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1.
Pathology ; 56(3): 322-324, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38360444

ABSTRACT

The terms 'Bowen disease' and 'intraepidermal squamous cell carcinoma' are sometimes considered synonymous. In this paper we present historical, clinical, histological and molecular evidence that this is incorrect. The term Bowen disease should be reserved for a subset of intraepidermal squamous cell carcinoma with a distinctive and reproducible morphological pattern, described in detail by Bowen in 1912. One other common subset of intraepidermal squamous cell carcinoma represents progression of actinic keratosis. In some cases the separation of these two common patterns of intraepidermal squamous cell carcinoma can be challenging and there are patterns of intraepidermal squamous cell carcinoma which appear to represent other distinct pathways. However, there is emerging biological evidence to support this distinction and reason to suspect that the types of invasive squamous cell carcinoma which arise from these different pathways may show important clinical and biological differences, particularly in the era of targeted and immunomodulatory therapy for advanced disease.


Subject(s)
Anus Neoplasms , Bowen's Disease , Carcinoma, Squamous Cell , Keratosis, Actinic , Skin Neoplasms , Humans , Bowen's Disease/pathology , Skin Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Keratosis, Actinic/pathology
2.
Vaccines (Basel) ; 11(12)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38140222

ABSTRACT

The recent introduction of foot-and-mouth disease (FMD) virus serotype O (O/EA-2 topotype) in Southern Africa has changed the epidemiology of the disease and vaccine requirements of the region. Commercial and subsistence cattle herds in Zambia were vaccinated with an FMD virus serotype O Manisa vaccine according to a double- or single-dose vaccination schedule. Heterologous antibody responses induced by this vaccine against a representative O/EA-2 virus from Zambia were determined. Virus neutralisation tests (VNTs) showed double-dosed cattle had a mean reciprocal log virus neutralisation titre of 2.02 (standard error [SE] = 0.16, n = 9) for commercial herds and 1.65 (SE = 0.17, n = 5) for subsistence herds 56 days after the first vaccination (dpv). Significantly lower mean titres were observed for single-dosed commercial herds (0.90, SE = 0.08, n = 9) and subsistence herds (1.15, SE = 0.18, n = 3) 56 dpv. A comparison of these results and those generated by solid-phase competitive ELISA (SPCE) tests showed a statistically significant positive correlation by Cohen's kappa coefficient. Therefore, SPCE might be used in assessing the immunogenicity of vaccines in place of VNT. Furthermore, for this vaccine and field strain, a vaccination regime employing a two-dose primary course and revaccination after 4-6 months is likely to be appropriate.

3.
Vaccines (Basel) ; 11(12)2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38140247

ABSTRACT

Vaccination is widely used to control foot-and-mouth disease (FMD), but maternal antibodies may interfere with the response to vaccination in calves. This study, conducted on a regularly vaccinated Malaysian dairy farm, aimed to optimise the vaccination regime by measuring the in vitro neutralising virus antibody responses of 51 calves before and after vaccination with a one or two dose vaccination regime starting at 2-7 months old. The presence of maternal antibodies was associated with poor post-vaccination antibody responses after a single dose of vaccine in calves less than 6 months old. However, a second dose of vaccine given three weeks later, improved the antibody responses in all ages of calves. This confirms the view that in regularly vaccinated farms, some combination of delay and revaccination is needed to achieve effective immunization of calves. Sera from cows and pre-vaccinated calves neutralised homologous serotype A vaccine virus more strongly than a heterologous serotype A field virus, but this pattern was reversed in some calves after vaccination. The strength of heterologous responses in calves 49 days after first vaccination correlated to the amount of transferred maternal antibody, suggesting that pre-existing antibodies could have modulated the specificity of these active antibody responses. If confirmed, such an effect by pre-existing antibodies could have wider implications for broadening the coverage of FMD vaccine responses.

4.
J Surg Case Rep ; 2023(6): rjad338, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37305344

ABSTRACT

A 78-year-old female with a history of cosmetic breast implants presented with unilateral breast enlargement and was subsequently diagnosed with stage IA breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) as well as stage IB ipsilateral synchronous invasive ductal carcinoma (IDC). Her assessment included bilateral breast ultrasounds,mammograms and MRIs with right-sided fine needle aspiration of peri-implant fluid, core biopsy of right breast mass and a whole-body positron emission tomography scan. She was surgically treated with bilateral capsulectomy, implant removal and mastectomy. No adjuvant treatment was required for the BIA-ALCL. The IDC required adjuvant chemotherapy, radiotherapy and endocrine therapy. This rare case highlights the paramount importance of thorough evaluation of suspected BIA-ALCL patients for synchronous breast pathologies. We conclude with a concise summary of the salient points on evaluation and management of BIA-ALCL for surgeons.

