A Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases.

BACKGROUND: This exploratory pooled analysis investigated the efficacy and safety of trastuzumab deruxtecan (T-DXd) versus comparator treatment in patients with HER2-positive metastatic breast cancer (mBC) with brain metastases (BMs) at baseline, categorized according to previous local treatment. PATIENTS AND METHODS: T-DXd data were pooled from DESTINY-Breast01/-02/-03. Comparator data, from patients receiving physician's choice therapy and trastuzumab emtansine, were pooled from DESTINY-Breast02 and -03, respectively. Baseline BM status was assessed according to US Food and Drug Administration criteria. Endpoints included intracranial objective response rate (ORR; complete or partial response in brain) per blinded independent central review (BICR) by RECIST v1.1, time to intracranial response, intracranial duration of response (DoR), central nervous system progression-free survival (CNS-PFS) by BICR, overall survival (OS), and safety. RESULTS: 148 patients who received T-DXd and 83 patients who received comparator treatment had BMs at baseline. In those who were treated with T-DXd, the intracranial ORR of patients with treated/stable and untreated/active BMs was 45.2% and 45.5%, respectively. The median (range) time to intracranial response was 2.8 months (1.1-13.9 months) and 1.5 months (1.2-13.7 months) in patients with treated/stable and untreated/active BMs, respectively. For those with treated/stable BMs, the median (95% CI) intracranial DoR was 12.3 months (9.1-17.9 months), and for those with untreated/active BMs it was 17.5 months (13.6-31.6 months). The median (95% CI) CNS-PFS and OS was 12.3 months (11.1-13.8 months) and not reached (22.1 months-not estimable [NE]) in those with treated/stable BMs, and 18.5 months (13.6-23.3 months) and 30.2 months (21.3 months-NE) in those with untreated/active BMs, respectively. Drug-related TEAEs grade ≥3 were experienced by 43.2% of patients with BMs and 46.4% without BMs with T-DXd. CONCLUSIONS: T-DXd demonstrated meaningful intracranial efficacy and clinical benefit in OS, with an acceptable and manageable safety profile in patients with HER2-positive mBC with treated/stable and untreated/active BMs.

Utility of cranial MRI in non-traumatic headache patients with prior negative head CT within 1 month.

AIM: To investigate the importance of additional cranial magnetic resonance imaging (cMRI) in non-traumatic headache patients with a prior negative head computed tomography (CT) examination within 1 month. MATERIALS AND METHODS: This retrospective study analysed 162 adult patients with non-traumatic headache who underwent cMRI within 1 month of a negative initial head CT at the emergency department (ED). The diagnostic yield and false-referral rate were analysed according to the revisit duration (early [≤1 week] versus late [>1-4 weeks] revisits), patient care settings (ED versus outpatient clinics [OPC]), and clinical variables. Subsequent patient management change (PMC), such as admission and treatment (AT) or outpatient clinic treatment (OT), were also investigated. RESULTS: The overall diagnostic yield of cMRI was 17.3% (28/162) and the false-referral rate was 1.2% (2/162). The diagnostic yield of cMRI was significantly different according to the patient care settings (ED, 24.7% [21/85] versus OPC, 9.1% [7/77]; p=0.02). The diagnostic yield was highest in the ED-early-revisit group (25.4% [18/71]), 45% (9/20) in those with systemic signs, and 46.7% (14/30) in those with symptom change. Among patients with positive cMRI findings, 90% (27/30) received AT and 3.3% (1/30) received OT. Among OPC-revisit-negative cMRI patients, PMC occurred in 0% (0/50). CONCLUSION: The diagnostic yield of cMRI was relatively high for headache patients who revisited the ED earlier, especially in those with systemic signs or symptom change. Most positive cMRI cases experienced PMC. Negative cMRI in OPC-revisit patients might help clarify the benign nature of a condition.

Orbital angular momentum densities in the astigmatic transformation of Lissajous geometric laser modes.

Orbital angular momentum densities in the astigmatic transformation of Lissajous geometric laser modes are originally and systematically investigated. The quantum theory of the coherent state is exploited to derive an analytical wave representation for the transformed output beams. The derived wave function is further employed to numerically analyze the propagation dependent orbital angular momentum densities. The parts of the negative and positive regions in the orbital angular momentum density are found to rapidly change in the Rayleigh range behind the transformation.

