The Brief History of Complementary, Alternative, and Integrative Medicine Terminology and the Development and Creation of an Operational Definition.

The definition of complementary, alternative, and integrative medicine (CAIM) remains dynamic and complex despite a steady increase in the popularity/usage of CAIM therapies across the globe. A lack of consistency in how these terms are defined remains a challenge for researchers, clinicians, and national and international organizations (e.g., World Health Organization, National Center for Complementary and Integrative Health) alike. In the present article, we provide a brief history of the use of these terminologies, and then outline the process we took to develop and create an operational definition of complementary, alternative, and integrative medicine. Our operational definition is the first to be informed by a systematic search of four quality-assessed information resource types, ultimately yielding 604 unique CAIM therapies. We then developed a single search string for the most common bibliographic databases using the finalized operational definition list of CAIM therapies. These CAIM therapies were searched against the Therapeutic Research Center's "Natural Medicines" database for all 604 therapies, whereby each item's scientific name and/or synonym was included as a keyword or phrase in the search string. While the current definition is not without limitations and ongoing debates still surround the field, this work is arguably a steppingstone towards enabling increased collaboration and communication amongst healthcare clinicians, researchers, and the public. This operational definition provides a foundation for developing well-coordinated research efforts that will assist in the acceptance and understanding of this field, while also focusing on adopting knowledge translation techniques and efforts for further research advancement and use.

Metabolic signature for a dysbiotic microbiome in the female genital tract: A systematic review and meta-analysis.

BACKGROUND: The vaginal microbiome (VMB) is a critical determinant of reproductive health, where a microbial shift towards a dysbiotic environment has implications for susceptibility to, and clinical presentation of sexually transmitted infections (STIs). Metabolomic profiling of the vaginal microenvironment has led to the identification of metabolic responses to clinical conditions of dysbiosis. However, no studies have examined metabolic markers that are common across conditions and can serve as a signature for vaginal dysbiosis. METHOD OF STUDY: We have conducted a comprehensive systematic review and meta-analysis to identify consistently deregulated metabolites along with their impact on host and microbial metabolism during dysbiosis. We employed two complementary approaches including a vote counting analysis for all eligible studies identified in the systematic review, in addition to a meta-analysis for a subset of studies with sufficient available data. Significantly deregulated metabolites were then selected for pathway enrichment analysis. RESULTS: Our results revealed a total of 502 altered metabolites reported across 10 dysbiotic conditions from 16 studies. Following a rigorous, collective analysis, six metabolites which were consistently downregulated and could be generalized to all dysbiotic conditions were identified. In addition, five downregulated and one upregulated metabolite was identified from a bacterial vaginosis (BV) focused sub-analysis. These metabolites have the potential to serve as a metabolic signature for vaginal dysbiosis. Their role in eight altered metabolic pathways indicates a disruption of amino acid, carbohydrate, and energy metabolism during dysbiosis. CONCLUSION: Based on this analysis, we propose a schematic model outlining the common metabolic perturbations associated with vaginal dysbiosis, which can be potential targets for therapeutics and prophylaxis.

Equity, diversity & inclusion in academic radiology: An elusive dream.

BACKGROUND: Disparities in sex and race/ethnicity continue to persist in the academic radiology. This study addresses the sex/racial underrepresentation and evolution in the academic radiology. PURPOSE: To evaluate academic radiology temporal trends disparities by analyzing sex and race/ethnicity diversity in academic degree and tenure status. MATERIALS AND METHODS: A retrospective cross-sectional analysis conducted using American Association of Medical College database between 2007 and 2018. Trends in academic degree, tenure status, race/ethnicity, and sex assessed with linear regression analysis and Poisson regression model for annual percent change with statistical significance of p < 0.05. RESULTS: Out of 107,213 radiologists 72%, n = 76,893 males and 64%, n = 68,738 white faculty with 1277 males and 872 females. White MD-degree radiologists constitute 67.2%, Asian (20.9%), Black (2.5%), Hispanic (3.2%), multiple (3.4%), unknown (1.8%) and "other" (1%) races with a similar PhD/other doctoral and dual-degree. White faculty recruitment trend (n2007 = 955, n2018 = 703) and representation (-0.82% per year; 95% CI, -1.00 to -0.63; p < 0.0001) decreased, while Asian URM decreased respectively (n2007 = 152, n2018 = 205) (0.68% per year; 95% CI, 0.58 to 0.77; p < 0.0001). Females were underrepresented in all categories. CONCLUSION: URM and females are underrepresented in academic radiology. Academic degree types and tenure track may contribute to White and male academic radiologists overrepresentation.

