Association between HPV infection and penile cancer and penile intraepithelial neoplasia: A retrospective observational study.

BACKGROUND: Penile cancer is rising in most European countries. Several risk factors have been identified, namely human papillomavirus (HPV) infection. However, the exact role of HPV in penile cancer carcinogenesis is still unknown. Clarifying the contribution of HPV in penile cancer is crucial as it may improve prevention and treatment strategies. OBJECTIVE: To describe the characteristics of patients with penile cancer and penile intraepithelial neoplasia (PeIN), evaluate the prevalence of HPV-DNA in tumour tissue and identify differences between patients with and without HPV-DNA. METHODS: A retrospective observational study including patients with histological diagnosis of penile squamous cell carcinoma (SCC) or PeIN between 2012 and 2021 in a university hospital was carried out. HPV analysis was performed using Anyplex™ II HPV28 Detection that detects and identifies 28 HPV types. (sensitivity of 95.9%). RESULTS: A total of 25 patients were included. Most of the tumours identified were invasive SCC (n = 11) and SCC in situ (PeIN 3) (n = 8). PeIN1/2 was found in the remaining six patients. HPV-DNA was tested in all tissue specimens and was detected in 18 of them. High risk HPV DNA was identified in all positive HPV samples, except one. HPV types included in the nonavalent HPV vaccine were identified in 16 of the 18 samples positive for HPV-DNA. Stratifying patients according to HPV-DNA detection, we found that patients with HPV-DNA were younger (57.5 years vs. 70 years, p = 0.047), less likely to have phimosis (5.8% vs. 42.9%, p = 0.022) and more likely to have PeIN lesions than invasive SCC (85.7% vs. 27.8%, p = 0.025). CONCLUSION: This study shows a prevalence of HPV-DNA in penile SCC and premalignant lesions of 45.5% and 92.9%, respectively. Identifying HPV involvement in SCC and PeIN pathology has the potential to guide treatment and enhance follow-up strategies.

The spectrum of focal epithelial hyperplasia-a report of two cases.

Focal epithelial hyperplasia is a rare, benign, and asymptomatic disorder, characterized by soft papules on the oral cavity. It is primarily associated with human papillomavirus genotypes 13 and 32. It most commonly affects children and young adults. When it affects young adults, it is important to differentiate it from oral condyloma acuminata. Its diagnosis may be made clinically, but histologic examination and PCR genotyping are often useful. Treatment is not always mandatory.

Perianal warts as a risk marker for anal high-risk-human papillomavirus (HPV) detection and HPV-associated diseases.

BACKGROUND: Genital warts are the most common sexually transmitted infection (STI) and are caused by human papillomavirus (HPV). Persistent anal infection by oncogenic genotypes of HPV is a determinant for anal cancer. Currently, anal cancer screening is not widely implemented. OBJECTIVES: Our aim is to evaluate the role of perianal warts as a risk marker for anal high-risk (HR) HPV detection and anal dysplasia. METHODS: In this observational, retrospective, cohort study of attendees of a STI outpatient clinic between January 2010 and June 2018, all human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) who performed anal cytology, anal HPV DNA detection and anoscopy were included. A comparison was made between patients with and without perianal warts. Primary endpoint: proportion of patients with an abnormal anal cytology. Secondary endpoints: proportion of patients with (i) anal HR-HPV detection; (ii) anal HPV 16 detection; (iii) abnormal anal biopsy; and (iv) anal high-grade squamous intraepithelial lesion (HSIL). RESULTS: Seventy-eight individuals were included: 39 with perianal warts and 39 without perianal warts. Subjects with perianal warts more frequently had an abnormal anal cytology (71.8% vs. 38.5%; P = 0.003). This group also had a higher rate of anal HPV 16 detection (38.5% vs. 12.8%; P = 0.01). No differences were detected in the proportion of patients with anal HR-HPV detection, with an abnormal anal biopsy or with anal HSIL. Perianal warts was an independent risk factor for an abnormal anal cytology (OR: 7.2) and for anal HPV 16 detection (OR: 6.7). CONCLUSION: Given the high risk of anal cancer in HIV-positive MSM, effective screening strategies are greatly needed. This study suggests that the presence of perianal warts is a suitable risk marker for anal HPV 16 detection and anal dysplasia.