Facile preparation of porphyrin@g-C3N4/Ag nanocomposite for improved photocatalytic degradation of organic dyes in aqueous solution.

In the quest of improving the photocatalytic efficiency of photocatalysts, the combination of two and more semiconductors recently has garnered significant attention among scientists in the field. The doping of conductive metals is also an effective pathway to improve photocatalytic performance by avoiding electron/hole pair recombination and enhancing photon energy absorption. This work presented a design and fabrication of porphyrin@g-C3N4/Ag nanocomposite using acid-base neutralization-induced self-assembly approach from monomeric porphyrin and g-C3N4/Ag material. g-C3N4/Ag material was synthesized by a green reductant of Cleistocalyx operculatus leaf extract. Electron scanning microscopy (SEM), X-ray diffraction (XRD), FT-IR spectroscopy, and UV-vis spectrometer were utilized to analyse the properties of the prepared materials. The prepared porphyrin@g-C3N4/Ag nanocomposite showed well integration of porphyrin nanostructures on the g-C3N4/Ag's surface, in which porphyrin nanofiber was of the diameter in nanoscales and the length of several micrometers, and Ag NPs had an average particle size of less than 20 nm. The photocatalytic behavior of the resultant nanocomposite was tested for the degradation of Rhodamine B dye, which exhibited a remarkable RhB photodegrading percentage. The possible mechanism for photocatalysis of the porphyrin@g-C3N4/Ag nanocomposite toward Rhodamine B dye was also proposed and discussed.

The efficiency of potential food waste-degrading bacteria under harsh conditions.

AIMS: Investigate the impact of highly adapted bacterial strains and their ability in waste degradation under a wide range of temperatures. METHODS AND RESULTS: Bacteria isolated from soil and food waste were grown in various media under fluctuated temperatures. After screening for organic compound degradation, the seven strongest bacterial strains have been selected for further experiments. Their enzyme activities were expressed in terms of the size of the hydrolysis zone in a wide temperature range of 2·5-70°C. The enzyme production assay was carried out for each protease, cellulase and amylase. The waste degradation was determined with a maximum 80% decrease in the volume of food waste in 21 days compared to the control in lab scale with enriched bacterial cultures and soil bacteria as additives at room temperature around 18-20°C. CONCLUSION: These seven bacteria are promising candidates for food waste biodegradation in composting especially in the winter without heating expense for maintaining ambient temperature. SIGNIFICANCE AND IMPACT OF THE STUDY: It is necessary to coax the uncultured bacteria from the various environments into the laboratory for investigating their valuable functions. Herein, using enrichment culture of consortium and additive of soil has illustrated the significant mean in food waste degradation.

Can electrocoagulation technology be integrated with wastewater treatment systems to improve treatment efficiency?

Considerable amounts of domestic and industrial wastewater that should be treated before reuse are discharged into the environment annually. Electrocoagulation is an electrochemical technology in which electrical current is conducted through electrodes, it is mainly used to remove several types of wastewater pollutants, such as dyes, toxic materials, oil content, chemical oxygen demand, and salinity, individually or in combination with other processes. Electrocoagulation technology used in hybrid systems along with other technologies for wastewater treatment are reviewed in this work, and the articles reviewed herein were published from 2018 to 2021. Electrocoagulation is widely employed in integrated systems with other electrochemical technologies or conventional methods for effective removal of different pollutants with less cost and sometimes over shorter durations of operation. It has also been observed that the hybrid effects besides increasing the removal efficiency can overcome the disadvantages of using electrocoagulation alone, such as less sludge formation, high cost of operation and increased life of the used electrodes, and stable flux of water with longer periods of operation. More than 20 types of other technologies have been combined efficiently with electrocoagulation.

Novel pure α-, ß-, and mixed-phase α/ß-Bi2O3 photocatalysts for enhanced organic dye degradation under both visible light and solar irradiation.

