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Introduction: The International Classification of Diseases (ICD) is an international health information system for the collection, processing, classification, and presentation of mortality statistics. The ICD 10th Edition (ICD-10) is a tool for physicians and billing professionals to accurately bill for the care provided. However, physicians who treat female sexual health (FSH) disorders report difficulty in finding appropriate codes for diagnoses and clinical syndromes (Parish et al. 2021). These issues impede the process for appropriate treatment and allotting the correct reimbursement to providers. Additionally, quantitative and qualitative research on FSH is limited due to the lack of accurate ICD codes for FSH disorders in this cohort. Objective: This study aims to evaluate the ICD-10 coding system to assess the accuracy and quality of codes related to common FSH disorders. Methods: A list of 50 most commonly encountered clinical FSH diagnoses was created based on clinical practice findings and ISSWSH guidelines. The list was compared against existing ICD-10 codes to characterize current FSH disorders that are recognized in ICD-10 and determine which FSH disorders are billable (ICD10data.com categorizes codes as "billable" or "non-billable") or missing entirely. FSH diagnoses explicitly listed as an independent diagnosis or generally listed were considered ICD-10 coded. Diagnoses were considered to not have an existing code if they were not explicitly listed independently or under a more general term. Results: 44% (n=22) of the diagnoses did not have existing ICD-10 codes, and 6% (n=3) of the diagnoses had appropriate ICD-10 codes but were not billable (Figure 1, Table 1). FSH diagnoses such as "clitoral adhesions", "clitorodynia" and "persistent genital arousal disorder" were not coded in ICD-10. Many diagnoses were grouped under general terms - pelvic floor pain disorders were grouped under "R10.2: Pelvic and peroneal pain" which included both male and female diagnoses. Other codes had significant diagnostic overlap - "vulvodynia" was separately cataloged as "N94.810: vulvar vestibulitis", "N94.818: Other vulvodynia" and "N94.819: vulvodynia, unspecified". There were numerous common FSH diagnoses with incomplete, inaccurate, or outdated ICD codes. Conclusions: These findings highlight the pressing need for an expanded, comprehensive, and precise set of ICD codes dedicated to FSH disorders. Without appropriate coding for 50% of FSH diagnoses, clinical care, research, and healthcare billing are severely impeded. It is much more difficult for physicians to accurately classify and bill for their procedures, which may create problems with clinical documentation leading to delayed treatment and poor clinical outcomes. For example, existing codes for "vulvodynia," a common disorder affecting 16% of women, are vague and unclear, which lacks practicality for charting and billing purposes. Additionally, the limitations of ICD coding make it nearly impossible to research specific disorders, as they can not be searched in databases like TriNetX. These limitations may explain the large gaps in the literature regarding FSH disorders. Additionally, electronic medical records often have outdated ICD codes, further creating obstacles for clinicians. The current gap in classification, including ICD-10 coding and medical records, must be addressed to advance the understanding and management of FSH disorders. Disclosure: No. [ABSTRACT FROM AUTHOR]

Hemoglobin diseases like sickle cell disease (SCD) and β-thalassemia (BT) present fertility challenges for affected patients. SCD and BT result from abnormal hemoglobin production or structure and pose numerous health concerns. Despite medical advancements improving the quality of life or even providing cures, SCD and BT pose unique fertility concerns for women. Young women with these disorders already contend with reduced ovarian reserve and a narrower fertile window, a situation that is compounded by the gonadotoxic effects of treatments like medications, transfusions, stem cell transplants, and gene therapy. While crucial for disease control, these interventions may lead to reproductive health issues, increasing infertility and early menopause risks. Ovarian tissue cryopreservation (OTC) offers potential for future motherhood to women with hemoglobin disorders facing infertility related to curative treatments. OTC involves surgically removing, preparing, and freezing ovarian tissue containing primordial follicles capable of producing mature oocytes, offering advantages over oocyte cryopreservation alone. However, the application of OTC for patients with hemoglobin disorders presents unique challenges, including special health risks, financial barriers, and access to care. This comprehensive literature review delves into the current state of ovarian tissue cryopreservation for fertility preservation in patients with hemoglobin disorders. Empowering patients with informed reproductive choices in the context of their hemoglobin disorders stands as the ultimate goal.

