related to the nitric oxide pathway, deconditioning may primarily be associated with activation of vasoconstrictor pathways. The effects of deconditioning on the vasculature are therefore not simply the opposite of those in response to exercise training. Given the importance of sedentary behavior, future studies should provide further insight into the impact of inactivity on the vasculature and other (novel) markers of vascular health. Moreover, studies should examine the role of (hemodynamic) stimuli that underlie the characteristic vascular adaptations during deconditioning. Our review concludes with some suggestions for future research directions.

scholarly journals Transcriptional and Epigenomic Regulation of Adipogenesis

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Ji-Eun Lee ◽  
Hannah Schmidt ◽  
Binbin Lai ◽  
Kai Ge
Keyword(s):  
Transcription Factors ◽  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Future Research ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Future Research Directions ◽  
Epigenomic Regulation ◽  
Adipocyte Development

ABSTRACT Understanding adipogenesis, the process of adipocyte development, may provide new ways to treat obesity and related metabolic diseases. Adipogenesis is controlled by coordinated actions of lineage-determining transcription factors and epigenomic regulators. Peroxisome proliferator-activated receptor gamma (PPARγ) and C/EBPα are master “adipogenic” transcription factors. In recent years, a growing number of studies have reported the identification of novel transcriptional and epigenomic regulators of adipogenesis. However, many of these novel regulators have not been validated in adipocyte development in vivo and their working mechanisms are often far from clear. In this minireview, we discuss recent advances in transcriptional and epigenomic regulation of adipogenesis, with a focus on factors and mechanisms shared by both white adipogenesis and brown adipogenesis. Studies on the transcriptional regulation of adipogenesis highlight the importance of investigating adipocyte differentiation in vivo rather than drawing conclusions based on knockdown experiments in cell culture. Advances in understanding of epigenomic regulation of adipogenesis have revealed critical roles of histone methylation/demethylation, histone acetylation/deacetylation, chromatin remodeling, DNA methylation, and microRNAs in adipocyte differentiation. We also discuss future research directions that may help identify novel factors and mechanisms regulating adipogenesis.

scholarly journals History, Present, and Progress of Frontotemporal Dementia in China: A Systematic Review

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ru-Jing Ren ◽  
Yue Huang ◽  
Gang Xu ◽  
Chun-Bo Li ◽  
Qi Cheng ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Age Of Onset ◽  
Case Reports ◽  
Small Sample ◽  
Current Status ◽  
Future Research ◽  
Clinical Presentations ◽  
Neuropathological Diagnosis ◽  
Future Research Directions ◽  
Small Sample Sizes

We aim to provide an overview of clinical and demographical features and neuropathological research on frontotemporal dementia (FTD) from China over the past decade. We reviewed the demographic features, clinical presentations, and neuropathology of the FTD-spectrum disorders from the 49 cases in China published since 1998. On the basis of these findings, we retrospect the history and speculate on future progress in terms of FTD in China. We found that most published papers comprise case reports with a few retrospective studies with small sample sizes. Behavior variant FTD (bvFTD) was the most common diagnostic subtype, of which 35% were associated with amyotrophic lateral sclerosis or Parkinsonian syndrome. More than 47% patients with FTD had age onset before 65. There were no differences in age of onset and sex distribution between diagnostic subtypes. The spectrum of neuropathological diagnosis of bvFTD was frontotemporal lobe degeneration (FTLD) with tau protein or ubiquitin-immunopositive inclusions, and FTLD without intracellular inclusions. Median survival in bvFTD was 14 years. This paper provides an overview of the current status and pointers for future research directions of FTD in China.

scholarly journals Glioma-on-a-Chip Models

Micromachines ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 490
Author(s):  
Merve Ustun ◽  
Sajjad Rahmani Dabbagh ◽  
Irem Sultan Ilci ◽  
Tugba Bagci-Onder ◽  
Savas Tasoglu
Keyword(s):  
Future Research ◽  
Cell Behavior ◽  
Therapeutic Approaches ◽  
Term Survival ◽  
Research Directions ◽  
Metabolic Functions ◽  
Future Research Directions ◽  
On Chip

