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Basal cell carcinomas (BCCs) are slow growing keratinocyte tumours with limited literature reporting the natural history of untreated BCCs. This study evaluated the natural progression and patient outcomes of BCCs whilst awaiting surgical intervention. Only patients with histologically proven BCCs were included in the data collection. Retrospective data analysis was performed on 55 patients (total of 70 lesions) and showed a statistically significant correlation between average growth of BCCs and time waiting for a procedure. Twenty percent of the cases had a larger procedure than originally planned at the time of booking. The top three symptoms reported include itching (39.4%), crusting (36.4%) and bleeding (30.3%). In conclusion, we reported a positive relationship between BCC growth and length of time from initial presentation to surgical treatment where patients often ended up with more symptoms, larger and complex surgical procedure than originally planned especially on the head and neck., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Conflicts of interest the authors declare they have no conflicts of interest.

The problem in language comprehension in people with right hemisphere damage (RHD) is more equivocal than people with left hemisphere damage. This study explores the reading and listening comprehension of Cantonese-speaking individuals with RHD, left hemisphere damage, and neurotypical healthy controls using the Cantonese Computerized Revised Token Test (CRTT-Cantonese) adapted from the English CRTT. Eighteen native Cantonese-speaking individuals with RHD, 32 individuals with left hemisphere damage and aphasia (PWA), and 42 healthy controls participated in this study. All the participants completed the Cantonese Aphasia Battery, Hong Kong Oxford Cognitive Screen, the listening comprehension version of CRTT-Cantonese (CRTT-L-Cantonese), and the reading comprehension version of CRTT-Cantonese (CRTT-R- WF -Cantonese) across different sessions. Linear mixed-effect analysis revealed significant differences among the groups in CRTT-Cantonese tests. However, there were no significant difference between CRTT-L-Cantonese and CRTT-R- WF -Cantonese within the PWA, RHD and healthy control groups. Tukey post-hoc pairwise comparisons showed that PWA scored significantly lower than RHD and healthy control groups ( p  < 0.0001) in both CRTT-L-Cantonese and CRTT-R- WF -Cantonese, and the RHD group scored significantly lower than healthy control group only on the CRTT-R- WF -Cantonese. The results demonstrate that the CRTT-L-Cantonese and CRTT-R- WF -Cantonese differentiate language comprehension abilities among PWA, RHD and healthy control groups. Although the current findings did not show any diversion between reading and listening comprehension in RHD group, this group showed poorer performance in reading comprehension when compared to healthy controls. The latter findings may support the view that the right hemisphere contributes to reading comprehension in Chinese.

An intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18-55 and COVID-19 vaccines naïve, between March and September 2021. Participants were enrolled and randomly assigned (2:2:1) into the low and high dose DelNS1-nCoV-RBD LAIV manufactured in chicken embryonated eggs or placebo groups. The low and high-dose vaccine were composed of 1 × 10 7 EID 50 / dose and 1 × 10 7.7 EID 50 / dose in 0.2 mL respectively. The placebo vaccine was composed of inert excipients/dose in 0.2 mL. Recruited participants were administered the vaccine intranasally on day 0 and day 28. The primary end-point was the safety of the vaccine. The secondary endpoints included cellular, humoral, and mucosal immune responses post-vaccination at pre-specified time-points. The cellular response was measured by the T-cell ELISpot assay. The humoral response was measured by the serum anti-RBD IgG and live-virus neutralizing antibody against SARS-CoV-2. The saliva total Ig antibody responses in mucosal secretion against SARS-CoV-2 RBD was also assessed. Twenty-nine healthy Chinese participants were vaccinated (low-dose: 11; high-dose: 12 and placebo: 6). The median age was 26 years. Twenty participants (69%) were male. No participant was discontinued due to an adverse event or COVID-19 infection during the clinical trial. There was no significant difference in the incidence of adverse events ( p = 0.620). For the T-cell response elicited after full vaccination, the positive PBMC in the high-dose group increased to 12.5 SFU/10 6 PMBC (day 42) from 0 (baseline), while it increased to 5 SFU/10 6 PBMC (day 42) from 2.5 SFU/10 6 PBMC (baseline) in the placebo group. The high-dose group showed a slightly higher level of mucosal Ig than the control group after receiving two doses of the vaccine (day 31, 0.24 vs. 0.21, p = 0.046; day 56 0.31 vs. 0.15, p = 0.45). There was no difference in the T-cell and saliva Ig response between the low-dose and placebo groups. The serum anti-RBD IgG and live virus neutralizing antibody against SARS-CoV-2 were undetectable in all samples. The high-dose intranasal DelNS1-nCoV-RBD LAIV is safe with moderate mucosal immunogenicity. A phase-2 booster trial with a two-dose regimen of the high-dose intranasal DelNS1-nCoV-RBD LAIV is warranted.

