SURGICAL DRAINAGE METHODS DURING PARS PLANA VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT: A Systematic Review and Meta-Analysis.

PURPOSE: To assess efficacy and safety outcomes of subretinal fluid drainage methods during pars plana vitrectomy for rhegmatogenous retinal detachment. METHODS: A systematic search strategy was conducted for studies published between January 2000 and October 2022. Included studies reported on either the safety or efficacy of two or more drainage methods during pars plana vitrectomy for patients with rhegmatogenous retinal detachment. RESULTS: Two randomized and five observational studies consisting of 1,524 eyes were included. Best-corrected visual acuity at the last study observation and primary reattachment rates were similar across groups. A significantly lower risk of epiretinal membrane formation was associated with draining subretinal fluid through preexisting retinal breaks (risk ratio = 0.70, 95% confidence interval = [0.60, 0.83], P = <0.01, I 2 = 0%) or with perfluorocarbon liquid (risk ratios = 0.70, 95% confidence interval = [0.59, 0.83], P = <0.01, I 2 = 0%) compared with posterior retinotomy. The risk of an abnormal foveal contour was significantly greater in perfluorocarbon liquid-treated eyes relative to posterior retinotomy (risk ratios = 1.56, 95% confidence interval = [1.13, 2.17], P = <0.01, I 2 = 0%). CONCLUSION: No significant differences were observed in the final best-corrected visual acuity at the last study observation and primary reattachment rates across different drainage methods. There remains limited information on the topic, so future research is warranted.

Acute intraocular pressure responses to high-intensity interval-training protocols in men and women.

We aimed (1) to test the acute impact of two high-intensity interval-training (HIIT) protocols differing in the level of effort on intraocular pressure (IOP) responses, and (2) to elucidate whether the IOP responses differ between men and women. Twenty-four physically active collegiate (12 men and 12 women) performed three protocols: low-fatigue HIIT (eight 30-m sprints with 60-s of rest), high-fatigue HIIT (eight 30-m sprints with 30-s of rest), and control (walking). IOP was taken at baseline, after sprints and recovery by rebound tonometry. Our data revealed an acute IOP reduction during both HIIT protocols compared to the control condition (effect size [ES]:0.81-1.65). The differences between both HIIT protocols were generally negligible (ES<0.30), however, the reduction of IOP was moderately higher for the low-fatigue HIIT protocol after the 7th (ES: 0.67) and 8th (ES: 0.74) sprints. Women showed a more prominent lowering effect on IOP during the control condition (ES: 0.42-1.02), and during the two first sprints of both HIIT protocols (ES: 0.54-1.03). These findings highlight that a time-efficient HIIT protocol may acutely reduce IOP levels, while low-fatigue HIIT protocol could be recommended since it induced a higher reduction on IOP than the high-fatigue HIIT protocol.

Blunted satellite cell response is associated with dysregulated IGF-1 expression after exercise with age.

PURPOSE: Insulin-like growth factor-1 (IGF-1) regulates protein synthesis and cell cycle kinetics. Given that aging is associated with anabolic resistance, we sought to determine if the attenuated exercise-induced satellite cell (SC) expression in older muscle is associated with a blunted IGF-1 response. METHODS: SC expression (Pax7+ cells) and protein (Western blot) and mRNA (RT-PCR) expression of IGF-1 splice variants and ubiquitous (IGFBP4) and muscle-specific (IGFBP3 and -5) IGF-1 binding proteins were measured in skeletal muscle of young (Y: 22 ± 2, n = 7) and older (O: 70 ± 2, n = 7) adults up to 48 h after an acute bout of resistance exercise. RESULTS: SC expression was greater in Y compared to O (age; P < 0.01) and increased (interaction; P < 0.05) by 24 h after exercise in Y only. IGF-1Ea and IGF-1Eb mRNA tended to be greater in O (age; P < 0.06-0.09). IGF-1Eb mRNA increased at 48 h (time; P < 0.05), whereas IGF-1Ec mRNA increased (interaction; P < 0.05) at 24 and 48 h in O only. IGF binding protein (IGFBP)4 mRNA was greater (age; P < 0.01) in O with the increase at 24 h and 48 h (time; P < 0.01) primarily driven by changes in O (interaction; P < 0.01). Despite IGFBP3 mRNA being greater in O (age; P < 0.01) and increasing at 48 h (time; P < 0.01), there was no effect of age or exercise on IGFBP3 protein expression. In contrast, IGFBP5 mRNA was greater (age; P < 0.01) despite IGFBP5 protein expression being lower (age; P < 0.01) in O compared to Y. CONCLUSIONS: The greater muscle-specific expression of IGF-1 family members with a blunted post-exercise SC expression may be a compensatory attempt to rescue age-related anabolic resistance.

