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Background: PLA2G6-Associated Neurodegeneration, PLAN, is subdivided into: Infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and adult-onset dystonia parkinsonism [1]. It is elicited by a biallelic pathogenic variant in phospholipase A2 group VI (PLA2G6) gene. In this study we describe new cases and provide a comprehensive review of previously published cases., Methods: Eleven patients, from four different institutions and four different countries. All underwent a comprehensive chart review., Results: Ages at onset ranged from 1 to 36 years, with a median of 16 and a mean of 16.18 ± 11.91 years. Phenotypic characteristics were heterogenous and resembled that of patients with infantile neuroaxonal dystrophy (n = 2), atypical neuroaxonal dystrophy (n = 1), adult-onset dystonia parkinsonism (n = 1), complex hereditary spastic paraparesis (n = 3), and early onset Parkinson's disease (n = 2). Parental genetic studies were performed for all patients and confirmed with sanger sequencing in five. Visual evoked potential illustrated optic atrophy in P4. Mineralization was evident in brain magnetic resonance imaging of P1, P2, P4, P5, P7, and P11. Single photon emission computed tomography was conducted for three patients, revealed decreased perfusion in the occipital lobes for P10. DaTscan was performed for P11 and showed decreased uptake in the deep gray matter, bilateral caudate nuclei, and bilateral putamen. Positive response to Apomorphine was noted for P10 and to Baclofen in P2, and P3., Conclusions: PLAN encompasses a wide clinical spectrum. Age and symptom at onset are crucial when classifying patients. Reporting new variants is critical to draw more attention to this condition and identify biomarkers to arrive at potential therapeutics., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Clinical trials in spinocerebellar ataxia type 3 (SCA3) will require biomarkers for use as outcome measures., Methods: To evaluate total tau (t-tau), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and neurofilament light-chain (NfL) as fluid biomarkers in SCA3, ATXN3 mutation carriers (n = 143) and controls (n = 172) were clinically assessed, and the plasma concentrations of the four proteins were analysed on the Simoa HD-1 platform. Eleven ATXN3 mutation carrier cerebrospinal fluid samples were analysed for t-tau and phosphorylated tau (p-tau 181 ). A transgenic SCA3 mouse model (MJDTg) was used to measure cerebellar t-tau levels., Results: Plasma t-tau levels were higher in mutation carriers below the age of 50 compared to controls, and the Inventory of Non-Ataxia Signs was associated with t-tau in ataxic patients (p = 0.004). Pre-ataxic carriers showed higher cerebrospinal fluid t-tau and p-tau 181 concentrations compared to ataxic patients (p = 0.025 and p = 0.014, respectively). Cerebellar t-tau was elevated in MJDTg mice compared to wild-type (p = 0.033) only in the early stages of the disease. GFAP and UCHL1 did not show higher levels in mutation carriers compared to controls. Plasma NfL concentrations were higher in mutation carriers compared to controls, and differences were greater for younger carriers. The Scale for the Assessment and Rating of Ataxia was the strongest predictor of NfL in ataxic patients (p < 0.001)., Conclusion: Our results suggest that tau might be a marker of early disease stages in SCA3. NfL can discriminate mutation carriers from controls and is associated with different clinical variables. Longitudinal studies are required to confirm their potential role as biomarkers in clinical trials., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Tobacco is strongly associated with socioeconomic status (SES), however evidence on differences in tobacco cessation by socio-economic attributes remains fragmented, especially in developing countries. The present study aims to estimate socioeconomic inequalities in tobacco cessation among Indian men and women above 15 years of age., Methods: Two rounds of the Global Adult Tobacco Survey (2009-2010 and 2016-2017), India was used to estimate the association between socioeconomic indicators (wealth index and educational attainment) with tobacco cessation using a multinomial modeling approach., Results: After adjusting for SES and demographic variables, we found significantly lower odds in tobacco cessation rates among respondents of GATS-2 (2016-2017) compared to GATS-1 (2009-2010). Additionally, huge regional variations in smoking and smokeless tobacco cessation rates were observed. Population belonging to the low wealth-asset score had higher odds of cessation compared to the high asset index. While greater educational attainment was seen to have a positive effect on cessation, the results were insignificant. Individuals belonging to the northeastern geographic region were seen to have the lowest odds of cessation. Though awareness about the health hazards of tobacco increased, cessation declined for both men and women. Quitting smokeless tobacco among men and women was observed to be lower than smoking., Conclusion: This study is the first to provide national-level evidence on the association between tobacco cessation and socioeconomic attributes among Indians above 15 years of age. Findings suggest the need to scale up tobacco cessation services separately for men and women, and also for smoking and smokeless tobacco forms., (© 2022. The Author(s).)

Objective: Clinical manifestations of blue rubber bleb nevus syndrome (BRBNS) and multifocal venous malformation (MVM) vary depending on the location of the lesions. The aim of this study was to assess the risk of developing CSF leaks in patients with epidural venous malformations (VMs)., Methods: The authors retrospectively investigated the relationship between the development of a CSF leak and the presence of epidural VMs., Results: Nine patients (5 females) had epidural VMs and presentation that was confirmatory or suggestive of a CSF leak: 4 had BRBNS, 4 had MVMs, and 1 had a solitary VM. Of 66 patients with BRBNS, clinical and imaging features of CSF leak were noted in 3 (4.5%) with epidural VMs at the age of 11-44 years. A fourth patient had suggestive symptoms without imaging confirmation. An epidural blood patch was ineffective in 2 patients, both with more than one source of leakage, requiring surgical repair or decompression. Symptomatic downward displacement of the cerebellar tonsils was noted in 3 patients with MVM and 1 with a solitary VM; 3 required surgical decompression., Conclusions: These findings suggest an increased risk of CSF leak in patients with epidural VM, including BRBNS, MVMs, and solitary VMs. Awareness of the association between epidural VM and CSF leakage may facilitate earlier diagnosis and therapeutic intervention.