Background: Studies on stigmatization of cancer patients show a moderate or high relevance of perceived stigmatization. To date, there are no studies with explicit focus on stigma in relation to oncological therapy. We investigated the role of oncological therapy on perceived stigma in a large sample., Methods: Quantitative data from 770 patients (47,4% women; 88%≥50 years) with breast, colorectal, lung, or prostate cancer were analyzed as part of a registry-based bicentric study. Stigma was assessed with the German version of the SIS-D; the validated instrument includes four subscales in addition to a total score. Data were analyzed using the t-test and multiple regression with various sociodemographic and medical predictors., Results: Of the 770 cancer patients, 367 (47,7%) received chemotherapy, possibly in combination with other therapy (surgery, radiotherapy). All stigma scales showed significant mean differences (effect sizes up to d=0,49) with higher scores for patients receiving chemotherapy. The multiple regression analyses of the respective SIS-scales demonstrate a significant influence of the variables age (ß≤- 0,266) and depressivity (ß≤0,627) on perceived stigma in all five models, and (in four models) a significant influence of the variable chemotherapy (ß≤0,140). Radiotherapy shows only a weak influence in all models and surgery has no relevance. The explained variance ranges from R2=27 to 46,5%., Discussion and Conclusion: The findings support the assumption of an association of oncological therapy, especially chemotherapy, on the perceived stigmatization of cancer patients. Relevant predictors are depression and younger (<50) age. These (vulnerable) groups should therefore receive special attention and psycho-oncological care in clinical practice. Further research on the course and mechanisms of therapy-related stigmatization is also necessary., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Hepatitis B virus (HBV) infection remains a global health threat. The World Health Organization (WHO) established a goal to eliminate HBV infection as a public health threat by 2030, and defined targets for key interventions to achieve that goal. We evaluated HBV burden and relevant national recommendations for progress towards WHO targets in circumpolar countries. Viral hepatitis experts of circumpolar countries were surveyed regarding their country's burden of HBV, achievement of WHO targets and national public health authority recommendations for HBV prevention and control. Eight of nine circumpolar countries responded. All countries continue to see new HBV infections. Data about HBV prevalence and progress in reaching WHO 2030 elimination targets are lacking. No country was able to report data for all seven WHO target measures. All countries have recommendations targeting the prevention of mother-to-child transmission. Only the USA and Greenland recommend universal birth dose vaccination. Four countries have recommendations to screen persons at high risk for HBV. Existing recommendations largely address prevention; however, recommendations for universal birth dose vaccination have not been widely introduced. Opportunities remain for the development of trackable targets and national elimination planning to screen and treat for HBV to reduce incidence and mortality.

An action that produced an effect is perceived later in time compared to an action that did not produce an effect. Likewise, the effect of an action is perceived earlier in time compared to a stimulus that was not produced by an action. Despite numerous studies on this phenomenon-referred to as Intentional Binding effect (IB)-the underlying mechanisms are still not fully understood. Typically, IB is investigated in settings where the action produces just one single effect, whereas in everyday action contexts, it rather causes a sequence of effects before leading to the desired outcome. Therefore, we investigated IB of two consecutive effects. We observed substantially more IB of a first effect tone compared to a second tone. This pattern was observed for second tones that were temporally predictable (Exp. 1) or not (Exp. 2 and 3). Interestingly, the second tone yielded stronger IB when it was less delayed (Exp. 4). Thus, also an event occurring later in an unfolding action-effect sequence can be bound to its causing action, but it might be less bound to the action than a first effect. Instead of the fact that it is the second of two consecutive effects, this, however, rather seems to be influenced by the longer delay of a second and, therefore, later occurring effect.