Skeletal Muscle Regeneration, Repair and Remodelling in Aging: The Importance of Muscle Stem Cells and Vascularization.

Sarcopenia is the age-related loss of skeletal muscle mass and strength. Ultimately, sarcopenia results in the loss of independence, which imposes a large financial burden on healthcare systems worldwide. A critical facet of sarcopenia is the diminished ability for aged muscle to regenerate, repair and remodel. Over the years, research has focused on elucidating underlying mechanisms of sarcopenia and the impaired ability of muscle to respond to stimuli with aging. Muscle-specific stem cells, termed satellite cells (SC), play an important role in maintaining muscle health throughout the lifespan. It is well established that SC are essential in skeletal muscle regeneration, and it has been hypothesized that a reduction and/or dysregulation of the SC pool, may contribute to accelerated loss of skeletal muscle mass that is observed with advancing age. The preservation of skeletal muscle tissue and its ability to respond to stimuli may be impacted by reduced SC content and impaired function observed with aging. Aging is also associated with a reduction in capillarization of skeletal muscle. We have recently demonstrated that the distance between type II fibre-associated SC and capillaries is greater in older compared to younger adults. The greater distance between SC and capillaries in older adults may contribute to the dysregulation in SC activation ultimately impairing muscle's ability to remodel and, in extreme circumstances, regenerate. This viewpoint will highlight the importance of optimal SC activation in addition to skeletal muscle capillarization to maximize the regenerative potential of skeletal muscle in older adults.

Effects of age and unaccustomed resistance exercise on mitochondrial transcript and protein abundance in skeletal muscle of men.

Mitochondrial dysfunction may contribute to age-associated muscle atrophy. Previous data has shown that resistance exercise (RE) increases mitochondrial gene expression and enzyme activity in older adults; however, the acute response to RE has not been well characterized. To characterize the acute mitochondrial response to unaccustomed RE, healthy young (21 ± 3 yr) and older (70 ± 4 yr) men performed a unilateral RE bout for the knee extensors. Muscle biopsies were taken at rest and 3, 24, and 48 h following leg press and knee extension exercise. The expression of the mitochondrial transcriptional regulator proliferator-activated receptor γ coactivator 1-α (PGC-1α) mRNA was increased at 3 h postexercise; however, all other mitochondrial variables decreased over the postexercise period, irrespective of age. ND1, ND4, and citrate synthase (CS) mRNA were all lower at 48 h postexercise, along with specific protein subunits of complex II, III, IV, and ATP synthase. Mitochondrial DNA (mtDNA) copy number decreased by 48 h postexercise, and mtDNA deletions were higher in the older adults and remained unaffected by acute exercise. Elevated mitophagy could not explain the reduction in mitochondrial proteins and DNA, because there was no increase in ubiquitinated voltage-dependent anion channel (VDAC) or its association with PTEN-induced putative kinase 1 (Pink1) or Parkin, and elevated p62 content indicated an impairment or reduction in autophagocytic flux. In conclusion, age did not influence the response of specific mitochondrial transcripts, proteins, and DNA to a bout of RE.

Satellite cell activity, without expansion, after nonhypertrophic stimuli.

