Analysis of editor in chief gender and associated journal variables among 126 pathology journals.

OBJECTIVES: Gender equity studies have shown that women are underrepresented in journal editor in chief positions, which confer major professional opportunities and influence. We sought to systematically investigate editor in chief gender and journal attributes within pathology. METHODS: We constructed a journal data set using the Scimago Journal & Country Rank and Clarivate Journal Citation Reports databases. We also included official journals of the major medical societies for the 12 pathology subspecialties recognized by the Association of American Medical Colleges. The final data set included 126 journals. We obtained editor in chief gender, impact factor, publication model (ie, hybrid access vs open access), year of founding, and geographic location for all included pathology journals. RESULTS: Women made up only 18% of the 141 total editor in chief positions. This inequity was present irrespective of all pathology journal variables studied. Among 10 journals with 2 editor in chief positions, 5 had only men and 5 had 1 man and 1 woman. All 3 journals with 3 editor in chief positions had 2 men and 1 woman. CONCLUSIONS: Women are significantly underrepresented among editor in chiefs across pathology journals. Journals and affiliated members should advocate for diversity among these influential positions, given their impact on research, science, and medicine.

Breastfeeding following bariatric surgery among obese women with and without diabetes mellitus.

BACKGROUND: Information on exclusive breastfeeding (BF) and BF initiation following bariatric surgery (BS) among obese women with diabetes mellitus (DM) and without DM (non-DM) is limited. METHODS: Retrospective cohort study. Obesity was defined by BMI (kg/m2) as grade 1 (30-34.9), grade 2 (35-39.9) or grade 3 (≥40). The 65 women in the DM group (40 women with gestational, 19 with Type 2 and 6 with Type 1) was similar to 84 with non-DM in BS type: Roux-en-Y (51 vs 55%), sleeve gastrectomy (32 vs 35%), laparoscopic gastric banding (17 vs 7%) and gastro-duodenal anastomosis (0 vs 4%). RESULTS: Women with DM were older (35 vs 33y), of advanced age (54 vs 27%), with higher prevalence of grade 3 obesity (66 vs 46%), chronic hypertension (31 vs 10%), delivery of late-preterm infants (23 vs 10%) and neonatal hypoglycemia (25 vs 12%). Although infant feeding intention was similar: BF (66 vs 79%), partial BF (9 vs 7%) or formula (25 vs 14%), at discharge women with DM had lower exclusive BF (29 vs 41%) and BF initiation rates (68 vs 76%) than those with non-DM. Women with grade 3 obesity (52% were DM) differed from those with grades 1-2 (34% were DM) in exclusive BF (27 vs 52%), and BF initiation rates (66 vs 86%). CONCLUSION: After BS, women with DM, especially those with grade 3 obesity, had higher rates of chronic hypertension and preeclampsia and lower rates of exclusive BF and BF initiation than those who had DM but had less severe obesity.

Histones direct site-specific CRISPR spacer acquisition in model archaeon.

CRISPR-Cas systems provide heritable immunity against viruses and other mobile genetic elements by incorporating fragments of invader DNA into the host CRISPR array as spacers. Integration of new spacers is localized to the 5' end of the array, and in certain Gram-negative Bacteria this polarized localization is accomplished by the integration host factor. For most other Bacteria and Archaea, the mechanism for 5' end localization is unknown. Here we show that archaeal histones play a key role in directing integration of CRISPR spacers. In Pyrococcus furiosus, deletion of either histone A or B impairs integration. In vitro, purified histones are sufficient to direct integration to the 5' end of the CRISPR array. Archaeal histone tetramers and bacterial integration host factor induce similar U-turn bends in bound DNA. These findings indicate a co-evolution of CRISPR arrays with chromosomal DNA binding proteins and a widespread role for binding and bending of DNA to facilitate accurate spacer integration.

Quantifying antimicrobial use on Canadian dairy farms using garbage can audits.