5.
Indian J Radiol Imaging ; 33(2): 187-194, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37123587

ABSTRACT

Objectives Cerebral venous sinus thrombosis is an important cause of stroke in young adults. Noncontrast-enhanced CT head (NECT) is almost always the first investigation. Our objectives were as follows: 1. How accurately does venous sinus density on NECT predict the presence of clot on CT venogram (CTV)? 2. Whether repeated measurements changed the confidence? 3. How many venous sinus thrombus would be missed if we do not do a CTV? 4. Can clot density measurement replace CTV? Methods Multicenter case-control study was designed with data from seven hospitals. Inclusion criteria: all CT and magnetic resonance imaging venograms with a prior NECT, performed between 1.1.2018 and 31.12.2018 (12 months), were included. Hounsfield unit (HU) values were calculated at the site of highest density on the NECT. Logistic regression analysis was performed using STATA. Result Two-hundred seventy-seven cases met the criteria with 33 positive cerebral venous thrombosis (density on NECT 60-92 HU) and 244 negative examinations (density on NECT 31-68 HU). Area under the curve for average clot density on NECT was 0.9984. Conclusion We found a strong relationship between sinus density on NECT and outcome of CTV. Repeating density measurements did not add any predictive value or changed outcome. Advances in Knowledge Density 70 HU or higher on NECT always resulted in a positive CTV but would miss a fifth of the positives. Cutoff at 60 HU would not miss any but result in significant false positives. An efficient option could be to limit CTV to sinus densities 60 to 70 HU only. However, a larger study would be required for such change in practice.

6.
Issues Law Med ; 38(2): 127-146, 2023.
Article in English | MEDLINE | ID: mdl-38165258

ABSTRACT

Many people worldwide, particularly those with disabilities and the elderly, suffered greatly not only as a result of the Covid-19 pandemic but also as a result of the lockdowns. In this article we set out widely-accepted ethical criteria for assessing when coercive public health measures are justified. We then review the empirical evidence, not least concerning the benefits and costs of the lockdowns, and conclude that lockdowns as instituted in the UK (and, presumptively, in many other jurisdictions) appeared to breach those criteria. We conclude that any future proposal to lockdown should be subjected to the strictest ethical scrutiny, and that a lockdown should not be contemplated unless it could be convincingly demonstrated that the benefits would substantially outweigh the harms; that it would be proportionate, and that legal coercion would be strictly necessary.


Subject(s)
COVID-19 , Pandemics , Aged , Humans , Academies and Institutes , COVID-19/epidemiology , COVID-19/prevention & control , Coercion , Public Health
7.
Front Vet Sci ; 9: 1027006, 2022.
Article in English | MEDLINE | ID: mdl-36532344

ABSTRACT

Serology is widely used to predict whether vaccinated individuals and populations will be protected against infectious diseases, including foot-and-mouth disease (FMD), which affects cloven-hoofed animals. Neutralising antibody titres to FMD challenge viruses correlate to protection against FMD, for vaccinated cattle that are infected with the same strain as in the vaccine (homologous protection). Similar relationships exist for cross-strain protection between different vaccine and challenge viruses, although much less data are available for these heterologous studies. Poor inter-laboratory reproducibility of the virus neutralisation test (VNT) also hampers comparisons between studies. Therefore, day-of-challenge sera (n = 180) were assembled from 13 previous FMD cross-protection experiments for serotypes O (n = 2), A (n = 10), and SAT 2 (n = 1). These were tested by VNT against the challenge viruses at the FMD FAO World Reference Laboratory (WRLFMD) and the titres were compared to challenge outcomes (protected or not). This dataset was combined with equivalent serology and protection data for 61 sera from four cross-protection experiments carried out at WRLFMD for serotypes O (n = 2), A (n = 1), and Asia 1 (n = 1). VNT results and protection outcomes were also analysed for a serotype O cross-protection experiment involving 39 cattle, where the sera were not available for retesting at WRLFMD. Three categories of association between heterologous neutralising antibody titre and heterologous protection were found (Group 1-3). The log10 reciprocal titres associated on average with 75% protection (with 95% credible limits) were: Group 1: 2.46 (2.11-2.97); Group 2: 1.67 (1.49-1.92); Group 3: 1.17 (1.06-1.30). Further cross-protection data are needed to understand the factors that underpin this variability and to develop more robust antibody thresholds. Establishing cut-off serological titres that can be used to score the adequacy of vaccine-induced immunity will facilitate the monitoring and thereby the performance of FMD vaccination in the field.

