Cutaneous larva migrans on the scalp: atypical presentation of a common disease

Cutaneous larva migrans is a pruritic dermatitis due to the inoculation of helminths larvae in the skin, and it often occurs in children in tropical and subtropical areas. The authors describe an atypical case of cutaneous larva migrans in a 11 year-old child with scalp involvement, an unusual topography for this lesion.     

Routine childhood vaccination programme coverage,El Salvador, 2011—In search of timeliness

While assessing immunization programmes, not only vaccination coverage is important, but also timely receipt of vaccines. We estimated both vaccination coverage and timeliness, as well as reasons for non-vaccination, and identified predictors of delayed or missed vaccination, for vaccines of the first two years of age, in El Salvador.     

Effect of silica coating and laser treatment on the flexural strength,surface characteristics,and bond strength of a dental zirconia

This study investigated the effect of irradiation with an erbium‐doped yttrium aluminium garnet (Er:YAG) laser and coating with silica on the surface characteristics, bond strength, and flexural strength of dental zirconia. Three hundred and forty‐three standard zirconia specimens were created, and 49 were assigned to each of seven surface treatment groups: (i) no treatment; Er:YAG laser (80 mJ/2 Hz) with pulse widths of 50 μs (ii), 100 μs (iii), 300 μs (iv), or 600 μs (v); or tribochemical silica coating at the partially sintered stage (vi) or after sintering was complete (vii). All specimens were sintered after the surface treatments, except for the group in which specimens were sintered before treatment. The study outcomes were roughness, surface loss, microshear bond strength (μSBS), and biaxial flexural strength (BFS). Mean roughness and surface loss values were significantly higher in specimens from irradiated groups than in those from silica‐coated groups. Regarding μSBS, after aging, specimens from all experimental groups presented very low and similar μSBS values, irrespective of the surface treatment. Silica coating after sintering yielded the highest BFS (1149.5 ± 167.6 MPa), while coating partially sintered specimens with silica resulted a BFS (826.9 ± 60.9 MPa) similar to that of the untreated control group (794.9 ± 101.7 MPa). Laser treatments, irrespective of pulse width used, significantly decreased the BFS. In the group treated with laser at 300 μs pulse width, specimens exhibited the lowest BFS value (514.1 ± 71.5 MPa). Adhesion to zirconia was not stable after aging, regardless of the surface treatment implemented.     

Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation,a target of melatonin

The connection between the innate immune system, clock genes, and mitochondrial bioenergetics was analyzed during aging and sepsis in mouse heart. Our results suggest that the sole NF‐κB activation does not explain the inflammatory process underlying aging; the former also triggers the NLRP3 inflammasome that enhances caspase‐1‐dependent maturation of IL‐1β. In this way, aged mice enter into a vicious cycle as IL‐1β further activates the NF‐κB/NLRP3 inflammasome link. The origin of NF‐κB activation was related to the age‐dependent Bmal1/Clock/RORα/Rev‐Erbα loop disruption, which lowers NAD⁺ levels, reducing the SIRT1 deacetylase ability to inactivate NF‐κB. Consequently, NF‐κB binding to DNA increases, raising the formation of proinflammatory mediators and inducing mitochondrial impairment. The cycle is then closed with the subsequent NLRP3 inflammasome activation. This paired contribution of the innate immune pathways serves as a catalyst to magnify the response to sepsis in aged compared with young mice. Melatonin administration blunted the septic response, reducing inflammation and oxidative stress, and enhancing mitochondrial function at the levels of nonseptic aged mice, but it did not counteract the age‐related inflammation. Together, our results suggest that, although with different strengths, chronoinflammaging constitutes the biochemical substrate of aging and sepsis, and identifies the NLRP3 inflammasome as a new molecular target for melatonin, providing a rationale for its use in NLRP3‐dependent diseases.     

Hypoxia and its therapeutic possibilities in paediatric cancers

In tumours, hypoxia—a condition in which the demand for oxygen is higher than its availability—is well known to be associated with reduced sensitivity to radiotherapy and chemotherapy, and with immunosuppression. The consequences of hypoxia on tumour biology and patient outcomes have therefore led to the investigation of strategies that can alleviate hypoxia in cancer cells, with the aim of sensitising cells to treatments. An alternative therapeutic approach involves the design of prodrugs that are activated by hypoxic cells. Increasing evidence indicates that hypoxia is not just clinically significant in adult cancers but also in paediatric cancers. We evaluate relevant methods to assess the levels and extent of hypoxia in childhood cancers, including novel imaging strategies such as oxygen-enhanced magnetic resonance imaging (MRI). Preclinical and clinical evidence largely supports the use of hypoxia-targeting drugs in children, and we describe the critical need to identify robust predictive biomarkers for the use of such drugs in future paediatric clinical trials. Ultimately, a more personalised approach to treatment that includes targeting hypoxic tumour cells might improve outcomes in subgroups of paediatric cancer patients.Subject terms: Tumour biomarkers, Paediatric cancer, Cancer microenvironment, Cancer therapy     

Enhanced Heterosexual Transmission Hypothesis for the Origin of Pandemic HIV-1

HIV-1 M originated from SIVcpz endemic in chimpanzees from southeast Cameroon or neighboring areas, and it started to spread in the early 20th century. Here we examine the factors that may have contributed to simian-to-human transmission, local transmission between humans, and export to a city. The region had intense ape hunting, social disruption, commercial sex work, STDs, and traffic to/from Kinshasa in the period 1899–1923. Injection treatments increased sharply around 1930; however, their frequency among local patients was far lower than among modern groups experiencing parenteral HIV-1 outbreaks. Recent molecular datings of HIV-1 M fit better the period of maximal resource exploitation and trade links than the period of high injection intensity. We conclude that although local parenteral outbreaks might have occurred, these are unlikely to have caused massive transmission. World War I led to additional, and hitherto unrecognized, risks of HIV-1 emergence. We propose an Enhanced Heterosexual Transmission Hypothesis for the origin of HIV-1 M, featuring at the time and place of its origin a coincidence of favorable co-factors (ape hunting, social disruption, STDs, and mobility) for both cross-species transmission and heterosexual spread. Our hypothesis does not exclude a role for parenteral transmission in the initial viral adaptation.