Pain, gastrointestinal function and fertility outcomes of modified nerve-vessel sparing segmental and full thickness discoid resection for deep colorectal endometriosis - A prospective cohort study.

INTRODUCTION: There is an ongoing debate on surgical techniques for colorectal deep endometriosis (DE) and their effects on gastrointestinal (GI) function. The aim of this study was to prospectively investigate the differences in pre- and postsurgical GI function, health profiles and pain symptoms in women undergoing colorectal surgery for symptomatic DE either with a modified segmental resection technique, so-called nerve-vessel sparing segmental resection (NVSSR), or full thickness discoid resection (FTDR). Complication rates and fertility outcomes were also evaluated. MATERIAL AND METHODS: A total of 162 consecutive patients, 125 (77.2%) of whom underwent NVSSR and 37 (22.8%) FTDR, were evaluated regarding complication rates. Furthermore a lower anterior resection syndrome (LARS) scores, gastrointestinal function-related quality of life index (GIQLI), pain symptoms, endometriosis health profile (EHP-30) parameters were analyzed pre- and post-surgery in a final cohort of 121 patients. RESULTS: There was no difference between postsurgical prevalence of LARS in either surgery group (14/98, 14.1% NVSSR; 2/23, 8.6% FTDR), with significantly decreased LARS scores and increased GIQLI values before vs after surgery in both groups (P < 0.001). The overall grade III complication rate was 7/162 (4.3%) with no significant differences between NVSSR and FTDR groups. Overall, EHP-30 and pain scores significantly decreased after a median follow-up of 41 (± 17.6) months (EHP-30 51.1, SD 21.5 vs 12.7, SD 19.3, P < 0.001; dysmenorrhea, dyspareunia, dyschezia all P < 0.001 both cohorts, respectively). The overall life birth rate and postsurgical pregnancy in infertile patients undergoing NVSSR and FTDR was respectively 58.1% in 25/43 patients; 55.6% in 5/9 patients; 56.0% in 14/25 patients and 100% in 5/5 patients. CONCLUSIONS: NVSSR and FTDR for symptomatic colorectal DE confer a significant amelioration of GI function reflected by decreased LARS symptoms and increased GIQLI scores with no differences in postsurgical function in between the two techniques. Both techniques confer similar complication rates and effects on pain reduction and health profiles.

The Effect of Prone Positioning After Lung Transplantation.

BACKGROUND: Prone positioning has become a standard therapy in acute respiratory distress syndrome to improve oxygenation and decrease mortality. However, little is known about prone positioning in lung transplant recipients. This large, singe-center analysis investigated whether prone positioning improves gas exchange after lung transplantation. METHODS: Clinical data of 583 patients were analyzed. Prone position was considered in case of impaired gas exchange Pao2/fraction of oxygen in inhaled air (<250), signs of edema after lung transplantation, and/or evidence of reperfusion injury. Patients with hemodynamic instability or active bleeding were not proned. Impact of prone positioning (n = 165) on gas exchange, early outcome and survival were determined and compared with patients in supine positioning (n = 418). RESULTS: Patients in prone position were younger, more likely to have interstitial lung disease, and had a higher lung allocation score. Patients were proned for a median of 19 hours (interquartile range,15-26) hours). They had significantly lower Pao2/fraction of oxygen in inhaled air (227 ± 96 vs 303 ± 127 mm Hg, P = .004), and lower lung compliance (24.8 ± 9.1 mL/mbar vs 29.8 ± 9.7 mL/mbar, P < .001) immediately after lung transplantation. Both values significantly improved after prone positioning for 24 hours (Pao2/fraction of oxygen ratio: 331 ± 91 mm Hg; lung compliance: 31.7 ± 20.2 mL/mbar). Survival at 90 days was similar between the 2 groups (93% vs 96%, P = .105). CONCLUSIONS: Prone positioning led to a significant improvement in lung compliance and oxygenation after lung transplantation. Prospective studies are needed to confirm the benefit of prone positioning in lung transplantation.

Distinct maternal amino acids and oxylipins predict infant fat mass and fat-free mass indices.

Interested in maternal determinants of infant fat mass index (FMI) and fat-free mass index (FFMI), considered as predictors for later development of obesity, we analysed amino acids (AA) and oxylipins in maternal serum and breast milk (BM). FMI and FFMI were calculated in 47 term infants aged 4 months (T4). Serum AA were analysed in pregnancy (T1, T2) and 6-8 weeks postpartum (T3). At T3, AA and oxylipins were analysed in BM. Biomarker-index-associations were identified by regression analysis. Infant FMI (4.1 ± 1.31 kg/m2; MW ± SD) was predicted by T2 proline (R2 adj.: 7.6%, p = .036) and T3 BM 11-hydroxy-eicosatetraenoic-acid (11-HETE) and 13-hydroxy-docosahexaenoic-acid (13-HDHA; together:35.5% R2 adj., p < .001). Maternal peripartum antibiotics (AB) emerged as confounders (+AB: 23.5% higher FMI; p = .025). Infant FFMI (12.1 ± 1.19 kg/m2; MW ± SD) was predicted by histidine (R2 adj.: 14.5%, p < .001) and 17-HDHA (BM, R2 adj.:19.3%, p < .001), determined at T3. Confirmed in a larger cohort, the parameters could elucidate connections between maternal metabolic status, nutrition, and infant body development.

Investigating New Sensory Methods Related to Taste Sensitivity, Preferences, and Diet of Mother-Infant Pairs and Their Relationship With Body Composition and Biomarkers: Protocol for an Explorative Study.