LAMP3/CD63 Expression in Early and Late Endosomes in Human Vaginal Epithelial Cells Is Associated with Enhancement of HSV-2 Infection.

Herpes simplex virus 2 (HSV-2) is a lifelong sexually transmitted virus that disproportionately infects women through heterosexual transmission in the vaginal tract. The vaginal epithelium is known to be highly susceptible to HSV-2 infection; however, the cellular mechanism of HSV-2 uptake and replication in vaginal epithelium has not been extensively studied. Previously, we observed that lysosomal-associated membrane protein-3 (LAMP3/CD63) was among the highly upregulated genes during HSV-2 infection of human vaginal epithelial cell line VK2, leading us to posit that LAMP3/CD63 may play a role in HSV-2 infection. Consequently, we generated two gene-altered VK2-derived cell lines, a LAMP3-overexpressed (OE) line and a LAMP3 knockout (KO) line. The wild-type VK2 and the LAMP3 OE and KO cell lines were grown in air-liquid interface (ALI) cultures for 7 days and infected with HSV-2. Twenty-four hours postinfection, LAMP3 OE cells produced and released significantly higher numbers of HSV-2 virions than wild-type VK2 cells, while virus production was greatly attenuated in LAMP3 KO cells, indicating a functional association between LAMP3/CD63 expression and HSV-2 replication. Fluorescence microscopy of HSV-2-infected cells revealed that HSV-2 colocalized with LAMP3 in both early endosomes and lysosomal compartments. In addition, blocking endosomal maturation or late endosomal/lysosomal fusion using specific inhibitors resulted in reduced HSV-2 replication in VK2 cells. Similarly, LAMP3 KO cells exhibited very low viral entry and association with endosomes, while LAMP3 OE cells demonstrated large amounts of virus that colocalized with LAMP3/CD63 in endosomes and lysosomes. IMPORTANCE Collectively, these results showed that HSV-2 is taken up by human vaginal epithelial cells through an endosomal-lysosomal pathway in association with LAMP3, which plays a crucial role in the enhancement of HSV-2 replication. These findings provide the basis for the future design of antiviral agents for prophylactic measures against HSV-2 infection.

A comprehensive search string informed by an operational definition of complementary, alternative, and integrative medicine for systematic bibliographic database search strategies.

BACKGROUND: Determining which therapies fall under the umbrella of complementary, alternative, and/or integrative medicine (CAIM) is difficult for several reasons. An operational definition is dynamic, and changes depending on both historical time period and geographical location, with many countries integrating or considering their traditional system(s) of medicine as conventional care. We have previously reported the first operational definition of CAIM informed by a systematic search. In the present study, we have developed a comprehensive search string informed by an operational definition of CAIM for systematic bibliographic database search strategies. METHODS: We developed a single search string for the most common bibliographic databases, including those searchable on the OVID platform (e.g., MEDLINE, EMBASE, PsycINFO, AMED), the EBSCO platform (e.g., ERIC, CINAHL), Scopus, and Web of Science, using the finalised operational definition of CAIM's 604 therapies. We searched the Therapeutic Research Center's "Natural Medicines" database for all 604 therapies, and each item's scientific name and/or synonym was included as a keyword or phrase in the search string. RESULTS: This developed search string provides a standardised list of CAIM terms (i.e., keywords and phrases) that may be searched on bibliographic databases including those found on the OVID platform (e.g., MEDLINE, EMBASE, PsycINFO, AMED), the EBSCO platform (e.g., ERIC, CINAHL), Scopus, and Web of Science. CONCLUSION: Researchers can select relevant terms for their CAIM study and insert the keywords/phrases into these databases to receive all accessible data. This search technique can simply be copied and pasted into the search bar of each database to identify research by keywords, which is the most inclusive, or by words in the article title, which is more selective. Given its versatility across multiple commonly used academic platforms/databases, it is expected that this search string will be of great value to those conducting research on CAIM topics involving systematic search strategies.

