Modulation of beta-hydroxybutyrate in traumatic brain injury.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) is a significant public health concern with substantial morbidity and mortality rates in the United States. Current management strategies primarily focus on symptomatic approaches and prevention of secondary complications. However, recent research highlights the potential role of ketone bodies, particularly beta-hydroxybutyrate (BHB), in modulating cellular processes involved in TBI. This article reviews the metabolism of BHB, its effect in TBI, and its potential therapeutic impact in TBI. RECENT FINDINGS: BHB can be produced endogenously through fasting or administered exogenously through ketogenic diets, and oral or intravenous supplements. Studies suggest that BHB may offer several benefits in TBI, including reducing oxidative stress, inflammation, controlling excitotoxicity, promoting mitochondrial respiration, and supporting brain regeneration. Various strategies to modulate BHB levels are discussed, with exogenous ketone preparations emerging as a rapid and effective option. SUMMARY: BHB offers potential therapeutic advantages in the comprehensive approach to improve outcomes for TBI patients. However, careful consideration of safety and efficacy is essential when incorporating it into TBI treatment protocols. The timing, dosage, and long-term effects of ketone use in TBI patients require further investigation to fully understand its potential benefits and limitations.

Recent Advances in Management of Neuropathic, Nociceptive, and Chronic Pain: A Narrative Review with Focus on Nanomedicine, Gene Therapy, Stem Cell Therapy, and Newer Therapeutic Options.

PURPOSE OF REVIEW: This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain. RECENT FINDINGS: Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians.

The Role of Platelet Rich Plasma in Vertebrogenic and Discogenic Pain: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: The present investigation evaluates clinical uses and roles of platelet rich plasma in the management of vetrebrogenic and discogenic mediated pain states. RECENT FINDINGS: Back pain is a common and significant condition that affects millions of people around the world. The cause of back pain is often complex and multifactorial, with discogenic and vertebrogenic pain being two subtypes of back pain. Currently, there are numerous methods and modalities in which back pain is managed and treated such as physical therapy, electrical nerve stimulation, pharmacotherapies, and platelet-rich plasma. To conduct this systematic review, the authors used the keywords "platelet-rich plasma", "vertebrogenic pain", and "discogenic pain", on PubMed, EuroPMC, Who ICTRP, and clinicaltrials.gov to better elucidate the role of this treatment method for combating vertebrogenic and discogenic back pain. In recent decades, there has been a rise in popularity of the use of platelet-rich plasma for the treatment of numerous musculoskeletal conditions. Related to high concentration of platelets, growth factors, cytokines, and chemokines, platelet-rich plasma is effective in reducing pain related symptoms and in the treatment of back pain. Platelet-rich plasma use has evolved and gained popularity for pain related conditions, including vertebrogenic and discogenic back pain. Additional well-designed studies are warranted in the future to better determine best practice strategies to provide future clinicians with a solid foundation of evidence to make advancements with regenerative medical therapies such as platelet-rich plasma.

Liquid biopsy in the setting of leptomeningeal metastases: a systematic review and meta-analysis.

PURPOSE: The blood-brain barrier can prevent circulating tumor DNA (ctDNA) derived from the central nervous system from entering the blood making it challenging to evaluate molecular features of leptomeningeal metastasis (LM). Accordingly, we sought to systematically compare the diagnostic power or significance of ctDNA derived from cerebrospinal fluid (CSF) compared to plasma ctDNA in patients with LM. METHODS: A systematic review and meta-analysis was performed under the PRISMA guideline. We used PubMed, EMBASE, and the EuroPMC to search the literature using combinations of the following terms: circulating tumor DNA, ctDNA, circulating tumor cell, brain metastasis, leptomeningeal metastasis, outcome(s), and prognosis. We included all available English language studies that compared the diagnostic significance of CSF derived and serum ctDNA. All eligible studies level of bias was assessed using the New Castle Ottawa Scale (NOS). RESULTS: Our meta-analysis from 6 included studies (n = 226) that confirmed the diagnostic power of liquid biopsies in detecting genomic alteration is better when taking a CSF-derived samples than from the plasma (RR 1.46 [0.93; 2.29]; I2 = 92%; p-value < 0.01). CONCLUSION: CSF ctDNA is better at describing molecular landscape for LM; such an understanding may ultimately help inform patient treatment and responses to therapy.

