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The GTPase Cdc42 regulates polarized growth in most eukaryotes. In the bipolar yeast Schizosaccharomyces pombe, Cdc42 activation cycles periodically at sites of polarized growth. These periodic cycles are caused by alternating positive feedback and time-delayed negative feedback loops. At each polarized end, negative feedback is established when active Cdc42 recruits the Pak1 kinase to prevent further Cdc42 activation. It is unclear how Cdc42 activation returns to each end after Pak1-dependent negative feedback. We find that disrupting branched actin-mediated endocytosis disables Cdc42 reactivation at the cell ends. Using experimental and mathematical approaches, we show that endocytosis-dependent Pak1 removal from the cell ends allows the Cdc42 activator Scd1 to return to that end to enable reactivation of Cdc42. Moreover, we show that Pak1 elicits its own removal via activation of endocytosis. These findings provide a deeper insight into the self-organization of Cdc42 regulation and reveal previously unknown feedback with endocytosis in the establishment of cell polarity., (© 2024 Harrell et al.)

Fission yeast cytokinesis is driven by simultaneous septum synthesis, membrane furrowing and actomyosin ring constriction. The septum consists of a primary septum flanked by secondary septa. First, delivery of the glucan synthase Bgs1 and membrane vesicles initiate primary septum synthesis and furrowing. Next, Bgs4 is delivered for secondary septum formation. It is unclear how septum synthesis is coordinated with membrane furrowing. Cdc42 promotes delivery of Bgs1 but not Bgs4. We find that after primary septum initiation, Cdc42 inactivators Rga4 and Rga6 localize to the division site. In rga4Δrga6Δ mutants, Cdc42 activity is enhanced during late cytokinesis and cells take longer to separate. Electron micrographs of the division site in these mutants exhibit malformed septum with irregular membrane structures. These mutants have a larger division plane with enhanced Bgs1 delivery but fail to enhance accumulation of Bgs4 and several exocytic proteins. Additionally, these mutants show endocytic defects at the division site. This suggests that Cdc42 regulates primary septum formation and only certain membrane trafficking events. As cytokinesis progresses Rga4 and Rga6 localize to the division site to decrease Cdc42 activity to allow coupling of Cdc42-independent membrane trafficking events with septum formation for proper septum morphology., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Centrifugation is a common procedure to improve the quality of chilled and frozen canine semen by removing debris and seminal plasma and adding semen extenders. The aim of this study was to evaluate the efficacy and influence of a second centrifugation after 48 h of storage at 5 °C on the sperm quality of canine semen. The ejaculates of 45 healthy male dogs, divided into three groups according to body weight, were analyzed for macro- and microparameters such as ejaculate volume, sperm concentration, kinematic parameters, morphology, and integrity of plasma membrane. Samples were analyzed at baseline conditions (T0), after 24 h (T24) and after 48 h (T48) to assess the effects of the different treatments on sperm quality. Results: The results showed a significant effect of a second centrifugation on the improvement of chilled sperm quality compared to the other techniques, especially up to 48 h. Conclusions: Analysis of the data showed that the semen samples centrifuged and then cooled at 5 °C had acceptable semen parameters, especially in terms of motility, with a gradual decrease in serial evaluations after 24 and 48 h. A second centrifugation after 48 h of storage may lead to better semen quality and improve the kinetics of sperm parameters, the percentage of morphologically normal sperm and the percentage of sperm with intact membranes. [ABSTRACT FROM AUTHOR]

Objective: To identify high-risk categories for high-order multiple pregnancy (HMP) in in vitro fertilization (IVF), establish clinic-specific HMP risk data for counseling use, and verify their utility in reducing HMP., Design: Before and after intervention study., Setting: Two IVF programs using the same embryology laboratory and IVF protocols., Patient(s): All IVF patients undergoing fresh embryo transfers., Intervention(s): Use of clinic-specific age, diagnosis, and embryo score (ES) risk data in assessing individual HMP risk during informed consent., Main Outcome Measure(s): HMP and pregnancy outcomes., Result(s): In determining clinic-specific high risk categories and developing outcomes-based HMP risk data for counseling, the good outcome rate (GR) was defined as the percentage of singleton or twin deliveries per cycle and the bad outcome rate included no pregnancy or nondelivered pregnancies (miscarriages, multifetal reduction) and HMP per cycle. During 1995 to 1999, age <35 years, calculated morphologic ES, and donor egg (DE) cycles were factors shown by logistic regression to statistically significantly affect the GR. The optimal GRs for DE <35 and >or=35 years (donor age), and non-DE cycles <35 years were achieved with two (57.7%), three (43.2%), and three (43.2%) embryos transferred, respectively. A DE <35 years with >or=3 embryos transferred had the highest risk for HMP. The GR correlated (0.91) with the ES according to the formula: GR = 3.3 + 2.0 ES, when ES range was between 4 and 26. Clinic-specific risks for HMP based on age, diagnosis, and ES were developed and considered while counseling for ET during 2004. The clinic-specific HMP risk data made for a reduction in the HMP rate of 90.9% for DE-IVF (11.8% to 1%) and 53.8% for all IVF (9.1% to 4.2%), without decreases in clinical pregnancy or delivery rates. Physicians showing the greatest decline (64%) in HMP had no reduction in pregnancy or delivery rates., Conclusion(s): The use of clinic-specific HMP risk data in counseling based on age, diagnosis, and ES provided a 53% to 64% reduction in HMP without affecting rates of pregnancy or delivery. The clinic-specific ES system correlated closely with good outcomes. A standardized ES system may provide useful information for counseling during ET informed consent.

