Ureteropelvic junction obstruction secondary to parapelvic cyst encased ureter.

We present a 64-year-old male who presented with right-sided flank pain secondary to a parapelvic cyst impinging on the proximal ureter. However, intraoperative findings showed that the ureter was encased within the parapelvic cyst and secondarily obstructed at the UPJ rather than extrinsically compressed by the cyst. This specific anatomic variant is exceedingly rare as no published cases with similar anatomy could be identified.

Cooperative and Orthogonal Switching in the Solid State Enabled by Metal-Organic Framework Confinement Leading to a Thermo-Photochromic Platform.

Cooperative behavior and orthogonal responses of two classes of coordinatively integrated photochromic molecules towards distinct external stimuli were demonstrated on the first example of a photo-thermo-responsive hierarchical platform. Synergetic and orthogonal responses to temperature and excitation wavelength are achieved by confining the stimuli-responsive moieties within a metal-organic framework (MOF), leading to the preparation of a novel photo-thermo-responsive spiropyran-diarylethene based material. Synergistic behavior of two photoswitches enables the study of stimuli-responsive resonance energy transfer as well as control of the photoinduced charge transfer processes, milestones required to advance optoelectronics development. Spectroscopic studies in combination with theoretical modeling revealed a nonlinear effect on the material electronic structure arising from the coordinative integration of photoresponsive molecules with distinct photoisomerization mechanisms. Thus, the reported work covers multivariable facets of not only fundamental aspects of photoswitch cooperativity, but also provides a pathway to modulate photophysics and electronics of multidimensional functional materials exhibiting thermo-photochromism.

Is Pain in the Uninjured Arm Associated With Unhelpful Thoughts and Distress Regarding Symptoms During Recovery From Upper-Extremity Injury?

PURPOSE: During recovery from upper-extremity injury, patients sometimes express concerns regarding pain associated with increased use of the uninjured limb. Concerns about discomfort associated with increased use may represent a manifestation of unhelpful thoughts such as catastrophic thinking or kinesiophobia. We asked the following questions: (1) Among people recovering from an isolated unilateral upper-extremity injury, is pain intensity in the uninjured arm associated with unhelpful thoughts and feelings of distress regarding symptoms, accounting for other factors? (2) Is pain intensity in the injured extremity, magnitude of capability, or accommodation of pain associated with unhelpful thoughts and feelings of distress regarding symptoms? METHODS: In this cross-sectional study of new or returning patients presenting to a musculoskeletal specialist for care for an upper-extremity injury, the patients completed scales that were used to measure the following: pain intensity in the uninjured arm, pain intensity in the injured arm, upper-extremity-specific magnitude of capability, symptoms of depression, symptoms of health anxiety, catastrophic thinking, and accommodation of pain. Multivariable analysis was used to evaluate factors associated with pain intensity in the uninjured arm, pain intensity in the injured arm, magnitude of capability, and pain accommodation, controlling for other demographic and injury-related factors. RESULTS: Greater pain intensity in both uninjured and injured arms was independently associated with greater unhelpful thinking regarding symptoms. A greater magnitude of capability and pain accommodation were independently associated with less unhelpful thinking regarding symptoms. CONCLUSIONS: Given that greater pain intensity in the uninjured upper extremity is associated with greater unhelpful thinking, clinicians can be attuned to patient concerns about contralateral pain. Clinicians can facilitate recovery from upper-extremity injury by evaluating the uninjured limb as well as identifying and ameliorating unhelpful thinking regarding symptoms. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Is Pain in the Uninjured Leg Associated With Unhelpful Thoughts and Distress Regarding Symptoms During Recovery From Lower Extremity Injury?

