Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes.

Establishing a nonproductive, quiescent infection within monocytes is essential for the spread of human cytomegalovirus (HCMV). We investigated the mechanisms through which HCMV establishes a quiescent infection in monocytes. US28 is a virally encoded G protein-coupled receptor (GPCR) that is essential for silent infections within cells of the myeloid lineage. We found that preformed US28 was rapidly delivered to monocytes by HCMV viral particles, whereas the de novo synthesis of US28 was delayed for several days. A recombinant mutant virus lacking US28 (US28Δ) was unable to establish a quiescent infection, resulting in a fully productive lytic infection able to produce progeny virus. Infection with US28Δ HCMV resulted in the phosphorylation of the serine and threonine kinase Akt at Ser473 and Thr308, in contrast with the phosphorylation of Akt only at Ser473 after WT viral infection. Inhibiting the dual phosphorylation of Akt prevented the lytic replication of US28Δ, and ectopic expression of a constitutively phosphorylated Akt variant triggered lytic replication of wild-type HCMV. Mechanistically, we found that US28 was necessary and sufficient to attenuate epidermal growth factor receptor (EGFR) signaling induced during the entry of WT virus, which led to the site-specific phosphorylation of Akt at Ser473. Thus, particle-delivered US28 fine-tunes Akt activity by limiting HCMV-induced EGFR activation during viral entry, enabling quiescent infection in monocytes.

Factors Associated With Increased Health Care Utilization for Patients With Dementia With Lewy Bodies: A Narrative Review.

Numerous studies have demonstrated that dementia is associated with increased utilization of health care services, which in turn results in increased costs of care. Dementia with Lewy bodies (DLB) is associated with greater costs of care relative to other forms of dementia due to higher rates of hospitalization and nursing home placement directly related to neuropsychiatric symptoms, parkinsonism, increased susceptibility to delirium, and elevated rates of caregiver burden. There is a critical need for researchers to identify potentially modifiable factors contributing to increased costs of care and poor clinical outcomes for patients with DLB, which may include comorbidities, polypharmacy/contraindicated medications, and access to specialty care. Previous research has utilized Medicare claims data, limiting the ability to study patients with early-onset (ie, prior to age 65) DLB. Integrated health systems offer the ability to combine electronic medical record data with Medicare, Medicaid, and commercial claims data and may therefore be ideal for utilization research in this population. The goals of this narrative review are to 1) synthesize and describe the current literature on health care utilization studies for patients with DLB, 2) highlight the current gaps in the literature, and 3) provide recommendations for stakeholders, including researchers, health systems, and policymakers. It is important to improve current understanding of potentially modifiable factors associated with increased costs of care among patients with DLB to inform public health policies and clinical decision-making, as this will ultimately improve the quality of patient care.

Female-Specific Health Care of Military Female-Designated Service Members and Veterans: A Systematic Overview of Reviews.

INTRODUCTION: Since the War in Afghanistan began in 2001, service members have faced significant health effects related to service during war, with female-designated service members facing unique challenges. Numerous high-quality review articles have been published on the health and care of female-designated service members and veterans. Given the increasing volume of literature, we completed an overview of reviews on the health and health care of female-designated military populations. Our objective was to conduct an overview of reviews on the obstetrics and gynecologic health and health care of female-designated military populations since 2000 to understand female-specific health consequences of military service during war and make clinical recommendations. MATERIALS AND METHODS: On May 10, 2022, a medical librarian performed a comprehensive search across five databases (Ovid Medline, Embase, CINAHL, PsycINFO, Ovid All EBM Reviews, and Web of Science) for all relevant reviews published from 2000 to May 10, 2022. Results were limited to English language. After the removal of duplicates, 2,438 records were reviewed, and 69 studies were included in the final review. The search strategy and methods were registered with PROSPERO and are reported according to the Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines. Two independent reviewers conducted title and abstract screening and subsequent full text review using Covidence Systematic Review Software. Reviews addressing female-specific and obstetrics and gynecologic health of female-designated service members or veterans, utilizing a clear and systematic methodology, were eligible for inclusion. Quality assessment was conducted by teams of two reviewers. RESULTS: A total of 69 studies were included in the final review. Themes included mental health and impact of sexual assault on service members or veterans, veteran health care, issues of menstruation, pregnancy, and urogenital concerns. Areas with few reviews included occupational risks of military service and impact on obstetric outcomes, eating disorders, and menopause. There were insufficient or no reviews on the impact of military service on fertility, access to abortion care, reproductive health outcomes of lesbian, bisexual and transgender service members, surgical treatment of gynecologic conditions, and screening and treatment for breast, gynecologic, and non-pelvic organ cancers. CONCLUSIONS: Female-designated military populations serving during periods of war face unique health challenges that should be considered in screening practices and the delivery of trauma informed care. Further research and reviews are needed for female-specific oncology, fertility, abortion access, and sexual and non-binary and expansive gender identities to better capture female-designated service member and veteran health during wartime and beyond.

Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes.

Human cytomegalovirus (HCMV) utilizes peripheral blood monocytes as a means to systemically disseminate throughout the host. Following viral entry, HCMV stimulates non-canonical Akt signaling leading to the activation of mTORC1 and the subsequent translation of select antiapoptotic proteins within infected monocytes. However, the full extent to which the HCMV-initiated Akt/mTORC1 signaling axis reshapes the monocyte translatome is unclear. We found HCMV entry alone was able to stimulate widescale changes to mRNA translation levels and that inhibition of mTOR, a component of mTORC1, dramatically attenuated HCMV-induced protein synthesis. Although monocytes treated with normal myeloid growth factors also exhibited increased levels of translation, mTOR inhibition had no effect, suggesting HCMV activation of mTOR stimulates the acquisition of a unique translatome within infected monocytes. Indeed, polyribosomal profiling of HCMV-infected monocytes identified distinct prosurvival transcripts that were preferentially loaded with ribosomes when compared to growth factor-treated cells. Sirtuin 1 (SIRT1), a deacetylase that exerts prosurvival effects through regulation of the PI3K/Akt pathway, was found to be highly enriched following HCMV infection in an mTOR-dependent manner. Importantly, SIRT1 inhibition led to the death of HCMV-infected monocytes while having minimal effect on uninfected cells. SIRT1 also supported a positive feedback loop to sustain Akt/mTORC1 signaling following viral entry. Taken together, HCMV profoundly reshapes mRNA translation in an mTOR-dependent manner to enhance the synthesis of select factors necessary for the survival of infected monocytes.IMPORTANCEHuman cytomegalovirus (HCMV) infection is a significant cause of morbidity and mortality among the immunonaïve and immunocompromised. Peripheral blood monocytes are a major cell type responsible for disseminating the virus from the initial site of infection. In order for monocytes to mediate viral spread within the host, HCMV must subvert the naturally short lifespan of these cells. In this study, we performed polysomal profiling analysis, which demonstrated HCMV to globally redirect mRNA translation toward the synthesis of cellular prosurvival factors within infected monocytes. Specifically, HCMV entry into monocytes induced the translation of cellular SIRT1 to generate an antiapoptotic state. Defining the precise mechanisms through which HCMV stimulates survival will provide insight into novel anti-HCMV drugs able to target infected monocytes.

Beyond Antiretroviral Treatment: Patterns and Factors Associated With Composite Medication Adherence Before and During the COVID-19 Pandemic in Patients With HIV With Multiple Chronic Conditions.

