Comparison of treatment outcomes of 360° intraoperative laser retinopexy and focal laser retinopexy with pars plans vitrectomy in patients with primary rhegmatogenous retinal detachment.

BACKGROUND: This study was to compare the outcomes of 360° intra-operative laser retinopexy (ILR) and focal laser retinopexy in treating patients with pars plans vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). To identify other potential risk factors for retinal re-detachment after primary PPV. METHODS: This was a retrospective cohort study. Three hundred and forty-four consecutive cases of primary rhegmatogenous retinal detachment treated with PPV were included between July 2013 and July 2018. Clinical characteristics and surgical outcomes were compared between focal laser retinopexy and additional 360° intra-operative laser retinopexy groups. Both univariate and multiple variable analysis were used to identify potential risk factors for retinal re-detachment. RESULTS: Median follow-up was 6.2 months (Q1, Q3:2.0, 17.2). As estimated with survival analysis, the 360º ILR group had the incidence of 9.74% and focal laser 19.54% at 6 months postoperatively. At 12 months postoperatively the difference was 10.78% vs. 25.21%. The difference in survival rates was significant (p = 0.0021). In multivariate Cox regression, the risk factors for retinal re-detachment were without additional 360° ILR, diabetes and macula off before the primary surgery (relatively OR = 0.456, 95%-CI [0.245-0.848], p < 0.05; OR = 2.301, 95% CI [1.130-4.687], p < 0.05; OR = 2.243, 95% CI [1.212-4.149], p < 0.05). CONCLUSION: Additional 360° ILR group had a significantly lower rate of retinal re-detachment when compared with focal laser retinopexy group. Our study also elucidated that diabetes and macular off before the primary surgery might also be the potential risk factors for higher rate of retinal re-detachment outcome. TRIAL REGISTRATION: This was a retrospective cohort study.

An HPA-1a-positive platelet-depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo-controlled, single-center, phase 1/2 proof-of-concept study.

BACKGROUND: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT. OBJECTIVES: To investigate whether a single dose of anti-HPA-1a (1000 IU) could markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA-1a-negative participants as compared with placebo. METHODS: This randomized, single-blind, placebo-controlled, single-center, phase 1/2 proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a- and HLA-A2-negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by platelet transfusion 1 week later. Primary endpoint was the half-life of transfused platelets in circulation after administration of RLYB211 or placebo, determined by flow cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo. RESULTS: Twelve participants were allocated to cohort 1 or 1B and randomized to receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment-emergent adverse events were possibly related to treatment, both in RLYB211-treated participants. No participants developed HPA-1a antibodies at 12 or 24 weeks. CONCLUSION: These data support the hypothesis that anti-HPA-1a could be used as prophylaxis in women at risk of having an FNAIT-affected pregnancy.

Establishment and Evaluation of an In Vitro System for Biophysical Stimulation of Human Osteoblasts.

While several studies investigated the effects of mechanical or electrical stimulation on osseointegration and bone fracture healing, little is known about the molecular and cellular impact of combined biophysical stimulation on peri-implant osseointegration. Therefore, we established an in vitro system, capable of applying shear stress and electric fields simultaneously. Capacitively coupled electric fields were used for electrical stimulation, while roughened Ti6Al4V bodies conducted harmonically oscillating micromotions on collagen scaffolds seeded with human osteoblasts. Different variations of single and combined stimulation were applied for three days, while samples loaded with Ti6Al4V bodies and untreated samples served as control. Metabolic activity, expression of osteogenic markers and bone remodeling markers were investigated. While combined stimulation showed no substantial benefit compared to sole mechanical stimulation, we observed that 25 µm micromotions applied by roughened Ti6Al4V bodies led to a significant increase in gene expression of osteocalcin and tissue inhibitor of metalloprotease 1. Additionally, we found an increase in metabolic activity and expression of bone remodeling markers with reduced procollagen type 1 synthesis after 100 mVRMS electrical stimulation. We were able to trigger specific cellular behaviors using different biophysical stimuli. In future studies, different variations of electrical stimulation will be combined with interfacial micromotions.