The purpose of the present studies was to determine the effect of various nonhypertrophic exercise stimuli on satellite cell (SC) pool activity in human skeletal muscle. Previously untrained men and women (men: 29 ± 9 yr and women: 29 ± 2 yr, n = 7 each) completed 6 wk of very low-volume high-intensity sprint interval training. In a separate study, recreationally active men (n = 16) and women (n = 3) completed 6 wk of either traditional moderate-intensity continuous exercise (n = 9, 21 ± 4 yr) or low-volume sprint interval training (n = 10, 21 ± 2 yr). Muscle biopsies were obtained from the vastus lateralis before and after training. The fiber type-specific SC response to training was determined, as was the activity of the SC pool using immunofluorescent microscopy of muscle cross sections. Training did not induce hypertrophy, as assessed by muscle cross-sectional area, nor did the SC pool expand in any group. However, there was an increase in the number of active SCs after each intervention. Specifically, the number of activated (Pax7(+)/MyoD(+), P ≤ 0.05) and differentiating (Pax7(-)/MyoD(+), P ≤ 0.05) SCs increased after each training intervention. Here, we report evidence of activated and cycling SCs that may or may not contribute to exercise-induced adaptations while the SC pool remains constant after three nonhypertrophic exercise training protocols.

The unfolded protein response is triggered following a single, unaccustomed resistance-exercise bout.

Endoplasmic reticulum (ER) stress results from an imbalance between the abundance of synthesized proteins and the folding capacity of the ER. In response, the unfolded protein response (UPR) attempts to restore ER function by attenuating protein synthesis and inducing chaperone expression. Resistance exercise (RE) stimulates protein synthesis; however, a postexercise accumulation of unfolded proteins may activate the UPR. Aging may impair protein folding, and the accumulation of oxidized and misfolded proteins may stimulate the UPR at rest in aged muscle. Eighteen younger (n = 9; 21 ± 3 yr) and older (n = 9; 70 ± 4 yr) untrained men completed a single, unilateral bout of RE using the knee extensors (four sets of 10 repetitions at 75% of one repetition maximum on the leg press and leg extension) to determine whether the UPR is increased in resting, aged muscle and whether RE stimulates the UPR. Muscle biopsies were taken from the nonexercised and exercised vastus lateralis at 3, 24, and 48 h postexercise. Age did not affect any of the proteins and transcripts related to the UPR. Glucose-regulated protein 78 (GRP78) and protein kinase R-like ER protein kinase (PERK) proteins were increased at 48 h postexercise, whereas inositol-requiring enzyme 1 alpha (IRE1α) was elevated at 24 h and 48 h. Despite elevated protein, GRP78 and PERK mRNA was unchanged; however, IRE1α mRNA was increased at 24 h postexercise. Activating transcription factor 6 (ATF6) mRNA increased at 24 h and 48 h, whereas ATF4, CCAAT/enhancer-binding protein homologous protein (CHOP), and growth arrest and DNA damage protein 34 mRNA were unchanged. These data suggest that RE activates specific pathways of the UPR (ATF6/IRE1α), whereas PERK/eukaryotic initiation factor 2 alpha/CHOP does not. In conclusion, acute RE results in UPR activation, irrespective of age.

Acute dietary protein intake restriction is associated with changes in myostatin expression after a single bout of resistance exercise in healthy young men.

Skeletal muscle satellite cells (SCs) play an important role in the myogenic adaptive response to exercise. It remains to be established whether nutrition plays a role in SC activation in response to exercise. In the present study, we assessed whether dietary protein alters the SC response to a single bout of resistance exercise. Twenty healthy young (aged 21 ± 2 y) males were randomly assigned to consume a 4-d controlled diet that provided either 1.2 g protein ⋅ kg body weight(-1) ⋅ d(-1) [normal protein diet (NPD)] or 0.1 g protein ⋅ kg body weight(-1) ⋅ d(-1) [low protein diet (LPD)]. On the second day of the controlled diet, participants performed a single bout of resistance exercise. Muscle biopsies from the vastus lateralis were collected before and after 12, 24, 48, and 72 h of post-exercise recovery. SC content and activation status were determined using immunohistochemistry. Protein and mRNA expression were determined using Western blotting and reverse transcription polymerase chain reaction. The number of myostatin + SCs decreased significantly at 12, 24, and 48 h (range, -14 to -49%; P < 0.05) after exercise cessation, with no differences between groups. Although the number of myostatin + SCs returned to baseline in the type II fibers on the NPD after 72 h of recovery, the number remained low on the LPD. At the 48 and 72 h time points, myostatin protein expression was elevated (86 ± 26% and 88 ± 29%, respectively) on the NPD (P < 0.05), whereas it was reduced at 72 h (-36 ± 12% compared with baseline) in the LPD group (P < 0.05). This study demonstrates that dietary protein intake does not modulate the post-exercise increase in SC content but modifies myostatin expression in skeletal muscle tissue. This trial was registered at clinicaltrials.gov as NCT01220037.

