Nevin Manimala

Opt Lett. 2021 May 15;46(10):2505-2508. doi: 10.1364/OL.422062.

ABSTRACT

We present a quantitative model to provide robust estimation of the decorrelation time using laser speckle auto-inverse covariance. It has the advantages of independence from the statistical sample size, speckle size, static scattering, and detector noise. We have shown cerebral blood flow imaging through an intact mouse skull using this model. Phantom experiments and two animal models, middle cerebral artery occlusion, and cortical spreading depression were used to evaluate its performance.

PMID:33988621 | DOI:10.1364/OL.422062

J Bone Joint Surg Am. 2021 May 14. doi: 10.2106/JBJS.20.00940. Online ahead of print.

ABSTRACT

BACKGROUND: Spherical periacetabular osteotomy (SPO) is a novel osteotomy involving splitting the teardrop, using patient-specific preoperative planning, and requiring only a 7-cm skin incision. We report preoperative planning methods and short-term results of SPO.

METHODS: In preoperative planning, computed tomography (CT) images were imported into 3-dimensional templating software. The radius of the curved chisel was mapped to pass through the teardrop, the infracotyloid groove of the ischium, and the area between the anterior superior iliac spine and the anterior inferior iliac spine. The osteotomy height and the predicted depth of osteotome insertion were measured, and those values were reproduced during surgery. We performed a retrospective analysis of data on 52 consecutive patients (55 hips) with hip dysplasia who underwent SPO and were followed for at least 2 years: 27 hips had Tönnis grade 0, 21 had grade 1, and 7 had grade 2. The mean age at surgery was 38 years (range, 17 to 56 years). The rotated bone fragment and iliac crest were fixed with absorbable screws. Statistical analysis was performed with the paired t test.

RESULTS: The mean (range) of the lateral center-edge and sourcil angles were 6.0° (-20° to 18°) and 26.0 (13° to 38°), respectively, before surgery and 30.0° (15° to 43°) and 3.8° (-4° to 27°), respectively, after surgery (p < 0.001). However, 11 hips (20%) showed a loss of correction of bone rotation (<3 mm) or the sourcil angle (<3°). Radiographs showed bone union in all hips within 3 months after the surgery. Early second surgery related to absorbable screws was performed in 2 hips. No patient had required conversion to total hip arthroplasty at the time of writing. Clinical scores were significantly improved at the 2-year follow-up (p < 0.001). Paresthesia of the lateral femoral cutaneous nerve area was very common but had resolved in 92% of the patients at the 2-year follow-up.

CONCLUSIONS: SPO is a novel minimally invasive periacetabular osteotomy that has the potential disadvantage of early loss of correction (observed in 20% of the hips in the present study) but may provide the benefit of decreasing the risk of nonunion at the pubis osteotomy site.

LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

PMID:33988546 | DOI:10.2106/JBJS.20.00940

NPJ Parkinsons Dis. 2021 May 13;7(1):40. doi: 10.1038/s41531-021-00184-9.

ABSTRACT

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of Lewy-type synucleinopathies (LTS), which can present either with an initial predominant parkinsonism (Parkinson’s disease (PD)) or dementia (dementia with Lewy bodies (DLB)). To provide insights into the underlying pathogenic mechanisms, the lipoprotein and protein glycosylation profile of 82 iRBD patients, collected before and/or after their conversion to an overt LTS, and 29 matched control serum samples were assessed by nuclear magnetic resonance (NMR) spectroscopy. Data were statistically analyzed to identify altered metabolites and construct predictive models. Univariant analysis detected no differences between iRBD patients with an LTS compared to controls. However, significant differences were found when the analysis distinguished between iRBD patients that manifested initially predominant parkinsonism (pre-PD) or dementia (pre-DLB). Significant differences were also found in the analysis of paired iRBD samples pre- and post-LTS diagnosis. Predictive models were built and distinguished between controls and pre-DLB patients, and between pre-DLB and pre-PD patients. This allowed a prediction of the possible future clinical outcome of iRBD patients. We provide evidence of altered lipoprotein and glycosylation profiles in subgroups of iRBD patients. Our results indicate that metabolic alterations and inflammation are involved in iRBD pathophysiology, and suggest biological differences underlying the progression of LTS in iRBD patients. Our data also indicate that profiling of serum samples by NMR may be a useful tool for identifying short-term high-risk iRBD patients for conversion to parkinsonism or dementia.

PMID:33986284 | DOI:10.1038/s41531-021-00184-9

NPJ Vaccines. 2021 May 13;6(1):69. doi: 10.1038/s41541-021-00329-0.