Mastiha (Pistacia lentiscus) Improves Gut Microbiota Diversity, Hepatic Steatosis, and Disease Activity in a Biopsy-Confirmed Mouse Model of Advanced Non-Alcoholic Steatohepatitis and Fibrosis.

SCOPE: As a result of the obesity epidemic, the prevalence of non-alcoholic steatohepatitis (NASH) is increasing. No drug is approved for the treatment of NASH. In this study, the effect of a nutritional supplement, Mastiha or Chios mastic gum, on metabolic and histological parameters and on the gut microbiome in mice with NASH and fibrosis was investigated. METHODS AND RESULTS: Advanced NASH was induced by feeding C57BL/6J mice a diet rich in fat, sucrose, and cholesterol for 41 weeks. After randomization, animals received the NASH-inducing diet with or without 0.2% (w/w) Mastiha for a further 8 weeks. Disease activity was assessed by liver histology and determination of plasma transaminase activities. Fecal microbiota DNA extraction and 16S rRNA amplicon sequencing were used to determine the composition of the gut microbiome. Mastiha supplementation led to a significant reduction in circulating alanine aminotransferase (ALT) activity, improvement in hepatic steatosis and collagen content, and a reduction in NAFLD activity score. Furthermore, it resulted in a partial but significant recovery of gut microbiota diversity and changes in identity and abundance of specific taxa. CONCLUSION: This is the first study demonstrating an improvement in disease activity in mice with advanced NASH with fibrosis by a diet containing Mastiha.

Biosynthetic Studies on Acetosellin and Structure Elucidation of a New Acetosellin Derivative.

Natural products from fungi, especially Ascomycota, play a major role in therapy and drug discovery. Fungal strains originating from marine habitats offer a new avenue for finding unusual molecular skeletons. Here, the marine-derived fungus Epicoccum nigrum (strain 749) was found to produce the azaphilonoid compounds acetosellin and 5',6'-dihydroxyacetosellin. The latter is a new natural product. The biosynthesis of these polyketide-type compounds is intriguing, since two polyketide chains are assembled to the final product. Here we performed 13C labeling studies on solid cultures to prove this hypothesis for acetosellin biosynthesis.

Carbon dioxide solubility in 1-hexyl-3-methylimidazolium bis(trifluormethylsulfonyl)imide in a wide range of temperatures and pressures.

Solubility measurement data of carbon dioxide (CO2) in the ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [HMIM][NTf2] at T = 273.15-413.15 K and pressures up to p = 4.5 MPa using an isochoric method in decrements of ΔT = 20 K are presented. The temperature dependency of the Henry's law constant was calculated, and the average deviation of the Henry's law constant is always better than ±1%. Thermodynamic properties of solution such as the free energy of solvation, the enthalpy of solvation, the entropy of solvation, and the heat capacity of solvation were calculated to evaluate the solute-solvent molecular interactions.

Type 2 diabetes phenotype and progression is significantly different if diagnosed before versus after 65 years of age.

BACKGROUND: The incidence of type 2 diabetes is increasing disproportionately in individuals <65 years of age. It is not known whether disease characteristics in these younger patients are similar to "classic" late-onset type 2 diabetes. METHODS: In the epidemiological cohort study entitled "Retrolective Study: Self-Monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes," a total of 3268 patients from randomly contacted primary care practices were documented during a mean follow-up period of 6.5 years. All newly diagnosed patients of these practices were included. RESULTS: At diagnosis, 64.2% of the patients were aged < or =65 years. Thereof, 57.2% were male, whereas in the age group >65 years only 35.0% were male (p < 0.001). The younger group exhibited more severe metabolic deterioration at diagnosis and in the following years than the older group. Conversely, the older group presented at diagnosis with a higher prevalence of cardiovascular risk factors. Self-monitoring of blood glucose (SMBG) was more prominent in the younger group. In both age groups, the use of SMBG was associated with a significantly lower risk (p = 0.003) of a combined end point (severe diabetic complication or all-cause mortality). CONCLUSIONS: There are considerable differences in disease characteristics between people diagnosed with type 2 diabetes during 45-65 years of age versus diagnosis at a later age. Type 2 diabetes diagnosed before the age of 65 years disproportionately affected men and exhibited a more severe disease course, but was characterized by significantly less cardiovascular risk factors in comparison to type 2 diabetes diagnosed at a later age. The use of SMBG was associated with a better clinical outcome in both age groups.

