Probing Molecular Packing of Amorphous Pharmaceutical Solids Using X-ray Atomic Pair Distribution Function and Solid-State NMR.

The structural investigation of amorphous pharmaceuticals is of paramount importance in comprehending their physicochemical stability. However, it has remained a relatively underexplored realm primarily due to the limited availability of high-resolution analytical tools. In this study, we utilized the combined power of X-ray pair distribution functions (PDFs) and solid-state nuclear magnetic resonance (ssNMR) techniques to probe the molecular packing of amorphous posaconazole and its amorphous solid dispersion at the molecular level. Leveraging synchrotron X-ray PDF data and employing the empirical potential structure refinement (EPSR) methodology, we unraveled the existence of a rigid conformation and discerned short-range intermolecular C-F contacts within amorphous posaconazole. Encouragingly, our ssNMR 19F-13C distance measurements offered corroborative evidence supporting these findings. Furthermore, employing principal component analysis on the X-ray PDF and ssNMR data sets enabled us to gain invaluable insights into the chemical nature of the intermolecular interactions governing the drug-polymer interplay. These outcomes not only furnish crucial structural insights facilitating the comprehension of the underlying mechanisms governing the physicochemical stability but also underscore the efficacy of synergistically harnessing X-ray PDF and ssNMR techniques, complemented by robust modeling strategies, to achieve a high-resolution exploration of amorphous structures.

Barriers and facilitators to engaging in smoking cessation support among lung screening participants.

INTRODUCTION: Embedded smoking cessation support within lung cancer screening is recommended in the UK; however, little is known about why individuals decline smoking cessation support in this setting. This study identified psychosocial factors that influence smoking cessation and quit motivation among those who declined support for quitting smoking alongside lung cancer screening. METHODS: Qualitative interviews conducted between August 2019 - April 2021 with thirty adults with a smoking history, recruited from the Yorkshire Lung Screening Trial. Participants had declined smoking cessation support. Verbatim interview transcripts were thematically analysed. RESULTS: Fifty percent of participants were male and the majority were from the most deprived groups. Participants reported low motivation and a variety of barriers to stopping smoking. Participants described modifiable behavioural factors that influenced their quit motivation including self-efficacy, perceived effectiveness of stop-smoking services including smoking cessation aids, risk-minimising beliefs, lack of social support, absence of positive influences on smoking and beliefs about smoking/smoking cessation. Broader contextual factors included social isolation and stigma, COVID-19 and comorbid mental and physical health conditions that deterred smoking cessation. CONCLUSIONS: To encourage engagement in smoking cessation support during lung cancer screening, interventions should seek to encourage positive beliefs about the effectiveness of smoking cessation aids and increase confidence in quitting as part of supportive, person-centred care. Interventions should also acknowledge the wider social determinants of health among the lung screening-eligible population. IMPLICATIONS: This study provides an in-depth understanding of the beliefs surrounding smoking and smoking cessation and further potential psychosocial factors that influence those attending lung cancer screening. Many of the barriers to smoking cessation found in the present study are similar to those outside of a lung screening setting however this work offers an understanding of potential facilitators that should be considered in future lung screening programmes.

Readmissions and perioperative outcomes for same-day versus next-day discharge after prolapse surgery.

INTRODUCTION AND HYPOTHESIS: We aimed to evaluate the safety of same-day discharge (SDD) compared with next-day discharge (NDD) after prolapse surgery on a national level hypothesizing that readmission and complication rates after SDD would not be higher than NDD. METHODS: We performed a retrospective cohort study using the National Surgical Quality Improvement Program database including 2014-2018. Current Procedural Terminology (CPT) codes were used to identify minimally invasive apical suspensions or obliterative procedures. Exclusion criteria were length of stay > 1 day, unrelated concomitant procedures, serious medical comorbidities, American Society of Anesthesiologists (ASA) Class >2, and complication during index admission. The primary outcome was 30-day readmission, and secondary outcomes included 30-day complications. RESULTS: 12,583 were included in analysis. SDD rate was 16.7%. The majority of women were white (91%) with a mean age of 59 years and mean body mass index of 28 kg/m². Medical comorbidities were similar between the SDD and NDD groups. Overall incidence of 30-day readmission was 1.7%. SDD had lower odds of 30-day readmission than NDD (aOR 0.63, 95% CI 0.41-0.98). SDD had lower odds of 30-day complications but this failed to reach statistical significance (aOR 0.67, 95% CI 0.44-1.03). CONCLUSIONS: In this cohort, 30-day readmission and complication rates were not higher after SDD compared to NDD in women undergoing minimally-invasive apical suspension or obliterative procedures. We interpret these findings carefully given study limitations but believe our findings support the safety of SDD after minimally invasive apical suspension or obliterative procedures in a low-risk population.