Preclassification of raw infrared spectra has often been neglected in scientific literature. Separating spectra of low spectral quality, due to low signal-to-noise ratio, presence of artifacts, and low analyte presence, is crucial for accurate model development. Furthermore, it is very important for sparse data, where it becomes challenging to visually inspect spectra of different natures. Hence, a preclassification approach to separate infrared spectra for sparse data is needed. In this study, we propose a preclassification approach based on Multiplicative Signal Correction (MSC). The MSC approach was applied on human and the bovine knee cartilage broadband Fourier Transform Infrared (FTIR) spectra and on a sparse data subset comprising of only seven wavelengths. The goal of the preclassification was to separate spectra with analyte-rich signals (i.e., cartilage) from spectra with analyte-poor (and high-matrix) signals (i.e., water). The human datasets 1 and 2 contained 814 and 815 spectra, while the bovine dataset contained 396 spectra. A pure water spectrum was used as a reference spectrum in the MSC approach. A threshold for the root mean square error (RMSE) was used to separate cartilage from water spectra for broadband and the sparse spectral data. Additionally, standard noise-to-ratio and principle component analysis were applied on broadband spectra. The fully automated MSC preclassification approach, using water as reference spectrum, performed as well as the manual visual inspection. Moreover, it enabled not only separation of cartilage from water spectra in broadband spectral datasets, but also in sparse datasets where manual visual inspection cannot be applied.

Background: Evidence regarding the progression of the tobacco epidemic remains fragmented in low- and middle-income countries. In India, most of the studies that examined tobacco consumption focused on one time point, on the country as a whole, and on men. Despite important gender differences in tobacco consumption, vast economic and cultural differences exist within India. We, therefore, assessed the progression of the tobacco epidemic in India on both the national and the regional level, by gender., Methods: We use information on current tobacco use among Indians aged 15-49 from three rounds of the National Family Health Survey (NFHS) (1998-99, 2005-06, 2015-16) to estimate the age-standardized sex specific smoking and smokeless tobacco prevalence across India and its states., Results: Age-standardized tobacco use prevalence in India increased between 1998-1999 and 2005-2006, and declined from 2005-2006 to 2015-2016, simultaneously for men and women. There are substantial spatial differences in the progression of the tobacco epidemic in India. While tobacco use declined in the majority of states, we observe high and increasing use for men in the north-eastern states of Manipur, Mizoram and Nagaland, and for women in the western state of Gujarat and north-eastern state of Manipur. We observed even more states with a recent increasing prevalence in either tobacco smoking or smokeless tobacco. Throughout, prevalence of tobacco use has been higher among men than women for all Indian regions, and remained higher than the national average in the north-eastern states., Conclusions: Our results suggest that India and the majority of its states experienced a 'compressed tobacco epidemic' in which the prevalence of tobacco consumption increased and decreased simultaneously for women and men over a comparatively short period of time. Despite the overall progress India made in reducing tobacco use, further lowering tobacco consumption remains a public health priority, as the prevalence of smoking and/or smokeless tobacco use remains high in a number of states. We therefore conclude that tobacco regulations should be expanded with the aim of reducing the overall health burden associated with tobacco consumption across India., (© 2022. The Author(s).)

Objective: Clinical diagnostic sequencing of circulating tumour DNA (ctDNA) is well advanced for adult patients, but application to paediatric cancer patients lags behind., Methods: To address this, we have developed a clinically relevant (67 gene) NGS capture panel and accompanying workflow that enables sensitive and reliable detection of low-frequency genetic variants in cell-free DNA (cfDNA) from children with solid tumours. We combined gene panel sequencing with low pass whole-genome sequencing of the same library to inform on genome-wide copy number changes in the blood., Results: Analytical validity was evaluated using control materials, and the method was found to be highly sensitive (0.96 for SNVs and 0.97 for INDEL), specific (0.82 for SNVs and 0.978 for INDEL), repeatable (>0.93 [95% CI: 0.89-0.95]) and reproducible (>0.87 [95% CI: 0.87-0.95]). Potential for clinical application was demonstrated in 39 childhood cancer patients with a spectrum of solid tumours in which the single nucleotide variants expected from tumour sequencing were detected in cfDNA in 94.4% (17/18) of cases with active extracranial disease. In 13 patients, where serial samples were available, we show a close correlation between events detected in cfDNA and treatment response, demonstrate that cfDNA analysis could be a useful tool to monitor disease progression, and show cfDNA sequencing has the potential to identify targetable variants that were not detected in tumour samples., Conclusions: This is the first pan-cancer DNA sequencing panel that we know to be optimised for cfDNA in children for blood-based molecular diagnostics in paediatric solid tumours., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of the study was to optimize preprocessing of sparse infrared spectral data. The sparse data were obtained by reducing broadband Fourier transform infrared attenuated total reflectance spectra of bovine and human cartilage, as well as of simulated spectral data, comprising several thousand spectral variables into datasets comprising only seven spectral variables. Different preprocessing approaches were compared, including simple baseline correction and normalization procedures, and model-based preprocessing, such as multiplicative signal correction (MSC). The optimal preprocessing was selected based on the quality of classification models established by partial least squares discriminant analysis for discriminating healthy and damaged cartilage samples. The best results for the sparse data were obtained by preprocessing using a baseline offset correction at 1800 cm -1 , followed by peak normalization at 850 cm -1 and preprocessing by MSC.

Background: Despite its controversial nature, the use of recreational marijuana and cannabis-derived products continue to increase in popularity. Cannabis consumption is currently legal in certain American states as well as Canada, and it is also frequently used by Canadian youth. However, cannabis use during childhood and adolescence can contribute to significant harm. Materials and Methods: A review of current literature regarding the impacts of cannabis consumption among Canadian youth was conducted. Medline, Cochrane, Embase and PubMed databases were utilized to identify journal articles published within 10 years that highlighted the impacts of cannabis consumption in its different forms among the North American pediatric population. Results: Our review identified harms include structural and functional impairments in the developing brain, the development of mental health conditions such as depression and anxiety, impaired road safety while driving under the influence of cannabis, and the significant consequences of accidental ingestion of cannabis products by children. We also ascertained that cannabis cessation strategies that employed an affective model, which explores the root causes of adolescents turning to cannabis, are most effective in reducing substance use among adolescents. Conclusions: In light of the recent legalization of cannabis in Canada, the purpose of this article was to provide background on cannabis consumption and its legalization in Canada, the impacts of cannabis on Canadian youth, and evidence-based strategies to help mitigate them.

