Category: Nevin Manimala

ACS Macro Lett. 2023 Jan 27:234-240. doi: 10.1021/acsmacrolett.2c00600. Online ahead of print.

ABSTRACT

We investigate the effect of helicity in isolated polymers on the topological chirality of their knots with computer simulations. Polymers are described by generic worm-like chains (WLC), where helical conformations are promoted by chiral coupling between segments that are neighbors along the chain contour. The sign and magnitude of the coupling coefficient u determine the sense and strength of helicity. The corrugation of the helix is adjusted via the radius R of a spherical, hard excluded volume around each WLC segment. Open and compact helices are, respectively, obtained for R that is either zero or smaller than the length of the WLC bond, and R that is a few times larger than the bond length. We use a Monte Carlo algorithm to sample polymer conformations for different values of u, spanning the range from achiral polymers to chains with well-developed helices. Monitoring the average helix torsion and fluctuations of chiral order as a function of u, for two very different chain lengths, demonstrates that the coil-helix transition in this model is not a phase transition but a crossover. Statistical analysis of conformations forming the simplest chiral knots, 3₁, 5₁, and 5₂, demonstrates that topological mirror symmetry is broken─knots formed by helices with a given sense prefer one handedness over the other. For the 3₁ and 5₁ knots, positive helical sense favors positive handedness. Intriguingly, an opposite trend is observed for 5₂ knots, where positive helical sense promotes negative handedness. We argue that this special coupling between helicity and topological chirality stems from a generic mechanism: conformations where some of the knot crossings are found in “braids” formed by two tightly interwoven sections of the polymer.

PMID:36706453 | DOI:10.1021/acsmacrolett.2c00600

J Neurosurg Anesthesiol. 2023 Jan 30. doi: 10.1097/ANA.0000000000000905. Online ahead of print.

ABSTRACT

Desflurane is an inhalational anesthetic agent with an appealing recovery profile. The present systematic review investigates the clinical effects and adverse events associated with desflurane use during supratentorial craniotomy for brain tumor resection in adults in comparison with other inhalational and intravenous anesthetic agents. A literature search was conducted across the MEDLINE, Library of Congress and LISTA (EBSCO) databases from January 2001 to January 2021. Twelve studies published between 2003 and 2020 were included in this systematic review. Desflurane was compared with either isoflurane, sevoflurane, or propofol for anesthesia maintenance. Brain relaxation scores showed no statistically significant difference between desflurane and the other anesthetic agents. Recovery timepoints, such as time to recovery, time to eye opening, time to extubation, time to follow commands, and time to reach a modified Aldrete score ≥9 were significantly shorter with desflurane in the majority of studies. Systemic hemodynamic variables (mean arterial pressure and heart rate) and cerebral hemodynamics (intracranial pressure and cerebrospinal fluid pressure) were comparable between desflurane and other anesthetic agents in each study. The results of this systematic review demonstrate that desflurane is associated with few adverse events when used for anesthesia maintenance in adult patients undergoing supratentorial brain tumor surgery. Large, prospective, comprehensive studies, utilizing standardized parameter evaluation could provide higher levels of evidence to support these findings.

PMID:36706431 | DOI:10.1097/ANA.0000000000000905

Lymphat Res Biol. 2023 Jan 27. doi: 10.1089/lrb.2022.0041. Online ahead of print.

