Understanding Psychiatric Disorders in Idiopathic and Inherited (Monogenic) Forms of Isolated and Combined Dystonia: A Systematic Review.

OBJECTIVE: The relationship between idiopathic and inherited (monogenic) forms of isolated and combined dystonia and psychiatric disorders remains unclear. In the present review, the authors aimed to provide increased clarity on this association through a systematic review of all controlled quantitative studies using a structured or semi-structured psychiatric interview to diagnose psychiatric disorders in individuals with these conditions. METHODS: Three databases were searched to identify 20 eligible studies, with a total of 1,275 participants fulfilling inclusion criteria. Eligible articles were quality appraised and divided into four sections (idiopathic forms of dystonia [N=11], early-onset torsion dystonia [N=2], gene mutation positive myoclonus dystonia; DYT-SGCE [N=6], and rapid-onset dystonia-parkinsonism [N=1]). RESULTS: For each study, results were grouped into subcategories (overall psychiatric comorbidity, anxiety disorders, mood disorders, substance misuse, and other [personality disorder and cognitive impairment]). For idiopathic dystonia, higher rates of psychiatric comorbidity, including mood and anxiety disorders, were noted when cases were compared with both healthy control subjects and control groups with a medical comorbidity. However, for major depressive disorder and obsessive-compulsive disorder (OCD) specifically, no differences were seen between groups. Study subjects with DYT-SGCE appeared to be at higher risk of psychiatric comorbidity, major depressive disorder, OCD, and alcohol dependence than control populations. CONCLUSIONS: Overall, the prevalence of psychiatric comorbidity appears to be increased in individuals with idiopathic and inherited (monogenic) forms of isolated and combined dystonia compared with control subjects. This finding is not consistent for all comparisons, and further research is required to understand the nature of these associations and the underlying causative etiologies.

A comparison of intravenous methylprednisolone and hydrocortisone for the treatment of acute inflammatory bowel disease.

BACKGROUND AND AIM: Despite widespread recommendations and use of intravenous corticosteroids (IVCS) for the treatment of acute flares of ulcerative colitis and Crohn's disease, limited evidence exists comparing outcomes of the two most common regimens, intravenous methylprednisolone (IVMP) and intravenous hydrocortisone (IVHC). IVHC has stronger mineralocorticoid effects compared with IVMP and may cause higher rates of hypokalemia. We aimed to determine differences in clinical outcomes including requirement for inpatient rescue therapy, bowel resection, and rates of hypokalemia. METHODS: We conducted a multicenter cohort study of all adult patients admitted with an acute flare of inflammatory bowel disease (IBD) to the three tertiary hospitals in Auckland, New Zealand, where the protocol at each institution is either IVMP 60 mg daily or IVHC 100 mg four times daily. All patients requiring IVCS between 20 June 2016 and 30 June 2018 were included. The IVCS protocol was then changed at one hospital, where further data were collected for a further 12 months from 30 January 2019 until 30 December 2019. RESULTS: There were 359 patients, including 129 (35.9%) patients receiving IVMP and 230 (64.1%) patients receiving IVHC. IVMP treatment was associated with a greater requirement for rescue therapy than IVHC (36.4% vs 19.6%, P = 0.001; odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.64-4.75, P < 0.001), but also reduced rates of hypokalemia (55.8% vs 67.0%, P = 0.04; OR = 0.49; 95% CI, 0.30-0.81, P = 0.005). There was no difference between treatment groups for the median length of admission (5 days, interquartile range [IQR] 3-8), median duration of IVCS treatment (3 days, IQR 2-5), or bowel resection within 30 days of admission (12.4% vs 11.7%; OR = 1.04). CONCLUSION: For the treatment of an acute flare of IBD, treatment with IVMP results in significantly more requirement for inpatient rescue biologic or cyclosporin. In addition, it causes statistically significant less hypokalemia than IVHC, although in practice differences are negligible.

Antigen-presenting cells in ocular surface diseases.

