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Introduction: Degenerative spondylolisthesis causes translational and angular malalignment, resulting in a loss of segmental lordosis. This leads to compensatory adjustments in adjacent levels to maintain balance. Lateral lumbar interbody fusion (LLIF) and transforaminal lumbar interbody fusion (TLIF) are common techniques at L4-5. This study compares compensatory changes at adjacent L3-4 and L5-S1 levels six months post LLIF versus TLIF for grade 1 degenerative spondylolisthesis at L4-5., Methods: A retrospective study included patients undergoing L4-5 LLIF or TLIF with posterior pedicle screw instrumentation (no posterior osteotomy) for grade 1 spondylolisthesis. Pre-op and 6-month post-op radiographs measured segmental lordosis (L3-L4, L4-L5, L5-S1), lumbar lordosis (LL), and pelvic incidence (PI), along with PI-LL mismatch. Multiple regressions were used for hypothesis testing., Results: 113 patients (61 LLIF, 52 TLIF) were studied. TLIF showed less change in L4-5 lordosis (mean = 1.04°, SD = 4.34) compared to LLIF (mean = 4.99°, SD = 5.53) (p = 0.003). L4-5 angle changes didn't correlate with L3-4 changes, and no disparity between LLIF and TLIF was found (all p > 0.16). In LLIF, greater L4-5 lordosis change predicted reduced compensatory L5-S1 lordosis (p = 0.04), while no significant relationship was observed in TLIF patients (p = 0.12)., Conclusion: LLIF at L4-5 increases lordosis at the operated level, with compensatory decrease at L5-S1 but not L3-4. This reciprocal loss at adjacent L5-S1 may explain inconsistent improvement in lumbar lordosis (PI-LL) post L4-5 fusion., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Iron is an essential element for human health. In humans, dysregulated iron homeostasis can result in a variety of disorders and the development of cancers. Enhanced uptake, redistribution, and retention of iron in cancer cells have been suggested as an "iron addiction" pattern in cancer cells. This increased iron in cancer cells positively correlates with rapid tumor growth and the epithelial-to-mesenchymal transition, which forms the basis for tumor metastasis. However, the source of iron and the mechanisms cancer cells adopt to actively acquire iron is not well understood. In the present study, we report, for the first time, that the peptide hormone, prolactin, exhibits a novel function in regulating iron distribution, on top of its well-known pro-lactating role. When stimulated by prolactin, breast cancer cells increase CD44, a surface receptor mediating the endocytosis of hyaluronate-bound iron, resulting in the accumulation of iron in cancer cells. In contrast, macrophages, when treated by prolactin, express more ferroportin, the only iron exporter in cells, giving rise to net iron output. Interestingly, when co-culturing macrophages with pre-stained labile iron pools and cancer cells without any iron staining, in an iron free condition, we demonstrate direct iron flow from macrophages to cancer cells. As macrophages are one of the major iron-storage cells and it is known that macrophages infiltrate tumors and facilitate their progression, our work therefore presents a novel regulatory role of prolactin to drive iron flow, which provides new information on fine-tuning immune responses in tumor microenvironment and could potentially benefit the development of novel therapeutics.