Historically, polymers have been excluded from registration and evaluation under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) program, the European chemical management program. Recently, interest has increased to include polymers. A tiered registration system has been envisioned and would begin with classes of polymers of greater interest based on certain properties. Cationic polymers are one such class. There is a pressing need to understand the quality and limitations of historical cationic polymer studies and to identify key sources of uncertainty in environmental hazard assessments so we can move toward scientifically robust analyses. To that end, we performed a critical review of the existing cationic polymer environmental effects literature to evaluate polymer characterization and test methodologies to understand how these parameters may affect test interpretation. The relationship between physicochemical parameters, acute and chronic toxicity, and relative trophic level sensitivity were explored. To advance our understanding of the environmental hazard and subsequent risk characterization of cationic polymers, there is a clear need for a consistent testing approach as many polymers are characterized as difficult-to-test substances. Experimental parameters such as dissolved organic carbon and solution renewal approaches can alter cationic polymer bioavailability and toxicity. It is recommended that OECD TG 23 "Aqueous-Phase Aquatic Toxicity Testing of Difficult Test Substances" testing considerations be applied when conducting environmental toxicity assays with cationic polymers. Integr Environ Assess Manag 2023;19:312-325. © 2021 SETAC., (© 2021 SETAC.)

Background: Recent literature shows that most practicing psychiatrists do not receive training in measurement-based care (MBC). Among the primary barriers to MBC implementation are the lack of formal training and curriculums. We present the first comprehensive MBC curriculum for use in adult psychiatric practice, and describe how the curriculum is adapted and implemented in psychiatry residency training programs., Methods: The Standard for Clinicians' Interview in Psychiatry (SCIP) was developed as a measurement-based care tool for clinicians' use. The SCIP is the only instrument that includes 18 reliable and validated clinician-rated scales covering most adult psychiatric disorders. The SCIP has simple, unified rules of measurement that apply to the 18 scales. The MBC curriculum includes 2 instruction manuals, 4 didactic lectures, and 12 videotaped interviews. We describe the annual learning and implementation of MBC curriculum in residency programs., Results: The curriculum implementation at West Virginia University and Delaware Psychiatric Center began in 2019 and is ongoing. We present 3 case demonstrations of the implementation of MBC in clinical settings., Conclusions: Comprehensive implementation of MBC curriculum in residency programs has the potential to facilitate research and create a "culture" of MBC in future generations of psychiatrists.