PURPOSE: To review the role of antigen-presenting cells (APC) in the pathogenesis of ocular surface diseases (OSD). METHODS: A thorough literature search was performed in PubMed database. An additional search was made in Google Scholar to complete the collected items. RESULTS: APCs have the ability to initiate and direct immune responses and are found in most lymphoid and non-lymphoid tissues. APCs continuously sample their environment, present antigens to T cells and co-ordinate immune tolerance and responses. Many different types of APCs have been described and there is growing evidence that these cells are involved in the pathogenesis of OSD. OSD is a complex term for a myriad of disorders that are often characterized by ocular surface inflammation, tear film instability and impairment of vision. CONCLUSIONS: This review summarizes the current knowledge concerning the immunotopographical distribution of APCs in the normal ocular surface. APCs appear to play a critical role in the pathology of a number of conditions associated with OSD including infectious keratitis, ocular allergy, dry eye disease and pterygium.

VISUALIZATION OF CHOROIDAL NEOVASCULARIZATION USING TWO COMMERCIALLY AVAILABLE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DEVICES.

PURPOSE: To compare the sensitivity of detection and the measured size of choroidal neovascularization (CNV) on two commercially available spectral domain optical coherence tomography angiography (OCTA) devices, the Optovue RTVue XR Avanti with AngioVue and the Zeiss Cirrus HD-OCT with AngioPlex. METHODS: Patients with CNV lesions were imaged consecutively on both OCTA devices on the same day of their visit. 3 × 3 mm and 6 × 6 mm scans centered at the fovea were obtained. Two independent masked readers evaluated the OCTA images for CNV identification and its area measurements. RESULTS: No significant differences were observed between the 2 OCTA devices in CNV area measurements on their 3 × 3 mm and 6 × 6 mm scans. However, there was suboptimal performance of their automated segmentation algorithms as compared to manually adjusted segmentation for visualizing CNV lesions. CONCLUSION: There was no significant difference in the size of the CNV lesion as measured on either commercially available spectral domain OCTA device. Both devices were comparable in their detection of CNV lesions on manual adjustment of segmentation lines. However, their automated segmentation algorithms need improvement to allow for accurate measurement of CNV lesions for routine clinical application.

Treating Diabetic Macular Oedema (DMO): real world UK clinical outcomes for the 0.19mg Fluocinolone Acetonide intravitreal implant (Iluvien™) at 2 years.

BACKGROUND: To compare visual function and structural improvements in pseudophakic eyes with diabetic macular oedema (DMO) treated with the 0.19mg Fluocinolone Acetonide (FAc) intravitreal implant (IluvienTM) in a 'real world' setting. METHODS: A single centre retrospective evaluation of patients with DMO unresponsive to conventional treatment treated with the FAc implant according to UK guidelines. Primary efficacy endpoint was best corrected visual acuity (BCVA); secondary endpoints included optical coherence tomography evaluations of the macula (a) central retinal and (b) peak macular thickness collected at annual time points. Primary safety endpoint was new rise in IOP >27mmHg or glaucoma surgery. Patients with <1 year follow-up were excluded. RESULTS: Twenty-nine eyes were included, with mean(SD) follow up of 792(270) days. Improvement in BCVA and reduction in macular oedema was noted at all timepoints. Mean improvement in BCVA from baseline was 6 ETDRS letters at year 1(n=29), 6.5L at year 2(n=22) and 11L at year 3(n=6). Mean central retinal thickness at baseline was 451 microns, 337 microns at year 1, 342 microns at year 2 and 314 microns at year 3. Two eyes required IOP-lowering drops post implant. Supplementary treatment for persistence or recurrence of DMO was necessary in 18 eyes over the total study period of 3 years with mean time to supplementary treatment being 12 months. CONCLUSIONS: Our evaluation of the 0.19mg FAc implant delivered in a real-world setting, provides additional evidence that it is effective and safe in the treatment of patients with DMO, and can provide sustained benefit for patients with previously refractory disease.

Proximity of Lateral Critical Structures to the All-Epiphyseal Outside-In Femoral Tunnels in Pediatric Anterior Cruciate Ligament Reconstruction.