Evidence for the contribution of muscle stem cells to nonhypertrophic skeletal muscle remodeling in humans.

The purpose of this study was to explore the possible role of muscle stem cells, also referred to as satellite cells (SCs), in adaptation and remodeling following a nonhypertrophic stimulus in humans. Muscle biopsies were obtained from the vastus lateralis of previously untrained women (n=15; age: 27±8 yr, BMI: 29±6 kg/m(2)) before and after 6 wk of aerobic interval training. The fiber type-specific SC response to training was analyzed using immunofluorescent microscopy of muscle cross sections. Following training, the number of SCs associated with fibers expressing myosin heavy-chain type I and II isoforms (hybrid fibers) increased (pre: 0.062±0.035 SC/hybrid fiber; post: 0.38±0.063 SC/hybrid fiber; P<0.01). In addition, there was a greater number of MyoD(+)/Pax7(-) SCs, indicative of differentiating SCs, associated with hybrid fibers (0.18±0.096 MyoD(+)/Pax7(-) SC/hybrid fiber) compared to type I (0.015±0.00615 MyoD(+)/Pax7(-) SC/type I fiber) or II (0.012±0.00454 MyoD(+)/Pax7(-) SC/type II fiber) fibers (P<0.05). There was also a training-induced increase in the number of hybrid fibers containing centrally located nuclei (15.1%) compared to either type I (3.4%) or II fibers (3.6%) (P<0.01). These data are consistent with the hypothesis that SCs contribute to the remodeling of muscle fibers even in the absence of hypertrophy.

Two-year outcomes of different subretinal fluid drainage techniques during vitrectomy for fovea-off rhegmatogenous retinal detachments: ELLIPSOID-2 Study.

BACKGROUND: The purpose of the study is to compare visual acuity, complications and outer retinal integrity following subretinal fluid (SRF) drainage from the peripheral retinal breaks (PRBs) versus posterior retinotomy (PR) versus perfluorocarbon liquid (PFCL) for macula-off rhegmatogenous retinal detachments (RRDs) at 2 years post-surgery. METHODS: Retrospective analysis of 300 consecutive patients with primary RRD undergoing 23-gauge pars plana vitrectomy with SRF drainage through (1) PRB (n=100), (2) PR (n=100) or (3) with PFCL (n=100). Primary outcomes were visual acuity (best-corrected visual acuity (BCVA)) and complications (cystoid macular oedema (CMO) and epiretinal membrane (ERM)). Secondary outcomes were discontinuity of the external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IDZ) at 2 years post-surgery. RESULTS: Mean (±SD) logMAR BCVA at 24 months was better in the PRB compared with PR and PFCL, with PFCL having the worst BCVA (PRB 0.5±0.6; PR 0.7±0.5; PFCL 0.9±0.7, p=0.001). CMO was higher with PFCL (PRB 29.7%; PR 30.2%; PFCL 45.9%, p=0.0015) and ERM formation was higher in PR (PRB 62.6%; PR 93.0%; PFCL 68.9%, p=0.002). There were no differences in ELM or EZ discontinuity. However, IDZ discontinuity was higher in PFCL (PRB 34%; PR 27%; PFCL 46%, p=0.002) at 2 years. CONCLUSIONS: Visual acuity was worse and discontinuity of the IDZ and CMO was greater in eyes with PFCL-assisted drainage compared with PRB or PR. Drainage technique may impact long-term visual acuity and photoreceptor integrity.

Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction.