ABSTRACT

Fentanyl is a major contributor to the devastating increase in overdose deaths from substance use disorders (SUD). A vaccine targeting fentanyl could be a powerful immunotherapeutic. Here, we evaluated adjuvant and delivery strategies for conjugate antigen vaccination with fentanyl-based haptens. We tested adjuvants derived from the heat-labile toxin of E. coli including dmLT and LTA1 by intramuscular, sublingual or intranasal delivery. Our results show anti-fentanyl serum antibodies and antibody secreting cells in the bone-marrow after vaccination with highest levels observed with an adjuvant (alum, dmLT, or LTA1). Vaccine adjuvanted with LTA1 or dmLT elicited the highest levels of anti-fentanyl antibodies, whereas alum achieved highest levels against the carrier protein. Vaccination with sublingual dmLT or intranasal LTA1 provided the most robust blockade of fentanyl-induced analgesia and CNS penetration correlating strongly to anti-FEN IgA. In conclusion, this study demonstrates dmLT or LTA1 adjuvant as well as mucosal delivery may be attractive strategies for improving the efficacy of vaccines against SUD.

PMID:33986280 | DOI:10.1038/s41541-021-00329-0

Nat Commun. 2021 May 13;12(1):2781. doi: 10.1038/s41467-021-23043-w.

ABSTRACT

Elucidating metal oxide growth mechanisms is essential for precisely designing and fabricating nanostructured oxides with broad applications in energy and electronics. However, current epitaxial oxide growth methods are based on macroscopic empirical knowledge, lacking fundamental guidance at the nanoscale. Using correlated in situ environmental transmission electron microscopy, statistically-validated quantitative analysis, and density functional theory calculations, we show epitaxial Cu₂O nano-island growth on Cu is layer-by-layer along Cu₂O(110) planes, regardless of substrate orientation, contradicting classical models that predict multi-layer growth parallel to substrate surfaces. Growth kinetics show cubic relationships with time, indicating individual oxide monolayers follow Frank-van der Merwe growth whereas oxide islands follow Stranski-Krastanov growth. Cu sources for island growth transition from step edges to bulk substrates during oxidation, contrasting with classical corrosion theories which assume subsurface sources predominate. Our results resolve alternative epitaxial island growth mechanisms, improving the understanding of oxidation dynamics critical for advanced manufacturing at the nanoscale.

PMID:33986274 | DOI:10.1038/s41467-021-23043-w

Nat Commun. 2021 May 13;12(1):2785. doi: 10.1038/s41467-021-22856-z.

ABSTRACT

With the availability of cellular-resolution connectivity maps, connectomes, from the mammalian nervous system, it is in question how informative such massive connectomic data can be for the distinction of local circuit models in the mammalian cerebral cortex. Here, we investigated whether cellular-resolution connectomic data can in principle allow model discrimination for local circuit modules in layer 4 of mouse primary somatosensory cortex. We used approximate Bayesian model selection based on a set of simple connectome statistics to compute the posterior probability over proposed models given a to-be-measured connectome. We find that the distinction of the investigated local cortical models is faithfully possible based on purely structural connectomic data with an accuracy of more than 90%, and that such distinction is stable against substantial errors in the connectome measurement. Furthermore, mapping a fraction of only 10% of the local connectome is sufficient for connectome-based model distinction under realistic experimental constraints. Together, these results show for a concrete local circuit example that connectomic data allows model selection in the cerebral cortex and define the experimental strategy for obtaining such connectomic data.

PMID:33986261 | DOI:10.1038/s41467-021-22856-z

J Am Acad Orthop Surg Glob Res Rev. 2021 Feb 2;5(2). doi: 10.5435/JAAOSGlobal-D-20-00172.

ABSTRACT

INTRODUCTION: State legalization and widespread marketing efforts have increased the accessibility and consumption of off-label, non-FDA-approved, cannabinoid (CBD) products. Although clinical evidence is largely absent for the treatment of musculoskeletal pain, patients are experimenting with these products in efforts to relieve joint pain. Assessment of the prevalence, perceived efficacy compared with other nonsurgical modalities, and usage patterns is warranted. The purpose of this study was to report the prevalence and perceived self-efficacy of CBD products in patients with symptomatic hip and/or knee osteoarthritis (OA).

METHODS: Two-hundred consecutive patients presenting with painful hip or knee OA were surveyed at their initial evaluation at a large academic center. Using Single Assessment Numeric Evaluation (SANE) scores, survey questions assessed perceived pain and effectiveness of CBD products, in addition to other nonsurgical treatment modalities. Chart review provided demographic factors. Descriptive statistics were used to characterize the data.

RESULTS: Of the 200 patients (80 hip OA, 108 knee OA, and 12 both), 66% were female, and average age was 67 years (range 36 to 89 years). Twenty-four percent (48/200) of patients endorsed use of CBD products before their presentation. The average presenting SANE score (range 0 to 100) for non-CBD users was 50.8 compared with 41.3 among CBD users (P = 0.012). Sixty percent of patients learned about CBD through friends, and 67% purchased CBD directly from a dispensary. Oral tinctures (43%) and topical applications (36%) were the most commonly used forms. In addition, 8% of participants in this study had tried marijuana for their pain.