Background: The aspartate aminotransferase-to-platelet ratio index (APRI) and a fibrosis index calculated using platelets (FIB-4) have been proposed as noninvasive markers of liver fibrosis., Goals: To determine APRI/FIB-4 accuracy for predicting histologic liver fibrosis and evaluate whether incorporating change in index improves test accuracy in hepatitis C virus (HCV)-infected Alaska Native persons., Study: Using liver histology as the gold standard, we determined the test characteristics of APRI to predict Metavir ≥F2 fibrosis and FIB-4 to predict Metavir ≥F3 fibrosis. Index discrimination was measured as the area under the receiver operator characteristic curve. We fit a logistic regression model to determine whether incorporating change in APRI/FIB-4 over time improved index discrimination., Results: Among 283 participants, 46% were female, 48% had a body mass index >30, 11% had diabetes mellitus, 8% reported current heavy alcohol use. Participants were infected with HCV genotypes 1 (68%), 2 (17%), or 3 (15%). On liver histology, 30% of study participants had ≥F2 fibrosis and 15% had ≥F3 fibrosis. The positive predictive value of an APRI>1.5/FIB-4>3.25 for identifying fibrosis was 77%/78%. The negative predictive value of an APRI<0.5/FIB-4<1.45 was 91%/87%. The area under the receiver operator characteristic curve of an APRI/FIB-4 for identifying fibrosis was 0.82/0.84. Incorporating change in APRI/FIB-4 did not improve index discrimination., Conclusions: The accuracy of APRI/FIB-4 for identifying liver fibrosis in HCV-infected Alaska Native persons is similar to that reported in other populations and could help prioritize patients for treatment living in areas without access to liver biopsy. Change in APRI/FIB-4 was not predictive of degree of fibrosis.

Several studies have demonstrated that the expression of odorant receptors (ORs) occurs in various tissues. These findings have served as a basis for functional studies that demonstrate the potential of ORs as drug targets for a clinical application. To the best of our knowledge, this report describes the first evaluation of the mRNA expression of ORs and the localization of OR proteins in the human retina that set a stage for subsequent functional analyses. RNA-Sequencing datasets of three individual neural retinae were generated using Next-generation sequencing and were compared to previously published but reanalyzed datasets of the peripheral and the macular human retina and to reference tissues. The protein localization of several ORs was investigated by immunohistochemistry. The transcriptome analyses detected an average of 14 OR transcripts in the neural retina, of which OR6B3 is one of the most highly expressed ORs. Immunohistochemical stainings of retina sections localized OR2W3 to the photosensitive outer segment membranes of cones, whereas OR6B3 was found in various cell types. OR5P3 and OR10AD1 were detected at the base of the photoreceptor connecting cilium, and OR10AD1 was also localized to the nuclear envelope of all of the nuclei of the retina. The cell type-specific expression of the ORs in the retina suggests that there are unique biological functions for those receptors.

It is generally agreed that in olfactory sensory neurons (OSNs), the binding of odorant molecules to their specific olfactory receptor (OR) triggers a cAMP-dependent signaling cascade, activating cyclic-nucleotide gated (CNG) channels. However, considerable controversy dating back more than 20 years has surrounded the question of whether alternate signaling plays a role in mammalian olfactory transduction. In this study, we demonstrate a specific alternate signaling pathway in Olfr73-expressing OSNs. Methylisoeugenol (MIEG) and at least one other known weak Olfr73 agonist (Raspberry Ketone) trigger a signaling cascade independent from the canonical pathway, leading to the depolarization of the cell. Interestingly, this pathway is mediated by Gnao activation, leading to Cl(-) efflux; however, the activation of adenylyl cyclase III (ACIII), the recruitment of Ca(2+) from extra-or intracellular stores, and phosphatidylinositol 3-kinase-dependent signaling (PI signaling) are not involved. Furthermore, we demonstrated that our newly identified pathway coexists with the canonical olfactory cAMP pathway in the same OSN and can be triggered by the same OR in a ligand-selective manner. We suggest that this pathway might reflect a mechanism for odor recognition predominantly used in early developmental stages before olfactory cAMP signaling is fully developed. Taken together, our findings support the existence of at least one odor-induced alternate signal transduction pathway in native OSNs mediated by Olfr73 in a ligand-selective manner.