Comparison of ReLEx SMILE and PRK in terms of visual and refractive outcomes for the correction of low myopia.

PURPOSE: To compare the objective and subjective quality of vision after femtosecond laser-assisted small incision lenticule extraction (SMILE) and photorefractive keratectomy (PRK) for low myopia. METHODS: One hundred and twenty eyes from 60 patients (34 females, 26 males) undergoing bilateral correction of low myopia (≤-4 D SE) with either ReLEx SMILE or PRK were included. Visual acuity, contrast sensitivity and higher-order aberrations were recorded preoperatively and compared postoperatively. A quality of vision questionnaire was scored and analyzed 3 months postoperatively. RESULTS: At 3 months, the SMILE group had significantly better uncorrected and corrected distant visual acuity (CDVA), compared to PRK group (p = 0.01). Post-op spherical equivalent (SE) was comparable in both groups (SMILE = -0.15 ± 0.19 D, PRK = -0.14 ± 0.23 D, p = 0.72). However, SE predictability was better in SMILE group with 97% eyes within ±0.05 D compared to 93% eyes in the PRK group. Total higher-order aberrations (HOAs) were significantly higher in PRK compared to the SMILE group (p = 0.022). The SMILE group demonstrated slightly better contrast sensitivity, which was significant at spatial frequency of 12 cpd (p = 0.03). Four eyes in the PRK group had loss of CDVA by one line due to mild haze. CONCLUSIONS: Both SMILE and PRK were effective procedures for correction of low myopia. However, SMILE offered superior quality of vision and patient satisfaction due to better postoperative comfort and lower induction of aberrations at 3 months.

Assessment of goat activin receptor type IIB knockdown by short hairpin RNAs in vitro.

BACKGROUND: Targeted knockdown of ACVR2B, a receptor for TGF beta superfamily, has been seen as a potential candidate to enhance the muscle mass through RNAi approach. METHODS: We have evaluated the potential short hairpin RNAs targeting goat ACVR2B in human HEK293T cells and goat myoblasts cells by transient transfection and measured their knockdown efficiency and possible undesired interferon response by quantitative real-time PCR. RESULTS: We observed a significant silencing (64-81%) of ACVR2B in 293T cells with all seven shRNAs (sh1 to sh7) constructs and 16-46% silencing with maximum of 46% by sh6 (p = 0.0318) against endogenous ACVR2B whereas up to 66% (p = 0.0002) silencing by sh6 against exogenously expressed ACVR2B in goat myoblasts cells. Transient knockdown of ACVR2B in goat myoblasts cells by shRNAs did not show significant correlation with the expression of MyoD (r = 0.547; p = 0.102), myogenin (r = 0.517; p = 0.126) and Myf5 (r = 0.262; p = 0.465). As reported earlier, transfection of plasmid DNA induced potent interferon response in 293T and goat myoblasts cells. CONCLUSIONS: The present study demonstrates the targeted knockdown of ACVR2B by shRNAs in HEK293T and goat myoblasts cells in vitro. The transient knockdown of ACVR2B by shRNAs in goat myoblasts did not alter the myogenic gene expression program. However, shRNAs showing significant knockdown efficiency in our study may further be tested for long term and stable knockdown to assess their potential to use for enhancing muscle mass in vivo. As reported earlier, expression of shRNAs through plasmid expression vectors induces potent interferon response raising the concern of safety of its application in vivo.

A Systematic Review of Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis Following Coronavirus Disease 2019 Vaccination: A 2024 Update.

