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1.
Hong Kong Med J ; 30(2): 94-101, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577838

RESUMO

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

2.
Med J Malaysia ; 79(3): 257-267, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38817057

RESUMO

INTRODUCTION: Ischaemic heart disease including ST-segment elevation myocardial infarction (STEMI) is the leading cause of death among Malaysians. Total ischaemic time (TIT) which consists of patient delay and systemic delay is a strong predictor of cardiovascular outcome in STEMI. Primary percutaneous coronary intervention (PPCI) is superior to medical thrombolysis in improving STEMI patients' survival outcomes. Our study aims to provide an insight into the clinical and geographical characteristics of STEMI patients, their health-seeking behaviour, TIT, interventions received and short-term cardiac mortality outcomes in the effort to improve the existing coronary care service. MATERIALS AND METHODS: This is a descriptive study looking into patients who were diagnosed with STEMI and presented to or were referred to Sarawak Heart Centre between 1st July 2022 and 31st December 2022. RESULTS: A total of 183 patients were recruited and 33.3% were <50 years old. The majority were in a different division during symptom onset from where the local PPCI centre is located and some underwent one or two transits before arrival at the revascularisation centre. More presented outof- hour and they were more likely to present within the PPCI window. The median TIT for the study population was 3.3 hours. The short-term cardiac mortalities were 9.3% and only the Killip class was found to have a significant association. In this study, TIT was not significantly associated with short-term mortalities but those who died had a longer median TIT. CONCLUSION: A local STEMI network should be set up using the 'Hub-and-Spoke' model in a staged-wise approach to reduce TIT given that PPCI is now the gold standard of treatment alongside continuous effort in patient education.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Pessoa de Meia-Idade , Feminino , Masculino , Malásia , Intervenção Coronária Percutânea/mortalidade , Idoso , Tempo para o Tratamento , Adulto , Países em Desenvolvimento , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Fatores de Tempo
3.
Chembiochem ; 24(6): e202200686, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36534957

RESUMO

The glycopeptide antibiotics (GPAs) are a clinically approved class of antimicrobial agents that classically function through the inhibition of bacterial cell-wall biosynthesis by sequestration of the precursor lipid II. The oxidative crosslinking of the core peptide by cytochrome P450 (Oxy) enzymes during GPA biosynthesis is both essential to their function and the source of their synthetic challenge. Thus, understanding the activity and selectivity of these Oxy enzymes is of key importance for the future engineering of this important compound class. Recent reports of GPAs that display an alternative mode of action and a wider range of core peptide structures compared to classic lipid II-binding GPAs raises the question of the tolerance of Oxy enzymes for larger changes in their peptide substrates. In this work, we explore the ability of Oxy enzymes from the biosynthesis pathways of lipid II-binding GPAs to accept altered peptide substrates based on a vancomycin template. Our results show that Oxy enzymes are more tolerant of changes at the N terminus of their substrates, whilst C-terminal extension of the peptide substrates is deleterious to the activity of all Oxy enzymes. Thus, future studies should prioritise the study of Oxy enzymes from atypical GPA biosynthesis pathways bearing C-terminal peptide extension to increase the substrate scope of these important cyclisation enzymes.


Assuntos
Antibacterianos , Glicopeptídeos , Antibacterianos/química , Glicopeptídeos/química , Peptídeos , Vancomicina/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo
4.
Chemistry ; 29(11): e202202491, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36451579

RESUMO

A highly effective 2-step system for site-specific antibody modification and conjugation of the monoclonal antibody Herceptin (commercially available under Trastuzumab) in a cysteine-independent manner was used to generate labelled antibodies for in vivo imaging. The first step contains redox-activated chemical tagging (ReACT) of thioethers via engineered methionine residues to introduce specific alkyne moieties, thereby offering a novel easy way to fundamentally change the process of antibody bioconjugation. The second step involves modification of the introduced alkyne via azide-alkyne cycloaddition 'click' conjugation. The versatility of this 2-step approach is demonstrated here by the selective incorporation of a fluorescent dye but can also be applied to a wide variety of different conjugation partners depending on the desired application in a facile manner. Methionine-modified antibodies were characterised in vitro, and the diagnostic potential of the most promising variant was further analysed in an in vivo xenograft animal model using a fluorescence imaging modality. This study demonstrates how methionine-mediated antibody conjugation offers an orthogonal and versatile route to the generation of tailored antibody conjugates with in vivo applicability.