BACKGROUND: Patients recovering from lower extremity injuries often interpret discomfort associated with increased use of the uninjured leg as a potential indication of harm. If expressed concerns regarding contralateral leg pain are associated with unhelpful thinking regarding symptoms, they can signal orthopaedic surgeons to gently reorient these thoughts to help improve comfort and capability during recovery. QUESTIONS/PURPOSES: We asked: (1) Among people recovering from isolated traumatic lower extremity injury, is pain intensity in the uninjured leg associated with unhelpful thoughts and feelings of distress regarding symptoms, accounting for other factors? (2) Are pain intensity in the injured leg, magnitude of capability, and accommodation of pain associated with unhelpful thoughts and feelings of distress regarding symptoms? METHODS: Between February 2020 and February 2022, we enrolled 139 patients presenting for an initial evaluation or return visit for any traumatic lower extremity injury at the offices of one of three musculoskeletal specialists. Patients had the option to decline filling out our surveys, but because of the cross-sectional design, required fields on the electronic survey tools, and monitored completion, there were few declines and few incomplete surveys. The median age of participants was 41 years (IQR 32 to 58), and 48% (67 of 139) were women. Fifty percent (70 of 139) injured their right leg. Sixty-five percent (91 of 139) had operative treatment of their fracture. Patients completed measures of pain intensity in the uninjured leg, pain intensity in the injured leg, lower extremity-specific magnitude of capability, symptoms of depression, symptoms of health anxiety, catastrophic thinking, and accommodation of pain. Multivariable analysis sought factors independently associated with pain intensity in the uninjured leg, pain intensity in the injured leg, magnitude of capability, and pain accommodation, controlling for other demographic and injury-related factors. RESULTS: Greater pain intensity in the uninjured leg (regression coefficient [RC] 0.09 [95% CI 0.02 to 0.16]; p < 0.01) was moderately associated with more unhelpful thinking regarding symptoms. This indicates that for every one-unit increase in unhelpful thinking regarding symptoms on the 17-point scale we used to measure pain catastrophizing, pain intensity in the uninjured leg increases by 0.94 points on the 11-point scale that we used to measure pain intensity, holding all other independent variables constant. Greater pain intensity in the injured leg (RC 0.18 [95% CI 0.08 to 0.27]; p < 0.01) was modestly associated with more unhelpful thinking regarding symptoms. Greater pain accommodation (RC -0.25 [95% CI -0.38 to -0.12]; p < 0.01) was modestly associated with less unhelpful thinking regarding symptoms. Greater magnitude of capability was not independently associated with less unhelpful thinking regarding symptoms. CONCLUSION: A patient's report of concerns regarding pain in the uninjured limb (such as, "I'm overcompensating for the pain in my other leg") can be considered an indicator of unhelpful thinking regarding symptoms. Orthopaedic surgeons can use such reports to recognize unhelpful thinking and begin guiding patients toward healthier thoughts and behaviors. LEVEL OF EVIDENCE: Level II, prognostic study.

AAV5-miHTT-mediated huntingtin lowering improves brain health in a Huntington's disease mouse model.