8.
Drugs Today (Barc) ; 58(10): 509-517, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36305544

ABSTRACT

Growth hormone deficiency (GHD) is characterized by inadequate HG production from the anterior pituitary gland. Adult patients with GHD have increased fat mass, an abnormal lipid profile, decreased lean body mass and bone mineral density, decreased muscle strength and exercise endurance, and a diminished quality of life. Adult GHD (AGHD) has been treated with GH replacement therapy by daily subcutaneous injections. However, the administration of daily injections can be burdensome for some patients and affect treatment adherence. Somapacitan is a new long-acting human GH (hGH) analogue that is administered once a week by subcutaneous injection. It was first approved by the U.S. Food and Drug Administration (FDA) as GH replacement therapy for adults with GHD, becoming the first hGH therapy for AGHD administered by once-weekly injection, compared with other approved hGH therapies for AGHD administered by daily injection. This article reviews the pharmacokinetic, clinical and safety data that led to the approval of somapacitan as the first long-acting GH therapy for adults with GHD.


Subject(s)
Dwarfism, Pituitary , Human Growth Hormone , Adult , Humans , Dwarfism, Pituitary/diagnosis , Dwarfism, Pituitary/drug therapy , Human Growth Hormone/therapeutic use , Quality of Life
9.
Drugs Today (Barc) ; 58(9): 451-456, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36102905

ABSTRACT

Achondroplasia is the commonest form of dwarfism and results from a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene on chromosome 4p16.3. The mutation is at nucleotide 1138 resulting in a G-to-A transition (134934.0001). This condition is characterized by full penetration meaning that everyone with this genetic mutation will exhibit the phenotypic characteristics of achondroplasia. It is a gain-of function mutation that causes increased inhibition of cartilage formation. C-type natriuretic peptide (CNP) acts on the growth plate through the natriuretic peptide receptor-B (NPR-B) causing the transformation of guanosine 5'-triphosphate into cyclic guanosine monophosphate. However, CNP cannot be used in the treatment of achondroplasia because it is rapidly degraded by neutral endopeptidase. Vosoritide is a modified recombinant human CNP and has a half-life 10 times that of CNP. Clinical trials have demonstrated that vosoritide is effective in significantly increasing the annualized growth velocity in children with achondroplasia before the fusion of the epiphyses.


Subject(s)
Achondroplasia , Natriuretic Peptide, C-Type , Achondroplasia/drug therapy , Achondroplasia/genetics , Child , Humans , Mutation , Natriuretic Peptide, C-Type/analogs & derivatives , Natriuretic Peptide, C-Type/genetics , Natriuretic Peptide, C-Type/metabolism , Natriuretic Peptide, C-Type/therapeutic use , Neprilysin
10.
Viruses ; 14(7)2022 07 08.
Article in English | MEDLINE | ID: mdl-35891476

ABSTRACT

Antibodies to the foot-and-mouth disease virus (FMDV) capsid induced by infection or vaccination can provide serotype-specific protection and be measured using virus neutralization tests and viral structural-protein (SP-)ELISAs. Separate tests are needed for each serotype, but cross-serotype reactions complicate serotyping. In this study, inter-serotypic responses were quantified for five SP-ELISA formats by testing 294 monovalent mainly bovine sera collected following infection, vaccination, or vaccination and infection with one of five serotypes of FMDV. Over half of the samples, representing all three immunization categories, scored positive for at least one heterologous serotype and some scored positive for all serotypes tested. A comparative approach to identifying the strongest reaction amongst serotypes O, A and Asia 1 improved the accuracy of serotyping to 73-100% depending on the serotype and test system, but this method will be undermined where animals have been infected and/or vaccinated with multiple FMDV serotypes. Preliminary studies with stabilized recombinant capsid antigens of serotypes O and A that do not expose internal epitopes showed reduced cross-reactivity, supporting the hypothesis that capsid integrity can affect the serotype-specificity of the SP-ELISAs. The residual cross-reactivity associated with capsid surface epitopes was consistent with the evidence of cross-serotype virus neutralization.


