Thyroid Stem Cells But Not Differentiated Thyrocytes Are Sensitive to Slightly Increased Concentrations of Heavy Metals

Thyroid cancer incidence is markedly increased in volcanic areas where residents are biocontaminated by chronic lifelong exposure to slightly increased metals in the environment. Metals can influence the biology of living cells by a variety of mechanisms, depending not only on the dose and length of exposure but also on the type and stage of differentiation of target cells. We explored the effect of five heavy metals (Cu, Hg, Pd, W and Zn) at nanomolar concentrations (the biocontamination level in residents of the volcanic area in Sicily where thyroid cancer is increased) on stimulating the proliferation of undifferentiated (thyrospheres) and differentiated human thyroid cells. Thyrosphere proliferation was significantly increased after exposure to each individual metal and a greater stimulating effect was observed when a mixture of the examined metals was used. No effect was seen in differentiated thyrocytes. For all metals, the dose-response curve followed a biphasic pattern that is typical of hormesis. Thyrosphere growth concerned the size rather than number, except with the metal mixture. An altered morphology was also observed in metal-treated thyrospheres. Metal-induced proliferation was due to activation of the ERK1/2 pathway, as confirmed by growth inhibition when ERK1/2 signaling was blocked. These studies show that stem/precursor thyroid cells are sensitive to small increases in environmental metal concentrations that are harmless for differentiated thyrocytes.

Pulmonary Adenofibroma in an Elderly Male with Recurrent Soft Tissue Sarcoma

Pulmonary Adenofibroma (PAF) is a rare soft tissue tumour of the lung. It is a benign lesion, having a biphasic pattern with an admixture of epithelial and stromal components and has resemblance to fibroadenoma of the breast and adenofibroma of the female genital tract. The diagnosis can be challenging and it has to be delineated from other entities with biphasic pattern, like pulmonary hamartoma, pulmonary blastoma, intrapulmonary solitary fibrous tumour and metastases from soft tissue and visceral sarcomas, as each tumour has its own therapeutic and prognostic implications. Here, we report a case of a 73-year-old male, a known case of recurrent soft tissue sarcoma of the thigh, who presented with solitary pulmonary lesion. The patient was a non-smoker and did not have any specific respiratory complaints. On staging work-up with a Positron Emission Tomography and Computed Tomography (PET-CT), a hypermetabolic lesion was identified in the anterior segment of right upper lobe of the lung, following which he underwent right lobectomy. The tumour was a solitary lesion located near the hilum and on histology showed a biphasic pattern with scattered glandular spaces lined by columnar epithelium set in a hyalinised spindle cell stroma. The cells showed mild pleomorphism with oval to elongated nuclei and indistinct cytoplasm. On immunohistochemistry, the epithelial component showed positivity for Cytokeratin (CK), Epithelial Membrane Antigen (EMA), Thyroid Transcription Factor-1 (TTF-1) and Napsin-A and the stromal component showed positivity for Vimentin, Desmin, Smooth Muscle Actin (SMA) and H-Caldesmon (High molecular weight isoform-Caldesmon). With the given histological and immunohistochemistry findings, a diagnosis of PAF was rendered.

Echocardiographic characteristics of patients with SARS-CoV-2 infection

Background Myocardial involvement induced by SARS-CoV-2 infection might be important for long-term prognosis. The aim of this observational study was to characterize the myocardial effects during SARS-CoV-2 infections by echocardiography. Results and methods An extended echocardiographic image acquisition protocol was performed in 18 patients with SARS-CoV-2 infection assessing LV longitudinal, radial, and circumferential deformation including rotation, twist, and untwisting. Furthermore, LV deformation was analyzed in an age-matched control group of healthy individuals (n = 20). The most prevalent finding was a reduced longitudinal strain observed predominantly in more than one basal LV segment (n = 10/14 patients, 71%). This pattern reminded of a “reverse tako-tsubo” morphology that is not typical for other viral myocarditis. Additional findings included a biphasic pattern with maximum post-systolic or negative regional radial strain predominantly basal (n = 5/14 patients, 36%); the absence or dispersion of basal LV rotation (n = 6/14 patients, 43%); a reduced or positive regional circumferential strain in more than one segment (n = 7/14 patients, 50%); a net rotation showing late post-systolic twist or biphasic pattern (n = 8/14 patients, 57%); a net rotation showing polyphasic pattern and/or higher maximum net values during diastole (n = 8/14 patients, 57%). Conclusion Myocardial involvement due to SARS-CoV-2-infection was highly prevalent in the present cohort—even in patients with mild symptoms. It appears to be characterized by specific speckle tracking deformation abnormalities in the basal LV segments. These data set the stage to prospectively test whether these parameters are helpful for risk stratification and for the long-term follow-up of these patients.