ABSTRACT

Objective: Generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), kaposiform lymphangiomatosis (KLA), and central conducting lymphatic anomaly (CCLA) are rare, multisystem lymphatic disorders, referred to as complex lymphatic anomalies (CLAs). Their etiology remains poorly understood; however, somatic activating mutations have recently been discovered, and the results of targeted treatments are promising. This study aimed to elaborate on the phenotypic description of CLA. Methods: Thirty-six consecutive patients were recruited for the “GLA/GSD Registry” of the University Hospital of Freiburg, Germany (2015-2021). Clinical data were prospectively collected provided that a signed informed consent form was obtained. The latest proposed diagnostic guidelines were retrospectively applied. Results: Thirty-two patients (38% males) were included in the study; 15 GLA, 10 GSD, 3 KLA, and 4 CCLA patients were identified. Eighty-four percent already had symptoms by the age of 15 years. Osteolysis and periosseous soft-tissue infiltration were associated with GSD (p < 0.001 and p = 0.011, respectively), ascites and protein-losing enteropathy with CCLA (p = 0.007 and p = 0.004, respectively), and consumption coagulopathy with KLA (p = 0.006). No statistically significant differences were found in organ involvement, distribution of osteolytic lesions, number of affected bones and fractures. Twenty-five patients had complications; one patient with GLA died despite multimodal treatment. Spontaneous regression was seen in one patient with untreated KLA. Conclusions: CLA are rare, and their overlapping clinical presentations make differential diagnosis difficult. The characterization of our case series contributes to the phenotypic description and differentiation of these four clinical entities. A further understanding of their pathogenesis is crucial for evaluating targeted therapies and optimizing medical care.

PMID:36706428 | DOI:10.1089/lrb.2022.0041

Phys Rev Lett. 2023 Jan 13;130(2):023003. doi: 10.1103/PhysRevLett.130.023003.

ABSTRACT

We characterize numerically the dominant dynamical regimes in a superfluid ultracold fermionic Josephson junction. Beyond the coherent Josephson plasma regime, we discuss the onset and physical mechanism of dissipation due to the superflow exceeding a characteristic speed, and provide clear evidence distinguishing its physical mechanism across the weakly and strongly interacting limits, despite qualitative dynamics of global characteristics being only weakly sensitive to the operating dissipative mechanism. Specifically, dissipation in the strongly interacting regime occurs through the phase-slippage process, caused by the emission and propagation of quantum vortices, and sound waves-similar to the Bose-Einstein condensation limit. Instead, in the weak interaction limit, the main dissipative channel arises through the pair-breaking mechanism.

PMID:36706420 | DOI:10.1103/PhysRevLett.130.023003

Asia Pac J Ophthalmol (Phila). 2023 Jan-Feb 01;12(1):38-43. doi: 10.1097/APO.0000000000000591. Epub 2023 Jan 11.

ABSTRACT

PURPOSE: To develop and validate models to predict who will develop myopia in the following year based on cycloplegic refraction or ocular biometry and to identify thresholds of premyopia.

METHODS: Prospective longitudinal data of nonmyopic children at baseline from the Guangzhou Twins Eye Study and the Guangzhou Outdoor Activity Longitudinal Study were used as the training set, and the Singapore Cohort Study of the Risk factors for Myopia study formed the external validation set. Age, sex, cycloplegic refraction, ocular biometry, uncorrected visual acuity, and parental myopia were integrated into 3 logistic regression models to predict the onset of myopia in the following year. Premyopia cutoffs and an integer risk score system were derived based on the identified risk.

RESULTS: In total, 2896 subjects with at least 2 visits were included. Cycloplegic refraction at baseline is a better predictor to identify the children with myopia onset [C-statistic=0.91, 95% confidence interval (CI), 0.87-0.94; C-statistic=0.92, 95% CI, 0.92-0.92 for internal and external validation, respectively], comparing to axial length, corneal curvature radius (CR) and anterior chamber depth (C-statistic=0.81, 95% CI, 0.73-0.88; C-statistic=0.80, 95% CI, 0.79-0.80, respectively), and axial length/CR (C-statistic=0.78, 95% CI, 0.71-0.85; C-statistic=0.76, 95% CI, 0.75-0.76). With a risk of >70%, the definitions of premyopia indicating approaching myopia onset were 0.00 D for 6-8 years and -0.25 D for ≥9 years in children with 2 myopic parents.

CONCLUSIONS: Either cycloplegic refraction or ocular biometry can predict 1-year risk of myopia. Premyopia can be successfully defined through risk assessments based on children’s age and predict who would require more aggressive myopia prophylaxis.

PMID:36706333 | DOI:10.1097/APO.0000000000000591

Alzheimer Dis Assoc Disord. 2023 Jan 18. doi: 10.1097/WAD.0000000000000537. Online ahead of print.