Antimicrobial resistance in pathogenic bacteria is one of the preeminent concerns for the future of global health. There is a dose-dependent relationship between antimicrobial use (AMU) and the prevalence of antimicrobial-resistant pathogens. As most AMU in Canada is related to animal agriculture, there is a need to reduce overall AMU, which could be accomplished through surveillance of AMU in animal agriculture, including the dairy industry. The objective of this study was to quantify AMU on dairy farms across Canada. This study had two parts: a description of data collected in 2019-2020, and a meta-analysis comparing this data to previous estimates of AMU in the Canadian dairy industry. The first included a garbage can audit (GCA) on 107 farms in four Canadian provinces (British Columbia, Alberta, Ontario, and Nova Scotia) in 2020; AMU data were converted to the dose-based metrics of defined course doses (DCD) and defined daily doses (DDD). Mixed-effect linear models were fit to determine the relationship between province and use of different classes of antimicrobials. On average, for every 100 animals on the farm, 117 DCD of antimicrobials were administered per year (IQR: 55, 158). These treatments amounted to 623 DDD / 100 animal-yr (IQR: 302, 677 DDD/100 animal-years). Penicillins were the most used class of antimicrobials, followed by first-and third-generation cephalosporins. Farms in Ontario used more third-generation cephalosporins than other provinces. The second part of this study compared AMU in 2020 to previously reported Canadian studies through a meta-analysis. A GCA was conducted in 2007-2008 in Alberta, Ontario, Québec, and the Maritime provinces (Prince Edward Island, New Brunswick and Nova Scotia); another GCA was conducted in Québec in 2018. Overall, AMU was lower in 2018-2020 than in 2007-2008, with the exception of third-generation cephalosporin use, which increased.

Comparison of Patient-Reported Outcomes With or Without Prophylactic Carpal Tunnel Release After Distal Radius Fracture Stabilization.

Distal radius fractures (DRFs) are frequently complicated by acute carpal tunnel syndrome (CTS), which, if unrecognized, can cause permanent median neuropathy. Some surgeons recommend "prophylactic" carpal tunnel release (CTR) during open reduction and internal fixation (ORIF) of DRF. Patient-reported outcomes (PROs) and safety data regarding prophylactic vs symptomatic CTR strategies during DRF fixation are lacking. We conducted a retrospective review of two management strategies for DRFs at our institution (2017 to 2019). Group 1 consisted of patients operated on by two surgeons performing ORIF and symptomatic CTR only for acute CTS. Group 2 consisted of patients operated on by a third surgeon performing ORIF and prophylactic CTR on all patients irrespective of median nerve symptoms. The PROs included QuickDASH Wrist and PROMIS physical/mental health preoperatively vs at final follow-up. Demographic information, complications, and return to the operating room were recorded. Group 1 (36 patients) and group 2 (76 patients) were demographically similar. The mechanism of injury was more severe in group 1 (P<.05), but preoperative PROs were similar between the two groups. Eight patients (22.2%) in group 1 had symptomatic CTR for acute CTS. Significant improvement occurred within both groups from preoperative to final follow-up for PROMIS physical function and QuickDASH Wrist scores (P<.05). Intergroup PROs were not significantly different at either time point. One patient in group 1 (2.8%) and 2 patients in group 2 (2.6%) returned to the operating room due to median nerve symptoms (P>.05). A prophylactic CTR strategy is not associated with improved PROs compared with a symptomatic strategy during ORIF of DRF. [Orthopedics. 2023;46(6):e362-e368.].

Should We Hire Our Current Fellow? Hiring Trends and Preferences in Spine Surgery.

OBJECTIVE: To provide insight into hiring trends/preferences in Academic Orthopaedic Spine Surgery after fellowship training. METHODS: Fellowship directors (FDs) listed by the North American Spine Society were surveyed regarding new faculty hiring preferences. Surveys were analyzed/stratified by response using the Kruskal-Wallis with Dunn multiple comparisons test, the Fisher exact test, and the Mann-Whitney U test for univariate comparisons. RESULTS: Thirty-two of 52 (61.5%) FDs responded. 32.3% of graduated fellows pursued academic medicine, which was preferred by FDs (3.59 ± 0.67; 1 to 5 scale). From 2015 to 2020, of the 2.25 ± 1.46 faculty members hired per program, 45.8% were former residents/fellows. Top listed hiring qualities were "strong recommendation from a trusted colleague" (84.4%), "prior personal experience, as a resident/fellow" (78.1%), and "amicable personality" (53.1%). Twelve (38%) answered "no", six (19%) "yes", and 14 (44%) "other", regarding if hiring former residents/fellows benefits the field of spine surgery. "Other" answers endorsing in-house hiring most commonly mentioned consistency/stability (28.6%) while those opposed most commonly mentioned lack of diversity of training/novel techniques (42.9%). When considering programmatic size, while the stated perception of FDs regarding in-house hiring at larger (>2 fellows) versus smaller (1 to 2 fellows) programs was equivalent, the mean percentage of in-house hires at larger programs (67.8% ± 35.8%) was significantly greater than that of smaller programs (33.3% ± 44.8%, P = 0.04). CONCLUSIONS: In-house hiring in spine surgery appears to occur more commonly than perceived by program leadership, particularly at larger fellowship programs. Further study of hiring preferences and their impact on the field of spine surgery is warranted. STUDY DESIGN: Prospective Survey Study.