Operational definition of complementary, alternative, and integrative medicine derived from a systematic search.

BACKGROUND: Identifying what therapies constitute complementary, alternative, and/or integrative medicine (CAIM) is complex for a multitude of reasons. An operational definition is dynamic, and changes based on both historical time period and geographical location whereby many jurisdictions may integrate or consider their traditional system(s) of medicine as conventional care. To date, only one operational definition of "complementary and alternative medicine" has been proposed, by Cochrane researchers in 2011. This definition is not only over a decade old but also did not use systematic methods to compile the therapies. Furthermore, it did not capture the concept "integrative medicine", which is an increasingly popular aspect of the use of complementary therapies in practice. An updated operational definition reflective of CAIM is warranted given the rapidly increasing body of CAIM research literature published each year. METHODS: Four peer-reviewed or otherwise quality-assessed information resource types were used to inform the development of the operational definition: peer-reviewed articles resulting from searches across seven academic databases (MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, Scopus and Web of Science); the "aims and scope" webpages of peer-reviewed CAIM journals; CAIM entries found in online encyclopedias, and highly-ranked websites identified through searches of CAIM-related terms on HONcode. Screening of eligible resources, and data extraction of CAIM therapies across them, were each conducted independently and in duplicate. CAIM therapies across eligible sources were deduplicated. RESULTS: A total of 101 eligible resources were identified: peer-reviewed articles (n = 19), journal "aims and scope" webpages (n = 22), encyclopedia entries (n = 11), and HONcode-searched websites (n = 49). Six hundred four unique CAIM terms were included in this operational definition. CONCLUSIONS: This updated operational definition is the first to be informed by systematic methods, and could support the harmonization of CAIM-related research through the provision of a standard of classification, as well as support improved collaboration between different research groups.

Does Hamstring Graft Size Affect Functional Outcome and Incidence of Revision Surgery After Primary Anterior Cruciate Ligament (ACL) Reconstruction?

Purpose The primary outcome measure of this study was to determine the effect of hamstring graft size on the functional outcome of arthroscopic anterior cruciate ligament reconstruction (ACL-R) and the secondary outcome was to ascertain the effect on revision surgery at the two-year follow-up. Methods This is a prospective comparative study of 144 consecutive patients undergoing primary ACL reconstruction using a hamstring autograft. All patients underwent graft harvesting and ACL reconstruction with the standard technique. The graft diameter was recorded intraoperatively using a graft sizer. All patients were followed up with the Knee Injury and Osteoarthritis Outcome Score (KOOS) recorded at preop, six weeks, six months, one year, and two years and whether they underwent revision during this period was documented. Results The mean KOOS for patients with a ≤ 7mm graft diameter was 80.5±13.1, which was significantly lower compared to those with graft > 7 mm of 88.3±8.5, respectively (p<0.001) at the two years follow-up. Patients with graft ≤ 7mm did poorly, especially with mean KOOS subscores of sports and recreation and quality of life (p<0.05). Twenty-three point one percent (23.1%; 3 out 13) of patients with a graft < 7mm underwent revision, whereas only 5.8% and 2.6% of patients underwent revision with a graft diameter of 7.1-8.0 and 8.1-9.0 (p=0.027). Conclusions The smaller Hamstring graft diameter leads to poorer functional outcomes of the patient's ACL reconstruction. Though the number of revisions was high among those with a graft diameter of ≤ 7mm, multicentric studies with many revisions are required to confirm the relation.