Subject(s)
Foot-and-Mouth Disease Virus , Foot-and-Mouth Disease , Animals , Antibodies, Viral , Capsid Proteins/genetics , Cattle , Enzyme-Linked Immunosorbent Assay/methods , Epitopes , Serogroup
11.
Drugs Today (Barc) ; 58(1): 1-8, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35107089

ABSTRACT

Estetrol (E4) is a natural human estrogen produced during human pregnancy in the fetal liver with a unique mechanism of action that displays tissue-selective activity, and behaves as a natural selective estrogen receptor modulator. E4 acts as an estrogen agonist on the vagina, the uterus and the endometrium, and also shows bone-sparing activity. Its mechanism of action results in neutral impact on endocrine, metabolic and hemostatic parameters, compared with other oral contraceptives. In 2021, Health Canada approved the combination 15 mg E4/3 mg drospirenone (DRSP), the first and only combined oral contraceptive based on the native estrogen E4, which has been synthesized from plant-based sources. Shortly afterwards, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) also approved the combination 14.2 mg E4/3 mg DRSP as a female contraceptive.


Subject(s)
Estetrol , Androstenes/adverse effects , Contraceptives, Oral , Estetrol/adverse effects , Estrogens , Female , Humans , United States
12.
Drugs Today (Barc) ; 58(2): 77-84, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35188142

ABSTRACT

Loteprednol etabonate is a soft corticosteroid that is rapidly deactivated after reaching the general circulation, displaying good local activity and a high therapeutic index without inducing systemic side effects. In 2021, Kala Pharmaceuticals launched Eysuvis (loteprednol etabonate ophthalmic suspension) 0.25% in the U.S. for the short-term (up to 2 weeks) treatment of the signs and symptoms of dry eye disease. Approval by the Food and Drug Administration (FDA) was based on results from one phase II trial and three phase III trials showing Eysuvis significantly improved both the signs and symptoms of dry eye disease and was well tolerated. Eysuvis is a novel loteprednol etabonate nanosuspension formulation developed by Kala using its AMPPLIFY mucus-penetrating particle (MPP) drug delivery technology. Use of this MPP formulation results in enhanced penetration of loteprednol etabonate into target tissue on the ocular surface. Eysuvis is the first FDA-approved ocular corticosteroid indicated for dry eye disease.


Subject(s)
Dry Eye Syndromes , Loteprednol Etabonate , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Dry Eye Syndromes/drug therapy , Humans , Loteprednol Etabonate/therapeutic use , Ophthalmic Solutions/therapeutic use , United States , United States Food and Drug Administration
13.
Transbound Emerg Dis ; 69(5): 3041-3046, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34331827

ABSTRACT

Livestock markets are considered vital parts of the agricultural economy, particularly in developing countries where livestock keeping contributes to both food security and economic stability. Animals from diverse sources are moved to markets, they mix while they are there and are subsequently redistributed over wide geographic areas. Consequently, markets provide an opportunity for targeted surveillance for circulating pathogens. This study investigated the use of environmental sampling at a live goat market in Nepal for the detection of foot-and-mouth disease virus (FMDV) and peste des petits ruminants virus (PPRV), both of which are endemic. Five visits to the market were carried out between November 2016 and April 2018, with FMDV RNA detected on four visits and PPRV RNA detected on all five visits. Overall, 4.1% of samples (nine out of 217) were positive for FMDV RNA and 60.8% (132 out of 217) were positive for PPRV RNA, though the proportion of positive samples varied amongst visits. These results demonstrate that non-invasive, environmental sampling methods have the potential to be used to detect circulation of high priority livestock diseases at a live animal market and, hence, to contribute to their surveillance and control.