CONCLUSION: A 24% incidence of CBD usage was found among patients presenting with hip or knee OA. No significant perceived benefit of CBD use seems to exist compared with its nonuse, as patients who used CBD reported significantly worse SANE and visual analogue scale scores than nonusers at baseline. Follow-up studies are warranted to assess these findings.

PMID:33986220 | DOI:10.5435/JAAOSGlobal-D-20-00172

J Am Acad Orthop Surg Glob Res Rev. 2020 Dec 4;4(12):e20.00194. doi: 10.5435/JAAOSGlobal-D-20-00194.

ABSTRACT

BACKGROUND: Patient-reported outcome measures (PROMs) are critical and frequently used to assess clinical outcomes to support medical decision-making.

QUESTIONS/PURPOSE: The purpose of this meta-analysis was to compare differences in the modes of administration of PROMs within the field of orthopaedics to determine their impact on clinical outcome assessment.

PATIENTS AND METHODS: The PubMed database was used to conduct a review of literature from 1990 to 2018 with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. All articles comparing PROMs for orthopaedic procedures were included and classified by the mode of administration. Each specific survey was standardized to a scale of 0 to 100, and a repeated random effectsmodel meta-analysis was conducted to determine the mean effect of each mode of survey.

RESULTS: Eighteen studies were initially included in the study, with 10 ultimately used in the meta-analysis that encompassed 2384 separate patient survey encounters. Six of these studies demonstrated a statistically notable difference in PROM scores by mode of administration. The meta-analysis found that the standardized mean effect size for telephone-based surveys on a 100-point scale was 71.7 (SE 5.0) that was significantly higher (P , 0.0001) than survey scores obtained via online/tech based (65.3 [SE 0.70]) or self-administered/paper surveys (61.2 [SE 0.70]).

CONCLUSIONS: Overall, this study demonstrated that a documented difference exists in PROM quality depending on the mode of administration. PROM scores obtained via telephone (71.7) are 8.9% higher than scores obtained online (65.3, P , 0.0001), and 13.8% higher than scores obtained via self-administered on paper (61.8, P , 0.0001). Few studies have quantified statistically notable differences between PROM scores based solely on the mode of acquisition in orthopaedic.

PMID:33986216 | DOI:10.5435/JAAOSGlobal-D-20-00194

Science. 2021 May 14;372(6543):694. doi: 10.1126/science.abj0016.

NO ABSTRACT

PMID:33986172 | DOI:10.1126/science.abj0016

J Immunother Cancer. 2021 May;9(5):e002254. doi: 10.1136/jitc-2020-002254.

ABSTRACT

BACKGROUND: Sipuleucel-T is a US Food and Drug Administration-approved autologous cellular immunotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We examined whether administering ipilimumab after sipuleucel-T could modify immune and/or clinical responses to this treatment.

METHODS: A total of 50 patients with mCRPC were enrolled into a clinical trial (NCT01804465, ClinicalTrials.gov) where they received ipilimumab either immediately or delayed 3 weeks following completion of sipuleucel-T treatment. Blood was collected at various timepoints of the study. Luminex assay for anti-prostatic acid phosphatase (PAP) and anti-PA2024-specific serum immunoglobulin G (IgG) and ELISpot for interferon-γ (IFN-γ) production against PAP and PA2024 were used to assess antigen-specific B and T cell responses, respectively. Clinical response was defined as >30% reduction in serum prostate-specific antigen levels compared with pretreatment levels. The frequency and state of circulating immune cells were determined by mass cytometry by time-of-flight and statistical scaffold analysis.

RESULTS: We found the combination to be well tolerated with no unexpected adverse events occurring. The timing of ipilimumab did not significantly alter the rates of antigen-specific B and T cell responses, the primary endpoint of the clinical trial. Clinical responses were observed in 6 of 50 patients, with 3 having responses lasting longer than 3 months. The timing of ipilimumab did not significantly associate with clinical response or toxicity. The combination treatment did induce CD4 and CD8 T cell activation that was most pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells, even prior to treatment, were associated with better clinical outcomes. Interestingly, these differences in CTLA-4 expression were associated with prior localized radiation therapy (RT) to the prostate or prostatic fossa. Prior radiation treatment was also associated with improved radiographic progression-free survival.

CONCLUSION: Combining CTLA-4 blockade with sipuleucel-T resulted in modest clinical activity. The timing of CTLA-4 blockade following sipuleucel-T did not alter antigen-specific responses. Clinical responses were associated with both lower baseline frequencies of CTLA-4 expressing T cells and a history of RT. Prior cancer therapy may therefore result in long-lasting immune changes that influence responsiveness to immunotherapy with sipuleucel-T and anti-CTLA-4.

PMID:33986125 | DOI:10.1136/jitc-2020-002254