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is an immune-mediated kidney disease characterized by the inflammation of small blood vessels in the kidney, leading to renal impairment and potentially irreversible damage. Concerns have been raised over the reports of myeloperoxidase/perinuclear (MPO/p) ANCA GN following the coronavirus disease 2019 (COVID-19) vaccination. Our study provides a comprehensive insight into perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) GN after COVID-19 vaccination. We conducted a comprehensive literature search on PubMed, Cochrane Library, and EMBASE using the Medical Subject Headings (MeSH) terms related to "covid-19 vaccine," "glomerulonephritis," "p-ANCA," and "MPO-ANCA" up to March 5, 2024, to include cases of p-ANCA-associated GN following COVID-19 vaccination. Of the 4,102 articles, we included 29, reporting 35 patients demonstrating COVID-19 vaccine-induced p-ANCA GN, with 23 (65.7%) females and a median age of 69 years (mean ± SD = 63.22 ± 16). Twenty-six (74.28%) patients received the mRNA vaccine (Pfizer = 19, Moderna = 7). Seventeen (48.57%) patients presented with p-ANCA GN after the second dose of the COVID-19 vaccine, with a median gap of 19 days (1-84 days). Constitutional symptoms (54.28%) and acute kidney injury (42.85%) were the most reported initial presentations, and elevated serum creatinine (mean peak serum creatinine = 4.98 ± 5.02 mg/dL), hematuria, and proteinuria were the laboratory findings. MPO/p-ANCA was positive in 31 (88.6%) patients. All patients underwent renal biopsy, and crescentic GN was the most common finding among 27 (77.14%) patients. Management of p-ANCA GN included steroids in 30 (85.71%) patients, followed by rituximab (28.57%), and plasmapheresis (22.86%). Most patients responded well to treatment, with complete remission in 29 (82.86%) and relapse in four (11.42%) patients. Two patients did not achieve remission and became dialysis dependent. ANCA-associated GN is a rare and life-threatening complication of the COVID-19 vaccine, necessitating urgent evaluation and management. COVID-19 vaccine-induced p-ANCA GN should be included in the differential diagnoses of patients presenting with kidney injury after vaccination.

A Neonatal Patient Diagnosed with Chromosome 18p 11.1 Microdeletion Syndrome Presented with Trisomy 18Like Phenotype.

Microdeletion of the short arm of chromosome 18 is one of the most common chromosome deletion syndromes. Its estimated frequency is 1 in 50,000 live-born infants, with female prevalence over males. Around 150 cases have been described till now. The reported abnormalities include growth deficiency, hypotonia, microcephaly, dysmorphic facial features such as ptosis, epicanthal folds, hypertelorism and micrognathia, and relatively small hands and feet. Our patient was a full-term low birth weight (2150 gm) female newborn, showing cleft upper lip and palate (hard and soft palate), bilateral congenital Talipes Equinovarus with rocker bottom foot, microcephaly, atrial septal defect. She was initially conservatively managed with gavage feeding, then shifted into paladai feeding of expressed breast milk. A multidisciplinary approach was adopted due to various malformations and for the potential occurring complications. To our knowledge, this is the first case diagnosed during the neonatal period.

A Systematic Review of COVID-19 Vaccine-Induced Takotsubo Cardiomyopathy: A 2023 Update.

Takotsubo cardiomyopathy (TCM) is a life-threatening transient left ventricular dysfunction triggered by either physical or emotional stressors. Concerns have been raised on reports of TCM after the coronavirus disease 2019 (COVID-19) vaccine. Our study provides comprehensive detail on COVID-19 vaccine-induced TCM. We conducted a systemic literature search using major databases, including PubMed, EMBASE, and Google Scholar up to November 2023, to identify cases of COVID-19 vaccine-induced TCM using the MeSH terms and keywords "covid-19 vaccines" and "takotsubo cardiomyopathy". We identified 15 case reports, including 16 patients with COVID-19 vaccine-induced TCM. The mean age was 55.81 ± 19.13 years, and 75% of the patients were female. The most common presentation was chest pain (62.5%), and the average time to first symptom onset was 3.12 ± 2.24 days. COVID-19 vaccine-induced TCM was reported in 43.75% of patients receiving the first and second dose each, and 87% of patients had messenger ribonucleic acid (mRNA) COVID-19 vaccine (Pfizer, Moderna). The elevated level of cardiac troponins was found in all the patients with a left ventricular ejection fraction (LVEF) of <50% in 15 patients, and T-wave inversion (50%) was the most common electrocardiographic finding. The mean length of the hospital stay was 7.27 ± 3.95 days, and 87% of patients were discharged. COVID-19 vaccine-induced TCM is a rare but life-threatening complication. TCM should be included in the differential diagnosis of chest pain or dyspnea in patients recently receiving the COVID-19 vaccine.

Validation of a High-Sensitivity Assay for Detection of Chimeric Antigen Receptor T-Cell Vectors Using Low-Partition Digital PCR Technology.