Self-alignments to detect mutually exclusive exon usage.

The surprisingly low number of about 25,000 genes in the human genome [1] confirmed a fairly accurate estimate given by King and Jukes in 1969 based on population genetical arguments [2]. On the other hand, the number of different transcripts vastly exceeds gene number. This fact intensified the search for alternatively spliced genes. Recent results [1,3,4-7] suggest that more than 60% of the human genes are alternatively spliced, some of them with a myriad of different splice forms. Alternative splicing is found in all higher eukaryotic species in varying frequency. In this paper we focus on a particular form of alternative splicing, the so-called mutually exclusive exon usage (MEEU). In most known examples mutually exclusive exons are arranged in cassettes of highly similar exons suggesting that they have been derived by exon duplication [8-10]. Since classical gene-finding programs may fail to correctly predict such genes [11-16], we present a method, which is based on local similarity of exons, to detect gene candidates with mutually exclusive exon usage. We have screened the entire genome of D. melanogaster and found five new genes with MEEU in addition to eight previously described cases. Additional 1703 candidate regions of putative mutually exclusive exons were identified.

Electron-poor 2,3-Dihydro-1,3-Diborolyl Complexes of Iron and Ruthenium: Synthesis, Reactivity, and Crystal and Electronic Structures of an Iron Sandwich Complex.

The addition product of sodium hydride and the 2,3-dihydro-1,3-diborole (CiPr)2 (BEt)2 CHMe (3c) reacted with [{(C5 Me5 )FeCl}x ] to produce the green sandwich complex [(C5 Me5 )Fe{n5 -(CiPr)2 (BEt)2 CMe}] (2 c), which formally contains 16 valence electrons (VE). Complex 2c has unexpected structural properties in the solid state: the 1,3-diborolyl ring is extremely folded (41°), and the Fe-C2 distance is short (1.90 Å). Analogously, violet Ru complexes 4a,c,d were obtained from 3a,c, NaH or tBuLi, and [{(C5 Me5 )RuCl}4 ]. With the less bulky heterocycles 3 b,e the new 30 VE triple-decker complexes [(C5 Me5 )Ru{µ,n5 -(CR1 )2 (BR2 )2 CMe}RuH(C5 Me5 )] (5b,e) were formed, which contain a Ru-H bond. Cyclic voltammetric studies revealed the existence of stable anions 2c- and 4d- formed by reversible one-electron reduction at -1.26 and -1.40 V, respectively (vs. SCE). The red-brown anions were further characterized by ESR spectroscopy following stepwise reduction of the neutral species with potassium in THF. Addition of CO to 4a and 4d led to formation of the monocarbonyl complexes [(C5 Me5 )Ru(CO){n5 -(CR1 )2 -(BR2 )2 CMe}] (6a,d), and 6d was characterized by X-ray structure analysis. The heterocycle in 6d is less folded (19°) than in 2 c. Its CO ligand causes a 28.5° tilt of the cyclic ligands. Reaction of CO with 2 c yielded a red product of unknown structure. The electronic structure of 2 was studied by EH-MO theory, which revealed a unique bonding in the sandwich. The s̀ electron density of the B-C bonds participates in the bonding to the iron atom; this demonstrates that the number of bonding electrons is the same as in ferrocene. Thus, the complexes 2 actually have 18 VE.