Subject(s)
Foot-and-Mouth Disease Virus , Goat Diseases , Peste-des-Petits-Ruminants , Peste-des-petits-ruminants virus , Animals , Foot-and-Mouth Disease Virus/genetics , Goat Diseases/diagnosis , Goat Diseases/epidemiology , Goats , Nepal/epidemiology , Peste-des-Petits-Ruminants/diagnosis , Peste-des-Petits-Ruminants/epidemiology , Peste-des-petits-ruminants virus/genetics , RNA, Viral/genetics
14.
Front Vet Sci ; 9: 1029075, 2022.
Article in English | MEDLINE | ID: mdl-36590816

ABSTRACT

Antigen banks have been established to supply foot-and-mouth disease virus (FMDV) vaccines at short notice to respond to incursions or upsurges in cases of FMDV infection. Multiple vaccine strains are needed to protect against specific FMDV lineages that circulate within six viral serotypes that are unevenly distributed across the world. The optimal selection of distinct antigens held in a bank must carefully balance the desire to cover these risks with the costs of purchasing and maintaining vaccine antigens. PRAGMATIST is a semi-quantitative FMD vaccine strain selection tool combining three strands of evidence: (1) estimates of the risk of incursion from specific areas (source area score); (2) estimates of the relative prevalence of FMD viral lineages in each specific area (lineage distribution score); and (3) effectiveness of each vaccine against specific FMDV lineages based on laboratory vaccine matching tests (vaccine coverage score). The output is a vaccine score, which identifies vaccine strains that best address the threats, and consequently which are the highest priority for inclusion in vaccine antigen banks. In this paper, data used to populate PRAGMATIST are described, including the results from expert elicitations regarding FMD risk and viral lineage circulation, while vaccine coverage data is provided from vaccine matching tests performed at the WRLFMD between 2011 and 2021 (n = 2,150). These data were tailored to working examples for three hypothetical vaccine antigen bank perspectives (Europe, North America, and Australia). The results highlight the variation in the vaccine antigens required for storage in these different regions, dependent on risk. While the tool outputs are largely robust to uncertainty in the input parameters, variation in vaccine coverage score had the most noticeable impact on the estimated risk covered by each vaccine, particularly for vaccines that provide substantial risk coverage across several lineages.

15.
Viruses ; 13(5)2021 05 01.
Article in English | MEDLINE | ID: mdl-34062811

ABSTRACT

It is well known that approximately 50% of cattle infected with foot-and-mouth disease (FMD) virus (FMDV) may become asymptomatic carrier (persistently infected) animals. Although transmission of FMDV from carrier cattle to naïve cattle has not been demonstrated experimentally, circumstantial evidence from field studies has linked FMDV-carrier cattle to cause subsequent outbreaks. Therefore, the asymptomatic carrier state complicates the control and eradication of FMD. Current serological diagnosis using tests for antibodies to the viral non-structural proteins (NSP-ELISA) are not sensitive enough to detect all carrier animals, if persistently infected after vaccination and do not distinguish between carriers and non-carriers. The specificity of the NSP ELISA may also be reduced after vaccination, in particular after multiple vaccination. FMDV-specific mucosal antibodies (IgA) are not produced in vaccinated cattle but are elevated transiently during the acute phase of infection and can be detected at a high level in cattle persistently infected with FMDV, irrespective of their vaccination status. Therefore, detection of IgA by ELISA may be considered a diagnostic alternative to RT-PCR for assessing FMDV persistent infection in ruminants in both vaccinated and unvaccinated infected populations. This study reports on the development and validation of a new mucosal IgA ELISA for the detection of carrier animals using nasal, saliva, and oro-pharyngeal fluid (OPF) samples. The diagnostic performance of the IgA ELISA using nasal samples from experimentally vaccinated and infected cattle demonstrated a high level of specificity (99%) and an improved level of sensitivity (76.5%). Furthermore, the detection of carrier animals reached 96.9% when parallel testing of samples was carried out using both the IgA-ELISA and NSP-ELISA.


Subject(s)
Cattle Diseases/immunology , Cattle Diseases/virology , Foot-and-Mouth Disease Virus/immunology , Foot-and-Mouth Disease/immunology , Foot-and-Mouth Disease/virology , Immunoglobulin A, Secretory/immunology , Mucous Membrane/immunology , Animals , Cattle , Cattle Diseases/diagnosis , Cattle Diseases/epidemiology , Disease Outbreaks , Enzyme-Linked Immunosorbent Assay , Foot-and-Mouth Disease/diagnosis , Foot-and-Mouth Disease/epidemiology , Mucous Membrane/metabolism , ROC Curve , Vaccines/immunology
16.
Viruses ; 13(5)2021 05 15.
Article in English | MEDLINE | ID: mdl-34063385