Background: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known., Objectives: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation., Methods: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours within the first 24 hours postoperatively, cardiac index ≥2.2 L/min/m 2 and systemic vascular resistance <800 dyne/s/cm 5 , and vasodilatory shock not attributable to other causes. Prolonged vasoplegia was defined as that lasting 12 to 24 hours; transient vasoplegia was that lasting 6 to <12 hours. Patient characteristics, outcomes, and risk factors were analyzed., Results: Of the 600 patients who underwent CF-LVAD implantation during the study period, 182 (30.3%) developed vasoplegia. Mean patient age was similar between the vasoplegia and no-vasoplegia groups. Prolonged vasoplegia (n = 78; 13.0%), compared with transient vasoplegia (n = 104; 17.3%), was associated with greater 30-day mortality (16.7% vs 5.8%; P  = 0.02). Risk factors for prolonged vasoplegia included preoperative dialysis and elevated body mass index., Conclusions: Compared with vasoplegia overall, prolonged vasoplegia was associated with worse survival after CF-LVAD implantation. Treatment to avoid or minimize progression to prolonged vasoplegia may be warranted., Competing Interests: Dr Nair is a consultant for Abbott; and has received speaking fees from Abbott and Impulse Dynamics. Dr Frazier has received travel support from BiVACOR Inc. Dr Loor has received institutional grant support to Baylor College of Medicine from Abiomed, Transmedics, Abbott, and Maquet; and is a consultant for Abiomed & TransMedics, and is a scientific advisor for TransMedics. Dr Shafii has received institutional grant support to Baylor College of Medicine from Abbott and Evaheart, Inc. Dr Chatterjee has served on advisory boards for Edwards Lifesciences, La Jolla Pharmaceutical Company, Baxter Pharmaceuticals, and Eagle Pharmaceuticals, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Introduction: We performed Thyroseq v2 molecular testing on indeterminate thyroid nodules and evaluated whether they underwent a management change from the standard of thyroid lobectomy., Methods: We conducted a retrospective analysis of all indeterminate thyroid nodules that underwent Thyroseq v2 molecular testing from 2014 to 2019 at a large academic center. Pathology was reviewed by thyroid cytopathologists. Thyroseq results were reported benign (malignancy probability less than 10%) or suspicious (malignancy probability greater than 30%). The primary endpoint was a management change from a diagnostic lobectomy., Results: A total of 142 nodules were included: 113 (80%) Bethesda III and 29 (20%) Bethesda IV. Seventy-three nodules underwent surgical management and 69 did not. We noted a change in management in 64% (91/142) of nodules. Patients who underwent a change in management to no surgery had a significantly higher rate of benign Thyroseq result than those without a change (75.8% vs. 49.0%, p = 0.001). On logistic regression analysis, a benign Thyroseq result was a positive independent predictor of a change to no surgery (OR 3.87, 95% CI 1.69-8.89). Nodule size, multiple nodules, compressive symptoms, and history of hypothyroidism were not significant. Of the 91 patients who underwent a management change, 71% (65/91) did not undergo surgery. On follow-up (average 985 ± 615 days), 12% (8/65) of those nodules were growing or developed suspicious features requiring surgery., Conclusions: Molecular testing helped avoid surgery in almost half our population with indeterminate thyroid nodules, and benign results may help avoid surgery in asymptomatic patients with indeterminate thyroid nodules., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Left ventricular assist devices (LVADs) are increasingly used as destination therapy or as a bridge to future cardiac transplant in patients with end-stage heart failure. Extracorporeal membrane oxygenation (ECMO) can be used to bridge patients in cardiogenic shock or with decompensated heart failure to durable mechanical circulatory support. We assessed outcomes in patients in critical cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1) who underwent implantation of a continuous-flow (CF)-LVAD, with or without preoperative ECMO bridging. For this retrospective study, we selected INTERMACS profile 1 patients who underwent CF-LVAD implantation at our institution between Sep 1, 2004 and Nov 30, 2018. Of 768 patients identified, 133 (17.3%) were INTERMACS profile 1; 26 (19.5%) received preoperative ECMO support, and 107 (80.5%) did not. Postimplantation outcomes were compared between the ECMO and no-ECMO groups. No significant differences were found in 30-day mortality (15.4 vs. 15.9%, P = 0.95) or survival at 1 year (53.8 vs. 60.9%, P = 0.51). Three patients who received ECMO before CF-LVAD implantation subsequently underwent cardiac transplant. In the ECMO group, the lactate level 1 day after ECMO initiation was lower in survivors than nonsurvivors (2.7 ± 2.2 vs. 7.4 ± 4.2 mmol/L, P = 0.02; area under the curve = 0.85, P = 0.01) after CF-LVAD implantation. Bridging with ECMO to CF-LVAD implantation in carefully selected INTERMACS profile 1 patients (those who are at the highest risk for critical cardiogenic shock and for whom palliation may be the only other option) produced acceptable postoperative outcomes.Field of research: Artificial lung/ECMO., (© 2021. The Japanese Society for Artificial Organs.)