Soft tissue assessment before and after mandibular advancement or setback surgery using three-dimensional images: systematic review and meta-analysis.

The aim of this systematic review was to evaluate the effects of mandibular advancement or setback surgery on the facial soft tissue assessed using three-dimensional images. An electronic search was performed in the MEDLINE, Cochrane Library, Scopus, Virtual Health Library (VHL), Web of Science, and OpenGrey databases. Inclusion criteria comprised studies that evaluated the soft tissues of adult patients before and after mandibular advancement or setback surgery using computed tomography or magnetic resonance imaging. The risk of bias was analyzed. A total of 3501 studies were retrieved. The titles and abstracts of 2071 studies were read and 2040 of them were excluded. Thirty-one articles were read in full and six fulfilled the eligibility criteria and were included. A meta-analysis was performed using three of these articles. The correlation was significant and strong in the chin area (r=0.876 and r=0.868) and moderate for the lower lip/lower incisor (r=0.690). The ratio for lower lip/infradentale was 78% and for Pog'/Pog was 98%. Due to the limited number of articles included, there is weak evidence to infer that changes in the facial soft tissue due to mandibular advancement or setback are significant, but changes in the lower lip tend to be smaller than changes in the chin area.

Epidemiology of human papillomavirus on anogenital warts in Portugal - The HERCOLES study.

BACKGROUND: Anogenital warts (AGW) are one of the most prevalent sexually transmitted disease worldwide. Approximately, 90% of AGWs are related to infection by HPV 6 and 11. However, AGW have been associated with infection by multiple genotypes, including HR-HPV, which may be associated with a long-term increased risk of anogenital cancer. OBJECTIVE: This observational prospective epidemiological study aims to estimate the type-specific HPV distribution on incident AGWs in both genders, and additionally to assess the frequency of anal and oral HPV infection in patients with AGWs. METHODS: According to defined inclusion criteria, individuals with incident clinical diagnosis of AGWs were recruited in seven Portuguese Centres. HPV genotyping was performed using CLART HPV2 test. RESULTS: Between November 2012 and March 2014, 162 women and 400 men (mean age: 34 years), were enrolled. After exclusion of patients with unqualified AGW samples, HPV was detected in 95.3% (505/530) AGW patients, 96.8% males and 91.6% females. Among men who have sex with men, HPV was detected in 98.5% patients. HPV 6 and/or HPV 11 were the most frequent genotypes (87.5%), and HPV 16 the most common HR-HPV (9.2%). Infection with HPV 6/11 and any HR-HPV was observed in 35.8% patients. HPV prevalence on the anal canal and oral mucosa was 83.1% and 15.0%, respectively. CONCLUSION: Incident AGWs were more frequent in males than in females. LR-HPVs were more common among males and HR-HPVs among females. HPV 6 and 11 were the most common genotypes on both genders. However, there was also a high prevalence of HR-HPVs, particularly of HPV 16. AGWs represent a clinical marker of both anal and oral HPV infections, including anal HR-HPV infections in women and men who have sex with men. The HERCOLES study could be a clue to further investigations concerning HPV burden of disease by gender and sexual behaviour.

Upper airway dimensions in patients undergoing orthognathic surgery: a systematic review and meta-analysis.

