A Visual and Narrative Timeline Review of Spinal Cord Stimulation Technology and US Food and Drug Administration Milestones.

OBJECTIVES: The aim of this study was to present key technologic and regulatory milestones in spinal cord stimulation (SCS) for managing chronic pain on a narrative timeline with visual representation, relying on original sources to the extent possible. MATERIALS AND METHODS: We identified technical advances in SCS that facilitated and enhanced treatment on the basis of scientific publications and approvals from the United States (US) Food and Drug Administration (FDA). We presented milestones limited to first use in key indications and in the context of new technology validation. We focused primarily on pain management, but other indications (eg, motor disorder in multiple sclerosis) were included when they affected technology development. RESULTS: We developed a comprehensive visual and narrative timeline of SCS technology and US FDA milestones. Since its conception in the 1960s, the science and technology of SCS neuromodulation have continuously evolved. Advances span lead design (from paddle-type to percutaneous, and increased electrode contacts) and stimulator technology (from wireless power to internally powered and rechargeable, with miniaturized components, and programmable multichannel devices), with expanding stimulation program flexibility (such as burst and kilohertz stimulation frequencies), as well as usage features (such as remote programming and magnetic resonance imaging conditional compatibility). CONCLUSIONS: This timeline represents the evolution of SCS technology alongside expanding FDA-approved indications for use.

Leaning in and moving forward: a call to action and review of diversity initiatives in SAGES.

BACKGROUND: Diversity, equity, and inclusion have been an intentional focus for SAGES well before the COVID-19 pandemic and the coincident societal recognition of social injustices and racism. Longstanding inequities within our society, healthcare, and the surgery profession have come to light in the aftermath of events that rose to attention around the time of Covid. In so doing, they have brought into focus disparities, injustices, and inequalities that have long been present in the field of surgery, selectively affecting the most vulnerable. METHODS: This White paper examines the current state of diversity within the field of surgery and SAGES (Society of American Gastrointestinal and Endoscopic Surgeons) approach and effort to pave the way forward to meaningful change. We delineate the imperative for diversity, equity, and inclusion for all. By all, we mean to be inclusive of the diversity of gender and sexual orientation, race, ethnicity, geography, sex, and disability in the field of surgery. RESULTS: SAGES is an organization that lives at the intersection of education and innovation. It has a vital role in assisting the surgical profession in addressing these issues and needs and being a force alongside others for sustained and necessary change. SAGES can only realize these goals through a commitment across all aspects of the organization to embed diversity, equity, and inclusion into our very fabric. CONCLUSION: True diversity, equity, and inclusion within a surgical organization is vital for its longevity, growth, relevance, and impact. Unfortunately, the absence of DEI limits opportunity, robs the organization of collective intelligence in an environment in which its presence is critical, contributes to health inequities, and impoverishes all within the society and its value to all with whom it interfaces. SAGES is an organization that lives at the intersection of education and innovation. It has a vital role in assisting the surgical profession in addressing these issues and needs and being a force alongside others for sustained and necessary change. SAGES can only realize these goals through a commitment across all aspects of the organization to embed diversity, equity, and inclusion into our very fabric. Strategies like those highlighted in this White Paper, may be within our grasp and we can learn yet more if we remain in a place of humility and teachability in the future.

Influence of Packed Food Labeling on Shopping Practices: A Cross-Sectional Study.

Background: The basic product information, health, safety, and nutritional details, as well as food marketing, advertising, and promotion, are all provided on a packed food label. This study was carried out to assess the knowledge, attitude, and practices of the shoppers regarding food labels as there are few studies done in India and none in Pune. Methodology: A cross-sectional study was carried out among 226 participants using a validated semi-structured questionnaire, which consisted of sociodemographic details and questions on their knowledge, attitude, and practice regarding food labels while purchasing a packed food item. Quantitative data are presented in the form of mean, standard deviation, 95% confidence interval (CI) of mean, median, and interquartile range (IQR). Qualitative data are in terms of number (N), percentages (%), and 95% CI of percentage. Results: Of the 226 participants, 163 (72.12) were aware of the label on packaged foods. One hundred seventy-seven (78.32%) participants in all read the label on the packaged food. The maximum retail price (MRP) and expiration date were the most frequent labels sought. Although 17.7% of consumers did not consider nutrient composition when making a purchase, energy and protein were the most often considered nutrients. The majority (70.35%) falsely believed that juice was healthy. The packed food label's tiny font made it difficult to read for 30.38% of the customers. Conclusion: Despite the increased awareness about packed food labeling, a fraction of shoppers were not concerned about nutritional information. In contrast to the prevailing knowledge, the majority believes packed food has a positive effect on health.

Fetal lower urinary tract obstruction: international Delphi consensus on management and core outcomes set.