BACKGROUND: Polypharmacy for multiple chronic conditions (MCCs) poses an increasing challenge in people with HIV (PWH). This research explores medication adherence in PWH with MCCs before and during COVID-19. SETTING: Kaiser Permanente Mid-Atlantic States. METHODS: Medical and pharmacy records of a continuously enrolled cohort (September 2018-September 2021) of adult PWH were used. To estimate medication adherence, monthly proportion of days covered (PDC) was measured individually for antiretrovirals (ARVs), diabetes medications (DMs), renin-angiotensin antagonists (RASMs), and statins (SMs) and combined into composite measures (CMs) with and without ARVs. Descriptive statistics, time-series models, and multivariable population-averaged panel general estimating equations were used to profile trends, effects, and factors associated with adherence. RESULTS: The cohort (n = 543) was predominantly 51-64 years old (59.3%), Black (73.1%), male (69.2%), and commercially insured (65.4%). Two-thirds (63.7%) of patients were taking medications in 2 medication groups (ie, ARVs and either DMs, RASMs, or SMs), 28.9% were taking medications in 3 medication groups, and 7.4% were taking medications in all 4 medication groups. Overall, PDC for CMs without ARVs was 77.2% and 70.2% with ARVs. After March 2020, negative monthly trends in PDC were observed for CMs without ARVs (ß = -0.1%, P = 0.003) and with ARVs (ß = -0.3%, P = 0.001). For CMs with ARVs, Black race (aOR = 0.5; P < 0.001; ref: White) and taking medications for 3 medication groups (aOR = 0.8; P < 0.02; ref: 2) were associated with lower adherence. CONCLUSION: Decreasing medication adherence trends were observed during the COVID-19 pandemic with variations among population subgroups. Opportunity exists to improve medication adherence for non-White populations and those taking medications for MCCs beyond ARVs.

Is Bitterness Only a Taste? The Expanding Area of Health Benefits of Brassica Vegetables and Potential for Bitter Taste Receptors to Support Health Benefits.

The list of known health benefits from inclusion of brassica vegetables in the diet is long and growing. Once limited to cancer prevention, a role for brassica in prevention of oxidative stress and anti-inflammation has aided in our understanding that brassica provide far broader benefits. These include prevention and treatment of chronic diseases of aging such as diabetes, neurological deterioration, and heart disease. Although animal and cell culture studies are consistent, clinical studies often show too great a variation to confirm these benefits in humans. In this review, we discuss causes of variation in clinical studies, focusing on the impact of the wide variation across humans in commensal bacterial composition, which potentially result in variations in microbial metabolism of glucosinolates. In addition, as research into host-microbiome interactions develops, a role for bitter-tasting receptors, termed T2Rs, in the gastrointestinal tract and their role in entero-endocrine hormone regulation is developing. Here, we summarize the growing literature on mechanisms of health benefits by brassica-derived isothiocyanates and the potential for extra-oral T2Rs as a novel mechanism that may in part describe the variability in response to brassica among free-living humans, not seen in research animal and cell culture studies.

Pediatric Intracranial Arteriovenous Malformation: Long-Term Outcomes with Linear Accelerator (LINAC)-Based Radiosurgery.

PURPOSE: To analyze and report the long-term outcomes of intracranial arteriovenous malformations (AVM) treated with linear accelerator (LINAC)-based radiosurgery (LBRS) in the pediatric population. METHODS AND MATERIALS: A series of 34 pediatric patients (≤18 years old) who were treated between 2002 and 2016 were analyzed. All patients were treated with LBRS in a single fraction, with a median dose of 16.8 Gy to the 80% isodose line. Median age at treatment was 14.4 years (range 5.5-18.9). Median AVM volume was 2.91 mL (range 0.228-27.313). Median modified radiosurgery-based AVM score was 0.83 (range 0.18-2.96). The most common presenting symptom was intracranial hemorrhage (ICH) (n = 22, 64.7%). Nine patients underwent intervention before LBRS, which included prior embolization or resection. Seven lesions were in eloquent locations, defined as basal ganglia, thalamus, or brainstem. Cerebral angiography was done to confirm obliteration. RESULTS: Median follow-up time was 98 months (range 36-200 months). Twenty-two of the 34 lesions were obliterated (64.7%) with median time to obliteration of 37 months (range 14-79). No deaths occurred during the follow up period; however, two patients experienced ICH after treatment. Three other patients were treated for symptomatic radiation necrosis. CONCLUSIONS: Treatment of intracranial AVM with LBRS in the pediatric population is demonstrated to be safe and effective with long-term follow up.

Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes.