Objective: To evaluate pregnancy rates (PRs) in women undergoing artificial insemination with sperm alternately prepared by one of five techniques: sperm washing, Percoll gradient centrifugation, swim-up, swim-down, or refrigeration/heparin treatment., Design: Each treatment group alternated in a different order through the five sperm preparations. Pregnancy rates were compared for each sperm preparation., Setting: Two infertility centers, one located in an academic institution and the other a regional hospital., Patient(s): Three hundred sixty-three women undergoing 898 artificial inseminations with husband semen with a progressive motile sperm count of >20 million sperm per mL were randomly placed in the five treatment groups., Main Outcome Measure(s): Pregnancy rates., Result(s): The overall ongoing PR per insemination was 9.7% (87/898), including 6.12% for natural cycles (n = 196), 12.8% for clomiphene citrate-stimulated cycles (n = 101), and 10.3% for gonadotropin-stimulated cycles (n = 601). The highest ongoing PRs for sperm preparations followed the swim-up technique (13.2%, 26/197) and the Percoll gradient centrifugation technique (12.7%, 26/204)., Conclusion(s): These data suggest that the swim-up and Percoll gradient preparations result in higher PRs than the wash, swim-down, and refrigeration/heparin techniques.

A simple technique for high-resolution imaging of distant objects is described and experimentally demonstrated. The technique, referred to as Fourier telescopy, is a variant of Fourier microscopy, which additionally uses phase closure for correction of intervening aberrations. It is an active-illumination technique that is scalable to angular resolutions of 1 nrad and to illuminators of extremely low power. A laboratory experiment demonstrates reconstruction of images of two simple objects with an angular resolution of 83 µrad.

This article discusses the use of balanced incomplete block design for process evaluation and presents a case study of its use. This technique produces a weighted ranking of program elements, showing the relative importance of each element and allowing comparison of process and content elements. The article presents a case study in which the technique was used to evaluate the Chronic Disease Self-Management Program. Participants and lay course leaders were asked to rank 13 course elements for their helpfulness. The most valued element, sharing or unstructured interactions among participants, was not an explicitly planned part of the intervention. Some of the elements least valued (nutrition, use of community resources, and medication use) are elements most emphasized by the health care system and by patient education. We found that balanced incomplete block design was easy to administer and tally. The results could be readily applied to program redesign and to needs assessment.

Joint ventures between service and academia are designed to enhance the quality of client services, enrich faculty teaching experiences and skills, and strengthen communication channels. The joint venture described in this article is an example of how public health nursing services and academia can be united through faculty participation in administration. Included in the discussion are the impetus for the project, the contract negotiations, the positive outcomes and disadvantages of the venture, and questions that should be raised when a similar venture is considered.

The rattail fish, Coryphaenoides armatus, lives at ocean depths of 3000 m. As an adaptation for pumping oxygen into the swim bladder against the extreme pressures at the ocean bottom, the hemoglobin from this fish at low pH exhibits an extraordinarily low affinity for ligands. In this study, continuous wave and time-resolved Raman techniques are used to probe the binding site in this hemoglobin. The findings show an association between the low-affinity material and a highly strained heme-proximal histidine linkage. The transient Raman studies reveal differences in the protein structural dynamics at pH 6 and 8. The emerging picture derived from both this and earlier studies is that in vertebrate hemoglobins the heme-proximal histidine linkage represents a key channel through which species- and solution-dependent variations in the globin are communicated both statically and dynamically to the heme to produce an extensive range of ligand binding properties. Also presented is a new model that relates both intensity and frequency of the resonance Raman band involving the iron-proximal histidine stretching mode to specific protein controlled structural degrees of freedom. There emerges from this model a mechanism whereby modifications in the proximal heme pocket can further reduce the affinity of an already highly strained T state structure of hemoglobin.

The geminate recombination of CO with carboxy hemoglobin (Hb4(CO)3) following a ten nanosecond laser pulse and the overall combination of the fourth CO with Hb4(CO)3 has been studied as a function of pH in the presence and absence of inositol hexaphosphate. The results indicate that the kinetics of both reactions are independent of pH and phosphate concentration. The results are discussed in terms of a two-step mechanism: a pre-equilibrium step followed by heme--ligand bond formation. The latter is also known as the geminate recombination reaction (Hb + CO in equilibrium Hb X CO in equilibrium HbCO).

The geminate recombination of CO with Hb following dissociation by a 10-ns laser pulse has been studied as a function of pH (9.2 and 7.0 without inositol hexaphosphate and 6.0 with inositol hexaphosphate) and temperature (5-35 degrees C). The hemoglobins studied included adult, Rothschild, rabbit, opossum, and carp. Despite significant differences in their structural and functional properties, the first four of these hemoglobins show similar trends in the yields, rates, and activation energies of the geminate recombination. The nature of the "cage recombination" in hemoglobin is discussed in the light of such findings. Neither a slow diffusion model nor a model based upon a specific non-heme binding site accounts for the observations.

