Supplementation with rumen-inert fat in the growing phase altered adipogenic gene expression and the size and number of adipocytes in Hanwoo steers.

We hypothesized that the provision of rumen-inert fat (RIF) to growing cattle (9 to 13 mo of age) would affect the expression of genes involved in lipid metabolism and thereby affect the size and number of adipocytes of steers slaughtered at 30 mo of age. Thirty steers with an average initial body weight (BW) of 239 ±â€…25 kg were allocated to six pens, balanced for BW and genetic merit for marbling, and assigned to one of two treatment groups: control (only basal diet) or test diet (basal diet with 200 g of RIF per day, on an as-fed basis) for 5 mo. Biopsy samples of longissimus lumborum (LM) muscle were then collected for analysis of fatty acid composition and gene expression. Both groups were then fed the same basal diets during the early and late fattening phases, without RIF, until slaughter (average shrunk BW = 759 kg). Supplementation with RIF increased the longissimus thoracis (LT) intramuscular fatty acid concentration at slaughter (P = 0.087) and numerically increased the quality grade score (P = 0.106). The LM intramuscular relative mRNA expression of genes such as PPARα, ZFP423 and SREBP1, FASN, SCD, FABP4, GPAT1, and DGAT2 were downregulated (P < 0.1) following RIF supplementation. Supplementation of RIF decreased (P < 0.1) diameter and concomitantly increased intramuscular adipocytes per viewing section at slaughter. This likely was caused by promotion of triacylglycerol hydrolysis during the growing phase. Another possible explanation is that the relative mRNA expression of gene ATGL was upregulated by RIF supplementation during the growing (P < 0.1) and the fattening phases (P < 0.05), while the genes associated with fatty acid uptake (FABP4) and esterification (DGAT2) were downregulated during the growing phase and upregulated (P < 0.1) during the fattening phase. This implies that the lipid turnover rate was higher for steers during the growing than fattening phase. This study demonstrated that RIF supplementation during the growing phase induced a carryover effect on the lipogenic transcriptional regulation involved in adipocyte lipid content of intramuscular adipose tissue; increased triacylglycerol hydrolysis during the growing phase subsequently was followed by increased lipid accumulation during the fattening phases.

Rumen inert fat (RIF) is a type of fat supplement that is used in the diets of beef cattle as early as 6 mo of age in calves and continues through the finishing period to improve the dietary energy density which can be used by the animal to deposit more lipid in the muscle tissue. However, for Hanwoo beef cattle, the precise time of RIF supplementation has not yet been determined. This study hypothesized that supplementing RIF at the growing phase (9 to 13 mo of age) would have a positive influence on the marbling characteristics of meat at slaughter. The growth rate and performance of steers were not improved by RIF supplementation, however, an increase in intramuscular fatty acid content was noted that was accompanied by the increased number of intramuscular adipocytes and decreased intramuscular adipocyte diameter. Supportively, upregulation of the genes associated with fatty acid uptake and esterification during the fattening phase of RIF-fed animals was noted. Overall, supplementing RIF at the growing stage could improve the lipid content of the meat which is supported by the increased lipid hydrolysis during the growing phase and followed by increased lipid accumulation during the fattening phases.

Development of Optimized Vitrification Procedures Using Closed Carrier System to Improve the Survival and Developmental Competence of Vitrified Mouse Oocytes.

The open carrier system (OC) is used for vitrification due to its high efficiency in preserving female fertility, but concerns remain that it bears possible risks of cross-contamination. Closed carrier systems (CC) could be an alternative to the OC to increase safety. However, the viability and developmental competence of vitrified/warmed (VW) oocytes using the CC were significantly lower than with OC. We aimed to improve the efficiency of the CC. Metaphase II oocytes were collected from mice after superovulation and subjected to in vitro fertilization after vitrification/warming. Increasing the cooling/warming rate and exposure time to cryoprotectants as key parameters for the CC effectively improved the survival rate and developmental competence of VW oocytes. When all the conditions that improved the outcomes were applied to the conventional CC, hereafter named the modified vitrification/warming procedure using CC (mVW-CC), the viability and developmental competence of VW oocytes were significantly improved as compared to those of VW oocytes in the CC. Furthermore, mVW-CC increased the spindle normality of VW oocytes, as well as the cell number of blastocysts developed from VW oocytes. Collectively, our mVW-CC optimized for mouse oocytes can be utilized for humans without concerns regarding possible cross-contamination during vitrification in the future.