Although in vivo engraftment, expansion, and persistence of chimeric antigen receptor (CAR) T cells are pivotal components of treatment efficacy, quantitative monitoring has not been implemented in routine clinical practice. We describe the development and analytical validation of a digital PCR assay for ultrasensitive detection of CAR constructs after treatment, circumventing known technical limitations of low-partitioning platforms. Primers and probes, designed for detection of axicabtagene, brexucabtagene, and Memorial Sloan Kettering CAR constructs, were employed to validate testing on the Bio-Rad digital PCR low-partitioning platform; results were compared with Raindrop, a high-partitioning system, as reference method. Bio-Rad protocols were modified to enable testing of DNA inputs as high as 500 ng. Using dual-input reactions (20 and 500 ng) and a combined analysis approach, the assay demonstrated consistent target detection around 1 × 10-5 (0.001%) with excellent specificity and reproducibility and 100% accuracy compared with the reference method. Dedicated analysis of 53 clinical samples received during validation/implementation phases showed the assay effectively enabled monitoring across multiple time points of early expansion (day 6 to 28) and long-term persistence (up to 479 days). CAR vectors were detected at levels ranging from 0.005% to 74% (vector versus reference gene copies). The highest levels observed in our cohort correlated strongly with the temporal diagnosis of grade 2 and 3 cytokine release syndrome diagnosis (P < 0.005). Only three patients with undetectable constructs had disease progression at the time of sampling.

OcularTrauma Score: a useful predictor of visual outcome at six weeks in patients with traumatic cataract.

OBJECTIVE: To validate the predictive value of the Ocular Trauma Score (OTS) in injury cases with traumatic cataracts. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 787 eyes. METHODS: A total of 787 eyes of 787 subjects with traumatic cataracts were enrolled using specific inclusion criteria. The eyes were examined to review comorbidities caused by trauma. Surgery was performed for traumatic cataracts, lenses were implanted, and patients were treated for amblyopia, as applicable. The patients were reexamined 6 weeks postoperatively. On the basis of ocular trauma described according to the Birmingham Eye Trauma Terminology System, the patients were divided into 2 traumatic cataract groups: open globe injury and closed globe injury. The relationship of visual acuity (VA) with demographic and clinical variables was analyzed. The visual outcomes were predicted using the OTS, and the predictions were compared with the actual outcomes using statistical tests. MAIN OUTCOME MEASURES: Visual acuity. RESULTS: At 6 weeks postoperatively, 245 eyes (31%) had a VA ≥ 20/40 and 480 eyes (61.0%) had a VA >20/200. The OTS prediction was not significantly different when compared with actual visual outcome at 6 weeks postoperatively in all OTS categories. CONCLUSIONS: The relationship of VA at 6 weeks with demographic and clinical variables was analyzed. In this study, the OTS was found as a reliable tool to predict visual outcome in cases of traumatic cataracts 6 weeks postoperatively.

Long-term exposure of the binary mixture of cadmium and mercury damages the developed ovary of adult zebrafish.

The toxicity of the binary mixture of cadmium (Cd) and mercury (Hg) on the ovary of adult zebrafish was evaluated in the present study. Adult female zebrafish were exposed to cadmium chloride (1 mg/L), mercury chloride (30 µg/L), and a binary mixture of both metals for 21 days. The toxic effects of both metals on the ovary were investigated by evaluating the oxidative stress markers and related gene expression in ovarian tissue along with the histopathological examination. The significantly decreased level of GSH and increased level of MDA in ovarian tissue of adult female zebrafish exposed to Cd + Hg indicated that the exposure of binary mixture of Cd and Hg caused more lipid peroxidation in the ovary. The significant changes in expression of mRNA of catalase (CAT) and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) were not observed in the ovary of zebrafish exposed to the binary mixture. Upon histological evaluation, a decreased number of full-growth (mature) oocytes along with degenerative changes due to Cd exposure were noticed, while ovary of zebrafish of the Hg-exposed group had shown a decreased number of pre-and early vitellogenic oocytes along with atretic previtellogenic oocytes compared to the control group. The ovary of zebrafish of the Cd + Hg-exposed group had shown a decreased number of previtellogenic oocytes with marked pathological changes in mature oocytes. Present findings elucidate that simultaneous long-term exposure of Cd and Hg compared to individual exposure significantly damaged the various stages of oocytes of an ovary of adult zebrafish.

Cancer-Causative Mutations Occurring in Early Embryogenesis.