Polycarboxylate polymers have been common components of consumer and institutional cleaning products for decades. With interest heightened in the potential environmental impact of polymers, the American Cleaning Institute, the industry trade association of the cleaning products industry in the United States, is reassessing the state of the science regarding the environmental safety of polymers in cleaning products. In this case study, acrylic acid homopolymers and acrylic acid-maleic acid copolymers are evaluated using historical ecotoxicity data that have been reported over the past three decades. The evaluation includes an environmental exposure assessment that is based on recent information regarding the occurrence of those ingredients in cleaning products and market sales data for cleaning products sold in the United States. The ecotoxicity of polycarboxylate polymers is generally low. Consequently, the potential environmental risks associated with their use in cleaning products in the United States are low even when applying very conservative assumptions to the environmental exposure assessment. In addition, there are recent supporting conclusions from assessments by the governments of Australia and Canada that polycarboxylate polymers are polymers of low concern, and the U.S. Environmental Protection Agency has included a number of polycarboxylate polymers among the ingredients on its Safer Chemical Ingredients List based on their low hazard profile., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

History A 47-year-old man presented with palpitations and decreased exercise tolerance. A peripheral blood smear revealed anemia, thrombocytopenia, and blast cells, and a diagnosis of acute myeloid leukemia was made. Immunohistochemistry revealed positivity for cluster of differentiation (or CD) markers, which have been reported to be associated with an increased risk of extramedullary leukemic involvement. Thus, contrast material-enhanced computed tomography (CT) of the thorax, abdomen, and pelvis was requested to enable exclusion of any extramedullary extension of leukemia. Unenhanced and contrast-enhanced nephrographic phase CT was performed. Follow-up CT 3 months later showed minimal interval change in the lesion (images not shown).

OBJECTIVES. To examine the effectiveness and feasibility of a community-based aquatic exercise programme for elders with osteoarthritis of the knee. DESIGN. Prospective intervention study, with a before-and-after design. SETTING. Community elders. PARTICIPANTS. Twenty elders aged 65 years or above (mean, 72 years) attending four Elderly Health Centres of the Department of Health who had suffered from osteoarthritis of the knee for at least 3 years and with mild-to-severe knee pain. INTERVENTION. A 10-week aquatic exercise programme designed and led by physiotherapists. MAIN OUTCOME MEASURES. Range of motion and power of extension of the knees, functional reach test, repeated sit-to-stand test, and the Chinese Arthritis Impact Measurement Scales 2. RESULTS. There was an improvement in the median range of knee flexion from 115° to 125° (P<0.01) and the median strength of the quadriceps from 9 kg to 21 kg (P<0.001). The median score of the functional reach test increased from 20 cm to 28 cm (P<0.001) and the repeated sit-to-stand test from 10 to 14 repetitions (P<0.001). Also, there was an improvement in the mobility level (P<0.01), walking and bending ability of the trunk (P<0.05), levels of pain (P<0.01) and mood (P<0.01), and the total score (P<0.01) in the Chinese Arthritis Impact Measurement Scales 2. CONCLUSIONS. Physiotherapist-designed aquatic exercise has definite benefits in terms of physical and psychosocial functioning, and should be promoted as one of the strategies to enhance long-term self-management of community elders with knee osteoarthritis.

Purpose: The purpose of this study was to compare clinical and health-related quality-of-life (HRQL) outcomes within a group of patients treated for pectus excavatum (PE)., Methods: A retrospective 3-year review of patients undergoing Nuss or Ravitch correction of PE was performed. Health-related quality-of-life assessment was performed using the Child Health Questionnaire (CHQ-CF87) and the 17-item Pectus Excavatum Evaluation Questionnaire, and results were compared between groups and with age-matched CHQ-CF87 normative data., Results: Forty-three patients (39 males; 91%) underwent surgery; 19 (44%) by Nuss procedure. Duration of postoperative opioid analgesia and length of hospital stay (LOS) were significantly longer in Nuss patients. The overall survey response rate was 53%. The groups differed significantly in the CHQ on one item (Change in Health). On the Pectus Excavatum Evaluation Questionnaire, Nuss patients reported being "less bothered" by the appearance of their chest. Compared to Australian age-matched norms, the aggregate PE sample showed better scores for family activity domain and worse scores in mental health, general health perceptions, change in health, bodily pain, and self-esteem., Conclusions: Patients undergoing surgery for PE by either Nuss or Ravitch procedure have similar clinical and HRQL outcomes, but as a group have poorer HRQL scores than age-matched population norms.

