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European Journal of Human Genetics :... Nov 2021Individuals with Birt-Hogg-Dubé syndrome (BHDS) may develop fibrofolliculomas, pneumothorax and/or renal cell carcinoma (RCC). Currently, all patients with pathogenic...
Individuals with Birt-Hogg-Dubé syndrome (BHDS) may develop fibrofolliculomas, pneumothorax and/or renal cell carcinoma (RCC). Currently, all patients with pathogenic FLCN variants are recommended to have renal surveillance. It has however been suggested that some FLCN variants only cause pneumothorax, which would make surveillance unnecessary in certain cases. This review assesses this possibility. We provide an up-to-date analysis of clinical and genetic features of BHDS. The PUBMED database was systematically searched to find all articles describing patients with pathogenic FLCN variants. The relevant clinical and genetic features of these patients were recorded and analysed. The prevalence of pneumothorax, pulmonary cysts, RCC and characteristic skin lesions in BHDS were 50.9% (n = 1038), 91.9% (n = 720), 22.5% (n = 929) and 47.9% (n = 989), respectively. There was a higher prevalence of pneumothoraces (p < 0.0001) but lower prevalence of dermatological findings (p < 0.0001) in patients from East Asia compared to North America or Europe. Of the 194 pathogenic FLCN variants, 76 could be defined as 'pneumothorax-only'. Pneumothorax only pathogenic variants (POPVs) were distributed throughout the gene, and there were no statistical differences in variant type. The majority of POPVs (65/76) affected no more than three individuals. Individuals with 'POPVs' also tended to be younger (45 vs. 47 years, p < 0.05). Many apparent POPVs in the literature could result from variable expressivity, age-related penetrance and other confounding factors. We therefore recommend that all individuals found to carry a pathogenic FLCN variant be enroled in lifelong surveillance for RCC.
Topics: Birt-Hogg-Dube Syndrome; Humans; Kidney Neoplasms; Mutation; Phenotype; Pneumothorax; Proto-Oncogene Proteins; Tumor Suppressor Proteins
PubMed: 34267338
DOI: 10.1038/s41431-021-00921-x -
Journal of Toxicology and Environmental... Apr 2022Percutaneous absorption is of importance given its role in topical medicaments, transdermal drug systems, and dermatotoxicology. Many factors influence percutaneous...
Percutaneous absorption is of importance given its role in topical medicaments, transdermal drug systems, and dermatotoxicology. Many factors influence percutaneous penetration, including anatomical region, although little is currently known regarding this parameter. Hence, the aim of this study was to summarize existing data on regional variation in percutaneous penetration in human models. PubMed, Embase, Web of Science, and US patent literature were explored, and relevant data collected. Eight eligible articles were identified, which together, explored 15 anatomical locations. Four investigations compared percutaneous penetration between scalp and abdominal skin, and all concluded that the former was more permeable. Within those four studies, 10 penetrants of varying physical/chemical properties were tested indicating that in those particular study conditions, anatomical location exerted a greater effect on percutaneous absorption than the physicochemical properties of the penetrants. In addition, torso area was less absorptive than scrotum in both studies in which these sites were compared. In conclusion, the scrotum and scalp appear to be highly susceptible to percutaneous absorption compared to other locations such as the abdomen. This is postulated to be largely due to the high density of hair follicles in these areas, enabling greater penetration via the appendageal pathway. However, there is a paucity of conclusive data regarding the penetrability of other anatomical locations. Investigations testing and ranking the susceptibility of different anatomical regions is of vital importance given the importance of (1) transdermal drug delivery and decontamination protocols and (2) understanding the underlying mechanisms and degree of these variances might aid our pharmacologic/toxicologic judgments.
Topics: Humans; Male; Skin; Skin Absorption
PubMed: 35094673
DOI: 10.1080/10937404.2022.2032517 -
Clinical Genetics Jun 2024HDR syndrome is a rare disease characterized by hypoparathyroidism, deafness, and renal dysplasia. An autosomal dominant disease caused by heterozygous pathogenic GATA3...