PURPOSE: To describe the proximity of the lateral critical structures (peroneal nerve [PN], popliteus tendon [PT], lateral collateral ligament [LCL], and articular cartilage [AC]) to the femoral tunnel for outside-in all-epiphyseal anterior cruciate ligament (ACL) reconstruction in reference to knee flexion angle. METHODS: All-epiphyseal ACL reconstructions were performed in 12 human cadaveric knees using arthroscopy and outside-in drilling for anatomic femoral tunnel placement that was ensured by identifying the center of the total ACL footprint. Fluoroscopy was used to confirm tunnel position and reconstructions were performed with quadrupled semitendinosus and gracilis autograft with Xtendobutton (Smith & Nephew, Andover, MA) fixation on the femoral side. After reconstruction, the lateral side of the knee was dissected and the LCL, PT, distal and posterior AC, and the PN were identified. The distances of these structures from the center of the exiting femoral tunnel were then measured using a digital caliper at 0°, 30°, 60°, 90°, and 120° of knee flexion. Any gross damage to these structures caused by the femoral drilling was also noted. Data were compiled and the mean and standard deviations (SD) of the distances from the pin to the structures of interest were calculated. The normality of the data at each flexion angle was assessed using Shapiro-Wilk tests (P > .05), and the relationship between flexion angle and average distance was evaluated using repeated measures analysis of variance (P < .05). Any significant relationships were then evaluated using paired t-tests (P < .05) with a Benjamini-Hochberg adjustment for each possible pair of flexion angles. Averages, SD, and P values are reported. A post hoc power analysis was performed. RESULTS: The violation of the LCL was noted in 3 specimens and that of the PT in 1 specimen as a result of femoral tunnel drilling at flexion angles ranging from 90° to 120°. The distance between the PT and the femoral tunnel also decreased significantly (P < .001) with knee flexion with average distances to the center of 8.07 mm at 0°, 7.75 mm at 30°, 6.33 mm at 60°, 4.12 mm at 90°, and 1.89 mm at 120°. The mean ± SD for distances from the femoral tunnel to the center of the PT at 0° was 8.07 ± 7.15, at 30° 7.75 ± 6.66, at 60° 6.33 ± 6.79, at 90° 4.12 ± 5.71, and at 120° 1.89 ± 5.56. As the knee was progressively flexed, the distance between the LCL and the femoral tunnel decreased significantly (P < .001) with an average distance of 6.52 mm at 0°, 6.26 mm at 30°, 4.23 mm at 60°, 2.38 mm at 90°, and 0.4 mm at 120°. The mean ± SD for distances from the femoral tunnel to the center of the LCL at 0° was 6.52 ± 5.93, at 30° 6.26 ± 7.32, at 60° 4.23 ± 7.82, 90° 2.38 ± 7.31, and at 120° 0.4 ± 7.01. The PN was remote from the femoral tunnel at all flexion angles with a mean distance of 42.83 to 59.22 mm. The PN to guide pin distance increased significantly with progressive knee flexion (P < .001). The AC was not damaged in all specimens. CONCLUSIONS: The LCL and PT are at significant risk during percutaneous femoral drilling for all-epiphyseal anatomic ACL reconstruction using an outside-in technique. This risk was maximized at 120° flexion and minimized in full extension. These findings suggest that the optimal position for femoral drilling in all-epiphyseal ACL reconstruction is full or near-full extension of the knee that can be accomplished by placing the knee in 30° of flexion (after using fluoroscopic guidance to pass the guide pin past the lateral critical structures) to visualize the footprint of the ACL. CLINICAL RELEVANCE: Information garnered from this study may help clinicians better understand the risk to the lateral critical structures when an outside-in femoral tunnel is not drilled in the appropriate degree of knee flexion.

Surgical management of retinal detachment and macular holes secondary to ocular toxoplasmosis: a systematic review and meta-analysis.

BACKGROUND: Toxoplasma gondii causes ocular toxoplasmosis (OT), involving inflammation, scarring, and retinal complications. The OT complications were retinal detachment (RD), and retinal breakage (RB). Surgical interventions like scleral buckling (SB) and vitrectomy are common. Limited understanding exists of the safety and efficacy of surgical management of RD/RB secondary to OT. Another complication is toxoplasmosis-related macular holes (tMH), with sparse evidence on surgical outcomes. This meta-analysis aims to clarify clinical characteristics, and surgical results, and enhance understanding of RD, RB, and MH secondary to OT. METHODS: PubMed, Cochrane, Embase and Web of Science database were queried for retrospective studies, case series and case reports that provided information on RD, RB and MH associated with OT and reported the outcomes of: (1) Retinal reattachment of RD/RB and tMH closure; (2) Best-corrected visual acuity (BCVA) improvement; and (3) Complications. Heterogeneity was examined with I2 statistics. A random-effects model was used for outcomes with high heterogeneity. Statistical analysis was performed using the software R (version 4.2.3, R Foundation for Statistical Computing, Vienna, Austria). RESULTS: Fourteen final studies, comprising a total of 96 patients were analyzed, 81 with RD or RB and 15 with tMH. Overall, surgical management was associated with several advantages: a high rate of retinal reattachment of RD/RB of 97% (95% Confidence Interval [CI] 92-100%; I2 = 0%), retinal reattachment of just RD of 96% (95% CI 89-100%; I2 = 30%) and tMH closure 97% (95% CI 87-100; I2 = 12%). There were significant differences in BCVA after surgeries in studies of RD/RB (MD 0.60; 95% CI 0.35-0.65; I2 = 20%) and MH (MD 0.67; 95% CI 0.50-0.84; I2 = 0%). The overall complication rate associated with surgical procedures in RD/RB secondary to OT was confirmed to be 25%. CONCLUSIONS: The systematic review and meta-analysis showed that the treatment approaches currently in use are effective, with a remarkable rate of retinal reattachment of RD/RB, tMH closure, and substantial improvements in visual acuity. More randomized, long-term studies on disease and surgical factors can provide valuable insights into their impact on anatomical and visual outcomes.