A longstanding issue in biomedical research concerns the biophysical factors affecting the color diversity of the human irides and its connection with ocular diseases. Although the pigmentation and morphological characteristics of heavily and moderately pigmented irides have been extensively discussed in the literature, similar studies are scarce for lightly pigmented irides. We present computer experiments indicating that the spectral signature of these specimens may be directly affected by still undetectable melanin distributions in the outermost iridal layers. Our findings represent in silico evidence of this relationship which, in turn, may have implications in the investigation of the higher risk of death from metastatic ocular melanoma verified in individuals with light-colored irides.

Background: MannDB was created to meet a need for rapid, comprehensive automated protein sequence analyses to support selection of proteins suitable as targets for driving the development of reagents for pathogen or protein toxin detection. Because a large number of open-source tools were needed, it was necessary to produce a software system to scale the computations for whole-proteome analysis. Thus, we built a fully automated system for executing software tools and for storage, integration, and display of automated protein sequence analysis and annotation data., Description: MannDB is a relational database that organizes data resulting from fully automated, high-throughput protein-sequence analyses using open-source tools. Types of analyses provided include predictions of cleavage, chemical properties, classification, features, functional assignment, post-translational modifications, motifs, antigenicity, and secondary structure. Proteomes (lists of hypothetical and known proteins) are downloaded and parsed from Genbank and then inserted into MannDB, and annotations from SwissProt are downloaded when identifiers are found in the Genbank entry or when identical sequences are identified. Currently 36 open-source tools are run against MannDB protein sequences either on local systems or by means of batch submission to external servers. In addition, BLAST against protein entries in MvirDB, our database of microbial virulence factors, is performed. A web client browser enables viewing of computational results and downloaded annotations, and a query tool enables structured and free-text search capabilities. When available, links to external databases, including MvirDB, are provided. MannDB contains whole-proteome analyses for at least one representative organism from each category of biological threat organism listed by APHIS, CDC, HHS, NIAID, USDA, USFDA, and WHO., Conclusion: MannDB comprises a large number of genomes and comprehensive protein sequence analyses representing organisms listed as high-priority agents on the websites of several governmental organizations concerned with bio-terrorism. MannDB provides the user with a BLAST interface for comparison of native and non-native sequences and a query tool for conveniently selecting proteins of interest. In addition, the user has access to a web-based browser that compiles comprehensive and extensive reports. Access to MannDB is freely available at http://manndb.llnl.gov/.

Sequencing pathogen genomes is costly, demanding careful allocation of limited sequencing resources. We built a computational Sequencing Analysis Pipeline (SAP) to guide decisions regarding the amount of genomic sequencing necessary to develop high-quality diagnostic DNA and protein signatures. SAP uses simulations to estimate the number of target genomes and close phylogenetic relatives (near neighbors or NNs) to sequence. We use SAP to assess whether draft data are sufficient or finished sequencing is required using Marburg and variola virus sequences. Simulations indicate that intermediate to high-quality draft with error rates of 10(-3)-10(-5) (approximately 8x coverage) of target organisms is suitable for DNA signature prediction. Low-quality draft with error rates of approximately 1% (3x to 6x coverage) of target isolates is inadequate for DNA signature prediction, although low-quality draft of NNs is sufficient, as long as the target genomes are of high quality. For protein signature prediction, sequencing errors in target genomes substantially reduce the detection of amino acid sequence conservation, even if the draft is of high quality. In summary, high-quality draft of target and low-quality draft of NNs appears to be a cost-effective investment for DNA signature prediction, but may lead to underestimation of predicted protein signatures.