BACKGROUND: Early experiences with different flavors play an important role in infant development, including food and taste acceptance. Flavors are already perceived in utero with the development of the taste and olfactory system and are passed on to the child through breast and bottle feeding. Therefore, the first 1000 days of life are considered a critical window for infant developmental programming. OBJECTIVE: The objective of our study is to investigate, both in the prenatal and postnatal period, taste sensitivity, preferences, and dietary diversity of mother-infant pairs. The explorative study design will also report on the impact of these variables on body composition (BC) and biomarkers. In contrast to conventional methods, this study involves long-term follow-up data collection from mother-infant pairs; moreover, the integration of audiovisual tools for recording infants' expressions pertaining to taste stimuli is a novelty of this study. Considering these new methodological approaches, the study aims to assess taste-related data in conjunction with BC parameters like fat-free mass or fat mass, biomarkers, and nutritional intake in infants and children. METHODS: Healthy pregnant women aged between 18 and 50 years (BMI≥18.5 kg/m2 to ≤30 kg/m2; <28 weeks of gestation) were recruited from January 2014 to October 2014. The explorative design implies 2 center visits during pregnancy (24-28 weeks of gestation and 32-34 weeks of gestation) and 2 center visits after delivery (6-8 weeks postpartum and 14-16 weeks postpartum) as well as follow-up visits at 1, 3-3.5, and 6 years after delivery. Data collection encompasses anthropometric and biochemical measurements as well as BC analyses with air displacement plethysmography, taste perception assessments, and multicomponent questionnaires on demographics, feeding practices, and nutritional and lifestyle behaviors. Audiovisual data from infants' reactions to sensory stimuli are collected and coded by trained staff using Baby Facial Action Coding and the Body Action Posture System. Birth outcomes and weight development are obtained from medical records, and additional qualitative data are gathered from 24 semistructured interviews. RESULTS: Our cohort represents a homogenous group of healthy women with stringent exclusion criteria. A total of 54 women met the eligibility criteria, whereas 47 mother-child pairs completed data collection at 4 center visits during and after pregnancy. Follow-up phases, data analyses, and dissemination of the findings are scheduled for the end of 2023. The study was approved by the ethics committee of the Medical University of Graz (EC No 26-066 ex 13/14), and all participants provided informed consent. CONCLUSIONS: The results of this study could be useful for elucidating the connections between maternal and infant statuses regarding diet, taste, biomarkers, and prenatal and postnatal weight development. This study may also be relevant to the establishment of further diagnostic and interventional strategies targeting childhood obesity and early body fat development. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37279.

Membrane-permeable Triphosphate Prodrugs of Nucleoside Analogues.

The metabolic conversion of nucleoside analogues into their triphosphates often proceeds insufficiently. Rate-limitations can be at the mono-, but also at the di- and triphosphorylation steps. We developed a nucleoside triphosphate (NTP) delivery system (TriPPPro-approach). In this approach, NTPs are masked by two bioreversible units at the γ-phosphate. Using a procedure involving H-phosphonate chemistry, a series of derivatives bearing approved, as well as potentially antivirally active, nucleoside analogues was synthesized. The enzyme-triggered delivery of NTPs was demonstrated by pig liver esterase, in human T-lymphocyte cell extracts and by a polymerase chain reaction using a prodrug of thymidine triphosphate. The TriPPPro-compounds of some HIV-inactive nucleoside analogues showed marked anti-HIV activity. For cellular uptake studies, a fluorescent TriPPPro-compound was prepared that delivered the triphosphorylated metabolite to intact CEM cells.

Genetically encoded tools for RNA imaging in living cells.

RNA imaging probes help us investigate how transport and dynamics of RNA contribute to subcellular RNA localization or regulation of gene expression. Out of the plethora of strategies that have been developed to image RNA in living cells, genetically encoded probes are interesting because they can be produced by the cellular machinery and do not require transfection of the cell. These probes can be grouped into fluorophore-binding aptamers and RNA-binding proteins fused to whole or split fluorescent proteins. In this review, we highlight recent developments in the field of genetically encoded probes for RNA imaging and discuss the strengths and limitations of the different approaches.

Programmable design of functional ribonucleoprotein complexes.

Ribonucleoprotein (RNP) complexes are widespread in nature and play crucial roles in gene regulation, RNA processing, and translation. Novel technologies, such as CRISPR-mediated genome engineering, stress the potential of RNP complexes to carry out complex tasks in molecular biology. Here we report a bottom-up approach for the programmable self-assembly of RNP complexes. The building blocks for RNP complex formation are RNAs and Pumilio proteins that can bind to RNA sequence-specifically. Correct RNP assembly triggers protein complementation of a tripartite GFP, thereby resulting in up to 25-fold increased fluorescence, and is strictly dependent on the correct RNA sequences. Our results indicate that Pumilio and guide RNAs are suitable building blocks for the correct self-assembly of RNP complexes consisting of up to six different components. Self-assembling RNP complexes might prove useful for complex biotechnological applications in RNA sensing, imaging, or processing.

Tetramolecular fluorescence complementation for detection of specific RNAs in vitro.

Short fuses: RNA can be detected sequence specifically by using two RNA binding proteins fused to short strands derived from GFP and an additional large GFP fragment. The tetramolecular system has a high signal-to-noise ratio, discriminates between closely related RNA, and works in RNA preparations as well as E. coli cell lysate.