Effect of a Porous Suture Containing Transforming Growth Factor Beta 1 on Healing After Rotator Cuff Repair in a Rat Model.

BACKGROUND: The healing failure rate after rotator cuff repair is considerably high. PURPOSE: To evaluate the effect of a porous suture containing transforming growth factor beta 1 (TGF-ß1) on the sustained release of TGF-ß1 and rotator cuff healing in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: A porous suture was developed, and its tensile strength was measured. TGF-ß1 was delivered using the porous suture, and a TGF-ß1 release test and human fibroblast proliferation assay were performed. For the animal experiment, 30 rats were randomly allocated into 3 groups (n = 10 each). A bilateral supraspinatus tendon tear was made in all the rats, and repair was performed. Group 1 received repair only; group 2, repair and a single injection of TGF-ß1; and group 3, repair using the porous suture containing TGF-ß1. Eight weeks after repair, biomechanical and histological analyses were performed. RESULTS: The porous suture was successfully developed with mechanical properties compatible with the conventional suture, and the sustained release of TGF-ß1 from the porous suture was confirmed. In addition, the cell proliferation assay confirmed the biological safety of the porous suture. In the animal experiment, group 3 biomechanically exhibited the largest cross-sectional area and the highest ultimate failure load and ultimate stress (all P < .05). Histological examination revealed that group 3 showed significantly better collagen fiber density and tendon-to-bone maturation than did groups 1 and 2 (all P < .05). CONCLUSION: The porous suture containing TGF-ß1 could sustainedly and safely release TGF-ß1, and its use during rotator cuff repair could improve rotator cuff healing, as assessed on the basis of the biomechanical and histological changes in the rat model in this study. Considering the effectiveness, safety, and convenience of the porous suture without extra effort in surgery, the findings of the present study will have a far-reaching effect on the treatment of rotator cuff tears. CLINICAL RELEVANCE: The porous suture containing TGF-ß1 might improve healing after rotator cuff repair.

Advanced Maternal Age Deteriorates the Developmental Competence of Vitrified Oocytes in Mice.

Advanced maternal age (AMA) is known to be related to the decrease in the quality and quantity of oocytes. Oocyte vitrification is now considered an established assisted reproductive technology for fertility preservation. However, it remains unclear whether the oocytes in older women are more sensitive to various insults during vitrification. Thus, we evaluated whether AMA affects cellular and molecular features and developmental outcomes of oocytes after vitrification in mice. The oocytes were grouped as young fresh (YF), young vitrified/warmed (YV), aged fresh (AF), and aged vitrified/warmed (AV). The survival rate of AV oocytes was significantly lower than that of YV oocytes. The rates of fertilization, cleavage, and blastocyst formation of AV oocytes were significantly lower than those of other groups. AV oocytes were represented as aberrations in mitochondria distribution, microvacuole size, and autophagosome formation, leading to delayed embryo development in mice. This delay was associated with a reduced number of total cells and trophectoderm in the blastocyst developed from AV oocytes. Collectively, AMA exaggerates the vulnerability of oocytes to cryo-damage that occurs during vitrification in mice, suggesting that the current vitrification protocols optimized for oocytes from young females should be modified for oocytes from aged women.

Lipidomic changes in mouse oocytes vitrified in PEG 8000-supplemented vitrification solutions.

Cryopreserved oocytes are inevitably exposed to cold stress, which negatively affects the cellular aspects of the oocytes. Lipidomic analysis of the oocytes reveals quantitative changes in lipid classes under conditions of cold stress, leading to potential freezing-vulnerability. We had previously shown that specific phospholipids are significantly downregulated in vitrified-warmed mouse oocytes compared to those in fresh oocytes. In this study, we examined whether supplementation of polyethylene glycol 8000 (PEG 8000) during vitrification influences the lipidome of the oocytes. We used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to study the alteration in the lipidome in three groups of mouse oocytes: fresh, vitrified-warmed, and vitrified with PEG 8000-warmed during vitrification. In these groups, we targeted to analyze 21 lipid classes. We profiled 132 lipid species in the oocytes and statistical analyses revealed lipid classes that were up- or downregulated in these groups. Overall, our data revealed that several classes of lipids were affected during vitrification, and that oocytes vitrified with PEG 8000 to some extent alleviated the levels of changes in phospholipid and sphingolipid contents during vitrification. These results suggest that phospholipids and sphingolipids are influenced by PEG 8000 during vitrification and that PEG 8000 can be considered as a potential candidate for preserving membrane integrity during oocyte cryopreservation.