Huntingtin (HTT)-lowering therapies show great promise in treating Huntington's disease. We have developed a microRNA targeting human HTT that is delivered in an adeno-associated serotype 5 viral vector (AAV5-miHTT), and here use animal behaviour, MRI, non-invasive proton magnetic resonance spectroscopy and striatal RNA sequencing as outcome measures in preclinical mouse studies of AAV5-miHTT. The effects of AAV5-miHTT treatment were evaluated in homozygous Q175FDN mice, a mouse model of Huntington's disease with severe neuropathological and behavioural phenotypes. Homozygous mice were used instead of the more commonly used heterozygous strain, which exhibit milder phenotypes. Three-month-old homozygous Q175FDN mice, which had developed acute phenotypes by the time of treatment, were injected bilaterally into the striatum with either formulation buffer (phosphate-buffered saline + 5% sucrose), low dose (5.2 × 109 genome copies/mouse) or high dose (1.3 × 1011 genome copies/mouse) AAV5-miHTT. Wild-type mice injected with formulation buffer served as controls. Behavioural assessments of cognition, T1-weighted structural MRI and striatal proton magnetic resonance spectroscopy were performed 3 months after injection, and shortly afterwards the animals were sacrificed to collect brain tissue for protein and RNA analysis. Motor coordination was assessed at 1-month intervals beginning at 2 months of age until sacrifice. Dose-dependent changes in AAV5 vector DNA level, miHTT expression and mutant HTT were observed in striatum and cortex of AAV5-miHTT-treated Huntington's disease model mice. This pattern of microRNA expression and mutant HTT lowering rescued weight loss in homozygous Q175FDN mice but did not affect motor or cognitive phenotypes. MRI volumetric analysis detected atrophy in four brain regions in homozygous Q175FDN mice, and treatment with high dose AAV5-miHTT rescued this effect in the hippocampus. Like previous magnetic resonance spectroscopy studies in Huntington's disease patients, decreased total N-acetyl aspartate and increased myo-inositol levels were found in the striatum of homozygous Q175FDN mice. These neurochemical findings were partially reversed with AAV5-miHTT treatment. Striatal transcriptional analysis using RNA sequencing revealed mutant HTT-induced changes that were partially reversed by HTT lowering with AAV5-miHTT. Striatal proton magnetic resonance spectroscopy analysis suggests a restoration of neuronal function, and striatal RNA sequencing analysis shows a reversal of transcriptional dysregulation following AAV5-miHTT in a homozygous Huntington's disease mouse model with severe pathology. The results of this study support the use of magnetic resonance spectroscopy in HTT-lowering clinical trials and strengthen the therapeutic potential of AAV5-miHTT in reversing severe striatal dysfunction in Huntington's disease.

Confinement-Driven Photophysics in Hydrazone-Based Hierarchical Materials.

Confinement-imposed photophysics was probed for novel stimuli-responsive hydrazone-based compounds demonstrating a conceptual difference in their behavior within 2D versus 3D porous matrices for the first time. The challenges associated with photoswitch isomerization arising from host interactions with photochromic compounds in 2D scaffolds could be overcome in 3D materials. Solution-like photoisomerization rate constants were realized for sterically demanding hydrazone derivatives in the solid state through their coordinative immobilization in 3D scaffolds. According to steady-state and time-resolved photophysical measurements and theoretical modeling, this approach provides access to hydrazone-based materials with fast photoisomerization kinetics in the solid state. Fast isomerization of integrated hydrazone derivatives allows for probing and tailoring resonance energy transfer (ET) processes as a function of excitation wavelength, providing a novel pathway for ET modulation.

Huntingtin Overexpression Does Not Alter Overall Survival in Murine Cancer Models.

A reduced incidence of various forms of cancer has been reported in Huntington's disease patients and may be due to pro-apoptotic effects of mutant huntingtin. We tested this hypothesis by assessing the effects of huntingtin protein overexpression on survival in two murine cancer models. We generated YAC HD mice containing human huntingtin transgenes with various CAG tract lengths (YAC18, YAC72, YAC128) on either an Msh2 or p53 null background which have increased cancer incidence. In both mouse models of cancer, the overexpression of either mutant or wild-type huntingtin had no significant effect on overall survival. These results do not support the hypothesis that mutant huntingtin expression is protective against cancer.

LNP-mediated delivery of CRISPR RNP for wide-spread in vivo genome editing in mouse cornea.

CRISPR/Cas9-based genome-editing therapies are poised to change the clinical outcome for many diseases with validated therapeutic targets awaiting an appropriate delivery system. Recent advances in lipid nanoparticle (LNP) technology make them an attractive platform for the delivery of various forms of CRISPR/Cas9, including the efficient and transient Cas9/gRNA ribonucleoprotein (RNP) complexes. In this study, we initially tested our novel LNP platform by delivering pre-complexed RNPs and template DNA to cultured mouse cortical neurons, and obtained successful ex vivo genome editing. We then directly injected LNP-packaged RNPs and DNA template into the mouse cornea to evaluate in vivo delivery. For the first time, we demonstrated wide-spread genome editing in the cornea using our LNP-RNPs. The ability of our LNPs to transfect the cornea highlights the potential of our novel delivery platform to be used in CRISPR/Cas9-based genome editing therapies of corneal diseases.