Interpersonal touch behavior differs across cultures, yet no study to date has systematically tested for cultural variation in affective touch, nor examined the factors that might account for this variability. Here, over 14,000 individuals from 45 countries were asked whether they embraced, stroked, kissed, or hugged their partner, friends, and youngest child during the week preceding the study. We then examined a range of hypothesized individual-level factors (sex, age, parasitic history, conservatism, religiosity, and preferred interpersonal distance) and cultural-level factors (regional temperature, parasite stress, regional conservatism, collectivism, and religiosity) in predicting these affective-touching behaviors. Our results indicate that affective touch was most prevalent in relationships with partners and children, and its diversity was relatively higher in warmer, less conservative, and religious countries, and among younger, female, and liberal people. This research allows for a broad and integrated view of the bases of cross-cultural variability in affective touch.

Purpose of the Study: Alcohol use is the third leading risk factor for premature mortality. India is one of the largest markets for alcoholic beverages. Existing research in India is localized to specific settings lacking national generalizability. The present study aims to estimate the trends in alcohol use in India by gender and regions and to estimate the current projected number of the population involved in problematic drinking., Methods: The National Family Health Survey (NFHS) is used to estimate the age-standardized alcohol prevalence by gender and region. World Bank, 2019 population estimates are used to estimate the total population currently involved in problematic drinking, using the recent alcohol prevalence estimates., Findings: Nationally, the age-standardized prevalence of alcohol use increased between 1998-1999 and 2005-2006 and declined thereafter, being higher among men than women. Exceptions to the declines after 2005 are seen in some regions where alcohol use still increased. A 43.6% increase and 8.5% decrease in the age-standardized prevalence of problematic drinking is observed among men and women, respectively, between 2005-2006 and 2015-2016. However, problematic drinking increased in some regions for both men and women. 103.62 million men and 3.34 million women in India were involved in problematic drinking during 2019, with the highest incidences being among men aged 40-44 years and among women aged 45-49 years., Conclusion: Despite the overall progress India has made in reducing its alcohol prevalence, lowering it further remains a public health priority. There was a substantial rise in the prevalence of problematic drinking among the population, which warrants immediate action. Spreading knowledge and awareness about the negative health effects of problematic drinking among the adult population seems necessary. Strict implementation of policies would therefore not only aid in reducing the prevalence of alcohol use and problematic drinking, but, in turn, would also help to reduce the burden of alcohol-related morbidity and associated mortality in India., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Joint injuries may lead to degeneration of cartilage tissue and initiate development of posttraumatic osteoarthritis. Arthroscopic surgeries can be used to treat joint injuries, but arthroscopic evaluation of articular cartilage quality is subjective. Fourier transform infrared spectroscopy combined with fiber optics and attenuated total reflectance crystal could be used for the assessment of tissue quality during arthroscopy. We hypothesize that fiber-optic mid-infrared spectroscopy can detect enzymatically and mechanically induced damage similar to changes occurring during progression of osteoarthritis., Design: Bovine patellar cartilage plugs were extracted and degraded enzymatically and mechanically. Adjacent untreated samples were utilized as controls. Enzymatic degradation was done using collagenase and trypsin enzymes. Mechanical damage was induced by (1) dropping a weight impactor on the cartilage plugs and (2) abrading the cartilage surface with a rotating sandpaper. Fiber-optic mid-infrared spectroscopic measurements were conducted before and after treatments, and spectral changes were assessed with random forest, partial least squares discriminant analysis, and support vector machine classifiers., Results: All models had excellent classification performance for detecting the different enzymatic and mechanical damage on cartilage matrix. Random forest models achieved accuracies between 90.3% and 77.8%, while partial least squares model accuracies ranged from 95.8% to 84.7%, and support vector machine accuracies from 91.7% to 80.6%., Conclusions: The results suggest that fiber-optic Fourier transform infrared spectroscopy attenuated total reflectance spectroscopy is a viable way to detect minor and major degeneration of articular cartilage. Objective measures provided by fiber-optic spectroscopic methods could improve arthroscopic evaluation of cartilage damage.

Diagnoses of autism spectrum disorders (ASD) are typically made after toddlerhood by examining behavioural patterns. Earlier identification of ASD enables earlier intervention and better outcomes. Machine learning provides a data-driven approach of diagnosing autism at an earlier age. This review aims to summarize recent studies and technologies utilizing machine learning based strategies to screen infants and children under the age of 18 months for ASD, and identify gaps that can be addressed in the future. We reviewed nine studies based on our search criteria, which includes primary studies and technologies conducted within the last 10 years that examine children with ASD or at high risk of ASD with a mean age of less than 18 months old. The studies must use machine learning analysis of behavioural features of ASD as major methodology. A total of nine studies were reviewed, of which the sensitivity ranges from 60.7% to 95.6%, the specificity ranges from 50% to 100%, and the accuracy ranges from 60.9% to 97.7%. Factors that contribute to the inconsistent findings include the varied presentation of ASD among patients and study design differences. Previous studies have shown moderate accuracy, sensitivity and specificity in the differentiation of ASD and non-ASD individuals under the age of 18 months. The application of machine learning and artificial intelligence in the screening of ASD in infants is still in its infancy, as observed by the granularity of data available for review. As such, much work needs to be done before the aforementioned technologies can be applied into clinical practice to facilitate early screening of ASD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Siddiqui et al.)