ABSTRACT

In foot-and-mouth disease (FMD)-endemic countries, vaccination is commonly used to control the disease, whilst in FMD-free countries, vaccination is considered as an option, in addition to culling the infected and in contact animals. FMD vaccines are mainly comprised of inactivated virions and stimulate protective antibodies to virus structural proteins. In contrast, infection with FMD virus leads to virus replication and additional antibody responses to viral nonstructural proteins (NSP). Therefore, antibodies against NSPs are used to differentiate infection in vaccinated animals (DIVA), in order to estimate the prevalence of infection or its absence. Another advantage of NSP antibody tests is that they detect FMD infection in the field, irrespective of the serotypes of virus in circulation. In cattle, the NSP tests that target the 3ABC polyprotein provides the highest sensitivity, detecting up to 90% of vaccinated animals that become carriers after exposure to infection, with a specificity of around 99%. Due to insufficient diagnostic sensitivity and specificity, detection of a low level of infection is difficult at the population level with a high degree of confidence. The low level of non-specific responses can be overcome by retesting samples scored positive using a second confirmatory test, which should have at least comparable sensitivity to the first test. In this study, six in-house tests were developed incorporating different NSP antigens, and validated using bovine sera from naïve animals, field cases and experimentally vaccinated and/or infected animals. In addition, two (short and long incubation) new commercial NSP tests based on 3ABC competitive blocking ELISAs (ID Screen® FMD NSP Competition, IDvet, France) were validated in this study. The two commercial ELISAs had very similar sensitivities and specificities that were not improved by lengthening the incubation period. Several of the new in-house tests had performance characteristics that were nearly as good as the commercial ELISAs. Finally, the in-house tests were evaluated for use as confirmatory tests following screening with the PrioCHECK® and ID Screen® FMDV NS commercial kits, to assess the diagnostic performance produced by a multiple testing strategy. The in-house tests could be used in series (to confirm) or in parallel (to augment) with the PrioCHECK® and IDvet® FMDV NS commercial kits, in order to improve either the specificity or sensitivity of the overall test system, although this comes at the cost of a reduction in the counterpart (sensitivity/specificity) parameter.


Subject(s)
Antibodies, Viral/immunology , Enzyme-Linked Immunosorbent Assay/standards , Foot-and-Mouth Disease Virus/immunology , Foot-and-Mouth Disease/diagnosis , Foot-and-Mouth Disease/immunology , Vaccination/statistics & numerical data , Vaccination/veterinary , Animals , Antibody Formation , Cattle , Cattle Diseases/diagnosis , Cattle Diseases/epidemiology , Enzyme-Linked Immunosorbent Assay/methods , Sensitivity and Specificity
17.
Am J Dermatopathol ; 43(3): 217-220, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33464748

ABSTRACT

ABSTRACT: Mesenchymal neoplasms with oncogenic kinase activity due to genomic alterations in receptor tyrosine kinase genes are a morphologically heterogeneous group with a variable biologic potential. A subset of these neoplasms are characterized by immunophenotypic property of dual S100 protein/CD34 expression, histopathological resemblance to lipofibromatosis or peripheral nerve sheath tumors, and often alterations in neurotrophic tropomyosin-related kinase genes. In this article, we present a case of an S100 protein/CD34-positive spindle cell neoplasm harboring a rare BRAF gene rearrangement (KIAA1549-BRAF fusion) and discuss the clinical, histopathological, and molecular variations associated with such neoplasms.


Subject(s)
Membrane Proteins/genetics , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Antigens, CD34/metabolism , Humans , Male , S100 Proteins/metabolism , Skin Neoplasms/metabolism , Young Adult
18.
BMJ Case Rep ; 14(1)2021 Jan 11.
Article in English | MEDLINE | ID: mdl-33431461