Mosaic mutations in normal tissues can occur early in embryogenesis and be associated with hereditary cancer syndromes when affecting cancer susceptibility genes (CSG). Their contribution to apparently sporadic cancers is currently unknown. Analysis of paired tumor/blood sequencing data of 35,310 patients with cancer revealed 36 pathogenic mosaic variants affecting CSGs, most of which were not detected by prior clinical genetic testing. These CSG mosaic variants were consistently detected at varying variant allelic fractions in microdissected normal tissues (n = 48) from distinct embryonic lineages in all individuals tested, indicating their early embryonic origin, likely prior to gastrulation, and likely asymmetrical propagation. Tumor-specific biallelic inactivation of the CSG affected by a mosaic variant was observed in 91.7% (33/36) of cases, and tumors displayed the hallmark pathologic and/or genomic features of inactivation of the respective CSGs, establishing a causal link between CSG mosaic variants arising in early embryogenesis and the development of apparently sporadic cancers. SIGNIFICANCE: Here, we demonstrate that mosaic variants in CSGs arising in early embryogenesis contribute to the oncogenesis of seemingly sporadic cancers. These variants can be systematically detected through the analysis of tumor/normal sequencing data, and their detection may affect therapeutic decisions as well as prophylactic measures for patients and their offspring. See related commentary by Liggett and Sankaran, p. 889. This article is highlighted in the In This Issue feature, p. 873.

Comparative study of final visual outcome between open- and closed-globe injuries following surgical treatment of traumatic cataract.

OBJECTIVE: The objective of this work is to compare final visual outcomes in cases of surgically treated traumatic cataract between open-globe and closed-globe groups, as classified by the Birmingham Eye Trauma Terminology system. DESIGN: Observational cohort study. SETTING: Tertiary eye-care center at the trijunction of Gujarat, Madhya Pradesh, and Rajasthan states in central western India. METHODS: We enrolled patients meeting specific inclusion criteria, examined their eyes to review any co-morbidities due to trauma, performed surgery for traumatic cataracts, and implanted lenses. The patients were re-examined 6 weeks postoperatively. We classified the cases of traumatic cataract as either open-globe (group 1) or closed-globe (group 2), according to the Birmingham Eye Trauma Terminology (BETT) system, and compared visual acuity. OUTCOME MEASURES: Visual Acuity. RESULTS: Our cohort of 687 eyes with traumatic cataracts included 496 eyes in group 1 and 191 in group 2. Six weeks postoperatively, the visual acuity was >20/60 in 298 (58%) and 75 (39.1%) operated eyes in groups 1 and 2, respectively (p < 0.001, ANOVA). At follow-up, >20/60 vision was significantly higher in group 1 than in group 2 (OR = 1.61; 95% CI, 0.85-3.02). Overall, 373 eyes (54.3%) regained final visual acuity >20/60. CONCLUSIONS: Open-globe injury has a more favorable prognosis for satisfactory (>20/60) visual recovery after management of traumatic cataracts.

COVID surveillance robot: Monitoring social distancing constraints in indoor scenarios.

Observing social/physical distancing norms between humans has become an indispensable precaution to slow down the transmission of COVID-19. We present a novel method to automatically detect pairs of humans in a crowded scenario who are not maintaining social distancing, i.e. about 2 meters of space between them using an autonomous mobile robot and existing CCTV (Closed-Circuit TeleVision) cameras. The robot is equipped with commodity sensors, namely an RGB-D (Red Green Blue-Depth) camera and a 2-D lidar to detect social distancing breaches within their sensing range and navigate towards the location of the breach. Moreover, it discreetly alerts the relevant people to move apart by using a mounted display. In addition, we also equip the robot with a thermal camera that transmits thermal images to security/healthcare personnel who monitors COVID symptoms such as a fever. In indoor scenarios, we integrate the mobile robot setup with a static wall-mounted CCTV camera to further improve the number of social distancing breaches detected, accurately pursuing walking groups of people etc. We highlight the performance benefits of our robot + CCTV approach in different static and dynamic indoor scenarios.

Prevalence of myocardial bridge in angiographic population-A study from rural part of western India.