OBJECTIVE: To reach a Delphi-generated international expert consensus on the diagnosis, prognostic, management, and core outcome set (COS) of fetal Lower Urinary Tract Obstruction (LUTO). METHODS: A three-round Delphi procedure was conducted among an international panel of LUTO experts. The panel was provided with a list of literature review-generated parameters for the diagnosis, prognostic, management, and outcomes. A parallel procedure was conducted along with patient groups during the development of COS. RESULTS: A total of 160 experts were approached, of whom 99 completed the first round and 80 (80/99, 80.8%) completed all three rounds. In the first trimester, an objective measurement of longitudinal bladder diameter (with ≥7 mm being abnormal) should be used to suspect LUTO. In the second trimester, imaging parameters of LUTO could include: a) an enlarged bladder, b) a keyhole sign, c) bladder wall thickening, d) bilateral hydro (uretero) nephrosis, and e) male sex. There was a lack of consensus on the current prognostic scoring literature. However, experts agreed on the value of amniotic fluid volume (< 24 weeks) to predict survival and that the value of fetal intervention is to improve neonatal survival. While experts endorsed the role of sonographic parameters of renal dysplasia, at least one vesicocentesis, and urine biochemistry for prognosis and counseling, these items did not reach a consensus for determining fetal intervention candidacy. On the other hand, imaging parameters suggestive of LUTO, absence of life-limiting structural or genetic anomalies, gestational age of ≥16 weeks, and oligohydramnios defined as deepest vertical pocket (DVP) <2 cm should be used as candidacy criteria for fetal intervention based on experts' consensus. If a bladder refill was evaluated, it should be assessed subjectively. Vesicoamniotic shunt should be the first line of fetal intervention. In the presence of suspected fetal renal failure, serial amnioinfusion should only be offered as an experimental procedure under research protocols. The core outcome set for future studies was agreed upon. CONCLUSION: International consensus on the diagnosis, prognosis, and management of fetal LUTO, as well as the Core Outcome Set, should inform clinical care and research to optimize perinatal outcomes. This article is protected by copyright. All rights reserved.

Psychological wellbeing in parents of children with Down syndrome: A systematic review and meta-analysis.

We report a review examining the psychological wellbeing of parents of children with Down syndrome (DS) relative to that of parents of typically developing (TD) children. A systematic search identified 57 relevant studies, which were synthesised meta-analytically. Relative to their counterparts with TD children, mothers and fathers of children with DS reported higher levels of parenting stress (mothers: g = 0.57, 95% CI [0.33, 0.81]; fathers: g = 0.40, [0.24, 0.56]), depressive symptoms (mothers: g = 0.42, [0.23, 0.61]; fathers: g = 0.25, [0.02, 0.48]) and psychological distress (mothers: g = 0.45, [0.30, 0.60]; fathers: g = 0.63, [0.26, 0.99]). Small effects were found for anxiety for mothers (g = 0.16, [0.03, 0.29]), with no differences for fathers (g = 0.03, [-0.25, 0.32]). No group differences were found for positive impact of parenting (mothers: g = -0.09, [-0.25, 0.07]; fathers: g = -0.04, [-0.30, 0.22]), while evidence concerning other positive wellbeing outcomes was limited. No significant moderating effects of child age range, country income level, or group differences in parental education level were identified, but limited subgroup analyses were possible. Raising a child with DS may be associated with elevated stress, depressive symptoms, and psychological distress for mothers and fathers. However, levels of parenting reward appear equivalent to those experienced by parents raising TD children.

The effect of psychiatric decision unit services on inpatient admissions and mental health presentations in emergency departments: an interrupted time series analysis from two cities and one rural area in England.