In the current study, we investigate whether sense of agency over an effect coincides with the perceived time of the effect that occurs either at its usual time or earlier or later than usual. One group of participants usually perceived an action effect immediately after the action, another group delayed by 250 ms. In test blocks the effect stimulus was sometimes presented earlier or later than usual. Participants judged either the degree of experienced agency over the effect or whether the effect had appeared at its usual time, or earlier or later than usual. In both groups experienced agency and the perception of the effect's time 'as usual' were highly correlated. To rule out that time judgments influenced sense of agency, we replicated the pattern of agency judgments in Experiment 2 in which participants only judged agency. Taken together, we demonstrated that agency and time judgments vary similarly across temporal deviations of effects irrespective of to which delay participants were adapted to. The high correlation of judgment types indicates that perceiving an effect at its usual time and sensing to have caused the effect are closely related. In contrast, physical temporal proximity of actions and effects has only a minor impact on experienced agency.

Purpose: Tear duct obstruction can be treated with probing and stenting, providing a reduced reoperation rate. A new instrument combining punctual dilation with the graduated diameter probe and bony-rasp was developed to assist the procedure., Methods: Laterality, type of nasolacrimal disorder, type of procedure, patient age, and postoperative outcome were monitored for one surgeon for two decades., Results: From 617 cases of pediatric tear duct obstruction, 494 used the bilateral, monocanalicular Farson method, yielding a 1.7% reoperation rate and 0.6% wire-strip rate. The nasolacrimal duct dilator rasp multi-tool, used since 1996, had a similarly low rate of complications., Conclusions: The Farson technique with the multi-tool provides an affordable, effective procedure for childhood nasolacrimal obstruction, allowing home removal of the stent., (Copyright 2016, SLACK Incorporated.)

Olfaction is one of the most crucial senses for vertebrates regarding foraging and social behavior. Therefore, it is of particular interest to investigate the sense of smell, its function on a molecular level, the signaling proteins involved in the process and the mechanism of required ion transport. In recent years, the precise role of the ion transporter NKCC1 in olfactory sensory neuron (OSN) chloride accumulation has been a controversial subject. NKCC1 is expressed in OSNs and is involved in chloride accumulation of dissociated neurons, but it had not been shown to play a role in mouse odorant sensation. Here, we present electro-olfactogram recordings (EOG) demonstrating that NKCC1-deficient mice exhibit significant defects in perception of a complex odorant mixture (Henkel100) in both air-phase and submerged approaches. Using next generation sequencing (NGS) and RT-PCR experiments of NKCC1-deficient and wild type mouse transcriptomes, we confirmed the absence of a highly expressed ion transporter that could compensate for NKCC1. Additional histological investigations demonstrated a reduced number of cells in the olfactory epithelium (OE), resulting in a thinner neuronal layer. Therefore, we conclude that NKCC1 is an important transporter involved in chloride ion accumulation in the olfactory epithelium, but it is also involved in OSN neurogenesis., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Sense of agency, the feeling of causing a certain event, depends largely on the delay between an action and its ensuing effect: The feeling to control an effect that is caused by our preceding action is stronger the closer the effect follows the action in time. Yet, repeatedly experiencing an effect after a constant delay might alter this general rule. Here, we assessed sense of agency for effects that occurred 0-250 ms after an action in conditions in which the effect either mostly occurred immediately or mostly delayed after 250 ms after the action. Participants who experienced mostly delayed effects rated their influence over the effect's occurrence to be larger the longer the action-effect interval was. Thus, sense of agency is not always stronger at shorter action-effect intervals, but rather depends on the match between the agent's expectations and the actual timing of events., (Copyright © 2014 Elsevier B.V. All rights reserved.)