The relationship of anterior cruciate ligament injuries with MRI based calculation of femoral notch width, notch width index, notch shape - A randomized control study.

BACKGROUND: ACL injuries are infamously known for disability in young adults and require surgical reconstruction. The need of time is to predict predisposing factors and prevent ACL injuries.The incidence of ACL injuries has been associated with various factors related to the morphology of distal femur and proximal tibia.Hence, purpose of this study was to assess the relationship of morphology of distal femur by assessing Notch Width(NW), Notch Width Index (NWI), and Notch shape calculated preoperatively on MRI in association with an ACL tear. METHODS: The following randomized control study had 60 patients enrolled with non contact injury to knee who were equally divided into 2 groups i.e. ACL injury group and control group. ACL group had patients who had MRI proven ACL tear along with clinical findings suggestive of ACL tear whereas control contained patients with intact ACL. Demographic data was collected and NW, NWI and Notch shape were determined on coronal sections of MRI sequences. RESULTS: Positive correlation of ACL tear was seen with NW, BCW, NWI, NWP, and NWJ. Smaller Notch Width showed higher incidence of ACL tear (p = 0.019). The mean NWI in the injured and control knee is 0.31 ± 0.01 and 0.27 ± 0.01 respectively and was statistically significant(p < 0.001). A shaped Notch (60%) was commonly seen in ACL tear group and U shaped notch (73.3%) was commonly seen in control group.We found the cut off value for the prediction of ACL tear of NWI was 0.29 with a sensitivity of 90% and specificity of 86.7%. CONCLUSION: ACL injuries in the given population have shown higher incidence with narrow femoral intercondylar notch, smaller notch width index, 'A' shaped femoral notch. If any of the above findings are present in the MRI, its important to counsel the subjects about the increased risk of ACL injuries in them and take preventive measures.

TRIM26 Facilitates HSV-2 Infection by Downregulating Antiviral Responses through the IRF3 Pathway.

Herpes simplex virus type 2 (HSV-2) is the primary cause of genital herpes which results in significant morbidity and mortality, especially in women, worldwide. HSV-2 is transmitted primarily through infection of epithelial cells at skin and mucosal surfaces. Our earlier work to examine interactions between HSV-2 and vaginal epithelial cells demonstrated that infection of the human vaginal epithelial cell line (VK2) with HSV-2 resulted in increased expression of TRIM26, a negative regulator of the Type I interferon pathway. Given that upregulation of TRIM26 could negatively affect anti-viral pathways, we decided to further study the role of TRIM26 in HSV-2 infection and replication. To do this, we designed and generated two cell lines derived from VK2s with TRIM26 overexpressed (OE) and knocked out (KO). Both, along with wildtype (WT) VK2, were infected with HSV-2 and viral titres were measured in supernatants 24 h later. Our results showed significantly enhanced virus production by TRIM26 OE cells, but very little replication in TRIM26 KO cells. We next examined interferon-ß production and expression of two distinct interferon stimulated genes (ISGs), MX1 and ISG15, in all three cell lines, prior to and following HSV-2 infection. The absence of TRIM26 (KO) significantly upregulated interferon-ß production at baseline and even further after HSV-2 infection. TRIM26 KO cells also showed significant increase in the expression of MX1 and ISG15 before and after HSV-2 infection. Immunofluorescent staining indicated that overexpression of TRIM26 substantially decreased the nuclear localization of IRF3, the primary mediator of ISG activation, before and after HSV-2 infection. Taken together, our data indicate that HSV-2 utilizes host factor TRIM26 to evade anti-viral response and thereby increase its replication in vaginal epithelial cells.