Psychosocial stress and ovarian function in adolescent and young adult cancer survivors.

STUDY QUESTION: Is psychosocial stress associated with ovarian function in reproductive-aged survivors of cancer diagnosed as adolescents and young adults (AYA survivors)? SUMMARY ANSWER: We observed no association between self-reported and biomarkers of psychosocial stress and ovarian function in AYA survivors. WHAT IS KNOWN ALREADY: Psychosocial stress suppresses hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction, decreased sex steroidogenesis and lower fertility in reproductive-aged women. Many cancer survivors experience high psychosocial stress and hypothalamic-pituitary-adrenal axis dysregulation. The menstrual pattern disturbances and infertility they experience have been attributed to ovarian follicle destruction, but the contribution of psychosocial stress to these phenotypes is unknown. STUDY DESIGN, SIZE, DURATION: A cross-sectional study was conducted estimating the association between perceived stress, measured by self-report and saliva cortisol, and ovarian function, measured by bleeding pattern, dried blood spot (DBS) FSH and LH, and saliva estradiol. We included 377 AYA survivor participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: AYA survivor participants were ages 15-35 at cancer diagnosis and ages 18-40 at study enrollment, had completed primary cancer treatment, had a uterus and at least one ovary, did not have uncontrolled endocrinopathy and were not on hormone therapy. Recruited from cancer registries, physician referrals and cancer advocacy groups, participants provided self-reported information on psychosocial stress (Perceived Stress Scale-10 (PSS-10)) and on cancer and reproductive (fertility, contraception, menstrual pattern) characteristics. DBS samples were collected timed to the early follicular phase (cycle Days 3-7) for menstruating individuals and on a random day for amenorrheic individuals; saliva samples were collected three time points within 1 day. FSH and LH were measured by DBS ELISAs, cortisol was measured by ELISA and estradiol was measured by liquid chromatography tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: The median age of participants was 34.0 years (range 19-41) at a median of 6.0 years since cancer diagnosis. The most common cancer was breast (32.1%). Median PSS-10 score was 15 (range 0-36), with 5.3% scoring ≥26, the cut point suggestive of severe stress. Cortisol levels followed a diurnal pattern and cortisol AUC was negatively correlated with PSS-10 scores (P = 0.03). Neither PSS-10 scores nor cortisol AUC were associated with FSH, LH, estradiol levels or menstrual pattern. Waking and evening cortisol and the cortisol awakening response also were not related to ovarian function measures. LIMITATIONS, REASONS FOR CAUTION: Our analysis is limited by its cross-sectional nature, heterogeneity of cancer diagnosis and treatments and low prevalence of severe stress. WIDER IMPLICATIONS OF THE FINDINGS: The lack of association between psychosocial stress and a variety of ovarian function measures in female AYA cancer survivors suggests that psychosocial stress does not have a significant impact on the reproductive axis of AYA survivors. This finding is important in counseling this population on their menstrual pattern and family building plans. STUDY FUNDING/COMPETING INTEREST(S): NIH HD080952, South Korea Health Industry Development Institute HI18C1837 (JK). Dr A.D. works for Bluebird Bio, Inc., Dr D.Z. works for ZRT Labs and Dr P.M.S. works for Ansh Labs, which did not sponsor, support or have oversight of this research. Other authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Relationship between fatty infiltration and gene expression in patients with medium rotator cuff tear.

BACKGROUND: Fatty infiltration (FI) is a key prognostic factor that affects outcomes after rotator cuff repair and is radiologically evaluated using the Goutallier classification. The purpose of this study was to assess alterations in gene and protein expression according to the Goutallier classification in the supraspinatus muscle and any relationships among various gene expression profiles. METHODS: Twenty-four samples of the supraspinatus muscle from 12 patients with a high FI grade (grade 3 or 4) and 12 patients with a low FI grade (grade 1 or 2) with medium-sized tears were acquired during arthroscopic surgery. Alterations in the expression of genes and proteins associated with adipogenesis, fibrosis, inflammation, and muscle atrophy were compared between the high- and low-FI groups using reverse-transcription quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. RESULTS: mRNA expression of not only the adipogenic genes (peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α; P < .001 and P = .020) but also the fibrosis-related gene (α-smooth muscle actin; P < .001), inflammation-related genes (interleukin [IL]-1ß and tumor necrosis factor α; P = .041 and P = .039), and muscle atrophy-related genes (atrogin 1 and myostatin; P = .006 and P < .001) was higher in the high-FI group compared with that in the low-FI group. In addition, adipogenic gene expression was significantly correlated with the expression of other categories of genes (all P < .05, except atrogin 1). A correlation of gene and protein expression was observed for IL-1ß (P = .027) and myostatin (P = .029). CONCLUSIONS: The radiologic grading of FI was associated with the expression of various genes, including adipogenic, fibrotic, inflammatory, and atrophy-related genes, and these genes were closely correlated with each other in terms of expression. This information could be helpful in patient counseling.