AIMS: High-quality evidence is lacking for the impact on healthcare utilisation of short-stay alternatives to psychiatric inpatient services for people experiencing acute and/or complex mental health crises (known in England as psychiatric decision units [PDUs]). We assessed the extent to which changes in psychiatric hospital and emergency department (ED) activity were explained by implementation of PDUs in England using a quasi-experimental approach. METHODS: We conducted an interrupted time series (ITS) analysis of weekly aggregated data pre- and post-PDU implementation in one rural and two urban sites using segmented regression, adjusting for temporal and seasonal trends. Primary outcomes were changes in the number of voluntary inpatient admissions to (acute) adult psychiatric wards and number of ED adult mental health-related attendances in the 24 months post-PDU implementation compared to that in the 24 months pre-PDU implementation. RESULTS: The two PDUs (one urban and one rural) with longer (average) stays and high staff-to-patient ratios observed post-PDU decreases in the pattern of weekly voluntary psychiatric admissions relative to pre-PDU trend (Rural: -0.45%/week, 95% confidence interval [CI] = -0.78%, -0.12%; Urban: -0.49%/week, 95% CI = -0.73%, -0.25%); PDU implementation in each was associated with an estimated 35-38% reduction in total voluntary admissions in the post-PDU period. The (urban) PDU with the highest throughput, lowest staff-to-patient ratio and shortest average stay observed a 20% (-20.4%, CI = -29.7%, -10.0%) level reduction in mental health-related ED attendances post-PDU, although there was little impact on long-term trend. Pooled analyses across sites indicated a significant reduction in the number of voluntary admissions following PDU implementation (-16.6%, 95% CI = -23.9%, -8.5%) but no significant (long-term) trend change (-0.20%/week, 95% CI = -0.74%, 0.34%) and no short- (-2.8%, 95% CI = -19.3%, 17.0%) or long-term (0.08%/week, 95% CI = -0.13, 0.28%) effects on mental health-related ED attendances. Findings were largely unchanged in secondary (ITS) analyses that considered the introduction of other service initiatives in the study period. CONCLUSIONS: The introduction of PDUs was associated with an immediate reduction of voluntary psychiatric inpatient admissions. The extent to which PDUs change long-term trends of voluntary psychiatric admissions or impact on psychiatric presentations at ED may be linked to their configuration. PDUs with a large capacity, short length of stay and low staff-to-patient ratio can positively impact ED mental health presentations, while PDUs with longer length of stay and higher staff-to-patient ratios have potential to reduce voluntary psychiatric admissions over an extended period. Taken as a whole, our analyses suggest that when establishing a PDU, consideration of the primary crisis-care need that underlies the creation of the unit is key.

Incomplete resupination during floral development leads to pollination failure in a slipper orchid.

In many families, plants undergo floral resupination by twisting through approximately 180° during floral development so that the flower is effectively positioned upside down. In most orchids, resupination results in the median petal (i.e., the labellum) becoming lowermost, which plays a crucial role in pollination by serving as a landing platform or as a trapping device, or both. Incomplete resupination is predicted to lead to reduced pollination, although tests of this assumption are still lacking. We investigated the effect of resupination using Phragmipedium vittatum, a rare lady's slipper orchid whose specialized labellum forms a trapping device. First, we surveyed the natural occurrence of incomplete resupination. Then we manipulated flowers into non- (≈0°), half- (≈90°), and fully resupinate (≈180°) positions to test the effect of orientation on pollen smear removal and deposition by pollinators (female hoverflies). We found that ca. 10% of flowers in the natural population were not fully resupinate, being either non- (upward, 0-60°) or half-resupinate (sideward, 60-120°). The change in orientation prevented the effectiveness of pollination by hoverflies since no pollen smear removal or deposition were found in flowers from non- and half-resupinate treatments. Although these flowers still attracted hoverflies, they were not trapped effectively. As this orchid is incapable of autonomous self-pollination, flowers that do not resupinate fail to set fruits. These results highlight the importance of correct floral orientation provided by resupination to ensure pollination in orchids and other resupinate flowers.

Flower orientation and corolla length as reproductive barriers in the pollinator-driven divergence of Erica shannonea and Erica ampullacea.

A variety of reproductive barriers can enable reproductive isolation and stable coexistence of plant species. Differing floral traits might play an important role in reproductive isolation imposed by pollinators. Such shifts in pollinator use have been hypothesized to contribute to the radiation of Erica (Ericaceae) in the Cape Floristic Region, South Africa. The sister species Erica shannonea and Erica ampullacea co-occur and overlap in flowering phenology. Both have unscented long-tubed flowers consistent with adaptations for pollination by long-proboscid flies (LPFs), but differences in flower orientation and corolla tube length are indicative of a shift in pollinator species. We conducted controlled pollination experiments and pollinator observations to determine the breeding system and pollinators of the two species. Both species are self-incompatible and require pollinator visits for seed production, suggesting that pollinators could strongly influence flower evolution. The horizontally orientated flowers of E. shannonea were found to be pollinated by Philoliche rostrata (Tabanidae), which has a long, fixed forward-pointing proboscis, while the vertically upright orientated flowers of E. ampullacea were found to be pollinated by Prosoeca westermanni (Nemestrinidae), which has a shorter proboscis that can swivel downwards. The nemestrinid fly's proboscis is too short to access the nectar in the relative long-tubed flowers of E. shannonea and the tabanid fly's proboscis cannot swivel down to access the upright flowers of E. ampullacea. Consequently, these traits are likely to act as reproductive barriers between the two Erica species and thereby might have contributed to speciation and enable stable coexistence.

A US-based national surveillance study for the susceptibility and epidemiology of Clostridioides difficile isolates with special reference to ridinilazole: 2020-2021.

We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype.

Ramsey Spectroscopy of the 2S_{1/2} Hyperfine Interval in Atomic Hydrogen.