Combining the pure α- and ß-phases of bismuth oxide enhances its photocatalytic activity under both visible and solar irradiation. α-Bi2O3, ß-Bi2O3, and α/ß-Bi2O3 were synthesized by a solvothermal calcination method. The structural, optical, and morphological properties of the as-synthesized catalysts were analyzed using XRD, UV-DRS, XPS, SEM, TEM, and PL. The bandgaps of α/ß-Bi2O3, α-Bi2O3, and ß-Bi2O3 were calculated to be 2.59, 2.73, and 2.34 eV, respectively. The photocatalytic activities of the catalysts under visible and solar irradiation were examined by the degradation of carcinogenic reactive blue 198 and reactive black 5 dyes. The kinetic plots of the degradation reactions followed pseudo-first-order kinetics. α/ß-Bi2O3 exhibited higher photocatalytic activity (∼99%) than α-Bi2O3 and ß-Bi2O3 under visible and solar irradiation. The TOC and COD results confirmed the maximum degradation ability of α/ß-Bi2O3, and the decolorization percentage remained above 90%, even after five cycles under visible irradiation. The photocatalytic dye degradation mechanism employed by α/ß-Bi2O3 was proposed based on active species trapping experiments.

The association of BMI and physical activity on acetabular dysplasia in children.

BACKGROUND: Acetabular dysplasia is an important pre-disposing factor for osteoarthritis of the hip. However, it is not completely known how acetabular dysplasia develops during childhood. OBJECTIVE: To study the prevalence of acetabular dysplasia and its association with body mass index (BMI) and physical activity in 9 year old children. DESIGN: The population for this cross-sectional study was drawn from the ongoing prospective cohort study: Generation R. 9,778 mothers with a delivery date from March 2002 until January 2006 were enrolled. In a random subgroup of these children Dual-energy X-ray absorptiometry (DXA) scanning was performed at age 9. EXPOSURES: BMI, standardized for the Dutch population and categorized in four groups based on extended international Obesity Task Force cut-offs: underweight, normal, overweight and obesity. Physical activity was based on time spent on playing outdoors, playing sports and walking/cycling to school. MAIN OUTCOMES AND MEASURES: The degree of acetabular dysplasia was determined with the centre-edge angle (CEA) and acetabular depth-width ratio (ADR) in DXA images of the hip. RESULTS: 1,188 DXA images of children's hips were available for analysis. The median age of the children was 9.86 years. Prevalence of dysplasia and mild dysplasia was respectively 6.3%; 25.6% with CEA and 4.8%; 25.0% with ADR. BMI was negatively associated with mild dysplasia (OR 0.80 CI 0.71-0.90). Obese children showed less mild dysplasia compared to normal children (OR 0.48 CI 0.24-0.97) in unadjusted analysis. Physical activity represented by walking to school showed a statistically significant negative association with mild dysplasia (OR 0.87 CI 0.76-0.99). After adjustment for age, ethnicity, sex, first born, breech presentation, birthweight, gestational age and Caesarean section, the patterns of association with dysplasia remained for both BMI and physical activity. CONCLUSIONS: In this study, being overweight and light physical activity were negatively associated with the development of (mild) acetabular dysplasia at the age of 9 years.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

The risk of anti-osteoporotic agent-induced severe cutaneous adverse drug reactions and their association with HLA.

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.

Racial and Ethnic Differences in BRCA1/2 and Multigene Panel Testing Among Young Breast Cancer Patients.

Genetic testing for hereditary breast and ovarian cancer (HBOC) is recommended for breast cancer patients diagnosed at age ≤ 50 years. Our objective was to examine racial/ethnic differences in genetic testing frequency and results among diverse breast cancer patients. A retrospective cohort study among women diagnosed with breast cancer at age ≤ 50 years from January 2007 to December 2017 at Columbia University in New York, NY. Among 1503 diverse young breast cancer patients, nearly half (46.2%) completed HBOC genetic testing. Genetic testing completion was associated with younger age, family history of breast cancer, and earlier stage, but not race/ethnicity or health insurance status. Blacks had the highest frequency of pathogenic/likely pathogenic (P/LP) variants (18.6%), and Hispanics and Asians had the most variants of uncertain significance (VUS), 19.0% and 21.9%, respectively. The percentage of women undergoing genetic testing increased over time from 15.3% in 2007 to a peak of 72.8% in 2015. Over the same time period, there was a significant increase in P/LP and VUS results. Due to uncertainty about the clinical implications of P/LP variants in moderate penetrance genes and VUSs, our findings underscore the need for targeted genetic counseling education, particularly among young minority breast cancer patients.

ORE identifies extreme expression effects enriched for rare variants.