The effect of mindfulness-based stress reduction on the urinary microbiome in interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the impact of mindfulness-based stress reduction therapy on the urinary microbiome of patients with interstitial cystitis/bladder pain syndrome. METHODS: In this Institutional Review Board-approved prospective cohort study, patients with interstitial cystitis/bladder pain syndrome were recruited to attend an 8-week mindfulness-based stress reduction course involving yoga and meditation. Eligible participants were English-speaking women aged 18 or older with interstitial cystitis/bladder pain syndrome. All participants had a negative urinalysis within 2 months of enrollment and were currently undergoing first- or second-line treatment at the time of recruitment. The mindfulness-based stress reduction course met weekly for 1 h. A straight-catheter urine sample was obtained prior to and following the mindfulness-based stress reduction series. DNA from urine samples underwent bacterial 16S ribosomal gene sequencing at Johns Hopkins University Laboratories followed by taxonomic abundance and diversity analysis by Resphera Biosciences Laboratory. Participants completed validated symptom questionnaires pre- and post-intervention. RESULTS: A total of 12 participants completed the 8-week course and were included in the analysis. The average age was 59 and the majority identified as white. Patient symptoms, measured by the Urogenital Distress Inventory Short Form and Interstitial Cystitis Symptom and Pain Indices, improved significantly (all p < 0.05). Overall composition of the urinary microbiome changed significantly (p < 0.01) and demonstrated an increase in diversity following the intervention. CONCLUSIONS: Mindfulness-based stress reduction therapy improves patient symptoms and was associated with significant changes in the urinary microbiome in patients with interstitial cystitis/bladder pain syndrome.

Chlorhexidine Versus Iodine for Vaginal Preparation Before Hysterectomy: A Randomized Clinical Trial.

OBJECTIVE: The American College of Obstetricians and Gynecologists does not provide a recommendation regarding the preferred vaginal preparation solution. We intended to compare the effectiveness of chlorhexidine versus iodine in decreasing vaginal bacterial counts. METHODS: In this institutional review board-approved study, participants undergoing total hysterectomy via vaginal or laparoscopic approach were randomized to 4% chlorhexidine or 10% iodine for presurgical vaginal preparation. Swabs were collected from the vaginal mucosa before, then 30, 60, and 90 minutes after preparation. Our primary outcome was the number of positive cultures (≥5,000 bacteria) at 90 minutes. The secondary outcomes included the presence of selected pathogens, postoperative complications, and infections. The sample size of 71 per arm was calculated using ɑP = 0.05, 80% power, and anticipating a 22% difference in positive cultures. RESULTS: Between May 2018 and August 2019, 85 participants were randomized. The average age was 59.8 years (SD, 11.4), and the median Charlson Comorbidity Index score was 2 (minimum, 0; maximum, 6). Baseline bacterial counts were similar in both groups. Chlorhexidine demonstrated a lower percentage of positive cultures at 90 minutes (47.6% vs 85.4%; odds ratio, 10.6; P = 0.001). In addition, the median bacterial count in the chlorhexidine group was significantly lower than the iodine group (3,000 vs 24,000 colony-forming units, P < 0.001) at 90 minutes. No surgical site infections were identified in either group during the 30-day postoperative period, and there were no reported adverse reactions to either solution. CONCLUSIONS: Chlorhexidine resulted in substantially lower bacterial counts after preparation compared with iodine. Gynecologic surgeons may consider switching to 4% chlorhexidine for vaginal preparation before hysterectomy.