This study aims to investigate the influence of institutional capacity on the relationship between financial development and environmental quality and also examines the moderating role of corruption on the link between institutional quality and environmental quality. By using yearly data from 33 developing countries for 7 years from 2011 to 2017, this paper applies a dynamic technique system GMM. The results suggest that financial development increases environmental degradation due to possible higher energy-intensive investment. However, institutional capacity moderates its impact on environmental quality by channelizing the funds to energy-efficient investment. The findings of this study suggest that financial development improves the environmental quality when institutional capacity is higher than 3.5 on the scale of 0 to 6. Interestingly, institutional capacity is unable to control environmental degradation in the presence of corruption. The results propose that financial development has a positive relation with environmental degradation in the presence of corruption. Nevertheless, relationship between institutional capacity and environmental degradation turns to negative when corruption improves in the economies. Furthermore, the findings show that institutional capacity may only control environmental degradation when corruption improves to 40 or higher on a scale of 0 to 100. The policy implications of this study are useful for policy departments, environmental regulatory bodies, and financial institutions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Optical properties of biological tissues in the NIR spectral range have demonstrated significant potential for in vivo diagnostic applications and are critical parameters for modelling light interaction in biological tissues. This study aims to investigate the optical properties of articular cartilage as a function of tissue depth and integrity. The results suggest consistent wavelength-dependent variation in optical properties between cartilage depth-wise zones, as well as between healthy and degenerated tissue. Also, statistically significant differences (p<0.05) in both optical properties were observed between the different cartilage depth-wise zones and as a result of tissue degeneration. When taken into account, the outcome of this study could enable accurate modelling of light interaction in cartilage matrix and could provide useful diagnostic information on cartilage integrity., Competing Interests: The authors declare no conflict of interest., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Introduction: Accumulation of polyglutamine (polyQ) ataxin-3 (ATXN3) contributes to the pathobiology of spinocerebellar ataxia type 3 (SCA3). Recently, we showed that polyQ ATXN3 is elevated in the plasma and cerebrospinal fluid (CSF) of SCA3 patients, and has the potential to serve as a biological marker for this disease [1]. Based on these findings, we investigated whether polyQ ATXN3 can also be detected in urine samples from SCA3 patients., Methods: We analyzed urine samples from 30 SCA3 subjects (including one pre-symptomatic subject), 35 subjects with other forms of ataxia, and 37 healthy controls. To quantify polyQ ATXN3 protein levels, we used our previously developed immunoassay., Results: PolyQ ATXN3 can be detected in the urine of SCA3 patients, but not in urine samples from healthy controls or other forms of ataxia. There was a significant statistical association between polyQ ATXN3 levels in urine samples and those in plasma. Further, the levels of polyQ ATXN3 urine associated with an earlier age of SCA3 disease onset., Conclusion: As clinical trials for SCA3 advance, urine polyQ ATXN3 protein has potential to be a useful, non-invasive and inexpensive biomarker for SCA3., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fibrolamellar carcinoma (FLC) is a rare malignant entity arising from the liver and primarily affecting patients in late adolescence and young adulthood. FLC tumors are characterized by their unique histologic features and an only recently discovered genomic alteration: a chimeric fusion protein found in nearly all tumors. The rarity of these tumors coupled with the only recent acknowledgement of this genomic abnormality has likely led to disease under-recognition and de-prioritization of collaborative efforts aimed at establishing an evidence-guided standard of care. Surgical resection undoubtedly remains a mainstay of therapy and a necessity for cure but given the incidence of metastatic disease at diagnosis and high rates of distant relapse, systemic therapies remain a key component of disease control. There are few systemic therapies that have demonstrated proven benefit. Recent efforts have galvanized around single-institute or small consortia-based studies specifically focused on the enrollment of patients with FLC or use of agents with biologic rationale. This review will outline the current state of FLC epidemiology, histology, biology and trialed therapies derived from available published literature., (Copyright © 2021. Published by Elsevier Inc.)

Discovery of novel cocrystal systems and improvement of their physicochemical properties dominates the current literature on cocrystals yet the required end-product formulation is rarely addressed. Drug product manufacturing includes complex API solid state processing steps such as milling, granulation, and tableting. These all require high mechanical stress which can lead to solid-state phase transformations into polymorphs and solvates, or lead to dissociation of cocrystals into their individual components. Here we measured the effect of tablet excipients on solid-state processing of a range of pharmaceutical cocrystal formulations. Our findings were rationalised using Density Functional Theory (DFT) calculations of intermolecular binding energies of cocrystal constituents and co-milling excipients. A 1:1 stoichiometric ratio of API Theophylline (THP) and co-former 4-Aminobenzoic acid (4ABA) was co-milled with five different excipients: hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), lactose, and microcrystalline cellulose (MCC). The experiments were carried out in 10 and 25 ml milling jars at 30 Hz for different milling times. Co-milled samples were characterised for formation of cocrystals and phase transformation using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). Our data shows that co-milling in the presence of PEG, HMPC or lactose yields purer cocrystals, supported by the calculated stronger excipient interactions for PVP and MCC. We identify a suitably-prepared THP-4ABA pharmaceutical cocrystal formulation that is stable under extended milling conditions., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To describe the use of the internal mammary vein as an alternative access for central venous catheters., Methods: We performed a retrospective review of patients who underwent placement of central venous catheters via the internal mammary vein. Patient demographics, indication for venous access, technical success, catheter type, dwell time and indication for exchange or removal were recorded., Results: Placement of central venous catheters via the internal mammary vein was attempted in 11 patients including 8 children (4 males, mean age 5.7 years) and 3 adults. The most common indication was parenteral nutrition in patients with intestinal failure (7/11). Initial needle access of the vein was successful in all patients. Catheter placement was successful in 9 and unsuccessful in 2 patients due to occlusion of the superior vena cava. There were no immediate complications. A total of 20 catheters of various sizes (3-14.5 French) and lengths (8-23 cm) were either placed (n = 12) or exchanged (n = 8). The most common indications for catheter exchange were poor function and malposition (7/8). Four catheters were removed for infection and 4 were accidentally removed. The mean dwell time was 141 days (range 0-963 days) per catheter for a total of 2829 catheter days. The total mean dwell time per patient, including primarily placed and exchanged catheters, was 314 days (range 5-963 days)., Conclusions: The internal mammary vein may provide a safe alternative route for patients who have lost their traditional access veins., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This case-controlled study determined the utility of the READMIT index to identify the risk for 30-day readmission of patients discharged from an urban community hospital psychiatric inpatient unit. Data was collected from 118 matched patient pairs from 2017 to 2018. Findings demonstrated the READMIT index did not effectively discriminate those patients who were likely to readmit within 30 days. However, the following factors were associated with likelihood of 30-day readmission: the inability to care for self, number of lifetime readmissions, the comorbidity of liver disease, as well as a history of substance abuse.