A Systematic Review of the Barriers to the Implementation of Artificial Intelligence in Healthcare.

Artificial intelligence (AI) is expected to improve healthcare outcomes by facilitating early diagnosis, reducing the medical administrative burden, aiding drug development, personalising medical and oncological management, monitoring healthcare parameters on an individual basis, and allowing clinicians to spend more time with their patients. In the post-pandemic world where there is a drive for efficient delivery of healthcare and manage long waiting times for patients to access care, AI has an important role in supporting clinicians and healthcare systems to streamline the care pathways and provide timely and high-quality care for the patients. Despite AI technologies being used in healthcare for some decades, and all the theoretical potential of AI, the uptake in healthcare has been uneven and slower than anticipated and there remain a number of barriers, both overt and covert, which have limited its incorporation. This literature review highlighted barriers in six key areas: ethical, technological, liability and regulatory, workforce, social, and patient safety barriers. Defining and understanding the barriers preventing the acceptance and implementation of AI in the setting of healthcare will enable clinical staff and healthcare leaders to overcome the identified hurdles and incorporate AI technologies for the benefit of patients and clinical staff.

Dual Antibiotic Prophylaxis in Primary Total Knee Arthroplasty-No Benefit for Extremely Obese Patients.

We performed this study to assess the effectiveness of multimodal total knee arthroplasty prosthetic joint infection (TKA-PJI) prophylaxis including "on-time" dual-antibiotic prophylaxis, and the influence of body mass index (BMI) on prophylaxis effectiveness. After obtaining Institutional Review Board approval, we assessed 1,802 primary TKAs (1,496 patients) who received cefazolin alone or cefazolin combined with vancomycin for TKA-PJI prophylaxis. A detailed chart review was performed to determine patient demographic features (age, gender, BMI, American Society of Anesthesiologists Score), antibiotic selection, vancomycin administration timing, and 1-year PJI rates. Statistical assessment was accomplished using a two-sided Student's t-test or Fisher's exact test. Patients who received dual-antibiotic prophylaxis with "on time" vancomycin infusion (Group CVt) had significantly lower infection rates than other TKA patients (0.8 vs. 2.7%, p < 0.01). "On Time" vancomycin administration was associated with a lower TKA-PJI rate for patients with a BMI < 45 kg/m2 (0.5 vs. 2.6%, p < 0.01) with no infections in 120 TKA patients with a BMI between 40 and 44.9 kg/m2 (p < 0.01). No difference was noted for patients with a BMI ≥ 45 kg/m2 (3.3 vs. 2.6%, p = 0.71). There were no infections in 150 TKA patients with a normal BMI (18-25 kg/m2) in any PJI-prophylaxis treatment group. Adoption of a dual-antibiotic prophylaxis approach can successfully reduce TKA-PJI rates among overweight and moderately obese patients. The approach does not appear to influence outcomes for low risk patients with a normal BMI (18-25 kg/m2) or for higher risk patients with a BMI > 45 kg/m2.

Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats.

Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

Improved detection of adenomas and sessile serrated polyps is maintained with continuous audit of colonoscopy.