Footprint evidence of early hominin locomotor diversity at Laetoli, Tanzania.

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage1-3. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity3-5. In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli.

Intracerebroventricular Administration of AAV9-PHP.B SYN1-EmGFP Induces Widespread Transgene Expression in the Mouse and Monkey Central Nervous System.

Viral vectors made from adeno-associated virus (AAV) have emerged as preferred tools in basic and translational neuroscience research to introduce or modify genetic material in cells of interest. The use of viral vectors is particularly attractive in nontransgenic species, such as nonhuman primates. Injection of AAV solutions into the cerebrospinal fluid is an effective method to achieve a broad distribution of a transgene in the central nervous system. In this study, we conducted injections of AAV9-PHP.B, a recently described AAV capsid mutant, in the lateral ventricle of mice and rhesus macaques. To enhance the expression of the transgene (the tag protein emerald green fluorescent protein [EmGFP]), we used a gene promoter that confers high neuron-specific expression of the transgene, the human synapsin 1 (SYN1) promoter. The efficacy of the viral vector was first tested in mice. Our results show that intracerebroventricular injections of AAV9-PHP.B SYN1-EmGFP-woodchuck hepatitis virus posttranscriptional regulatory element resulted in neuronal EmGFP expression throughout the mice and monkey brains. We have provided a thorough characterization of the brain regions expressing EmGFP in both species. EmGFP was observed in neuronal cell bodies over the whole cerebral cortex and in the cerebellum, as well as in some subcortical regions, including the striatum and hippocampus. We also observed densely labeled neuropil in areas known to receive projections from these regions. Double fluorescence studies demonstrated that EmGFP was expressed by several types of neurons throughout the mouse and monkey brain. Our results demonstrate that a single injection in the lateral ventricle is an efficient method to obtain transgene expression in many cortical and subcortical regions, obviating the need of multiple intraparenchymal injections to cover large brain areas. The use of intraventricular injections of AAV9-PHP.B SYN1-EmGFP could provide a powerful approach to transduce widespread areas of the brain and may contribute to further development of methods to genetically target-specific populations of neurons.

Mapping past human land use using archaeological data: A new classification for global land use synthesis and data harmonization.

In the 12,000 years preceding the Industrial Revolution, human activities led to significant changes in land cover, plant and animal distributions, surface hydrology, and biochemical cycles. Earth system models suggest that this anthropogenic land cover change influenced regional and global climate. However, the representation of past land use in earth system models is currently oversimplified. As a result, there are large uncertainties in the current understanding of the past and current state of the earth system. In order to improve representation of the variety and scale of impacts that past land use had on the earth system, a global effort is underway to aggregate and synthesize archaeological and historical evidence of land use systems. Here we present a simple, hierarchical classification of land use systems designed to be used with archaeological and historical data at a global scale and a schema of codes that identify land use practices common to a range of systems, both implemented in a geospatial database. The classification scheme and database resulted from an extensive process of consultation with researchers worldwide. Our scheme is designed to deliver consistent, empirically robust data for the improvement of land use models, while simultaneously allowing for a comparative, detailed mapping of land use relevant to the needs of historical scholars. To illustrate the benefits of the classification scheme and methods for mapping historical land use, we apply it to Mesopotamia and Arabia at 6 kya (c. 4000 BCE). The scheme will be used to describe land use by the Past Global Changes (PAGES) LandCover6k working group, an international project comprised of archaeologists, historians, geographers, paleoecologists, and modelers. Beyond this, the scheme has a wide utility for creating a common language between research and policy communities, linking archaeologists with climate modelers, biodiversity conservation workers and initiatives.

Utilization of a Mirror During Pelvic Examinations: Does it Improve the Patient's Experience?