Tau accumulation is a major pathological hallmark of Alzheimer's disease (AD) and other tauopathies, but the mechanism(s) of tau aggregation remains unclear. Taking advantage of the identification of tau filament cores by cryoelectron microscopy, we demonstrate that the AD tau core possesses the intrinsic ability to spontaneously aggregate in the absence of an inducer, with antibodies generated against AD tau core filaments detecting AD tau pathology. The AD tau core also drives aggregation of full-length wild-type tau, increases seeding potential, and templates abnormal forms of tau present in brain homogenates and antemortem cerebrospinal fluid (CSF) from patients with AD in an ultrasensitive real-time quaking-induced conversion (QuIC) assay. Finally, we show that the filament cores in corticobasal degeneration (CBD) and Pick's disease (PiD) similarly assemble into filaments under physiological conditions. These results document an approach to modeling tau aggregation and have significant implications for in vivo investigation of tau transmission and biomarker development., Competing Interests: Declaration of interests The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Photon-counting detector computed tomography (PCD-CT) is a modern spectral imaging technique utilizing photon-counting detectors (PCDs). PCDs detect individual photons and classify them into fixed energy bins, thus enabling energy selective imaging, contrary to energy integrating detectors that detects and sums the total energy from all photons during acquisition. The structure and composition of the articular cartilage cannot be detected with native CT imaging but can be assessed using contrast-enhancement. Spectral imaging allows simultaneous decomposition of multiple contrast agents, which can be used to target and highlight discrete cartilage properties. Here we report, for the first time, the use of PCD-CT to quantify a cationic iodinated CA4+ (targeting proteoglycans) and a non-ionic gadolinium-based gadoteridol (reflecting water content) contrast agents inside human osteochondral tissue (n = 53). We performed PCD-CT scanning at diffusion equilibrium and compared the results against reference data of biomechanical and optical density measurements, and Mankin scoring. PCD-CT enables simultaneous quantification of the two contrast agent concentrations inside cartilage and the results correlate with the structural and functional reference parameters. With improved soft tissue contrast and assessment of proteoglycan and water contents, PCD-CT with the dual contrast agent method is of potential use for the detection and monitoring of osteoarthritis.

Objective: To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects., Method: Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network., Results: In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ = 0.473) and instantaneous modulus (ρ = 0.498). These networks were used to predict the reference properties at baseline and at follow-up time points. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, a significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks., Conclusion: NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints were found more vulnerable to cartilage degeneration after damage than intercarpal joints., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To report MRI findings of changes seen in aneurysmal bone cysts after percutaneous sclerotherapy treatment., Materials and Methods: After applying exclusion criteria, a total of 36 patients who had aneurysmal bone cysts and undergone percutaneous sclerotherapy were included in this study. The pre-treatment and post-treatment MRIs were reviewed and multiple pre-determined MRI findings were evaluated. The presence of each post-treatment finding, as well as the time for each finding to develop, was recorded., Results: Early post-sclerotherapy changes include increased perilesional edema and enhancement, which appear on MRI on average 5.1 months after the initial sclerotherapy. This is followed by decreased cystic areas, which can be seen on average 5.9 months after the initial treatment. The presence of fibrosis, improved cortical integrity, and improving mass effect are later post-treatment changes and appear on MRI on average 9.7 months, 10.6 months, and 16.1 months after the initial sclerotherapy, respectively., Conclusion: The early and late post-sclerotherapy MR findings of aneurysmal bone cysts were reported in this study.

Near-infrared (NIR) spectroscopy is a powerful analytical method for rapid, non-destructive and label-free assessment of biological materials. Compared to mid-infrared spectroscopy, NIR spectroscopy excels in penetration depth, allowing intact biological tissue assessment, albeit at the cost of reduced molecular specificity. Furthermore, it is relatively safe compared to Raman spectroscopy, with no risk of laser-induced photothermal damage. A typical NIR spectroscopy workflow for biological tissue characterization involves sample preparation, spectral acquisition, pre-processing and analysis. The resulting spectrum embeds intrinsic information on the tissue's biomolecular, structural and functional properties. Here we demonstrate the analytical power of NIR spectroscopy for exploratory and diagnostic applications by providing instructions for acquiring NIR spectra, maps and images in biological tissues. By adapting and extending this protocol from the demonstrated application in connective tissues to other biological tissues, we expect that a typical NIR spectroscopic study can be performed by a non-specialist user to characterize biological tissues in basic research or clinical settings. We also describe how to use this protocol for exploratory study on connective tissues, including differentiating among ligament types, non-destructively monitoring changes in matrix formation during engineered cartilage development, mapping articular cartilage proteoglycan content across bovine patella and spectral imaging across the depth-wise zones of articular cartilage and subchondral bone. Depending on acquisition mode and experiment objectives, a typical exploratory study can be completed within 6 h, including sample preparation and data analysis.

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation., Competing Interests: The authors declare no competing interest.