A pilot randomized controlled trial of vaginal estrogen on postpartum atrophy, perineal pain, and sexual function.

INTRODUCTION AND HYPOTHESIS: Vulvovaginal symptoms following perineal laceration may be worsened by atrophy related to decreased estrogen. Our objective was to evaluate the effect of local estrogen therapy in this setting. METHODS: We conducted a single-center, pilot, randomized, placebo-controlled trial of local estradiol in primiparous women with a second-degree or greater perineal laceration following a term vaginal delivery. Participants were randomized to twice weekly estradiol or placebo cream from delivery through 3 months postpartum. The primary outcome was a validated measure of vulvovaginal symptoms at 12 weeks postpartum. Secondary outcomes included measures of perineal pain, quality of life, sexual function, ease of use, likelihood of continued use, and adverse events. RESULTS: We planned to enroll 70 women; however, due to human subjects research restrictions related to the COVID-19 pandemic, enrollment was stopped early. A total of 59 women were randomized, 31 to the estradiol group and 28 to the placebo group. Nearly all participants (95%) were followed through 12 weeks with suggestion of marginal improvement in Vulvar Assessment Scale scores [-0.10; 90% CI = (-0.20, 0.01)] in those randomized to estradiol compared to placebo. Local estradiol was not associated with improvement in other measures, and only one non-serious adverse event was observed. CONCLUSIONS: In primiparous women with a perineal laceration, use of local estradiol showed minimal clinical benefit in vulvovaginal atrophy and related symptoms but appears to be acceptable and safe for postpartum use. Larger adequately powered trials enrolling a diverse group of postpartum women are needed to affirm these findings.

Co-development of an evidence-based personalised smoking cessation intervention for use in a lung cancer screening context.

BACKGROUND: Optimising smoking cessation services within a low radiation-dose computed tomography (LDCT) lung cancer screening programme has the potential to improve cost-effectiveness and overall efficacy of the programme. However, evidence on the optimal design and integration of cessation services is limited. We co-developed a personalised cessation and relapse prevention intervention incorporating medical imaging collected during lung cancer screening. The intervention is designed to initiate and support quit attempts among smokers attending screening as part of the Yorkshire Enhanced Stop Smoking study (YESS: ISRCTN63825779). Patients and public were involved in the development of an intervention designed to meet the needs of the target population. METHODS: An iterative co-development approach was used. Eight members of the public with a history of smoking completed an online survey to inform the visual presentation of risk information in subsequent focus groups for acceptability testing. Three focus groups (n = 13) were conducted in deprived areas of Yorkshire and South Wales with members of the public who were current smokers or recent quitters (within the last year). Exemplar images of the heart and lungs acquired by LDCT, absolute and relative lung cancer risk, and lung age were shown. Data were analysed thematically, and discussed in stakeholder workshops. Draft versions of the intervention were developed, underpinned by the Extended Parallel Processing Model to increase self-efficacy and response-efficacy. The intervention was further refined in a second stakeholder workshop with a patient panel. RESULTS: Individual LDCT scan images of the lungs and heart, in conjunction with artistic impressions to facilitate interpretation, were considered by public participants to be most impactful in prompting cessation. Public participants thought it important to have a trained practitioner guiding them through the intervention and emphasising the short-term benefits of quitting. Presentation of absolute and relative risk of lung cancer and lung age were considered highly demotivating due to reinforcement of fatalistic beliefs. CONCLUSION: An acceptable personalised intervention booklet utilising LDCT scan images has been developed for delivery by a trained smoking cessation practitioner. Our findings highlight the benefit of co-development during intervention development and the need for further evaluation of effectiveness.