Atrogin1-induced loss of aquaporin 4 in myocytes leads to skeletal muscle atrophy.

The water channel aquaporin 4 (AQP4) regulates the flux of water across the cell membrane, maintaining cellular homeostasis. Since AQP4 is enriched in the sarcolemma of skeletal muscle, a functional defect in AQP4 may cause skeletal muscle dysfunction. To investigate a novel mechanism underlying skeletal muscle atrophy, we examined AQP4 expression and its regulation in muscle using the rotator cuff tear (RCT) model. Human and mouse AQP4 expression was significantly decreased in atrophied muscle resulting from RCT. The size and the number of myotubes were reduced following AQP4 knockdown. Atrogin 1-mediated ubiquitination of AQP4 was verified with an ubiquitination assay after immunoprecipitation of AQP4 with an anti-AQP4 antibody. In this study, we identified high mobility group box 1 (HMGB1) as a potent upstream regulator of atrogin 1 expression. Atrogin 1 expression was increased by recombinant mouse HMGB1 protein, and the HMGB1-induced atrogin 1 expression was mediated via NF-κB signaling. Our study suggests that loss of AQP4 appears to be involved in myocyte shrinkage after RCT, and its degradation is mediated by atrogin 1-dependent ubiquitination. HMGB1, in its function as a signaling molecule upstream of the ubiquitin ligase atrogin 1, was found to be a novel regulator of muscle atrophy.

Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities.

The prognostic and therapeutic relevance of molecular subtypes for the most aggressive isocitrate dehydrogenase 1/2 (IDH) wild-type glioblastoma (GBM) is currently limited due to high molecular heterogeneity of the tumors that impedes patient stratification. Here, we describe a distinct binary classification of IDH wild-type GBM tumors derived from a quantitative proteomic analysis of 39 IDH wild-type GBMs as well as IDH mutant and low-grade glioma controls. Specifically, GBM proteomic cluster 1 (GPC1) tumors exhibit Warburg-like features, neural stem-cell markers, immune checkpoint ligands, and a poor prognostic biomarker, FKBP prolyl isomerase 9 (FKBP9). Meanwhile, GPC2 tumors show elevated oxidative phosphorylation-related proteins, differentiated oligodendrocyte and astrocyte markers, and a favorable prognostic biomarker, phosphoglycerate dehydrogenase (PHGDH). Integrating these proteomic features with the pharmacological profiles of matched patient-derived cells (PDCs) reveals that the mTORC1/2 dual inhibitor AZD2014 is cytotoxic to the poor prognostic PDCs. Our analyses will guide GBM prognosis and precision treatment strategies.

Molecular analysis of lipid uptake- and necroptosis-associated factor expression in vitrified-warmed mouse oocytes.