The objective of this systematic review was to evaluate the effect of different types of orthognathic surgery on the dimensions of the upper airways assessed using three-dimensional images. An electronic search was performed in Cochrane Library, Medline, Scopus, VHL, Web of Science, and the System for Information on Grey Literature in Europe, ending January 2015. Inclusion criteria encompassed clinical studies in humans, patient age >15 years, patients submitted to maxillary or mandibular advancement or setback surgery, isolated or in combination, and presentation of airway measures, specifically volume and/or minimum cross-sectional area (CSA), obtained from computed tomography or magnetic resonance imaging. Additional searches were conducted on the references of included articles and in the NLM catalogue. An assessment of the risk of bias was performed. A total of 1180 studies were retrieved, of which 28 met the eligibility criteria; one was later excluded as it presented a high risk of bias. A meta-analysis was performed. There is moderate evidence to conclude that the upper airway minimum CSA increases significantly (124.13 mm(2)) after maxillomandibular advancement (MMA); the total volume increases significantly after MMA (7416.10mm(3)) and decreases significantly after maxillary advancement+mandibular setback (-1552.90 mm(3)) and isolated mandibular setback (-1894.65 mm(3)).

Anti-TNF-alpha induced psoriasiform eruptions with severe scalp involvement and alopecia: report of five cases and review of the literature.

We describe 5 cases of anti-tumor necrosis factor-alpha (anti-TNF-α) induced psoriasiform eruptions with severe scalp involvement inducing inflammatory alopecia and review the literature on this subject. All our 5 patients were provided topical therapy, with good results in only 1 case. The remaining 4 were provided systemic therapy (methotrexate ± cyclosporine): 3 concomitantly suspended the anti-TNF-α treatment (2 are currently clear/almost clear but 1 has so far only observed mild improvement) and 1 switched anti-TNF-α (recurrent flare-ups of the disease continue). So far, no patient has developed scarring alopecia. To our knowledge, a total of 15 cases of anti-TNF-α induced psoriatic alopecia have been described. Anti-TNF-α was discontinued in 9 of the 15 patients and systemic therapy was provided to 9 of the 15 patients. Nonetheless, 2 patients developed scarring alopecia. We conclude that in anti-TNF-α induced psoriasiform eruptions some patients may respond to topical treatment, however in cases of severe scalp involvement anti-TNF-α suspension and systemic treatment should be considered in order to avoid scarring alopecia.

Protease expression analysis in recently field-isolated strains of Trypanosoma cruzi: a heterogeneous profile of cysteine protease activities between TC I and TC II major phylogenetic groups.

Protease expression among TCI and TCII field isolates was analysed. Gelatin-containing gels revealed hydrolysis bands with molecular masses ranging from 45 to 66 kDa. The general protease expression profile showed that TCII isolates presented higher heterogeneity compared to TCI. By utilizing protease inhibitors, we showed that all active proteases at acid pH are cysteine-proteases and all proteases active at alkaline pH are metalloproteases. However, the expression of cruzipain, the T. cruzi major cysteine-protease, did not reproduce a heterogeneous TCII cysteine zymogram profile. Dendogram analyses based on presence/absence matrices of proteases and cruzipain bands showed a TCI separation from the TCII group with 50-60% similarity. We suggest that the observed cysteine protease diversification contributes to differential host infection between TCI and II genotypes.

Tuberculosis in a child presenting as asymptomatic oropharyngeal and laryngeal lesions.

We describe an 11-year-old boy who had several, asymptomatic, erythematous papules in the oropharynx and larynx with recent onset, two cervical lymphadenopathies, and a painless, erythematous plaque on the right wrist with a 2.5-year history of slow growth. Histologic examination of the mucocutaneous lesions revealed a submucous infiltrate of lymphocytes and Langhans giant cells in the papules and granulomatous dermatitis in the plaque. The cervical lymph node was biopsied and on the surgical scar, an erythematous, nodular lesion developed. A biopsy specimen of this lesion showed tuberculoid granulomas with prominent caseation necrosis, and culture was positive for Mycobacterium tuberculosis. The Mantoux test was strongly positive with a vesicular response. A diagnosis of mucocutaneous lupus vulgaris and scrofuloderma secondary to cervical tuberculous lymphadenitis was made. Two months after initiation of antituberculosis therapy there was a complete resolution of mucous lesions and healing with atrophic scars on the neck and wrist. This is a rare presentation in the literature and reminds clinicians that tuberculosis should be kept in mind in the differential diagnosis of oral cavity lesions.