HDR syndrome is a rare disease characterized by hypoparathyroidism, deafness, and renal dysplasia. An autosomal dominant disease caused by heterozygous pathogenic GATA3 variants, the penetrance of each associated condition is variable. Literature reviews have provided some answers, but many questions remain, in particular what the relationship is between genotype and phenotype. The current study examines 28 patients with HDR syndrome combined with an exhaustive review of the literature. Some conditions such as hearing loss are almost always present, while others described as rare initially, do not seem to be so rare after all (genital malformations and basal ganglia calcifications). By modeling pathogenic GATA3 variants found in HDR syndrome, we found that missense variations appear to always be located in the same area (close to the two Zinc Finger domain). We describe new pathogenic GATA3 variants, of which some seem to always be associated with certain conditions. Many audiograms were studied to establish a typical audiometric profile associated with a phenotype in HDR. As mentioned in the literature, hearing function should always be assessed as early as possible and follow up of patients with HDR syndrome should include monitoring of parathyroid function and vesicoureteral reflux in order to prevent complications.
PubMed: 38940299
DOI: 10.1111/cge.14583 -
Expert Review of Clinical Immunology Aug 2021: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare inborn immune error characterized by a triad of chronic mucocutaneous candidiasis...
: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare inborn immune error characterized by a triad of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HP), and adrenal insufficiency (ADI).: Literature search was conducted in PubMed, Web of Science, and Scopus databases using related keywords, and included studies were systematically evaluated.: We reviewed 938 APECED patients and the classic triad of APECED was detected in 57.3% (460 of 803) of patients. CMC (82.5%) was reported as the earliest, HP (84.2%) as the most prevalent, and ADI (72.2%) as the latest presentation within the classic triad. A broad spectrum of non-triad involvements has also been reported; mainly included ectodermal dystrophy (64.5%), infections (58.7%), gastrointestinal disorders (52.0%), gonadal failure (42.0%), neurologic involvements (36.4%), and ocular manifestations (34.3%). A significant positive correlation was detected between certain tissue-specific autoantibodies and particular manifestations including ADI and HP. Neutralizing autoantibodies were detected in at least 60.0% of patients. Nonsense and/or frameshift insertion-deletion mutations were detected in 73.8% of patients with CMC, 70.9% of patients with HP, and 74.6% of patients with primary ADI.: Besides penetrance diversity, our review revealed a diverse affected ethnicity (mainly from Italy followed by Finland and Ireland). APECED can initially present in adolescence as 5.2% of the patients were older than 18 years at the disease onset. According to the variety of clinical conditions, which in the majority of patients appear gradually over time, clinical management deserves a separate analysis.
Topics: Adolescent; Autoantibodies; Frameshift Mutation; Humans; Mutation; Polyendocrinopathies, Autoimmune; Transcription Factors
PubMed: 33957837
DOI: 10.1080/1744666X.2021.1925543 -
Clinical & Experimental Metastasis Apr 2024Brain metastases represent a growing healthcare challenge with a rising incidence attributed to earlier detection and improved systemic cancer treatments. We conducted a... (Meta-Analysis)
Meta-Analysis
Brain metastases represent a growing healthcare challenge with a rising incidence attributed to earlier detection and improved systemic cancer treatments. We conducted a systematic review and meta-analysis to investigate the local recurrence rate following surgical resection of a brain metastasis without adjuvant therapy. The analysis included four studies with a total of 235 cases. It was found that the rate of local recurrence by 12-months was 48.1% (95% CI 41.2-58.9). These findings underscore the high rate of patients who will experience local recurrence within 12-months of surgery, emphasising the need for vigilant surveillance when omitting adjuvant radiotherapy in favour of systemic treatments with potential but unproven CNS penetrance. The analysis highlights unmet needs in this patient population.
Topics: Humans; Brain Neoplasms; Radiotherapy, Adjuvant; Combined Modality Therapy; Radiosurgery; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 38353933
DOI: 10.1007/s10585-024-10274-6 -
European Journal of Ophthalmology Sep 2020Topical steroids may induce a rise in intraocular pressure. The risk may increase with prolonged use, high frequency of administration, young age, higher ocular...