MOTIVATION: Non-coding rare variants (RVs) may contribute to Mendelian disorders but have been challenging to study due to small sample sizes, genetic heterogeneity and uncertainty about relevant non-coding features. Previous studies identified RVs associated with expression outliers, but varying outlier definitions were employed and no comprehensive open-source software was developed. RESULTS: We developed Outlier-RV Enrichment (ORE) to identify biologically-meaningful non-coding RVs. We implemented ORE combining whole-genome sequencing and cardiac RNAseq from congenital heart defect patients from the Pediatric Cardiac Genomics Consortium and deceased adults from Genotype-Tissue Expression. Use of rank-based outliers maximized sensitivity while a most extreme outlier approach maximized specificity. Rarer variants had stronger associations, suggesting they are under negative selective pressure and providing a basis for investigating their contribution to Mendelian disorders. AVAILABILITY AND IMPLEMENTATION: ORE, source code, and documentation are available at https://pypi.python.org/pypi/ore under the MIT license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Complications of Elbow Arthroscopy in a Community-Based Practice.

PURPOSE: The purpose of this study was to report the complications of elbow arthroscopy in a large community practice with multiple surgeons and to analyze potential risk factors for these complications. METHODS: Patient demographic information, surgical variables, surgeon variables, and complications were retrospectively reviewed for all elbow arthroscopies performed within the health network from 2006 to 2014. Inclusion criteria included patients of any age undergoing a primary and revision elbow arthroscopy, which may have been performed in conjunction with other procedures. Exclusion criteria included incorrectly coded procedures where arthroscopy was not performed and no postoperative follow-up. Statistical calculations were performed using a binary logistic regression analysis to fit a logistic regression model. RESULTS: 560 consecutive elbow arthroscopies in 528 patients performed between 2006 and 2014, by 42 surgeons at 14 facilities, were reviewed. 113 procedures were performed in pediatric patients under the age of 18. The average age was 38.6 years (range: 5-88). There were 444 males. The average length of follow-up was 375.8 days (2 to 2,739 days). Overall, heterotopic ossification occurred in 14 of 560 cases (2.5%) (all males), and 20 of 560 (3.5%) cases developed transient nerve palsies (8 ulnar, 8 radial, 1 median, 3 medial antebrachial cutaneous). There were 3 (0.5%) deep and 11 (2%) superficial infections. There were no vascular injuries, compartment syndrome, deep vein thrombosis, or pulmonary embolism. Elevated blood sugar was a significantly higher risk for infection (odds ratio [OR] 4.11, 95% confidence interval [CI] 1.337 to 12.645; P = .0136). Previous elbow surgery (OR 3.57, 95% CI 1.440 to 8.938; P = .006) and female sex (OR 4.05; 95% CI 1.642 to 9.970; P = .002) had a significantly higher risk for nerve injury. Relative to pediatric patients, there were higher odds in adults for nerve injury, infection, and heterotopic ossification, but none reached significance. CONCLUSIONS: Elbow arthroscopy is a safe procedure with low complication rates. Diabetes is a risk factor for infection. Prior surgery and female sex are risk factors for nerve injury. LEVEL OF EVIDENCE: Case series, level 4.

ALK-positive histiocytosis: an expanded clinicopathologic spectrum and frequent presence of KIF5B-ALK fusion.

In 2008, we presented three cases of ALK-positive histiocytosis as a novel systemic histiocytic proliferation of early infancy with hepatosplenomegaly and dramatic hematological disturbances. This series of 10 cases (including the original three cases) describes an expanded clinicopathological spectrum and the molecular findings of this histiocytic proliferation. Six patients had disseminated disease: five presented in early infancy with eventual disease resolution, and the sixth presented at 2 years of age and died of intestinal, bone marrow, and brain involvement. The other four patients had localized disease involving nasal skin, foot, breast, and intracranial cavernous sinus - the first three had no recurrence after surgical resection, while the cavernous sinus lesion showed complete resolution with crizotinib therapy. The lesional histiocytes were very large, with irregularly folded nuclei, fine chromatin, and abundant eosinophilic cytoplasm, sometimes with emperipolesis. There could be an increase in foamy histiocytes and Touton giant cells with time, resembling juvenile xanthogranuloma. Immunostaining showed that the histiocytes were positive for ALK, histiocytic markers (CD68, CD163) and variably S100, while being negative for CD1a, CD207, and BRAF-V600E. Next-generation sequencing-based anchored multiplex PCR (Archer® FusionPlex®) performed in six cases identified KIF5B-ALK gene fusion in five and COL1A2-ALK fusion in one. There was no correlation of gene fusion type with disease localization or dissemination. The clinicopathological spectrum of ALK-positive histiocytosis is broader than originally described, and this entity is characterized by frequent presence of KIF5B-ALK gene fusion. We recommend that every unusual histiocytic proliferative disorder, especially disseminated lesions, be tested for ALK expression because of the potential efficacy of ALK inhibitor therapy in unresectable or disseminated disease.