Efecto del bromuro de ipratropio sobre la hiperinflación pulmonar dinámica en pacientes con enfermedad pulmonar obstructiva crónica / Effect of ipratropium bromide on lung dynamic hyperinflation in patients with chronic obstructive lung disease

BACKGROUND: The six minute walk test (6 MW) elicits dynamic hyperinflation (DH) in severe COPD patients, which can be evaluated by reductions in inspiratory capacity (IC). Although IC is currently used to determine the effects of bronchodilators on DH during exercise tests on a cycle ergometer, its usefulness during a walking test has not been evaluated. AIM: To study the acute effects of ipratropium bromide (IB) on forced expiratory volume at l second (FEV1) and IC at rest and on DH during exercise assessed by the 6 MW. SUBJECTS AND METHODS: Fifteen stable COPD patients were randomly allocated in a double-blind, placebo-controlled, crossover fashion to 2 treatment periods using a single dose of nebulized IB 500 mg or placebo. Spirometry, including IC, and 6 MW were measured at baseline and after IB and placebo. IC was also measured 15 min after exercise. Dyspnea, oxygen saturation (SpO2) and heart rate were assessed at the end of exercise. RESULTS: After IB, 8/15 patients exhibited a clinically significant increase in IC (> or = 10 per cent predicted). A similar increase in FEV1 was observed in only one patient. No changes were observed with placebo. A significant increase in 6 MW from baseline (p = 0.007) was found after IB (45 +/- 14 m) compared to placebo (0.5 +/- 9 m), whereas dyspnea was significantly lower. Inspiratory capacity fell after 6 MW with both treatments, but it reached their baseline values at 15 min after exercise only with IB. CONCLUSIONS: Our results demonstrate that IC provides additional information to conventional spirometry on the acute effects of bronchodilators and confirm its value to assess DH during a walking test.

Cd8(+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin.

We report a case of CD8(+)/V beta 5.1(+) T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3(+)/TCR alpha beta(+)/CD8(+bright)/CD11c(+)/CD57(-)/CD56(-) large granular lymphocytes with expression of the TCR-V beta 5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR beta-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V beta monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease.

Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal flow limitation at rest.

Expiratory flow limitation (FL) at rest is frequently present in chronic obstructive pulmonary disease (COPD) patients. It promotes dynamic hyperinflation with a consequent decrease in inspiratory capacity (IC). Since in COPD resting IC is strongly correlated with exercise tolerance, this study hypothesized that this is due to limitation of the maximal tidal volume (VT,max) during exercise by the reduced IC. The present study investigated the role of tidal FL at rest on: 1) the relationship of resting IC to VT,max; and 2) on gas exchange during peak exercise in COPD patients. Fifty-two stable COPD patients were studied at rest, using the negative expiratory pressure technique to assess the presence of FL, and during incremental symptom-limited cycling exercise to evaluate exercise performance. At rest, FL was present in 29 patients. In the 52 patients, a close relationship of VT,max to IC was found using non-normalized values (r=0.77; p < 0.0001), and stepwise regression analysis selected IC as the only significant predictor of VT,max. Subgroup analysis showed that this was also the case for patients both with and without FL (r=0.70 and 0.76, respectively). In addition, in FL patients there was an increase (p < 0.002) in arterial carbon dioxide partial pressure at peak exercise, mainly due to a relatively low VT,max and consequent increase in the physiological dead space (VD)/VT ratio. The arterial oxygen partial pressure also decreased at peak exercise in the FL patients (p < 0.05). In conclusion, in chronic obstructive pulmonary disease patients the maximal tidal volume, and hence maximal oxygen consumption, are closely related to the reduced inspiratory capacity. The flow limited patients also exhibit a significant increase in arterial carbon dioxide partial pressure and a decrease in arterial oxygen partial pressure during peak exercise.