Ultrasound Measurements of the Median Nerve at the Distal Wrist Crease Correlate With Electrodiagnostic Studies.

Background: Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy and is commonly evaluated using electrodiagnostic studies (EDSs). Ultrasound (US) has emerged as a potentially easier and more comfortable alternative to EDSs. The purpose of this study is to evaluate whether measurements of the cross-sectional area (CSA) of the median nerve via US correlate with the severity rating of CTS based on EDSs. Methods: A retrospective review of patients aged 18 years or older who underwent US and EDSs of the median nerve for CTS was performed. Sensory nerve action potential, distal motor latency, and compound muscle action potential were measured, and severity was graded on American Association of Neuromuscular and Electrodiagnostic Medicine guidelines. Cross-sectional area of the median nerve was measured via US at the wrist crease. Results: There was a significant association between increasing CSA and increasing EDS severity (P < .0001). The mean CSA for normal, mild, moderate, and severe CTS was 7.48 ± 2.00, 10.36 ± 2.53, 12.01 ± 3.64, and 14.34 ± 4.77 mm2, respectively. The area under the curve demonstrated the ability of median nerve CSA to discriminate between normal and abnormal EDSs with an optimal cutoff CSA of ≥10 mm2, as well as, the ability to discriminate between mild CTS and moderate to severe CTS at a cutoff CSA of greater than or equal to 12 mm2. Conclusions: The results of this study show that US measurements of the median nerve at the distal wrist crease discriminate between normal and abnormal EDSs, and between mild CTS and moderate to severe CTS.

Hyper-stimulation of Pyrococcus furiosus CRISPR DNA uptake by a self-transmissible plasmid.

Pyrococcus furiosus is a hyperthermophilic archaeon with three effector CRISPR complexes (types I-A, I-B, and III-B) that each employ crRNAs derived from seven CRISPR arrays. Here, we investigate the CRISPR adaptation response to a newly discovered and self-transmissible plasmid, pT33.3. Transconjugant strains of Pyrococcus furiosus exhibited dramatically elevated levels of new spacer integration at CRISPR loci relative to the strain harboring a commonly employed, laboratory-constructed plasmid. High-throughput sequence analysis demonstrated that the vast majority of the newly acquired spacers were preferentially selected from DNA surrounding a particular region of the pT33.3 plasmid and exhibited a bi-directional pattern of strand bias that is a hallmark of primed adaptation by type I systems. We observed that one of the CRISPR arrays of our Pyrococcus furiosus laboratory strain encodes a spacer that closely matches the region of the conjugative plasmid that is targeted for adaptation. The hyper-adaptation phenotype was found to strictly depend both on the presence of this single matching spacer as well as the I-B effector complex, known to mediate primed adaptation. Our results indicate that Pyrococcus furiosus naturally encountered this conjugative plasmid or a related mobile genetic element in the past and responds to reinfection with robust primed adaptation.

Prediction of large-for-gestational-age infant by fetal growth charts and hemoglobin A1c level in pregnancy complicated by pregestational diabetes.

