The Glacier Ice Worm, Mesenchytraeus solifugus, Elevates Mitochondrial Inorganic Polyphosphate (PolyP) Levels in Response to Stress.

The inorganic polymer, polyphosphate (polyP), is present in all organisms examined to date with putative functions ranging from the maintenance of bioenergetics to stress resilience and protein homeostasis. Bioenergetics in the glacier-obligate, segmented worm, Mesenchytraeus solifugus, is characterized by a paradoxical increase in intracellular ATP levels as temperatures decline. We show here that steady-state, mitochondrial polyP levels vary among species of Annelida, but were elevated only in M. solifugus in response to thermal stress. In contrast, polyP levels decreased with temperature in the mesophilic worm, Enchytraeus crypticus. These results identify fundamentally different bioenergetic strategies between closely related annelid worms, and suggest that I worm mitochondria maintain ATP and polyP in a dynamic equilibrium.

COVID-19 and neurodegeneration: The mitochondrial connection.

There is still a significant lack of knowledge regarding many aspects of the etiopathology and consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. For example, the variety of molecular mechanisms mediating this infection, and the long-term consequences of the disease remain poorly understood. It first seemed like the SARS-CoV-2 infection primarily caused a serious respiratory syndrome. However, over the last years, an increasing number of studies also pointed towards the damaging effects of this infection has on the central nervous system (CNS). In fact, evidence suggests a possible disruption of the blood-brain barrier and deleterious effects on the CNS, especially in patients who already suffer from other pathologies, such as neurodegenerative disorders. The molecular mechanisms behind these effects on the CNS could involve the dysregulation of mitochondrial physiology, a well-known early marker of neurodegeneration and a hallmark of aging. Moreover, mitochondria are involved in the activation of the inflammatory response, which has also been broadly described in the CNS in COVID-19. Here, we critically review the current bibliography regarding the presence of neurodegenerative symptoms in COVID-19 patients, with a special emphasis on the mitochondrial mechanisms of these disorders.

External laryngeal nerve landmarks revisited.

BACKGROUND: Because external laryngeal nerve (ELN) iatrogenic damage is frequent during neck surgery, its precise localization has been highly recommended. This study analyzes the different surgical landmarks previously proposed and the anatomy of the collateral and terminal branches of the ELN. METHODS: The necks of 157 (77 men and 80 women) human adult embalmed cadavers were examined. The ELN origin, length, and relationship to different landmarks were recorded and results statistically compared with those previously reported. RESULTS: The ELN is located deep to the ascending pharyngeal vein in 100% of patients. In most patients, it crosses the carotid axis at the thyroid artery origin level (47% of patients), passes medial to it (89% of patients), and shows an intramuscular trajectory through the inferior constrictor of the pharynx (80% of patients). CONCLUSION: The ELN position, in relation to classical landmarks, is highly variable. The most reliable relationships are those with the ascending pharyngeal vein or with the superior thyroid artery.

Is Chlamydia trachomatis related to human papillomavirus infection in young women of southern European population? A self-sampling study.

BACKGROUND: It is well established the role of human papillomavirus (HPV) in cervical cancer (CC) etiology. Chlamydia trachomatis (CT) infection seems to synergize with HPV in CC multistage process. The aim of this study was to assess the correlation of HPV and CT infection in young student women. MATERIAL AND METHODS: Cervicovaginal samples were obtained by self-sampling method from young women (n = 432; mean age 18.0 ± 2.46 years) recruited among the student community and tested for HPV and CT DNA by polymerase chain reaction. RESULTS: In CT positive cases, there is an increased risk of HPV detection [odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.03-6.27, p < 0.037]. The highest rate of coinfection with HPV and CT were observed in the mean age of 20.6 years, and all coinfection cases were found in young women who referred no previous history or symptoms of sexually transmitted infections. Within HPV-positive young women, there was no significant difference between CT and high-risk HPV. CONCLUSIONS: Our results suggest a causal association between HPV and CT infection in young women; infection with this bacterium may be a predisposing factor for subsequent infection with HPV, or vice versa, due to similar mode of sexual transmission, inferring the promising role of CT in CC development. However, the specific question on multistage process of HPV-associated carcinogenesis, which may be affected by CT, remains unclear.