Aging is associated with increased circulating interleukin-6 (IL-6) and a reduced myogenic capacity, marked by reduced muscle stem cell [satellite cell (SC)] activity. Although IL-6 is important for normal SC function, it is unclear whether elevated IL-6 associated with aging alters SC function. We hypothesized that mild chronically elevated IL-6 would be associated with a blunted SC response through altered IL-6 signaling and elevated suppressor of cytokine signaling-3 (SOCS3) in the elderly. Nine healthy older adult men (OA; 69.6 ± 3.9 yr) and 9 young male controls (YC; 21. 3 ± 3.1 yr) completed 4 sets of 10 repetitions of unilateral leg press and knee extension (75% of 1-RM). Muscle biopsies and blood were obtained before and 3, 24, and 48 h after exercise. Basal SC number was 33% lower in OA vs. YC, and the response was blunted in OA. IL-6(+)/Pax7(+) cells demonstrated a divergent response in OA, with YC increasing to 69% at 3 h and peaking at 24 h (72%), while IL-6(+)/Pax7(+) cells were not increased until 48 h in OA (61%). Type II fiber-associated phosphorylated signal transducer and activator of transcription (pSTAT3)(+)/Pax7(+) cells demonstrated a similar delay in OA, not increasing until 48 h (vs. 3 h in YC). SOCS3 protein was 86% higher in OA. These data demonstrate an age-related impairment in normal SC function that appears to be influenced by SOCS3 protein and delayed induction of IL-6 and pSTAT3 in the SCs of OA. Collectively, these data suggest dysregulated IL-6 signaling as a consequence of aging contributes to the blunted muscle stem cell response.

Myostatin is associated with age-related human muscle stem cell dysfunction.

Human aging is accompanied by a progressive loss of muscle mass (sarcopenia). We tested the hypothesis that older males (OMs, 70±4 yr, n=9) would have a blunted myogenic response to a physiological stimulus compared to younger controls (21±3 yr, n=9). Subjects completed an acute bout of intense unilateral muscle loading. Young healthy males matched for body mass and activity level served as the control group. Muscle biopsies and blood were obtained before and at 3, 24, and 48 h after muscle loading. The muscle stem cell response was analyzed using flow cytometry, immunofluorescent microscopy, and standard protein and mRNA analysis. OMs had 35% fewer basal stem cells and a type II fiber-specific impairment in stem cell content and proliferation. Myogenic determination factor staining and cell cycle analysis illustrated a severely blunted progression through the myogenic program. Myostatin protein and mRNA were 2-fold higher in OMs. Stem cell-specific myostatin levels were not different at baseline; however, there were 67% more myostatin-positive type II-associated stem cells in OMs at 24 h. These data illustrate an age-related impairment of stem cell function in a fiber type-specific manner. The greater colocalization of myostatin with stem cells provides a mechanism for the impaired myogenic capacity of aged muscle.

A single bout of exercise activates skeletal muscle satellite cells during subsequent overnight recovery.

Skeletal muscle satellite cell (SC) content has been reported to increase following a single bout of exercise. Data on muscle fibre type-specific SC content and/or SC activation status are presently lacking. The objective of the study was to determine the impact of a single bout of exercise on muscle fibre type-specific SC content and activation status following subsequent overnight recovery. Eight healthy men (age, 20 ± 1 years) performed a single bout of combined endurance- and resistance-type exercise. Muscle biopsies were collected before and immediately after exercise, and following 9 h of postexercise, overnight recovery. Muscle fibre type-specific SC and myonuclear content and SC activation status were determined by immunohistochemical analyses. Satellite cell activation status was assessed by immunohistochemical staining for both Delta-like homologue 1 (DLK1) and Ki-67. Muscle fibre size and fibre area per nucleus were greater in type II compared with type I muscle fibres (P < 0.05). At baseline, no differences were observed in the percentage of SCs staining positive for DLK1 and/or Ki67 between fibre types. No significant changes were observed in SC content following 9 h of postexercise, overnight recovery; however, the percentage of DLK1-positive SCs increased significantly during overnight recovery, from 22 ± 5 to 41 ± 5% and from 24 ± 6 to 51 ± 9% in the type I and II muscle fibres, respectively. No changes were observed in the percentage of Ki-67-positive SCs. A single bout of exercise activates both type I and II skeletal muscle fibre SCs within a single night of postexercise recovery, preceding the subsequent increase in SC content.

Evaluation of Subretinal fluid Drainage Techniques During Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment-ELLIPSOID Study.