Supporting patients to stop smoking when they attend lung cancer screening will improve the overall benefit and value for money of the service. This study developed a booklet containing pictures of a person's own lungs and heart taken during a lung cancer screening scan. The booklet shows areas of damage to the heart and lungs caused by smoking, delivered alongside positive messages to build confidence to stop smoking and let patients know about the benefits of stopping smoking. To develop the booklet, we worked with members of public who currently or used to smoke. Eight members of public completed a survey asking about the best ways to present information about risk. Thirteen members of the public took part in focus groups to co-develop the booklet. One workshop with academic and healthcare professionals and one workshop with a public involvement panel were held to develop and finalise the booklet. Members of the public said they wanted information about the short-term benefits of quitting smoking, and that coloured drawings next to the scan picture would help them to understand what the scan picture meant. Having someone specially trained to guide them through the booklet was considered important. Being told about their risk for lung cancer in the future was off-putting and might discourage a quit attempt. We have co-developed a booklet to support people to quit smoking when they go for lung cancer screening. The booklet is currently being tested to see whether it can support people to quit smoking.

Salts and Polymorph Screens for Bedaquiline.

Bedaquiline is used to treat multi-resistant tuberculosis in adults. The fumarate salt is commercially available and used in the product Sirturo. To provide open access to bedaquiline molecule once the patent on the chemical substance expires, new salts were screened. This work offers additional information on the bedaquiline system, as new salts may present better pharmacokinetic properties. The current studies focus on the attempted isolation of the acetate, benzoate, benzenesulfonate, hydrobromide, succinate, hydrochloride, tartrate, lactate, maleate, malate, and mesylate salts of bedaquiline. Potential salts were screened using a unique combination of conventional screening, and small-scale experiments supplemented by crystallographic analysis and infrared microspectroscopy. Salts were prepared on a larger scale by dissolving 1:1 ratios of the individual salt formers and bedaquiline base (30 mg, 0.055 mmol) in different solvents and allowing the solutions to evaporate or crystallize. X-ray diffraction (XRD) techniques and spectroscopic and thermal analyses were employed to characterize the salts. The benzoate and maleate salts were selected as lead candidates after reviewing preliminary characterization data. To determine the most stable forms for the leads, a polymorph screen was conducted using solvents of various polarities. These salt screens successfully generated five new salts of bedaquiline, namely, benzoate, maleate, hydrochloride, besylate, and mesylate. The existence of these salts was confirmed by powder XRD, proton NMR, and IR spectroscopies. TGA and DSC thermal analysis along with hot-stage optical microscopy were further used to characterize the salts. The polymorph screen conducted on the salts suggested the absence of additional polymorphs at 1 g scale.

A multicenter retrospective cohort study comparing urethral diverticulectomy with and without pubovaginal sling.