The low-temperature recombination of CO with myoglobin was studied using Fourier transform infrared spectroscopy. The bound state of carbon monoxide myoglobin has two distinct conformers observed at 1926 and 1945 cm-1 with an intensity ratio of 1 to 8. The recombination of these bands after complete photolysis at 10 K followed by a temperature jump shows distinct kinetics for the two bands. Although both bands apparently follow the nonexponential kinetics originally described by Frauenfelder and co-workers (Austin, R., Beeson, K., Eisenstein, L., Frauenfelder, H., and Gunsalus, I. (1975) Biochemistry 14, 5355-5373), the 1926 cm-1 band does not appear appreciably below 70 K. In fact, after 20 min of recombination at 70 K the 1945 cm-1 band is fully recovered, while no detectable amount of the 1926 cm-1 band is present. This is the first association of a spectroscopic marker of protein substructure with reaction kinetics.

Variations in the v2 region of the Raman spectra of cryogenically trapped photoproducts of different liganded myoglobins as a function of ligand (CO, O2, and n-butyl isocyanide) and species (whale, tuna, elephant) are reported. These variations are attributed to differences in the population of "open" (ligand accessible) and "closed" (ligand inaccessible) conformations of the distal heme pocket. Based on these findings and those derived from other spectroscopies including x-ray crystallography, NMR, IR spectra, and ESR, a working model is presented which accounts for how the conformation of the distal heme pocket, the geometry of the bound ligand, the identity of the ligand, and the dynamics of the dissociated ligand are all interconnected.

Inhomogeneous broadening of the 760-nanometer photoproduct band of carboxymyoglobin at cryogenic temperatures has been demonstrated with a dynamic hole burning technique. Line-shape changes and frequency shifts in this spectral band are generated by ligand recombination and are shown not to be the result of structural relaxation below 60 K. The observation of dynamic hole burning exposes the relation between the structural disorder responsible for the inhomogeneous broadening and the well-known distributed ligand rebinding kinetics. The findings provide direct evidence for the functional relevance of conformational substrates in myoglobin rebinding. In addition, a general protocol for evaluating the relative contributions of structural relaxation and hole burning to the spectral changes accompanying rebinding in hemeproteins is presented.

A high incidence of luteal phase defect (LPD) has been reported using subcutaneous pulsatile gonadotropin-releasing hormone for induction of ovulation. We reviewed all patients treated with the combination of subcutaneous pulsatile gonadotropin-releasing hormone during the follicular phase and human chorionic gonadotropin during the luteal phase (GnRH-hCG) who underwent endometrial biopsy during a treatment cycle. All of these patients had biopsy-proven LPD which persisted despite traditional therapy with progesterone vaginal suppositories and/or clomiphene citrate. The mean number of biopsies out of phase per patient prior to GnRH-hCG treatment was 2.8 +/- 0.2 (+/- SEM). When treated with GnRH-hCG, 15/16 patients (94%) showed a normal endometrial biopsy. The probability of this result occurring by chance alone allowing for a 50% treatment independent correction rate is less than .001. These results show that the combination of subcutaneous pulsatile gonadotropin-releasing hormone and luteal-phase human chorionic gonadotropin can result in normal endometrial maturation in a high percentage of cycles when administered as described. It appears to be an effective alternative to traditional treatment modalities for luteal phase defect should one be needed.

A 15-year-old girl presented with a large abdominopelvic mass that proved to be a retroperitoneal right ovarian cystadenofibroma. The patient's left ovary contained a small adenofibroma and was also retroperitoneal but otherwise grossly normal, as were the left tube and uterus. This is the first published report in which a patient's only ovaries appeared to have been located retroperitoneally.

We studied the effect of the opiate antagonist naloxone on the peripheral GH response to the alpha 2-receptor agonist clonidine in eight normally cycling women during the mid-luteal phase. In a randomized, double-blind, cross-over design, each subject received clonidine and naloxone on one occasion and clonidine and placebo on the other. In seven of eight subjects, an attenuation of the GH response was associated with naloxone administration. The maximal GH increment above baseline (delta GHMAX) of 7.8 +/- 2.0 micrograms/L (mean +/- SEM) with placebo was higher than the delta GHMAX of 4.2 +/- 0.9 micrograms/L with naloxone (p = 0.05). Likewise, the area above baseline under the GH level-time curve following clonidine (delta GHAREA) was higher with placebo compared to naloxone (477 +/- 175 micrograms/L x min vs. 228 +/- 62 micrograms/L x min), although this difference was not quite statistically significant (p = 0.09). As expected, with placebo the increase in GH following clonidine was statistically significant by repeated measures analysis of variance (p = 0.001). The smaller increase in GH levels when naloxone was given was not significant. Both delta GHMAX and delta GHAREA values were significantly positively correlated with estradiol levels when placebo was given, but not when naloxone was given. GHRH was not detectable following clonidine administration under either the placebo or the naloxone conditions. Our data support the hypothesis that estrogen enhances the response of GH to provocative stimuli in women, at least in part by increasing endogenous opioid tone in the hypothalamus.