Circadian Rhythm of Deaths in a Cardiology Department: A Five-Year Analysis

Background: Previous studies have described a circadian pattern of death from cardiovascular causes with a morning peak. Our aim is to describe the daytime oscillations in mortality in hospitalized patients with cardiovascular diseases. Methods: Our retrospective registry including all patients who died in the Cardiology Department, including the cardiac intensive care unit, Madrid, Spain. Results: From a total of 500 patients, time of death was registered in 373 (74.6%), which are the focus of our study; 354 (70.8%) died in the cardiac intensive care unit and 146 (29.2%) in the conventional ward. Mean age was 74.2 ± 13.1 years, and 239 (64.1%) were male. Cardiovascular causes were the leading cause of death (308 patients; 82.6%). Mortality followed a circadian biphasic pattern with a peak at dawn (00.00–05.59 a.m.: 104 patients [27.9%]) and in the afternoon (12.00–17.59 p.m.: 135 patients [36.2%]), irrespective of the cause of death. The peak of mortality occurred in the afternoon (12.00–17.59 p.m.) in the case of cardiovascular mortality (119 deaths [38.6%]) and in the evening (18.00–23.59 p.m.) for non-cardiovascular deaths (21 deaths [32.3%], p = 0.03). This pattern was present regardless from the place of death (conventional ward or cardiac intensive care unit) and also throughout the four seasons. Conclusions: Mortality in hospitalized patients with cardiovascular diseases follows a circadian biphasic pattern.

Anterior pituitary function in critical illness

Critical illness is hallmarked by major changes in all hypothalamic–pituitary–peripheral hormonal axes. Extensive animal and human studies have identified a biphasic pattern in circulating pituitary and peripheral hormone levels throughout critical illness by analogy with the fasting state. In the acute phase of critical illness, following a deleterious event, rapid neuroendocrine changes try to direct the human body toward a catabolic state to ensure provision of elementary energy sources, whereas costly anabolic processes are postponed. Thanks to new technologies and improvements in critical care, the majority of patients survive the acute insult and recover within a week. However, an important part of patients admitted to the ICU fail to recover sufficiently, and a prolonged phase of critical illness sets in. This prolonged phase of critical illness is characterized by a uniform suppression of the hypothalamic–pituitary–peripheral hormonal axes. Whereas the alterations in hormonal levels during the first hours and days after the onset of critical illness are evolutionary selected and are likely beneficial for survival, endocrine changes in prolonged critically ill patients could be harmful and may hamper recovery. Most studies investigating the substitution of peripheral hormones or strategies to overcome resistance to anabolic stimuli failed to show benefit for morbidity and mortality. Research on treatment with selected and combined hypothalamic hormones has shown promising results. Well-controlled RCTs to corroborate these findings are needed.

Costal and crural diaphragm function during sustained hypoxia in awake canines

In humans and other mammals, isocapnic hypoxia sustained for 20–60 min exhibits a biphasic ventilation pattern: initial increase followed by a significant ventilatory decline (“roll-off”) to a lesser intermediate plateau. During sustained hypoxia, the mechanical action and activity of the diaphragm have not been studied; thus we assessed diaphragm function in response to hypoxic breathing. Thirteen spontaneously breathing awake canines were exposed to moderate levels of sustained isocapnic hypoxia lasting 20–25 min (80 ± 2% pulse oximeter oxygen saturation). Breathing pattern and changes in muscle length and electromyogram (EMG) activity of the costal and crural diaphragm were continuously recorded. Mean tidal shortening and EMG activity of the costal and crural diaphragm exhibited an overall biphasic pattern, with initial brisk increase followed by a significant decline ( P < 0.01). Although costal and crural shortening did not differ significantly with sustained hypoxia, this equivalence in segmental shortening occurred despite distinct and differing EMG activities of the costal and crural segments. Specifically, initial hypoxia elicited a greater costal EMG activity compared with crural ( P < 0.05), whereas sustained hypoxia resulted in a lesser crural EMG decline/attenuation than costal ( P < 0.05). We conclude that sustained isocapnic hypoxia elicits a biphasic response in both ventilation and diaphragmatic function and there is clear differential activation and contribution of the two diaphragmatic segments. This different diaphragm segmental action is consistent with greater neural activation of costal diaphragm during initial hypoxia, then preferential sparing of crural activation as hypoxia is sustained. NEW & NOTEWORTHY In humans and other mammals, during isocapnic hypoxia sustained for 20–60 min ventilation exhibits a biphasic pattern: initial increase followed by significant ventilatory decline (“roll-off”). During sustained hypoxia, the function of the diaphragm is unknown. This study demonstrates that the diaphragm reveals a biphasic action during the time-dependent hypoxic “roll-off” in ventilation. These results also highlight that the two diaphragm segments, costal and crural, show differing, distinctive contributions to diaphragm function during sustained hypoxia.

Extraskeletal Mesenchymal Chondrosarcoma

Extraskeletal mesenchymal chondrosarcoma is a rare soft tissue sarcoma arising from soft tissues, mainly of the lower extremities, meninges, and orbits. It usually presents during the second to third decades of life, and has a slight predominance in females. Histologically, it has a typical biphasic pattern comprising small cells and islands of hyaline cartilage. It can pose a diagnostic challenge in small biopsy specimens where 1 of the 2 components can be absent. The prognosis is extremely variable; survival varies depending on the location of the tumor.