When an action produces an effect, both events are perceived to be shifted in time toward each other. This shift is called Intentional Binding (IB) effect. First evidence shows that this shift does not depend on the statistical predictability of the produced effect's identity (Desantis, Hughes, & Waszak, 2012). We confirm this result by comparing the perceived duration of action-effect intervals before valid and invalid action effects using the method of constant stimuli. The perceived duration of action-effect intervals did not differ for valid and invalid effects. This result was true for different durations of the action-effect interval (Experiments 1-4: 250 ms, Experiments 1 & 2: 400 ms), different effect modalities (Experiments 1 & 3: visual, Experiments 2-4: auditive), and two types of validity variations (Experiments 1 & 2: 80% valid, Experiments 3 & 4: 100% valid vs. random). We validated our results by using a clock paradigm and a numerical duration estimation task (Experiment 4). We conclude that the IB effect is not the result of internal prediction due to action-effect bindings, but might rely on higher-order processes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: An experiment was conducted to investigate the impacts of length and variability of system response time (SRT) on user behavior and user experience (UX) in sequential computing tasks., Background: Length is widely considered to be the most important aspect of SRTs in human-computer interaction. Research on temporal attention shows that humans adjust to temporal structures and that performance substantially improves with temporal predictability., Method: Participants performed a sequential task with simulated office software. Duration and variability, that is, the number of different SRTs, was manipulated. Lower variability came at the expense of on average higher durations. User response times, task execution times, and failure rates were measured to assess user performance. UX was measured with a questionnaire., Results: A reduction in variability improved user performance significantly. Whereas task load and failure rates remained constant, responses were significantly faster. Although a reduction in variability came along with, on average, increased SRTs, no difference in UX was found., Conclusion: Considering SRT variability when designing software can yield considerable performance benefits for the users. Although reduced variability comes at the expense of overall longer SRTs, the interface is not subjectively evaluated to be less satisfactory or demanding. Time design should aim not only at reducing average SRT length but also at finding the optimum balance of length and variability., Application: Our findings can easily be applied in any user interface for sequential tasks. User performance can be improved without loss of satisfaction by selectively prolonging particular SRTs to reduce variability.

Intentional binding describes the phenomenon that actions and their effects are perceived to be temporally approximated. We introduced a new method of duration estimation to the research field, the method of constant stimuli. Participants freely chose to press one of two keys or experienced passive key presses. After an interval of 250 ms or 600 ms a visual effect occurred. In Experiment 1, each key produced an effect after a specific interval. In Experiment 2, both keys produced an effect after the same interval that varied between sessions. Participants compared the duration of the action-effect interval with a tone of varying duration. To assess intentional binding, we compared the perceived duration of the action-effect interval between the active and passive condition. We showed intentional binding for 600 ms, but not for 250 ms action-effect intervals in both experiments. Thus, the method of constant stimuli is suitable to assess intentional binding., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Action effects do not occur randomly in time but follow our actions at specific delays. The ideomotor principle (IMP) is widely used to explain how the relation between actions and contingently following effects is acquired and numerous studies demonstrate robust action-effect learning. Yet, little is known about the acquisition of temporal delays of action effects. Here, we demonstrate that participants learn that action effects occur at specific delays. Participants responded slower to action effects that occurred earlier than usual. In addition, participants often prematurely responded before the effect when it occurred later than expected. Thus, in contrast to biases of time perception in action contexts (e.g., Haggard, Trends Cogn Sci 9:290-295, 2005; Stetson et al., Neuron 51:651-659, 2006), participants learn and exploit temporal regularities between actions and effects for behavioral control.