Introduction: Nigeria is one of the most populated countries in the world; however, there is a scarcity of studies in patients with age-related neurodegenerative diseases, such as Parkinson disease (PD). The aim of this study was to screen patients with PD including a small cohort of early-onset PD (EOPD) cases from Nigeria for PRKN, PINK1, DJ1, SNCA multiplication, and LRRK2 p.G2019S. Methods: We assembled a cohort of 109 Nigerian patients with PD from the four main Nigerian tribes: Yoruba, Igbo, Edo, and Hausa. Fifteen cases [14 from the Yoruba tribe (93.3%)] had EOPD (defined as age-at-onset <50 years). All patients with EOPD were sequenced for the coding regions of PRKN, PINK1 , and DJ1 . Exon dosage analysis was performed with a multiplex ligation-dependent probe amplification assay, which also included a SNCA probe and LRRK2 p.G2019S. We screened for LRRK2 p.G2019S in the entire PD cohort using a genotyping assay. The PINK1 p.R501Q functional analysis was conducted. Results: In 15 patients with EOPD, 22 variants were observed [ PRKN , 9 (40.9%); PINK1 , 10 (45.5%); and DJ1 , 3 (13.6%)]. Three (13.6%) rare, nonsynonymous variants were identified, but no homozygous or compound heterozygous carriers were found. No exonic rearrangements were present in the three genes, and no carriers of SNCA genomic multiplications or LRRK2 p.G2019S were identified. The PINK1 p.R501Q functional analysis revealed pathogenic loss of function. Conclusion: More studies on age-related neurodegenerative diseases are needed in sub-Saharan African countries, including Nigeria. Population-specific variation may provide insight into the genes involved in PD in the local population but may also contribute to larger studiesperformed in White and Asian populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potentialconflict of interest. The handling Editor declared a past co-authorship with several of the authors OR, ZW at time of review., (Copyright © 2021 Milanowski, Oshinaike, Broadway, Lindemann, Soto-Beasley, Walton, Hanna Al-Shaikh, Strongosky, Fiesel, Ross, Springer, Ogun and Wszolek.)

Introduction: Individual's early life style and health behaviors are directly linked to chronic non-communicable diseases. Considering the increased burden of NCDs during the last two decades, the aim of this study is to assess co-occurrence/clustering of lifestyle risk factors and its association with different socio-demographic and economic characteristics among adult men and women in India from 2005-2016., Methods: This study utilized the data from the National Family Health Survey 2005-06 and 2015-16 survey rounds. Multinomial logistic regression is employed to evaluate co-occurrence of multiple risk factors among adult men and women of different socio-economic and demographic characteristics to identify the subgroups with elevated risk of clustering of multiple unhealthy lifestyle risk factors., Results: More adult men in India tend to exhibit clustering of multiple non-communicable disease risk factors than females. Individuals between 30-49 years of age, residing in urban areas, the population with no education, separated couples and those from poor economic strata are the specific population subgroups show higher prevalence of co-occurrence of multiple risk factors. The regional pattern of clustering of risk factors shows that the prevalence of co-occurrence of multiple risk factors is higher among men and women from the North-Eastern part of India compared to the other regions of the country., Conclusion: The prevalence of clustering of multiple risk factors associated with chronic NCDs is substantially high and has increased between 2005-06 to 2015-16. India may therefore experience a significant increase in the burden of chronic non-communicable diseases in the coming years. We therefore conclude that appropriate strategies should be implemented by policy makers and the government to reduce the overall health burden of NCDs due to lifestyle habits., Competing Interests: The authors have declared that no competing interest exist.

The demand for interventional oncological (IO) treatment of pediatric cancers is becoming increasingly common, at least at several tertiary care institutions. The data and techniques used in pediatric IO are largely extrapolated from experience in adult patients. The management of pediatric tumors differs from that in adults in several categories, such as, the curative intent of treatment, wide use of general anesthesia, aggressive pain management, potentially longer hospital stay, variation in chemotherapy dosing etc. Additionally, pediatric cancers are managed by protocols directed by national and international oncology groups such as the Children's Oncology Group (COG). Consequently, the translation and adoption of these techniques is gradual, but there is a noticeable uptrend due to the growing need. This review will update the current endovascular IO treatments for common pediatric liver, renal, bone and soft tissue tumors.

The Triangular Theory of Love (measured with Sternberg's Triangular Love Scale - STLS) is a prominent theoretical concept in empirical research on love. To expand the culturally homogeneous body of previous psychometric research regarding the STLS, we conducted a large-scale cross-cultural study with the use of this scale. In total, we examined more than 11,000 respondents, but as a result of applied exclusion criteria, the final analyses were based on a sample of 7332 participants from 25 countries (from all inhabited continents). We tested configural invariance, metric invariance, and scalar invariance, all of which confirmed the cultural universality of the theoretical construct of love analyzed in our study. We also observed that levels of love components differ depending on relationship duration, following the dynamics suggested in the Triangular Theory of Love. Supplementary files with all our data, including results on love intensity across different countries along with STLS versions adapted in a few dozen languages, will further enable more extensive research on the Triangular Theory of Love.

The five melanocortin receptors regulate numerous physiological functions. Although many ligands have been developed for the melanocortin-4 receptor (MC4R), the melanocortin-3 receptor (MC3R) has been less-well characterized, in part due to the lack of potent, selective tool compounds. Previously an Ac-His-Arg-(pI)DPhe-Tic-NH 2 scaffold, inverting the Phe-Arg motif of the native melanocortin signal sequence, was identified to possess mMC3R over mMC4R selective agonist activity. In this study, a library of 12 compounds derived from this scaffold was synthesized and assayed at the mouse melanocortin receptors (MCRs), utilizing substitutions previously shown to increase mMC3R agonist potency and/or selectivity. One compound ( 8 , Ac-Val-Gln-DBip-DTic-NH 2 ) was identified as greater than 140-fold selective for the mMC3R over the mMC4R, possessed 70 nM potency at the mMC3R, and partially stimulated the mMC4R at 100 μM concentrations without antagonist activity. This pharmacological profile may be useful in developing new tool and therapeutic ligands that selective signal through the MC3R., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

