Paula Boaventura

As a major cancer hallmark, there is a sustained interest in understanding the telomerase contribution to carcinogenesis in order to therapeutically target this enzyme. This is particularly relevant in primary cutaneous T-cell lymphomas (CTCL), a malignancy showing telomerase dysregulation with few investigative data available. In CTCL, we examined the mechanisms involved in telomerase transcriptional activation and activity regulation. We analyzed 94 CTCL patients from a Franco-Portuguese cohort, as well as 8 cell lines, in comparison to 101 healthy controls. Our results showed that not only polymorphisms (SNPs) located at the promoter of human telomerase reverse transcriptase (hTERT) gene (rs2735940 and rs2853672) but also an SNP located within the coding region (rs2853676) could influence CTCL occurrence. Furthermore, our results sustained that the post-transcriptional regulation of hTERT contributes to CTCL lymphomagenesis. Indeed, CTCL cells present a different pattern of hTERT spliced transcripts distribution from the controls, mostly marked by an increase in the hTERT β+ variants proportion. This increase seems to be associated with CTCL development and progression. Through hTERT splicing transcriptome modulation with shRNAs, we observed that the decrease in the α-β+ transcript induced a decrease in the cell proliferation and tumorigenic capacities of T-MF cells in vitro. Taken together, our data highlight the major role of post-transcriptional mechanisms regulating telomerase non canonical functions in CTCL and suggest a new potential role for the α-β+ hTERT transcript variant.

Background: Cutaneous basal cell carcinoma (cBCC) incidence has been increasing, but there are no available data on its epidemiological, clinical, and pathological patterns in Northeast Portugal. cBCC is mainly located in the head and neck, where the ear, neck, and throat (ENT) surgeon may have a major role. We aimed to verify the clinicopathological characteristics of basal cell carcinomas diagnosed in an ENT department. Methods: We performed a retrospective clinicopathological evaluation of the head and neck cBCC cases followed up at the Centro Hospitalar de Trás-os-Montes e Alto Douro (CHTMAD) ENT Department between January 2007 and April 2021. Results: One hundred seventy-four patients with 293 cBCCs were included in this retrospective study. We observed that about one-third of the patients had multiple cBCCs (30.5%) and an infiltrative-type growth pattern (39.3%), both features considered as patterns that are more aggressive. Infiltrative-type growth pattern cBCCs were significantly larger when compared with the indolent-type growth pattern (16.2 mm vs 10.8 mm). Conclusions: To the best of our knowledge, this is the first study about cBCC in a patient population followed up at an ENT hospital department. This study has shown that these patients had cBCCs with more aggressive features, making these tumors an important issue for the ENT surgeon.

Yoga and qigong are ancient mind–body practices used in the East for thousands of years to promote inner peace and mental clarity. Both share breathing techniques and slow movements and are being used as alternative/complementary approaches to the management of disease, especially chronic problems with no effective conventional treatments. However, information comparing the health benefits of both approaches is scarce, and the choice between yoga or qigong practice may only depend on patients’ preferences or practice availability. The aim of the present paper was to overview yoga and qigong use for health benefits under different pathological conditions. Yoga and qigong seem to have similar effects, which might be expected, since both are similar mind–body approaches with the same concept of vital life-force energy and the practice of meditative movements. Problematic research issues within the literature on yoga and qigong are the small sample sizes, use of different styles, significant variance in practice duration and frequency, short duration of intervention effects, and the usage of a non-active control group, thus emphasizing the need for further high-quality randomized trials. Studies comparing yoga and qigong are warranted in order to assess differences/similarities between the two approaches for health benefits.

COVID-19 is currently considered a systemic infection involving multiple systems and causing chronic complications. Compared to other post-viral fatigue syndromes, these complications are wider and more intense. The most frequent symptoms are profound fatigue, dyspnea, sleep difficulties, anxiety or depression, reduced lung capacity, memory/cognitive impairment, and hyposmia/anosmia. Risk factors for this condition are severity of illness, more than five symptoms in the first week of the disease, female sex, older age, the presence of comorbidities, and a weak anti-SARS-CoV-2 antibody response. Different lines of research have attempted to explain these protracted symptoms; chronic persistent inflammation, autonomic nervous system disruption, hypometabolism, and autoimmunity may play a role. Due to thyroid high ACE expression, the key molecular complex SARS-CoV-2 uses to infect the host cells, thyroid may be a target for the coronavirus infection. Thyroid dysfunction after SARS-CoV-2 infection may be a combination of numerous mechanisms, and its role in long-COVID manifestations is not yet established. The proposed mechanisms are a direct effect of SARS-CoV-2 on target cells, an indirect effect of systemic inflammatory immune response, and a dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis leading to decreased serum TSH. Only a few studies have reported the thyroid gland status in the post-COVID-19 condition. The presence of post-COVID symptoms deserves recognition of COVID-19 as a cause of post-viral fatigue syndrome. It is important to recognize the affected individuals at an early stage so we can offer them the most adequate treatments, helping them thrive through the uncertainty of their condition.