Background and Objective: Best-worst scaling is a theory-driven method that can be used to prioritize objects in health. We sought to characterize all studies of best-worst scaling to prioritize objects in health, to assess trends of using best-worst scaling in prioritization over time, and to assess the relationship between a legacy measure of quality (PREFS) and a novel assessment of subjective quality and policy relevance.Methods: A systematic review identified studies published through to the end of 2021 that applied best-worst scaling to study priorities in health (PROSPERO CRD42020209745), updating a prior review published in 2016. The PubMed, EBSCOhost, Embase, Scopus, APA PsychInfo, Web of Science, and Google Scholar databases were used and were supplemented by a hand search. Data describing the application, development, design, administration/analysis, quality, and policy relevance were summarized and we tested for trends by comparing articles before and after 1 January, 2017. Multivariate statistics were then used to assess the relationships between PREFS, subjective quality, policy relevance, and other possible indicators.Results: From a total of 2826 unique papers identified, 165 best-worst scaling studies were included in this review. Applications of best-worst scaling to study priorities in health have continued to grow (p < 0.01) and are now used in all regions of the world, most often to study the priorities of patients/consumers (67%). Several key trends can be observed over time: increased use of pretesting (p < 0.05); increased use of online administration (p < 0.01), and decreased use of paper self-administered surveys (p = 0.02); increased use of heterogeneity analysis (p = 0.02); an increase in having a clearly stated purpose (p < 0.01); and a decrease in comparing respondents to non-respondents (p = 0.01). The average sample size has more than doubled, from 228 to 472 respondents, but formal sample size justifications remain low (5.3%) and unchanged over time (p = 0.68). While the average PREFS score remained unchanged at 3.1/5, both subjective quality and policy relevance trended up, but changes were not statistically significant (p = 0.06 and p = 0.13). Most of the variation in subjective quality was driven by PREFS (R2 = 0.42), but it was also positively assosciated with policy relevance, heterogeneity analysis, and using a balanced incomplete block design, and was negatively associated with not using developmental methods and an increasing sample size.Conclusions: Using best-worst scaling to prioritize objects is now commonly used around the world to assess the priorities of patients and other stakeholders in health. Best practices are clearly emerging for best-worst scaling. Although legacy measures (PREFS) to measure study quality are reasonable, there may need to be new tools to assess both study quality and policy relevance. [ABSTRACT FROM AUTHOR]

Background: Ginsenoside Rg-1 (Rg-1), a triterpenoid saponin abundantly present in Panax ginseng, is a type of naturally occurring steroid with known anti-diabetic and anti-inflammatory effects. In this study, we sought to confirm the effects and mechanisms of action of Rg-1 on store-operated Ca2+ entry (SOCE) in human vascular endothelial cell line (EA) and murine aortic vascular smooth muscle cell line (MOVAS) cells exposed to high glucose. Methods: Cytosolic Ca2+ concentrations in EA and MOVAS cells were measured by monitoring fluorescence of the ratiometric Ca2+-indicator, Fura-2 AM. Results: High glucose significantly increased Ca2+ influx by abnormally activating SOCE in EA and MOVAS cells. Notably, this high glucose-induced increase in SOCE was restored to normal levels in EA and MOVAS cells by Rg-1. Moreover, Rg-1 induced reductions in SOCE in cells exposed to high glucose were significantly inhibited by the plasma membrane Ca2+ ATPase (PMCA) blocker lanthanum, the Na+/K+-ATPase blocker ouabain, or the Na+/Ca2+ exchanger (NCX) blockers Ni2+ and KB-R7943. These observations suggest that the mechanism of action of Rg-1 inhibition of SOCE involves PMCA and Na+/K+-ATPase, and an increase in Ca2+ efflux via NCXs in both EA and MOVAS cells exposed to high glucose. Conclusions: These findings indicate that Rg-1 may protect vascular endothelial and smooth muscle cells from Ca2+ increases following exposure to hyperglycemic conditions. [ABSTRACT FROM AUTHOR]

Introduction: The Chronic Disease Self‐Management Programme (CDSMP) has resulted in improved health outcomes for patients. However, research has focused mainly on those with chronic conditions and has not extensively explored prevention programmes targeting individuals with specific vulnerability profiles. Aim: This study aimed to understand the effects of the CDSMP on the lived experience of vulnerable patients included in the EFFICHRONIC project in France, based on their needs and expectations before and after participation. Methods: We conducted a qualitative phenomenological semio‐pragmatic study based on 37 in‐depth interviews with 20 patients (20 before/17 after CDSMP). Results: By transforming existential dimensions (identity, relationship with others and bodily experience), chronic illness generates new needs in the vulnerable person. By resonating with the expectations and needs of participants, the CDSMP induces motivation and a sense of belonging to a community of peers. It has enabled the participants to become actors of their own health until empowerment. Although some limitations are reported, the programme has awakened a desire in the participants to take better care of their health and to develop personal skills with, for some, a desire to become involved in health education. Conclusion: Our phenomenological approach highlighted the resonance between the programme (its design and implementation) and the lived experience of patients, as an effective element of empowerment. This necessitates training the facilitators to elicit the lived experience of patients. Furthermore, as a patient‐centred approach is required, the facilitators need to learn how to adapt the design of the programme to the singularity of the patient. Patient or Public Contribution: Patients provided the data that were collected through in‐depth interviews, and their experiences before and after the programme were analysed. [ABSTRACT FROM AUTHOR]