Aberrant redox signaling underlies the pathophysiology of many chronic metabolic diseases, including type 2 diabetes (T2D). Methodologies aimed at rebalancing systemic redox homeostasis have had limited success. A noninvasive, sustained approach would enable the long-term control of redox signaling for the treatment of T2D. We report that static magnetic and electric fields (sBE) noninvasively modulate the systemic GSH-to-GSSG redox couple to promote a healthier systemic redox environment that is reducing. Strikingly, when applied to mouse models of T2D, sBE rapidly ameliorates insulin resistance and glucose intolerance in as few as 3 days with no observed adverse effects. Scavenging paramagnetic byproducts of oxygen metabolism with SOD2 in hepatic mitochondria fully abolishes these insulin sensitizing effects, demonstrating that mitochondrial superoxide mediates induction of these therapeutic changes. Our findings introduce a remarkable redox-modulating phenomenon that exploits endogenous electromagneto-receptive mechanisms for the noninvasive treatment of T2D, and potentially other redox-related diseases.

Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health.

Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsistencies in health benefits in the human population. Here, we focused on the plasma metabolite profile and composition of the gut microbiome in rats, a relatively homogenous population in terms of gut microbiota, genetics, sex and diet, to determine if changes in the plasma metabolite profiles caused by dietary broccoli relate to molecular changes in liver. Our aim was to identify plasma indicators that reflect how liver health is impacted by dietary broccoli. Rats were fed a 10% broccoli diet for 14 days. We examined the plasma metabolite composition by metabolomics analysis using GC-MS and gut microbiota using 16S sequencing after 0, 1, 2, 4, 7, 14 days of broccoli feeding. We identified 25 plasma metabolites that changed with broccoli consumption, including metabolites associated with hepatic glutathione synthesis, and with de novo fatty acid synthesis. Glutamine, stearic acid, and S-methyl-L-cysteine (SMC) relative abundance changes correlated with changes in gut bacteria previously implicated in metabolic disease and with validated increases in expression of hepatic NAD(P)H dehydrogenase [quinone] 1 (NQO1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), associated with elevated hepatic glutathione synthesis. Circulating biomarkers following broccoli consumption reflect gut-liver axis health.

Human Cytomegalovirus Mediates Unique Monocyte-to-Macrophage Differentiation through the PI3K/SHIP1/Akt Signaling Network.

Blood monocytes mediate the hematogenous dissemination of human cytomegalovirus (HCMV) in the host. However, monocytes have a short 48-hour (h) lifespan and are not permissive for viral replication. We previously established that HCMV infection drives differentiation of monocytes into long-lived macrophages to mediate viral dissemination, though the mechanism was unclear. Here, we found that HCMV infection promoted monocyte polarization into distinct macrophages by inducing select M1 and M2 differentiation markers and that Akt played a central role in driving differentiation. Akt's upstream positive regulators, PI3K and SHIP1, facilitated the expression of the M1/M2 differentiation markers with p110δ being the predominant PI3K isoform inducing differentiation. Downstream of Akt, M1/M2 differentiation was mediated by caspase 3, whose activity was tightly regulated by Akt in a temporal manner. Overall, this study highlights that HCMV employs the PI3K/SHIP1/Akt pathway to regulate caspase 3 activity and drive monocyte differentiation into unique macrophages, which is critical for viral dissemination.

Human Cytomegalovirus Glycoprotein-Initiated Signaling Mediates the Aberrant Activation of Akt.