Assuntos
Metionina , Neoplasias , Animais , Humanos , Trastuzumab , Anticorpos Monoclonais/química , Racemetionina , Alcinos/química , Azidas/química
5.
J Public Health Manag Pract ; 29(1): 71-76, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36070579

RESUMO

OBJECTIVE: To understand how the San Francisco (SF) COVID-19 case investigation and contact tracing (CICT) workforce documented sexual orientation and gender identity (SOGI) data, as well as a qualitative assessment of the workforce's capacity to successfully collect that data. METHODS: This mixed-methods project analyzed data from 2 sources: SOGI item completeness among adult completed/partially completed interviews in the SF digital CICT COVID-19 database, and a secondary data analysis of qualitative data from 16 semistructured 90-minute virtual interviews with the SF CICT workforce, between November 14, 2020, and April 14, 2021. RESULTS: Among 15 416 COVID-19 cases and 7836 close contacts, sexual orientation data are missing from 20% of cases and 17% of contacts. The proportion of transgender/nonbinary individuals was 0.32% and 0.5%, respectively. The SF CICTs participants discussed challenges in collecting SOGI data, not understanding SOGI measure rationale, and feeling uncomfortable asking the questions. CONCLUSION: Qualitative interviews with the COVID-19 CICT workforce and quantitative data on SOGI parameters in COVID-19 surveillance suggest that these data may have been underreported. Our results strongly suggest that comprehensive training is crucial in the collection of SOGI data among COVID-19 cases and their close contacts. If SOGI data are not collected accurately, the true impact of COVID-19 among lesbian, gay, bisexual, transgender, and queer populations remains unknown, preventing data-driven allocation of COVID-19 funds to lesbian, gay, bisexual, transgender, and queer communities.


Assuntos
COVID-19 , Minorias Sexuais e de Gênero , Adulto , Feminino , Humanos , Masculino , Identidade de Gênero , Busca de Comunicante , COVID-19/diagnóstico , COVID-19/epidemiologia , São Francisco/epidemiologia , Comportamento Sexual
6.
Med J Malaysia ; 78(1): 1-6, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36715183

RESUMO

INTRODUCTION: Tuberculosis (TB) in Malaysia has estimated incidence and mortality rates of 81 cases per 100,000 people-year and 4.9 per 100,000 populations, respectively. This study aimed to study the characteristics of rural TB patients and their mortality outcomes. MATERIALS AND METHODS: This is a retrospective observational study involving real-world data analysis, looking into TB patients in Lubok Antu Health Clinic by obtaining data through clinic cards, from 1 January 2019 till 31 December 2020. Statistical significance was p < 0.05. RESULTS: Eighty-four patients were included. Fifty-two (61.9%) were male. Median age was 58.5 (39-67). Forty-six (54.8%) had smear-positive TB. Seventy-eight (92.9%) were alive at treatment completion. Fifteen (17.9%) experienced adverse drug reactions. Estimated prevalence and mortality rate were 7.1% and 10.7 per 100,000 populations, respectively. Regression analyses revealed that drug reaction was significantly associated with compliance [OR = 8.38 (95% CI: 1.26, 55.53), p = 0.029]. Patients compliant with treatment were more likely to survive [OR = 12.5 (95% CI: 1.61, 97.34), p = 0.028]. CONCLUSION: Compliance with TB treatment should be emphasised to reduce TB-related mortality.