OBJECTIVE: This study was conducted to assess the utility of a mirror in improving pain and vulnerability during a pelvic examination. METHODS: In this prospective, institutional review board-approved, 2-cohort trial, all "new" patients presenting to a urogynecology office were offered to have a mirror or no-mirror present during their pelvic examination. Patients completed 100-mm visual analog scales regarding pain, anxiety, knowledge, control, embarrassment, and vulnerability before and after examination. The primary outcome was difference in level of pain and vulnerability between groups. Secondary outcomes included comparisons from baseline to postexamination scores within groups, patient satisfaction, and examination duration. A sample size of 68 participants in each arm was planned. RESULTS: From April 2019 to May 2020, 147 participants were enrolled. Two participants were excluded, 145 were included in the final analysis; 74 in the no-mirror group and 71 in the mirror group. The average age was 55.9 (±13) years, and the groups were overall similar. There was no difference in primary outcomes of pain or vulnerability, but the mirror group showed improved levels of control (P = 0.006) and knowledge (P = 0.018) following examination. All participants reported high satisfaction, and those that selected a mirror reported strong preference for future use. CONCLUSIONS: Patients who chose to use the mirror did not demonstrate a difference in pain or vulnerability scores; however, they exhibited benefit to their sense of control and knowledge after the pelvic examination. Although the mirror did not benefit all patients, this is a simple option that could improve the examination experience for some.Clinical Trial Registration:ClinicalTrials.gov, NCT03785548.

Development of an α-synuclein knockdown peptide and evaluation of its efficacy in Parkinson's disease models.

Convincing evidence supports the premise that reducing α-synuclein levels may be an effective therapy for Parkinson's disease (PD); however, there has been lack of a clinically applicable α-synuclein reducing therapeutic strategy. This study was undertaken to develop a blood-brain barrier and plasma membrane-permeable α-synuclein knockdown peptide, Tat-ßsyn-degron, that may have therapeutic potential. The peptide effectively reduced the level of α-synuclein via proteasomal degradation both in cell cultures and in animals. Tat-ßsyn-degron decreased α-synuclein aggregates and microglial activation in an α-synuclein pre-formed fibril model of spreading synucleinopathy in transgenic mice overexpressing human A53T α-synuclein. Moreover, Tat-ßsyn-degron reduced α-synuclein levels and significantly decreased the parkinsonian toxin-induced neuronal damage and motor impairment in a mouse toxicity model of PD. These results show the promising efficacy of Tat-ßsyn-degron in two different animal models of PD and suggest its potential use as an effective PD therapeutic that directly targets the disease-causing process.

PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington's disease.

DNA damage repair genes are modifiers of disease onset in Huntington's disease (HD), but how this process intersects with associated disease pathways remains unclear. Here we evaluated the mechanistic contributions of protein inhibitor of activated STAT-1 (PIAS1) in HD mice and HD patient-derived induced pluripotent stem cells (iPSCs) and find a link between PIAS1 and DNA damage repair pathways. We show that PIAS1 is a component of the transcription-coupled repair complex, that includes the DNA damage end processing enzyme polynucleotide kinase-phosphatase (PNKP), and that PIAS1 is a SUMO E3 ligase for PNKP. Pias1 knockdown (KD) in HD mice had a normalizing effect on HD transcriptional dysregulation associated with synaptic function and disease-associated transcriptional coexpression modules enriched for DNA damage repair mechanisms as did reduction of PIAS1 in HD iPSC-derived neurons. KD also restored mutant HTT-perturbed enzymatic activity of PNKP and modulated genomic integrity of several transcriptionally normalized genes. The findings here now link SUMO modifying machinery to DNA damage repair responses and transcriptional modulation in neurodegenerative disease.

Dynamic magnetic resonance imaging following native tissue vaginal reconstructive surgery; a prospective study.