BACKGROUND: Urethral diverticulum is a rare entity and requires a high suspicion for diagnosis based on symptoms and physical exam with confirmation by imaging. A common presenting symptom is stress urinary incontinence (SUI). The recommended treatment is surgical excision with urethral diverticulectomy. Postoperatively, approximately 37% of patients may have persistent and 16% may have de novo SUI. An autologous fascial pubovaginal sling (PVS) placed at the time of urethral diverticulectomy (UD) has the potential to prevent and treat postoperative SUI. However, little has been published about the safety and efficacy of a concomitant pubovaginal sling. OBJECTIVE: The objective of this study was to compare the clinical presentation, outcomes, complications, and diverticulum recurrence rates in women who underwent a urethral diverticulectomy with vs without a concurrent pubovaginal sling. STUDY DESIGN: This multicenter, retrospective cohort study included women who underwent a urethral diverticulectomy between January 1, 2000, and December 31, 2016. Study participants were identified by Current Procedure Terminology codes, and their records were reviewed for demographics, medical or surgical history, symptoms, preoperative testing, concomitant surgeries, and postoperative outcomes. Symptoms, recurrence rates, and complications were compared between women with and without a concomitant pubovaginal sling. The primary outcome was the presence of postoperative stress urinary incontinence symptoms. Based on a stress urinary incontinence rate of 50% with no pubovaginal sling and 10% with a pubovaginal sling, we needed a sample size of 141 participants who underwent diverticulectomy without a pubovaginal sling and 8 participants with a pubovaginal sling to achieve 83% power with P<.05. RESULTS: We identified 485 diverticulectomy cases from 11 institutions who met the inclusion criteria; of these, 96 (19.7%) cases had a concomitant pubovaginal sling. Women with a pubovaginal sling were older than those without a pubovaginal sling (53 years vs 46 years; P<.001), and a greater number of women with pubovaginal sling had undergone diverticulectomy previously (31% vs 8%; P<.001). Postoperative follow-up period (14.6±26.9 months) was similar between the groups. The pubovaginal sling group had greater preoperative stress urinary incontinence (71% vs 33%; P<.0001), dysuria (47% vs 30%; P=.002), and recurrent urinary tract infection (49% vs 33%; P=.004). The addition of a pubovaginal sling at the time of diverticulectomy significantly improved the odds of stress urinary incontinence resolution after adjusting for prior diverticulectomy, prior incontinence surgery, age, race, and parity (adjusted odds ratio, 2.27; 95% confidence interval, 1.02-5.03; P=.043). It was not significantly protective against de novo stress urinary incontinence (adjusted odds ratio, 0.86; 95% confidence interval, 0.25-2.92; P=.807). Concomitant pubovaginal sling increased the odds of postoperative short-term (<6 weeks) urinary retention (adjusted odds ratio, 2.5; 95% confidence interval, 1.04-6.22; P=.039) and long-term urinary retention (>6 weeks) (adjusted odds ratio, 6.98; 95% confidence interval, 2.20-22.11; P=.001), as well as recurrent urinary tract infections (adjusted odds ratio, 3.27; 95% confidence interval, 1.26-7.76; P=.013). There was no significant risk to develop a de novo overactive bladder (adjusted odds ratio, 1.48; 95% confidence interval, 0.56-3.91; P=.423) or urgency urinary incontinence (adjusted odds ratio, 1.47; 95% confidence interval, 0.71-3.06; P=.30). A concomitant pubovaginal sling was not protective against a recurrent diverticulum (adjusted odds ratio, 1.38; 95% confidence interval, 0.67-2.82; P=.374). Overall, the diverticulum recurrence rate was 10.1% and did not differ between the groups. CONCLUSION: This large retrospective cohort study demonstrated a greater resolution of stress urinary incontinence with the addition of a pubovaginal sling at the time of a urethral diverticulectomy. There was a considerable risk of postoperative urinary retention and recurrent urinary tract infections in the pubovaginal sling group.

Mode of anesthesia and major perioperative outcomes associated with vaginal surgery.

INTRODUCTION AND HYPOTHESIS: The primary aim was to compare the incidence of major perioperative complications in women undergoing vaginal reconstructive surgery with general, regional, and monitored anesthesia care using a national database. The secondary aim was to compare length of hospital stay, 30-day readmission rates, urinary tract infections, and reoperation rates between anesthesia types. MATERIALS AND METHODS: The National Surgical Quality Improvement Program database was used to study women undergoing vaginal surgery for pelvic floor disorders from 2006 to 2015 via Current Procedural Terminology codes. Demographic and clinical variables were abstracted. The incidence of major perioperative complications was defined as the occurrence of any of the following within 30 days of surgery: death, surgical-site infection, pneumonia, venous thromboembolism, intensive care unit admission, stroke, transfusion, sepsis, and myocardial infarction. Regression analysis was used to estimate the relative risks (RR) associated with anesthesia type for each outcome. RESULTS: From the database, we gathered data on 37,426 women who underwent vaginal reconstructive surgery between 2006 and 2015; 87.2% (n = 32,623) underwent general, 6.9% (n = 2565) regional, and 5.9% (n = 2238) monitored anesthesia care. Major perioperative complications occurred in 560 women (1.5%). Relative to general anesthesia, the adjusted risk of major perioperative complications was not significantly different in those receiving monitored or regional anesthesia [monitored vs. general, adjusted RR 0.74, 95% confidence interval (CI) 0.45-1.20; regional vs. general, adjusted RR 1.23, 95% CI 0.92-1.65]. DISCUSSION: Major perioperative complications in vaginal reconstructive surgery were uncommon, and no differences were observed between monitored, regional, and general anesthesia outcomes.

Schooling the Eye and Hand: Performative Methods of Research and Pedagogy in the Making and Knowing Project.