The 2S_{1/2} hyperfine interval in atomic hydrogen was measured using Ramsey spectroscopy with a thermal beam cooled to cryogenic temperatures. The measured value is 177 556 838.87(85) Hz, which represents the most precise determination of this interval to date. The 1S_{1/2} hyperfine interval f(1S_{1/2}) and the 2S_{1/2} hyperfine interval f(2S_{1/2}) can be combined to give the quantity D_{21}=8f(2S_{1/2})-f(1S_{1/2}), which mostly eliminates uncertainty due to nuclear structure effects and is well described by bound-state quantum electrodynamics. Using the value of f(2S_{1/2}) from this work gives a value of D_{21}^{expt}=48 959.2(6.8) Hz, which is in agreement with the theoretical value of D_{21}^{Theory}=48 954.1(2.3) Hz.

Novel insights into diminished cardiac reserve in non-obstructive hypertrophic cardiomyopathy from four-dimensional flow cardiac magnetic resonance component analysis.

AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by hypercontractility and diastolic dysfunction, which alter blood flow haemodynamics and are linked with increased risk of adverse clinical events. Four-dimensional flow cardiac magnetic resonance (4D-flow CMR) enables comprehensive characterization of ventricular blood flow patterns. We characterized flow component changes in non-obstructive HCM and assessed their relationship with phenotypic severity and sudden cardiac death (SCD) risk. METHODS AND RESULTS: Fifty-one participants (37 non-obstructive HCM and 14 matched controls) underwent 4D-flow CMR. Left-ventricular (LV) end-diastolic volume was separated into four components: direct flow (blood transiting the ventricle within one cycle), retained inflow (blood entering the ventricle and retained for one cycle), delayed ejection flow (retained ventricular blood ejected during systole), and residual volume (ventricular blood retained for >two cycles). Flow component distribution and component end-diastolic kinetic energy/mL were estimated. HCM patients demonstrated greater direct flow proportions compared with controls (47.9 ± 9% vs. 39.4 ± 6%, P = 0.002), with reduction in other components. Direct flow proportions correlated with LV mass index (r = 0.40, P = 0.004), end-diastolic volume index (r = -0.40, P = 0.017), and SCD risk (r = 0.34, P = 0.039). In contrast to controls, in HCM, stroke volume decreased with increasing direct flow proportions, indicating diminished volumetric reserve. There was no difference in component end-diastolic kinetic energy/mL. CONCLUSION: Non-obstructive HCM possesses a distinctive flow component distribution pattern characterised by greater direct flow proportions, and direct flow-stroke volume uncoupling indicative of diminished cardiac reserve. The correlation of direct flow proportion with phenotypic severity and SCD risk highlight its potential as a novel and sensitive haemodynamic measure of cardiovascular risk in HCM.

Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

Taking the path of least resistance now, but not later: Pushing cognitive effort into the future reduces effort discounting.

Effort discounting describes the devaluation of rewards that require effort to obtain. The present study investigated whether discounting of cognitive effort depends on how near the effort is in time. The present study also investigated whether effort discounting, and its modulation by temporal distance to the effort, might depend on need for cognition, a personality trait that describes how much one enjoys cognitively demanding tasks. Participants performed a validated effort discounting task that measured the extent to which they subjectively devalued a $20 reward when effort was required to receive it. Immediacy of the effort was manipulated by having participants imagine exerting varying levels of effort either immediately, in a day, or in a month. Results revealed linear increases in discounting of rewards as a function of both how much effort was involved and how imminent the effort was. The extent to which both these variables influenced discounting correlated with need for cognition. Individuals low in need for cognition exhibited more effort discounting overall and a linear increase in effort discounting as the effort grew imminent. Individuals high in need for cognition engaged in less effort discounting, which was not modulated by how imminent the effort was. These results indicate that people exhibit dynamic inconsistency in effort-related decisions, such that the degree to which they discount effort depends on how soon the effort is. Additionally, this tendency is linked with systematic individual differences in need for cognition. Lastly, this study demonstrates that these tendencies can be quantitatively operationalized.

Bystander LECT2 amyloidosis in tumor nephrectomy.

Pathologic evaluation of the non-neoplastic renal parenchyma in tumor nephrectomy specimens is critical and can detect both renal-limited and systemic pathologies. We report the case of a 69-year-old Punjabi male who underwent cytoreductive nephrectomy for advanced renal cell carcinoma after immunotherapy. We detected clinically unexpected leukocyte chemotactic factor 2 (LECT2) amyloidosis during pathologic analysis of the surrounding non-neoplastic renal parenchyma, which was confirmed by mass spectrometry. LECT2 amyloidosis occurs predominantly in Hispanic patients and has only rarely been described in Punjabi patients. This case highlights the importance of careful pathologic evaluation of the non-neoplastic renal parenchyma of nephrectomy specimens and raises awareness that LECT2 amyloidosis can occur outside of the typical demographic of Hispanic patients.