INTRODUCTION: Intramural course of coronary artery is known as myocardial bridge (MB). Its prevalence is highly variable. Very few studies have been conducted in India, mostly from southern state and that too covering urban population. There are no studies from western India. In this study we aimed to estimate the prevalence of MB in coronary angiogram from rural part of western India. METHODS AND RESULTS: A total of 4,438 patients underwent coronary angiography for various indications during the study period of 69 months. Mean age of the study population was 53.6 ± 11.2 years. MB was found in 212 (4.77%) of patients, predominantly in males. Unstable angina was the most common presentation among males (28.7%), whereas chronic stable angina was being the most common presentation among females (22.6%). Majority of MBs were seen in left anterior descending artery in its mid part (61%). Mean diameter compression of the affected segment was 32.6% ± 11.8%, with no significant difference seen among males and females or between mid and distal left anterior descending artery. CONCLUSION: Our study showed the prevalence of MB similar to other Indian studies. Left anterior descending artery was most common artery involved. Mean compression was not statistically significant among either sex.

De Winter Sign in Inferior Leads: A Rare Presentation.

De Winter pattern in anterior leads has been extensively described. However, there is only one case report of this pattern in inferior leads in English literature. Here, we describe a case of acute inferior wall myocardial infarction with thrombotic right coronary artery occlusion who presented with the classical De Winter sign in inferior leads.

Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression.

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARLNC1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression and identify ARLNC1 as a novel therapeutic target.

Posterior corneal curvature changes following Refractive Small Incision Lenticule Extraction.

PURPOSE: To compare the posterior corneal curvature changes, in terms of corneal power and asphercity, following Refractive Small Incision Lenticule Extraction (ReLEx SMILE) procedure for low, moderate, and high myopia. METHODS: This retrospective, non randomized, comparative, interventional trial; included 52 eyes of 26 patients, divided in three groups: low myopia (myopia ≤3 D [diopters] spherical equivalent [SE]), moderate myopia (myopia >3 D and <6 D SE), and high myopia (myopia ≥6 D SE). All patients were treated for myopia and myopic astigmatism using ReLEx SMILE. The eyes were examined pre-operatively and 3 months post-operatively using SCHWIND SIRIUS, a three-dimensional rotating Scheimpflug camera with a Placido disc topographer to assess corneal changes with regard to keratometric power and asphericity of the cornea. RESULTS: A statistically significant increase in mean keratometric power in the 3, 5, and 7 mm zones of the posterior corneal surface compared with its pre-ReLEx SMILE value was detected after 3 months in the moderate myopia group (pre-operative [pre-op] -6.14±0.23, post-operative [post-op] -6.29±0.22, P<0.001) and high myopia group (pre-op -6.19±0.16, post-op -6.4±0.18, P<0.001), but there was no significant change in keratometric power of the posterior surface in the low myopia group (pre-op -5.87±0.17, post-op -6.06±0.29, P=0.143). Asphericity (Q-value) of the posterior surface changed significantly (P<0.001) after ReLEx SMILE in the moderate myopia group in the 3, 5, and 7 mm zones, and in the high myopia group in the 3 and 7 mm zones; but there was no significant change in the Q-value in the low myopia group in all three zones (pre-op 0.23±0.43, post-op -0.40±0.71, P=0.170), and in the high myopia group in the 5 mm zone (P=0.228). CONCLUSION: ReLEx SMILE causes significant changes in posterior corneal keratometric power and asphericity in moderate and high myopia, but the effect is subtle and insignificant in low myopia.

Stable suppression of myostatin gene expression in goat fetal fibroblast cells by lentiviral vector-mediated RNAi.

Myostatin (MSTN) is a secreted growth factor that negatively regulates skeletal muscle mass, and therefore, strategies to block myostatin-signaling pathway have been extensively pursued to increase the muscle mass in livestock. Here, we report a lentiviral vector-based delivery of shRNA to disrupt myostatin expression into goat fetal fibroblasts (GFFs) that were commonly used as karyoplast donors in somatic-cell nuclear transfer (SCNT) studies. Sh-RNA positive cells were screened by puromycin selection. Using real-time polymerase chain reaction (PCR), we demonstrated efficient knockdown of endogenous myostatin mRNA with 64% down-regulation in sh2 shRNA-treated GFF cells compared to GFF cells treated by control lentivirus without shRNA. Moreover, we have also demonstrated both the induction of interferon response and the expression of genes regulating myogenesis in GFF cells. The results indicate that myostatin-targeting siRNA produced endogenously could efficiently down-regulate myostatin expression. Therefore, targeted knockdown of the MSTN gene using lentivirus-mediated shRNA transgenics would facilitate customized cell engineering, allowing potential use in the establishment of stable cell lines to produce genetically engineered animals.