What are historians doing in the laboratory? Looking back over six years of collaborative work, researchers of the Making and Knowing Project at Columbia University discuss their experience with hands-on reconstruction as a historical method. This work engages practical forms of knowledge-from pigment-making to metal casting-recorded in the BnF Ms. Fr. 640, an anonymous French manuscript compiled in the later sixteenth century. Bodily encounters with materials and processes of the past offer insights into the material and mental worlds of early modern artists and artisans, and train the eye in the interpretation of historical objects. At the same time, reconstruction contributes to the interpretation of the text: it is only by attempting to implement the instructions of practical or recipe literature that these texts can be understood as vehicles of emergent knowledge that only fully manifests itself in the doing. Overall, our approach to reconstruction mirrors that of the anonymous author-practitioner, who explored a wide range of techniques through experimenting and writing.

Power in everyday life.

How does power manifest itself in everyday life? Using experience-sampling methodology, we investigated the prevalence, sources, and correlates of power in people's natural environments. Participants experienced power-relevant situations regularly, though not frequently. High power was not restricted to a limited few: almost half of the sample reported experiencing high-power positions. Positional power and subjective feelings of power were strongly related but had unique relations with several individual difference measures and independent effects on participants' affect, cognition, and interpersonal relations. Subjective feelings of power resulted more from within-participant situational fluctuation, such as the social roles participants held at different times, than from stable differences between people. Our data supported some theoretical predictions about power's effects on affect, cognition, and interpersonal relations, but qualified others, particularly highlighting the role of responsibility in power's effects. Although the power literature has focused on high power, we found stronger effects of low power than high power.

Predictive and Accelerated Formulation Design Using Synchrotron Methods.

Predictive formulation design and accelerated formulation design can lead to the discovery of useful formulations to support drug clinical studies and successful drug approval. Predictive formulation design can also lead to discovery of a path for commercialization, especially for poorly soluble drugs, when the target product profile is well defined and a "learning before doing" approach is implemented. One of the key components of predictive/accelerated formulation design is to understand and leverage the material properties of drug substance including solubility, BCS classification, polymorphs, salt formation, amorphous form, amorphous complex, and stability. In addition, utilizing synchrotron-based PDF (pair distribution function) analysis can provide important structural information for the formulation. This knowledge allows control of physical and chemical stability of the designed product. Finally, formulation design should link to process development following Quality by Design principles, and solid-state chemistry should play a critical role in many of the steps required to achieve Quality by Design, which can lead to successful product development.

Feasibility and acceptability of a cancer symptom awareness intervention for adults living in socioeconomically deprived communities.

BACKGROUND: Cancer survival rates in the UK are lower in comparison with similar countries in Europe and this may be linked to socioeconomic inequalities in stage of cancer diagnosis and survival. Targeted cancer awareness interventions have the potential to improve earlier symptomatic diagnosis and reduce socioeconomic inequalities in cancer outcomes. The health check is an innovative, theory-based intervention designed to increase awareness of cancer symptoms and risk factors, and encourage timely help seeking among adults living in deprived communities. METHODS: A prospective, non-randomised evaluation was undertaken to test the feasibility and acceptability of the health check for adults aged 40 years and over living in deprived areas of Wales. Primary outcomes included recruitment and retention of approximately 100 adults, reach to participants in the lowest deprivation quartile, and intervention acceptability. Secondary outcomes included self-reported cancer symptom recognition, help-seeking behaviours and state anxiety pre/post intervention. RESULTS: Of 185 individuals approached, 98 (53%) completed the intervention. Sixty-six of 98 participants were recruited from community settings (67%) and 32 from healthcare settings (33%), with 56 (57%) from the lowest deprivation quartile. Eighty-three (85%) participants completed follow-up assessment. Participants recognised on average one extra cancer symptom post intervention, with improved recognition of and anticipated presentation for non-specific symptoms. State anxiety scores remained stable. Qualitative interviews (n = 25) demonstrated that the intervention was well received and motivated change. CONCLUSIONS: Recruitment was feasible in community and healthcare settings, with good reach to adults from low socioeconomic groups. The health check intervention was acceptable and demonstrated potential for improved cancer awareness and symptom presentation, especially for non-specific symptoms, in communities most affected by cancer.

The Epstein-Barr virus encoded BART miRNAs potentiate tumor growth in vivo.