Ribosomally produced thiopeptide antibiotics are highly promising lead compounds targeting the GTPase-associated region (GAR) of the bacterial ribosome. A representative panel of GAR mutants suspected to confer resistance against thiopeptide antibiotics was reconstituted in vitro and quantitatively studied with fluorescent probes. It was found that single-site mutations of the ribosomal 23S rRNA binding site region directly affect thiopeptide affinity. Quantitative equilibrium binding data clearly identified A1067 as the base contributing most strongly to the binding environment. The P25 residue on the ribosomal protein L11 was essential for binding of the monocyclic thiopeptides micrococcin and promothiocin B, confirming that the mutation of this residue in the producer organism confers self-resistance. For the bicyclic thiopeptides thiostrepton and nosiheptide, all studied single-site resistance mutations on the L11 protein were still fully capable of ligand binding in the upper pM range, both in the RNA-protein complex and in isolated 70S ribosomes. These single-site mutants were then specifically reconstituted in Bacillus subtilis, confirming their efficacy as resistance-conferring. It is thus reasoned that, in contrast to modifications of the 23S rRNA in the GAR, mutations of the L11 protein do not counteract binding of bicyclic thiopeptides, but allow the ribosome to bypass the protein biosynthesis blockade enforced by these antibiotics in the wild type.

Background: Genetic manipulation of the allograft is an attractive approach to prevent the graft against chronic deterioration through stable expression of immunomodulatory or protective genes. However, the best strategy for prevention of chronic allograft deterioration remains unclear., Methods: The efficacies of adeno-associated viral vector-mediated stable expression of indoleamine 2,3-dioxygenase (IDO), cytotoxic T-lymphocyte associated antigen 4 with human immunoglobulin G(1) (CTLA4Ig) or interleukin-10 (IL-10) in the prevention of chronic allograft deterioration were compared in a rat heart transplantation model., Results: Transduction of grafts with IL-10 significantly prolonged allograft survival, whereas transduction of grafts with IDO did not improve graft survival compared to controls. Analysis of long-term survived heart allografts showed that both CTLA4Ig and IL-10 could significantly reduced the T cells and macrophage infiltration. However, stable expression of CTLA4Ig failed to prevent the development of transplant arteriosclerosis. By contrast, IL-10 suppressed the development of transplant arteriosclerosis effectively. The suppressive effects of IL-10 in preventing the development of chronic allograft deterioration were associated with lower transcript levels of transforming tumor growth factor beta 1 and macrophage migration inhibitory factor in the graft. In addition, higher transcript levels of heme oxygenase-1 were found in IL-10-transduced allograft., Conclusions: Targeting on IL-10 is superior to CTLA4Ig or IDO for the treatment of chronic allograft deterioration., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

The chromosome end-replicating enzyme telomerase is composed of a template-containing RNA subunit, a reverse transcriptase (TERT), and additional proteins. The importance of conserved amino acid residues in Trt1p, the TERT of Schizosaccharomyces pombe, was tested. Mutation to alanine of the proposed catalytic aspartates in reverse transcriptase motifs A and C and of conserved amino acids in motifs 1 and B' resulted in defective growth, progressive loss of telomeric DNA, and loss of detectable telomerase enzymatic activity in vitro. Mutation of the phenylalanine (F) in the conserved FYxTE of telomerase-specific motif T had no phenotype in vivo or in vitro whereas mutation of a conserved amino acid in RT motif 2 had an intermediate effect. In addition to identifying single amino acids of TERT required for telomere maintenance in the fission yeast, this work provides useful tools for S. pombe telomerase research: a functional epitope-tagged version of Trt1p that allows detection of the protein even in crude cellular extracts, and a convenient and robust in vitro enzymatic activity assay based on immunopurification of telomerase.