INTRODUCTION AND HYPOTHESIS: To describe the impact of native tissue vaginal reconstruction on pelvic anatomy using dynamic magnetic resonance imaging. METHODS: This prospective single-cohort observational study involved women undergoing native tissue reconstruction with intraperitoneal vaginal vault suspension for pelvic organ prolapse. Concomitant procedures such as hysterectomy, midurethral sling, and anterior or posterior colporrhaphy were allowed. Enrolled participants underwent dynamic pelvic imaging pre- and postoperatively. Radiographic and anatomic measurements were compared. Secondary outcomes included validated patient questionnaires. RESULTS: Fourteen participants were included in the analysis. The mean age was 62 years; all participants were Caucasian. Most participants had stage III pelvic organ prolapse. Significant improvements were noted in several radiographic measurements. The average H-line (representing levator hiatus width) with straining maneuvers improved following surgery (7.2 cm preoperatively vs. 6.6 cm postoperatively, p = 0.015). The average M-line (representing levator muscular descent) improved significantly with both straining (4.0 cm preoperatively vs. 3.0 cm postoperatively, p < 0.001) and defecatory maneuvers (6.2 cm preoperatively vs. 5.2 cm postoperatively, p = 0.001). The average size of cystocele improved from 5.6 cm (moderate) preoperatively to 0.7 cm (absent descent) postoperatively (p < 0.001). The average descent of the vaginal apex with defecation preoperatively was 3.0 cm (moderate) and 0 cm (absent descent) postoperatively (p = 0.003). Posterior compartment descent with defecation did not change following surgical intervention (5.8 cm preoperatively vs. 5.2 cm postoperatively, p = 0.056). Pelvic Organ Prolapse Quantification measurements improved in all compartments, and Pelvic Floor Distress Inventory-20 scores improved significantly following surgery (102 preoperatively vs. 30 postoperatively, p < 0.001). CONCLUSIONS: Native tissue reconstruction with intraperitoneal vaginal vault suspension resulted in significant anatomic improvements, as defined by physical examination and dynamic magnetic resonance imaging.

Spontaneous, solvent-free entrapment of siRNA within lipid nanoparticles.

Lipid nanoparticle (LNP) formulations of nucleic acid are leading vaccine candidates for COVID-19, and enabled the first approved RNAi therapeutic, Onpattro. LNPs are composed of ionizable cationic lipids, phosphatidylcholine, cholesterol, and polyethylene glycol (PEG)-lipids, and are produced using rapid-mixing techniques. These procedures involve dissolution of the lipid components in an organic phase and the nucleic acid in an acidic aqueous buffer (pH 4). These solutions are then combined using a continuous mixing device such as a T-mixer or microfluidic device. In this mixing step, particle formation and nucleic acid entrapment occur. Previous work from our group has shown that, in the absence of nucleic acid, the particles formed at pH 4 are vesicular in structure, a portion of these particles are converted to electron-dense structures in the presence of nucleic acid, and the proportion of electron-dense structures increases with nucleic acid content. What remained unclear from previous work was the mechanism by which vesicles form electron-dense structures. In this study, we use cryogenic transmission electron microscopy and dynamic light scattering to show that efficient siRNA entrapment occurs in the absence of ethanol (contrary to the established paradigm), and suggest that nucleic acid entrapment occurs through inversion of preformed vesicles. We also leverage this phenomenon to show that specialized mixers are not required for siRNA entrapment, and that preformed particles at pH 4 can be used for in vitro transfection.

The influence of postoperative environment on patient pain and satisfaction: a randomized trial.