PURPOSE: To compare visual acuity and photoreceptor integrity following pars plana vitrectomy with drainage from the peripheral retinal break(s) (PRB), posterior retinotomy (PR), or perfluorocarbon liquid (PFCL) for macula-off rhegmatogenous retinal detachment. DESIGN: Retrospective consecutive interventional comparative clinical study. METHODS: 300 consecutive patients (300 eyes) with primary macula-off rhegmatogenous retinal detachment underwent 23-gauge pars plana vitrectomy with subretinal fluid drainage through PRB (n = 100), PR (n = 100), or with PFCL (n = 100). Visual acuity and spectral-domain optical coherence tomography were performed preoperatively and at 3, 6, and 12 months postoperatively. Primary outcomes were visual acuity and discontinuity of the external limiting membrane, ellipsoid zone, interdigitation zone, and retinal pigment epithelium at 1 year. RESULTS: Baseline characteristics were similar. Single-operation reattachment rates were as follows: PRB 86%, PR 85%, and PFCL 83% (P = .9). Mean (±SD) logMAR visual acuity at 1 year was greater with PRB and PR compared with PFCL (PRB 0.6 ± 0.5, PR 0.7 ± 0.6, PFCL 0.9 ± 0.6, P = .002). There was an association between drainage technique and discontinuity of the external limiting membrane (PRB 26%, PR 24%, PFCL 44%, P = .001), ellipsoid zone (PRB 29%, PR 31%, PFCL 49%, P < .001), and interdigitation zone (PRB 43%, PR 39%, PFCL 56%, P = .004). There was an association between drainage technique and risk of cystoid macular edema (PRB 28%, PR 39%, PFCL 46%, P = .003) and epiretinal membrane (PRB 64%, PR 90%, PFCL 61%, P < .001). CONCLUSIONS: PFCL-assisted drainage is associated with worse visual acuity and greater risk of outer retinal band discontinuity and cystoid macular edema compared with PRB or PR. PR had a greater risk of epiretinal membrane compared with PRB and PFCL. PRB had the best outcomes overall. Drainage technique may impact long-term anatomic and functional outcomes.

Toxoplasmosis chorioretinitis mimicking cytomegalovirus retinitis in an immunocompromised pediatric patient following bone marrow transplantation.

Objective: To review a case of toxoplasmosis chorioretinitis mimicking cytomegalovirus retinitis in an immunocompromised patient following bone marrow transplantation. Methods: Retrospective chart review of a 14-year-old female who had a history of leukemia and allogeneic bone marrow transplants prior to her ocular symptoms. Results: Anterior chamber fluid analysis was positive for Toxoplasma gondii. The patient responded well when cytomegalovirus retinitis treatment was switched to intravitreal clindamycin with systemic sulfadiazine and prednisone. Conclusions: This case demonstrates the challenges of diagnosing and treating retinal infections in immunocompromised patients as they may present with atypical findings that mimic other pathologies and may have contraindications against standard treatment.

Satellite cell number and cell cycle kinetics in response to acute myotrauma in humans: immunohistochemistry versus flow cytometry.

In humans, muscle satellite cell (SC) enumeration is an important measurement used to determine the myogenic response to various stimuli. To date, the standard practice for enumeration is immunohistochemistry (IHC) using antibodies against common SC markers (Pax7, NCAM). Flow cytometry (FC) analysis may provide a more rapid and quantitative determination of changes in the SC pool with potential for additional analysis not easily achievable with standard IHC. In this study, FC analysis revealed that the number of Pax7(+) cells per milligram isolated from 50 mg of fresh tissue increased 36% 24 h after exercise-induced muscle injury (300 unilateral maximal eccentric contractions). IHC analysis of Pax7 and neural cell adhesion molecule (NCAM) appeared to sufficiently and similarly represent the expansion of SCs after injury (28-36% increase). IHC and FC data illustrated that Pax7 was the most widely expressed SC marker in muscle cross-sections and represented the majority of positive cells, while NCAM was expressed to a lesser degree. Moreover, FC and IHC demonstrated a similar percentage change 24 h after injury (36% increase, Pax7; 28% increase, NCAM). FC analysis of isolated SCs revealed that the number of Pax7(+) cells per milligram in G(2)/M phase of the cell cycle increased 202% 24 h after injury. Number of cells per milligram in G(0)/G(1) and cells in S-phase increased 32% and 59% respectively. Here we illustrate the use of FC as a method for enumerating SC number on a per milligram tissue basis, providing a more easily understandable relation to muscle mass (vs. percentage of myonuclei or per myofibre). Although IHC is a powerful tool for SC analysis, FC is a fast, reliable and effective method for SC quantification as well as a more informative method for cell cycle kinetics of the SC population in humans.