Debunking myths and building realities: Human body donation in times of crisis

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Oncogenic HPV Types Infection in Adolescents and University Women from North Portugal: From Self-Sampling to Cancer Prevention.

This study aimed to characterize the HPV infection status in adolescents and young university women in Portugal. The distribution of HPV genotypes was evaluated by PCR DNA genotyping after self-sampling collection from 435 women of exfoliated cervical cells using a commercial kit. We observed an overall frequency of HPV infection of 11.5%. Furthermore, HPV DNA prevalence was 16.6% in those young women that self-declared as sexually active. The more frequently detected HPV types were 31, 16, 53, and 61. Statistical analysis identified median age (OR = 3.56; P = 0.001), the number of lifetime sexual partners (OR = 4.50; P < 0.001), and years of sexual activity (OR = 2.36; P = 0.008) as risk factors for HPV acquisition. Hence, our study revealed that oncogenic HPV infection is common in young asymptomatic women Portuguese women, with a history of 2-5 sexual partners and over 2 year of sexual activity. Moreover, these results demonstrate that HPV detection performed in self-collected samples may be important to appraise better preventive strategies and to monitorize the influence of vaccination programmes within different populations.

Importance of xeroderma pigmentosum group D polymorphisms in susceptibility to ovarian cancer.

The purpose of this study was to evaluate the role of XPD genotypes as genetic indicator of susceptibility to ovarian cancer. We have used a case-control study. We analysed DNA samples from 141 ovarian cancer patients and 202 control subjects, for three XPD polymorphisms using PCR-RFLP. We observed that Asn312Asn XPD genotype carriers have increased susceptibility of ovarian cancer (OR=2.46 95% CI 1.20-5.06; P=0.015). Furthermore, we found that carriers of Gln751Gln XPD genotype have an increased susceptibility of ovarian cancer (OR=3.40 95% CI 1.61-7.15; P=0.001). Asn312Asn and Gln751Gln are particularly associated with an early-stage of disease. Our results suggest an important role for Asn312Asn and Gln751Gln XPD polymorphisms in the susceptibility to ovarian cancer.

Platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma: glutathione S-transferase genetic polymorphisms as predictive biomarkers of disease outcome.

BACKGROUND: The glutathione S-transferases (GSTs) are a group of multifunctional enzymes that catalyze the conjugation of glutathione with a variety of electrophilic compounds, including cytotoxic agents. A significant percentage of normal individuals exhibit genetic polymorphism with a homozygous deletion (null genotype) of the genes, leading to absence of the enzyme. METHODS: In the present study we analyzed GSTM1 and GSTT1 polymorphisms in the genomic DNA isolated from peripheral blood of patients with ovarian cancer treated with chemotherapy (paclitaxel and cisplatinum) after cytoreductive surgery and assessed its correlation with the clinical outcome of these patients. The median follow-up for the patients was 30 months. RESULTS: The estimated 3-year survival rate was 59.8% for all patients and 20.8% for carriers of GSTM1-wt/GSTT1-wt (wt indicates wild type) genotype combination (37.7% for GSTM1-wt alone) compared with 83.1% for non-GSTM1-wt/GSTT1-wt genotype carriers (100% for GSTM1-null). The mean survival time was significantly better in patients who are carriers of the GSTM1-null genotype (40.5 vs. 33.5; P=0.006) or carriers of non-GSTM1-wt/ GSTT1-wt genotypes (55.4 vs. 30.7; P=0.009). The progression-free interval was more favorable for GSTM1-null carriers (41.9 vs. 27.4; P=0.024). CONCLUSION: The study suggests that characterization of the drug-metabolizing genetic individual profile can be of great interest in clinical oncology. It can define the optimal chemotherapy for each patient, improve the efficiency, and reduce the incidence of drug toxicity and poor drug responses.