Assuntos
Antituberculosos , Tuberculose , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Malásia/epidemiologia , Antituberculosos/efeitos adversos , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Cooperação do Paciente , População Rural
7.
Med J Malaysia ; 78(6): 743-750, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38031215

RESUMO

INTRODUCTION: Despite recent advancements in the diagnosis and management of infective endocarditis (IE), it is associated with substantial morbidity and mortality. Our study objective is to determine the factors associated with in-hospital mortality in IE patients among the local population. MATERIALS AND METHODS: All IE patients who were diagnosed with definite or possible IE and were treated at Sarawak Heart Centre from 1st January 2020 to 31st December 2022 were recruited. We examined the demographic features of the subjects and the factors that contributed to in-hospital mortality. Multivariate logistic regression was used to analyse the associated factors and in-hospital mortality. RESULTS: Our study population comprised a total of 37 patients with a mean age of 46.4 years and male predominance. The in-hospital mortality rate of IE in this study was 44.4%. Haemodynamic instability and anaemia were found to be strong predictors of IE survival outcome, with an odds ratio of 51.5 and 35.7 respectively. Patients with vascular phenomenon and heart failure were at 10.5- and 6.0-times higher odds of dying, however, these two associations were found to be not statistically significant. CONCLUSION: The in-hospital mortality due to IE in our study was among the highest in developing countries. Factors of hypotension and optimal response to individual hemodynamic parameters may confer lower mortality. While anaemia is demonstrable as a risk factor for inpatient mortality, a target has yet to be reasonably established.


Assuntos
Anemia , Endocardite Bacteriana , Endocardite , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Mortalidade Hospitalar , Estudos Retrospectivos , Fatores de Risco
8.
Opt Lett ; 47(6): 1569, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35290366

RESUMO

We present an erratum to our Letter [Opt. Lett.41, 230 (2016)10.1364/OL.41.000230]. This erratum corrects three typing errors. The corrections have no influence on the results and conclusions of the original Letter.

9.
Drug Chem Toxicol ; 45(2): 834-838, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32538189

RESUMO

There are an estimated 1 billion cases of superficial fungal infection globally. Fungal pathogens form biofilms within wounds and delay the wound healing process. Miconazole and terbinafine are commonly used to treat fungal infections. They induce the accumulation of reactive oxygen species (ROS) in fungi, resulting in the death of fungal cells. ROS are highly reactive molecules, such as oxygen (O2), superoxide anion (O2•-), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). Although ROS generation is useful for killing pathogenic fungi, it is cytotoxic to human keratinocytes. To the best of our knowledge, the effect of miconazole and terbinafine on HaCaT cells has not been studied with respect to intracellular ROS stimulation. We hypothesized that miconazole and terbinafine have anti-wound healing effects on skin cells when used in antifungal treatment because they generate ROS in fungal cells. We used sulforhodamine B protein staining to investigate cytotoxicity and 2',7'-dichlorofluorescein diacetate to determine ROS accumulation at the 50% inhibitory concentrations of miconazole and terbinafine in HaCaT cells. Our preliminary results showed that topical treatment with miconazole and terbinafine induced cytotoxic responses, with miconazole showing higher cytotoxicity than terbinafine. Both the treatments stimulated ROS in keratinocytes, which may induce oxidative stress and cell death. This suggests a negative correlation between intracellular ROS accumulation in keratinocytes treated with miconazole or terbinafine and the healing of fungi-infected skin wounds.


Assuntos
Peróxido de Hidrogênio , Miconazol , Humanos , Peróxido de Hidrogênio/farmacologia , Queratinócitos , Miconazol/metabolismo , Miconazol/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Terbinafina/metabolismo , Terbinafina/toxicidade
10.
Chembiochem ; 22(1): 43-51, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32696500

RESUMO

The glycopeptide antibiotics (GPAs) are a fascinating example of complex natural product biosynthesis, with the nonribosomal synthesis of the peptide core coupled to a cytochrome P450-mediated cyclisation cascade that crosslinks aromatic side chains within this peptide. Given that the challenges associated with the synthesis of GPAs stems from their highly crosslinked structure, there is great interest in understanding how biosynthesis accomplishes this challenging set of transformations. In this regard, the use of in vitro experiments has delivered important insights into this process, including the identification of the unique role of the X-domain as a platform for P450 recruitment. In this minireview, we present an analysis of the results of in vitro studies into the GPA cyclisation cascade that have demonstrated both the tolerances and limitations of this process for modified substrates, and in turn developed rules for the future reengineering of this important antibiotic class.