OBJECTIVES: To compare the ability of three fetal growth charts (Fetal Medicine Foundation (FMF), Hadlock and National Institutes of Child Health and Human Development (NICHD) race/ethnicity-specific) to predict large-for-gestational age (LGA) at birth in pregnant individuals with pregestational diabetes, and to determine whether inclusion of hemoglobin A1c (HbA1c) level improves the predictive performance of the growth charts. METHODS: This was a retrospective analysis of individuals with Type-1 or Type-2 diabetes with a singleton pregnancy that resulted in a non-anomalous live birth. Fetal biometry was performed between 28 + 0 and 36 + 6 weeks of gestation. The primary exposure was suspected LGA, defined as estimated fetal weight ≥ 90th percentile using the Hadlock (Formula C), FMF and NICHD growth charts. The primary outcome was LGA at birth, defined as birth weight ≥ 90th percentile, using 2017 USA natality reference data. The performance of the three growth charts to predict LGA at birth, alone and in combination with HbA1c as a continuous measure, was assessed using the area under the receiver-operating-characteristics curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Of 358 assessed pregnant individuals with pregestational diabetes (34% with Type 1 and 66% with Type 2), 147 (41%) had a LGA infant at birth. Suspected LGA was identified in 123 (34.4%) by the Hadlock, 152 (42.5%) by the FMF and 152 (42.5%) by the NICHD growth chart. The FMF growth chart had the highest sensitivity (77% vs 69% (NICHD) vs 63% (Hadlock)) and the Hadlock growth chart had the highest specificity (86% vs 76% (NICHD) and 82% (FMF)) for predicting LGA at birth. The FMF growth chart had a significantly higher AUC (0.79 (95% CI, 0.74-0.84)) for LGA at birth compared with the NICHD (AUC, 0.72 (95% CI, 0.68-0.77); P < 0.001) and Hadlock (AUC, 0.75 (95% CI, 0.70-0.79); P < 0.01) growth charts. Prediction of LGA improved for all three growth charts with the inclusion of HbA1c measurement in comparison to each growth chart alone (P < 0.001 for all); the FMF growth chart remained more predictive of LGA at birth (AUC, 0.85 (95% CI, 0.81-0.90)) compared with the NICHD (AUC, 0.79 (95% CI, 0.73-0.84)) and Hadlock (AUC, 0.81 (95% CI, 0.76-0.86)) growth charts. CONCLUSIONS: The FMF fetal growth chart had the best predictive performance for LGA at birth in comparison with the Hadlock and NICHD race/ethnicity-specific growth charts in pregnant individuals with pregestational diabetes. Inclusion of HbA1c improved further the prediction of LGA for all three charts. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3 (Id3) gene therapy in rabbit eyes in vivo.

Previously we found that inhibitor of differentiation 3 (Id3) gene, a transcriptional repressor, efficiently inhibits corneal keratocyte differentiation to myofibroblasts in vitro. This study evaluated the potential of adeno-associated virus 5 (AAV5)-mediated Id3 gene therapy to treat corneal scarring using an established rabbit in vivo disease model. Corneal scarring/fibrosis in rabbit eyes was induced by alkali trauma, and 24 h thereafter corneas were administered with either balanced salt solution AAV5-naked vector, or AAV5-Id3 vector (n = 6/group) via an optimized reported method. Therapeutic effects of AAV5-Id3 gene therapy on corneal pathology and ocular health were evaluated with clinical, histological, and molecular techniques. Localized AAV5-Id3 gene therapy significantly inhibited corneal fibrosis/haze clinically from 2.7 to 0.7 on the Fantes scale in live animals (AAV5-naked versus AAV5-Id3; p < 0.001). Furthermore, AAV5-Id3 treatment significantly reduced profibrotic gene mRNA levels: α-smooth muscle actin (α-SMA) (2.8-fold; p < 0.001), fibronectin (3.2-fold; p < 0.001), collagen I (0.8-fold; p < 0.001), and collagen III (1.4-fold; p < 0.001), as well as protein levels of α-SMA (23.8%; p < 0.001) and collagens (1.8-fold; p < 0.001). The anti-fibrotic activity of AAV5-Id3 is attributed to reduced myofibroblast formation by disrupting the binding of E-box proteins to the promoter of α-SMA, a transforming growth factor-ß signaling downstream target gene. In conclusion, these results indicate that localized AAV5-Id3 delivery in stroma caused no clinically relevant ocular symptoms or corneal cellular toxicity in the rabbit eyes.

Factors Impacting Recurrence Rate After Open Ganglion Cyst Excision.

Background: The recurrence rate after open excision of ganglion cysts is approximately 20%. However, this literature is based on a small series of subjects. This study aims to determine the rate and risk of recurrence after open excision of ganglion cysts in a large patient series. Methods: This study included 628 patients who had ganglion cyst excision from 2010 to 2018. A retrospective chart review recorded the following: age, sex, laterality, volar/dorsal location, and recurrence. An overall recurrence rate was calculated. In addition, a 1-way analysis of variance test was used to compare recurrence rates among the individual surgeons, and unpaired t tests were used to compare age of recurrence, dorsal cyst recurrence, laterality of cyst, and recurrence based on sex. Finally, a comparison of recurrence rate over time was conducted for surgeon 3. Results: The overall recurrence rate was 3.8% (24 of 628). The recurrence rates for each surgeon were 3% (9 of 353), 2% (3 of 167), and 11% (12 of 107), P = .02. The age of those with and without a recurrence did not differ (32 years vs 38 years), P = .06. The recurrence rate of dorsal ganglion cysts was 4.1% (14 of 341) compared with 3.5% (10 of 286) for volar ganglion cysts, P = .69. Male patients had a recurrence in 6.4% (13 of 204) of cases compared with 2.6% (11 of 424) of female patients, P = 0.01. There was a decrease in the rate of recurrence from 42.9% to 5.3% over 5 years for surgeon 3. Conclusion: In our sample, male sex and surgeon experience were significant risk factors in ganglion cyst recurrence.