Glioma, as an aggressive type of cancer, accounts for virtually 80% of malignant brain tumors. Despite advances in therapeutic approaches, the long-term survival of glioma patients is poor (it is usually fatal within 12–14 months). Glioma-on-chip platforms, with continuous perfusion, mimic in vivo metabolic functions of cancer cells for analytical purposes. This offers an unprecedented opportunity for understanding the underlying reasons that arise glioma, determining the most effective radiotherapy approach, testing different drug combinations, and screening conceivable side effects of drugs on other organs. Glioma-on-chip technologies can ultimately enhance the efficacy of treatments, promote the survival rate of patients, and pave a path for personalized medicine. In this perspective paper, we briefly review the latest developments of glioma-on-chip technologies, such as therapy applications, drug screening, and cell behavior studies, and discuss the current challenges as well as future research directions in this field.

scholarly journals Vascularized Lower Respiratory-Physiology-On-A-Chip

2020 ◽  
Vol 10 (3) ◽  
pp. 900 ◽  
Author(s):  
Hyoryung Nam ◽  
Yoo-mi Choi ◽  
Jinah Jang
Keyword(s):  
Treatment Options ◽  
Respiratory Physiology ◽  
Future Research ◽  
Research Directions ◽  
Disease Mechanisms ◽  
Chip Technology ◽  
Future Research Directions ◽  
Respiratory Systems

Recently, respiratory systems are increasingly threatened by high levels of environmental pollution. Organ-on-a-chip technology has the advantage of enabling more accurate preclinical experiments by reproducing in vivo organ physiology. To investigate disease mechanisms and treatment options, respiratory-physiology-on-a-chip systems have been studied for the last decade. Here, we delineate the strategic approaches to develop respiratory-physiology-on-a-chip that can recapitulate respiratory system in vitro. The state-of-the-art biofabrication methods and biomaterials are considered as key contributions to constructing the chips. We also explore the vascularization strategies to investigate complicated pathophysiological phenomena including inflammation and immune responses, which are the critical aggravating factors causing the complications in the respiratory diseases. In addition, challenges and future research directions are delineated to improve the mimicry of respiratory systems in terms of both structural and biological behaviors.

scholarly journals Sulforaphane: A Broccoli Bioactive Phytocompound with Cancer Preventive Potential

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4796
Author(s):  
Anna E. Kaiser ◽  
Mojdeh Baniasadi ◽  
Derrek Giansiracusa ◽  
Matthew Giansiracusa ◽  
Michael Garcia ◽  
...  
Keyword(s):  
Human Cancer ◽  
Health Benefits ◽  
Mechanisms Of Action ◽  
Future Research ◽  
Research Directions ◽  
Chemopreventive Agent ◽  
Future Research Directions ◽  
Major Mediator

There is substantial and promising evidence on the health benefits of consuming broccoli and other cruciferous vegetables. The most important compound in broccoli, glucoraphanin, is metabolized to SFN by the thioglucosidase enzyme myrosinase. SFN is the major mediator of the health benefits that have been recognized for broccoli consumption. SFN represents a phytochemical of high interest as it may be useful in preventing the occurrence and/or mitigating the progression of cancer. Although several prior publications provide an excellent overview of the effect of SFN in cancer, these reports represent narrative reviews that focused mainly on SFN’s source, biosynthesis, and mechanisms of action in modulating specific pathways involved in cancer without a comprehensive review of SFN’s role or value for prevention of various human malignancies. This review evaluates the most recent state of knowledge concerning SFN’s efficacy in preventing or reversing a variety of neoplasms. In this work, we have analyzed published reports based on in vitro, in vivo, and clinical studies to determine SFN’s potential as a chemopreventive agent. Furthermore, we have discussed the current limitations and challenges associated with SFN research and suggested future research directions before broccoli-derived products, especially SFN, can be used for human cancer prevention and intervention.