Brain-derived neurotrophic factor is associated with human muscle satellite cell differentiation in response to muscle-damaging exercise.

Muscle satellite cell (SC) regulation is a complex process involving many key signalling molecules. Recently, the neurotrophin brain-derived neurotropic factor (BDNF) has implicated in SC regulation in animals. To date, little is known regarding the role of BDNF in human SC function in vivo. Twenty-nine males (age, 21 ± 0.5 years) participated in the study. Muscle biopsies from the thigh were obtained prior to a bout of 300 maximal eccentric contractions (Pre), and at 6 h, 24 h, 72 h, and 96 h postexercise. BDNF was not detected in any quiescent (Pax7+/MyoD-) SCs across the time-course. BDNF colocalized to 39% ± 5% of proliferating (Pax7+/MyoD+) cells at Pre, which increased to 84% ± 3% by 96 h (P < 0.05). BDNF was only detected in 13% ± 5% of differentiating (Pax7-/MyoD+) cells at Pre, which increased to 67% ± 4% by 96 h (P < 0.05). The number of myogenin+ cells increased 95% from Pre (1.6 ± 0.2 cells/100 myofibres (MF)) at 24 h (3.1 ± 0.3 cells/100 MF) and remained elevated until 96 h (cells/100 MF), P < 0.05. The proportion of BDNF+/myogenin+ cells was 26% ± 0.3% at Pre, peaking at 24 h (49% ± 3%, P < 0.05) and remained elevated at 96 h (P < 0.05). These data are the first to demonstrate an association between SC proliferation and differentiation and BDNF expression in humans in vivo, with BDNF colocalization to SCs increasing during the later stages of proliferation and early differentiation. Novelty BDNF is associated with SC response to muscle injury. BDNF was not detected in nonactivated (quiescent) SCs. BDNF is associated with late proliferation and early differentiation of SCs in vivo in humans.

Effect of short-term high-intensity interval training vs. continuous training on O2 uptake kinetics, muscle deoxygenation, and exercise performance.

The early time course of adaptation of pulmonary O(2) uptake (Vo(2)(p)) (reflecting muscle O(2) consumption) and muscle deoxygenation kinetics (reflecting the rate of O(2) extraction) were examined during high-intensity interval (HIT) and lower-intensity continuous endurance (END) training. Twelve male volunteers underwent eight sessions of either HIT (8-12 x 1-min intervals at 120% maximal O(2) uptake separated by 1 min of rest) or END (90-120 min at 65% maximal O(2) uptake). Subjects completed step transitions to a moderate-intensity work rate ( approximately 90% estimated lactate threshold) on five occasions throughout training, and ramp incremental and constant-load performance tests were conducted at pre-, mid-, and posttraining periods. Vo(2)(p) was measured breath-by-breath by mass spectrometry and volume turbine. Deoxygenation (change in deoxygenated hemoglobin concentration; Delta[HHb]) of the vastus lateralis muscle was monitored by near-infrared spectroscopy. The fundamental phase II time constants for Vo(2)(p) (tauVo(2)) and deoxygenation kinetics {effective time constant, tau' = (time delay + tau), Delta[HHb]} during moderate-intensity exercise were estimated using nonlinear least-squares regression techniques. The tauVo(2) was reduced by approximately 20% (P < 0.05) after only two training sessions and by approximately 40% (P < 0.05) after eight training sessions (i.e., posttraining), with no differences between HIT and END. The tau'Delta[HHb] ( approximately 20 s) did not change over the course of eight training sessions. These data suggest that faster activation of muscle O(2) utilization is an early adaptive response to both HIT and lower-intensity END training. That Delta[HHb] kinetics (a measure of fractional O(2) extraction) did not change despite faster Vo(2)(p) kinetics suggests that faster kinetics of muscle O(2) utilization were accompanied by adaptations in local muscle (microvascular) blood flow and O(2) delivery, resulting in a similar "matching" of blood flow to O(2) utilization. Thus faster kinetics of Vo(2)(p) during the transition to moderate-intensity exercise occurs after only 2 days HIT and END training and without changes to muscle deoxygenation kinetics, suggesting concurrent adaptations to microvascular perfusion.