The human herpes virus Epstein-Barr virus (EBV) latently infects and drives the proliferation of B lymphocytes in vitro and is associated with several forms of lymphoma and carcinoma in vivo. The virus encodes ~30 miRNAs in the BART region, the function of most of which remains elusive. Here we have used a new mouse xenograft model of EBV driven carcinomagenesis to demonstrate that the BART miRNAs potentiate tumor growth and development in vivo. No effect was seen on invasion or metastasis, and the growth promoting activity was not seen in vitro. In vivo tumor growth was not associated with the expression of specific BART miRNAs but with up regulation of all the BART miRNAs, consistent with previous observations that all the BART miRNAs are highly expressed in all of the EBV associated cancers. Based on these observations, we suggest that deregulated expression of the BART miRNAs potentiates tumor growth and represents a general mechanism behind EBV associated oncogenesis.

Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase.

Although cells express hundreds of metalloenzymes, the mechanisms by which apoenzymes receive their metal cofactors are largely unknown. Poly(rC)-binding proteins PCBP1 and PCBP2 are multifunctional adaptor proteins that bind iron and deliver it to ferritin for storage or to prolyl and asparagyl hydroxylases to metallate the mononuclear iron center. Here, we show that PCBP1 and PCBP2 also deliver iron to deoxyhypusine hydroxylase (DOHH), the dinuclear iron enzyme required for hypusine modification of the translation factor eukaryotic initiation factor 5A. Cells depleted of PCBP1 or PCBP2 exhibited loss of DOHH activity and loss of the holo form of the enzyme in cells, particularly when cells were made mildly iron-deficient. Lysates containing PCBP1 and PCBP2 converted apo-DOHH to holo-DOHH in vitro with greater efficiency than lysates lacking PCBP1 or PCBP2. PCBP1 bound to DOHH in iron-treated cells but not in control or iron-deficient cells. Depletion of PCBP1 or PCBP2 had no effect on the cytosolic Fe-S cluster enzyme xanthine oxidase but led to loss of cytosolic aconitase activity. Loss of aconitase activity was not accompanied by gain of RNA-binding activity, a pattern suggesting the incomplete disassembly of the [4Fe-4S] cluster. PCBP depletions had minimal effects on total cellular iron, mitochondrial iron levels, and heme synthesis. Thus, PCBP1 and PCBP2 may serve as iron chaperones to multiple classes of cytosolic nonheme iron enzymes and may have a particular role in restoring metal cofactors that are spontaneously lost in iron deficient cells.

Phase I study of bendamustine with concurrent whole brain radiation therapy in patients with brain metastases from solid tumors.

A phase I study was conducted to evaluate the dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD)/recommended phase II dose of bendamustine with concurrent whole brain radiation (WBR) in patients with brain metastases (BM) from solid tumors. Four doses of intravenous weekly bendamustine were administered with 3 weeks of WBR at three dose levels (60, 80, and 100 mg/m(2)) according to a standard 3 + 3 phase I design. A total of 12 patients with solid tumor BM were enrolled in the study (six with non-small cell lung cancer, four with melanoma, one with breast cancer, and one with neuroendocrine carcinoma). The first two dose levels had three patients each, and the third dose level had six total patients. Plasma pharmacokinetic studies of bendamustine demonstrated no significant differences from pharmacokinetic characteristics of bendamustine in other studies. No DLTs were noted at any dose levels, and no grade 4 toxicities occurred. The MTD of weekly bendamustine with concurrent WBR was 100 mg/m(2). The majority of trial patients died from progressive systemic disease rather than their brain disease. The combination of weekly bendamustine with concurrent WBR was acceptably tolerated. The efficacy of this combination may be evaluated in a phase II trial with stratification by histologies.

Software-based evaluation of toric IOL orientation in a multicenter clinical study.

PURPOSE: To evaluate the rotational stability of a new one-piece hydrophobic acrylic toric intraocular lens (IOL) using a custom-developed software for analysis of slit-lamp photographs. METHODS: In a prospective, multicenter study, 174 eyes were implanted with the TECNIS Toric IOL (Abbott Medical Optics, Inc., Santa Ana, CA). A custom-developed software was used to analyze high-resolution slit-lamp photographs of 156 eyes taken at day 1 (baseline) and 1, 3, and 6 months postoperatively. The software uses iris and sclera landmarks to align the baseline image and later images for comparison. Validation of software was performed through repeated analyses of protractor images rotated from 0.1° to 10.0° and randomly selected photographs of 20 eyes. RESULTS: Software validation showed precision (repeatability plus reproducibility variation) of 0.02° using protractor images and 2.22° using slit-lamp photographs. Good quality slit-lamp images and clear landmarks were necessary for precise measurements. At 6 months, 94.2% of eyes had 5° or less change in IOL orientation versus baseline; only 2 eyes (1.4%) had axis shift greater than 30°. Most eyes were within 5° or less of rotation between 1 and 3 months (92.9%) and 3 and 6 months (94.1%). Mean absolute axis change (± standard deviation) from 1 day to 6 months was 2.70° ± 5.51°. CONCLUSIONS: The new custom software was precise and quick in analyzing slit-lamp photographs to determine postoperative toric IOL rotation.