Human cytomegalovirus (HCMV) is a major cause of morbidity and mortality among immunocompromised and immunonaive individuals. HCMV-induced signaling initiated during viral entry stimulates a rapid noncanonical activation of Akt to drive the differentiation of short-lived monocytes into long-lived macrophages, which is essential for viral dissemination and persistence. We found that HCMV glycoproteins gB and gH directly bind and activate cellular epidermal growth factor receptor (EGFR) and integrin ß1, respectively, to reshape canonical Akt signaling within monocytes. The remodeling of the Akt signaling network was due to the recruitment of nontraditional Akt activators to either the gB- or gH-generated receptor signaling complexes. Phosphoinositide 3-kinase (PI3K) comprised of the p110ß catalytic subunit was recruited to the gB/EGFR complex despite p110δ being the primary PI3K isoform found within monocytes. Concomitantly, SH2 domain-containing inositol 5-phosphatase 1 (SHIP1) was recruited to the gH/integrin ß1 complex, which is critical to aberrant Akt activation, as SHIP1 diverts PI3K signaling toward a noncanonical pathway. Although integrin ß1 was required for SHIP1 recruitment, gB-activated EGFR mediated SHIP1 activation, underscoring the importance of the interplay between gB- and gH-mediated signaling to the unique activation of Akt during HCMV infection. Indeed, SHIP1 activation mediated the increased expression of Mcl-1 and HSP27, two Akt-dependent antiapoptotic proteins specifically upregulated during HCMV infection but not during growth factor treatment. Overall, our data indicate that HCMV glycoproteins gB and gH work in concert to initiate an HCMV-specific signalosome responsible for the atypical activation of Akt required for infected monocyte survival and ultimately viral persistence.IMPORTANCE Human cytomegalovirus (HCMV) infection is endemic throughout the world regardless of socioeconomic conditions and geographic locations with a seroprevalence reaching up to 100% in some developing countries. Although asymptomatic in healthy individuals, HCMV can cause severe multiorgan disease in immunocompromised or immunonaive patients. HCMV disease is a direct consequence of monocyte-mediated systematic spread of the virus following infection. Because monocytes are short-lived cells, HCMV must subvert the natural short life-span of these blood cells by inducing a distinct activation of Akt, a serine/theonine protein kinase. In this work, we demonstrate that HCMV glycoproteins gB and gH work in tandem to reroute classical host cellular receptor signaling to aberrantly activate Akt and drive survival of infected monocytes. Deciphering how HCMV modulates the cellular pathway to induce monocyte survival is important to develop a new class of anti-HCMV drugs that could target and prevent spread of the virus by eliminating infected monocytes.

Modern full-component aseptic revision total knee arthroplasties have similar recoveries compared with primary total knee arthroplasty patients when applying an enhanced recovery anaesthetic and analgesic protocol.

AIMS: Enhanced perioperative protocols have significantly improved patient recovery following primary total knee arthroplasty (TKA). Little has been investigated the effectiveness of these protocols for revision TKA (RTKA). We report on a matched group of aseptic revision and primary TKA patients treated with an identical pain and rehabilitation programmes. METHODS: Overall, 40 aseptic full-component RTKA patients were matched (surgical date, age, sex, and body mass index (BMI)) to a group of primary cemented TKA patients. All RTKAs had new uncemented stemmed femoral and tibial components with metaphyseal sleeves. Both groups were treated with an identical postoperative pain protocol. Patients were followed for at least two years. Knee Society Scores (KSS) at six weeks and at final follow-up were recorded for both groups. RESULTS: There was no difference in mean length of stay between the primary TKA (1.2 days (0.83 to 2.08)) and RTKA patients (1.4 days (0.91 to 2.08). Mean oral morphine milligram (mg) equivalent dosing (MED) during the hospitalization was 42 mg/day for the primary TKA and 38 mg/day for the RTKA groups. There were two readmissions: gastrointestinal disturbance (RTKA) and urinary retention (primary TKA). There no were reoperations, wound problems, thromboembolic events or manipulations in either group. Mean overall KSS for the RTKA group was 87.3 (45 to 99) at six-week follow-up and 89.1 (52 to 100) at final follow-up (mean 3.9 years, (3.9 to 9.0)). Mean overall KSS for the primary group was 89.9 (71 to 100) at six-week follow-up and 93.42 (73 to 100) at final follow-up (mean 3.5 years (2.5 to 9.2)). CONCLUSION: An identical pain and rehabilitation protocol used for primary TKA patients can enable certain full-component aseptic RTKA patients to have a similar early functional outcome. Cite this article: Bone Joint J 2020;102-B(6 Supple A):96-100.

Inframammary Fold Reconstruction in the Previously Reconstructed Breast: A Comprehensive Review.

The inframammary fold presents a reconstructive challenge once disrupted during total mastectomy or inadequately restored during breast reconstruction. Various methods of recreating the inframammary fold have been proposed, but reports are generally based on small sample sizes and lack long-term analyses and patient-reported outcomes. The authors herein review the literature on inframammary fold anatomy and reconstructive techniques, highlighting the need for more critical analysis of methodology to develop more predictable and durable outcomes.

FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery.

BACKGROUND: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking. OBJECTIVE: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. STUDY DESIGN: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. RESULTS: From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. CONCLUSION: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention. CLINICAL TRIAL REGISTRATION NUMBER: NCT00995878, clinicaltrials.gov.