Abstract: This tri-institutional study describes the outcomes of utilization of newly developed, standardized, rotation-specific evaluations for faculty assessment of resident achievement of the physical medicine and rehabilitation milestones. Thirty-six physical medicine and rehabilitation faculty, representing three distinct academic institutions, completed a prestudy survey on the adequacy of the rotation-generic resident evaluation tools historically in use at each institution. During the 2016-2017 academic year, faculty in all three institutions consistently used a new set of rotation-specific milestone-incorporated evaluation tools. The same faculty completed surveys assessing the new evaluation tools 6 and 12 months later. Ordinal logistic regression was used to compare survey results before and after implementation of the rotation-specific milestone-incorporated evaluation tools. Results demonstrate high tool satisfaction scores, and a statistically significant improvement in the adequacy and specificity of the new evaluation tools compared with the old ones. There was also a statistically significant improvement in both faculty understanding of the milestones and faculty ability to assess the milestones with use of the new tools compared with the old ones. The implementation of standardized physical medicine and rehabilitation rotation-specific milestone-incorporated faculty-of-resident evaluation tools across three institutions improves faculty ability to assess resident overall performance specifically related to resident achievement of the milestones in each rotation., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Hidradenitis suppurativa (HS) in pediatric patients has been understudied. Increased awareness and recognition of HS prevalence in children demand efforts to better understand this condition., Objective: To describe the demographics, clinical features, treatment, associated comorbidities, and outcomes in a large cohort of pediatric patients with HS., Design, Setting, and Participants: International, multicenter, retrospective medical record review of pediatric patients (aged 1-18 years) with a clinical diagnosis of HS carried out in 10 dermatology clinics across the US, Canada, Israel, Australia, and Italy from January 1996 to January 2017., Main Outcomes and Measures: Patient demographics, clinical features, severity, associated comorbidities, and treatments in pediatric patients with HS., Results: This cross-sectional study included 481 patients diagnosed with HS. Overall, 386 (80%) were girls. The mean (SD) age of disease onset was 12.5 (2.9) years, and the mean (SD) age at diagnosis was 14.4 (3.5) years. Family history of HS was present in 111 of 271 (41%) patients. First signs/symptoms reported at disease onset were cyst/abscess in 229 of 481 (48%), pain/tenderness in 118 of 481 (25%), and papules/pustules in 117 of 481 (24%). At initial dermatologic assessment, 233 of 481 (48%) patients already had evidence of skin scarring. Disease severity (Hurley staging) was documented in 288 of 481 (60%) patients (47% stage 1, 45% stage 2 and 8% stage 3). Comorbid conditions were reported in 406 of 481 (85%) patients, the most common being obesity (263/406 [65%]) and acne vulgaris (118/406 [29%]). Complications occurred in 378 of 481 (79%) patients, the most common of which were scars or contractures (301/378 [80%])., Conclusions and Relevance: The findings of this study indicate that there is a gap in recognizing and diagnosing pediatric HS. Pediatric patients with HS are likely to present with other comorbidities. Prospective observational and interventional studies are needed to better understand clinical course and optimal treatments for pediatric HS.

Introduction: While evidence-based medicine (EBM) is important in all fields of medicine, it can be specifically challenging for the field of physical medicine and rehabilitation (PM&R), a rapidly developing field where the standard hierarchy of evidence does not always apply and randomized controlled trials can be difficult to design. We developed an EBM curriculum for residents that improved EBM competency and was specific to the field of PM&R., Methods: We developed a blended learning longitudinal approach to EBM designed specifically for PM&R residents, with a pre- and postcourse assessment by the Evidence-Based Practice Questionnaire (EBPQ) and Assessing Competency in EBM (ACE) tool. Interactive presentations paired with structured presession assignments were held for five introductory sessions, followed by monthly EBM and journal club sessions over 1 academic year., Results: Fourteen residents of varying postgraduate years of training participated in the EBM curriculum from 2018 to 2019. EBPQ scores after completion of 1 academic year of this EBM curriculum were significantly improved compared to precurriculum EBPQ scores. Comparison of pre- and post-EBPQ and ACE tool scores stratified by postgraduate year did not show a significant correlation between resident levels and self-reported prior EBM education., Discussion: This longitudinal blended learning EBM curriculum resulted in an increase in residents' self-reported behaviors and knowledge/skills regarding EBM. The curriculum was also effective in advancing competency of the residents to an EBM Advanced level using the ACE tool. The curriculum can be easily replicated in other PM&R residency programs., (© 2020 Yoon et al.)