Computational analyses of genome sequences may elucidate protein signatures unique to a target pathogen. We constructed a Protein Signature Pipeline to guide the selection of short peptide sequences to serve as targets for detection and therapeutics. In silico identification of good target peptides that are conserved among strains and unique compared to other species generates a list of peptides. These peptides may be developed in the laboratory as targets of antibody, peptide, and ligand binding for detection assays and therapeutics or as targets for vaccine development. In this paper, we assess how the amount of sequence data affects our ability to identify conserved, unique protein signature candidates. To determine the amount of sequence data required to select good protein signature candidates, we have built a computationally intensive system called the Sequencing Analysis Pipeline (SAP). The SAP performs thousands of Monte Carlo simulations, each calling the Protein Signature Pipeline, to assess how the amount of sequence data for a target organism affects the ability to predict peptide signature candidates. Viral species differ substantially in the number of genomes required to predict protein signature targets. Patterns do not appear based on genome structure. There are more protein than DNA signatures due to greater intraspecific conservation at the protein than at the nucleotide level. We conclude that it is necessary to use the SAP as a dynamic system to assess the need for continued sequencing for each species individually and to update predictions with each additional genome that is sequenced.

Fluoxetine (FLX) was shown to be photoreactive in sunlit surface waters. FLX degraded in deionized water when exposed to simulated sunlight with a half-life of 55.2+/-3.6 h(-1). Photodegradation products were identified using high performance liquid chromatography-UV (HPLC-UV) and liquid chromatography tandem mass spectrometry (LC-MS-MS) using electrospray (ES) ionization. Defluorination of the trifluoromethyl group in FLX and in fluometuron and flutalanil,two other compounds containing this functional group, is suggested to be a common direct photolysis pathway for trifluoromethylated compounds. Products resulting from O-dealkylation of FLX were also observed. The rate of degradation was faster in synthetic field water where .OH was the likely dominant oxidant in the system. The bimolecular rate constant for the reaction between FLX and .OH was measured as (8.4+/-0.5) x 10(9) and (9.6 +/-0.8) x 10(9) M(-1) s(-1) using two different methods of competition kinetics. Indirect photodegradation reactions could lead to the production of hydroxylated and O-dealkylated compounds. Although direct photolysis could potentially limitthe persistence of FLX in surface waters, its degradation by indirect photolysis would proceed faster. Thus, this latter process could be important in the elimination of FLX in surface waters.

We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (near neighbors) that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near-neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near-neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. Severe acute respiratory syndrome and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near-neighbor sequences are urgently needed. Our results also indicate that double-stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.

Pharmaceuticals have been detected in surface waters of the US and Europe, originating largely from two sources, sewage effluent and agricultural runoff. These compounds often occur as mixtures leading to potential combined effects. In order to investigate the effects of a realistic pharmaceutical mixture on an ecosystem, a study utilizing 15 of 12,000 L aquatic microcosms treated with eight common pharmaceuticals (atorvastatin, acetaminophen, caffeine, sulfamethoxazole, carbamazepine, levofloxacin, sertraline, and trimethoprim) at total (summed) molar concentrations of 0, 0.044, 0.608, 2.664, and 24.538 micromol/L (n = 3) was conducted. Phytotoxicity was assessed on a variety of somatic and pigment endpoints in rooted (Myriophyllum sibiricum) and floating (Lemna gibba) macrophytes over a 35-day period. EC10, EC25 and EC50 values were calculated for each endpoint exhibiting a concentration-dependent response. Generally, M. sibiricum and L. gibba displayed similar sensitivity to the pharmaceutical mixture, with phytotoxic injury evident in both species, which was concentration dependent. Through single compound 7-day daily static renewal toxicity tests with L. gibba, the sulfonamide antibiotic sulfamethoxazole, the fluoroquinolone antibiotic levofloxacin and the blood lipid regulator atorvastatin were found to be the only compounds to elicit phytotoxic effects in the concentration range utilized (0-1000 microg/L). Atorvastatin concentration was highly correlated to decreased pigment content in L. gibba, likely inhibiting the known target enzyme HMGR, the rate-limiting enzyme in isoprenoid biosynthesis. Hazard quotients were calculated for both microcosm and laboratory studies; the highest HQ values were 0.235 (L. gibba) and 0.051 (L. gibba), which are below the threshold value of 1 for chronic risks. The microcosm data suggest that at an ecological effect size of >20%, biologically significant risks are low for L. gibba and M. sibiricum exposed to similar mixtures of pharmaceutical compounds. For M. sibiricum and L. gibba, respective minimum differences of 5 and 1%, were detectable, however, these effect sizes are not considered ecologically significant.