Long-Term Outcomes of Newly Diagnosed Resected Atypical Meningiomas and the Role of Adjuvant Radiotherapy.

OBJECTIVE: The role of adjuvant radiotherapy (ART) in patients with World Health Organization Grade II atypical meningiomas (AMs) remains controversial. METHODS: We retrospectively reviewed 149 patients with newly diagnosed resected AMs from 2000 to 2012. Gross total resection (GTR) was defined as Simpson Grades I-III and subtotal resection (STR) as Grades IV and V. Kaplan-Meier analyses of local control (LC), progression-free survival (PFS), and overall survival were performed with the log-rank test, and risk factors for progression/recurrence (P/R) were analyzed with multivariate Cox regression. RESULTS: Median follow-up was 74.2 months. GTR was achieved in 98 patients and STR in 51 patients. Fifty-three (35%) patients received ART. Overall, 46 patients (31%) experienced P/R with a median time to P/R of 32.4 months. ART was associated with a trend toward improved PFS (P = 0.0669) in the GTR subset but significantly improved LC (P = 0.0183) and PFS (P = 0.0034) in the STR subset. Age, tumor size, and STR were significant risk factors for worse PFS, whereas receiving ART was associated with improved PFS on multivariate analyses. Thirty-nine of the 46 progressive/recurrent patients underwent salvage therapy with only 22 patients experiencing long-term control. Five patients experienced transformation to World Health Organization Grade III malignant meningioma. CONCLUSIONS: Patients who undergo STR for newly diagnosed AM should receive ART based on improvements in LC and PFS. GTR patients should be considered for ART, but active surveillance is a reasonable management approach with the recognition that progressive/recurrent disease can act aggressively. Prospective, randomized trials are currently underway to evaluate the role of ART.

Novel 3-Dimensional Imaging Analysis of the Ryan Procedure for Inframammary Fold Elevation in the Reconstruction of the Revised Breast.

The inframammary fold (IMF) can be challenging to reconstruct after disruption during mastectomy or breast reconstruction. The Ryan procedure is a previously described technique with little long-term analysis. Our goal is to analyze the long-term results of the Ryan procedure using 3-dimensional (3D) technology, with the hypothesis that 3D measurements will provide quantitative outcomes that add to the qualitative assessment of the reconstruction. We retrospectively reviewed consecutive breast reconstruction patients by a single surgeon from January 1, 2012 to January 31, 2015 to identify patients who underwent the Ryan procedure. Previously obtained 3D photographs were then analyzed to compare breast base diameter, breast projection, and inter-IMF distance pre- and postoperatively. A survey was then given to 15 health professionals in our department to assess the IMF and symmetry pre- and postoperatively. Eight patients were eligible for inclusion. Four patients were unilateral reconstruction and 4 were bilateral. The Ryan procedure resulted in an inter-IMF discrepancy reduction of 39% and a breast projection increase of 18%. Average length of follow-up was 2.82 ± 0.75 years. One patient required a secondary IMF revision. The majority of survey respondents felt that the IMF and IMF symmetry were improved or stable postoperatively. The Ryan procedure seems to be a reliable and durable technique for IMF reconstruction with increased projection, decreased IMF discrepancy, and increased symmetry. Additionally, 3D imaging provides a useful approach in the assessment of breast reconstruction outcomes, adding quantitative outcomes measures to its evaluation.

Glutathione Utilization in Lactobacillus fermentum CECT 5716.

Glutathione, a tripeptide antioxidant, has recently been shown to be either utilized or synthesized by Gram-positive bacteria, such as lactic acid bacteria. Glutathione plays an important role in countering environmental stress, such as oxidative stress. In this study, cellular activity regarding glutathione in Lactobacillus fermentum CECT 5716 is characterized. We demonstrate that L. fermentum CECT 5716 has a better survival rate in the presence of glutathione under both oxidative and metal stress. As L. fermentum CECT 5716 does not possess the ability to synthesize glutathione under the conditions tested, it shows the ability to uptake both reduced and oxidized glutathione from the environment, regenerate reduced glutathione from oxidized glutathione, and perform secretion of glutathione to the environment.