Cell-Enhanced Acellular Nerve Allografts for Peripheral Nerve Reconstruction: A Systematic Review and a Meta-Analysis of the Literature

Neurosurgery ◽  
2018 ◽  
Vol 85 (5) ◽  
pp. 575-604 ◽  
Author(s):  
Francesca Alice Pedrini ◽  
Filippo Boriani ◽  
Federico Bolognesi ◽  
Nicola Fazio ◽  
Claudio Marchetti ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Case Reports ◽  
Case Series ◽  
Future Research ◽  
Nerve Reconstruction ◽  
Level Of Evidence ◽  
Promising Alternative ◽  
Positive Effects

Abstract BACKGROUND Peripheral nerve reconstruction is a difficult problem to solve. Acellular nerve allografts (ANAs) have been widely tested and are a promising alternative to the autologous gold standard. However, current reconstructive methods still yield unpredictable and unsuccessful results. Consequently, numerous studies have been carried out studying alternatives to plain ANAs, but it is not clear if nerve regeneration potential exists between current biological, chemical, and physical enrichment modes. OBJECTIVE To systematically review the effects of cell-enhanced ANAs on regeneration of peripheral nerve injuries. METHODS PubMed, ScienceDirect, Medline, and Scopus databases were searched for related articles published from 2007 to 2017. Inclusion criteria of selected articles consisted of (1) articles written in English; (2) the topic being cell-enhanced ANAs in peripheral nerve regeneration; (3) an in vivo study design; and (4) postgrafting neuroregenerative assessment of results. Exclusion criteria included all articles that (1) discussed central nervous system ANAs; (2) consisted of xenografts as the main topic; and (3) consisted of case series, case reports or reviews. RESULTS Forty papers were selected, and categorization included the animal model; the enhancing cell types; the decellularization method; and the neuroregenerative test performed. The effects of using diverse cellular enhancements combined with ANAs are discussed and also compared with the other treatments such as autologous nerve graft, and plain ANAs. CONCLUSION ANAs cellular enhancement demonstrated positive effects on recovery of nerve function. Future research should include clinical translation, in order to increase the level of evidence available on peripheral nerve reconstruction.

25c-nbome: Case report and literature review

2017 ◽  
Vol 41 (S1) ◽  
pp. s874-s875
Author(s):  
M. Preve ◽  
S. Casigliani ◽  
L. Tognola ◽  
R. Traber ◽  
R.A. Colombo
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Case Reports ◽  
Kidney Injury ◽  
Drug Market ◽  
Individual Case ◽  
Future Research ◽  
The Internet ◽  
Future Research Directions ◽  
Competing Interest

IntroductionNovel psychoactive drugs (NPS) have rapidly increase in the last years in the drug market as a recreational use. A new group of toxic phenethylamine derivates named NBOMe of 2 C class present have emerged recently, are frequently bought using the internet and have similar effects to other hallucinogenic drugs; however, they may pose larger risks, due to the limited knowledge about them, their relatively low price and availability via the internet. The purpose of this report is to review the clinical evidence for the potential of abuse of NBOMe compounds. We propose a case report and literature review.MethodWe conducted a systematic review of the literature with the principal database (PubMed, Enbase, PsychInfo) and we present a case report.ResultsThe effects of 25C-NBOMe is characterized by hallucination, violent agitation, rhabdomyolysis and kydney injury.Discussion and conclusionEffects from 25C-NBOMe in our case report were similar to previous individual case reports in literature. The clinical features were also similar to effects from other analogues in the class (25I-NBOMe, 25B-NBOMe). In our case, violent agitation (signs of serotonergic stimulation), rhabdomyolysis and kidney injury were observed. Further research is warranted to replicate our clinical and qualitative observations and, in general, quantitative studies in large samples followed up over time are needed. Methodological limitations, clinical implications and suggestions for future research directions are considered.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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