BACKGROUND: The audit process may help improve performance indicators for colonoscopy quality but it is unclear whether this is sustained over several years. METHODS: 44138 procedures for 28 endoscopists from 2004 to 2019 were analysed for polyp detection rate and withdrawal time. From 2012, 14 endoscopists were analysed with additional data on polyp histology and number of polyps removed. RESULTS: Polyp detection increased from 40.7% in 2004 to 62.2% in 2019; removal of polyps>1 cm remained constant (11%). Adenoma detection rate was 25.8% in 2012 and 28.3% in 2019. Sessile serrated polyp (SSP) detection rate increased from 4.5% to 14.7%; most of the increase was in the first 2 years of the histology part of the audit. There was a significant correlation of adenoma detection rate with mean number of adenomas (r=0.72, p=0.004) and a significant correlation of SSP detection with mean number of SSPs (r=0.85, p=0.0001). CONCLUSION: The audit process appears to encourage a higher rate of polyp detection. This was due to increased detection of smaller polyps and increased detection of SSPs.

Correction to: Iluvien™ (Fluocinolone Acetonide 0.19 mg Intravitreal Implant) in the Treatment of Diabetic Macular Edema: A Review.

This article was originally published with the copyright: the author(s) 2018, CC-BY-NC. However, the license should be the author(s) 2018, CC-BY.

Iluvien™ (Fluocinolone Acetonide 0.19 mg Intravitreal Implant) in the Treatment of Diabetic Macular Edema: A Review.

Diabetic macular edema (DMO) is a leading cause of blindness in the working age population. Although anti-vascular endothelial growth factor (VEGF) therapy provided a major advance in treatment of DMO for many patients, there is a significant proportion of patients who maintain persistent DMO and have minimal response to anti-VEGF treatment. Iluvien (fluocinolone acetonide 0.19 mg [FAc]) is an important additional treatment option for DMO. In this review we describe the clinical context and the evidence for the use of the FAc implant in treating DMO, from pilot to randomized controlled studies, to later phase real world data. These studies indicate that the FAc implant is effective, well tolerated and a cost-effective option in the treatment of insufficiently responsive DMO.

Multiple deprivation, vision loss, and ophthalmic disease in adults: global perspectives.

The association between socioeconomic position and morbidity and mortality has long been recognized. We evaluate the evidence for an association between multiple aspects of deprivation and ocular health in a global context. This is a systematic review of studies that evaluated deprivation in the adult population in the context of the major acquired causes of visual loss such as cataract, diabetic eye disease, glaucoma, age-related macular degeneration, and ocular trauma. The search strategy identified relevant studies reported between 1946 and August 2016, with randomized control trials, case-control, cohort, and cross-sectional study designs being selected for inclusion. The studies identified in this review from across the world demonstrate the extent to which the common themes such as low educational attainment and low income may be associated with increased incidence of various sight-threatening conditions and may adversely affect access to specialist assessment and delivery of treatment. Health inequality may always persist, but an increased recognition of the importance of the various impacts of deprivation may empower policy makers to target limited resources to the most vulnerable groups in order to deliver the greatest benefit.

Endothelial assessment of donated tectonic corneas: a viable option for posterior lamellar transplantation.

PURPOSE: Donated corneas are classified as tectonic if there are defects within any layers of the cornea which would prevent a satisfactory visual outcome after transplantation. This study aimed to evaluate whether some tectonic corneas have sufficient endothelial characteristics to allow their use in posterior lamellar keratoplasty, and explored their reclassification for use in this sight-improving procedure. METHODS: A retrospective review of all corneal tissues preserved by the Sorocaba Eye Bank from January to April of 2014 was performed. All donated corneas classified as tectonic were included. Endothelial tissue was defined as healthy and viable for posterior lamellar keratoplasty if endothelial cell density was ≥2000 cells/mm2. Additional parameters analyzed included Descemet folds and stretch marks, loss of endothelial cells, corneal endothelial polymegathism/ pleomorphism, pseudo-guttata, and reflectivity. RESULTS: During the study period, 2,847 corneas were preserved, of which 423 (14.85%) were classified as tectonic. Of these, 87 (20.56%) were reported as having endothelial viability and were included in the posterior lamellar keratoplasty group. Average corneal endothelial cell density of this group was 2,471 SD ± 256 cells/mm2 (range 2012-2967 cells/mm2). CONCLUSION: A significant number of corneas classified as tectonic showed endothelial viability and were included in the posterior lamellar keratoplasty group (20.56%). Despite stromal and/or epithelial alterations, these corneas could have been potentially distributed for posterior lamellar transplantation to improve vision, thus reducing the corneal transplantation waiting period. This study highlights how corneal tissue reclassification could increase the potential amount of corneal tissue available for optical transplantation.