Topical steroids may induce a rise in intraocular pressure. The risk may increase with prolonged use, high frequency of administration, young age, higher ocular penetrance and higher anti-inflammatory potency. We aimed to study this relationship by comparing published rates of intraocular pressure elevation following administration of topical steroids and compared the risk of higher versus lower dosage regimes, high- versus low-potency/penetration steroids and adults versus children. Data sources used were Ovid Embase, Ovid Medline, the Cochrane Central Register of Controlled Trials, Web of Science, Scopus, CINHAL Plus and LILACS. Eligible studies were randomised controlled trials of topical steroids versus any other topical steroid, nonsteroidal anti-inflammatory drugs, placebo or vehicle, or a different mode of administration administered for 7 days or longer that reported intraocular pressure elevation from baseline as >10, 6-15 or >15 mm Hg in adults or children. Risks of bias were reviewed using the GRADE quality approach. Data were extracted into the software package, RevMan, Version 5 (Cochrane Collaboration). In total, 43 studies were included. Meta-analysis was not possible. Topical steroids of lower anti-inflammatory potency, and with reduced intraocular penetration, are associated with reduced incidence of intraocular pressure elevation. A comparison of data in children and adults is limited by the use of different reporting systems. The principal obstacle to meta-analysis is the different reporting systems used to categorise intraocular pressure elevation. We recommend future studies should report intraocular pressure elevation >10 mm Hg from baseline to allow meta-analysis of data.
Topics: Administration, Ophthalmic; Adolescent; Adult; Child; Child, Preschool; Glaucoma; Glucocorticoids; Humans; Infant; Infant, Newborn; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Risk Factors
PubMed: 31668084
DOI: 10.1177/1120672119885050 -
Chemosphere Nov 2022Number of research on molecular simulation and design has emerged recently but there is currently a lack of review to present these studies in an organized manner to...
Number of research on molecular simulation and design has emerged recently but there is currently a lack of review to present these studies in an organized manner to highlight the advances and feasibility. This paper aims to review the development, structural, physical properties and separation performance of hybrid membranes using molecular simulation approach. The hybrid membranes under review include ionic liquid membrane, mixed matrix membrane, and functionalized hybrid membrane for understanding of the transport mechanism of molecules through the different structures. The understanding of molecular interactions, and alteration of pore sizes and transport channels at atomistic level post incorporation of different components in hybrid membranes posing impact to the selective transport of desired molecules are also covered. Incorporation of molecular simulation of hybrid membrane in related fields such as carbon dioxide (CO) removal, wastewater treatment, and desalination are also reviewed. Despite the limitations of current molecular simulation methodologies, i.e., not being able to simulate the membrane operation at the actual macroscale in processing plants, it is still able to demonstrate promising results in capturing molecule behaviours of penetrants and membranes at full atomic details with acceptable separation performance accuracy. From the review, it was found that the best performing ionic liquid membrane, mixed matrix membrane and functionalized hybrid membrane can enhance the performance of pristine membrane by 4 folds, 2.9 folds and 3.3 folds, respectively. The future prospects of molecular simulation in hybrid membranes are also presented. This review could provide understanding to the current advancement of molecular simulation approach in hybrid membranes separation. This could also provide a guideline to apply molecular simulation in the related sectors.
Topics: Carbon Dioxide; Ionic Liquids; Membranes; Membranes, Artificial; Water Purification
PubMed: 35952794
DOI: 10.1016/j.chemosphere.2022.135844 -
European Respiratory Review : An... Sep 2020The percentage of α-antitrypsin protease inhibitor ZZ (PiZZ) genotypes in patients with COPD is controversial, with large differences among various studies. We aimed to...
The percentage of α-antitrypsin protease inhibitor ZZ (PiZZ) genotypes in patients with COPD is controversial, with large differences among various studies. We aimed to estimate the prevalence of PiZZ in COPD patients from 20 European countries with available data, according to the number of PiZZ and COPD individuals in each country.A systematic review was conducted to select European countries with reliable data on the prevalence of PiZZ and COPD. We created a database with the following data: 1) total population and population aged ≥40 years according to the Eurostat database; 2) number and 95% CI of PiZZ patients aged ≥40 years; 3) application of a conversion factor of genetic penetrance of 60%; 4) number of COPD individuals, with 95% CI, aged ≥40 years; and 5) calculation of the PiZZ/COPD ratio. Finally, results were presented using an Inverse Distance Weighted Interpolation map.We found 36 298 (95% CI 23 643-56 594) PiZZ individuals at high risk and 30 849 709 (95% CI 21 411 293-40 344 496) COPD patients, with a PiZZ/COPD ratio of 0.12% (range 0.08-0.24%), and a prevalence of 1 out of 408 in Northern, 1 out of 944 in Western, 1 out of 1051 in Central, 1 out of 711 in Southern, and 1 out of 1274 in Eastern Europe.These data may be useful to plan strategies for future research and diagnosis, and to rationalise the available therapeutic resources.