BACKGROUND: Improving the patient experience, controlling pain with nonopiate therapies, and preparing for value-based reimbursement are increasingly important foci for both physicians and hospitals. OBJECTIVE: We aimed to determine whether the addition of music and a natural landscape image to postoperative hospital rooms would result in improved pain and satisfaction scores among inpatients undergoing pelvic reconstructive surgery. STUDY DESIGN: This randomized controlled trial was approved by an Institutional Review Board. Eligible candidates were 18-85 years old, English speaking, and scheduled to undergo native tissue vaginal vault suspension for symptomatic pelvic organ prolapse. Patients with history of a chronic pain or substance abuse were excluded. Subjects were advised that the purpose of the study was to assess the effect of changes to the hospital environment on patient experience but were blinded to their group and intervention details. Changes included a landscape image mounted to the wall and access to a speaker with preprogrammed music selections. The intervention group was instructed to listen to their preferred music for a minimum of 2 30-minute sessions postoperatively. The control group had a standard hospital room, without music or landscape. All patient rooms were private. The primary outcome was the visual analog scale for pain in the morning of postoperative day 1. Secondary outcomes included narcotic use, likelihood to refer family to the same hospital facility, satisfaction with care and the hospital, and perception of a healing environment. A sample size of 43 subjects per arm was calculated to detect a difference of 10 mm in visual analog scale pain score. RESULTS: A total of 133 subjects were enrolled; primary outcome data were available for 92 (46 per arm). The mean age was 63.8 (standard deviation, 9.5) years, median Charlson comorbidity score was 2 (min, 0; max, 7), and 94.6% of subjects were white. On postoperative day 1, median visual analog scale pain scores were low (28.8 mm [0, 86]; 24.5 mm [0, 81]) and did not differ between intervention and control, respectively (P=.57). Total morphine equivalents (P=.817) and nursing pain scores (P=.774) were also similar. However, the intervention group displayed a higher likelihood to refer family members to the hospital (98 mm (47, 100); 96 mm (65, 100); P=.037). At postoperative 2 weeks, the intervention group indicated higher satisfaction with their care (98 mm, (34, 100); 95 mm (42, 100); P=.032), the hospital (98 mm (71, 100); 94 mm (6, 100); P=.004), and the healing environment provided during their stay (98 mm; 92 mm (19, 100); P=.020) than those in the standard hospital rooms. CONCLUSION: In this randomized trial, we found music and landscape imagery did not substantially affect postoperative pain scores; however, they had a positive effect on the postoperative experience. Furthermore, this effect appeared to broaden 2 weeks after surgery. Given the importance of value-based care, interventions such as these should be emphasized to enhance patient satisfaction, quality scores, and overall well-being.

Addressing apical support during hysterectomy for prolapse: a NSQIP review.

OBJECTIVE: To describe national practice patterns regarding apical support procedures at time of hysterectomy for prolapse prior to the American College of Obstetricians and Gynecologists (ACOG) 2017 Practice Bulletin on pelvic organ prolapse. METHODS: This retrospective descriptive study analyzed 24 months of data from the National Surgical Quality Improvement Program (NSQIP) database, from 2015 and 2016. Patients undergoing hysterectomy for the indication of pelvic organ prolapse were included. Surgical details, diagnostic codes, subspecialty, patient demographics, and postoperative complications were collected. Comparisons were conducted between those who did and did not undergo apical support procedures. Further comparisons, including logistic regressions, were performed using subspecialty designation. RESULTS: During the study period, 3458 hysterectomies were performed for the indication of pelvic organ prolapse. Of this population, 76% were White, with an average age of 61 years, BMI of 27.6, and parity of 2, and 90.5% carried the diagnosis of apical prolapse. Slightly over half (51.8%) had a concurrent procedure to support the vaginal apex. When performed by Female Pelvic Medicine and Reconstructive Surgery (FPMRS) physicians, 65.7% underwent an apical suspension at time of hysterectomy for prolapse compared with 40.2% of non-FPMRS (p < 0.001). Annual rates of apical support procedures showed significant improvement from 49.5% in 2015 to 55.2% in 2016 (P < 0.001). Regarding surgical data, addition of apical support procedures increased operative time by 33 min, and reoperation was 1.3% higher (0.3% vs 1.6%). CONCLUSION: Our results demonstrate that in the 2 years prior to ACOG's recommendation only 51.8% of women undergoing hysterectomy for pelvic organ prolapse received concurrent procedures to address apical support.