De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.

Serum and blister-fluid elevation and decreased epidermal content of high-mobility group box 1 protein in drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: High-mobility group box 1 (HMGB1) is a damage-associated molecular-pattern protein. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are serious, immune-mediated skin-blistering conditions. OBJECTIVES: To determine serum and/or blister-fluid total HMGB1 levels in SJS/TEN cohorts, and HMGB1 expression in formalin-fixed, paraffin-embedded (FFPE) SJS/TEN skin vs. healthy and maculopapular exanthema (MPE) skin. Methods Serum HMGB1 was quantified in Malawian nevirapine-induced hypersensitivity, Taiwanese SJS/TEN and Spanish SJS/TEN cohorts. FFPE skin (healthy skin, MPE, SJS/TEN) was stained and assessed for HMGB1 expression. RESULTS: Serum total HMGB1 was not significantly elevated in patients with nevirapine-induced SJS/TEN (3·98 ± 2·17 ng mL-1 ), MPE (3·92 ± 2·75 ng mL-1 ) or drug reaction with eosinophilia and systemic symptoms (4·73 ± 3·00 ng mL-1 ) vs. tolerant controls (2·97 ± 3·00 ng mL-1 ). HMGB1 was significantly elevated in Taiwanese patients with SJS/TEN, highest during the acute phase (32·6 ± 26·6 ng mL-1 ) vs. the maximal (19·7 ± 23·2 ng mL-1 ; P = 0·007) and recovery (24·6 ± 25·3 ng mL-1 ; P = 0·027) phases. In blister fluid from Spanish patients with SJS/TEN, HMGB1 (486·8 ± 687·9 ng mL-1 ) was significantly higher than in serum (8·8 ± 7·6 ng mL-1 ; P <0·001). Preblistered SJS/TEN skin showed decreased epidermal nuclear HMGB1 expression in upper epidermis vs. healthy or MPE skin but retained basal/suprabasal expression. CONCLUSIONS: Epidermal HMGB1 expression was decreased in SJS/TEN skin. Retained basal/suprabasal epidermal HMGB1 expression may exacerbate localized injury in SJS/TEN.

Microplastics Can Change Soil Properties and Affect Plant Performance.

Microplastics can affect biophysical properties of the soil. However, little is known about the cascade of events in fundamental levels of terrestrial ecosystems, i.e., starting with the changes in soil abiotic properties and propagating across the various components of soil-plant interactions, including soil microbial communities and plant traits. We investigated here the effects of six different microplastics (polyester fibers, polyamide beads, and four fragment types: polyethylene, polyester terephthalate, polypropylene, and polystyrene) on a broad suite of proxies for soil health and performance of spring onion ( Allium fistulosum). Significant changes were observed in plant biomass, tissue elemental composition, root traits, and soil microbial activities. These plant and soil responses to microplastic exposure were used to propose a causal model for the mechanism of the effects. Impacts were dependent on particle type, i.e., microplastics with a shape similar to other natural soil particles elicited smaller differences from control. Changes in soil structure and water dynamics may explain the observed results in which polyester fibers and polyamide beads triggered the most pronounced impacts on plant traits and function. The findings reported here imply that the pervasive microplastic contamination in soil may have consequences for plant performance and thus for agroecosystems and terrestrial biodiversity.

Enhanced recovery after surgery for liver resection.

INTRODUCTION: Enhanced recovery after surgery (ERAS) reduces postoperative length of hospital stay and patient stress response to liver surgery. The aim of the present study was to evaluate the efficacy and feasibility of an ERAS programme for liver resection. METHODS: A multidisciplinary ERAS protocol was implemented for both open and laparoscopic liver resection in a tertiary hospital in Hong Kong. The clinical outcomes of patients who underwent liver resection and underwent the ERAS perioperative programme were compared with those who received a conventional perioperative programme between September 2015 and July 2016. Propensity score matching analysis was used to minimise background differences. RESULTS: A total of 20 patients who underwent liver resection were recruited to the ERAS programme. Their clinical outcomes were compared with another 20 patients who received hepatectomy under a conventional perioperative programme after propensity score matching. The ERAS programme was associated with a significantly shorter length of hospital stay (P=0.033) without an increase in complication rates in patients who underwent open liver resection. There was no such significant association in patients who underwent laparoscopic liver resection. No patients required readmission in this cohort. CONCLUSIONS: The ERAS perioperative programme for liver resection is safe and feasible. It significantly shortened the hospital stay after open liver resection but not after laparoscopic liver resection.