BACKGROUND: We had previously demonstrated that vitrification reduces the levels of certain phospholipid classes, and that oocytes from aged mice show a similar lipidome alteration, even without vitrification. In the current investigation, we examined if vitrification-warming of mouse oocytes from young and aged mice causes any changes in molecular aspects of lipid-associated features. METHODS: Metaphase II (MII) stage oocytes were harvested from young (10-14-week-old) and aged (45-54-week-old) mice by a superovulation regime with PMSG followed by hCG. We examined the status of the intracellular lipid pool and the integrity of the plasma membrane by staining oocytes with BODIPY 500/510 and CellMask live dyes. Expression of lipid uptake- and necroptosis-associated genes was assessed by quantitative PCR analyses, in oocytes from young and old mice, before and after vitrification. Localization patterns of two crucial necroptosis proteins, phosphorylated MLKL (pMLKL) and phosphorylated RIPK1 (pRIPK1) were examined in mouse oocytes by immunofluorescence staining. Necrostain-1 (Nec1), an inhibitor of RIPK1, was used to examine if RIPK1 activity is required to maintain oocyte quality during vitrification. RESULTS: We confirmed that vitrified-warmed oocytes from aged mice showed noticeable decrease in both CellMask and BODIPY 500/510 dyes. Among the lipid uptake-associated genes, Cd36 expression was higher in oocytes from aged mice. Necroptosis is a type of programmed cell death that involves damage to the plasma membrane, eventually resulting in cell rupture. The expression of necroptosis-associated genes did not significantly differ among groups. We observed that localization patterns of pMLKL and pRIPK1 were unique in mouse oocytes, showing association with microtubule organizing centers (MTOCs) and spindle poles. pMLKL was also localized on kinetochores of MII chromosomes. Oocytes treated with Nec1 during vitrification showed a decreased survival rate, indicating the importance of RIPK1 activity in oocyte vitrification. CONCLUSIONS: We report that oocytes from aged mice show differential expression of CD36, which suggests that CD36-mediated lipid uptake may be influenced by age. We also show for the first time that pMLKL and pRIPK1 exhibit unique localization pattern in mouse oocytes and this may suggest role(s) for these factors in non-necroptosis-associated cellular processes.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology.

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

Association between in vitro fertilization success rate and ambient air pollution: a possible explanation of within-year variation of in vitro fertilization success rate.

OBJECTIVE: To evaluate patterns in air pollution concentrations and in vitro fertilization (IVF) success rates using data from a large, long-term clinical database. METHODS: We conducted a retrospective cohort study investigating South Korean women who pursued IVF and embryo transfer (IVF-ET) between 2011 and 2017. Hourly concentrations of air pollutants measured at 318 air quality monitoring sites in South Korea between 2011 and 2017 were obtained from the National Institute of Environmental Research. Monthly trends in pregnancy rates and concentrations of air pollutants were assessed. RESULTS: A total of 34,427 IVF-ET cycles in 18,478 patients were analyzed. The mean age of women at the time of IVF-ET was 36.6 years. The clinical pregnancy rate in the IVF-ET cycle was 30%. Analysis of pregnancy failure rates by month showed that IVF-ET failure rates tended to be higher in March and April and lower in July and August. Concentrations of air pollutants including particulate matter (PM) less than 10 µm in diameter, PM less than 2.5 µm in diameter, sulfur dioxide, nitrogen dioxide, and carbon monoxide were highest in March and April and lowest between July and September. CONCLUSION: Within-year variations were similar between IVF-ET failure rates and air pollution concentrations based on analysis of a large, long-term database. Specifically, IVF-ET success rates were highest when PM concentrations were lowest. Further studies are warranted to examine the mechanisms accounting for the association between IVF success and air pollutant exposure.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology.

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

Influence of Smoking on the Expression of Genes and Proteins Related to Fat Infiltration, Inflammation, and Fibrosis in the Rotator Cuff Muscles of Patients With Chronic Rotator Cuff Tears: A Pilot Study.

PURPOSE: To evaluate the altered gene and protein expression patterns in the rotator cuff muscles of smokers and non-smokers with rotator cuff tears and to identify the smoking-associated key genetic factor(s) involved in rotator cuff muscle physiology. METHODS: Twenty-four samples of rotator cuff muscle from 12 current heavy smokers (mean age 61.8 ± 5.1 years) and age- and sex-matched 12 non-smokers (mean age 61.8 ± 6.9 years) with medium-sized tears were acquired during arthroscopic surgery. As a statistical method, the propensity score matching technique was used to select control group by 1:1 matching for age and sex. Inclusion criteria were patients who underwent arthroscopic repair for medium-sized full-thickness rotator cuff tears and those that were current smokers with a smoking history >20 packs/year. Patients lacking medium-sized tears, those with recent steroid injection history, isolated subscapularis tear, preoperative stiff shoulder, acute traumatic tear, or previous surgery on the same shoulder, or those that declined to participate were excluded. Alterations in the expression of genes and proteins associated with myogenesis, inflammation, adipogenesis, and muscle fibrosis were compared between smokers and non-smokers with reverse-transcription quantitative polymerase chain reaction, western blotting, and immunohistochemistry. RESULTS: Histologic analysis revealed increased inflammation and remarkable fat accumulation and fibrogenesis in the rotator cuff muscle from smokers compared with that from non-smokers. The mRNA expression levels of inflammatory high mobility group box 1 (HMGB1; P = .043), adipogenic CCAAT/enhancer-binding protein alpha (P = .046) and peroxisome proliferator-activated receptor gamma (PPARγ; P = .048), myogenic differentiation 1 (P = .032), fibrogenic alpha-smooth muscle actin (α-SMA; P = .033), and metalloproteinase 9 (P = .036) were significantly greater in samples from smokers than from non-smokers. A correlation was observed between gene and protein expression of HMGB1 (P = .034), PPARγ (P = .021), and α-SMA (P = .021). CONCLUSIONS: Smokers with rotator cuff tears showed high inflammation, large fat infiltration, and fibrosis in rotator cuff muscle that is associated with the increased expression of HMGB1, PPARγ, and α-SMA, respectively. LEVEL OF EVIDENCE: Case control study (Prognostic level III).