ABSTRACT

BACKGROUND: There is a lack of appreciation of the full dimensionality of the original 22-item Zarit Burden Interview (ZBI) in the development of short versions. Existing short versions are premised upon a 1-factor or 2-factor structure or statistical techniques for item selection. Thus, there is a need for ZBI short versions that considers the multidimensional constructs of role strain, personal strain, and worry about performance (WaP) during item selection to provide a more holistic and comprehensive evaluation.

PURPOSE: To develop and validate a short version of ZBI through a combined quantitative and qualitative approach that incorporates the validated 4-factor structure of role strain demands; role strain-control; personal strain, and WaP.

PATIENTS: We studied 202 caregivers of patients with dementia (84.2%) or mild cognitive impairment (15.8%) attending a memory clinic in Singapore.

METHODS: Confirmatory factor analysis and qualitative considerations from expert consensus were used for item selection. Confirmatory factor analysis fit statistics support the 4-factor structure. The 9-item ZBI-9 showed good internal consistency (Cronbach’s α=0.87) and convergent validity with anxiety and depression (Pearson correlation: Hospital Anxiety and Depression sub-scales, r≥0.56, P<0.001; ZBI- 22, r=0.95, P<0.001). Using a cut-off score of ≥13, ZBI-9 displayed good discriminatory ability for depressive symptoms (area under curve=0.79, P<0.001; sensitivity=70%, specificity=75%). The ZBI-9 also displayed comparable performance to the 22-item full version and three 12-item short versions.

CONCLUSION: The ZBI-9 is a multidimensional short-version assessment tool for caregivers of persons with dementia and mild cognitive impairment that is reliable, valid, and discriminates depressive symptoms.

PMID:36706328 | DOI:10.1097/WAD.0000000000000537

J Perinat Med. 2023 Jan 30. doi: 10.1515/jpm-2022-0550. Online ahead of print.

ABSTRACT

OBJECTIVES: The objective of this study was to compare the maximum 5-min Apgar score of 10 among different U.S. races and Hispanic ethnicity.

METHODS: Retrospective population-based cohort study from the National Center for Health Statistics (NCHS), and Division of Vital Statistics natality online database. We included only deliveries where the race and Hispanic ethnicity of the father and mother were listed as either Black, White, Chinese, or Asian Indian and as Hispanic or Latino origin or other. Proportions of 5-Minute Apgar scores of 10 were compared among different races and Hispanic ethnicity for six groups each for mother and father: Non-Hispanic or Latino White, Hispanic or Latino White, Non-Hispanic or Latino Black, Hispanic or Latino Black, Chinese, and Asian Indian.

RESULTS: The study population consists of 9,710,066 mothers and 8,138,475 fathers from the US natality birth data 2016-2019. Black newborns had a less than 50% chance of having a 5-min Apgar score of 10 when compared to white newborns (OR 0.47 for Black mother and Black father; p<0.001). White babies (non-Hispanic and Hispanic) had the highest proportion of Apgar scores of 10 across all races and ethnicities.

CONCLUSIONS: The Apgar score introduces a bias by systematically lowering the score in people of color. Embedding skin color scoring into basic data and decisions of health care propagates race-based medicine. By removing the skin color portion of the Apgar score and with it’s racial and ethnic bias, we will provide more accuracy and equity when evaluating newborn babies worldwide.

PMID:36706313 | DOI:10.1515/jpm-2022-0550

J Pediatr Hematol Oncol. 2023 Jan 10. doi: 10.1097/MPH.0000000000002618. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk of developing skin cancer. Engaging in sun-protective behaviors may ameliorate that risk, but prior work shows that survivors engage in suboptimal levels of sun-protective behaviors. Guided by the Health Belief Model (HBM), this study evaluated factors associated with sun-protective behavior among CCS.