Cutaneous basal cell carcinoma (cBCC) is an economic burden to health services, due to its great morbidity and increasing incidence in old people. Infiltrative cBCCs and cBCCs with micronodular pattern are considered as more aggressive. The role of p53 expression and TERTp mutation on cBCC behavior remains to be clarified. We aimed to assess TERTp mutations and p53 expression in relation to the cBCC histological subtype in a cohort of patients referred to an ENT Department of a tertiary Hospital of Northern Portugal. We performed a retrospective clinicopathological and histological review of the head and neck cBCCs followed-up at the otorhinolaryngology department of Trás-os-Montes e Alto Douro hospital (January 2007–June 2018). We assessed TERTp mutations in 142 cBCCs and p53 protein expression, through immunohistochemistry, in 157 cBCCs. We detected TERTp mutations in 43.7% of cBCCs and p53 overexpression in 60.5% of cBCCs. We spotted association of p53 overexpression and TERTp mutation with necrosis. In the infitrative-growth pattern cBCCs, there was no significant association with the clinical and histological features evaluated, except for necrosis. In the indolent-growth cBCCs, we identified a significant association of TERTp mutation status with female sex, necrosis, multiple cBCCs, and p53 positive expression. Our results suggest that TERTp mutation may be useful to identify more aggressive features in the indolent-growth pattern cBCCs (nodular and superficial subtypes). Further studies with larger cohorts are warranted to clarify the relevance of TERTp mutation in cBCCs.

Background/Objective Surgery is the main approach for skin cancer, with Mohs micrographic surgery (MMS) allowing the highest cure rates, best esthetics and superior functional outcomes. Ear, nose and throat (ENT) surgeons are often challenged with patients presenting skin cancer, needing appropriate expertise to its adequate management. This paper highlights the most important aspects of MMS, enabling ENT surgeons to become familiar with its fundamental aspects. Methods A review of the literature was performed, concomitantly presenting the author’s outcomes as an ENT surgeon. Results A total of 51 MMSs were performed in 41 patients, and 78.4% of the tumors were cutaneous basal cell carcinomas(cBCCs), 19.6% were cutaneous squamous cell carcinomas (cSCCs) , and one case was a microcystic adnexal carcinoma. Most tumors were located in high‐risk areas (88.2%), and 84.3% of them were ≥ 10 mm in diameter. Most tumors (90.2%) required no more than two MMS excision steps to be completely removed. All cases were managed by reconstruction either using flaps or grafts. Recurrence occurred in only 2% of the cases. Conclusions This study addressed the main issues of MMS, which may be important in ENT surgeons’ daily practice.

Radiobiology is moving towards a better understanding of the intercellular signaling that occurs upon radiation and how its effects relate to the dose applied. The mitochondrial role in orchestrating this biological response needs to be further explored. Cybrids (cytoplasmic hybrids) are useful cell models for studying the involvement of mitochondria in cellular processes. In the present study we used cybrid cell lines to investigate the role of mitochondria in the response to radiation exposure. Cybrid cell lines, derived from the osteosarcoma human cell line 143B, harboring, either wild-type mitochondrial DNA (Cy143Bwt), cells with mitochondria with mutated DNA that causes mitochondrial dysfunction (Cy143Bmut), as well as cells without mitochondrial DNA (mtDNA) (143B-Rho0), were irradiated with 0.2 Gy and 2.0 Gy. Evaluation of the non-targeted (or bystander) effects in non-irradiated cells were assessed by using conditioned media from the irradiated cells. DNA double stranded breaks were assessed with the γH2AX assay. Both directly irradiated cells and cells treated with the conditioned media, showed increased DNA damage. The effect of the irradiated cells media was different according to the cell line it derived from: from Cy143Bwt cells irradiated with 0.2 Gy (low dose) and from Cy143Bmut irradiated with 2.0 Gy (high dose) induced highest DNA damage. Notably, media obtained from cells without mtDNA, the143B-Rho0 cell line, produced no effect in DNA damage. These results point to a possible role of mitochondria in the radiation-induced non-targeted effects. Furthermore, it indicates that cybrid models are valuable tools for radiobiological studies.