Demonstration of a modelling-based multi-criteria decision analysis procedure for prioritisation of occupational risks from manufactured nanomaterials

Several tools to facilitate the risk assessment and management of manufactured nanomaterials (MN) have been developed. Most of them require input data on physicochemical properties, toxicity and scenario-specific exposure information. However, such data are yet not readily available, and tools that can handle data gaps in a structured way to ensure transparent risk analysis for industrial and regulatory decision making are needed. This paper proposes such a quantitative risk prioritisation tool, based on a multi-criteria decision analysis algorithm, which combines advanced exposure and dose-response modelling to calculate margins of exposure (MoE) for a number of MN in order to rank their occupational risks. We demonstrated the tool in a number of workplace exposure scenarios (ES) involving the production and handling of nanoscale titanium dioxide, zinc oxide (ZnO), silver and multi-walled carbon nanotubes. The results of this application demonstrated that bag/bin filling, manual un/loading and dumping of large amounts of dry powders led to high emissions, which resulted in high risk associated with these ES. The ZnO MN revealed considerable hazard potential in vivo, which significantly influenced the risk prioritisation results. In order to study how variations in the input data affect our results, we performed probabilistic Monte Carlo sensitivity/uncertainty analysis, which demonstrated that the performance of the proposed model is stable against changes in the exposure and hazard input variables.     

Hypoactive sexual desire disorder in postmenopausal women.

Decreases in sex hormone levels with menopause may bring about a number of consequences in women's general health and sexual well-being, especially when levels decline suddenly and prematurely, as in surgical menopause. In addition to the well-established role of estrogens in preserving the biological basis of sexual response, there is emerging evidence that androgens are significant independent determinants affecting sexual desire, activity and satisfaction, as well as mood, energy and other components of women's health. Hypoactive sexual desire disorder (HSDD), a persistent absence of sexual fantasies or thoughts and/or desire for and receptivity to sexual activity that causes personal distress, is experienced by some postmenopausal women. Even though conventional hormone therapy with estrogens or estrogens and progestogens may be effective for vaginal atrophy, increasing vaginal lubrication and reducing dyspareunia, it has not been shown to consistently increase sexual desire or activity and many women with sexual dysfunction remain unresponsive. Several recent, large, phase III studies have shown that the addition of transdermal testosterone to conventional hormone therapy can be helpful in surgically menopausal women presenting with HSDD. After 24 weeks of treatment in these studies, testosterone-treated women experienced significantly greater increases in satisfying sexual activity and sexual desire, and greater decreases in distress, than placebo-treated women. Accurate clinical assessment and individualized management of sexual symptoms are fundamentally important for all menopausal women with HSDD or other sexual problems.     

Monolateral hypoplasia of the motor vagal nuclei in a case of sudden infant death syndrome

During the development of motor vagal nuclei (MVN), the neuroblasts of the myeloencephalic basal plate migrate in the dorsolateral direction to form the dorsal motor vagal nucleus (DMVN) and ventrolaterally to form the ventral motor vagal nucleus (VMVN). Those neuroblasts that remain close to the median sulcus will form the hypoglossal nucleus. In support of the congenital origin of the alteration of the MVN in sudden infant death syndrome (SIDS), we report the case of an 8‐month‐old female child who was found dead in her cot. The neuropathological assessment revealed that the medullary triangle of the 4th ventricle floor was asymmetric, owing to the presence of three prominences to the left side of the median sulcus. The medial prominence corresponded to the hypoglossal nucleus, which showed a marked increase in the number of large neurons; the intermediate prominence corresponded to the DMVN whose large neurons were reduced and were recognizable mainly at the level of the medial fringe; the lateral prominence corresponded to the solitary nucleus. The left solitary tract showed a reduction of the transverse diameter. Also, the left VMVN showed marked reduction in the number of neurons. Inflammatory and astrocytic reactions were absent. We suggest that in SIDS cases the hypocellularity of the MVN and the increased number of neurons of the hypoglossal nucleus are intimately related, indicating a congenital alteration due to incomplete migration of the vagal neuroblasts with abnormality of the autonomic cardio‐respiratory control.     