METHODS: This is a secondary analysis of a survey study of 94 adult survivors of childhood cancer recruited from a long-term follow-up clinic. Participants reported their sun protection habits, skin type/sensitivity, barriers to sun protection, and perceived severity and susceptibility of getting skin cancer. Descriptive statistics were used to describe the prevalence of sun protection behaviors and hierarchical linear regression was used to evaluate predictors of sun protection behavior following the HBM.

RESULTS: On average, CCS engaged in moderate levels of sun-protective behaviors (M=2.53; SD=0.59). Hierarchical linear regression indicated that fair skin type (P=0.02) and higher perceived susceptibility relative to noncancer survivors (P=0.02) were associated with increased sun protection behaviors. Perceived barriers to sun protection were marginally significant (P=0.09), whereas other constructs from the HBM did not contribute significantly to the model.

CONCLUSIONS: Although CCS are at increased risk of developing skin cancer, they engage in suboptimal levels of sun protection behaviors. Findings suggest that interventions to educate survivors about their unique risk of skin cancer and effective prevention behaviors are needed.

PMID:36706312 | DOI:10.1097/MPH.0000000000002618

Anal Chem. 2023 Jan 27. doi: 10.1021/acs.analchem.2c04967. Online ahead of print.

ABSTRACT

Interest in covalent drug discovery has surged in recent years, following the high-profile FDA approvals of covalent inhibitors that target BTK and KRAS G12C. High-throughput screening by intact protein mass spectrometry is a popular method for identifying lead matter from covalent fragment libraries. While the technique is proven in its capacity to confirm covalent binding, it does not provide binding site information on its own. Follow-up assays to identify binding sites can be time- and resource-intensive, potentially extending the hit confirmation timeline by weeks or months. Here, we describe the development of CoMPAS, a novel, targeted mass spectrometry-based covalent screening method that provides binding site information in the initial screen. The high sensitivity of targeted detection confers additional advantages over the intact protein method, including the ability to characterize more potent binders and reduced protein reagent requirements. Interpretation of the structure-activity relationship is simplified by enabling the use of binding site-specific EC₅₀ values. To investigate higher-throughput screening beyond what is possible with standard liquid chromatography, we acquired data in parallel on an Agilent RapidFire system and compared the screening results by statistical analysis. To demonstrate the multiplexing capabilities of CoMPAS, we determined the target selectivity of screening hits against a pool of off-target kinases.

PMID:36706310 | DOI:10.1021/acs.analchem.2c04967

Games Health J. 2023 Feb;12(1):1-12. doi: 10.1089/g4h.2022.0088.

ABSTRACT

Objective: Interactive virtual reality (iVR) has been widely used for treatment purposes in patients with chronic musculoskeletal disorders. However, no consensus has been reached on the effects of iVR on pain, psychological distress, and functional disability. Therefore, this study aims to investigate the effects of iVR on pain, psychological distress, and functional disability in patients with chronic musculoskeletal disorders compared with no rehabilitation and conventional rehabilitation. Methods: Five electronic databases (PubMed, Cochrane CENTRAL, Scopus, EMBASE, and Web of Science) were searched from January 2016 to December 2021. All randomized controlled trials using iVR for treating pain, psychological distress, and functional disability in patients with chronic musculoskeletal disorders were included. A subgroup analysis was conducted to compare the effects of nonimmersive and immersive types of iVR on the outcomes of interest. Results: Our study provides good quality evidence that iVR reduced overall pain by 9.28 points as compared with no rehabilitation and by 8.09 points as compared with conventional rehabilitation. In the subgroup analysis, nonimmersive iVR showed a reduction in psychological distress (standardized mean differences = -0.35) as compared with no rehabilitation. However, no statistically significant difference in the outcomes existed between nonimmersive and immersive iVR. Furthermore, there were no statistically significant differences in the outcomes of functional disability. Conclusions: iVR is recommended for reducing pain intensity more than no rehabilitation or conventional rehabilitation. Meanwhile, nonimmersive iVR has been proposed for psychological distress improvement, with effects similar to those of conventional rehabilitation. However, iVR may not be an effective intervention in the case of functional disability.

PMID:36706260 | DOI:10.1089/g4h.2022.0088