Effect of Fatty Acid-Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis.

BACKGROUND: A rotator cuff tear (RCT) induces fatty acid-binding protein 4 (FABP4) expression, resulting in ectopic fat accumulation in the rotator cuff muscle. PURPOSE: To evaluate whether FABP4 inhibition reduces fatty infiltration and improves muscle physiology after RCT in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Human supraspinatus muscle and deltoid muscle tissues were acquired from patients with RCTs during arthroscopic surgery, and FABP4 expression in the supraspinatus muscle was evaluated as compared with the intact deltoid muscle. A rat RCT model was established by detaching the supraspinatus tendon, after which a specific FABP4 inhibitor was locally injected into the supraspinatus muscle 4 times at 3-day intervals starting 2 weeks after the surgery. Body weight and blood glucose levels were measured at 2 and 4 weeks after the RCT, and the mRNA and protein expressions of various target molecules (including FABP4), histological changes, and biomechanical tensile strength were assessed in the supraspinatus muscles at 4 weeks after the RCT. RESULTS: The expression of human FABP4 was significantly increased in the torn rotator cuff muscle as compared with the intact deltoid muscle. In the rat model, the mRNA and protein expressions of FABP4 and HIF1α were significantly increased by the RCT as compared with the control. The FABP4 inhibitor treatment significantly decreased FABP4 expression when compared with the vehicle treatment; however, HIF1α expression was not significantly decreased versus the vehicle treatment. Histologically, RCT induced noticeable muscle fatty infiltration, which was remarkably reduced by the local injection of the FABP4 inhibitor. Biomechanically, the tensile strength of the rotator cuff muscle after the RCT was significantly improved by the FABP4 inhibitor in terms of load to failure and total energy to failure. CONCLUSION: RCT induces FABP4 expression in human and rat rotator cuff muscles. The FABP4 inhibitor drastically decreased the histological fatty infiltration caused by RCT and improved the tensile strength of the rotator cuff muscle. CLINICAL RELEVANCE: FABP4 inhibitor may have a beneficial effect on the muscle quality after RCT.

Obstetrical, neonatal, and long-term outcomes of children conceived from in vitro matured oocytes.

OBJECTIVE: To investigate the obstetrical, neonatal, and long-term outcomes of in vitro maturation (IVM) compared with conventional in vitro fertilization (IVF) in women with polycystic ovarian syndrome (PCOS). DESIGN: Matched retrospective case-control study. SETTING: University fertility clinic. PATIENT(S): One hundred eighty-four patients undergoing IVM were compared with 366 patients undergoing conventional IVF. All had PCOS and were matched for patient age, gestational age at birth, and the number of fetuses. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Obstetrics, neonatal outcomes, and childhood medical problems and development. RESULT(S): Women's mean age at oocytes retrieval was 32.6 ± 2.9 years. Children's mean age was 7.5 ± 2.3 years. There were no differences in the frequency of obstetrical and neonatal outcomes between the two groups. No difference was found in birth weights between the two groups. The incidence of congenital anomalies was similar between the groups (4.3% in IVM group vs. 4.1% in IVF group). No significant difference was observed between the two groups in the frequency and duration of hospitalization during childhood. Growth developmental status of both groups was within normal range. CONCLUSION(S): In a matched setting between IVM and IVF babies born from women with PCOS, no significant increased risk associated with IVM was been identified after a mean follow-up of 7.5 years.