Assuntos
Antibacterianos/biossíntese , Reagentes de Ligações Cruzadas/metabolismo , Glicopeptídeos/biossíntese , Antibacterianos/química , Reagentes de Ligações Cruzadas/química , Glicopeptídeos/química , Conformação Molecular
11.
HIV Med ; 21(10): 650-658, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32876389

RESUMO

OBJECTIVES: The characteristics of critically ill HIV-positive patients and the causes of their admission to intensive care units (ICUs) are only known through retrospective and unicentric studies. This study aims to fill this knowledge gap. METHODS: This is a prospective, multicentre cohort study of short- and medium-term prognostic factors. The setting consisted of ICUs of three tertiary referral hospitals from the three largest metropolitan areas in Brazil in the period January 2014 to November 2015. In all, 161 HIV patients over 18 years old were included. RESULTS: The clinical data of the outcomes (ICU mortality, hospital mortality and 90-day survival) were extracted from medical records using the REDCap®ï¸ web-based form and analysed with the MedCalc®ï¸ application. Median age was 41.7 [interquartile range (IQR): 34-50] years, the Simplified Acute Physiologic Score 3 (SAPS 3) was 64 (IQR: 56-74), and the Sequential Organ Failure Assessment Score (SOFA) was 6 (IQR: 4-9) points. The main causes of admission were sepsis (54.5%) and acute respiratory failure (13.7%). ICU and hospital mortality rates were 32.3% and 40.4%, respectively. In a multivariate analysis, time until ICU admission ≥ 3 days (P = 0.0013), performance status (Eastern Cooperative Oncology Group score, P = 0.0344), coma (Glasgow Coma Scale ≤ 8 points, P = 0.0213) and sepsis (P = 0.0003) were associated with increased hospital mortality. Coma (P = 0.0002) and sepsis (P = 0.0008) were independently associated with 90-day survival. CONCLUSIONS: Delayed ICU admission and the severity of critical illness determine the short- and medium-term mortality rates of HIV-infected patients admitted to the ICU, rather than factors associated with HIV infection. These results suggest that prognostic factors of HIV-infected patients in the ICU are similar to those of non-HIV-infected populations.


Assuntos
Estado Terminal/mortalidade , Infecções por HIV/mortalidade , Insuficiência Respiratória/epidemiologia , Sepse/epidemiologia , Adulto , Idoso , Brasil/epidemiologia , Cuidados Críticos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Insuficiência Respiratória/mortalidade , Sepse/mortalidade
12.
Clin Genet ; 97(5): 723-730, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31898322

RESUMO

Disease-causing variants in TGFB3 cause an autosomal dominant connective tissue disorder which is hard to phenotypically delineate because of the small number of identified cases. The purpose of this retrospective cross-sectional multicenter study is to elucidate the genotype and phenotype in an international cohort of TGFB3 patients. Eleven (eight novel) TGFB3 disease-causing variants were identified in 32 patients (17 families). Aortic root dilatation and mitral valve disease represented the most common cardiovascular findings, reported in 29% and 32% of patients, respectively. Dissection involving distal aortic segments occurred in two patients at age 50 and 52 years. A high frequency of systemic features (65% high-arched palate, 63% arachnodactyly, 57% pectus deformity, 52% joint hypermobility) was observed. In familial cases, incomplete penetrance and variable clinical expressivity were noted. Our cohort included the first described homozygous patient, who presented with a more severe phenotype compared to her heterozygous relatives. In conclusion, TGFB3 variants were associated with a high percentage of systemic features and aortic disease (dilatation/dissection) in 35% of patients. No deaths occurred from cardiovascular events or pregnancy-related complications. Nevertheless, homozygosity may be driving a more severe phenotype.


Assuntos
Aracnodactilia/genética , Doenças do Tecido Conjuntivo/genética , Síndrome de Loeys-Dietz/genética , Fator de Crescimento Transformador beta3/genética , Adolescente , Adulto , Aracnodactilia/patologia , Criança , Pré-Escolar , Doenças do Tecido Conjuntivo/patologia , Feminino , Predisposição Genética para Doença , Genótipo , Heterozigoto , Homozigoto , Humanos , Síndrome de Loeys-Dietz/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linhagem , Fenótipo , Fator de Crescimento Transformador beta3/deficiência , Adulto Jovem
13.
Liver Int ; 40(9): 2263-2271, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32449588