In vitro phosphorylation of cytoskeletal proteins in the rat cerebral cortex is decreased by propionic acid.

In the present study we demonstrate that propionic acid (PA), a metabolite that accumulates in large amounts in propionic acidemia, is able to decrease in vitro incorporation of [32P]ATP into neurofilament subunits (NF-M and NF-L) and alpha- and beta-tubulin. Considering that the endogenous phosphorylating system associated with the cytoskeletal fraction contains cAMP-dependent protein kinase (PKA), Ca2+/calmodulin protein kinase II (CaMKII), and protein phosphatase 1 (PP1), we first assayed the effect of the acid on the kinase activities by using the specific activators cAMP and Ca2+/calmodulin or the inhibitors PKAI or KN-93 for PKA and CaMKII, respectively. Results demonstrated that the acid totally inhibited the stimulatory effect of cAMP and interfered with the inhibitory effect of PKAI. In addition, PA partially prevented the stimulatory effect of Ca2+/calmodulin and interfered with the effect of KN-93. In addition, we demonstrated that PA totally inhibited in vitro dephosphorylation of neurofilament subunits and tubulins mediated by PP1 in brain slices pretreated with the acid. Taken together, these results demonstrate that PA inhibits the in vitro activities of PKA, CaMKII, and PP1 associated with the cytoskeletal fraction of the cerebral cortex of rats. This study suggests that PA at the same concentrations found in tissues from propionic acidemic children may alter phosphorylation of cytoskeletal proteins, which may contribute to the neurological dysfunction characteristic of propionic acidemia.

The effects of behavioral tasks on the in vitro phosphorylation of intermediate filament subunits of rat hippocampus are mediated by CaMKII and PKA.

Neurofilaments (NF) are the most abundant constituents of the neuronal cytoskeleton, while glial fibrillary acidic protein (GFAP) is a major component of the glial astrocyte cytoskeleton. These proteins can be phosphorylated by different protein kinases and they are regulated in a complex way by phosphorylation. Using a hippocampal cytoskeletal fraction we demonstrated that the behavioral tasks of inhibitory avoidance and habituation can differently alter the in vitro phosphorylation of the 150 kDa (NF-M) and the 68 kDa (NF-L) neurofilament subunits and of the GFAP. In order to verify the effect of habituation and inhibitory avoidance training on the phosphatase activity, we performed the time course-dephosphorylation assay (5-30 min of incubation of the cytoskeletal fraction with 32P-ATP). Subsequently we investigated the effect of these behavioral tasks on the protein kinase activities associated with the cytoskeletal fraction, carring out the 32P incorporation assays in the presence of specific kinase inhibitors. Results suggest that phosphatase activity is not altered in the cytoskeletal fraction by the behavioral tasks and that the increased in vitro phosphorylation of NF-M and NF-L caused by habituation is probably mediated by the Ca2+/calmodulin dependent protein kinase (CaMKII). However, the inhibition of GFAP in vitro phosphorylation caused by inhibitory avoidance training is probably related to the cAMP dependent protein kinase (PKA).

Infecçäo por parvovirus: apresentaçäo atípica em três crianças / Infection due to parvovirus: atypical clinical aspects in three children

Os autores descrevem três casos de infecçäo causada por Parvovirus em escolares com apresentaçäo clínica atípica. Aspectos relativos ao exantema, enfartamento ganglionar, hepatomegalia, e outros comemorativos foram distintos do observado no eritema infeccioso classicamente descrito. Os autores ressaltam a dificuldade no diagnóstico e o significado dos achados frente as recentes descriçöes de quadros graves causados por Parvovirus