Undescended ovary (UO) is an uncommon congenital condition characterized by the presence of the adnexa above the common iliac vessels, with an estimated incidence of 0.3– 2%. Because of its rarity, it is usually presented as a case report. A thorough knowledge of the ovarian embryological development is essential for the clinician, who must be warned about the possibility of associated Müllerian and renal malformations. There may be asymptomatic patients, incidentally diagnosed during infertility evaluation, but when symptoms occur, these are unspecific and most often this disorder is misdiagnosed, the accurate diagnosis being established intraoperatory. The malignant potential of an UO is accepted, although no such cases were reported. The role of the UO in infertility is still unclear, despite evidence of its normal function. Complications are linked to the ovary (cyst formation, cyst ruptures or tumors) or to the undescended fallopian tube (ectopic pregnancies). The management should be conservative, but there is no consensus about whether it is necessary to excise the ipsilateral undescended tube. We included a short case presentation of an UO cystadenoma misdiagnosed as a renal cyst, which depicts all diagnostic and management dilemmas and inspired us to write this review. The present literature review includes all the cases reported from the early 20th century to the present, with updated data about epidemiology, pathophysiology, clinical and imaging diagnosis, treatment options and prognosis of this rare condition. This paper aims to establish some directions in the diagnosis and management of similar patients and to remind us that, no matter how advanced the imaging investigation techniques might be, a correct preoperative diagnosis may often be missed. [ABSTRACT FROM AUTHOR]

Purpose: Does IDEF mapping help monitor the technical process of IUI and explore the potential improvements which might contribute to increased pregnancy and live birth rates? Method: Retrospective analysis of 1729 homologous IUI cycles of couples attending a fertility clinic in a university hospital setting. Standardized conventional semen parameters were analyzed and the semen samples prepared via discontinuous density gradient centrifugation. Results: There was no significant association between sperm concentration, motility and morphology (analysis phase), and pregnancy outcome. Only female and male ages were significantly associated with the pregnancy outcome. There was a significant difference in the odds on clinical pregnancies and live births when analysis was ≤ 21 min initiated, and < 107 min between sample production and IUI, adjusted for male and female age. Conclusions: Adjusting for the couple's age, we could show that time intervals between semen production and analysis and IUI when kept low significantly influenced clinical pregnancies and live births. [ABSTRACT FROM AUTHOR]

Horizontal cells (HCs) are interneurons of the outer retina that undergo graded changes in membrane potential during the light response and provide feedback to photoreceptors. We characterized spontaneous Ca2+-based action potentials (APs) in isolated goldfish (Carassius auratus) HCs with electrophysiological and intracellular imaging techniques. Transient changes in intracellular Ca2+ concentration ([Ca2+]i) were observed with fura-2 and were abolished by removal of extracellular Ca2+ or by inhibition of Ca2+ channels by 50 µM Cd2+ or 100 µM nifedipine. Inhibition of Ca2+ release from stores with 20 µM ryanodine or 50 µM dantrolene abolished Ca2+ transients and increased baseline [Ca2+]i. This increased baseline was prevented by blocking L-type Ca2+ channels with nifedipine, suggesting that Ca2+-induced Ca2+ release from stores may be needed to inactivate membrane Ca2+ channels. Caffeine (3 mM) increased the frequency of Ca2+ transients, and the store-operated channel antagonist 2-aminoethyldiphenylborinate (100 µM) counteracted this effect. APs were detected with voltage-sensitive dye imaging (FluoVolt) and current-clamp electrophysiology. In current-clamp recordings, regenerative APs were abolished by removal of extracellular Ca2+ or in the presence of 5 mM Co2+ or 100 µM nifedipine, and APs were amplified with 15 mM Ba2+. Collectively, our data suggest that during APs Ca2+ enters through L-type Ca2+ channels and that Ca2+ stores (gated by ryanodine receptors) contribute to the rise in [Ca2+]i. This work may lead to further understanding of the possible role APs have in vision, such as transitioning from light to darkness or modulating feedback from HCs to photoreceptors. [ABSTRACT FROM AUTHOR]