RESUMO

BACKGROUND & AIMS: Regorafenib demonstrated a clinical benefit for patients with unresectable hepatocellular carcinoma (uHCC) in the phase III RESORCE trial. Considering the heterogeneity of uHCC and discrepancies in its characteristics between prospective trials and daily practice, real-life evidence is necessary. METHODS: This multicentre, retrospective analysis was performed by the Korean Cancer Study Group. In total, 440 patients who received regorafenib between January 2017 and November 2019 were identified in nine tertiary referral hospitals in Korea. RESULTS: All patients received prior sorafenib, and the median time-to-progression (TTP) on sorafenib was 3.9 months (range, 0.2-71.6). Regorafenib was used as the second, third and fourth to seventh lines of therapy in 305 (69.3%), 115 (26.1%) and 20 (4.5%) patients respectively. According to the RECIST v1.1, the overall response rate was 7.7% (n = 34), and the median progression-free survival (PFS) and overall survival (OS) were 3.2 (95% CI, 2.8-3.5) and 12.1 (95% CI, 9.7-14.5) months respectively. Immune checkpoint inhibitors (ICIs) were given in 115 patients (26.1%) prior to regorafenib. There were no differences in PFS and OS with regorafenib according to the prior use of ICIs (PFS, P = .61; OS, P = .63). The occurrence of hand-foot skin reaction (HFSR) was associated with a better OS (P < .001). CONCLUSIONS: The real-life clinical outcomes of regorafenib for patients who progressed on prior systemic therapy including ICIs were consistent with the phase III trial results. HFSR was significantly associated with better OS with regorafenib.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Imunoterapia , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Estudos Prospectivos , Piridinas , República da Coreia , Estudos Retrospectivos , Resultado do Tratamento
14.
J Appl Microbiol ; 129(5): 1374-1388, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32356362

RESUMO

AIMS: To determine the mechanism underlying the serum cholesterol reduction effect by probiotics isolated from local fermented tapioca (Tapai). METHODS AND RESULTS: Lactic acid bacteria strains were isolated and examined for acid tolerance, bile salt resistance and hypocholesterolemic properties. Among the isolates, Lactobacillus plantarum TAR4 showed the highest cholesterol reduction ability (48·01%). The focus in the in vivo trial was to elucidate the cholesterol balance from findings pertaining to serum cholesterol reduction in rat model fed with high fat diet via oral administration. Rats fed with high-cholesterol diet supplemented with Lact. plantarum TAR4 showed significant reduction in serum total cholesterol (29·55%), serum triglyceride (45·31%) and liver triglyceride (23·44%) as compared to high-cholesterol diet (HCD) group. There was a significant increment in faecal triglyceride (45·83%) and faecal total bile acid (384·95%) as compared to HCD group. CONCLUSIONS: The findings showed that probiotic Lact. plantarum TAR4 supplementation reduced the absorption of bile acids for enterohepatic recycling and increased the catabolism of cholesterol to bile acids and not by suppressing the rate of cholesterol synthesis. SIGNIFICANCE AND IMPACT OF STUDY: Probiotic supplements could provide a new nonpharmacological alternative to reduce cardiovascular risk factors.


Assuntos
Colesterol/metabolismo , Suplementos Nutricionais , Alimentos Fermentados/microbiologia , Homeostase , Probióticos/administração & dosagem , Animais , Ácidos e Sais Biliares/metabolismo , Dieta Hiperlipídica/efeitos adversos , Homeostase/efeitos dos fármacos , Lactobacillales/classificação , Lactobacillales/isolamento & purificação , Lactobacillales/metabolismo , Lactobacillus plantarum/isolamento & purificação , Lactobacillus plantarum/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Manihot , Probióticos/farmacologia , Ratos , Triglicerídeos/metabolismo
15.
Med J Malaysia ; 75(5): 555-560, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32918426