ABSTRACT

Peritoneal melanosis is an uncommon benign condition, the pathophysiology of which is unclear. Macroscopically, it appears as diffuse dark brown or black pigmentation within the peritoneum, mimicking more sinister conditions such as metastatic melanoma. It has been described in a variety of contexts, but only exceedingly rarely in association with metastatic melanoma, with only two previous published case reports. We present a case of peritoneal melanosis associated with metastatic melanoma involving the spleen, previously treated with targeted and immune checkpoint inhibitor therapy. With increasing reports of melanoma regression manifesting as cutaneous tumorous melanosis in patients treated with immune checkpoint inhibitors, we postulate that, similarly, immunotherapy and tumour regression might have a role to play in the pathogenesis of the peritoneal pigmentation in this case.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Melanoma/therapy , Melanosis/diagnosis , Peritoneal Diseases/diagnosis , Skin Neoplasms/therapy , Splenic Neoplasms/surgery , Biopsy , Chemotherapy, Adjuvant , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Melanoma/complications , Melanoma/immunology , Melanoma/secondary , Melanosis/chemically induced , Melanosis/immunology , Melanosis/pathology , Middle Aged , Peritoneal Diseases/chemically induced , Peritoneal Diseases/immunology , Peritoneal Diseases/pathology , Peritoneum/drug effects , Peritoneum/immunology , Peritoneum/pathology , Positron-Emission Tomography , Protein Kinase Inhibitors/adverse effects , Skin Neoplasms/complications , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Spleen/diagnostic imaging , Spleen/pathology , Spleen/surgery , Splenectomy , Splenic Neoplasms/diagnosis , Splenic Neoplasms/secondary
19.
Virus Evol ; 7(1): veab009, 2021 Jan.
Article in English | MEDLINE | ID: mdl-35186323

ABSTRACT

Foot-and-mouth disease (FMD) is a highly contagious animal disease caused by an RNA virus subdivided into seven serotypes that are unevenly distributed in Asia, Africa, and South America. Despite the challenges of controlling FMD, since 1996 there have been only two outbreaks attributed to serotype C, in Brazil and in Kenya, in 2004. This article describes the historical distribution and origins of serotype C and its disappearance. The serotype was first described in Europe in the 1920s, where it mainly affected pigs and cattle but as a less common cause of outbreaks than serotypes O and A. No serotype C outbreaks have been reported in Europe since vaccination stopped in 1990. FMD virus is presumed to have been introduced into South America from Europe in the nineteenth century, although whether serotype C evolved there or in Europe is not known. As in Europe, this serotype was less widely distributed and caused fewer outbreaks than serotypes O and A. Since 1994, serotype C had not been reported from South America until four small outbreaks were detected in the Amazon region in 2004. Elsewhere, serotype C was introduced to Asia, in the 1950s to the 1970s, persisting and evolving for several decades in the Indian subcontinent and for eighteen years in the Philippines. Serotype C virus also circulated in East Africa between 1957 and 2004. Many serotype C viruses from European and Kenyan outbreaks were closely related to vaccine strains, including the most recently recovered Kenyan isolate from 2004. International surveillance has not confirmed any serotype C cases, worldwide, for over 15 years, despite more than 2,000 clinical submissions per year to reference laboratories. Serology provides limited evidence for absence of this serotype, as unequivocal interpretation is hampered by incomplete intra-serotype specificity of immunoassays and the continued use of this serotype in vaccines. It is recommended to continue strengthening surveillance in regions of FMD endemicity, to stop vaccination against serotype C and to reduce working with the virus in laboratories, since inadvertent escape of virus during such activities is now the biggest risk for its reappearance in the field.

20.
Sci Rep ; 10(1): 21165, 2020 12 03.
Article in English | MEDLINE | ID: mdl-33273533

ABSTRACT

Knowledge about the movement ecology of endangered species is needed to identify biologically important areas and the spatio-temporal scale of potential human impacts on species. Blue whales (Balaenoptera musculus) are endangered due to twentieth century whaling and currently threatened by human activities. In Australia, they feed in the Great Southern Australian Coastal Upwelling System (GSACUS) during the austral summer. We investigate their movements, occupancy, behaviour, and environmental drivers to inform conservation management. Thirteen whales were satellite tagged, biopsy sampled and photo-identified in 2015. All were genetically confirmed to be of the pygmy subspecies (B. m. brevicauda). In the GSACUS, whales spent most of their time over the continental shelf and likely foraging in association with several seascape variables (sea surface temperature variability, depth, wind speed, sea surface height anomaly, and chlorophyll a). When whales left the region, they migrated west and then north along the Australian coast until they reached West Timor and Indonesia, where their movements indicated breeding or foraging behaviour. These results highlight the importance of the GSACUS as a foraging ground for pygmy blue whales inhabiting the eastern Indian Ocean and indicate the whales' migratory route to proposed breeding grounds off Indonesia. Information about the spatio-temporal scale of potential human impacts can now be used to protect this little-known subspecies of blue whale.


Subject(s)
Balaenoptera/physiology , Behavior, Animal/physiology , Movement/physiology , Satellite Communications , Animals , Australia , Female , Geography , Male , Models, Biological , Species Specificity
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