A comprehensive study regarding the effect of different solvent vapours on organolead halide perovskite properties is lacking. In the present work, the impact of exposing CH 3 NH 3 PbI 3 films to the vapours of commonly available solvents has been studied. The interaction with perovskite has been correlated to solvent properties like dielectric constant, molecular dipole moment, Gutmann donor number and boiling point. Changes in the crystallinity, phase, optical absorption, morphologies at both nanometer and micrometer scale, functional groups and structures were studied using X-ray diffraction, UV-visible absorption, FE-SEM, FTIR and Raman spectroscopies. Among the aprotic solvents DMSO and DMF vapours deteriorate the crystallinity, phase, and optical, morphological and structural properties of the perovskite films in a very short time, but due to the difference in solvent property values acetone affects the perovskite properties differently. Polar protic 2-propanol and water vapours moderately affect the perovskite properties. However 2-propanol can solvate the organic cation CH 3 NH 3 + more efficiently as compared to water and a considerable difference was found in the film properties especially the morphology at the nanoscale. Nonpolar chlorobenzene vapour minutely affects the perovskite morphology but toluene was found to enhance perovskite crystallinity. Solvent properties can be effectively used to interpret the coordination ability of a solvent. The present study can be immensely useful in understanding the effects of different solvent vapours and also their use for post-deposition processing (like solvent vapour annealing) to improve their properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background and Aims: To Investigate the factors associated with Diabetic Ketoacidosis (DKA) among patients with type 1 diabetes (T1D)., Methods: This was a descriptive, retrospective study conducted among 1118 patients with T1D, at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia. After, exclusion process, 336 patients were selected for analysis. Among these, 105 patients with T1D were hospitalized for DKA, whereas 231 patients without DKA were outpatients who visited the hospital for T1D follow-up treatment., Results: Bivariate analysis between patients with DKA and those without DKA revealed significant relationships in terms of gender (p = 0.014), age (p = 0.0001), body mass index (BMI) (p = 0.017), hemoglobin A1c (HbA1c) (p = 0.0001), duration of diabetes (p = 0.001) and clinic appointments (p = 0.001). From the logistic regression analysis, it was clear that females (OR 1.88; p = 0.038) had a higher risk for DKA. As compared to the age group of ≥30 years, those in the age category of 20-29 years (OR 1.35; p = 0.001) and teenagers (OR 3.64; p = 0.001) faced a higher risk of having DKA episodes. Compared with patients having HbA1c levels <8%, those showing HbA1c levels 8-9.9% (OR 1.77; p = 0.224) and ≥10% (OR 4.06; p = 0.003) revealed higher risk for DKA. Likewise, in comparison with the patients who were compliant to clinic appointments, those who were non-compliant to clinic appointments exhibited higher than six times the risk (OR 6.38; p = 0.0001) of being more prone to experiencing the DKA episodes., Conclusion: Patients with higher risk for DKA comprise, those having high HbA1c levels, longer period of diabetes duration, teenagers, female gender and non-compliant to clinic appointments., Competing Interests: Declaration of competing interest Authors have no conflict of interests., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objective: Following percutaneous liver biopsy performed at our institution on an outpatient basis, children traditionally were observed for 4 hours then discharged after verifying a stable hematocrit level. In June 2015, we adopted a quality improvement project with shorter 2-hour observation for patients with no known risks and the hematocrit test was abandoned.The purpose of this study is to evaluate the clinical and economic outcomes of early discharge of children following liver biopsy., Methods: We analyzed data on 2 groups of children who underwent ultrasound-guided nontargeted core needle liver biopsy performed on outpatient basis. Group A (100 procedures with 4-hour postprocedural observation time and hematocrit test) was compared with group B (100 procedures with 2-hour observation without hematocrit test)., Results: Group A consisted of 92 patients (43 boys; 49 girls) with a mean age of 11.1 years and mean weight of 52.6 kg. Group B had 92 patients (47 boys; 45 girls) with a mean age of 8.9 years and mean weight of 40.5 kg. The mean length of observation was 281 minutes (range 204-540 minutes) and 147 minutes (range 86-332 minutes) for groups A and B, respectively. The mean recovery charges were reduced by 35% per procedure in group B. The tissue obtained was sufficient for pathologic diagnosis in all procedures. There were no biopsy-related complications in either group., Conclusions: Enhanced recovery with early discharge of low-risk children after 2-hour observation following percutaneous liver biopsy can be safely implemented without adversely affecting the outcome. Shorter postbiopsy observation can be cost-saving and may potentially improve patient satisfaction.

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent., (© 2020 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

This study evaluates the feasibility of near infrared (NIR) spectroscopy to distinguish between different cartilage injury types associated with post-traumatic osteoarthritis and idiopathic osteoarthritis (OA) induced by mechanical and enzymatic damages. Bovine osteochondral samples (n = 72) were subjected to mechanical (n = 24) and enzymatic (n = 36) damage; NIR spectral measurements were acquired from each sample before and after damage, and from a separate control group (n = 12). Biomechanical measurements were then conducted to determine the functional integrity of the samples. NIR spectral variations resulting from different damage types were investigated and the samples classified using partial least squares discriminant analysis (PLS-DA). Partial least squares regression (PLSR) was then employed to investigate the relationship between the NIR spectra and biomechanical properties of the samples. Results of the study demonstrate that substantial spectral changes occur in the region of 1700-2200 nm due to tissue damages, while differences between enzymatically and mechanically induced damages can be observed mainly in the region of 1780-1810 nm. We conclude that NIR spectroscopy, combined with multivariate analysis, is capable of discriminating between cartilage injuries that mimic idiopathic OA and traumatic injuries based on specific spectral features. This information could be useful in determining the optimal treatment strategy during cartilage repair in arthroscopy.

Introduction: Tissue from pediatric solid tumors is in high demand for use in high-impact research studies, making the allocation of tissue from an anatomic pathology laboratory challenging. We designed, implemented, and assessed an interdepartmental process to optimize tissue allocation of pediatric solid tumors for both clinical care and research., Methods: Oncologists, pathologists, surgeons, interventional radiologists, pathology technical staff, and clinical research coordinators participated in the workflow design. Procedures were created to address patient identification and consent, prioritization of protocols, electronic communication of requests, tissue preparation, and distribution. Pathologists were surveyed about the value of the new workflow., Results: Over a 5-year period, 644 pediatric solid tumor patients consented to one or more studies requesting archival or fresh tissue. Patients had a variety of tumor types, with many rare and singular diagnoses. Sixty-seven percent of 1768 research requests were fulfilled. Requests for archival tissue were fulfilled at a significantly higher rate than those for fresh tissue (P > .001), and requests from resection specimens were fulfilled at a significantly higher rate than those from biopsies (P > .0001). In an anonymous survey, seven of seven pathologists reported that the process had improved since the introduction of the electronic communication model., Conclusions: A collaborative and informed model for tissue allocation is successful in distributing archival and fresh tissue for clinical research studies. Our workflows and policies have gained pathologists' approval and streamlined our processes. As clinical and research programs evolve, a thoughtful tissue allocation process will facilitate ongoing research., (© 2020 Wiley Periodicals, Inc.)