Breastfeeding initiation among women with chronic hypertension superimposed on pregestational diabetes mellitus.

OBJECTIVE: To compare breastfeeding (BF) initiation among 317 women with chronic hypertension (CHTN) and 106 women with CHTN superimposed on pregestational diabetes (CHTN-DM) who intended exclusive or partial BF. METHODS: Retrospective cohort study of women who delivered at≥34 weeks of gestation. At discharge, exclusive BF was defined by direct BF or BF complemented with expressed breast milk (EBM) while partial BF was defined by formula supplementation. RESULTS: CHTN and CHTN-DM groups were similar in prior BF experience (42 vs 52%), intention to BF exclusively (89 vs 79%) and intention to partially BF (11 vs 21%). Women in the CHTN group were younger (31 vs 33y), more likely primiparous (44 vs 27%), and delivered vaginally (59 vs 36%) at term (85 vs 75%). Women in the CHTN-DM group had higher repeat cesarean rates (32 vs 18%), preterm birth (25 vs 15%), neonatal hypoglycemia (42 vs 14%) and NICU admission (38 vs 16%). At discharge, exclusive BF rates among CHTN was higher (48 vs 19%), while rates of partial BF (34 vs 44%) and FF (18 vs 37%) were lower than in the CHTN-DM group. BF initiation (exclusive plus partial BF) occurred in 82%of CHTN and in 63% of CHTN-DM. CONCLUSION: Although intention to BF was similar, BF initiation rates were higher for the CHTN compared to the CHTN-DM group. Exclusive BF was low in the CHTN and even lower in the CHTN-DM group signaling the need for targeted interventions if BF initiation rates are to be improved.

Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study.

OBJECTIVE: To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines. DESING: Cross-sectional study. SETTING: US commercial insurance beneficiaries from Market-Scan (late 2015 to 2018). STUDY DESIGN: We included women with GDM, singleton gestations, 15-51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin. MAIN OUTCOMES: Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin. RESULTS: Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide. CONCLUSIONS: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed. TWEETABLE ABSTRACT: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.

Characterization of the microbiota and resistome of bulk tank milk samples from Prince Edward Island dairy farms.

Bulk tank milk (BTM) is regularly used for surveillance on dairy farms for disease conditions such as mastitis and Johne's disease. In this study, we used 16S rRNA sequencing and bait-capture enrichment to characterize the microbiota and resistome of BTM, and investigate potential differences between the cream or pellet fractions. A total of 12 BTM samples were taken from 12 Prince Edward Island dairy farms, in Atlantic Canada, in duplicates. The DNA was analyzed by high-throughput sequencing of the 16S rRNA gene and a suite of antimicrobial resistance (AMR) genes. Target-capture enrichment of AMR genes was conducted before shotgun sequencing. The bioinformatics pipelines QIIME 2 and AMR++ were used for microbiota and resistome analysis, respectively. Differences between microbiotae were evaluated qualitatively with nonmetric multidimensional scaling and quantitatively with permutational ANOVA of UniFrac distances. A total of 47 phyla were present across the BTM samples. Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the most abundant phyla. At the genus level, Corynebacterium, Acinetobacter, Lactobacillus, and Turicibacter were the most abundant. There was no significant difference in the Faith's phylogenetic diversity between the cream and pellet fraction. Faith's phylogenetic diversity differed marginally by stall type. There were 10,217 hits across 80 unique AMR genes, with tetracycline resistance being the most common class.

Long-Term Safety and Tolerability of BMP7 and HGF Gene Overexpression in Rabbit Cornea.