Study Question: Are the guidelines for the technical aspects of IUI (WHO, 2010) still in accordance with the current literature?Summary Answer: In general, the laboratory guidelines of the World Health Organization (WHO) are a suitable protocol, although the evidence is not always conclusive and some changes are advisable.What Is Known Already: Lack of standardization of the technical procedures required for IUI might result in inter-laboratory variation in pregnancy rates. Most centers still use their own materials and methods even though some guidelines are available.Study Design, Size, Duration: A structural review focusing on the association between pregnancy rates and the procedures of semen collection (e.g. ejaculatory abstinence, collection place), semen processing (e.g. preparation method, temperature during centrifugation/storage), insemination (e.g. timing of IUI, bed rest after IUI) and the equipment used.Participants/materials, Setting, Methods: A literature search was performed in Medline and the Cochrane library. When no adequate studies of the impact of a parameter on pregnancy results were found, its association with sperm parameters was reviewed.Main Results and the Role Of Chance: For most variables, the literature review revealed a low level of evidence, a limited number of studies and/or an inadequate outcome measure. Moreover, the comparison of procedures (i.e. semen preparation technique, time interval between semen, collection, processing and IUI) revealed no consensus about their results. It was not possible to develop an evidence-based, optimal IUI treatment protocol.Limitations, Reasons For Caution: The included studies exhibited a lack of standardization in inclusion criteria and methods used.Wider Implications Of the Findings: This review emphasizes the need for more knowledge about and standardization of assisted reproduction technologies. Our literature search indicates that some of the recommendations in the laboratory guidelines could be adapted to improve standardization, comfort, quality control and to cut costs.Study Funding/competing Interest(s): The Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), Nijmegen, The Netherlands. S.K. and W.N. have no conflicts of interest to disclose. C.B. and A.W. are members of the board of the SKML. With a grant from SKML, L.L. was paid for her time to perform the research and write the publication. D.B. received grants from Merck Serono, Ferring and MSD, outside the submitted work.Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Protein- and peptide-based structural biopolymers are abundant building blocks of biological systems. Either in their natural forms, such as collagen, silk, and fibronectin, or as related synthetic materials, they can be used in various technologies. An emerging area is that of biomimetic materials inspired by protein-based biopolymers, which are made up of small molecules rather than macromolecules and can therefore be described as supramolecular polymers. These materials are very useful in biomedical applications because of their ability to imitate the extracellular matrix in both architecture and the capacity to signal cells. This article describes important features of the natural extracellular matrix and highlights how these features are being incorporated into biomaterials composed of biopolymers and supramolecular polymers. We particularly focus on the structures, properties, and functions of collagen, fibronectin, and silk, and the supramolecular polymers inspired by them as biomaterials for regenerative medicine. [ABSTRACT FROM AUTHOR]

Background Implementation of clinical practice guidelines into daily care is hampered by a variety of barriers related to professional knowledge and collaboration in teams and organizations. To improve guideline concordance by changing the clinical decision-making behavior of professionals, computerized decision support (CDS) has been shown to be one of the most effective instruments. However, to address barriers at the organizational level, additional interventions are needed. Continuous monitoring and systematic improvement of quality are increasingly used to achieve change at this level in complex health care systems. The study aims to assess the effectiveness of a web-based quality improvement (QI) system with indicator-based performance feedback and educational outreach visits to overcome organizational barriers for guideline concordance in multidisciplinary teams in the field of cardiac rehabilitation (CR). Methods A multicenter cluster-randomized trial with a balanced incomplete block design will be conducted in 18 Dutch CR clinics using an electronic patient record with CDS at the point of care. The intervention consists of (i) periodic performance feedback on quality indicators for CR and (ii) educational outreach visits to support local multidisciplinary QI teams focussing on systematically improving the care they provide. The intervention is supported by a webbased system which provides an overview of the feedback and facilitates development and monitoring of local QI plans. The primary outcome will be concordance to national CR guidelines with respect to the CR needs assessment and therapy indication procedure. Secondary outcomes are changes in performance of CR clinics as measured by structure, process and outcome indicators, and changes in practice variation on these indicators. We will also conduct a qualitative process evaluation (concept-mapping methodology) to assess experiences from participating CR clinics and to gain insight into factors which influence the implementation of the intervention. Discussion To our knowledge, this will be the first study to evaluate the effect of providing performance feedback with a web-based system that incorporates underlying QI concepts. The results may contribute to improving CR in the Netherlands, increasing knowledge on facilitators of guideline implementation in multidisciplinary health care teams and identifying success factors of multifaceted feedback interventions. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of gradient and swim-up semen preparation techniques on pregnancy rates in couples undergoing intrauterine insemination (IUI) cycles with low dose gonadotropin stimulation with the diagnosis of unexplained or mild male subfertility. Methods: Two hundred and twenty three couples were randomized into swim up or gradient technique groups for sperm preperation. The clinical and on going pregnancy rates per cycle and per patient were evaluated. Results: Both clinical and ongoing pregnancy rates per cycle were significantly higher in the 'gradient' group (19 % and 16.9 %) in comparision with the 'swim up' group (9.7 % and 6.9 %) ( p < 0.05). Clinical pregnancy and on-going pregnancy rates per patient were higher in the 'gradient' group (26.1 % and 23.4 %) when compared to the 'swim up' group (15.2 % and 10.7 %), ( p < 0.05). In the subgroup of 191 unexplained subfertile couples with 290 cycles; the 'gradient' group also revealed significantly higher clinical and ongoing pregnancy rates per cycle (21.6 % and 17.9 %) when compared with the 'swim up' group (10.3 % and 7.1 %) ( p < 0.05). In total of 48 treatment cycles upon 32 couples with mild male factor subfertility no significant difference were found between the two sperm preparation techniques in terms of clinical (% 5.3 vs %6.9, p > 0.05) and ongoing (% 5.3 vs %6.9, p > 0.05) pregnancy rates per cycle. Conclusion: The gradient technique significantly improves clinical outcome in IUI cycles of unexplained subfertile couples when compared to swim up technique. In male subfertile patients, both techniques yield similar clinical outcomes. [ABSTRACT FROM AUTHOR]