Introduction: There is poor penetration of evidence-based maternal health care provided under national health programs in resource-poor underserved regions. A well-planned locally acceptable community-driven comprehensive health promotion strategy and quality health care delivery mechanism is necessary to improve the situation., Objective: The main objective was to find the gaps in the existing system and promote health literacy and health-seeking behavior., Methodology: 80,000 tribal population living in isolated conflict zone of Bastar district was covered for 5 years between 2012 and 2017. An integrated health-care plan was developed with community leaders, panchayat, and the local government to promote and provide quality evidence-based maternal health care. Available resources were mobilized and health technologies introduced., Results: Regular home visits, point of care diagnostics, identification of high-risk mothers and their timely referral, and behavioral change communication increased the trust of the community. It resulted in higher demand for evidence-based health interventions. The adolescent pregnancy rate (<19 years) reduced to 6.8% (2016) from 13.5% (2012). Hemoglobin level >9 g% (third trimester) improved. Supervised births and high-risk referrals increased from 19.5% (2014) to 58% (2017) and 8.5% (2014) to 13.1% (2017), respectively. Although significant improvement was noted, key indicators continued to remain below rural Bastar (National Family Health Survey-4)., Conclusion: Promotion of existing good practices, behavior change, health technologies, and evidence-based emergency care improved the maternal health status of the secluded and underserved tribal community, but persistent effort is needed to enable women access the quality maternal health services provided under National Health Mission., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Community Medicine.)

Diabetic retinopathy (DR) is a microvascular complication of the retina of the eye and represents a major cause of blindness worldwide. It is a complex disorder characterized by both genetic and environmental factors. The vascular endothelial growth factor (VEGF) gene is among the main candidate genes for DR, as it is also involved in several other diseases, such as microvascular complications of diabetes mellitus and cancer. The VEGF gene is extremely polymorphic. The 18-bp fragment (insertion/deletion) polymorphism at the -2549 position of the promoter region of the VEGF gene is of great importance. In this review, we highlight the DR and VEGF gene (insertion/deletion) polymorphism. In addition, we assess this association in various DR populations and in other microvascular complications, such as diabetic nephropathy, diabetic peripheral neuropathy and cancer., (Copyright © 2019 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze outcomes and complications related to cataract surgery complicated by retained lens fragment (RLF) requiring pars plana vitrectomy (PPV) in a county hospital where procedures are performed by trainees., Methods: Retrospective study of consecutive patients who met inclusion criteria and underwent PPV for RLF in the vitreous cavity at an urban teaching hospital between January 2010 and January 2016 (N=20)., Main Outcomes/measures: Visual acuity was recorded pre- and post-operatively over a follow-up period of 3 to 12 months. Complications and patient factors contributing to outcomes were assessed using paired and unpaired t-tests and multiple linear regression., Results: The average rate of cataract surgery with RLF requiring PPV was 0.75%. Twenty patients met inclusion criteria. Mean pre-operative visual acuity (VA) was logMAR 1.7 (Snellen 20/1000). Nearly half (8/20) had nuclear cataracts grade 3+ or higher. The majority (14/20) had factors predisposing them to cataract surgery complications. Most patients underwent PPV within 1 week (median 6.5 days). At 12-month follow-up, significant (p=0.001) visual acuity (VA) improvement from initial VA was observed, with final mean logMAR 0.6 (± 0.75; Snellen 20/80) and median logMAR 0.35 (Snellen 20/45). Nearly half of the patients had a final Snellen VA ≥20/40. Factors associated with less VA improvement were older age and greater proportion of lens dropped (p<0.01). Complications following PPV included hypotony (5 patients), corneal edema (4), elevated intraocular pressure (IOP) (3), and cystoid macular edema (3)., Conclusions/relevance: Despite patients with advanced pathology and trainee surgeons, rates of cataract surgery-associated RLF requiring PPV at a large tertiary care teaching hospital are similar to reported rates in the literature., Competing Interests: Dr Christina Y Weng reports personal fees from Alcon, Inc., Allergan, Inc., Alimera Sciences, Inc., outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Lin et al.)

Background: Fibroadipose vascular anomaly (FAVA) is a recently-defined vascular malformation often involving the extremities and presenting in childhood. Patients may present to orthopaedic surgeons with pain, swelling, joint contractures, and leg length discrepancy. There is no established therapy or treatment paradigm. We report on outcomes following surgical excision for patients with this condition., Methods: Between 2007 and 2016, all 35 patients that underwent excision of lower-extremity FAVA were retrospectively reviewed using a combination of medical records, radiologic findings, and telemedicine reviews., Results: Mean age at initial presentation was 12.3±6.8 years. Mean follow-up from time of definitive diagnosis at our institution was 66 months (range: 12 to 161 mo). Mean follow-up after surgery was 35 months (range: 6 to 138 mo). Females were affected more than males (71% vs. 29%). The most common location of FAVA was in the calf (49%), followed by the thigh (40%). The most commonly involved muscle was gastrocnemius (29%), followed by the quadriceps (26%). At latest follow-up after surgery, there was an improvement in the proportion of patients with pain at rest (63% vs. 29%), pain with activity (100% vs. 60%), as well as analgesia use (94% vs. 37%). Fourteen patients (40%) had symptomatic residual disease or recurrence of FAVA requiring further treatment. Six patients (17%) required further surgery and 6 (17%) required further interventional radiologic procedures. Three patients (9%) required eventual amputation for intractable pain and loss of function. Lesions with direct nerve involvement were associated with persistent neuropathic symptoms at latest follow-up (P=0.002) as well as symptomatic residual disease and/or recurrence requiring further treatment (P=0.01). Seventeen patients (49%) had 19 preoperative joint contractures. Eighteen of the 19 contractures (95%) had sustained improvement at latest follow-up., Conclusions: In carefully selected patients, surgical excision of FAVA results in improvement of symptoms. However, symptomatic residual disease and/or recurrence are not uncommon. Direct nerve involvement is associated with a worse outcome., Level of Evidence: Level IV-case series.