Investigations on the possible involvement of the dopaminergic system in the modulation of the growth and steroidogenic capacity of the rat adrenal zona glomerulosa: A coupled morphometric and biochemical study

The effects of metoclopramide (MTC) and bromocriptine (BRC) (two drugs which act as antagonist and agonist of DOPA-receptors, respectively) on the zona glomerulosa of dexamethasone/ACTH-treated rats were investigated by coupled biochemical and morphometric techniques. Short-term (1-h) MTC administration significantly increased the plasma concentration of aldosterone, while long-term (7-day) MTC administration, as well as short- and long-term treatment with BRC did not cause any apparent change. Long-term MTC administration was found to significantly potentiate both the rise in the plasma level of aldosterone and the hypertrophy of the zona glomerulosa and its parenchymal cells induced by a prolonged treatment with angiotensin II (AII), but not those evoked by a chronic sodium deprivation alone or combined with AII infusion. Long-term BRC administration notably counteracted the effects of sodium restriction (coupled or not with AII infusion), but not those induced by the administration of AII alone. Long-term MTC administration partially reversed both the lowering of the plasma concentration of aldosterone and the atrophy of the zona glomerulosa and its parenchymal cells caused by a prolonged sodium-loading (combined or not with captopril infusion), but not those produced by the administration of captopril alone. On the other hand, long-term BRC treatment induced a further significant reduction in the blood level of aldosterone and the volume of zona glomerulosa and its cells only in captopril-treated animals. These findings are consistent with the view that the dopaminergic system exerts a maximal tonic inhibitory effect not only on the secretory activity, but also on the growth and steroidogenic capacity of the rat zona glomerulosa. Furthermore, they suggest that the activity of the dopaminergic system is in turn controlled by the sodium balance, being almost completely suppressed by a prolonged sodium deprivation.     

TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations

The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β‐tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron‐specific expression pattern. A recurrent heterozygous mutation, c.1228G > A; p.E410K, in TUBB3 gene is responsible of a rare disorder clinically characterized by congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability and a wide range of neurological and endocrine abnormalities. Other mutations have been described spanning the entire gene and genotype–phenotype correlations have been proposed. We report on a 3‐year‐old boy in whom clinical exome sequencing allowed to identify a de novo TUBB3 E410K mutation as the molecular cause underlying a complex phenotype characterized by a severe bilateral palpebral ptosis refractory to eye surgery, psychomotor delay, absent speech, hypogonadism, celiac disease, and cyclic vomiting. Brain MRI revealed thinning of the corpus callosum with no evidence of malformation cortical dysplasia. We reviewed available records of patients with TUBB3 E410K mutation and compared their phenotype with the clinical outcome of patients with other mutations in TUBB3 gene. The present study confirms that TUBB3 E410K results in a clinically recognizable phenotype, unassociated to the distinct cortical dysplasia caused by other mutations in the same gene. Early molecular characterization of TUBB3 E410K syndrome is critical for targeted genetic counseling and prompt prospective care in term of neurological, ophthalmological, endocrine, and gastrointestinal follow‐up.     

Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.     

Impact of 970 nm photobiomodulation therapy on wound healing in cellular models of hidradenitis suppurativa

Lasers in Medical Science -     

The competitive NMDA antagonists CGP 43487 and APV potentiate dopaminergic function

The administration to rats of different doses of the non competitive NMDA receptor blocker MK-801 (0.03–1 mg/kg IP) induced stimulation or reduction of locomotor activity, depending on the dose, whereas the competitive NMDA antagonists CGP 43487 (0.188–6 mg/kg IP) and APV (2.5–20 g/rat ICV) inhibited locomotion at the highest doses. Unlike MK-801 and APV treatment, the administration of CGP 43487 did not induce impairment of rota-rod test performance. Both competitive and non-competitive NMDA antagonists, at doses devoid of any behavioral effect per se, potentiated the responses elicited by apomorphine (0.25 mg/kg SC). In particular, the occurrence of episodes of licking was weakly affected by MK-801 administration, but significantly increased by CGP 43487 and APV treatment; the presence of gnawing was augmented by all the pretreatments; sniffing, locomotion, grooming and rearing occurrence were not affected by the administration of NMDA antagonists. The results suggest that the competitive antagonists which facilitated dopaminergic function without causing motor impairment could be useful supplements in the treatment of Parkinson's disease.