The persistence of eight pharmaceuticals from multiple classes was studied in aquatic outdoor field microcosms. A method was developed for the determination of a mixture of acetaminophen, atorvastatin, caffeine, carbamazepine, levofloxacin, sertraline, sulfamethoxazole, and trimethoprim at microg/L levels from surface water of the microcosms using solid phase extraction and high-performance liquid chromatography-ultraviolet (HPLC-UV) and liquid chromatography tandem mass spectrometry (LC-MS-MS). Half-lives in the field ranged from 1.5 to 82 d. Laboratory persistence tests were performed to determine the relative importance of possible loss processes in the microcosms over the course of the study. Results from dark control experiments suggest hydrolysis was not important in the loss of the compounds. No significant differences were observed between measured half-lives of the pharmaceuticals in sunlight-exposed pond water and autoclaved pond water, which suggests photodegradation was important in limiting their persistence, and biodegradation was not an important loss process in surface water over the duration of the study. Observed photoproducts of several of the pharmaceuticals remained photoreactive, which led to further degradation in irradiated surface waters.

A convenient and rapid method for screening and identifying rod mutants of Bacillus subtilis is described. At the restrictive temperature (45 degrees C), all rod mutants of B. subtilis screened lost their ability to sporulate. The morphology and colour of mutant colonies grown on sporulation agar plates differed from those of rod+ cells, which were able to sporulate even at elevated temperature. These characteristics provide an alternative approach for the identification of rod mutants in B. subtilis culture by streaking the cells onto a minimal glucose agar plate and incubating at the restrictive temperature. After 30 h of incubation at this temperature, rod mutants are easily identified. This method will facilitate the screening and isolation of rod mutants of B. subtilis., (Copyright 2003 Springer-Verlag)

A new approach was developed to account for the contribution of indirect photolysis of pesticides and pharmaceuticals in which laboratory test conditions are similar to those prevalent in the aqueous environment. Rates of photolysis as a function of water composition were investigated for several aquatic contaminants. Using the laboratory-based test system, PhotoFate, the dependence of phototransformation rates on concentrations of natural water constituents that are radical producers and scavengers (nitrate, colored dissolved organic matter, bicarbonate) was studied. Mean half-lives of the model compounds in the presence of water constituents were compared to their direct photolysis half-lives to assess the contribution of photosensitized reactions to their fate in surface waters. Reactions mediated by .OH were predominant in waters with high nitrate concentrations. Colored dissolved organic matter (cDOM) acted mainly as a radiation filter and had a more important role in scavenging radicals than in their production. However, in low nitrate waters, the contribution of cDOM-derived reactive intermediates to the degradation of parent compounds became more apparent

Acute haemorrhagic conjunctivitis occurred in epidemic in Hong Kong in 1971 and 1975 respectively. Two picornaviruses, the Enterovirus type 70 and an antigenic variant of Coxsackie virus type A24, were isolated during the 1971 outbreak, while only the latter virus was detected in the 1975 outbreak. In 1972 and 1974, sporadic cases of conjunctivitis associated with Enterovirus type 70 were observed. Serological survey in late 1975 showed a high proportion of the population might still be susceptible to both viruses. Recrudescence of the disease is conceivable when environmental condition is favourable for the spread of these viruses.