Summary Chlamydia trachomatis is an important bacterial cause of infertility. In men, the recommended specimen for diagnosing chlamydial infection is urine, with little or no emphasis placed on testing semen. A systematic review of the literature was conducted to search for studies in which men undergoing investigations for infertility produced both samples of urine and semen that were tested concurrently for C. trachomatis. An analysis of these studies was then performed. From 322 papers identified from the US National Library of Medicine PubMed database, 14 were selected for a detailed review and 11 were analysed further. Overall, the size of the study groups was only modest and differences between the studies included variation in geography and test methodology, especially whether commercial testing systems had been used. There was also a lack of consistency with regard to including men with azoospermia. Patients were typically 30-35 years old and the median duration of infertility was about 4 years. Of those patients positive for C. trachomatis in the 11 studies, 56% could be detected in both semen and urine, 20% only in urine and 23% only in semen. Deficiencies in existing studies would not allow for a meta-analysis, emphasizing the need for further research in this area for which a number of recommendations are made. [ABSTRACT FROM AUTHOR]

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Intrauterine insemination (IUI) consists of sperm cell extraction from seminal plasma and artificial transfer into the uterine cavity. We investigated whether tenaculum application to the cervix during IUI affects pregnancy rates. A prospective study was done on 468 primary infertile women. Recombinant follicle stimulating hormone was used in ovulation induction. The women were divided randomly into Group 1 (n=236) and Group 2 (n=232) without and with tenaculum application to the cervix, respectively. After IUI, a five-minute sagittal plane uterine ultrasound scan was done in all cases. Uterine contraction was recorded. The women were evaluated for pregnancy rates. Uterine contraction was significantly higher in Group 2 (p<0.001). In all, 24 patients in Group 1 (10.7%) and 38 in Group 2 (17.6%) achieved pregnancy (OR = 1.78, 95% CI 1.03-3.08; p=0.038). Tenaculum application to the cervix increases immediate uterine contraction, but higher pregnancy rates may be obtained. [ABSTRACT FROM AUTHOR]

Contents Semen availability in ram semen processing facilities is of great importance for the genetic improvement of sheep. Accordingly, any method that would increase sperm viability in low viability ejaculates could be useful. In this study, the possibility of a glass beads filtration method by estimating the beads total surface provided (TSP) for adhesion of spermatozoa, was evaluated. Initially, two different TSP (102 and 154 cm2) achieved by various sizes of beads (1500, 2000 and 3000 μm) were tested and no significant difference in sperm viability improvement was noticed for the same TSP by different beads (p > 0.05). Next optimization tests were performed in which three different funnels were used for filtration at a standard TSP (154 cm2). The pear-shaped funnel was found to be the most appropriate for filtration, as semen volume recovery and sperm viability improvement were more pronounced (p < 0.05). Finally, filtration tests were conducted with pear-shaped funnels with different TSP (102 and 154 cm2) obtained by the aforementioned beads sizes (1500, 2000 and 3000 μm) in equal aliquots. Total surface provided of 102 cm2 proved to be the more appropriate for filtration than 154 cm2, as shown by the significant improvement of sperm viability (p < 0.01) and the significantly higher filtrate semen volume (p < 0.05). In conclusion, ram sperm viability improvement by more than 20% of its initial value and semen volume recovery by more than 60%, along with the fact that the total filtration time did not exceed 6 min in any case, suggest that through further development this method could be successfully used during ram semen processing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence-based morphological embryo scoring models for ranking of implantation potential are still scarce, and the need for a precise model increases when aiming for singleton pregnancies. METHODS: Prospectively, 2266 IVF/ICSI double-embryo, day 2 transfers were studied. The five variables scored in 3- to 5-step scales for the embryos transferred are blastomere number (BL), fragmentation, blastomere size variation (‘equality’, EQ), symmetry of the cleavage and mononuclearity in the blastomeres (NU). The scoring results of embryos with an individual traceability from scoring to implantation, i.e. treatments resulting in either no implantation (n = 1385) or twin implantation (n = 228), were studied for prognostic potential. RESULTS: Although all five variables correlated highly with implantation potential, only BL, NU and EQ remained independently significant after regression analysis. The equation thus derived formed the basis for a 10-point integrated morphology cleavage (IMC) embryo score. A table with the scoring point for each possible combination of the embryo variables is presented. The scoring model was statistically validated on the singleton pregnancy group (n = 653). CONCLUSIONS: We suggest that this IMC embryo scoring, incorporating cleavage stage and information on the variation in blastomere size and the number of mononucleated blastomeres, may optimize embryo ranking and selection for day 2 transfers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this prospective study was to investigate whether ovarian blood flow is related to embryological parameters and whether it could be a predictor of outcomes of IVF/ICSI. METHODS: Eighty infertile women underwent ovarian stimulation with gonadotrophins after a long protocol with GnRH agonists. The ovarian volume (OV), number of follicles (NF) and follicular volume (FV) of all follicles >10 mm and vascularization index (VI), flow index (FI) and vascularization–flow index (VFI) were obtained by three-dimensional (3D) ultrasonography and power Doppler angiography (PDA) on the day of HCG administration. These parameters were tested for their relation with IVF laboratory parameters. RESULTS: The OV, FV, VI, FI and VFI were significantly greater in the pregnant group. The NF and FV were the only independent predictors of the number of oocytes retrieved, mature and fertilized, and the number of embryos developed and their cumulative embryo score. Nevertheless, the number of grade 1 embryos depends on the NF and the VI. The ovarian FI and the number of transferred grade 1 embryos can predict gestation in 76% of IVF patients. A low FI and non-grade 1 embryo transferred are also associated with an increased pregnancy loss. CONCLUSION: 3D ultrasonography and PDA allow for an easier ovarian assessment in IVF cycles. The predictive value of IVF outcome suggests a high clinical usefulness of this new technique. [ABSTRACT FROM AUTHOR]