Self-control signals and affords power.

Whom do we perceive as more powerful and prefer to give power to: Those who have self-control or those who lack it? Past theory and research provide divergent predictions. Low self-control can be seen as a form of disinhibition, and disinhibition has been associated with greater power. However, high self-control can be seen as a form of agency, which is associated with greater power. Across seven studies, we found that individuals who exhibited high self-control were seen as more powerful, and given more power, than individuals who exhibited low self-control. This result held when the low or high self-control behavior was chosen either quickly or slowly (Studies 3 and 4), and when exhibiting low versus high self-control entailed the same action but different goals (Studies 5 and 6). Study 6 demonstrated important implications of our findings for goal setting: People were perceived as more powerful and given more power when they had a modest goal but exceeded it than when they had an ambitious goal but failed to meet it, even though in both cases they performed the same action. A meta-analysis of our mediation results showed that people perceived individuals higher in self-control as more assertive and competent, which was associated with greater power perception and then with greater power conferral. Perceived competence also directly mediated the effect of self-control on power conferral. The current research addresses a theoretical debate in the power literature and contributes to a better understanding of how power is perceived and accrued. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Vosoritide Therapy in Children with Achondroplasia: Early Experience and Practical Considerations for Clinical Practice.

INTRODUCTION: Vosoritide is the first precision medical therapy approved to increase growth velocity in children with achondroplasia. Sharing early prescribing experiences across different regions could provide a framework for developing practical guidance for the real-world use of vosoritide. METHODS: Two meetings were held to gather insight and early experience from experts in Europe, the Middle East, and the USA. The group comprised geneticists, pediatric endocrinologists, pediatricians, and orthopedic surgeons. Current practices and considerations for vosoritide were discussed, including administration practicalities, assessments, and how to manage expectations. RESULTS: A crucial step in the management of achondroplasia is to determine if adequate multidisciplinary support is in place. Training for families is essential, including practical information on administration of vosoritide, and how to recognize and manage injection-site reactions. Advocated techniques include establishing a routine, empowering patients by allowing them to choose injection sites, and managing pain. Patients may discontinue vosoritide if they cannot tolerate daily injections or are invited to participate in a clinical trial. Clinicians in Europe and the Middle East emphasized the importance of assessing adherence to daily injections, as non-adherence may impact response and reimbursement. Protocols for monitoring patients receiving vosoritide may be influenced by regional differences in reimbursement and healthcare systems. Core assessments may include pubertal staging, anthropometry, radiography to confirm open physes, the review of adverse events, and discussion of concomitant or new medications-but timing of these assessments may also differ regionally and vary across institutions. Patients and families should be informed that response to vosoritide can vary in both magnitude and timing. Keeping families informed regarding vosoritide clinical trial data is encouraged. CONCLUSION: The early real-world experience with vosoritide is generally positive. Sharing these insights is important to increase understanding of the practicalities of treatment with vosoritide in the clinical setting.

Biogenesis of the cytochrome bc(1) complex and role of assembly factors.

The cytochrome bc(1) complex is an essential component of the electron transport chain in most prokaryotes and in eukaryotic mitochondria. The catalytic subunits of the complex that are responsible for its redox functions are largely conserved across kingdoms. In eukarya, the bc(1) complex contains supernumerary subunits in addition to the catalytic core, and the biogenesis of the functional bc(1) complex occurs as a modular assembly pathway. Individual steps of this biogenesis have been recently investigated and are discussed in this review with an emphasis on the assembly of the bc(1) complex in the model eukaryote Saccharomyces cerevisiae. Additionally, a number of assembly factors have been recently identified. Their roles in bc(1) complex biogenesis are described, with special emphasis on the maturation and topogenesis of the yeast Rieske iron-sulfur protein and its role in completing the assembly of functional bc(1) complex. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.