Effects of backpack and double pack loads on postural stability.

Measurement of postural stability is crucial for identifying predictors of performance, determining the efficacy of physical training and rehabilitation techniques and evaluating and preventing injuries, particularly for heavy load carriage in hikers, mountain search and rescue personnel and soldiers. This study investigated the effect of load distribution on postural stability in an upright stance using backpack and double pack loads under conflicting or impaired somatosensory, visual and vestibular conditions. The sensory organisation tests were conducted on 20 young adults before and after a 10-min level walking exercise. Young adults' ability to use inputs from somatosensory and visual systems to maintain postural stability was significantly reduced following a 10-min walking exercise with a heavy backpack (30% of body weight), whereas no significant changes were observed for double pack carriage. Thus, the distribution of heavy loads to the front and back provides superior balance control compared with back-only loading. Practitioner summary: This study investigated the effects of heavy (30% of body weight) load distribution on postural stability after a 10-min walking exercise. Backpack carriage significantly reduced postural stability, whereas there was no significant effect under double pack loads. Distribution of heavy loads on the front-and-back is desirable for superior balance control.

Alpha galactosidase A activity in Parkinson's disease.

Glucocerebrosidase (GCase, deficient in Gaucher disease) enzymatic activity measured in dried blood spots of Parkinson's Disease (PD) cases is within healthy range but reduced compared to controls. It is not known whether activities of additional lysosomal enzymes are reduced in dried blood spots in PD. To test whether reduction in lysosomal enzymatic activity in PD is specific to GCase, we measured GCase, acid sphingomyelinase (deficient in Niemann-Pick disease types A and B), alpha galactosidase A (deficient in Fabry), acid alpha-glucosidase (deficient in Pompe) and galactosylceramidase (deficient in Krabbe) enzymatic activities in dried blood spots of PD patients (n = 648) and controls (n = 317) recruited from Columbia University. Full sequencing of glucocerebrosidase (GBA) and the LRRK2 G2019S mutation was performed. Enzymatic activities were compared between PD cases and controls using t-test and regression models adjusted for age, gender, and GBA and LRRK2 G2019S mutation status. Alpha galactosidase A activity was lower in PD cases compared to controls both when only non-carriers were included (excluding all GBA and LRRK2 G2019S carriers and PD cases with age-at-onset below 40) [2.85 µmol/l/h versus 3.12 µmol/l/h, p = 0.018; after controlling for batch effect, p = 0.006 (468 PD cases and 296 controls)], and when including the entire cohort (2.89 µmol/l/h versus 3.10 µmol/l/h, p = 0.040; after controlling for batch effect, p = 0.011). Because the alpha galactosidase A gene is X-linked, we stratified the analyses by sex. Among women who were non-carriers of GBA and LRRK2 G2019S mutations (PD, n = 155; control, n = 194), alpha galactosidase A activity was lower in PD compared to controls (2.77 µmol/l/h versus 3.10 µmol/l/h, p = 0.044; after controlling for a batch effect, p = 0.001). The enzymatic activity of acid sphingomyelinase, acid alpha-glucosidase and galactosylceramidase was not significantly different between PD and controls. In non-carriers, most lysosomal enzyme activities were correlated, with the strongest association in GCase, acid alpha-glucosidase, and alpha galactosidase A (Pearson correlation coefficient between 0.382 and 0.532). In a regression model with all five enzymes among non-carriers (adjusted for sex and age), higher alpha galactosidase A activity was associated with lower odds of PD status (OR = 0.54; 95% CI:0.31-0.95; p = 0.032). When LRRK2 G2019S PD carriers (n = 37) were compared to non-carriers with PD, carriers had higher GCase, acid sphingomyelinase and alpha galactosidase A activity. We conclude that alpha galactosidase A may have a potential independent role in PD, in addition to GCase.