Combined branch retinal artery and branch retinal vein occlusion from a globe penetrating nail gun injury.

Background: Nail gun injuries represent a significant proportion of work-related ocular trauma. Here we report a rare case of a combined branch retinal arterial occlusion (BRAO) and branch retinal venous occlusion (BRVO) from a nail gun injury in a patient who was wearing eye protection. Case description: A 23-year-old male presented with a left globe penetrating injury from a pneumatic nail gun. The nail ricochet bypassed the patient's protective eyewear, penetrating the left globe causing multiple retinal tears and a combined BRAO and BRVO in the inferior temporal vascular arcade. The patient underwent prompt surgical repair obtaining an excellent anatomic outcome. However, the visual outcome was 20/200 OS at one and two years post injury primarily due to extensive ischemic damage of the retina. Conclusion: This case is the first to describe a combined BRAO and BRVO from a globe penetrating injury. What makes this case even rarer is that the patient was wearing eye protection at the time of the injury. Despite appropriate emergency management, rapid referral for ophthalmologist assessment, and timely surgical management of this patient, the visual outcome was poor. The vascular injury ultimately compromised a significant segment of the retina, including the macula.

Adherence to World Glaucoma Association Guidelines for Surgical Trials in the Era of Microinvasive Glaucoma Surgeries.

PURPOSE: To determine how well microinvasive glaucoma surgical (MIGS) trials conform to the World Glaucoma Association (WGA) guidelines. Lack of well-designed MIGS studies hinders meaningful evaluation of these technologies. DESIGN: Cross-sectional literature survey. METHODS: Using a predefined search strategy, the following databases were searched for comparative trials involving MIGS in the English peer-reviewed literature from January 1, 2000, through June 21, 2018: Medline, EMBASE, BIOSIS, Cochrane, and Web of Science. From the WGA guidelines, 53 outcomes were selected for evaluation: methodology (n = 31), definition of success (n = 7), ethics (n = 10), postoperative complications (n = 1), economic evaluation (n = 1), and statistical reporting (n = 3). Each article was assessed by 2 reviewers; differences were resolved by consensus. RESULTS: Twenty-five eligible publications were identified: 10 randomized controlled trials (RCTs) and 15 nonrandomized comparative trials (non-RCTs). The mean follow-up was 19.9±11.6 months (range, 6-48 months). The mean number of outcomes adhering to the WGA guidelines of the 53 evaluated was 24.2±6.1 (45.6% compliance): 28.0±6.2 (52.8%) and 21.6±4.7 (40.8%) for RCTs and non-RCTs, respectively (P = 0.01). Mean percent compliance for each subsection were: methodology, 48.8%; definition of success, 21.1%; ethics, 55.6%; postoperative complications, 88%; economic evaluation, 0%; and statistical reporting, 37.3%. In 16 studies (64%), at least 1 author reported an association with the industry. Thirty-two percent of studies reported an author being a shareholder. Twenty-four percent of studies had an industry employee author. The primary intraocular pressure (IOP) end point was defined as both an upper limit and percentage reduction in only 4 studies (16%; 1 RCT, 3 non-RCTs). An IOP-based survival curve was provided in 7 studies (28%; none of the RCTs). Two studies (8%) included an IOP scatterplot. Twelve studies (48%) reported 95% confidence intervals. Only 4 studies (16%) used the mean of 3 diurnal IOP readings as the baseline IOP. CONCLUSIONS: Published comparative MIGS trials show low adherence (45.6%) to the WGA guidelines. Development of standardized methodology and outcomes could enhance interpretation and transparency of study results and facilitate comparisons between trials. Authors and journals should be encouraged to follow the WGA guidelines.