Ciliary muscle in avian is derived from mesenchymal and epithelial cells.

It has long been maintained that the ciliary muscle derives from mesenchymal cells. The embryonic development of the avian ciliary muscle was studied in chick embryos from stage 25 HH to the time of hatching. Serial sections of the eye were stained routinely or immunocytochemically using the monoclonal antibody 13F4, which recognizes a cytoplasmic antigen specific for all types of muscle cells. We found that the mesenchymal immunoreactive cells, at stage 37 HH, are arranged in two distinct orientations forming the anterior and posterior portions of the ciliary muscle. At stages 38 and 39 HH the pigmented epithelium contained 13F4 positive cells, which detach from the epithelium and apparently migrate into stroma. These epithelial cells may differentiate into muscle cells. Within this same time period a progressive accumulation of myoblasts was detected between the pigmented epithelium and the ciliary muscle. Some myoblasts containing melanin were also observed. At stage 40 HH the internal portion of the ciliary muscle was visible. These findings indicate that the immunopositive epithelial cells participate in the formation of the internal portion of the muscle. We conclude that the ciliary muscle derives not only from the mesenchymal cells but also from the pigmented epithelium.

The influence of altered circulating blood volume on ventricular morphogenesis in the chick embryo: analysis by scanning electron microscopy / Influencia del volumen sanguíneo circulante alterado sobre la morfogénesis ventricular en el embrión de pollo: análisis con el microscopio electrónico de barrido

Cardiac morphogenesis represents a balance of myocardial differentiation, growth and remodelling, and congenital cardiovascular malformations likely reflect a range of similar final common pathways generated by numerous primary genetic and environmental abnormalities. In the present work, we analyzed the morphology of the developing ventricle in the chick embryo following experimental alterations in total circulating volume. In parallel experiments, we injected three different volumes of blood into a branch of the right vitelline vein at stages 22, 25 and 29 of Hamburger and Hamilton (n?10 per group). The embryos were reincubated to stage 35 of Hamburger and Hamilton and then processed for morphological analysis using scanning electron microscopy. 39% of the surviving operated embryos contained ventricular malformations, including disordered trabeculation and patterns of either cardiac dilation or cardiac hyperplasia. Despite the high prevalence of disordered trabecular morphogenesis, we identified very few ventricular septal defects. Thus, while alterations in ventricular loading conditions may alter morphogenesis, cardiomyopathic phenotypes may be separated from defects in ventricular septation (AU)

La morfogénesis cardiaca representa un balance de la diferenciación, crecimiento y remodelación miocárdica y las malformaciones cardiovasculares congénitas probablemente reflejan un rango de vías comunes finales generadas por numerosos defectos genéticos y ambientales primarios. En el presente trabajo analizamos la morfología del ventrículo en desarrollo del embrión de pollo después de alteraciones experimentales del volumen total circulante. En experimentos paralelos inyectamos tres volúmenes de sangre diferentes en una rama de la vena vitelina derecha en los estadios 22, 25 y 29 de Hamburger y Hamilton (n ?10 por grupo). Los embriones fueron reincubados hasta el estadio 35 de Hamburger y Hamilton y luego se procesaron para su análisis morfológico con el microscopio electrónico de barrido. El 39 por ciento de los embriones operados supervivientes contenían malformaciones ventriculares, que incluían una trabeculación alterada y patrones de dilatación o de hiperplasia cardiaca. A pesar de la alta prevalencia de morfogénesis trabecular alterada, identificamos muy pocos defectos septales ventriculares. Por ello, mientras que las alteraciones en condiciones de carga ventricular pueden alterar la morfogénesis, los fenotipos cardiomiopáticos pueden ser separados de los defectos en la formación del septo ventricular (AU)

Diagnóstico rápido de la Ciudad de El Alto / I diagnose fast of the City of The Alto

Este documento contiene el diagnóstico de la Ciudad de El Alto, del mes de abril a junio del año 2001 en los distritos y establecimientos de salud públicos y con administración delegada