Objectives: We tested whether supplementing with pomegranate polyphenols can enhance cognitive/functional recovery after stroke. Methods: In this parallel, block-randomized clinical trial, we administered commercially-available pomegranate polyphenol or placebo pills twice per day for one week to adult inpatients in a comprehensive rehabilitation setting starting approximately 2 weeks after stroke. Pills contained 1 g of polyphenols derived from whole pomegranate, equivalent to levels in approximately 8 oz of juice. Placebo pills were similar to the pomegranate pills except that they contained only lactose. Of the 163 patients that were screened, 22 were eligible and 16 were randomized (8 per group). We excluded one subject per group from the neuropsychological analyses since they were lost to follow-up, but we included all subjects in the analysis of functional data since outcome data were available. Clinicians and subjects were blinded to group assignment. Neuropsychological testing (primary outcome: Repeatable Battery for the Assessment of Neuropsychological Status) and functional independence scores were used to determine changes in cognitive and functional ability. Results: Pomegranate-treated subjects demonstrated more neuropsychological and functional improvement and spent less time in the hospital than placebo controls. Discussion: Pomegranate polyphenols enhanced cognitive and functional recovery after stroke, justifying pursuing larger clinical trials.

The development of a practical, asymmetric synthesis of the hepatitis C virus (HCV) protease inhibitor MK-5172 (1), an 18-membered macrocycle, is described.

An anaplastic large cell lymphoma (ALCL) arising from the breast tissue is an extremely rare cancer possibly associated with breast implants. According to the FDA database, there are only approximately 60 reported cases of ALCLs in women with breast implants worldwide, and there is the possibility that some of those are duplicate reports of a single case. Here, we present a case of ALCL in a woman who had breast implants for more than 10 years. We discuss preoperative imaging and intraoperative findings, along with the histopathology features and the postoperative management. We suggest that the possibility of late presentation of ALCL be discussed with the patients when we offer and consent them for implant reconstructions following breast surgeries. Increased awareness of the patients and the physicians would make the diagnosis of this entity less of a challenge.

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been increasingly reported over the past decade, including in Asian/Pacific Islanders (A/PIs)., Methods: We conducted ethnographic interviews in O'ahu and Kaua'i, Hawai'i, with 10 Asian/Pacific Islanders identified as having a history of CA-MRSA infections., Results: Most (7/10) thought skin infections were not a new problem in Hawai'i. Most (8/9) attempted to self-treat the infection prior to seeking medical care with a range of home remedies and store- bought solutions. Most respondents did not initially comprehend the severity of their infection and only sought medical treatment after concern from family, unbearable pain, and/or other symptoms of illness., Conclusion: Clinicians should be aware of the reportedly frequent use of home remedies by this population, as it may potentially contribute to interactions when treatments are combined. If clinicians and public health professionals do not address perceptions and misperceptions of how MRSA is acquired, it will be very difficult to prevent infection, and may also delay individuals from seeking treatment., (Hawaii Medical Journal Copyright 2010.)

The preparation and characterization of new model complexes for the molybdenum cofactor are reported. The new models are distinctive for the inclusion of pterin-substituted dithiolene chelates and have the formulation Tp(*)MoX(pterin-R-dithiolene) (Tp(*)=tris(3,5,-dimethylpyrazolyl)borate), X=O, S, R=aryl. Syntheses of Mo(4+) and (5+) complexes of two pterin-dithiolene derivatives as both oxo and sulfido compounds, and improved syntheses for pterinyl alkynes and [Et(4)N][Tp(*)Mo(IV)(S)S(4)] reagents are described. Characterization methods include electrospray ionization mass spectrometry, electrochemistry, infrared spectroscopy, electron paramagnetic resonance and magnetic circular dichroism. Cyclic voltammetry reveals that the Mo(5+/4+) reduction potential is intermediate between that for dithiolenes with electron-withdrawing substituents and simple dithiolates chelates. Electron paramagnetic resonance and magnetic circular dichroism of Mo(5+) complexes where X=O, R=aryl indicates that the molybdenum environment in the new models is electronically similar to that in Tp(*)MoO(benzenedithiolate).