RESUMO

INTRODUCTION: Hyperhidrosis is a disorder of excessive and uncontrollable sweating beyond the body's physiological needs. It can be categorised into primary or secondary hyperhidrosis based on its aetiology. Detailed history review including onset of symptoms, laterality of disease and family history are crucial which may suggest primary hyperhidrosis. Secondary causes such as neurological diseases, endocrine disorders, haematological malignancies, neuroendocrine tumours and drugs should be adequately examined and investigated prior to deciding on further management. The diagnosis of primary hyperhidrosis should only be made only after excluding secondary causes. Hyperhidrosis is a troublesome disorder that often results in social, professional, and psychological distress in sufferers. It remains, however, a treatment dilemma among some healthcare providers in this region. METHODS: The medical records and clinical outcomes of 35 patients who underwent endoscopic thoracic sympathectomy for primary hyperhidrosis from 2008 to 2018 in Department of Cardiothoracic Surgery were reviewed. RESULTS: The mean age of the patients was 27±10.1years, with male and female distribution of 18 and 17, respectively. Fifty-one percent of patients complained of palmar hyperhidrosis, while 35% of them had concurrent palmaraxillary and 14% had palmar-plantar-axillary hyperhidrosis. Our data showed that 77% (n=27) of patients were not investigated for secondary causes of hyperhidrosis, and they were not counselled on the non-surgical therapies. All patients underwent single-staged bilateral endoscopic thoracic sympathectomy. There was resolution of symptoms in all 35 (100%) patients with palmar hyperhidrosis, 13(76%) patients with axillary hyperhidrosis and only 2 (50%) patients with plantar hyperhidrosis. Postoperatively 34.3% (n=12) of patients reported compensatory hyperhidrosis. There were no other complications such as pneumothorax, chylothorax, haemothorax and Horner's Syndrome. CONCLUSION: Clinical evaluation of hyperhidrosis in local context has not been well described, which may inadvertently result in the delay of appropriate management, causing significant social and emotional embarrassment and impair the quality of life of the subjects. Detailed clinical assessment and appropriate timely treatment, be it surgical or non-surgical therapies, are crucial in managing this uncommon yet distressing disease.


Assuntos
Endoscopia , Hiperidrose/diagnóstico , Hiperidrose/cirurgia , Satisfação do Paciente , Simpatectomia/métodos , Toracoscopia/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Auditoria Médica , Prontuários Médicos , Avaliação de Resultados em Cuidados de Saúde , Adulto Jovem
16.
Angew Chem Int Ed Engl ; 59(27): 10899-10903, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32297389

RESUMO

Glycopeptide antibiotics (GPAs) are important antibiotics that are highly challenging to synthesise due to their unique and heavily crosslinked structure. Given this, the synthetic production and diversification of this key compound class remains impractical. Furthermore, the possibility of biosynthetic reengineering of GPAs is not yet feasible since the selectivity of the biosynthetic crosslinking enzymes for altered substrates is largely unknown. We show that combining peptide synthesis with enzymatic cyclisation enables the formation of novel examples of GPAs and provides an indication of the utility of these crucial enzymes. By accessing the biosynthetic process in vitro, we identified peptide modifications that are enzymatically tolerated and can also reveal the mechanistic basis for substrate intolerance where present. Using this approach, we next specifically activated modified residues within GPAs for functionalisation at previously inaccessible positions, thereby offering the possibility of late-stage chemical functionalisation after GPA cyclisation is complete.


Assuntos
Antibacterianos/síntese química , Glicopeptídeos/síntese química , Antibacterianos/química , Ciclização , Glicopeptídeos/química
17.
Gene Ther ; 27(10-11): 482-494, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-32341483

RESUMO

Transfection of surface adherent cells remain as a standard methodology for lentiviral production for early phase clinical studies and research purposes. Production today is based on transient co-transfection of three or four plasmids, where the viral elements are encoded separately for safety reasons. Assembly of functional lentiviral particles requires all plasmids to be efficiently transfected into each cell, a notable challenge with many currently available methods for transient transfection. We have previously demonstrated the significant improvement of cationic polymer-based transfection in various cell types using a combination of fusogenic lipids and histone deacetylase 6 inhibitor (Enhancers). In this report, we focused on the transfection step and the feasibility of improving lentiviral production using the Enhancers. After optimization of DNA amount and N/P ratio, transfection using seven commercial gene carriers showed comparable maximal efficiency of production with high cell viability. In the presence of Enhancers, the production of functional lentivirus using LPEI was increased by as much as tenfold and outperformed lentiviral production using Lipofectamine 3000. We demonstrate a scalable and optimized workflow where the use of the Enhancers significantly improved the lentiviral particle production in various HEK293 cell lines.