Correlation between Morphologic Grading and Euploidy Rates of Blastocysts, and Clinical Outcomes in In Vitro Fertilization Preimplantation Genetic Screening.

BACKGROUND: The standard morphological evaluation has been widely used for embryo selection, but it has limitations. This study aimed to investigate the correlation between morphologic grading and euploidy rate of in vitro fertilization (IVF) preimplantation genetic screening (PGS) and compare the pregnancy rates in young and old ages. METHODS: This is a retrospective study using the medical records of patients who underwent IVF procedures with PGS between January 2016 and February 2017 in a single center. The embryo grades were categorized into 4 groups: excellent, good, fair, and poor. Basic characteristics, euploidy rates, clinical pregnancy (CP) rates and ongoing pregnancy rates were analyzed. RESULTS: The excellent group had significantly higher rate of euploid embryos than fair group (47.82% vs. 29.33%; P = 0.023) and poor group (47.82% vs. 29.60%; P = 0.005). When the four groups were recategorized into two groups (excellent and good vs. fair and poor), they also showed significant difference in euploidy rates (44.52% vs. 29.53%; P = 0.002). When the patients were divided into two groups by age 35, the CP rates for those under and over 35 years old were 44.74% and 47.83%, respectively, which showed no significant difference. CONCLUSION: The significant differences among the euploidy rates of different morphologic embryo grades demonstrated the positive correlations between the morphologic grading of the embryo and the euploidy rate of PGS. Additionally, there was no significant difference between the younger and older patients' CP rates. These findings emphasize the fact that old age patients might benefit from PGS whatever the indication of PGS is.

Changes in Perianchor Cyst Formation Over Time After Rotator Cuff Repair: Influential Factors and Outcomes.

BACKGROUND: There is a lack of knowledge about the changes in perianchor cysts over time and the factors related to perianchor cysts. PURPOSE: To evaluate the changes in perianchor cyst formation and anchor absorption over time after arthroscopic rotator cuff repair with a biocomposite suture anchor and to evaluate the factors affecting perianchor cyst persistence and their relationship with patient outcomes. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Forty consecutive patients (mean age, 61.10 ± 5.79 years) who underwent arthroscopic repair for medium- to large-sized rotator cuff tears using a single type of biocomposite (poly-L-lactic acid/polyglycolic acid-beta tricalcium phosphate) medial-row anchor were prospectively enrolled. Postoperative magnetic resonance imaging (MRI) at 2 different time points (6 and 18 months) was performed, and perianchor cyst formation, anchor absorption, and healing failures were evaluated using postoperative MRI. Demographic and clinical data were collected, and functional outcomes at a minimum of 18 months after surgery were assessed. RESULTS: Perianchor cysts were observed in 24 patients (60.0% total; grade 1: 35.0%; grade 2: 10.0%; grade 3: 7.5%; grade 4: 7.5%) at 6 months, and 7 patients (18.4% total; grade 1: 7.9%; grade 2: 5.3%; grade 3: 2.6%; grade 4: 2.6%) had a persistent perianchor cyst at 18 months after surgery. No anchors were absorbed at 6 months, but 73.7% of patients revealed complete or near-full absorption at 18 months. Patients with persistent perianchor cysts showed a significantly larger tear size in the anteroposterior dimension ( P = .002) and greater retraction ( P < .001). There were no differences in healing failures and functional outcomes between patients with and without persisting perianchor cysts (all P > .05). No differences were found in perianchor cyst formation and anchor absorption between anchors inserted in the greater tuberosity and the lesser tuberosity (all P > .05). CONCLUSION: The incidence and severity of perianchor cysts decreased with time, and most biocomposite suture anchors were absorbed at 18 months after surgery. Persisting perianchor cysts correlated with a larger tear size in the anteroposterior dimension and greater retraction.

Improvement in Light Extraction Efficiency of InGaN/GaN Blue Light Emitting Diodes Using Sidewall Texturing.

Herein, we reported the effects of the geometric morphology of the sidewall on the extraction efficiency of GaN-based light-emitting diodes (LEDs). We performed numerical analysis based on the ray-tracing method. We found that the extraction efficiency of the LEDs increased with the texturing of the sidewall. The light output intensity of the LEDs (at an injection current of 100 mA) increased by 13.8% after sidewall texturing. These results confirmed that the geometric morphology of the sidewall plays an important role in improving the extraction efficiency of LEDs.