Purpose: Tissue-targeted localized BMP7+HGF genes delivered into the stroma via nanoparticle effectively treats corneal fibrosis and rehabilitates transparency in vivo without acute toxicity. This study evaluated the long-term safety and tolerability of BMP7+HGF nanomedicine for the eye in vivo. Methods: One eye each of 36 rabbits received balanced salt solution (group 1, naïve; n = 12), naked vector with polyethylenimine-conjugated gold nanoparticles (PEI2-GNP; group 2, naked-vector; n = 12), or BMP7+HGF genes with PEI2-GNP (group 3, BMP7+HGF; n = 12) via a topical delivery technique. Safety and tolerability measurements were performed by clinical biomicroscopy in live rabbits at predetermined time intervals up to 7 months. Corneal tissues were collected at 2 months and 7 months after treatment and subjected to histology, immunofluorescence, and quantitative real-time PCR analyses. Results: Clinical ophthalmic examinations and modified MacDonald-Shadduck scores showed no significant changes in corneal thickness (P = 0.3389), tear flow (P = 0.2121), intraocular pressure (P = 0.9958), epithelial abrasion, or ocular abnormality. Slit-lamp, stereo, confocal, and specular biomicroscopy showed no signs of blepharospasm chemosis, erythema, epiphora, abnormal ocular discharge, or changes in epithelium, stroma, and endothelium after BMP7+HGF therapy for up to 7 months, as compared with control groups. Throughout the 7-month period, no significant changes were recorded in endothelial density (P = 0.9581). Histological and molecular data were well corroborated with the subjective clinical analyses and showed no differences in the naïve, naked-vector, and BMP7+HGF groups. Conclusions: Localized BMP7+HGF therapy is a safe, tolerable, and innovative modality for the treatment of corneal fibrosis. Translational Relevance: Nanoparticle-mediated BMP7+HGF combination gene therapy has the potential to treat corneal fibrosis in vivo without short- or long-term toxicity.

Hsp90 inhibition protects the brain microvascular endothelium against oxidative stress.

The brain endothelium is an integral element of the blood-brain barrier (BBB). Dysfunction of this formation due to increased generation of reactive oxygen species (ROS) progresses the establishment of neurological disorders including stroke and traumatic brain injury. Heat shock protein 90 inhibitors are anti-inflammatory agents, and their activities are mediated, at least in part, by P53. This is a tumor suppressor protein which regulates the opposing activities of Rac1 and RhoA in the cellular cytoskeleton. In the present study we investigated the role of Hsp90 inhibitors in the H2O2-induced brain endothelium breakdown, by employing human cerebral microvascular endothelial cells (hCMEC/D3). Our findings suggest that H2O2 downregulates P53 by enhancing the P53 suppressor mouse double minute 2 homolog (MDM2), as well as by increasing the apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref1). The H2O2 - triggered violation of the brain endothelium barrier was reflected in measurements of transendothelial resistance, and the increased expression of the key cytoskeletal modulators cofilin and myosin light chain 2 (MLC2). Treatment of the hCMEC/D3 cells with Hsp90 inhibitors counteracted those events, and reduced the generation of the hydrogen peroxide - induced reactive oxygen species. Hence, our study suggests that Hsp90 inhibition supports the BBB integrity, and may represent a promising therapeutic approach for disorders associated with brain endothelium breakdown; including COVID-19.

Breastfeeding initiation among women with preeclampsia with and without severe features.

BACKGROUND: Timely delivery and magnesium sulfate (MgSO4) are mainstay in the treatment of preeclampsia with severe features (PWSF). Premature delivery, severity of illness and mother-infant separation may increase the risk for breastfeeding (BF) initiation failure. OBJECTIVE: To compare BF initiation among women with late-onset PWSF treated with MgSO4 to women with late-onset preeclampsia without severe features (WOSF) who did not receive MgSO4. METHODS: Retrospective study of 158 women with PWSF and 104 with WOSF who delivered at ≥34 weeks. Intention to BF, formula feed (FF) or partially BF was declared prenatally. At discharge, exclusive BF included direct BF or direct BF with expressed breast milk (EBM). RESULTS: PWSF and WOSF groups were similar in age, race, and obstetric history. PWSF and WSOF differed in primiparity (65 & 51%), late preterm births (73 vs 15%), admission to NICU (44 &17%) and mother (5 & 4d) and infant (6 & 3d) hospital stay. Both groups were similar in intention to BF (80 & 84%), to FF (16 & 13%) and to partially BF (5 & 5%). At discharge, exclusive BF (37 & 39%), partial BF (33 & 31%) and FF (30 & 30%) were similar. Exclusive BF in the PWSF group was 43% direct BF, 28% direct BF and EBM and 29% EBM alone whereas in the WOSF group exclusive BF was 93% direct BF and 7% direct BF and EBM. CONCLUSION: BF initiation rates for women with PWSF and WOSF were similar. EBM alone or with direct BF enabled infants in the PWSF group to exclusively BF at discharge.