Topics: Europe; Genotype; Humans; Prevalence; Pulmonary Disease, Chronic Obstructive; alpha 1-Antitrypsin Deficiency
PubMed: 32699024
DOI: 10.1183/16000617.0014-2020 -
Journal of Clinical Neuroscience :... Apr 2021Acute brain injury is a leading cause of morbidity and mortality worldwide. The term is inclusive of traumatic brain injury, cerebral ischemia, subarachnoid hemorrhage,...
Acute brain injury is a leading cause of morbidity and mortality worldwide. The term is inclusive of traumatic brain injury, cerebral ischemia, subarachnoid hemorrhage, and intracerebral hemorrhage. Current pharmacologic treatments have had minimal effect on improving neurological outcomes leading to a significant interest in the development neuroprotective agents. Minocycline is a second-generation tetracycline with high blood brain barrier penetrance due to its lipophilic properties. It functions across multiple molecular pathways involved in secondary-injury cascades following acute brain injury. Animal model studies suggest that minocycline might lead to improved neurologic outcomes, but few such trials exist in humans. Clinical investigations have been limited to small randomized trials in ischemic stroke patients which have not demonstrated a clear advantage in neurologic outcomes, but also have not been sufficiently powered to draw definitive conclusions. The potential neuroprotective effect of minocycline in the setting of traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage have all been limited to pilot studies with phase II/III investigations pending. The authors aim to synthesize what is currently known about minocycline as a neuroprotective agent against acute brain injury in humans.
Topics: Animals; Brain Injuries; Humans; Minocycline; Neuroprotective Agents
PubMed: 33775346
DOI: 10.1016/j.jocn.2021.01.005 -
Dermatology (Basel, Switzerland) 2021Increasing availability of panel testing for known high-penetrance familial melanoma genes has made it possible to improve risk awareness in those at greatest risk....
BACKGROUND
Increasing availability of panel testing for known high-penetrance familial melanoma genes has made it possible to improve risk awareness in those at greatest risk. Prior to wider implementation, the role of genetic testing in preventing melanoma, through influencing primary and secondary preventative behaviours, requires clarification.
METHODS
Database searches of PubMed, Embase, CINAHL, PsycINFO and the Cochrane Library were conducted for studies describing preventative behaviour outcomes in response to genetic testing for melanoma risk. Publications describing original research of any study type were screened for eligibility.
RESULTS
Eighteen publications describing 11 unique studies were reviewed. Outcomes assessed are based on health behaviour recommendations for those at increased risk: adherence to sun-protective behaviour (SPB); clinical skin examinations (CSE); skin self-examinations (SSE); and family discussion of risk. Overall, modest increases in adherence to primary prevention strategies of SPB were observed following genetic testing. Importantly, there were no net decreases in SPB found amongst non-carriers. For secondary preventative behaviour outcomes, including CSE and SSE, increases in post-test intentions and long-term adherence were reported across several subgroups in approximately half of the studies. While this increase reached significance in mutation carriers in some studies, one study reported a significant decline in annual CSE adherence of non-mutation carriers.
CONCLUSIONS
Evidence reviewed suggests that genetic testing has a modestly positive impact on preventative behaviour in high-risk individuals. Furthermore, improvements are observed regardless of mutation carrier status, although greater adherence is found in carriers. While additional studies of more diverse cohorts would be needed to inform clinical recommendations, the findings are encouraging and suggest that genetic testing for melanoma has a positive impact on preventative behaviours.
Topics: Genetic Testing; Health Behavior; Humans; Melanoma; Patient Compliance; Primary Prevention; Secondary Prevention; Self-Examination; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 33588421
DOI: 10.1159/000513919