Purpose : To determine if embryo cleavage state or morphology on day 3 correlates with implantation or live birth rates. A retrospective cohort study of all fresh embryo transfers over 2 years. Methods : Patients were grouped by the average cleavage state and morphology. Cleavage state groups were: <6, ≥6, <8, and ≥8 cells. Morphology groups by average grade were: group 1 (best) = 1, group 2 = >1 ≤ 2, group 3 = > 2 ≤ 3, and group 4 (worst) = > 3≤ 4. Results : The overall implantation rate for 158 cycles was 28.1% with a live birth rate of 37.3%. Morphologic state was highly predictive of both implantation rate and live birth rate. Implantation rates by group were 54.8% (group 1), 30.4% (group 2), 23.8% (group 3), and 11.1% (group 4). Likewise, live birth rates among groups were 61.5, 39, 20, and 21%, respectively. Cleavage state was not predictive of outcome. Conclusions : Embryo grade is highly predictive of implantation and live birth rate and can be used to determine the number of embryos to transfer. Cleavage state is not predictive of outcome. [ABSTRACT FROM AUTHOR]

Density gradient centrifugation is a widely used technique for the separation of motile from non-motile sperm, for the removal of contaminating agents such as bacteria and viruses, and for the removal of seminal plasma or cryoprotectant. In the choice of a density gradient medium for a new species, it is important to perform toxicity tests. The present study was carried out to evaluate the potential toxic effects of two silica-based density gradient products (Percoll and PureSperm), on the sperm of the common marmoset. We assessed two different batches of Percoll(polyvinylpyrrolidone (PVP)-coated colloidal silica particles) and one of PureSperm (saline-coated colloidal silica suspension) by means of a computer-aided sperm analysis on semen collected by vibrostimulation. The results showed that although some of the sperm patterns of movement and viability changed significantly over time, and provide a first description of marmoset sperm motility changes under capacitating conditions, there was no significant difference in the sperm treated with Percoll or PureSperm in comparison with the control. We conclude that simple exposure to either of these products does not have a negative effect on viability or motility of marmoset sperm. [ABSTRACT FROM AUTHOR]

Recent results of spectral diffusion experiments by spectral hole-burning techniques carried out at cryogenic temperatures on various monomeric heme proteins unequivocally show interesting new features of conformational dynamics of globular proteins that were not emphasized in the literature until now. These new aspects of the protein dynamics are anomalous diffusion and the aging effect. Here, using the similarities between proteins and glassy systems, we present a model which can interpret the line broadening and—through this effect—the aging phenomenon as well. Leaving untouched the widely accepted energy landscape (EL) concept for the general description of protein dynamics, we concentrate on the bottom of the funnel-like EL, because this part corresponds to the native state(s) at low temperature. We suggest that the overall shape of the EL at the lowest energy range is rather smooth, but on a finer scale it consists of traps. The dynamics is defined by sequential jumps among these traps and the process is described by a Master equation, where the hopping rate only depends on the parameters of the starting state. This model was adapted to interpret the common results of spectral diffusion experiments. We tested our model in the simplest case by computer simulation, and it shows excellent agreement with the experimental data. To our knowledge this is the first work where a theoretical interpretation of the aging dynamics of proteins is directly and quantitatively related to the experimental observations. We also show that the model, after the generalization that the traps are hierarchically organized, is in accordance with the concept of other well-known EL models. [ABSTRACT FROM AUTHOR]

A potential cost of polygyny that may have restrained its evolution in some avian species is the presence of extra-pair offspring in the nests of males mated with several females. However, this relationship is not frequently found and an experimental approach investigating the association between extra-pair offspring and polygyny, while controlling for male traits related to polygyny, has not been undertaken. In this study, we manipulated the testosterone levels of facultatively polygynous spotless starlings, Sturnus unicolor, to establish experimentally different groups of polygyny and analyse its influence on levels of extra-pair offspring in males for which other traits were randomised. During two consecutive breeding seasons, we examined the effects of harem size on the ability of males to assure genetic paternity, assessed by DNA fingerprinting, and on reproductive success in their own nests. The frequency of extra-pair fertilisations varied between 10% (14/140) in 1996 and 20% (39/194) in 1997. Year-to-year analyses of extra-pair paternity variables with treatment as factor and harem size (number of simultaneous mated females) as covariate, were significant only in relation to harem size. Males with few simultaneously mated females were less cuckolded than more polygynous males in 1997 but not in 1996, indicating that mating costs of polygyny occurred, at least in the year with the higher rate of extra-pair paternity. Because polygynous males have more social mates, they may accrue higher reproductive success irrespective of their risk of being cuckolded. However, our results suggest that to be polygynous is costly in terms of paternity loss when we experimentally induce mating status controlling for individual male traits. However, the low values of our power tests for the statistically non-significant results of hormone on cuckoldry do not allow us to discard this hormone effect altogether. [ABSTRACT FROM AUTHOR]

The article describes the intervention Coping Effectiveness Training and its impact on HIV patients. It offers an overview of coping effectiveness training for chronic illnesses, like HIV, which include adaptive coping and maladaptive coping. The Coping Effectiveness Training intervention was developed with elements of stress management and based in the theory of stress and coping.