Objectives: We conducted a retrospective study to determine trends and characteristics of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Hawaii., Methods: We reviewed medical records of patients with MRSA infections during July 2001-June 2003 in four healthcare facilities. A case was defined as a patient with MRSA infection (colonization excluded), diagnosed in ambulatory settings or < or = 48 h after hospitalization, without previous MRSA or healthcare risk factors. Pulsed-field gel electrophoresis (PFGE) and typing of resistance and toxin genes was performed in 40 MRSA isolates., Results: CA-MRSA infections increased from 28 (23% of MRSA infections) to 65 (32%) per quarter over the 2-year period (P<0.05). Pacific islanders accounted for 51% of 389 case-patients, but only 24% of the Hawaii population. In the pediatric hospital, Pacific Islanders represented 76% of 90 case-patients versus 35% of the hospital population. Hospital admission, required for 40% (154/389), was associated with prior antimicrobial treatment (P<0.01). The staphylococcal cassette chromosome mec type IV was detected in 38/40 isolates; 31 isolates carried Panton-Valentine leukocidin genes and 22 belonged to the same staphylococcal lineage., Conclusions: In Hawaii, prevention strategies for CA-MRSA infections should focus on Pacific Islanders. CA-MRSA infections in Hawaii appear to be related to strains causing disease throughout the United States.

The complete genome of Aeromonas hydrophila ATCC 7966(T) was sequenced. Aeromonas, a ubiquitous waterborne bacterium, has been placed by the Environmental Protection Agency on the Contaminant Candidate List because of its potential to cause human disease. The 4.7-Mb genome of this emerging pathogen shows a physiologically adroit organism with broad metabolic capabilities and considerable virulence potential. A large array of virulence genes, including some identified in clinical isolates of Aeromonas spp. or Vibrio spp., may confer upon this organism the ability to infect a wide range of hosts. However, two recognized virulence markers, a type III secretion system and a lateral flagellum, that are reported in other A. hydrophila strains are not identified in the sequenced isolate, ATCC 7966(T). Given the ubiquity and free-living lifestyle of this organism, there is relatively little evidence of fluidity in terms of mobile elements in the genome of this particular strain. Notable aspects of the metabolic repertoire of A. hydrophila include dissimilatory sulfate reduction and resistance mechanisms (such as thiopurine reductase, arsenate reductase, and phosphonate degradation enzymes) against toxic compounds encountered in polluted waters. These enzymes may have bioremediative as well as industrial potential. Thus, the A. hydrophila genome sequence provides valuable insights into its ability to flourish in both aquatic and host environments.

Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.

In the present study, we examined the impact of cultural value orientations (i.e., the personally oriented value of individualism, and the socially oriented values of collectivism, familism, romanticism, and spiritualism) on accommodation (i.e., voice and loyalty, rather than exit and neglect, responses to partners' anger or criticism) in heterosexual and gay relationships; and we examined the impact of internalized homophobia (i.e., attitudes toward self, other, and disclosure) on accommodation specifically in gay relationships. A total of 262 heterosexuals (102 men and 162 women) and 857 gays (474 men and 383 women) participated in the present study. Consistent with hypotheses, among heterosexuals and gays, socially oriented values were significantly and positively related to accommodation (whereas the personally oriented value of individualism was unrelated to accommodation); and among gays in particular, internalized homophobia was significantly and negatively related to accommodation. Implications for the study of heterosexual and gay relationships are discussed.

Centromeres are the last frontiers of complex eukaryotic genomes, consisting of highly repetitive sequences that resist mapping, cloning and sequencing. The centromere of rice Chromosome 8 (Cen8) has an unusually low abundance of highly repetitive satellite DNA, which allowed us to determine its sequence. A region of approximately 750 kb in Cen8 binds rice CENH3, the centromere-specific H3 histone. CENH3 binding is contained within a larger region that has abundant dimethylation of histone H3 at Lys9 (H3-Lys9), consistent with Cen8 being embedded in heterochromatin. Fourteen predicted and at least four active genes are interspersed in Cen8, along with CENH3 binding sites. The retrotransposons located in and outside of the CENH3 binding domain have similar ages and structural dynamics. These results suggest that Cen8 may represent an intermediate stage in the evolution of centromeres from genic regions, as in human neocentromeres, to fully mature centromeres that accumulate megabases of homogeneous satellite arrays.