The Interval Between VNS-Tone Pairings Determines the Extent of Cortical Map Plasticity.

Repeatedly pairing vagus nerve stimulation (VNS) with a tone or movement drives highly specific and long-lasting plasticity in auditory or motor cortex, respectively. Based on this robust enhancement of plasticity, VNS paired with rehabilitative training has emerged as a potential therapy to improve recovery, even when delivered long after the neurological insult. Development of VNS delivery paradigms that reduce therapy duration and maximize efficacy would facilitate clinical translation. The goal of the current study was to determine whether primary auditory cortex (A1) plasticity can be generated more quickly by shortening the interval between VNS-tone pairing events or by delivering fewer VNS-tone pairing events. While shortening the inter-stimulus interval between VNS-tone pairing events resulted in significant A1 plasticity, reducing the number of VNS-tone pairing events failed to alter A1 responses. Additionally, shortening the inter-stimulus interval between VNS-tone pairing events failed to normalize neural and behavioral responses following acoustic trauma. Extending the interval between VNS-tone pairing events yielded comparable A1 frequency map plasticity to the standard protocol, but did so without increasing neural excitability. These results indicate that the duration of the VNS-event pairing session is an important parameter that can be adjusted to optimize neural plasticity for different clinical needs.

Calorie restriction mimetics: an emerging research field.

When considering all possible aging interventions evaluated to date, it is clear that calorie restriction (CR) remains the most robust. Studies in numerous species have demonstrated that reduction of calories 30-50% below ad libitum levels of a nutritious diet can increase lifespan, reduce the incidence and delay the onset of age-related diseases, improve stress resistance, and decelerate functional decline. A current major focus of this research area is whether this nutritional intervention is relevant to human aging. Evidence emerging from studies in rhesus monkeys suggests that their response to CR parallels that observed in rodents. To assess CR effects in humans, clinical trials have been initiated. However, even if results from these studies could eventually substantiate CR as an effective pro-longevity strategy for humans, the utility of this intervention would be hampered because of the degree and length of restriction required. As an alternative strategy, new research has focused on the development of 'CR mimetics'. The objective of this strategy is to identify compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. For example, drugs that inhibit glycolysis (2-deoxyglucose), enhance insulin action (metformin), or affect stress signaling pathways (resveratrol), are being assessed as CR mimetics (CRM). Promising results have emerged from initial studies regarding physiological responses which resemble those observed in CR (e.g. reduced body temperature and plasma insulin) as well as protection against neurotoxicity (e.g. enhanced dopamine action and up-regulated neurotrophic factors). Ultimately, lifespan analyses in addition to expanded toxicity studies must be accomplished to fully assess the potential of any CRM. Nonetheless, this strategy clearly offers a very promising and expanding research endeavor.

Caloric restriction mimetics: a novel approach for biogerontology.

Caloric restriction remains the only nongenetic intervention that has been consistently and reproducibly shown to extend both average and maximal lifespan in a wide variety of species. If shown to be applicable to human aging, it is unlikely that most people would be able to maintain the 30-40% reduction in food intake apparently required for this intervention. Therefore, an alternative approach is needed. We first proposed the concept of caloric restriction (CR) mimetics in 1998. Since its introduction, this research area has witnessed a significant expansion of interest in academic, government, and private sectors. CR mimetics target alteration of pathways of energy metabolism to potentially mimic the beneficial health-promoting and anti-aging effects of CR without the need to reduce food intake significantly. To date, a number of candidate CR mimetics including glycolytic inhibitors, antioxidants and specific gene-modulators have been investigated and appear to validate the potential of this approach.

Exercise-Induced Acute Bilateral Upper-Arm Compartment Syndrome.

We present a rare case of acute exercise-induced bilateral upper-arm compartment syndrome in a patient who, after a year-long hiatus from exercise, subjected his upper-extremities to the stress of over 100 pushups. The patient presented with severe pain of the bilateral biceps and triceps and complaints of dark urine. Decompressive fasciotomy was performed followed by an intensive care unit (ICU) stay for associated myoglobinuria secondary to rhabdomyolysis. The patient suffered no long-term sequelae as a result of his conditions and recovered full function of the bilateral upper-extremities. Albeit rare, acute exercise-induced compartment syndrome should be considered as a diagnosis following unaccustomed bouts of exercise.