Assuntos
Laboratórios , Lentivirus , Vetores Genéticos/genética , Células HEK293 , Humanos , Lentivirus/genética , Plasmídeos/genética , Transfecção
18.
Langmuir ; 35(52): 17156-17165, 2019 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-31790261

RESUMO

This work presents the first reported imbibition mechanism of femtoliter (fL)-scale droplets produced by microchannel cantilever spotting (µCS) of DNA molecular inks into porous substrates (hydrophilic nylon). Differently from macroscopic or picoliter droplets, the downscaling to the fL-size leads to an imbibition process controlled by the subtle interplay of evaporation, spreading, viscosity, and capillarity, with gravitational forces being quasi-negligible. In particular, the minimization of droplet evaporation, surface tension, and viscosity allows for a reproducible droplet imbibition process. The dwell time on the nylon surface permits further tuning of the droplet lateral size, in accord with liquid ink diffusion mechanisms. The functionality of the printed DNA molecules is demonstrated at different imbibed oligonucleotide concentrations by hybridization with a fluorolabeled complementary sequence, resulting in a homogeneous coverage of DNA within the imbibed droplet. This study represents a first step toward the µCS-enabled fabrication of DNA-based biosensors and microarrays into porous substrates.


Assuntos
DNA/química , Impressão Molecular , Nylons/química , Água/química , Interações Hidrofóbicas e Hidrofílicas , Hibridização de Ácido Nucleico , Porosidade , Tensão Superficial
20.
J Hepatol ; 69(1): 121-128, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29551711

RESUMO

BACKGROUND & AIMS: Recreational ketamine use has emerged as an important health and social issue worldwide. Although ketamine is associated with biliary tract damage, the clinical and radiological profiles of ketamine-related cholangiopathy have not been well described. METHODS: Chinese individuals who had used ketamine recreationally at least twice per month for six months in the previous two years via a territory-wide community network of charitable organizations tackling substance abuse were recruited. Magnetic resonance cholangiography (MRC) was performed, and the findings were interpreted independently by two radiologists, with the findings analysed in association with clinical characteristics. RESULTS: Among the 343 ketamine users referred, 257 (74.9%) were recruited. The mean age and ketamine exposure duration were 28.7 (±5.8) and 10.5 (±3.7) years, respectively. A total of 159 (61.9%) had biliary tract anomalies on MRC, categorized as diffuse extrahepatic dilatation (n = 73), fusiform extrahepatic dilatation (n = 64), and intrahepatic ductal changes (n = 22) with no extrahepatic involvement. Serum alkaline phosphatase (ALP) level (odds ratio [OR] 1.007; 95% CI 1.002-1.102), lack of concomitant recreational drug use (OR 1.99; 95% CI 1.11-3.58), and prior emergency attendance for urinary symptoms (OR 1.95; 95% CI 1.03-3.70) had high predictive values for biliary anomalies on MRC. Among sole ketamine users, ALP level had an AUC of 0.800 in predicting biliary anomalies, with an optimal level of ≥113 U/L having a positive predictive value of 85.4%. Cholangiographic anomalies were reversible after ketamine abstinence, whereas decompensated cirrhosis and death were possible after prolonged exposure. CONCLUSIONS: We have identified distinctive MRC patterns in a large cohort of ketamine users. ALP level and lack of concomitant drug use predicted biliary anomalies, which were reversible after abstinence. The study findings may aid public health efforts in combating the growing epidemic of ketamine abuse. LAY SUMMARY: Recreational inhalation of ketamine is currently an important substance abuse issue worldwide, and can result in anomalies of the biliary system as demonstrated by magnetic resonance imaging. Although prolonged exposure may lead to further clinical deterioration, such biliary system anomalies might be reversible after ketamine abstinence. Clinical trial number: NCT02165488.


Assuntos
Doenças dos Ductos Biliares/diagnóstico , Colangiopancreatografia por Ressonância Magnética/métodos , Usuários de Drogas , Drogas Ilícitas/efeitos adversos , Ketamina/efeitos adversos , Adulto , Doenças dos Ductos Biliares/induzido quimicamente , Dilatação Patológica/induzido quimicamente , Dilatação Patológica/diagnóstico , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos
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